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Purpose: Patients with chronic kidney disease (CKD) usually represent an aging population, and both older age and CKD are associated with a higher risk of falling. Studies on risk factors among subjects with CKD are lacking. Methods: Records of outpatients from one geriatric clinic in Turkey were retrospectively reviewed. A result of ≥ 13.5 s on the timed up and go (TUG) test was accepted as a high risk of falls. Independent predictors of an increased risk of falls among subjects with CKD (estimated glomerular filtration rate of < 60 mL/min/1.73 m2) were identified using logistic regression models. Results: Patients with CKD (n = 205), represented the 20.2% of the entire cohort and was identified as an independent predictor of increased fall risk (OR 2.59). Within the CKD cohort, serum folic acid levels and frailty were independent predictors of an increased risk of falls. The CKD/fall risk group was older, had a lower median years of education, lower vitamin D levels, and lower serum folic acid levels than the CKD/non-fall risk group. In addition to higher serum creatinine and potassium levels, the only significant difference between patients with CKD/fall risk and a matched non-CKD/fall risk was a lower median folic acid level in the former group. Conclusions: Frailty and low folic acid levels are independently associated with an increased risk of falls among elderly outpatients with CKD. Prevention of frailty may reduce the risk of falls in these subjects. Possible benefit of folic acid supplementation requires further studies. © 2021, The Author(s), under exclusive licence to Springer Nature B.V.

Preclinical models propose that increased hippocampal activity drives subcortical dopaminergic dysfunction and leads to psychosis-like symptoms and behaviors. Here, we used multimodal neuroimaging to examine the relationship between hippocampal regional cerebral blood flow (rCBF) and striatal dopamine synthesis capacity in people at clinical high risk (CHR) for psychosis and investigated its association with subsequent clinical and functional outcomes. Ninety-five participants (67 CHR and 28 healthy controls) underwent arterial spin labeling MRI and 18F-DOPA PET imaging at baseline. CHR participants were followed up for a median of 15 months to determine functional outcomes with the global assessment of function (GAF) scale and clinical outcomes using the comprehensive assessment of at-risk mental states (CAARMS). CHR participants with poor functional outcomes (follow-up GAF n = 25) showed higher rCBF in the right hippocampus compared to CHRs with good functional outcomes (GAF ≥ 65, n = 25) (pfwe = 0.026). The relationship between rCBF in this right hippocampal region and striatal dopamine synthesis capacity was also significantly different between groups (pfwe = 0.035); the association was negative in CHR with poor outcomes (pfwe = 0.012), but non-significant in CHR with good outcomes. Furthermore, the correlation between right hippocampal rCBF and striatal dopamine function predicted a longitudinal increase in the severity of positive psychotic symptoms within the total CHR group (p = 0.041). There were no differences in rCBF, dopamine, or their associations in the total CHR group relative to controls. These findings indicate that altered interactions between the hippocampus and the subcortical dopamine system are implicated in the pathophysiology of adverse outcomes in the CHR state.

This statement addresses the need to provide clinically relevant and practical guidance for long-term care staff working in care homes and other stakeholders engaged in the care of residents who require consideration for dexamethasone and oxygen therapy. It had been provided following a series of consensus discussions between the EDWPOP and the EuGMS in January and February 2021. Its main aim is to minimise morbidity and mortality from serious acute illnesses including COVID-19 requiring these treatments within the long-term care sector.

Background:\ud \ud There are currently no studies on visual impairment and sarcopenia. We investigated the cross-sectional association between objectively measured far vision impairment and sarcopenia in a nationally representative sample of older adults aged 65 years and over from six low- and middle-income countries (LMICs).\ud \ud Methods:\ud \ud Cross-sectional, community-based data from the study on global ageing and adult health (SAGE) were analyzed. Far vision acuity was measured using the tumbling E LogMAR chart and classified as: no vision impairment (6/12 or better); mild vision impairment (6/18 or better but worse than 6/12); moderate vision impairment (6/60 or better but worse than 6/18); severe vision impairment (worse than 6/60). Sarcopenia was defined as having low skeletal muscle mass and either a slow gait speed or a weak handgrip strength. Associations were assessed with multivariable logistic regression.\ud \ud Results:\ud \ud Fourteen thousand five hundred and eighty five individuals aged ≥ 65 years were included in the analysis [mean (SD) age 72.6 (11.5) years; 54.1% females]. After adjustment for multiple potential confounders, compared to those with no vision impairment, the OR (95% CI) for sarcopenia in those with mild, moderate, and severe vision impairment were 1.10 (0.87–1.40), 1.69 (1.25–2.27), and 3.38 (1.69–6.77), respectively. The estimates for females and males were similar.\ud \ud Conclusions:\ud \ud The odds for sarcopenia increased with increasing severity of far vision impairment among older people in LMICs. The mere co-occurrence of these conditions is concerning, and it may be prudent to implement interventions to address/prevent sarcopenia in those with far vision impairment through the promotion of physical activity and appropriate nutrition.

Chronic lymphocytic leukemia (CLL) is characterized by the existence of subsets of patients with (quasi)identical, stereotyped B-cell receptor (BcR) immunoglobulins. Patients in certain major stereotyped subsets often display remarkably consistent clinicobiological profiles, suggesting that the study of BcR immunoglobulin stereotypy in CLL has important implications for understanding disease pathophysiology and refining clinical decision-making. Nevertheless, several issues remain open, especially pertaining to the actual frequency of BcR immunoglobulin stereotypy and major subsets, as well as the existence of higher-order connections between individual subsets. To address these issues, we investigated clonotypic IGHV-IGHD-IGHJ gene rearrangements in a series of 29 856 patients with CLL, by far the largest series worldwide. We report that the stereotyped fraction of CLL peaks at 41% of the entire cohort and that all 19 previously identified major subsets retained their relative size and ranking, while 10 new ones emerged; overall, major stereotyped subsets had a cumulative frequency of 13.5%. Higher-level relationships were evident between subsets, particularly for major stereotyped subsets with unmutated IGHV genes (U-CLL), for which close relations with other subsets, termed “satellites,” were identified. Satellite subsets accounted for 3% of the entire cohort. These results confirm our previous notion that major subsets can be robustly identified and are consistent in relative size, hence representing distinct disease variants amenable to compartmentalized research with the potential of overcoming the pronounced heterogeneity of CLL. Furthermore, the existence of satellite subsets reveals a novel aspect of repertoire restriction with implications for refined molecular classification of CLL. Key Points: • In a series of 29 856 CLL patients, the incidence of BcR stereotypy peaked at 41%. • Higher-order relations exist between stereotyped subsets, particularly for those from U-CLL, for which satellite subsets were identified.

Aim: The association between visual impairment and mild cognitive impairment (MCI) has not been investigated to date. Thus, we assessed this association among older adults from six low- and middle-income countries (LMICs) (China, India, Ghana, Mexico, Russia, and South Africa) using nationally representative datasets. Methods: Cross-sectional, community-based data from the WHO Study on global AGEing and adult health (SAGE) were analyzed. Visual acuity was measured using the tumbling ElogMAR chart, and vision impairment (at distance and near) was defined as visual acuity worse than 6/18 (0.48 logMAR) in the better-seeing eye. The definition of MCI was based on the National Institute on Aging-Alzheimer’s Association criteria. Multivariable logistic regression was conducted. Results: Data on 32,715 individuals aged ≥ 50years [mean (SD) age 62.1 (15.6) years; 51.2% females] were analyzed. Compared to those without far or near vision impairment, those with near vision impairment but not far vision impairment (OR = 1.33; 95% CI = 1.16–1.52), and those with both far and near vision impairment (OR = 1.70; 95% CI = 1.27–2.29) had significantly higher odds for MCI. Only having far vision impairment was not significantly associated with MCI. Conclusions: Visual impairment is associated with increased odds for MCI among older adults in LMICs with the exception of far vision impairment only. Future longitudinal and intervention studies should examine causality and whether improvements in visual acuity, or early intervention, can reduce risk for MCI and ultimately, dementia. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.

BackgroundOne can assume a relatively high prevalence of urinary incontinence (UI) in people with multimorbidity. However, literature in this area is scarce. There is a need for further robust research to aid GPs to identify patients at a particular risk for UI, and to initiate the early treatment and multidisciplinary management of this condition.AimTo examine the association between multimorbidity and UI in 23 089 individuals aged ≥15 years and residing in Spain.Design and settingThis study used data from the Spanish National Health Survey 2017, a cross-sectional sample of 23 089 participants aged ≥15 years residing in Spain (54.1% female; mean [standard deviation] age = 53.4 [18.9] years).MethodUI and 30 other physical and mental chronic conditions were self-reported. Multimorbidity was defined as the presence of ≥2 physical and/or mental chronic conditions (excluding UI). Control variables included sex, age, marital status, education, smoking, and alcohol consumption. Multivariable logistic regression analyses were conducted to assess the association between multimorbidity and UI.ResultsThe prevalence of UI was 5.9% in this sample. UI was more frequent in the presence than in the absence of each one of the 30 chronic conditions (PPPConclusionIn this large sample of Spanish individuals aged ≥15 years, suffering from multimorbidity was associated with a significantly higher level of UI.

Objectives Antimicrobial resistance (AMR) is one of the major health issues worldwide. Clinicians should play a central role to fight AMR, and medical training is a pivotal issue to combat it; therefore, assessing levels of knowledge, attitudes and practices among young doctors is essential for future antimicrobial stewardship (AMS) programmes. Methods A nationwide, cross-sectional, multicentre survey was conducted in Italy. A descriptive analysis of knowledge and attitudes was performed, along with a univariate and multivariate analysis of their determinants. Results Overall, 1179 young doctors accessed the survey and 1055 (89.5%) completed all sections. Regarding the knowledge section of the questionnaire, almost all participants declared to know the different species of bacteria proposed, however the percentage of participants who correctly responded to clinical quizzes was 23% for the question on vancomycin-resistant enterococci (VRE), 42% on carbapenem-resistant Enterobacteriaceae (CRE), 32% on extended-spectrum β-lactamase-producing enterobacteria (ESBL) and 27% on methicillin-resistantStaphylococcus aureus (MRSA). Similarly, 81% of participants disagreed in stating that AMR was adequately addressed during their medical training and 71% disagreed that they received the right example from their tutors. Finally, a high rate of agreement with the proposed actions to combat AMR was documented; in particular, the percentage agreement was 76% for respondents who agreed to be part of an active surveillance system or AMS programme. Conclusions Tackling AMR should be a priority for politicians and for all health workers. Inclusion of competencies in antibiotic use in all specialty curricula is urgently needed.

Jingyuan Lin,1,* Tianyou Guo,2,* Benjamin Becker,3 Qian Yu,2 Si-Tong Chen,4 Stubbs Brendon,5 Md Mahbub Hossain,6 Paolo M Cunha,7 Fernanda Cunha Soares,8 Nicola Veronese,9 Jane Jie Yu,10 Igor Grabovac,11 Lee Smith,12 Albert Yeung,13 Liye Zou,2 Hong Li1 1Research Centre of Brain Function and Psychological Science; Center for Language and Brain, Shenzhen Institute of Neuroscience; Shenzhen Key Laboratory of Affective and Social Cognitive Science, School of Psychology, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 2Exercise and Mental Health Laboratory, School of Psychology, Shenzhen University, Shenzhen 518060, People’s Republic of China; 3The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, People’s Republic of China; 4Institute for Health and Sport, Victoria University, Melbourne, VIC, 8001, Australia; 5Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK; 6Department of Health Promotion and Community Health Sciences, School of Public Health, Texas A&M University, College Station, TX 77843, USA; 7Metabolism, Nutrition, and Exercise Laboratory, Londrina State University, Londrina, Paraná 86010-580, Brazil; 8Superior School of Physical Education, University of Pernambuco, Recife, PE, Brazil; 9Geriatric Unit, Department of Internal Medicine and Geriatrics, University of Palermo, Palermo 90100, Italy; 10Department of Sports Science and Physical Education, The Chinese University of Hong Kong, Shatin, New Territories 999077, Hong Kong; 11Department of Social and Preventive Medicine, Center for Public Health, Medical University of Vienna, 1090 Wien, Austria; 12The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge CB1 1PT, UK; 13Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA 02114, USA*These authors contributed equally to this workCorrespondence: Hong LiResearch Centre of Brain Function and Psychological Science; Center for Language and Brain, Shenzhen Institute of Neuroscience; Shenzhen Key Laboratory of Affective and Social Cognitive Science, School of Psychology, Shenzhen University, Shenzhen 518060, People’s Republic of ChinaEmail lihongwrm@vip.sina.comPurpose: The novel coronavirus disease (COVID-19) pandemic and associated restrictive measures have implications for depressive symptoms (henceforth depression) of young people and risk may be associated with their reduced physical activity (PA) level. Therefore, we aimed to examine the association between depressive symptoms and PA among college students with different gender and gender role (masculinity traits and femininity traits) during the COVID-19 pandemic.Participants and Methods: Cross-sectional study included 628 healthy college students from nineteen different locations. The Center for Epidemiological Studies Depression Scales (CES-D), the International Physical Activity Questionnaire - Short Form (IPAQ-SF), and the 50-item Chinese Sex-Role Inventory (CSRI-50) were used to measure depressive symptoms, PA continuous (weekly metabolic equivalent minutes, MET-minutes/week) and categorical indicators (activity level category) and gender role, respectively. The statistical analyses were used in partial correlation analysis, t-test, one-way ANOVA, moderation model tests, and linear regression model tests.Results: Total of 34.72% participants had clinically relevant depression (16, CES-D scale). Total of 58.6% participants were classified as a “low” activity level for spending less time on PA. Depression significantly negatively correlated with MET-minutes/week in moderate-intensity PA but not vigorous and walking scores. Of note, the depression-PA association was only moderated by the “low” activity level group in terms of categorical scores across gender groups. Participants with higher masculinity traits were less likely to have depression among all participants. Moreover, more recovered cases and fewer deaths could also predict the lower depression risk in the “high” activity level group.Conclusion: Moderate-intensity PA is beneficial for reducing depression risk among college students at a low activity level. College students with fewer masculinity traits (regardless of gender) are highly vulnerable to depression during the outbreak of COVID-19. Effective control of the COVID-19 pandemic seems critical to alleviating the burden of mental disorders of the public including depression.Keywords: depression, physical activity, gender, masculinity, femininity, COVID-19

Author(s): Kinoshita, Shotaro; Cortright, Kelley; Crawford, Allison; Mizuno, Yuya; Yoshida, Kazunari; Hilty, Donald; Guinart, Daniel; Torous, John; Correll, Christoph U; Castle, David J; Rocha, Deyvis; Yang, Yuan; Xiang, Yu-Tao; Kolbaek, Pernille; Dines, David; ElShami, Mohammad; Jain, Prakhar; Kallivayalil, Roy; Solmi, Marco; Favaro, Angela; Veronese, Nicola; Seedat, Soraya; Shin, Sangho; Salazar de Pablo, Gonzalo; Chang, Chun-Hung; Su, Kuan-Pin; Karas, Hakan; Kane, John M; Yellowlees, Peter; Kishimoto, Taishiro | Abstract: BackgroundDuring the COVID-19 pandemic, the use of telemedicine as a way to reduce COVID-19 infections was noted and consequently deregulated. However, the degree of telemedicine regulation varies from country to country, which may alter the widespread use of telemedicine. This study aimed to clarify the telepsychiatry regulations for each collaborating country/region before and during the COVID-19 pandemic.MethodsWe used snowball sampling within a global network of international telepsychiatry experts. Thirty collaborators from 17 different countries/regions responded to a questionnaire on barriers to the use and implementation of telepsychiatric care, including policy factors such as regulations and reimbursement at the end of 2019 and as of May 2020.ResultsThirteen of 17 regions reported a relaxation of regulations due to the pandemic; consequently, all regions surveyed stated that telepsychiatry was now possible within their public healthcare systems. In some regions, restrictions on prescription medications allowed via telepsychiatry were eased, but in 11 of the 17 regions, there were still restrictions on prescribing medications via telepsychiatry. Lower insurance reimbursement amounts for telepsychiatry consultations v. in-person consultations were reevaluated in four regions, and consequently, in 15 regions telepsychiatry services were reimbursed at the same rate (or higher) than in-person consultations during the COVID-19 pandemic.ConclusionsOur results confirm that, due to COVID-19, the majority of countries surveyed are altering telemedicine regulations that had previously restricted the spread of telemedicine. These findings provide information that could guide future policy and regulatory decisions, which facilitate greater scale and spread of telepsychiatry globally.

Background: Coronavirus disease 19 (COVID-19) is a global outbreak. COVID-19 patients seem to have relevant coagulative abnormalities, even if they are not typical of disseminated intravascular coagulopathy (DIC) of the kind seen in septicaemia. Therefore, anticoagulant therapy with heparins is increasing in interest for a clinical approach to these patients, particularly if older. Studies comparing if prophylactic doses are more effective than therapeutic ones are still missing. Methods: Data were collected in the Geriatric Section of the Dolo Hospital, ULSS 3 “Serenissima”, Venice from 31st March to 01st May 2020. Heparins (calciparin, fondaparinux, enoxaparine) were divided into prophylactic or therapeutic doses. People previously treated with oral anticoagulants were removed. Vital status was assessed using administrative data. Cox’s regression analysis, adjusted for potential confounders, was used for assessing the strength of the association between heparins and mortality. The data were reported as hazard ratio (HR) with 95% confidence intervals (CIs). Results: 81 older people (mean age 84.1years; females = 61.9%) were included. No significant differences in terms of demographic and clinical characteristics emerged between people treated with prophylactic or therapeutic doses, including age, gender, X-rays findings or severity of disease. Therapeutic doses were not associated to a better survival rate (HR 1.06; 95% CI 0.47–2.60; p = 0.89), even after adjusting for 15 confounders related to mortality (HR 0.89; 95% CI 0.30–2.71; p = 0.84). Conclusions: Our paper indicates that in older people affected by COVID-19 there is no justification for using therapeutic doses instead of prophylactic ones, having a similar impact on mortality risk. © 2020, Springer Nature Switzerland AG.

BACKGROUND Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. OBJECTIVES This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. METHODS A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms

Tea is one of the most widely consumed beverages, but its association with cancer risk remains controversial and unclear. We performed an umbrella review to clarify and determine the associations between tea consumption and various types of cancer by summarizing and recalculating the existing meta-analyses. Meta-analyses of observational studies reporting associations between tea consumption and cancer risk were searched on PubMed and Embase. Associations found to be statistically significant were further classified into levels of evidence (convincing, suggestive, or weak), based on P value, between-study heterogeneity, prediction intervals, and small study effects. Sixty-four observational studies (case-control or cohort) corresponding to 154 effect sizes on the incidence of 25 types of cancer were included. Forty-three (27.9%) results in 15 different types of cancer were statistically significant. When combining all studies on the same type of cancer, 19 results in 11 different types of cancer showed significant associations with lower risk of gastrointestinal tract organ cancer (oral, gastric, colorectal, biliary tract, and liver cancer), breast cancer, and gynecological cancer (endometrial and ovarian cancer) as well as leukemia, lung cancer, and thyroid cancer. Only the reduced risk of oral cancer in tea-consuming populations (OR = 0.62; 95% CI: 0.55, 0.72; P value < 10-6) was supported by convincing evidence. Suggestive evidence was found for 6 results on biliary tract, breast, endometrial, liver, and oral cancer. To summarize, tea consumption was shown to have protective effects on some types of cancer, particularly oral cancer. More well-designed prospective studies are needed with consideration of other factors that can cause biases.

Aim: The economic recognition of disability is of importance in daily practice, but the tools used in older people are still limited. Therefore, we aimed to investigate the effectiveness of the multidimensional prognostic index (MPI) to identify frail older subjects to be submitted to civil invalidity application for disability benefits including Attendance Allowance (AA) indemnity, Carer’s Leave (Law 104) and/or Parking Card for people with disabilities. Methods: From March 2018 to January 2019, 80 older people were included. The MPI was calculated from comprehensive geriatric assessment information including eight different domains. Civil benefits included attendance allowance (AA) indemnity by the Local Medico-Legal Committee (MLC-NHS) and by the National Institute of Social Security Committee (INPS), Carer’s Leave (Law 104), and Parking Card for people with disabilities. Results: MPI values were associated with an increased probability to obtain a 100% civil disability, AA indemnity, Carer’s Leave and a parking card for people with disabilities. MPI score showed a very good accuracy in predicting the civil invalidity benefits with a area-under-curve (AUC) of 87.3 (95% CI 80.6–97.4) to predict the release of AA indemnity, 81.3 (95% CI 68.5–91.1) to predict Care’s leave and 70.7 (95% CI 59.4–84.7) to predict the Parking Card release. Moreover, data showed that a cut-off score of MPI ≥ 0.75 could identify the 100% of older subjects who successfully obtained the indemnity release. Conclusion: MPI is an excellent predictor of social benefits’ release by local and national agencies. © 2020, Springer Nature Switzerland AG.

Background Sexual activity can be referred to as a health behavior and may also act as an indicator of health status. Aim To evaluate temporal trends in sexual activity and to examine associations of sexual activity with all-cause and cause-specific mortality risk. Methods We examined the trends and prevalence of sexual activity and association of sexual activity with all-cause and cause-specific mortality in a nationally representative sample using data from the US National Health and Nutrition Examination Survey from 2005 to 2016 and the National Health and Nutrition Examination Survey 2005-2014 Linked Mortality File (through December 31, 2015). Outcomes All-cause, cardiovascular disease, and cancer mortality. Results A total of 15,269 US adults (mean age, 39.1 years [standard error, 0.18 years]) were included in the trend analysis. In the 2015-2016 cycle, while 71.7% (95% CI, 67.7–75.7%) US adults aged 20-59 years engaged in sexual activity ≥ 12 times/year (monthly), only 36.1% (95% CI, 31.6–40.7%) of them engaged in sexual activity ≥ 52 times/year (weekly). Since the 2005–2006 cycle, the estimated prevalence of sexual activity, ≥52 times/year and ≥12 times/year, were both stable over time among overall and each age group (all P for trend >0.1). During a median follow-up of 5.7 years (range, 1–11 years) and 71,960 person-years of observation, among 12,598 participants with eligible information on mortality status, 228 deaths occurred, including 29 associated with cardiovascular disease and 62 associated with cancer. Overall, participants with higher sexual activity frequency were at a lower risk of all-cause death in a dose-response manner (P for trend = 0.020) during the follow-up period. In addition, the multivariable-adjusted hazard ratios for all-cause mortality, CVD mortality, cancer mortality, and other cause mortality among participants who had sex ≥52 times/year compared with those having sex 0–1 time/year were 0.51 (95% CI, 0.34 to 0.76), 0.79 (95% CI, 0.19 to 3.21), 0.31 (95% CI, 0.11 to 0.84), and 0.52 (95% CI, 0.28 to 0.96), respectively. Clinical Implications Sexual activity appears to be a health indicator of all-cause and cancer mortality in US middle-aged adults. Strengths & Limitations Clear strengths of the present study include the large representative sample of the noninstitutionalized US population as well as the identification of precise estimates in relation to sexual activity and mortality. However, because of the observational nature of the study design, causality could not be determined. Conclusions Sexual activity was found to be associated with a lower risk of mortality from all cause and cancer.

Background In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. Aims The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. Methods This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. Results The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure. Conclusion The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by extensive local invasion and systemic spread. In this study, we employed a three-dimensional organoid model of human pancreatic cancer to characterize the molecular alterations critical for invasion. Time-lapse microscopy was used to observe invasion in organoids from 25 surgically resected human PDAC samples in collagen I. Subsequent lentiviral modification and small-molecule inhibitors were used to investigate the molecular programs underlying invasion in PDAC organoids. When cultured in collagen I, PDAC organoids exhibited two distinct, morphologically defined invasive phenotypes, mesenchymal and collective. Each individual PDAC gave rise to organoids with a predominant phenotype, and PDAC that generated organoids with predominantly mesenchymal invasion showed a worse prognosis. Collective invasion predominated in organoids from cancers with somatic mutations in the driver gene SMAD4 (or its signaling partner TGFBR2). Reexpression of SMAD4 abrogated the collective invasion phenotype in SMAD4-mutant PDAC organoids, indicating that SMAD4 loss is required for collective invasion in PDAC organoids. Surprisingly, invasion in passaged SMAD4-mutant PDAC organoids required exogenous TGFβ, suggesting that invasion in SMAD4-mutant organoids is mediated through noncanonical TGFβ signaling. The Rho-like GTPases RAC1 and CDC42 acted as potential mediators of TGFβ-stimulated invasion in SMAD4-mutant PDAC organoids, as inhibition of these GTPases suppressed collective invasion in our model. These data suggest that PDAC utilizes different invasion programs depending on SMAD4 status, with collective invasion uniquely present in PDAC with SMAD4 loss. Significance: Organoid models of PDAC highlight the importance of SMAD4 loss in invasion, demonstrating that invasion programs in SMAD4-mutant and SMAD4 wild-type tumors are different in both morphology and molecular mechanism.

Background: Hand osteoarthritis (OA) is common, but the efficacy/safety of treatment interventions aimed to improve health outcomes in this population are not well understood. Therefore, the aim of this study was to map and grade the effect of interventions for health outcomes in hand OA. Methods: Umbrella review of systematic reviews with meta-analyses of randomized controlled trials (RCTs) using placebo/no intervention as control group. For outcomes with ap-value

The purpose of this study was to explore mental health workers’ perceptions and concerns about the psychosocial interventions provided to third-generation Palestinian refugee children. Our sample comprised 30 mental health practitioners aged 26–35 years, who were purposively selected at five Palestinian refugee camps in the West Bank of Palestine. Thematic content analysis was applied to transcripts of interviews with the practitioners, with a view to identifying key themes. It emerged that psychosocial service providers typically deliver consultation, group, and individual counselling, debriefing, and life skills training to children in Palestinian camps. The main challenges faced by the psychosocial service providers in the camps include a lack of qualified specialist staff, insufficient funding, the political conflict, and poor community awareness of psychosocial services, as well as low salaries and unemployment among psychosocial practitioners. The participants suggested that improving psychosocial services in the future will require investment in the sector, working alongside families and schools, establishing permanent psychosocial centres, and offering professional development opportunities to Palestinian psychosocial service providers.

Objectives: This review aims to: (1) map the use of sonification in human movement tasks for physical therapy; (2) identify methods of data capture, tasks and its effects on human subjects; (3) suggest future research directions. News: Sonification can be described as a technique to translate data into sound. It has been used for human motion analysis tasks even if it is not part of most physical therapist's lexicon. Prospects and projects: Identify and analyze publications where sonification was used as an audio-feedback technique for physical therapy. Thirty-five papers were included, 13 randomized-control-trials. Thirteen papers reported an investigation on a specific dysfunction, while upper limb movements were investigated in fifteen papers. Inertial measurement units were the most commonly used technology to capture human movement, 10 papers reported improvements in motor control and/or movement quality. Gaps in the literature were identified: (1) absence of sonification framework for rehabilitation, (2) no long-term comparison with gold-standard interventions for specific populations, (3) approaches for cardio-respiratory physical therapy and injury prevention were absent. Conclusion: Sonification has the potential to support rehabilitation for physical therapy. Effects of sonification were varied and ranged from improvements in movement quality/control, increased movement and body-awareness and improvements in performance when compared with activities with audio-visual or non-specific audio-feedback among others. Data for sonification was mainly captured using inertial measurement units, smartphones and optical tracking devices but others are also commonly used. Well-designed clinical trials supported by current promising results need to be developed. We recommend testing different sonification techniques in common physical therapy disfunctions using significant outcome measures to understand and maximize its effects on motor learning and control while scoping for further benefits. © 2020 Elsevier Masson SAS

This systematic review aims to investigate the effects of intermittent energy restriction (IER) on anthropometric outcomes and intermediate disease markers. A systematic literature search was conducted in three electronic databases. Randomized controlled trials (RCTs) were included if the intervention lasted ≥12 weeks and IER was compared with either continuous energy restriction (CER) or a usual diet. Random-effects meta-analysis was performed for eight outcomes. Certainty of evidence was assessed using GRADE. Seventeen RCTs with 1328 participants were included. IER in comparison to a usual diet may reduce body weight (mean difference [MD]: −4.83 kg, 95%-CI: −5.46, −4.21; n = 6 RCTs), waist circumference (MD: −1.73 cm, 95%-CI: −3.69, 0.24; n = 2), fat mass (MD: −2.54 kg, 95%-CI: −3.78, −1.31; n = 6), triacylglycerols (MD: −0.20 mmol/L, 95%-CI: −0.38, −0.03; n = 5) and systolic blood pressure (MD: −6.11 mmHg, 95%-CI: −9.59, −2.64; n = 5). No effects were observed for LDL-cholesterol, fasting glucose, and glycosylated-hemoglobin. Both, IER and CER have similar effect on body weight (MD: −0.55 kg, 95%-CI: −1.01, −0.09; n = 13), and fat mass (MD: −0.66 kg, 95%-CI: −1.14, −0.19; n = 10), and all other outcomes. In conclusion, IER improves anthropometric outcomes and intermediate disease markers when compared to a usual diet. The effects of IER on weight loss are similar to weight loss achieved by CER.

Background & aims: The literature regarding enteral nutrition and mortality in older frail people is limited and still conflicting. Moreover, the potential role of comprehensive geriatric assessment is poorly explored. We therefore aimed to investigate whether the Multidimensional Prognostic Index (MPI), an established tool that assesses measures of frailty and predicts mortality, may help physicians in identifying patients in whom ETF (enteral tube feeding) is effective in terms of reduced mortality. Methods: Observational, longitudinal, multicenter study with one year of follow-up. Data regarding ETF were recorded through medical records. A standardized comprehensive geriatric assessment was used to calculate the MPI. Participants were divided in low (MPI-1), moderate (MPI-2) or severe (MPI-3) risk of mortality. Data regarding mortality were recorded through administrative information. Results: 1064 patients were included, with 79 (13 in MPI 1–2 and 66 in MPI-3 class) receiving ETF. In multivariable analysis, patients receiving ETF experienced a higher risk of death (odds ratio, OR = 2.00; 95% confidence intervals, CI: 1.19–3.38). However, after stratifying for their MPI at admission, mortality was higher in MPI-3 class patients (OR = 2.03; 95%CI: 1.09–3.76), but not in MPI 1–2 class patients (OR = 1.51; 95%CI: 0.44–5.25). The use of propensity score confirmed these findings. Conclusions: ETF is associated with a higher risk of death. However, this is limited to more frail patients, suggesting the importance of the MPI in the prognostic evaluation of ETF. © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism

The objective of the present study was to investigate the association between angiotensin-converting enzyme (ACE) inhibitor use and cancer incidence (overall, and breast, prostate, and colorectal cancers specifically) in a large representative sample of US adults. Cross-sectional data on cancer diagnosis, timing of cancer diagnosis, ACE inhibitor use, and other characteristics were extracted from 49 512 adults aged ≥ 20years participating in the National Health and Nutrition Examination Survey (1999–2016). Multivariable-logistic and propensity score matching (PSM) regressions examined the relationship between pre-diagnosis use of ACE inhibitors and diagnosis of all cancers, and breast, prostate, and colorectal cancers specifically. Overall, we observed an increased likelihood of cancer diagnosis [odds ratio (OR) 1.269, 95% confidence interval (CI) 1.088–1.480] among those who used ACE inhibitors compared to non-ACE inhibitor use, and for prostate cancer diagnosis (OR 1.438, 95% CI 1.090–1.897), after adjusting for age, sex, body mass index, race/ethnicity, educational attainment, physical activity, alcohol drinking status, smoking status, and high blood pressure. PSM regression retrieved more conservative estimates such that the increased likelihood of cancer diagnosis was only observed when comparing ACE inhibitor users with non-drug users (OR 1.022, 95% CI 1.016–1.027). Compared with non-ACE inhibitor use, ACE inhibitor use was associated with an increased risk of prostate cancer. In conclusion, in this large representative sample of US adults, it was found that ACE inhibitor use may have a marginal influence on some cancers. © 2020, Springer Nature Switzerland AG.

Osteoarthritis (OA) is the most common joint condition and, with a burgeoning ageing population, is due to increase in prevalence. Beyond conventional medical and surgical interventions, there are an increasing number of ‘alternative’ therapies. These alternative therapies may have a limited evidence base and, for this reason, are often only afforded brief reference (or completely excluded) from current OA guidelines. Thus, the aim of this review was to synthesize the current evidence regarding autologous chondrocyte implantation (ACI), mesenchymal stem cell (MSC) therapy, platelet-rich plasma (PRP), vitamin D and other alternative therapies. The majority of studies were in knee OA or chondral defects. Matrix-assisted ACI has demonstrated exceedingly limited, symptomatic improvements in the treatment of cartilage defects of the knee and is not supported for the treatment of knee OA. There is some evidence to suggest symptomatic improvement with MSC injection in knee OA, with the suggestion of minimal structural improvement demonstrated on MRI and there are positive signals that PRP may also lead to symptomatic improvement, though variation in preparation makes inter-study comparison difficult. There is variability in findings with vitamin D supplementation in OA, and the only recommendation which can be made, at this time, is for replacement when vitamin D is deplete. Other alternative therapies reviewed have some evidence (though from small, poor-quality studies) to support improvement in symptoms and again there is often a wide variation in dosage and regimens. For all these therapeutic modalities, although controlled studies have been undertaken to evaluate effectiveness in OA, these have often been of small size, limited statistical power, uncertain blindness and using various methodologies. These deficiencies must leave the question as to whether they have been validated as effective therapies in OA (or chondral defects). The conclusions of this review are that all alternative interventions definitely require clinical trials with robust methodology, to assess their efficacy and safety in the treatment of OA beyond contextual and placebo effects. Electronic supplementary material The online version of this article (10.1007/s40520-020-01515-1) contains supplementary material, which is available to authorized users.

Alberto Cella,1 Alberto Ferrari,2 Giuseppe Rengo,3 Vincenzo Solfrizzi,4 Nicola Veronese,5 Matteo Puntoni,6 Sabrina Zora,1 Alberto Pilotto,1,4 Filippo Fimognari7 On behalf of the SELFY-MPI SIGOT Investigators1Geriatric Unit, Department of Geriatric Care, Orthogeriatrics and Rehabilitation, EO Galliera Hospital, Genova, Italy; 2Geriatric Unit, Arcispedale S. Maria Nuova, AUSL Reggio Emilia, Reggio Emilia, Italy; 3Department of Translational Medical Sciences, Division of Geriatrics, Federico II University, Napoli, Italy; 4Department of Interdisciplinary Medicine, University of Bari, Bari, Italy; 5Primary Care Department, Azienda ULSS 3 Serenissima, Venice, Italy; 6Scientific Coordination Unit, EO Galliera Hospital, Genova, Italy; 7Geriatric Unit, Department of Internal Medicine, Azienda Ospedaliera di Cosenza, Cosenza, ItalyCorrespondence: Sabrina ZoraGeriatric Unit, Department of Geriatric Care, Orthogeriatrics and Rehabilitation, EO Galliera Hospital, Genova, ItalyEmail sabrina.zora@galliera.itBackground: The Multidimensional Prognostic Index (MPI) is a comprehensive geriatric assessment (CGA)-based tool that has shown excellent accuracy in predicting negative health outcomes in older people. Recently, the self-administered version of MPI (SELFY-MPI) has been validated in a community-dwelling sample, revealing excellent agreement with the original MPI. In the SELFY-MPI, Gijon’s social-familial evaluation scale (SFES) was used to assess socio-relational and economic aspects. Completion of the SELFY-MPI, however, requires a significant amount of time in people aged over 60 years, particularly to fill in the SFES scale. The aim of this study was to validate, in a sample of community-dwelling older people, a short-form version of the SELFY-MPI (SELFY-MPI-SF), in which the SFES scale was replaced by the “co-habitation status” domain, as in the original version of the MPI.Methods: All participants included in the study completed both versions of the self-administered MPI, which share the following seven domains: 1) basic and 2) instrumental activities of daily living, 3) mobility, 4) cognition, 5) nutrition, 6) comorbidity, and 7) number of medications. Moreover, in the SELFY-MPI-SF, the 8th domain “co-habitation status” (ie living alone, with family or in a residential facility) replaced the SFES scale. The Bland–Altman methodology was applied in order to measure the agreement between the two instruments. Finally, the time to complete the SFES scale and the question on co-habitation was measured.Results: The final study sample was composed of 129 participants (mean age=76.8 years, range=65– 93 years, 64.3% women) were enrolled. The mean SELFY-MPI and SELFY-MPI-SF values were 0.221± 0.196 and 0.246± 0.188, respectively. The mean difference was clinically irrelevant (− 0.025± 0.058). None of the 129 observations showed values outside the established 5% limits of agreement. The agreement between SELFY-MPI and SELFY-MPI-SF was excellent (k=0.762; rho=0.924, p< 0.0001 for both). Stratified analyses of agreement among subgroups of participants of different ages did not show any significant differences between the two versions. Completion of the SFES required about 7mins, on average, while the question on habitation status required about 10 s.Conclusion: The SELFY-MPI-SF showed strong agreement and precision when compared with the standard SELFY-MPI in people aged 65 and older and can therefore be successfully used as a quicker self-administered frailty instrument in community-dwelling older people.Keywords: comprehensive geriatric assessment, multidimensional prognostic index, frailty, self assessment

Background and aims: Increasing literature data show that adherence to the Mediterranean diet is undergoing profound changes in recent years, albeit with marked differences across nations. In Italy, one of the cradles of the Mediterranean diet, the literature regarding the trend for Mediterranean diet adherence is conflicting. Thus, we aimed to explore the trends of adherence to the Mediterranean diet in a large cohort of participants living in South Italy, over 20 years from 1985–86 to 2005–06. Methods and results: Cross-sectional study with two evaluations, one made in 1985–86 and another in 2005–06; all participants were adults aged 30–70 years of age. The adherence to the Mediterranean diet was evaluated using the score proposed by Panagiotakos et al. This score features values ranging from 0 to 55, higher scores reflecting a greater adherence. The data are reported by age (30–49 vs. 50–69 years). Overall, 2451 subjects were included in 1985–86 and 2375 in 2005–06. A significant reduction was observed in the adherence to the Mediterranean diet (age 30–49 years: 31.82 ± 4.18 in 1985–86 vs. 29.20 ± 4.48 in 2005–06, reduction by 8.2%, p < 0.0001; age 50–69: 32.20 ± 4.09 in 1985–86 vs.30.15 ± 4.27 in 2005–06, reduction by 6.3%, p < 0.0001). Among all these items, the most dramatic change was observed for olive oil consumption, that decreased by 2.35 points in younger and 0.89 in older people. Conclusion: The adherence to the Mediterranean diet decreased from 1985–86 to 2005–06 in South Italy, particularly in younger people, above all due to a decreased olive oil consumption. © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University

Acute myocarditis (AM), a recent-onset inflammation of the heart, has heterogeneous clinical presentations, varying from minor symptoms to high-risk cardiac conditions with severe heart failure, refractory arrhythmias, and cardiogenic shock. AM is moving from being a definitive diagnosis based on histological evidence of inflammatory infiltrates on cardiac tissue to a working diagnosis supported by high sensitivity troponin increase in association with specific cardiac magnetic resonance imaging (CMRI) findings. Though experts still diverge between those advocating for histological definition versus those supporting a mainly clinical definition of myocarditis, in the real-world practice the diagnosis of AM has undoubtedly shifted from being mainly biopsy-based to solely CMRI-based in most of clinical scenarios. It is thus important to clearly define selected settings where EMB is a must, as information derived from histology is essential for an optimal management. As in other medical conditions, a risk-based approach should be promoted in order to identify the most severe AM cases requiring appropriate bundles of care, including early recognition, transfer to tertiary centers, aggressive circulatory supports with inotropes and mechanical devices, histologic confirmation and eventual immunosuppressive therapy. Despite improvements in recognition and treatment of AM, including a broader use of promising mechanical circulatory supports, severe forms of AM are still burdened by dismal outcomes. This review is focused on recent clinical studies and registries that shed new insights on AM. Attention will be paid to contemporary outcomes and predictors of prognosis, the emerging entity of immune checkpoint inhibitors-associated myocarditis, updated CMRI diagnostic criteria, new data on the use of temporary mechanical circulatory supports in fulminant myocarditis. The role of viruses as etiologic agents will be reviewed and a brief update on pediatric AM is also provided. Finally, we summarize a risk-based approach to AM, based on available evidence and clinical experience.

Background: Fournier’s gangrene (FG) is a rare necrotising soft tissue infection localised in the genital areas with possible dramatic outcomes. Recently, sodium glucose co-transporter-2 (SGLT2) inhibitors were identified as a risk factor. Methods: We present a case report of a 57-year-old female patient with type 2 diabetes mellitus (T2DM) in treatment with empagliflozin which led to the development of FG. Moreover, we performed a systematic review assessing the association between empagliflozin use and FG. Results: The female patient with 15-years treated diabetes presented a massive FG after 6 months from starting empagliflozin. Over the period of two months, she was successfully treated in a low-income setting. The systematic review included two studies with a total of 9915 participants. Although no participant had FG, there was an increased rate of urinary and genital infection in patients treated with empagliflozin compared to those treated with other antidiabetics or placebo. Conclusions: FG should be considered as a possible complication in patients using SGLT2. Patients should be educated to report early signs of genital infection and healthy behaviours as well as a balanced diet should be promoted to aid in the prevention of FG.

Introduction Ventricular septal rupture (VSR) is a serious mechanical complication after acute coronary syndrome and is related to high mortality. Even with advances in the management of acute myocardial infarction (AMI) such as reperfusion therapies, complication rates are still high. During quarantine, patients presenting mechanical complications after AMI have increased in our institution. Methods From a retrospective database analysis in our institution between the years 2004 and 2020, we identified 37 cases of VSR after AMI. Four chronic cases were excluded from our analysis. The primary endpoint was to identify baseline characteristics that increased 30-day mortality. Results Among 33 acute cases of VSR, 24 cases were submitted to surgery. The 30-day mortality of the operated patients was 45.8%. From 2004 to 2019 our average number of operations of VSR was 1.9 cases/year with an increase to 4 cases/year in 2020. Diabetes mellitus, age, cardiogenic shock, and use of intra-aortic balloon pump were associated with significantly increased mortality using logistic regression. Conclusion We reported an increased number of mechanical complication cases from April to September 2020, compared to our historical records. Despite therapeutic advances, mortality rates remain high. Although the number of cases is small to conclude that the pandemic was responsible for this augmentation, we believe that it is related to the decreased number of patients seeking medical assistance.

ObjectiveThe mitochondrial 18-kDa translocator protein (TSPO) is expressed by activated microglia and positron emission tomography enables the measurement of TSPO levels in the brain. Findings in schizophrenia have shown to vary depending on the outcome measure used and this discrepancy in TSPO results could be explained by lower non-displaceable binding (VND) in schizophrenia, which could obscure increases in specific binding. In this study, we have used the TSPO ligand XBD173 to block the TSPO radioligand [11C]-PBR28 and used an occupancy plot to quantifyVNDin patients with schizophrenia.MethodsA total of 7 patients with a diagnosis of schizophrenia were recruited for this study. Each patient received two separate PET scans with [11C]PBR28, one at baseline and one after the administration of the TSPO ligand XBD173. All patients were high-affinity binders (HABs) for the TSPO gene. We used an occupancy plot to quantify the non-displaceable component (VND) using 2TCM kinetic estimates with and without vascular correction. Finally we computed theVNDat a single subject level using the SIME method.ResultsAll patients showed a global and generalized reduction in [11C]PBR28 uptake after the administration of XBD173. Constraining theVNDto be equal for all patients, the populationVNDwas estimated to be 1.99 mL/cm3(95% CI 1.90 to 2.08). When we used vascular correction, the fractional TSPO occupancy remained similar.ConclusionsIn schizophrenia patients, a substantial component of the [11C]PBR28 signal represents specific binding to TSPO. Furthermore, theVNDin patients with schizophrenia is similar to that previously reported in healthy controls. These results suggest that changes in non-specific binding between schizophrenia patients and healthy controls do not account for discrepant PET findings in this disorder.

We describe a case of cutaneous Larva Migrans in an 8-year-old Caucasian girl. The lesion appeared ten days after a bath in the river in a valley in the north-east of Piedmont. The patient was successfully treated with Albendazole 400 mg daily for 5 days. Autochthonous cases are rare, particularly in northern Italy. Probably the high temperatures and the high degree of humidity favored by the climate changes to which Europe is subjected are favorable to the development of larvae. The diagnosis of cutaneous Larva Migrans should, therefore, be considered also in individuals who have not traveled in geographic areas at risk for the climate.

Background Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID‐19) pandemic. Methods A national registry, named DA‐COVID‐19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID‐19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID‐19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician‐ and patient‐reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. Results A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS‐CoV‐2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS‐CoV‐2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID‐related death occurred. Conclusions Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab‐treated patients., Among 1831 studied AD patients, 86.1% were treated with dupilumab. Patients continuing therapy experienced a marked reduction of disease severity during pandemic. The causes of treatment interruption included: fear of increased susceptibility to SARS‐CoV‐2 infection (24.8%), occurrence of comorbidities (5.9%), age above 60 years (5.2%), SARS‐CoV‐2 infection (2.8%), close contact with SARS‐CoV‐2‐positive subject (2.4%), other reasons, for example, inability to maintain drug supply, non‐medical/unspecified causes (58.7%).

Numerous observational studies have investigated the role of the Dietary Inflammatory Index (DII®) in chronic disease risk. The aims of this umbrella review and integrated meta-analyses were to systematically synthesize the observational evidence reporting on the associations between the DII and health outcomes based on meta-analyses, and to assess the quality and strength of the evidence for each associated outcome. This umbrella review with integrated meta-analyses investigated the association between the DII and a range of health outcomes based on meta-analyses of observational data. A credibility assessment was conducted for each outcome using the following criteria: Statistical heterogeneity, 95% prediction intervals, evidence for small-study effect and/or excess significance bias, as well as effect sizes and P values using calculated random effects meta-analyses. In total, 15 meta-analyses reporting on 38 chronic disease-related outcomes were included, incorporating a total population of 4,360,111 subjects. Outcomes (n = 38) were examined through various study designs including case-control (n = 8), cross-sectional (n = 5), prospective (n = 5), and combination (n = 20) study designs. Adherence to a pro-inflammatory dietary pattern had a significant positive association with 27 (71%) of the included health outcomes (P value < 0.05). Using the credibility assessment, Class I (Convincing) evidence was identified for myocardial infarction only, Class II (Highly suggestive) evidence was identified for increased risk of all-cause mortality, overall risk of incident cancer, and risk of incident site-specific cancers (colorectal, pancreatic, respiratory, and oral cancers) with increasing (more pro-inflammatory) DII score. Most outcomes (n = 31) presented Class III (Suggestive) or lower evidence (Weak or No association). Pro-inflammatory dietary patterns were nominally associated with an increased risk of many chronic disease outcomes. However, the strength of evidence for most outcomes was limited. Further prospective studies are required to improve the precision of the effect size. © 2021 The Author(s). Published by Oxford University Press on behalf of the American Society for Nutrition.

The re-emergence (i.e. ‘breakthrough’) of depressive symptoms despite maintenance treatment of depression with antidepressant drugs is a complex clinical phenomenon referred to as tolerance. Herein we critically appraise evidence from both pre-clinical and clinical studies, focusing on putative mechanisms as well as clinical correlates and implications of the emergence tolerance during antidepressant treatment for major depressive disorder (MDD). It is firstly unclear to what extent this phenotype reflects a pharmacological effect of an antidepressant, is driven by non-adherence, is a marker of latent bipolarity or another comorbidity, a marker of neuroprogression of the underlying disorder or the intrusion of the impact of psychosocial variables into the clinical course. The operational definitions of tolerance and its related phenomena have also been largely inconsistent. Several protective clinical indicators have been proposed, including a rapid-cycling course and comorbid chronic anxiety, whilst poor treatment adherence, proneness to emotional blunting and sub-threshold bipolarity have been identified as possible correlates of tolerance to antidepressant treatment in MDD. Putative neurobiological underpinnings include adaptations in the hypothalamic–pituitary–adrenal (HPA) axis and the serotonergic system. Due to the clinical and diagnostic challenges imposed by the emergence of tolerance to antidepressants, there is an urgent need for upcoming international guidelines to reach a consensus on operational definitions for this complex clinical phenomenon, thus enabling a more precise appreciation of the incidence and correlates of tolerance to antidepressants. Taken together, the present review underscores the need to cautiously weight benefits and risks prior to considering long-term antidepressant treatment for patients with MDD as tolerance may emerge in a subset of patients. © 2018 Elsevier Ltd

The prediction of acute and maintenance lithium treatment response carries major clinical and neurobiological implications, warranting systematic review. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant review searched major electronic databases from inception until December 2017 for studies documenting a clinical diagnosis of bipolar disorder (BD) made according to the mainstream diagnostic manuals and confirmed by a structured interview. Eligible studies allowed a quantitative comparison of endpoint vs baseline mean values of a given biomarker, regardless of the mood phase of patients with BD, and the disorder was assessed for severity using validated rating tool(s). Owing to the purposely applied stringent selection criteria, 16 acute and 12 maintenance studies could be included. The anticipated publication bias limited the chances of reportable generalizable findings, hindering a side-by-side comparison of different records across varying biomarkers and subsequent meta-analyses. The PRISMA approach was nonetheless preferred; it aimed at enhancing the homogeneity of the included results and minimizing the chances of “apples and oranges” with respect to the present research theme. The present critical review confirms the need for future research to specifically assess either pretreatment and/or posttreatment putative biomarkers of patients with BD and treated with lithium. © 2018 Elsevier B.V.

Background Diet is a common source of inflammation, and inflammation is associated with depression. We examined the association between the dietary inflammatory index (DII®), a validated measure of inflammatory potential of the diet, and risk of depression in a cohort of older North American adults. Methods This longitudinal study, with a follow-up of 8 years, included 3648 participants (1577 males, 2071 females; mean age: 60.6 years) with/at risk of knee osteoarthritis. DII® scores were calculated using the validated Block Brief 2000 Food-Frequency Questionnaire. Center for Epidemiological Studies Depression-20 scale was used to define depressive symptoms. The relationship between baseline DII® score and incident depression was assessed through Cox's regression analysis, adjusted for potential confounders, and reported as hazard ratios (HRs). Results In total, 837 individuals (310 men and 527 women) developed incident depressive symptoms over the course of 8 years. Participants in the most pro-inflammatory group (quartile 4) had approximately 24% higher risk of developing depressive symptoms compared to subjects with the most anti-inflammatory diet (HR: 1.24; 95% CI: 1.01–1.53; p = 0.04). Conclusion These results suggest that a pro-inflammatory diet may be associated with higher incidence of depressive symptoms in a cohort of older Americans. Transitioning to a more anti-inflammatory diet may reduce depression risk.

Background: Due to its poor survival, intrahepatic cholangiocarcinoma (ICC) is held to be a much more aggressive cancer than hepatocellular carcinoma (HCC). In most published series, patients were diagnosed when symptomatic. However, ICC is now increasingly being discovered during the surveillance for HCC in cirrhosis. Whether this earlier detection of ICC is associated with an equally dismal prognosis or not is unknown. Methods: This is amulticenter retrospective study of consecutive ICC patients. Patients were stratified into subgroups according to the absence/presence of cirrhosis. A propensity score matching was performed to reduce the potential biases. Cirrhotic patients were further stratified according to their surveillance status. The lead-time bias and its potential effects were also estimated. Results: We gathered 184 patients. Eighty-five patients (46.2%) were cirrhotic. Liver cirrhosis was not related to a worse overall survival (33.0 vs. 32.0 months, p = 0.800) even after the propensity score analysis (43.0 in vs. 44.0 months in 54 pairs of patients, p = 0.878). Among the cirrhotic population, 47 (55.3%) patients had received a diagnosis of ICC during a surveillance programme. The 2 subgroups differed in maximum tumour dimensions (30 vs. 48 mm in surveyed and non-surveyed patients, respectively). Surveyed patients were more likely to receive surgical treatments (59.8 vs. 28.9%, p = 0.003). Overall survival was higher in surveyed patients (51.0 vs. 21.0 months, p < 0.001). These benefits were confirmed after correcting for the lead-time bias. Conclusions: Cirrhotic patients have different clinical presentation and outcomes of ICC according to their surveillance status. In our series, ICC in cirrhosis was not associated with worse OS. Cirrhosis itself should not discourage either surgical or non-surgical treatments.

Background: Higher Dietary Inflammatory Index (DII®) scores are associated with increased morbidity and mortality. However, little is known about the effects of DII on mortality in Mediterranean countries. Therefore, in the present study, we aimed to investigate the potential association between DII scores and overall, cancer and cardiovascular disease (CVD) mortality in people living in a Mediterranean area. Methods: DII scores were calculated using a validated food-frequency questionnaire. DII scores were then categorised into tertiles. Mortality was ascertained via death certificates. The association between DII scores with overall and cause-specific mortality was assessed via a multivariable Cox's regression analysis and reported as hazard ratios (HRs) with their 95% confidence intervals (CIs). Results: The study included 1565 participants (mean age65.5years; females44.7%). After a median follow-up of 12years (2005–2017), 366 (23.4%) participants died. After adjusting for 17 potential confounders, people with higher DII scores had an increased risk of death compared to those in the lowest (most anti-inflammatory) tertile (HR=1.38; 95% CI=1.04–1.82 for the second tertile; HR=1.38; 95% CI=1.03–1.86 for the third tertile). Each 1 SD increase in DII score increased the risk of death by 13%. No association was found between DII scores and cancer or CVD death when considered separately. Conclusions: Higher DII scores were associated with a significantly higher mortality risk, whereas the association with cause-specific mortality was less clear. These findings highlight the potential importance of diet in modulating inflammation and preventing death. © 2019 The British Dietetic Association Ltd.

Background: Literature regarding cardiovascular disease (CVD) and incident physical performance limitations and disability in older people is equivocal. Aims: This study aimed to investigate whether CVD is longitudinally associated with incident physical performance limitations and disability in alarge population-based sample. Methods: This was an 8‑year prospective study using data collected as part of the Osteoarthritis Initiative. Participants were community-dwelling adults with knee osteoarthritis or at high risk for this condition. Diagnosed CVD was self-reported. Physical performance was assessed with measures of chair stand time and gait speed, whereas disability was assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Longitudinal associations between CVD and changes in physical performance tests (chair stand time and gait speed) and disability score were analyzed using generalized linear models with repeated measurements. Results: The analyzed sample comprised 4796 adults (mean age 61.2 years, 58.5% female), of whom 313 people (6.5%) reported CVD at baseline. During 8years of follow-up, after adjustment for 11 potential confounders measured at baseline, those with CVD experienced aworse profile in chair stand time over the 8‑year follow-up period than those without CVD (p = 0.006). Conclusion: In acohort of middle-aged and older adults with knee osteoarthritis or at high risk for this condition those with CVD experienced aworse profile in chair stand time over the 8‑year follow-up period than those without CVD; however, CVD was not significantly associated with an increased incidence of poor gait speed and disability over 8years of follow-up. Importantly, no associations were observed when utilizing propensity score matching. © 2019, Springer-Verlag GmbH Austria, part of Springer Nature.

PurposeWe evaluated myelin changes throughout the central nervous system in Multiple Sclerosis (MS) patients by using hybrid [18F]florbetapir PET-MR imaging.MethodsWe included 18 relapsing-remitting MS patients and 12 healthy controls. Each subject performed a hybrid [18F]florbetapir PET-MR and both a clinical and cognitive assessment. [18F]florbetapir binding was measured as distribution volume ratio (DVR), through the Logan graphical reference method and the supervised cluster analysis to extract a reference region, and standard uptake value (SUV) in the 70–90 min interval after injection. The two quantification approaches were compared. We also evaluated changes in the measures derived from diffusion tensor imaging and arterial spin labeling.Results[18F]florbetapir DVRs decreased from normal-appearing white matter to the centre of T2 lesion (P coeff. = −0.15, P coeff. = −0.12, P coeff. = −0.16, P P = 0.005). SUV70–90 and DVR are equally able to discriminate between intact and damaged myelin (area under the curve 0.76 and 0.66, respectively; P = 0.26).ConclusionOur findings demonstrate that [18F]florbetapir PET imaging can measure in-vivo myelin damage in patients with MS. Demyelination in MS is not restricted to lesions detected through conventional MRI but also involves the normal appearing white matter. Although longitudinal studies are needed, [18F]florbetapir PET imaging may have a role in clinical settings in the management of MS patients.

The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from "nutrient supplements", such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta-analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta-review of this top-tier evidence, we identified, synthesized and appraised all meta-analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta-analyses of placebo-controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention-deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate-based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high-dose methylfolate in major depressive disorder. There was emergent evidence for N-acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence-based supplements, to further elucidate the underlying mechanisms. ispartof: WORLD PSYCHIATRY vol:18 issue:3 pages:308-324 ispartof: location:Italy status: published

The objective of this study was to investigate cross-sectional and longitudinal associations between declines in sexual activity and function and health outcomes in a large population-based sample of older adults. Data were from 2577 men and 3195 women aged ≥ 50 years participating in the English Longitudinal Study of Ageing. Past-year changes in sexual desire, frequency of sexual activity, and ability to have an erection (men)/become sexually aroused (women) were assessed at baseline by self-completion questionnaire. Health outcomes (self-rated health, limiting long-standing illness, doctor-diagnosed diseases of the vascular system, and cancer) were self-reported at baseline (2012/2013) and 4-year follow-up (2016/2017). Data were analyzed using logistic regression, adjusted for sociodemographics, health behaviors, and depressive symptoms. Prospectively, men who reported a decline in sexual desire had higher odds of incident limiting long-standing illness (OR 1.41, 95% CI 1.04–1.91) and incident cancer (OR 1.63, 95% CI 1.06–2.50) than those who maintained their sexual desire. Men who reported a decline in the frequency of sexual activities had higher odds of deterioration in self-rated health (OR 1.47, 95% CI 1.04–2.08) and incident limiting long-standing illness (OR 1.69, 95% CI 1.20–2.37). In women, a decline in frequency of sexual activities was associated with deterioration of self-rated health (OR 1.64, 95% CI 1.07–2.51). Erectile dysfunction was longitudinally associated with poorer health outcomes including incident cancer (OR 1.73, 95% CI 1.11–2.70), coronary heart disease (OR 2.29, 95% CI 1.29–4.07), and fair/poor self-rated health (OR 1.66, 95% CI 1.19–2.32). Practitioners should be mindful that a decline in sexual activity, desire, or function in older age may be an important indicator of future adverse health outcomes. Electronic supplementary material The online version of this article (10.1007/s10508-019-1443-4) contains supplementary material, which is available to authorized users.

Following a socio-ecological approach focused on multidimensional aspects of psychological functioning, this pilot study investigated the relationship between subjective well-being across different domains (e.g., positive experience, social relations, human insecurity, negative experience, self-competence, hope for the future) and psychological distress, in a sample (n = 225) of internally displaced (internally displaced people, IDPs) adolescents hosted in refugee camps in Niger. The Subjective Well-Being Assessment Scale and General Health Questionnaire-12 were administered to the sample by trained interviewers. Participants displayed a low level of psychological distress despite the multiple traumatic experiences they had faced and ongoing stressful conditions at the host camps. Positive experience was found to act as an effective protection factor, enhancing psychological functioning, and mitigating psychological distress. A preserved sense of self-competence and hope for the future were confirmed to play a key role in protecting adolescents from the effects of psychological distress. Youths seem to maintain positive psychological functioning when subjective well-being and other personal and relational resources are active as protection factors.

Introduction There are some controversies about treatment modalities in osteoarthritis (OA), including chondroitin sulfate (CS). The objective of this study was to determine whether CS is effective at alleviating pain and improving function in patients with knee OA and to identify the factors that explain inconsistencies in clinical trial results. Methods We conducted a systematic review of randomized, placebo-controlled trials, searching the databases Medline, Cochrane central register for controlled trials and Scopus. Random effects meta-analysis was then performed, using tau2 and I2 statistics to assess heterogeneity. The pain and Lequesne index (LI) scores were expressed as standardized mean differences (SMDs), with a 95% confidence interval (CI). Heterogeneity was explored by stratifying the analyses according to pre-specified study-level characteristics and assessing the sources of funnel plot asymmetry. Results The inclusion criteria yielded 18 trials. Overall, CS significantly but inconsistently reduced pain (SMD: − 0.63; 95% CI: − 0.91, − 0.35; I2 = 94%) and improved function (SMD: − 0.82; 95% CI: − 1.31, − 0.33; I2 = 95%). When limiting the analysis to studies with a low risk of bias, the pharmaceutical grade CS of IBSA origin showed a greater reduction in pain (SMD: − 0.25; 95% CI: − 0.34, − 0.16; I2 = 75%) and function (SMD: − 0.33; 95% CI: − 0.47, − 0.20; I2 = 53%, p = 0.07) compared with the other preparations (SMDPain: − 0.08; 95% CI: − 0.19, + 0.02; I2 = 20%; SMDFunction: − 0.18; 95% CI: − 0.36, +0.01; I2 = 0%). Assessing funnel plot asymmetry in the studies with a low risk of bias, we found strong correlations between the treatment effects and study size (pain: rS = 0.93; LI: rS = 0.86; p

Fulminant myocarditis (FM) is a form of acute myocardial inflammation leading to rapid-onset hemodynamic instability due to cardiogenic shock or life-threatening arrhythmias. As highlighted by recent registries, FM is associated with high rates of death and heart transplantation, regardless of the underlying histology. Because of a paucity of evidence-based management strategies exists for this disease, an International workshop on FM was held in Wuhan, China, in October 2019, in order to share knowledge on the disease and identify areas of consensus. The present report highlights both agreements and controversies in FM management across the world, focusing the attention on areas of opportunity, FM definition, the use of endomyocardial biopsy and viral identification on heart specimens, treatment algorithms including immunosuppression and the timing of circulatory support escalation. This report incorporates the most recent recommendations from national and international professional societies. Main areas of interest and aims of future prospective observational registries and randomized controlled trials were finally identified and suggested.

Purpose The aim of this study was to investigate the use of spectral analysis (SA) for voxel-wise analysis of TSPO PET imaging studies. TSPO PET quantification is methodologically complicated by the heterogeneity of TSPO expression and its cell-dependent modulation during neuroinflammatory response. Compartmental models to account for this complexity exist, but they are unreliable at the high noise typical of voxel data. On the contrary, SA is noise-robust for parametric mapping and provides useful information about tracer kinetics with a free compartmental structure. Procedures SA impulse response function (IRF) calculated at 90 min after tracer injection was used as main parameter of interest in 3 independent PET imaging studies to investigate its sensitivity to (1) a TSPO genetic polymorphism (rs6971) known to affect tracer binding in a cross-sectional analysis of healthy controls scanned with [11C]PBR28 PET; (2) TSPO density with [11C]PBR28 in a competitive blocking study with a TSPO blocker, XBD173; and (3) the higher affinity of a second radiotracer for TSPO, by using data from a head-to-head comparison between [11C]PBR28 and [11C]ER176 scans. Results SA-IRF produced parametric maps of visually good quality. These were sensitive to TSPO genotype (mean relative difference between high- and mixed-affinity binders = 25 %) and TSPO availability (mean signal displacement after 90 mg oral administration of XBD173 = 39 %). Regional averages of voxel-wise IRF estimates were strongly associated with regional total distribution volume (VT) estimated with a 2-tissue compartmental model with vascular compartment (Pearson’s r = 0.86 ± 0.11) but less strongly with standard 2TCM-VT (Pearson’s r = 0.76 ± 0.32). Finally, SA-IRF estimates for [11C]ER176 were significantly higher than [11C]PBR28 ones, consistent with the higher amount of specific binding of the former tracer. Conclusions SA-IRF can be used for voxel-wise quantification of TSPO PET data because it generates high-quality parametric maps, it is sensitive to TSPO availability and genotype, and it accounts for the complexity of TSPO tracer kinetics with no additional assumptions.

The relationship between peripheral and central immunity and how these ultimately may cause depressed behaviour has been the focus of a number of imaging studies conducted with Positron Emission Tomography (PET). These studies aimed at testing the immune-mediated model of depression that proposes a direct effect of peripheral cytokines and immune cells on the brain to elicit a neuroinflammatory response via a leaky blood–brain barrier and ultimately depressive behaviour. However, studies conducted so far using PET radioligands targeting the neuroinflammatory marker 18 kDa translocator protein (TSPO) in patient cohorts with depression have demonstrated mild inflammatory brain status but no correlation between central and peripheral immunity. To gain a better insight into the relationship between heightened peripheral immunity and neuroinflammation, we estimated blood-to-brain and blood-to-CSF perfusion rates for two TSPO radiotracers collected in two separate studies, one large cross-sectional study of neuroinflammation in normal and depressed cohorts (N = 51 patients and N = 25 controls) and a second study where peripheral inflammation in N = 7 healthy controls was induced via subcutaneous injection of interferon (IFN)-α. In both studies we observed a consistent negative association between peripheral inflammation, measured with c-reactive protein P (CRP), and radiotracer perfusion into and from the brain parenchyma and CSF. Importantly, there was no association of this effect with the marker of BBB leakage S100β, that was unchanged. These results suggest a different model of peripheral-to-central immunity interaction whereas peripheral inflammation may cause a reduction in BBB permeability. This effect, on the long term, is likely to disrupt brain homeostasis and induce depressive behavioural symptoms.

Background Corynebacterium diphtheriae (C. diphtheriae) infections, usually related to upper airways involvement, could be highly invasive. Especially in developing countries, non-toxigenic C. diphtheriae strains are now emerging as cause of invasive disease like endocarditis. The present case stands out for reinforcing the high virulence of this pathogen, demonstrated by the multiple systemic embolism and severe valve deterioration. It also emphasizes the importance of a coordinated interdisciplinary work to address all these challenges related to infectious endocarditis. Case presentation A 21-year-old male cocaine drug abuser presented to the emergency department with a 1-week history of fever, asthenia and dyspnea. His physical examination revealed a mitral systolic murmur, signs of acute arterial occlusion of the left lower limb, severe arterial hypotension and acute respiratory failure, with need of vasoactive drugs, orotracheal intubation/mechanical ventilation, empiric antimicrobial therapy and emergent endovascular treatment. The clinical suspicion of acute infective endocarditis was confirmed by transesophageal echocardiography, demonstrating a large vegetation on the mitral valve associated with severe valvular regurgitation. Abdominal ultrasound was normal with no hepatic, renal, or spleen abscess. Serial blood cultures and thrombus culture, obtained in the vascular procedure, identified non-toxigenic C. diphtheriae, with antibiotic therapy adjustment to monotherapy with ampicillin. Since the patient had a severe septic shock with sustained fever, despite antimicrobial therapy, urgent cardiac surgical intervention was planned. Anatomical findings were compatible with an aggressive endocarditis, requiring mitral valve replacement for a biological prosthesis. During the postoperative period, despite an initial clinical recovery and successfully weaning from mechanical ventilation, the patient presented with a recrudescent daily fever. Computed tomography of the abdomen revealed a hypoattenuating and extensive splenic lesion suggestive of abscess. After sonographically guided bridging percutaneous catheter drainage, surgical splenectomy was performed. Despite left limb revascularization, a forefoot amputation was required due to gangrene. The patient had a good clinical recovery, fulfilling 4-weeks of antimicrobial treatment. Conclusion Despite the effectiveness of toxoid-based vaccines, recent global outbreaks of invasive C. diphtheriae infectious related to non-toxigenic strains have been described. These infectious could be highly invasive as demonstrated in this case. Interdisciplinary work with an institutional “endocarditis team” is essential to achieve favorable clinical outcomes in such defiant scenarios.

Background Cardiac injury, as measured by troponin elevation, has been reported among hospitalized coronavirus disease 2019 (COVID-19) patients and portends a poor prognosis. However, how the dynamics of troponin elevation interplay with inflammation and coagulation biomarkers over time is unknown. We assessed longitudinal follow-up of cardiac injury, inflammation and coagulation markers in relation to disease severity and outcome. Methods We retrospectively assessed 2068 patients with laboratory-confirmed COVID-19 between January 29 and April 1, 2020 at Tongji Hospital in Wuhan, China. We defined cardiac injury as an increase in high sensitivity cardiac troponin-I (hs-cTnI) above the 99th of the upper reference limit. We explored the dynamics of elevation in hs-cTnI and the relationship with inflammation (interleukin [IL]-6, IL-8, IL-10, IL-2 receptor, tumor necrosis factor-α, C-reactive protein) and coagulation (d-dimer, fibrinogen, international normalized ratio) markers in non-critically ill versus critically ill patients longitudinally and further correlated these markers to survivors and non-survivors. Results Median age was 63 years (first to third quartile 51–70 years), 51.4% of whom were women. When compared to non-critically ill patients (N = 1592, 77.0%), critically ill (defined as requiring mechanical ventilation, in shock or multiorgan failure) patients (N = 476, 23.0%), had more frequent cardiac injury on admission (30.3% vs. 2.3%, p, Graphical abstract Unlabelled Image, Highlights • In COVID-19 patients increased levels of hs-cTnI beyond day 3 since admission portend a poor prognosis. • A consistent positive correlation of hs-cTnI with IL-6 and d-dimer could suggest nonspecific cytokine-mediated cardiotoxicity. • The risk for cardiac arrest and rhythm disturbances in patients with elevated hs-cTnI suggest an arrhythmogenic nature.

Although antipsychotic drugs are effective for relieving the psychotic symptoms of first-episode psychosis (FEP), psychotic relapse is common during the course of the illness. While some FEPs remain remitted even without medication, antipsychotic discontinuation is regarded as the most common risk factor for the relapse. Considering the actions of antipsychotic drugs on presynaptic and postsynaptic dopamine dysregulation, this study evaluated possible mechanisms underlying relapse after antipsychotic discontinuation. Twenty five FEPs who were clinically stable and 14 matched healthy controls were enrolled. Striatal dopamine activity was assessed as Kicer value using [18F]DOPA PET before and 6 weeks after antipsychotic discontinuation. The D2/3 receptor availability was measured as BPND using [11C]raclopride PET after antipsychotic discontinuation. Healthy controls also underwent PET scans according to the corresponding schedule of the patients. Patients were monitored for psychotic relapse during 12 weeks after antipsychotic discontinuation. 40% of the patients showed psychotic relapse after antipsychotic discontinuation. The change in Kicer value over time significantly differed between relapsed, non-relapsed patients and healthy controls (Week*Group: F = 4.827, df = 2,253.193, p = 0.009). In relapsed patients, a significant correlation was found between baseline striatal Kicer values and time to relapse after antipsychotic discontinuation (R2 = 0.518, p = 0.018). BPND were not significantly different between relapsed, non-relapsed patients and healthy controls (F = 1.402, df = 2,32.000, p = 0.261). These results suggest that dysfunctional dopamine autoregulation might precipitate psychotic relapse after antipsychotic discontinuation in FEP. This finding could be used for developing a strategy for the prevention of psychotic relapse related to antipsychotic discontinuation.