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Gaussian graphical models (GGMs) provide a framework for modeling conditional dependencies in multivariate data. In this tutorial, we provide an overview of GGM theory and a demonstration of various GGM tools in R. The mathematical foundations of GGMs are introduced with the goal of enabling the researcher to draw practical conclusions by interpreting model results. Background literature is presented, emphasizing methods recently developed for high-dimensional applications such as genomics, proteomics, or metabolomics. The application of these methods is illustrated using a publicly available dataset of gene expression profiles from 578 participants with ovarian cancer in The Cancer Genome Atlas. Stand-alone code for the demonstration is available as an RMarkdown file at https://github.com/katehoffshutta/ggmTutorial.

Introduction: Schistosoma (S.) haematobium is the aetiological agent of urogenital schistosomiasis endemic in Sub-Saharan Africa and the Middle East. Microhaematuria is strongly associated with schistosomiasis diagnosis. Praziquantel (PZQ) is the treatment of choice. Methodology: We conducted a monocentric survey among African migrants from January 2017 to December 2018. The diagnosis of S. haematobium was performed by direct microscopic examination of urine. The treatment was PZQ 40 mg/Kg/die for three days. Results: We enrolled 91 male patients with a median age of 20.2 years (IQR 18.9-23.4)]. Forty-five (49.5%) described a history of haematuria. Sixteen (17.6%) evidenced the presence of red blood cells (RBCs) during urine microscopy. Eighteen (19.8%) had urogenital schistosomiasis. Their median white blood count (WBC) was 5.15 x 109/L (IQR 4.45-6.08) and it was 6.37 x 109 /L (IQR 5.14-8.27), p = 0.009, after 15 days from treatment. Baseline eosinophil count was 0.5 x 109/L (IQR 0.3-0.6) and 0.7 x 109/L (IQR 0.2-1.9; p = 0.032). According to the univariate analysis, origin from Mali [odds ratio (OR) 3.6 (CI 1.2-10.9), p = 0.022] and microscopic evidence of RBCs [OR of 10.7 (CI 2.5-45.1), p = 0.001] were main predictors of urogenital schistosomiasis diagnosis. One (5.6%) treatment failure was registered. Three (16.7%) patients had bladder cancer. Conclusions: Detection of RBCs was a significant predictor of S. haematobium infection and could be used as a screening method in migrants coming from endemic areas. Early urogenital schistosomiasis diagnosis and ultrasound diagnostic tools are crucial for reducing the risk of potential neoplastic evolution.

Over time, the primary treatment modality of oropharyngeal squamous cell cancers (OPSCC) is intensity-modulated radiation therapy (IMRT), eventually associated with chemotherapy (CHT). This treatment modality is preferred for reduced impact on the quality of life rather than aggressive open surgical approaches. The advent of TransOral Robotic Surgery (TORS) has rediscovered the role of surgery in the treatment of OPSCC. Although the primary chemoradiation therapy (CRT) and transoral robotic surgery (TORS) are competing for similar oncologic results, CRT may result in significant functional complaints such as severe dysphagia and feeding tube dependence and, on the other hand, TORS might result in surgical defects depending on the size of the resection and anatomic location. Nevertheless, TORS may intercept the locoregionally advanced population through pathologic downstaging as well as the potential for improvement in oncologic outcomes. The available reconstructive options allow an expanding role of this minimally invasive surgery, even in locally advanced tumours. Finally, the surgical management of OPSCC with TORS identifies areas of opportunity in shortening the overall treatment package time compared to traditional surgery.

Purpose Cryptorchidism associated with gastroschisis has been poorly investigated. We aimed to assess the prevalence of this association, and to address the management and outcome of cryptorchidism in this context. Materials and methods In this systematic review, we searched electronic databases (PubMed, Web of Science, and Google Scholar), without language restrictions from inception to March 31, 2021, for studies on cryptorchidism and gastroschisis co-occurrence. Random effects meta-analysis was used to calculate pooled prevalence estimates of cryptorchidism in gastroschisis and spontaneous testicular descent in this population. Results Twenty-five studies were included for the systematic review. All were retrospective case reports or series for a total of 175 patients. Pooled prevalence estimate for cryptorchidism in gastroschisis was 19% (95% CI 13–26). Complete data sets for management and outcome analysis were available in 94 patients, involving 120 undescended testes [63 (52.5%) nonpalpable, 34 (28.3%) prolapsed outside the abdominal wall defect, and 23 (19.2%) palpable]. Fifty-five descended spontaneously, with a pooled prevalence estimate of 50% (95% CI 31–69). Twelve testes/remnants were primarily removed or absent, while 49 testes underwent orchiopexy (success rate, 63%). Excluding 4 testes still awaiting orchiopexy, 30 of the remaining 116 (25.8%) testes had a dismal outcome, including testicular loss (19), hypoplasia (8) or recurrent cryptorchidism (3). Conclusion Cryptorchidism in gastroschisis appears to occur more frequently than in the normal population. The overall mediocre testicular outcome seems to reflect the most unfavorable presentation of cryptorchidism in gastroschisis, which is represented by originally intrabdominal or prolapsed testis in the majority of cases. Level of evidence IV.

Aim of this study was to assess the predictors of virological failure (VF) among patients living with HIV (PLWHIV) switching from an effective first-line antiretroviral therapy (ART) regimen, and to evaluate the emergence of resistance-associated mutations. All adult patients enrolled in the Antiviral Response Cohort Analysis cohort who started ART after 2010, with at least 6 months of virological suppression (VS) before ART switch and with an available genotypic resistance test (GRT) at baseline were included. Thirty-two patients out of the 607 PLWHIV included (5.3%) experienced VF after a median of 11 months from ART switch. Younger age (adjusted Hazard Ratio [aHR] 0.96, 95% confidence interval [CI] 0.92-0.99

BACKGROUND AND PURPOSE: Controversy exists as to whether ADC histograms are capable to distinguish human papillomavirus–positive (HPV+) from human papillomavirus–negative (HPV–) oropharyngeal squamous cell carcinoma. We investigated how the choice of b-values influences the capability of ADC histograms to distinguish between the two tumor types. MATERIALS AND METHODS: Thirty-four consecutive patients with histologically proved primary oropharyngeal squamous cell carcinoma (11 HPV+ and 23 HPV–) underwent 3T MR imaging with a single-shot EPI DWI sequence with 6 b-values (0, 50, 100, 500, 750, 1000 s/mm(2)). Monoexponentially calculated perfusion-sensitive (including b=0 s/mm(2)) and perfusion-insensitive/true diffusion ADC maps (with b ≥ 100 s/mm(2) as the lowest b-value) were generated using Matlab. The choice of b-values included 2 b-values (ADC(b0–1000), ADC(b100–1000), ADC(b500–1000), ADC(b750–1000)) and 3–6 b-values (ADC(b0–750–1000), ADC(b0–500–750–1000), ADC(b0–50–100–1000), ADC(b0–50–100–750–1000), ADC(b0–50–100–500–750–1000)). Readers blinded to the HPV– status contoured all tumors. ROIs were then copied onto ADC maps, and their histograms were compared. RESULTS: ADC histogram metrics in HPV+ and HPV– oropharyngeal squamous cell carcinoma changed significantly depending on the b-values. The mean ADC was lower, and skewness was higher in HPV+ than in HPV– oropharyngeal squamous cell carcinoma only for ADC(b0–1000,) ADC(b0–750–1000), and ADC(b0–500–750–1000) (P < .05), allowing distinction between the 2 tumor types. Kurtosis was significantly higher in HPV+ versus HPV– oropharyngeal squamous cell carcinoma for all b-value combinations except 2 perfusion-insensitive maps (ADC(b500–1000) and ADC(b750–1000)). Among all b-value combinations, kurtosis on ADC(b0–1000) had the highest diagnostic performance to distinguish HPV+ from HPV– oropharyngeal squamous cell carcinoma (area under the curve = 0.893; sensitivity = 100%, specificity = 82.6%). Acquiring multiple b-values for ADC calculation did not improve the distinction between HPV+ and HPV– oropharyngeal squamous cell carcinoma. CONCLUSIONS: The choice of b-values significantly affects ADC histogram metrics in oropharyngeal squamous cell carcinoma. Distinguishing HPV+ from HPV– oropharyngeal squamous cell carcinoma is best possible on the ADC(b0–1000) map.

Background: World Health Organization (WHO) has increasingly improved the guidelines to tackle the spread of Coronavirus Disease 2019 (COVID-19) among the worldwide population. In this context, each country has introduced specific social, healthcare, political and macroeconomic measures to face COVID pandemic locally. Objective: The general aim of this comparative overview is to highlight the most significant effects of COVID-19 pandemic on the main healthcare systems. Also, we critically analyzed the macroeconomic variables and the most promising solutions to improve both healthcare system and its related risk management, taking into specific consideration the most industrialized countries. Method: The main strategy has been built on a renewed concept of the hospital, rebuilding the old concepts of “triage” and “intensive care”. Recently, COVID-19 hospitals have allowed to cater the patients affected by COVID-19. Moreover, the reshaping of several healthcare policies and requirements has led to several positive effects, such as the recruitment of a huge number of human resources in the healthcare systems. Nevertheless, several negative effects have also impacted the communities mostly subjected to infections. Conclusion: Undoubtedly, the national healthcare systems have somehow addressed the people’s needs, trying not to neglect the social, healthcare, economic and political aspects. In our overview, we have reported how the different actions taken in the last months, have resulted in different outcomes.

COVID-19 pandemic has generated a million deaths worldwide. The efficiency of the immune system can modulate individual vulnerability with variable outcomes. However, the relationships between disease severity and the titer of antibodies produced against SARS-CoV-2 in non-vaccinated, recently infected subjects need to be fully elucidated.A total of 99 patients admitted to a COVID-unit underwent clinical assessment and measurement of serum levels of anti-spike protein (S1) IgM, and anti-nucleocapsid protein IgG. Patients were stratified according to the clinical outcome (i.e., discharged at home or in-hospital death).Following hospitalization, 18 died during the hospital stay. They were older, had lymphopenia, a higher co-morbidity rate, and longer hospital stay than 81 patients who were discharged after healing. Patients in this latter group had, at hospital admittance, 7.9-fold higher serum concentration of IgM, and 2.4-fold higher IgG levels. Multivariate Cox regression models indicated age and anti-nucleocapsid protein IgG concentration at admission as independently associated with the risk of in-hospital death.An efficient immunological response during the early phase of COVID-19 protects from mortality, irrespective of age. Advanced age is a critical risk factor for poor outcome in infected subjects. Further studies must explore potential therapeutic strategies able to restore a valid functional humoral immunity in elderly patients with poor antibody response during the early stage of COVID-19 infection.

OBJECTIVES/HYPOTHESIS: The aim of this study was to evaluate the correlations between the severity and duration of olfactory dysfunctions (OD), assessed with psychophysical tests, and the viral load on the rhino-pharyngeal swab determined with a direct method, in patients affected by coronavirus disease 2019 (COVID-19). STUDY DESIGN: Prospective cohort study. METHODS: Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and determination of the normalized viral load on nasopharyngeal swab within 10 days of the clinical onset of COVID-19. RESULTS: Sixty COVID-19 patients were included in this study. On psychophysical testing, 12 patients (20% of the cohort) presented with anosmia, 11 (18.3%) severe hyposmia, 13 (18.3%) moderate hyposmia, and 10 (16.7%) mild hyposmia with an overall prevalence of OD of 76.7%. The overall median olfactory score was 50 (interquartile range [IQR] 30-72.5) with no significant differences between clinical severity subgroups. The median normalized viral load detected in the series was 2.56E+06 viral copies/106 copies of human beta-2microglobulin mRNA present in the sample (IQR 3.17E+04-1.58E+07) without any significant correlations with COVID-19 severity. The correlation between viral load and olfactory scores at baseline (R2 = 0.0007; P = .844) and 60-day follow-up (R2 = 0.0077; P = .519) was weak and not significant. CONCLUSIONS: The presence of OD does not seem to be useful in identifying subjects at risk for being super-spreaders or who is at risk of developing long-term OD. Similarly, the pathogenesis of OD is probably related to individual factors rather than to viral load and activity. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2312-2318, 2021.

State-of-the-art MR imaging of the larynx and hypopharynx with high-resolution surface coils, parallel imaging techniques, and DWI has several advantages over CT for assessing submucosal tumor spread, in particular neoplastic involvement of the paraglottic space, laryngeal cartilages, and extralaryngeal soft tissues. Current diagnostic MR imaging criteria based on a combination of distinct imaging features on morphologic sequences combined with DWI allow improved discrimination between tumor, peritumoral inflammation, and fibrosis and, ultimately, an increased precision for submucosal tumor delineation, which is a key prerequisite for tailored treatment options. Multiparametric MR imaging with DWI has a higher diagnostic performance than CT.

Glioblastoma multiforme (GBM), also known as grade IV astrocytoma, represents the most aggressive primary brain tumor. The complex genetic heterogeneity, the acquired drug resistance, and the presence of the blood-brain barrier (BBB) limit the efficacy of the current therapies, with effectiveness demonstrated only in a small subset of patients. To overcome these issues, here we propose an anticancer approach based on ultrasound-responsive drug-loaded organic piezoelectric nanoparticles. This anticancer nanoplatform consists of nutlin-3a-loaded ApoE-functionalized P(VDF-TrFE) nanoparticles, that can be remotely activated with ultrasound-based mechanical stimulations to induce drug release and to locally deliver anticancer electric cues. The combination of chemotherapy treatment with chronic piezoelectric stimulation resulted in activation of cell apoptosis and anti-proliferation pathways, induction of cell necrosis, inhibition of cancer migration, and reduction of cell invasiveness in drug-resistant GBM cells. Obtained results pave the way for the use of innovative multifunctional nanomaterials in less invasive and more focused anticancer treatments, able to reduce drug resistance in GBM. Statement of significance Piezoelectric hybrid lipid-polymeric nanoparticles, efficiently encapsulating a non-genotoxic drug (nutlin-3a) and functionalized with a peptide (ApoE) that enhances their passage through the BBB, are proposed. Upon ultrasound stimulation, nanovectors resulted able to reduce cell migration, actin polymerization, and invasion ability of glioma cells, while fostering apoptotic and necrotic events. This wireless activation of anticancer action paves the way to a less invasive, more focused and efficient therapeutic strategy.

Thyroid hormones, T3(triiodothyronine) and T4(thyroxine), induce a variety of long-term effects on important physiological functions, ranging from development and growth to metabolism regulation, by interacting with specific nuclear or cytosolic receptors. Extranuclear or nongenomic effects of thyroid hormones are mediated by plasma membrane or cytoplasmic receptors, mainly by αvβ3 integrin, and are independent of protein synthesis. A wide variety of nongenomic effects have now been recognized to be elicited through the binding of thyroid hormones to this receptor, which is mainly involved in angiogenesis, as well as in cell cancer proliferation. Several signal transduction pathways are modulated by thyroid hormone binding to αvβ3 integrin: protein kinase C, protein kinase A, Src, or mitogen-activated kinases. Thyroid hormone-activated nongenomic effects are also involved in the regulation of Na+-dependent transport systems, such as glucose uptake, Na+/K+-ATPase, Na+/H+exchanger, and amino acid transport System A. Of note, the modulation of these transport systems is cell-type and developmental stage-dependent. In particular, dysregulation of Na+/K+-ATPase activity is involved in several pathological situations, from viral infection to cancer. Therefore, this transport system represents a promising pharmacological tool in these pathologies.

INTRODUCTION High intensity functional trainings (HIFT), a recent development of high intensity trainings, includes in the same training session components of endurance exercises, elements of Olympic weightlifting and powerlifting, gymnastics, plyometrics and calisthenics exercises. Therefore, subjects practicing this type of activity are supposed to show physiological features that represent a combination of both endurance and power athletes. The aim of this study was to compare the physiological profile of three groups of age-matched endurance, HIFT and power athletes. METHODS A total of 30 participants, 18 to 38-year-old men were enrolled in the study. Participants were divided in three groups: HIFT (n = 10), endurance (END, n = 10), and power (POW, weightlifters, n = 10) athletes. All were evaluated for anthropometric characteristics, VO2peak, handgrip, lower limb maximal isometric and isokinetic strength, countermovement vertical jump and anaerobic power through a shuttle run test on the field. RESULTS VO2peak/kg was higher in END and HIFT than POW athletes (p = 0.001 and p = 0.007, respectively), but there were no significant differences between the first two. POW and HIFT athletes showed significant greater strength at the handgrip, countermovement jump and leg extension/flexion tests than END athletes. HIFT athletes showed highest results at the dynamic isokinetic test, while there were no significant differences at the shuttle run test among groups. CONCLUSIONS As HIFT reach aerobic levels similar to END athletes and power and strength output similar to POW athletes, it appears that HIFT programs are effective to improve both endurance-related and power-related physical fitness components.

Tissue fibrosis is a key driver of end-stage organ failure and cancer, overall accounting for up to 45% of deaths in developed countries. There is a large unmet medical need for antifibrotic therapies. Claudin-1 (CLDN1) is a member of the tight junction protein family. Although the role of CLDN1 incorporated in tight junctions is well established, the function of nonjunctional CLDN1 (njCLDN1) is largely unknown. Using highly specific monoclonal antibodies targeting a conformation-dependent epitope of exposed njCLDN1, we show in patient-derived liver three-dimensional fibrosis and human liver chimeric mouse models that CLDN1 is a mediator and target for liver fibrosis. Targeting CLDN1 reverted inflammation-induced hepatocyte profibrogenic signaling and cell fate and suppressed the myofibroblast differentiation of hepatic stellate cells. Safety studies of a fully humanized antibody in nonhuman primates did not reveal any serious adverse events even at high steady-state concentrations. Our results provide preclinical proof of concept for CLDN1-specific monoclonal antibodies for the treatment of advanced liver fibrosis and cancer prevention. Antifibrotic effects in lung and kidney fibrosis models further indicate a role of CLDN1 as a therapeutic target for tissue fibrosis across organs. In conclusion, our data pave the way for further therapeutic exploration of CLDN1-targeting therapies for fibrotic diseases in patients.

Background In next fall and winter, SARS-CoV-2 could circulate in parallel with seasonal influenza. The dual epidemics will result in considerable morbidity and mortality; therefore, influenza vaccination may be essential. Recent studies found increased risk of coronavirus in individuals receiving influenza vaccination. Aims Our aim is to analyse the association between influenza vaccination and COVID-19 in a population of healthcare workers (HCWs). Methods IgG antibodies against SARS-CoV-2 were detected in 3520 HCWs at a large hospital in Northern Italy. For each participant, we collected data on flu immunization status for the last five flu seasons. Logistic regression was used to test associations between seasonal flu vaccination status and a positive serology tests for COVID-19. Results During the last five flu seasons, 2492 vaccinations were administered. Serology tests were negative for 3196 (91%) HCWs and residents and only 21 (1%) people had an equivocal test (12.0–15.0 AU/mL). Only 128 (4%) people received a diagnosis of COVID-19, with a positive swab test. No flu vaccinations for the last five flu seasons were specifically associated with diagnosis of COVID-19 or with positive results of serology tests. Conclusions Flu vaccinations did not appear to be associated with SARS-CoV-2 infection. Influenza vaccination should continue to be recommended for HCWs and for individuals at increased risk for severe illness from respiratory infection.

PURPOSE: No study to date has described the overall landscape of sleep disorders management and training in otolaryngology departments of different countries. The aim of our study was to investigate and compare settings, diagnostic and therapeutic approaches and training programmes. METHODS: An international online survey was developed with the collaboration of the YO-IFOS (Young Otolaryngologists-International Federation of Otorhinolaryngological Societies) to assess the current practice of otolaryngologists in the management of sleep disorders. The survey also included a session dedicated to training. RESULTS: A total of 126 otolaryngologists completed the survey. The larger part of responses was collected from Central/South America and Europe. The majority of responders from South/Central America (97%) declared to be certified as sleep specialist while 49% of Europeans stated the opposite. Of responders 83% perform a drug-induced sleep endoscopy (DISE) before planning a possible surgical intervention. Soft palate and base of tongue interventions were the most common procedure, respectively performed in 94% and 79% of the cases. Residents were allowed to perform soft palate surgery in 77% of the cases. Upper airway stimulation (26% vs 10%), trans-oral robotic surgery (36% vs 11%) and radiofrequency of the base of the tongue (58% vs 25%) were preferred more frequently by European responders. The highest caseloads of soft palate surgery and bi-maxillary advancement were registered in the academic institutions. CONCLUSION: Significant concordance and few interesting divergences in diagnosis and treatment of sleep disorders were observed between nationalities and types of institution. Economic resources might have played a significant role in the therapeutic choice. Trainees' lack of exposure to certain interventions and to a sufficient caseload appeared to be the main burden to overcome.

To observe the effectiveness of preoperative drug-induced sleep endoscopy in improving surgical results of patients undergoing single-level barbed pharyngoplasty surgery for OSA, using a prospective randomized model. A single-center randomized controlled trial with two prospective arms was carried out to compare functional results in patients treated with barbed reposition pharyngoplasty (BRP) surgery without a preoperative drug-induced sleep endoscopy (DISE) evaluation vs patients treated with BRP surgery performed after DISE evaluation of sites/patterns of collapse. We compared 50 patients who underwent BRP without a preoperative DISE evaluation (Group A) and 42 patients (Group B) treated with BRP surgery but preoperatively selected by means of a preoperative DISE. In this second group of patients, after DISE evaluation, 70% of patients were selected for single-level BRP surgery because they showed an isolated velopharyngeal collapse at the DISE evaluation, without obstruction at other upper airway levels evaluated. Both groups of patients showed a statistically significant difference between preoperative and postoperative values of AHI, ODI, and LOS (p

BACKGROUND Results from clinical trials and observational studies suggest that dolutegravir plus lamivudine could be an effective and well-tolerated option for simplification in HIV-1-positive patients. We aimed to assess long-time efficacy and safety in our multicenter cohort. METHODS This was a retrospective study enrolling HIV-1-infected, virologically suppressed patients switching to dolutegravir + lamivudine. We performed survival analysis to evaluate time to virological failure (VF, defined by a single HIV-RNA ≥1000 copies/mL or by 2 consecutive HIV-RNA ≥ 50 copies/mL) and treatment discontinuation (defined as the interruption of either 3TC or dolutegravir), assessing predictors via Cox regression analyses. RESULTS Seven-hundred eighty-five patients were considered for the analysis: 554 were men (70.6%), with a median age of 52 years (interquartile range 45-58 years). Estimated probabilities of maintaining virological suppression at weeks 96, 144, and 240 were 97.7% (SD ±0.6), 96.9% (SD ±0.8), and 96.4% (SD ±0.9), respectively. A non-B HIV subtype (P = 0.014) and a previous VF (P = 0.037) resulted predictors of VF. We did not observe differences in probability of VF in people living with HIV with an M184V resistance mutation (P = 0.689); however, in a deeper analysis, M184V mutation was a predictor of VF (P = 0.038) in patients with time of virological suppression

Routine systems for monitoring vascular access (VA) performance are lacking. We developed a vascular access triage system to evaluate the monthly performance of the access, developed a specific score and assessed the association between score improvement and clinical outcomes. Vascular access was triaged (Green, Yellow or Red) according to a score generated by dialytic and clinical parameters in all patients who, from 1/1/2014 to 31/03/2014, had been receiving haemodialysis treatment for at least 3 consecutive months in our Unit and who were then followed up for 4 years. We enrolled 130 patients, 78 with arteriovenous fistula (AVF) and 52 with tunnelled central venous catheter (CVC). During a median of 29 ± 11 months of follow up (range 3–46 months), 28 deaths and 303 hospitalizations (lasting 16 ± 30 days) were recorded. Vascular access triage scores improved over time (2014 vs 2015 vs 2016 vs 2017) in the population with an AVF (Green from 25% to 58% to 77% to 79%, Yellow from 65% to 39% to 18% to 20% and Red from 10% to 3% to 5% to 1%, respectively; χ2 p

Paediatric obesity is a well-known risk factor for metabolic-associated fatty liver disease (MAFLD). The aim of this study was to evaluate the effects of laparoscopic sleeve gastrectomy (LSG) on the levels of total homocysteine (tHcy) and total glutathione (tGSH) plasma levels in children with MAFLD. Twenty-four children with severe obesity who underwent LSG were included in the study. The metabolic parameters, systemic inflammatory markers, one-carbon metabolism products, ultrasound and histological improvement were evaluated at baseline (T0M) and after 12 months from LSG (T12M). The patients exhibited a significant amelioration of several metabolic parameters at T12M. A significant reduction of steatosis was observed at ultrasound (from 72.7% of moderate-severe grade to 0% severe steatosis), accompanied by a statistically significant improvement of ballooning, portal and lobular inflammation and fibrosis. A statistically significant decrease of tumour necrosis factor circulating levels was also observed (T0M median = 290.3, IQR = 281.0–317.0 pg/mL; T12M median = 260.4, IQR = 240.0–279.0 pg/mL; p

International audience; Plant-based proteins are generally characterised by lower Indispensable Amino Acid (IAA) content, digestibility, and anabolic properties, compared to animal-based proteins. However, they are environmentally friendlier, and wider consumption is advocated. Older adults have higher dietary protein needs to prevent sarcopenia, a disease marked by an accelerated loss of muscle mass and function. Given the lower environmental footprint of plant-based proteins and the importance of optimising dietary protein quality among older adults, this paper aims to assess the net peripheral Amino Acid (AA) appearance after ingestion of three different plant protein and fibre (PPF) products, compared to whey protein with added fibre (WPF), in healthy older adults. In a randomised, single-blind, crossover design, nine healthy men and women aged ≥65 years consumed four test meals balanced in AA according to the FAO reference protein for humans, matched for leucine, to optimally stimulate muscle protein synthesis in older adults. A fasted blood sample was drawn at each visit before consuming the test meal, followed by postprandial arterialise blood sampling every 30 min for 3 h. The test meal was composed of a soup containing either WPF or PPF 1–3. The PPF blends comprised pea proteins with varying additional rice, pumpkin, soy, oat, and/or almond protein. PPF product ingestion resulted in a lower maximal increase of postprandial leucine concentration and the sum of branched-chain AA (BCAA) and IAA concentrations, compared to WPF, with no effect on their incremental area under the curve. Plasma methionine and cysteine, and to a lesser extent threonine, appearance were limited after consuming the PPF products, but not WPF. Despite equal leucine doses, the WPF induced greater postprandial insulin concentrations than the PPF products. In conclusion, the postprandial appearance of AA is highly dependent on the protein source in older adults, despite providing equivalent IAA levels and dietary fibre. Coupled with lower insulin concentrations, this could imply less anabolic potential. Further investigation is required to understand the applicability of plant-based proteins in healthy older adults.

BackgroundTo safely resume in-person activities during the COVID-19 pandemic, Sapienza University of Rome implemented rigorous infection prevention and control measures, a successful communication campaign and a free SARS-CoV-2 testing program. In this study, we describe the University's experience in carrying out such a program in the context of the COVID-19 response and identify risk factors for infection.MethodsHaving identified resources, space, supplies and staff, from March to June 2021 Sapienza offered to all its enrollees a molecular test service (8.30 AM to 4 PM, Monday to Thursday). A test-negative case-control study was conducted within the program. Participants underwent structured interviews that investigated activity-related exposures in the 2 weeks before testing. Multivariable conditional logistic regression analyses were performed. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were calculated.ResultsA total of 8,959 tests were administered, of which 56 were positive. The detection trend followed regional tendencies. Among 40 cases and 80 controls, multivariable analysis showed that a known exposure to a COVID-19 case increased the likelihood of infection (aOR: 8.39, 95% CI: 2.38–29.54), while having a job decreased it (aOR: 0.23, 95% CI: 0.06–0.88). Of factors that almost reached statistical significance, participation in activities in the university tended to reduce the risk (aOR: 0.32, 95% CI: 0.09–1.06), while attendance at private gatherings showed an increasing risk trend (aOR: 3.48, 95% CI: 0.95–12.79). Age, gender, activities in the community, visiting bars or restaurants, and use of public transportation were not relevant risk factors. When those students regularly attending the university campus were excluded from the analysis, the results were comparable, except that attending activities in the community came close to having a statistically significant effect (aOR: 8.13, 95% CI: 0.91–72.84).ConclusionsThe testing program helped create a safe university environment. Furthermore, promoting preventive behavior and implementing rigorous measures in public places, as was the case in the university setting, contributed to limit the virus transmission.

Neuropsychology trainees have identified mentorship as an important factor in their training. Limited past work has been conducted on mentorship within neuropsychology, and there is a need to better understand the experiences and perspectives of neuropsychology mentors.Self-identified mentors in clinical neuropsychology completed a survey about their mentorship practices, including culturally responsive mentorship, as well as perceived barriers and challenges to providing effective mentorship. Themes were derived using qualitative analyses for free response questions, and descriptive statistics were calculated for quantitative variables.Mentors identified assessment, professionalism, and ethics as top priorities in mentorship, which may reflect the overlap within neuropsychology of assessment supervision and mentoring. Reported best practices included being self-aware and engaging in a personalized approach to mentorship relationships that varies depending upon the needs of the mentee. A majority reported that their training program is not diverse and they themselves do not mentor trainees from diverse backgrounds which provides a clear area for targeted efforts to recruit and retain diversity in the discipline. Mentors described practices related to discussing diversity-related differences with their trainees including self-disclosure, creating a safe space for conversations, and tailoring discussions to the individual trainee. They reported an interest in more training on how to engage in culturally competent mentorship. Two barriers to providing effective mentorship identified most by mentors were time constraints and a lack of training.These results highlight a variety of perspectives and approaches to mentorship, which may be beneficial for mentors to consider as they reflect on their mentorship practices and/or for trainees as part of their professional development toward becoming future mentors themselves. These results also highlight the need for a greater emphasis on mentorship training within neuropsychology, including training in culturally responsive mentorship practices.

Elevated levels of specific proinflammatory molecules in the cerebrospinal fluid (CSF) have been associated with disability progression, enhanced neurodegeneration and higher incidence of mood disorders in people with multiple sclerosis (MS). Studies in animal models of MS suggest that preventive exercise may play an immunomodulatory activity, with beneficial effects on both motor deficits and behavioral alterations. Here we explored the impact of lifestyle physical activity on clinical presentation and associated central inflammation in a large group of newly diagnosed patients with MS. Furthermore, we addressed the causal link between exercise-mediated immunomodulation and mood symptoms in the animal setting.A cross-sectional study was conducted on 235 relapsing-remitting MS patients at the time of the diagnosis. Patients were divided into 3 groups ("sedentary", "lifestyle physical activity" and "exercise") according to the level of physical activity in the six months preceding the evaluation. Patients underwent clinical, neuropsychological and psychiatric evaluation, magnetic resonance imaging and lumbar puncture for diagnostic purposes. The CSF levels of proinflammatory and anti-inflammatory cytokines were analyzed and compared with a group of 80 individuals with non-inflammatory and non-degenerative diseases. Behavioral and electrophysiological studies were carried out in control mice receiving intracerebral injection of IL-2 or vehicle. Behavior was also assessed in mice with experimental autoimmune encephalomyelitis (EAE), animal model of MS, reared in standard (sedentary group) or running wheel-equipped (exercise group) cages.In exercising MS patients, depression and anxiety were reduced compared to sedentary patients. The CSF levels of the interleukin-2 and 6 (IL-2, IL-6) were increased in MS patients compared with control individuals. In MS subjects exercise was associated with normalized CSF levels of IL-2. In EAE mice exercise started before disease onset reduced both behavioral alterations and striatal IL-2 expression. Notably, a causal role of IL-2 in mood disorders was shown. IL-2 administration in control healthy mice induced anxious- and depressive-like behaviors and impaired type-1 cannabinoid (CB1) receptor-mediated neurotransmission at GABAergic synapses, mimicking EAE-induced synaptic dysfunction.Our results indicate an immunomodulatory effect of exercise in MS patients, associated with reduced CSF expression of IL-2, which might result in reduced mood disorders. These data suggest that exercise in the early stages may act as a disease-modifying therapy in MS although further longitudinal studies are needed to clarify this issue.

Since the start of the SARS-CoV-2 pandemic, several treatment options have been proposed (e.g. steroids, heparin, antivirals and monoclonal antibodies). Remdesivir was the first antiviral approved for the treatment of COVID-19, even though controversial evidence exists concerning the efficacy. Therefore, we aimed to conduct a study to evaluate whether the use of remdesivir was associated with lower mortality in patients with COVID-19.We conducted a nested case-control study of a retrospective cohort collecting medical records of people with SARS-CoV-2 infection admitted in the infectious Disease Unit of Sassari University Hospital (S.C. Clinica di Malattie Infettive, AOU di Sassari, Italy), or in the Infectious Disease Unit of Foggia (AOU "Ospedali Riuniti" Foggia), between 1 July 2020 and 10 November 2021. The outcome considered was death; thus, we matched death (cases) to survivors (controls) by sex and age (1:1).We included in the study 342 patients, with 171 deaths (cases) and 171 survivors (controls). Remdesivir was administered to 60 people in the control group and to 18 people in the case group (35.1% vs. 10.5%,Our study showed lower mortality in people with SARS-CoV-2 infection treated with remdesivir.

Most patients with Post COVID Syndrome (PCS) present with a plethora of symptoms without clear evidence of organ dysfunction. A subset of them fulfills diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Symptom severity of ME/CFS correlates with natural regulatory autoantibody (AAB) levels targeting several G-protein coupled receptors (GPCR). In this exploratory study, we analyzed serum AAB levels against vaso- and immunoregulatory receptors, mostly GPCRs, in 80 PCS patients following mild-to-moderate COVID-19, with 40 of them fulfilling diagnostic criteria of ME/CFS. Healthy seronegative (n=38) and asymptomatic post COVID-19 controls (n=40) were also included in the study as control groups. We found lower levels for various AABs in PCS compared to at least one control group, accompanied by alterations in the correlations among AABs. Classification using random forest indicated AABs targeting ADRB2, STAB1, and ADRA2A as the strongest classifiers (AABs stratifying patients according to disease outcomes) of post COVID-19 outcomes. Several AABs correlated with symptom severity in PCS groups. Remarkably, severity of fatigue and vasomotor symptoms were associated with ADRB2 AAB levels in PCS/ME/CFS patients. Our study identified dysregulation of AAB against various receptors involved in the autonomous nervous system (ANS), vaso-, and immunoregulation and their correlation with symptom severity, pointing to their role in the pathogenesis of PCS.

Background: University students are known to have higher sleep disorders prevalence than the general population. Among them, nursing students are even more susceptible to sleep disorders. This study evaluates sleep disorders’ risk factors among nursing students and their potential association with symptoms and assesses whether night shifts affect sleep quality by increasing the prevalence of sleep disorders. Methods: A total of 202 nursing students were included; a self-administered questionnaire was used to collect data on sociodemographic and academic characteristics (i.e., gender, age, height, weight, and year of nursing program) and risk factors for sleep disorders (e.g., smoking, lack of physical activity, and coffee intake late in the evening). The survey included the General Health Questionnaire to assess perceived stress, the Sleep and Daytime Habits Questionnaire, and the Epworth Sleepiness Scale to assess sleep disorders symptoms. Results: A high level of perceived stress is associated with sleep disorders symptoms and with poor sleep quality. Daytime symptoms are also associated with smoking. Students who drink coffee late in the evening report fewer nighttime symptoms. Night shifts and their increasing number are not associated with sleep disorders symptoms. The perception of an unsatisfying academic performance is associated with daytime symptoms and poor sleep quality. Conclusions: Although night shifts seem to not affect sleep quality among nursing students, sleep disorders represent a critical issue in this population since sleep disorders symptoms may result in errors, accidents, or low academic performance.

BackgroundThe spread of COVID-19 has been characterized by unprecedented global lock-downs. Although, the extent of containment policies cannot be explained only through epidemic data. Previous studies already focused on the relationship between the economy and healthcare, focusing on the impact of diseases in countries with a precarious economic situation. However, the pandemic caused by SARS-CoV-2 drew most countries of the world into a precarious economic situation mostly caused by the global and local lock-downs policies.MethodsA discriminant analysis performed via partial least squares procedure was applied to evaluate the impact of economic and healthcare variables on the containment measures adopted by 39 countries. To collect the input variables (macroeconomic, healthcare, and medical services), we relied on official databases of international organizations, such as The World Bank and WHO.ResultsThe stringency lock-down policies could not only be influenced by the epidemical data, but also by previous features of the selected countries, such as economic and healthcare conditions.ConclusionsIndeed, economic and healthcare variables also contributed to shaping the implemented lock-down policies.

Aim: We recently proposed miR-142-3p as a molecular player in inflammatory synaptopathy, a new pathogenic hallmark of multiple sclerosis (MS) and of its mouse model experimental autoimmune encephalomyelitis (EAE), that leads to neuronal loss independently of demyelination. MiR-142-3p seems to be unique among potential biomarker candidates in MS, since it is an inflammatory miRNA playing a dual role in the immune and central nervous systems. Here, we aimed to verify the impact of miR-142-3p circulating in the cerebrospinal fluid (CSF) of MS patients on clinical parameters, neuronal excitability and its potential interaction with disease modifying therapies (DMTs). Methods and Results: In a cohort of 151 MS patients, we found positive correlations between CSF miR-142-3p levels and clinical progression, IL-1β signalling as well as synaptic excitability measured by transcranial magnetic stimulation. Furthermore, therapy response of patients with ‘low miR-142-3p’ to dimethyl fumarate (DMF), an established disease-modifying treatment (DMT), was superior to that of patients with ‘high miR-142-3p’ levels. Accordingly, the EAE clinical course of heterozygous miR-142 mice was ameliorated by peripheral DMF treatment with a greater impact relative to their wild type littermates. In addition, a central protective effect of this drug was observed following intracerebroventricular and ex vivo acute treatments of EAE wild type mice, showing a rescue of miR-142-3p-dependent glutamatergic alterations. By means of electrophysiology, molecular and biochemical analysis, we suggest miR-142-3p as a molecular target of DMF. Conclusion: MiR-142-3p is a novel and potential negative prognostic CSF marker of MS and a promising tool for identifying personalised therapies.

BACKGROUND: The aim of this study was to estimate the prevalence of self-reported chemosensory dysfunction in a study cohort of subjects who developed a mild-to-moderate coronavirus disease 2019 (COVID-19) in the period from January 17, 2022, to February 4, 2022 (Omicron proxy period) and compared that with a historical series of patients testing positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection between March and April, 2020 (comparator period). METHODS: Prospective study based on the 22-item Sino-Nasal Outcome Tool (SNOT-22), item "sense of smell or taste" and additional outcomes. RESULTS: Patients' characteristics and clinical presentations of COVID-19 were evaluated and compared in 779 patients, 338 of the study cohort and 441 of the historical series. The prevalence of self-reported chemosensory dysfunction during the proxy Omicron period (32.5%; 95% confidence interval [CI], 27.6-37.8) was significantly lower from that during the comparator period (66.9%; 95% CI, 62.3-71.3) (p < 0.001). Nearly one-quarter of patients (24.6%; 95% CI, 20.1-29.5) reported an altered sense of smell during the proxy Omicron period compared to 62.6% (95% CI, 57.9-67.1) during the comparator period (p < 0.001). Similarly, the prevalence of an altered sense of taste dropped to 26.9% (95% CI, 22.3-32.0) during the proxy Omicron period from 57.4% (95% CI, 52.6-62.0) during the comparator period (p < 0.001). The severity of chemosensory dysfunction was lower in the proxy Omicron period compared to the comparator period (p < 0.001). CONCLUSION: The prevalence and the severity of COVID-19-associated smell and taste dysfunction has dropped significantly with the advent of the Omicron variant but it still remains above 30%.

The aim of the present study was to compare the efficacy and durability of treatment switch to two-drug (2DR) vs. three-drug (3DR) integrase inhibitor (InSTI)-based regimens in a real-life setting.Within the ODOACRE cohort, we selected adult patients with HIV RNA 50 copies/mL switching to an InSTI-based 2DR or 3DR. Survival analyses were performed to estimate the probability of virological failure (VF, defined as one HIV RNA 1000 copies/mL or two consecutive HIV RNA 50 copies/mL) and treatment discontinuation (TD, defined as any modification, intensification or interruption of the regimen), and to evaluate their predictors.Overall, 1666 patients were included, of whom 1334 (80%) were treated with a 3DR (19.9%, 25.0% and 55.1% elvitegravir-, raltegravir- and dolutegravir-based, respectively) and 332 (20%) with a 2DR (79.2% dolutegravir + lamivudine and 20.8% dolutegravir + rilpivirine). Over a median (interquartile range) follow-up of 100 (52-150) weeks, 52 (3.1%) patients experienced VF with an incidence of 1.5/100 person-year of follow-up (PYFU). The estimated 96-week probability of VF was similar for the 2DR and 3DR groups (2.3% vs. 2.8%, P = 0.53), but it was higher for elvitegravir (4.9%) and raltegravir (5.0%) than for dolutegravir (1.5%) (P = 0.04). Four hundred (24%) patients discontinued their InSTI-based regimen, with an incidence of 11.3/100 PYFU. At 96 weeks, 3DRs showed a higher probability of TD for any reason (20.6% vs. 11.2%, P 0.001) and TD for toxicity (9.0% vs. 6.6%, P = 0.02) when compared with 2DRs. A higher risk of TD for central nervous system toxicity was observed for dolutegravir than for elvitegravir and raltegravir (4.0% vs. 2.5% vs. 0.6%, P = 0.005).In virologically suppressed HIV-infected patients, 2DRs showed an efficacy similar to 3DRs but with better tolerability.

Extra-osseous Ewing sarcoma (ES) is a rare and aggressive malignant tumor found in a variety of organs. Primary ES of the thyroid is exceedingly rare and few cases have been documented to date. We describe the case of a 54-year old woman with a history of breast carcinoma in whom a unique hypermetabolic left thyroid nodule was identified during a follow-up PET-CT scan. An ultrasound examination showed a hypoechogenic nodule of 3.7 cm. A cytological diagnosis of poorly differentiated thyroid carcinoma was made, and a total thyroidectomy was performed. The surgical specimen revealed a poorly differentiated neoplasm composed of medium-sized cells with scant cytoplasm, expressing pancytokeratin, CD99 and NKX2.2 but lacking p63 and p40 expression. Molecular analysis revealed a EWSR1-FLI1 fusion transcript supporting the diagnosis of a primary extra-osseous ES of the thyroid. The patient received adjuvant chemotherapy and has no evidence of recurrent disease.

ObjectiveTo investigate the age-dependent impact of traditional stroke risk factors on the occurrence of intracerebral haemorrhage (ICH).MethodsWe performed a case–control analysis, comparing consecutive patients with ICH with age-matched and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy) between 2002 and 2014 by multivariable logistic regression model within subgroups stratified by age quartiles (Q1–Q4).ResultsWe analysed 3492 patients and 3492 controls. The impact of untreated hypertension on the risk of ICH was higher in the lower than in the upper age quartile (OR 11.64, 95% CI 7.68 to 17.63 in Q1 vs OR 6.05, 95% CI 3.09 to 11.85 in Q4 with intermediate ORs in Q2 and Q3), while the opposite trend was observed for untreated hypercholesterolaemia (OR 0.63, 95% CI 0.45 to 0.97 in Q1 vs OR 0.36, 95% CI 0.26 to 0.56 in Q4 with intermediate ORs in Q2 and Q3). The effect of untreated diabetes and excessive alcohol intake was detected only in the older age group (OR 3.63, 95% CI 1.22 to 10.73, and OR 1.69, 95% CI 1.13 to 2.51, respectively).ConclusionsOur findings provide evidence of age-dependent differences in the effects of susceptibility factors on the risk of ICH.

Weak grip strength is a strong predictor of multiple adverse health outcomes and an integral diagnostic component of sarcopenia. However, the limited availability of normative data for certain populations impedes the interpretation of grip performance across adulthood. This study aimed to establish normative data and low grip strength thresholds in a large adult population, and to examine associations between grip strength and clinically relevant health variables. A total of 9431 adults aged between 18 and 92 years participated in this study (mean age: 44.8 ± 13.4 years; 57% females). Grip strength, body composition, and cardiorespiratory (CR) fitness were assessed using hand dynamometry, dual-energy x-ray absorptiometry and physical work capacity tests, respectively. Low grip strength was established according to criteria of the European Working Group on Sarcopenia in Older People. Normative data and t-scores, stratified by sex and age groups, are presented. Grip performance was associated with lean mass, skeletal muscle index (SMI), fat mass, CR fitness, bone mineral density (BMD), android/gynoid ratio, disease prevalence and physical activity levels (all p p p = 0.001), and higher disease prevalence (p

Introduction: Our aim was to evaluate a screening program, with active case-finding and treatment for active tuberculosis (TB), latent tuberculosis infection (LTBI), blood-borne viruses (BBV), and sexually transmitted diseases (STDs) among refugees living in facility centers. Methodology: We collected data on refugees arriving to our attention in migrant centers in Sardinia, Italy. Socio-demographical data, anamnesis, and clinical features were collected. TST Mantoux was conducted, and X-ray chest (XRC) was performed if TST was positive. Blood-borne virus screening was proposed to all patients. Screening for STDs was offered according to guidelines, anamnesis, and physical examination. Results: Eighty-one patients were included. Seventy (86.4%) were male, and the mean age was 24.8±5.7 years. Thirty-three (40.7%) had scabies. Overall, 40/81 (49.4%) had a positive TST Mantoux. One (2.5%) was hospitalized and died for multi-drug-resistant TB. One (2.5%) patient had intestinal-TB. 52/81 (64.2%) refused HIV screening, whereas no positivity was found among tested migrants. Sixty-two (76.5%) accepted HCV screening, and one (1.6%) had a positive test. Fifty-eight (71.6%%) accepted HBV testing, and 29 (50%) of them had positive serology. Ten (12.3%) patients had anal or genital lesions due to syphilis, Molluscum contagiosum, and HPV in 7 (70%), 2 (20%), and one (10%) case, respectively. Conclusions: Infectious diseases control and prevention are a key strategy among refugees. The stay in a migrant center is an extraordinary occasion for healthcare provision. This condition could allow a broad screening program in which quick BBV screening tests could be a good method to implement uptake. More information and educational programs would allow a higher understanding and acceptance of HIV screening.

Background During the intensive care units’ (ICUs) reorganization that was forced by the COVID-19 emergency, attention to traditional infection control measures may have been reduced. Nevertheless, evidence on the effect of the COVID-19 pandemic on healthcare-associated infections (HAIs) is still limited and mixed. In this study, we estimated the pandemic impact on HAI incidence and investigated the HAI type occurring in COVID-19 patients. Methods Patients admitted to the main ICU of the Umberto I teaching hospital of Rome from March 1st and April 4th 2020 were compared with patients hospitalized in 2019. We assessed the association of risk factors and time-to-first event through multivariable Fine and Grey’s regression models, that consider the competitive risk of death on the development of HAI (Model 1) or device related-HAI (dr-HAI, Model 2) and provide estimates of the sub-distribution hazard ratio (SHR) and its associated confidence interval (CI). A subgroup analysis was performed on the 2020 cohort. Results Data from 104 patients were retrieved. Overall, 59 HAIs were recorded, 32 of which occurred in the COVID-19 group. Patients admitted in 2020 were found to be positively associated with both HAI and dr-HAI onset (SHR: 2.66, 95% CI 1.31–5.38, and SHR: 10.0, 95% CI 1.84–54.41, respectively). Despite being not confirmed at the multivariable analysis, a greater proportion of dr-HAIs seemed to occur in COVID-19 patients, especially ventilator-associated pneumonia, and catheter-related urinary tract infections. Conclusions We observed an increase in the incidence of patients with HAIs, especially dr-HAIs, mainly sustained by COVID-19 patients. A greater susceptibility of these patients to device-related infections was hypothesized, but further studies are needed.

Introduction: Ethnical segregation and migration influence sexual health. Differences in sexual networks and the risk of sexually transmitted diseases (STDs) between racial/ethnic minorities and the native population have been described in the literature. Methodology: We collected data on sexual behavior and physical examination. Basing on CDC 2015 guidelines on STDs, anamnesis, and clinical features, screening for HIV/STDs was proposed. Results: We enrolled 209 migrants, the median age was 32.5 (26-40) years, and 146 (69.9%) were male. The most represented nationalities were Nigerian, Senegalese, and Somali, with 85 (40.7%), 68 (32.5%), and 16 (7.7%) people, respectively. Twenty-two (10.5%) patients referred perianal/genital lesions, 6 (2.9%) abdominal/pelvic discomfort, and 183 (87.6%) were asymptomatic. Almost all symptomatic patients accepted the tests. 52/183 (28.4%) asymptomatic subjects accepted the tests, and only 24/52(46.2%) performed them. Among symptomatic patients were 6 (24%) HBsAg positivities and one (4%) HCV infection. Four (16%) people had latent syphilis; in 12 (48%) people, HPV-related genital warts were present, 7 (28%) people had Molluscum contagiosum, and 6 (24%) women had pelvic inflammatory diseases. Among patients referring no symptoms, there were 10 (41.7%) HBsAg positivities, one (4.2%) HIV infection, four (16.7%) latent syphilis, one (4.2%) HPV-related genital infection, and one (4.2%) PID. Being Nigerian and having symptoms were associated with a more high acceptance of the STDs test. Having a high-risk behavior was significantly associated with the development of at least one STD. Conclusions: migrants have high-risk sexual behavior. Despite this, they have a low perception of HIV/STDs risk and healthcare needs. Particular attention should be given to improve access to HIV/STDs services that provide screening and treatment and increase the perception of healthcare needs.

Background and Purpose: We designed SITS (Safe Implementation of Treatment in Stroke) Open to determine benefit and safety of thrombectomy in clinical practice for large artery occlusion stroke, using selected stent retrievers plus standard care versus standard care alone. Methods: SITS Open was a prospective, open, blinded evaluation, international, multicenter, controlled, nonrandomized registry study. Centers lacking access to thrombectomy contributed controls. Primary end point was categorical shift in modified Rankin Scale score at 3 months in the per protocol (PP) population. Principal secondary outcomes were symptomatic intracranial hemorrhage, functional independency (modified Rankin Scale score 0–2) and death at 3 months. Patients independently evaluated by video-recorded modified Rankin Scale interviews blinded to treatment or center identity by central core laboratory were regarded as PP population. Propensity score matching with covariate adjusted analysis was performed. Results: During 2014 to 2017, 293 patients (257 thrombectomy, 36 control) from 26 centers in 10 countries fulfilled intention-to-treat and 200 (170 thrombectomy, 30 control) PP criteria; enrollment of controls was limited by rapid uptake of thrombectomy. In PP analysis, median age was 71 versus 71 years, and baseline National Institutes of Health Stroke Scale 17 versus 17 in the thrombectomy and control arms, respectively. The propensity score matching analysis for PP showed a significant shift for modified Rankin Scale at 3 months favoring the thrombectomy group (odds ratio, 3.8 [95% CI, 1.61–8.95]; P =0.002). Regarding safety, there were 4 cases of symptomatic intracranial hemorrhage in the thrombectomy group (2.4%) and none in the control group. Conclusions: In clinical practice, thrombectomy for patients with large artery occlusion stroke is superior to standard of care in our study. Registration: URL: https://www.clinicaltrials.gov . Unique Identifier: NCT02326428.

This study evaluates the frequency and causes of dolutegravir (DTG) discontinuation along 5 years of follow-up, in both antiretroviral treatment (ART)-naive and experienced people living with HIV (PLWH). This is a prospective multi-center cohort study enrolling PLWH on DTG from July 2014 until November 2020. DTG-durability was investigated using the Kaplan-Meier survival curve. The Cox proportional-hazards model was used for estimating the hazard ratio (HR) of DTG discontinuation for any cause, and for adverse events (AEs). Nine hundred sixty-three PLWH were included, 25.3% were women and 28.0% were ART-naive. Discontinuations for any causes were 10.1 [95% confidence interval (95% CI) 8.9-11.5] per 100 person-years, similar in most regimens, with the apparent exception of tenofovir alafenamide/emtricitabine+DTG (p

HCV infection has been hypothesized as a contributor of poor CD4+ recovery in patients living with HIV (PLWHIV). Aim of this study was to evaluate CD4+, CD8+ cells and CD4/CD8 ratio trends before and after HCV treatment with direct acting agents (DAA) in PLWHIV. HIV/HCV patients enrolled in ICONA and HepaICONA cohorts with HIV-RNA≤50copies/ml who achieved a sustained viral response after DAA treatment were studied. A linear regression model was used to investigate CD4+, CD8+ and CD4/CD8 changes 12months before and after DAA treatment. A total of 939 HIV/HCV patients were included, 225 (24.0%) female, median age: 53years (IQR 50–56). At DAA initiation, CD4+ T cell count was 12.5kPa. Trends of CD4+ and CD4/CD8 ratio were similar before and after DAA in all study populations (CD4+ change +17.6 cells/mm3 (95%CI −33.5; 69.4, p=0.494); CD4/CD8 change 0.013 (95%CI −0.061; 0.036, p=0.611). However, patients treated with ribavirin (RBV)-free DAA showed a significant decrease in CD8+ cells (−204.3 cells/mm3, 95%CI −375.0;-33.4, p=0.019), while patients treated with RBV experienced CD8+ cell increase (+141.2 cells/mm3, 95%CI 40.3; 242.1, p=0.006). In conclusion, HCV eradication following DAA treatment does not seem to have an impact on CD4+ T cell recovery in PLWHIV. However, a fast decline of CD8+T cells has been observed in patients treated without RBV, suggesting a favourable effect of HCV clearance on the general state of immune activation.

The hyper-inflammatory response, also known as multisystem inflammatory syndrome in children (MIS-C), represents a major concern in children with SARS-CoV-2 infection. We report bone marrow features of three patients with MIS-C who were diagnosed during the first wave of the SARS-CoV-2 pandemic. A bone marrow evaluation was performed at onset of the inflammatory condition in order to exclude secondary hemophagocytic lymphohistiocytosis (sHLH). The bone marrows of the patients presented common features: the erythroid and megakaryocytic lineages were prominently affected and hemophagocytosis was moderately increased, differently than observed in sHLH. Megakaryocytopoiesis was increased, representing a peculiar feature of MIS-C differing from sHLH. SARS-CoV-2 RT-PCR and viral panel were studied in bone marrow aspiration samples. MIS-C is a rare complication of SARS-CoV-2 infections in children. An immuno-dysregulation considering both innate and adaptive immunity together with vascular inflammation and endothelial dysfunction play a major role. Our observations, although limited due to the small sample size, suggest that there are unique features in the bone marrow of patients with MIS-C that are likely secondary to immuno-dysregulation, and there are notable differences in bone marrow features compared to those reported in sHLH.

The benefit of vaccination for preventing reinfection among individuals who have been previously infected with SARS-CoV-2 is largely unknown.To obtain population-based estimates of the probability of SARS-CoV-2 reinfection and the effectiveness associated with vaccination after recovery from COVID-19.This cohort study used Rhode Island statewide surveillance data from March 1, 2020, to December 9, 2021, on COVID-19 vaccinations, laboratory-confirmed cases, hospitalizations, and fatalities to conduct a population-based, retrospective study during periods when wild type, Alpha, and Delta strains of SARS-CoV-2 were predominant. Participants included Rhode Island residents aged 12 years and older who were previously diagnosed with COVID-19 and unvaccinated at the time of first infection, stratified into 3 subpopulations: long-term congregate care (LTCC) residents, LTCC employees, and the general population (ie, individuals not associated with congregate settings). Data were analyzed from October 2021 to January 2022.Completion of the primary vaccination series, defined as 14 days after the second dose of an mRNA vaccine or 1 dose of vector virus vaccine.The main outcome was SARS-CoV-2 reinfection, defined as a laboratory-confirmed positive result on a polymerase chain reaction (PCR) or antigen test at least 90 days after the first laboratory-confirmed positive result on a PCR or antigen test.Overall, 3124 LTCC residents (median [IQR] age, 81 [71-89]; 1675 [53.6%] females), 2877 LTCC employees (median [IQR] age, 41 [30-53]; 2186 [76.0%] females), and 94 516 members of the general population (median [IQR] age, 35 [24-52] years; 45 030 [47.6%] females) met eligibility criteria. Probability of reinfection at 9 months for those who remained unvaccinated after recovery from prior COVID-19 was 13.0% (95% CI, 12.0%-14.0%) among LTCC residents, 10.0% (95% CI, 8.8%-11.5%) among LTCC employees, and 1.9% (95% CI, 1.8%-2.0%) among the general population. Completion of the primary vaccination series after infection was associated with 49% (95% CI, 27%-65%) protection among LTCC residents, 47% (95% CI, 19%-65%) protection among LTCC employees, and 62% (95% CI, 56%-68%) protection in the general population against reinfection, adjusting for potential sociodemographic and clinical confounders and temporal variation in infection rates.These findings suggest that risk of SARS-CoV-2 reinfection after recovery from COVID-19 was relatively high among individuals who remained unvaccinated. Vaccination after recovery from COVID-19 was associated with reducing risk of reinfection by approximately half.

Background Hepatitis C virus (HCV) infection is more frequent among incarcerated people than in general population. In the DAAs era, the short schedules and the low risk of adverse reactions, increased the number of HCV treatments. However, the most part of literature reports lack of incarcerated women inclusion in studies on field. Our aim is to assess the screening execution, HCV prevalence, and DAAs treatment among incarcerated women. A focused insight on quick vs standard diagnosis and staging approach will be also provided. Methods Incarcerated women from 4 Italian regions’ penitentiary institutes were included. HCV screening was executed with HCV saliva test (QuickOral Test®) or phlebotomy. Stage of liver fibrosis was evaluated with FIB-4 value or fibroscan®, based on physicians’ decision. Treatment prescription followed national protocols. Results We included 156 women, 89 (57%) were Italian, mean age was 41 ± 10 years, and 28 (17.9%) were people who inject drugs (PWIDs). Overall, the HCV seroprevalence was 20.5%. Being PWID and on opioid substitution therapy (OST) were significantly associated with serological status (p-value ® on SVR12, FIB-4 use showed higher performance for retainment in treatment during prison staying (p = 0.015), while the use of quick saliva test had no influence on the outcome (p = 0.22). Conclusion HCV seroprevalence and active infections are very high among incarcerated women. More tailored interventions should be focused on HCV diagnosis and treatment in female prison population. The use of quick staging methods (FIB-4) is useful to increase SVR12 achievement without delays caused by the fibroscan® awaiting.

BackgroundWorldwide, concerns rise on how COVID-19 pandemic impacted heavily on women, even on those belonging to the scientific community. The Italian scientific production regarding the COVID-19 throughout the first months of the health emergency could help to understand the heft of female researchers in this unique period.ObjectivesThis study aims to investigate the gender gap in the scientific production on COVID-19 in Italy during the first months of the pandemic.MethodsA systematic search of the literature was conducted and, for each included study, first and last author's gender, type of study, number of co-authors, type of affiliation, journal's Impact Factor (IF) and specialization were extracted. Descriptive and univariate analyses were performed.Results22.2% of the articles were signed by a woman as first author, 18.1% as last authors. Female authorship was less frequent than male authorship regardless of the type of study, number of co-authors, type of affiliation and field of specialization.ConclusionThis analysis reveal a low prevalence of studies with a female first or last author and suggests that the low share of female authors publishing on COVID-19 during the considered timespan is a transversal issue throughout the Italian medical field.

Since the start of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, several treatments have been proposed to cure coronavirus disease 2019 (COVID-19) and prevent it. Molnupiravir is a ribonucleoside prodrug of N-hydroxycytidine with an in vitro and in vivo activity against SARS-CoV-2. We conducted a retrospective cohort study that included all people treated with molnupiravir between January 10, 2022, and March 31, 2022, at the University Hospital of Sassari. Molnupiravir was prescribed, according to the Italian Agency of Drug indications, to patients with recent symptom onset (≤5 days), no need for oxygen supplementation, and with a high risk of disease progression for the presence of chronic diseases. We included 192 people with a mean age of 70.4 ± 15.4 years, with 144 (75%) patients over 60 years. During the follow-up, 20 (10.4%) patients showed a disease progression. At the multivariate analysis, older age, having neurological disease, having dyspnea at the onset of the symptoms, and acquiring SARS-CoV-2 infection during hospital admission were associated with an increased risk of progression. In contrast, an early start of treatment was associated with a reduced risk of disease progression. Molnupiravir was also extremely safe since 13 (6.8%) adverse events were reported, with only one interruption. Our study shows that monlupiravir confirmed its efficacy and safety in a real-life cohort that included a high percentage of elderly people with a high comorbidity burden.

Osteomyelitis is a relatively understudied disease with no standardized and evidence-based approach to treatment. We aimed to evaluate a cohort of patients with osteomyelitis, comparing the outcomes between intravenous (IV) and oral treatment.We performed an observational retrospective study on osteomyelitis cases in adult patients seen for care between 2017 and 2019. We collected information on patient characteristics, microbiological etiology, infection treatment, and outcome. In addition, we divided osteomyelitis cases by antibiotic regimens [oral (OTG) vs. intravenous±oral (ITG)] and therapy durations to evaluate outcomes differences.A total of 235 episodes of osteomyelitis were evaluated, with a higher prevalence in male gender. Staphylococci, especially S. aureus, were the most common strains. Out of the 235 evaluated episodes, we selected 142 cases. Of these, 75 were treated with OTG and 67 with ITG. Gram-positive bacteria were the most frequent aetiological agents, with 81 isolates (61.8%). Full recovery was observed in 79 (55.6%) cases; of these, 36 (53.7%) were in the ITG and 43 (57.3%) in the OTG (p = 0.666). At the logistic regression, a polymicrobial infection [OR 4.16 (95%CI 1.28-13.4), p = 0.017] and a less than six weeks treatment duration [OR 4.24 (95%CI 1.38-5.43) p = 0.004] were significantly associated with a higher risk of treatment failure.Our study suggests that oral treatment efficacy is comparable to ITG therapy for osteomyelitis, confirming the most recent evidence suggesting that oral therapy is non-inferior to intravenous therapy to treat osteomyelitis.