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Introduction. Surgery of the primary tumor following extended course of chemoimmunotherapy has only recently been recognized as a feasible and safe option for selected groups of patients with initially unresectable non-small cell lung cancer. Case outline. Here we report a case of a 49-year-old female patient, who never smoked, that was diagnosed with metastatic non-small cell lung cancer. Lesions were evident in both lungs and the brain. She underwent stereotactic radiosurgery for brain metastases and combination therapy of chemotherapy, atezolizumab and bevacizumab. Response to therapy was both remarkable and durable. Ten cycles into treatment, magnetic resonance imaging of the brain revealed no metastatic lesions. Positron emission tomography / computed tomography revealed a single lesion in the right upper lobe 22 × 23 mm in diameter. The patient underwent a right upper lobectomy. Pathohistological evaluation of the specimen revealed complete pathologic response. The patient recovered from surgery and continued chemoimmunotherapy. Four months post-surgery she is disease free and of excellent performance status. Conclusion. Primary tumor surgery following extensive chemoimmunotherapy regiment is feasible and could be considered as a treatment option. Further research is warranted to define a patient population that stands to benefit the most from this modality.

The synthesis of an angular triquinane, which could serve as a suitable platform for the synthesis of several natural products (panaginsene, silphinene, senoxydene) is described. The synthesis is based on two consecutive cyclopentene annulations, where alkenes were used as latent carbonyl functionalities (via Wacker reaction), and cyclopentenone annulation was effected by aldol condensation.

Simple Summary: This study analyzes real-world outcomes for advanced, non-oncogene addicted non-small cell lung cancer patients treated with atezolizumab monotherapy following platinum-based chemotherapy, based on data from two academic institutions in Serbia. Progression-free survival did not significantly differ between patients receiving atezolizumab as a second, third, or later line of therapy, indicating consistent efficacy across treatment lines. Additionally, the number of prior chemotherapy cycles had no significant impact on progression-free survival, suggesting that a higher prior treatment burden did not compromise atezolizumab effectiveness. Importantly, a good ECOG performance status emerged as the strongest predictor of prolonged progression-free survival, highlighting the importance of patients' health status at treatment initiation. Immune checkpoint inhibitors (ICIs) like atezolizumab have improved outcomes in advanced non-small cell lung cancer (NSCLC) patients, especially in the second-line setting after progression on platinum-based chemotherapy. However, access to ICIs remains limited in many developing nations. This study evaluated the efficacy of atezolizumab as a second-line versus later-line treatment for advanced NSCLC patients in Serbia. Methods: This retrospective study involved 147 advanced NSCLC patients treated with atezolizumab following progression on prior platinum-based chemotherapy at two academic centers in Serbia. Data on demographics and clinical, pathological, and molecular characteristics were collected. Median progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and multivariable Cox proportional hazards regression identified outcome predictors. Results: The median PFS was 7.13 months, and median OS was 38.6 months. The overall response rate (ORR) was 15%, with a disease control rate (DCR) of 57.9%. No significant PFS differences were observed between patients treated with atezolizumab in the second line versus later lines. Patients with good performance status (ECOG 0–1) had significantly better PFS compared to those with poorer status (12.03 vs. 1.63 months, p < 0.0001). Conclusions: Atezolizumab is effective in both second-line and later-line settings for advanced NSCLC, particularly in patients with good performance status. This highlights the importance of patient selection based on performance status, as well as the need for wider access to ICIs in resource-limited regions. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores the association of immune-related adverse events during atezolizumab therapy with better outcomes for patients with advanced non-small-cell lung cancer who had already received chemotherapy in previous lines of treatment. This study found that patients who experienced an immune-related adverse event while undergoing atezolizumab treatment had longer median progression-free survival compared to those who did not. Specifically, patients that experienced side effects had a median progression-free survival of 13.03 months, compared to just 3.4 months for those without side effects. Additionally, these side effects were more common in patients who were in better overall health when they started the treatment. The findings suggest that immune-related adverse events could be predictive in this patient population. Immune checkpoint inhibitors (ICIs) are pivotal in managing metastatic non-oncogene addicted non-small-cell lung cancer (NSCLC). They have unique toxicities known as immune-related adverse events (irAEs). Previous studies have linked irAEs during atezolizumab-based first-line treatments in advanced NSCLC with improved outcomes. This study explored the association between irAEs and the efficacy of atezolizumab in advanced NSCLC patients who had previously received platinum-based chemotherapy. The study involved 105 advanced NSCLC patients who received atezolizumab monotherapy after progressing on at least one line of platinum-based chemotherapy from a single academic institution in Serbia. Data were obtained from a hospital lung cancer registry. Among the participants, 63.8% were male, with the majority being current (53.3%) or former smokers (37.1%). About half had a good performance status (ECOG PS 0–1) at the start of atezolizumab treatment. irAEs occurred in 23 patients (21.9%). The median progression-free survival (mPFS) was significantly longer for patients with irAEs (13.03 months) compared to those without (3.4 months) (HR 0.365 [95% CI, 0.195–0.681], p = 0.002). irAEs and ECOG PS 0–1 were predictors of longer mPFS, with irAEs being more common in patients with good performance status (p = 0.01). irAEs were linked to improved mPFS in NSCLC patients treated with atezolizumab after multiple lines of platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction. COVID-19 is responsible for the current global pandemic. Globally, over 15 million people are currently infected, and just over 600,000 have died due to being infected. It is known that people with chronic illnesses and compromised immune systems can develop more severe clinical presentation. Tuberculosis (TB) is still one of the biggest epidemiological problems worldwide. Both of these diseases can be misdiagnosed and can manifest in a similar way. We will present a case study of a patient who was initially treated as a COVID-19 infection, with TB being diagnosed later on. The recovery began only after being treated for both diseases simultaneously. Case report. The patient is a 27-year-old male, non-smoker, with no history of any significant diseases. He presented with fever, fatigue and hemoptysis. Computed tomography pulmoangiography had shown massive consolidations and excavations, which could be caused by COVID-19. Despite being treated for COVID-19, there was no clinical improvement. On the follow-up chest X-ray, beside signs of COVID-19, there were also changes that could indicate TB. TB was detected in sputum, using PCR and Mycobacteria Growth Indicator Tube, and only after being treated for both diseases did his condition improve. Conclusion. There are a few reported cases of COVID-19 and TB coinfections, and we believe that there are many more patients with this coinfection being unrecognized

Sarcoidosis afflicts the central nervous system more frequently than previously believed. Neurological symptoms are present in roughly one-half of patients, and depend on the location in the central nervous system. The probability of spontaneous regression is significantly less when compared to other forms of sarcoidosis, which means that the proper diagnosis and treatment is paramount. Even when properly treated, functional defects are not uncommon. Majority of these patients require immunomodulating drugs and continuous follow-up. New immunomodulating drugs, especially biological agents, have shown to be significantly more effective, with fewer side effects, and are important when corticosteroids could not be applied. Less invasive methods, such as cerebrospinal analysis, help greatly in the diagnostics procedure, and require further research and improvement.

Introduction. COVID-19 pneumonia does not have a characteristic course and prognosis. Many facts still remain hidden, mainly why certain patients develop complications with serious tissue damage and whether it causes a permanent organ impairment. If and when will fibrosis develop in COVID-19 pneumonia requires further research, but a link between the amount of tissue afflicted and the development of fibrosis exists. Case outline. A previously healthy, non-smoker, woman with minor symptoms on admission had suddenly developed a serious respiratory insufficiency and whose radiographic finding on computed tomography scan had shown a serious progression with the development of fibrosis in a matter of days. The exact mechanism and correlation of this clinical course remains unknown; however, it is clear that the pulmonary fibrosis is caused by COVID-19 pneumonia. Follow-up computed tomography scan, performed 50 days after initial symptoms, had shown a partial regression of consolidations and post-inflammatory fibrosis. Conclusion. Pulmonary fibrosis is the most severe complication of COVID-19 infection on the respiratory system. Who, when or if a patient will develop any complication is still unclear, as well as whether these changes are reversible? Also, the number of recovered patients who later develop some chronic complications remains to be seen.

Introduction. Orbit is one of the rarer locations for the metastasis of malignant tumors. The symptoms of orbital tumors are nonspecific, but require detail diagnostics. Methods of visualization, such as ultrasound, radiography, computed tomography scan and/or magnetic resonance imaging of the endocranium are a mandatory step in the diagnostics in order to determine not only the spread of the malignancy but also the affliction of the surrounding structures. The orbital manifestations can be the first sign of the malignant disease. Outline of cases. The first case report presents a female patient with ocular symptomatology as a result of a metastasis of previously undiscovered breast cancer, and the second report presents a male patient with undiscovered lung cancer also presenting with ocular symptomatology. Conclusion. An orbital tumor should instigate further diagnostic procedures, as it can be the first sign of a disseminated malignant disease. [Projects of the Serbian Ministry of Education, Science and Technological Development, Grant no.175046 and Grant no.175081]

Background/Aim. The Chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is a simple and reliable tool designed to measure overall COPD related health status and complement physician assessment in routine clinical practice. Objective of this study was to evaluate the validity of the Serbian version of CAT. Methods. Study included 140 outpatients in the stable COPD, recruited from two centres: Clinic for Pulmonology, Clinical Center of Serbia, Belgrade, and Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica. All patients completed pulmonary function testing – spirometry, the CAT and the modified Medical Research Council (mMRC) dyspnea scale at baseline visit. The CAT test-retest reliability was tested in 20 patients by the same investigator (physician). Results. We demonstrated that Serbian version of CAT had high internal consistency with Cronbach’s alpha 0.88. Test-retest analysis showed good correlation between CAT scores in two time points (Spearman’s ρ = 0.681, p < 0.01). In our study the CAT correlated moderately to mMRC scale (ρ = +0.57), weakly to FEV1 (ρ -0.214), was positively related to number of exacerbations, but did not showed exact regularity with change in the Global Initiative for Chronic Obstructive lung disease (GOLD) stage. Conclusion. The Serbian version of CAT is a reliable, simple and easy-to-use tool that can be used in everyday clinical practice to assess the health status of COPD patients in Serbia.

Introduction. Unilateral absence of pulmonary artery is a rare vascular malformation. Because of this anomaly, the lungs are supplied by the system of collateral arteries. Case outline. We present a case of the right pulmonary artery agenesis in a female patient. She was admitted to the hospital because of hemoptysis. A computed tomography scan revealed a congenital malformation – the right lung was smaller in size, the right principal pulmonary artery had not been developed along with aberrant tortuous blood vessels. Conclusion. Symptomatic therapy was applied in the case of our patient. There was no need for any surgical treatment. However, in case of massive hemoptysis embolisation or lobectomy/ pneumonectomy will probably be applied.

Introduction: Cough is frequent symptom in sarcoidosis and there are no specifi c tools for measurement of its severity in Serbia. Aim: the goal of this study was to translate and validate the Serbian version of the Leices-ter Cough Questionnaire (LCQ) in a population of sarcoidosis patients. Methods: After the LCQ forward-backward translation process, in the cross-sectional study in 275 (180 female) sarcoidosis patients Serbian version of the LCQ was administered together with other standardized instruments for measurement of Patient Reported Outcomes (PROs)-symptoms of dyspnea (assessed by MRC and Borg scales) and fatigue (measured by Fatigue Assessment Scale and List of Daily Activities), and patients' health status (assessed by generic tool-15D). Pulmonary function tests (spirometry and diff using capacity for carbon monoxide) were also measured. Results: Serbian LCQ version showed excellent internal consistency (Cronbach's Alpha of its diff erent scores ranged between 0.901 for physical domain and 0.951 for the total score). Concurent validity assessed by correlations of all LCQ scores with other PROs and pulmonary function tests was very good, since all these correlations were statistically signifi cant. Conclusions: Our results confi rmed that the Serbian version of LCQ is a valid instrument to monitor the infl uence of chronic cough on quality of life in sarcoidosis patients.

Background: Until now, a proper biomarker(s) to evaluate sarcoidosis activity has not been recognized. The aims of this study were to evaluate the sensitivity and specificity of the two biomarkers of sarcoidosis activity already in use (serum angiotensin converting enzyme - ACE and serum chitotriosidase) in a population of 430 sarcoidosis patients. The activities of these markers were also analyzed in a group of 264 healthy controls. Methods: Four hundred and thirty biopsy positive sarcoidosis patients were divided into groups with active and inactive disease, and groups with acute or chronic disease. In a subgroup of 55 sarcoidosis patients, activity was also assessed by F-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) scanning. Both serum chitotriosidase and ACE levels showed non-normal distribution, so nonparametric tests were used in statistical analysis. Results: Serum chitotriosidase activities were almost 6 times higher in patients with active sarcoidosis than in healthy controls and inactive disease. A serum chitotriosidase value of 100 nmol/mL/h had the sensitivity of 82.5% and specificity of 70.0%. A serum ACE activity cutoff value of 32.0 U/L had the sensitivity of 66.0% and the specificity of 54%. A statistically significant correlation was obtained between the focal granulomatous activity detected on 18F-FDG PET/CT and serum chitotriosidase levels, but no such correlation was found with ACE. The levels of serum chitotriosidase activity significantly correlated with the disease duration (P< 0.0001). Also, serum chitotriosidase significantly correlated with clinical outcome status (COS) categories (p = 0.272, P = 0.001). Conclusions: Serum chitotriosidase proved to be a reliable biomarker of sarcoidosis activity and disease chronicity.

Introduction. Retroperitoneal hematoma may occur as a result of trauma, but also from rupture of arterial aneurysms (aortic or iliac), surgical complications, tumors or anticoagulation therapy. Case report. We presented a patient on permanent anticoagulation therapy. On the day of admission to our institution, the patient had the value of his INR 5.57 which required immediate suspension of the therapy. The main symptom in this patient was pain in the right inguinal canal with propagation along the right leg, which was indicated in clinical picture of spontaneous retroperitoneal haematoma. After three days the fall of hemoglobin occurred, so the additonal diagnostics was done. A computed tomography of the abdomen was performed showing well limited, large retroperitoneal hematoma (213 x 79 x 91 mm). Transfusion of concentrated red blood cells was performed twice with satisfactory correction of hemoglobin level, and four units of fresh frozen plasma. The patient was hemodynamically stabilized and discharged after a two-month long intensive care unit treatment, with the advice to use low-molecular weight heparin 2 x 0.4 mg subcutaneusly, due to persistent arrhythmia. Conclusion. In patients on anti-coagulation therapy regular monitoring of the anticoagulant status is extremely important, because of the possibility of fatal complications development, such as retroperitoneal hematoma.

Background/Aim. Global budget per calendar year is a traditional method of funding hospitals in Serbia. Diagnose related groups (DGR) is a method of hospital payment based on classification of patients into groups with clinically similar problems and similar utilization of hospital resources. The aim of this study was to compare current methods of hospital services payment with the projected costs by DRG payment method in urology. Methods. The data were obtained from the information system used in the Clinical Hospital Center “Dr. Dragiša Mišović” - Dedinje in Belgrade, Serbia. The implemented hospital information system was the main criterion for selection of healthcare institutions. The study included 994 randomly selected patients treated surgically and conservatively in 2012. Results. Average costs under the current payment method were slightly higher than those projected by DRG, however, the variability was twice as high (54,111 ± 69,789 compared to 53,434 ± 32,509, p < 0,001) respectively. The univariate analysis showed that the highest correlation with the current payment method as well as with the projected one by DRG was observed in relation to the number of days of hospitalization (ρ = 0.842, p < 0.001, and ρ = 0.637, p < 0.001, respectively). Multivariate regression models confirmed the influence of the number of hospitalization days to costs under the current payment system (β = 0.843, p < 0.001) as well as under the projected DRG payment system (β = 0.737, p < 0.001). The same predictor was crucial for the difference in the current payment method and the projected DRG payment methods (β = 0.501, p

Introduction. Pleural involvement is an uncommon manifestation of sarcoidosis. It may manifest as pleural effusion, pneumothorax, pleural thickening and nodules, hydropneumothorax, trapped lung, hemothorax, or chylothorax. The incidence of pleural effusion with sarcoidosis ranges from 0% to 5% but has been reported to be as high as 7.5%. Pleural effusions complicate sarcoidosis in < 3% of patients. Case report. We reported a 64-year-old male patient with chronic multiorgan sarcoidosis. This patient developed pleural sarcoidosis with massive pleural effusion several years after the diagnosis of sarcoidosis. A definitive diagnosis of a sarcoid pleural effusion was based on a biopsy demonstrating noncaseating granuloma. The patient responded well to the treatment (methotrexate and methylprednisolone) with a complete withdrawal of pleural effusion following five weeks of the treatment beginning. Conclusion. The presented patient is a rare case of pleural involvement of sarcoidosis with massive effusion, who responded well to the treatment. [Projekat Ministarstva nauke Republike Srbije, br. 175046]

Vitamin D has an important role in numerous physiological functions. Vitamin D receptors are characterized by polymorphisms and presence in different tissues including a number of cells of the immune system. The role of vitamin D as a biological inhibitor of inflammatory hyperactivity is of particular importance. Hypovitaminosis D has been associated with many serious chronic diseases, such as autoimmune, infectious and cardiovascular diseases as well as some types of cancer. Vitamin D has an influence on the immune response to tuberculosis. Calcitriol (1,25-dihydroxycholecalciferol), the major active form of vitamin D, has shown in vitro activity against Mycobacterium tuberculosis. It has been found that susceptibility to chronic mycobacterial infections is strongly correlated with a low vitamin D intake and particular VDR alleles. Vitamin D deficiency might predispose the individuals infected with Mycobacterium tuberculosis to develop tuberculosis. Calcitriol binds to vitamin D receptors and modulates immune responses by regulating the transcription of genes responsive to vitamin D. Faster conversion of sputum mycobacterial culture in patients with pulmonary tuberculosis is associated with being a carrier of the t allele of the TaqI vitamin D receptor polymorphism. On the contrary, slower sputum culture conversion in pulmonary tuberculosis has been found in the carriers of the f allele of the FokI vitamin D receptor polymorphism. The results of in vitro studies, clinical research and population studies indicated that vitamin D deficiency might be a strong risk factor for developing TB. Vitamin D is an inexpensive, easily accessible vitamin, relevant for the prevention of tuberculosis. In addition, vitamin D could contribute to the success of tuberculosis treatment.

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Introduction. This is a presentation of a 61-year-old female patient. Since 44 years have passed from the onset of her first symptoms until the final diagnosis of sarcoidosis, this was the reason of our decision to publish the case. Case Outline. During the follow-up period of 44 years the patient had ocassional polymorphic complains, such as adynamia, nausea, abdominal pains, myalgia, arthralgia, body weight loss (8-10 kg) etc. The clinical course was predominated by splenomegaly, hepatitis and arthralgia, and later chronic renal failure also developed. Laboratory findings showed elevated markers of acute inflammation and autoantibodies. The patient was hospitalized in different university internal hospitals (gastroenterology, allergology, rheumatology, nephrology and pulmology). Liver biopsy was performed three times, rectum and kidney biopsy once each and finally bronchoscopy and pulmonary biopsy was done. At last, about 40 years from the onset of the first symptoms, in 2006 the diagnosis of lung sarcoidosis was established. Conclusion. The final diagnosis of spleen sarcoidosis was confirmed by pathologically verified sarcoidosis of the lungs. This case is particularly interesting because of the presence of familial sarcoidosis (the patient’s son also had recurrent pulmonary sarcoidosis). [Projekat Ministarstva nauke Republike Srbije, br. 175046]

Recently published data indicate that vitamin D abnormalities are common in sarcoidosis patients. The purpose of this study was to compare serum vitamin 25(OH)D levels among sarcoidosis patients with different clinical courses of the disease. The study also included the first observations on cognitive functions (i.e. depression and fatigue syndrome) in relation to vitamin D deficiency in sarcoidosis patients. At the Biochemical Laboratory of the Clinical Center of Serbia, Belgrade, vitamin D25(OH)D was measured using the Elecsys® Vitamin D total test. A total of 226 patients with biopsy-positive sarcoidosis were analyzed. The average median value of serum vitamin D was 9.47 mg/L, suggesting severe deficiency. Statistically significant correlation was found in patients with chronic disease and low levels of serum vitamin 25(OH)D (Chi-Square=6.044; df=2; p=0.014). The patient group with vitamin D serum levels higher than 20 mg/L showed higher levels of the mean forced vital capacity (FVC) by 380 mL, and forced expiratory volume in one second (FEV1) by 220 mL, when compared to the patient group with lower serum vitamin D. A statistically significant role was established for serum vitamin 25(OH)D levels as the predictor of fatigue (R2=0.878; p=0.038 (b=0.216)) and depression in patients with sarcoidosis (R2=0.80; p=0.000 (b=0.391)). The insufficiency of 25(OH)D seems to be an important factor in predicting the course of chronic disease, significant lung function impairments and cognitive failures such as fatigue and depression. The fact that the majority of the analyzed sarcoidosis patients had totally deficient serum 25(OH)D levels made this finding even more notable.

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Introduction: Sarcoidosis affects the central nervous system more frequently than it used to be believed. While the cranial nerves are most frequently affected, neurosarcoidosis can involve other nervous system tissues as well. Treatment of Neurosarcoidosis: Although a lot of drugs have proved useful in treating neurosarcoidosis, corticosteroids are still the gold standard in treatment of these patients. Therapeutic protocols differ regarding the dose of these drugs. Symptomatic neurosarcoidosis should always be treated with pulse corticosteroid therapy. People with diabetes, high blood pressure, osteoporosis and tuberculosis should be carefully monitored, as they are prone to complications associated with treatment with corticosteroids. In cases when treatment with corticosteroids does not show the desired results or therapy is discontinued due to the development of side effects, there are other pharmacologic options, such as methotrexate, mycophenolate mofetil, cyclophosphamide, chloroquine, azathioprine, thalidomide, and infliximab. It should be noted that the treatment response to the above mentioned regimens, except for infliximab, is relatively slow compared to corticosteroids; therefore, corticosteroids should be taken into account in all states and particularly in the acute phase of the disease. Conclusion: It is the existence of different forms of the disease, lack of local diagnostic criteria and different and non standardized therapy that makes the treatment of this disease difficult. Despite advances in pharmacotherapy and radiological diagnosis, it is necessary to develop better diagnostic strategies in order to set the optimal therapeutic approach. [ABSTRACT FROM AUTHOR]

Introduction. In diagnostics of neurosarcoidosis, radiological diagnostic procedures are available, non-invasive and they contribute significantly to the diagnosis of this disease. The aim of this paper is to present a brief overview of the radiological diagnostic methods, their application, and their importance in daily clinical work with these patients. Radiological Presentation of Neurosarcoidosis. Magnetic resonance is the method of choice in diagnostics of this disease. Computed tomography can also be helpful in patients with contraindications for magnetic resonance, although it is less precise in assessing the involvement of the periventricular white matter, hypothalamus, and cranial nerves. The number of lesions and the degree of involvement of the parenchyma and leptomeninges are better seen by magnetic resonance than by computed tomography scan. It is important to note that the magnetic resonance imaging may be normal in patients with neurosarcoidosis, especially in patients with cranial neuropathy, or in patients treated with corticosteroids. There is a number of variability in the occurrence of neurosarcoidosis on radiological images. Conclusion. Radiological procedures are on the very top of diagnostic pyramid of this disease due to their availability, non-invasiveness, and precision. [ABSTRACT FROM AUTHOR]