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1. Work Ability in Patients With Stage I to IV Colon Cancer

Author: Mira D, Franken, Geraldine, Vink, Wilhelmina M U, van Grevenstein, Helena M, Verkooijen, Cornelis J A, Punt, Miriam, Koopman, Anne M, May, David D E, Zimmerman, Interne Geneeskunde, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and MUMC+: MA Medische Oncologie (9)
Subjects: medicine.medical_specialty, Colorectal cancer, Population, Work Capacity Evaluation, Disease, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], All institutes and research themes of the Radboud University Medical Center, Internal medicine, medicine, Humans, Prospective Studies, Stage (cooking), Prospective cohort study, education, Neoplasm Staging, Retrospective Studies, education.field_of_study, business.industry, Colonic Neoplasms/surgery, Gastroenterology, Cancer, General Medicine, medicine.disease, Comorbidity, Cohort, business
Abstract: BACKGROUND: Colon cancer affects a patient's ability to work. Many patients who have colon cancer are employed at the time of diagnosis.OBJECTIVE: We evaluated work ability during the first 2 years after colon cancer diagnosis.DESIGN: This study is a national prospective study, the Prospective Dutch ColoRectal Cancer cohort, including clinical data and patient-reported outcomes.SETTINGS: Data were collected in 59 medical centers in the Netherlands.PATIENTS: Patients MAIN OUTCOME MEASURES: Work ability was assessed at baseline, 3, 6, 12, 18, and 24 months. The Work Ability Index (range, 0 to 49) was evaluated using linear mixed models. Outcomes were matched to population controls without cancer.RESULTS: Of 390 patients, 84% had paid employment. Work ability of patients with stage I to IV colon cancer was significantly lower at the time of diagnosis than in matched population controls (31 ± 8.2 and 41 ± 5.6). Patients with stage I to III disease receiving surgery only regained Work Ability Index scores comparable to matched population controls at 18 months. Patients receiving adjuvant systemic treatment initially demonstrated a decrease in work ability with improvements from 6 months onward and normalization at 24 months. Patients with stage IV disease did not demonstrate improvements in work ability outcomes over time. Work ability scores were negatively influenced by the administration of systemic treatment and ≥1 comorbidities.LIMITATIONS: Only patients with patient-reported outcomes and work at baseline were included in this analysis. Also, questionnaire response rates decreased over time.CONCLUSIONS: Work ability in patients with colon cancer is decreased for a prolonged time. Recovery depends on disease stage, type of treatment, and comorbidities. Patients with stage I to III disease treated with curative surgery alone were the first to regain work ability, followed by patients who receive adjuvant chemotherapy. Patients with stage IV disease did not regain work ability. See Video Abstract at http://links.lww.com/DCR/B759 .CAPACIDAD LABORAL EN PACIENTES CON CNCER DE COLON EN ESTADIO IIV RESULTADOS PROSPECTIVOS DE CNCER COLORECTAL EN UNA COHORTE HOLANDESA: ANTECEDENTES:El cáncer de colon afecta la capacidad de trabajo en un paciente. Muchos pacientes con cáncer de colon están empleados en el momento del diagnóstico.OBJETIVO:Evaluamos la capacidad laboral durante los dos primeros años posteriores al diagnóstico de cáncer de colon.DISEÑO:Es un estudio prospectivo nacional, la cohorte de cáncer colorrectal holandés, incluye datos clínicos y resultados informados por los pacientes.ENTORNO CLINICO:Se recopilaron datos de 59 centros médicos en los Países Bajos.PACIENTES:Se seleccionaron pacientes < 67 años, con cáncer de colon en estadio I-IV, que completaron los cuestionarios de índice de capacidad para el trabajo.PRINCIPALES MEDIDAS DE VALORACIÓN:La capacidad para el trabajo se evaluó al inicio, a los 3, 6, 12, 18 y 24 meses. El índice de capacidad para el trabajo (que va de 0 a 49) se evaluó mediante modelos lineales mixtos. Los resultados fueron comparados con el grupo control sin cáncer.RESULTADOS:De 390 pacientes, el 84% tenía un empleo remunerado. La capacidad de trabajo de los pacientes en estadio I-IV fue significativamente menor en el momento del diagnóstico en comparación con el grupo control (31 ± 8,2 y 41 ± 5,6, respectivamente). Los pacientes con enfermedad en estadio I-III que recibieron cirugía lograron recuperar puntajes del índice de capacidad laboral comparables a los controles a los 18 meses. Los pacientes que recibieron tratamiento sistémico adyuvante inicialmente demostraron una disminución en la capacidad de trabajo con mejoras a partir de los 6 meses en adelante y una normalización a los 24 meses. Los pacientes en estadio IV no demostraron mejoras en los resultados de la capacidad laboral a lo largo del tiempo. Las puntuaciones de capacidad para el trabajo se vieron influidas negativamente por la administración del tratamiento sistémico y la existencia de ≥1 comorbilidades.LIMITACIONES:En este análisis solo se incluyeron los pacientes con resultados y trabajo desde el inicio del estudio. Además, las tasas de respuesta al cuestionario disminuyeron con el tiempo.CONCLUSIONES:La capacidad de trabajo en pacientes con cáncer de colon se reduce durante un tiempo prolongado. La recuperación depende del estadio de la enfermedad, el tipo de tratamiento y la comorbilidad. Los pacientes con enfermedad en estadio I-III tratados con cirugía curativa exclusivamente, son los primeros en recuperar la capacidad para trabajar, seguidos de los pacientes que reciben quimioterapia adyuvante. Los pacientes con enfermedad en estadio IV no recuperan la capacidad para trabajar. Consulte Video Resumen en http://links.lww.com/DCR/B759 . (Traducción- Dr. Ingrid Melo ).
Published: 2023
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2. Clinical characterization of the first Belgian SCN5A founder mutation cohort

Author: Pieter Koopman, Maaike Alaerts, Bart Loeys, Hein Heidbuchel, Ewa Sieliwonczyk, Bert Vandendriessche, Anniek Corveleyn, Charlotte Claes, Aleksandra Nijak, Lut Van Laer, Christiaan J. Vrints, Geert Mortier, Eline Simons, Johan Saenen, Rik Willems, Emeline M. Van Craenenbroeck, Dorien Schepers, Tomas Robyns, Robyns, Tomas/0000-0002-8676-4874, Willems, Rik/0000-0002-5469-9609, Sieliwonczyk, Ewa/0000-0002-8603-7044, Koopman, Pieter/0000-0002-6373-180X, Sieliwonczyk, Ewa, Alaerts, Maaike, Robyns, Tomas, Schepers, Dorien, Claes, Charlotte, Corveleyn, Anniek, Willems, Rik, Van Craenenbroeck, Emeline M., Simons, Eline, Nijak, Aleksandra, Vandendriessche, Bert, Mortier, Geert, Vrints, Christiaan, KOOPMAN, Pieter, HEIDBUCHEL, Hein, Van Laer, Lut, Saenen, Johan, and Loeys, Bart
Subjects: Proband, medicine.medical_specialty, conduction defects, Atrial dysrhythmia, 030204 cardiovascular system & hematology, Sudden death, NAV1.5 Voltage-Gated Sodium Channel, Electrocardiography, 03 medical and health sciences, 0302 clinical medicine, Belgium, Physiology (medical), Internal medicine, Brugada syndrome, SCN5A, Founder mutation, Cardiac, Cardiac conduction, medicine, Humans, cardiovascular diseases, Biology, Brugada Syndrome, 030304 developmental biology, 0303 health sciences, business.industry, Haplotype, medicine.disease, Penetrance, 3. Good health, Phenotype, Mutation, Mutation (genetic algorithm), cardiovascular system, Human medicine, Cardiology and Cardiovascular Medicine, business, Founder effect
Abstract: Aims We identified the first Belgian SCN5A founder mutation, c.4813 + 3_4813 + 6dupGGGT. To describe the clinical spectrum and disease severity associated with this mutation, clinical data of 101 SCN5A founder mutation carriers and 46 non-mutation carrying family members from 25 Belgian families were collected. Methods and results The SCN5A founder mutation was confirmed by haplotype analysis. The clinical history and electrocardiographic parameters of the mutation carriers and their family members were gathered and compared. A cardiac electrical abnormality was observed in the majority (82%) of the mutation carriers. Cardiac conduction defects, defined as PR or QRS prolongation on electrocardiogram (ECG), were most frequent, occurring in 65% of the mutation carriers. Brugada syndrome (BrS) was the second most prevalent phenotype identified in 52%, followed by atrial dysrythmia in 11%. Overall, 33% of tested mutation carriers had a normal sodium channel blocker test. Negative tests were more common in family members distantly related to the proband. Overall, 23% of the mutation carriers were symptomatic, with 8% displaying major adverse events. As many as 13% of the patients tested with a sodium blocker developed ventricular arrhythmia. One family member who did not carry the founder mutation was diagnosed with BrS. Conclusion The high prevalence of symptoms and sensitivity to sodium channel blockers in our founder population highlights the adverse effect of the founder mutation on cardiac conduction. The large phenotypical heterogeneity, variable penetrance, and even non-segregation suggest that other genetic (and environmental) factors modify the disease expression, severity, and outcome in these families.
Published: 2020
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3. In-depth assessment of health-related quality of life after in-hospital cardiac arrest

Author: Sanne E. Hoeks, B. van den Bogaard, A.H.M. Knook, Robert Jan Stolker, T. van Melsen, Evert-Jan Wils, R. J. G. Peters, M. Schluep, Chris Hukshorn, Michiel J. Blans, Koen S. Simons, Henrik Endeman, C. Kuijs, B.J.M. van der Meer, G. Spijkers, A.W.M.M. Koopman Van Gemert, J.W. Vermeijden, B.Y. Gravesteijn, Anesthesiology, and Intensive Care
Subjects: Adult, Male, medicine.medical_specialty, Population, Critical Care and Intensive Care Medicine, Quality of life, SDG 3 - Good Health and Well-being, Surveys and Questionnaires, medicine, Humans, Prospective Studies, Survivors, education, Prospective cohort study, Health related quality of life, education.field_of_study, business.industry, Psychological distress, humanities, Hospitals, Heart Arrest, Index score, Functional independence, Physical therapy, Quality of Life, Functional status, business
Abstract: Introduction Evidence on physical and psychological well-being of in-hospital cardiac arrest (IHCA) survivors is scarce. The aim of this study is to describe long-term health-related quality of life (HRQoL), functional independence and psychological distress 3 and 12 months post-IHCA. Methods A multicenter prospective cohort study in 25 hospitals between January 2017 – May 2018. Adult IHCA survivors were included. HRQoL (EQ-5D-5L, SF-12), psychological distress (HADS, CSI) and functional independence (mRS) were assessed at 3 and 12 months post-IHCA. Results At 3-month follow-up 136 of 212 survivors responded to the questionnaire and at 12 months 110 of 198 responded. The median (IQR) EQ-utility Index score was 0.77 (0.65–0.87) at 3 months and 0.81 (0.70–0.91) at 12 months. At 3 months, patients reported a median SF-12 (IQR) physical component scale (PCS) of 38.9 (32.8–46.5) and mental component scale (MCS) of 43.5 (34.0–39.7) and at 12 months a PCS of 43.1 (34.6–52.3) and MCS 46.9 (38.5–54.5). Discussion Using various tools most IHCA survivors report an acceptable HRQoL and a substantial part experiences lower HRQoL compared to population norms. Our data suggest that younger (male) patients and those with poor functional status prior to admission are at highest risk of impaired HRQoL.
Published: 2022

4. Cell salvage in burn excisional surgery

Author: Ankie W. M. M. Koopman-van Gemert, Cornelis H. van der Vlies, Tjaco M Ossewaarde, Veerle Verhees, Seppe S H A Koopman, Rolf K. Gigengack, Stephan A. Loer, I.M.M.H. Oen, Anesthesiology, ACS - Diabetes & metabolism, and Surgery
Subjects: Adult, Male, medicine.medical_specialty, Erythrocytes, DNA Repair, medicine.medical_treatment, Cell, Blood Loss, Surgical, Hematocrit, Critical Care and Intensive Care Medicine, Cell saver, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Blood loss, medicine, Humans, Blood Transfusion, Prospective Studies, Saline, Aged, Salvage Therapy, medicine.diagnostic_test, business.industry, 030208 emergency & critical care medicine, General Medicine, Middle Aged, Surgery, Red blood cell, medicine.anatomical_structure, Hemostasis, Cell Body, Emergency Medicine, Female, Hemoglobin, business
Abstract: BACKGROUND: Hemostasis during burn surgery is difficult to achieve, and high blood loss commonly occurs. Bleeding control measures are limited, and many patients require allogeneic blood transfusions. Cell salvage is a well-known method used to reduce transfusions. However, its evidence in burns is limited. Therefore, this study aimed to examine the feasibility of cell salvage during burn surgery.STUDY DESIGN AND METHODS: A prospective, observational study was conducted with 16 patients (20 measurements) scheduled for major burn surgery. Blood was recovered by washing saturated gauze pads with heparinized saline, which was then processed using the Cell Saver. Erythrocyte concentrate quality was analyzed by measuring hemoglobin, hematocrit, potassium, and free hemoglobin concentration. Microbial contamination was assessed based on cultures at every step of the process. Differences in blood samples were tested using the Student's t-test.RESULTS: The red blood cell mass recovered was 29 ± 11% of the mass lost. Patients' preoperative hemoglobin and hematocrit levels were 10.5 ± 1.8 g/dL and 0.33 ± 0.05 L/L, respectively. The erythrocyte concentrate showed hemoglobin and hematocrit levels of 13.2 ± 3.9 g/dL and 0.40 ± 0.11 L/L thus showing a concentration effect. The potassium level was lower in the erythrocyte concentrate (2.5 ± 1.5 vs. 4.1 ± 0.4 mmol/L, p CONCLUSION: Recovering erythrocytes during burn excisional surgery using cell salvage is possible. Despite strict sterile handling, erythrocyte concentrates of all patients showed bacterial contamination. The consequence of this contamination remains unclear and should be investigated in future studies.
Published: 2021
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5. Sixty-Day Mortality of Patients With Metastatic Colorectal Cancer Randomized to Systemic Treatment vs Primary Tumor Resection Followed by Systemic Treatment

Author: van der Kruijssen, Dave E W, Elias, Sjoerd G, Vink, Geraldine R, van Rooijen, Karlijn L, 't Lam-Boer, Jorine, Mol, Linda, Punt, Cornelis J A, de Wilt, Johannes H W, Koopman, Miriam, De Hingh, Ignace, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Epidemiologie, Oncology, and CCA - Cancer Treatment and Quality of Life
Subjects: Male, medicine.medical_specialty, Palliative care, Bevacizumab, Colorectal cancer, SURGERY, IMPACT, medicine.medical_treatment, Denmark, MULTICENTER, Netherlands/epidemiology, Gastroenterology, law.invention, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], Randomized controlled trial, INFLAMMATION, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, NO RESECTION, Medicine, Humans, LOCATION, Netherlands, Aged, Chemotherapy, biology, business.industry, Mortality rate, Colorectal Neoplasms/drug therapy, Middle Aged, medicine.disease, Primary tumor, Editorial from the ACHBPT, Denmark/epidemiology, PROGNOSTIC VALUE, Alanine transaminase, Biomarkers, Tumor/blood, biology.protein, SURVIVAL, Tumor/blood, Female, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, business, Colorectal Neoplasms, Biomarkers, medicine.drug
Abstract: Importance: The role of primary tumor resection (PTR) in synchronous patients with metastatic colorectal cancer (mCRC) who had unresectable metastases and few or absent symptoms of their primary tumor is unclear. Studying subgroups with low postoperative mortality may identify patients who potentially benefit from PTR.Objective: To determine the difference in 60-day mortality between patients randomized to systemic treatment only vs PTR followed by systemic treatment, and to explore risk factors associated with 60-day mortality.Design, Setting, and Participants: CAIRO4 is a randomized phase 3 trial initiated in 2012 in which patients with mCRC were randomized to systemic treatment only or PTR followed by systemic treatment with palliative intent. This multicenter study was conducted by the Danish and Dutch Colorectal Cancer Group in general and academic hospitals in Denmark and the Netherlands. Patients included between August 2012 and December 2019 with histologically proven colorectal cancer, unresectable metastases, and a primary tumor with few or absent symptoms were eligible.Interventions: Systemic treatment, consisting of fluoropyrimidine-based chemotherapy with bevacizumab vs PTR followed by fluoropyrimidine-based chemotherapy with bevacizumab.Main Outcomes and Measures: The aim of the current analysis was to compare 60-day mortality rates in both treatment arms. A secondary aim was the identification of risk factors for 60-day mortality in the treatment arms. These aims were not predefined in the study protocol.Results: A total of 196 patients were included in the intention-to-treat analysis (112 [57%] men; median [IQR] age, 65 [59-70] years). Sixty-day mortality was 3% (95% CI, 1%-9%) in the systemic treatment arm and 11% (95% CI, 6%-19%) in the PTR arm (P = .03). In a per-protocol analysis, 60-day mortality was 2% (95% CI, 1%-7%) vs 10% (95% CI, 5%-18%; P = .048). Patients with elevated serum levels of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and/or neutrophils who were randomized to PTR had a significantly higher 60-day mortality than patients without these characteristics.Conclusions and Relevance: Patients with mCRC who were randomized to PTR followed by systemic treatment had a higher 60-day mortality than patients randomized to systemic treatment. Especially patients randomized to the PTR arm with elevated serum levels of lactate dehydrogenase, neutrophils, aspartate aminotransferase, and/or alanine aminotransferase were at high risk of postoperative mortality. Final study results on overall survival have to be awaited.Trial Registration: ClinicalTrials.gov Identifier: NCT01606098.
Published: 2021
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6. Evaluation of the long-term effect and complication rate of single-incision slings for female stress urinary incontinence

Author: Hugo W F van Eijndhoven, Marian K. Engberts, Liz S Koopman, and Nienke J E Osse
Subjects: medicine.medical_specialty, Urinary Incontinence, Stress, Subjective improvement, Urinary incontinence, Sling (weapon), Statistical significance, medicine, Humans, Complication rate, Retrospective Studies, Suburethral Slings, Stress urinary incontinence, business.industry, Genitourinary system, Obstetrics and Gynecology, Midurethral sling, Surgery, Single-incision sling, Distress, Treatment Outcome, Reproductive Medicine, Female, medicine.symptom, business, Follow-Up Studies, Cohort study
Abstract: Objective: To evaluate the long-term outcomes of single-incision midurethral slings (SIMS) in real-life practice. Study Design: This retrospective, single-arm, patient cohort study was performed in a large Dutch teaching hospital, including 397 consecutive women who underwent a SIMS-procedure between 2009 and 2018. Data were obtained through questionnaires and patient record study. Subjective improvement was the primary outcome, defined as a Patient Global Impression of Improvement (PGI-I) of ‘(very) much better’. Secondary outcomes were subjective cure rate (defined as a negative Urogenital Distress Inventory - item 4 ‘Do you experience involuntary urine leakage related to physical activity, coughing or sneezing?’), complication rate and sling failure (defined as the need for additional research or treatment for persisting stress urinary incontinence (SUI)). All data was analysed with a statistical significance level of 5%. Results: The mean follow-up time was 54 months. All patients received SIMS (Ajust® or Altis®). Of all respondents, 75% reported a (very) much improved burden of disease. The subjective cure rate was 61%. In 93 patients a total of 120 complications were registered. In 10% of patients a sling failure was observed, 76% of these failures appeared in the first two years post-surgery. Conclusion: This study showed that, in real life practice, SIMS are both effective and safe over a long period of time.
Published: 2021
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7. Deferred Consent in an Acute Stroke Trial from a Patient, Proxy, and Physician Perspective: A Cross-Sectional Survey

Author: Féline E. V. Scheijmans, Gabriel J.E. Rinkel, Inez Koopman, W. Peter Vandertop, Martine Corrette Ploem, René Post, Dagmar Verbaan, Wouter M Sluis, Bert A Coert, Rieke van der Graaf, Erwin J. O. Kompanje, Mervyn D.I. Vergouwen, Neurosurgery, Amsterdam Neuroscience - Neurovascular Disorders, Amsterdam Neuroscience - Systems & Network Neuroscience, Graduate School, Ethics, Law & Medical humanities, APH - Personalized Medicine, APH - Quality of Care, and Intensive Care
Subjects: medicine.medical_specialty, Future studies, Patients, Referral, Cross-sectional study, Critical Care and Intensive Care Medicine, Proxy (climate), Informed consent, Physicians, Acute care, medicine, Humans, Subarachnoid hemorrhage, Deferral, Acute stroke, Ethics, Informed Consent, business.industry, Proxy, humanities, Stroke, Critical care, Cross-Sectional Studies, Family medicine, Deferred consent, Physician perspective, Neurology (clinical), business
Abstract: Background In some acute care trials, immediate informed consent is not possible, but deferred consent is often considered problematic. We investigated the opinions of patients, proxies, and physicians about deferred consent in an acute stroke trial to gain insight into its acceptability and effects. Methods Paper-based surveys were sent to patients who were randomly assigned in the Ultra-early Tranexamic Acid After Subarachnoid Hemorrhage (ULTRA) trial between 2015 and 2018 in two tertiary referral centers and to physicians of centers who agreed or declined to participate. The primary outcome measure was the proportion of respondents who agreed with deferral of consent in the ULTRA trial. Secondary outcomes included respondents’ preferred consent procedure for the ULTRA trial, the effect of deferred consent on trust in physicians and scientific research, and the willingness to participate in future research. Results Eighty-nine of 135 (66%) patients or proxies and 20 of 30 (67%) physicians completed the survey. Of these, 82 of 89 (92%) patients or proxies and 14 of 20 (70%) physicians agreed with deferral of consent in the ULTRA trial. When asked for their preferred consent procedure for the ULTRA trial, 31 of 89 (35%) patients or proxies indicated deferred consent, 15 of 89 (17%) preferred immediate informed consent, and 32 of 89 (36%) had no preference. None of the patients’ or proxies’ trust in physicians or scientific research had decreased because of the deferred consent procedure. Willingness to participate in future studies remained the same or increased in 84 of 89 (94%) patients or proxies. Conclusions A large majority of the surveyed patients and proxies and a somewhat smaller majority of the surveyed physicians agreed with deferred consent in the ULTRA trial. Deferred consent may enable acute care trials in an acceptable manner without decreasing trust in medicine. Future research should investigate factors facilitating the responsible use of deferred consent, such as in-depth interviews, to study the minority of participants who agreed with deferred consent but still preferred immediate informed consent.
Published: 2021
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8. Long-term survival and health-related quality of life after in-hospital cardiac arrest

Author: Patrick Perik, Henrik Endeman, Marco Knook, Chris Hukshorn, Gerben Spijkers, Sanne E. Hoeks, Koen S. Simons, Evert-Jan Wils, Marc Schluep, Bas van den Bogaard, Wytze J. Vermeijden, Cees Kuijs, Michiel J. Blans, R. J. G. Peters, Nardo J. M. van der Meer, Ankie W. M. M. Koopman-van Gemert, Trudy van Melsen, Robert-Jan Stolker, Anesthesiology, and Intensive Care
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Emergency Nursing, Quality of life, Modified Rankin Scale, Internal medicine, Long term survival, medicine, Humans, Prospective Studies, Cardiopulmonary resuscitation, Adverse effect, Prospective cohort study, Aged, Health related quality of life, business.industry, Incidence (epidemiology), Middle Aged, Cardiopulmonary Resuscitation, Hospitals, Heart Arrest, Quality of Life, Emergency Medicine, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Introduction: In-hospital cardiac arrest (IHCA) is an adverse event associated with high mortality. Because of the impact of IHCA more data is needed on incidence, outcomes and associated factors that are present prior to cardiac arrest. The aim was to assess one-year survival, patient-centred outcomes after IHCA and their associated pre-arrest factors. Methods: A multicentre prospective cohort study in 25 hospitals between January 1st 2017 and May 31st 2018. Patients ≥ 18 years receiving cardiopulmonary resuscitation (CPR) for IHCA were included. Data were collected using Utstein and COSCA-criteria, supplemented by pre-arrest Modified Rankin Scale (MRS, functional status) and morbidity through the Charlson Comorbidity Index (CCI). Main outcomes were survival, health-related quality of life (HRQoL, EuroQoL) and functional status (MRS) after one-year. Results: A total of 713 patients were included, 64.5% was male, median age was 63 years (IQR 52–72) and 72.8% had a non-shockable rhythm, 394 (55.3%) achieved ROSC, 231 (32.4%) survived to hospital discharge and 198 (27.8%) survived one year after cardiac arrest. Higher pre-arrest MRS, age and CCI were associated with mortality. At one year, patients rated HRQoL 72/100 points on the EQ-VAS and 69.7% was functionally independent. Conclusion: One-year survival after IHCA in this study is 27.8%, which is relatively high compared to previous studies. Survival is associated with a patient's pre-arrest functional status and morbidity. HRQoL appears acceptable, however functional rehabilitation warrants attention. These findings provide a comprehensive insight in in-hospital cardiac arrest prognosis.
Published: 2021
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9. Mortality associated with early changes in ARDS severity in COVID-19 patients

Author: Michiel T.U. Schuijt, Ignacio Martin-Loeches, Marcus J. Schultz, Frederique Paulus, Ary Serpa Neto, J.P. van Akkeren, A.G. Algera, C.K. Algoe, R.B. van Amstel, O.L. Baur, P. van de Berg, A.E. van den Berg, D.C.J.J. Bergmans, D.I. van den Bersselaar, F.A. Bertens, A.J.G.H. Bindels, M.M. de Boer, S. den Boer, L.S. Boers, M. Bogerd, L.D.J. Bos, M. Botta, J.S. Breel, H. de Bruin, S. de Bruin, C.L. Bruna, L.A. Buiteman-Kruizinga, O. Cremer, R.M. Determann, W. Dieperink, D.A. Dongelmans, H.S. Franke, M.S. Galek Aldridge, M.J. de Graaff, L.A. Hagens, J.J. Haringman, N.F.L. Heijnen, S. Hiel, S.T. van der Heide, P.L.J. van der Heiden, L.L. Hoeijmakers, L. Hol, M.W. Hollmann, M.E. Hoogendoorn, J. Horn, R. van der Horst, E.L.K. Ie, D. Ivanov, N.P. Juffermans, E. Kho, E.S. de Klerk, A.W.M. Koopman, M. Koopmans, S. Kucukcelebi, M.A. Kuiper, D.W. de Lange, N. van Mourik, I. Martin-Loeches, S.G. Nijbroek, M. Onrust, E.A.N. Oostdijk, F. Paulus, C.J. Pennartz, J. Pillay, L. Pisani, I.M. Purmer, T.C.D. Rettig, J.P. Roozeman, M.T.U. Schuijt, M.J. Schultz, A. Serpa Neto, M.E. Sleeswijk, M.R. Smit, P.E. Spronk, W. Stilma, A.C. Strang, A.M. Tsonas, P.R. Tuinman, C.M.A. Valk, F.L. Veen, A.P.J. Vlaar, L.I. Veldhuis, P. van Velzen, W.H. van der Ven, P. van Vliet, P. van der Voort, H.H. van der Wier, L. van Welie, H.J.F.T. Wesselink, B. van Wijk, T. Winters, W.Y. Wong, A.R.H. van Zanten, Anesthesiology, Graduate School, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, AII - Inflammatory diseases, Nursing, Amsterdam institute for Infection and Immunity, ACS - Diabetes & metabolism, ACS - Microcirculation, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Lectoraat Critical Care, Faculteit Gezondheid, Urban Vitality, PRoVENT-COVID, Critical Care, RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA Arts Assistenten IC (9), Intensive Care, and MUMC+: MA Medische Staf IC (9)
Subjects: medicine.medical_specialty, 2019-20 coronavirus outbreak, ARDS, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), macromolecular substances, Critical Care and Intensive Care Medicine, Article, lung, Internal medicine, mensen, medicine, Clinical endpoint, COVID–19, In patient, Mortality, humans, longen, Coronavirus disease 2019, Acute respiratory distress syndrome, business.industry, SARS-CoV-2, COVID-19, ademhaling, medicine.disease, Respiration, Artificial, respiratory distress syndrome, Cohort, Artificial, Breathing, business, corona, respiration
Abstract: Purpose We investigated changes in ARDS severity and associations with outcome in COVID–19 ARDS patients. Methods We compared outcomes in patients with ARDS classified as ‘mild’, ‘moderate’ or ‘severe’ at calendar day 1, and after reclassification at calendar day 2. The primary endpoint was 28–day mortality. We also identified which ventilatory parameters had an association with presence of severe ARDS at day 2. We repeated the analysis for reclassification at calendar day 4. Results Of 895 patients, 8.5%, 60.1% and 31.4% had mild, moderate and severe ARDS at day 1. These proportions were 13.5%, 72.6% and 13.9% at day 2. 28–day mortality was 25.3%, 31.3% and 32.0% in patients with mild, moderate and severe ARDS at day 1 (p = 0.537), compared to 28.6%, 29.2% and 44.3% in patients reclassified at day 2 (p = 0.005). No ventilatory parameter had an independent association with presence of severe ARDS at day 2. Findings were not different reclassifying at day 4. Conclusions In this cohort of COVID–19 patients, ARDS severity and mortality between severity classes changed substantially over the first 4 days of ventilation. These findings are important, as reclassification could help identify target patients that may benefit from alternative approaches., Graphical abstract Unlabelled Image
Published: 2021
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10. Association of homozygous variants of STING1 with outcome in human cervical cancer

Author: Bettien M. van Hemel, Nienke van Rooij, Bart Koopman, Timco Koopman, Marco de Bruyn, Harry Pijper, Harry Hollema, Bea Wisman, Joyce M Lubbers, Jessica M de Klerk-Sluis, Hans W. Nijman, Annechien Plat, Targeted Gynaecologic Oncology (TARGON), and Translational Immunology Groningen (TRIGR)
Subjects: 0301 basic medicine, Oncology, Cancer Research, cervical cancer, medicine.medical_treatment, Uterine Cervical Neoplasms, MICROENVIRONMENT, CD8-Positive T-Lymphocytes, SUSCEPTIBILITY, Cohort Studies, TMEM173, Basic and Clinical Immunology, 0302 clinical medicine, Genotype, Medicine, human papillomavirus, Aged, 80 and over, Cervical cancer, General Medicine, Middle Aged, allelic variants, 030220 oncology & carcinogenesis, Stimulator of interferon genes, Female, Original Article, interferon signaling, SQUAMOUS-CELL CARCINOMA, Signal Transduction, Adult, medicine.medical_specialty, Young Adult, 03 medical and health sciences, Internal medicine, Humans, RNA, Messenger, STING/TMEM173, Allele, Genetic Association Studies, Aged, business.industry, Genetic Variation, Membrane Proteins, Cancer, Immunotherapy, medicine.disease, Sting, 030104 developmental biology, Neoplasm Recurrence, Local, business, CD8, STING
Abstract: DNA‐sensing receptor Cyclic GMP–AMP Synthase (cGAS) and its downstream signaling effector STimulator of INterferon Genes (STING) have gained significant interest in the field of tumor immunology, as a dysfunctional cGAS‐STING pathway is associated with poor prognosis and worse response to immunotherapy. However, studies so far have not taken into account the polymorphic nature of the STING‐encoding STING1 gene. We hypothesized that the presence of allelic variance in STING1 would cause variation between individuals as to their susceptibility to cancer development, cancer progression, and potential response to (immuno)therapy. To start to address this, we defined the genetic landscapes of STING1 in cervical scrapings and investigated their corresponding clinical characteristics across a unique cohort of cervical cancer patients and compared them with independent control cohorts. Although we did not observe an enrichment of particular STING1 allelic variants in cervical cancer patients, we did find that the occurrence of homozygous variants HAQ/HAQ and R232H/R232H of STING1 were associated with both younger age of diagnosis and higher recurrence rate. These findings were accompanied by worse survival, despite comparable mRNA and protein levels of STING and numbers of infiltrated CD8+ T cells. Our findings suggest that patients with HAQ/HAQ and R232H/R232H genotypes may have a dysfunctional cGAS‐STING pathway that fails to promote efficient anticancer immunity. Interestingly, the occurrence of these genotypes coincided with homozygous presence of the V48V variant, which was found to be individually associated with worse outcome. Therefore, we propose V48V to be further evaluated as a novel prognostic marker for cervical cancer., Homozygous variants of the STING1 gene are associated with poor outcome in human cervical cancer. Moreover, patients with homozygous variants of STING1 are diagnosed at an earlier age and have a higher recurrence rate. Likely, these patients have a dysfunctional cGAS‐STING pathway that fails to promote efficient anticancer immunity.
Published: 2020
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11. Post-hemorrhagic ventricular dilatation affects white matter maturation in extremely preterm infants

Author: Jeroen Dudink, Astrid Nieuwets, Linda S. de Vries, Niek E. van der Aa, Floris Groenendaal, Manon J.N.L. Benders, Mehmet N. Cizmeci, Lara M. Leijser, and Corine Koopman
Subjects: medicine.medical_specialty, business.industry, Extremely preterm, Ventricular dilatation, Corpus callosum, Confidence interval, White matter, medicine.anatomical_structure, Internal medicine, Pediatrics, Perinatology and Child Health, Fractional anisotropy, medicine, Cardiology, Gestation, business, Diffusion MRI
Abstract: Data on microstructural white matter integrity in preterm infants with post-hemorrhagic ventricular dilatation (PHVD) using diffusion tensor imaging (DTI) are limited. Also, to date, no study has focused on the DTI changes in extremely preterm (EP) infants with PHVD. A case–control study of EP infants
Published: 2021
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12. Perioperative Systemic Therapy vs Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Alone for Resectable Colorectal Peritoneal Metastases A Phase 2 Randomized Clinical Trial

Author: Arjen J. Witkamp, Joost Nederend, Andreas J A Bremers, Philip R. de Reuver, Wilhelmina M U van Grevenstein, Henk M.W. Verheul, Koen P. Rovers, Max J. Lahaye, Niels F. M. Kok, Jurriaan B. Tuynman, Checca Bakkers, Maartje Los, Ignace H. J. T. de Hingh, Anna M.J. Thijs, Patrick H. J. Hemmer, Alexandra R. M. Brandt-Kerkhof, Miriam Koopman, Onno Kranenburg, Petur Snaebjornsson, Marcel G. W. Dijkgraaf, Simon W. Nienhuijs, Arend G. J. Aalbers, Schelto Kruijff, Jacobus W. A. Burger, Tineke E. Buffart, Derk Jan A. de Groot, Esther van Meerten, Iris van 't Erve, Geert-Jan Creemers, Miranda Kusters, Pieter J. Tanis, Eva V. E. Madsen, Remond J.A. Fijneman, Kathelijn S. Versteeg, Djamila Boerma, Cornelis J A Punt, Marinus J. Wiezer, Surgery, CCA - Cancer Treatment and quality of life, Amsterdam Gastroenterology Endocrinology Metabolism, Internal medicine, VU University medical center, Epidemiology and Data Science, APH - Methodology, Oncology, CCA - Cancer Treatment and Quality of Life, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Epidemiologie, and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
Subjects: Male, PROGNOSIS, medicine.medical_treatment, CARCINOMATOSIS, MULTICENTER, Hyperthermic Intraperitoneal Chemotherapy, 030230 surgery, Peritoneal Neoplasms/secondary, law.invention, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], NEOADJUVANT CHEMOTHERAPY, 0302 clinical medicine, FOLFOX, Randomized controlled trial, law, Adenocarcinoma/secondary, Adjuvant/adverse effects, Neoadjuvant therapy, Original Investigation, Bevacizumab/administration & dosage, Cytoreduction Surgical Procedures, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Middle Aged, OPEN-LABEL, CANCER, Neoadjuvant Therapy, Fluorouracil/administration & dosage, Capecitabine/administration & dosage, 030220 oncology & carcinogenesis, FOLFIRI, Leucovorin/administration & dosage, Hyperthermic intraperitoneal chemotherapy, Female, medicine.drug, medicine.medical_specialty, Camptothecin/administration & dosage, Capecitabine, 03 medical and health sciences, Chemotherapy, Adjuvant/adverse effects, Oxaliplatin/administration & dosage, REGRESSION, medicine, MANAGEMENT, Chemotherapy, Humans, Organoplatinum Compounds/administration & dosage, Perioperative Period, Response Evaluation Criteria in Solid Tumors, Aged, Colorectal Neoplasms/pathology, HIPEC, business.industry, Perioperative, Surgery, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Irinotecan, Mitomycin/administration & dosage, Feasibility Studies, business, CONSENSUS
Abstract: Contains fulltext : 238268.pdf (Publisher’s version ) (Closed access) IMPORTANCE: To date, no randomized clinical trials have investigated perioperative systemic therapy relative to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone for resectable colorectal peritoneal metastases (CPM). OBJECTIVE: To assess the feasibility and safety of perioperative systemic therapy in patients with resectable CPM and the response of CPM to neoadjuvant treatment. DESIGN, SETTING, AND PARTICIPANTS: An open-label, parallel-group phase 2 randomized clinical trial in all 9 Dutch tertiary centers for the surgical treatment of CPM enrolled participants between June 15, 2017, and January 9, 2019. Participants were patients with pathologically proven isolated resectable CPM who did not receive systemic therapy within 6 months before enrollment. INTERVENTIONS: Randomization to perioperative systemic therapy or CRS-HIPEC alone. Perioperative systemic therapy comprised either four 3-week neoadjuvant and adjuvant cycles of CAPOX (capecitabine and oxaliplatin), six 2-week neoadjuvant and adjuvant cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin), or six 2-week neoadjuvant cycles of FOLFIRI (fluorouracil, leucovorin, and irinotecan) and either four 3-week adjuvant cycles of capecitabine or six 2-week adjuvant cycles of fluorouracil with leucovorin. Bevacizumab was added to the first 3 (CAPOX) or 4 (FOLFOX/FOLFIRI) neoadjuvant cycles. MAIN OUTCOMES AND MEASURES: Proportions of macroscopic complete CRS-HIPEC and Clavien-Dindo grade 3 or higher postoperative morbidity. Key secondary outcomes were centrally assessed rates of objective radiologic and major pathologic response of CPM to neoadjuvant treatment. Analyses were done modified intention-to-treat in patients starting neoadjuvant treatment (experimental arm) or undergoing upfront surgery (control arm). RESULTS: In 79 patients included in the analysis (43 [54%] men; mean [SD] age, 62 [10] years), experimental (n = 37) and control (n = 42) arms did not differ significantly regarding the proportions of macroscopic complete CRS-HIPEC (33 of 37 [89%] vs 36 of 42 [86%] patients; risk ratio, 1.04; 95% CI, 0.88-1.23; P = .74) and Clavien-Dindo grade 3 or higher postoperative morbidity (8 of 37 [22%] vs 14 of 42 [33%] patients; risk ratio, 0.65; 95% CI, 0.31-1.37; P = .25). No treatment-related deaths occurred. Objective radiologic and major pathologic response rates of CPM to neoadjuvant treatment were 28% (9 of 32 evaluable patients) and 38% (13 of 34 evaluable patients), respectively. CONCLUSIONS AND RELEVANCE: In this randomized phase 2 trial in patients diagnosed with resectable CPM, perioperative systemic therapy seemed feasible, safe, and able to induce response of CPM, justifying a phase 3 trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02758951.
Published: 2021
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13. Longitudinal effects of adjuvant chemotherapy and related neuropathy on health utility in stage II and III colon cancer patients

Author: Marjolein J.E. Greuter, Felice N. van Erning, Cornelis J A Punt, Gabrielle Jongeneel, Geraldine R. Vink, Jos W. R. Twisk, Veerle M.H. Coupé, Miriam Koopman, Epidemiology and Data Science, APH - Health Behaviors & Chronic Diseases, APH - Methodology, Orthopedic Surgery and Sports Medicine, CCA - Cancer Treatment and quality of life, and CCA - Cancer Treatment and Quality of Life
Subjects: Male, Cancer Research, medicine.medical_specialty, longitudinal data, Colorectal cancer, Clinical Decision-Making, Capecitabine, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, medicine, Humans, Clinical significance, Longitudinal Studies, Prospective Studies, Prospective cohort study, Aged, Neoplasm Staging, business.industry, Peripheral Nervous System Diseases, Middle Aged, medicine.disease, Oxaliplatin, adjuvant chemotherapy, Peripheral neuropathy, Treatment Outcome, Oncology, colon cancer, quality of life, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Cohort, Female, business, Colorectal Neoplasms, Cancer Epidemiology, medicine.drug
Abstract: Patient's quality of life should be included in clinical decision making regarding the administration of adjuvant chemotherapy (ACT) in stage II/III colon cancer. Therefore, quality of life, summarized as health utility (HU), was evaluated for patients treated with and without ACT. Furthermore, the role of chemotherapy–induced peripheral neuropathy (CIPN) on HU was evaluated. Patients diagnosed with stage II/III colon cancer between 2011 and 2019 and participating in the Prospective Dutch ColoRectal Cancer cohort were included (n = 914). HU scores were assessed with the EQ‐5D‐5L at baseline, 3, 6, 12, 18, and 24 months. Patients treated with ACT received mainly capecitabine and oxaliplatin (57%) or capecitabine monotherapy (40%) (average duration: 3.5 months). HU 3 to 18 months after diagnosis (potential ACT period + 12 months follow‐up) was compared between patients treated with and without ACT using a mixed model adjusted for age, sex and education level. Subsequently, the CIPN sensory, motor and autonomy scales, measured using the EORTC QLQ‐CIPN20, were independently included in the model to evaluate the impact of neuropathy. Using a mixed model, a significant difference of −0.039 (95% confidence interval: −0.062; −0.015) in HU was found between patients treated with and without ACT. Including the CIPN sensory, motor and autonomy scales decreased the difference with 0.019, 0.015 and 0.02, respectively. HU 3 to 18 months after diagnosis is significantly lower in patients treated with ACT vs without ACT. This difference is on the boundary of clinical relevance and appears to be partly related to the sensory and motor neuropathy‐related side effects of ACT., What's new? Given its potentially serious side effects, patient quality of life should be included in clinical decision‐making regarding the administration of adjuvant chemotherapy in stage II/III colon cancer. Using a mixed model which was corrected for relevant covariates, here the authors found a statistically‐significant but small decrease in HU of −0.039 during chemotherapy and the following 12 months for patients treated with adjuvant chemotherapy compared to patients without adjuvant chemotherapy. The decrease in HU, which is on the boundary of clinical relevance, appears to be partly related to sensory and motor neuropathy side effects of adjuvant chemotherapy.
Published: 2021
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14. Severe acute respiratory syndrome coronavirus 2 placental infection and inflammation leading to fetal distress and neonatal multi-organ failure in an asymptomatic woman

Author: Marion Koopmans, Pauline Snijder, Pieter L.A. Fraaij, Thomas B Krasemann, Irwin K M Reiss, Sam Schoenmakers, Melek Rousian, Robert M. Verdijk, Laurens P. Koopman, Thijs Kuiken, Sylvia Kamphuis, Michelle Broekhuizen, Eric A.P. Steegers, Obstetrics & Gynecology, Pediatrics, Pathology, and Virology
Subjects: Neonatal intensive care unit, Kawasaki-like syndrome, viruses, Placental Finding, Umbilical cord, 0302 clinical medicine, Pregnancy, Fetal distress, 030212 general & internal medicine, Pregnancy Complications, Infectious, skin and connective tissue diseases, 0303 health sciences, Obstetrics, food and beverages, virus diseases, fetal distress, General Medicine, AcademicSubjects/MED00290, Infectious Diseases, medicine.anatomical_structure, Original Article, Female, medicine.symptom, Infant, Premature, Adult, medicine.medical_specialty, placenta, Multiple Organ Failure, Pneumonia, Viral, Asymptomatic, 03 medical and health sciences, Placenta, medicine, Humans, Pediatrics, Perinatology, and Child Health, 030304 developmental biology, Fetus, SARS-CoV-2, Cesarean Section, business.industry, fungi, Infant, Newborn, COVID-19, medicine.disease, Infectious Disease Transmission, Vertical, inflammation, Pediatrics, Perinatology and Child Health, AcademicSubjects/MED00670, business
Abstract: Placental severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a specific histiocytic intervillositis. Placental fibrin depositions can decrease the maternal-fetal interface causing fetal distress. Coronavirus disease 2019-related placental inflammation can lead to SARS-CoV-2-associated pediatric inflammatory multisystem syndrome., Background In general, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy is not considered to be an increased risk for severe maternal outcomes but has been associated with an increased risk for fetal distress. Maternal-fetal transmission of SARS-CoV-2 was initially deemed uncertain; however, recently a few cases of vertical transmission have been reported. The intrauterine mechanisms, besides direct vertical transmission, leading to the perinatal adverse outcomes are not well understood. Methods Multiple maternal, placental, and neonatal swabs were collected for the detection of SARS-CoV-2 using real-time quantitative polymerase chain reaction (RT-qPCR). Serology of immunoglobulins against SARS-CoV-2 was tested in maternal, umbilical cord, and neonatal blood. Placental examination included immunohistochemical investigation against SARS-CoV-2 antigen expression, with SARS-CoV-2 ribonucleic acid (RNA) in situ hybridization and transmission electron microscopy. Results RT-qPCRs of the oropharynx, maternal blood, vagina, placenta, and urine were all positive over a period of 6 days, while breast milk, feces, and all neonatal samples tested negative. Placental findings showed the presence of SARS-CoV-2 particles with generalized inflammation characterized by histiocytic intervillositis with diffuse perivillous fibrin depositions with damage to the syncytiotrophoblasts. Conclusions Placental infection by SARS-CoV-2 leads to fibrin depositions hampering fetal-maternal gas exchange with resulting fetal distress necessitating a premature emergency cesarean section. Postpartum, the neonate showed a fetal or pediatric inflammatory multisystem-like syndrome with coronary artery ectasia temporarily associated with SARS-CoV-2 for which admittance and care on the neonatal intensive care unit (NICU) were required, despite being negative for SARS-CoV-2. This highlights the need for awareness of adverse fetal and neonatal outcomes during the current coronavirus disease 2019 pandemic, especially considering that the majority of pregnant women appear asymptomatic.
Published: 2021

15. Iron accumulation in skeletal muscles of old mice is associated with impaired regeneration after ischaemia–reperfusion damage

Author: Gordon S. Lynch, Francesca M. Alves, Scott Ayton, Ashley I. Bush, Justin P. Hardee, Kai Kysenius, Marissa K. Caldow, René Koopman, and Peter J. Crouch
Subjects: 0301 basic medicine, medicine.medical_specialty, Sarcopenia, Iron, Lipid peroxidation, Diseases of the musculoskeletal system, medicine.disease_cause, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Ischemia, Physiology (medical), Internal medicine, medicine, Animals, Regeneration, Orthopedics and Sports Medicine, Muscle, Skeletal, Wasting, business.industry, QM1-695, Skeletal muscle, Muscle mass, Original Articles, medicine.disease, Muscle atrophy, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, chemistry, RC925-935, Ageing, Reperfusion Injury, 030220 oncology & carcinogenesis, Human anatomy, Original Article, medicine.symptom, business, Reperfusion injury, Oxidative stress
Abstract: Background Oxidative stress is implicated in the insidious loss of muscle mass and strength that occurs with age. However, few studies have investigated the role of iron, which is elevated during ageing, in age‐related muscle wasting and blunted repair after injury. We hypothesized that iron accumulation leads to membrane lipid peroxidation, muscle wasting, increased susceptibility to injury, and impaired muscle regeneration. Methods To examine the role of iron in age‐related muscle atrophy, we compared the skeletal muscles of 3‐month‐old with 22‐ to 24‐month‐old 129SvEv FVBM mice. We assessed iron distribution and total elemental iron using laser ablation inductively coupled plasma mass spectrometry and Perls' stain on skeletal muscle cross‐sections. In addition, old mice underwent ischaemia–reperfusion (IR) injury (90 min ischaemia), and muscle regeneration was assessed 14 days after injury. Immunoblotting was used to determine lipid peroxidation (4HNE) and iron‐related proteins. To determine whether muscle iron content can be altered, old mice were treated with deferiprone (DFP) in the drinking water, and we assessed its effects on muscle regeneration after injury. Results We observed a significant increase in total elemental iron (+43%, P
Published: 2021

16. Patient-derived organoids as a predictive biomarker for treatment response in cancer patients

Author: Onno Kranenburg, Jasper Mullenders, Sylvia F. Boj, Miriam Koopman, Sjoerd G. Elias, G. Emerens Wensink, and Jeanine M.L. Roodhart
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Treatment response, Cancer therapy, MEDLINE, Review Article, Predictive markers, 03 medical and health sciences, 0302 clinical medicine, Text mining, Internal medicine, medicine, RC254-282, Predictive biomarker, business.industry, Cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Translational research, medicine.disease, Treatment efficacy, 030104 developmental biology, Pooled analysis, 030220 oncology & carcinogenesis, Personalized medicine, business
Abstract: Effective predictive biomarkers are needed to enable personalized medicine and increase treatment efficacy and survival for cancer patients, thereby reducing toxic side effects and treatment costs. Patient-derived organoids (PDOs) enable individualized tumour response testing. Since 2018, 17 publications have examined PDOs as a potential predictive biomarker in the treatment of cancer patients. We review and provide a pooled analysis of the results regarding the use of PDOs in individualized tumour response testing, focusing on evidence for analytical validity, clinical validity and clinical utility. We identify future perspectives to accelerate the implementation of PDOs as a predictive biomarker in the treatment of cancer patients.
Published: 2021

17. Multiparametric functional MRI and 18F-FDG-PET for survival prediction in patients with head and neck squamous cell carcinoma treated with (chemo)radiation

Author: Daniel P. Noij, Remco de Bree, Roland M. Martens, C. René Leemans, Pim de Graaf, Meedie Ali, Ronald Boellaard, J. Tim Marcus, Thomas Koopman, G.J.C. Zwezerijnen, Carel F.W. Peeters, Jonas A. Castelijns, Marije R. Vergeer, Cristina Lavini, Radiology and nuclear medicine, Neurosurgery, Epidemiology and Data Science, CCA - Imaging and biomarkers, ACS - Pulmonary hypertension & thrombosis, Radiation Oncology, CCA - Cancer Treatment and quality of life, Otolaryngology / Head & Neck Surgery, CCA - Cancer biology and immunology, Amsterdam Neuroscience - Brain Imaging, AII - Cancer immunology, Radiology and Nuclear Medicine, and Other Research
Subjects: Oncology, medicine.medical_specialty, Diffusion magnetic resonance imaging, medicine.medical_treatment, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Magnetic resonance imaging, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, In patient, Squamous cell carcinoma of head and neck, Lymph node, Intravoxel incoherent motion, Survival analysis, Neuroradiology, medicine.diagnostic_test, business.industry, Positron emission tomography computed tomography, General Medicine, medicine.disease, Head and neck squamous-cell carcinoma, Radiation therapy, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Radiology, business
Abstract: Objectives To assess (I) correlations between diffusion-weighted (DWI), intravoxel incoherent motion (IVIM), dynamic contrast-enhanced (DCE) MRI, and 18F-FDG-PET/CT imaging parameters capturing tumor characteristics and (II) their predictive value of locoregional recurrence-free survival (LRFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy. Methods Between 2014 and 2018, patients with histopathologically proven HNSCC, planned for curative (chemo) radiotherapy, were prospectively included. Pretreatment clinical, anatomical, and functional imaging parameters (obtained by DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT) were extracted for primary tumors (PT) and lymph node metastases. Correlations and differences between parameters were assessed. The predictive value of LRFS and OS was assessed, performing univariable, multivariable Cox and CoxBoost regression analyses. Results In total, 70 patients were included. Significant correlations between 18F-FDG-PET parameters and DWI-/DCE volume parameters were found (r > 0.442, p GTV (HR = 1.252), Ktrans (HR = 1.223), and Ve (HR = 1.215) was predictive for LRFS (C-index = 0.546; p = 0.023). N-stage (HR = 1.058), HPV positivity (HR = 0.886), hypopharyngeal tumor location (HR = 1.111), ADCGTV (HR = 1.102), ADCmean (HR = 1.137), D* (HR = 0.862), Ktrans (HR = 1.106), Ve (HR = 1.195), SUVmax (HR = 1.094), and TLG (HR = 1.433) were predictive for OS (C-index = 0.664; p = 0.046). Conclusions Functional imaging parameters, performing DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT, yielded complementary value in capturing tumor characteristics. More specific, intoxications, HPV-negative status, large tumor volume-related parameters, high permeability (Ktrans), and high extravascular extracellular space (Ve) parameters were predictive for adverse locoregional recurrence-free survival and adverse overall survival. Low cellularity (high ADC) and high metabolism (high SUV) were additionally predictive for decreased overall survival. These different predictive factors added to estimated locoregional and overall survival. Key Points • Parameters of DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT were able to capture complementary tumor characteristics. • Multivariable analysis revealed that intoxications, HPV negativity, large tumor volume and high vascular permeability (Ktrans), and extravascular extracellular space (Ve) were complementary predictive for locoregional recurrence. • In addition to predictive parameters for locoregional recurrence, also high cellularity (low ADC) and high metabolism (high SUV) were complementary predictive for overall survival.
Published: 2021
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18. Comparison of de novo versus upgrade cardiac resynchronisation therapy on clinical effect and long-term outcome

Author: Jan Verwerft, Jan Stassen, Lieven Herbots, Philippe Timmermans, Dagmara Dilling-Boer, Pieter Koopman, Matthew Schroyens, Martijn Scherrenberg, Johan Vijgen, and Joris Schurmans
Subjects: medicine.medical_specialty, business.industry, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, Outcome (game theory), Term (time), 03 medical and health sciences, 0302 clinical medicine, Upgrade, Internal medicine, Heart failure, cardiovascular system, medicine, Cardiology, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business
Abstract: The benefit of de novo cardiac resynchronisation therapy (CRT) implantation in selected patients with heart failure is well known. The number of upgrade procedures is increasing but data on clinica...
Published: 2021
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19. Functional electrical stimulation in-bed cycle ergometry in mechanically ventilated patients: a multicentre randomised controlled trial

Author: Elizabeth Colantuoni, Ramona O. Hopkins, Zudin Puthucheary, Linda Denehy, Dale M. Needham, Joleen W. Rose, Susan C Berney, Selina M Parry, Ian Gordon, Amy M. Pastva, and René Koopman
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critical Illness, medicine.medical_treatment, law.invention, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Randomized controlled trial, law, medicine, Humans, Functional electrical stimulation, Single-Blind Method, Muscle Strength, 030212 general & internal medicine, Aged, Rehabilitation, business.industry, Incidence (epidemiology), Middle Aged, medicine.disease, Respiration, Artificial, Intensive care unit, Electric Stimulation, Exercise Therapy, Systemic inflammatory response syndrome, Intensive Care Units, 030228 respiratory system, Quality of Life, Physical therapy, Female, business
Abstract: PurposeTo investigate the effect of functional electrical stimulation-assisted cycle ergometry (FES-cycling) on muscle strength, cognitive impairment and related outcomes.MethodsMechanically ventilated patients aged ≥18 years with sepsis or systemic inflammatory response syndrome were randomised to either 60 min of FES-cycling >5 days/week while in the intensive care unit (ICU) plus usual care rehabilitation versus usual care rehabilitation alone, with evaluation of two primary outcomes: (1) muscle strength at hospital discharge and (2) cognitive impairment at 6-month follow-up.ResultsWe enrolled 162 participants, across four study sites experienced in ICU rehabilitation in Australia and the USA, to FES-cycling (n=80; mean age±SD 59±15) versus control (n=82; 56±14). Intervention participants received a median (IQR) of 5 (3–9) FES-cycling sessions with duration of 56 (34–63) min/day plus 15 (10–23) min/day of usual care rehabilitation. The control group received 15 (8–15) min/day of usual care rehabilitation. In the intervention versus control group, there was no significant differences for muscle strength at hospital discharge (mean difference (95% CI) 3.3 (−5.0 to 12.1) Nm), prevalence of cognitive impairment at 6 months (OR 1.1 (95% CI 0.30 to 3.8)) or secondary outcomes measured in-hospital and at 6 and 12 months follow-up.ConclusionIn this randomised controlled trial, undertaken at four centres with established rehabilitation programmes, the addition of FES-cycling to usual care rehabilitation did not substantially increase muscle strength at hospital discharge. At 6 months, the incidence of cognitive impairment was almost identical between groups, but potential benefit or harm of the intervention on cognition cannot be excluded due to imprecision of the estimated effect.Trial registration numberACTRN 12612000528853, NCT02214823.
Published: 2020
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20. Multicenter Comparison of Molecular Tumor Boards in The Netherlands

Author: Nienke Solleveld, Arja ter Elst, Hans Gelderblom, Jan H. von der Thüsen, Ernst-Jan M. Speel, Ed Schuuring, Harry J.M. Groen, Berber Piet, Wendy W.J. de Leng, Anthonie J. van der Wekken, Katrien Grünberg, Stefan M. Willems, Leonie I. Kroeze, Tom E. J. Theunissen, Adrianus J. de Langen, Léon C van Kempen, Lizza E.L. Hendriks, Sayed M S Hashemi, Bart Koopman, Marthe S. Paats, Anne S R van Lindert, Ruud W. J. Meijers, Niven Mehra, Kim Monkhorst, Daniëlle A M Heideman, Winand N.M. Dinjens, Mirjam C. Boelens, Marjolijn J. L. Ligtenberg, Tom van Wezel, Wim Timens, Teodora Radonic, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Pulmonologie, MUMC+: MA Med Staf Spec Longziekten (9), RS: GROW - R2 - Basic and Translational Cancer Biology, Pathologie, Pathology, Pulmonary medicine, CCA - Cancer Treatment and quality of life, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Groningen Research Institute for Asthma and COPD (GRIAC), Targeted Gynaecologic Oncology (TARGON), Pulmonary Medicine, and Immunology
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Cancer Diagnostics and Molecular Pathology, Referral, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], medicine.medical_treatment, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], Molecular tumor board, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Multidisciplinary approach, Neoplasms, Physicians, Rare mutations, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Molecular diagnostics, Humans, Medicine, Tumor board, Target therapy, Pathology, Molecular, Composition methods, Netherlands, Multidisciplinary, business.industry, Cancer, medicine.disease, CANCER, PATHOLOGY, 030104 developmental biology, Workflow, Oncology, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, Family medicine, business, Decision making, GENOMICS
Abstract: Background Molecular tumor boards (MTBs) provide rational, genomics‐driven, patient‐tailored treatment recommendations. Worldwide, MTBs differ in terms of scope, composition, methods, and recommendations. This study aimed to assess differences in methods and agreement in treatment recommendations among MTBs from tertiary cancer referral centers in The Netherlands. Materials and Methods MTBs from all tertiary cancer referral centers in The Netherlands were invited to participate. A survey assessing scope, value, logistics, composition, decision‐making method, reporting, and registration of the MTBs was completed through on‐site interviews with members from each MTB. Targeted therapy recommendations were compared using 10 anonymized cases. Participating MTBs were asked to provide a treatment recommendation in accordance with their own methods. Agreement was based on which molecular alteration(s) was considered actionable with the next line of targeted therapy. Results Interviews with 24 members of eight MTBs revealed that all participating MTBs focused on rare or complex mutational cancer profiles, operated independently of cancer type–specific multidisciplinary teams, and consisted of at least (thoracic and/or medical) oncologists, pathologists, and clinical scientists in molecular pathology. Differences were the types of cancer discussed and the methods used to achieve a recommendation. Nevertheless, agreement among MTB recommendations, based on identified actionable molecular alteration(s), was high for the 10 evaluated cases (86%). Conclusion MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational cancer profiles. We propose a “Dutch MTB model” for an optimal, collaborative, and nationally aligned MTB workflow. Implications for Practice Interpretation of genomic analyses for optimal choice of target therapy for patients with cancer is becoming increasingly complex. A molecular tumor board (MTB) supports oncologists in rationalizing therapy options. However, there is no consensus on the most optimal setup for an MTB, which can affect the quality of recommendations. This study reveals that the eight MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational profiles. The Dutch MTB model is based on a collaborative and nationally aligned workflow with interinstitutional collaboration and data sharing., Worldwide, molecular tumor boards (MTBs) differ in terms of scope, composition, methods, and recommendations. This article assesses differences in methods and agreement in treatment recommendations among MTBs from tertiary cancer referral centers in The Netherlands.
Published: 2020
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21. Dynamic Takotsubo Syndrome

Author: Siddharth Jogani, Philippe Timmermans, Walter Desmet, and Pieter Koopman
Subjects: 0301 basic medicine, medicine.medical_specialty, Acute coronary syndrome, TC, Takotsubo cardiomyopathy, Case Report: Clinical Case Series, FMD - Fibromuscular dysplasia, ACE, angiotensin-converting enzyme, FMD, fibromuscular dysplasia, Cardiomyopathy, 030105 genetics & heredity, acute coronary syndrome, 03 medical and health sciences, ECG, electrocardiography, 0302 clinical medicine, Mini-Focus Issue: Cardiomyopathies, Internal medicine, spontaneous coronary artery dissection, medicine, Diseases of the circulatory (Cardiovascular) system, Artery dissection, LCX, left circumflex artery, Takotsubo syndrome, Distal portion, business.industry, case series, takotsubo cardiomyopathy, medicine.disease, SCAD, spontaneous coronary artery dissection, medicine.anatomical_structure, LAD, left anterior descending artery, TTE, transthoracic echocardiography, RC666-701, PE, pulmonary embolism, Cardiology, coronary angiography, Cardiology and Cardiovascular Medicine, Scad, business, 030217 neurology & neurosurgery, RCA, right coronary artery, Artery
Abstract: Both Takotsubo cardiomyopathy and spontaneous coronary artery dissection (SCAD) of the distal portion of the left anterior descending artery affect the apical myocardium. It is important to distinguish between both diseases, because therapy and follow-up differ. Revascularization may be lifesaving in SCAD, whereas heart failure management is vital in Takotsubo cardiomyopathy. (Level of Difficulty: Intermediate.), Graphical abstract
Published: 2020

22. Patient-Related Outcomes of Arthroscopic Resection of Ganglion Cysts of the Wrist

Author: Philip N. d'Ailly, Zulfiquar O. Rahimtoola, Niels W. L. Schep, Caroline A. Selles, and Jaimy E. Koopman
Subjects: 030222 orthopedics, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Arthroscopy, Retrospective cohort study, Wrist, medicine.disease, Surgery, Ganglion cyst, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Tendinitis, Interquartile range, Open Resection, Extensor Carpi Ulnaris, medicine, Orthopedics and Sports Medicine, 030212 general & internal medicine, business
Abstract: Background Ganglion cysts of the wrist can cause pain and loss of functionality. No consensus exist on optimal treatment. Arthroscopic resection shows promising results but is poorly studied. Furthermore, only few studies have used patient-related outcomes to evaluate arthroscopic treatment. Purpose The purpose of this study was to assess patient-related outcomes following arthroscopic resection of wrist ganglion cysts. Patients and Methods This was a retrospective study of all consecutive patients that underwent arthroscopic resection of a dorsal or volar wrist ganglion. Minimum follow-up was 6 months. The primary outcome was the patient-rated wrist evaluation (PRWE). Secondary outcomes were recurrence rate and complications. Results A total of 53 patients were included with a mean follow-up of 13 months (interquartile range: 6–23 months). Twenty-six patients (49%) presented with a recurrence following prior treatment. Mean PRWE was 13 (standard deviation [SD] = 1.8), with no difference between patients with dorsal or volar ganglion cysts. There were five recurrences (9%), of which three occurred in the first five patients who were operated. There were three patients with complications (6%), consisting of neuropraxia, extensor carpi ulnaris tendinitis, and painful scar tissue. Conclusion Arthroscopic resection results in good patient-related outcome and low complication and recurrence rates when performed by an experienced surgeon. Recurrence and complication rates are similar to arthroscopic resections described in literature and superior to open resection and needle aspiration. Well-designed randomized clinical trials will be necessary to confirm these findings. Level of Evidence This is a level IV, retrospective study.
Published: 2020
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23. Comparing Circulating Tumor Cell Counts with Dynamic Tumor Size Changes as Predictor of Overall Survival

Author: Miriam Koopman, Cornelis J. A. Punt, Leon W.M.M. Terstappen, Ida Netterberg, Lena E. Friberg, Mats O. Karlsson, TechMed Centre, and Medical Cell Biophysics
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Colorectal cancer, medicine.medical_treatment, Cetuximab, Cell Count, Kaplan-Meier Estimate, Targeted therapy, 0302 clinical medicine, Circulating tumor cell, Antineoplastic Combined Chemotherapy Protocols, Multicenter Studies as Topic, education.field_of_study, Tumor size, Middle Aged, Neoplastic Cells, Circulating, Prognosis, Tumor Burden, Bevacizumab, Oxaliplatin, Prostatic Neoplasms, Castration-Resistant, 030220 oncology & carcinogenesis, medicine.medical_specialty, Population, Models, Biological, Risk Assessment, Drug Administration Schedule, 03 medical and health sciences, Internal medicine, medicine, Overall survival, Humans, education, Capecitabine, Response Evaluation Criteria in Solid Tumors, Aged, Chemotherapy, Dose-Response Relationship, Drug, business.industry, 22/2 OA procedure, medicine.disease, digestive system diseases, 030104 developmental biology, Clinical Trials, Phase III as Topic, Drug Resistance, Neoplasm, Pharmacodynamics, Feasibility Studies, business, Follow-Up Studies
Abstract: Purpose:Quantitative relationships between treatment-induced changes in tumor size and circulating tumor cell (CTC) counts, and their links to overall survival (OS), are lacking. We present a population modeling framework identifying and quantifying such relationships, based on longitudinal data collected in patients with metastatic colorectal cancer (mCRC) to evaluate the value of tumor size and CTC counts as predictors of OS.Experimental Design:A pharmacometric approach (i.e., population pharmacodynamic modeling) was used to characterize the changes in tumor size and CTC count and evaluate them as predictors of OS in 451 patients with mCRC treated with chemotherapy and targeted therapy in a prospectively randomized phase III study (CAIRO2).Results:A tumor size model of tumor quiescence and drug resistance was used to characterize the tumor size time-course, and was, in addition to the total normalized dose (i.e., of all administered drugs) in a given cycle, related to the CTC counts through a negative binomial model (CTC model). Tumor size changes did not contribute additional predictive value when the mean CTC count was a predictor of OS. Treatment reduced the typical mean count from 1.43 to 0.477 (HR = 3.94). The modeling framework was applied to explore whether dose modifications (increased and reduced) would result in a CTC count below 1/7.5 mL after 1 to 2 weeks of treatment.Conclusions:Time-varying CTC counts can be useful for early predicting OS in patients with mCRC, and may therefore have potential for model-based treatment individualization. Although tumor size was connected to CTC, its link to OS was weaker.
Published: 2020
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24. A cross-sectional investigation of communication in Do-Not-Resuscitate orders in Dutch hospitals

Author: T. van Melsen, Koen S. Simons, Evert-Jan Wils, Henrik Endeman, Tessa M M Romijn, M. Schluep, A.W.M.M. Koopman-van Gemert, M. van Dijk, Sanne E. Hoeks, Susanne IJmkers, Alexander D. Cornet, Robert Jan Stolker, Frank H. Bosch, Jelmer Alsma, A.H.M. Knook, R. J. G. Peters, Anesthesiology, Intensive Care, and Internal Medicine
Subjects: medicine.medical_specialty, Resuscitation, health care facilities, manpower, and services, medicine.medical_treatment, education, Do Not Resuscitate Order, 030204 cardiovascular system & hematology, Emergency Nursing, 03 medical and health sciences, 0302 clinical medicine, health services administration, Humans, Medicine, In patient, Cardiopulmonary resuscitation, health care economics and organizations, Resuscitation Orders, business.industry, Communication, Do not resuscitate, 030208 emergency & critical care medicine, medicine.disease, Comorbidity, Cardiopulmonary Resuscitation, Hospitals, Cross-Sectional Studies, Emergency medicine, Emergency Medicine, Population study, Observational study, Cardiology and Cardiovascular Medicine, business
Abstract: Background The decision to attempt or refrain from resuscitation is preferably based on prognostic factors for outcome and subsequently communicated with patients. Both patients and physicians consider good communication important, however little is known about patient involvement in and understanding of cardiopulmonary resuscitation (CPR) directives. Aim To determine the prevalence of Do Not Resuscitate (DNR)-orders, to describe recollection of CPR-directive conversations and factors associated with patient recollection and understanding. Methods This was a two-week nationwide multicentre cross-sectional observational study using a study-specific survey. The study population consisted of patients admitted to non-monitored wards in 13 hospitals. Data were collected from the electronic medical record (EMR) concerning CPR-directive, comorbidity and at-home medication. Patients reported their perception and expectations about CPR-counselling through a questionnaire. Results A total of 1136 patients completed the questionnaire. Patients’ CPR-directives were documented in the EMR as follows: 63.7% full code, 27.5% DNR and in 8.8% no directive was documented. DNR was most often documented for patients >80 years (66.4%) and in patients using >10 medications (45.3%). Overall, 55.8% of patients recalled having had a conversation about their CPR-directive and 48.1% patients reported the same CPR-directive as the EMR. Most patients had a good experience with the CPR-directive conversation in general (66.1%), as well as its timing (84%) and location (94%) specifically. Conclusions The average DNR-prevalence is 27.5%. Correct understanding of their CPR-directive is lowest in patients aged ≥80 years and multimorbid patients. CPR-directive counselling should focus more on patient involvement and their correct understanding.
Published: 2020
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25. The association between changes in muscle mass and quality of life in patients with metastatic colorectal cancer

Author: Peter Nieboer, Petra H.M. Peeters, Sophie A Kurk, Marion Jourdan, Cornelis J. A. Punt, Anne M. May, Miriam Koopman, Aafke H. Honkoop, Bram Dorresteijn, Jeroen W.G. Derksen, Robert S. De Jong, Ankie M.T. van der Velden, Oncology, and CCA - Cancer Treatment and Quality of Life
Subjects: 0301 basic medicine, Male, Quality of life, medicine.medical_specialty, Randomization, lcsh:Diseases of the musculoskeletal system, Bevacizumab, Colorectal cancer, law.invention, lcsh:QM1-695, Capecitabine, 03 medical and health sciences, Skeletal muscle mass, 0302 clinical medicine, Randomized controlled trial, law, Physiology (medical), Internal medicine, medicine, Humans, Orthopedics and Sports Medicine, Neoplasm Metastasis, business.industry, Metastatic colorectal cancer, Original Articles, lcsh:Human anatomy, Middle Aged, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, Concomitant, Female, Original Article, lcsh:RC925-935, business, Colorectal Neoplasms, Supportive care, medicine.drug
Abstract: Background Skeletal muscle mass (SMM) loss is common in metastatic colorectal cancer (mCRC) patients and associated with poor clinical outcomes, including increased treatment‐related toxicities and reduced survival. Muscle loss may contribute to reduced health‐related quality of life (HRQoL), including fatigue. Our aim was to study associations between changes in SMM and concomitant changes in patient‐reported HRQoL. Methods This was a secondary analysis of mCRC patients in the CAIRO3 randomized clinical trial who were—after initial treatment—randomized between maintenance treatment with capecitabine plus bevacizumab (CAP‐B) and observation until first disease progression (PD1). Included patients had computed tomography images for SMM quantification, together with HRQoL assessments available at randomization and PD1. Changes in SMM (categorized as >2% loss, stable, and >2% gain) and HRQoL were computed between randomization and PD1. Changes in HRQoL score >10 points were considered clinically relevant. Associations between SMM and HRQoL changes were studied by multiple linear regression models. We also investigated whether associations differed by treatment arm for global health and the 13 other HRQoL subscales. Results Of 221 patients included (mean age 63.5 ± 8.4 years), 24% lost, 27% remained stable, and 49% gained SMM. At randomization, mean global health status was 73.5 ± 15.9 in the CAP‐B arm and 75.1 ± 17.5 in the observation arm (P = 0.48). A stable or gain in SMM was significantly associated with a clinically relevant improvement in global health status (9.9 and 14.7 points, respectively), compared with patients who lost SMM. From the subscales that did not show significant differences between the two treatment arms, we found significant and clinically relevant associations for stable or gain in SMM with improved role functioning (12.0 and 17.9, respectively) and with less fatigue (−10.0 and −15.0, respectively) and pain (−16.3 for SMM gain). From the subscales that did show significantly different associations with SMM between the two treatment arms, we only found significant results in the observation arm. Here, associations were found for stable or gain in SMM with clinically relevant improved physical (12.4 for SMM gain), cognitive (10.7 and 9.7, respectively), and social functioning (15.5 and 15.6, respectively) as well as reduced appetite loss (−28.5 and −30.7, respectively). Conclusions In mCRC, SMM preservation during CAP‐B and observation treatment is associated with significant and clinically relevant improvements in global health status and multiple functional and symptom scales. Studies are warranted to investigate whether interventions targeting SMM lead to improved HRQoL, fewer symptoms, and better functioning.
Published: 2020

26. Informing metastatic colorectal cancer patients by quantifying multiple scenarios for survival time based on real‐life data

Author: Rebecca K. Stellato, Patricia A. H. Hamers, Anne M. May, Geraldine R. Vink, Marloes A. G. Elferink, Miriam Koopman, Cornelis J. A. Punt, Oncology, CCA - Cancer Treatment and Quality of Life, and CCA -Cancer Center Amsterdam
Subjects: Adult, Male, real-world, Cancer Research, Percentile, medicine.medical_specialty, Colorectal cancer, Population, scenarios for survival, Systemic therapy, 03 medical and health sciences, 0302 clinical medicine, population‐based, Internal medicine, Humans, Medicine, Registries, education, Aged, Neoplasm Staging, Netherlands, Aged, 80 and over, education.field_of_study, business.industry, metastatic colorectal cancer, Middle Aged, real‐world, medicine.disease, Survival Analysis, population-based, Cancer registry, Clinical trial, Oncology, 030220 oncology & carcinogenesis, Life expectancy, Female, prognosis, Metastasectomy, Colorectal Neoplasms, business, Cancer Epidemiology
Abstract: Reported median overall survival (mOS) in metastatic colorectal cancer (mCRC) patients participating in systemic therapy trials has increased to over 30 months. It is uncertain whether trial results translate to real‐life populations. Moreover, patients prefer presentation of multiple survival scenarios. Population‐based data of all stage IV CRC patients diagnosed between 2008 and 2016 were obtained from the Netherlands Cancer Registry, which has a case ascertainment completeness surpassing 95%. We calculated the following percentiles (scenarios) of OS per year of diagnosis for the total population, and for treatment subgroups: 10th (best‐case), 25th (upper‐typical), 50th (median), 75th (lower‐typical) and 90th (worst‐case). Twenty‐five percent of patients did not receive any antitumor treatment. From 2008 to 2016, mOS of the total population (n = 27275) remained unchanged at approximately 12 months. OS improved only for the upper‐typical and best‐case patients; by 4.2 to 29.1 months (P, What's new? Clinical trials on first‐line systemic therapy in metastatic colorectal cancer (mCRC) patients suggest a marked improvement in median overall survival (mOS). However, uncertainty exists in how the survival reported in trials relates to the real‐life mCRC population. This is the first population‐based study providing multiple scenarios for patient survival. The results show that real‐life mCRC patients receiving systemic therapy have a shorter mOS compared to trial patients, likely reflecting patient selection in clinical trials. Clinicians should consider presenting multiple scenarios for survival based on real‐life data instead of point estimates from clinical trials when informing patients about their life expectancy.
Published: 2020
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27. Espundia: a tropical infectious disease making its way to Europe. A case report of nasal mucocutaneous leishmaniasis in the Netherlands

Author: J.P. Koopman, E.F. Schippers, A.C. Westgeest, A.A. Schenck, and E.J.C. Teunissen
Subjects: medicine.medical_specialty, mucocutaneous, parasitology, business.industry, nasal obstruction, General Medicine, Mucocutaneous leishmaniasis, Dermatology, nasal swelling, tropical infectious disease, Otorhinolaryngology, RF1-547, Infectious disease (medical specialty), Medicine, business, leishmaniasis
Abstract: Background: We present a case history of a patient with nasal mucocutaneous leishmaniasis, also known as Espundia. Knowledge of this tropical infectious disease is usually limited among otorhinolaryngologists, but is of importance because patients may present with symptoms in nose or mouth. Case presentation: A 25-year old healthy man was referred to our outpatient clinic with nasal obstruction and swelling at the left part of the nose since two weeks. The patient had travelled to Peru several months ago. After extensive diagnostic testing, mucocutaneous leishmaniasis was diagnosed. Leishmaniasis is a tropical infectious disease caused by a parasite of the Leishmania-family. Depending on the species, it can cause cutaneous, mucocutaneous or visceral disease. Mucocutaneous leishmaniasis, called ‘Espundia’, has a preference for the nasal mucosa and can lead to severe tissue destruction in the nasopharyngeal region. This disease should always be treated. Conclusion: This case is presented for two reasons. Firstly, knowledge of this disease is important in reducing doctors’ delay, because mucocutaneous leishmaniasis may lead to secondary infection and facial deformation. Secondly, due to globalisation and climate change an increase in incidence of leishmaniasis in Europe is expected. Therefore, otorhinolaryngologists will more frequently be confronted with leishmaniasis and should be able to recognise it.
Published: 2020
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28. Ovotesticular disorders of sex development in FGF9 mouse models of human synostosis syndromes

Author: Stefan Bagheri-Fam, Brittany Croft, Lingyun Tang, Zhenhua Ming, Peter Koopman, Vincent R. Harley, Liang Zhao, Anthony Daniel Bird, Keiichi Akita, Masayo Harada, and Zhugang Wang
Subjects: Fibroblast Growth Factor 9, Male, medicine.medical_specialty, Male sex determination, Mutation, Missense, SOX9, Biology, 010402 general chemistry, 01 natural sciences, Mice, 03 medical and health sciences, FGF9, Internal medicine, Genetics, medicine, Animals, Humans, Disorders of sex development, Receptor, Fibroblast Growth Factor, Type 2, Gonads, Molecular Biology, Genetics (clinical), 030304 developmental biology, Phenocopy, 0303 health sciences, Sexual Development, Gene Expression Regulation, Developmental, SOX9 Transcription Factor, General Medicine, Sex Determination Processes, Sex reversal, medicine.disease, Phenotype, Ovotesticular Disorders of Sex Development, 0104 chemical sciences, Disease Models, Animal, stomatognathic diseases, Endocrinology, Synostosis, Female, Development of the gonads
Abstract: In mice, male sex determination depends on FGF9 signalling via FGFR2c in the bipotential gonads to maintain the expression of the key testis gene SOX9. In humans, however, while FGFR2 mutations have been linked to 46,XY disorders of sex development (DSD), the role of FGF9 is unresolved. The only reported pathogenic mutations in human FGF9, FGF9S99N and FGF9R62G, are dominant and result in craniosynostosis (fusion of cranial sutures) or multiple synostoses (fusion of limb joints). Whether these synostosis-causing FGF9 mutations impact upon gonadal development and DSD etiology has not been explored. We therefore examined embryonic gonads in the well-characterized Fgf9 missense mouse mutants, Fgf9S99N and Fgf9N143T, which phenocopy the skeletal defects of FGF9S99N and FGF9R62G variants, respectively. XY Fgf9S99N/S99N and XY Fgf9N143T/N143T fetal mouse gonads showed severely disorganized testis cords and partial XY sex reversal at 12.5 days post coitum (dpc), suggesting loss of FGF9 function. By 15.5 dpc, testis development in both mutants had partly recovered. Mitotic analysis in vivo and in vitro suggested that the testicular phenotypes in these mutants arise in part through reduced proliferation of the gonadal supporting cells. These data raise the possibility that human FGF9 mutations causative for dominant skeletal conditions can also lead to loss of FGF9 function in the developing testis, at least in mice. Our data suggest that, in humans, testis development is largely tolerant of deleterious FGF9 mutations which lead to skeletal defects, thus offering an explanation as to why XY DSDs are rare in patients with pathogenic FGF9 variants.
Published: 2020
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29. Efficacy of a physical activity programme combining individualized aerobic exercise and coaching to improve physical fitness in neuromuscular diseases (I'M FINE)

Author: Fieke S. Koopman, Eric L. Voorn, Camiel Verhamme, Annerieke C. van Groenestijn, Filip Eftimov, Frans Nollet, Sander Oorschot, Harald T. Jørstad, Judith G. M. Jelsma, M.A. Brehm, Public and occupational health, Amsterdam Neuroscience - Neuroinfection & -inflammation, AMS - Rehabilitation & Development, APH - Quality of Care, APH - Health Behaviors & Chronic Diseases, Rehabilitation medicine, Neurology, ANS - Neuroinfection & -inflammation, ACS - Atherosclerosis & ischemic syndromes, Cardiology, AMS - Sports & Work, ARD - Amsterdam Reproduction and Development, AMS - Sports, ACS - Heart failure & arrhythmias, and Faculty of Behavioural and Movement Sciences
Subjects: Adult, medicine.medical_specialty, Physical fitness, Motivational interviewing, Coaching, lcsh:RC346-429, law.invention, 03 medical and health sciences, Study Protocol, 0302 clinical medicine, Quality of life, Randomized controlled trial, SDG 3 - Good Health and Well-being, law, Intervention (counseling), medicine, Aerobic exercise, Humans, Multicenter Studies as Topic, 030212 general & internal medicine, lcsh:Neurology. Diseases of the nervous system, Netherlands, Randomized Controlled Trials as Topic, Active lifestyle, business.industry, VO2 max, Mentoring, General Medicine, Exercise Therapy, Neuromuscular diseases, Treatment Outcome, Research Design, Physical therapy, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background In individuals with neuromuscular diseases (NMD), symptoms of muscle weakness, fatigue and pain may limit physical activity. Inactivity leads to reduced physical fitness, which further complicates daily life functioning. Due to inconclusive evidence regarding exercise in NMD, the optimal training approach and strategies to preserve an active lifestyle remain to be determined. The physical activity programme I’M FINE, consisting of individualized aerobic exercise to improve physical fitness and coaching to preserve an active lifestyle, was therefore developed. The primary objective of this study will be to evaluate the efficacy of the I’M FINE programme in terms of improved physical fitness in individuals with slowly progressive NMD, compared to usual care. Methods A multicentre, assessor-blinded, two armed, randomized controlled trial will be conducted in a sample of 90 individuals with slowly progressive NMD. Participants motivated to improve their reduced physical fitness will be randomized (ratio 1:1) to the I’M FINE intervention or usual care. The I’M FINE intervention consists of a six-month physical activity programme, including individualized home-based aerobic exercise to improve physical fitness (i.e. peak oxygen uptake), and motivational interviewing coaching (e.g. goal setting, self-management) to adopt and preserve an active lifestyle. Measurements will be performed at baseline, post-intervention, and at 12- and 18-months follow-up. The primary outcome is peak oxygen uptake (VO2 peak) directly post intervention. Main secondary outcomes are physical capacity, muscle strength, self-efficacy, daily activity, quality of life and markers of metabolic syndrome. The primary analysis compares change in VO2 peak post-intervention between the intervention and usual care group, with analysis of covariance. Discussion The I’M FINE study will provide evidence regarding the efficacy of a physical activity intervention on the physical fitness and active lifestyle over the short- and long-term in individuals with slowly progressive NMD. These outcomes could potentially improve the (inter)national guidelines for efficacy of aerobic exercise programmes and provide insight in achieving a more active lifestyle in NMD. Trial registration (5/11/2018): Netherlands Trial Register NTR7609 (retrospectively registered), https://www.trialregister.nl/trial/7344. However, the Ethics Review Committee of the Amsterdam Medical Center (AMC) approved the study protocol on 7/11/2017. No adjustments were made to the approved study protocol before the first participant enrolment and registration. Registration was done after the second participant enrolment and the information in the register corresponds one on one with the approved study protocol.
Published: 2020
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30. Relevance and Effectiveness of Molecular Tumor Board Recommendations for Patients With Non-Small-Cell Lung Cancer With Rare or Complex Mutational Profiles

Author: Birgitta I. Hiddinga, Arja ter Elst, T. Jeroen N. Hiltermann, Matthew Groves, Bart Koopman, Harry J.M. Groen, Anthonie J. van der Wekken, Ed Schuuring, Lucie Hijmering-Kappelle, Wim Timens, Anke van den Berg, Juliana F Vilacha, Léon C van Kempen, Jos A. Stigt, Drug Design, Medicinal Chemistry and Bioanalysis (MCB), Translational Immunology Groningen (TRIGR), Stem Cell Aging Leukemia and Lymphoma (SALL), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Research Institute for Asthma and COPD (GRIAC), Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Targeted Gynaecologic Oncology (TARGON)
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, UNIVERSITY-OF-CALIFORNIA, business.industry, medicine.disease, DIAGNOSIS, ONCOLOGY, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, SEQUENCE VARIANTS, Medicine, Tumor board, Relevance (information retrieval), Non small cell, CLINICAL-PRACTICE GUIDELINES, business, Lung cancer
Abstract: PURPOSE Molecular tumor boards (MTBs) provide physicians with a treatment recommendation for complex tumor-specific genomic alterations. National and international consensus to reach a recommendation is lacking. In this article, we analyze the effectiveness of an MTB decision-making methodology for patients with non–small-cell lung cancer (NSCLC) with rare or complex mutational profiles as implemented in the University Medical Center Groningen (UMCG). METHODS The UMCG-MTB comprises (pulmonary) oncologists, pathologists, clinical scientists in molecular pathology, and structural biologists. Recommendations are based on reported actionability of variants and molecular interpretation of pathways affected by the variant and supported by molecular modeling. A retrospective analysis of 110 NSCLC cases (representing 106 patients) with suggested treatment of complex genomic alterations and corresponding treatment outcomes for targeted therapy was performed. RESULTS The MTB recommended targeted therapy for 59 of 110 NSCLC cases with complex molecular profiles: 24 within a clinical trial, 15 in accordance with guidelines (on label) and 20 off label. All but 16 recommendations involved patients with an EGFR or ALK mutation. Treatment outcome was analyzed for patients with available follow-up (10 on label and 16 off label). Adherence to the MTB recommendation (21 of 26; 81%) resulted in an objective response rate of 67% (14 of 21), with a median progression-free survival of 6.3 months (interquartile range, 3.2-10.6 months) and an overall survival of 10.4 months (interquartile range, 6.3-14.6 months). CONCLUSION Targeted therapy recommendations resulting from the UMCG-MTB workflow for complex molecular profiles were highly adhered to and resulted in a positive clinical response in the majority of patients with metastatic NSCLC.
Published: 2020
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31. PATCH trial: explanatory analyses

Author: Rustam Al-Shahi Salman, Yvo B.W.E.M. Roos, Sophie Susen, Charlotte Cordonnier, M. Irem Baharoglu, Lynn Manson, Maria M. W. Koopman, Ludo F. M. Beenen, Henk A. Marquering, Charles B. L. M. Majoie, Graduate School, ACS - Atherosclerosis & ischemic syndromes, ANS - Neurovascular Disorders, Radiology and Nuclear Medicine, ACS - Microcirculation, ACS - Pulmonary hypertension & thrombosis, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, and Neurology
Subjects: medicine.medical_specialty, business.industry, Immunology, Brain, Cell Biology, Hematology, Platelet Transfusion, Biochemistry, Magnetic Resonance Imaging, Platelet transfusion, Internal medicine, Cardiology, Medicine, Humans, Platelet, business, Tomography, X-Ray Computed, Platelet Aggregation Inhibitors, Cerebral Hemorrhage
Published: 2020
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32. Clinical Practice Guideline: Ménière’s Disease Executive Summary

Author: Jennifer Derebery, Matthew L. Bush, Meredith E. Adams, Kevin A. Kerber, Erin M. Buchanan, Brian J. McKinnon, Elizabeth A. Kelly, Patrick J. Antonelli, Nui Dhepyasuwan, Lorraine C. Nnacheta, Carla V. Valenzuela, Michael J. Ruckenstein, Julie Bykowski, Gregory J. Basura, Ashkan Monfared, Evie Marcolini, Seth R. Schwartz, Amy Angie Kuch, Charles F. Koopman, Sandra A. Walsh, Robert Burkard, Alexis Vosooney, and Maria Colandrea
Subjects: Pediatrics, medicine.medical_specialty, biology, business.industry, Guideline, Disease, Electrocochleography, medicine.disease, biology.organism_classification, Otorhinolaryngology, Quality of life, Vertigo, otorhinolaryngologic diseases, medicine, Humans, Surgery, Sensorineural hearing loss, Endolymphatic hydrops, business, Meniere Disease, Meniere's disease
Abstract: Ménière's disease (MD) is a clinical condition defined by spontaneous vertigo attacks (each lasting 20 minutes to 12 hours) with documented low- to midfrequency sensorineural hearing loss in the affected ear before, during, or after one of the episodes of vertigo. It also presents with fluctuating aural symptoms (hearing loss, tinnitus, or ear fullness) in the affected ear. The underlying etiology of MD is not completely clear, yet it has been associated with inner ear fluid volume increases, culminating in episodic ear symptoms (vertigo, fluctuating hearing loss, tinnitus, and aural fullness). Physical examination findings are often unremarkable, and audiometric testing may or may not show low- to midfrequency sensorineural hearing loss. Imaging, if performed, is also typically normal. The goals of MD treatment are to prevent or reduce vertigo severity and frequency; relieve or prevent hearing loss, tinnitus, and aural fullness; and improve quality of life. Treatment approaches to MD are many, and approaches typically include modifications of lifestyle factors (eg, diet) and medical, surgical, or a combination of therapies.The primary purpose of this clinical practice guideline is to improve the quality of the diagnostic workup and treatment outcomes of MD. To achieve this purpose, the goals of this guideline are to use the best available published scientific and/or clinical evidence to enhance diagnostic accuracy and appropriate therapeutic interventions (medical and surgical) while reducing unindicated diagnostic testing and/or imaging.
Published: 2020
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33. An update on pulmonary rehabilitation techniques for patients with chronic obstructive pulmonary disease

Author: Maud Koopman, Rein Posthuma, Frits M.E. Franssen, Martijn A. Spruit, Manu Sastry, Emiel F. M. Wouters, Wai-Yan Liu, Maurice J.H. Sillen, and Bita Hajian
Subjects: Sleep Wake Disorders, Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.medical_treatment, Psychological intervention, nutritional support, gait, sleep disturbances, Pulmonary Disease, Chronic Obstructive, Quality of life (healthcare), lung volume reduction, QUALITY-OF-LIFE, Intervention (counseling), medicine, COPD PATIENTS, Humans, Immunology and Allergy, COPD, Pulmonary rehabilitation, Intensive care medicine, NEUROMUSCULAR ELECTRICAL-STIMULATION, Physical Therapy Modalities, Modalities, POSITIVE-PRESSURE VENTILATION, business.industry, Public Health, Environmental and Occupational Health, noninvasive ventilation, HUMAN SKELETAL-MUSCLE, medicine.disease, Pulmonary hypertension, CHRONIC HEART-FAILURE, Exercise Therapy, neuromuscular stimulation, INDUCED OXYGEN DESATURATION, Gait analysis, SUPPLEMENTAL OXYGEN, RESPIRATORY SOCIETY STATEMENT, business, exercise training
Abstract: Introduction: Pulmonary rehabilitation (PR) is one of the core components in the management of patients with chronic obstructive pulmonary disease (COPD). In order to achieve the maximal level of independence, autonomy, and functioning of the patient, targeted therapies and interventions based on the identification of physical, emotional and social traits need to be provided by a dedicated, interdisciplinary PR team. Areas covered: The review discusses cardiopulmonary exercise testing in the selection of different modes of training modalities. Neuromuscular electrical stimulation as well as gait assessment and training are discussed as well as add-on therapies as oxygen, noninvasive ventilator support or endoscopic lung volume reduction in selected patients. The potentials of pulsed inhaled nitric oxide in patients with underlying pulmonary hypertension is explored as well as nutritional support. The impact of sleep quality on outcomes of PR is reviewed. Expert opinion: Individualized, comprehensive intervention based on thorough assessment of physical, emotional, and social traits in COPD patients forms a continuous challenge for health-care professionals and PR organizations in order to dynamically implement and adapt these strategies based on dynamic, more optimal understanding of underlying pathophysiological mechanisms.
Published: 2020
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34. Spatiotemporal Mapping Reveals Regional Gastrointestinal Dysfunction in mdx Dystrophic Mice Ameliorated by Oral L-arginine Supplementation

Author: Jennifer Trieu, Anita J. L. Leembruggen, Rebecka Bindon, Joel C. Bornstein, Timur Naim, Shana Schokman, René Koopman, Kristy Swiderski, Gordon S. Lynch, Mathusi Swaminathan, and Elisa L. Hill-Yardin
Subjects: medicine.medical_specialty, Nitric oxide synthase type I, Duchenne muscular dystrophy, Arginine, Nitric oxide, chemistry.chemical_compound, Glycoprotein complex, Internal medicine, medicine, Citrulline, Muscular dystrophy, Gastrointestinal diseases, Migrating motor complex, colon, biology, business.industry, Gastroenterology, Skeletal muscle, Duchenne, medicine.disease, Nitric oxide synthase, Endocrinology, medicine.anatomical_structure, chemistry, biology.protein, Original Article, Neurology (clinical), business
Abstract: Background/Aims: Patients with Duchenne muscular dystrophy exhibit significant, ongoing impairments in gastrointestinal (GI) function likely resulting from dysregulated nitric oxide production. Compounds increasing neuronal nitric oxide synthase expression and/or activity could improve GI dysfunction and enhance quality of life for dystrophic patients. We used video imaging and spatiotemporal mapping to identify GI dysfunction in mdx dystrophic mice and determine whether dietary intervention to enhance nitric oxide could alleviate aberrant colonic activity in muscular dystrophy. Methods: Four-week-old male C57BL/10 and mdx mice received a specialized diet either with no supplementation (control) or supplemented (1 g/kg/day) with L-alanine, L-arginine, or L-citrulline for 8 weeks. At the conclusion of treatment, mice were sacrificed by cervical dislocation and colon motility examined by spatiotemporal (ST) mapping ex vivo. Results: ST mapping identified increased contraction number in the mid and distal colon of mdx mice on control and L-alanine supplemented diets relative to C57BL/10 mice (P < 0.05). Administration of either L-arginine or L-citrulline attenuated contraction number in distal colons of mdx mice relative to C57BL/10 mice. Conclusions: GI dysfunction in Duchenne muscular dystrophy has been sadly neglected as an issue affecting quality of life. ST mapping identified regional GI dysfunction in the mdx dystrophic mouse. Dietary interventions to increase nitric oxide signaling in the GI tract reduced the number of colonic contractions and alleviated colonic constriction at rest. These findings in mdx mice reveal that L-arginine can improve colonic motility and has potential therapeutic relevance for alleviating GI discomfort, improving clinical care, and enhancing quality of life in Duchenne muscular dystrophy.
Published: 2020
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35. Incorporation of differentiated dysplasia improves prediction of oral leukoplakia at increased risk of malignant progression

Author: Elisabeth Bloemena, Jos B. Poell, Leon J. Wils, E.R.E.A. Brouns, Ilkay Evren, Jan G.A.M. de Visscher, Ruud H. Brakenhoff, Marit S. Koopman, Maxillofacial Surgery (VUmc), Otolaryngology / Head & Neck Surgery, Oral and Maxillofacial Surgery / Oral Pathology, CCA - Cancer Treatment and quality of life, Pathology, and Amsterdam Gastroenterology Endocrinology Metabolism
Subjects: 0301 basic medicine, Male, Pathology, Gastroenterology, Malignant transformation, Prognostic markers, 0302 clinical medicine, Oral mucosa, Aged, 80 and over, Oral cancer, Hazard ratio, Middle Aged, Immunohistochemistry, Oral leukoplakia, medicine.anatomical_structure, Cell Transformation, Neoplastic, 030220 oncology & carcinogenesis, Disease Progression, Female, Mouth Neoplasms, Oral Surgery, Leukoplakia, Oral, Risk assessment, Adult, medicine.medical_specialty, Article, Pathology and Forensic Medicine, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Dentistry (miscellaneous), Clinical significance, Pathological, Grading (tumors), Aged, Retrospective Studies, Oral Dysplasia, Hyperplasia, business.industry, Squamous Cell Carcinoma of Head and Neck, Mouth Mucosa, Retrospective cohort study, medicine.disease, stomatognathic diseases, 030104 developmental biology, Dysplasia, Surgery, business, Precancerous Conditions
Abstract: Oral leukoplakia is the most common oral potentially malignant disorder with a malignant transformation rate into oral squamous cell carcinoma of 1–3% annually. The presence and grade of World Health Organization defined dysplasia is an important histological marker to assess the risk for malignant transformation, but is not sufficiently accurate to personalize treatment and surveillance. Differentiated dysplasia, known from differentiated vulvar intraepithelial neoplasia, is hitherto not used in oral dysplasia grading. We hypothesized that assessing differentiated dysplasia besides World Health Organization defined (classic) dysplasia will improve risk assessment of malignant transformation of oral leukoplakia. We investigated a retrospective cohort consisting of 84 oral leukoplakia patients. Biopsies were assessed for dysplasia presence and grade, and the expression of keratins 13 (CK13) and 17, known to be dysregulated in dysplastic vulvar mucosa. In dysplastic oral lesions, differentiated dysplasia is as common as classic dysplasia. In 25 out of 84 (30%) patients, squamous cell carcinoma of the upper aerodigestive tract developed during follow-up. Considering only classic dysplasia, 11 out of 56 (20%) patients with nondysplastic lesions progressed. With the incorporation of differentiated dysplasia, only 2 out of 30 (7%) patients with nondysplastic lesions progressed. The risk of progression increased from 3.26 (Hazard ratio, p = 0.002) when only classic dysplasia is considered to 7.43 (Hazard ratio, p = 0.001) when classic and differentiated dysplasia are combined. Loss of CK13, combined with presence of dysplasia, is associated with greater risk of malignant progression (p = 0.006). This study demonstrates that differentiated dysplasia should be recognized as a separate type of dysplasia in the oral mucosa and that its distinction from classic dysplasia is of pathological and clinical significance since it is a strong (co)prognostic histopathological marker for oral malignant transformation. In oral lesions without dysplasia and retained CK13 staining the risk for progression is very low.
Published: 2020
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36. Effect of Endotracheal Tube Size, Respiratory System Mechanics, and Ventilator Settings on Driving Pressure

Author: Pauline de Jager, Robert G T Blokpoel, Johannes G. M. Burgerhof, Patrick van Schelven, Alette A. Koopman, D.G. Markhorst, Stavroula Ilia, Martin C. J. Kneyber, Life Course Epidemiology (LCE), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Pediatric surgery, ACS - Diabetes & metabolism, and Amsterdam Reproduction & Development (AR&D)
Subjects: medicine.medical_specialty, Maximal Respiratory Pressures, medicine.medical_treatment, Respiratory System, CHILDREN, Respiratory physiology, Peak inspiratory pressure, driving pressure, mechanical ventilation, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, ACUTE LUNG INJURY, Positive-Pressure Respiration, 03 medical and health sciences, Plateau pressure, 0302 clinical medicine, Airway resistance, Internal medicine, Intubation, Intratracheal, Humans, Medicine, Respiratory system, METAANALYSIS, Mechanical ventilation, Ventilators, Mechanical, business.industry, Airway Resistance, in vitro techniques, MORTALITY, 030208 emergency & critical care medicine, Equipment Design, Models, Theoretical, Respiration, Artificial, Compliance (physiology), Volume (thermodynamics), pressure controlled ventilation, VOLUME, Pediatrics, Perinatology and Child Health, Linear Models, Respiratory Mechanics, Cardiology, resistive pressure, business, pediatric intensive care unit
Abstract: Objectives: We sought to investigate factors that affect the difference between the peak inspiratory pressure measured at the Y-piece under dynamic flow conditions and plateau pressure measured under zero-flow conditions (resistive pressure) during pressure controlled ventilation across a range of endotracheal tube sizes, respiratory mechanics, and ventilator settings. Design: In vitro study. Setting: Research laboratory. Patients: None. Interventions: An in vitro bench model of the intubated respiratory system during pressure controlled ventilation was used to obtain the difference between peak inspiratory pressure measured at the Y-piece under dynamic flow conditions and plateau pressure measured under zero-flow conditions across a range of endotracheal tubes sizes (3.0–8.0 mm). Measurements were taken at combinations of pressure above positive end-expiratory pressure (10, 15, and 20 cm H2O), airway resistance (no, low, high), respiratory system compliance (ranging from normal to extremely severe), and inspiratory time at constant positive end-expiratory pressure (5 cm H2O). Multiple regression analysis was used to construct models predicting resistive pressure stratified by endotracheal tube size. Measurements and Main Results: On univariate regression analysis, respiratory system compliance (β –1.5; 95% CI, –1.7 to –1.4; p < 0.001), respiratory system resistance (β 1.7; 95% CI, 1.5–2.0; p < 0.001), pressure above positive end-expiratory pressure (β 1.7; 95% CI, 1.4–2.0; p < 0.001), and inspiratory time (β –0.7; 95% CI, –1.0 to –0.4; p < 0.001) were associated with resistive pressure. Multiple linear regression analysis showed the independent association between increasing respiratory system compliance, increasing airway resistance, increasing pressure above positive end-expiratory pressure, and decreasing inspiratory time and resistive pressure across all endotracheal tube sizes. Inspiratory time was the strongest variable associated with a proportional increase in resistive pressure. The contribution of airway resistance became more prominent with increasing endotracheal tube size. Conclusions: Peak inspiratory pressures measured during pressure controlled ventilation overestimated plateau pressure irrespective of endotracheal tube size, especially with decreased inspiratory time or increased airway resistance.
Published: 2020
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37. Cerebrospinal Fluid of Preeclamptic and Normotensive Pregnant Women Compared to Nonpregnant Women Analyzed with Mass Spectrometry

Author: Christoph Stingl, Seppe Koopman, Johannes J. Duvekot, Coşkun Güzel, Marcel P. Stoop, Theo M. Luider, Caroline B van den Berg, Robbert Jan van Krugten, Neurology, and Obstetrics & Gynecology
Subjects: medicine.medical_specialty, Pregnancy, business.industry, General Chemical Engineering, Cerebrospinal fluid proteins, General Chemistry, medicine.disease, medicine.disease_cause, Article, Preeclampsia, Chemistry, Cerebrospinal fluid, Endocrinology, Internal medicine, Secondary analysis, medicine, In patient, Pregnancy proteins, business, QD1-999, Oxidative stress
Abstract: Preeclampsia is a pregnancy-specific multiorgan disorder in which impaired placental functioning and excessive oxidative stress play an important role. We previously showed distinct differences between cerebrospinal fluid proteins in patients with preeclampsia and normotensive pregnant women. An additional group of nonpregnant women was included to study the presence of pregnancy-related proteins in normotensive and preeclamptic pregnancies and whether pregnancy-related proteins were associated with preeclampsia. Cerebrospinal fluid samples were tryptically digested and subsequently measured with a nano-LC-tribrid Orbitrap mass spectrometry system. Proteins were identified by shotgun proteomic analysis based on a data-dependent acquisition method. Proteins identified in preeclampsia, normotensive pregnant controls, and nonpregnant groups were compared to the Progenesis method according to the criteria as previously described and with a secondary analysis using a Scaffold method including Benjamini-Hochberg correction for multiple testing. For preeclampsia, the Progenesis and the Scaffold method together identified 15 (eight proteins for both analyses with one overlap) proteins that were significantly different compared to normotensive control pregnancies. Three of these 15 proteins, which were elevated in cerebrospinal fluid of preeclamptic women, were described to be pregnancy proteins with a calcium-binding function. Using two analysis methods (Progenesis and Scaffold), four out of 15 differential proteins were associated with pregnancy, as described in the literature. Three out of the four pregnancy-related proteins were elevated in preeclampsia. Furthermore, the contribution of elevated (n = 4/15) and downregulated (n = 2/15) calcium-binding proteins in preeclampsia is remarkably high (40%) and needs to be elucidated further.
Published: 2020
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38. Estimated all-day and evening whole-brain radiofrequency electromagnetic fields doses, and sleep in preadolescents

Author: Cabré-Riera, Alba, van Wel, Luuk, Liorni, Ilaria, Koopman-Verhoeff, M Elisabeth, Imaz, Liher, Ibarluzea, Jesús, Huss, Anke, Wiart, Joe, Vermeulen, Roel, Joseph, Wout, Capstick, Myles, Vrijheid, Martine, Cardis, Elisabeth, Röösli, Martin, Eeftens, Marloes, Thielens, Arno, Tiemeier, Henning, Guxens, Mònica, One Health Chemisch, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, LS IRAS EEPI ME (Milieu epidemiologie), One Health Chemisch, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, LS IRAS EEPI ME (Milieu epidemiologie), European Commission, Child and Adolescent Psychiatry / Psychology, and Erasmus MC other
Subjects: medicine.medical_specialty, Evening, Technology and Engineering, SYMPTOMS, DEVICES, animal structures, Wireless technology, Adolescent, Population, Audiology, Biochemistry, PHONE BASE STATIONS, Phone, Environmental Science(all), Medicine, Humans, QUALITY, EXPOSURE, education, Child, ADOLESCENT SLEEP, General Environmental Science, education.field_of_study, Sleep disorder, business.industry, Radio waves, TECHNOLOGY USE, Brain, Electromagnetic fields, Environmental Exposure, medicine.disease, Sleep time, Mobile phone, MEDIA USE, technology, Telecommunications, Wireless, UPDATE, Generation R, Sleep (system call), RF-EMF, business, Sleep, Cell phone use, Cell Phone
Abstract: [EN] Objective: To investigate the association of estimated all-day and evening whole-brain radiofrequency electromagnetic field (RF-EMF) doses with sleep disturbances and objective sleep measures in preadolescents. Methods: We included preadolescents aged 9-12 years from two population-based birth cohorts, the Dutch Generation R Study (n = 974) and the Spanish INfancia y Medio Ambiente Project (n = 868). All-day and evening overall whole-brain RF-EMF doses (mJ/kg/day) were estimated for several RF-EMF sources including mobile and Digital Enhanced Cordless Telecommunications (DECT) phone calls (named phone calls), other mobile phone uses, tablet use, laptop use (named screen activities), and far-field sources. We also estimated all-day and evening whole-brain RF-EMF doses in these three groups separately (i.e. phone calls, screen activities, and far-field). The Sleep Disturbance Scale for Children was completed by mothers to assess sleep disturbances. Wrist accelerometers together with sleep diaries were used to measure sleep characteristics objectively for 7 consecutive days. Results: All-day whole-brain RF-EMF doses were not associated with self-reported sleep disturbances and objective sleep measures. Regarding evening doses, preadolescents with high evening whole-brain RF-EMF dose from phone calls had a shorter total sleep time compared to preadolescents with zero evening whole-brain RF-EMF dose from phone calls [-11.9 min (95%CI -21.2; -2.5)]. Conclusions: Our findings suggest the evening as a potentially relevant window of RF-EMF exposure for sleep. However, we cannot exclude that observed associations are due to the activities or reasons motivating the phone calls rather than the RF-EMF exposure itself or due to chance finding. This work was supported by the European Union Seventh Framework Program (FP7/2007-2013 No. 603794 GERoNiMO project) . Arno Thielens is a postdoctoral fellow of the Research Foundation Flanders (FWO) under grant agreement no. 12U1417N. INMA-Sabadell: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; PI12/01890 incl. FEDER funds; CP13/00054 incl. FEDER funds, MS13/00054, CPII18/00018; PI17/01340 incl. FEDER funds) , CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR (2009 SGR 501, 2014 SGR 822) , Fundacio La Marato de TV3 (090430) , Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds) , French Agency for Food, Environmental and Occupational Health & Safety (EST-2016 RF-21, EST/2013/2/22) , EU Commission (261357, 308333, 603794 and 634453) .We also acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S) , and support from the Generalitat de Catalunya through the CERCA Program". INMA-Gipuzkoa: This study was funded by grants from Instituto de Salud Carlos III (FIS-PI13/02187) , CIBERESP, Department of Health of the Basque Government (2015111065) , and the Provincial Government of Gipuzkoa (DFG15/221) and annual agreements with the municipal-ities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain) . The Generation R Study: The general design of the Generation R Study is supported by the Erasmus Medical Center-Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development, the Netherlands Organization for Scientific Research, and the Dutch Ministry of Health, Welfare and Sport, and the Stichting Trombosedienst and Artsenlaboratorium Rijnmond. This study was funded by a grantfromthe Netherlands organization for Health Research and Development (85500036) . Henning Tiemeier was sup-ported by a grant of the Netherlands Organization for Scientific Research (NWO/ZonMW grant 016.VICI.170.200) and of Erasmus Medical Center Efficiency Grant (MRC-2013-169) .
Published: 2022

39. Driving pressure is associated with outcome in pediatric acute respiratory failure

Author: Johannes G. M. Burgerhof, Martin C. J. Kneyber, D.G. Markhorst, Robert G T Blokpoel, Patrick van Schelven, Alette A. Koopman, Life Course Epidemiology (LCE), and Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE)
Subjects: Mechanical ventilation, medicine.medical_specialty, Respiratory Distress Syndrome, business.industry, medicine.medical_treatment, Peak inspiratory pressure, Critical Care and Intensive Care Medicine, Respiration, Artificial, Article, Positive-Pressure Respiration, Plateau pressure, Internal medicine, Pediatrics, Perinatology and Child Health, Cohort, medicine, Risk of mortality, Cardiology, Tidal Volume, Humans, Respiratory system, business, Child, Respiratory Insufficiency, Tidal volume, Pressure gradient
Abstract: OBJECTIVES: Driving pressure (ratio of tidal volume over respiratory system compliance) is associated with mortality in acute respiratory distress syndrome. We sought to evaluate if such association could be identified in critically ill children.DESIGN: We studied the association between driving pressure on day 1 of mechanical ventilation and ventilator-free days at day 28 through secondary analyses of prospectively collected physiology data.SETTING: Medical-surgical university hospital PICU.PATIENTS: Children younger than 18 years (stratified by Pediatric Mechanical Ventilation Consensus Conference clinical phenotype definitions) without evidence of spontaneous respiration.INTERVENTIONS: Inspiratory hold maneuvers.MEASUREMENTS AND MAIN RESULTS: Data of 222 patients with median age 11 months (2-51 mo) were analyzed. Sixty-five patients (29.3%) met Pediatric Mechanical Ventilation Consensus Conference criteria for restrictive and 78 patients (35.1%) for mixed lung disease, and 10.4% of all patients had acute respiratory distress syndrome. Driving pressure calculated by the ratio of tidal volume over respiratory system compliance for the whole cohort was 16 cm H2O (12-21 cm H2O) and correlated with the static airway pressure gradient (plateau pressure minus positive end-expiratory pressure) (Spearman correlation coefficient = 0.797; p < 0.001). Bland-Altman analysis showed that the dynamic pressure gradient (peak inspiratory pressure minus positive end-expiratory pressure) overestimated driving pressure (levels of agreement -2.295 to 7.268). Rematching the cohort through a double stratification procedure (obtaining subgroups of patients with matched mean levels for one variable but different mean levels for another ranking variable) showed a reduction in ventilator-free days at day 28 with increasing driving pressure in patients ventilated for a direct pulmonary indication. Competing risk regression analysis showed that increasing driving pressure remained independently associated with increased time to extubation (p < 0.001) after adjusting for Pediatric Risk of Mortality III 24-hour score, presence of direct pulmonary indication jury, and oxygenation index.CONCLUSIONS: Higher driving pressure was independently associated with increased time to extubation in mechanically ventilated children. Dynamic assessments of driving pressure should be cautiously interpreted.
Published: 2022

40. β-Hydroxy-β-methylbutyrate (HMB) supplementation and functional outcomes in multi-trauma patients: a study protocol for a pilot randomised clinical trial (BOOST trial)

Author: Jeffery J Presneill, Yasmine Ali Abdelhamid, Lisa Beach, Kate Fetterplace, Kym Wittholz, Benjamin N. J. Thomson, David J Read, Adam M. Deane, and René Koopman
Subjects: Protocol (science), Medicine (General), medicine.medical_specialty, Multi trauma, business.industry, Medicine (miscellaneous), Muscle mass, Trauma, β-Hydroxy-β-methylbutyrate, Clinical trial, Study Protocol, Nutrition therapy, R5-920, Internal medicine, medicine, Amino acids, business, Critical illness, Enteral nutrition
Abstract: Background There are no therapies proven to diminish the muscle wasting that occurs in patients after major trauma who are admitted to the intensive care unit (ICU). β-Hydroxy-β-methylbutyrate (HMB) is a nutrition intervention that may attenuate muscle loss and, thereby, improve recovery. The primary aim of this study is to determine the feasibility of a blinded randomised clinical trial of HMB supplementation to patients after major trauma who are admitted to the ICU. Secondary aims are to establish estimates for the impact of HMB when compared to placebo on muscle mass and nutrition-related patient outcomes. Methods This prospective, single-centre, blinded, randomised, placebo-controlled, parallel-group, feasibility trial with allocation concealment will recruit 50 participants over 18 months. After informed consent, participants will be randomised [1:1] to receive either the intervention (three grams of HMB dissolved in either 150 ml of orange juice for those allowed oral intake or 150 ml of water for those being enterally fed) or placebo (150 ml of orange juice for those allowed oral intake or 150 ml of water for those being enterally fed). The intervention will be commenced in ICU, continued after ICU discharge and ceased at hospital discharge or day 28 post randomisation, whichever occurs first. The primary outcome is the feasibility of administering the intervention. Secondary outcomes include change in muscle thickness using ultrasound and other nutritional and patient-centred outcomes. Discussion This study aims to determine the feasibility of administering HMB to critically ill multi-trauma patients throughout ICU admission until hospital discharge. Results will inform design of a larger randomised clinical trial. Trial registration The protocol is registered with Australian New Zealand Clinical Trials Registry (ANZCTR) ANZCTR: 12620001305910. UTN: U1111-1259-5534.
Published: 2022
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41. Longitudinal respiratory subphenotypes in patients with COVID-19-related acute respiratory distress syndrome: results from three observational cohorts

Author: Lieuwe D J Bos, Michael Sjoding, Pratik Sinha, Sivasubramanium V Bhavani, Patrick G Lyons, Alice F Bewley, Michela Botta, Anissa M Tsonas, Ary Serpa Neto, Marcus J Schultz, Robert P Dickson, Frederique Paulus, J.P. van Akkeren, A.G. Algera, C.K. Algoe, R.B. van Amstel, A. Artigas, O.L. Baur, P. van de Berg, A.E. van den Berg, D.C.J.J. Bergmans, D.I. van den Bersselaar, F.A. Bertens, A.J.G.H. Bindels, M.M. de Boer, S. den Boer, L.S. Boers, M. Bogerd, L.D.J. Bos, M. Botta, J.S. Breel, H. de Bruin, S. de Bruin, C.L. Bruna, L.A. Buiteman-Kruizinga, O. Cremer, R.M. Determann, W. Dieperink, D.A. Dongelmans, H.S. Franke, M.S. Galek-Aldridge, M.J. de Graaff, L.A. Hagens, J.J. Haringman, S.T. van der Heide, P.L.J. van der Heiden, N.F.L. Heijnen, S.J.P. Hiel, L.L. Hoeijmakers, L. Hol, M.W. Hollmann, M.E. Hoogendoorn, J. Horn, R. van der Horst, E.L.K. Ie, D. Ivanov, N.P. Juffermans, E. Kho, E.S. de Klerk, A.W.M.M. Koopman-van Gemert, M. Koopmans, S. Kucukcelebi, M.A. Kuiper, D.W. de Lange, I. Martin-Loeches, G. Mazzinari, D.M.P. van Meenen, L. Morales-Quinteros, N. van Mourik, S.G. Nijbroek, M. Onrust, E.A.N. Oostdijk, F. Paulus, C.J. Pennartz, J. Pillay, L. Pisani, I.M. Purmer, T.C.D. Rettig, J.P. Roozeman, M.T.U. Schuijt, M.J. Schultz, A. Serpa Neto, M.E. Sleeswijk, M.R. Smit, P.E. Spronk, W. Stilma, A.C. Strang, A.M. Tsonas, P.R. Tuinman, C.M.A. Valk, F.L. Veen-Schra, L.I. Veldhuis, P. van Velzen, W.H. van der Ven, A.P.J. Vlaar, P. van Vliet, P.H.J. van der Voort, L. van Welie, H.J.F.T. Wesselink, H.H. van der Wier-Lubbers, B. van Wijk, T. Winters, W.Y. Wong, A.R.H. van Zanten, Pulmonary medicine, Intensive care medicine, ACS - Pulmonary hypertension & thrombosis, ACS - Heart failure & arrhythmias, ACS - Diabetes & metabolism, RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA Arts Assistenten IC (9), Intensive Care, MUMC+: MA Medische Staf IC (9), Intensive Care Medicine, AII - Inflammatory diseases, Nursing, AII - Infectious diseases, Graduate School, AII - Amsterdam institute for Infection and Immunity, APH - Quality of Care, Anesthesiology, ANS - Neuroinfection & -inflammation, 06 Operations Centre and intensive care, ARD - Amsterdam Reproduction and Development, General Internal Medicine, ACS - Microcirculation, APH - Global Health, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), and Critical Care
Subjects: Pulmonary and Respiratory Medicine, Mechanical ventilation, medicine.medical_specialty, ARDS, business.industry, medicine.medical_treatment, COVID-19, Articles, acute respiratory distress syndrome, medicine.disease, Latent class model, critical care, respiratory subphenotypes, kritieke zorg, Internal medicine, Intensive care, Cohort, medicine, Breathing, business, Respiratory minute volume, Cohort study
Abstract: Background Patients with COVID-19-related acute respiratory distress syndrome (ARDS) have been postulated to present with distinct respiratory subphenotypes. However, most phenotyping schema have been limited by sample size, disregard for temporal dynamics, and insufficient validation. We aimed to identify respiratory subphenotypes of COVID-19-related ARDS using unbiased data-driven approaches.Methods PRoVENT-COVID was an investigator-initiated, national, multicentre, prospective, observational cohort study at 22 intensive care units (ICUs) in the Netherlands. Consecutive patients who had received invasive mechanical ventilation for COVID-19 (aged 18 years or older) served as the derivation cohort, and similar patients from two ICUs in the USA served as the replication cohorts. COVID-19 was confirmed by positive RT-PCR. We used latent class analysis to identify subphenotypes using clinically available respiratory data cross-sectionally at baseline, and longitudinally using 8-hourly data from the first 4 days of invasive ventilation. We used group-based trajectory modelling to evaluate trajectories of individual variables and to facilitate potential clinical translation. The PRoVENT-COVID study is registered with ClinicalTrials.gov, NCT04346342.Findings Between March 1, 2020, and May 15, 2020, 1007 patients were admitted to participating ICUs in the Netherlands, and included in the derivation cohort. Data for 288 patients were included in replication cohort 1 and 326 in replication cohort 2. Cross-sectional latent class analysis did not identify any underlying subphenotypes. Longitudinal latent dass analysis identified two distinct subphenotypes. Subphenotype 2 was characterised by higher mechanical power, minute ventilation, and ventilatory ratio over the first 4 days of invasive mechanical ventilation than subphenotype 1, but PaO2/FiO(2), pH, and compliance of the respiratory system did not differ between the two subphenotypes. 185 (28%) of 671 patients with subphenotype 1 and 109 (32%) of 336 patients with subphenotype 2 had died at day 28 (p=0.10). However, patients with subphenotype 2 had fewer ventilator-free days at day 28 (median 0, IQR 0-15 vs 5, 0-17; p=0.016) and more frequent venous thrombotic events (109[32%] of 336 patients vs 176 [26%] of 671 patients; p=0.048) compared with subphenotype 1. Group-based trajectory modelling revealed trajectories of ventilatory ratio and mechanical power with similar dynamics to those observed in latent class analysis-derived trajectory subphenotypes. The two trajectories were: a stable value for ventilatory ratio or mechanical power over the first 4 days of invasive mechanical ventilation (trajectory A) or an upward trajectory (trajectory B). However, upward trajectories were better independent prognosticators for 28-day mortality (OR 1.64, 95% CI 1.17-2.29 for ventilatory ratio; 1.82, 1.24-2.66 for mechanical power). The association between upward ventilatory ratio trajectories (trajectory B) and 28-day mortality was confirmed in the replication cohorts (OR 4.65, 95% CI 1. 87-11 6 for ventilatory ratio in replication cohort 1; 1-89, 1.05-3-37 for ventilatory ratio in replication cohort 2).Interpretation At baseline, COVID-19-related ARDS has no consistent respiratory subphenotype. Patients diverged from a fairly homogenous to a more heterogeneous population, with trajectories of ventilatory ratio and mechanical power being the most discriminatory. Modelling these parameters alone provided prognostic value for duration of mechanical ventilation and mortality. Copyright (C) 2021 Published by Elsevier Ltd. All rights reserved.
Published: 2021
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42. Striatal dopamine transporter availability is not associated with food craving in lean and obese humans; a molecular imaging study

Author: Jamie van Son, Susanne E. la Fleur, Katy A. van Galen, Jan Booij, Ruth I. Versteeg, Anne Marijn Bruijn, Karin E. Koopman, Mireille J. Serlie, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Graduate School, Endocrinology, ANS - Cellular & Molecular Mechanisms, ANS - Compulsivity, Impulsivity & Attention, Laboratory for Endocrinology, Radiology and Nuclear Medicine, and ANS - Brain Imaging
Subjects: Striatal dopamine, medicine.medical_specialty, Food craving, Neurosciences. Biological psychiatry. Neuropsychiatry, Craving, behavioral disciplines and activities, Article, Neuroimaging, Dopamine, Internal medicine, mental disorders, medicine, Obesity, Dopamine transporter, biology, business.industry, General Neuroscience, Dopaminergic, digestive, oral, and skin physiology, Transporter, Endocrinology, SPECT, biology.protein, behavior and behavior mechanisms, medicine.symptom, business, psychological phenomena and processes, RC321-571, medicine.drug
Abstract: Brain dopamine signaling is essential for the motivation to eat, and obesity is associated with altered dopaminergic signaling and increased food craving. We used molecular neuroimaging to explore whether striatal dopamine transporter (DAT) availability is associated with craving as measured with the General Food Craving Questionnaire-Trait (G-FCQ-T). We here show that humans with obesity (n = 34) experienced significantly more craving for food compared with lean subjects (n = 32), but food craving did not correlate significantly with striatal DAT availability as assessed with 123I-FP-CIT single-photon emission computed tomography. We conclude that food craving is increased in obesity, but the scores for food craving are not related to changes in striatal DAT availability.
Published: 2021
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43. Detectable A Disintegrin and Metalloproteinase With Thrombospondin Motifs-1 in Serum Is Associated With Adverse Outcome in Pediatric Sepsis

Author: Navin P. Boeddha, MD, PhD, Gertjan J. Driessen, MD, PhD, Nienke N. Hagedoorn, MD, Daniela S. Kohlfuerst, MD, Clive J. Hoggart, PhD, Angelique L. van Rijswijk, MSc, Ebru Ekinci, MD, Debby Priem, BSc, Luregn J. Schlapbach, MD, PhD, Jethro A. Herberg, MD, PhD, Ronald de Groot, MD, PhD, Suzanne T. Anderson, MD, PhD, Colin G. Fink, PhD, Enitan D. Carrol, MD, PhD, Michiel van der Flier, MD, PhD, Federico Martinón-Torres, MD, PhD, Michael Levin, MD, PhD, Frank W. Leebeek, MD, PhD, Werner Zenz, MD, PhD, Moniek P. M. de Maat, PhD, Jan A. Hazelzet, MD, PhD, Marieke Emonts, MD, PhD, Willem A. Dik, PhD, on behalf of the EUCLIDS consortium, Michael Levin, Lachlan Coin, Stuart Gormley, Shea Hamilton, Jethro Herberg, Bernardo Hourmat, Clive Hoggart, Myrsini Kaforou, Vanessa Sancho-Shimizu, Victoria Wright, Amina Abdulla, Paul Agapow, Maeve Bartlett, Evangelos Bellos, Hariklia Eleftherohorinou, Rachel Galassini, David Inwald, Meg Mashbat, Stefanie Menikou, Sobia Mustafa, Simon Nadel, Rahmeen Rahman, Clare Thakker, S Bokhandi, Sue Power, Heather Barham, N Pathan, Jenna Ridout, Deborah White, Sarah Thurston, S Faust, S Patel, Jenni McCorkell, P Davies, Lindsey Crate, Helen Navarra, Stephanie Carter, R Ramaiah, Rekha Patel, Catherine Tuffrey, Andrew Gribbin, Sharon McCready, Mark Peters, Katie Hardy, Fran Standing, Lauren O’Neill, Eugenia Abelake, Akash Deep, Eniola Nsirim, A Pollard, Louise Willis, Zoe Young, C Royad, Sonia White, PM Fortune, Phil Hudnott, Federico Martinón-Torres, Antonio Salas, Fernando Álvez González, Ruth Barral-Arca, Miriam Cebey-López, María José CurrasTuala, Natalia García, Luisa García Vicente, Alberto Gómez-Carballa, Jose Gómez Rial, Andrea Grela Beiroa, Antonio Justicia Grande, Pilar Leboráns Iglesias, Alba Elena Martínez Santos, Nazareth Martinón-Torres, José María Martinón Sánchez, Beatriz Morillo Gutiérrez, Belén Mosquera Pérez, Pablo Obando Pacheco, Jacobo Pardo-Seco, Sara Pischedda, Irene Rivero Calle, Carmen Rodríguez-Tenreiro, Lorenzo Redondo-Collazo, Antonio Salas Ellacuriaga, Sonia Serén Fernández, María del Sol Porto Silva, Ana Vega, Lucía Vilanova Trillo, Susana Beatriz Reyes, María Cruz León León, Álvaro Navarro Mingorance, Xavier Gabaldó Barrios, Eider Oñate Vergara, Andrés Concha Torre, Ana Vivanco, Reyes Fernández, Francisco Giménez Sánchez, Miguel Sánchez Forte, Pablo Rojo, J.Ruiz Contreras, Alba Palacios, Cristina Epalza Ibarrondo, Elizabeth Fernández Cooke, Marisa Navarro, Cristina Álvarez Álvarez, María José Lozano, Eduardo Carreras, Sonia Brió Sanagustín, Olaf Neth, Mª del Carmen Martínez Padilla, Luis Manuel Prieto Tato, Sara Guillén, Laura Fernández Silveira, David Moreno, R. de Groot, A.M. Tutu van Furth, M. van der Flier, N.P. Boeddha, G.J.A. Driessen, M. Emonts, J.A. Hazelzet, T.W. Kuijpers, D. Pajkrt, E.A.M. Sanders, D. van de Beek, A. van der Ende, H.L.A. Philipsen, A.O.A. Adeel, M.A. Breukels, D.M.C. Brinkman, C.C.M.M. de Korte, E. de Vries, W.J. de Waal, R. Dekkers, A. Dings-Lammertink, R.A. Doedens, A.E. Donker, M. Dousma, T.E. Faber, G.P.J.M. Gerrits, J.A.M. Gerver, J. Heidema, J. Homan-van der Veen, M.A.M. Jacobs, N.J.G. Jansen, P. Kawczynski, K. Klucovska, M.C.J. Kneyber, Y. Koopman-Keemink, V.J. Langenhorst, J. Leusink, B.F. Loza, I.T. Merth, C.J. Miedema, C. Neeleman, J.G. Noordzij, C.C. Obihara, A.L.T. van Overbeek – van Gils, G.H. Poortman, S.T. Potgieter, J. Potjewijd, P.P.R. Rosias, T. Sprong, G.W. ten Tussher, B.J. Thio, G.A. Tramper-Strander, M. van Deuren, H. van der Meer, A.J.M. van Kuppevelt, A.M. van Wermeskerken, W.A. Verwijs, T.F.W. Wolfs, Luregn J Schlapbach, Philipp Agyeman, Christoph Aebi, Eric Giannoni, Martin Stocker, Klara M Posfay-Barbe, Ulrich Heininger, Sara Bernhard-Stirnemann, Anita Niederer-Loher, Christian Kahlert, Paul Hasters, Christa Relly, Walter Baer, Christoph Berger, Enitan Carrol, Stéphane Paulus, Hannah Frederick, Rebecca Jennings, Joanne Johnston, Rhian Kenwright, Colin G Fink, Elli Pinnock, Marieke Emonts, Rachel Agbeko, Suzanne Anderson, Fatou Secka, Kalifa Bojang, Isatou Sarr, Ngane Kebbeh, Gibbi Sey, Momodou Saidykhan, Fatoumatta Cole, Gilleh Thomas, Martin Antonio, Werner Zenz, Daniela S. Klobassa, Alexander Binder, Nina A. Schweintzger, Manfred Sagmeister, Hinrich Baumgart, Markus Baumgartner, Uta Behrends, Ariane Biebl, Robert Birnbacher, Jan-Gerd Blanke, Carsten Boelke, Kai Breuling, Jürgen Brunner, Maria Buller, Peter Dahlem, Beate Dietrich, Ernst Eber, Johannes Elias, Josef Emhofer, Rosa Etschmaier, Sebastian Farr, Ylenia Girtler, Irina Grigorow, Konrad Heimann, Ulrike Ihm, Zdenek Jaros, Hermann Kalhoff, Wilhelm Kaulfersch, Christoph Kemen, Nina Klocker, Bernhard Köster, Benno Kohlmaier, Eleni Komini, Lydia Kramer, Antje Neubert, Daniel Ortner, Lydia Pescollderungg, Klaus Pfurtscheller, Karl Reiter, Goran Ristic, Siegfried Rödl, Andrea Sellner, Astrid Sonnleitner, Matthias Sperl, Wolfgang Stelzl, Holger Till, Andreas Trobisch, Anne Vierzig, Ulrich Vogel, Christina Weingarten, Stefanie Welke, Andreas Wimmer, Uwe Wintergerst, Daniel Wüller, Andrew Zaunschirm, Ieva Ziuraite, Veslava Žukovskaja, Pediatrics, Immunology, Hematology, Public Health, European Commission, Kindergeneeskunde, and RS: GROW - R4 - Reproductive and Perinatal Medicine
Subjects: medicine.medical_specialty, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Observational Study, medicine.disease_cause, Sepsis, sepsis, Internal medicine, medicine, Disintegrin, A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 protein, Prospective cohort study, Metalloproteinase, Thrombospondin, biology, business.industry, RC86-88.9, Neisseria meningitidis, biomarkers, Medical emergencies. Critical care. Intensive care. First aid, General Medicine, medicine.disease, mortality, bacterial infections, inflammation, Cohort, biology.protein, Etiology, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, business
Abstract: Supplemental Digital Content is available in the text., IMPORTANCE: A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 is hypothesized to play a role in the pathogenesis of invasive infection, but studies in sepsis are lacking. OBJECTIVES: To study A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 protein level in pediatric sepsis and to study the association with outcome. DESIGN: Data from two prospective cohort studies. SETTING AND PARTICIPANTS: Cohort 1 is from a single-center study involving children admitted to PICU with meningococcal sepsis (samples obtained at three time points). Cohort 2 includes patients from a multicenter study involving children admitted to the hospital with invasive bacterial infections of differing etiologies (samples obtained within 48 hr after hospital admission). MAIN OUTCOMES AND MEASURES: Primary outcome measure was mortality. Secondary outcome measures were PICU-free days at day 28 and hospital length of stay. RESULTS: In cohort 1 (n = 59), nonsurvivors more frequently had A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels above the detection limit than survivors at admission to PICU (8/11 [73%] and 6/23 [26%], respectively; p = 0.02) and at t = 24 hours (2/3 [67%] and 3/37 [8%], respectively; p = 0.04). In cohort 2 (n = 240), A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels in patients within 48 hours after hospital admission were more frequently above the detection limit than in healthy controls (110/240 [46%] and 14/64 [22%], respectively; p = 0.001). Nonsurvivors more often had detectable A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels than survivors (16/21 [76%] and 94/219 [43%], respectively; p = 0.003), which was mostly attributable to patients with Neisseria meningitidis. CONCLUSIONS AND RELEVANCE: In children with bacterial infection, detection of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 within 48 hours after hospital admission is associated with death, particularly in meningococcal sepsis. Future studies should confirm the prognostic value of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 and should study pathophysiologic mechanisms.
Published: 2021

44. Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Author: Proietti, M., Vitolo, M., Harrison, S. L., Lane, D. A., Fauchier, L., Marin, F., Nabauer, M., Potpara, T. S., Dan, G. -A., Boriani, G., Lip, G. Y. H., Boriani (Chair), G., Tavazzi, L., Maggioni, A. P., Potpara, T., Kalarus, Z., Ferrari, R., Shantsila, A., Goda, A., Mairesse, G., Shalganov, T., Antoniades, L., Taborsky, M., Riahi, S., Muda, P., Garcia Bolao, I., Piot, O., Etsadashvili, K., Simantirakis, E. N., Haim, M., Azhari, A., Najafian, J., Santini, M., Mirrakhimov, E., Kulzida, K., Erglis, A., Poposka, L., Burg, M. R., Crijns, H., Erkuner, O., Atar, D., Lenarczyk, R., Martins Oliveira, M., Shah, D., Serdechnaya, E., Diker, E., Lane, D., Zera, E., Ekmekciu, U., Paparisto, V., Tase, M., Gjergo, H., Dragoti, J., Ciutea, M., Ahadi, N., el Husseini, Z., Raepers, M., Leroy, J., Haushan, P., Jourdan, A., Lepiece, C., Desteghe, L., Vijgen, J., Koopman, P., Van Genechten, G., Heidbuchel, H., Boussy, T., De Coninck, M., Van Eeckhoutte, H., Bouckaert, N., Friart, A., Boreux, J., Arend, C., Evrard, P., Stefan, L., Hoffer, E., Herzet, J., Massoz, M., Celentano, C., Sprynger, M., Pierard, L., Melon, P., Van Hauwaert, B., Kuppens, C., Faes, D., Van Lier, D., Van Dorpe, A., Gerardy, A., Deceuninck, O., Xhaet, O., Dormal, F., Ballant, E., Blommaert, D., Yakova, D., Hristov, M., Yncheva, T., Stancheva, N., Tisheva, S., Tokmakova, M., Nikolov, F., Gencheva, D., Kunev, B., Stoyanov, M., Marchov, D., Gelev, V., Traykov, V., Kisheva, A., Tsvyatkov, H., Shtereva, R., Bakalska-Georgieva, S., Slavcheva, S., Yotov, Y., Kubickova, M., Marni Joensen, A., Gammelmark, A., Hvilsted Rasmussen, L., Dinesen, P., Krogh Veno, S., Sorensen, B., Korsgaard, A., Andersen, K., Fragtrup Hellum, C., Svenningsen, A., Nyvad, O., Wiggers, P., May, O., Aarup, A., Graversen, B., Jensen, L., Andersen, M., Svejgaard, M., Vester, S., Hansen, S., Lynggaard, V., Ciudad, M., Vettus, R., Maestre, A., Castano, S., Cheggour, S., Poulard, J., Mouquet, V., Leparree, S., Bouet, J., Taieb, J., Doucy, A., Duquenne, H., Furber, A., Dupuis, J., Rautureau, J., Font, M., Damiano, P., Lacrimini, M., Abalea, J., Boismal, S., Menez, T., Mansourati, J., Range, G., Gorka, H., Laure, C., Vassaliere, C., Elbaz, N., Lellouche, N., Djouadi, K., Roubille, F., Dietz, D., Davy, J., Granier, M., Winum, P., Leperchois-Jacquey, C., Kassim, H., Marijon, E., Le Heuzey, J., Fedida, J., Maupain, C., Himbert, C., Gandjbakhch, E., Hidden-Lucet, F., Duthoit, G., Badenco, N., Chastre, T., Waintraub, X., Oudihat, M., Lacoste, J., Stephan, C., Bader, H., Delarche, N., Giry, L., Arnaud, D., Lopez, C., Boury, F., Brunello, I., Lefevre, M., Mingam, R., Haissaguerre, M., Le Bidan, M., Pavin, D., Le Moal, V., Leclercq, C., Beitar, T., Martel, I., Schmid, A., Sadki, N., Romeyer-Bouchard, C., Da Costa, A., Arnault, I., Boyer, M., Piat, C., Lozance, N., Nastevska, S., Doneva, A., Fortomaroska Milevska, B., Sheshoski, B., Petroska, K., Taneska, N., Bakrecheski, N., Lazarovska, K., Jovevska, S., Ristovski, V., Antovski, A., Lazarova, E., Kotlar, I., Taleski, J., Kedev, S., Zlatanovik, N., Jordanova, S., Bajraktarova Proseva, T., Doncovska, S., Maisuradze, D., Esakia, A., Sagirashvili, E., Lartsuliani, K., Natelashvili, N., Gumberidze, N., Gvenetadze, R., Gotonelia, N., Kuridze, N., Papiashvili, G., Menabde, I., Gloggler, S., Napp, A., Lebherz, C., Romero, H., Schmitz, K., Berger, M., Zink, M., Koster, S., Sachse, J., Vonderhagen, E., Soiron, G., Mischke, K., Reith, R., Schneider, M., Rieker, W., Boscher, D., Taschareck, A., Beer, A., Oster, D., Ritter, O., Adamczewski, J., Walter, S., Frommhold, A., Luckner, E., Richter, J., Schellner, M., Landgraf, S., Bartholome, S., Naumann, R., Schoeler, J., Westermeier, D., William, F., Wilhelm, K., Maerkl, M., Oekinghaus, R., Denart, M., Kriete, M., Tebbe, U., Scheibner, T., Gruber, M., Gerlach, A., Beckendorf, C., Anneken, L., Arnold, M., Lengerer, S., Bal, Z., Uecker, C., Fortsch, H., Fechner, S., Mages, V., Martens, E., Methe, H., Schmidt, T., Schaeffer, B., Hoffmann, B., Moser, J., Heitmann, K., Willems, S., Klaus, C., Lange, I., Durak, M., Esen, E., Mibach, F., Mibach, H., Utech, A., Gabelmann, M., Stumm, R., Landle, V., Gartner, C., Goerg, C., Kaul, N., Messer, S., Burkhardt, D., Sander, C., Orthen, R., Kaes, S., Baumer, A., Dodos, F., Barth, A., Schaeffer, G., Gaertner, J., Winkler, J., Fahrig, A., Aring, J., Wenzel, I., Steiner, S., Kliesch, A., Kratz, E., Winter, K., Schneider, P., Haag, A., Mutscher, I., Bosch, R., Taggeselle, J., Meixner, S., Schnabel, A., Shamalla, A., Hotz, H., Korinth, A., Rheinert, C., Mehltretter, G., Schon, B., Schon, N., Starflinger, A., Englmann, E., Baytok, G., Laschinger, T., Ritscher, G., Gerth, A., Dechering, D., Eckardt, L., Kuhlmann, M., Proskynitopoulos, N., Brunn, J., Foth, K., Axthelm, C., Hohensee, H., Eberhard, K., Turbanisch, S., Hassler, N., Koestler, A., Stenzel, G., Kschiwan, D., Schwefer, M., Neiner, S., Hettwer, S., Haeussler-Schuchardt, M., Degenhardt, R., Sennhenn, S., Brendel, M., Stoehr, A., Widjaja, W., Loehndorf, S., Logemann, A., Hoskamp, J., Grundt, J., Block, M., Ulrych, R., Reithmeier, A., Panagopoulos, V., Martignani, C., Bernucci, D., Fantecchi, E., Diemberger, I., Ziacchi, M., Biffi, M., Cimaglia, P., Frisoni, J., Giannini, I., Boni, S., Fumagalli, S., Pupo, S., Di Chiara, A., Mirone, P., Pesce, F., Zoccali, C., Malavasi, V. L., Mussagaliyeva, A., Ahyt, B., Salihova, Z., Koshum-Bayeva, K., Kerimkulova, A., Bairamukova, A., Lurina, B., Zuzans, R., Jegere, S., Mintale, I., Kupics, K., Jubele, K., Kalejs, O., Vanhear, K., Burg, M., Cachia, M., Abela, E., Warwicker, S., Tabone, T., Xuereb, R., Asanovic, D., Drakalovic, D., Vukmirovic, M., Pavlovic, N., Music, L., Bulatovic, N., Boskovic, A., Uiterwaal, H., Bijsterveld, N., De Groot, J., Neefs, J., van den Berg, N., Piersma, F., Wilde, A., Hagens, V., Van Es, J., Van Opstal, J., Van Rennes, B., Verheij, H., Breukers, W., Tjeerdsma, G., Nijmeijer, R., Wegink, D., Binnema, R., Said, S., Philippens, S., van Doorn, W., Szili-Torok, T., Bhagwandien, R., Janse, P., Muskens, A., van Eck, M., Gevers, R., van der Ven, N., Duygun, A., Rahel, B., Meeder, J., Vold, A., Holst Hansen, C., Engset, I., Dyduch-Fejklowicz, B., Koba, E., Cichocka, M., Sokal, A., Kubicius, A., Pruchniewicz, E., Kowalik-Sztylc, A., Czapla, W., Mroz, I., Kozlowski, M., Pawlowski, T., Tendera, M., Winiarska-Filipek, A., Fidyk, A., Slowikowski, A., Haberka, M., Lachor-Broda, M., Biedron, M., Gasior, Z., Kolodziej, M., Janion, M., Gorczyca-Michta, I., Wozakowska-Kaplon, B., Stasiak, M., Jakubowski, P., Ciurus, T., Drozdz, J., Simiera, M., Zajac, P., Wcislo, T., Zycinski, P., Kasprzak, J., Olejnik, A., Harc-Dyl, E., Miarka, J., Pasieka, M., Zieminska-Luc, M., Bujak, W., Sliwinski, A., Grech, A., Morka, J., Petrykowska, K., Prasal, M., Hordynski, G., Feusette, P., Lipski, P., Wester, A., Streb, W., Romanek, J., Wozniak, P., Chlebus, M., Szafarz, P., Stanik, W., Zakrzewski, M., Kazmierczak, J., Przybylska, A., Skorek, E., Blaszczyk, H., Stepien, M., Szabowski, S., Krysiak, W., Szymanska, M., Karasinski, J., Blicharz, J., Skura, M., Halas, K., Michalczyk, L., Orski, Z., Krzyzanowski, K., Skrobowski, A., Zielinski, L., Tomaszewska-Kiecana, M., Dluzniewski, M., Kiliszek, M., Peller, M., Budnik, M., Balsam, P., Opolski, G., Tyminska, A., Ozieranski, K., Wancerz, A., Borowiec, A., Majos, E., Dabrowski, R., Szwed, H., Musialik-Lydka, A., Leopold-Jadczyk, A., Jedrzejczyk-Patej, E., Koziel, M., Mazurek, M., Krzemien-Wolska, K., Starosta, P., Nowalany-Kozielska, E., Orzechowska, A., Szpot, M., Staszel, M., Almeida, S., Pereira, H., Brandao Alves, L., Miranda, R., Ribeiro, L., Costa, F., Morgado, F., Carmo, P., Galvao Santos, P., Bernardo, R., Adragao, P., Ferreira da Silva, G., Peres, M., Alves, M., Leal, M., Cordeiro, A., Magalhaes, P., Fontes, P., Leao, S., Delgado, A., Costa, A., Marmelo, B., Rodrigues, B., Moreira, D., Santos, J., Santos, L., Terchet, A., Darabantiu, D., Mercea, S., Turcin Halka, V., Pop Moldovan, A., Gabor, A., Doka, B., Catanescu, G., Rus, H., Oboroceanu, L., Bobescu, E., Popescu, R., Dan, A., Buzea, A., Daha, I., Dan, G., Neuhoff, I., Baluta, M., Ploesteanu, R., Dumitrache, N., Vintila, M., Daraban, A., Japie, C., Badila, E., Tewelde, H., Hostiuc, M., Frunza, S., Tintea, E., Bartos, D., Ciobanu, A., Popescu, I., Toma, N., Gherghinescu, C., Cretu, D., Patrascu, N., Stoicescu, C., Udroiu, C., Bicescu, G., Vintila, V., Vinereanu, D., Cinteza, M., Rimbas, R., Grecu, M., Cozma, A., Boros, F., Ille, M., Tica, O., Tor, R., Corina, A., Jeewooth, A., Maria, B., Georgiana, C., Natalia, C., Alin, D., Dinu-Andrei, D., Livia, M., Daniela, R., Larisa, R., Umaar, S., Tamara, T., Loachim Popescu, M., Nistor, D., Sus, I., Coborosanu, O., Alina-Ramona, N., Dan, R., Petrescu, L., Ionescu, G., Vacarescu, C., Goanta, E., Mangea, M., Ionac, A., Mornos, C., Cozma, D., Pescariu, S., Solodovnicova, E., Soldatova, I., Shutova, J., Tjuleneva, L., Zubova, T., Uskov, V., Obukhov, D., Rusanova, G., Isakova, N., Odinsova, S., Arhipova, T., Kazakevich, E., Zavyalova, O., Novikova, T., Riabaia, I., Zhigalov, S., Drozdova, E., Luchkina, I., Monogarova, Y., Hegya, D., Rodionova, L., Nevzorova, V., Lusanova, O., Arandjelovic, A., Toncev, D., Milanov, M., Sekularac, N., Zdravkovic, M., Hinic, S., Dimkovic, S., Acimovic, T., Saric, J., Polovina, M., Vujisic-Tesic, B., Nedeljkovic, M., Zlatar, M., Asanin, M., Vasic, V., Popovic, Z., Djikic, D., Sipic, M., Peric, V., Dejanovic, B., Milosevic, N., Stevanovic, A., Andric, A., Pencic, B., Pavlovic-Kleut, M., Celic, V., Pavlovic, M., Petrovic, M., Vuleta, M., Petrovic, N., Simovic, S., Savovic, Z., Milanov, S., Davidovic, G., Iric-Cupic, V., Simonovic, D., Stojanovic, M., Stojanovic, S., Mitic, V., Ilic, V., Petrovic, D., Deljanin Ilic, M., Ilic, S., Stoickov, V., Markovic, S., Kovacevic, S., Garcia Fernandez, A., Perez Cabeza, A., Anguita, M., Tercedor Sanchez, L., Mau, E., Loayssa, J., Ayarra, M., Carpintero, M., Roldan Rabadan, I., Gil Ortega, M., Tello Montoliu, A., Orenes Pinero, E., Manzano Fernandez, S., Romero Aniorte, A., Veliz Martinez, A., Quintana Giner, M., Ballesteros, G., Palacio, M., Alcalde, O., Garcia-Bolao, I., Bertomeu Gonzalez, V., Otero-Ravina, F., Garcia Seara, J., Gonzalez Juanatey, J., Dayal, N., Maziarski, P., Gentil-Baron, P., Koc, M., Onrat, E., Dural, I. E., Yilmaz, K., Ozin, B., Tan Kurklu, S., Atmaca, Y., Canpolat, U., Tokgozoglu, L., Dolu, A. K., Demirtas, B., Sahin, D., Ozcan Celebi, O., Gagirci, G., Turk, U. O., Ari, H., Polat, N., Toprak, N., Sucu, M., Akin Serdar, O., Taha Alper, A., Kepez, A., Yuksel, Y., Uzunselvi, A., Yuksel, S., Sahin, M., Kayapinar, O., Ozcan, T., Kaya, H., Yilmaz, M. B., Kutlu, M., Demir, M., Gibbs, C., Kaminskiene, S., Bryce, M., Skinner, A., Belcher, G., Hunt, J., Stancombe, L., Holbrook, B., Peters, C., Tettersell, S., Senoo, K., Russell, K., Domingos, P., Hussain, S., Partridge, J., Haynes, R., Bahadur, S., Brown, R., Mcmahon, S., Lip, G., Mcdonald, J., Balachandran, K., Singh, R., Garg, S., Desai, H., Davies, K., Goddard, W., Galasko, G., Rahman, I., Chua, Y., Payne, O., Preston, S., Brennan, O., Pedley, L., Whiteside, C., Dickinson, C., Brown, J., Jones, K., Benham, L., Brady, R., Buchanan, L., Ashton, A., Crowther, H., Fairlamb, H., Thornthwaite, S., Relph, C., Mcskeane, A., Poultney, U., Kelsall, N., Rice, P., Wilson, T., Wrigley, M., Kaba, R., Patel, T., Young, E., Law, J., Runnett, C., Thomas, H., Mckie, H., Fuller, J., Pick, S., Sharp, A., Hunt, A., Thorpe, K., Hardman, C., Cusack, E., Adams, L., Hough, M., Keenan, S., Bowring, A., Watts, J., Zaman, J., Goffin, K., Nutt, H., Beerachee, Y., Featherstone, J., Mills, C., Pearson, J., Stephenson, L., Grant, S., Wilson, A., Hawksworth, C., Alam, I., Robinson, M., Ryan, S., Egdell, R., Gibson, E., Holland, M., Leonard, D., Mishra, B., Ahmad, S., Randall, H., Hill, J., Reid, L., George, M., Mckinley, S., Brockway, L., Milligan, W., Sobolewska, J., Muir, J., Tuckis, L., Winstanley, L., Jacob, P., Kaye, S., Morby, L., Jan, A., Sewell, T., Boos, C., Wadams, B., Cope, C., Jefferey, P., Andrews, N., Getty, A., Suttling, A., Turner, C., Hudson, K., Austin, R., Howe, S., Iqbal, R., Gandhi, N., Brophy, K., Mirza, P., Willard, E., Collins, S., Ndlovu, N., Subkovas, E., Karthikeyan, V., Waggett, L., Wood, A., Bolger, A., Stockport, J., Evans, L., Harman, E., Starling, J., Williams, L., Saul, V., Sinha, M., Bell, L., Tudgay, S., Kemp, S., Frost, L., Ingram, T., Loughlin, A., Adams, C., Adams, M., Hurford, F., Owen, C., Miller, C., Donaldson, D., Tivenan, H., Button, H., Nasser, A., Jhagra, O., Stidolph, B., Brown, C., Livingstone, C., Duffy, M., Madgwick, P., Roberts, P., Greenwood, E., Fletcher, L., Beveridge, M., Earles, S., Mckenzie, D., Beacock, D., Dayer, M., Seddon, M., Greenwell, D., Luxton, F., Venn, F., Mills, H., Rewbury, J., James, K., Roberts, K., Tonks, L., Felmeden, D., Taggu, W., Summerhayes, A., Hughes, D., Sutton, J., Felmeden, L., Khan, M., Walker, E., Norris, L., O'Donohoe, L., Mozid, A., Dymond, H., Lloyd-Jones, H., Saunders, G., Simmons, D., Coles, D., Cotterill, D., Beech, S., Kidd, S., Wrigley, B., Petkar, S., Smallwood, A., Jones, R., Radford, E., Milgate, S., Metherell, S., Cottam, V., Buckley, C., Broadley, A., Wood, D., Allison, J., Rennie, K., Balian, L., Howard, L., Pippard, L., Board, S., Pitt-Kerby, T., Proietti M, Vitolo M, Harrison SL, Lane DA, Fauchier L, Marin F, Nabauer M, Potpara TS, Dan GA, Boriani G, Lip GYH, ESC-EHRA EORP-AF Long-Term General Registry Investigators, Diemberger I, Ziacchi M, Frisoni J, Cardiology, ACS - Heart failure & arrhythmias, Graduate School, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service de cardiologie
Subjects: Registrie, Research Report, medicine.medical_specialty, Major adverse outcome, Cardiovascular risk factors, Cluster analysis, Risk Factors, Internal medicine, Clinical phenotype, Atrial Fibrillation, Epidemiology, Humans, Medicine, Registries, Cluster analysi, Atrial fibrillation, Clinical management, Clinical phenotypes, Major adverse outcomes, Phenotype, business.industry, Proportional hazards model, Risk Factor, Hazard ratio, General Medicine, medicine.disease, Confidence interval, Cohort, Observational study, business, Research Article, Human
Abstract: Background Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients’ clinical phenotypes and analyse the differential clinical course. Methods We performed a hierarchical cluster analysis based on Ward’s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients’ prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P < .001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27–3.62; HR 3.42, 95%CI 2.72–4.31; HR 2.79, 95%CI 2.32–3.35), and Cluster 1 (HR 1.88, 95%CI 1.48–2.38; HR 2.50, 95%CI 1.98–3.15; HR 2.09, 95%CI 1.74–2.51) reported a higher risk for the three outcomes respectively. Conclusions In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes.
Published: 2021
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45. Critical care admission following elective surgery was not associated with survival benefit

Author: Kahan, Brennan C., Desponia, Koulenti, Kostoula, Arvaniti, Vanessa, Beavis, Douglas, Campbell, Matthew, Chan, Rui, Moreno, Pearse, Rupert M., Scott, Beattie, Pierre-Alain, Clavien, Nicolas, Demartines, Lee, A Fleisher, Mike, Grocott, James, Haddow, Andreas, Hoeft, Peter, Holt, Naomi, Pritchard, Andrew, Rhodes, Duminda, Wijeysundera, Matt, Wilson, Tahania, Ahmed, Kirsty, Everingham, Russell, Hewson, Marta, Januszewska, Rupert, M Pearse, Mandeep-Kaur, Phull, Richard, Halliwell, Mark, Shulman, Paul, Myles, Werner, Schmid, Michael, Hiesmayr, Patrick, Wouters, Stefan de Hert, Suzana, Lobo, Xiangming, Fang, Lars, Rasmussen, Emmanuel, Futier, Matthieu, Biais, Aurélien, Venara, Karem, Slim, Michael, Sander, Despoina, Koulenti, Mathew, Chan, Atul, Kulkarni, Susilo, Chandra, Aida, Tantri, Emad, Geddoa, Muntadhar, Abbas, Giorgio Della Rocca, Datin, Sivasakthi, Marzida, Mansor, Pastor, Luna, Arthur, Bouwman, Wolfgang, Buhre, Tim, Short, Tunde, Osinaike, Ricardo, Matos, Ioana, Grigoras, Mikhail, Kirov, Denis, Protsenko, Bruce, Biccard, Cesar, Aldecoa, Michelle, Chew, Christoph, Hofer, Martin, Hubner, James, Ditai, Tamas, Szakmany, Lee, Fleisher, Marissa, Ferguson, Michael, Macmahon, Ritchie, Cherian, Helen, Currow, Kathirgamanathan, Kanathiban, David, Gillespie, Edward, Pathmanathan, Katherine, Phillips, Jenifer, Reynolds, Joanne, Rowley, Jeanene, Douglas, Ross, Kerridge, Sameer, Garg, Michael, Bennett, Megha, Jain, David, Alcock, Nico, Terblanche, Rochelle, Cotter, Kate, Leslie, Marcelle, Stewart, Nicolette, Zingerle, Antony, Clyde, Oliver, Hambidge, Adam, Rehak, Sharon, Cotterell, Wilson Binh Quan Huynh, Timothy, Mcculloch, Erez, Ben-Menachem, Thomas, Egan, Jennifer, Cope, Paul, Fellinger, Simone, Haselberger, Caroline, Holaubek, Paul, Lichtenegger, Florian, Scherz, Franz, Hoffer, Veronika, Cakova, Andreas, Eichwalder, Norbert, Fischbach, Reinhold, Klug, Elisabeth, Schneider, Martin, Vesely, Reinhart, Wickenhauser, Karl Gernot Grubmueller, Marion, Leitgeb, Friedrich, Lang, Nancy, Toro, Marlene, Bauer, Friedrich, Laengle, Thomas, Mayrhofer, Christian, Buerkle, Karin, Forstner, Reinhard, Germann, Harald, Rinoesl, Elke, Schindler, Ernst, Trampitsch, Gerhard, Fritsch, Christian, Szabo, Jawad, Bidgoli, Hans, Verdoodt, Patrice, Forget, David, Kahn, Fernande, Lois, Mona, Momeni, Caroline, Prégardien, Audrey, Pospiech, Arnaud, Steyaert, Laurent, Veevaete, Dirk De Kegel, Karen De Jongh, Luc, Foubert, Carine, Smitz, Marcel, Vercauteren, Jan, Poelaert, Veerle Van Mossevelde, Jacques, Abeloos, Stefaan, Bouchez, Marc, Coppens, Luc De Baerdemaeker, Isabel, Deblaere, Ann De Bruyne, Stefan De Hert, Kristine, Fonck, Bjorn, Heyse, Tom, Jacobs, Koen, Lapage, Anneliese, Moerman, Martine, Neckebroek, Aliaksandra, Parashchanka, Nathalie, Roels, Nancy Van Den Eynde, Michael, Vandenheuvel, Jurgen Van Limmen, Ann, Vanluchene, Caroline, Vanpeteghem, Piet, Wyffels, Christel, Huygens, Punitha, Vandenbempt, Marc Van de Velde, Dimitri, Dylst, Bruno, Janssen, Evelien, Schreurs, Fábia Berganton Aleixo, Keulle, Candido, Hugo Dias Batista, Mario, Guimarães, Jaqueline, Guizeline, João, Hoffmann, Suzana, M Lobo, Francisco Ricardo Lobo, Vinícius, Nascimento, Katia, Nishiyama, Lucas, Pazetto, Daniela, Souza, Rodrigo Souza Rodrigues, Ana Maria Vilela Dos Santos, Jaquelline, Jardim, Joao, Silva, Paulo do Nascimento Junior, Thalissa Hermínia Baio, Gabriel Isaac Pereira de Castro, Henri Roger Watanabe Oliveira, Cristina Prata Amendola, Gutemberg, Cardoso, Daniela, Ortega, Ana Flavia Brotto, Mirella Cristine De Oliveira, Álvaro, Réa-Neto, Fernando, Dias, Pedro, Azambuja, Marcos Freitas Knibel, Antonio, Martins, William, Almeida, Calim Neder Neto, Maria Angela Tardelli, Eliana, Caser, Marcio, Machado, Crisitiano, Aguzzoli, Sérgio, Baldisserotto, Fernanda Beck Tabajara, Fernanda, Bettega, La Hore Correa Rodrigues Júnior, Julia de Gasperi, Lais, Faina, Marcos Farias Nolasco, Bruna Ferreira da Costa Fischer, Mariana Fosch de Campos Ferreira, Cristina, Hartmann, 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Woon, Yuan Liang, Abd Hadi, Husni Zaeem, Ahmad Azam, Ummi Azmira, Alias, Abdul Hafiz, Kesut, Saiful Aizar, Lee, Jun May, Ooi, Dar Vin, Sulaiman, Hetty Ayuni, Tengku Lih, Tengku Alini, Veerakumaran, Jeyaganesh, Rojas, Eder, Resendiz, Gerardo Esteban Alvarez, Zapata, Darcy Danitza Mari, Aguilar López, Julio Cesar Jesú, Flores, Armando Adolfo Alvarez, Amador, Juan Carlosc Bravo, Avila, Erendira Jocelin Dominguez, Aquino, Laura Patricia González, Rodriguez, Ricardo Lopez, Landa, Mariana Torre, Urias, Emma, Hollmann, Marku, Hulst, Abraham, Kirzner, Osne, Preckel, Benedikt, Koopman-van Gemert, Ankie, Buise, Marc, Tolenaar, Noortje, Weber, Eric, de Fretes, Jennifer, Houweling, Peter, Ormskerk, Patricia, Van Bommel, Jasper, Lance, Marcu, Smit-Fun, Valerie, van Zundert, Tom, Baas, Peter, de Boer, Hans Donald, Sprakel, Joost, Elferink-Vonk, Renske, Noordzij, Peter, van Zeggeren, Laura, Brand, Bastiaan, spanjersberg, Rob, ten Bokkel-Andela, Janneke, Numan, Janneke, van Klei, Wilton, van Zaane, 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Tsiligiannis, Sophia, Peat, William, Stephenson, Lorraine, Bradburn, Mike, Pick, Sara, Cunha, Pedro, Olagbaiye, Olufemi, Tayeh, Salim, Abernethy, Caroline, Balasubramaniam, Madhu, Bennett, Rachael, Bolton, David, Martinson, Victoria, Naylor, Charde, Bell, Stephanie, Heather, Blaylock, Kushakovsky, Vlad, Alcock, Liam, Alexander, Hazel, Anderson, Colette, Baker, Paul, Brookes, Morag, Cawthorn, Louise, Cirstea, Emanuel, Colling, Kerry, Coulter, Ian, Das, Suparna, Haigh, Kathryn, Hamdan, Alhafidz, Hugill, Keith, Kottam, Lucksy, Lisseter, Emily, Mawdsley, Matthew, McGivern, Julie, Padala, Krishnaveni, Phelps, Victoria, kumar, Vineshykaa Ramesh, Stewart, Kirsten, Towse, Kayley, Tregonning, Julie, Vahedi, Ali, Walker, Alycon, Baines, Duncan, Bilolikar, Anjali, Chande, Shiv, Copley, Edward, Dunk, Nigel, Kulkarni, Raghavendra, Kumar, Pawan, Metodiev, Yavor, Ncomanzi, Dumisani, Raithatha, Bhavesh, Raymode, Parizade, Szafranski, Jan, Twohey, Linda, Watt, Philip, Weatherall, Lucie, Weatherill, J., Whitman, Zoe, Wighton, Elinor, Abayasinghe, Chamika, Chan, Alexander, Darwish, Sharif, Gill, Jame, Glasgow, Emma, Hadfield, Daniel, Harris, Clair, Kochhar, Arun, Mellis, Clare, Pool, Andrew, Riozzi, Paul, Selman, Andrew, Smith, Emma-Jane, Vele, Liana, Gercek, Yuksel, Guy, Kramer, Holden, Dougla, Watson, Nichola, Whysall, Karen, Andreou, Prematie, Hales, Dawn, Thompson, Jonathan, Bowrey, Sarah, McDonald, Shara, Gilmore, Jemma, Hills, Vicky, Kelly, Chan, Kelly, Sinead, Lloyd, Geraint, Abbott, Tom, Gall, Lewi, Torrance, Hew, Vivian, Mark, Berntsen, Emer, Nolan, Tracey, Turner, Angu, Vohra, Akbar, Brown, Andrew, Clark, Richard, Coughlan, Elaine, Daniel, Conway, Patvardhan, Chinmay, Pearson, Rachel, Predeep, Sheba, Saad, Hesham, Shanmugam, Mohanakrishnan, Varley, Simon, Wylie, Katharine, Cooper, Lucy, Makowski, Arystarch, Misztal, Beata, Moldovan, Eliza, Pegg, Claire, Donovan, Andrew, Foot, Jayne, Large, Simon, Claxton, Andrew, Netke, Bhagyashree, Armstrong, Richard, Calderwood, Claire, Kwok, Andy, Mohr, Otto, Oyeniyi, Peter, Patnaik, Lisa, Post, Benjamin, Ali, Sarah, Arshad, Homa, Baker, Gerard, Brenner, Laura, Brincat, Maximilian, Brunswicker, Annemarie, Cox, Hannah, Cozar, Octavian Ionut, Durst, Alexander, Fengas, Lior, Flatt, Jim, Glister, Georgina, Narwani, Vishal, Photi, Evangelo, Rankin, Adeline, Rosbergen, Melissa, Tan, Mark, Beaton, Ceri, Horn, Rachel, Hunt, Jane, Rousseau, Guy, Stancombe, Lucia, Absar, Mohammed, Allsop, Joanne, Drinkwater, Zoe, Hodgkiss, Tracey, Smith, Kirsty, Brown, Jamie, Alexander-Sefre, Farhad, Campey, Lorraine, Dudgeon, Lucy, Hall, Kathryn, Hitchcock, Rachael, James, Lynne, Smith, Kate, Winstone, Ulrika, Ahmad, Norfaizan, Bauchmuller, Kri, Harrison, Jonathan, Jeffery, Holly, Miller, Duncan, Pinder, Angela, Pothuneedi, Sailaja, Rosser, Jonathan, Sanghera, Sumayer, Swift, Diane, Walker, Rachel, Bester, Delia, Cavanagh, Sarah, Cripps, Heather, Daniel, Harvey, Lynch, Julie, Paton, Alison, Pyke, Shirley, Scholefield, John, Whitworth, Helen, Bottrill, Fiona, Ramalingam, Ganesh, Webb, Stephen, Akerman, Nik, Antill, Philip, Bourner, Lynsey, Buckley, Sarah, Castle, Gail, Charles, Rob, Eggleston, Christopher, Foster, Rebecca, Gill, Satwant, Lindley, Kate, Lklouk, Mohamed, Lowery, Tracey, Martin, Oliver, Milne, David, O’Connor, Patrick, Ratcliffe, Andrew, Rose, Alastair, Smith, Annie, Varma, Sandeep, Ward, Jackie, Barcraft-Barnes, Helena, Camsooksai, Julie, Colvin, Carolyn, Reschreiter, Henrik, Tbaily, Lee, Venner, Nicola, Hamilton, Caroline, Kelly, Lewi, Toth-Tarsoly, Piroska, Dodsworth, Kerry, Foord, Denise, Gordon, Paul, Hawes, Elizabeth, Lamb, Nikki, Mouland, Johanna, Nightingale, Jeremy, Rose, Steve, Schrieber, Joe, Al ‘Amri, Khalid, Aladin, Hafiz, Arshad, Mohammed Asif, Barraclough, Jame, Bentley, Conor, Bergin, Colin, Carrera, Ronald, Clarkson, Aisling, Collins, Michelle, Cooper, Lauren, Denham, Samuel, Griffiths, Ewen, Ip, Peter, Jeyanthan, Somasundaram, Joory, Kavita, Kaur, Satwant, Marriott, Paul, Mitchell, Natalie, Nagaiah, Sukumar, Nilsson, Annette, Parekh, Nilesh, Pope, Martin, Seager, Joseph, Serag, Hosam, Tameem, Alifia, Thomas, Anna, Thunder, Joanne, Torrance, Andrew, Vohra, Ravinder, whitehouse, Arlo, Wong, Tony, Blunt, Mark, Wong, Kate, Giles, Julian, Reed, Isabelle, Weller, Debbie, Bell, Gillian, Birch, Julie, Damant, Rose, Maiden, Jane, Mewies, Clare, Prince, Claire, Radford, Jane, Balain, Birender, Banerjee, Robin, Barnett, Andrew, Burston, Ben, Davies, Kirsty, Edwards, Jayne, Evans, Chri, Ford, David, Gallacher, Pete, Hill, Simon, Jaffray, David, Karlakki, Sudheer, Kelly, Cormac, Kennedy, Julia, Kiely, Nigel, Lewthwaite, Simon, Marquis, Chri, Ockendon, Matthew, Phillips, Stephen, Pickard, Simon, Richardson, Jame, Roach, Richard, Smith, Tony, Spencer-Jones, Richard, Steele, Niall, Steen, Julie, Van Liefland, Marck, White, Steve, Faulds, Matthew, Harris, Meredyth, Kelly, Carrie, Nicol, Scott, Pearson, Sally Anne, Chukkambotla, Srikanth, Andrew, Alyson, Attrill, Elizabeth, Campbell, Graham, Datson, Amanda, Fouracres, Anna, Graterol, Juan, Graves, Lynne, Hong, Bosun, Ishimaru, Alexander, Karthikeyan, Arvind, King, Helen, Lawson, Tom, Lee, Gregory, Lyons, Saoirse, Macalister Hall, Andrew, Mathoulin, Sophie, Mcintyre, Eilidh, Mclaughlin, Danny, Mulcahy, Kathleen, Ratcliffe, Anna, Robbins, Jame, Sung, Weilin, Tayo, Adeoluwa, Trembath, Lisa, Venugopal, Suneetha, Walker, Robert, Wigmore, Geoffrey, Boereboom, Catherine, Downes, Charlotte, Humphries, Ryan, Melbourne, Susan, Smith, Coral, Tou, Samson, Ullah, Shafa, Batchelor, Nick, Boxall, Leigh, Broomby, Rupert, Deen, Tariq, Hellewell, Alistair, Helliwell, Laurence, Hutchings, Melanie, Hutchins, David, Keenan, Samantha, Mackie, Donna, Donna, Alison, Smith, France, Stone, Lucy, Thorpe, Kevin, Wassall, Richard, Woodgate, Andrew, Baillie, Shelley, Campbell, Tara, James, Sarah, King, Chri, Marques de Araujo, Daniela, Martin, Daniel, Morkane, Clare, Neely, Julia, Rajendram, Rajkumar, Burton, Megan, James, Kathryn, Keevil, Edward, Minik, Orsolya, Morgan, Jenna, Musgrave, Anna, Rajanna, Harish, Roberts, Tracey, Adamson, Michael, Jumbe, Sandra, Kendall, Jennie, Muthuswamy, Mohan Babu, Anderson, Charlotte, Cruikshanks, Andrew, Wrench, Ian, Zeidan, Lisa, Ardern, Diane, Harris, Benjamin, Hellstrom, Johanna, Martin, Jane, Thomas, Richard, Varsani, Nimu, Wrey Brown, Caroline, Docherty, Philip, Gillies, Michael, McGregor, Euan, Usher, Helen, Craig, Jayne, Smith, Andrew, Ahmad, Tahania, Bodger, Phoebe, Creary, Thai, Fowler, Alexander, Hewson, Ru, Ijuo, Eke, Jones, Timothy, Kantsedikas, Ilya, Lahiri, Sumitra, McLean, Aaron Lawson, Niebrzegowska, Edyta, Phull, Mandeep, Wang, Difei, Wickboldt, Nadine, Baldwin, Jacqueline, Doyle, Donna, Mcmullan, Sean, Oladapo, Michelle, Owen, Thoma, Williams, Alexandra, Daniel, Hull, Gregory, Peter, Husain, Tauqeer, Kirk-Bayley, Justin, Mathers, Edward, Montague, Laura, White, Stuart, Avis, Joanne, Cook, Tim, Dali-Kemmery, Lola, Kerslake, Ian, Lambourne, Victoria, Pearson, Annabel, 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Knaggs, Alison, Markar, Sheraz, Perera, Anisha, Scott, Alasdair, Shida, Asako, Sirha, Ravneet, Wright, Sally, Frost, Victoria, Gray, Catherine, MacGregor, Mark, Andrews, Emma, Arrandale, Lindsay, Barrett, Stephen, Cifra, Elna, Cooper, Mariese, Dragnea, Drago, Elna, Cifra, Maclean, Jennifer, Meier, Sonja, Milliken, Donald, Munns, Christopher, Ratanshi, Nadir, Salvana, Abegail, Watson, Anthony, Ali, Hani, Campbell, Gill, Critchley, Rebecca, Hicks, Catherine, Liddle, Alison, Pass, Marc, Ritchie, Charlotte, Thomas, Charlotte, Too, Lingxi, Welsh, Sarah, Gill, Talvinder, Johnson, Joanne, Reed, Joanne, Davis, Edward, Papadopoullos, Sam, Attwood, Clare, Biffen, Andrew, Boulton, Kerenza, Gray, Sophie, Hay, David, Mills, Sarah, Montgomery, Jane, Riddell, Rory, Simpson, Jame, Bhardwaj, Neeraj, Paul, Elaine, Uwubamwen, Nosakhare, Alexander, Maini, Arrich, Jame, Arumugam, Swarna, Blackwood, Dougla, Boggiano, Victoria, Brown, Robyn, Lam Chan, Yik, Chatterjee, Devnandan, Chhabra, Ashok, Christian, Rachel, Costelloe, Hannah, Coxwell Matthewman, Madeline, Dalton, Emma, Darko, Julia, Davari, Maria, Dave, Tejal, Deacon, Matthew, Deepak, Shantal, Edmond, Holly, Ellis, Jessica, El-Sayed, Ahmed, Eneje, Philip, English, Rose, Ewe, Renee, Foers, William, Franklin, John, Gallego, Laura, Garrett, Emily, Goldberg, Olivia, Goss, Harry, Greaves, Rosanna, Harris, Rudy, Hennings, Charle, Jones, Eleanor, Kamali, Nelson, Kokkinos, Naomi, Lewis, Cary, Lignos, Leda, Malgapo, Evaleen Victoria, Malik, Rizwana, Milne, Andrew, Mulligan, John-Patrick, Nicklin, Philippa, Palipane, Natasha, Parsons, Thoma, Piper, Rebecca, Prakash, Rohan, Ramesh, Byron, Rasip, Sarah, Reading, Jacob, Rela, Mariam, Reyes, Anna, Robert, Stephen, Rooms, Martin, Shah, Karishma, Simons, Henry, Solanki, Shalil, Spowart, Emma, Stevens, Amy, Thomas, Christopher, Waggett, Helena, Yassaee, Arrash, Kennedy, Anthony, Scott, Sara, Somanath, Sameer, Berg, Andrew, Hernandez, Miguel, Nanda, Rajesh, Tank, Ghanshyambhai, Wilson, Natalie, 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Kumara, P., Simeson, K., Yarwood, J., Browning, J., Hatton, J., Julian, H., Mitra, A., Newton, M., Pernu, P., Wilson, A., Commey, T., Foot, H., Glover, L., Gupta, A., Lancaster, N., Levin, J., Mackenzie, F., Mestanza, C., Nofal, E., Pout, L., Varden, R., Wild, J., Jones, S., Moreton, S., Pulletz, M., Davies, C., Martin, M., Thomas, S., Burns, K., McArthur, C., Patel, P., Lau, G., Rich, N., Davis, F., Lyons, R., Port, B., Prout, R., Smith, C., Adelaja, Y., Bennett, V., Bidd, H., Dumitrescu, A., Murphy, J.F., Keen, A., Mguni, N., Ong, C., Adams, G., Boshier, P., Brown, R., Butryn, I., Chatterjee, J., Freethy, A., Lockwood, G., Tsakok, M., Tsiligiannis, S., Peat, W., Stephenson, L., Bradburn, M., Pick, S., Cunha, P., Olagbaiye, O., Tayeh, S., Abernethy, C., Balasubramaniam, M., Bennett, R., Bolton, D., Martinson, V., Bell, S., Heather, B., Kushakovsky, V., Alcock, L., Alexander, H., Anderson, C., Baker, P., Brookes, M., Cawthorn, L., Cirstea, E., Colling, K., Coulter, I., Das, S., Haigh, K., Hamdan, A., Hugill, K., Kottam, L., Lisseter, E., Mawdsley, M., McGivern, J., Padala, K., Phelps, V., Kumar, V.R., Stewart, K., Towse, K., Tregonning, J., Vahedi, A., Walker, A., Baines, D., Bilolikar, A., Chande, S., Copley, E., Dunk, N., Kulkarni, R., Kumar, P., Metodiev, Y., Ncomanzi, D., Raithatha, B., Raymode, P., Szafranski, J., Twohey, L., Watt, P., Weatherall, L., Whitman, Z., Wighton, E., Abayasinghe, C., Chan, A., Darwish, S., Gill, J., Glasgow, E., Hadfield, D., Harris, C., Kochhar, A., Mellis, C., Pool, A., Riozzi, P., Selman, A., Smith, E.J., Vele, L., Gercek, Y., Guy, K., Holden, D., Watson, N., Whysall, K., Andreou, P., Hales, D., Thompson, J., Bowrey, S., McDonald, S., Gilmore, J., Hills, V., Kelly, C., Kelly, S., Lloyd, G., Abbott, T., Gall, L., Torrance, H., Vivian, M., Berntsen, E., Nolan, T., Turner, A., Vohra, A., Brown, A., Clark, R., Coughlan, E., Daniel, C., Patvardhan, C., Pearson, R., Predeep, S., Saad, H., Shanmugam, M., Varley, S., Wylie, K., Cooper, L., Makowski, A., Misztal, B., Moldovan, E., Pegg, C., Donovan, A., Foot, J., Large, S., Claxton, A., Netke, B., Armstrong, R., Calderwood, C., Kwok, A., Mohr, O., Oyeniyi, P., Patnaik, L., Post, B., Ali, S., Arshad, H., Baker, G., Brenner, L., Brincat, M., Brunswicker, A., Cox, H., Cozar, O.I., Durst, A., Fengas, L., Flatt, J., Glister, G., Narwani, V., Photi, E., Rankin, A., Rosbergen, M., Beaton, C., Horn, R., Hunt, J., Rousseau, G., Stancombe, L., Absar, M., Allsop, J., Drinkwater, Z., Hodgkiss, T., Smith, K., Alexander-Sefre, F., Campey, L., Dudgeon, L., Hall, K., Hitchcock, R., James, L., Winstone, U., Ahmad, N., Bauchmuller, K., Harrison, J., Jeffery, H., Miller, D., Pinder, A., Pothuneedi, S., Rosser, J., Sanghera, S., Swift, D., Walker, R., Bester, D., Cavanagh, S., Cripps, H., Daniel, H., Lynch, J., Pyke, S., Scholefield, J., Whitworth, H., Bottrill, F., Ramalingam, G., Webb, S., Akerman, N., Antill, P., Bourner, L., Buckley, S., Castle, G., Charles, R., Eggleston, C., Foster, R., Gill, S., Lindley, K., Lklouk, M., Lowery, T., Martin, O., Milne, D., O'Connor, P., Ratcliffe, A., Rose, A., Smith, A., Varma, S., Ward, J., Barcraft-Barnes, H., Camsooksai, J., Colvin, C., Reschreiter, H., Tbaily, L., Venner, N., Hamilton, C., Kelly, L., Toth-Tarsoly, P., Dodsworth, K., Foord, D., Gordon, P., Hawes, E., Lamb, N., Mouland, J., Nightingale, J., Rose, S., Schrieber, J., Al 'Amri, K., Aladin, H., Arshad, M.A., Barraclough, J., Bentley, C., Bergin, C., Carrera, R., Clarkson, A., Collins, M., Denham, S., Griffiths, E., Ip, P., Jeyanthan, S., Joory, K., Kaur, S., Marriott, P., Mitchell, N., Nagaiah, S., Nilsson, A., Parekh, N., Pope, M., Seager, J., Serag, H., Tameem, A., Thomas, A., Thunder, J., Torrance, A., Vohra, R., Whitehouse, A., Wong, T., Blunt, M., Wong, K., Giles, J., Reed, I., Weller, D., Bell, G., Birch, J., Damant, R., Maiden, J., Mewies, C., Prince, C., Radford, J., Balain, B., Banerjee, R., Barnett, A., Burston, B., Edwards, J., Evans, C., Ford, D., Gallacher, P., Hill, S., Jaffray, D., Karlakki, S., Kennedy, J., Kiely, N., Lewthwaite, S., Marquis, C., Ockendon, M., Phillips, S., Pickard, S., Richardson, J., Roach, R., Smith, T., Spencer-Jones, R., Steele, N., Steen, J., Van Liefland, M., White, S., Faulds, M., Harris, M., Nicol, S., Pearson, S.A., Chukkambotla, S., Andrew, A., Attrill, E., Campbell, G., Datson, A., Fouracres, A., Graterol, J., Graves, L., Hong, B., Ishimaru, A., Karthikeyan, A., King, H., Lawson, T., Lee, G., Lyons, S., Macalister Hall, A., Mathoulin, S., Mcintyre, E., Mclaughlin, D., Mulcahy, K., Robbins, J., Sung, W., Tayo, A., Trembath, L., Venugopal, S., Wigmore, G., Boereboom, C., Downes, C., Humphries, R., Melbourne, S., Tou, S., Ullah, S., Batchelor, N., Boxall, L., Broomby, R., Deen, T., Hellewell, A., Helliwell, L., Hutchings, M., Hutchins, D., Keenan, S., Mackie, D., Donna, A., Smith, F., Stone, L., Thorpe, K., Wassall, R., Woodgate, A., Baillie, S., Campbell, T., James, S., King, C., Marques de Araujo, D., Martin, D., Morkane, C., Neely, J., Rajendram, R., Burton, M., James, K., Keevil, E., Minik, O., Morgan, J., Musgrave, A., Rajanna, H., Roberts, T., Adamson, M., Jumbe, S., Kendall, J., Muthuswamy, M.B., Cruikshanks, A., Wrench, I., Zeidan, L., Ardern, D., Harris, B., Hellstrom, J., Martin, J., Thomas, R., Varsani, N., Wrey Brown, C., Docherty, P., Gillies, M., McGregor, E., Usher, H., Craig, J., Ahmad, T., Bodger, P., Creary, T., Fowler, A., Ijuo, E., Jones, T., Kantsedikas, I., Lahiri, S., McLean, A.L., Niebrzegowska, E., Phull, M., Wickboldt, N., Baldwin, J., Doyle, D., Mcmullan, S., Oladapo, M., Owen, T., Williams, A., Gregory, P., Husain, T., Kirk-Bayley, J., Mathers, E., Montague, L., Avis, J., Cook, T., Dali-Kemmery, L., Kerslake, I., Lambourne, V., Pearson, A., Boyd, C., Callaghan, M., Lawson, C., McCrossan, R., Nesbitt, V., O'connor, L., Sinclair, R., Farid, N., Morgese, C., Bhatia, K., Karmarkar, S., Ahmed, J., Branagan, G., Hutton, M., Swain, A., Brookes, J., Cornell, J., Dolan, R., Hulme, J., Jansen van Vuuren, A., Jowitt, T., Kalashetty, G., Lloyd, F., Patel, K., Sherwood, N., Brown, L., Chandler, B., Deighton, K., Emma, T., Haunch, K., Cheeseman, M., Dent, K., Gray, C., Hood, M., Jones, D., Juj, J., Rao, R., Walker, T., Al Anizi, M., Cheah, C., Cheing, Y., Coutinho, F., Gondo, P., Hadebe, B., Onie Hove, M., Khader, A., Krishnachetty, B., Rhodes, K., Sokhi, J., Baker, K.A., Bertram, W., Looseley, A., Mouton, R., Arnold, G., Arya, S., Balfoussia, D., Baxter, L., Harris, J., Jones, C., Knaggs, A., Markar, S., Perera, A., Scott, A., Shida, A., Sirha, R., Wright, S., Frost, V., MacGregor, M., Andrews, E., Arrandale, L., Barrett, S., Cifra, E., Cooper, M., Dragnea, D., Elna, C., Maclean, J., Meier, S., Milliken, D., Munns, C., Ratanshi, N., Salvana, A., Watson, A., Ali, H., Critchley, R., Hicks, C., Liddle, A., Pass, M., Ritchie, C., Thomas, C., Too, L., Welsh, S., Gill, T., Johnson, J., Reed, J., Davis, E., Papadopoullos, S., Attwood, C., Biffen, A., Boulton, K., Gray, S., Hay, D., Mills, S., Montgomery, J., Riddell, R., Simpson, J., Bhardwaj, N., Paul, E., Uwubamwen, N., Alexander, M., Arrich, J., Arumugam, S., Blackwood, D., Boggiano, V., Lam Chan, Y., Chatterjee, D., Chhabra, A., Christian, R., Costelloe, H., Coxwell Matthewman, M., Dalton, E., Darko, J., Davari, M., Dave, T., Deacon, M., Deepak, S., Edmond, H., Ellis, J., El-Sayed, A., Eneje, P., English, R., Ewe, R., Foers, W., Franklin, J., Gallego, L., Garrett, E., Goldberg, O., Goss, H., Greaves, R., Harris, R., Hennings, C., Jones, E., Kamali, N., Kokkinos, N., Lewis, C., Lignos, L., Malgapo, E.V., Malik, R., Milne, A., Mulligan, J.P., Nicklin, P., Palipane, N., Parsons, T., Piper, R., Prakash, R., Ramesh, B., Rasip, S., Reading, J., Rela, M., Reyes, A., Robert, S., Rooms, M., Shah, K., Simons, H., Solanki, S., Spowart, E., Stevens, A., Waggett, H., Yassaee, A., Kennedy, A., Scott, S., Somanath, S., Berg, A., Hernandez, M., Nanda, R., Tank, G., Wilson, N., Wilson, D., Al-Soudaine, Y., Baldwin, M., Cornish, J., Davies, Z., Davies, L., Edwards, M., Frewer, N., Gallard, S., Glasbey, J., Harries, R., Hopkins, L., Kim, T., Koompirochana, V., Lawson, S., Lewis, M., Makzal, Z., Scourfield, S., Ahmad, Y., Bates, S., Blackwell, C., Bryant, H., Coulter, S., Cruickshank, R., Daniel, S., Daubeny, T., Golder, K., Hawkins, L., Helen, B., Hinxman, H., Levett, D., Skinner, B., Walsgrove, J., Dickson, J., Constantin, K., Karen, M., O'Brien, P., O'Donohoe, L., Payne, H., Sundayi, S., Walker, E., Brooke, J., Cardy, J., Humphreys, S., Kessack, L., Kubitzek, C., Kumar, S., Cotterill, D., Hodzovic, E., Hosdurga, G., Miles, E., Saunders, G., Campbell, M., Chan, P., Jemmett, K., Raj, A., Naik, A., Ramamoorthy, R., Shah, N., Sylvan, A., Blyth, K., Burtenshaw, A., Freeman, D., Johnson, E., Lo, P., Martin, T., Plunkett, E., Wollaston, J., Allison, J., Carroll, C., Craw, N., Craw, S., Pitt-Kerby, T., Rowland-Axe, R., Spurdle, K., McDonald, A., Simon, D., Sinha, V., Banner-Goodspeed, V., Boone, M., Campbell, K., Lu, F., Scannell, J., Sobol, J., Balajonda, N., Clemmons, K., Conde, C., Funk, B., Hopkins, T., Olaleye, O., Omer, O., Pender, M., Porto, A., Waweru, P., Yeh, E., Bodansky, D., Evans, A., Kleopoulos, S., Maril, R., Mathney, E., Sanchez, A., Tinuoye, E., Bateman, B., Eng, K., Jiang, N., Ladha, K., Needleman, J., Chen, L.L., Lane, R., Robinowitz, D., Ghushe, N., Irshad, M., Patel, S., Takemoto, S., Wallace, A., Mazzeffi, M., Rock, P., Wallace, K., Zhu, X., Chua, P., Mattera, M., Sharar, R., Thilen, S., Treggiari, M., Morgan, A., Sofjan, I., Subramaniam, K., Avidan, M., Maybrier, H., Muench, M., and Wildes, T.
Subjects: Male, HSJ UCI, Critical Care and Intensive Care Medicine, law.invention, Perioperative Care/methods, 0302 clinical medicine, Surgical procedures, 030202 anesthesiology, law, Critical care/utilisation, Postoperative care/methods, Postoperative care/statistics and numerical data, Surgical procedures, operative/mortality, statistics and numerical data, Prospective Studies, Postoperative Period, Postoperative care/methods, education.field_of_study, Postoperative care/method, Elective Surgical Procedures/mortality, fluid output, Middle Aged, fluid administration, Intensive care unit, Hospitalization, Length of Stay/statistics & numerical data, operative/mortality, Intensive Care Units/statistics & numerical data, outcome, Female, Elective Surgical Procedure, Human, Adult, medicine.medical_specialty, Logistic Model, Postoperative care/statistics and numerical data, Critical care/utilisation, Population, Intensive Care Unit, Elective Surgical Procedures/statistics & numerical data, Hospitalization/statistics & numerical data, Humans, Logistic Models, Surgical procedures, operative/mortality, Postoperative care, methods, Perioperative Care, NO, 03 medical and health sciences, Anesthesiology, Intensive care, medicine, Elective surgery, Intensive care medicine, education, business.industry, 030208 emergency & critical care medicine, Perioperative, Length of Stay, Clinical trial, Prospective Studie, septic shock, business
Abstract: PURPOSE: As global initiatives increase patient access to surgical treatments, there is a need to define optimal levels of perioperative care. Our aim was to describe the relationship between the provision and use of critical care resources and postoperative mortality. METHODS: Planned analysis of data collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. We used risk-adjusted mixed-effects logistic regression models to evaluate the association between admission to critical care immediately after surgery and in-hospital mortality. We evaluated hospital-level associations between mortality and critical care admission immediately after surgery, critical care admission to treat life-threatening complications, and hospital provision of critical care beds. We evaluated the effect of national income using interaction tests. RESULTS: 44,814 patients from 474 hospitals in 27 countries were available for analysis. Death was more frequent amongst patients admitted directly to critical care after surgery (critical care: 103/4317 patients [2%], standard ward: 99/39,566 patients [0.3%]; adjusted OR 3.01 [2.10-5.21]; p < 0.001). This association may differ with national income (high income countries OR 2.50 vs. low and middle income countries OR 4.68; p = 0.07). At hospital level, there was no association between mortality and critical care admission directly after surgery (p = 0.26), critical care admission to treat complications (p = 0.33), or provision of critical care beds (p = 0.70). Findings of the hospital-level analyses were not affected by national income status. A sensitivity analysis including only high-risk patients yielded similar findings. CONCLUSIONS: We did not identify any survival benefit from critical care admission following surgery. info:eu-repo/semantics/publishedVersion
Published: 2017
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46. Artificial vision: the effectiveness of the OrCam in patients with advanced inherited retinal dystrophies

Author: Maria M. van Genderen, Camiel J. F. Boon, Xuan-Thanh-An Nguyen, Jan Koopman, Henk L M Stam, Ophthalmology, and ANS - Complex Trait Genetics
Subjects: medicine.medical_specialty, Visual acuity, genetic structures, medicine.medical_treatment, low vision, Quality of life, Artificial vision, Sickness Impact Profile, Surveys and Questionnaires, retinitis pigmentosa, Retinitis pigmentosa, medicine, Humans, cone-rod dystrophies, In patient, Vision, Ocular, OrCam, Rehabilitation, business.industry, National Eye Institute (U.S.), General Medicine, medicine.disease, United States, eye diseases, Ophthalmology, visual aids, quality of life, Clinical diagnosis, Physical therapy, medicine.symptom, business, Retinal Dystrophies
Abstract: Purpose To investigate the impact of the OrCam MyEye 2.0 (OrCam) on the quality of life and rehabilitation needs in patients with advanced retinitis pigmentosa (RP) or cone-rod dystrophies (CRD). The OrCam is a wearable low-vision aid that converts visual information to auditive feedback (e.g. text-to-speech, barcode and facial recognition). Methods Patients with a clinical diagnosis of RP (n = 9, 45%) or CRD (n = 11; 55%), and a best-corrected visual acuity of
Published: 2021

47. Ankle-foot orthoses for improving walking in people with calf muscle weakness due to neuromuscular disorders

Author: Sarah Tyson, Merel-Anne Brehm, Frans Nollet, Alberto Esquenazi, Fieke S. Koopman, Niels F.J. Waterval, Elza van Duijnhoven, Graduate School, Rehabilitation medicine, AMS - Amsterdam Movement Sciences, AMS - Rehabilitation & Development, ARD - Amsterdam Reproduction and Development, and EURO-NMD
Subjects: medicine.medical_specialty, Physical medicine and rehabilitation, genetic structures, business.industry, Ankle foot orthoses, education, medicine, Pharmacology (medical), Calf muscle weakness, business
Abstract: Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the effects of AFOs for improving walking in adults with calf muscle weakness due to slowly progressive NMD.
Published: 2021
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48. Treatment breaks in first line treatment of advanced colorectal cancer: An individual patient data meta-analysis

Author: Kaitlyn K.H. Goey, Harpreet Wasan, Aimery de Gramont, Benoist Chibaudel, Tim Maughan, Axel Hinke, Roberto Labianca, Cornelis J A Punt, Kjell Magne Tveit, Susanna Hegewisch-Becker, Louise J. Brown, David E. Fisher, Richard Kaplan, Richard Adams, Eduardo Diaz Rubio, Dirk Arnold, and Miriam Koopman
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Active monitoring, Drug Administration Schedule, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, Clinical Trials, Phase II as Topic, Maintenance therapy, Quality of life, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Chemotherapy, Radiology, Nuclear Medicine and imaging, Randomized Controlled Trials as Topic, Thrombocytosis, business.industry, General Medicine, Evidence-based medicine, Treatment breaks, Intermittent therapy, medicine.disease, Prognosis, Oxaliplatin, 030104 developmental biology, Clinical Trials, Phase III as Topic, 030220 oncology & carcinogenesis, Meta-analysis, business, Colorectal Neoplasms, medicine.drug
Abstract: Background\ud Intermittent systemic anti-cancer therapy in patients with advanced colorectal cancer (aCRC) may improve quality of life without compromising overall survival (OS). We aimed to use individual patient data meta-analysis (IPDMA) from multiple randomised controlled trials evaluating intermittent strategies to inform clinical practice. We also aimed to validate whether thrombocytosis as a predictive biomarker identified patients with significantly reduced OS receiving a complete treatment break.\ud Patients and Methods\ud An IPDMA of intermittent strategy impact on survival was undertaken, including all relevant trials in which data were available. Intermittent strategies were classified into two groups: a planned stopping of all therapy (“treatment break strategy”; 6 trials; 2,907 patients) or to the same treatment omitting oxaliplatin (“maintenance strategy”; 3 trials; 1,271 patients). The primary analysis sample was of patients successfully completing induction therapy. Additionally, a pre-planned analysis of the predictive value of thrombocytosis on survival under a continuous versus an intermittent strategy was undertaken.\ud Results\ud All trials had comparable inclusion criteria. The overall IPDMA of intermittent therapy versus continuous therapy demonstrated no detriment in OS (HR=1.03 [95% CI 0.93-1.14]), whether from complete break (HR 1.04 [95% CI 0.87-1.26]) or maintenance strategies (HR 0.99 [95% CI 0.87-1.13]). Thrombocytosis was confirmed as a marker of poor prognosis in aCRC, but did not predict for OS detriment from treatment break strategies (interaction HR=0.97 [95% CI 0.66-1.40] compared to continuous therapy).\ud Conclusion\ud The highest levels of evidence from this IPMDA indicate no detriment in survival for patients receiving an intermittent therapy strategy, either for maintenance or complete break strategies. Although, thrombocytosis is confirmed as a marker of poor prognosis, it is not predictive of poor outcome for patients treated with intermittent therapy. An intermittent chemotherapy strategy can therefore be applied irrespective of baseline platelet count and does not result in inferior OS compared to continuous chemotherapy.
Published: 2021

49. Early cost-effectiveness analysis of risk-based selection strategies for adjuvant treatment in stage II colon cancer:The potential value of prognostic molecular markers

Author: Geraldine R. Vink, Miriam Koopman, Marjolein J.E. Greuter, Cornelis J A Punt, Jan Paul Medema, Gabrielle Jongeneel, Louis Vermeulen, Veerle M.H. Coupé, Jan N. M. IJzermans, Felice N. van Erning, Natalia Kunst, Center of Experimental and Molecular Medicine, Radiotherapy, Oncology, Amsterdam Gastroenterology Endocrinology Metabolism, CCA - Cancer Treatment and Quality of Life, Epidemiology and Data Science, Orthopedic Surgery and Sports Medicine, APH - Methodology, CCA - Imaging and biomarkers, CCA - Cancer Treatment and quality of life, and Surgery
Subjects: Oncology, medicine.medical_specialty, Epidemiology, Colorectal cancer, Cost-Benefit Analysis, MEDLINE, Risk Assessment, Article, Value of information, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, Selection (genetic algorithm), Neoplasm Staging, Netherlands, business.industry, Cohort model, Cost-effectiveness analysis, Guideline, medicine.disease, Markov Chains, Chemotherapy, Adjuvant, Mutation (genetic algorithm), Colonic Neoplasms, Quality-Adjusted Life Years, business
Abstract: Background: To explore the potential value of consensus molecular subtypes (CMS) in stage II colon cancer treatment selection, we carried out an early cost-effectiveness assessment of a CMS-based strategy for adjuvant chemotherapy. Methods: We used a Markov cohort model to evaluate three selection strategies: (i) the Dutch guideline strategy (MSS+pT4), (ii) the mutation-based strategy (MSS plus a BRAF and/or KRAS mutation or MSS plus pT4), and (iii) the CMS-based strategy (CMS4 or pT4). Outcomes were number of colon cancer deaths per 1,000 patients, total discounted costs per patient (pp), and quality-adjusted life-years (QALY) pp. The analyses were conducted from a Dutch societal perspective. The robustness of model predictions was assessed in sensitivity analyses. To evaluate the value of future research, we performed a value of information (VOI) analysis. Results: The Dutch guideline strategy resulted in 8.10 QALYs pp and total costs of €23,660 pp. The CMS-based and mutation-based strategies were more effective and more costly, with 8.12 and 8.13 QALYs pp and €24,643 and €24,542 pp, respectively. Assuming a threshold of €50,000/QALY, the mutation-based strategy was considered as the optimal strategy in an incremental analysis. However, the VOI analysis showed substantial decision uncertainty driven by the molecular markers (expected value of partial perfect information: €18M). Conclusions: On the basis of current evidence, our analyses suggest that the mutation-based selection strategy would be the best use of resources. However, the extensive decision uncertainty for the molecular markers does not allow selection of an optimal strategy at present. Impact: Future research is needed to eliminate decision uncertainty driven by molecular markers.
Published: 2021
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50. Telemonitoring-based feedback improves adherence to non-vitamin K antagonist oral anticoagulants intake in patients with atrial fibrillation

Author: Dagmara Dilling-Boer, Joris Schurmans, Hein Heidbuchel, Lien Desteghe, Johan Vijgen, Pieter Koopman, Paul Dendale, DESTEGHE, Lien, VIJGEN, Johan, Dilling-Boer, Dagmara, KOOPMAN, Pieter, SCHURMANS, Joris, DENDALE, Paul, and HEIDBUCHEL, Hein
Subjects: Male, medicine.medical_specialty, Pyridones, medicine.drug_class, Cost-Benefit Analysis, Administration, Oral, Monitoring, Ambulatory, 030204 cardiovascular system & hematology, Feedback, Medication Adherence, law.invention, 03 medical and health sciences, 0302 clinical medicine, Rivaroxaban, Randomized controlled trial, law, Internal medicine, Atrial Fibrillation, medicine, Humans, Single-Blind Method, In patient, 030212 general & internal medicine, Stroke, Aged, Cross-Over Studies, business.industry, Antagonist, Anticoagulants, Atrial fibrillation, Vitamin K antagonist, medicine.disease, Crossover study, Regimen, Cardiology, Pyrazoles, Female, Human medicine, Cardiology and Cardiovascular Medicine, business
Abstract: Aims To evaluate the effect of telemonitoring on adherence to non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients. Methods and results A randomized, single-blind, crossover, controlled trial in 48 AF patients on once or twice daily (OD or BID) NOAC. The Medication Event Monitoring System tracked NOAC intake during three phases of 3 months each: daily telemonitoring, telemonitoring with immediate telephone feedback in case of intake errors, and an observation phase without daily transmissions. Unprotected days were defined as >= 3 or >= 1 consecutively missed doses for a BID or OD NOAC, respectively, or excess dose intake. Cost-effectiveness was calculated based on anticipated stroke reduction derived from patients' risk profile and measured intake. Persistence over the entire study was 98%. Telemonitoring-only already led to very high taking and regimen adherence (97.4% respectively 93.8%). Nevertheless, direct feedback further improved both to 99.0% and 96.8%, respectively (P < 0.001 respectively P =0.002). Observation without daily monitoring resulted in a significant waning of taking adherence (94.3%; P =0.049). Taking adherence was significantly higher for OD compared to BID NOAC, although unprotected days were similar. Feedback intervention had an incremental cost of (sic)344 289 to prevent one stroke, but this could be as low as (sic)15 488 in high-risk patients with low adherence and optimized technology. Conclusion Telemonitoring resulted in high NOAC adherence due to the notion of being watched, as evidenced by the rapid decline during the observation period. Feedback further optimized adherence. Telemonitoring with or without feedback may be a cost-effective approach in high-risk patients deemed poorly adherent.
Published: 2018
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