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Aggression occurs frequently and severely between rival groups. Although there has been much study into the psychological and socio-ecological determinants of intergroup aggression, the neuroscience of this phenomenon remains incomplete. To examine the neural correlates of aggression directed at outgroup (versus ingroup) targets, we recruited 35 healthy young male participants who were current or former students of the same university. While undergoing functional MRI, participants completed an aggression task against both an ingroup and an outgroup opponent in which their opponents repeatedly provoked them at varying levels and then participants could retaliate. Participants were then socially included and then excluded by two outgroup members and then completed the same aggression task against the same two opponents. Both before and after outgroup exclusion, aggression toward outgroup members was positively associated with activity in the ventral striatum during decisions about how aggressive to be toward their outgroup opponent. Aggression toward outgroup members was also linked to greater post-exclusion activity in the rostral and dorsal medial prefrontal cortex during provocation from their outgroup opponent. These altered patterns of brain activity suggest that frontostriatal mechanisms may play a significant role in motivating aggression toward outgroup members.

Cryoballoon-guided pulmonary vein isolation (CB-PVI) for symptomatic atrial fibrillation (AF) has become an established treatment option with encouraging results in terms of safety and efficacy. Data reporting on long-term data beyond a follow-up (FU) period of 5 years is scarce. This prospective study aimed to evaluate very long-term outcome after CB-PVI for AF.Data from consecutive patients treated with CB-PVI for symptomatic and drug refractory AF between 2005 and 2012 were analyzed. Patients with a FU of ≥9 years after index CB-PVI were included. All patients were continuously followed-up in our outpatient clinic. Arrhythmia recurrence was defined as AF or atrial tachycardia (AT) lasting30 s beyond a 3-month blanking period.A total of 385 patients (71% male) were included. Mean age was 58 ± 10 years and paroxysmal AF was present in 93% of patients. Mean FU duration was 124 ± 24 months. At the end of the observational period, 73% of all patients were in stable sinus rhythm after a mean of 2 ± 0.8 ablation procedures. Patients with AF/AT recurrence were older (60 ± 8 vs. 57 ± 10 years; p = .019), had a higher CHACB-PVI as index procedure for AF ablation resulted in favorable long-term outcome in symptomatic AF. CB-PVI might be recommended as interventional therapy in patients with lower LA remodeling.

PURPOSE OF REVIEW: Traditional histopathology of the kidney biopsy specimen has been an essential and successful tool for the diagnosis and staging of kidney diseases. However, it is likely that the full potential of the kidney biopsy has not been tapped so far. Indeed, there is now a concerted worldwide effort to interrogate kidney biopsy samples at the cellular and molecular levels with unprecedented rigor and depth. This review examines these novel approaches to study kidney biopsy specimens and highlights their potential to refine our understanding of the pathophysiology of kidney disease and lead to precision-based diagnosis and therapy. RECENT FINDINGS: Several consortia are now active at studying kidney biopsy samples from various patient cohorts with state-of-the art cellular and molecular techniques. These include advanced imaging approaches as well as deep molecular interrogation with tools such as epigenetics, transcriptomics, proteomics and metabolomics. The emphasis throughout is on rigor, reproducibility and quality control. SUMMARY: While these techniques to study kidney biopsies are complementary, each on its own can yield novel ways to define and classify kidney disease. Therefore, great efforts are needed in order to generate an integrated output that can propel the diagnosis and treatment of kidney disease into the realm of precision medicine.

Background The Multinational Association for Supportive Care in Cancer (MASCC) risk index has been utilized to determine the risk for poor clinical outcomes in patients with febrile neutropenia (FN) in an emergency center (EC). However, this index comprises subjective elements and elaborated metrics limiting its use in ECs. We sought to determine whether procalcitonin (PCT) level (biomarker of bacterial infection) with or without lactate level (marker of inadequate tissue perfusion) offers a potential alternative to MASSC score in predicting the outcomes of patients with FN presenting to an EC. Methods We retrospectively identified 550 cancer patients with FN who presented to our EC between April 2018, and April 2019, and had serum PCT and lactate levels measured. Results Compared with patients with PCT levels 2.2 mmol/L were more likely to be admitted and have an LOS >7 days, BSI, and 14‐day mortality than patients with lower levels. PCT level was a significantly better predictor of BSI than MASSC score (p = 0.003) or lactate level (p, Procalcitonin can be used as a more objective and practical alternative to the Multinational Association for Supportive Care in Cancer score to predict the outcomes of cancer patients with febrile neutropenia in an emergency center.

Inadequate initial antibiotic treatment of ESBL urinary tract infections (UTI) can lead to increase in the number of antibiotics used, return visits, longer hospitalizations, increased morbidity and mortality and increased costs. Given the important health implications on patients, this study aimed to examine the prevalence and predictors of ESBL UTIs among Emergency Department (ED) patients of a tertiary care center in Beirut, Lebanon.Single-center retrospective observational study involving all adult UTI patients who presented to the ED of the American University of Beirut Medical Center, a tertiary care center between August 2019 and August 2020.Out of the 886 patients that were included, 24.9% had an ESBL organism identified by urine culture. They had higher bladder catheter use within the previous 90 days, antibiotic use within last 90 days, and were more likely to have a history of an ESBL producing isolate from any body site in the last year. Antibiotic use in the last 90 days and a history of ESBL producing isolate at any site in the previous year were significantly associated with developing an ESBL UTI (OR = 1.66, p = 0.001 and OR = 2.53, p0.001 respectively). Patients diagnosed with cystitis were less likely to have an ESBL organism (OR = 0.4 95%CI [0.20-0.81], p = 0.01) CONCLUSION: The prevalence of ESBL organisms was found to be 24.9% in urinary tract infections. The predictors of an ESBL UTI infection were antibiotic use in the last 90 days, a history of ESBL producing isolate at any site in the previous year. Based on the findings of our study, we can consider modifying initial empiric antibiotic treatment for patients presenting with a UTI with the above stated risk factors.

The Fracture Risk Assessment Tool (FRAX) is the most widely used tool for fracture prediction. It provides 10-year probabilities for hip and major osteoporotic fracture (MOF). It uses country-specific hip fracture incidence and life expectancy data, and for most countries, MOF/hip fracture incidence rate ratios (IRRs) from Malmo Sweden. However, the risk of MOF varies by age, sex, and geography. The objective is to compare the MOF/hip IRRs across countries, by sex and age. This systematic review targeted observational studies of MOF and hip fractures in individuals >50 years (PROSPERO 2019 CRD42019129259). One reviewer screened potential articles. Two reviewers completed duplicate and independent data abstraction, and assessed study quality based on population representativeness, study design and duration, definition of ethnicity, and fracture characteristics. We calculated the MOF/hip IRRs (95% confidence interval) and Z-values to compare IRRs in various countries to those for Sweden. We included 27 studies, of fair to good quality in the majority, from Europe (15), US and Canada (7), Asia (3), and Australia (2). The IRRs were twofold to 10-fold higher in younger compared to older age categories, and in women compared to men, with few exceptions. Within Europe, and using Sweden as a reference, MOF/Hip IRRs in women 50-54 years from Finland, Italy, Netherlands, Denmark, and UK were significantly lower by 38% to 60%. Findings were similar in men. At older ages, MOF/Hip IRRs were consistently lower in women from European countries compared to Sweden, by 10%-40% and 11%-51%, at 75-79 years and 85-89 years, respectively. Findings were heterogenous in men and in non-European countries. In conclusion, the MOF/hip fracture IRR may vary between countries. The variability at older ages may affect FRAX prediction when country-specific fracture IRRs are not used. Further research is needed to elucidate the implication of our findings to FRAX-derived MOF estimates in various countries. © 2021 American Society for Bone and Mineral Research (ASBMR).

Background Out-of-hospital cardiac arrest (OHCA) remains one of the most common causes of death. There is a scarcity of evidence concerning the prevalence of bacteraemia in cardiac arrest patients presenting to the Emergency Department (ED). We aimed to determine the prevalence of bacteraemia in OHCA patients presenting to the ED, as well as study the association between bacteraemia and in-hospital mortality in OHCA patients. In addition, the association between antibiotic use during resuscitation and in-hospital mortality was examined. Methods and results This was a study of 200 adult OHCA patients who presented to the ED between 2015 and 2019. Bacteraemia was confirmed if at least one of the blood culture bottles grew a non-skin flora pathogen or if two blood culture bottles grew a skin flora pathogen from two different sites. The prevalence of bacteraemia was 46.5%. Gram positive bacteria, specifically Staphylococcus species, were the most common pathogens isolated from the bacteremic group. 42 patients survived to hospital admission. The multivariate analysis revealed that there was no association between bacteraemia and hospital mortality in OHCA patients (OR = 1.3, 95% CI= 0.2–9.2) with a p-value of .8. There was no association between antibiotic administration during resuscitation and hospital mortality (OR = 0.6, 95% CI= 0.1 − 3.8) with a p-value of .6. Conclusion In our study, the prevalence of bacteraemia among OHCA patients presenting to the ED was found to be 46.5%. Bacteremic and non-bacteremic OHCA patients had similar initial baseline characteristics and laboratory parameters except for higher serum creatinine and BUN in the bacteremic group. In OHCA patients who survived their ED stay there was no association between hospital mortality and bacteraemia or antibiotic administration during resuscitation. There is a need for randomised controlled trials with a strong patient oriented primary outcome to better understand the association between in-hospital mortality and bacteraemia or antibiotic administration in OHCA patients.KEY MESSAGESWe aimed to determine the prevalence of bacteraemia in OHCA patients presenting to the Emergency Department. In our study, we found that 46.5% of patients presenting to our ED with OHCA were bacteremic.Bacteremic and non-bacteremic OHCA patients had similar initial baseline characteristics and laboratory parameters except for higher serum creatinine and BUN in the bacteremic group.We found no association between bacteraemia and hospital mortality. There was no association between antibiotic administration during resuscitation and hospital mortality.There is a need for randomised controlled trials with a strong patient oriented primary outcome to better understand the association between in-hospital mortality and bacteraemia or antibiotic administration in OHCA patients.

Objective: Obesity’s prevalence has created a plethora of questionnaires characterizing psychological aspects of eating behaviour, such as reward-related eating (RRE). The Reward-based Eating Drive questionnaires (RED-9, RED-13) broadly and deeply assesses the RRE construct. However, large-sample research designs require shorter questionnaires that capture RRE quickly and precisely. We sought to develop a brief, reliable, and valid version of the RED questionnaire.Methods: We used all-subset correlation to find a subset that maximally associated with the full RED-13 in two separate samples. We validated results in a third independent sample. We also assessed internal consistency, test-retest reliability, and ability to explain variance in external outcomes. Results: A 5-item questionnaire (RED-X5) correlated strongly with RED-13 in the independent sample (r = .95). RED-X5 demonstrated high internal consistency (omega total ≥ .80) and 6-month test-retest reliability (r = .72). RED-X5 accurately reproduced known associations between RED-13 and body mass index, diabetes status, and craving for sweet and savory foods. As a novel finding, RED questionnaires predicted laboratory intake of chips.Conclusions: The RED-X5 is a short, reliable, and valid measure of the RRE construct and can be readily implemented in large-sample research designs where questionnaire space is limited. Materials are available at https://osf.io/bd3mg/.

Background: There is no clear consensus over the optimal width of resection margin for colorectal liver metastases (CRLM), with evolving definitions alongside the advances on the management of the disease. In addition, data on the impact of resection margin after laparoscopic liver resection are still scarce. Methods: Prospectively maintained databases of patients undergoing open or laparoscopic CRLM resection in 7 European tertiary hepatobiliary referral centres were reviewed. After propensity score matching (PSM), the influence of 1mm and wider margins on OS and DFS were evaluated in open and laparoscopic cohorts. Results: After PSM, 648 patients were comparable in each group. The incidence of positive margins (< 1mm) was similar in open and laparoscopic groups (17% vs 13%, p = 0,142). Margins < 1mm were associated with shorter RFS in open (12 vs 26months, p = 0.042) and in laparoscopic group (13 vs 23, p = 0,002). Margins < 1mm were associated with shorter OS in open (36 vs 57months, p = 0.027), but not in laparoscopic group (49 vs 60, p = 0,177). Subgroups with margins ≥ 1mm (1–4mm, 5–9mm, ≥ 10mm) presented similar RFS in open (p = 0,251) or laparoscopic cohorts (p = 0.117), as well as similar OS in open (p = 0.295) or laparoscopic cohorts (p = 0.908). In the presence of liver recurrence, repeat liver resection was performed in 70 (30%) patients in the open group and 88 (48%) in the laparoscopic group (p < 0.001). Conclusions: Our study suggests that a positive resection margin (less than 1mm) width does not impact OS after laparoscopic resection of CRLMs as it does in open liver resection. However, a positive margin continues to affect RFS in open and laparoscopic resection. Wider margins than 1mm do not seem to improve oncological results in open or laparoscopic surgery.

Introduction: A stronger evidence level is needed to confirm the benefits and limits of laparoscopic hemihepatectomies. Methods: Laparoscopic and open hemihepatectomies from nine European referral centers were compared after propensity score matching (right and left hemihepatectomies separately, and benign and malignant diseases sub-analyses). Results: Five hundred and forty-five laparoscopic hemihepatectomies were compared with 545 open. Laparoscopy was associated with reduced blood loss (P < 0.001), postoperative stay (P&nbsp

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development. This paper reports activation patterns for fMRI tasks assessing response inhibition, working memory and reward processing obtained at baseline in the longitudinal ABCD Study, providing a reference for research into adolescent brain development.

Background Specific details about cardiovascular complications, especially arrhythmias, related to the coronavirus disease of 2019 (COVID‐19) are not well described. Objective We sought to evaluate the incidence and predictive factors of cardiovascular complications and new‐onset arrhythmias in Black and White hospitalized COVID‐19 patients and determine the impact of new‐onset arrhythmia on outcomes. Methods We collected and analyzed baseline demographic and clinical data from COVID‐19 patients hospitalized at the Tulane Medical Center in New Orleans, Louisiana, between March 1 and May 1, 2020. Results Among 310 hospitalized COVID‐19 patients, the mean age was 61.4 ± 16.5 years, with 58,7% females, and 67% Black patients. Black patients were more likely to be younger, have diabetes and obesity. The incidence of cardiac complications was 20%, with 9% of patients having new‐onset arrhythmia. There was no significant difference in cardiovascular outcomes between Black and White patients. A multivariate analysis determined age ≥60 years to be a predictor of new‐onset arrhythmia (OR = 7.36, 95% CI [1.95;27.76], p = .003). D‐dimer levels positively correlated with cardiac and new‐onset arrhythmic event. New onset atrial arrhythmias predicted in‐hospital mortality (OR = 2.99 95% CI [1.35;6.63], p = .007), a longer intensive care unit length of stay (mean of 6.14 days, 95% CI [2.51;9.77], p = .001) and mechanical ventilation duration(mean of 9.08 days, 95% CI [3.75;14.40], p = .001). Conclusion Our results indicate that new onset atrial arrhythmias are commonly encountered in COVID‐19 patients and can predict in‐hospital mortality. Early elevation in D‐dimer in COVID‐19 patients is a significant predictor of new onset arrhythmias. Our finding suggest continuous rhythm monitoring should be adopted in this patient population during hospitalization to better risk stratify hospitalized patients and prompt earlier intervention.

Human variation in brain morphology and behavior are related and highly heritable. Yet, it is largely unknown to what extent specific features of brain morphology and behavior are genetically related. Here, we introduce a computationally efficient approach for multivariate genomic-relatedness-based restricted maximum likelihood (MGREML) to estimate the genetic correlation between a large number of phenotypes simultaneously. Using individual-level data (N = 20,190) from the UK Biobank, we provide estimates of the heritability of gray-matter volume in 74 regions of interest (ROIs) in the brain and we map genetic correlations between these ROIs and health-relevant behavioral outcomes, including intelligence. We find four genetically distinct clusters in the brain that are aligned with standard anatomical subdivision in neuroscience. Behavioral traits have distinct genetic correlations with brain morphology which suggests trait-specific relevance of ROIs. These empirical results illustrate how MGREML can be used to estimate internally consistent and high-dimensional genetic correlation matrices in large datasets., Ronald de Vlaming and Eric Slob et al. present MGREML, a multivariate tool to estimate pairwise genetic correlations between multiple traits. They apply MGREML to UK Biobank data for 74 brain imaging phenotypes and 8 behavioral traits, demonstrating that these phenotypes have distinct genetic correlations with brain morphology.

Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12–68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = −0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = −0.690, pspin = 0.006), BD (rho = −0.672, pspin = 0.009), and MDD (rho = −0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.

Importance Extracellular matrix proteins and enzymes involved in degradation have been found to be associated with tissue fibrosis and ureteropelvic junction obstruction (UPJO). In this study we developed a promising urinary biomarker model which can identify reduced renal function in UPJ obstruction patients. This can potentially serve as a non-invasive way to enhance surgical decision making for patients and urologists. Objective We sought to develop a predictive model to identify UPJO patients at risk for reduced renal function. Design Prospective cohort study Setting Pre-operative urine samples were collected in a prospectively enrolled UPJO biomarker registry at our institution. Urinary MMP-2, MMP-7, TIMP-2, and NGAL were measured as well as clinical characteristics including hydronephrosis grade, differential renal function, t1/2, and UPJO etiology. Participants Children who underwent pyeloplasty for UPJO Main outcome measurement Primary outcome was reduced renal function defined as MAG3 function Results We included 71 patients with UPJO in the original training cohort and 39 in the validation cohort. Median age was 3.3 years (70% male). By univariate analysis, reduced renal function was associated with higher MMP-2 (p = 0.064), MMP-7 (p = 0.047), NGAL (p = 0.001), and lower TIMP-2 (p = 0.033). Combining MMP-7 with TIMP-2, the multivariable logistic regression model predicted reduced renal function with good performance (AUC = 0.830; 95% CI: 0.722–0.938). The independent testing dataset validated the results with good predictive performance (AUC = 0.738). Conclusions and relevance Combination of urinary MMP-7 and TIMP-2 can identify reduced renal function in UPJO patients. With the high sensitivity cutoffs, patients can be categorized into high risk (aggressive management) versus lower risk (observation).

Background Ethnoracial groups in high-income countries have a 2-fold higher risk of SARS-CoV-2 infection, associated hospitalizations, and mortality than Whites. Migrants are an ethnoracial subset that may have worse COVID-19 outcomes due to additional barriers accessing care, but there are limited data on in-hospital outcomes. We aimed to disaggregate and compare COVID-19 associated hospital outcomes by ethnicity, immigrant status and region of birth. Methods Adults with community-acquired SARS-CoV-2 infection, hospitalized March 1–June 30, 2020, at four hospitals in Montréal, Quebec, Canada, were included. Age, sex, socioeconomic status, comorbidities, migration status, region of birth, self-identified ethnicity [White, Black, Asian, Latino, Middle East/North African], intensive care unit (ICU) admissions and mortality were collected. Adjusted hazard ratios (aHR) for ICU admission and mortality by immigrant status, ethnicity and region of birth adjusted for age, sex, socioeconomic status and comorbidities were estimated using Fine and Gray competing risk models. Results Of 1104 patients (median [IQR] age, 63.0 [51.0–76.0] years; 56% males), 57% were immigrants and 54% were White. Immigrants were slightly younger (62 vs 65 years; p = 0.050), had fewer comorbidities (1.0 vs 1.2; p Conclusions Data disaggregated by region of birth identified subgroups of immigrants at increased risk of COVID-19 ICU admission, providing more actionable data for health policymakers to address health inequities.

Music's ability to induce feelings of pleasure has been the subject of intense neuroscientific research lately. Prior neuroimaging studies have shown that music-induced pleasure engages cortico-striatal circuits related to the anticipation and receipt of biologically relevant rewards/incentives, but these reports are necessarily correlational. Here, we studied both the causal role of this circuitry and its temporal dynamics by applying Transcranial Magnetic Stimulation (TMS) over the left dorsolateral prefrontal cortex combined with functional Magnetic Resonance Imaging (fMRI) in 17 male and female participants. Behaviorally, we found that, in accord with previous findings, excitation of fronto-striatal pathways enhanced subjective reports of music-induced pleasure and motivation; whereas inhibition of the same circuitry led to the reduction of both. fMRI activity patterns indicated that these behavioral changes were driven by bidirectional TMS-induced alteration of fronto-striatal function. Specifically, changes in activity in the nucleus accumbens (NAcc) predicted modulation of both hedonic and motivational responses, with a dissociation between pre-experiential vs. experiential components of musical reward. In addition, TMS-induced changes in the fMRI functional connectivity between the NAcc and frontal and auditory cortices predicted the degree of modulation of hedonic responses. These results indicate that the engagement of cortico-striatal pathways and the NAcc, in particular, is indispensable to experience rewarding feelings from music.SIGNIFICANCE STATEMENT:Neuroimaging studies have shown that music-induced pleasure engages cortico-striatal circuits involved in the processing of biologically relevant rewards. Yet, these reports are necessarily correlational. Here, we studied both the causal role of this circuitry and its temporal dynamics by combining brain stimulation over the frontal cortex with functional imaging. Behaviorally, we found that excitation and inhibition of fronto-striatal pathways enhanced and disrupted, respectively, subjective reports of music-induced pleasure and motivation. These changes were associated with changes in nucleus accumbens (NAcc) activity and NAcc coupling with frontal and auditory cortices, dissociating between pre-experimental vs. experiential components of musical reward. These results indicate that the engagement of cortico-striatal pathways, and the NAcc in particular, is indispensable to experience rewarding feeling from music.

BACKGROUND The weekend effect is the increased mortality in hospitalized patients admitted on the weekend. The aim of this study was to examine the effect of weekend admissions on septic shock patients. METHODS This is a retrospective observational study of the 2014 Nationwide Emergency Department Sample Database. Septic shock patients were included in this study using ICD-9-CM codes. Descriptive analysis was done, in addition to bivariate analysis to compare variables based on admission day. Multivariate analysis was conducted to examine the association between admission day and mortality in septic shock patients after adjusting for potential confounding factors. RESULTS A total of 364,604 septic shock patients were included in this study. The average age was 67.19 years, and 51.1% were males. 73.0% of patients presented on weekdays. 32.3% of septic shock patients died during their hospital stay. After adjusting for confounders, there was no significant difference in the emergency department or in-hospital mortality of septic shock patients admitted on the weekend compared with those admitted during weekdays, (OR = 1.00 [95% CI: 0.97-1.03], P value = 0.985). CONCLUSION There was no statistically significant difference in overall mortality between septic shock patients admitted on the weekend or weekday. Our results are contradictory to previous studies showing an increased mortality with the weekend effect. The previous observations that have been made may not stand up with current treatment protocols.

Objectives This study aims to examine the outcome of end-stage renal disease (ESRD) patients admitted with sepsis to the intensive care unit (ICU). Design Single centre, retrospective cohort study Setting The study was conducted in the Intensive Care Department of King Abdulaziz Medical City, Riyadh, Saudi Arabia. Participants Data were extracted from a prospectively collected ICU database from 2002 to 2017. Patients were considered to have sepsis based on the sepsis-3 definition and were stratified into 2 groups based on the presence or absence of ESRD. Primary and secondary outcomes The primary outcome of the study was in-hospital mortality. Secondary outcomes included ICU mortality, ICU and hospital lengths of stay, and mechanical ventilation duration. Results A total of 8803 patients were admitted to the ICU with sepsis during the study period. 730 (8.3%) patients had ESRD. 49.04% of ESRD patients with sepsis died within their hospital stay vs. 31.78% of non-ESRD patients. ESRD septic patients had 1.44 greater odds of dying within their hospital stay as compared to septic non-ESRD patients (OR 1.44, 95% CI 1.03–1.53). Finally, the predictors of hospital mortality in septic ESRD patients were found to be mechanical ventilation (OR 3.36; 95% CI 2.27–5.00), a history of chronic liver disease (OR 2.26; 95% CI 1.26–4.07), and use of vasopressors (OR 1.74; 95% CI 1.19–2.54). Among patients with ESRD, hospital mortality was higher in subgroups of patients with chronic cardiac (OR 1.86 (1.36–2.53) vs. 1.19 (0.96–1.47)) and chronic respiratory illnesses (OR 2.20 (1.52–3.20) vs. 1.21 (0.99–1.48)). Conclusion ESRD patients admitted to the intensive care unit with sepsis are at greater odds of mortality compared to patients with non-ESRD. This risk is particularly increased if these patients have a concomitant history of chronic cardiac and respiratory illnesses.Key MessagesSepsis and bacterial infections are very common in ESRD patients and following cardiovascular disease; sepsis is the second leading cause of death in patients with ESRD.This study aims to examine the outcome of patients with end-stage renal disease (ESRD) patients admitted with sepsis to the intensive care unit (ICU).The results of this study have shown that end-stage renal disease is associated with greater odds of ICU and hospital mortality among septic patients admitted to an intensive care unit.ESRD patients were also more likely to be started on vasopressors and mechanical ventilation.

Neutrophils are the most abundant white blood cell in the body and are key participants in the defense against fungal infections. Fungal infections occur often in patients with cirrhosis and are associated with increased 30‐day and 90‐day mortality. Previous studies have shown that specific neutrophil functions are abnormal in patients with cirrhosis, although the extent of neutrophil dysfunction is not well understood. We tested the ability of neutrophils from 21 hospitalized patients with cirrhosis and 23 healthy control patients to kill Candida albicans, a common fungal pathogen in patients with cirrhosis. Using an assay, we also measured the ability of neutrophils to coordinate multicellular, synchronized control of C. albicans hyphae through a process known as swarming. We found that neutrophils from patients with cirrhosis have significantly decreased fungicidal capacity compared with healthy control neutrophils (53% vs. 74%, P, Neutrophils from patients with cirrhosis are defective in coordinated swarming response to the human fungal pathogen, Candida albicans.

Objective Isolated (or idiopathic) rapid eye movement sleep behavior disorder (iRBD) is associated with dementia with Lewy bodies (DLB) and Parkinson's disease (PD). Biomarkers are lacking to predict conversion to a dementia or a motor-first phenotype. Here, we aimed at identifying a brain-clinical signature that predicts dementia in iRBD. Methods A brain-clinical signature was identified in 48 patients with polysomnography-confirmed iRBD using partial least squares between brain deformation and 27 clinical variables. The resulting variable was applied to 78 patients with iRBD followed longitudinally to predict conversion to a synucleinopathy, specifically DLB. The deformation scores from patients with iRBD were compared with 207 patients with PD, DLB, or prodromal DLB to assess if scores were higher in DLB compared to PD. Results One latent variable explained 31% of the brain-clinical covariance in iRBD, combining cortical and subcortical deformation and subarachnoid/ventricular expansion to cognitive and motor variables. The deformation score of this signature predicted conversion to a synucleinopathy in iRBD (p = 0.036, odds ratio [OR] = 2.249; 95% confidence interval [CI] = 1.053-4.803), specifically to DLB (OR = 4.754; 95% CI = 1.283-17.618, p = 0.020) and not PD (p = 0.286). Patients with iRBD who developed dementia had scores similar to clinical and prodromal patients with DLB but higher scores compared with patients with PD. The deformation score also predicted cognitive performance over 1, 2, and 4 years in patients with PD. Interpretation We identified a brain-clinical signature that predicts conversion in iRBD to more severe/dementing forms of synucleinopathy. This pattern may serve as a new biomarker to optimize patient care, target risk reduction strategies, and administer neuroprotective trials. ANN NEUROL 2021;89:341-357.

Contains fulltext : 219494.pdf (Publisher’s version ) (Closed access) While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics - the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD) - that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures. 15 p.

Aim: To evaluate sorafenib treatment in Latin American patients with unresectable hepatocellular carcinoma in the real-world GIDEON study. Patients & methods: Sorafenib administration, safety and efficacy were analyzed by Child–Pugh status. Results: Of 90 evaluable patients (37% Child–Pugh A, 46% Child–Pugh B and 3% Child–Pugh C at study entry), 97% started sorafenib at 800 mg/day. Patients with Child–Pugh B7 had the longest median treatment duration of sorafenib (33.1 weeks). Sorafenib-related adverse events occurred in 58% of patients with Child–Pugh A (21% grade 3/4) and 46% with Child–Pugh B (7% grade 3/4). Conclusion: Sorafenib had a similar safety profile across patients with Child–Pugh A and B and is a treatment option for both groups.

Although certain risk factors have been associated with increased morbidity and mortality in patients admitted with Coronavirus Disease 2019 (COVID-19), the impact of cardiac injury and high-sensitivity troponin-I (hs-cTnI) concentrations are not well described. In this large retrospective longitudinal cohort study, we analyzed the cases of 1,044 consecutively admitted patients with COVID-19 from March 9 until April 15. Cardiac injury was defined by hs-cTnI concentration >99th percentile. Patient characteristics, laboratory data, and outcomes were described in patients with cardiac injury and different hs-cTnI cut-offs. The primary outcome was mortality, and the secondary outcomes were length of stay, need for intensive care unit care or mechanical ventilation, and their different composites. The final analyzed cohort included 1,020 patients. The median age was 63 years, 511 (50% patients were female, and 403 (40% were white. 390 (38%) patients had cardiac injury on presentation. These patients were older (median age 70 years), had a higher cardiovascular disease burden, in addition to higher serum concentrations of inflammatory markers. They also exhibited an increased risk for our primary and secondary outcomes, with the risk increasing with higher hs-cTnI concentrations. Peak hs-cTnI concentrations continued to be significantly associated with mortality after a multivariate regression controlling for comorbid conditions, inflammatory markers, acute kidney injury, and acute respiratory distress syndrome. Within the same multivariate regression model, presenting hs-cTnI concentrations were not significantly associated with outcomes, and undetectable hs-cTnI concentrations on presentation did not completely rule out the risk for mechanical ventilation or death. In conclusion, cardiac injury was common in patients admitted with COVID-19. The extent of cardiac injury and peak hs-cTnI concentrations were associated with worse outcomes.

Objective: To assess the risk factors associated with R1 resection in patients undergoing OLS and LLS for CRLMs. Background: The clinical impact of R1 resection in liver surgery for CRLMs has been continuously appraised, but R1 risk factors have not been clearly defined yet. Methods: A cohort study of patients who underwent OLS and LLS for CRLMs in 9 European high-volume referral centers was performed. A multivariate analysis and the receiver operating characteristic curves were used to investigate the risk factors for R1 resection. A model predicting the likelihood of R1 resection was developed. Results: Overall, 3387 consecutive liver resections for CRLMs were included. OLS was performed in 1792 cases whereas LLS in 1595; the R1 resection rate was 14% and 14.2%, respectively. The risk factors for R1 resection were: the type of resection (nonanatomic and anatomic/nonanatomic), the number of nodules and the size of tumor. In the LLS group only, blood loss was a risk factor, whereas the Pringle maneuver had a protective effect. The predictive size of tumor for R1 resection was >45 mm in OLS and >30 mm in LLS, > 2 lesions was significative in both groups and blood loss >350 cc in LLS. The model was able to predict R1 resection in OLS (area under curve 0.712; 95% confidence interval 0.665 – 0.739) and in LLS (area under curve 0.724; 95% confidence interval 0.671 – 0.745). Conclusions: The study describes the risk factors for R1 resection after liver surgery for CRLMs, which may be used to plan better the perioperative strategies to reduce the incidence of R1 resection during OLS and LLS.

Despite advances in treating gastric staple line leaks after bariatric surgical procedures, chronic leaks have been reported. Failure of their treatment frequently leads to radical surgery. We aimed to describe a strategy for preventing occurrence of chronic gastric leaks after complicated sleeve gastrectomy in patients necessitating relaparoscopy and external drainage as a first step of gastric leak management. METHODS: Data from 14 consecutive patients admitted for gastric leak after laparoscopic sleeve gastrectomy were prospectively collected and retrospectively analyzed. Patients included underwent relaparoscopy and external drainage as first step of management. RESULTS: Median time to gastric leak detection was 4 days. Emergency relaparoscopy allowed peritoneal lavage and external drainage placement next to the leak. Median time between surgery and endoscopic internal drainage (EID) was 4 days. Progressive external drainage mobilization started after 2 days. Control endoscopy was performed every 4 weeks until healing. A median interval of 112 days was necessary before healing in 13 patients. Thirteen patients (92.8%) had no gastric leak recurrence at 1 year. In one patient, EID was considerably delayed and external drainage mobilization prolonged, leading to chronic gastric leak and total gastrectomy after 18 months. CONCLUSION: This study reports for the first time a well-standardized protocol of early EID after relaparoscopy coupled to rapid external drainage removal for effectively treating complicated cases of sleeve gastrectomy. Bariatric surgeons should be aware of such therapeutic strategies and include them in their arsenal against postoperative gastric staple line leaks in severely obese patients.

RATIONALE AND OBJECTIVE: The use of kidney histopathology for predicting kidney failure is not established. We hypothesized that use of histopathological features of kidney biopsy specimens would improve prediction of clinical outcomes made using demographic and clinical variables alone. STUDY DESIGN: Retrospective cohort study and development of a clinical prediction model. SETTING AND PARTICIPANTS: All 2720 individuals from the Biopsy Biobank Cohort of Indiana who underwent a kidney biopsy between 2002 and 2015 and had at least two years of follow-up. NEW PREDICTORS & ESTABLISHED PREDICTORS: Demographic variables, comorbidities, baseline clinical characteristics, and histopathological features. OUTCOMES: Time to kidney failure, defined as sustained estimated glomerular filtration rate

Cryoballoon (CB)-guided ablation of atrial fibrillation (AF) is established in symptomatic AF patients. This study sought to determine the safety and efficacy of CB pulmonary vein isolation (PVI) in young adults.A total of 93 consecutive patients aged45 years referred to our center for AF ablation were included in this observational study. All patients received CB-guided PVI according to a standardized institutional protocol. Follow-up was performed in our outpatient clinic using 72-h Holter monitoring and periodic telephone interview. Recurrence was defined as any AF/atrial tachycardia (AT) episode30 s following a 3-month blanking period. A propensity matched control group consisting of patients older than 45 years were used for further evaluation. Mean age was 35 ± 7 years, 22% suffered from persistent AF, 85% were male. Mean follow-up was 2.6 ± 2 years. At the end of the observational period, 83% of patients were free of any AF/AT episodes. There was an excellent overall 12-month success rate of 92%. In comparison to a matched group the overall recurrence rate was noticeably lower in the young group (15% vs. 27%). Increasing age was associated with a hazard ratio of 1.16 for recurrence. In a multivariate analysis model, left atrial diameter remained as significant predictor of AF/AT recurrence. The complication rate was low, no permanent phrenic nerve palsy was observed.CB-guided PVI in young adults is safe and effective with favorable long-term results. It may be considered as first-line therapy in this relatively healthy population.

In cats, assessment of the testicular function is mainly based on sperm evaluation. Whatever the technique used, the volume of collected sperm is often small, which may lead to technical difficulties to achieve the semen evaluation in routine practice. Fine-needle aspiration (FNA) biopsy of the testicular parenchyma is one of the other methods used to assess testicular function. The aim of this study was to explore the relevance of FNA in the assessment of testicular cells in sexually mature cats. Eighteen cats over one year of age were recruited among animals presented for surgical neutering. Semen was collected by electroejaculation before it was evaluated. FNA biopsies of the testicles were taken using a 21-gauge needle. After castration, histological analysis of the testes was performed. Semen evaluation and histological analysis showed no anomalies, which confirmed normal spermatogenesis in all the cats and allowed a proper interpretation of the cytological findings. The cells identified through cytological examination were spermatogonia (1.99 ± 0.17%), primary spermatocytes (10.49 ± 0.74%), round spermatids (34.80 ± 1.57%), elongated spermatids (23.59 ± 2.02%), spermatozoa (21.56 ± 1.86%), Sertoli cells (7.53 ± 1.23%) and Leydig cells (0.04 ± 0.03%). However, spermatocytes II were not identified. This is due to the low proportions of these cells, related to their very short lifespan. Likewise, the very low number of Leydig cells observed is probably due to the damage caused during the aspiration stage. This study showed that fine-needle aspiration is an efficient method to describe cytologically normal testicular populations, a cornerstone for future research aimed to study abnormal spermatogenesis and to correlate it to cytological proportion of germ cells.

Ghrelin has a key role in modulating energy metabolism and weight gain. The present study aimed at studying the potential role of ghrelin in the development and/or exacerbation of organ damage in a mouse model of diet-induced obesity. Adult mice were fed one of two diets for 20 weeks: standard high carbohydrate (HC) or high-fat high-sugar (HFHS). Starting week 17, the animals were given regular intraperitoneal ghrelin (160 µg/kg) or saline injections Abdominal fat, serum creatinine, and glucose levels, as well as kidney, liver and heart weight and pathology were assessed. Ghrelin-injected mice showed significant organ damage, which was more exacerbated in HFHS-fed animals. While the HFHS diet was associated with significant liver damage, ghrelin administration did not reverse it. Interestingly, ghrelin administration induced moderate kidney damage and significantly affected the heart by increasing perivascular and myocardium fibrosis, steatosis as well as inflammation. Moreover, serum creatinine levels were higher in the animal group injected with ghrelin. Ghrelin administration was associated with increased functional and structural organ damage, regardless of diet. The present study provides novel evidence of multi-organ physiologic alterations secondary to ghrelin administration.

The complement system is a vital component of the innate immune system, though its role in bacteremia is poorly understood. We present complement levels in Staphylococcus aureus bacteremia (SAB) and Gram-negative bacteremia (GNB) and describe observed associations of complement levels with clinical outcomes. Complement and cytokine levels were measured in serum samples from 20 hospitalized patients with SAB, 20 hospitalized patients with GNB, 10 non-infected hospitalized patients, and 10 community controls. C5a levels were significantly higher in patients with SAB as compared to patients with GNB. Low C4 and C3 levels were associated with septic shock and 30-day mortality in patients with GNB, and elevated C3 was associated with a desirable outcome defined as absence of (1) septic shock, (2) acute renal failure, and (3) death within 30 days of bacteremia. Low levels of C9 were associated with septic shock in patients with GNB but not SAB. Elevated IL-10 was associated with increased 30-day mortality in patients with SAB. Complement profiles differ in patients with SAB and those with GNB. Measurement of IL-10 in patients with SAB and of C4, C3, and C9 in patients with GNB may help to identify those at higher risk for poor outcomes. Electronic supplementary material The online version of this article (10.1007/s10096-020-03955-z) contains supplementary material, which is available to authorized users.

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal syndrome classically encountered in patients receiving typical antipsychotic agents. However, many physicians have also reported the occurrence of NMS with atypical antipsychotics, notably with atypical presentations. In this report, we present a case in which a patient's antipsychotic regimen during a psychotic episode (which involved both typical and atypical antipsychotics) subsequently led to NMS. During his stay, the patient developed an altered level of consciousness, elevation of creatine phosphokinase, hemodynamic instability, and a fever. However, the patient did not have signs of rigidity, the cardinal sign of this syndrome. The authors concluded that patients could develop NMS without rigidity while receiving an antipsychotic. Given this presentation, the authors suggest that clinicians have a high level of suspicion for NMS to avoid misdiagnosis and subsequent adverse consequences. Hence, clinicians must be vigilant about atypical presentations of NMS without rigidity.

Efforts to reduce postoperative venous thromboembolism are challenging due to heterogeneity in thromboprophylaxis practice. As a result, a 'one-size-fits-all' approach that accounts for surgery-specific risk, but fails to account for patient-level variation, is often adopted by healthcare networks. Updated clinical practice guidelines have advocated an individualised risk-stratified approach that balances the risk:benefit ratio associated with thromboprophylaxis; however, there are limited data confirming effectiveness of these recommendations on the incidence of postoperative venous thromboembolism and bleeding. We developed the surgical-thrombo-embolism-prevention protocol, a novel risk-stratified algorithm that classified patients into low-, intermediate-, and high-risk profiles according to surgical procedure and patient baseline medical risk. Expert-endorsed risk-specific thromboprophylaxis strategies were then applied. A staged quality improvement program was developed to implement the protocol. We postulated that compliance with the protocol would reduce postoperative venous thromboembolism rates without increasing the incidence of postoperative bleeding. Between June 2013 and March 2018, we evaluated the efficacy, safety and sustainability of this risk-stratified approach in 24,953 surgical admissions at a dedicated cancer centre. By final implementation, program compliance was 91%. Postoperative venous thromboembolism rates reduced from 3.1 per 1000 surgical admissions to 0.6 per 1000 surgical admissions (relative risk reduction 79%; p < 0.005). Postoperative bleeding rates also declined from 10.0 per 1000 surgical admissions to 6.3 per 1000 surgical admissions (relative risk reduction 37%; p = 0.02). Sustained improvement was evident more than 3 years after implementation. Implementation of the surgical-thrombo-embolism-prevention protocol significantly reduced the incidence of postoperative venous thromboembolism supporting its validation at other institutions.

Current models of decision-making assume that the brain gradually accumulates evidence and drifts toward a threshold that, once crossed, results in a choice selection. These models have been especially successful in primate research; however, transposing them to human fMRI paradigms has proved it to be challenging. Here, we exploit the face-selective visual system and test whether decoded emotional facial features from multivariate fMRI signals during a dynamic perceptual decision-making task are related to the parameters of computational models of decision-making. We show that trial-by-trial variations in the pattern of neural activity in the fusiform gyrus reflect facial emotional information and modulate drift rates during deliberation. We also observed an inverse-urgency signal based in the caudate nucleus that was independent of sensory information but appeared to slow decisions, particularly when information in the task was ambiguous. Taken together, our results characterize how decision parameters from a computational model (i.e., drift rate and urgency signal) are involved in perceptual decision-making and reflected in the activity of the human brain.