Radioiodine therapy accelerates apoptosis in peripheral blood lymphocytes of patients with differentiated thyroid cancer.

Both apoptosis and micronuclei formation reflect cytogenetic damage in cells and could contribute to cell homeostasis. The aim of this study was to evaluate apoptosis in peripheral blood lymphocytes (PBLs) of patients with differentiated thyroid cancer (DTC) before and after 131-iodine (131-I)-therapy and its correlation with micronuclei (MN) frequency. The study population included 18 DTC patients and 18 healthy donors. Apoptotic cells were detected using the Annexin V-FITC/7-AAD kit and MN frequency by cytokinesis-block MN assay. The difference between early apoptosis in PBLs of DTC patients before therapy and controls (9.88 ± 4.99% vs. 6.64 ± 2.07%, p = 0.003) was significant, as well as between early apoptosis in PBLs of DTC patients before and after 131-I-therapy (9.88 ± 4.99% vs. 13.53 ± 6.57%, p = 0.008). The MN frequency and early apoptosis in PBLs of DTC patients was positively correlated before (r = 0.540, p= 0.021) and after 131-I-therapy (r = 0.585, p= 0.014). Thyroid cancer patients had a significantly increased early apoptosis in PBLs, which further increased after 131-I-therapy in association with MN frequency.

Preoperative skin tumours thickness determination by high-frequency ultrasound on head and neck region.

BACKGROUND: High-frequency ultrasound is non-invasive imaging method for examination of skin tumours. OBJECTIVE: The aim of our study was to examine validity of 20-MHz ultrasound in preoperative determination of skin tumour thickness localized on head and neck region as a potentially useful tool for planning of the surgical intervention. METHODS: Seventy-three different skin tumours were preoperatively examined using Dermascan C (Cortex Technology, Denmark) 20-MHz ultrasound equipment. Maximal vertical thickness of tumours was preoperatively determined by ultrasound, and after surgical excision of tumours, on pathohistological preparations using Nippon-Kogaku ocular micrometre. All patohistological specimens were controlled for presence of tumour cells on specimens' margins. RESULTS: Obtained correlation was very high, r = 0.82, without significant statistical difference (P < 0.01) between dimensions determined by 20-MHz ultrasound and histometry. There were no pathohistological specimens with tumours cells found on margins. CONCLUSION: Examination of skin tumours by 20-MHz ultrasound gives reliable additional information about tumour dimensions, sometimes important for therapeutic strategy.

Burnout syndrome among employees in a clinical center in Montenegro during COVID-19.

OBJECTIVE: Burnout syndrome occurs as a result of the influence of stressors in the workplace. The chronic disproportion between the demands placed on the worker and the resources available to fulfill the demands makes a significant contribution to the development of this syndrome. The occurrence of burnout syndrome has been shown to occur in a wide range of jobs, and it is taking on epidemic proportions among healthcare workers. So far, there have been no large-scale studies dealing with burnout syndrome in healthcare workers in Montenegro. SUBJECTS AND METHODS: The research was conducted as a cross-sectional study. All full-time employees of the Clinical Center of Montenegro who participated in the treatment of patients with COVID-19 during 2020 and 2021 were included in the research. Questionnaires used in the research were: a general questionnaire for collecting socio-demographic data, a questionnaire for the assessment of burnout syndrome at work - Maslach Burnout Inventory and a COVID-19 stress scale. RESULTS: The prevalence of burnout syndrome was 16.8% among employees who were engaged around COVID-19 patients. Predictors of burnout syndrome identified were occupation (nurses/technicians have a 2.8 times higher chance of burnout syndrome than doctors as a reference category), confirmed COVID-19 infection (subjects with confirmed COVID-19 infection have more than 2 times higher chance for burnout syndrome), higher CSS scores (subjects with high CSS score have a 3% higher chance of developing burnout syndrome). CONCLUSIONS: In order to reduce losses due to reduced productivity of employees and prevent long-term detrimental consequences on the mental health of employees, evidence-based preventive measures are needed.

Oxidative stress and inflammation parameters-novel biomarkers for idiopathic pulmonary fibrosis.

OBJECTIVE: The pathophysiological mechanisms of idiopathic pulmonary fibrosis (IPF) are not well elucidated. It is assumed that oxidative stress and inflammation are the key underlying culprits for its onset and progression. To gain deeper insight into these processes, we have evaluated several oxidative stress parameters, inflammation markers [i.e., high sensitivity C-reactive protein (hsCRP), serum amyloid A1 (SAA1)], soluble programmed cell death-ligand 1 (sPD-L1), and 25-hydroxyvitamin D [25(OH)D] in IPF patients. PATIENTS AND METHODS: Biochemistry analyses were done in 30 consecutive IPF patients and 30 age and gender-matched healthy control group (CG). RESULTS: IPF patients had significantly higher advanced oxidation protein products (p<0.001), pro-oxidant-antioxidant balance (p=0.010), total oxidative status (p<0.001), and ischemia modified albumin (p<0.001) compared to CG. Lower total antioxidant status and total sulfhydryl groups (tSGH) and significantly higher sPD-L1, hsCRP (p<0.001 for all), SAA1 proteins (p=0.014) and [25(OH)D] severe deficiency [11.0 (9.6-15.1) nmol/L] in IPF patients compared to CG were observed. Paraoxonase 1 activity and hsCRP level were lower, while tSHG and sPD-L1 were higher in IPF patients with more severe disease (i.e., II+III stage compared to I stage, p<0.05 for all). CONCLUSIONS: IPF patients are in a state of profound oxidative stress compared to healthy people. The inflammatory component of the disease was confirmed by higher hsCRP and SAA1, but lower [25(OH)D] in IPF than in healthy people. Also, higher levels of sPD-L1 in patients with IPF compared to healthy individuals suggest that sPD-L1 may have a significant role in immune response in IPF.

Total costs of inpatient treatment for COVID-19 in a tertiary hospital in Serbia.

BACKGROUND: Our study aimed to identify the total costs of inpatient treatment for coronavirus disease 2019 (COVID-19) in a tertiary institution in Serbia, an upper-middle-income country in Southeast Europe. METHODS: An observational, retrospective, cost-of-illness study was performed from the perspective of the National Health Insurance Fund and included a cohort of 78 females and 118 males admitted to the COVID-19 ward units of a tertiary center during the first wave of the pandemic. RESULTS: The median of the total costs in the non-survivors subgroup (n =43) was 3,279.16 Euros [interquartile range (IQR): 4,023.34; range: 355.20-9,909.61) which is higher than in the survivors (n =153) subgroup 747.10 Euros (IQR: 1,088.21; 46.71-3,265.91). The cut-off value of 156.46 Euros regarding the total costs per day was estimated to have 95.3 % sensitivity and 91.5 % specificity for predicting patients' dismal prognosis, with the area under the curve (AUC) of 0.968 (95 % confidence interval: 0.940-0.996, p <0.001). CONCLUSIONS: Direct medical inpatient treatment costs for COVID-19 represent a significant economic burden. The link between increased costs and an ultimate unfavorable outcome should be further explored.HIPPOKRATIA 2022, 26 (2):62-69.

Intravenous thrombolytic therapy in patients with stroke mimics: baseline characteristics and safety profile.

BACKGROUND: The decision to treat with intravenous (i.v.) rt-PA a patient with acute cerebral ischaemia is based on clinical and imaging criteria recorded in emergency. In such an emergency situation stroke mimics may sometimes be misdiagnosed, and lead to an erroneous prescription of rtPA. The objective of this study was to determine the baseline profile and the outcome in patients with stroke mimics who received i.v. rtPA. METHODS: We analysed clinical characteristics, and outcomes in patients diagnosed at discharge as having a stroke mimic who received rtPA in the university hospitals of Lille and Belgrade. RESULTS: Amongst 488 patients, seven (1.4%) were diagnosed at discharge with stroke mimics: four had somatoform disturbances, one had migraine aura, one had Bell palsy, and one had a probable Todd's palsy. Patients with stroke mimics were younger, and had milder deficits. Six were investigated by computed tomographic-scan and the only one who had an emergency magnetic resonance imaging, had no abnormality on diffusion weighted images. Five patients had a modified Rankin scale 0-1 and there was no case of intracranial bleeding. CONCLUSION: Patients with stroke mimics have a good safety profile when treated with rt-PA. In case of doubt, physicians should not postpone thrombolysis, because its potential benefit in confirmed ischaemic stroke might be higher than the risk of complications in stroke mimics. A combined analysis of such small series of cases would be useful to have a better delineation of the clinical profile of these patients.

Gallbladder emptying in patients with major depression: a case series.

INTRODUCTION: Although several adverse effects of antidepressants on the gastrointestinal tract have been described (bleeding, constipation, dolichocolon), their influence on gallbladder motility was not investigated.The aim of our study was to investigate the effects of selected antidepressants on gallbladder emptying in patients with major depression. METHODS: The study was set up as an open clinical trial, with the same intervention (ingestion of test meal provoking gallbladder emptying) undertaken in 112 patients with major depression. There were 30 patients not taking antidepressants (the control group), 25 patients taking amitriptyline, 30 patients taking maprotiline, and 27 patients taking fluoxetine. The volume of gallbladder in the study patients was measured by ultrasonography before the test meal, and 15, 30, 45 and 60 min after the meal. RESULTS: 1 h after ingestion of the study meal, the amitriptyline group showed incomplete gallbladder emptying (F=10.829, df=3, p=0.000; mean residual volume 11.0±6.1 mL), while in the control, maprotiline and fluoxetine groups emptying of gallbladder was complete (mean residual volumes 5.0±3.3 mL, 5.6±3.7 mL and 5.7±2.3 mL, respectively). DISCUSSION: In patients with cholecystitis, it would be wise to use antidepressants which do not impair gallbladder emptying, like maprotiline or fluoxetine, and to avoid amitriptyline.

One-stage transanal surgical technique for Hirschsprung's disease: is the age of a patient a limiting factor?

Hirschsprung's disease in the adolescent is a rare and often misdiagnosed cause of lifelong refractory constipation. In this particular case, a male patient spent 13 years with an unrecognized illness that was eventually diagnosed as Hirschsprung's disease. The age of the patient is considered a limiting factor due to over-distention and hypertrophy of the rectosigmoid colon that has to be pulled through a muscular cylinder in a limited operative field. This report of a successfully treated teenage boy using a one-stage transanal endorectal approach without conversion to laparotomy, his uneventful recovery and excellent functional results supports the opinion that practically all patients with Hirschsprung's disease can be treated using this technique, regardless of age and size of colon, on condition that the operation is performed by experienced surgeons familiar with classic operative procedures to avoid possible operative pitfalls.

Psychological well-being in advanced NSCLC patients in Serbia: impact of sociodemographic and clinical factors.

UNLABELLED: Patients with advanced non-small cell lung cancer (NSCLC) usually undergo toxic treatment (chemotherapy and/or radiotherapy). They can experience devastating effects of illness and therapies on their psychological and emotional well-being. On the other hand, untreated psychological distress is associated with reduced quality of life and inadequate palliation of physical symptoms.
In order to estimate frequency of anxiety and depressive symptoms and influence of demographic, socioeconomic and clinical factors on psychological well-being, we performed this cross-sectional study in group of 100 patients with advanced stage of disease. Symptoms of anxiety and depression were assessed using the Hamilton Anxiety Rating Scale (HARS) and Hamilton Depression Rating scale (HDRS). Health-related quality of life data are obtained by EORTC QLC C30 and SF 36.
Patients with poor performance status (PS) experienced significantly more anxiety and depressive symptoms (p=0.001) and worse emotional (p=0.001) and mental functioning (p=0.001). Treated patients had significantly better mental (p=0.011) and emotional (p=0.001) functioning in compared to newly diagnosed ones. Somewhat unusual, unemployed participants reported significantly less anxiety (p=0.029) and depressive (p=0.002) symptoms, better mental (p=0.030) and emotional functioning (p=0.007). Additionally, nausea and vomiting adversely affected mental health and emotional functioning and correlated significantly positively with HARS and HDRS scores.
Our findings suggest significant impact of some disease-related factors (PS, active treatment) and treatment-related factors (chemotherapy -induced nausea and vomiting) on psychological well-being of patients with advanced NSCLC. This should be taking an account when appropriate interventions are planned. KEYWORDS: lung cancer, anxiety, depression, quality of life, chemotherapy, chemotherapy-induced nausea and vomiting.

Health-related quality of life in lung cancer patients in Serbia: correlation with socio-economic and clinical parameters.

The objective of this study was to assess health-related quality of life (HRQoL) in patients with advanced non-small cell lung cancer (NSCLC). In Serbia, there is the lack of available data on HRQoL in lung cancer patients. The special attention in our study has been paid on relationships between socio-economic factors and HRQoL. This cross-sectional study was undertaken in group of 100 NSCLC patients with advanced stage diseases. HRQoL was measured using three standard instruments: 36-item Short Form Health Survey, EORTC QLQ-C30 and its Lung Cancer module (EORTC QLQ-LC13). Unexpected, highly educated patients reported significantly worse social functioning (P=0.044), and higher degree of financial difficulties (P=0.047), in comparison with less-educated. Also unusual, unemployed patients had significantly better HRQoL in all domains and significantly lower symptom distress. Significantly better overall HRQoL (P=0.043), social (P=0.024), emotional (P=0.001) and mental functioning (P=0.011) were observed in patients treated with chemotherapy in comparison with newly diagnosed ones. In addition, the most prominent side effects of chemotherapy were nausea and vomiting, and all QoL domains correlated significantly with them. Patients who undergo active treatment improve their HRQoL but chemotherapy-induced emesis adversely affects many HRQoL domains. Additionally, HRQoL is highly dependent on patient's socio-economic characteristic.

Could depression be a new branch of MIA syndrome?

The aims of the present study were to determine the prevalence of depression in our dialysis patients, to detect the most powerful variables associated with depression, and to determine the role of depression in prediction of mortality. The prospective follow-up study of 128 patients (77 HD and 51 CAPD, 65 male, aged 53.8 +/- 13.5 years, dialysis duration 64.7 +/- 64.8 months) was carried out over 36 months. Depression by the Beck Depression Inventory-BDI-II score, laboratory parameters (hemoglobin, serum albumin and creatinine concentration), immunological status (cytokines and hsCRP), comorbidity by Index of Physical Impairment (IPI) and adequacy of dialysis by Kt/V were monitored. The overall prevalence of depression in the dialysis patients (BDI score > or = 14) was 45.3%, and 28.2%, respectively, for moderate and severe depression (BDI > or = 20). The most powerful variable associated with depression was IL-6, but associations with albumin, hemoglobin, creatinine and IPI score were also found. During the follow-up period 36 patients died, 7 patients left the cohort and 2 patients were transplanted. If IPI score was not included in the multivariate Cox analysis, the BDI score remained one of the best predictors of mortality along with albumin. In conclusion, because of the close association of depression with inflammation, malnutrition, and cardiovascular mortality, it could be speculated that depression is one branch of the MIA (malnutrition, inflammation, atherosclerosis) syndrome.

Hemodialysis modality, percentage of body fat, and patient survival.

BACKGROUND: A number of studies have reported lower mortality of overweight hemodialysis patients. This post hoc analysis of an observational prospective single-center study was aimed at elucidating whether both being overweight and surviving longer could result from changes in the hemodialysis modality. METHODS: The study included a cohort of 242 patients who were gradually switched from cuprophane membrane and acetate dialysis to polysulfone (including high-flux) membranes and bicarbonate dialysis. The analysis involved 12 months of baseline data obtained during the first calendar year after the patients entered the study (1994-2001) and repeated measurements for up to 132 months of follow-up (until 2004). Anthropometric measurements were made during the winter season and the percentage of body fat (%fat) was calculated from triceps, biceps, subscapular, and suprailiac skinfolds (K/DOQI guidelines).Kt/V, normalized protein catabolic rate, and cardiovascular comorbidity were also determined and laboratory analyses undertaken. RESULTS: Significant correlations were found between %fat and bicarbonate dialysate as well as polysulfone membrane and high-flux membrane. The linear mixed model showed dependence of %fat on polysulfone and high-flux membrane (p<0.01) Multivariate Cox regression (time-dependent covariates) found %fat to be an independent factor for longer survival, in addition to polysulfone and high-flux membranes. CONCLUSION: Changes in hemodialysis modality were followed by both higher body fat percentage and patient survival. The reverse epidemiology of overweight patients might be at least partially the result of the influence of nonnutritional factors, such as a change in hemodialysis modality (introducing biocompatible high-flux and low-flux membranes and bicarbonate dialysis).

Relation between serum urea and mortality of hemodialysis patients.

BACKGROUND: It is well known that serum urea concentration is not a good predictor of mortality in hemodialysis patients. On the other hand, urea kinetic modeling has been very successfully used to measure dialysis dose by the Kt/V index, which was found to be a good predictor of mortality. Could there be a relation between urea and mortality, but in some more complex way? METHODS: This is a post-hoc analysis of a single center observation study that included 242 patients and an 11-year observation period. Mortality rates between the quartiles of serum urea levels were examined by a 2 x 4 table with the chi(2) test. Both univariate and multivariate survival analyses were performed with standard and segmented extended Cox regression. RESULTS: The relation between mean urea in the baseline period and mortality showed an irregular U-shaped curve. The lowest mortality was observed in the third quartile (28 to 31 mmol/L). The relation between mean urea in the whole observation period and mortality was a J-shaped curve. The lowest mortality was in the second quartile (25-27 mmol/L). Urea was not a predictor of mortality in the whole cohort, but low-urea (binary) and high-urea (binary) were independent predictors of mortality in the corresponding models using standard or extended Cox regression. CONCLUSION: This study revealed a complex relationship between urea and mortality in hemodialysis patients. Patients with low or high urea levels exhibited higher mortality than those with medium levels, while both low and high levels of urea were independent predictors of all-cause mortality.

Expression of HER2/neu, estrogen and progesterone receptors, CA 125 and CA19-9 on cancer cell membrane in patients with serous and mucinous carcinoma of the ovary.

PURPOSE: To examine the expression of the membrane markers of estrogen (ER) and progesterone receptors (PR), CA-125, CA 19-9 and HER2/neu in ovarian cancer tissues. METHODS: Fifty-four samples of ovarian cancer tissues originating from 55 patients were examined by immunohistochemistry. Forty-three had serous papillary ovarian cancer, 9 of which were grade I, 12 grade II and 2 grade III. Twelve patients had a classic mucinous ovarian cancer, 5 of which were grade I, 4 grade II and 0 grade III. RESULTS: Out of 43 patients with serous ovarian cancer, 7 expressed both steroid receptors, 22 had only one (10 ER and 12 PR), while 14 were negative. Only 2/12 patients with classic mucinous ovarian cancer expressed of both receptors. CA-125 was expressed in 37/43 patients with serous ovarian cancer and in 4/12 patients with classic mucinous ovarian cancer. CA 19-9 was expressed in 3/43 patients with serous ovarian cancer, and coexpressed with CA-125 in 2/3 patients. In patients with classic mucinous ovarian cancer, 4/12 had expression of CA 19-9 without coexpression with CA-125. HER2/neu positivity (3+) was proven in only one case with classic mucinous ovarian cancer, and any other expression (1+) in 7 additional patients (1 mucinous and 6 serous ovarian cancers). CONCLUSION: Positive HER2/neu expression in the cells of ovarian cancer is very rare and HER2/neu overexpression is even rarer. Expression of ER and PR does not depend on tumor grade and/or at least not in grade I and II. Positive CA 19-9 expression may be present not only in cases of classic mucinous ovarian cancer but also in typical serous ovarian cancer. However, in the classic mucinous ovarian cancer, CA-125 may be expressed, though in relatively low percentage.

Radiotherapy-induced changes of peripheral blood lymphocyte subpopulations in cervical cancer patients: relationship to clinical response.

PURPOSE: To determine the absolute number and percentage of peripheral blood lymphocyte subpopulations positive (+) cells CD8(+), CD8(+)NKG2D(+), CD8(+), Granzyme B(+) (GrB), CD16(+), CD16(+)NKG2D(+), CD56(+) and CD56(+)NKG2D(+) in cervical cancer patients before and after radiotherapy (RT), and to analyze whether their changes are related to the clinical response. MATERIALS AND METHODS: Stage IIB - IVA cervical cancer patients received external irradiation and concomitant intracavitary brachytherapy. Blood samples for immunophenotypic analysis by flow cytometry were collected from each patient one day before starting RT and one day after completing RT. Fifteen healthy volunteers served as controls. Surface marker expression and granzyme B positivity were quantified on FACSCalibur flow cytometer. RESULTS: Unlike their absolute numbers, the percentages of all analyzed lymphocyte subsets of all patients, including those with complete response (CR), were significantly increased (p <0.05) after RT. Only in patients with progressive disease (PD), CD8(+), CD8(+)NKG2D(+), CD16(+) and CD56(+)NKG2D(+) lymphocytes were not significantly increased. In healthy volunteers, the percentage of CD8(+)GrB(+) lymphocytes was lower than in patients after RT, while the percentages of CD56(+) and CD56(+)NKG2D(+) cells were higher than in patients before RT (p <0.05). CONCLUSION: Our data indicate that RT, besides its direct cytoreductive effect on tumor cells, may contribute to better immunological control of cervical cancer.

Brain metastases as late breast cancer relapse. Single institution experience and review of the literature.

PURPOSE: Approximately 40% of HER2-positive breast cancer patients will develop brain metastases, usually during the first 2-3 years following initial diagnosis and up to 2 years after overt metastatic spread. However, there are no data about brain metastases development as a late disease relapse. In addition, there are no data whether the high incidence of brain metastases is maintained in patients with HER2 overexpression even in late brain metastases. The aim of this paper was to determine the incidence of brain metastases and the HER2 status in patients who developed late relapse, at least 5 years after the initial diagnosis. PATIENTS AND METHODS: Among 384 consecutive breast cancer patients with late relapse, only 8 developed brain metastases. Archival pathological specimens of the primary tumors of those 8 patients were tested by immunohistochemistry (IHC) for HER2 status. RESULTS: The incidence of late brain metastases was 2% (8/384). None of these patients had HER2 3+ primary breast cancer. CONCLUSION: This study shows that the risk for brain metastases in HER2 3+ breast cancer patients is very low or might be even absent as a late relapse. Absence of late brain metastases in HER2 3+ breast cancer might be attributed to specific biological characteristics of HER2 3+ carcinomas to develop brain metastases mostly in the early course of metastatic disease.

Refraction and band isotropy in 2D square-like Archimedean photonic crystal lattices.

In this paper we theoretically study refraction effects in the 2D square-like Archimedean photonic crystals (3(2), 4, 3, 4) and (4, 8(2)) made of dielectric rods in air. In addition, we investigated a band isotropy and band gap structure in these lattices. We compared the square and square-like structures as well, their refraction characteristics, zone structures and the level of band and band gap isotropy (bandwidth and band gap dependence on the wave vector). We found that square-like structures can have some advantages over the square ones regarding the completeness of the gap, its isotropy and the gap width. Also, due to the same square primitive unit cell and the first Brillouin zone, the square and square-like lattices have similar optical response in lower bands.

Clinical and epidemiological evaluation of tuberculosis in Serbia, 1990-2004.

SETTING: Republic of Serbia, excluding Kosovo. OBJECTIVE: To estimate the clinical and epidemiological pattern of tuberculosis (TB) in Serbia during the period 1990-2004. DESIGN: A retrospective analysis of clinical and epidemiological data on TB patients registered in annual TB reports. RESULTS: During the 15-year period, TB incidence levelled off in Serbia. The slightly decreasing trend occurred in both total pulmonary TB (PTB) and laboratory confirmed PTB (PTB+) incidence (P > 0.05), while the trend of extra-pulmonary TB (EPTB) incidence increased slightly (P > 0.05). During the same period, TB mortality showed a significantly decreasing trend (P < 0.05). The mean annual proportion of PTB+ cases among newly reported PTB cases was 62.7%. The mean proportion of EPTB cases among total TB cases was 6.1%. The mean percentage of cases with resistance to at least one anti-tuberculosis drug was 4.8%. CONCLUSION: Thanks to the good organisation and efficient work of anti-tuberculosis dispensaries in Serbia, as well as to the low incidence of AIDS and low frequency of Mycobacterium tuberculosis resistant strains, TB incidence did not increase during the period observed and TB mortality significantly decreased, despite markedly deteriorated socio-economic conditions during the 1990s.