Xanthan-based chlorhexidine gel effects in non-surgical periodontal therapy? A meta-analysis.

OBJECTIVE: To carry out a systematic review and meta-analysis of randomized controlled clinical trials (RCTs) and controlled clinical trials (CCTs) comparing scaling and root planing (SRP) or placebo with subgingival application of xanthan-based CHX (chlorhexidine) gel as adjunct to SRP. MATERIALS AND METHODS: The literature search was carried out in PubMed/MEDLINE, EMBASE, and SCOPUS; primary outcomes were probing pocket depth (PPD) reduction and gain in clinical attachment level (CAL). RESULTS: Overall, 15 studies were included. Three studies were judged to be at moderate risk of bias while the remaining 12 were rated at high risk of bias. A significant improvement in PPD reduction (standardized mean difference, SMD, 0.87, 95% CI, 0.41-1.34) and CAL gain (SMD = 0.84, 95% CI, 0.36-1.33) emerged for the SRP + CXH gel compared to the SRP alone group, in the presence of significant high heterogeneity among the studies. CONCLUSIONS: Our systematic review and meta-analysis showed that xanthan-based chlorhexidine gel as adjunct to non-surgical periodontal therapy gives benefit in terms of PPD reduction and CAL gain as compared to non-surgical periodontal therapy only. Since there was high heterogeneity among studies and the quality of the evidence is low, further studies characterized by a better methodology, adequate sample size and longer follow-up are warranted in the next future. REGISTRATION: The protocol of this scoping review was registered in the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/PROSPERO) with ID: CRD42023391589.

Incidence of young-onset dementia in Italy: The Brescia register study.

INTRODUCTION: The goal of the present work was to assess the incidence of dementia with onset before the age of 65 years (i.e., young-onset dementia [YOD]) and define the frequencies of young-onset Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), and dementia with Lewy bodies (DLB) in the general population. METHODS: The study was conducted from January 1, 2019 to December 31, 2019 in Brescia province (population: 1,268,455). During the study period, all new YOD cases (incident YOD) were counted, and all patients' records reviewed. The incidence was standardized to the Italian general population in 2019. RESULTS: A total of 29 YOD patients were diagnosed. The age-sex standardized incidence rate was 4.58 (95% confidence interval, 3.07-6.58) per 100,000 person-years. No difference in incidence rate between YOD due to AD or FTLD (P = 0.83) and between sexes (P = 0.81) was observed. YOD incidence increased with age, reaching its peak after 60 years. DISCUSSION: Presenting neurodegenerative YOD phenotypes encompasses both AD and FTLD. Improved knowledge on YOD epidemiology is essential to adequately plan and organize health services.

Use of nebulized liposomal amphotericin B and posaconazole as antifungal prophylaxis in patients with severe SARS-CoV2 infection in intensive care unit.

PURPOSE: COVID-19 associated pulmonary aspergillosis (CAPA) is common and linked with high fatality rates. To assess the impact on the incidence and outcome of CAPA of an antifungal prophylaxis (AFP) we compared two cohorts of COVID-19 patients admitted to intensive care units (ICU) in Brescia, Italy, from January to August 2021. METHODS: The study cohort included all mechanically ventilated patients observed between April 2021 and August 2021 with SARS-CoV-2-pneumonia, who received AFP with oral posaconazole (200 mg every 6 h) and nebulized liposomal amphotericin B (50 mg every 2 weeks) from ICU admission to 7 days after discharge or, if applicable, until tracheostomy removal. The control cohort included COVID-19 patients admitted to the same ICU between January and March 2021 who did not receive any AFP. Subjects with CAPA at ICU admission were excluded. RESULTS: We included 270 patients, of whom 64 (23.7%) received AFP. In patients in the study group, CAPA-related mortality was significantly reduced (29% vs. 48% p = 0.04), as well as the incidence of CAPA (3.1% vs 12.1%, p = 0.03). Patients who developed CAPA were older (mean of 70-y-old vs 63-y-old, p < 0.001). One subject discontinued posaconazole due to an adverse reaction. Among the 46 patients who received it, only one patient reached an effective plasma concentration of posaconazole. CONCLUSION: AFP was associated with reduced incidence and mortality from CAPA and was well tolerated in patients with severe COVID-19. Posaconazole concentrations below the efficacy threshold in almost all patients may be attributable to drug interactions and prompt further studies to define its clinical significance.

Mesothelioma among seamen: a systematic review and meta-analysis.

OBJECTIVES: Navy personnel and seafarers live and work 24 h per day in the shipboard environment and they are exposed to asbestos fibers released into the confined spaces aboard ships. We conducted a systematic review and meta-analysis to quantify the mesothelioma risk of seamen working aboard ships, either commercial or naval vessels, as compared to that of the general population. METHODS: We carried out a literature search in MEDLINE through PubMed and EMBASE, from inception to 31 December 2021, of all studies on seamen working aboard ships, either commercial or naval vessels, characterized by exposure to asbestos and providing mesothelioma risk estimates. The Newcastle-Ottawa Scale was used to assess the quality of the studies included. The pooled standardized mortality ratio (SMR) was computed across eligible studies. The study protocol was registered on PROSPERO and reporting followed the preferred reporting items for systematic reviews and meta-analyses guidelines. RESULTS: A total of 10 studies published from 1990 to 2020 were considered eligible and included in the systematic review and meta-analysis. All the included studies were of good quality, with a median score of seven out of nine. Overall, there were 235 mesothelioma cases/deaths in the included studies versus 115.6 expected, with a pooled SMR of 2.11 (95% confidence intervals, 1.70-2.62), in the absence of a significant between-study heterogeneity (I2 = 39%, P = 0.11). CONCLUSION: A more than double excess risk for mesothelioma among seamen working aboard ships emerged from our meta-analysis.

Dose-response association between cigarette smoking and gastric cancer risk: a systematic review and meta-analysis.

This study aims at providing an accurate and up-to-date quantification of the dose-response association between cigarette smoking and gastric cancer (GC) risk, overall and by subsite. We conducted a systematic review and meta-analysis of case-control and cohort studies on the association between cigarette smoking and GC risk published up to January 2023. We estimated pooled relative risks (RR) of GC and its subsites according to smoking status, intensity, duration, and time since quitting. Among 271 eligible articles, 205 original studies were included in this meta-analysis. Compared with never smokers, the pooled RR for GC was 1.53 (95% confidence interval; CI 1.44-1.62; n = 92) for current and 1.30 (95% CI 1.23-1.37; n = 82) for former smokers. The RR for current compared with never smokers was 2.08 (95% CI 1.66-2.61; n = 21) for gastric cardia and 1.48 (95% CI 1.33-1.66; n = 8) for distal stomach cancer. GC risk nonlinearly increased with smoking intensity up to 20 cigarettes/day (RR:1.69; 95% CI 1.55-1.84) and levelled thereafter. GC risk significantly increased linearly with increasing smoking duration (RR: 1.31; 95% CI 1.25-1.37 for 20 years) and significantly decreased linearly with increasing time since quitting (RR: 0.65; 95% CI 0.44-0.95 for 30 years since cessation). The present meta-analysis confirms that cigarette smoking is an independent risk factor for GC, particularly for gastric cardia. GC risk increases with a low number of cigarettes up to 20 cigarettes/day and increases in a dose-dependent manner with smoking duration.

Ecological monitoring of physical activity, emotions and daily life activities in schizophrenia: the DiAPAson study.

BACKGROUND: Schizophrenia spectrum disorders (SSD) compromise psychosocial functioning, including daily time use, emotional expression and physical activity (PA). OBJECTIVE: We performed a cohort study aimed at investigating: (1) the differences in PA, daily activities and emotions between patients with SSD and healthy controls (HC); (2) the strength of the association between these variables and clinical features among patients with SSD. METHODS: Ninety-nine patients with SSD (53 residential patients, 46 outpatients) and 111 matched HC were assessed for several clinical variables, and levels of functioning by means of standardised clinical measures. Self-reported daily activities and emotions were assessed with a smartphone application for ecological momentary assessment (EMA), and PA levels were assessed with a wearable accelerometer for 7 consecutive days.FindingsPatients with SSD, especially those living in residential facilities, spent more time being sedentary, and self-reported more sedentary and self-care activities, experiencing higher levels of negative emotions compared with HC. Moreover, higher functioning levels among patients were associated with more time spent in moderate-to-vigorous activity. CONCLUSIONS: Sedentary behaviour and negative emotions are particularly critical among patients with SSD and are associated with more impaired clinical outcomes. CLINICAL IMPLICATIONS: Mobile-EMA and wearable sensors are useful for monitoring the daily life of patients with SSD and the level of PA. This population needs to be targeted with specific rehabilitative programmes aimed at improving their commitment to structured daily activities.

Differences between cardiogenic shock related to acute decompensated heart failure and acute myocardial infarction.

AIMS: The present analysis from the multicentre prospective Altshock-2 registry aims to better define clinical features, in-hospital course, and management of cardiogenic shock complicating acutely decompensated heart failure (ADHF-CS) as compared with that complicating acute myocardial infarction (AMI-CS). METHODS AND RESULTS: All patients with AMI-CS or ADHF-CS enrolled in the Altshock-2 registry between March 2020 and February 2022 were selected. The primary objective was the characterization of ADHF-CS patients as compared with AMI-CS. In-hospital length of stay and mortality were secondary endpoints. One-hundred-ninety of the 238 CS patients enrolled in the aforementioned period were considered for the present analysis: 101 AMI-CS (80% ST-elevated myocardial infarction and 20% non-ST-elevated myocardial infarction) and 89 ADHF-CS. As compared with AMI-CS, ADHF-CS patients were younger [63 (IQR 59-76) vs. 67 (IQR 54-73) years, P = 0.01], but presented with higher creatinine [1.6 (IQR 1.0-2.6) vs. 1.2 (IQR 1.0-1.4) mg/dL, P < 0.001], bilirubin [1.3 (IQR 0.9-2.3) vs. 0.6 (IQR 0.4-1.1) mg/dL, P = 0.01], and central venous pressure values [14 mmHg (IQR 8-12) vs. 10 mmHg (IQR 7-14),P = 0.01]. Norepinephrine was the most common catecholamine used in AMI-CS (79.3%), whereas epinephrine was used more commonly in ADHF-CS (65.5%); 75.8% vs. 46.6% received a temporary mechanical support in AMI-CS and ADHF-CS, respectively (P < 0.001). Length of hospital stay was longer in the latter [28 (IQR 13-48) vs. 17 (IQR 9-29) days, P = 0.001]. Heart replacement therapies were more frequently used in the ADHF-CS group (heart transplantation 13.5% vs. 0% and left ventricular assist device 11% vs. 2%, P < 0.01 and 0.01, respectively). In-hospital mortality was 41.1% (38.6% AMI-CS vs. 43.8% ADHF-CS, P = 0.5). CONCLUSIONS: ADHF-CS is characterized by a higher prevalence of end-organ and biventricular dysfunction at presentation, a longer hospital length of stay, and higher need of heart replacement therapies when compared with AMI-CS. In-hospital mortality was similar between the two aetiologies. Our data warrant development of new management protocols focused on CS aetiology.

Interplay between negative symptoms, time spent doing nothing, and negative emotions in patients with schizophrenia spectrum disorders: results from a 37-site study.

This study evaluated the relationship between negative symptoms, daily time use (productive/non-productive activities, PA/NPA), and negative emotions in schizophrenia-spectrum disorders (SSDs): 618 individuals with SSDs (311 residential care patients [RCPs], 307 outpatients) were surveyed about socio-demographic, clinical (BPRS, BNSS) and daily time use (paper-and-pencil Time Use Survey completed twice/week) characteristics. Among them 57 RCPs and 46 outpatients, matched to 112 healthy controls, also underwent ecological monitoring of emotions (8 times/day for a week) through Experience Sampling Method (ESM). RCPs spent significantly less time in PA than outpatients. Patients with more negative symptomatology spent more time in NPA and less in PA compared to patients with milder symptoms. Higher time spent in NPA was associated with negative emotions (p < 0.001 during workdays) even when correcting for BNSS total and antipsychotic polypharmacy (p = 0.002 for workdays, p = 0.006 for Sundays). Future studies are needed to explore in more detail the relationship between negative emotions, negative symptoms, time use, and functioning in individuals with SSDs, providing opportunities for more informed and personalised clinical treatment planning and research into interactions between different motivational, saliency and behavioural aspects in individuals with SSDs.

Leisure-time physical activity and gastric cancer risk: A pooled study within the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Although physical activity (PA) has been recognized as a favourable factor in the prevention of various diseases, including certain forms of cancer, the relationship between PA and gastric cancer (GC) is not yet fully understood. This study aims to provide data from a pooled analysis of case-control studies within the Stomach cancer Pooling (StoP) Project to estimate the association between leisure-time PA and the occurrence of GC. METHODS: Six case-control studies from StoP project collected data on leisure-time PA, for a total of 2,343 cases and 8,614 controls. Subjects were classified into three leisure-time PA categories, either none/low, intermediate or high, based on study-specific tertiles. We used a two-stage approach. Firstly, we applied multivariable logistic regression models to obtain study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) then, we used a random-effect models to obtain pooled effect estimates. We performed stratified analyses according to demographic, lifestyle and clinical covariates. RESULTS: The meta-analysis showed ORs of GC with no significant differences between intermediate vs low and high vs low PA level (OR 1.05 [95%CI 0.76-1.45]; OR 1.23 [95%CI 0.78-1.94], respectively). GC risk estimates did not strongly differ across strata of selected covariates except for age ≤ 55 years old (high vs low level: OR 0.72 [95%CI 0.55-0.94]) and for control population-based studies (high vs low level: OR 0.79 [95%CI 0.68-0.93]). CONCLUSIONS: No association was found between leisure time PA and GC, apart from a slight suggestion of decreased risk below age 55 and in control population-based studies. These results may reflect specific characteristics of GC at a younger age, or the presence of a cohort effect mediating and interacting with socioeconomic determinants of GC The different distribution of PA levels among hospitalized controls could have led to an underestimated effect of PA on GC risk.

Shared and distinct abnormalities in sleep-wake patterns and their relationship with the negative symptoms of Schizophrenia Spectrum Disorder patients.

Sleep and rest-activity-rhythm (RAR) abnormalities are commonly reported in schizophrenia spectrum disorder (SSD) patients. However, an in-depth characterization of sleep/RAR alterations in SSD, including patients in different treatment settings, and the relationship between these alterations and SSD clinical features (e.g., negative symptoms) is lacking. SSD (N = 137 altogether, N = 79 residential and N = 58 outpatients) and healthy control (HC) subjects (N = 113) were recruited for the DiAPAson project. Participants wore an ActiGraph for seven consecutive days to monitor habitual sleep-RAR patterns. Sleep/rest duration, activity (i.e., M10, calculated on the 10 most active hours), rhythm fragmentation within days (i.e., intra-daily variability, IV; beta, steepness of rest-active changes), and rhythm regularity across days (i.e., inter-daily stability, IS) were computed in each study participant. Negative symptoms were assessed in SSD patients with the Brief Negative Symptom Scale (BNSS). Both SSD groups showed lower M10 and longer sleep/rest duration vs. HC, while only residential patients had more fragmented and irregular rhythms than HC. Compared to outpatients, residential patients had lower M10 and higher beta, IV and IS. Furthermore, residential patients had worse BNSS scores relative to outpatients, and higher IS contributed to between-group differences in BNSS score severity. Altogether, residentials and outpatients SSD had both shared and unique abnormalities in Sleep/RAR measures vs. HC and relative to one another, which also contributed to the patients' negative symptom severity. Future work will help establish whether improving some of these measures may ameliorate the quality of life and clinical symptoms of SSD patients.

Efficacy of Small versus Large-Bore Chest Drain in Pleural Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Pleural infection represents a significant clinical challenge worldwide. Although prompt drainage of pleural fluid is thought to play a key role in pleural infection management, the optimal size of intrapleural catheter has yet to be defined. OBJECTIVES: The aim of this systematic review and meta-analysis was to summarize data on efficacy and complications of small-bore drain (SBD), defined as ≤14F, in comparison to large-bore drain (LBD) in patients with pleural infection. METHOD: We searched MEDLINE and Embase for all studies reporting outcomes of interest published up to October 2021. Two authors reviewed selected full text to identify studies according to predefined eligibility criteria. Summary estimates were derived using the random-effects model. RESULTS: Twelve original studies were included for qualitative analysis and 7 of these for quantitative analysis. The surgical referral rate of SBD and LBD were, respectively, 0.16 (95% confidence interval [CI], 0.12-0.21) and 0.20 (95% CI, 0.10-0.32), the pooled mortality were 0.12 (95% CI, 0.05-0.21) and 0.20 (95% CI, 0.10-0.32), and the length of hospital stay was 24 days in both groups. Data on complications suggest similar proportions of tube dislodgement. Intensity of pain was evaluated in one study only, reporting higher scores for LBD. CONCLUSIONS: This systematic review and meta-analysis provide the first synthesis of data on performance of SBD and LBD in management of pleural infection, and, overall, clinical outcomes and complications did not substantially differ, although the limited number of studies and the absence of dedicated randomized trials does limit the reliability of results.

Adult height and risk of gastric cancer: a pooled analysis within the Stomach cancer Pooling Project.

BACKGROUND: The association between height and risk of gastric cancer has been studied in several epidemiological studies with contrasting results. The aim of this study is to examine the association between adult height and gastric cancer within a large pooled analysis of case-control studies members of the Stomach cancer Pooling (StoP) Project consortium. METHODS: Data from 18 studies members of the StoP consortium were collected and analyzed. A multivariable logistic regression model was used to estimate the study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between 10-cm increase in height and risk of gastric cancer. Age, sex, tobacco smoking, alcohol consumption, social class, geographical area and Helicobacter pylori (H. pylori ) status were included in the regression model. Resulting estimates were then pooled with random-effect model. Analyses were conducted overall and in strata of selected variables. RESULTS: A total of 7562 cases and 19 033 controls were included in the analysis. The pooled OR was 0.96 (95% CI 0.87-1.05). A sensitivity analysis was performed restricting the results to the studies with information on H. pylori status, resulting in an OR of 0.97 (95% CI 0.79-1.20). CONCLUSION: Our study does not support a strong and consistent association between adult height and gastric cancer.

SCAI stage reclassification at 24 h predicts outcome of cardiogenic shock: Insights from the Altshock-2 registry.

BACKGROUND: Cardiogenic shock (CS) includes several phenotypes with heterogenous hemodynamic features. Timely prognostication is warranted to identify patients requiring treatment escalation. We explored the association of the updated Society for Cardiovascular Angiography and Interventions (SCAI) stages classification with in-hospital mortality using a prospective national registry. METHODS: Between March 2020 and February 2022 the Altshock-2 Registry has included 237 patients with CS of all etiologies at 11 Italian Centers. Patients were classified according to their admission SCAI stage (assigned prospectively and independently updated according to the recently released version). In-hospital mortality was evaluated for association with both admission and 24-h SCAI stages. RESULTS: The overall in-hospital mortality was 38%. Of the 237 patients included and staged according to the updated SCAI classification, 20 (8%) had SCAI shock stage B, 131 (55%) SCAI stage C, 61 (26%) SCAI stage D and 25 (11%) SCAI stage E. In-hospital mortality stratified according to the SCAI classification at 24 h was 18% for patients in SCAI stage B, 27% for SCAI stage C, 63% for SCAI stage D and 100% for SCAI stage E. Both the revised SCAI stages on admission and at 24 h were associated with in-hospital mortality, but the classification potential slightly increased at 24-h. After adjusting for age, sex, lactate level, eGFR, CVP, inotropic score and mechanical circulatory support [MCS], SCAI classification at 24 h was an independent predictor of in-hospital mortality. CONCLUSIONS: In the Altshock-2 registry the utility of SCAI shock stages to identify risk of in-hospital mortality increased at 24 h after admission. Escalation of treatment (either pharmacological or with MCS) should be tailored to achieve prompt clinical improvement within the first 24 h after admission. Registration: http://www. CLINICALTRIALS: gov; Unique identifier: NCT04295252.

Development and Rasch Validation of an Observational Assessment Tool of Upper Limb Functional Impairment in Stroke Survivors: Functional Assessment Test for Upper Limb.

OBJECTIVE: To develop and validate a quick observational clinical tool, the Functional ASsessment Test for Upper Limb (FAST-UL), for the evaluation of upper limb impairment in goal-directed functional-oriented motor tasks after stroke. DESIGN: Observational, cross-sectional, psychometric study. SETTING: Inpatient and outpatient rehabilitation clinic. PARTICIPANTS: A total of 188 post-stroke survivors (mean age 65.2±17.7 years, 61% men, 48% with ischemic stroke and 66% in the sub-acute phase; N=188). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Principal component analysis and Rasch analysis through a Partial Credit Model were used to assess the structure and psychometric properties of the 5 items of the FAST-UL (Hand to Mouth [HtM], Reach to Target, Prono-Supination, Grasp and Release, and Pinch and Release [PaR]). RESULTS: The Cronbach's α equal to 0.96 was indicative of an acceptable internal consistency; the reliability, as measured through the Person Separation Reliability equal to 0.87, was good. The FAST-UL tool was unidimensional. All the FAST-UL items were found to fit well the Rasch measurement model. The easiest to perform FAST-UL item was the HtM movement while the most difficult was the PaR movement. CONCLUSIONS: The FAST-UL is a quick, easy-to-administer observational assessment tool of upper limb motor impairment in post-stroke survivors with good item-level psychometric properties.

Polychlorinated Biphenyls and Semen Quality in Healthy Young Men Living in a Contaminated Area.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants and endocrine disruptors that have been implicated in potential damage to human semen. However, the studies conducted so far provide contrasting results. Our study aimed to investigate the associations between PCB serum and semen levels and semen quality in high school and university students living in a highly PCB-polluted area of Italy. Subjects with a normal body mass index who did not make daily use of tobacco, alcohol, drugs, or medication were selected. All participants provided a fasting blood and a semen sample. Gas chromatography-mass spectrometry was used to determine the concentrations of 26 PCB congeners. The concentrations of PCB functional groups and total PCBs were also computed. A total of 143 subjects (median age 20, range 18-22 years) were enrolled. The median total PCB concentrations were 3.85 ng/mL (range 3.43-4.56 ng/mL) and 0.29 ng/mL (range 0.26-0.32 ng/mL) in serum and semen, respectively. The analysis of the associations between sperm PCB concentration and semen parameters showed (a) negative associations between some PCB congeners, functional groups and total PCBs and sperm total motility; (b) negative associations of total PCBs with sperm normal morphology; and (c) no association of PCBs with sperm concentration. Subjects at the highest quartile of semen total PCB concentration had 19% and 23% mean reductions in total motility and normal morphology, respectively, compared to those at the lowest quartile. The analysis of the associations of serum PCB levels with sperm parameters yielded null or mixed (some positive, other negative) results. In conclusion, the present study provides evidence of a negative effect of some PCB congeners and total PCBs in semen on sperm motility and normal morphology. However, the associations between the concentration of serum and semen PCB congeners and functional groups and sperm quality parameters were inconsistent.

Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis.

Many clinical trials have investigated the role of ICIs in PM, with contrasting results. We performed a systematic review and meta-analysis of clinical trials testing single-agent anti-Programmed Death -1 (PD-1)/Programmed Death-Ligand 1 (PD-L1), anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) or combined treatment in PM patients, analyzing response and survival rate as well as safety data. We selected 17 studies including 2328 patients. Both OS and PFS rates were significantly higher with combined ICI treatments than with single agent anti-PD-1/PD-L1 (p < 0.001 and p = 0.006, respectively) or anti CTLA-4 (p < 0.001) treatments. ORR and DCR for all ICI treatments were 20% (95% CI 13−27%) and 56% (95% CI 45−67%), respectively, and they did not significantly differ between combined and single agent treatments (p = 0.088 and p = 0.058, respectively). The 12-month OS and 6-month PFS rates did not differ significantly (p = 0.0545 and p = 0.1464, respectively) among pre-treated or untreated patients. Combined ICI treatments had a significantly higher rate of Adverse Events (AEs) (p = 0.01). PD-L1-positive patients had a higher probability of response and survival. In conclusion, combined ICI treatments have higher efficacy than single agents but are limited by higher toxicity. Efficacy was independent of treatment line, so a customized sequential strategy should still be speculated. PD-L1 expression could influence response to ICIs; however, reliable biomarkers are warranted.

Impact of COVID-19-Related Social Isolation on Behavioral Outcomes in Young Adults Residing in Northern Italy.

Social isolation affects our emotions, behavior and interactions. Worldwide, individuals experienced prolonged periods of isolation during the first wave of the COVID-19 pandemic when authorities-imposed restrictions to reduce the spread of the virus. In this study, we investigated the effects of social isolation on emotional and behavioral outcomes in young adults from Lombardy, Italy, a global hotspot of COVID-19. We leveraged baseline (pre-social isolation) and follow-up (mid- or post-isolation) data collected from young adults enrolled in the ongoing, longitudinal Public Health Impact of Metals Exposure (PHIME) study. At baseline, 167 participants completed the ASEBA questionnaires (ASR/YSR) by web link or in person; 65 completed the ASR 12-18 weeks after the onset of restrictions. Using the sign test and multiple linear regression models, we examined differences in ASR scores between baseline and follow-up adjusting for sex, age, pre-pandemic IQ and time with social restrictions (weeks). Further, we examined interactions between sex and time in social isolation. Participants completed the ASR after spending an average of 14 weeks in social isolation (range 12-18 weeks). Thought problems increased between baseline and follow-up (median difference 1.0; 1st, 3rd quartile: -1.0, 4.0; p = 0.049). Among males, a longer time in social isolation (≥14 weeks) was associated with increased rule-breaking behaviors of 2.8 points. These results suggest the social isolation related to COVID-19 adversely impacted mental health. In particular, males seem to externalize their condition. These findings might help future interventions and treatment to minimize the consequences of social isolation experience in young adults.

Covered self-expandable metal stents for pancreatic duct stricture: a systematic review and meta-analysis.

Background and study aims Placement of a covered (C)-self-expandable metal stent (SEMS) has been recently investigated as an alternative endoscopic treatment for main pancreatic duct stricture (MPDS) in chronic pancreatitis. Our aim was to carry out a systematic review and meta-analysis of studies quantifying efficacy and safety of C-SEMSs in the management of MPDS. Methods A multiple database search was performed, including MEDLINE, Embase and Cochrane Library, from January 2000 to September 2020, to identify studies reporting the efficacy and safety of C-SEMSs in patients with MPDS. Stricture and pain resolution were investigated. Other outcomes included technical success, stent migration, stricture recurrence and need for repeated stent placement. Pancreatitis, severe abdominal pain requiring stent removal and de-novo stricture were recorded as complications. Results Nineteen studies were identified, which included a total of 300 patients. C-SEMSs showed a pooled stricture resolution rate of 91 % [95 % confidence interval (CI), 85 %-96 %] and a pooled pain resolution rate of 92 % (95 % CI, 85 %-98 %). The pooled proportion for stricture recurrence was equal to 6 % (95 % CI, 1 %-14 %), while stent migration occurred in 33 of 300 patients, the pooled proportion being 7 % (95 % CI 1 %-15 %). The pooled mean stent duration was 133 days (95 % CI, 100-166 days). The most common complication was pancreatitis (3 %, 95 % CI 0 %-8 %), while de-novo stricture pooled proportion was 2 % (95 % CI, 0 %-5 %). Conclusions C-SEMSs are effective and safe in the treatment of MPDS. However, there is a significant need for further high-quality, well-designed studies to produce evidence-based data on short and long-term efficacy, safety, costs of C-SEMSs, and also optimal stent duration.

Lung Ultrasound Findings and Endothelial Perturbation in a COVID-19 Low-Intensity Care Unit.

Hypercoagulability and endothelial dysfunction related to inflammation have been clearly demonstrated in COVID-19. However, their influence on thromboembolism, lung alterations and mortality in low-intensity-care patients with COVID-19 is not completely clarified. Our aims were to evaluate the prevalence of deep vein thrombosis (DVT) with compressive ultrasound (CUS); to describe lung ultrasound (LUS) features; and to study coagulation, inflammatory and endothelial perturbation biomarkers in COVID-19 patients at low-intensity care unit admission. The predictive value of these biomarkers on mortality, need for oxygen support and duration of hospitalization was also evaluated. Of the 65 patients included, 8 were non-survivors. CUS was negative for DVT in all patients. LUS Soldati and Vetrugno scores were strongly correlated (rho = 0.95) with each other, and both significantly differed in patients who needed oxygen therapy vs. those who did not (Soldati p = 0.017; Vetrugno p = 0.023), with coalescent B lines as the most prevalent pattern in patients with a worse prognosis. Mean (SD) levels of thrombomodulin and VCAM-1 were higher in non-survivors than in survivors (7283.9 pg/mL (3961.9 pg/mL) vs. 4800.7 pg/mL (1771.0 pg/mL), p = 0.004 and 2299 ng/mL (730.35 ng/mL) vs. 1451 ng/mL (456.2 ng/mL), p < 0.001, respectively). Finally, in a multivariate analysis model adjusted for age, sex and Charlson score, VCAM-1 level increase was independently associated with death [OR 1.31 (1.06, 1.81; p = 0.036)]. In conclusion, in a cohort of mild COVID-19 patients, we found no DVT events despite the highly abnormal inflammatory, endothelial and coagulation parameters. The presence of lung alterations at admission could not predict outcome. The endothelial perturbation biomarker VCAM-1 emerged as a promising prognostic tool for mortality in COVID-19.

Diagnostic Role of Bronchoalveolar Lavage in Patients with Suspected SARS-CoV-2 Pneumonia and Negative Upper Respiratory Tract Swab: A Systematic Review and Meta-Analysis.

The added role of bronchoalveolar lavage (BAL) in SARS-CoV-2 detection in hospitalized patients with suspected COVID-19 pneumonia and at least one negative nasopharyngeal swab (NPS) has yet to be definitively established. We aimed to provide a systematic review and meta-analysis to summarize data from the literature on the diagnostic yield of BAL in this context. We searched Medline and Embase for all studies reporting outcomes of interest published up to October 2021. Two authors reviewed all titles/abstracts and retrieved the selected full texts according to predefined selection criteria. The summary estimate was derived using the random-effects model. Thirteen original studies, involving 868 patients, were included. The summary estimate of proportions of SARS-CoV-2 positivity in BAL fluid in patients with at least one previous negative NPS was 20% (95% confidence interval [CI]; 11-30%). Moreover, microbiological tests of BAL fluid led to the identification of other pathogens, mainly bacteria, in up to two-thirds of cases. BAL plays a crucial role in the diagnostic work-up of patients with clinical suspicion of COVID-19 and previous negative NPS, as it allowed to detect the infection in a significant proportion of subjects, who would have been otherwise misclassified, with relevant implications in the prevention of disease spread, especially in hospital settings.