Metabolomics investigation of post-mortem human pericardial fluid.

INTRODUCTION: Due to its peculiar anatomy and physiology, the pericardial fluid is a biological matrix of particular interest in the forensic field. Despite this, the available literature has mainly focused on post-mortem biochemistry and forensic toxicology, while to the best of authors' knowledge post-mortem metabolomics has never been applied. Similarly, estimation of the time since death or post-mortem interval based on pericardial fluids has still rarely been attempted. OBJECTIVES: We applied a metabolomic approach based on 1H nuclear magnetic resonance spectroscopy to ascertain the feasibility of monitoring post-mortem metabolite changes on human pericardial fluids with the aim of building a multivariate regression model for post-mortem interval estimation. METHODS: Pericardial fluid samples were collected in 24 consecutive judicial autopsies, in a time frame ranging from 16 to 170 h after death. The only exclusion criterion was the quantitative and/or qualitative alteration of the sample. Two different extraction protocols were applied for low molecular weight metabolites selection, namely ultrafiltration and liquid-liquid extraction. Our metabolomic approach was based on the use of 1H nuclear magnetic resonance and multivariate statistical data analysis. RESULTS: The pericardial fluid samples treated with the two experimental protocols did not show significant differences in the distribution of the metabolites detected. A post-mortem interval estimation model based on 18 pericardial fluid samples was validated with an independent set of 6 samples, giving a prediction error of 33-34 h depending on the experimental protocol used. By narrowing the window to post-mortem intervals below 100 h, the prediction power of the model was significantly improved with an error of 13-15 h depending on the extraction protocol. Choline, glycine, ethanolamine, and hypoxanthine were the most relevant metabolites in the prediction model. CONCLUSION: The present study, although preliminary, shows that PF samples collected from a real forensic scenario represent a biofluid of interest for post-mortem metabolomics, with particular regard to the estimation of the time since death.

Pharmacological Treatment of Bipolar Depression: A Review of Observational Studies.

The persistence of depressive morbidity is frequent in bipolar disorder, and the pharmacological management of this symptomatology often lacks effectiveness. This systematic review aimed to summarize the results of the naturalistic observational studies on the pharmacological treatment of bipolar depression published through April 2022. The certainty of evidence was evaluated according to the GRADE approach. In sum, 16 studies on anticonvulsants, 20 on atypical antipsychotics, 2 on lithium, 28 on antidepressants, and 9 on other compounds were found. Lamotrigine, quetiapine, aripiprazole, and ketamine were the most investigated compounds. Overall, the results support the recommendations regarding the effectiveness of lamotrigine and quetiapine. In contrast to the current recommendations, aripiprazole was shown to be effective and generally well tolerated. Additionally, SSRIs were shown to be effective, but, since they were associated with a possibly higher switch risk, they should be used as an adjunctive therapy to mood stabilizers. Lithium was only studied in two trials but was shown to be effective, although the serum concentrations levels were not associated with clinical response. Finally, ketamine showed divergent response rates with a low certainty of evidence and, so far, unclear long-term effects. Heterogeneity in diagnosis, sample sizes, study designs, reporting of bias, and side effects limited the possibility of a head-to-head comparison.

PMI estimation through metabolomics and potassium analysis on animal vitreous humour.

INTRODUCTION: The estimation of post-mortem interval (PMI) remains a major challenge in forensic science. Most of the proposed approaches lack the reliability required to meet the rigorous forensic standards. OBJECTIVES: We applied 1H NMR metabolomics to estimate PMI on ovine vitreous humour comparing the results with the actual scientific gold standard, namely vitreous potassium concentrations. METHODS: Vitreous humour samples were collected in a time frame ranging from 6 to 86 h after death. Experiments were performed by using 1H NMR metabolomics and ion capillary analysis. Data were submitted to multivariate statistical data analysis. RESULTS: A multivariate calibration model was built to estimate PMI based on 47 vitreous humour samples. The model was validated with an independent test set of 24 samples, obtaining a prediction error on the entire range of 6.9 h for PMI < 24 h, 7.4 h for PMI between 24 and 48 h, and 10.3 h for PMI > 48 h. Time-related modifications of the 1H NMR vitreous metabolomic profile could predict PMI better than potassium up to 48 h after death, whilst a combination of the two is better than the single approach for higher PMI estimation. CONCLUSION: The present study, although in a proof-of-concept animal model, shows that vitreous metabolomics can be a powerful tool to predict PMI providing a more accurate estimation compared to the widely studied approach based on vitreous potassium concentrations.

Patient Involvement in Shared Decision-Making: Do Patients Rate Physicians and Nurses Differently?

BACKGROUND: Shared decision-making implies that patients and healthcare professionals make decisions together about clinical exams, available treatments, choice of options, and the benefit or downside of every choice. Patients involved in the shared decision-making process are more compliant with treatments and have a reduced risk of complications related to the pathology. In Italy, patient involvement in caring processes is still barely investigated. AIM: To investigate patients' perceptions about shared decision-making with physicians and nurses, respectively, and to examine the relationship between shared decision-making and patient satisfaction and perceived quality of care/treatment. METHODS: The study was performed between March and June 2019 in two wards of one Italian hospital. A questionnaire was administered to inpatients at the time of admission and again at discharge, including demographic information and measurement scales regarding patient involvement in shared decision-making, patient satisfaction, and perceived quality of treatment/care. RESULTS: A total of 151 out of 301 patients completed questionnaires at both admission and discharge. Patients' scores for shared decision-making (information, patient needs, treatment planning) were significantly different for physicians and nurses. At both admission and discharge, patients rated shared decision-making significantly higher for physicians compared to nurses, while there were no differences in their satisfaction ratings. Patient ratings of physicians did not change from admission (information: mean (M) = 3.50, standard deviation (SD) = 0.81; patient need: M = 3.05, SD = 1.05; treatment planning: M = 2.75, SD = 1.23) to discharge (information: M = 3.50, SD = 0.79; patient need: M = 3.17, SD = 1.02; treatment planning: M = 2.66, SD = 1.23) (p = 0.924, p = 0.098, p = 0.293, respectively), but patients' ratings of nurses' behavior increased significantly from admission (information: M = 2.44, SD = 1.23; patient need: M = 2.27, SD = 1.17; treatment planning: M = 2.12, SD = 1.19) to discharge (information: M = 2.62, SD = 1.22; patient need: M = 2.53, SD = 1.24; treatment planning: M = 2.35, SD = 1.21) (p = 0.019, p = 0.001, p = 0.003, respectively). Attention to patients' needs was the key determinant of both satisfaction with nurses (OR = 3.65, 95% CI = 1.31-10.14, p = 0.013) and perceived quality of care (OR = 3.97, 95% CI = 1.49-10.55, p = 0.006). Providing appropriate information about disease progress and treatments was a key determinant of both satisfaction with physicians (OR = 19.75, 95% CI = 7.29-53.55, p < 0.001) and perceived quality of treatment (OR = 8.03, 95% CI = 3.25-19.81, p < 0.001). DISCUSSION: Nurses should be sensitized to involving patients in the decision-making process, especially upon hospital admission. Specific training about effective communication techniques can be implemented to manage relationships with patients in different caring situations. Practical implications and future directions are discussed.

The Influence of Eyelid Position and Environmental Conditions on the Corneal Changes in Early Postmortem Interval: A Prospective, Multicentric OCT Study.

In the current study, using portable optical coherence tomography, we evaluated 46 corneas of 23 individuals in a multicenter setting during the first 17 h after death. Twenty-three eyes were kept open, and twenty three were kept closed. Furthermore, the experiment was carried out for 12 samples in summer and 11 in winter. Our data show that postmortem corneal alterations largely depend on the phenomena of dehydration (in particular in open eyes) and swelling of the stroma in closed eyes, probably due in the first phase to hypoxia/anoxia and subsequently to the passage by osmosis of the aqueous humor from the anterior chamber to the corneal tissue. Our findings could have significant repercussions in forensic pathology for estimating the postmortem interval and transplantation to optimize the conservation of the tissue before the explant.

Blood Biomarkers and Metabolomic Profiling for the Early Diagnosis of Vancomycin-Associated Acute Kidney Injury: A Systematic Review and Meta-Analysis of Experimental Studies.

BACKGROUND: several blood-based biomarkers have been proposed for predicting vancomycin-associated kidney injury (VIKI). However, no systematic analysis has compared their prognostic value. OBJECTIVE: this systematic review and meta-analysis was designed to investigate the role of blood biomarkers and metabolomic profiling as diagnostic and prognostic predictors in pre-clinical studies of VIKI. METHODS: a systematic search of PubMed was conducted for relevant articles from January 2000 to May 2022. Animal studies that administered vancomycin and studied VIKI were eligible for inclusion. Clinical studies, reviews, and non-English literature were excluded. The primary outcome was to investigate the relationship between the extent of VIKI as measured by blood biomarkers and metabolomic profiling. Risk of bias was assessed with the CAMARADES checklist the SYRCLE's risk of bias tool. Standard meta-analysis methods (random-effects models) were used. RESULTS: there were four studies for the same species, dosage, duration of vancomycin administration and measurement only for serum creatine and blood urea nitrogen in rats. A statistically significant increase was observed between serum creatinine in the vancomycin group compared to controls (pooled p = 0.037; Standardized Mean Difference: 2.93; 95% CI: 0.17 to 5.69; I2 = 92.11%). Serum BUN levels were not significantly different between control and vancomycin groups (pooled p = 0.11; SMD: 3.05; 95% CI: 0.69 to 6.8; I2 = 94.84%). We did not identify experimental studies using metabolomic analyses in animals with VIKI. CONCLUSIONS: a total of four studies in rodents only described outcomes of kidney injury as defined by blood biomarkers. Blood biomarkers represented included serum creatinine and BUN. Novel blood biomarkers have not been explored.

Predictive risk factors of phenoconversion in idiopathic REM sleep behavior disorder: the Italian study "FARPRESTO".

Most patients with idiopathic REM sleep behavior disorder (iRBD) will develop an overt α-synucleinopathy over time, with a rate of phenoconversion of 73.5% after 12 years from diagnosis. Several markers of phenoconversion were identified; however, most studies investigated biomarkers separately, with retrospective study designs, in small cohorts or without standardized data collection methods. The risk FActoRs PREdictive of phenoconversion in idiopathic REM sleep behavior disorder: the Italian STudy (FARPRESTO) is a multicentric longitudinal retrospective and prospective study with a cohort of incident (prospective recruitment) and prevalent (retrospective recruitment) iRBD patients, whose primary aim is to stratify the risk of phenoconversion, through the systematic collection by means of electronic case report forms of different biomarkers. Secondary aims are to (1) describe the sociodemographic and clinical characteristics of patients with iRBD; (2) collect longitudinal data about the development of α-synucleinopathies; (3) monitor the impact of iRBD on quality of life and sleep quality; (4) assess the correlation between phenoconversion, cognitive performance, and loss of normal muscle atony during REM sleep; (5) identify RBD phenotypes through evaluating clinical, biological, neurophysiological, neuropsychological, and imaging biomarkers; and (6) validate vPSG criteria for RBD diagnosis. The FARPRESTO study will collect a large and harmonized dataset, assessing the role of different biomarkers providing a unique opportunity for a holistic, multidimensional, and personalized approach to iRBD, with several possible application and impact at different levels, from basic to clinical research, and from prevention to management. The FARPRESTO has been registered at clinicaltrials.gov (NCT05262543).

New Perspectives for Postmortem Human Satellite Cells of Different Embryological Origin.

Human postmortem skeletal muscles are a unique source of satellite cells for skeletal muscle regenerative studies. Presomite and somite satellite cells obtained by postmortem muscles have been established as populations of human skeletal muscle precursor cells able to proliferate and differentiate in vitro. It is extremely interesting to have access to a large amount of postmortem human skeletal muscle precursor cells, especially from craniofacial as well as limb skeletal muscles in order to evaluate their potential application not only for the fundamental understanding of muscle physiology and diseases but also for drug testing in a challenging 3D-shaping muscles like skeletal muscle microphysiological systems.

Urinary Metabolomics From a Dose-Fractionated Polymyxin B Rat Model of Acute Kidney Injury.

BACKGROUND: Polymyxin B treatment is limited by kidney injury. This study sought to identify Polymyxin B-related urinary metabolomic profile modifications for early detection of polymyxin-associated nephrotoxicity. METHODS: Samples were obtained from a previously conducted study. Male Sprague-Dawley rats received dose-fractionated polymyxin B (12 mg/kg/day) once daily (QD), twice daily (BID), and thrice daily (TID) for three days, with urinary biomarkers and kidney histopathology scores determined. Daily urine was analysed for metabolites via 1H nuclear magnetic resonance (NMR). Principal components analyses identified spectral data trends with orthogonal partial least square discriminant analysis applied to classify metabolic differences. Metabolomes were compared across groups (i.e., those receiving QD, BID, TID, and control) using a mixed-effects models. Spearman correlation was performed for injury biomarkers and the metabolome. RESULTS: A total of 25 rats were treated with Polymyxin B, and n = 2 received saline, contributing 77 urinary samples. Pre-dosing samples clustered well, characterised by higher amounts of citrate, 2-oxoglutarate, and hippurate. Day 1 samples showed higher taurine; day 3 samples had higher lactate, acetate and creatine. Taurine was the only metabolite that significantly increased in both BID and TID compared with the QD group. Day 1 taurine correlated with increasing histopathology scores (rho = 0.4167, P = 0.038) and kidney injury molecule-1 (KIM-1) (rho = 0.4052, P = 0.036), whereas KIM-1 on day 1 and day 3 did not reach significance with histopathology (rho = 0.3248, P = 0.11 and rho = 0.3739, P = 0.066). CONCLUSIONS: Polymyxin B causes increased amounts of urinary taurine on day 1, which then normalizes to baseline concentrations. Taurine may provide one of the earlier signals of acute kidney damage caused by polymyxin B.

Infant urinary metabolomic profile in a fatal acute methadone intoxication.

A case report suspicious for a Sudden Infant Death Syndrome is here described. Pathological findings were consistent with an acute respiratory failure while toxicological analysis revealed an elevated blood methadone concentration. Death was then ascribed to an acute methadone intoxication. In addition to the routinary approach, the urinary sample collected at autopsy was investigated with a 1H NMR metabolomic approach and the identified metabolomic profile was challenged with the urinary metabolomic profiles previously obtained from 10 newborns who experienced perinatal asphyxia and 16 healthy control newborns. Intriguingly, the urinary profile of the methadone intoxicated infant was very similar to those belonging to the perinatal asphyxia newborns, especially to those belonging to the newborns characterised by the worst outcome. The results offer several hints on a shared metabolic derangement between different mechanisms of asphyxia/hypoxia. To the best of the authors' knowledge, this is the first report of the use of a metabolomic approach in a pathological case, in which metabolomics offers useful additional information regarding the mechanism and the cause of death.

Dual Corneal-Graft Rejection after mRNA Vaccine (BNT162b2) for COVID-19 during the First Six Months of Follow-Up: Case Report, State of the Art and Ethical Concerns.

Present mass vaccination against Coronavirus Disease-19 (COVID-19) is the most widely used health policy and the most promising approach to curb the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic globally. However, new side effects are emerging from the mass vaccination not described during the experimental stages. In the present study, we discuss a case of acute corneal graft rejection, which has occurred 25 years after transplantation and 13 days after the administration of the BNT162b2 vaccine (Comirnaty, BioNTech/Pfizer), which was followed-up for a period of six months. In this period, the corneal inflammation appeared twice but was successfully managed with topical therapy and supplementation of Vitamin D. A risk of corneal graft rejection must be included in the list of potential vaccine complications, in order to inform the transplanted patient to undergo a preliminary and a follow-up ocular examination, and eventually to include corneal graft in the list of contraindications to vaccination.

Dying "from" or "with" COVID-19 during the Pandemic: Medico-Legal Issues According to a Population Perspective.

There is still a lack of knowledge concerning the pathophysiology of death among COVID-19-deceased patients, and the question of whether a patient has died with or due to COVID-19 is still very much debated. In Italy, all deaths of patients who tested positive for SARS-CoV-2 are defined as COVID-19-related, without considering pre-existing diseases that may either contribute to or even cause death. Our study included nine subjects from two different nursing homes (Cases 1-4, Group A; Cases 5-9, Group B). The latter included patients who presumably died from CO poisoning due to a heating system malfunction. All subjects tested positive for COVID-19 both ante- and post-mortem and were examined using post-mortem computed tomography prior to autopsy. COVID-19 was determined to be a contributing cause in the deaths of four out of nine subjects (death due to COVID-19; i.e., pneumonia and sudden cardiac death). In the other five cases, for which CO poisoning was identified as the cause of death, the infection presumably had no role in exitus (death with COVID-19). In our attempt to classify our patients as dying with or due to COVID-19, we found the use of complete assessments (both histological analyses and computed tomography examination) fundamental.

Looking for Post-Mortem Metabolomic Standardization: Waiting for Godot-The Importance of Post-Mortem Interval in Forensic Metabolomics.

A growing body of evidence suggests that the post-mortem interval exerts a strong effect on the metabolome, independently of the biological matrix or the cause of death. A sound and shared approach in standardization is mandatory.

Worries, Preparedness, and Perceived Impact of Covid-19 Pandemic on Nurses' Mental Health.

Background: In times of global public health emergency, such as the COVID-19 pandemic, nurses stand at the front line, working in close contact with infected individuals. Being actively engaged in fighting against COVID-19 exposes nurses to a high risk of being infected but can also have a serious impact on their mental health, as they are faced with excessive workload and emotional burden in many front-line operating contexts. Purpose: The aim of the study is to analyze how risk factors such as perceived impact, preparedness to the pandemic, and worries were associated with mental health outcomes (crying, rumination and stress) in nurses. Methods: A cross-sectional study design was performed via an online questionnaire survey. Participants included 894 registered nurses from Italy. Participation was voluntary and anonymous. Multiple binary logistic regression was carried out to analyze the relationship between risk factors and health outcomes. Results: Increased job stress was related to higher levels of rumination about the pandemic (OR = 4.04, p < 0.001), job demand (OR = 2.00, p < 0.001), impact on job role (OR = 2.56, p < 0.001), watching coworkers crying at work (OR = 1.50, p < 0.05), non-work-related concerns (OR = 2.28, p < 0.001), and fear of getting infected (OR = 2.05, p < 0.001). Job stress (OR = 2.52, p < 0.01), rumination (OR = 2.28, p < 0.001), and watching colleagues crying (OR = 7.92, p < 0.001) were associated with crying at work. Rumination was associated with caring for patients who died of COVID-19 (OR = 1.54, p < 0.05), job demand (OR = 1.70, p < 0.01), watching colleagues crying (OR = 1.81, p < 0.001), non-work-related worries (OR = 1.57, p < 0.05), and fear of getting infected (OR = 2.02, p < 0.001). Conclusions: The psychological impact that this pandemic may cause in the medium/long term could be greater than the economical one. This is the main challenge that health organizations will have to face in the future. This study highlights that the perceived impact and worries about the pandemic affect nurses' mental health and can impact on their overall effectiveness during the pandemic. Measures to enhance nurses' protection and to lessen the risk of depressive symptoms and post-traumatic stress should be planned promptly.

Metabolomics improves the histopathological diagnosis of asphyxial deaths: an animal proof-of-concept model.

The diagnosis of mechanical asphyxia remains one of the most difficult issues in forensic pathology. Asphyxia ultimately results in cardiac arrest (CA) and, as there are no specific markers, the differential diagnosis of primitive CA and CA secondary to asphyxiation relies on circumstantial details and on the pathologist experience, lacking objective evidence. Histological examination is currently considered the gold standard for CA post-mortem diagnosis. Here we present the comparative results of histopathology versus those previously obtained by 1H nuclear magnetic resonance (NMR) metabolomics in a swine model, originally designed for clinical purposes, exposed to two different CA causes, namely ventricular fibrillation and asphyxia. While heart and brain microscopical analysis could identify the damage induced by CA without providing any additional information on the CA cause, metabolomics allowed the identification of clearly different profiles between the two groups and showed major differences between asphyxiated animals with good and poor outcomes. Minute-by-minute plasma sampling allowed to associate these modifications to the pre-arrest asphyxial phase showing a clear correlation to the cellular effect of mechanical asphyxia reproduced in the experiment. The results suggest that metabolomics provides additional evidence beyond that obtained by histology and immunohistochemistry in the differential diagnosis of CA.

Biomarkers of Low-Level Environmental Exposure to Benzene and Oxidative DNA Damage in Primary School Children in Sardinia, Italy.

BACKGROUND: The main anthropic sources of exposure to airborne benzene include vehicular traffic, cigarette smoke, and industrial emissions. METHODS: To detect early genotoxic effects of environmental exposure to benzene, we monitored environmental, personal, and indoor airborne benzene in children living in an urban area and an area near a petrochemical plant. We also used urinary benzene and S-phenylmercapturic acid (S-PMA) as biomarkers of benzene exposure and urinary 8-hydroxydeoxyguanosine (8-OHdG) as a biomarker of early genotoxic effects. RESULTS: Although always below the European Union limit of 5 µg/m3, airborne benzene levels were more elevated in the indoor, outdoor, and personal samples from the industrial surroundings compared to the urban area (p = 0.026, p = 0.005, and p = 0.001, respectively). Children living in the surroundings of the petrochemical plant had urinary benzene values significantly higher than those from the urban area in both the morning and evening samples (p = 0.01 and p = 0.02, respectively). Results of multiple regression modelling showed that age was a significant predictor of 8-OHdG excretion, independent of the sampling hour. Moreover, at the low exposure level experienced by the children participating in this study, neither personal or indoor airborne benzene level, nor personal monitoring data, affected 8-OHdG excretion. CONCLUSIONS: Our results suggest the importance of biological monitoring of low-level environmental exposure and its relation to risk of genotoxic effects among children.

Dealing With COVID-19 Patients: A Moderated Mediation Model of Exposure to Patients' Death and Mental Health of Italian Health Care Workers.

Introduction: The COVID-19 pandemic is asking health care workers (HCWs) to meet extraordinary challenges. In turn, HCWs were experiencing tremendous psycho-social crisis as they have had to deal with unexpected emotional requirements (ERs) arising from caring for suffering and dying patients on a daily basis. In that context, recent studies have highlighted how HCWs working during the COVID-19 outbreak manifested extreme emotional and behavioral reactions that may have impacted their mental health, increasing the risk for developing post-traumatic stress symptoms. Purpose: The aim of the study was to investigate post-traumatic stress symptoms, such as intrusion symptoms, as a potential mediator of the link between ERs and crying at work, and whether rumination moderates the relationship between ERs and intrusion-based PTS symptoms among HCWs who have had to deal with patients dying from COVID-19. Methods: An online cross-sectional study design was performed. A total of 543 Italian HCWs (physicians and nurses) participated in the study. Participation was voluntary and anonymous. We used the SPSS version of bootstrap-based PROCESS macro for testing the moderated mediation model. Results: ERs had an indirect effect on crying at work through the mediating role of intrusion symptoms. Results from the moderated mediation model showed that rumination moderated the indirect effect of ERs on crying at work via intrusion symptoms, and this effect was significant only for high rumination. Furthermore, when we tested for an alternative model where rumination moderates the direct effect of ERs on crying at work, this moderation was not significant. Conclusions: As the second wave of the COVID-19 pandemic is ongoing, there is an urgent need for decision-makers to rapidly implement interventions aimed at offering timely psychological support to HCWs, especially in those contexts where the risk of emotional labor associated to patients dying from COVID-19 is higher.

Concerns, Perceived Impact, Preparedness in Coronavirus Disease (COVID-19) Pandemic and Health Outcomes among Italian Physicians: A Cross-Sectional Study.

BACKGROUND: Health care workers (HCWs) are among the professionals at serious risk for the impact of the COVID-19 pandemic on their mental health. In this sense, the next public health challenge globally will be to preserving healthy HCWs during this pandemic. AIM: The present study has the aim of investigating the relationship among concerns, perceived impact, preparedness for the COVID-19 pandemic and the mental health of Italian physicians. METHODS: From March 29th to April 15th 2020, we conducted an online survey using snowball sampling techniques through Limesurvey platform. Data were analyzed using descriptive statistics and multiple binary logistic regressions. RESULTS: Multivariate analysis showed that the risk factors for perceived job stress were concerns about catching COVID-19 (OR = 3.18 [95% CI = 2.00-5.05] P < .001), perceived impact on job demands (OR = 1.63 [95% CI = 1.05-2.52] P < .05), perceived impact on job role (OR = 2.50 [95% CI = 1.60-3.90] P < .001), and non-working concerns (OR = 1.86 [95% CI = 1.15-3.03] P < .05). With respect to the risk factors for rumination about the pandemic emerged concerns about catching COVID-19 (OR 1.74, [95% CI = 1.12-2.71] P < .05), perceived impact on job role (OR = 1.68 [95% CI = 1.12-2.52] P < .05), and impact on personal life (OR = 2.04 [95% CI = 1.08-3.86] P < .05). Finally, the risk factors for crying at work were perceived impact on job role (OR = 2.47, [95% CI = 1.20-5.09] P < .05), rumination about the pandemic (OR = 3.027 [95% CI = 1.27-7.19] P < .01), watching colleagues crying at work (OR = 3.82 [95% CI = 1.88-7.77] P < .01), and perceived job stress (OR = 3.53 [95% CI = 1.24-10.07] P < .05). CONCLUSION: In general, our results highlighted that being concerned about being infected/infecting other people, carrying out new and unusual tasks, and witnessing colleagues crying at work were important risk factors for physicians' well-being. Additional data are necessary to advance understanding of these risk factors in a long-term perspective.