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Objective: This study evaluated the nationwide trends in care and accompanied postoperative outcomes for patients with distal esophageal and gastro-esophageal junction cancer.Summary of Background Data: The introduction of transthoracic esophagectomy, minimally invasive surgery, and neo-adjuvant chemo(radio)therapy changed care for patients with esophageal cancer.Methods: Patients after elective transthoracic and transhiatal esophagectomy for distal esophageal or gastroesophageal junction carcinoma in the Netherlands between 2007-2016 were included. The primary aim was to evaluate trends in both care and postoperative outcomes for the included patients. Additionally, postoperative outcomes after transthoracic and tran-shiatal esophagectomy were compared, stratified by time periods.Results: Among 4712 patients included, 74% had distal esophageal tumors and 87% had adenocarcinomas. Between 2007 and 2016, the proportion of transthoracic esophagectomy increased from 41% to 81%, and neo-adjuvant treatment and minimally invasive esophagectomy increased from 31% to 96%, and from 7% to 80%, respectively. Over this 10-year period, postoperative outcomes improved: postoperative morbidity decreased from 66.6% to 61.8% (P = 0.001), R0 resection rate increased from 90.0% to 96.5% (P Conclusion: In this nationwide cohort, a transition towards more neo-adju-vant treatment, transthoracic esophagectomy and minimally invasive surgery was observed over a 10-year period, accompanied by decreased postoperative morbidity, improved surgical radicality and lymph node harvest, and improved survival.

Intensive care medicine 47(10), 1115-1129 (2021). doi:10.1007/s00134-021-06484-1, Published by Springer, Berlin

BackgroundOver the last decades, a decrease in short-term mortality in cancer patients admitted to the ICU has been described in literature. However, it is unclear whether this decrease also results in a decrease in long-term mortality. Therefore, we examined the 1-year mortality of cancer patients (either haematological or solid) with an unplanned ICU admission.Methods and dataAll adult patients registered in the National Intensive Care Evaluation registry with an unplanned ICU admission in the Netherlands between 2008 and 2017 were included. The primary outcome was 1-year mortality, analysed with a mixed-effects cox-proportional hazard regression. We examined the trend in mortality rates over the inclusion period. Furthermore, we compared the 1-year mortality of cancer patients to that of patients without cancer. ResultsWe included 470,305 patients: 10,401 with haematological cancer, 35,920 with solid tumours, and 423,984 without cancer. The 1-year mortality rates were 60.1%, 46.2%, and 28.3% (pConclusionThe 1-year mortality in cancer patients with an unplanned ICU admission (either haematological or solid) was significantly higher than that of patients without cancer. A visual inspection showed a slight decrease in 1-year mortality in haematological patients, while the 1-year mortality in patients with a solid tumour varied per year. After hospital discharge, a considerable part of the patients with a malignancy died within 1 year. Physicians should discuss the long-term prognosis after an ICU admission with patients and relatives in order to manage treatments and expectations. Future research should focus on identifying cancer patients who will benefit from an ICU admission.

Objectives This study aimed to summarise the competencies and legal position of the dental hygienist (DH) regarding oral radiology through a worldwide review. Methods A structured and peer-reviewed online questionnaire of 27 questions was developed. This was emailed to all DH associations that are members of the International Federation of Dental Hygienists (IFDH) or European Dental Hygienists Federation (EDHF). After obtaining the data, all responding associations were contacted to confirm that the data were summarised in the correct order and were asked to provide further clarification of answers if necessary. A descriptive analysis was performed to summarise the data. Results The response rate was 84%, as 26 out of 31 countries completed the questionnaire. In 78% of the countries, the DH can legally take intraoral radiographs, but in 42% of the countries, the dentist first needs to provide a referral or indication for a radiograph. In 46% of the countries, the DH may not formulate a diagnosis based on a radiograph. In only 27% of the countries, the DH can independently own radiographic equipment. Conclusions The required qualifications, skills, and scope of practice of the DH regarding oral radiology vary by country and, within some countries, even vary by state or province.

Background Fecal metabolomic profiles differ between pediatric inflammatory bowel disease (IBD) patients and controls and may provide new insights in the pathophysiology of IBD. The role of amino acids, however, is not fully elucidated. We aimed to assess fecal amino acid profiles in pediatric IBD. Methods In this case-control study, treatment-naïve, newly diagnosed pediatric IBD patients and a non-IBD control group, matched based on sex and age, were included in 2 tertiary centres. Fecal amino acid profiles were assessed using a targeted high-performance liquid chromatography technique. A random forest classifier method was used to develop a prediction model differentiating IBD from controls and predicting IBD phenotype. The association between IBD localization and amino acid concentrations was tested with ordinal regression models. Results We included 78 newly diagnosed IBD patients (40 Crohn’s disease [CD], 38 ulcerative colitis [UC]) and 105 controls. Patients with IBD could be differentiated from controls with an accuracy of 82% (sensitivity 63%, specificity 97%). Twenty-nine out of the 42 measured unique amino acids were included in the prediction model. Increased levels of tryptophan, taurine, alanine, ornithine, valine, histidine, and leucine were the most differentiating features. Children with CD and UC could be differentiated from the controls with an accuracy of 80% and 90%, respectively. Inflammatory bowel disease phenotype could not be predicted. Tryptophan, valine, and histidine levels were positively associated with more extended disease in UC patients (P < .05). Conclusions Fecal amino acids may enhance understanding of the role of host-microbial interactions in the pathophysiology of IBD and may evolve into biomarkers for pediatric IBD diagnostic and personalized medicine.

Randomized clinical trials have shown that transcatheter aortic valve replacement is noninferior to surgery in low surgical risk patients. We compared outcomes in patients treated with a sutured (stented or stentless) or sutureless surgical valve from the Evolut Low Risk Trial.The Evolut Low Risk Trial enrolled patients with severe aortic stenosis and low surgical risk. Patients were randomized to self-expanding transcatheter aortic valve replacement or surgery. Use of sutureless or sutured valves was at the surgeons' discretion.Six hundred eighty patients underwent surgical aortic valve implantation (205 sutureless, 475 sutured). The Valve Academic Research Consortium-2 30-day safety composite endpoint was similar in the sutureless and sutured group (10.8% vs 11.0%, P = .93). All-cause mortality between groups was similar at 30 days (0.5% vs 1.5%, P = .28) and 1 year (3.3% vs 2.6%, P = .74). Disabling stroke was also similar at 30 days (2.0% vs 1.5%, P = .65) and 1 year (2.6% vs 2.2%, P = .76). Permanent pacemaker implantation at 30 days was significantly higher in the sutureless compared with the sutured group (14.4% vs 2.9%, P.001). Aortic valve-related hospitalizations occurred more often at 1 year with sutureless valves (9.1% vs 5.1%, P = .04). Mean gradients 1 year after sutureless and sutured aortic valve replacement were 9.9 ± 4.2 versus 11.7 ± 4.7 mm Hg (P.001).Among low-risk patients, sutureless versus sutured valve use did not demonstrate a benefit in terms of 30-day complications and produced marginally better hemodynamics but with an increased rate of pacemaker implantation and valve-related hospitalizations.

Background and Aim: Wound healing is a dynamic and complex process that requires an appropriate environment to promote healing process. The healing of distant flaps in cats is determined by vascularization, nutrient sufficiency for the cells, and stability of skin flaps. This study aims to evaluate the healing of distant flaps treated with moist wound dressing through subjective and objective observation in five cats with wounds in the forelimb and hindlimb area to determine the time to cut the skin flaps from the donor site. Materials and Methods: In this study, five Indonesian local cats with wounds of various sizes in the limb were brought to the Veterinary Teaching Hospital. The sterile wound treatment included the administration of anesthesia, wound debridement, and distant flap closure in the thoracic and abdominal area. The distant flap and time to cut the skin flaps from the donor site were evaluated through subjective and objective examinations. Results: The subjective observation on the color of the distant skin flaps showed redness and response to pain on day 3 after surgery, whereas the objective observation, which was based on drug absorption capability and drug effect showed good results. On day 7 after surgery, the skin flaps from the donor site were cut and showed good progress. Conclusion: Overall, moist dressing helps in stabilizing the distant flap, allowing the distant flaps from the donor site to be cut on day 7 after surgery.

Background The coronavirus disease 2019 (COVID-19) pandemic dramatically increased the number of patients requiring treatment in an intensive care unit or invasive mechanical ventilation worldwide. Delirium is a well-known neuropsychiatric complication of patients with acute respiratory diseases, representing the most frequent clinical expression of acute brain dysfunction in critically ill patients, especially in those undergoing invasive mechanical ventilation. Among hospitalized patients with COVID-19, delirium incidence ranges from 11% to 80%, depending on the studied population and hospital setting. Objective To determine risk factors for the development of delirium in hospitalized patients with COVID-19 pneumonia. Methods We retrospectively studied consecutive hospitalized adult (≥18 y) patients with confirmed COVID-19 pneumonia from March 15 to July 15, 2020, in a tertiary-care hospital in Mexico City. Delirium was assessed by the attending physician or trained nurse, with either the Confusion Assessment Method for the intensive care unit or the Confusion Assessment Method brief version, according to the appropriate diagnostic tool for each hospital setting. Consultation-liaison psychiatrists and neurologists confirmed all diagnoses. We calculated adjusted hazard ratios (aHR) with 95% confidence interval (CI) using a Cox proportional-hazards regression model. Results We studied 1017 (64.2% men; median age, 54 y; interquartile range 44–64), of whom 166 (16.3%) developed delirium (hyperactive in 75.3%); 78.9% of our delirium cases were detected in patients under invasive mechanical ventilation. The median of days from admission to diagnosis was 14 (interquartile range 8–21) days. Unadjusted mortality rates between delirium and no delirium groups were similar (23.3% vs. 24.1; risk ratio 0.962, 95% CI 0.70–1.33). Age (aHR 1.02, 95% CI 1.01–1.04; P = 0.006), an initial neutrophil-to-lymphocyte ratio ≥9 (aHR 1.81, 95% CI 1.23–2.65; P = 0.003), and requirement of invasive mechanical ventilation (aHR 3.39, 95% CI 1.47–7.84; P = 0.004) were independent risk factors for in-hospital delirium development. Conclusions Delirium is a common in-hospital complication of patients with COVID-19 pneumonia, associated with disease severity; given the extensive number of active COVID-19 cases worldwide, it is essential to detect patients who are most likely to develop delirium during hospitalization. Improving its preventive measures may reduce the risk of the long-term cognitive and functional sequelae associated with this neuropsychiatric complication.

Contains fulltext : 251531.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To quantify the impact of individual complications on mortality, organ failure, hospital stay, and readmission after pancreatoduodenectomy. SUMMARY OF BACKGROUND DATA: An initial complication may provoke a sequence of adverse events potentially leading to mortality after pancreatoduodenectomy. This study was conducted to aid prioritization of quality improvement initiatives. METHODS: Data from consecutive patients undergoing pancreatoduodenectomy (2014-2017) were extracted from the Dutch Pancreatic Cancer Audit. Population attributable fractions (PAF) were calculated for the association of each complication (ie, postoperative pancreatic fistula, postpancreatectomy hemorrhage, bile leakage, delayed gastric emptying, wound infection, and pneumonia) with each unfavorable outcome [ie, in-hospital mortality, organ failure, prolonged hospital stay (>75th percentile), and unplanned readmission), whereas adjusting for confounders and other complications. The PAF represents the proportion of an outcome that could be prevented if a complication would be eliminated completely. RESULTS: Overall, 2620 patients were analyzed. In-hospital mortality occurred in 95 patients (3.6%), organ failure in 198 patients (7.6%), and readmission in 427 patients (16.2%). Postoperative pancreatic fistula and postpancreatectomy hemorrhage had the greatest independent impact on mortality [PAF 25.7% (95% CI 13.4-37.9) and 32.8% (21.9-43.8), respectively] and organ failure [PAF 21.8% (95% CI 12.9-30.6) and 22.1% (15.0-29.1), respectively]. Delayed gastric emptying had the greatest independent impact on prolonged hospital stay [PAF 27.6% (95% CI 23.5-31.8)]. The impact of individual complications on unplanned readmission was smaller than 11%. CONCLUSION: Interventions focusing on postoperative pancreatic fistula and postpancreatectomy hemorrhage may have the greatest impact on in-hospital mortality and organ failure. To prevent prolonged hospital stay, initiatives should in addition focus on delayed gastric emptying.

This paper describes the design of the Armed4Stroke program. Patients after stroke and their caregivers are included as a couple. The caregiver is trained as a co-therapist by a physiotherapist experienced in providing caregiver-mediated exercises (CME) to support and motivate the patient. The program consists of 8 weeks of gait and gait-related exercises, complementary to regular rehabilitation therapy. The couple will receive a tailor-made exercise program, which is adapted to the patients’ abilities and goals and is progressive in nature. The program is supported by videos with exercise instructions, which are accessible using a web-based tele-rehabilitation system. It is hypothesized that CME, supported with tele-rehabilitation is able to promote daily mobility and to reduce anxiety and depression in patients after stroke and their caregivers.

Background: Stomach cancer is the fifth most common malignancy. In 2012, 952,000 cancers were diagnosed worldwide, which led to 723,000 deaths. Elderly men are the most frequently observed category of gastric cancer patients, mostly affecting the antrum. The objective of this study was to analyze the association of age with sex, tumor sites, types of surgical intervention, and diagnosed anatomical pathologies in cases of gastric cancer. Methods: This cross-sectional descriptive study analyzed the associations between age, sex, tumor sites, types of surgical intervention, and diagnosed anatomical pathologies among the total gastric cancer incidences during medical treatments from January 2016 to May 2019. The study samples were collected from the total gastric cancer respondents who met the inclusion criteria during medical treatments within the study period. Results: Gastric cancer was most frequently observed among females (56%) and those aged 50–70 years old (47%). Most respondents had advanced stages of gastric cancer at first enrollment at our institution. The most frequently found tumor site was the corpus (43%). The most frequently performed type of surgical intervention was jejunostomy feeding (26%), and the most frequently diagnosed anatomical pathology was adenocarcinoma with poorly differentiation (39%). Overall, age had statistically significant correlations with sex (p 50 years old), gastric cancer was more prevalent in women than men, and the gastric tumor tended to be more distal. Non-cardia gastric cancers were more prevalent than cardia gastric cancers.

OBJECTIVES: To evaluate current international practice in PICUs regarding components of the "Assessing Pain, Both Spontaneous Awakening and Breathing Trials, Choice of Sedation, Delirium Monitoring/Management, Early Exercise/ Mobility, and Family Engagement/Empowerment"(ABCDEF) bundle. DESIGN: Online surveys conducted between 2017 and 2019. SETTING: One-hundred sixty-one PICUs across the United States (n = 82), Canada (n = 14), Brazil (n = 27), and Europe (n = 38) participating in the Prevalence of Acute Rehabilitation for Kids in the PICU study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 161 participating PICUs, 83% were in academic teaching hospitals and 42% were in free-standing children's hospitals. Median size was 16 beds (interquartile range, 10-24 beds). Only 15 PICUs (9%) had incorporated all six ABCDEF bundle components into routine practice. Standardized pain assessment (A) was the most common (91%), followed by family engagement (F, 88%) and routine sedation assessment (C) with validated scales (84%). Protocols for testing extubation readiness or conducting spontaneous breathing trials (B) were reported in 57%, with 34% reporting a ventilator weaning protocol. Routine delirium monitoring with a validated screening tool (D) was reported by 44% of PICUs, and 26% had a guideline, protocol, or policy for early exercise/mobility (E). Practices for spontaneous breathing trials were variable in 29% of Canadian PICUs versus greater than 50% in the other regions. Delirium monitoring was lowest in Brazilian PICUs (18%) versus greater than 40% in other regions, and family engagement was reported in 55% of European PICUs versus greater than 90% in other regions. CONCLUSIONS: ABCDEF bundle components have been adopted with substantial variability across regions. Additional research must rigorously evaluate the efficacy of specific elements with a focus on B, D, E, and full ABCDEF bundle implementation. Implementation science is needed to facilitate an understanding of the barriers to ABCDEF implementation and sustainability with a focus on specific cultural and regional differences.

Background & Aims Nonpedunculated colorectal polyps are normally endoscopically removed to prevent neoplastic progression. Delayed bleeding is the most common major adverse event. Clipping the resection defect has been suggested to reduce delayed bleedings. Our aim was to determine if prophylactic clipping reduces delayed bleedings and to analyze the contribution of polyp characteristics, extent of defect closure, and antithrombotic use. Methods An individual patient data meta-analysis was performed. Studies on prophylactic clipping in nonpedunculated colorectal polyps were selected from PubMed, Embase, Web of Science, and Cochrane database (last selection, April 2020). Authors were invited to share original study data. The primary outcome was delayed bleeding ≤30 days. Multivariable mixed models were used to determine the efficacy of prophylactic clipping in various subgroups adjusted for confounders. Results Data of 5380 patients with 8948 resected polyps were included from 3 randomized controlled trials, 2 prospective, and 8 retrospective studies. Prophylactic clipping reduced delayed bleeding in proximal polyps ≥20 mm (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.44–0.88; number needed to treat = 32), especially with antithrombotics (OR, 0.59; 95% CI, 0.35–0.99; number needed to treat = 23; subgroup of anticoagulants/double platelet inhibitors: n = 226; OR, 0.40; 95% CI, 0.16–1.01; number needed to treat = 12). Prophylactic clipping did not benefit distal polyps ≥20 mm with antithrombotics (OR, 1.41; 95% CI, 0.79–2.52). Conclusions Prophylactic clipping reduces delayed bleeding after resection of nonpedunculated, proximal colorectal polyps ≥20 mm, especially in patients using antithrombotics. No benefit was found for distal polyps. Based on this study, patients can be identified who may benefit from prophylactic clipping. (PROSPERO registration number CRD42020104317.)

This field experiment examined whether the well-documented benefit of spaced over massed training for humans and other animals generalizes to horses. Twenty-nine randomly selected horses (Equus ferus caballus) repeatedly encountered a novel obstacle-crossing task while under saddle. Horses were randomly assigned to the spaced-training condition (2 min work, 2 min rest, 2 min work, 2 min rest) or the massed-training condition (4 min work, 4 min rest). Total training time per session and total rest per session were held constant. Days between sessions (M = 3) were held as consistent as possible given the constraints of conducting research on a working ranch and safety–threatening weather conditions. During each training session, the same hypothesis-naïve rider shaped horses to cross a novel obstacle. Fifteen of 16 horses in the spaced-training condition reached performance criterion (94% success) while only 5 of 13 horses in the massed-training condition reached performance criterion (39% success). Horses in the spaced-training condition also initiated their first obstacle-crossing faster than horses in the massed-training condition and were faster at completing eight crossings than horses in the massed-training condition. Overall, task acquisition was higher for horses undergoing spaced training despite both groups experiencing the same total work and rest time per session. These findings generalize the learning-performance benefit observed in human spaced practice to horses and offer applied benefit to equine training.

Background Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent, paralleling the obesity epidemic. Ketone bodies are produced in the liver, but it is currently uncertain whether circulating ketone bodies are increased in the context of NAFLD. We investigated the association between NAFLD and circulating ketone bodies and determined the extent to which NAFLD and circulating ketone bodies are associated with all-cause mortality.Methods Plasma ketone bodies were measured by nuclear magnetic resonance spectroscopy in participants of the general population-based PREVEND study. A fatty liver index (FLI) >= 60 was regarded as a proxy of NAFLD. Associations of an elevated FLI and ketone bodies with all-cause mortality were investigated using Cox regression analyses.Results The study included 6,297 participants aged 54 +/- 12 years, of whom 1,970 (31%) had elevated FLI. Participants with elevated FLI had higher total ketone bodies (194 [153-259] vs 170 [133-243] mu mol/L; P < .001) than participants without elevated FLI. During 7.9 [7.8-8.9] years of follow-up, 387 (6%) participants died. An elevated FLI was independently associated with an increased risk of mortality (HR: 1.34 [1.06-1.70]; P = .02). Higher total ketone bodies were also associated with an increased mortality risk (HR per doubling: 1.29 [1.12-1.49]; P < .001). Mediation analysis suggested that the association of elevated FLI with all-cause mortality was in part mediated by ketone bodies (proportion mediated: 10%, P < .001).Conclusion Circulating ketone bodies were increased in participants with suspected NAFLD. Both suspected NAFLD and higher circulating ketone bodies are associated with an increased risk of all-cause mortality.

Status Epilepticus (SE) is often a neurological emergency characterized by abnormally sustained, longer than habitual seizures. The new ILAE classification reports that SE "…can have long-term consequences including neuronal death, neuronal injury…depending on the type and duration of seizures". While it is accepted that generalized convulsive SE exerts detrimental effects on the brain, it is not clear if other forms of SE, such as focal non-convulsive SE, leads to brain pathology and contributes to long-term deficits in patients. With the available clinical and experimental data, it is hard to discriminate the specific action of the underlying SE etiologies from that exerted by epileptiform activity. This information is highly relevant in the clinic for better treatment stratification, which may include both medical and surgical intervention for seizure control. Here we review experimental studies of focal SE, with an emphasis on focal non-convulsive SE. We present a repertoire of brain pathologies observed in the most commonly used animal models and attempt to establish a link between experimental findings and human condition(s). The extensive literature on focal SE animal models suggest that the current approaches have significant limitations in terms of translatability of the findings to the clinic. We highlight the need for a more stringent description of SE features and brain pathology in experimental studies in animal models, to improve the accuracy in predicting clinical translation.

Women with early-stage breast cancer have an excellent prognosis with current therapy, but could presumably be treated less invasively, without the need for surgery. The primary goal of this meta-analysis was to examine whether thermal ablation is an effective method to treat early-stage breast cancer. Studies reporting on complete ablation rate after thermal ablation as a treatment of small breast cancers (≤ 2 cm) were included. Methodologic quality of included studies was assessed using MINORS criteria. Complete ablation rates are given as proportions, and meta-regression and subgroup analyses were performed. The overall complete ablation rate in 1266 patients was 86% and was highest after radiofrequency ablation (RFA) (92%). Local recurrence rates varied from 0% to 3%, with a median follow-up of 15 to 61 months. Overall, complication rates were low (5%-18% across techniques) and were highest after high-intensity focused ultrasound ablation and lowest after cryoablation. Cosmetic outcome was good to excellent in at least 85% of patients but was reported infrequently and long-term results of cosmetic outcome after thermal ablation and radiotherapy are still lacking. Thermal ablation techniques treating early-stage breast cancer (≤ 2 cm) are safe and effective based on complete ablation rate and short-term local recurrence rates. Especially, RFA, microwave ablation, and cryoablation are promising techniques as an alternative to surgical resection without jeopardizing current treatment effectiveness or safety. Owing to great heterogeneity in the included studies, a formal recommendation on the best technique is not possible. These findings warrant the design of large randomized controlled trials comparing thermal ablation and breast-conserving surgery in the treatment of T1 breast cancer.

OBJECTIVE: The present study aims to evaluate the performance of the Diabetes Risk Index (DRI), a metabolomic index based on lipoprotein particles and branched chain amino acids, on the incidence of newly developed hypertension in a large community dwelling cohort.METHODS: The DRI was calculated by combining 6 lipoprotein parameters [sizes of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), concentrations of large VLDL, small LDL, and large HDL particles], and the concentrations of valine and leucine. DRI scores were estimated in 4169 participants from the PREVEND prospective cohort. Cox proportional hazards regression was used to evaluate the association of DRI scores with incident hypertension.RESULTS: During a median follow-up of 8.6 years, 924 new hypertension cases were ascertained. In analyses adjusted for age and sex, there was a significant association between DRI and incident hypertension with a hazard ratio (HR) per 1 SD increase of 1.45 (95% CI 1.36,1.54; p < 0.001). After additional adjustment for traditional risk factors, the HR remained significant (HRadj 1.21, 95% CI 1.10, 1.33, p CONCLUSION: Higher DRI scores were associated with an increased risk of incident hypertension. Such association was independent of traditional clinical risk factors for hypertension.

OBJECTIVE Heterotaxy or isomerism of the atrial appendages is a congenital disorder with variable presentation, associated with both cardiac and non-cardiac anomalies, which may have a serious impact on fetal outcome. The aim of this exploratory study was to assess the value of fetal magnetic resonance imaging (MRI), as a complementary tool to ultrasound, for describing the morphological spectrum encountered in heterotaxy. METHODS This retrospective study included 27 fetuses that underwent fetal MRI following prenatal suspicion of heterotaxy on ultrasound from 1998 to 2019 in a tertiary referral center. Heterotaxy was classified as left atrial isomerism (LAI) or right atrial isomerism (RAI) based on fetal echocardiography (FE) examination. In addition to routine prenatal ultrasound, fetal MRI was offered routinely to enhance the diagnosis of non-cardiac anomalies, which might have been missed on ultrasound. Prenatal findings on ultrasound, FE and MRI were reviewed systematically and compared with those of postnatal imaging and autopsy reports. RESULTS Twenty-seven fetuses with heterotaxy and cardiovascular pathology, of which 19 (70%) had LAI and eight (30%) had RAI, were included. Seven (7/19 (37%)) fetuses with LAI had normal intracardiac anatomy, whereas all fetuses with RAI had a cardiac malformation. All 27 fetuses had non-cardiac anomalies on fetal MRI, including situs and splenic anomalies. In 12/19 (63%) fetuses with LAI, a specific abnormal configuration of the liver was observed on MRI. In three fetuses, fetal MRI revealed signs of total anomalous pulmonary venous connection obstruction. An abnormal bronchial tree pattern was suspected on prenatal MRI in 6/19 (32%) fetuses with LAI and 3/8 (38%) fetuses with RAI. CONCLUSIONS Visualization on MRI of non-cardiac anomalies in fetuses with suspected heterotaxy is feasible and can assist the complex diagnosis of this condition, despite its limitations. This modality potentially enables differentiation of less severe cases from more complex ones, which may have a poorer prognosis. Fetal MRI can assist in prenatal counseling and planning postnatal management. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The interaction of ectoparasite in correlation to its host’s skin is important. The extent of interaction somewhat makes these parasites able to survive in the harsh conditon of the host’s skin. Their existence mostly in the context of gaining their nutrition and perhaps continue its regeneration. Because these diseases caused by ectoparasite are easility transmitted, widespread, and the state of polyparasitism is often took place in a single vulnerable host, and significant primary and secondary morbidity and or complication occurs, which can worsen the course of the inital disease. This minireview aim to discuss about the interlinkage of some EPSD agents in correlation to its host’s skin, their interaction and what makes these endoparasites able to survive in the skin in the context of gaining their nutrition.

Introduction: Bullous haemorrhagic dermatosis is a rare clinical disorder which is usually related to a treatment with unfractionated heparin (UFH) or low molecular weight heparin (LMWH), characterized by multiple intra-epidermal haemorrhages distant from the site of injection. Presentation of Case: A 62-year-old male patient with coronary heart disease who received heparin treatment experienced several tense, haemorrhagic bullae located on the right arm area, close to the injection site, and followed by the formation of several hematomas on his back trunk 2 days after he had received UFH. The lesions regressed after discontinuation of heparin and supportive topical treatments. Discussion: The lesions in this patient have similar characteristic with heparin-induced skin necrosis and demonstrate thrombocytopenia probably related to heparin. There are some proposed hypotheses of pathophysiology which include hypersensitivity reaction and idiosyncratic dose-related reaction. Given the clinically course, the discontinuation of heparin treatment was essential for lesion regression in addition other supportive measures. Conclusion: Heparin-induced skin lesions may indicate the presence of life-threatening heparin-induced thrombocytopenia. An early diagnosis is crucial to enable discontinuation of heparin if required.

Most historical articles have named Johann Jacob Wepfer as the first author to describe a case of chronic subdural hematoma (CSDH). However, the question arises whether these cases truly describe CSDH. Two other names that appear in literature as the first authors to describe a case of CSDH are Thomas Willis and Giovanni Battista Morgagni. In our attempt to find the first description of a CSDH, we studied the original cases described by Willis, Wepfer, and Morgagni. The cases described by Willis and Wepfer cannot be interpreted as cases of CSDH. Willis’s university scholar is more likely to have experienced venous infarction with an underlying septic thrombosis than a CSDH. Wepfer’s cases seem to represent an intraparenchymal hemorrhage from the rupture of a branch or branches of the internal carotid artery, a subarachnoid hemorrhage complicated with hydrocephalus, and a hydrocephalus in tuberculous meningitis. Morgagni’s case described in Letter III, Article 20 in the Sedibus in 1761 seems to be the first accurate historical description of a CSDH, and we believe it should be cited as such. With these early cases of alleged CSDH, we emphasize the importance of misquotation and blind copying of references, which are important citation errors.

Purpose: High-field magnetic resonance-linear accelerators (MR-Linacs), linear accelerators combined with a diagnostic magnetic resonance imaging (MRI) scanner and online adaptive workflow, potentially give rise to novel online anatomic and response adaptive radiation therapy paradigms. The first high-field (1.5T) MR-Linac received regulatory approval in late 2018, and little is known about clinical use, patient tolerability of daily high-field MRI, and toxicity of treatments. Herein we report the initial experience within the MOMENTUM Study (NCT04075305), a prospective international registry of the MRLinac Consortium. Methods and Materials: Patients were included between February 2019 and October 2020 at 7 institutions in 4 countries. We used descriptive statistics to describe the patterns of care, tolerability (the percentage of patients discontinuing their course early), and safety (grade 3-5 Common Terminology Criteria for Adverse Events v.5 acute toxicity within 3 months after the end of treatment). Results: A total 943 patients participated in the MOMENTUM Study, 702 of whom had complete baseline data at the time of this analysis. Patients were primarily male (79%) with a median age of 68 years (range, 22-93) and were treated for 39 different indications. The most frequent indications were prostate (40%), oligometastatic lymph node (17%), brain (12%), and rectal (10%) cancers. The median number of fractions was 5 (range, 1-35). Six patients discontinued MR-Linac treatments, but none due to an inability to tolerate repeated high-field MRI. Of the 415 patients with complete data on acute toxicity at 3 month follow-up, 18 (4%) patients experienced grade 3 acute toxicity related to radiation. No grade 4 or 5 acute toxicity related to radiation was observed. Conclusions: In the first 21 months of our study, patterns of care were diverse with respect to clinical utilization, body sites, and radiation prescriptions. No patient discontinued treatment due to inability to tolerate daily high-field MRI scans, and the acute radiation toxicity experience was encouraging. (c) 2021 Published by Elsevier Inc.

Summary: Standard nitinol stents (SNS), with or without drug eluting technology, are an essential tool within the interventional armamentarium in the treatment of patients with peripheral arterial disease. However, they are plagued by a number of limitations: a.) stent fractures, although observed predominately in first-generation stents, do still occur in state-of-the art stent platforms, b.) lack of radial strength, resulting in inadequate stent expansion, c.) kinking up to a complete collapse of the stent, therefore compromising its use in areas of high mechanical stress such as bending zones. In contrast, the interwoven design of the SuperaTM stent, also referred to as “vascular mimetic implant”, overcomes all of the above limitations of SNS. Several registries and studies not only confirmed its mechanical superiority (lack of stent fractures etc.) but also demonstrated remarkable clinical performance (patency and freedom from target lesion revascularization), despite its use in challenging lesions (calcification etc.) and territories (popliteal arteries etc.). Increasing confidence in the mechanical properties of the SuperaTM stent platform prompted interventionalists to further “push the limits” of this unique implant. The present article summarizes the clinical data and shows examples of “extreme” applications of this dedicated stent platform.

Background Combination of immune checkpoint inhibitors and mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKi) has been proposed to enhance the durability of anti-tumour responses induced by MAPKi. Here, we present phase I safety results from an open-label, phase I/II study of pembrolizumab (PEM), encorafenib (ENC) and binimetinib (BIN) triplet therapy in advanced, B-Raf proto-oncogene serine/threonine kinase (BRAF)V600–mutated melanoma (IMMU-TARGET, NCT02902042 ). Methods The dose finding phase I part used a 3 + 3 design, starting with the approved doses of PEM (200 mg every three weeks), ENC (450 mg once daily [QD]) and BIN (45 mg twice daily [BID]) as dose level (DL) 0. Reduction of the ENC and BIN doses (300 mg QD and 30 mg BID at DL-1 and 200 mg QD and 30 mg BID at DL-2) was preplanned in case of ≥2 dose-limiting toxicities (DLTs). Primary objectives were to estimate the recommended phase II dose of the triplet combination, DLT and safety. As per the sponsor's decision, the study was terminated after the phase I part, as the clinical efficacy of the combination is currently being investigated in a pivotal, placebo-controlled (PEM mono), double-blinded phase III trial (STARBOARD, NCT04657991 ). Results Fifteen patients were enrolled. DLTs of DL0 were creatine phosphokinase (CPK) elevation plus cytokine release syndrome (n = 1) and gamma glutamyl transferase (GGT) increase (n = 1). No DLT was observed in further 3 + 3 patients at DL-1. One (isolated GGT elevations) DLT of DL0 was questionable, as the patient had further episodes of isolated GGT elevations after treatment discontinuation. Hence, further 6 patients were enrolled at DL0: here, no DLT occurred. In total, 13 of 15 patients (87%) experienced a treatment-related adverse event (TRAE) and 8 patients (53%), a grade ≥III TRAE; there were no TRAE-related deaths. Increases in aspartate aminotransferases, GGT (6/15 patients) and CPK elevations (4/15) were the most common grade III–IV TRAE. In median, patients received triplet therapy for 24 weeks (interquartile range [IQR], 12–45). Of the 14 patients evaluable for efficacy, the overall response rate was 64% (95% confidence interval [CI], 35–87). At a median follow-up of 25 months (IQR, 9–28), progression-free survival at 12 months was 41% (95% CI, 13–68). Conclusions Triplet therapy with PEM, ENC and BIN as used in the study was feasible and safe and led to clinically meaningful disease control.

Aim Households are a significant venue for the transmission of SARS-CoV-2. We conducted a study to characterise the transmission dynamics and identify risk factors for household transmission of SARS-CoV-2 in Negeri Sembilan, Malaysia. Methods This retrospective observational study included 185 families of paediatric COVID-19 cases from 1 February 2020 to 31 December 2020. We identified the index case for each household and gathered the socio-demographic, epidemiological investigation results and risk factors for household transmission from medical case records. The secondary attack rate was calculated, and logistic regression analyses were used to identify risk factors associated with secondary household transmission of SARS-CoV-2. Results Of the 848 household contacts, 466 acquired secondary infections, resulting in a secondary attack rate of 55%. The median age of the secondary cases was 12 years. Female household contacts and household contacts who slept in the same room with the index case were significantly associated with increased risk for COVID-19. Other independent risk factors associated with higher transmission risk in the household included an index case who was symptomatic, a household index case aged greater than 18 years and a male household index case. Conclusions High rates of household transmission of COVID-19 were found, indicating households were a major setting of transmission of SARS-CoV-2. Our data provide insight into the risk factors for household transmission of SARS-CoV-2 in Malaysia.

BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified. OBJECTIVES The study sought to assess COVID-19`s impact on global cardiovascular diagnostic procedural volumes and safety practices. METHODS The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained. RESULTS Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoradc echocardiography decreased by 59%, transesophageat echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p < 0.001 for each procedure). hi multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower-middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and teteheatth. CONCLUSIONS COVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world's economically challenged. Further study of cardiovascular outcomes and COVID-19-related changes in care delivery is warranted. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Background The implementation of quality of life (QoL) concepts in routine care, is still an open matter. We followed the Medical Research Council framework for complex interventions to implement a model of QoL diagnosis and therapeutic options, and investigated its effectiveness in patients with colorectal cancer. Methods This randomised, single-blind, multicentre, clinical trial enrolled patients diagnosed with primary colorectal cancer aged 18 years or older who were surgically treated in one of four recruiting hospitals in Germany. All patients received aftercare from one of 178 coordinating practitioners (CPs) who had access to 75 healthcare professionals providing tailored therapies. QoL was measured (EORTC QLQ-C30, QLQ-CR29) in all patients after surgery (baseline) and during aftercare (3, 6, 12, 18 months). Patients were randomised (1:1) into two groups: a care pathway, including QoL-profiles consisting of 13 QoL scales plus specific therapeutic recommendations forwarded to the patient’s CP or standard postoperative care adhering to the German national guideline for colorectal cancer (control). The primary endpoint was the proportion of patients in each group with a need for QoL therapy 12 months after surgery. Analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov , number NCT02321813 and closed to accrual. Findings Between Jan 13, 2014, and Oct 28, 2015, 220 patients were enrolled and randomly assigned (n = 110 per group). At baseline (in hospital after surgery), a need for QoL therapy was diagnosed in 92/103 (89%) of intervention and 86/104 (83%) of control group patients. At 12 months (primary endpoint) the proportion of patients with a need for QoL therapy was 35/83 (42%; 95% CI 31–54%) in the intervention group versus 50/87 (57%; 95% CI: 46–68%) in the control group (p = 0·046, number needed to treat = 7; 95% CI 3–225). Interpretation Patients profited from the diagnosis of QoL deficits and tailored therapeutic options in their treatment of colorectal cancer. This trial confirmed the results of a previous RCT in breast cancer patients. The implementation of QoL concepts should become standard in treatment guidelines on cancer care. Funding Federal Ministry of Education and Research (BMBF; grant no. 01GY1339). Clinical trial information NCT02321813.

BACKGROUND: Adding rapid Exome Sequencing (rES) to conventional genetic tests improves the diagnostic yield of pregnancies showing ultrasound abnormalities but also carries a higher chance of unsolicited findings. We evaluated how rES, including pre- and post-test counseling, was experienced by parents investigating its impact on decision-making and experienced levels of anxiety.METHODS: A mixed-methods approach was adopted. Participating couples (n=46) were asked to fill in two surveys (pre-test and post-test counseling) and 11 couples were approached for an additional interview.RESULTS: All couples accepted the rES test-offer with the most important reason for testing emphasizing their hope of finding an underlying diagnosis that would aid decision-making. The actual impact on decision-making was low, however, since most parents decided to terminate the pregnancy based on the major and multiple fetal ultrasound anomalies and did not wait for their rES results. Anxiety was elevated for most participants and decreased over time.CONCLUSION: Major congenital anomalies detected on ultrasound seem to have more impact on prenatal parental decision-making and anxiety then the offer and results of rES. However, the impact of rES on reproductive decision-making and experienced anxiety requires further investigation, especially in pregnancies where less (severe) fetal anomalies are detected on ultrasound. This article is protected by copyright. All rights reserved.

Background: Circulating ketone bodies (KBs) are increased in patients with heart failure (HF), corresponding with increased cardiac KB metabolism and HF severity. However, the role of circulating KBs in ischemia/reperfusion remains unknown. Objectives: This study sought to investigate longitudinal changes of KBs and their associations with functional outcomes in patients presenting with ST-segment elevation myocardial infarction (STEMI). Methods: KBs were measured in 369 participants from a randomized trial on early metformin therapy after STEMI. Nonfasting plasma concentrations of KBs (β-hydroxybutyrate, acetoacetate, and acetone) were measured by nuclear magnetic resonance spectroscopy at presentation, at 24 hours, and after 4 months. Myocardial infarct size and left ventricular ejection fraction (LVEF) were determined by cardiac magnetic resonance imaging at 4 months. Associations of circulating KBs with infarct size and LVEF were determined using multivariable linear regression analyses. Results: Circulating KBs were high at presentation with STEMI (median total KBs: 520 μmol/L; interquartile range [IQR]: 315-997 μmol/L). At 24 hours after reperfusion, KBs were still high compared with levels at 4-month follow-up (206 μmol/L [IQR: 174-246] vs 166 μmol/L [IQR: 143-201], respectively; P < 0.001). Increased KB concentrations at 24 hours were independently associated with larger myocardial infarct size (total KBs, per 100 μmol/L: β = 1.56; 95% confidence interval: 0.29-2.83; P = 0.016) and lower LVEF (β = −1.78; 95% CI: (−3.17 to −0.39; P = 0.012). Conclusions: Circulating KBs are increased in patients presenting with STEMI. Higher KBs at 24 hours are associated with functional outcomes after STEMI, which suggests a potential role for ketone metabolism in response to myocardial ischemia. (Metabolic Modulation With Metformin to Reduce Heart Failure After Acute Myocardial Infarction: Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III): a Randomized Controlled Trial; NCT01217307)

Damage control surgery (DCS) is a standardized treatment concept in severe abdominal injury. Despite its evident advantages, DCS bears the risk of substantial morbidity and mortality, due to open abdomen therapy (OAT). Thus, identifying the suitable patients for that approach is of utmost importance. Furthermore, little is known about the use of DCS and the related outcome, especially in blunt abdominal trauma. Patients recorded in the TraumaRegister DGU® from 2008 to 2017, and with an Injury Severity Score (ISS) ≥ 9 and an abdominal injury with an Abbreviated Injury Scale (AIS) score ≥ 3 were included in that registry-based analysis. Patients with DCS and temporary abdominal closure (TAC) were compared with patients who were treated with a laparotomy and primary closure (non-DCS) and those who did receive non-operative management (NOM). Following descriptive analysis, a matched-pairs study was conducted to evaluate differences and outcomes between DCS and non-DCS group. Matching criteria were age, abdominal trauma severity, and hemodynamical instability at the scene. The injury mechanism was predominantly blunt (87.1%). Of the 8226 patients included, 2351 received NOM, 5011 underwent laparotomy and primary abdominal closure (non-DCS), and 864 were managed with DCS. Thus, 785 patient pairs were analysed. The rate of hepatic injuries AIS > 3 differed between the groups (DCS 50.3% vs. non-DCS 18.1%). DCS patients had a higher ISS (p = 0.023), required more significant volumes of fluids, more catecholamines, and transfusions (p

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.

Introduction Severe acquired hypothyroidism in childhood is a rare condition, mostly caused by autoimmune thyroiditis. Scarce and inconsistent data based on small patient numbers exist concerning its impact on growth in height. Methods Patient files at a single centre university hospital over 8 years were retrospectively reviewed. We identified 43 patients (mean age 10.6 years, 3.3–15.25, 59% prepubertal, 88% females) in a cohort of children older than 3 years with an initial TSH>30 mIU/l and reduced T4 or fT4; congenital and drug-induced hypothyroidism were excluded. Results All patients had signs of autoimmune thyroiditis (93% positive autoantibodies, 95% typical ultrasonography, 63% goiter). Median TSH was 100 mIU/l [0.3–4 mIU/l]), median fT4 3.55 pg/ml [8–19 pg/ml], median T4 2.85 µg/dl [5.3–11 µg/dl]. Presenting symptoms included goiter (26%), tiredness (23%), weight gain (19%), and growth retardation (19%). The diagnosis was made incidentally in 26% patients. In 75% growth was retarded (median height standard deviation score (SDS)-0.55), in 17% height SDS was Conclusion This so far largest pediatric cohort with severe acquired hypothyroidism confirms a serious impact on growth which, however in most cases, showed a certain catch-up growth after adequate L-thyroxine therapy. The pubertal state seems to be important for catch-up growth. A significant number of patients were not diagnosed clinically, although affected by severe hypothyroidism.

Background: Atrial fibrillation is one of the factors forming thromboembolism. The thromboembolism can be prevented with warfarin. A side effect of warfarin is increasing the occurrence of bleeding, these therapy requires an evaluation of its usage. These evaluations can be seen in the Time in Therapeutic Range (TTR) patients. TTR is the duration in which the International Normalized Ratio (INR) patients in referral value are 2.0-3.0. TTR > 70% can prevent bleeding on FA patients with warfarin therapy.Aim: To determine TTR in patients receiving warfarin with atrial fibrillation.Methods: This study was descriptive with a cross-sectional design for six months at Dr. Kariadi Hospital Semarang. TTR was calculated using Rosendaal's Methods after collecting three INRs and patients' demographics.Results: Total subject was 111 patients with an average age of 52,63 and the TTR average is 53,75. TTR in this study was divided into two groups, that groups were poor TTR (TTR < 70%) with 82 patients (73.88%) and good TTR (≥70%) with 29 patients (26.12%).Conclusions: The average TTR in FA patients with warfarin therapy was 53,75%.

Albuminuria is an under-recognized component of chronic kidney disease definition, staging, and prognosis. Guidelines, particularly for hypertension, conflict on recommendations for urine albumin-to-creatinine ratio (ACR) measurement. Separately among 1 344 594 adults with diabetes and 2 334 461 nondiabetic adults with hypertension from the chronic kidney disease Prognosis Consortium, we assessed ACR testing, estimated the prevalence and incidence of ACR ≥30 mg/g and developed risk models for ACR ≥30 mg/g. The ACR screening rate (cohort range) was 35.1% (12.3%–74.5%) in diabetes and 4.1% (1.3%–20.7%) in hypertension. Screening was largely unrelated to the predicted risk of prevalent albuminuria. The median prevalence of ACR ≥30 mg/g across cohorts was 32.1% in diabetes and 21.8% in hypertension. Higher systolic blood pressure was associated with a higher prevalence of albuminuria (odds ratio [95% CI] per 20 mm Hg in diabetes, 1.50 [1.42–1.60]; in hypertension, 1.36 [1.28–1.45]). The ratio of undetected (due to lack of screening) to detected ACR ≥30 mg/g was estimated at 1.8 in diabetes and 19.5 in hypertension. Among those with ACR

Aims Focal cortical dysplasia (FCD) type 2 is an epileptogenic malformation of the neocortex associated with somatic mutations in the mammalian target of rapamycin (mTOR) pathway. Histopathologically, FCD 2 is subdivided into FCD 2a and FCD 2b, the only discriminator being the presence of balloon cells (BCs) in FCD 2b. While pro‐epileptogenic immune system activation and inflammatory responses are commonly detected in both subtypes, it is unknown what contextual role BCs play. Methods The present study employed RNA sequencing of surgically resected brain tissue from FCD 2a (n = 11) and FCD 2b (n = 20) patients compared to autopsy control (n = 9) focusing on three immune system processes: adaptive immunity, innate immunity and cytokine production. This analysis was followed by immunohistochemistry on a clinically well‐characterised FCD 2 cohort. Results Differential expression analysis revealed stronger expression of components of innate immunity, adaptive immunity and cytokine production in FCD 2b than in FCD 2a, particularly complement activation and antigen presentation. Immunohistochemical analysis confirmed these findings, with strong expression of leukocyte antigen I and II in FCD 2b as compared to FCD 2a. Moreover, T‐lymphocyte tissue infiltration was elevated in FCD 2b. Expression of markers of immune system activation in FCD 2b was concentrated in subcortical white matter. Lastly, antigen presentation was strongly correlated with BC load in FCD 2b lesions. Conclusion We conclude that, next to mutation‐driven mTOR activation and seizure activity, BCs are crucial drivers of inflammation in FCD 2b. Our findings indicate that therapies targeting inflammation may be beneficial in FCD 2b., Focal cortical dysplasia (FCD) type 2 is an epileptogenic malformation of the neocortex associated with somatic mutations in the mammalian target of rapamycin (mTOR) pathway. Histopathologically, FCD 2 is subdivided into FCD 2a and FCD 2b, the only discriminator being the presence of balloon cells in FCD 2b. We conclude that, next to mutation‐driven mTOR activation and seizure activity, balloon cells are crucial drivers of inflammation in FCD 2b.

Objective Seasonal allergic rhinitis (SAR) is an exaggerated immunological reaction to allergens (pollen) in the air. In a small subgroup of patients, SAR can be difficult to control with first‐line therapy. Intramuscular corticosteroid injections (IMCIs) are an additional treatment in this subgroup of SAR patients. The aim of this systematic review is to investigate the efficacy and safety of IMCIs in SAR. Methods Titles and abstracts were independently screened, followed by full‐text screening based on predefined criteria. Included articles were critically appraised using the Cochrane Risk of Bias 2 (RoB 2) tool. The primary outcome is reported as the final conclusion about efficacy that was stated in the included studies. The secondary outcome is the safety of IMCIs with regard to long lasting side‐effects. Results The search yielded 2139 records, of which 10 were relevant and valid for our clinical question. Critical appraisal showed high risk of bias, which was due to unclear description of methods. Four out of four placebo‐controlled, randomized controlled trials reported a significant and relevant difference in efficacy in favor of IMCIs compared with placebo. The occurrence of side‐effects was not different between IMCIs and placebo or oral corticosteroids (OCs). Conclusion The outcome of this systematic review on trials concerning intramuscular steroid injections, despite being based on individual studies claiming favorable outcome with their use, is “inconclusive.” This is because of the epidemiological high risk of bias in these studies that were mostly executed more than 30 years ago. The “inconclusive” rating allows for a description as an “optional therapy” for severe cases in guideline formation.

Introduction: Osmotic demyelination syndrome (ODS) is a non-inflammatory process of the central nervous system caused by extracellular osmotic changes, which leads to oligodendrocyte apoptosis and disruption of myelin sheaths, usually affecting patients with underlying systemic conditions that impose susceptibility to osmotic stress. Description of ODS in patients with non-Hodgkin lymphoma (NHL) is limited to a few case reports.Methods: Here, we report a 44-year-old man with NHL that had an incidental diagnosis of ODS. We conducted a literature review of the published cases of ODS in NHL patients from 1959 to 2020, aiming to describe the characteristics of these patients.Results: A total of seven patients were summarized (four men and three women), including our case and six patients from published reports. Risk factors such as weight loss and alcoholism were reported in five (71.4%) patients. Hyponatremia was found in six (85.7%) of the cases, and none of them had overly rapid sodium correction. Four cases were asymptomatic, and diffuse large B-cell lymphoma was the most common subtype of NHL (85.7%). The outcome was favorable in most cases; only two deaths not directly related to ODS were reported.Conclusion: We wish to suggest that systemic and metabolic stress induced by NHL may be associated with the development of central osmotic demyelination, and therefore, NHL may be a novel risk factor for ODS. Clinicians should be aware of ODS in patients with hematological malignancies, even in the absence of traditional risk factors.

Introduction: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in patients with Acquired Immune Deficiency Syndrome (AIDS). Almost all Human Immunodeficiency Virus (HIV) infected patients develop CMV rapidly with manifestation in the central nervous system. Most CMV encephalitis is preceded by the presence of CMV in other places. Therefore, immediate therapy will be more effective and the delay in therapy can be detrimental. Case: A 40-year-old man with the major complaint of vision decrease in both eyes for 3 months claimed that he felt worse after 7 days, accompanied by headache and fever. This patient was diagnosed with HIV 2 years ago. The examination obtained GCS 456, negative meningeal sign, headache with NRS 7. The visual acuity of the right eye was negative light perception and in the left eye of vision 1/300. The patient experienced clinical improvement after oral Valganciclovir therapy with a dose of 2x450 mg. Conclusion: CMV encephalitis must be considered to diagnose earlier in HIV patients with complaints of decreased vision. With valganciclovir 2x450 mg tablets improve reduction of headache scale NRS from 7 to 2, increasing left eye vision from 1/300 to 6/60. Keywords: Encephalitis CMV, HIV, Valganciclovir.

Introduction: In the spring of 2020, coronavirus disease 2019 posed a substantial challenge for countries and their healthcare systems. In Germany, over 70% of all cancer patients are treated in an outpatient setting, so gynecologic oncology practices are the guarantors of optimal patient care. We developed a survey to evaluate the management of gynecologic oncology patients. Methods: The survey consisted of 38 questions and was sent to the members of the Berufsverband Niedergelassener Gynäkologischer Onkologen in Deutschland e.V. (BNGO), a professional association of gynecologic oncologists in the outpatient sector in Germany. Results: The survey was completed by 54 out of 133 (41%) gynecologic oncologists from 14 out of 15 (93%) federal states where the BNGO is represented. Facing the pandemic, popular measures were mask requirements (100%), restriction of access to practices (94%), increased number of disinfectant dispensers (85%), installment of panes of acrylic glass (76%), or spatial alterations (67%). For most patients the pandemic had no influence on prioritization of therapies (82%) or prescribed systemic treatments (87%). Despite an increase in perceived psychological burden among the staff (72%), 85% (45/54) of the practices were not offered any additional psychological support. Discussion and Conclusion: As most cancer patients in Germany are treated in an outpatient setting, a suitable reaction of oncology centers to the new circumstances was crucial to secure optimal treatment and patient care. Nevertheless, the low prioritization of mental health or distress of healthcare workers poses a serious threat to the maintenance of optimal medical care in further waves of the pandemic.

Malaria is a potentially fatal disease caused by Plasmodium spp. Transmission occurs via the bite of female mosquito, Anopheles spp. Epidemiologically, global number of malaria patient are located in Southeast Asia and Africa. Until nowadays, millions of people still living in endemic area, with children and pregnant women are among the most vulnerable group in the population. Although there have been many advances in treatment and management, but the potential for harm remains; one of the example is lung involvement in patients with severe malaria. This paper aim to discuss briefly about lung derangement in the severe malaria and the inflammatory response related to the lung dysfunction. The severity of pulmonary impairment due to complications of malaria is determined not only by the initiation of antimalarial treatment but also by the hosts associated immune response Keywords: Blood protozoan; obligate intracellular; complication; ARDS; pulmonary vascular occlusion; inflammation.

As multiple different treatment options are available for prostate cancer (PCa) and YouTube is commonly used as a source for medical information, we performed a systematic and comparative assessment of available videos guiding patients on their choice for the optimal treatment. An independent search for surgical therapy or radiotherapy of PCa on YouTube was performed and the 40 most viewed videos of both groups were analyzed. The validated DISCERN questionnaire and PEMAT were utilized to evaluate their quality and misinformation. The median overall quality of the videos was found to be low for surgery videos, while radiotherapy videos results reached a moderate quality. The median PEMAT understandability score was 60% (range 0–100%) for radiotherapy and 75% (range 40–100) for surgery videos. The radiotherapy videos contained less misinformation and were judged to be of higher quality. Summarized, the majority of the provided videos offer insufficient quality of content and are potentially subject to commercial bias without reports on possible conflict of interest. Thus, most of available videos on YouTube informing PCa patients about possible treatment methods are not suited for a balanced patient education or as a basis for the patient’s decision.

Kurzfassung Als „assistierter Suizid“ wird die Selbsttotung mit helfender Beteiligung eines anderen bezeichnet. Diese soll kunftig in Osterreich straffrei sein. Der Verfassungsgerichtshof stufte den zugehorigen § 78 StGB als verfassungswidrig ein, da er das Selbstbestimmungsrecht eines Menschen beeintrachtigt, der nicht mehr in der Lage ist, sich selbst zu toten. Als nicht verfassungswidrig erachtete der Verfassungsgerichtshof hingegen den § 77 StGB, in welchem es um die Totung auf Verlangen geht. In Hospiz- und Palliativeinrichtungen werden diese Themen nicht nur theoretisch diskutiert, sondern taglich mit Patienten und deren Angehorigen angesprochen. Wenige Tage vor seinem Tod schilderte ein Patient des Albert Schweitzer Hospizes, warum der assistierte Suizid fur ihn keine Losungsoption ist. Ein Alternativvorschlag zu einer Liberalisierung der Sterbehilfe ist die Aufklarung uber die bereits bestehenden Moglichkeiten der Selbstbestimmung (z. B. Patientenverfugung) sowie der weitere Ausbau der Hospiz- und Palliativversorgung.

Purpose There is limited information on treatment recommendations for glioblastoma patients with poor performance status. Here, we aim to evaluate the association of radiotherapy on survival in glioblastoma patients presenting with poor postoperative performance status in first-line setting. Methods We retrospectively analyzed data of 93 glioblastoma patients presenting with poor postoperative performance status (ECOG 2–4) at the University Hospital Zurich, Switzerland, in the years 2005–2019. A total of 43 patients received radiotherapy with or without systemic therapy in the first-line setting, whereas 50 patients received no additive local or systemic treatment after initial biopsy or resection. Overall survival was calculated from primary diagnosis and from the end of radiotherapy. In addition, factors influencing survival were analyzed. Results Median overall survival from primary diagnosis was 6.2 months in the radiotherapy group (95% CI 6.2–14.8 weeks, range 2–149 weeks) and 2.3 months in the group without additive treatment (95% CI 1.3–7.4 weeks, range 0–28 weeks) (p n = 11) early termination of treatment and 83.7% (n = 36) requiring radiotherapy as in-patients. Performance status improved in 27.9% (n = 12) of patients after radiotherapy. Conclusion In this retrospective single-institution analysis, radiotherapy improved overall survival in patients with poor performance status, especially in patients who were amendable to neurosurgical resection.