A phase II trial proposal of total neoadjuvant treatment with primary chemotherapy, stereotactic body radiation therapy, and intraoperative radiation therapy in borderline resectable pancreatic adenocarcinoma.

BACKGROUND: The current management guidelines recommend that patients with borderline resectable pancreatic adenocarcinoma (BRPC) should initially receive neoadjuvant chemotherapy. The addition of advanced radiation therapy modalities, including stereotactic body radiation therapy (SBRT) and intraoperative radiation therapy (IORT), could result in a more effective neoadjuvant strategy, with higher rates of margin-free resections and improved survival outcomes. METHODS/DESIGN: In this single-center, single-arm, intention-to-treat, phase II trial newly diagnosed BRPC will receive a "total neoadjuvant" therapy with FOLFIRINOX (5-fluorouracil, irinotecan and oxaliplatin) and hypofractionated SBRT (5 fractions, total dose of 30 Gy with simultaneous integrated boost of 50 Gy on tumor-vessel interface). Following surgical exploration or resection, IORT will be also delivered (10 Gy). The primary endpoint is 3-year survival. Secondary endpoints include completion of neoadjuvant treatment, resection rate, acute and late toxicities, and progression-free survival. In the subset of patients undergoing resection, per-protocol analysis of disease-free and disease-specific survival will be performed. The estimated sample size is 100 patients over a 36-month period. The trial is currently recruiting. TRIAL REGISTRATION: NCT04090463 at clinicaltrials.gov.

Evaluation of three immunochromatographic tests in COVID-19 serologic diagnosis and their clinical usefulness.

Results of three rapid immunochromatographic tests (ICTs) were compared with those obtained with two automated immunoassays for evaluation of their usefulness. One hundred fifty-nine patients and 67 healthy volunteers were included. Different assays demonstrate 41-45% of diagnostic sensitivities and 91-98% of specificities, with substantial agreement (89.3-91.2%), but a high percentage of weak positive results (13-22%) was observed with ICTs. ICTs performances were comparable to those of automated immunoassays. ICTs could have a role as screening approach due to their easy usability. Subjective interpretation, significant rate of uncertain results, uncertainty on viral antigens source are undoubtedly drawbacks.

Cost-effectiveness and quality of life analysis of laparoscopic and robotic distal pancreatectomy: a propensity score-matched study.

BACKGROUND: This study analyzed the Quality of Life (QoL) and cost-effectiveness of laparoscopic (LDP) versus robotic distal pancreatectomy (RDP). METHOD: All patients who underwent LDP or RDP from 2011 to 2017 and with a minimum postoperative follow-up of 12 months were included in the study. To minimize bias, a propensity score-matched analysis (1:2) was performed. Two different questionnaires (EORTC QLQ-C30 and EQ-5D) were completed by the patients. The mean differential cost and mean differential Quality Adjusted Life Years (QALY) were calculated and plotted on a cost-utility plane. RESULTS: The study population consisted of 152 patients. After having applied the propensity score matching, the final population included 103 patients divided into RDP group (n = 37, 36%) and LDP (n = 66, 64%). No differences were found between groups regarding the baseline, intraoperative, postoperative, and pathological variables (p > 0.05). The QoL analysis showed a significant improvement in the RDP group on the postoperative social function, nausea, vomiting, and financial status (p = 0.010, p = 0.050, and p = 0.030, respectively). As expected, the crude costs analysis confirmed that RDP was more expensive than LDP (12,053 Euros vs. 5519 Euros, p < 0.001). However, the robotic approach had a higher probability of being more cost-effective than the laparoscopic procedure when a willingness to pay of more than 4800 Euros/QALY was accepted. CONCLUSION: RDP was associated with QoL improvement in specific domains. Crude costs were higher relative to LDP. Cost-effectiveness threshold resulted to be 4800 euros/QALY. The increasing worldwide diffusion of the robotic technology, with easier access and possible cost reduction, could increase the sustainability of this procedure.

Carotid Endarterectomy with Modified Eversion Technique: Results of a Single Center.

BACKGROUND: Carotid endarterectomy (CEA) has a wide range of approaches based on personal expertise and preference. We evaluated our outcome with CEA with modified eversion technique (meCEA) under local anesthesia and whether the surgeon's experience could influence it. METHODS: at our Institution, 837 patients underwent CEA across 8 years. Although the surgical technique was standardized, 2 groups were considered further: meCEA performed by a single Senior Operator (Group A) and meCEA performed by 4 young Consultants (Group B). RESULTS: A selective shunting policy was needed in 5.1%, together with general anesthesia. Overall operative time was 63.9 ± 15.1 minutes (61.4 ± 12.5 and 66 ± 16.9 minutes in Group A and Group B respectively; P < 0.001) and cross-clamp time 19.3 ± 2.9 minutes (19.0 ± 3.2 vs. 19.5 ± 2.8, P = 0.009). At 30 days, 0.7% TIA and 0.8% strokes were recorded. No differences (p = N.S.) between the 2 study groups in terms of postoperative neurological complications, with postoperative ipsilateral strokes always < 1%. At a median imaging follow-up of 22.5 months, the overall percentage of restenosis was 3.7%, with no difference between the 2 groups (P = 0.954). Twenty-two patients (2.6%) underwent reintervention for significant restenosis, and none of them had an ipsilateral stroke or TIA. Freedom from reintervention for restenosis at 24 months was 97.9% in Group A and 95.9% in Group B, with no between-group difference (P = 0.14). At the median survival follow-up of 37 months, the overall survival rate at 24 months was 97.9%in Group A, and 97.9% in Group B, with no between-group difference (P = 0.070). CONCLUSIONS: In our experience, CEA with a modified technique is safe and achieves comparable outcomes to those of other established techniques. The reported short cross-clamp time, also in less experienced hands, is an additional strength.

Prognostic Impact of Preoperative Nutritional Risk in Patients Who Undergo Surgery for Pancreatic Adenocarcinoma.

BACKGROUND: Nutritional derangements are common hallmarks of pancreatic cancer (PC). Their early detection and management are usually overlooked in routine practice. This study aimed to explore preoperative nutritional status and its prognostic value in patients undergoing surgery for PC. METHODS: Data from 73 patients who underwent surgery for PC from November 2015 to January 2018 at the General and Pancreatic Surgery Unit, The Pancreas Institute, University Hospital of Verona Hospital, Verona, Italy, were retrospectively evaluated. The Nutritional Risk Screening (NRS)-2002 was used to evaluate the preoperative nutritional risk. Body composition was assessed using bioimpedance vectorial analysis (BIVA) on the day prior to surgery. The effect of clinical, pathological, and nutritional characteristics on overall survival (OS) was investigated using a Cox and logistic regression model. Kaplan-Meier curves were compared using the log-rank test. RESULTS: Most patients (80.8%) were at preoperative risk of malnutrition (NRS-2002 ≥ 3) despite a mean BMI of 24.1 kg/m2(± 4.3). Twenty-four patients (32.9%) received neoadjuvant therapy prior to surgery. Preoperative NRS-2002 was significantly higher in this subset of patients (p = 0.026), with a significant difference by chemotherapy regimens (in favor of FOLFIRINOX, p = 0.035). In a multivariate analysis, the only independent prognostic factor for OS was the NRS-2002 score (HR 5.24, p = 0.013). Particularly, the likelihood of 2-year survival was higher in NRS < 3 (p = 0.009). CONCLUSIONS: Our analysis confirms that preoperative malnutrition has a detrimental impact on OS in PC patients undergoing radical surgery for PC. Careful preoperative nutritional evaluation of PC patients should be mandatory, especially in those who are candidates for neoadjuvant therapy.

Psychological and social interventions for the prevention of mental disorders in people living in low- and middle-income countries affected by humanitarian crises.

BACKGROUND: People living in 'humanitarian settings' in low- and middle-income countries (LMICs) are exposed to a constellation of physical and psychological stressors that make them vulnerable to developing mental disorders. A range of psychological and social interventions have been implemented with the aim to prevent the onset of mental disorders and/or lower psychological distress in populations at risk, and it is not known whether interventions are effective. OBJECTIVES: To compare the efficacy and acceptability of psychological and social interventions versus control conditions (wait list, treatment as usual, attention placebo, psychological placebo, or no treatment) aimed at preventing the onset of non-psychotic mental disorders in people living in LMICs affected by humanitarian crises. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMD-CTR), the Cochrane Drugs and Alcohol Review Group (CDAG) Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), Embase (OVID), PsycINFO (OVID), and ProQuest PILOTS database with results incorporated from searches to February 2020. We also searched the World Health Organization's (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov to identify unpublished or ongoing studies. We checked the reference lists of relevant studies and reviews. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing psychological and social interventions versus control conditions to prevent the onset of mental disorders in adults and children living in LMICs affected by humanitarian crises. We excluded studies that enrolled participants based on a positive diagnosis of mental disorder (or based on a proxy of scoring above a cut-off score on a screening measure). DATA COLLECTION AND ANALYSIS: We calculated standardised mean differences for continuous outcomes and risk ratios for dichotomous data, using a random-effects model. We analysed data at endpoint (zero to four weeks after therapy) and at medium term (one to four months after intervention). No data were available at long term (six months or longer). We used GRADE to assess the quality of evidence. MAIN RESULTS: In the present review we included seven RCTs with a total of 2398 participants, coming from both children/adolescents (five RCTs), and adults (two RCTs). Together, the seven RCTs compared six different psychosocial interventions against a control comparator (waiting list in all studies). All the interventions were delivered by paraprofessionals and, with the exception of one study, delivered at a group level. None of the included studies provided data on the efficacy of interventions to prevent the onset of mental disorders (incidence). For the primary outcome of acceptability, there may be no evidence of a difference between psychological and social interventions and control at endpoint for children and adolescents (RR 0.93, 95% CI 0.78 to 1.10; 5 studies, 1372 participants; low-quality evidence) or adults (RR 0.96, 95% CI 0.61 to 1.50; 2 studies, 767 participants; very low quality evidence). No information on adverse events related to the interventions was available. For children's and adolescents' secondary outcomes of prevention interventions, there may be no evidence of a difference between psychological and social intervention groups and control groups for reducing PTSD symptoms (standardised mean difference (SMD) -0.16, 95% CI -0.50 to 0.18; 3 studies, 590 participants; very low quality evidence), depressive symptoms (SMD -0.01, 95% CI -0.29 to 0.31; 4 RCTs, 746 participants; very low quality evidence) and anxiety symptoms (SMD 0.11, 95% CI -0.09 to 0.31; 3 studies, 632 participants; very low quality evidence) at study endpoint. In adults' secondary outcomes of prevention interventions, psychological counselling may be effective for reducing depressive symptoms (MD -7.50, 95% CI -9.19 to -5.81; 1 study, 258 participants; very low quality evidence) and anxiety symptoms (MD -6.10, 95% CI -7.57 to -4.63; 1 study, 258 participants; very low quality evidence) at endpoint. No data were available for PTSD symptoms in the adult population. Owing to the small number of RCTs included in the present review, it was not possible to carry out neither sensitivity nor subgroup analyses. AUTHORS' CONCLUSIONS: Of the seven prevention studies included in this review, none assessed whether prevention interventions reduced the incidence of mental disorders and there may be no evidence for any differences in acceptability. Additionally, for both child and adolescent populations and adult populations, a very small number of RCTs with low quality evidence on the review's secondary outcomes (changes in symptomatology at endpoint) did not suggest any beneficial effect for the studied prevention interventions. Confidence in the findings is hampered by the scarcity of prevention studies eligible for inclusion in the review, by risk of bias in the studies, and by substantial levels of heterogeneity. Moreover, it is possible that random error had a role in distorting results, and that a more thorough picture of the efficacy of prevention interventions will be provided by future studies. For this reason, prevention studies are urgently needed to assess the impact of interventions on the incidence of mental disorders in children and adults, with extended periods of follow-up.

Maternal mental health and reproductive outcomes: a scoping review of the current literature.

PURPOSE: Current data show that maternal mental conditions affect about 10% of pregnant women worldwide. Assessing timing and patterns of mental health illness, therefore, is critical to ensure the wellbeing of the mother, the new-born and the whole family. The aim of this review is to summarize the latest evidence linking maternal mental disorders and adverse reproductive outcomes. METHODS: Following the PRISMA guidelines for systematic reviews, a literature search was conducted to ascertain the possible impact of mental health conditions on reproductive outcomes before and during pregnancy. The comprehensive strategy included cohort studies, randomised controlled trials and literature reviews on women with Primary Maternal Mental Illness (PMMI) and Secondary Maternal Mental Illness (SMMI) considering periconceptional, obstetric and foetal-neonatal outcomes. PubMed, WoS, CINAHL and Google scholar were used for the search. Cross-referencing in bibliographies of the selected papers ensured wider study capture. RESULTS: Evidence linking depressive disorders and infertility among PMMI is weak. Given this, women with prior mental conditions experience additional distress when undergoing fertility treatments. Primary mental disorders may also increase the risk of miscarriage and other pregnancy complications (e.g., gestational diabetes). For SMMI, there is more robust evidence correlating Preterm Birth (PTB) and Low Birth Weight (LBW) with common mental disorders which develop during pregnancy. CONCLUSION: Prevention and management of maternal mental health diseases and minor mental conditions within the first 1000 days' timeframe, should have a place in the holistic approach to women going through reproductive decisions, infertility treatment and pregnancy.

Pure stress urinary incontinence: analysis of prevalence, estimation of costs, and financial impact.

BACKGROUND: The prevalence of pure stress urinary incontinence (P-SUI) and the role of urodynamic investigation (UDI) prior to surgery for stress urinary incontinence (SUI) is debated. Since the exact prevalence of P-SUI is not clear, its clinical and economic impact is not well defined. The aims of this study were to evaluate the prevalence of P-SUI in a population of women who underwent UDI for urinary incontinence (UI), also assessing: 1) the correspondence between clinical diagnosis of P-SUI and urodynamic findings; 2) the analysis of costs in terms of UDI and eventually post-UDI avoided surgical procedures. METHODS: A single cohort of women who underwent UDI for UI between January 2012 and July 2016 was prospectively collected and retrospectively analyzed. Clinical P-SUI was defined by the strict criteria of the International Continence Society. For each patient, history, physical examination and UDI were collected. The correspondence between clinical and urodynamic findings of P-SUI was analyzed. The rate of clinical P-SUI changed after performing UDI and the number of unnecessary intervention after UDI were reported. A wide cost analysis of UDIs, and the amount of surgical procedures that were believed unnecessary after UDI was reported. RESULTS: Stress urinary incontinence was present in 323/544 (59.4%) patients. The prevalence of clinical P-SUI was 20.7% (67/323), while the prevalence of complicated SUI (C-SUI) was 79.3% (256/323). After UDI, diagnosis of P-SUI decreased to 18.3% (59/232). In 10.2% of cases (6/59) the scheduled middle urethral sling (MUS) was suppressed after the UDI results because 3/6 cases had detrusor overactivity and urge incontinence, in 2/6 cases SUI was treated with a conservative management, in 1/6 case an important voiding dysfunction was detected. Considering the national reimbursement in our country, the cost of each UDI was 296.5 euros and the total amount was 17,493.5 euros. So far the surgery-related savings covered 61.7-105.0% of the costs of total number of UDIs performed in the uncomplicated patients. CONCLUSIONS: The prevalence of clinical P-SUI is relevant, involving about 20% of women with clinical SUI. Although the correspondence between clinical and urodynamic diagnosis was high, we demonstrated that UDI may help in some cases to avoid an inappropriate surgical treatment. Therefore, UDI prior to SUI surgery should be considered to achieve a correct diagnosis and a proper therapeutic strategy.

Impact of blood cell counts and volumes on glucose concentration in uncentrifuged serum and lithium-heparin blood tubes.

BACKGROUND: Although it is known that glucose concentration exhibits a time-dependent decay in uncentrifuged serum and lithium-heparin blood tubes, no evidence exists on how this variation may depend on blood cell counts (CBC) and volumes. METHODS: Venous blood was drawn from 30 non fasting healthy volunteers into three serum and three lithium-heparin tubes. One serum and lithium-heparin tubes were centrifuged within 15 min after collection and glucose was measured with a hexokinase assay. The second and third serum and lithium-heparin tubes were maintained at room temperature for 1 and 2 h after the first tubes were centrifuged. These other tubes were then centrifuged and glucose was measured. CBC was performed in the first lithium-heparin tube, before centrifugation. RESULTS: The mean decrease of glucose was higher in lithium-heparin plasma than in serum (0.33 vs. 0.24 mmol/L/h; p<0.001). Glucose concentration decreased by 7% and 5% per hour in lithium-heparin plasma and serum, respectively. In univariate analysis, the absolute decrease of glucose concentration was associated with sex (higher in men than in women), red blood cell (RBC) count, hematocrit, white blood cell (WBC) count, neutrophils and monocytes in both lithium-heparin plasma and serum. In multivariate analysis, the decrease of glucose concentration remained independently associated with RBC, WBC, neutrophils and monocytes in both sample matrices. No significant association was found with platelet number and erythrocyte or platelet volume. CONCLUSIONS: Glucose concentration decrease in uncentrifuged lithium-heparin and serum tubes depends on the baseline number of RBC, WBC, neutrophils and monocytes within the tubes.

Red Blood Cell Distribution Width Is an Independent Predictor of Outcome in Patients Undergoing Thrombolysis for Ischemic Stroke.

An appropriate and timely management, including early diagnosis and accurate prognostication, is the mainstay for managed care of patients with acute ischemic stroke. Since red blood cell distribution width (RDW) was found to be an independent predictor of clinical outcomes in patients with thrombotic disorders, we designed a retrospective observational study to investigate whether the RDW value may also retain predictive significance in stoke patients undergoing thrombolytic therapy. This retrospective study was based on all patients admitted to the Emergency Department (ED) of the University Hospital of Verona (Italy) with a diagnosis of ischemic stroke, who underwent systemic thrombolysis between January 2013 and June 2015. The RDW value along with basal clinical characteristics was recorded at ED admission. The final study population consisted of 316 patients. A significant association was found between stroke severity (NIHSS score) and RDW (r = 0.322; p < 0.001). The median RDW value in patients with clinical improvement after thrombolysis was significantly lower than in patients without (13.4 vs. 14.1%; p < 0.001). The diagnostic accuracy (area under the curve) of RDW for predicting the lack of neurological improvement was 0.667. In univariate analysis, RDW >14.5% was associated with increased rate of no neurological improvement (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.37-4.13), an association remaining significant also in multivariate analysis (OR, 1.85; 95% CI, 1.13-3.32). Survivor curve analysis showed that patients with RDW values ≥14.5% had a higher risk of 1-year mortality and shorter survival. These results suggest that RDW assessment at ED admission may provide valuable diagnostic and prognostic information in patients with acute ischemic stroke.

Rapid screening for malignancy in organ donors: 15-year experience with the Verona "Alert" protocol and review of the literature.

BACKGROUND: Prevention of transmission of malignancy from donors to recipients is an aim of donor assessment. We report the most stringent interpretation of the Italian National Guidelines. METHODS: A two-step ALERT process was used: ALERT1 consisting of clinical, radiological, and laboratory tests; ALERT2, consisting of intraoperative assessment in suspicious lesions. RESULTS: Four hundred of 506 potential deceased donors entered the ALERT system. Forty-one of 400 (10%) donors were excluded due to unacceptable risk of transmission. Of the remaining 359 193 required histopathology, which excluded malignancy or determined acceptable risk in 161/193 (83%). Thirty-five malignancies were identified: 19 (54%) at ALERT1, four (11%) at ALERT2, nine (26%) picked up at ALERT1 and confirmed by ALERT2. Three (9%) were missed by ALERT and diagnosed at postmortem examination. Prostate (n=12%, 34%) and renal cell (n=7%, 20%) were the most frequent carcinomas. The majority (92%) of prostate adenocarcinomas were of low risk and donation proceeded compared to 43% of renal carcinomas. Four renal carcinomas, two breast carcinomas, and a single case of nine different malignancies excluded donation. Positive ALERT donors had statistically more malignant reports than negative ALERT donors (P=<.05). CONCLUSION: Histopathology is an essential component of the multidisciplinary assessment of donors.

Plasma Expression Levels of Circulating miR-21 are not Useful for Diagnosing and Monitoring Colorectal Cancer.

BACKGROUND: Recent evidence suggests that microRNAs play an important role in cancer diagnostics. We assessed plasma microRNA-21 levels in patients with colorectal cancer (CRC) at different stages and in patients with benign polyps. METHODS: Plasma levels of miR-21 were assessed by quantitative reverse transcription polymerase chain reaction assay in plasma samples of 76 CRC patients and in 20 patients with benign polyps. Differences between groups were evaluated with Mann-Whitney and Kruskal-Wallis tests. RESULTS: No significant differences of miR-21 plasma levels were observed between CRC patients and subjects with benign polyps (p > 0.05). Also, no significant differences were found between CRC patients with advanced (III-IV) or early cancer stages (I-II) (p > 0.05). CONCLUSIONS: These results do not support the hypothesis that circulating miR-21 expression is increased in adenoma-carcinoma-advanced carcinoma sequence. Accordingly, plasma miR-21 assessment does not appear to be a useful biomarker for diagnosing and staging CRC.

Diffusion-weighted magnetic resonance imaging in the characterization of axillary lymph nodes in patients with breast cancer.

PURPOSE: To assess prospectively the accuracy of diffusion-weighted magnetic resonance imaging (DWI) in differentiating between metastatic and benign axillary lymph nodes in patients with breast cancer. MATERIALS AND METHODS: In all, 215 patients with histologically proven breast cancer, prior to axillary dissection, underwent breast and axillary 1.5 T MRI. In 102 patients in whom at least one axillary lymph node with a short axis of 6 mm or more was found the apparent diffusion coefficient (ADC) was measured in one lymph node per patient by means of an echo planar, parallel imaging DWI sequence. Forty-three lymph nodes were finally included which, on histological examination, either contained a metastasis larger than 5 mm or were metastasis-free; nodes with metastases smaller than 5 mm were excluded. RESULTS: From histological examination, 19/43 lymph nodes had a metastasis at least 5 mm, while in 24/43 no malignant cells were found. The ADC values of the lymph nodes with metastases (mean: 0.878 × 10(-3) mm(2) /s; range: 0.30 -1.20) were significantly lower (P < 0.001) than those of the benign lymph nodes (mean: 1.494; range: 0.60 -2.50). Adopting a threshold value of 1.09 × 10(-3) mm(2) /s DWI resulted in 94.7% sensitivity, 91.7% specificity, and 93.0% accuracy in the identification of metastasis in this series of lymph nodes. CONCLUSION: From these preliminary data DWI seems a promising method in the differential diagnosis between metastatic and benign axillary lymph nodes in patients with breast cancer.

Anything New about Paternal Contribution to Reproductive Outcomes? A Review of the Evidence.

Paternal health and behavioral lifestyles affect reproductive and neonatal outcomes and yet the magnitude of these effects remain underestimated. Even though these impacts have been formally recognized as a central aspect of reproductive health, health care services in Europe often neglect the involvement of fathers in their reproductive programs. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for systematic reviews, a literature search was carried out to assess the possible impact of paternal health on reproductive outcomes. The comprehensive strategy included cohort studies and meta-analysis available on PubMed, Web of Science, CINAHL, and Google scholar. Cross-referencing of bibliographies of the selected papers ensured wider study capture. Paternal factors were grouped into two categories respectively identified with the terms "Biological Paternal Factors" and "Lifestyle Paternal Factors". Advanced age may impair male fertility and affect early pregnancy stages. Increased body mass index, smoking, alcohol and recreational drugs, all alter seminal fluid parameters. Hazardous alcohol use correlates with low birthweight in pregnancy and harmful behavioral lifestyles have been linked to congenital heart defects, metabolic and neurodevelopmental disorders in the offspring. Measures targeting paternal health and lifestyle within the first 1,000 days' timeframe need to be implemented in couples undergoing reproductive decisions. Health professionals, as well as future fathers, must be aware of the benefits for the offspring associated with correct paternal behaviors. More research is needed to build guidelines and to implement specific programs aiming at reproductive health promotion.

Levels of burn-out among healthcare workers during the COVID-19 pandemic and their associated factors: a cross-sectional study in a tertiary hospital of a highly burdened area of north-east Italy.

OBJECTIVE: To determine burn-out levels and associated factors among healthcare personnel working in a tertiary hospital of a highly burdened area of north-east Italy during the COVID-19 pandemic. DESIGN: Observational study conducted from 21 April to 6 May 2020 using a web-based questionnaire. SETTING: Research conducted in the Verona University Hospital (Veneto, Italy). PARTICIPANTS: Out of 2195 eligible participants, 1961 healthcare workers with the full range of professional profiles (89.3%) completed the survey. PRIMARY OUTCOME MEASURE: Levels of burn-out, assessed by the Maslach Burnout Inventory-General Survey (MBI-GS). Multivariable logistic regression analysis was performed to identify factors associated with burn-out in each MBI-GS dimension (emotional exhaustion, EX; professional efficacy, EF; cynicism, CY). RESULTS: Overall, 38.3% displayed high EX, 46.5% low EF and 26.5% high CY. Burn-out was frequent among staff working in intensive care units (EX 57.0%; EF 47.8%; CY 40.1%), and among residents (EX 34.9%; EF 63.9%; CY 33.4%) and nurses (EX 49.2%; EF 46.9%; CY 29.7%). Being a resident increased the risk of burn-out (by nearly 2.5 times) in all the three MBI subscales and being a nurse increased the risk of burn-out in the EX dimension in comparison to physicians. Healthcare staff directly engaged with patients with COVID-19 showed more EX and CY than those working in non-COVID wards. Finally, the risk of burn-out was higher in staff showing pre-existing psychological problems, in those having experienced a COVID-related traumatic event and in those having experienced interpersonal avoidance in the workplace and personal life. CONCLUSIONS: Burn-out represents a great concern for healthcare staff working in a large tertiary hospital during the COVID-19 pandemic and its impact is more burdensome for front-line junior physicians. This study underlines the need to carefully address psychological well-being of healthcare workers to prevent the increase of burn-out in the event of a new COVID-19 healthcare emergency.