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Current management guidelines for urea cycle disorders (UCDs) offer clear strategies, incorporating both authorized and non-authorized medicinal products (including intravenous formulations and products regulated as food). These varying product categories are subject to specific accessibility challenges related to availability, reimbursement, and pricing. The aim of this study is to identify potential obstacles to optimal UCD treatment implementation in European clinical practice. A survey aimed at metabolic healthcare professionals (HCPs) managing patients with UCDs in Europe was disseminated through the European Reference Network for Hereditary Metabolic Disorders and the European registry and network for intoxication type metabolic diseases. Forty-eight survey responses were collected from 21 European countries. In 16 of these countries, at least one metabolic HCP reported challenges in accessing UCD products. Reimbursement issues were reported for most products (8/10), including both authorized and non-authorized products. Availability-related challenges were also reported for 8/10 products, although unavailability was limited to non-authorized products. Prices impacted accessibility for all authorized products (3/3) and one non-authorized IV product. The accessibility of UCD treatment products varied across Europe, although no clear regional variations could be discerned. Survey data revealed that metabolic HCPs experience challenges in accessing both authorized and non-authorized products for UCD management in the majority of European countries. This indicates that registering unauthorized products may not resolve all issues. Improved reimbursement policies and fair pricing models, as well as (adjusted) authorization procedures may help address these concerns, thereby optimizing treatment access for UCD patients., (© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Objective: Management of Differences of Sex Development (DSD) is complex and in resource limited settings the psychosexual and psychosocial aspects of DSD care have received limited attention. This review aims to explore recent literature on psychosocial care of DSD in low and upper middle-income countries (L/UMIC)., Materials and Methods: Scientific databases were searched and papers on management of DSD were reviewed according to predefined inclusion criteria., Results: Papers published between January 2010 and July 2024 were screened for eligibility. Seventy studies specifically focusing on psychosexual and psychosocial aspects were identified. In these papers, the following aspects were studied in detail: gender identity, sexual behaviour, quality of life, perception of parents and society, communication and family counselling and socio-cultural and religious aspects., Conclusions: The geographical distribution and volume of studies on the psychosexual and psychosocial aspects of DSD in L/UMIC are mostly originating from East-and South-Asia and South & Central America. The findings underscore the need for integrated and culturally sensitive interventions to support the psychosocial well-being of patients and their families affected by DSD within resource-limited contexts. We highly recommend providing specific guidelines recognising the socio-cultural milieu and resource restricted settings. International collaboration providing education and training should be encouraged.

There is considerable variability in the management of common orofacial clefts across Europe, reflecting differing opinions on optimal treatments. An updated overview of treatment protocols for orofacial clefts across 26 expert centres in the European Reference Network CRANIO is presented here. A structured questionnaire was distributed to map the surgical protocol and additional standard procedures for cleft palate (CP), unilateral cleft lip and palate (UCLP), and bilateral cleft lip and palate (BCLP). A surgical protocol was defined as the unique combination of a sequence of standard surgeries, their timing, and the surgical techniques employed. Overall, 33 unique surgical protocols for CP, 54 for UCLP, and 51 for BCLP were identified. Notable findings included the trend towards early hard palate closure, uniform timing of lip closure, and the popularity of primary cleft rhinoplasty. Nevertheless, practice variations were most pronounced in the timing of alveolar closure, the number of standard surgeries, and the application of additional standard procedures. This study highlights the diversity of treatment protocols across Europe, despite considerable convergence of treatment practices over time. To allow for further convergence, establishing objective criteria for protocol selection, adequate documentation of customizations, and consensus on the terminology of surgical techniques, are necessary., Competing Interests: Conflict of Interest This research is generated within the European Reference Network for rare and/or complex craniofacial anomalies and ear, nose and throat (ENT) disorders (ERN CRANIO). ERN CRANIO is funded by the European Union. The content of this paper represents the views of the authors only and it is their sole responsibility; it cannot be considered to reflect the views of the European Commission and/or the European Health and Digital Executive Agency (HaDEA) or any other body of the European Union. The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains. Thus, the authors of current study had no competing interest caused by the (partial) funding of this research. The authors that contributed to current study also have no other competing interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In previous studies, surgical specialties accounted for most malpractice claims. The objective of the present study was to determine the risk for malpractice claims for physicians working in hospitals. A retrospective observational study using anonymized closed malpractice claims between 2007 up to 2021 from two Dutch insurers was carried out. Main outcomes involved claim volume & outcome, and the estimated annual risk (EAR) for a claim per year for the individual physician from all specialties. Sustained or settled claims were considered unfavorable for the physician (UOP). Surgical specialists, involving surgical specialties and specialties with surgical characteristics accounted for 77% (14,330/18,649) of the claims closed. Liability was denied in 51% of the claims (n = 9,487). The remaining claims were sustained (granted) (n = 4,600; 25%), settled (n = 3,444; 18%) or closed without decision (n = 1118; 6%). Surgeons faced an average EAR of 21.6% (range 6.5 - 28%) which was higher compared to colleagues from specialties with surgical characteristics (EAR 7.3%; range 2.9 - 10.1%) and non-surgical specialties (EAR 2.5%; range 0.9 - 4.4%). Surgical specialists received more claims than their non-surgical colleagues. Relative to specialty size, surgeons faced a higher risk for a claim in general, as well as for a claim with an unfavorable outcome., Competing Interests: Declarations. Competing interests: Clemens Dirven and Peter Vandertop gave independent medical advice in some of the claims that were included in the present study. Quirine Amelink contributed to the present study in a personal capacity, not in relationship with her current affiliation through the Dutch Health and Youth Care Inspectorate.Wouter Dronkers, Jan van Rees, Désirée Klemann, Dennis Buis, Dirk Grünhagen, Mostafa Mokhles, Marike Broekman, Aart Hendriks, Eric Boersma, Markus Klimek, and Jochem Spoor have no disclosures. Ethical considerations: The present study was approved by the Institutional Review Board of the Erasmus University Medical Centre, Rotterdam, (METC 2020 − 0972) and was performed in accordance with the Declaration of Helsinki. Patients and public involvement: Patients or the public (Centramed and MediRisk) were not involved in the design, or conduct, or reporting, or dissemination plans of our research., (© 2024. The Author(s).)

We present an exceptional case of a lung transplant recipient successfully treated by multiple courses of alemtuzumab for refractory acute cellular rejection (ACR). The patient experienced multiple episodes of ACR following the transplantation procedure. Alemtuzumab was initiated as a third-line rejection treatment and was repeated 6 times. Each treatment course resulted in complete recovery of the pulmonary function and depletion of T- and B-lymphocytes and natural killer cells (NK cells). The onset of rejection was consistently preceded by the recovery of NK cells, while T- and B-lymphocytes remained depleted. This suggests a rejection process mediated by NK cells. This case contributes to recent research findings suggesting that NK cells play a significant role in ACR in lung transplant recipients and stresses the importance to further investigate the role of NK cells in rejection. Furthermore, it demonstrates that ACR following lung transplantation can be repeatedly managed by treatment with alemtuzumab., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Gyrate atrophy of the choroid and retina (GACR) is an autosomal recessive inherited metabolic disorder (IMD) characterised by progressive retinal degeneration, leading to severe visual impairment. The rapid developments in ophthalmic genetic therapies warrant knowledge on clinical phenotype of eligible diseases such as GACR to define future therapeutic parameters in clinical trials., Methods: Retrospective chart analysis was performed in nineteen patients. Data were analysed using IBM SPSS Statistics version 28.0.1.1., Results: Nineteen patients were included with a mean age of 32.6 years (range 8-58). Mean age at onset of ophthalmic symptoms was 7.9 years (range 3-16). Median logMAR of visual acuity at inclusion was 0.26 (range -0.18-3.00). Mean age at cataract surgery was 28.8 years (n = 11 patients). Mean spherical equivalent of the refractive error was -8.96 (range -20.87 to -2.25). Cystoid maculopathy was present in 68% of patients, with a loss of integrity of the foveal ellipsoid zone (EZ) in 24/38 eyes. Of the 14 patients treated with dietary protein restriction, the four patients who started the diet before age 10 showed most benefit., Conclusion: This study demonstrates the severe ophthalmic disease course associated with GACR, as well as possible benefit of early dietary treatment. In addition to visual loss, patients experience severe myopia, early-onset cataract, and CME. There is a loss of foveal EZ integrity at a young age, emphasising the need for early diagnosis enabling current and future therapeutic interventions., (© 2024. The Author(s).)

Background: Despite uncertain benefit-risk profile near the end of life, antithrombotic therapy (ATT) is prevalent in patients with terminal cancer., Objectives: To examine adherence and persistence with ATT in terminally ill cancer patients and investigate risks of major and clinically relevant bleeding, venous thromboembolism (VTE), and arterial thromboembolism (ATE) by ATT exposure., Methods: Using a Danish nationwide cohort of terminal cancer patients, ATT adherence in the year following terminal illness declaration was measured by the proportion of days covered (PDC) by prescription. Discontinuation was defined as a treatment gap of ≥30 days between prescription renewals. One-year cumulative incidences of bleeding complications, VTE, and ATE were calculated, considering the competing risk of death., Results: During 2013-2022, 86 732 terminally ill cancer patients were identified (median age, 75 years; 47% female; median survival, 57 days). At terminal illness declaration, 37.5% were receiving ATT (66.6% platelet inhibitors, 23.0% direct oral anticoagulants, and 10.4% vitamin K antagonists [VKAs]). The mean PDC with ATT was 88% (SD, 30%), highest among platelet inhibitor users (mean PDC, 89%) and lowest among VKA users (73%). One-year ATT discontinuation incidence was 7.9% (95% CI, 7.7%-8.1%). Most patients continued ATT until death (74.8% platelet inhibitors, 58.8% direct oral anticoagulants, and 61.6% VKAs). Patients receiving ATT had a lower 1-year VTE risk but higher risks of ATE and major bleeding., Conclusion: Despite uncertain benefit-risk profile, most terminally ill cancer patients continue ATT until the end of life. These findings provide insights into current ATT utilization and discontinuation dynamics in the challenging context of terminal illness., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Many patients with post COVID-19 condition (PCC) require healthcare services. However, qualitative studies indicate that patients with PCC encounter many barriers to healthcare access. This cross-sectional study aimed to determine how many PCC patients report barriers to healthcare access and which barriers are reported, and to explore differences between subgroups., Methods: Data were collected via an online survey from 10,462 adult patients with a confirmed or suspected COVID-19 infection in the Netherlands, who experienced persisting symptoms ≥ 3 months after the initial infection. To study self-perceived barriers, a list of eleven possible barriers was used, covering multiple aspects of healthcare access. Differences between subgroups based on sociodemographic characteristics, medical characteristics, PCC symptoms (fatigue, dyspnoea, cognitive problems, anxiety and depression), and healthcare use (general practitioner, paramedical professional, medical specialist, occupational physician and mental health professional) were studied through multivariable multinomial (0 vs. 1 vs. > 1 barrier) and binomial regression analyses (for each individual barrier)., Results: A total of 83.2% of respondents reported at least one barrier to healthcare access. Respondents reported a median of 2.0 (IQR = 3.0) barriers. The barriers "I didn't know who to turn to for help" (50.9%) and "No one with the right knowledge/skills was available" (36.8%) were most frequently reported. Respondents with younger age, higher educational level, not hospitalized during acute COVID-19 infection, longer disease duration, who had more severe PCC symptoms, and who did not consult an occupational physician or paramedical professional, were more likely to report barriers. Analyses per barrier showed that women were more likely to report financial and help-seeking barriers, while men were more likely to report barriers related to availability of care. Hospitalized respondents were less likely to report barriers related to availability of care, but not less likely to report financial or help-seeking barriers., Conclusions: This study shows that the majority of patients with PCC experiences barriers to healthcare access. Particular attention should be paid to younger, non-hospitalized patients with a long disease duration and severe PCC symptoms. Efforts to remove barriers should focus not only on improving availability of care, but also on helping patients navigate care pathways., (© 2024. The Author(s).)

Background and Objectives: Studying malpractice claims is important to improve quality of health care and patient safety and to educate the individual healthcare providers. The objective of this study was to describe characteristics of neurosurgical claims in the Netherlands., Methods: A nationwide retrospective observational study of neurosurgery-related claims closed by Centramed and MediRisk, 2 major insurance companies in the Netherlands, was performed. Relevant data, including type of neurosurgical pathology, theme and category of the claim, type and severity of injury, outcome, and financial burden, were extracted from anonymized claim files. The estimated annual risk was used to determine the risk for claims by adjusting for the number of annually practicing neurosurgeons in the Netherlands., Results: A total of 388 claims against neurosurgeons were closed between 2007 and 2021. Liability was denied in a slight majority of claims (n = 230; 59%). The total burden during this period was €6 165 000 (amount paid out to patients: €5 497 000). The estimated annual risk per Dutch neurosurgeon for a claim was 15.5%, meaning 1 claim per 6.5 years. The case-level analysis of 238 available anonymized claims revealed that most claims were related to spinal pathology (81.5%), followed by cranial pathology (10.9%) and peripheral nerve (7.6%). The motivations for filing claims were mostly related to alleged surgical (56.3%) or diagnostic errors (22.3%). Most of these claims were denied (151/238; 63.4%), and fewer were settled (42/238; 17.6%), sustained (31/238; 13.0%), or closed without final decision (14/238; 5.9%)., Conclusion: Neurosurgery-related malpractice claims primarily involved spinal pathology and were mostly related to alleged treatment errors. Most claims did not result in compensation because there seemed to be no liability or culpable injury. However, the annual risk for a claim for Dutch neurosurgeons is considerable., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Background: Patients with hidradenitis suppurativa have substantial unmet clinical needs and scarce therapeutic options. We aimed to assess the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with moderate-to-severe hidradenitis suppurativa., Methods: BE HEARD I and II were two identically designed, 48-week randomised, double-blind, placebo-controlled, multicentre phase 3 trials. Patients aged 18 years or older with moderate-to-severe hidradenitis suppurativa were randomly assigned 2:2:2:1 using interactive response technology (stratified by worst Hurley Stage at baseline and baseline systemic antibiotic use) to receive subcutaneous bimekizumab 320 mg every 2 weeks; bimekizumab 320 mg every 2 weeks to week 16, then every 4 weeks to week 48; bimekizumab 320 mg every 4 weeks to week 48; or placebo to week 16, then bimekizumab 320 mg every 2 weeks. The primary outcome was an hidradenitis suppurativa clinical response of at least 50%, defined as a reduction in total abscess and inflammatory nodule count of at least 50% from baseline with no increase from baseline in abscess or draining tunnel count (HiSCR50) at week 16. Efficacy analyses included all randomly assigned study patients (intention-to-treat population). Safety analyses included all patients who received at least one full or partial dose of study treatment in the safety set, and of bimekizumab in the active-medication set. These trials are registered at ClinicalTrials.gov, NCT04242446 and NCT04242498, and both are completed., Findings: Patients for BE HEARD I were recruited from Feb 19, 2020, to Oct 27, 2021, and 505 patients were enrolled and randomly assigned. Patients for BE HEARD II were recruited from March 2, 2020, to July 28, 2021, and 509 patients were enrolled and randomly assigned. The primary outcome at week 16 was met in the group who received bimekizumab every 2 weeks using modified non-responder imputation; higher responder rates were observed with bimekizumab versus placebo in both trials: 138 (48%) of 289 patients versus 21 (29%) of 72 patients in BE HEARD I (odds ratio [OR] 2·23 [97·5% CI 1·16-4·31]; p=0·0060) and 151 (52%) of 291 patients versus 24 (32%) of 74 patients in BE HEARD II (2·29 [1·22-4·29]; p=0·0032). In BE HEARD II, HiSCR50 was also met in the group who were administered bimekizumab every 4 weeks (77 [54%] of 144 vs 24 [32%] of 74 with placebo; 2·42 [1·22-4·80]; p=0·0038). Responses were maintained or increased to week 48. Serious treatment-emergent adverse events were reported in 40 (8%) patients in BE HEARD I and in 24 (5%) patients in BE HEARD II treated with bimekizumab over 48 weeks. The most frequently reported treatment-emergent adverse events to week 48 were hidradenitis in both trials, in addition to coronavirus infection and diarrhoea in BE HEARD I, and oral candidiasis and headache in BE HEARD II. One death was reported across the two trials, and was due to congestive heart failure in a patient with substantial cardiovascular history treated with bimekizumab every 2 weeks in BE HEARD I (considered unrelated to bimekizumab treatment by the investigator). No new safety signals were observed., Interpretation: Bimekizumab was well tolerated by patients with hidradenitis suppurativa and produced rapid and deep clinically meaningful responses that were maintained up to 48 weeks. Data from these two trials support the use of bimekizumab for the treatment of patients with moderate-to-severe hidradenitis suppurativa., Funding: UCB Pharma., Competing Interests: Declaration of interests ABK reports grants paid to the institution from AbbVie, Admirx, Anapyts Bio, Aristea, Bristol Myers Squibb, Eli Lilly and Company, Incyte, Janssen, MoonLake Immunotherapeutics, Novartis, Pfizer, Prometheus, Sonoma Bio, and UCB Pharma; consulting fees from AbbVie, Alumis, Bayer, Boehringer Ingelheim, Eli Lilly and Company, Janssen, MoonLake Immunotherapeutics, Novartis, Pfizer, Priovant, Sonoma Bio, Sanofi, Target RWE, UCB Pharma, Union, and Ventyx; and serves on the board of directors of Almirall. GBEJ reports honoraria for participation on advisory boards from AbbVie, Boehringer Ingelheim, Chemocentryx, Incyte, Janssen-Cilag, LEO Pharma, Novartis, and UCB Pharma; and acted as an investigator for AbbVie, CJSL, InflaRx, Janssen-Cilag, LEO Pharma, Novartis, Regeneron, Sanofi, and UCB Pharma. CJS acted as an investigator for AbbVie, Chemocentryx, GSK, Incyte, InflaRx, Novartis, and UCB Pharma; reports consultancy fees from AbbVie, Alumis, InflaRx, Incyte, Logical Images, Sonoma Biotherapeutics, and UCB Pharma; and acted as a speaker for AbbVie and Novartis. JSK reports personal fees from AbbVie, ChemoCentryx, CJSL Behring, DermTech, Incyte, Insmed, Janssen, MoonLake, Novartis, and UCB Pharma; personal fees and grants from Incyte; is a co-copyright holder of HiSQOL; has been a consultant for and received honoraria from AbbVie, Alumis, DermTech, Incyte, Insmed, Janssen, MoonLake Immunotherapeutics, Novartis, and UCB Pharma; and has been a speaker for AbbVie, Janssen, Novartis, and UCB Pharma. EP has been a consultant, advisory board member, speaker for, and received honoraria from Almirall, Janssen-Cilag, GSK, MoonLake Immunotherapeutics, Novartis, and UCB Pharma; and his department received investigator-initiated grant support from AbbVie, Celgene, CHDR, Citryll, Kymera, Janssen-Cilag, and UCB Pharma. JRI receives a stipend as Editor‑in‑Chief of the British Journal of Dermatology and an authorship honorarium from UpToDate; has been a consultant for AbbVie, Boehringer Ingelheim, ChemoCentryx, Citryll, MoonLake Immunotherapeutics, Novartis, UCB Pharma, and Union Therapeutics, and has served on advisory boards for Insmed, Kymera Therapeutics, and Viela Bio; is a co‑copyright holder of the Hidradenitis Suppurativa Quality of Life score (HiSQOL) and hidradenitis suppurativa-Investigator Global Assessment; and his department receives income from copyright of the Dermatology Life Quality Instrument and related instruments. AG has been a consultant and receives honoraria from AbbVie, Aclaris Therapeutics, AnaptysBio, Aristea Therapeutics, Bristol Myers Squibb, Boehringer Ingelheim, Incyte, Insmed, Janssen, Novartis, Pfizer, Sonoma Biotherapeutics, UCB Pharma, Union Therapeutics, Ventyx Biosciences, and Viela Biosciences; has received research grants from AbbVie, C3, National Psoriasis Foundation, and UCB Pharma; and is a co-copyright holder of HiSQOL and hidradenitis suppurativa-IGA. ABG reports honoraria as an advisory board member and consultant for Amgen, Almirall, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dice Therapeutics, Eli Lilly and Company, Janssen, Novartis, Sanofi, UCB Pharma, and Xbiotech; and research or educational grants from AnaptysBio, Bristol Myers Squibb, MoonLake Immunotherapeutics, Novartis, and UCB Pharma (all paid to Mount Sinai School of Medicine). JCJS has acted as a consultant and advisory board member of AbbVie, LEO Pharma, Novartis, Pierre Fabre, Sanofi Genzyme, and Trevi Therapeutics; acted as a speaker for AbbVie, Almirall, Eli Lilly and Company, LEO Pharma, Novartis, Pfizer, Pierre-Fabre, Sanofi, and UCB Pharma; and has acted as an investigator for AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Galderma, Incyte, InflaRX, Janssen, Kliniksa, Kymab Limited, Menlo Therapeutics, Merck, Novartis, Pfizer, Regereron Pharmaceuticals, Trevi Therapeutics, and UCB Pharma. FGB reports honoraria for participation in advisory boards, in clinical trials, and as a speaker from AbbVie, AbbVie Deutschland, Boehringer Ingelheim, Celltrion, Dr. Wolff, Incyte, Janssen, Mölnlycke, MoonLake Immunotherapeutics, Novartis, and UCB Pharma. EJG-B reports honoraria from Abbott Products Operations, bioMérieux, Brahms, GSK, InflaRX, Sobi and XBiotech; independent educational grants from Abbott Products Operations, AxisShield, bioMérieux, InflaRx, Johnson & Johnson, MSD, Novartis, Sobi, and XBiotech; and funding from the Horizon2020 Marie Skłodowska-Curie International Training Network the European Sepsis Academy (granted to the National and Kapodistrian University of Athens), the Horizon 2020 European Grants ImmunoSep and RISCinCOVID (granted to the Hellenic Institute for the Study of Sepsis) and the Horizon Health grant EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis). HF reports honoraria or fees for serving on advisory boards, as a speaker, and as a consultant; and grants as an investigator from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Eli Lilly and Company, Janssen, Japan Blood Products Organization, JMEC, Kaken Pharmaceutical, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nihon Pharmaceutical, Novartis, Otsuka Pharmaceutical, Sanofi, Sato Pharmaceutical, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, UCB Pharma, and Ushio. RR, PJ, PD, EM, and LP are employees and shareholders of UCB Pharma. CM is a former employee and shareholder of UCB Pharma. MB is an employee of UCB Pharma. CCZ reports grants paid to the institution from AstraZeneca, Boehringer Ingelheim, GSK, InflaRx, Novartis, Relaxera, and UCB Pharma for participation as a clinical and research investigator; consultant honoraria from AccureAcne, Almirall, Boehringer Ingelheim, Incyte, InflaRx, Janssen, L'Oréal, Luvos, NAOS-BIODERMA, Novartis, PPM, Sanofi, UCB Pharma, and Viatris; lecture fees from Almirall, Biogen, Novartis, Sobi, and UCB Pharma; and is the president of the European Hidradenitis Suppurativa Foundation, coordinator of the ALLOCATE Skin group of the European Reference Network for rare skin diseases, and chair of the Acne, Rosacea and Hidradenitis Suppurativa Task Force group of the European Academy of Dermatology and Venereology (EADV); is the editor of the EADV News; and co-copyright holder of the International Hidradenitis Suppurativa Severity Score System on behalf of the European Hidradenitis Supurativa Foundation., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: One of the most robust risk factors for developing a mood disorder is having a parent with a mood disorder. Unfortunately, mechanisms explaining the transmission of mood disorders from one generation to the next remain largely elusive. Since timely intervention is associated with a better outcome and prognosis, early detection of intergenerational transmission of mood disorders is of paramount importance. Here, we describe the design of the Mood and Resilience in Offspring (MARIO) cohort study in which we investigate: 1. differences in clinical, biological and environmental (e.g., psychosocial factors, substance use or stressful life events) risk and resilience factors in children of parents with and without mood disorders, and 2. mechanisms of intergenerational transmission of mood disorders via clinical, biological and environmental risk and resilience factors., Methods: MARIO is an observational, longitudinal cohort study that aims to include 450 offspring of parents with a mood disorder (uni- or bipolar mood disorders) and 100-150 offspring of parents without a mood disorder aged 10-25 years. Power analyses indicate that this sample size is sufficient to detect small to medium sized effects. Offspring are recruited via existing Dutch studies involving patients with a mood disorder and healthy controls, for which detailed clinical, environmental and biological data of the index-parent (i.e., the initially identified parent with or without a mood disorder) is available. Over a period of three years, four assessments will take place, in which extensive clinical, biological and environmental data and data on risk and resilience are collected through e.g., blood sampling, face-to-face interviews, online questionnaires, actigraphy and Experience Sampling Method assessment. For co-parents, information on demographics, mental disorder status and a DNA-sample are collected., Discussion: The MARIO cohort study is a large longitudinal cohort study among offspring of parents with and without mood disorders. A unique aspect is the collection of granular data on clinical, biological and environmental risk and resilience factors in offspring, in addition to available parental data on many similar factors. We aim to investigate the mechanisms underlying intergenerational transmission of mood disorders, which will ultimately lead to better outcomes for offspring at high familial risk., (© 2024. The Author(s).)

Background: Previous studies showed that there is a positive association between mothers' and children's autistic traits. We also tested if this association is more pronounced in mothers with a higher pre-pregnancy body mass index (BMI)., Method: The study was embedded in two cohorts with information available for 4,659 participants from the Generation R and for 179 participants from the Cambridge Ultrasound Siblings and Parents Project (CUSP) cohort. In both cohorts, maternal autistic traits were assessed using the short form of the Autism Spectrum Quotient, and information about maternal height and weight before pregnancy was obtained by questionnaire. Child autistic traits were assessed with the short form of Social Responsiveness Scale in Generation R (M = 13.5 years) and with the Quantitative Checklist for Autism in Toddlers (Q-CHAT) in the CUSP cohort (M = 1.6 years)., Result: Higher maternal autistic traits were associated with higher autistic traits in toddlerhood (CUSP cohort; β adjusted  = 0.20, p < 0.01), in early childhood (Generation R; β adjusted  = 0.19, p < 0.01), and in early adolescence (Generation R; β adjusted  = 0.16, p < 0.01). Furthermore, a higher maternal pre-pregnancy BMI was associated with higher child autistic traits, but only in Generation R (β adjusted  = 0.03, p < 0.01). There was no significant moderating effect of maternal pre-pregnancy BMI on the association between autistic traits of mothers and children, neither in Generation R nor in CUSP. In addition, child autistic traits scores were significantly higher in mothers who were underweight and in mothers who were overweight compared to mothers with a healthy weight., Conclusion: We confirm the association between maternal and child autistic traits in toddlerhood, early childhood, and early adolescence. Potential interacting neurobiological processes remain to be confirmed., (© 2023. The Author(s).)

Background: The genetic risk haplotype DPP6 has been linked to familial idiopathic ventricular fibrillation (IVF), but the associated long-term outcomes are unknown., Methods: DPP6 risk haplotype-positive family members (DPP6 cases) and their risk haplotype-negative relatives (DPP6 controls) were included. Clinical follow-up data were collected through March 2023. Implantable cardioverter-defibrillator (ICD) indication was divided in primary or secondary prevention. Cumulative survival and event rates were calculated., Results: We included 327 DPP6 cases and 315 DPP6 controls. Median follow-up time was 9 years (interquartile range: 4-12). Of the DPP6 cases, 129 (39%) reached the composite endpoint of appropriate ICD shock, sudden cardiac arrest or death, at a median age of 45 years (range: 15-97). Median overall survival was 83 years and 87 years for DPP6 cases and DPP6 controls, respectively (p < 0.001). In DPP6 cases, median overall survival was shorter for males (74 years) than females (85 years) (p < 0.001). Of the DPP6 cases, 97 (30%) died, at a median age of 50 years. With a prophylactic ICD implantation advise based on risk haplotype, sex and age, 137 (42%) of DPP6 cases received an ICD, for primary prevention (n = 109) or secondary prevention (n = 28). In the primary prevention subgroup, 10 patients experienced a total of 34 appropriate ICD shocks, and there were no deaths during follow-up. DPP6 cases with a secondary prevention ICD experienced a total of 231 appropriate ICD shocks., Conclusion: Patients with the DPP6 risk haplotype, particularly males, are at an increased risk of IVF and sudden cardiac death. Using a risk stratification approach based on risk haplotype, sex and age, a substantial proportion of patients with a primary prevention ICD experienced appropriate ICD shocks, showing the benefit of prophylactic ICD implantation with this strategy., (© 2023. The Author(s).)

Introduction: Emicizumab effectively prevents bleeding in people with haemophilia A (PwHA), but is a burden for national healthcare budgets and consequently may limit access. According to the drug label, dosing of emicizumab is based on body weight with fixed intervals of 7, 14 or 28 days, which leads to mean plasma concentrations of 55 µg/mL (SD 15 µg/mL). However, a moderate variability of concentrations and a minimal effective concentration of 30 µg/mL have been suggested in studies. Therefore, a dose of emicizumab that targets a trough concentration of 30 µg/mL is hypothesised to be equally effective as conventional dosing in the prevention of bleeding., Methods and Analysis: We designed a phase IV, multicentre, open-label, crossover study to evaluate non-inferiority of bleed control of ≥6 months on conventional dosing in comparison to ≥6 months on dose intervention. This dose intervention consists of reducing the dose of emicizumab to target a trough concentrations of 30 µg/mL using individual pharmacokinetic (PK) parameters. Ninety-five PwHA aged >1 years who received conventional dosing of emicizumab for ≥12 months with good bleeding control during the last 6 months will be recruited from all Dutch haemophilia treatment centres. The study is powered to detect a clinically relevant decrease (risk difference) of 15% in the proportion of patients without treated bleeds during follow-up. Secondary endpoints are spontaneous joint or muscle bleeds, and annualised treated bleeding rates (using negative binomial regression). Cost-effectivity between conventional dosing and individualised PK-guided dosing of emicizumab will be compared., Ethics and Dissemination: The DosEmi study was approved by the Medical Ethics Review Committee NedMec of the University Medical Center of Utrecht, The Netherlands. Study results will be communicated through publications in international scientific journals and presentations at (inter)national conferences., Trial Registration Number: EUCTR2021-004039-10-NL at https://trialsearch.who.int., Protocol Version: V.4.1 on 28 October 2022 (DosEmi protocol&#95;V4.1; NL81112.041.22)., Competing Interests: Competing interests: KFij reported her institution has received unrestricted research grants from CSL Behring, SOBI and Novo Nordisk and her institution has received consultancy fees from SOBI, Grifols, Takeda, Novo Nordisk and Roche. RM reports research grants from Bayer, CSL Behring, Shire and ZonMW, served as advisor for Bayer, CSL Behring, Merck Sharp & Dohme, Shire, Zeria, all payment made to institution. MHC reports her institution has received investigator-initiated research and travel grants as well as speaker fees over the years from the Netherlands Organisation for Scientific Research (NWO) and Netherlands National research Agenda (NWA), the Netherlands Organization for Health Research and Development (ZonMw), the Dutch Innovatiefonds Zorgverzekeraars, Stichting Haemophilia, Baxter/Baxalta/Shire/ Takeda, Pfizer, Bayer Schering Pharma, CSL Behring, Sobi Biogen, Novo Nordisk, Novartis, Roche, and Nordic Pharma, and for serving as a steering board member for Roche, Bayer and Novartis. All grants and fees were paid to Erasmus MC as an institution. RS reports grants from Bayer, CSL Behring, Hemab, Novo Nordisk, Novartis, Octapharma, Roche, Sobi, all payment made to institution. RTU reports Hemab Therapeutics Research funding, Research along routes by Consortia (NWA-ORC), Dutch Research Counsil (NWO) Grant and Synapse Research Institute Research funding, all payment made to institution. KFis reports grants from Bayer AG, Novo Nordisk, Pfizer, consulting fees from Biogen, Freeeline, Roche, CSL Behring, Novo Nordisk, SOBI and honoraria for presentations from CSL Behring and Novo Nordisk, all payment made to institution., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Endovascular treatment (EVT) has been proven to be both effective and cost-effective for patients with acute ischaemic stroke. We investigated the budget impact of large-scale implementation of EVT for acute ischaemic stroke patients in the Netherlands for 2015-2021., Methods: An analysis was performed from a healthcare perspective as a preplanned substudy of the Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN). Estimated yearly costs during follow-up after stroke for patients who had or had not been treated with EVT as add-on to usual care were linked to numbers of new patients retrieved from 2 Dutch registries of EVT that started after the last inclusion in MR CLEAN (2014). Aggregated costs and costs per care sector were calculated based on prevalence using a population dynamic tool., Results: From 2015, the yearly number of new acute ischaemic stroke patients receiving EVT increased almost threefold, from 812 in 2015 to 2,370 in 2021. The introduction of EVT plus usual care resulted in estimated net annual savings that increased from € 2.9 million in 2015 to € 58 million in 2021., Conclusion: Offering EVT as add-on to usual care for acute ischaemic stroke patients was increasingly cost saving from a national healthcare perspective but affected distinct healthcare sectors differently., (© 2023. The Author(s).)

Introduction: Care for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers. In the EU, a unique opportunity is provided by the European Reference Networks (ERN). The ERN EURACAN is dedicated to rare adults solid cancers, here we present the protocol of the EURACAN registry on rare head and neck cancers (ClinicalTrials.gov Identifier: NCT05483374)., Study Design: Registry-based cohort study including only people with rare head and neck cancers., Objectives: to help describe the natural history of rare head and neck cancers;to evaluate factors that influence prognosis;to assess treatment effectiveness;to measure indicators of quality of care., Methods: Settings and participants It is an hospital based registry established in hospitals with expertise in head and neck cancers. Only adult patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses; salivary gland cancer in large and small salivary glands; and middle ear will be included in the registry. This registry won't select a sample of patients. Each patient in the facility who meets the above mentioned inclusion criteria will be followed prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for the patient follow-up. Variables Data will be collected on patient characteristics (eg. patient demographics, lifestyle, medical history, health status); exposure data (eg. disease, procedures, treatments of interest) and outcomes (e.g. survival, progression, progression-free survival, etc.). In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will be also collected. Statistical methods The data analyses will include descriptive statistics showing patterns of patients' and cancers' variables and indicators describing the quality of care. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause specific mortality will be used to determine independent predictors of overall survival, recurrence etc. Variables to include in the multivariable regression model will be selected based on the results of univariable analysis. The role of confounding or effect modifiers will be evaluated using stratified analysis or sensitivity analysis. To assess treatment effectiveness, multivariable models with propensity score adjustment and progression-free survival will be performed. Adequate statistical (eg. marginal structural model) methods will be used if time-varying treatments/confounders and confounding by indication (selective prescribing) will be present., Results: The registry initiated recruiting in May 2022. The estimated completion date is December 2030 upon agreement on the achievement of all the registry objectives. As of October 2022, the registry is recruiting. There will be a risk of limited representativeness due to the hospital-based nature of the registry and to the fact that hospital contributing to the registry are expert centres for these rare cancers. Clinical Follow-up could also be an issue but active search of the life status of the patients will be guaranteed., Competing Interests: Paolo Bossi was part of the Advisory board or conference honoraria for: Merck, Sanofi-Regeneron, Merck Sharp & Dohme, Sun Pharma, Angelini, Bristol-Myers Squibb, Nestlè Christoph Benedikt Westphalen received honoraria from Bayer, Celgene, Ipsen, F. Hoffmann-La Roche Ltd, Servier, and Taiho, served in a consulting/advisory role for BMS, Celgene, Merck, Shire/Baxalta, Rafael Pharmaceuticals, RedHill BioPharma, and F. Hoffmann-La Roche Ltd, has received travel/accommodation expenses from Bayer, Celgene, RedHill BioPharma, F. Hoffmann-La Roche Ltd, Servier, and Taiho and has received research funding from F. Hoffmann-La Roche Ltd. Lisa Licitra participated to clinical studies that received research funding intended directly to Fondazione IRCCS Istituto Nazionale dei Tumori from Astrazeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, Hoffmann – La Roche ltd, IRX Therapeutics, Medpace, Merck-Serono, MSD, Novartis, Pfizer, Roche, Buran. Also, she declares that she recived occasional payment for her participation as a speaker at conferences/congresses or as a scientific consultant for advisory boards from Astrazeneca, Bayer, MSD, Merck-Serono, AccMed, Neutron Therapeutics, Inc All the other authors declare that they have no competing interests. I confirm that this does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Trama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Clinical practice guidelines (CPG) are statements that provide recommendations regarding the approach to different diseases and aim to increase quality while decreasing the risk of complications in health care. Numerous guidelines in the field of perioperative care have been published in the previous decade but their methodological quality and transparency are relatively unknown., Objective: To critically evaluate the transparency and methodological quality of published CPG in the preoperative assessment and management of adult patients undergoing elective surgery., Design: Systematic review and methodological appraisal study., Data Sources: We searched for eligible CPG published in English or Spanish between January 1, 2010, and June 30, 2022, in Pubmed MEDLINE, TRIP Database, Embase, the Cochrane Library, as well as in representatives' medical societies of Anaesthesiology and developers of CPG., Eligibility Criteria: CPG dedicated on preoperative fasting, cardiac assessment for non-cardiac surgery, and the use of routine preoperative tests were included. Methodological quality and transparency of CPG were assessed by 3 evaluators using the 6 domains of the AGREE-II tool., Results: We included 20 CPG of which 14 were classified as recommended guidelines. The domain of "applicability" scored the lowest (44%), while the domains "scope and objective" and "editorial interdependence" received the highest median scores of 93% and 97% respectively. The remaining domains received scores ranging from 44% to 84%. The top mean scored CPG in preoperative fasting was ASA 2017 (93%); among cardiac evaluation, CPG for non-cardiac surgery were CCS 2017 (91%), ESC-ESA 2014 (90%), and AHA-ACC 2014 (89%); in preoperative testing ICSI 2020 (97%)., Conclusions: In the last ten years, most published CPG in the preoperative assessment or management of adult patients undergoing elective surgery focused on preoperative fasting, cardiac assessment for non-cardiac surgery, and use of routine preoperative tests, present moderate to high methodological quality and can be recommended for their use or adaptation. Applicability and stakeholder involvement domains must be improved in the development of future guidelines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Angel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A tumour-positive proximal margin (PPM) after extended gastrectomy for oesophagogastric junction (OGJ) adenocarcinoma is observed in approximately 2-20% of patients. Although a PPM is an unfavourable prognostic factor, the clinical relevance remains unclear as it may reflect poor tumour biology. This narrative review analyses the most relevant literature on PPM after gastrectomy for OGJ cancers. Awareness of the risk factors and possible measures that can be taken to reduce the risk of PPM are important. In patients with a PPM, surgical and non-surgical treatments are available but the effectiveness remains unclear., (© 2022. The Author(s).)

Background: Living in socially disadvantaged circumstances has a widespread impact on one's physical and mental health. That is why individuals living in this situation are often considered vulnerable. When pregnant, not only the woman's health is affected, but also that of her (unborn) child. It is well accepted that vulnerable populations experience worse (perinatal) health, however, little is known about the lived adversities and health of these vulnerable individuals., Objectives: With this article, insights into this group of highly vulnerable pregnant women are provided by describing the adversities these women face and their experienced well-being., Methods: Highly vulnerable women were recruited when referred to tailored social care during pregnancy. Being highly vulnerable was defined as facing at least three different adversities divided over two or more life-domains. The heat map method was used to assess the interplay between adversities from the different life domains. Demographics and results from the baseline questionnaires on self-sufficiency and perceived health and well-being were presented., Results: Nine hundred nineteen pregnant women were referred to social care (2016-2020). Overall, women had a median of six adversities, distributed over four life-domains. The heat map revealed a large variety in lived adversities, which originated from two parental clusters, one dominated by financial adversities and the other by a the combination of a broad range of adversities. The perceived health was moderate, and 25-34% experienced moderate to severe levels of depression, anxiety or stress. This did not differ between the two parental clusters., Conclusions: This study shows that highly vulnerable pregnant women deal with multiple adversities affecting not only their social and economic position but also their health and well-being., (© 2023. The Author(s).)

Laparoscopic gastrectomy has evolved differently in Eastern and Western countries. Feasibility, safety and oncological outcomes of laparoscopic gastrectomy were addressed step-by-step by several randomized controlled trials from the East. Few phase III studies were published from the West that largely did not show a difference between the laparoscopic and open approach. Despite this, laparoscopic gastrectomy is seen as the standard for the surgical treatment of early and advanced gastric cancer in many European countries. Here, we review and comment on some important studies on laparoscopic gastrectomy for gastric cancer from Eastern and Western countries and also comment on current and future challenges., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (Copyright ©2022 Chinese Journal of Cancer Research. All rights reserved.)

Infections by meningococcal species are extremely rare in the first days of life. We present a fatal case of early-onset sepsis presenting at birth, caused by intrauterine transmission of serogroup Y N. meningitidis, evidenced clinically and histologically by corresponding chorioamnionitis and N. meningitidis-positive amniotic fluid. This case confirms a long-standing suspicion that N. meningitidis can be transmitted in utero., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: In the past decade there has been an increasing interest in the field of patient-reported outcome measures (PROMs) which are now commonly used alongside traditional outcome measures, such as morbidity and mortality. Since the FACE-Q Aesthetic development in 2010, it has been widely used in clinical practice and research, measuring the quality of life and patient satisfaction. It quantifies the impact and change across different aspects of cosmetic facial surgery and minimally invasive treatments. We review how researchers have utilized the FACE-Q Aesthetic module to date, and aim to understand better whether and how it has enhanced our understanding and practice of aesthetic facial procedures., Methods: We performed a systematic search of the literature. Publications that used the FACE-Q Aesthetic module to evaluate patient outcomes were included. Publications about the development of PROMs or modifications of the FACE-Q Aesthetic, translation or validation studies of the FACE-Q Aesthetic scales, papers not published in English, reviews, comments/discussions, or letters to the editor were excluded., Results: Our search produced 1189 different articles; 70 remained after applying in- and exclusion criteria. Significant findings and associations were further explored. The need for evidence-based patient-reported outcome caused a growing uptake of the FACE-Q Aesthetic in cosmetic surgery and dermatology an increasing amount of evidence concerning facelift surgery, botulinum toxin, rhinoplasty, soft tissue fillers, scar treatments, and experimental areas., Discussion: The FACE-Q Aesthetic has been used to contribute substantial evidence about the outcome from the patient perspective in cosmetic facial surgery and minimally invasive treatments. The FACE-Q Aesthetic holds great potential to improve quality of care and may fundamentally change the way we measure success in plastic surgery and dermatology., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2022. The Author(s).)

Objectives: Mathematical modeling is increasingly used to inform cervical cancer control policies, and model-based evaluations of such policies in women living with human immunodeficiency virus (HIV) are an emerging research area. We did a scoping review of published literature to identify research gaps and inform future work in this field., Methods: We systematically searched literature up to April 2022 and included mathematical modeling studies evaluating the effectiveness or cost-effectiveness of cervical cancer prevention strategies in populations including women living with HIV. We extracted information on prevention strategies and modeling approaches., Results: We screened 1504 records and included 22 studies, almost half of which focused on South Africa. We found substantial between-study heterogeneity in terms of strategies assessed and modeling approaches used. Fourteen studies evaluated cervical cancer screening strategies, 7 studies assessed human papillomavirus vaccination (with or without screening), and 1 study evaluated the impact of HIV control measures on cervical cancer incidence and mortality. Thirteen conducted cost-effectiveness analyses. Markov cohort state-transition models were used most commonly (n = 12). Most studies (n = 17) modeled the effect of HIV by creating HIV-related health states. Thirteen studies performed model calibration, but 11 did not report the calibration methods used. Only 1 study stated that model code was available upon request., Conclusions: Few model-based evaluations of cervical cancer control strategies have specifically considered women living with HIV. Improvements in model transparency, by sharing information and making model code publicly available, could facilitate the utility of these evaluations for other high disease-burden countries, where they are needed for assisting policy makers., (Copyright © 2022 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Intensive care unit (ICU) patients with end-organ failure will require specialised machines or extracorporeal therapies to support the failing organs that would otherwise lead to death. ICU patients with severe acute kidney injury may require renal replacement therapy (RRT) to remove fluid and wastes from the body, and patients with severe cardiorespiratory failure will require extracorporeal membrane oxygenation (ECMO) to maintain adequate oxygen delivery whilst the underlying pathology is evaluated and managed. The presence of ECMO and RRT machines can further augment the existing pharmacokinetic (PK) alterations during critical illness. Significant changes in the apparent volume of distribution (V d ) and drug clearance (CL) for many important drugs have been reported during ECMO and RRT. Conventional antimicrobial dosing regimens rarely consider the impact of these changes and consequently, are unlikely to achieve effective antimicrobial exposures in critically ill patients receiving ECMO and/or RRT. Therefore, an in-depth understanding on potential PK changes during ECMO and/or RRT is required to inform antimicrobial dosing strategies in patients receiving ECMO and/or RRT. In this narrative review, we aim to discuss the potential impact of ECMO and RRT on the PK of antimicrobials and antimicrobial dosing requirements whilst receiving these extracorporeal therapies. The potential benefits of therapeutic drug monitoring (TDM) and dosing software to facilitate antimicrobial therapy for critically ill patients receiving ECMO and/or RRT are also reviewed and highlighted., (© 2022. The Author(s).)

Background: Obesity is a well-established risk factor for atrial fibrillation (AF). Whether body fat depots differentially associate with AF development remains unknown., Methods: In the prospective population-based Rotterdam Study, body composition was assessed using dual-energy X-ray absorptiometry (DXA) and liver and epicardial fat using computed tomography (CT). A body composition score was constructed by adding tertile scores of each fat depot. Principal component analysis was conducted to identify potential body fat distribution patterns. Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals (HR; 95% CI) per 1-standard deviation increase in corresponding fat depots to enable comparisons., Results: Over a median follow-up of 9.6 and 8.6 years, 395 (11.4%) and 172 (8.0%) AF cases were ascertained in the DXA and the CT analyses, respectively. After adjustments for cardiovascular risk factors, absolute fat mass (HR; 95% CI 1.33; 1.05-1.68), gynoid fat mass (HR; 95% CI 1.36; 1.12-1.65), epicardial fat mass (HR; 95% CI 1.27; 1.09-1.48), and android-to-gynoid fat ratio (HR; 95% CI 0.81; 0.70-0.94) were independently associated with new-onset AF. After further adjustment for lean mass, associations between fat mass (HR; 95% CI 1.17; 1.04-1.32), gynoid fat mass (HR; 95% CI 1.21; 1.08-1.37), and android-to-gynoid fat ratio (HR; 95% CI 0.84; 0.72-0.97) remained statistically significant. Larger body fat score was associated with a higher AF risk (HR; 95% CI 1.10; 1.02-1.20). Borderline significant association was found between a subcutaneous fat predominant pattern with AF onset (HR; 95% CI 1.21; 0.98-1.49)., Conclusions: Various body fat depots were associated with new-onset AF. Total fat mass and gynoid fat mass were independently associated with AF after adjustment for body size. The inverse association between android-to-gynoid fat ratio with AF presents a novel finding. A significant dose-response relationship between body fat accumulation and AF was observed. Our results underscore the predominant role of subcutaneous fat on AF development among a middle-aged and elderly population. Associations betw2een body fat depots, fat distribution and new-onset atrial fibrillation., Abbreviations: AF, atrial fibrillation., (© 2022. The Author(s).)

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB). METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants. RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB. CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.

Aims: No consensus exists on the clinical value of tumour regression grading (TRG) systems for therapy effects of neoadjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma. Existing TRG systems lack standardization and reproducibility, and do not consider the morphological heterogeneity of tumour response. Therefore, we aim to identify morphological tumour regression patterns of oesophageal adenocarcinoma after nCRT and their association with survival., Methods and Results: Patients with oesophageal adenocarcinoma, who underwent nCRT followed by surgery and achieved a partial response to nCRT, were identified from two Dutch upper-gastrointestinal (GI) centres (2005-18; test cohort). Resection specimens were scored for regression patterns by two independent observers according to a pre-defined three-step flowchart. The results were validated in an external cohort (2001-17). In total, 110 patients were included in the test cohort and 115 in the validation cohort. In the test cohort, two major regression patterns were identified: fragmentation (60%) and shrinkage (40%), with an excellent interobserver agreement (κ = 0.87). Here, patients with a fragmented pattern had a significantly higher pathological stage (stages III/IV: 52 versus 16%; P < 0.001), less downstaging (48 versus 91%; P < 0.001), a higher risk of recurrence [risk ratio (RR) = 2.9, 95% confidence interval (CI) = 1.5-5.6] and poorer 5-year overall survival (30 versus 80% respectively, P = 0.001)., Conclusions: The validation cohort confirmed these findings, although had more advanced cases (case-stages = III/IV 91 versus 73%, P = 0.005) and a higher prevalence of fragmented-pattern cases (80 versus 60%, P = 0.002). When combining the cohorts in multivariate analysis, the pattern of response was an independent prognostic factor [hazard ratio (HR) = 1.76, 95% CI = 1.0-3.0]. In conclusion, we established an externally validated, reproducible and clinically relevant classification of tumour response., (© 2022 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Objectives: Lithium is an effective treatment for bipolar disorder, also during pregnancy to prevent the recurrence of episodes in the perinatal period. Little is known about the neuropsychological development of lithium-exposed offspring. The current study was designed to investigate neuropsychological functioning in lithium-exposed children with the aim to provide further knowledge on the long-term effects of lithium use during pregnancy., Methods: Participants were offspring of women with a diagnosis of bipolar spectrum disorder, aged 6-14 years. In total, 99 children participated in the study, 56 were exposed to lithium in utero and 43 were not exposed to lithium. Neuropsychological tests were administered, including the Snijders-Oomen Nonverbal Intelligence Test and the NEPSY-II-NL assessment. Linear and negative binomial regression models were used to investigate the association between prenatal lithium exposure and neuropsychological functioning. In secondary analyses, the association between lithium blood level during pregnancy and neuropsychological functioning was assessed. Additionally, norm scores and percentiles for task outcomes were calculated., Results: Lithium use during pregnancy was associated with the total number of mistakes made on the Auditory Attention task, but not statistically significant after full adjustment for potential confounding factors. No association between prenatal lithium exposure and IQ was found. Also, no relationship between lithium blood level during pregnancy and neuropsychological functioning was found after adjustment for potential confounders. Task outcomes in both groups were comparable to the general population., Conclusion: In this study, we found no evidence for significantly altered neuropsychological functioning of lithium-exposed children at the age of 6-14 years, when compared to non-lithium-exposed controls., (© 2021 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Background: Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin condition and is associated with several comorbidities. Previous studies report variable prevalence rates of HS, depending on the methodology. However, the exact prevalence remains unknown., Objectives: To estimate the prevalence of HS in a large population-based cohort in the Northern Netherlands, and to compare patients with HS to the general population, investigate characteristics and identify potential associated comorbidities., Methods: Data were collected through a cross-sectional survey-based study within the Lifelines Cohort Study (n = 167 729), based on the general population located in the Northern Netherlands. A digital self-reported questionnaire was developed consisting of validated questions for determining HS., Results: Among 56 084 respondents, the overall prevalence of HS was 2.1% [95% confidence interval (CI) 2.0-2.2]. The respondents with HS had lower socioeconomic status than the controls (P < 0.001) and more frequently currently smoked (P < 0.001). Several new significant associations in patients with HS were revealed, such as fibromyalgia (OR 2.26, 95% CI 1.64-3.11), irritable bowel syndrome (OR 1.63, 95% CI 1.18-2.26), chronic fatigue syndrome (OR 1.72, 95% CI 1.06-2.78) and migraine (OR 1.48, 95% CI 1.11-1.96). Fibromyalgia and chronic fatigue syndrome remained significantly associated with HS in the multivariate analysis after adjusting for age, sex, body mass index, smoking status and socioeconomic status., Conclusions: Our study showed a higher prevalence of HS in the Northern Netherlands compared with the overall estimated prevalence of 1% and identified several new associated comorbidities., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease that leads to lung scarring. Cough is reported by 85% of patients with IPF and can be a distressing symptom with a significant impact on patients' quality of life. There are no proven effective therapies for IPF-related cough. Whilst morphine is frequently used as a palliative agent for breathlessness in IPF, its effects on cough have never been tested. PAciFy Cough is a multicenter, double-blind, placebo-controlled, crossover trial of morphine sulphate for the treatment of cough in IPF., Methods: We will recruit 44 subjects with IPF prospectively from three interstitial lung disease units in the UK, namely the Royal Brompton Hospital, Manchester University NHS Foundation Trust (MFT) and Aintree University Hospital NHS Foundation Trust. Patients will be randomised (1:1) to either placebo twice daily or morphine sulphate 5 mg twice daily for 14 days. They will then crossover after a 7-day washout period. The primary endpoint is the percent change in daytime cough frequency (coughs per hour) from baseline as assessed by objective cough monitoring at day 14 of treatment., Discussion: This multicentre, randomised trial will assess the effect of opioids on cough counts and cough associated quality of life in IPF subjects. If proven to be an effective intervention, it represents a readily available treatment for patients., Trial Registration: The study was approved by the UK Medicines and Healthcare Regulatory Agency (Ref: CTA 21268/0224/001-0001 - EUDRACT 2019-003571-19 - Protocol Number RBH2019/001) on 08 April 2020, in compliance with the European Clinical Trials Directive and the Medicines for Human Use (Clinical Trials) Regulations 2004 and its subsequent amendments. The study was provided with ethical approval by the London Brent Research Ethics Committee (Ref: 20/LO/0368) on 21 May 2020 and is registered with clinicaltrials.gov (NCT04429516) on 12 June 2020, available at https://clinicaltrials.gov/ct2/show/NCT04429516., (© 2022. The Author(s).)

Objective: To evaluate current practice and outcomes of pregnancy in women previously diagnosed with Budd-Chiari syndrome and/or portal vein thrombosis, with and without concomitant portal hypertension., Design and Setting: Multicentre retrospective cohort study between 2008 and 2021., Population: Women who conceived in the predefined period after the diagnosis of Budd-Chiari syndrome and/or portal vein thrombosis., Methods and Main Outcome Measures: We collected data on diagnosis and clinical features. The primary outcomes were maternal mortality and live birth rate. Secondary outcomes included maternal, neonatal and obstetric complications., Results: Forty-five women (12 Budd-Chiari syndrome, 33 portal vein thrombosis; 76 pregnancies) were included. Underlying prothrombotic disorders were present in 23 of the 45 women (51%). Thirty-eight women (84%) received low-molecular-weight heparin during pregnancy. Of 45 first pregnancies, 11 (24%) ended in pregnancy loss and 34 (76%) resulted in live birth of which 27 were at term (79% of live births and 60% of pregnancies). No maternal deaths were observed; one woman developed pulmonary embolism during pregnancy and two women (4%) had variceal bleeding requiring intervention., Conclusions: The high number of term live births (79%) and lower than expected risk of pregnancy-related maternal and neonatal morbidity in our cohort suggest that Budd-Chiari syndrome and/or portal vein thrombosis should not be considered as an absolute contraindication for pregnancy. Individualised, nuanced counselling and a multidisciplinary pregnancy surveillance approach are essential in this patient population., Tweetable Abstract: Budd-Chiari syndrome and/or portal vein thrombosis should not be considered as an absolute contraindication for pregnancy., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Introduction: Information on the long-term performance of biosynthetic meshes is scarce. This study analyses the performance of biosynthetic mesh (Phasix™) over 24 months., Methods: A prospective, international European multi-center trial is described. Adult patients with a Ventral Hernia Working Group (VHWG) grade 3 incisional hernia larger than 10 cm 2 , scheduled for elective repair, were included. Biosynthetic mesh was placed in sublay position. Short-term outcomes included 3-month surgical site occurrences (SSO), and long-term outcomes comprised hernia recurrence, reoperation, and quality of life assessments until 24 months., Results: Eighty-four patients were treated with biosynthetic mesh. Twenty-two patients (26.2%) developed 34 SSOs, of which 32 occurred within 3 months (primary endpoint). Eight patients (11.0%) developed a hernia recurrence. In 13 patients (15.5%), 14 reoperations took place, of which 6 were performed for hernia recurrence (42.9%), 3 for mesh infection (21.4%), and in 7 of which the mesh was explanted (50%). Compared to baseline, quality of life outcomes showed no significant difference after 24 months. Despite theoretical resorption, 10.7% of patients reported presence of mesh sensation in daily life 24 months after surgery., Conclusion: After 2 years of follow-up, hernia repair with biosynthetic mesh shows manageable SSO rates and favorable recurrence rates in VHWG grade 3 patients. No statistically significant improvement in quality of life or reduction of pain was observed. Few patients report lasting presence of mesh sensation. Results of biosynthetic mesh after longer periods of follow-up on recurrences and remodeling will provide further valuable information to make clear recommendations., Trial Registration: Registered on clinicaltrials.gov (NCT02720042), March 25, 2016., (© 2021. The Author(s).)

Aims: Lifestyle changes, such as increasing physical activity (PA), are a cornerstone of treatment of patients with chronic heart failure (HF). However, improving PA in HF patients is challenging, and low participation rates for cardiac rehabilitation (CR) as well as relapse to low PA levels after CR are major issues. We designed a randomized controlled trial to investigate if PA monitoring with motivational feedback before and after centre-based CR in HF patients with reduced ejection fraction (HFrEF) will lead to a clinically meaningful increase in physical fitness., Methods and Results: A randomized controlled trial will be conducted in a sample of 180 HFrEF patients (New York Heart Association Class II/III) who are referred to 12-week standard CR. Patients will be randomized (2:1) to (1) standard of care (SoC) plus wearing a PA monitoring device (Fitbit Charge 3) with personalized step goals, feedback and motivation or (2) SoC only. The intervention lasts ±7 months: 4-5 weeks before CR, 12 weeks during CR and 12 weeks after CR. Measurements will take place at three time points. The primary endpoint is the change in the distance in 6-min walking test (6MWT) over the entire study period. Other endpoints include step count, grip strength, quality of life and all-cause mortality or hospitalization., Conclusions: HF-aPProACH will provide novel information on the effectiveness of remote PA stimulation and feedback before, during and after standard CR using a commercially available device to improve physical fitness in HFrEF patients., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Agonist bias occurs when different ligands produce distinct signalling outputs when acting at the same receptor. However, its physiological relevance is not always clear. Using primary human cells and gene editing techniques, we demonstrate endogenous agonist bias with physiological consequences for the calcitonin receptor-like receptor, CLR. By switching the receptor-activity modifying protein (RAMP) associated with CLR we can "re-route" the physiological pathways activated by endogenous agonists calcitonin gene-related peptide (CGRP), adrenomedullin (AM) and adrenomedullin 2 (AM2). AM2 promotes calcium-mediated nitric oxide signalling whereas CGRP and AM show pro-proliferative effects in cardiovascular cells, thus providing a rationale for the expression of the three peptides. CLR-based agonist bias occurs naturally in human cells and has a fundamental purpose for its existence. We anticipate this will be a starting point for more studies into RAMP function in native environments and their importance in endogenous GPCR signalling.

Background: A threshold Injury Severity Score (ISS) ≥ 16 is common in classifying major trauma (MT), although the Abbreviated Injury Scale (AIS) has been extensively revised over time. The aim of this study was to determine effects of different AIS revisions (1998, 2008 and 2015) on clinical outcome measures., Methods: A retrospective observational cohort study including all primary admitted trauma patients was performed (in 2013-2014 AIS98 was used, in 2015-2016 AIS08, AIS08 mapped to AIS15). Different ISS thresholds for MT and their corresponding observed mortality and intensive care (ICU) admission rates were compared between AIS98, AIS08, and AIS15 with Chi-square tests and logistic regression models., Results: Thirty-nine thousand three hundred seventeen patients were included. Thresholds ISS08 ≥ 11 and ISS15 ≥ 12 were similar to a threshold ISS98 ≥ 16 for in-hospital mortality (12.9, 12.9, 13.1% respectively) and ICU admission (46.7, 46.2, 46.8% respectively). AIS98 and AIS08 differed significantly for in-hospital mortality in ISS 4-8 (χ 2  = 9.926, p = 0.007), ISS 9-11 (χ 2  = 13.541, p = 0.001), ISS 25-40 (χ 2  = 13.905, p = 0.001) and ISS 41-75 (χ 2  = 7.217, p = 0.027). Mortality risks did not differ significantly between AIS08 and AIS15., Conclusion: ISS08 ≥ 11 and ISS15 ≥ 12 perform similarly to a threshold ISS98 ≥ 16 for in-hospital mortality and ICU admission. This confirms studies evaluating mapped datasets, and is the first to present an evaluation of implementation of AIS15 on registry datasets. Defining MT using appropriate ISS thresholds is important for quality indicators, comparing datasets and adjusting for injury severity., Level of Evidence: Prognostic and epidemiological, level III.

Light transmission aggregometry (LTA) is considered the gold standard method for evaluation of platelet function. However, there are a lot of variation in protocols (pre-analytical procedures and agonist concentrations) and results. The aim of our study was to establish a national LTA protocol, to investigate the effect of standardization and to define national reference values for LTA. The SSC guideline was used as base for a national procedure. Almost all recommendations of the SSC were followed e.g. no adjustment of PRP, citrate concentration of 109 mM, 21 needle gauge, fasting, resting time for whole blood and PRP, centrifugation time, speed and agonists concentrations. LTA of healthy volunteers was measured in a total of 16 hospitals with 5 hospitals before and after standardization. Results of more than 120 healthy volunteers (maximum aggregation %) were collected, with participating laboratories using 4 different analyzers with different reagents. Use of low agonist concentrations showed high variation before and after standardization, with the exception of collagen. For most high agonist concentrations (ADP, collagen, ristocetin, epinephrine and arachidonic acid) variability in healthy subjects decreased after standardization. We can conclude that a standardized Dutch protocol for LTA, based on the SSC guideline, does not result in smaller variability in healthy volunteers for all agonist concentrations.

Sexuality is frequently disturbed in prostate cancer (PC), the most common cancer in men. This article addresses aspects of sexuality in the diagnostic phase of PC. Combined with this information, the role of health care professionals (HCPs) is elucidated, with particular attention to assessment, information and education.

Campylobacter jejuni is the pathogen most commonly associated with Guillain-Barré syndrome (GBS). The present work describes the draft genome sequences of 3 C. jejuni strains, BD39, BD67, and BD75, isolated from stool specimens of patients with C. jejuni -triggered GBS using Illumina technologies., (Copyright © 2021 Islam et al.)

Objectives: To present the short-term and long-term outcomes of the psoas hitch procedure in a large cohort with long-term follow-up., Patients and Methods: A multicenter, retrospective cohort study was conducted. Patients were included if they had undergone an open psoas hitch procedure with ureteral reimplantation for different types of distal ureteral pathology between 1993 and 2017. Clinical failure was defined as radiologically-proven obstruction of the ureteroneocystostomy and/or post-operative complaints requiring additional surgery. Pre-operative demographic data and post-operative radiological imaging were collected. Complications were categorized as peri-operative, acute (<30 days), and long-term complications., Results: A total of 166 patients had undergone a psoas hitch procedure, with a median follow-up of 15 months (IQR 6-45). Indications for the procedure included intra-operative injury of the ureter during gynecological, urological or general surgery, transitional cell carcinoma of the distal ureter, fistulae, (radiation) fibrosis, and trauma. There was no significant difference in pre- and post-operative estimated glomerular filtration rate. Post-operative complications included urinary leakage, recurrent urinary tract symptoms, recurrent malignancy, and kidney failure. Postoperative imaging was available in 143 patients. Failure of the psoas hitch procedure was seen in 8% (11/143) of the patients. In 55% (6/11) of these patients, radiation fibrosis was the indication for the psoas hitch procedure., Conclusion: This study provides greater insight into the long-term complications of the open psoas hitch procedure in adults. The psoas hitch procedure can be considered a safe procedure for restoring the continuity of the ureter for different types of ureteral pathologies in adult patients. However, patients with a history of radiation therapy causing retroperitoneal fibrosis might be more prone to failure after the procedure., Competing Interests: We declare no competing interests., (© 2021 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Extracorporeal blood purification is considered an adjunct therapy in critically ill patients with life-threatening conditions such as sepsis and septic shock. It consists of cytokine removal, removal of endotoxins, a combination of both, or the removal of pathogens themselves. The latter technique was introduced for clinical application very recently. This case study describes a case of a 69-year-old female lung transplant recipient patient with a persistent VV-ECMO-related septic deep vein thrombosis with continuous renal replacement therapy-dependent acute kidney injury initiated on the Seraph®-100 Microbind Affinity Filter in order to control the persistent bacteraemia with coagulase-negative staphylococci. Drug plasma concentrations (vancomycin, tacrolimus, and mycophenolic acid) were measured before and after the device to calculate absorber-related drug clearance., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Rationale: Despite interventions to improve detection rates, domestic violence, and abuse (DVA) remains largely undetected by healthcare services. We therefore aimed to examine the acceptability, feasibility, and sustainability of an intervention aiming to improve DVA detection rates, which included a clear referral pathway (i.e., the BRAVE intervention) and to explore the acceptability and feasibility of DVA management and referrals in general, in the context of low detection rates. Methods: Qualitative study design with four focus groups of 16 community mental health (CMH) clinicians from both control and intervention arms. The focus groups discussed managing DVA in clinical practice and staff experiences with the BRAVE intervention in particular. Focus groups continued until saturation of the subject was reached. Interviews were analyzed using a thematic analysis approach. Results: DVA was seen to be highly relevant to mental healthcare but is also a very sensitive subject. Barriers in CMH professionals, institutions, and society meant CMH professionals often refrained from asking about DVA in patients. Barriers included communication difficulties between CMH professionals and DVA professionals, a fear of disrupting the therapeutic alliance with the patient, and a lack of appropriate services to help victims of DVA. Conclusion: The BRAVE intervention was acceptable but not feasible or sustainable. Personal, institutional, and public barriers make it not feasible for CMH professionals to detect DVA in mental healthcare. To increase the detection of DVA, professional standards should be combined with training, feedback sessions with peers and DVA counselors, and routine enquiry about DVA. Clinical Trial Registration: ISRCTN, trial registration number: ISRCTN14115257., (Copyright © 2020 Ruijne, Kamperman, Trevillion, Garofalo, van der Gaag, Zarchev, Bogaerts, Howard and Mulder.)

Background: Previous studies indicated that affect fluctuations, the use of antidepressant medication (ADM), as well as depression during pregnancy might have adverse effects on offspring outcomes. The aim of the current proof-of-principle study is to explore the effect of tapering ADM while receiving online preventive cognitive therapy (PCT) on pregnant women and the offspring as compared to pregnant women continuing ADM. Objectives: We sought to compare positive and negative affect fluctuations in pregnant women receiving online PCT while tapering ADM vs. pregnant women continuing ADM, and to investigate if affect fluctuations in early pregnancy were related to offspring birth weight. Method: An experience sampling methodology (ESM)-trial ran alongside a Dutch randomized controlled trial (RCT) and prospective observational cohort of women using ADM at the start of pregnancy. In the ESM-trial fluctuations of positive and negative affect were assessed in the first 8 weeks after inclusion. Recurrences of depression were assessed up to 12 weeks post-partum, and birth records were used to assess offspring birth weight. The RCT has been registered at the Netherlands Trial Register (NTR4694, https://www.trialregister.nl/trial/4551). Results: In total, 19 pregnant women using ADM at start of their pregnancy participated in the ESM-trial. There were no significant differences in positive and negative affect fluctuations, nor recurrence rates between women receiving PCT while tapering ADM vs. women continuing ADM. We found no association between affect fluctuations, pre-natal depressive symptoms, and birth weight (all p > 0.05). Conclusion: This explorative study showed that tapering ADM while receiving online PCT may protect pregnant women against recurrences of depression and affect fluctuations, without affecting birth weight. There is a high need for more controlled studies focusing on tapering ADM with (online) psychological interventions during pregnancy., (Copyright © 2020 Brouwer, Molenaar, Burger, Williams, Albers, Lambregtse-van den Berg and Bockting.)

Background: In this study, we explored the role of colonization in health care workers (HCWs) in transmission of methicillin-susceptible Staphylococcus aureus (MSSA) to neonates at a level IV neonatal intensive care unit (NICU)., Methods: All available screening and clinical MSSA isolates, from the period March 2015 through April 2016, isolated from HCWs and neonates at the level IV NICU, were included. MSSA isolates were initially genotyped using spa typing, and for the most prevalent spa types, whole-genome sequencing (WGS) was performed., Results: From March 2015 through April 2016, 159 neonates and 115 HCWs were found positive for MSSA, and all isolates were typed by means of spa typing. Twenty-three spa types were found in both HCWs and neonates. Within the most prevalent spa types (t002, t015 and t2787), 4 WGS clusters of genetically indistinguishable MSSA isolates were found in which 4 HCWs and 35 neonates were involved. A total of 10 neonates included in the 4 WGS clusters suffered from bacteremia., Conclusions: We showed that HCWs carried the same MSSA isolates as those found in neonates, and that HCWs might serve as a reservoir for transmission of MSSA to neonates. Ten neonates suffered from a bacteremia caused by a MSSA previously detected in a HCW., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Acute kidney injury is frequent in critically ill children; however, it varies in causality and epidemiology according to the level of patient care complexity. A multicenter prospective cohort study was conducted in four medium-complexity pediatric intensive care units from the Colombian southeast aimed to estimate the clinical prognosis of patients with diagnosis of acute kidney injury., Methods: We included children >28 days and <18 years of age, who were admitted with diagnosis of acute kidney injury classified by Kidney Disease Improving Global Outcomes (KDIGO), during the period from January to December 2017. Severe acute kidney injury was defined as stage 2 and stage 3 classifications. Maximum KDIGO was evaluated during the hospital stay and follow up. Length of hospital stay, use of mechanical ventilation and vasoactive drugs, use of renal replacement therapy, and mortality were assessed until discharge., Results: Prevalence at admission of acute kidney injury was 5.2% (95%CI 4.3% to 6.2%). It was found that 71% of the patients had their maximum KDIGO on day one; an increment in the maximum stage of acute kidney injury increased the pediatric intensive care unit stay. Patients with maximum KDIGO 3 were associated with greater use of mechanical ventilation (47%), compared with maximum KDIGO 2 (37%) and maximum KDIGO 1 (16%). Eight patients with maximum KDIGO 2 and 14 with maximum KDIGO 3 required renal replacement therapy. Mortality was at 11.8% (95%CI 6.4% to 19.4%)., Conclusion: Acute kidney injury, established and classified according to KDIGO as severe and its maximum stage, was associated with worse clinical outcomes; early therapeutic efforts should focus on preventing the progression to severe stages., Competing Interests: The authors have declared that no competing interests exist.