Risk factors for postoperative acute kidney injury after major abdominal surgery.

AIM: Acute kidney injury (AKI) worsens the outcome in a significant number of hospitalized patients. Risk models mainly address cardiac surgery, while significantly less attention is paid to AKI after major abdominal surgery (MAS). This study aims to evaluate the incidence, along with risk factors, and intrahospital outcomes of AKI after MAS. MATERIAL AND METHODS: Our retrospective study included 200 adult patients treated with MAS (in the same institution). Exclusion criteria were obstructive nephropathy, contrast-induced nephropathy, and dialysis dependence whether due to end-stage renal disease (ESRD) or AKI before MAS. Data on preoperative, intraoperative, as well as postoperative variables were collected from patients' medical history and electronic medical records. RESULTS: AKI was diagnosed in 33 (16.5%) patients, with 2 patients treated with hemodialysis. The multivariate logistic regression model showed that the number of intraoperative blood transfusions (p = 0.01), pneumonia (p < 0.001), and vasoactive drug use (p = 0.02) were independently associated with postoperative AKI. Each blood transfusion administered increased the risk of developing AKI by 1.41, vasoactive drug use by 4.13, and the risk of AKI in those with pneumonia was 15.32 times higher. The lethal outcome was observed significantly more frequently in patients with AKI (39.4 vs. 4.8%, p < 0.001). CONCLUSION: Identification of independent predictors of AKI after MAS such as the number of transfusions during surgery, sepsis, pneumonia, and the need for vasoactive drug therapy could help prevent AKI and lower the probability of lethal outcomes after MAS.

Updated Meta-Analysis of Randomized Controlled Trials Comparing External Fixation to Intramedullary Nailing in the Treatment of Open Tibial Fractures.

Background: The purpose of this study was to collect all available randomized controlled trials (RCT) on the treatment of open tibial fractures with an external fixator (EF) and intramedullary nailing (IMN) for meta-analysis to provide reliable evidence-based data for clinical decision-making. Material and methods: The systematic review was undertaken in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and AMSTAR (Assessing the Methodological Quality of Systematic Review). An electronic search of PubMed, Cochrane Library, and Web of Science was performed until 1 March 2023 to identify RCTs which compared either IMN or EF to fix the open tibial fracture. Outcome measures were: postoperative superficial and deep infection, time to union, delayed union, malunion, nonunion and hardware failure. In addition, pain and health-related quality of life were evaluated after 3 and 12 months of follow-up. Results: Sixteen publications comprising 1011 patients were included in the meta-analysis. The pooled results suggested that the IMN technique had a lower postoperative superficial infection and malunion rate (RR = 3.56, 95%CI = 2.56-4.95 and RR = 1.96, 95%CI = 1.12-3.44, respectively), but higher hardware failure occurrence in contrast to EF (RR = 0.30; 95%CI = 0.13-0.69). No significant differences were found in the union time, delayed union or nonunion rate, and postoperative deep infection rate between the treatments. Lower levels of pain were found in the EF group (RR = 0.05, 95%CI = 0.02-0.17, p < 0.001). A difference in quality of life favoring IMN after 3 months was found (RR = -0.04, 95%CI = -0.05-0.03, p < 0.001), however, no statistical difference was found after 12 months (RR = 0.03, 95%CI = -0.05-0.11, p = 0.44). Conclusions: Meta-analysis presented reduced incidence rates of superficial infection, malunion, and health-related quality of life 3 months after treatment in IMN. However, EF led to a significant reduction in pain and incidence rate of hardware failure. Postoperative deep infection, delayed union, nonunion and health-related quality of life 12 months following therapy were similar between groups. More high-quality RCTs should be conducted to provide reliable evidence-based data for clinical decision-making.

Clinicopathological Analysis of 907 Major and Minor Salivary Gland Tumors.

PURPOSE: The frequency and types of salivary gland tumors show significant geographical variations. The most common are primary epithelial tumors, with pleomorphic adenoma and mucoepidermoid carcinoma being the most frequent. This study aims to analyze the clinicopathological data of patients with major and minor salivary gland (MiSG) tumors. METHODS: The retrospective study included all patients with major and MiSG tumors diagnosed and treated between January 2000 and January 2019. Files of 907 patients were reviewed and investigated for clinicopathologic features of major and MiSG tumors in Serbia. RESULTS: The majority of tumors were of epithelial origin. Pleomorphic adenoma was the predominant type of tumor, with 35.1% among all tumors on all sites. Adenoid cystic carcinoma and mucoepider-moid carcinoma (with 7.1% and 2.7%, respectively) were the most common malignant ones. The most common localization was the parotid gland. Minor salivary gland tumors comprised 16.43% of all salivary gland tumors in our series, the most common localization being the oral cavity. The results of our study are mostly consistent with the results of other previously published studies. CONCLUSIONS: The most important finding, worth emphasizing, is that the most common malignant major and MiSG tumor in our population is adenoid cystic carcinoma, rather than mucoepidermoid carcinoma, in all investigated localizations. In addition, the nasal cavity is the most common localization among malignant MiSG tumors.

The Magnetic Resonance Imaging Pattern of the Lesions Caused by Knee Overuse in the Pediatric Population.

Background and Objectives: Excessive use of the knee in patients with immature locomotor systems leads to a whole spectrum of morphological changes with possible consequences in adulthood. This study aimed to examine the morphological pattern in magnetic resonance imaging (MRI) that is associated with recurrent pain due to increased physical activity in children. Materials and Methods: This was a retrospective study conducted among pediatric patients treated at the University Children's Hospital in Belgrade in 2018 and 2019. MRI findings of patients who reported recurrent pain in the knee joint during physical activity and who were without any pathological findings on both clinical examination and knee radiographs were included in the study. Results: MRI findings of 168 patients (73 boys and 95 girls, mean age 14.07 ± 3.34 years) were assessed. Meniscus and cartilage lesions were the most commonly detected morphological findings: meniscus lesions in 49.4%, cartilage ruptures in 44.6%, and cartilage edema in 26.2% of patients. The medial meniscus was more often injured in girls (p = 0.030), while boys were more prone to other joint injuries (p = 0.016), re-injury of the same joint (p = 0.036), bone bruises (p < 0.001), and ligament injuries (p = 0.001). In children older than 15 years, tibial plateau cartilage edema (p = 0.016), chondromalacia patellae (p = 0.005), and retropatellar effusion (p = 0.011) were detected more frequently compared to younger children. Conclusions: Children reporting recurrent knee pain due to increased physical activity, without any detected pathological findings on clinical examination and knee radiography, may have morphological changes that can be detected on MRI. Timely diagnosis of joint lesions should play a significant role in preventing permanent joint dysfunction in the pediatric population as well as in preventing the development of musculoskeletal diseases in adulthood.

Comparison of Post-Cesarean Pain Perception of General Versus Regional Anesthesia, a Single-Center Study.

Background and Objectives: Pain during and after the procedure remains the leading concern among women undergoing cesarean section. Numerous studies have concluded that the type of anesthesia used during a cesarean section undoubtedly affects the intensity and experience of pain after the operation. Materials and Methods: This prospective cohort study was conducted at the Clinic for Gynecology and Obstetrics, Clinical Center "Dragisa Misovic-Dedinje", Belgrade, Serbia. Patients at term pregnancy (37-42 weeks of gestation) with an ASA I score who delivered under general (GEA) or regional anesthesia (RA) by cesarean section were included in the study. Following the procedure, we assessed pain using the Serbian McGill questionnaire (SF-MPQ), Visual Analogue Scale (VAS) and the pain attributes questionnaire at pre-established time intervals of 2, 12, and 24 h after the procedure. Additionally, time to patient's functional recovery was noted. We also recorded the time to the first independent mobilization, first oral intake, and lactation establishment. Results: GEA was performed for 284 deliveries while RA was performed for 249. GEA had significantly higher postoperative sensory and affective pain levels within intervals of 2, 12, and 24 h after cesarean section. GEA had significantly higher postoperative VAS pain levels. On pain attribute scale intensity, GEA had significantly higher postoperative pain levels within all intervals. Patients who received RA had a shorter time to first oral food intake, first independent mobilization, and faster lactation onset in contrast to GEA. Conclusions: The application of RA presented superior postoperative pain relief, resulting in earlier mobilization, shorter time to first oral food intake, and faster lactation onset in contrast to GEA.

How accurate are citations of frequently cited papers in biomedical literature?

Citations are an important, but often overlooked, part of every scientific paper. They allow the reader to trace the flow of evidence, serving as a gateway to relevant literature. Most scientists are aware of citations' errors, but few appreciate the prevalence of these problems. The purpose of the present study was to examine how often frequently cited papers in biomedical scientific literature are cited inaccurately. The study included an active participation of the first authors of included papers; to first-hand verify the citations accuracy. Findings from feasibility study, where we reviewed 1540 articles containing 2526 citations of 14 most cited articles in which the authors were affiliated with the Faculty of Medicine University of Belgrade, were further evaluated for external confirmation in an independent verification set of articles. Verification set included 4912 citations identified in 2995 articles that cited 13 most cited articles published by authors affiliated with the Mayo Clinic Division of Nephrology and Hypertension. A citation was defined as being accurate if the cited article supported or was in accordance with the statement by citing authors. At least one inaccurate citation was found in 11 and 15% of articles in the feasibility study and verification set, respectively, suggesting that inaccurate citations are common in biomedical literature. The most common problem was the citation of nonexistent findings (38.4%), followed by an incorrect interpretation of findings (15.4%). One-fifth of inaccurate citations were due to chains of inaccurate citations. Based on these findings, several actions to reduce citation inaccuracies have been proposed.

Colonic Diverticulosis and Non-Alcoholic Fatty Liver Disease: Is There a Connection?

Background and Objectives: The development and severity of colonic diverticulosis and non-alcoholic fatty liver disease (NAFLD) has been associated with several components of metabolic syndrome (MetS). Therefore, this study aimed to evaluate a possible connection between NAFLD, colonic diverticulosis, and MetS. Materials and Methods: This retrospective study included patients diagnosed with diverticulosis between January 2017 and December 2019. Data regarding the patient demographics, Diverticular Inflammation and Complication Assessment (DICA) score and category, disease localization, hepatic steatosis, blood pressure, comprehensive metabolic panel, need for colonic surgery, and co-morbidities were collected from medical records. Results: A total of 407 patients with a median age of 68 years (range, 34-89 years) were included (male: 53.81%). The majority was diagnosed with left-sided diverticulosis (n = 367, 90.17%) and an uncomplicated disease course (DICA category 1, n = 347, 85.3%). Concomitant hepatic steatosis was detected in 47.42% (n = 193) of patients. The systolic blood pressure, triglycerides, total cholesterol, C-reactive protein (CRP), and fasting glucose were higher in the NAFLD group (p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively). A higher prevalence of hypertension (HTA), type 2 diabetes mellitus (T2DM), and hypothyroidism was noted in the same group of patients (p < 0.001, p < 0.001, and p = 0.008, respectively). High-density lipoprotein cholesterol was lower in patients with more severe forms of diverticulosis (DICA category 2 and 3), while CRP levels were significantly higher (p = 0.006 and p = 0.015, respectively). HTA and NAFLD were more common in patients with more severe forms of colonic diverticulosis (p = 0.016 and p = 0.025, respectively). Using a multivariate logistic regression, the DICA score, CRP, total cholesterol, HTA, and hypothyroidism were identified as discriminating factors for the presence of hepatic steatosis. Conclusion: Components of metabolic dysregulation were prominent in patients diagnosed with colonic diverticulosis and concomitant hepatic steatosis. HTA, T2DM, and hypothyroidism were more frequently observed in this group. Hepatic steatosis was more commonly detected in more severe forms of colonic diverticulosis.

Quality of Life of Informal Caregivers behind the Scene of the COVID-19 Epidemic in Serbia.

Background and objectives: The COVID-19 pandemic has had an unprecedented reliance on informal caregivers as one of the pillars of healthcare systems. The aim of this study was to assess the quality of life of informal caregivers during the COVID-19 epidemic in Serbia. Materials and Methods: A cross-sectional study was conducted among informal caregivers during the COVID-19 epidemic in Serbia. Physical and mental quality of life was measured by the 36-Item Short-Form Health Survey. Additional data included sociodemographic characteristics, caregiver and care recipient characteristics, and COVID-19 related concerns. The qualitative component was performed using focus groups and individual in-depth interviews. Results: Out of 112 informal caregivers enrolled, most were female (80%), and the average age was 51.1 ± 12.3 years. The majority was delivering care to one person, who was a family member, on a daily basis (86.4%, 92%, and 91.1%, respectively). In multiple regression models, significant predictors of caregivers' physical health were delivering care to a family member and a higher level of care complexity, while significant predictors of caregivers' mental health were a higher level of care complexity and increased concerns about self-health and the health of the person being cared for due to the COVID-19 epidemic. Conclusions: Informal caregivers are experiencing negative physical and mental health outcomes during the COVID-19 epidemic in Serbia.

Musculoskeletal Diseases as the Most Prevalent Component of Multimorbidity: A Population-Based Study.

Background/Objectives: Due to their high frequency, common risk factors, and similar pathogenic mechanisms, musculoskeletal disorders (MSDs) are more likely to occur with other chronic illnesses, making them a "component disorder" of multimorbidity. Our objective was to assess the prevalence of multimorbidity and to identify the most common clusters of diagnosis within multimorbidity states, with the primary hypothesis that the most common clusters of multimorbidity are MSDs. Methods: The current study employed data from a population-based 2019 European Health Interview Survey (EHIS). Multimorbidity was defined as a ≥2 diagnosis from the list of 17 chronic non-communicable diseases, and to define clusters, the statistical method of hierarchical cluster analysis (HCA) was performed. Results: Out of 13,178 respondents, multimorbidity was present among 4398 (33.4%). The HCA method yielded six multimorbidity clusters representing the most common diagnoses. The primary multimorbidity cluster, which was prevalent among both genders, age groups, incomes per capita, and statistical regions, consisted of three diagnoses: (1) lower spine deformity or other chronic back problem (back pain), (2) cervical deformity or other chronic problem with the cervical spine, and (3) osteoarthritis. Conclusions: Given the influence of musculoskeletal disorders on multimorbidity, it is imperative to implement appropriate measures to assist patients in relieving the physical discomfort and pain they endure. Public health information, programs, and campaigns should be utilized to promote a healthy lifestyle. Policymakers should prioritize the prevention of MSDs by encouraging increased physical activity and a healthy diet, as well as focusing on improving functional abilities.

Attitudes Toward Plagiarism Among PhD Medical Students in Serbia.

In this cross-sectional survey the Attitude Towards Plagiarism (ATP) questionnaire was administered to 100 PhD students to measure their attitudes towards plagiarism. The results showed that the students had low scores for positive attitudes and subjective norms, but moderate scores for negative attitudes towards plagiarism. Additional courses on plagiarism should be introduced in PhD studies to promote responsible research practices in Serbia.

Psychometric Properties of the Serbian Version of the Attitudes Towards Research Questionnaire.

Participating in research plays an essential role in improving the practice of healthcare. This cross-sectional study enrolled 100PhD students who attended the course "Informatics for researchers" at Medical Faculty University of Belgrade. The total ATR scale demonstrated excellent reliability (α=0.899) with 0.881 for Positive attitudes to 0.695 for Relevance to life. PhD students in Serbia showed high degree of positive attitudes toward research. Faculty could administer ATR scale to determine students' standpoints towards research, to maximize the impact of the research course and enhance participation in research.

The Predictive Value of Risk Factors and Prognostic Scores in Hospitalized COVID-19 Patients.

INTRODUCTION: Risk stratification in patients with COVID-19 is a challenging task. Early warning scores (EWSs) are commonly used tools in the initial assessment of critical patients. However, their utility in patients with COVID-19 is still undetermined. AIM: This study aimed to discover the most valuable predictive model among existing EWSs for ICU admissions and mortality in COVID-19 patients. MATERIALS AND METHODS: This was a single-center cohort study that included 3608 COVID-19 patients admitted to the University Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia, between 23 June 2020, and 14 April 2021. Various demographic, laboratory, and clinical data were collected to calculate several EWSs and determine their efficacy. For all 3608 patients, five EWSs were calculated (MEWS, NEWS, NEWS2, REMS, and qSOFA). Model discrimination performance was tested using sensitivity, specificity, and positive and negative predictive values. C statistic, representing the area under the receiver operating characteristic (ROC) curve, was used for the overall assessment of the predictive model. RESULTS: Among the evaluated prediction scores for 3068 patients with COVID-19, REMS demonstrated the highest diagnostic performance with the sensitivity, PPV, specificity, and NPV of 72.1%, 20.6%, 74.9%, and 96.8%, respectively. In the multivariate logistic regression analysis, aside from REMS, age (p < 0.001), higher CT score (p < 0.001), higher values of urea (p < 0.001), and the presence of bacterial superinfection (p < 0.001) were significant predictors of mortality. CONCLUSIONS: Among all evaluated EWSs to predict mortality and ICU admission in COVID-19 patients, the REMS score demonstrated the highest efficacy.

From Sarcopenia to Depressive Symptoms in Elderly: A Path Analysis.

BACKGROUND: Sarcopenia is an age-related progressive, generalized skeletal muscle disorder involving the accelerated loss of muscle function and muscle mass. The aim of this study was to assess the complex relationship between sarcopenia, malnutrition, cognitive impairment, physical activity, and depression in the elderly, with the potential role of quality of life as a mediator in these associations. METHODS: A cross-sectional study was conducted on a sample (n = 298) of elderly patients admitted to Special Hospital for Rehabilitation "Termal", Vrdnik, Serbia. Sarcopenia, the risk for malnutrition, cognitive impairment, physical activity, quality of life, and depressive symptoms were measured by standardized instruments. Additional data included sociodemographic characteristics. Simultaneous assessment of the direct and indirect relationships of all determinants was performed by path analysis. RESULTS: A total of 40% (n = 120) of the elderly were diagnosed with sarcopenia, and 42.6% had depression symptoms. The risk of malnutrition was present in 23.5%, cognitive impairment in 5.4%, and a low level of physical activity was reported in 26.2% of elderly participants. The mean reported quality of life measured by Sarcopenia and Quality of Life Questionnaire was 60 (on the scale ranging from 0 to 100; where a higher score reflects a higher quality of life). The best-fitted model (χ2/DF = 1.885, NFI = 0.987, CFI = 0.993, GFI = 0.997, RMSEA = 0.055) highlighted the mediating effect of quality of life between sarcopenia, malnutrition, cognitive impairment, lower level of physical activities and depression. According to the model, quality of life was a direct negative predictor of depressive symptoms in the elderly, while malnutrition positively affected depression. CONCLUSIONS: The presented path model may assist rehabilitation centers in developing strategies to screen for sarcopenia and risk of malnutrition, and promote physical activity in elderly, aiming to prevent their negative effects on mental health. For the elderly currently affected by sarcopenia, we consider regenerative medicine and stem cell therapy, which, in view of their etiology, could be a potential therapeutic strategy for sarcopenia.

Effect of regional vs general anesthesia on vital functions after cesarean section: a single center experience.

BACKGROUND: The aim was to determine the effect of regional anesthesia (RA) on postoperative vital functions in contrast to general endotracheal anesthesia (GEA) after the cesarean section. METHODS: Prospective cohort study included consecutive term pregnant women delivered by cesarean section (GEA, n = 284; RA, n = 249). RESULTS: Higher levels of blood pressure and heart rate, as well as lower levels of pulse oximetry were found for GEA in contrast to RA (p < 0.001). The application of RA presented less side-effects (p < 0.05). CONCLUSIONS: RA for cesarean section should be preferred when balancing the risks and benefits for the mother and fetus.

Correlation of Dyslipidemia and Inflammation With Obstructive Sleep Apnea Severity.

Introduction: Obstructive sleep apnea (OSA) is a serious condition linked with various metabolic disorders and associated with increased all-cause and cardiovascular mortality. Although the potential mechanisms of pathophysiological processes related to OSA are relatively well known, the data regarding the correlation between obstructive sleep apnea, dyslipidemia, and systemic inflammation are still inconclusive. Methods: The study was conducted as a retrospective cohort study including 328 patients with newly diagnosed obstructive sleep apnea during the period between April 2018, and May 2020, in University Clinical Hospital Center "Bezanijska kosa", Belgrade, Serbia. Polysomnography was performed in all patients according to the protocol. Numerous demographic, antropometric, laboratory, and clinical data were correlated to Apnea-Hypopnea Index (AHI) as a dependent variable, with a particular review on the relation between lipid abnormalities, inflammatory parameters, and obstructive sleep apnea severity. Multivariate logistic regression model was used to assess predictors of severe OSA (AHI ≥30 per hour). Results: A total of 328 patients were included in the study. The mean age of the patients was 54.0 ± 12.5 years and more than two-thirds were male (68.8%). The majority of the patients had an AHI of at least 30 events per hour. Patients with severe OSA were more frequently male, obese, hypertensive and hyperlipidemic, and had increased neck circumference (both male and female patients). One hundred and thirty-two patients had metabolic syndrome. Patients with severe OSA more frequently had metabolic syndrome and significantly higher levels of glucose, creatinine, uric acid, AST, ALT, CK, microalbumine/creatinine ratio, triglyceride, total cholesterol, HDL, total cholеsterol to HDL-C ratio, CRP, and ESR. In the multivariate linear regression model with AHI (≥30 per hour) as a dependent variable, of demographic and clinical data, triglycerides ≥1.7 mmol/L and CRP >5 mg/L were significantly associated with AHI≥30 per hour. Conclusion: The present study on 328 patients with newly diagnosed obstructive sleep apnea revealed significant relation of lipid abnormalities, inflammatory markers, and other clinically important data with obstructive sleep apnea severity. These results can lead to a better understanding of the underlying pathophysiological processes and open the door to a new world of potentially useful therapeutic modalities.

Obstructive Sleep Apnea and Cardiovascular Risk: The Role of Dyslipidemia, Inflammation, and Obesity.

Introduction: The present study aimed to establish the role of lipid abnormalities and inflammatory markers for developing cardiovascular risk, as well as to address the importance of obesity as a common comorbidity in patients with obstructive sleep apnea (OSA). Methods: The study was conducted as a prospective cohort study including 120 patients with newly diagnosed OSA between 2019 and 2020, at University Clinical Hospital Center "Bezanijska kosa", Belgrade, Serbia. The diagnosis was established by polysomnography. In all patients, sociodemographic data, respiratory, lipid, and inflammatory parameters were collected and complete echocardiographic study and 24-h blood pressure monitoring were performed. Results: The mean patient age was 55.7 ± 13.8 years. Study population was mostly male (70.0%) and obese (56.7%). At least 30 apneas or hypopneas per hour were present in 39.0% of patients. A strong positive correlation was found between OSA severity and BMI (r = 0.562, p < 0.001), both associated with lipid, inflammatory and respiratory parameters, and cardiovascular profile of patients with OSA (p < 0.05 for all). Echocardiographic study and 24-h blood pressure monitoring parameters were in turn correlated with lipid and inflammatory markers (p < 0.05 for all). Conclusion: The results of this study support the important role of dyslipidemia and inflammation, as well as coexistence of obesity in the pathogenesis of numerous conditions linked with an increased risk of cardiovascular morbidity and mortality in patients with OSA.

Point-of-Care Echocardiographic Characteristics of COVID-19 Patients with Pulmonary Embolism.

INTRODUCTION: Thrombotic complications, such as pulmonary embolism, are common in COVID-19 patients. Point-of-care ultrasound is a highly recommended tool for orientation in critically ill patients with suspected or confirmed complications. METHODS: An observational study was conducted on 32 consecutive patients with confirmed pulmonary embolism and COVID-19 infection treated in the Intensive Care Unit of the University Hospital Medical Center "Bezanijska kosa", Belgrade, Serbia, between April 2021 and March 2022. Predictors of the need for oxygen support were determined, while point-of-care echocardiographic parameters and various anamnestic, laboratory, and clinically significant parameters were correlated with the Pulmonary Embolism Severity Index (PESI) score. RESULTS: More than two-thirds of patients in our study had PE symptoms present at hospital admission (68.8%). The majority of patients had segmental pulmonary embolism (48.4%), with high to very high PESI score values in 31.3% of patients. Pneumonia was present in 68.8% of the study population. The PESI score was negatively correlated with diastolic blood pressure and SaO2 at the time of PE diagnosis, LV ejection fraction, and PVAT. A positive correlation was found between the PESI score, maximum CRP, and D-dimer at the time of PTE diagnosis. A larger right ventricular diameter was associated with a greater need for oxygen support. CONCLUSION: Point-of-care echocardiography is a valuable tool for the risk assessment of COVID-19 patients with pulmonary embolism. Right ventricular size stood out as a significant marker of disease severity.

Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL.

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. METHODS: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. RESULTS: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017-1.109 and OR = 2.438, 95%CI 1.023-5.813, respectively). CONCLUSIONS: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

Meta-Analysis of Circulating Cell-Free DNA's Role in the Prognosis of Pancreatic Cancer.

INTRODUCTION: The analysis of cell-free DNA (cfDNA) for genetic abnormalities is a promising new approach for the diagnosis and prognosis of pancreatic cancer patients. Insights into the molecular characteristics of pancreatic cancer may provide valuable information, leading to its earlier detection and the development of targeted therapies. MATERIAL AND METHODS: We conducted a systematic review and a meta-analysis of studies that reported cfDNA in pancreatic ductal adenocarcinoma (PDAC). The studies were considered eligible if they included patients with PDAC, if they had blood tests for cfDNA/ctDNA, and if they analyzed the prognostic value of cfDNA/ctDNA for patients' survival. The studies published before 22 October 2020 were identified through the PubMED, EMBASE, Web of Science and Cochrane Library databases. The assessed outcomes were the overall (OS) and progression-free survival (PFS), expressed as the log hazard ratio (HR) and standard error (SE). The summary of the HR effect size was estimated by pooling the individual trial results using the Review Manager, version 5.3, Cochrane Collaboration. The heterogeneity was assessed using the Cochran Q test and I2 statistic. RESULTS: In total, 48 studies were included in the qualitative review, while 44 were assessed in the quantitative synthesis, with the total number of patients included being 3524. Overall negative impacts of cfDNA and KRAS mutations on OS and PFS in PDAC (HR = 2.42, 95% CI: 1.95-2.99 and HR = 2.46, 95% CI: 2.01-3.00, respectively) were found. The subgroup analysis of the locally advanced and metastatic disease presented similar results (HR = 2.51, 95% CI: 1.90-3.31). In the studies assessing the pre-treatment presence of KRAS, there was a moderate to high degree of heterogeneity (I2 = 87% and I2 = 48%, for OS and PFS, respectively), which was remarkably decreased in the analysis of the studies measuring post-treatment KRAS (I2 = 24% and I2 = 0%, for OS and PFS, respectively). The patients who were KRAS positive before but KRAS negative after treatment had a better prognosis than the persistently KRAS-positive patients (HR = 5.30, 95% CI: 1.02-27.63). CONCLUSION: The assessment of KRAS mutation by liquid biopsy can be considered as an additional tool for the estimation of the disease course and outcome in PDAC patients.

From Burden to Depressive Symptoms in Informal Caregivers during the COVID-19 Pandemic: A Path Analysis.

BACKGROUND: The objective of this study was to assess the complex relationship between the multiple determinants of the caregiving process, the caregiver burden, and depression during the COVID-19 pandemic in Serbia. METHODS: A cross-sectional study was conducted on a nationally representative sample (n = 798) during the COVID-19 pandemic in Serbia from March to September 2020. A nine-section questionnaire designed for this study included the characteristics of caregivers, characteristics of care and care recipients, COVID-19 related questions, and the following standardized instruments: 12-Item Short-Form Health Survey, Fatigue Severity Scale, Activities of Daily Living Scale and Instrumental Activities of Daily Living Scale, Zarit Caregiver Burden Scale, and Beck Depression Inventory. Path analysis was used for the simultaneous assessment of the direct and indirect relationships of all determinants. RESULTS: More than two thirds (71.9%) of informal caregivers experienced a burden, and more than one quarter (27.1%) had depression symptomatology. Self-rated physical health, need for psychosocial support, and caregiver burden were the main direct predictors of depression. Multiple determinants of the caregiving process had indirect effects on depressive symptomatology via the caregiver burden as a mediating factor. CONCLUSIONS: The subjective burden presented a significant risk factor for depressive symptoms in caregivers during the COVID-19 pandemic. The provision of psychosocial support was identified as an important opportunity to reduce depressive risk in informal caregivers.