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Chronic pancreatitis is associated with impaired quality of life, high incidence of comorbidities, serious complications and mortality. Healthcare costs are exorbitant. Some medical societies have developed guidelines for treatment based on scientific evidence, but the gathered level of evidence for any individual topic is usually low and, therefore, recommendations tend to be vague or weak. In the present position papers on chronic pancreatitis from the Societat Catalana de Digestologia and the Societat Catalana de Pàncrees we aimed at providing defined position statements for the clinician based on updated review of published literature and on multidisciplinary expert agreement. The final goal is to propose the use of common terminology and rational diagnostic/therapeutic circuits based on current knowledge. To this end 51 sections related to chronic pancreatitis were reviewed by 21 specialists from 6 different fields to generate 88 statements altogether. Statements were designed to harmonize concepts or delineate recommendations. Part 2 of these paper series discuss topics on treatment and follow-up. The therapeutic approach should include assessment of etiological factors, clinical manifestations and complications. The complexity of these patients advocates for detailed evaluation in multidisciplinary committees where conservative, endoscopic, interventional radiology or surgical options are weighed. Specialized multidisciplinary units of Pancreatology should be constituted. Indications for surgery are refractory pain, local complications, and suspicion of malignancy. Enzyme replacement therapy is indicated if evidence of exocrine insufficiency or after pancreatic surgery. Response should be evaluated by nutritional parameters and assessment of symptoms. A follow-up program should be planned for every patient with chronic pancreatitis. © 2021 Elsevier España, S.L.U.

Objective The purpose of this study was to develop a natural language processing (NLP) pipeline to identify incidental thyroid nodules (ITNs) meeting criteria for sonographic follow-up and to assess both adherence rates to white paper recommendations and downstream outcomes related to these incidental findings. Methods 21583 non-contrast chest CT reports from 2017 and 2018 were retrospectively evaluated to identify reports which included either an explicit recommendation for thyroid ultrasound, a description of a nodule ≥ 1.5 cm, or description of a nodule with suspicious features. Reports from 2018 were used to train an NLP algorithm called fastText for automated identification of such reports. Algorithm performance was then evaluated on the 2017 reports. Next, any patient from 2017 with a report meeting criteria for ultrasound follow-up was further evaluated with manual chart review to determine follow-up adherence rates and nodule-related outcomes. Results NLP identified reports with ITNs meeting criteria for sonographic follow-up with an accuracy of 96.5% (95% CI 96.2-96.7) and sensitivity of 92.1% (95% CI 89.8-94.3). In 10006 chest CTs from 2017, ITN follow-up ultrasound was indicated according to white paper criteria in 81 patients (0.8%), explicitly recommended in 46.9% (38/81) of patients, and obtained in less than half of patients in which it was appropriately recommended (17/35, 48.6%). Discussion NLP accurately identified chest CT reports meeting criteria for ITN ultrasound follow-up. Radiologist adherence to white paper guidelines and subsequent referrer adherence to radiologist recommendations showed room for improvement.

Neonatal and infantile cholestasis (NIC) can represent the onset of a surgically correctable disease and of a genetic or metabolic disorder worthy of medical treatment. Timely recognition of NIC and identification of the underlying etiology are paramount to improve outcomes. Upon invitation by the Italian National Institute of Health (ISS), an expert working grouped was formed to formulate evidence-based positions on current knowledge about the diagnosis of NIC. A systematic literature search was conducted to collect evidence about epidemiology, etiology, clinical aspects and accuracy of available diagnostic tests in NIC. Evidence was scored using the GRADE system. All recommendations were approved by a panel of experts upon agreement of at least 75% of the members. The final document was approved by all the panel components. This position document summarizes the collected statements and defines the best-evidence diagnostic approach to cholestasis in the first year of life.

Palliative radiation therapy (pRT) is an effective tool for people with incurable cancer, in the treatment of many cancer-related symptoms such as pain, bleeding and dyspnea. As utilization rates for palliative radiation therapy increase, the demands on the healthcare system continue to grow. Radiation Therapists with advanced knowledge, skills and judgements began demonstrating their ability to practice autonomously in 2004, with the development of the Clinical Specialist Radiation Therapist (CSRT) role. Since this time, CSRTs with a specific focus in pRT (pCSRT) have been increasing in both numbers as well as their positive effects on the cancer care system. Integrating a pCSRT into the existing pRT system has resulted in increased access to and quality of pRT being delivered to palliative cancer patients. The benefits of the addition of pCSRTs to the cancer care system include increasing system capacity and increasing quality of care. This white paper provides information related to the improvements that can be realized in a RT program related to the care and treatment of its palliative patients by adding a pCSRT to the interprofessional healthcare team and suggest it as one of many strategies that can be undertaken to make improvements to access and quality of care.

Background Brugada syndrome is a rare inherited arrhythmic syndrome with a coved type 1 ST-segment elevation on ECG and an increased risk of sudden death. Many studies have evaluated risk stratification performance based on ECG-derived parameters. However, since historical Brugada patient cohorts included mostly paper ECGs, most studies have been based on manual ECG parameter measurements. We hypothesized that it would be possible to run automated algorithm-based analysis of paper ECGs. We aimed: 1) to validate the digitization process for paper ECGs in Brugada patients; and 2) to quantify the acute class I antiarrhythmic drug effect on relevant ECG parameters in Brugada syndrome. Methods A total of 176 patients (30% female, 43 ± 13 years old) with induced type 1 Brugada syndrome ECG were included in the study. All of the patients had paper ECGs before and during class I antiarrhythmic drug challenge. Twenty patients also had a digital ECG, in whom printouts were used to validate the digitization process. Paper ECGs were scanned and then digitized using ECGScan software, version 3.4.0 (AMPS, LLC, New York, NY, USA) to obtain FDA HL7 XML format ECGs. Measurements were automatically performed using the Bravo (AMPS, LLC, New York, NY, USA) and Glasgow algorithms. Results ECG parameters obtained from digital and digitized ECGs were closely correlated (r = 0.96 ± 0.07, R2 = 0.93 ± 0.12). Class I antiarrhythmic drugs significantly increased the global QRS duration (from 113 ± 20 to 138 ± 23, p Conclusions Automated algorithm-based measurements of depolarization and repolarization parameters from digitized paper ECGs are reliable and could quantify the acute effects of class 1 antiarrhythmic drug challenge in Brugada patients. Our results support using computerized automated algorithm-based analyses from digitized paper ECGs to establish risk stratification decision trees in Brugada syndrome.

This position paper, sponsored by the Asociación Española de Gastroenterología [Spanish Association of Gastroenterology], the Sociedad Española de Endoscopia Digestiva [Spanish Gastrointestinal Endoscopy Society] and the Sociedad Española de Anatomía Patológica [Spanish Anatomical Pathology Society], aims to establish recommendations for performing an high quality upper gastrointestinal endoscopy for the screening of gastric cancer precursor lesions (GCPL) in low-incidence populations, such as the Spanish population. To establish the quality of the evidence and the levels of recommendation, we used the methodology based on the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). We obtained a consensus among experts using a Delphi method. The document evaluates different measures to improve the quality of upper gastrointestinal endoscopy in this setting and makes recommendations on how to evaluate and treat the identified lesions. We recommend that upper gastrointestinal endoscopy for surveillance of GCPL should be performed by endoscopists with adequate training, administering oral premedication and use of sedation. To improve the identification of GCPL, we recommend the use of high definition endoscopes and conventional or digital chromoendoscopy and, for biopsies, NBI should be used to target the most suspicious areas of intestinal metaplasia. Regarding the evaluation of visible lesions, the risk of submucosal invasion should be evaluated with magnifying endoscopes and endoscopic ultrasound should be reserved for those with suspected deep invasion. In lesions amenable to endoscopic resection, submucosal endoscopic dissection is considered the technique of choice.

Most anticancer molecules are administered in body-size-based dosing schedules, bringing up unsolved issues regarding pharmacokinetic data in heavy patients. The worldwide spread of obesity has not been matched by improved methods and strategies for tailored drug dosage in this population. The weight or body surface area (BSA)-based approaches may fail to fully reflect the complexity of the anthropometric features besides obesity in cancer patients suffering from sarcopenia. Likewise, there is a lack of pharmacokinetic data on obese patients for the majority of chemotherapeutic agents as well as for new target drugs and immunotherapy. Therefore, although the available findings point to the role of dose intensity in cancer treatment, and support full weight-based dosing, empirical dose capping often occurs in clinical practice in order to avoid toxicity. Thus a panel of experts of the Associazione Italiana Oncologia Medica (AIOM), Associazione Medici Diabetologi (AMD), Società Italiana Endocrinologia (SIE), and Società Italiana Farmacologia (SIF), provides here a consensus statement for appropriate cytotoxic chemotherapy and new biological cancer drug dosing in obese patients., Highlights • The worldwide spread of obesity is an emerging challenge also in cancer patients • Weight or BSA-based approaches do not adequately address the critical issue of optimal dosing for cancer drugs under obesity • Empirical dose capping is often employed in clinical practice to avoid toxicities among overweight and obese patients • There is a lack of clinical and pharmacokinetic studies in this population • Clinical practice recommendations should guide suitable dosing of cytotoxic and biological cancer drugs in obese patients

During the COVID-19 pandemic, parents with sick or premature babies have faced challenges following admission to a neonatal unit due to the imposed lock-down restrictions on social contact, hospital visitation and the wearing of personal protective equipment. The negative short-term impact on neonatal care in relation to the prevention of close proximity, contact and bonding between parents and babies is potentially significant. However, an interesting finding has been reported of a reduction in premature birth admissions to the neonatal intensive care unit during the pandemic, raising important questions. Why was this? Was it related to the effect of the modifiable risk-factors for premature birth? This discussion paper focuses on an exploration of these factors in the light of the potential impact of COVID-19 restrictions on neonatal care. After contextualising both the effect of premature birth and the pandemic on neonatal and parental short-term outcomes, the discussion turns to the modifiable risk-factors for premature birth and makes recommendations relevant to the education, advice and care given to expectant mothers.

Penetrating head trauma (PHT) includes any traumatic injury where an object pierces the skull and breaches the dural membrane surrounding the brain. PHTs are less prevalent than blunt head injuries. However, they often have more complex damage, worse prognosis, and higher rates of morbidity and mortality. An 83-year-old man fell at his home and hit his head on the right side toward a shoji (a Japanese-style paper sliding door). He reported to the emergency room the following day with his family. He had a small wound before the right ear, which was sutured in the emergency room. A CT scan demonstrated tiny pieces of bone fragments inside the brain, as well as right temporal subcortical hemorrhage and pneumocephalus. He was admitted to the hospital and received intensive prophylaxis with antibiotics. He developed life-threatening skin disease and subsequent acute kidney disease requiring hemodialysis. He fully recovered from his life-threatening condition. Here, we report an unprecedented case of a penetrating head injury of an older adult caused by a shoji.

The publisher regrets we have been made aware of the below errors: 1) In Table 15, row NOVEOS chemiluminescent assay is written “utilizes 40 μL (0.04 ml) of sample per result”. The correct value would be “4 μL (0.004 ml)" of sample per result.2) In Table 16, is written “NOVEOS menu has 79 available allergens, consisting of 69 extracts and 10 molecular allergens”. It should say “NOVEOS menu continues to increase and it has 152 total allergens with 108 extracts and 44 components".3) In Table 15, row “Euroimmun”, column “Patient's serum”, is written “1000 ml”. The correct value would be “0.1 ml (-0.4 ml)”.The publisher would like to apologise for any inconvenience caused.

Acute respiratory distress syndrome (ARDS) is a heterogeneous clinical syndrome. Understanding of the complex pathways involved in lung injury pathogenesis, resolution, and repair has grown considerably in recent decades. Nevertheless, to date, only therapies targeting ventilation-induced lung injury have consistently proven beneficial, and despite these gains, ARDS morbidity and mortality remain high. Many candidate therapies with promise in preclinical studies have been ineffective in human trials, probably at least in part due to clinical and biological heterogeneity that modifies treatment responsiveness in human ARDS. A precision medicine approach to ARDS seeks to better account for this heterogeneity by matching therapies to subgroups of patients that are anticipated to be most likely to benefit, which initially might be identified in part by assessing for heterogeneity of treatment effect in clinical trials. In October 2019, the US National Heart, Lung, and Blood Institute convened a workshop of multidisciplinary experts to explore research opportunities and challenges for accelerating precision medicine in ARDS. Topics of discussion included the rationale and challenges for a precision medicine approach in ARDS, the roles of preclinical ARDS models in precision medicine, essential features of cohort studies to advance precision medicine, and novel approaches to clinical trials to support development and validation of a precision medicine strategy. In this Position Paper, we summarise workshop discussions, recommendations, and unresolved questions for advancing precision medicine in ARDS. Although the workshop took place before the COVID-19 pandemic began, the pandemic has highlighted the urgent need for precision therapies for ARDS as the global scientific community grapples with many of the key concepts, innovations, and challenges discussed at this workshop.

Over one hundred clinical trials since 2005 have failed to significantly improve the prognosis of glioblastoma. Since 2005, the standard of care has been maximal resection followed by 60Gy irradiation over six weeks with daily temozolomide. With this, a median survival of 2 years can be expected. This short paper reviewed how the pharmacodynamic attributes of an EMA/FDA approved, cheap, generic drug to treat pain, celecoxib, intersect with pathophysiological elements driving glioblastoma growth, such that growth drive inhibition can be expected from celecoxib. The two main attributes of celecoxib are carbonic anhydrase inhibition and cyclooxygenase-2 inhibition. Both attributes individually have been in active study as adjuncts during current cancer treatment, including that of glioblastoma. That research is briefly reviewed here. This paper concludes from the collected data, that starting celecoxib, 600 to 800mg twice daily before surgery and continuing it through the chemoirradiation phase of treatment would be a low-risk intervention with sound rationale.

Background Clinical guidelines on infection control strategies in healthcare workers (HCWs) play an important role in protecting them during the severe acute respiratory syndrome coronavirus 2 pandemic. Poorly constructed guidelines that are incomprehensive and/or ambiguous may compromise HCWs’ safety. Objective The objective of this study was to develop and validate a tool to appraise guidelines on infection control strategies in HCWs based on the guidelines published early in the coronavirus disease 2019 pandemic. Design, setting, and outcomes A three-stage, web-based, Delphi consensus-building process among a panel of diverse HCWs and healthcare managers was performed. The tool was validated by appraising 40 international, specialty-specific, and procedure-specific guidelines along with national guidelines from countries with a wide range of gross national income. Results Overall consensus (≥75%) was reached at the end of three rounds for all six domains included in the tool. The Delphi panel recommended an ideal infection control guideline should encompass six domains: general characteristics (domain 1), engineering recommendations (domain 2), personal protective equipment (PPE) use (domain 3), and administrative aspects (domain 4-6) of infection control. The appraisal tool performed well across the six domains, and the inter-rater agreement was excellent for the 40 guidelines. All included guidelines performed relatively better in domains 1–3 than in domains 4–6, and this was more evident in guidelines originating from lower income countries. Conclusion The guideline appraisal tool was robust and easy to use. Engineering recommendations aspects of infection control, administrative measures that promote optimal PPE use, and HCW wellbeing were generally lacking in assessed guidelines. This tool may enable health systems to adopt high-quality HCW infection control guidelines during the severe acute respiratory syndrome coronavirus 2 pandemic and may also provide a framework for future guideline development.

Maternal health and wellbeing is crucial to ensure the best outcomes for babies and children. Pregnancy and the perinatal period are particularly vulnerable times for mothers and children. Almost 1 in 5 mothers will experience some form of depression or anxiety during the perinatal period and other presentations, such as postpartum psychosis are specific to this period. Healthcare professionals, including paediatricians, whose clinical practice is devoted to the care of children often feel inadequately prepared to deal with these issues. Perinatal mental illnesses can feel daunting with anxiety about treatment impacting on the developing fetus, neonate or the breastfeeding infant. This short paper covers some common perinatal psychiatric presentations and aspects of treatment relevant for paediatricians.

Background: Acute effects of COVID-19 can be devastating and life-threatening. Alterations in mental health during the active infection have been documented, but the long-term consequences are less clear. Method: A systematic review was undertaken to investigate the effect of COVID-19 on long-term mental health outcomes. Three databases [PubMed, Medline (Ovid) and Cochrane library] were searched between 1st October 2019 and 29th August 2021 with additional hand searching to identify all published studies reporting symptoms of generalised anxiety, depression, post-traumatic stress disorder (PTSD), or sleep disturbance in participants at least one month after COVID-19 infection. The prevalence and mean symptom score of each were assessed. Results: Eight hundred and eighty five studies were found, of which 33 were included in the review involving a total of 6743 participants. The studies’ risk of bias were typically fair quality. The median study age of participants was 57.8 years old (IQR 49.3-60.7), with 63.0% male (IQR 57.0%-73.0%). Participants typically experienced no or mild symptoms of long-term anxiety (GAD-7, STAI-S, HADS) and depression (PHQ-9, BDI, PHQ-2, HADS). Prevalence varied depending on the measurement tool. Sleep disturbances (primarily insomnia) were most consistently reported as mild. PTSD prevalence was similar to anxiety and depression. Conclusion: The overall effect of the pandemic has been linked with worse psychiatric disorder symptoms. However, the long-term effect from direct COVID-19 infection has been associated with no or mild symptoms. Studies exhibited long-term prevalence of anxiety, depression, PTSD, and sleep disturbances were comparable to general population levels.

BackgroundThe Covid-19 pandemic resulted in repeated, prolonged restrictions in daily life. Social distancing policies as well as health anxiety are thought to lead to mental health impairment. However, there is lack of longitudinal data identifying at-risk populations particularly vulnerable for elevated Covid-19-related distress.MethodsWe collected data of N=1268 participants (n=622 healthy controls (HC), and n=646 patients with major depression, bipolar disorder, schizophrenia or schizoaffective disorder) at baseline (2014-2018) and during the first lockdown in Germany (April-May 2020). We obtained information on Covid-19 restrictions (number and subjective impact of Covid-19 events), and Covid-19-related distress (i.e., subjective fear and isolation). Using multiple linear regression models including trait variables and individual Covid-19 impact, we sought to predict Covid-19-related distress.ResultsHC and patients reported similar numbers of Covid-19-related events, and similar subjective impact rating. They did not differ in Covid-19-related subjective fear. Patients reported significantly higher subjective isolation. 30.5% of patients reported worsened self-rated symptoms since the pandemic. Subjective fear in all participants was predicted by four variables: trait anxiety (STAI-T), conscientiousness (NEO-FFI), Covid-19 impact, and sex. Subjective isolation in HC was predicted by social support (FSozu), Covid-19 impact, age, and sex; in patients, it was predicted by social support and Covid-19 impact.ConclusionOur data shed light on differential effects of the pandemic in psychiatric patients and HC. They identify relevant, easy-to-obtain variables for risk profiles related to interindividual differences in Covid-19-related distress for direct translation into clinical practice.

The aim of this study is to perform a retrospective analysis of the feasibility of the clinical application of SLNB using methylene blue dye (MBD) for the identification of SLN followed by frozen section biopsy to detect occult metastasis in clinically N0 necks. Hence, to know the reliability of MBD in reducing the need for extensive surgery. METHODS: We retrospectively analyzed the clinic pathological data of 48 patients with early oral cancer.The SLN identification rate (IR) was calculated in SLNB with MBD and the false-negative rate (FNR). Intra operative frozen section biopsy was done for all patients was compared with post-operative paraffin histopathology report and the prognosis of patients was analyzed. RESULTS: Analysis of the 48 SLNB cases showed that there were significant differences in SLN successful detection rate among patients with different site (p = 0.043) and clinical presentation (p = 0.007). Similar significant results (p

Background Any irregularity of the teeth or a mal-relationship of the dental arches is known as malocclusion. Among all the oro-facial problems, tooth decay is considered the most prevalent one followed by periodontal disease and dental malocclusion. Dental malocclusion is not a life-threatening condition. However, it is closely related to an individual's self-esteem and psychosocial wellbeing. The prevalence of malocclusion varies among different ethnic groups, age-groups, and gender. Objectives This study was conducted with the objective to find out the prevalence of normal occlusal traits and to identify the proportion of different types of malocclusions among dental and nursing students of Seven North-Eastern states studying at a tertiary care Medical Institute. Methods and materials This cross-sectional study included 432 students with a mean age of 21.42 years, who satisfied the inclusion criteria. Inclusion criteria consisted of the presence of all permanent teeth with or without third molars. The oral cavity was examined using a sterile mouth mirror and flashlight followed by evaluation of all the occlusal relationships in centric occlusion position (COP). COP was achieved by asking the participant to swallow, and then to bite on his or her teeth together. The occlusion traits were assessed as normal occlusion or malocclusion using the first permanent molars as described by E.H. Angle and deviation from line of occlusion. Descriptive statistics like mean and proportions were calculated. Results The prevalence of normal occlusal traits was 48.4%, and that of malocclusion was 51.6%. Class I malocclusion was most prevalent occlusal trait followed by Class II malocclusion and Class III malocclusion showed the least prevalence. Conclusions Class I malocclusion was most prevalent followed by Class II malocclusion and Class III malocclusion showed the least prevalence.

Background The amygdala is vital in processing psychological stress and predicting vulnerability or resilience to stress-related disorders. This study aimed to build the link between functional magnetic resonance imaging data obtained before the stress event and the subsequent stress-related depressive symptoms. Methods Neuroimaging data obtained before the coronavirus disease 2019 pandemic from 39 patients with major depressive disorder (MDD) and 61 health controls (HCs) were used in this study. The participants were divided retrospectively into four groups in accordance with the severity of depressive symptoms during the pandemic: remitted patients, non-remitted patients, depressed HCs (HCd) and non-depressed HCs (HCnd). Seed-based resting-state functional connectivity (rsFC) analyses of the amygdala and its subregions, including the centromedial (CM), the basolateral and the superficial (SF), were performed. Results Vulnerability to depression was suggested by decreased rsFC between the left CM amygdala and the bilateral lingual gyrus in the HCd group compared with the HCnd group, and decreased rsFC of the left CM or right SF amygdala with the precuneus and the postcentral gyrus in the HCd group compared with patients with MDD. No evidence supported the rsFC of the amygdala or its subregions as a biomarker for the resilience of patients with MDD to stress under antidepressant treatment. Limitations Smaller sample size and no longitudinal neuroimaging data. Conclusions Our findings suggested that the rsFC of amygdala subregions may represent a neurobiological marker of vulnerability to depression following stress.

INTRODUCTION: Periodontitis causes oxidative stress and reduce total antioxidant levels. The aim of this study was to determine the effect of non-surgical periodontal treatment on leptin levels and total antioxidant capacity in chronic periodontitis. MATERIALS AND METHODS: A total of 35 chronic periodontitis (ChP) patients and 35 systemically and periodontal healthy subjects were enrolled in this study. Further, the ChP group received nonsurgical periodontal therapy (NSPT). Leptin and total antioxidant capacity (TAOC) was measured in serum and saliva samples at baseline, 3 months and 6 months after non-surgical periodontal therapy. Clinical parameters measured were measured at baseline, 1, 3 and 6 months interval. RESULTS: The mean serum leptin and TAOC levels in control group were significantly higher compared to chronic periodontitis group (p

Objectives This study sought to describe expected changes in a mirror-image prone electrocardiogram (ECG) compared with normal supine, including a range of cardiac conditions. Background Unwell COVID-19 patients are at risk of cardiac complications. Prone ventilation is recommended but poses practical challenges to acquisition of a 12-lead ECG. The effects of prone positioning on the ECG remain unknown. Methods 100 patients each underwent 3 ECGs: standard supine front (SF); prone position with precordial leads attached to front (PF); and prone with precordial leads attached to back in a mirror image to front (PB). Results Prone positioning was associated with QTc prolongation (PF 437 ± 32 ms vs. SF 432 ± 31 ms; p, Central Illustration

COVID-19 has re-established the significance of analyzing the organism through a metabolic perspective to uncover the dynamic interconnections within the biological systems. The role of micronutrient status and metabolic health emerge as pivotal in COVID-19 pathogenesis and the immune system's response. Metabolic disruption, proceeding from modifiable factors, has been proposed as a significant risk factor accounting for infection susceptibility, disease severity and risk for post-COVID complications. Metabolomics, the comprehensive study and quantification of intermediates and products of metabolism, is a rapidly evolving field and a novel tool in biomarker discovery. In this article, we propose that leveraging insulin resistance biomarkers along with biomarkers of micronutrient deficiencies, will allow for a diagnostic window and provide functional therapeutic targets. Specifically, metabolomics can be applied as: a. At-home test to assess the risk of infection and propose nutritional support, b. A screening tool for high-risk COVID-19 patients to develop serious illness during hospital admission and prioritize medical support, c(i). A tool to match nutritional support with specific nutrient requirements for mildly ill patients to reduce the risk for hospitalization, and c(ii). for critically ill patients to reduce recovery time and risk of post-COVID complications, d. At-home test to monitor metabolic health and reduce post-COVID symptomatology. Metabolic rewiring offers potential virtues towards disease prevention, dissection of high-risk patients, taking actionable therapeutic measures, as well as shielding against post-COVID syndrome., Graphical abstract Image 1

SARS-CoV-2 vaccines protect against symptomatic and severe COVID-19. The BNT162b2/Pfizer and mRNA-1273/Moderna vaccines represent new vaccine technology relying on administration of mRNA encoding SARS-CoV-2 viral spike protein encased in lipid nanoparticles. The vaccines are administered as two doses into muscle, which elicits a strong response, typically within 14 days after the second dose. Neuromuscular diseases are characterized by the progressive loss of muscle and are often treated with chronic glucocorticoid steroids, both of which may contribute to a blunted immune response to vaccination. Herein, we measured IgG antibody content and neutralizing antibody response after mRNA COVID-19 vaccination in non-ambulatory neuromuscular disease patients. After two doses of mRNA COVID-19 vaccine, median anti-receptor binding domain IgG and percent surrogate viral neutralization in non-ambulatory neuromuscular disease samples were significantly elevated similar to healthy vaccinated controls. As in healthy controls, COVID-19 vaccines produce greater antibody levels compared to those with a history of outpatient COVID-19 infection. This data documents that non-ambulatory neuromuscular disease patients respond well to two doses of mRNA COVID-19 vaccine despite low muscle mass and even chronic steroid use.

Introduction Traumatic injuries and their resulting mortality and disability impose a disproportionate burden on sub-Saharan countries like Rwanda. An important facet of addressing injury burdens is to comprehend injury patterns and aetiologies of trauma. This study is a cross-sectional analysis of injuries, treatments and outcomes at the University Teaching Hospital-Kigali (CHUK). Methods A random sample of Emergency Centre (EC) injury patients presenting during August 2015 through July 2016 was accrued. Patients were excluded if they had non-traumatic illness. Data included demographics, clinical presentation, injury type(s), mechanism of injury, and EC disposition. Descriptive statics were utilised to explore characteristics of the population. Results A random sample of 786 trauma patients met inclusion criteria and were analysed. The median age was 28 (IQR 6–50) years and 69.4% were male. Of all trauma patients 49.4% presented secondary to road traffic injuries (RTIs), 23.9% due to falls, 10.9% due to penetrating trauma. Craniofacial trauma was the most frequent traumatic injury location at 36.3%. Lower limb trauma and upper limb trauma constituted 35.8% and 27.1% of all injuries. Admission was required in 68.2% of cases, 23.3% were admitted to the orthopaedic service with the second highest admission to the surgical service (19.2%). Of those admitted to the hospital, the median LOS was 6 days (IQR 3–14), in the subset of patients requiring operative intervention, the median LOS was also 6 days (IQR 3–16). Death occurred in 5.5% of admitted patients in the hospital. Conclusion The traumatic injury burden is borne more proportionally by young males in Kigali, Rwanda. Blunt trauma accounts for a majority of trauma patient presentations; of these RTIs constitute nearly half the injury mechanisms. These findings suggest that this population has substantial injury burdens and prevention and care interventions focused in this demographic group could provide positive impacts in the study setting.

International audience; The coronavirus disease 2019 (COVID-19) outbreak has had a major impact on medical and surgical activities. A decline in facial trauma incidence was noticed during the lockdown period. The aim of this study was to evaluate the decline in maxillofacial trauma in France during this particular period. A retrospective multicentre comparative study was initiated in 13 major French public hospital centres. The incidence of facial trauma requiring surgery during the first month of lockdown was compared to that during equivalent periods in 2018 and 2019. Differences in the types of trauma were also analysed. Thirteen maxillofacial departments participated in the study. A significant decline in maxillofacial trauma volumes was observed when compared to equivalent periods in 2018 and 2019 (106 patients compared to 318 and 296 patients, respectively), with an average reduction of 65.5% (P = 0.00087). The proportion of trauma due to sports and leisure was reduced when compared to reports in the literature. As a consequence, in the context of a pandemic, the material and human resources related to this activity could be reallocated to the management of other pathologies that cannot be postponed.

Current assessments of recovery following spinal cord injury (SCI) focus on clinical outcome measures. These assessments bear an inherent risk of bias, emphasizing the need for more reliable prognostic biomarkers to measure SCI severity. This study evaluated fluid biomarkers as an objective tool to aid with prognosticating outcomes following SCI. Using a 1H nuclear magnetic resonance (NMR)-based quantitative metabolomics approach of urine samples, the objectives were to determine (a) if alterations in metabolic profiles reflect the extent of recovery of individual SCI patients, (b) whether changes in urine metabolites correlate to patient outcomes, and (c) whether biological pathway analysis reflects mechanisms of neural damage and repair. An inception cohort exploratory pilot study collected morning urine samples from male SCI patients (n=6) following injury and again at 6-months post-injury. A 700 MHz Bruker Avance III HD NMR spectrometer was used to acquire the metabolic signatures of urine samples, which were used to derive metabolic pathways. Multivariate statistical analyses were used to identify changes in metabolic signatures, which were correlated to clinical outcomes in the Spinal Cord Independence Measure (SCIM). Among SCI-induced metabolic changes, biomarkers which significantly correlated to patient SCIM scores included caffeine (R = -0.76, p, Highlights • 1H nuclear magnetic resonance (NMR) spectroscopy identified robust urine biomarkers in patients with spinal cord injury (SCI). • Quantitative NMR-based metabolomics identified metabolic profiles linked to the extent of recovery among SCI patients. • Changes in urine metabolites correlated with patient functional outcomes. • Metabolomic biomarker analysis addresses the need for reliable prognostic biomarkers of spinal cord injury.

Hypertension is one of the most common morbidities in COVID-19. Previous studies demonstrated that hypertension increases composite poor outcomes in patients with COVID-19. Beta-blockers is widely used as one of the most common antihypertensive agents. Beta-blockers may hold potential benefits in COVID-19 treatment, with current evidence of the potential mechanism of beta-blockers remains scarce. However, several mechanisms were suggested, including decreasing RAAS pathway activity and lowering the ACE2 levels, reducing cytokine storms, and may be beneficial in reducing mortality in ARDS related COVID-19. Further large-scale randomized clinical trials should be conducted before a definite recommendation can be drawn.

Summary: Introduction: Neglected tropical diseases control programmes run separately. For settings with more than one endemic disease, combined mass drug administration (MDA) has potential practical advantages compared with separate programmes but needs confirmation of safety. We assessed the safety of combined MDA for multiple neglected tropical diseases using ivermectin, diethylcarbamazine, albendazole (IDA) and azithromycin (AZI). Methods: We conducted an open-label, cluster-randomized trial involving individuals living in 34 wards (smaller administrative division) in two study sites, Namatanai District and Lihir Island, Papua New Guinea. We randomly assigned wards to the combined treatment arm (which received a single dose of the triple combination IDA and a single dose of AZI at the same visit) or the control arm (which received IDA separately followed by AZI separately one week after). All participants underwent safety assessments one day after drug administration. Methodology for collecting the adverse events (AEs) was a general question (in Namatanai) and individual questions about specific AEs (in Lihir). The primary endpoint was the prevalence of AEs. Safety of combined treatment was taken to be non-inferior to that of IDA if the upper limit of the two-sided CI for the difference in rates was equal or lower than 5%. Findings: The study enrolled 15,656 participants. Of those enrolled, 7,281 (46.3%) received the combined regimen and 8,375 (53.3%) received standard treatment with IDA for lymphatic filariasis between Nov 1, 2018, and Apr 15, 2019. Of the individuals in the control group, 4,228 (50.5%) attended a second visit one week apart to receive AZI for yaws. In Namatanai, the proportion of AEs was similar in the combined group (0.8%) compared to the IDA group (1.3%, difference 0.5% [95CI -2.5% to 1.4%]) or the AZI group (3.6%, d -2.8% [95CI -8.6% to 2.8%]). In Lihir, the proportion of AEs was higher in the combined group (23.0%) compared to the IDA group (12.2%, d 10.8% [95% CI 1.5% to 20.2%]) or the AZI group (11.1%, d 11.9% [95% CI 2.7% to 21.1%]).We observed 21 (0.3%) grade-2 AEs in the combined treatment group, 33 (0.4%) in the IDA separately group, and 18 (0.2%) in the AZI separately group. No participants required treatment for any AE. We observed no deaths, serious AEs, or AEs of special interest. Interpretation: In the largest trial so far involving coadministration of regimens based on IDA and AZI, the combination was safe and feasible in a population of more than 15,000 people. Combined MDA based on these two regimens opens up new potential for the control of neglected tropical diseases in the Western Pacific region. Funding: International Trachoma Initiative, “la Caixa” Foundation, Kern Pharma.

Background: \ud Understanding trends in the incidence and outcomes of myocardial infarction and stroke, and how these are influenced by changes in cardiovascular risk factors can inform health policy and healthcare provision.\ud \ud Methods: \ud We identified all patients 30 years or older with myocardial infarction or stroke in Scotland. Risk factor levels were determined from national health surveys. Incidence, potential impact fractions and burden attributable to risk factor changes were calculated. Risk of subsequent fatal and non-fatal events (myocardial infarction, stroke, bleeding and heart failure hospitalization) were calculated with multi-state models.\ud \ud Findings: \ud From 1990 to 2014, there were 372,873 (71±13 years) myocardial infarctions and 290,927 (74±13 years) ischemic or hemorrhagic strokes. Age-standardized incidence per 100,000 fell from 1,069 (95% confidence interval, 1,024-1,116) to 276 (263-290) for myocardial infarction and from 608 (581-636) to 188 (178-197) for ischemic stroke. Systolic blood pressure, smoking and cholesterol decreased, but body-mass index increased, and diabetes prevalence doubled. Changes in risk factors accounted for a 74% (57-91%) reduction in myocardial infarction and 68% (55-83%) reduction in ischemic stroke. Following myocardial infarction, the risk of death decreased (30% to 20%), but non-fatal events increased (20% to 24%) whereas the risk of both death (47% to 34%) and non-fatal events (22% to 17%) decreased following stroke.\ud \ud Interpretation: \ud Over the last 25 years, substantial reductions in myocardial infarction and ischemic stroke incidence are attributable to major shifts in risk factor levels. Deaths following the index event decreased for both myocardial infarction and stroke, but rates remained substantially higher for stroke.\ud \ud Funding: \ud British heart foundation.

Optimum management of patients with cancer during the COVID-19 pandemic has proved extremely challenging. Patients, clinicians and hospital authorities have had to balance the risks to patients of attending hospital, many of whom are especially vulnerable, with the risks of delaying or modifying cancer treatment. Those whose care has been significantly impacted include patients suffering from the effects of cancer on bone, where delivering the usual standard of care for bone support has often not been possible and clinicians have been forced to seek alternative options for adequate management.\ud \ud \ud \ud At a virtual meeting of the Cancer and Bone Society in July 2020, an expert group shared experiences and solutions to this challenge, following which a questionnaire was sent internationally to the symposium’s participants, to explore the issues faced and solutions offered. 70 respondents, from 9 countries (majority USA, 39%, followed by UK, 19%) included 50 clinicians, spread across a diverse range of specialties (but with a high proportion, 64%, of medical oncologists) and 20 who classified themselves as non-clinical (solely lab-based). Spread of clinician specialty across tumour types was breast (65%), prostate (27%), followed by renal, myeloma and melanoma.\ud \ud \ud \ud Analysis showed that management of metastatic bone disease in all solid tumour types and myeloma, adjuvant bisphosphonate breast cancer therapy and cancer treatment induced bone loss, was substantially impacted. Respondents reported delays to routine CT scans (58%), standard bone scans (48%) and MRI scans (46%), though emergency scans were less affected. Delays in palliative radiotherapy for bone pain were reported by 31% of respondents with treatments often involving only a single dose without fractionation. Delays to, or cancellation of, prophylactic surgery for bone pain were reported by 35% of respondents. Access to treatments with intravenous bisphosphonates and subcutaneous denosumab was a major problem, mitigated by provision of drug administration at home or in a local clinic, reduced frequency of administration or switching to oral bisphosphonates taken at home. The questionnaire also revealed damaging delays or complete stopping of both clinical and laboratory research.\ud \ud \ud \ud In addition to an analysis of the questionnaire, this paper presents a rationale and recommendations for adaptation of the normal guidelines for protection of bone health during the pandemic.

Background: Allergen immunotherapy (AIT) is the only causal treatment for respiratory allergy. Long-term real-life effectiveness of AIT remains to be demonstrated beyond the evidence from randomised controlled trials (RCTs). Methods: REACT (Real world effectiveness in allergy immunotherapy) is a retrospective cohort study using claims data between 2007 and 2017. Study eligibility was a confirmed diagnosis of allergic rhinitis (AR), with or without asthma, and AIT. To ensure comparable groups, AIT-treated subjects were propensity score matched 1:1 with control subjects, using characteristic and potential confounding variables. Outcomes were analysed as within (pre vs post AIT) and between (AIT vs control) group differences across 9 years of follow-up (ClinicalTrial.gov: NCT04125888). Findings: 46,024 AIT-treated subjects were matched with control subjects and 14,614 were included in the pre-existing asthma cohort. AIT-treated subjects were 29·5 (16·3) years and 53% were male. Compared to pre-index year, AIT was consistently associated with greater reductions compared to control subjects in AR and asthma prescriptions, including both asthma controller and reliever prescriptions. Additionally, the AIT group had significantly greater likelihood of stepping down asthma treatment (P

Summary Background: Samoa is a Pacific Island country facing one of the highest burdens of non-communicable disease globally. Methods: In this study, we apply a cascade-of-care approach to understand gaps in the awareness, treatment, and control cascade of diabetes and hypertension in a cross-sectional, convenience sample of 703 young, high-risk Samoan adults (29.5-50.9 years). Findings: Non-communicable diseases were prevalent in the study sample: 19.5% (95% CI: 16.6%-22.7%) of participants had diabetes; 47.6% (95% CI: 43.7%-51.4%) presented with pre-diabetes or diabetes; 31.0% (95% CI: 27.5%-34.6%) had hypertension; and nearly 90% (95% CI: 86.7%-91.5%) had overweight or obesity. Among those with diabetes and hypertension, only 20.5% (95% CI: 13.9%-28.4%) and 11.8% (95% CI: 7.8%-16.9%) of participants were aware of their condition, respectively. Only 0.8% (95% CI: 0.0%-4.2%) of all participants with diabetes had achieved glycemic control; only 2.8% (95% CI: 1.1%-6.1%) of those with hypertension achieved control. Interpretation: We found a significant burden of diabetes and hypertension in Samoa, exceeding the recent prevalence estimates of other low- to middle-income countries by nearly two-fold. A severe unmet need in both detection and subsequent control and monitoring of these chronic conditions exists. Our results suggest that the initial diagnosis and surveillance stage in the cascade of care for chronic conditions should be a major focus of primary care efforts; national screening campaigns and programs that leverage village and district nurses to deliver community-based primary care may significantly impact gap closure in the NCD cascade. Funding: This study was supported by the U.S. National Institutes of Health R01HL140570 (PIs: McGarvey and DeLany); AR was supported by NIH FIC D43TW010540; HK and AR-C were supported by the Minority Health and Health Disparities International Research Training (MHIRT) Program at Brown University, NIH Grant # 5T37MD008655.

Background Obesity, cancer and diabetes frequently coexist. The association of glycaemic variability (GV) and obesity with cancer events had not been explored in diabetes. Methods In the prospective Hong Kong Diabetes Register cohort (1995-2019), we used cox proportional hazards models to examine the risk associations of GV with all-site cancer (primary outcome) and cause-specific death (secondary outcome). We also explored the joint association of obesity and GV with these outcomes and site-specific cancer. We expressed GV using HbA1c variability score (HVS) defined as percentage of HbA1c values varying by 0.5% compared with values in preceding visit. Findings We included 15,286 patients (type 2 diabetes: n=15,054, type 1 diabetes: n=232) with ≥10 years of diabetes and ≥3 years of observation (51.7% men, age (mean±SD): 61.04±10.73 years, HbA1c: 7.54±1.63%, body mass index [BMI]: 25.65±3.92 kg/m2, all-site cancer events: n=928, cancer death events: n=404). There were non-linear relationships between HVS and outcomes but there was linearity within the high and low HVS groups stratified by the median (IQR) value of HVS (42.31 [27.27, 56.28]). In the high HVS group, the adjusted hazard ratios (aHR) of each SD of HVS was 1.15 (95% CI: 1.04, 1.26) for all-site cancer (n=874). The respective aHRs for breast (n=77), liver (n=117) and colorectal (n=184) cancer were 1.44 (1.07, 1.94), 1.37 (1.08, 1.74), and 1.09 (0.90, 1.32). In the high GV group, the respective aHRs were 1.21 (1.06, 1.39), 1.27 (1.15, 1.40), and 1.15 (1.09, 1.22) for cancer, vascular, and noncancer nonvascular death. When stratified by obesity (BMI ≥25 kg/m2), the high HVS & obese group had the highest aHRs of 1.42 (1.16, 1.73), 2.44 (1.24, 4.82), and 2.63 (1.45, 4.74) respectively for all-site, breast, and liver cancer versus the low GV & non-obese group. The respective aHRs were 1.45 (1.07, 1.96), 1.47 (1.12, 1.93), and 1.35 (1.16, 1.57) for cancer, vascular, and noncancer nonvascular death. Interpretation Obesity and high GV were associated with increased risk of all-site, breast, liver cancer, and cancer-specific death in T2D. Funding The Chinese University of Hong Kong Diabetes Research Fund

Summary: Background: Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is a rare disease, which is often underdiagnosed due to its heterogeneous presentations and complex molecular genetic basis, leading to a lack of population-based epidemiology data, especially of prevalence and disease progression. Methods: Fujian Neuromedical Centre (FNMC) is a diagnosis centre for clinical-genetic FSHD in China, and the only one employing pulsed-field gel electrophoresis (PFGE)-based Southern blotting for all FSHD1 genetic tests. Three sources distributed across all six spatial zones in China, were used to obtain information regarding FSHD1 events, namely, FNMC, Genetic and Myopathy Group (branches of the Neurology Society of the Chinese Medical Association), and “FSHD-China” (an organization supported by FSHD patients). During 2001-2020, all genetically-confirmed FSHD1 from China were registered in FNMC. Follow-up was conducted in the 20-year period to obtain data on disease progression, which was mainly described in terms of independent ambulation loss. Findings: Of the 1,744 FSHD1 genetic tests (total test number 1,802) included in the analysis, 997 (57.2%) patients from 620 families were diagnosed with FSHD1. The estimated prevalence of genetically-confirmed FSHD1 in China is 0.75 per million (95% confidence interval [CI], 0.70-0.79) during 2001-2020, with 0.78 (95% CI, 0.72-0.85) in males and 0.71 (95% CI, 0.65-0.78) in females. The estimated prevalence increased from 0.22 (95% CI, 0.19-0.26) per million in 2001-2015 to 0.53 (95% CI, 0.49-0.57) per million in 2016-2020 (p < 0.001). The prevalence in Fujian province was 7.10 per million, 4.66 per million, and 2.44 per million, during 2001-2020, 2001-2015, and 2016-2020, respectively. Among the 861 symptomatic plus asymptomatic patients of the total 997 patients, the median onset age at first-ever muscle weakness was 16 years of age (range 1-81); the median number of contracted D4Z4 repeats was 5 units (range 1-9); the median 4qA-allele-specific methylation level was 41% (range 14%-69%). Of the 977 symptomatic patients followed-up during 2001-2020, 117 patients (12.0%) lost independent ambulation. The expected duration from onset of first-ever muscle weakness to onset of independent ambulation loss was 40 years. The group with loss of independent ambulation had a smaller number of contracted D4Z4 repeats (p < 0.001) and had an earlier onset age of first-ever muscle weakness (p < 0.001) compared to the group without loss of independent ambulation. Interpretation: Our research captures the largest genetically-confirmed FSHD1 population worldwide, to calculate its prevalence of 0.75 per million in China from 2001 to 2020. Approximately 12.0% of symptomatic plus asymptomatic patients of FSHD1 will lose independent ambulation in 40 years from onset of first-ever muscle weakness. Funding: This work has been supported by the grants (U2005201, 81870902, N.W.) and (81974193, 81671237, Z.Q.W.) from the National Natural Science Foundation of China; Joint Funds for the Innovation of Science and Technology of Fujian Province (2018Y9082) (N.W.), and the Key Clinical Specialty Discipline Construction Program of Fujian (N.W.).

Summary Background Previous research by our team identified factors associated with in-hospital mortality in patients with a diagnosis of COVID-19 in England between March and May 2020. The aim of the current paper was to investigate the changing role of demographics and co-morbidity, with a particular focus on ethnicity, as risk factors for in-hospital mortality over an extended period. Methods This was a retrospective observational study using the Hospital Episode Statistics administrative dataset. All patients aged ≥ 18 years in England with a diagnosis of COVID-19 who had a hospital stay that was completed (discharged alive or died) between 1st March and 30th September 2020 were included. In-hospital mortality was the primary outcome of interest. Multilevel logistic regression was used to model the relationship between in-hospital mortality with adjustment for the covariates: age, sex, deprivation, ethnicity, date of discharge and a number of comorbidities. Findings Compared to patients in March-May (n = 93,379), patients in June-September (n = 24,059) were younger, more likely to be female and of Asian ethnicity, but less likely to be of Black ethnicity. In-hospital mortality rates, adjusted for covariates, declined from 33–34% in March to 11–12% in September. Compared to the March-May period, Bangladeshi, Indian and Other Asian ethnicity patients had a lower relative odds of death (compared to White ethnicity patients) during June-September. For Pakistani patients, the decline in-hospital mortality rates was more modest across the same time periods with the relative odds of death increasing slightly (odds ratio (95% confidence interval)) 1.24 (1.10 to 1.40) and 1.35 (1.08 to 1.69) respectively. From March-May to June-September the relative odds of death in patients with a diagnosis of metastatic carcinoma increased (1.90 (1.73 to 2.08) vs 3.01 (2.55 to 3.54)) but decreased for male patients (1.44 (1.39 to 1.49) vs 1.27 (1.17 to 1.38)) and patients with obesity (1.42 (1.34 to 1.52) vs 0.97 (0.83 to 1.14)) and diabetes without complications (1.14 (1.10 to 1.19) vs 0.95 (0.87 to 1.05)). Interpretation In-hospital mortality rates for patients with a diagnosis of COVID-19 have fallen substantially and there is evidence that the relative importance of some covariates has changed since the start of the pandemic. These patterns should continue to be tracked as new variants of the virus emerge, vaccination programmes are rolled out and hospital pressures fluctuate. Funding None.

Background: Pulmonary tuberculosis (TB) is one of the most deadly pathogens on earth. However, the majority of people have resistance to active disease. Further, some individuals, termed resisters (RSTRs), do not develop traditional latent tuberculosis (LTBI). The RSTR phenotype is important for understanding pathogenesis and preventing TB. The host genetic underpinnings of RSTR are largely understudied. Methods: In a cohort of 908 Ugandan subjects with genome-wide data on single nucleotide polymorphisms, we assessed the heritability of the RSTR phenotype and other TB phenotypes using restricted maximum likelihood estimation (REML). We then used a subset of 263 RSTR and LTBI subjects with high quality phenotyping and long-term follow-up to identify DNA variants genome-wide associated with the RSTR phenotype relative to LTBI subjects in a case-control GWAS design, and annotated and enriched these variants to better understand their role in TB pathogenesis. Results: The heritability of the TB outcomes was very high, at 55% for TB vs. LTBI and 50.4% for RSTR vs. LTBI among HIV- subjects, controlling for age and sex. We identified 27 loci associated with the RSTR phenotype (P

Background:\ud Data on psychiatric disorders in survivors born very preterm (VP; 2499 g and/or gestational age ≥37 weeks), and 3) structured measure of psychiatric diagnoses using DSM or ICD criteria. Diagnoses of interest were Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Anxiety Disorder, Mood Disorder, Disruptive Behaviour Disorder (DBD), Eating Disorder, and Psychotic Disorder. A systematic search for eligible studies was conducted (PROSPERO Registration Number 47555).\ud \ud Findings:\ud Data were obtained from 10 studies (1385 VP/VLBW participants, 1780 controls), using a range of instruments and approaches to assigning diagnoses. Those born VP/VLBW had ten times higher odds of meeting criteria for ASD (odds ratio [OR] 10·6, 95% confidence interval [CI] 2·50, 44·7), five times higher odds of meeting criteria for ADHD (OR 5·42, 95% CI 3·10, 9·46), twice the odds of meeting criteria for Anxiety Disorder (OR 1·91, 95% CI 1·36, 2·69), and 1·5 times the odds of meeting criteria for Mood Disorder (OR 1·51, 95% CI 1·08, 2·12) than controls. This pattern of findings was consistent within age (

In Fabry disease, accumulation of glycolipids, predominantly globotriaosylceramide (Gb3), affects the kidneys, and nephropathy is one of the important disorders that influence the disease severity and prognosis of patients. Urinary Gb3 has been analyzed for diagnosis and monitoring of Fabry disease. In this study, we analyzed urinary Gb3 by thin-layer chromatography (TLC)-immunostaining and liquid chromatography (LC)-tandem mass spectrometry (MS/MS). An improved qualitative method, TLC-immunostaining, revealed excessive urinary Gb3 excretion in 100 (8/8), 88 (14/16), and 74% (45/61) of the classic Fabry males, later-onset Fabry males, and Fabry females examined, respectively. This authentic method is robust, easy, economic, and hardly affected by abundant urinary sediment, and this is useful for diagnosing individual Fabry patients. LC-MS/MS can determine the level of Gb3 in urine with high sensitivity, and it revealed that the Gb3 excretion level was higher in the order of classic Fabry males, later-onset Fabry males, Fabry females, and controls, respectively, and this is expected to be a useful quantitative method not only for diagnosis but also for predicting the progression of Fabry nephropathy. As to the relation of the urinary Gb3 level and renal events, our study revealed that the urinary Gb3 level in Fabry patients experiencing renal events tended to be higher than that in ones who did not have any renal events in each phenotypic group of the disease., Highlights • Urinary Gb3 excretion was analyzed by means of TLC-immunostaining and LC-MS/MS. • Excessive urinary Gb3 excretion was detected in most of the Fabry patients on TLC-immunostaining. • The urinary Gb3 levelwas higher in the order of classic Fabry males, later-onset Fabry males, Fabry females, and controls. • The urinary Gb3 level in the Fabry patients who exhibited renal events tended to be higher than that in those who did not.

Background: The mechanisms leading to atrial fibrosis in patients with atrial fibrillation (AF), especially in relation to inflammation, remain unclear. Methods and Results: Forty biomarkers were measured in peripheral blood samples collected prior to catheter ablation, and the association with left atrial (LVZ) was evaluated in 16 consecutive patients. The median %LVZ was 17%. In Pearson’s correlation analysis, interleukin(IL)-17A and interferon(IFN)-γ showed the most significant positive and negative correlations with %LVZ (R = 0.35 and 0.43, P

Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne viral zoonotic disease caused by Crimean-Congo hemorrhagic fever virus (CCHFV). The disease is usually asymptomatic in domestic and wild animals, both of which may act as reservoirs of the virus. CCHF is endemic in parts of Africa, Asia, the Middle East and Eastern Europe. During the last decade, the emergence or re-emergence of CCHF was described in several countries in the Eastern Mediterranean Region, with an increasing risk of extension into new areas. Given the public health importance, this study undertakes a semi-quantitative risk assessment to analyse the likelihood of entry and exposure of CCHFV into 9 CCHF-free countries in Southern and Western Europe. Based on a framework outlining the probability of the virus entry and exposure, the risk estimates were assessed for each individual country. The risk assessment was performed using information from public databases and the available scientific literature. The likelihood of entry was conducted considering 3 main pathways: infected tick vectors, wildlife and livestock. The likelihood of exposure was assessed considering the probability of survival of the infected ticks once introduced in CCHF-free countries (depending on abiotic and biotic factors), and the exposure of resident uninfected susceptible ticks to infected imported wildlife and livestock. The risk estimates (combined CCHFV introduction and exposure) were low for the majority of the countries (Austria, Belgium, Germany, Luxembourg, Netherlands, Slovenia and Switzerland) and medium for France and Italy, if accounting only for animal health consequences. Considering the public health consequences only, the risks were rated low for all the countries, except for Italy where it was assessed to be medium.

The prevalence of nonalcoholic steatohepatitis (NASH) caused by estrogen deficiency increased sharply in recent decades and has become a major threat to liver health in postmenopausal women. There is no effective strategy to control the incidence and development of NASH. Dehydroepiandrosterone (DHEA) is the most abundant circulating steroid with immune and metabolic regulatory properties, and its level markedly declines with increasing age in humans. Importantly, DHEA can convert into active sex hormones depending on the local needs of target tissues with little diffusion, which serves to avoid systemic side-effects from other tissues’ exposure to estrogen. Here, we found that DHEA prevented the incidence and development of NASH, which is characterized by the reduction of hepatic steatosis, fibrosis, and inflammation in female mice fed with high-fat/high-cholesterol diets and effectively attenuated lipid accumulation, inflammatory response, and oxidative stress in palmitic acid-challenged hepatocytes. Mechanistically, in vitro and in vivo studies showed that the anti-NASH function of DHEA depended on its biotransformation into estrogen rather than androgen, and which up-regulates the expression of G protein-coupled estrogen receptor (GPR30), a non-classical estrogen receptor. The activation of GPR30-mediated AMP-activated protein kinase signaling is a necessary prerequisite for the alleviative effects of DHEA on NASH. Collectively, our data show the mechanisms of DHEA treatment and its effects on NASH that were previously overlooked; the data also show that GPR30 can be used as a target for treating lipid metabolism disorders and related diseases, such as NASH. Furthermore, these findings have the potential to help researchers develop new strategies for preventing NASH in postmenopausal women., Graphical abstract Image 1, Highlights • DHEA has the capability in preventing the concurrence and development of NASH. • The mitigation effect of DHEA on NASH depends on its conversion into estradiol. • The protective effect of DHEA against NASH presents GPR30-dependent manner. • GPR30-mediated AMPK pathway activation is required for the anti-NASH of DHEA.

Background COVID-19 co-infections have been described with different pathogens, including filamentous and yeast fungi. Methodology A retrospective case series study conducted from February to December 2020, at a Brazilian university hospital. Data were collected from two hospital surveillance systems: Invasive fungal infection (IFI) surveillance (Mycosis Resistance Program - MIRE) and COVID-19 surveillance. Data from both surveillance systems were cross-checked to identify individuals diagnosed with SARS-CoV-2 (by positive polymerase chain reaction (PCR)) and IFI during hospital stays within the study period. Results During the study period, 716 inpatients with COVID-19 and 55 cases of IFI were identified. Fungal co-infection with SARS-CoV-2 was observed in eight (1%) patients: three cases of aspergillosis; four candidemia and one cryptococcosis. The median age of patients was 66 years (IQR 58-71 years; range of 28-77 years) and 62.5% were men. Diagnosis of IFI occurred a median of 11.5 days (IQR 4.5-23 days) after admission and 11 days (IQR 6.5-16 days) after a positive PCR result for SARS-CoV-2. In 75% of cases, IFI was diagnosed in the intensive care unit (ICU). Cases of aspergillosis emerged earlier than those of candidemia: an average of 8.6 and 28.6 days after a positive PCR for SARS-CoV-2, respectively. All the patients with both infections ultimately died. Conclusion A low rate of COVID-19 co-infection with IFI was observed, with high mortality. Most cases were diagnosed in ICU patients. Aspergillosis diagnosis is highly complex in this context and requires different criteria.

Rabies is a major public health problem and the incidence of suspected rabid animal bites remains high in China. This study aimed to assess the knowledge, attitudes, and practices (KAP) about rabies of bite victims in Wuhan, China. A cross-sectional study was conducted among 1015 bite victims visiting rabies prevention clinics. We performed a face-to-face interview to investigate the rabies KAP of these victims using a self-designed questionnaire. Factors associated with the KAP were evaluated using logistic regression models. Only 56.85% of respondents knew that rabies is infectious. More than 20% of respondents thought that it is not necessary to vaccinate dogs and cats against rabies usually. About 70% of participants stated that they never need to be reminded to vaccinate when they were bitten. Lower education level (odds ratio [OR] = 3.77, 95% confidence interval [CI]: 2.65–5.38 for secondary school or less and OR = 1.74, 95% CI: 1.28–2.38 for high school or vocational school, p-trend60, p-trend, Highlights • The level of rabies KAP among bite victims in China was suboptimal. • Most bite victims had some knowledge gaps such as the severity of rabies. • Most respondents had positive attitudes, but their practices might be insufficient.