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.

Epstein-Barr virus infection as potential indicator of the occurrence and clinical presentation of systemic lupus erythematosus.

Introduction: The relationship between Systemic lupus erythematosus (SLE) and Epstein-Barr virus (EBV) infection has been suggested for decades, but the underlying mechanism of the EBV influence on SLE development remains to be elucidated. Methods: The goals of this research, which included 103 SLE patients and 99 controls, were to investigate the association of the parameters of EBV infection and SLE, to explore whether pooled demographic, clinical and EBV markers achieve a more significant effect on SLE development than each of them individually, and to evaluate EBV nuclear antigen 1 (EBNA1) and latent membrane protein 1 (LMP1) gene polymorphisms in isolates from SLE patients. Results: Comprehensive results related to serological, molecular and sequence markers of EBV infection in SLE patients demonstrated even 24 times higher possibility of having SLE if there is the presence of anti-EBV-EA(D) (early antigen) IgG antibodies (OR=24.086 95%CI OR=2.86-216.07, p=0.004). There was the same distribution of glucocorticoids (p=0.130), antimalarials (p=0.213), and immunosuppressives (p=0.712) in anti-EBV-EA(D) IgG positive and negative SLE patients. Further, higher anti-EBV-EA(D) IgG antibodies titers were identified as independent factors associated with lymphopenia, hematological SLE manifestation (OR=1.041, 95%CI OR=1.01-1.08, p=0.025, while a higher titer of anti-CA (viral capsid antigen) IgG antibodies (OR=1.015, 95%CI OR=1.01-1.03, p=0.019) and positive RF (rheumatoid factors) (OR=4.871, 95%CI OR=1.52-15.61, p=0.008) were identified as independent factors associated with alopecia within SLE. Finally, novel data on EBV EBNA1 and LMP1 gene polymorphisms in lupus are reported. Conclusion: The results support further investigation targeting EBV as a prognostic marker and therapeutic goal for lupus.

Uncovering the Role of Epstein-Barr Virus Infection Markers for Remission in Rheumatoid Arthritis.

Epstein-Barr virus (EBV) infection has been shown as a potential risk factor for the development of rheumatoid arthritis (RA). This prospective research aimed to investigate whether EBV infection markers changed during the six-month follow-up period in 133 RA patients (80 newly diagnosed on methotrexate (MTX)-RA-A, and 53 on biologic therapy-RA-B) and whether it was related to a disease outcome. Reduction of disease activity and inflammation was obtained. A significant decline in seroprevalence and titer for anti-VCA-IgM (p = 0.022 and p = 0.026) and anti-EA(D)-IgM (p = 0.022 and p = 0.006) in RA-A, and in seroprevalence and titer of anti-EA(D)-IgG in the RA-B subgroup (p = 0.021 and p = 0.006) were detected after the follow-up. A lower titer of anti-EBNA1-IgG could be considered a significant marker of RA remission in all RA patients regardless of age and gender (OR = 0.99, 95% CI OR = 0.98-0.99, p = 0.038), and also in RA-B patients separately (OR = 0.988, 95% CI OR = 0.98-0.99, p = 0.041). This study supported the basic hypothesis that the immune response to EBV infection is involved in the RA pathogenesis, at the beginning of the disease or during the RA evolution. Moreover, the potential influence of MTX or TNF-alpha inhibitors on the impairment of the host to control EBV infection was indirectly refuted.

Doppler Indices of the Uterine, Umbilical and Fetal Middle Cerebral Artery in Diabetic versus Non-Diabetic Pregnancy: Systematic Review and Meta-Analysis.

Background and Objectives: The aim of this study was to assess the differences in Doppler indices of the uterine (Ut), umbilical (UA), and middle cerebral artery (MCA) in diabetic versus non-diabetic pregnancies by conducting a comprehensive systematic review of the literature with a meta-analysis. Materials and Methods: PubMed, Web of Science, and SCOPUS were searched for studies that measured the pulsatility index (PI), resistance index (RI), and systolic/diastolic ratio index (S/D ratio) of the umbilical artery, middle cerebral artery, and uterine artery in diabetic versus non-diabetic pregnancies. Two reviewers independently evaluated the eligibility of studies, abstracted data, and performed quality assessments according to standardized protocols. The standardized mean difference (SMD) was used as a measure of effect size. Heterogeneity was assessed using the I2 statistic. Publication bias was evaluated by means of funnel plots. Results: A total of 62 publications were included in the qualitative and 43 in quantitative analysis. The UA-RI, UtA-PI, and UtA-S/D ratios were increased in diabetic compared with non-diabetic pregnancies. Subgroup analysis showed that levels of UtA-PI were significantly higher during the third, but not during the first trimester of pregnancy in diabetic versus non-diabetic pregnancies. No differences were found for the UA-PI, UA-S/D ratio, MCA-PI, MCA-RI, MCA-S/D ratio, or UtA-RI between diabetic and non-diabetic pregnancies. Conclusions: This meta-analysis revealed the presence of hemodynamic changes in uterine and umbilical arteries, but not in the middle cerebral artery in pregnancies complicated by diabetes.

Markers of Epstein-Barr Virus Infection in Association with the Onset and Poor Control of Rheumatoid Arthritis: A Prospective Cohort Study.

Although the connection between Epstein-Barr virus (EBV) and rheumatoid arthritis (RA) has been studied for over 40 years, many questions still need clarification. The study aimed to analyze the possible association between anti-EBV antibody titers, EBV DNA viremia, EBV infection status and EBNA1 (Epstein-Barr nuclear antigen 1-EBNA1) variants and clinical parameters of RA patients. This prospective cohort study included 133 RA patients and 50 healthy controls. Active/recent EBV infection was more prevalent in RA patients than in controls (42% vs. 16%, p < 0.001). RA patients had higher titers of anti-EBV-CA-IgM (capsid antigen-CA) and anti-EBV-EA(D)-IgG (early antigen-EA) antibodies than controls (p = 0.003 and p = 0.023, respectively). Lower levels of anti-EBNA1-IgG and anti-EBV-CA-IgG were observed in RA patients who received methotrexate (anti-EBNA1 IgG p < 0.001; anti-EBV-CA IgG p < 0.001). Based on amino acid residue on position 487, two EBNA1 prototypes were detected: P-Thr and P-Ala. Patients with active/recent EBV infection had a five times more chance of having RA and a nearly six times more chance of getting RA. Also, EBV active/recent infection is twice more likely in newly diagnosed than in methotrexate-treated patients. Further studies are needed to clarify "who is the chicken and who is the egg" in this EBV-RA relationship.

IL-23/IL-17 Axis in Chronic Hepatitis C and Non-Alcoholic Steatohepatitis-New Insight into Immunohepatotoxicity of Different Chronic Liver Diseases.

Considering the relevance of the research of pathogenesis of different liver diseases, we investigated the possible activity of the IL-23/IL-17 axis on the immunohepatotoxicity of two etiologically different chronic liver diseases. A total of 36 chronic hepatitis C (CHC) patients, 16 with (CHC-SF) and 20 without significant fibrosis (CHC-NSF), 19 patients with non-alcoholic steatohepatitis (NASH), and 20 healthy controls (CG) were recruited. Anthropometric, biochemical, and immunological cytokines (IL-6, IL-10, IL-17 and IL-23) tests were performed in accordance with standard procedure. Our analysis revealed that a higher concentration of plasma IL-23 was associated with NASH (p = 0.005), and a higher concentration of plasma IL-17A but a lower concentration of plasma IL-10 was associated with CHC in comparison with CG. A lower concentration of plasma IL-10 was specific for CHC-NSF, while a higher concentration of plasma IL-17A was specific for CHC-SF in comparison with CG. CHC-NSF and CHC-SF groups were distinguished from NASH according to a lower concentration of plasma IL-17A. Liver tissue levels of IL-17A and IL-23 in CHC-NSF were significantly lower in comparison with NASH, regardless of the same stage of the liver fibrosis, whereas only IL-17A tissue levels showed a difference between the CHC-NSF and CHC-SF groups, namely, a lower concentration in CHC-NSF in comparison with CHC-SF. In CHC-SF and NASH liver tissue, IL17-A and IL-23 were significantly higher in comparison with plasma. Diagnostic accuracy analysis showed significance only in the concentration of plasma cytokines. Plasma IL-6, IL-17A and IL-23 could be possible markers that could differentiate CHC patients from controls. Plasma IL-23 could be considered a possible biomarker of CHC-NSF patients in comparison with controls, while plasma IL-6 and IL-17-A could be biomarkers of CHC-SF patients in comparison with controls. The most sophisticated difference was between the CHC-SF and CHC-NSF groups in the plasma levels of IL-10, which could make this cytokine a useful biomarker of liver fibrosis.

Association of IL10RA, IL10RB, and IL22RA Polymorphisms/Haplotypes with Susceptibility to and Clinical Manifestations of SLE.

Systemic lupus erythematosus (SLE) is characterized by an imbalance between proinflammatory and anti-inflammatory mediators. Single-nucleotide polymorphisms (SNPs) in genes coding IL10RA, IL10RB, and IL22RA could affect their expression or function and disrupt immune homeostasis. We aimed to analyze the associations of IL10RA, IL10RB, and IL22RA polymorphisms/haplotypes with patients' susceptibility to and clinical manifestations of SLE. Our study included 103 SLE patients and 99 healthy controls. The genotypes of the selected polymorphisms within IL10RA (rs10892202, rs4252270, rs3135932, rs2228055, rs2229113, and rs9610), IL10RB (rs999788, rs2834167, and rs1058867), and IL22RA (rs3795299 and rs16829204) genes were determined by TaqMan® Assays. IL10RB rs1058867 G allele carriers were significantly more frequent among the controls than among the SLE patients (76.8% vs. 61.2%; p = 0.017, OR = 0.477, 95% CI: 0.258-0.879). The IL10RB CAA haplotype was more frequent among the SLE patients than in the control group (42.7% vs. 30.7%; p = 0.027). The IL22RA rs3795299 C allele and rs16829204 CC genotype were associated with Hashimoto thyroiditis in the SLE patients (n = 103; p = 0.002 and p = 0.026, respectively), and in all the included participants (n = 202, p < 0.000 and p = 0.007, respectively), and the IL22RA CC haplotype was more frequent in the SLE patients with Hashimoto thyroiditis (p = 0.047) and in the overall participants with Hashimoto thyroiditis (n = 32, p = 0.004). The IL10RA, IL10RB, and IL22RA polymorphisms/haplotypes could be associated with SLE susceptibility and various clinical manifestations, and the IL22RA CC haplotype could be associated with Hashimoto thyroiditis.

Oxidative Stress and Inflammation Biomarkers in Postoperative Pain Modulation in Surgically Treated Patients with Laryngeal Cancer-Pilot Study.

(1) Background: Surgical treatment of laryngeal carcinoma includes different types of laryngectomies with neck dissection. Surgical tissue damage triggers an inflammatory response, leading to the release of pro-inflammatory molecules. This increases reactive oxygen species production and decreases antioxidant defense mechanisms, leading to postoperative oxidative stress. The aim of this study was to assess the correlation between oxidative stress (malondialdehyde, MDA; glutathione peroxidase, GPX; superoxide dismutase, SOD) and inflammation (interleukin 1, IL-1; interleukin-6, IL-6; C-reactive protein, CRP) parameters and postoperative pain management in patients surgically treated with laryngeal cancer. (2) Methods: This prospective study included 28 patients with surgically treated laryngeal cancer. Blood samples were taken for the analysis of oxidative stress and inflammation parameters before the operative treatment and after the operative treatment (1st postoperative day and 7th postoperative day). The concentrations of MDA, SOD, GPX, IL-1, IL-6, and CRP in the serum were determined by coated enzyme-linked immunosorbent assay (ELISA). The visual analog scale (VAS) was used for pain assessment. (3) Results and conclusion: There was a correlation between oxidative stress and inflammation biomarkers and postoperative pain modulation in surgically treated patients with laryngeal cancer. Age, more extensive surgery, CRP values, and use of tramadol were predictors for oxidative stress parameters.

The main predictive factors of worse outcome in patients with COVID-19 infection hospitalized in temporary COVID hospital.

INTRODUCTION: After the Serbian community hospitals had reached their full capacity during the pandemic, new institutions were enrolled into the coronavirus disease 2019 (COVID-19) system as temporary COVID hospitals (TCH). These hospitals usually had no intensive care units (ICU) and no possibility to treat severely ill patients. The aim of this study was to identify risk factors at the time of triage that could help identify patients that will require ICU treatment and cannot be treated in a TCH. METHODOLOGY: In this retrospective study, a total of 158 patients with COVID-19 infection were enrolled. The demographic information, underlying comorbidities, laboratory findings, chest X-rays, computed tomography scans, and clinical outcomes were obtained from medical records. Deterioration of a patient's condition was regarded as a need for further transfer to ICU. RESULTS: During the hospitalization 15.2% of patients required transfer to ICU. Patients with deterioration were significantly older and there was no difference between genders. We observed a higher prevalence of hypertension, other cardiovascular diseases, lower lymphocyte and platelet counts, and higher IL-6 and troponin T in patients with deterioration. The multivariate logistical regression model showed that only age was an independent risk factor for deterioration and with each year of age, the risk for poor outcome increased by 8%. CONCLUSIONS: Patients with cardiovascular risk factors, low lymphocyte and platelet counts, high IL-6 and troponin T and, especially, increased age should not be treated in a TCH because of the high possibility for deterioration and need for transfer to an ICU.

Epstein-Barr Virus Reactivation as a New Predictor of Achieving Remission or Lupus Low Disease Activity State in Patients with Systemic Lupus Erythematosus with Cutaneous Involvement.

Although Epstein-Barr virus (EBV) reactivation has long been associated with the pathogenesis of systemic lupus erythematosus (SLE), many aspects of this relationship remain unclear. Our objective was to investigate the association between EBV reactivation and the achievement of SLE remission and lupus low disease activity state (LLDAS) over a six-month period. Clinical, laboratory, and virological tests (anti-EBV antibodies and EBV DNA) were performed among 51 patients with the active form of SLE on two occasions six months apart. SLE remission and LLDAS achievement were assessed at the end of the follow-up period. Active EBV infection was detected in 45% of active SLE patients at baseline, and 77% transitioned to latent EBV infection at six months (p < 0.001). Multivariate regression revealed a higher titer of anti-EA(D) IgM-Abs and the presence of anti-EA(D) IgM-Abs as independent predictors of remission and LLDAS in SLE patients with mucocutaneous manifestations (p = 0.042) and rash only (p = 0.023), respectively. Since a higher C3 level was an independent predictor of transition to latent EBV infection (p = 0.027), the estimated cut-off value that could identify active SLE patients who will transition to latent EBV infection after six months was ≥0.780 g/L with a sensitivity of 70.6% and a specificity of 75.0% (AUC = 0.756, p = 0.003). EBV reactivation is common in patients with active SLE, and most of them transition to latent EBV infection after six months. Achieving remission and LLDAS in SLE patients with mucocutaneous manifestations can be predicted by a higher titer, whereas in SLE patients who have only a rash, the presence of anti-EA (D) IgM-Abs was a predictor of remission and LLDAS.

Molecular profiling of rare thymoma using next-generation sequencing: meta-analysis.

BACKGROUND: Thymomas belong to rare tumors giving rise to thymic epithelial tissue. There is a classification of several forms of thymoma: A, AB, B1, B2, B3, thymic carcinoma (TC) and thymic neuroendocrine thymoma. In this meta-analysis study, we have focused on thymoma using articles based on the disease's next-generation sequencing (NGS) genomic profiling. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of the prevalence of studies that discovered the genes and variants occurring in the less aggressive forms of the thymic epithelial tumors. Studies published before 12th December 2022 were identified through PubMed, Web of Science (WoS), and SCOPUS databases. Two reviewers have searched for the bases and selected the articles for the final analysis, based on well-defined exclusion and inclusion criteria. RESULTS: Finally, 12 publications were included in the qualitative as well as quantitative analysis. The three genes, GTF2I, TP53, and HRAS, emerged as disease-significant in the observed studies. The Odds Ratio for all three extracted genes GTF2I (OR = 1.58, CI [1.51, 1.66] p < 0.00001), TP53 (OR = 1.36, CI [1.12, 1.65], p < 0.002), and HRAS (OR = 1.02, CI [1.00, 1.04], p < 0.001). CONCLUSIONS: According to obtained data, we noticed that the GTF2I gene exhibits a significant prevalence in the cohort of observed thymoma patients. Moreover, analyzing published articles NGS has suggested GTF2I, TP53, and HRAS genes as the most frequently mutated genes in thymoma that have pathogenic single nucleotide variants (SNV) and Insertion/Deletion (InDel), which contribute to disease development and progression. These variants could be valuable biomarkers and target points specific to thymoma.

Clinical efficacy of anti-SARS-CoV-2 monoclonal antibodies in preventing hospitalisation and mortality among patients infected with Omicron variants: A systematic review and meta-analysis.

Until now, the treatment protocols for COVID-19 have been revised multiple times. The use and approval of therapeutic monoclonal antibodies (mAbs) for COVID-19 treatment represent exceptional achievements in modern science, technology and medicine. SARS-CoV-2 Omicron evasion of pre-existing immunity represents a serious public health problem nowadays. This systematic review with meta-analysis provided comprehensive and up-to-date evidence of the clinical efficacy of therapeutic anti-SARS-CoV-2 mAbs against Omicron subvariants in COVID-19 patients and included 10 articles. The prevalence of hospitalisation among Omicron-positive patients treated with anti-SARS-CoV-2 mAbs was 2.8% (89/3169) while it controls (Omicron-positive patients treated with other therapies) 11% (154/1371). There was a statistically significantly different number of hospitalisations between the two studied groups in favour of the anti-SARS-CoV-2 mAbs treated group. (OR = 0.56, 95% CI OR = 0.41-0.77, p < 0.001, respectively). Eight deaths (0.30%) out of 2619 Omicron-positive patients occurred in the anti-SARS-CoV-2 mAbs treated group, while in the control group (Omicron-positive patients treated with other therapies), 27 patients died out of 1401 (1.93%). There was a significantly different number of deaths between the two studied groups in favour of Omicron-positive patients treated with anti-SARS-CoV-2 mAbs (OR = 0.38, 95% CI OR = 0.17-0.85, p = 0.020). Using sotrovimab in treating Omicron-positive patients indicated a reduction of hospitalisation and mortality for 49% and 89% in favour of sotrovimab, respectively (OR = 0.51, 95% CI OR = 0.34-0.79, p = 0.002; OR = 0.11, 95% CI OR = 0.03-0.39, p = 0.001). We could only provide evidence of the positive impact in reducing hospitalisation and mortality rates when anti-SARS-CoV-2 mAbs were used to treat patients infected with Omicron variants BA.1 or BA.2 and not on other Omicron variants.

Systematic review with meta-analysis of active herpesvirus infections in patients with COVID-19: Old players on the new field.

OBJECTIVES: Herpesviruses are ubiquitous and after primary infection they establish lifelong latency. The impairment of maintaining latency with short-term or long-term consequences could be triggered by other infection. Therefore, reactivation of herpesviruses in COVID-19 patients represents an emerging issue. DESIGN AND METHODS: This study provided the first systematic review with meta-analysis of studies that evaluated active human herpesvirus (HHV) infection (defined as the presence of IgM antibodies or HHV-DNA) in COVID-19 patients and included 36 publications collected by searching through PubMed, SCOPUS, and Web of science until November 2022. RESULTS: The prevalence of active EBV, HHV6, HSV, CMV, HSV1, and VZV infection in COVID-19 population was 41% (95% CI =27%-57%), 3% (95% CI=17%-54%), 28% (95% CI=1%-85%), 25% (95% CI=1%-63%), 22% (95% CI=10%-35%), and 18% (95% CI=4%-34%), respectively. There was a 6 times higher chance for active EBV infection in patients with severe COVID-19 than in non-COVID-19 controls (OR=6.45, 95% CI=1.09-38.13, p=0.040), although there was no difference in the prevalence of all evaluated active herpesvirus infections between COVID-19 patients and non-COVID-19 controls. CONCLUSIONS: Future research of herpesvirus and SARS-CoV-2 coinfections must be prioritized to define: who, when and how to be tested, as well as how to effectively treat HHVs reactivations in acute and long COVID-19 patients.

Hemostatic Markers as Predictors of Massive Blood Transfusion in Orthotopic Liver Transplantation.

BACKGROUND: The aim of this study was to determine which standard preoperative laboratory results correlate to intraoperative transfusion requirement during orthotopic liver transplantation (OLT). MATERIALS AND METHODS: We retrospectively analyzed data from 305 adult patients who underwent OLT between 2009 and 2013 using laboratory results: International Normalization Ratio, platelet count, fibrinogen, and hemoglobin and total blood transfusion requirements (group L ≤ 1 L, group M > 1 L). All statistical analyses were conducted using the Statistical Package for Social Sciences software (IBM Corp. Released 2012. IBM SPSS for Windows, Version 21.0; IBM Corp., Armonk, NY, United States). RESULTS: We found a positive correlation with hemoglobin and fibrinogen using multivariate analysis (P < .001). The receiver operating characteristic analysis in favor of total blood replacement > 1 L has shown a correlation with fibrinogen (cut-off value of 2.3 g/L, sensitivity of 85.8%, and specificity of 37.4%) and hemoglobin (cut-off 111 g/L, sensitivity of 69.9%, and specificity of 71.6%). DISCUSSION AND CONCLUSION: This study has confirmed that preoperative fibrinogen and hemoglobin level, but not International Normalization Ratio and platelet count, are indicators of potential massive perioperative blood loss during OLT and that within our patient cohort a cut-off fibrinogen value of 2.3 g/L and Hb level of 110g/L can predict a blood replacement of >1 L.

New Evidence of Significant Association between EBV Presence and Lymphoproliferative Disorders Susceptibility in Patients with Rheumatoid Arthritis: A Systematic Review with Meta-Analysis.

Development of lymphoproliferative disorders (LPDs) is one of the well-known life-threatening complications in rheumatoid arthritis (RA) patients. However, there is a lack of definitive conclusions regarding the role of Epstein-Barr virus (EBV) activity in RA initiation and progression, especially in promoting LPDs. A systematic review and meta-analysis of studies that reported an EBV positive result in RA-LPD patients and controls were conducted. Studies published before 27 July 2021 were identified through PubMed, Web of Science, and SCOPUS. A total of 79 articles were included in the systematic review. The prevalence of EBV positive result among RA-LPD patients was 54% (OR = 1.54, 95% CI = 1.45-1.64). There was a statistically significant association between EBV presence and LPD susceptibility in RA patients in comparison with all controls (OR = 1.88, 95% CI = 1.29-2.73) and in comparison with LPD patients only (OR = 1.92, 95% CI = 1.15-3.19). This association was not shown in comparison with patients with autoimmune diseases other than RA who developed LPD (OR = 0.79, 95% CI = 0.30-2.09). This meta-analysis confirmed a high prevalence of EBV in the RA-LPD population. Furthermore, it provides evidence for the association between EBV presence and LPD susceptibility in RA patients, but not in those with other autoimmune diseases who developed LPD.

Implementation of Best Practice Guidelines as an Effort in Reducing Hospital Readmission following Coronary Artery Bypass Surgery.

OBJECTIVES: The present study aimed to identify significant causes of readmission within 30 days following coronary artery bypass graft (CABG) surgery and compare readmission incidence related to surgical site infections (SSIs) before and after implementing international recommendations for antibiotic prophylaxis. METHODS: We analyzed 2,225 CABG patients who received either guideline-directed antibiotic prophylaxis (GDAP = 568) or institutional antibiotic prophylaxis (non-GDAP = 1,657) between January 2017 and December 2019. The primary outcome was a composite of sternal wound infection (SWI) or harvest SWI. Secondary outcomes consisted of the individual components of composite end point, the incidence of in-hospital SSIs, and prolonged postoperative length of hospital stay (LOS) (>7 days). Propensity matching was used to select pairs for final comparison. RESULTS: Before implementing GDAP, the most frequent reason for readmission were SSIs, causing 58.2% of all readmissions within 30 days. Of 429 matched pairs, 48 patients in the GDAP group and 67 patients in the non-GDAP group were readmitted to a hospital within 30 days for any cause (11.2 vs. 15.6%, p = 0.048). We found a decreased readmission incidence for reasons related to SSIs, although these differences did not reach statistical significance (7.4 vs. 10.0%, p = 0.069). Adherence to GDAP was associated with reduced in-hospital risks of SSIs and prolonged postoperative LOS (19.6 vs. 26.6%, p = 0.015). CONCLUSIONS: In this contemporary clinical practice study, the adherence to GDAP was an insufficient measure to decrease rehospitalization due to SSIs. The present findings warrant further investigation on factors that may contribute to SSIs development after hospital discharge.

PD-L1 Expression in Different Segments and Histological Types of Ovarian Cancer According to Lymphocytic Infiltrate.

Background and Objectives: Ovarian cancer is the leading cause of death among gynecological tumors. PD-1/PD-L1 immunoregulatory mechanism is activated in ovarian cancers. Lymphocyte infiltration is a significant factor that affects its expression. We analyzed the correlation between localization of lymphocytic infiltrate and PD-L1 expression in epithelial ovarian tumors. Materials and Methods: PD-L1 expression was analyzed in 328 subjects, 122 with epithelial ovarian carcinoma, 42 with atypical proliferative tumor, and 164 with benign epithelial ovarian tumor. Expression in central and invasive tumor parts in epithelial ovarian carcinoma was combined with the most pronounced lymphocyte reaction. Immunohistochemical analysis was performed using the tissue microarray and correlated with a set of histopathology parameters. Results: PD-L1 expression was most prominent in epithelial ovarian carcinoma with different levels of expression observed between invasive and central tumor segments. A high level of PD-L1 expression on tumor cells was more frequently present in the invasive than in the central tumor parts (p < 0.001) only in high-grade serous ovarian carcinoma (HGSC). There was no significant correlation between peritumoral lymphocytic infiltrate and PD-L1 expression regardless of tumor segment. In the central tumor parts of HGSC, there was a correlation of intratumoral lymphocytic infiltrate with a higher level of PD-L1 expression (p = 0.003). Conclusions: The most prominent PD-L1 expression was observed in the invasive tumor parts of HGSC. Only the central parts of the HGSC exhibited significant PD-L1 expression in association with considerable intratumoral lymphocytic infiltrate.

The Impact of COVID-19 on the Profile of Hospital-Acquired Infections in Adult Intensive Care Units.

Hospital-acquired infections (HAIs) are a global public health concern. As the COVID-19 pandemic continues, its contribution to mortality and antimicrobial resistance (AMR) grows, particularly in intensive care units (ICUs). A two-year retrospective study from April 2019-April 2021 was conducted in an adult ICU at the Hospital for Infectious and Tropical Diseases, Belgrade, Serbia to assess causative agents of HAIs and AMR rates, with the COVID-19 pandemic ensuing halfway through the study. Resistance rates >80% were observed for the majority of tested antimicrobials. In COVID-19 patients, Acinetobacter spp. was the dominant cause of HAIs and more frequently isolated than in non-COVID-19 patients. (67 vs. 18, p = 0.001). Also, resistance was higher for imipenem (56.8% vs. 24.5%, p < 0.001), meropenem (61.1% vs. 24.3%, p < 0.001) and ciprofloxacin (59.5% vs. 36.9%, p = 0.04). AMR rates were aggregated with findings from our previous study to identify resistance trends and establish empiric treatment recommendations. The increased presence of Acinetobacter spp. and a positive trend in Klebsiella spp. resistance to fluoroquinolones (R2 = 0.980, p = 0.01) and carbapenems (R2 = 0.963, p = 0.02) could have contributed to alarming resistance rates across bloodstream infections (BSIs), pneumonia (PN), and urinary tract infections (UTIs). Exceptions were vancomycin (16.0%) and linezolid (2.6%) in BSIs; tigecycline (14.3%) and colistin (0%) in PNs; and colistin (12.0%) and linezolid (0%) in UTIs. COVID-19 has changed the landscape of HAIs in our ICUs. Approval of new drugs and rigorous surveillance is urgently needed.

Dietary Habits of Older Adults in Serbia: Findings From the National Health Survey.

Objectives: Adults aged 65 years and older comprise one fifth of the Serbian population. Many of them have multiple, often diet-related comorbidities. We aimed to investigate their dietary habits by comparing them with younger adults' and to determine the relation of the differing ones to demographic, socioeconomic and health factors. Methods: We performed a secondary analysis of 2013 Serbian National Health Survey data on 14,082 adults. Binary logistic regression was used to determine dietary habits associated with older age (≥65 years) compared to younger age (18-64 years) and to assess their independent predictors in older adults. Results: Older adults more often reported everyday breakfast (OR = 2.085, 95%CI = 1.622-2.680) and brown/wholegrain bread consumption (OR = 1.681, 95% CI = 1.537-1.839), while using margarine (OR = 0.578, 95%CI = 0.397-0.839), discretionary salt (sometimes: OR = 0.648, 95%CI = 0.596-0.705, almost always: OR = 0.522, 95%CI = 0.445-0.614) and consuming fish (two or more times a week: OR = 0.465, 95%CI = 0.383-0.566) less frequently than younger adults. This was mainly positively related to urban environment, affluence, higher education and poor health. Conclusion: Using nationally representative data, we found that older adults reported healthier dietary habits compared to younger adults, which requires timely public health action.

A Systematic Review of Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) Gene Variants in Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is an aggressive tumor with a complex etiology. Although Epstein-Barr virus (EBV) infection is known environmental factor for NPC development, the degree to which EBV naturally infects nasopharyngeal epithelium and the moment when and why the virus actively begins to affect cell transformation remains questionable. The aim of this study was to explore the association between LMP1 gene variability and potential contribution to NPC development. A systematic review was performed through searches of PubMed, Web of Science (WoS) and SCOPUS electronic databases. Additionally, meta-analysis of the difference in the frequency of seven LMP1 gene variants in NPC and control individuals was accomplished. The results from this study give a proof of concept for the association between 30 bp deletion (OR = 3.53, 95% CI = 1.48-8.43) and Xhol loss (OR = 14.17, 95% CI = 4.99-40.20) and NPC susceptibility when comparing biopsies from NPC and healthy individuals. Otherwise, 30 bp deletion from NPC biopsies could not distinguish NPC from EBV-associated non-NPC tumors (OR = 1.74, 95% CI = 0.81-3.75). However, B95-8, China1 and North Carolina variants were uncommon for NPC individuals. Much more efforts remains to be done to verify the biological significance of the differences observed, define so-called "high-risk" EBV variants and make it available for clinical application.