New Therapeutic Approaches for the Treatment of Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Increased Cardiovascular Risk.

Metabolic dysfunction-associated steatotic liver disease (MASLD) was previously known as nonalcoholic fatty liver disease (NAFLD). The main characteristic of the disease is the process of long-term liver inflammation, which leads to hepatocyte damage followed by liver fibrosis and eventually cirrhosis. Additionally, these patients are at a greater risk for developing cardiovascular diseases (CVD). They have several pathophysiological mechanisms in common, primarily lipid metabolism disorders and lipotoxicity. Lipotoxicity is a factor that leads to the occurrence of heart disease and the occurrence and progression of atherosclerosis. Atherosclerosis, as a multifactorial disease, is one of the predominant risk factors for the development of ischemic heart disease. Therefore, CVD are one of the most significant carriers of mortality in patients with metabolic syndrome. So far, no pharmacotherapy has been established for the treatment of MASLD, but patients are advised to reduce their body weight and change their lifestyle. In recent years, several trials of different drugs, whose basic therapeutic indications include other diseases, have been conducted. Because it has been concluded that they can have beneficial effects in the treatment of these conditions as well, in this paper, the most significant results of these studies will be presented.

Obstructive jaundice treatment during the COVID-19 pandemic: retrospective cohort study at a single tertiary care center in Serbia.

OBJECTIVE: We aimed to compare mortality and complication rates in patients treated for obstructive jaundice before and during the COVID-19 pandemic in a tertiary care center in Serbia. METHODS: We conducted a retrospective cohort study among a first group of patients treated between 1 January 2017 and 1 January 2019. The second group was treated between 1 March 2020 and 1 March 2022. RESULTS: The first group comprised 35 patients, and the second group (in which all patients were SARS-CoV-2 positive) included 18 patients; 37 and 16 patients were treated for malignant and benign diseases, respectively. The groups did not differ significantly regarding the diagnoses and treatment received. The second group showed significantly higher aspartate aminotransferase levels and lower white blood cell, C-reactive protein, and interleukin 6 levels. Mortality and complication rates did not differ significantly between groups. All deceased patients in the second group had significant radiologic findings associated with COVID-19 pneumonia. CONCLUSIONS: COVID-19 infection is a risk factor in treating obstructive jaundice. This study illustrates the potential influence of COVID-19 on mortality after obstructive jaundice treatment. COVID-19 pneumonia may be a significant risk factor for mortality in patients treated for obstructive jaundice.

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.

Bradykinin and Galectin-3 in Survived and Deceased Patients with COVID-19 Pneumonia: An Increasingly Promising Biochemical Target.

Introduction: There are still no definite curative or preventive strategies for COVID-19 disease. It is crucial to fully comprehend the pathogenesis of COVID-19 infection so that we can develop expedient pharmacological protocols. While the impact of cytokine storm on COVID-19 severity has been one of the most tested hypotheses, the role of bradykinin and various other oxidative stress markers has been relatively under-researched. Their levels can be determined immediately after a hospital admission so they could be used as early predictors of the further development of the disease. Aim: The study aims at evaluating the possibility of using bradykinin and galectin-3 levels as early predictors that COVID-19 disease will progress into a severe case. Material and methods. The study was conducted as a prospective cross-sectional study. It included 47 consecutive adult patients with confirmed SARS-CoV-2 infection and COVID-19 pneumonia. All study subjects were admitted for a hospital treatment to the tertiary Clinical Hospital Center Bezanijska kosa, Belgrade, Serbia on June 2021. The blood samples were collected at the patients' admission. The analyses of demographic, radiological, and clinical data were later conducted for both groups (the deceased patients and those who survived). In addition, we analyzed the potential relations between the outcome and the levels of bradykinin and galectin-3 measured immediately after the patients were admitted to the hospital. Results: The patients who passed away were predominantly older men with comorbidities. We recorded higher CT scores in the deceased patients and the significantly higher levels of urea, creatinine, CK, troponine, CRP, and other laboratory markers. They stayed at the ICU unit longer and required mechanical ventilation more frequently than the patients who survived. On the other hand, no differences were recorded in the time periods passing from the onset of the systems to the hospital admissions. Finally, we can highlight several independent predictors of mortality in patients with COVID-19 pneumonia, including the following: (1) patients who are 50 or more years old, (2) with in-hospital stays are longer that 4 days, (3) bradykinin levels surpass 220000 pg/ml, (4) D-dimer, creatinine, and CRP are elevated, and (5) comorbidities were present (such as hypertension and diabetes). Conclusion: The present study strongly supports the bradykinin storm hypothesis. Since elevated bradykinin levels have been found in most COVID-19 cases with fatal outcomes, the future therapeutical strategies for COVID-19 have to be focused on reducing bradykinin serum concentrations.

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.

Scoring Systems in Assessing Survival of Critically Ill ICU Patients.

BACKGROUND: The aim of this study was to determine which of the most commonly used scoring systems for evaluation of critically ill patients in the ICU is the best and simplest to use in our hospital. MATERIAL AND METHODS: This prospective study included 60 critically ill patients. After admittance to the ICU, APACHE II, SAPS II, and MPM II0 were calculated. During further treatment in the ICU, SOFA and MPM II were calculated at 24 h, 48 h, and 72 h and 7 days after admittance using laboratory and radiological measures. RESULTS: In comparison with survivors, non-survivors were older (p<0.01) and spent significantly more days on mechanical ventilation (p<0.01). ARDS was significantly more common in patients who survived compared to those who did not (chi-square=7.02, p<0.01), which is not the case with sepsis (chi-square=0.388, p=0.53). AUROC SAPS II was 0.690, and is only slightly higher than the other 2 AUROC incipient scoring systems, MPM II and APACHE II (0.654 and 0.623). The APACHE II has the highest specificity (81.8%) and MPM II the highest sensitivity (85.2%). MPM II(7day) AUROC (1.0) shows the best discrimination between patients who survived and those who did not. MPM II(48) (0.836), SOFA(72) (0.821) and MPM II(72) (0.817) also had good discrimination scores. CONCLUSIONS: APACHE II and SAPS II measured on admission to the ICU were significant predictors of complications. MPM II(7day) has the best discriminatory power, followed by SOFA(7day) and MPM II(48). MPM II(7day) has the best calibration followed by SOFA(7day) and APACHE II.

Influence of spinal and general anesthesia on the metabolic, hormonal, and hemodynamic response in elective surgical patients.

BACKGROUND: The aim of the study was to determine the significance of spinal anesthesia in the suppression of the metabolic, hormonal, and hemodynamic response to surgical stress in elective surgical patients compared to general anesthesia. MATERIAL AND METHODS: The study was clinical, prospective, and controlled and it involved 2 groups of patients (the spinal and the general anesthesia group) who underwent the same surgery. We monitored the metabolic and hormonal response to perioperative stress based on serum cortisol level and glycemia. We also examined how the different techniques of anesthesia affect these hemodynamic parameters: systolic arterial pressure (AP), diastolic AP, heart rate (HR), and arterial oxygen saturation (SpO2). These parameters were measured before induction on anesthesia (T1), 30 min after the surgical incisions (T2), 1 h postoperatively (T3) and 24 h after surgery (T4). RESULTS: Serum cortisol levels were significantly higher in the general anesthesia group compared to the spinal anesthesia group (p<0.01). Glycemia was significantly higher in the general anesthesia group (p<0.05). There was a statistically significant, positive correlation between serum cortisol levels and glycemia at all times observed (p<0.01). Systolic and diastolic AP did not differ significantly between the groups (p=0.191, p=0.101). The HR was significantly higher in the general anesthesia group (p<0.01). SpO2 values did not differ significantly between the groups (p=0.081). CONCLUSIONS: Based on metabolic, hormonal, and hemodynamic responses, spinal anesthesia proved more effective than general anesthesia in suppressing stress response in elective surgical patients.

[Outcome among patients suffering from in-hospital cardiac arrest].

INTRODUCTION: In relation to pre-hospital treatment of patients with cardiac arrest (CA) in the field where resuscitation is often started by nonprofessionals, resuscitation in hospital is most commonly performed by well-trained personnel. OBJECTIVE: The aim was to define the factors associated with an improved outcome among patients suffering from the in-hospital CA (IHCA). METHODS: The prospective study included a total of 100 patients in the Emergency Center over two-year period.The patterns by the Utstein-Style guidelines recorded the following: age, sex, reason for hospital admission, comorbidity, cause and origin of CA, continuous monitoring, time of arrival of the medical emergency team and time of delivery of the first defibrillation shock (DC). RESULTS: Most patients (61%) had cardiac etiology. Return of spontaneous circulation (ROSC) was achieved in 58% of patients. ROSC was more frequently achieved in younger patients (57.69 +/- 11.37), (p < 0.05), non-surgical patients (76.1%), (p < 0.01) and in patients who were in continuous monitoring (66.7%) (p < 0.05). The outcome of CPR was significantly better in patients who received advanced life support (ALS) (76.6%) (p < 0.01). Time until the delivery of the first DC shock was significantly shorter in patients who achieved ROSC (1.67 +/- 1.13 min), (p < 0.01). A total of 5% of IHCA patients survived to hospital discharge. CONCLUSION: In our study, the outcome of CPR was better in patients who were younger and with non-surgical diseases, which are prognostic factors that we cannot control. Factors associated with better outcome of IHCA patients were: continuous monitoring, shorter time until the delivery of the first DC and ALS. This means that better education of medical staff, better organization and up-to-dated technical equipment are needed.