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.

Diagnosis and treatment of adult asthma patients in Serbia: a 2022 experts group position statement.

INTRODUCTION: Asthma is the most common non-communicable chronic lung condition across all ages. Epidemiological data indicate that many asthma patients in Serbia remain undiagnosed and untreated. The implementation of recent global advances in asthma management is limited due to the lack of a systematic approach, drug availability and regulatory affairs. In addition, the global coronavirus disease pandemic has posed a significant challenge, particularly in resource-limited settings. AREAS COVERED: In this paper, we propose an algorithm for treating adult asthma patients in Serbia. We performed PubMed database search on published asthma clinical trials and guidelines from 1 January 2015 to 10 March 2020. The consensus process incorporated a modified Delphi method that included two rounds of e-mail questionnaires and three rounds of national asthma expert meetings. We focus on 1) objective diagnosis of asthma, 2) the implementation of up-to-date therapeutic options, and 3) the identification and referral of severe asthma patients to newly established severe asthma centers. EXPERT OPINION: Regional specificities and variations in healthcare systems require the adaptation of evidence-based knowledge. Practical, clinically oriented algorithms designed to overcome local barriers in healthcare delivery may facilitate timely and adequate asthma diagnosis and the local implementation of current advances in asthma management.

Obstructive Sleep Apnea Is Associated With Low Testosterone Levels in Severely Obese Men.

Background: Disrupted sleep affects cardio-metabolic and reproductive health. Obstructive sleep apnea syndrome represents a major complication of obesity and has been associated with gonadal axis activity changes and lower serum testosterone concentration in men. However, there is no consistent opinion on the effect of obstructive sleep apnea on testosterone levels in men. Objective: The aim of this study was to determine the influence of obstructive sleep apnea on total and free testosterone levels in severely obese men. Materials and methods: The study included 104 severely obese (Body Mass Index (BMI) ≥ 35 kg/m2) men, aged 20 to 60, who underwent anthropometric, blood pressure, fasting plasma glucose, lipid profile, and sex hormone measurements. All participants were subjected to polysomnography. According to apnea-hypopnea index (AHI) patients were divided into 3 groups: <15 (n = 20), 15 - 29.9 (n = 17) and ≥ 30 (n = 67). Results: There was a significant difference between AHI groups in age (29.1 ± 7.2, 43.2 ± 13.2, 45.2 ± 10.2 years; p < 0.001), BMI (42.8 ± 5.9, 43.2 ± 5.9, 47.1 ± 7.8 kg/m2; p = 0.023), the prevalence of metabolic syndrome (MetS) (55%, 82.4%, 83.6%, p = 0.017), continuous metabolic syndrome score (siMS) (4.01 ± 1.21, 3.42 ± 0.80, 3.94 ± 1.81, 4.20 ± 1.07; p = 0.038), total testosterone (TT) (16.6 ± 6.1, 15.2 ± 5.3, 11.3 ± 4.44 nmol/l; p < 0.001) and free testosterone (FT) levels (440.4 ± 160.8, 389.6 ± 162.5, 294.5 ± 107.0 pmol/l; p < 0.001). TT level was in a significant negative correlation with AHI, oxygen desaturation index (ODI), BMI, MetS and siMS. Also, FT was in a significant negative correlation with AHI, ODI, BMI, age, MetS and siMS. The multiple regression analysis revealed that both AHI and ODI were in significant correlation with TT and FT after adjustment for age, BMI, siMS score and MetS components. Conclusion: Obstructive sleep apnea is associated with low TT and FT levels in severely obese men.

Diagnosis and management of chronic obstructive pulmonary disease in Serbia: an expert group position statement.

In recent years, several national chronic obstructive pulmonary disease (COPD) guidelines have been issued. In Serbia, the burden of COPD is high and most of the patients are diagnosed at late stages. Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy is poorly implemented in real-life practice, as many patients are still prescribed inhaled corticosteroids (ICS)-containing regimens and slow-release theophylline. In this document, we propose an algorithm for treating COPD patients in Serbia based on national experts' opinion, taking into account global recommendations and recent findings from clinical trials that are tailored according to local needs. We identified four major components of COPD treatment based on country specifics: active case finding and early diagnosis in high-risk population, therapeutic algorithm for initiation and escalation of therapy that is simple and easy to use in real-life practice, de-escalation of ICS in low-risk non-exacerbators, and individual choice of inhaler device based on patients' ability and preferences. With this approach we aim to facilitate implementation of the recommendation, initiate the treatment in early stages, improve cost-effectiveness, reduce possible side effects, and ensure efficient treatment.

[Contribution of novel anticoagulants fondaparinux and dabigatran to venous thromboembolism prevention].

The data that episodes and sequels of venous thromboembolism (VTE) are recorded in a significant percentage of patients receiving standard anticoagulants as VTE prophylaxis (unfractionated, low-molecular-weight heparin and vitamin K inhibitors) as well as the fact that these drugs have significant limitations and that they may cause serious side-effects in some patients indicate the need for the introduction of new anticoagulant drugs. Fondaparinux, a selective inhibitor of Factor Xa, administered following major orthopedic surgeries having a high risk for the development of VTE, is more efficient than enoxaparin sodium used in European and North-American approved doses. The increased incidence of major bleeding (excluding fatal) due to fondaparinux could be perhaps lowered by dosage reduction in patients with a mildly decreased creatinine clearance. Dabigatran, a peroral direct thrombin inhibitor, administered for VIE prophylaxis in elective hip and knee surgery, showed in to date studies the efficacv comparable (if dabiqatran is given in both dosage regimes of 150 mg and 220 mg daily) or superior (if dabigatran is given at a dose of 220 mg daily) to enoxaparin administered in European-approved doses, while North American-approved doses of enoxaparin were superior than dabigatran in VTE reduction. No significant differences in bleeding rates were determined in any of the study groups. We consider that the introduction of new anticoagulants, including fondaparinux and dabigatran, will contribute to the establishment of a better safety profile and efficacy, and will also enable adequate therapy individualization for each patient depending on his/hers clinical characteristics. The introduction of novel peroral anticoagulants will, inter alia, significantly contribute to improvement in the quality of life, release the patient from numerous limitations in nutrition, interreaction, frequent laboratory monitoring, and also significantly improve therapeutic predictability.

[Contemporary approach to primary prophylaxis of venous thromboembolism regarding the impact of risk factors on anticoagulation therapy duration].

Adequate thromboprophylaxis primarily requires timely detection of reversible and irreversible risk factors of venous thromboembolism (VTE) and their categorization. It is important to note that the highest percentage ofVTE episodes occur in non-surgical (medical) patients and that VTE develops in a large number of surgical patients upon hospital discharge; this emphasizes the need for adequate VTE prevention in inflammatory diseases, acute medical illness and other medical diseases as well as for prolonging and optimizing the anticoagulant regimen after surgical intervention in the primary VTE prophylaxis. As almost completely unrecognized and neglected major risk factors of VTE in clinical practice, we particularly point out the chronic obstructive pulmonary disease (COPD) and heart failure, especially in NYHA functional class III and IV patients with significantly reduced left heart ventricle. It is necessary to raise clinicians' awareness of a potential danger from wrongly and one-sidedly interpreted dyspnea and coughing signs in patients with COPD as typical symptoms of basic respiratory disease as well as from ascribing the signs of disease aggravation in heart failure patients exclusively to cardial status worsening, neglecting the possibility of having unrecognized and untreated pulmonary embolism at issue. Contemporary way of life enhances the development of new VTE risk factors such as traveler's thrombosis, in particular during long-haul flights as well as in individuals sitting at a computer for prolonged periods (e-thrombosis). Determining and recognizing VTE risk factors, especially those formerly neglected nonsurgical ones and simultaneous presence of multiple risk factors within a given period is required for defining an adequate anticoagulant regimen in primary VTE prophylaxis for surgical and non-surgical (medical) patients.

Early left ventricular systolic and diastolic dysfunction in patients with newly diagnosed obstructive sleep apnoea and normal left ventricular ejection fraction.

UNLABELLED: The aim of the study was to evaluate whether obstructive sleep apnea (OSA) contributes directly to left ventricular (LV) diastolic and regional systolic dysfunction in newly diagnosed OSA with normal left ventricle ejection fraction. METHODS: 125 consecutive patients were prospectively enrolled in the study. Control group consisted of 78 asymptomatic age-matched healthy subjects who did not have any cardiovascular and respiratory diseases. All patients had undergone overnight polysomnography and standard transthoracic and tissue Doppler imaging echocardiogram. RESULTS: The E/A ratio and the peak E wave at mitral flow were significantly lower and the peak A wave at mitral flow was significantly higher in OSA patients compared with control subjects. Left ventricle isovolumetric relaxation time (IVRT) and mitral valve flow propagation (MVFP) were significantly longer in OSA patients than in controls. Tissue Doppler derived S' amplitude of lateral part at mitral valve (S'Lm) and E' wave amplitudes both at the lateral (E'Lm) and septal parts of the mitral valve (E'Sm) were significantly lower in OSA patients compared to controls. CONCLUSION: Newly diagnosed OSA patients with normal global LV function have significantly impaired diastolic function and regional longitudinal systolic function. OSA is independently associated with these changes in LV function.

A new method for respiratory-volume monitoring based on long-period fibre gratings.

Respiratory-volume monitoring is an indispensable part of mechanical ventilation. Here we present a new method of the respiratory-volume measurement based on a single fibre-optical long-period sensor of bending and the correlation between torso curvature and lung volume. Unlike the commonly used air-flow based measurement methods the proposed sensor is drift-free and immune to air-leaks. In the paper, we explain the working principle of sensors, a two-step calibration-test measurement procedure and present results that establish a linear correlation between the change in the local thorax curvature and the change of the lung volume. We also discuss the advantages and limitations of these sensors with respect to the current standards.

Home mechanical ventilation in children is feasible in developing countries.

BACKGROUND: The results of many national surveys on pediatric home mechanical ventilation (HMV) in developed countries have been presented elsewhere, but data from developing countries with low national incomes are scarce. METHODS: Twenty-nine pediatric patients, treated in the Mother and Child Institute of Serbia, who had been receiving long-term ventilatory support at home, were surveyed. The major criterion for initiating HMV was hypercapnia, diagnosed by blood gas analysis, performed in the morning, after awakening. Other criteria were either symptoms of hypoventilation during the night associated with an apnea index of >5, or apnoea-hypopnoea index of >15, or nocturnal hypoxemia, defined as an oxygen saturation rate of <90% for >5% of total sleep time. RESULTS: The mean age at initiation of HMV was 9.3 years (range 0.5-17.8 years). Patients waited for HMV initiation either in hospital or at home; the mean period was 6.3 months (range 1-18 months). The subjects received HMV for a mean of 25.06 months (range 3-119 months). There was a significant difference in the duration of HMV for different underlying diseases (P= 0.046), and mechanical malfunction was strongly dependent on the duration of HMV (P= 0.011). Eleven patients underwent invasive HMV via a tracheostomy, and 18 others received non-invasive ventilation, via nasal and full-face masks. CONCLUSION: HMV is feasible in developing countries. Valuable reimbursement policies as well as an organized and functional network are essential for its implementation, as a standard of care in leading national pediatric hospitals.

[Modalities in the treatment of obstructive breathing in sleep].

The goals of OSAS therapy are to improve daytime symptoms especially excessive sleepiness, prevent neurocognitve, metabolic and cardiovascular consequences and quality of life in patients with sleep apnea. A variety of therapy exist starting from general measures that include weight reduction, change in life style, postional therapy, oral devices, upper airway surgery and pharmacotherapy. However, CPAP has been demonstrated to be the most important and highly effective therapy in these disorders. CPAP therapy dramatically improves symptoms and decreases cadriovascular and metabolic consequences stoping the occurence of the apneas. Hoewer, not all patients tolerate CPAP especially patients with milder forms of the disease. The individualised approach wich pay attention to different phenotypes and genotype could select patients for selecitively acting treatment modalities such us mandibular advancement devices and electical stimulation of the upper airway muscles.

Acute patellar dislocation in adolescents: operative versus nonoperative treatment.

PURPOSE: The purpose of this prospective non-randomised study was to compare the efficacy of two opposed methods, operative and conservative. Our hypothesis was that if the method was selected correctly, on an individual basis, the results should be approximately equal. METHODS: The study included 37 adolescents aged between 12 and 16 years, with a mean follow up of 6.1 years. The presence of a significant loose body, confirmed by precise imaging, was the key for selecting operative or arthroscopic treatment. In both groups of patients, we evaluated functional knee scores and the incidence of residual patellofemoral disorders. RESULTS: We confirmed our hypothesis using the t-test to compare functional results and a test for comparison of proportions for incidence of residual disorders. There was no statistically significant difference (p=0.091) between operatively and conservatively treated groups with regard to functional results. The same statistical outcome emerged when comparing incidences of re-dislocation (p=0.854), or other major patellar instabilities (p=0.856), between the groups. CONCLUSIONS: The results obtained should not promote a non-operative method on the basis of lower risk, but do support an individual approach based on precise diagnosis and defined criteria.

Asthma and chronic bronchitis symptoms among adult population of Belgrade.

INTRODUCTION: Over the last three decades the prevalence of respiratory diseases has been increasing worldwide thus increasing economic burden on the healthcare system. Recent studies have shown that the prevalence of asthma in West European countries ranges from 6-9%, while of chronic obstructive pulmonary diseases (COPD) is 8.0% worldwide. OBJECTIVE: The aim of the study was to estimate the prevalence of respiratory symptoms and smoking habits, and to assess the prevalence of asthma and chronic bronchitis among adults in Belgrade, Serbia. METHODS: To collect data we used a questionnaire based on the European Community Respiratory Health Survey (ECRHS) protocol, which was mailed to 10,208 randomly selected subjects. RESULTS: There were 58.3% of responders to our questionnaire. We noted a higher prevalence of respiratory symptoms in subjects who responded promptly. The majority of the respondents were current or former smokers (37.5% and 17.5% respectively) and 79.9% of them reported respiratory symptoms. The most frequent symptoms were longstanding cough (32.2%), sputum production (30.4%) and wheezing (30.3%). Asthma attacks were reported in 4.4% of cases and 5.6% of subjects were using asthma medications. The prevalence of respiratory symptoms increased with age. Women reported coughing, attacks of breathlessness and coughing, chest tightness by night, allergic rhinitis and chronic coughing, more frequently than men. Productive cough was more frequent in men. The prevalence of almost all symptoms was higher in smokers compared to nonsmokers. CONCLUSION: In Serbia there is a high prevalence of respiratory symptoms, asthma and chronic bronchitis smoking addiction.

[Successful treatment of laryngomalacia and bilateral vocal cord paralysis with continuous positive airway pressure].

INTRODUCTION: Laryngomalacia is the most frequent congenital anomaly of airways, and it may cause obstructive sleep apneas. The associated vocal cord paralysis may aggravate the symptoms of upper airway obstruction. CASE REPORT: In a 14 month old boy severe laryngomalacia and bilateral vocal cord paralysis were diagnosed by flexible bronchoscopy. A sleep study showed a severe obstructive sleep apnoea (OSA). The patient was ventilated at home via the face mask with non invasive mechanical ventilation (CPAP) for a year. The level of pressure had to be set at 7 cm H2O to correct desaturation with an improvement in mean SpO2. On the follow up bronchoscopic examination laryngomalatia was improved, vocal cord paralysis persisted and sleep study revealed significant improvement. DISCUSSION: In the patient with severe laryngomalatia and bilateral vocal cord paralysis with OSA conservative treatment with CPAP was used instead of a surgical intervention. Non invasive ventilation was used every night, for at least 6 hours, without adverse events. Invasive measurement of transdiaphragmatic pressure is the best way of titrating of CPAP level. This case report suggests the efficacy of noninvasive titrating of CPAP level by the hemoglobin oxygen saturation trend measurement. CONCLUSION: In case of severe laryngomalatia and associated vocal cord paralysis, followed by OSA non invasive ventilation by nasal CPAP represents an effective and safe alternative to surgery.

[How to solve the problem of sleep apnea?].

The future of solving the problem of sleep apnea necessitates the systematic organization of activities that would include: 1) increase in the awareness of the significant prevalence of sleep apnea and its influence on health and economic burden in the population via media and educational campaign; 2) establishment of the work groups that will find the answers and set the scientific research according to the needs posed by the sleep diseases; 3) Check the existing and develop new diagnostic and therapeutic methods with special reference to home monitoring with the creation of the national research network which will connect researchers and their programs and research centers; 4) Organization at the national level of educational centers and laboratories that will adequately respond to the needs of the pathology present in the population.

Plasma and platelet serotonin levels in patients with liver cirrhosis.

AIM: To analyze the relationship between plasma and platelet serotonin levels and the degree of liver insufficiency. METHODS: The prospective study included 30 patients with liver cirrhosis and 30 healthy controls. The degree of liver failure was assessed according to the Child-Pugh classification. Platelet and platelet poor plasma serotonin levels were determined. RESULTS: The mean plasma serotonin level was higher in liver cirrhosis patients than in healthy subjects (215.0 +/- 26.1 vs 63.1 +/- 18.1 nmol/L; P < 0.0001). The mean platelet serotonin content was not significantly different in patients with liver cirrhosis compared with healthy individuals (4.8 +/- 0.6; 4.2 +/- 0.3 nmol/platelet; P > 0.05). Plasma serotonin levels were significantly higher in Child-Pugh grade A/B than in grade C patients (246.8 +/- 35.0 vs 132.3 +/- 30.7 nmol/L; P < 0.05). However, platelet serotonin content was not significantly different between Child-Pugh grade C and grade A/B (4.6 +/- 0.7 vs 5.2 +/- 0.8 nmol/platelet; P > 0.05). CONCLUSION: Plasma serotonin levels are significantly higher in patients with cirrhosis than in the controls and represent the degree of liver insufficiency. In addition, platelet poor plasma serotonin estimation is a better marker for liver insufficiency than platelet serotonin content.

Primary amyloidosis presenting with cholestasis and hyperkinetic portal hypertension.

Amyloidosis is not a single disease, but a series of diseases in which there is extracellular deposition of a protein in an abnormal fibrillar form. We report a 48-year old woman with subicteric coloration of scleras and hepatomegaly. Functional liver tests evidenced a high level of alkaline phosphatase and serum gamma-glutamyl transpeptidase with mild increase of bilirubin level. Color Doppler ultra-sonography, showed a hyperkinetic portal hypertension. The liver biopsy found amyloid in sinusoids subendothelially. Immunohistochemical staining for anti lambda light chain immunoglobulin was positive. Bone marrow morphology and immunohistochemistry confirmed lymphoplasmocytic lymphoma with amyloidosis.

Spontaneous gastrojejunal fistula is a complication of gastric ulcer.

Spontaneous gastrojejunal fistula formation is an extremely rare complication of gastric ulcer disease. We report a 77-year old woman who presented with diffuse abdominal pain, weight loss, malaise, nausea, and occasional dark stools. Laboratory tests showed extreme hyposideremic anemia with inflammatory syndrome. In addition, biochemical parameters of malnourishment were presented. Upper endoscopy revealed the patent esophagus along the full length without any pathological changes. Large and deep ulceration with perforation in the small intestine was detected in the posterior gastric wall. The small intestine loop was reached by endoscope through spontaneously developed gastrojejunal fistula. Polytopic biopsies of described ulcerative change were carried out. Histopathologically reepithelialized ulcerous zone was seen in the gastric mucosa. Also, gastrojejunal fistula was visualized after wide opening of hepatogastric and gastrocolic ligament. Jejunal loop 25 cm from ligament of Treitz was attached to mesocolon and posterior gastric wall because of ulcer penetration. Postoperative course was uneventful. Per oral intake started on the 4(th) postoperative day, and the patient was discharged on the 8(th) postoperative day. In summary, this case indicates that persistent symptoms of peptic ulcer disease associated with nutritional disturbances may be caused by gastrojejunal fistula.