Attitudes toward Death among Health Care Professionals in the Balkan Region.

Background and Objectives: Death is an unavoidable experience in any person's life and affects not only the dying person but also their caregivers. The dying process has been displaced from homes to health care facilities in the majority of cases. Facing death and dying has become an everyday life of health care professionals (HCP), especially in palliative care (PC) settings. This study aimed to investigate the death attitudes among HCPs in Serbia. Materials and Methods: The Serbian version of the Death Attitude Profile-Revised (DAP-RSp) was used as a measurement instrument. Results: The average age of the 180 included participants was 42.2 ± 9.9 years; the majority were females (70.0%), with more than 10 years of working experience (73.0%), physicians (70.0%) and those working in a non-oncological (non-ONC) field (57.78%). The mean total score of DAP-RSp was 124.80 ± 22.44. The highest mean score was observed in the neutral acceptance dimension (NA) (5.82 ± 0.90) and lowest in the Escape acceptance (EA) (2.57 ± 1.21). Higher negative death attitudes were reported among nurses compared to physicians (p = 0.002). Statistically significant differences were observed in the fear of death (FD) and death avoidance (DA) domains, favoring PC specialists and oncologists (p = 0.004; p = 0.015). Physicians working in Oncology (ONC) showed lower FD values (p = 0.001) compared to non-ONC departments. Conclusions: Attitudes toward death among HCPs are of great importance for the well-being of both HCPs and patients. Negative attitudes can lead to deficient care. The fear of death is highly represented among Serbian HCPs working in non-ONC fields, including both nurses and physicians. This study emphasizes the need for further research to comprehensively explore and understand HCPs' attitudes toward death. This research highlights the need for the development of an educational curriculum across all levels of medical education, aimed at overcoming the fear of death and enhancing coping strategies, which will improve the care for patients diagnosed with terminal illnesses.

RESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer.

PURPOSE: The phase III RESILIENT trial compared second-line liposomal irinotecan with topotecan in patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: Patients with SCLC and progression on or after first-line platinum-based chemotherapy were randomly assigned (1:1) to intravenous (IV) liposomal irinotecan (70 mg/m2 every 2 weeks in a 6-week cycle) or IV topotecan (1.5 mg/m2 daily for 5 consecutive days, every 3 weeks in a 6-week cycle). The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) and objective response rate (ORR). RESULTS: Among 461 randomly assigned patients, 229 received liposomal irinotecan and 232 received topotecan. The median follow-up was 18.4 months. The median OS was 7.9 months with liposomal irinotecan versus 8.3 months with topotecan (hazard ratio [HR], 1.11 [95% CI, 0.90 to 1.37]; P = .31). The median PFS per blinded independent central review (BICR) was 4.0 months with liposomal irinotecan and 3.3 months with topotecan (HR, 0.96 [95% CI, 0.77 to 1.20]; nominal P = .71); ORR per BICR was 44.1% (95% CI, 37.6 to 50.8) and 21.6% (16.4 to 27.4), respectively. Overall, 42.0% and 83.4% of patients receiving liposomal irinotecan and topotecan, respectively, experienced grade ≥3 related treatment-emergent adverse events (TEAEs). The most common grade ≥3 related TEAEs were diarrhea (13.7%), neutropenia (8.0%), and decreased neutrophil count (4.4%) with liposomal irinotecan and neutropenia (51.6%), anemia (30.9%), and leukopenia (29.1%) with topotecan. CONCLUSION: Liposomal irinotecan and topotecan demonstrated similar median OS and PFS in patients with relapsed SCLC. Although the primary end point of OS was not met, liposomal irinotecan demonstrated a higher ORR than topotecan. The safety profile of liposomal irinotecan was consistent with its known safety profile; no new safety concerns emerged.

Oral micro-electronic platform for temperature and humidity monitoring.

Intraoral theranostics, the integration of diagnostics and therapeutics within the oral cavity, is gaining significant traction. This pioneering approach primarily addresses issues like xerostomia (dry mouth), commonly resulting from cancer treatment, with a specific focus on monitoring temperature and humidity. This paper introduces the innovative Intra-Oral Portable Micro-Electronic (IOPM) fluidic theranostic device platform. It leverages conventional dental spoons by incorporating advanced sensors for precise measurements of oral temperature and humidity. Personalization options include a microfluidic chip and a tooth model, enabling targeted delivery of therapeutic agents to optimize treatment outcomes. The electronic control system simplifies the administration of fluid dosages, intelligently adjusted based on real-time oral cavity temperature and humidity readings. Rigorous experimental evaluations validate the platform's precision in delivering fluid volumes at predefined intervals. This platform represents a transformative advancement for individuals contending with oral health challenges such as xerostomia (dry mouth). Furthermore, it has the potential to elevate oral healthcare standards by providing advanced diagnostics and tailored therapeutic solutions, benefiting both patients and dental professionals alike.

Avelumab in Combination With Cetuximab and Chemotherapy as First-Line Treatment for Patients With Advanced Squamous NSCLC.

Introduction: We present the results of a phase 2a trial of first-line avelumab (anti-programmed death-ligand 1 antibody) plus cetuximab (anti-EGFR antibody) in patients with advanced squamous NSCLC. Methods: Patients with recurrent or metastatic squamous NSCLC received avelumab 800 mg (d 1 and 8), cetuximab 250 mg/m2 (d 1) and 500 mg/m2 (d 8), cisplatin 75 mg/m2 (d 1), and gemcitabine 1250 mg/m2 (d 1 and 8) for four 3-week cycles, followed by avelumab 800 mg and cetuximab 500 mg/m2 every 2 weeks. The primary end point was the best overall response; the secondary end points were progression-free survival, duration of response, overall survival, and safety. Efficacy analyses were reported from an updated data cutoff. Results: A total of 43 patients were enrolled. The median follow-up was 6.6 months for the primary analyses and 9.2 months for the efficacy analyses. In the efficacy analyses, 15 patients had a confirmed partial response (objective response rate, 34.9% [95% confidence interval: 21.0%-50.9%]), and the median duration of response was 7.1 months (95% confidence interval: 4.2-12.5 mo). The median progression-free survival and overall survival were 6.1 months and 10.0 months, respectively. In the safety analyses (primary analysis), 38 patients (88.4%) had a treatment-related adverse event, of whom 24 (55.8%) had a grade 3 or higher treatment-related adverse event. Conclusions: The combination of avelumab + cetuximab and chemotherapy showed antitumor activity and tolerable safety; however, the ORR was not improved compared with those reported for current standards of care (NCT03717155).

Multifunctional Arabinoxylan-functionalized-Graphene Oxide Based Composite Hydrogel for Skin Tissue Engineering.

Wound healing is an important physiological process involving a series of cellular and molecular developments. A multifunctional hydrogel that prevents infection and promotes wound healing has great significance for wound healing applications in biomedical engineering. We have functionalized arabinoxylan and graphene oxide (GO) using the hydrothermal method, through cross-linking GO-arabinoxylan and polyvinyl alcohol (PVA) with tetraethyl orthosilicate (TEOS) to get multifunctional composite hydrogels. These composite hydrogels were characterized by FTIR, SEM, water contact angle, and mechanical testing to determine structural, morphological, wetting, and mechanical behavior, respectively. Swelling and biodegradation were also conducted in different media. The enhanced antibacterial activities were observed against different bacterial strains (E. coli, S. aureus, and P. aeruginosa); anticancer activities and biocompatibility assays were found effective against U-87 and MC3T3-E1 cell lines due to the synergic effect of hydrogels. In vivo activities were conducted using a mouse full-thickness skin model, and accelerated wound healing was found without any major inflammation within 7 days with improved vascularization. From the results, these composite hydrogels might be potential wound dressing materials for biomedical applications.

Taurine Grafted Micro-Implants Improved Functions without Direct Dependency between Interleukin-6 and the Bile Acid Lithocholic Acid in Plasma.

A recent study showed an association between diabetes development and the bile acid lithocholic acid (LCA), while another study demonstrated positive biological effects of the conjugated bile acid, taurocholic acid (TCA), on pancreatic cells. Thus, this study aimed to encapsulate TCA with primary islets (graft) and study the biological effects of the graft, post-transplantation, in diabetic mice, including effects on LCA concentrations. Sixteen mature adult mice were made diabetic and randomly divided into two equal groups, control and test (transplanted encapsulated islets without or with TCA). Graft pharmaceutical features pre-transplantation, and biological effects including on LCA concentrations post-transplantation, were measured. TCA-microcapsules had an oval shape and similar size compared with the control. The treatment group survived longer, showed improved glucose and interleukin-6 concentrations, and lower LCA concentrations in plasma, large intestine, faeces, liver and spleen, compared with control. Results suggest that TCA incorporation with islets encapsulated graft exerted beneficial effects, but there was no direct and significant dependency between concentrations of interleukin-6 and LCA.

Polyelectrolytes Formulated with Primary Unconjugated Bile Acid Optimised Pharmacology of Bio-Engineered Implant.

INTRODUCTION: Several studies have shown that different biomaterials and hydrogels comprising various bile acids such as chenodeoxycholic acid (CDCA), as well as excipients such as poly-(styrene)-sulphonate (PSS) and poly-(allyl)-amine (PAA), exhibited positive biological effects on encapsulated viable pancreatic ß-cells. Hence, this study aimed to investigate whether incorporating CDCA with PSS and PAA will optimise the functions of encapsulated pancreatic islets post-transplantation in Type 1 diabetes (T1D). METHODS: Mice were made T1D, divided into two equal groups, and transplanted with encapsulated islets in PSS-PAA (control) or with CDCA-PSS-PAA (treatment) microcapsules. The effects of transplanted microcapsules on blood glucose, inflammation and the bile acid profile were measured post-transplantation. RESULTS AND CONCLUSION: Compared with control, the treatment group showed better survival rate, improved glycaemic control, and lower inflammatory profile, illustrated by ↓ interleukin 1-ß, interleukin-6, interleukin-12, and tumour-necrosis factor-α, and ↓ levels of the bile acid, as well as lithocholic acid in the plasma, liver, large intestine and faeces. The results suggest that CDCA incorporation with PSS-PAA microcapsules exerted beneficial effects on encapsulated islets and resulted in enhanced diabetes treatment, post-transplantation, at the local and systemic levels.

Relationship Between Socio-Demographic Characteristics, Reproductive Health Behaviors, and Health Literacy of Women in Serbia.

Introduction: Health literacy of women can significantly affect different aspects of reproductive health. The aim of this study was the assessment of relationship of health literacy, socio-demographic characteristics and reproductive health behaviors of women in Serbia. Methodology: This was a cross-sectional study on a random sample of women aged 18 and over from the territories of three Serbian regions, stratified according to age groups, region and type of settlement. A standardized version of the European Health Literacy Survey Questionnaire (HLS-EU-Q47) was used in assessing health literacy of women. Results: Based on the calculated index of health literacy, 9.6% of respondents had inadequate health literacy. Inadequate levels of health literacy were more common in women living in rural areas (OR = 1.111) and the poorer classes (OR = 5.122). Employed women (OP = 1.249), with good health (OR = 1.512) with a degree (OR = 1.535) had bigger odds to have adequate health literacy. Multivariate regression analysis showed the following significant predictors: commitment to the chosen gynecologist (OR = 1.530), contraceptive use (OR = 1.020), knowledge of the damages that could be caused by the human papillomavirus (HPV) (OR = 1.578), awareness of vaccine availability against HPV infection (OR = 1.217) and following the health-related topics (OR = 2.350). Conclusion: Limited levels of health literacy were significantly higher among middle-aged women, among those living in rural areas, among women who rated their health as poor or very poor, and who exhibited more negative patterns of reproductive health behavior, indicating the need for implementation of prevention programs and strategies with the aim of increasing the level of health literacy.

Association of the consumption of common food groups and beverages with mortality from cancer, ischaemic heart disease and diabetes mellitus in Serbia, 1991-2010: an ecological study.

OBJECTIVES: This paper reports association between mortality rates from cancer, ischaemic heart disease and diabetes mellitus and the consumption of common food groups and beverages in Serbia. DESIGN: In this ecological study, data on both mortality and the average annual consumption of common food groups and beverages per household's member were obtained from official data-collection sources. The multivariate linear regression analysis was used to determine the strength of the associations between consumption of common food groups and beverages and mortality rates. RESULTS: Markedly increasing trends of cancer, ischaemic heart disease and diabetes mellitus mortality rates were observed in Serbia in the period 1991-2010. Mortality rates from cancer were negatively associated with consumption of vegetable oil (p=0.005) and grains (p=0.001), and same was found for ischaemic heart disease (p=0.002 and 0.021, respectively), while consumption of other dairy products showed a significant positive association (p<0.001 and p=0.032, respectively). In men and women, mortality rates from diabetes mellitus showed a significant positive association with consumption of poultry (p=0.014 and 0.004, respectively). Consumption of beef and grains showed a significant negative association with cancer mortality rates in both genders (p=0.002 and p<0.001 in men, and p<0.001 and p=0.014 in women, respectively), while consumption of cheese was negatively associated only in men (p<0.001). Mortality from diabetes mellitus showed a significant positive association with consumption of animal fat and other dairy products only in women (p=0.003 and 0.046, respectively). CONCLUSIONS: Association between unfavourable mortality trends from cancer, ischaemic heart disease and diabetes mellitus, and common food groups and beverages consumption was observed and should be assessed in future analytical epidemiological studies. Promotion of healthy diet is sorely needed in Serbia.

Radial Endobronchial Ultrasound (EBUS) Guided Suction Catheter-Biopsy in Histological Diagnosis of Peripheral Pulmonary Lesions.

BACKGROUND: EBUS guided trans-bronchial biopsy became routine in diagnosis of peripheral pulmonary lesions (PPL). Suction catheter-biopsy is a technique for obtaining a tissue sample from peripheral lung parenchyma. Aim of this study was to evaluate diagnostic efficiency, feasibility and safety of EBUS guided suction catheter-biopsy (SCB) in comparison to trans-bronchial biopsy (TBB) in diagnosis of PPL. The main intention was to demonstrate non-inferiority of the technique over trans-bronchial biopsy, especially when used under navigation of the EBUS. METHODS: Radial EBUS probe (UM-3R, Olympus Co, Japan.) without guiding sheath was used to navigate suction catheter and TBB forceps to the PPL. The catheter was connected to the collection canister via vacuum pump. The SCB specimens were fixed with 10% buffered formalin. RESULTS: There were 168 patients enrolled in this study; 69.9% males and 30.1% females. Main lesion diameter was 4.1±1.9 cm. Majority of patients, 131(77.9%) were diagnosed with lung cancer. Per-biopsy calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for EBUS-SCB were 92.4%, 100%, 100% and 67.7%, respectively. Corresponding values for EBUS-TBB were 92.3%, 100%, 100% and 69.7%. Only the size of the lesion significantly influenced (p=0.005) diagnostic performance. Complications occurred in 2 patients; one pneumothorax and one excessive bleeding. CONCLUSION: EBUS guided SCB is efficient, feasible and safe in diagnosis of peripheral lung cancer. The technique is complementary to trans-bronchial biopsy.

Inflammatory Myofibroblastic Tumours of the Respiratory Tract: A Series of Three Cases with Varying Clinical Presentations and Treatment.

INTRODUCTION: Inflammatory myofibroblastic tumor in the respiratory system is a rare and controversial disease. It is macroscopically well-circumscribed, non-encapsulated, firm and usually a yellowish-white mass. Histologically it is composed of the following spindled and inflammatory cells: lymphocytes, plasma cells, and histiocytes, including Touton type multinucleated giant cells. CASE OUTLINE: The series included a 49-year-old man with a tracheal inflammatory myofibroblastic tumor who complained of hoarseness; a 42-year-old man who was coughing and had a blood-stained sputum, and inflammatory myofibroblastic tumor was in the right main and intermediate bronchus; and a 32-year-old man with chest pain and inflammatory myofibroblastic tumor as a solitary peripheral nodule in the left lower lobe. In all the cases, the tumor was resected bronchoscopically and surgically. CONCLUSION: Inflammatory myofibroblastic tumor of the lung and the trachea is rare. Complete resection, when possible, should be the choice of treatment. After the complete removal, prognosis is generally excellent and recurrences are rare.

Advanced bronchoscopic techniques in diagnosis and staging of lung cancer.

The role of advanced brochoscopic diagnostic techniques in detection and staging of lung cancer has steeply increased in recent years. Bronchoscopic imaging techniques became widely available and easy to use. Technical improvement led to merging in technologies making autofluorescence or narrow band imaging incorporated into one bronchoscope. New tools, such as autofluorescence imagining (AFI), narrow band imaging (NBI) or fuji intelligent chromo endoscopy (FICE), found their place in respiratory endoscopy suites. Development of endobronchial ultrasound (EBUS) improved minimally invasive mediastinal staging and diagnosis of peripheral lung lesions. Linear EBUS proven to be complementary to mediastinoscopy. This technique is now available in almost all high volume centers performing bronchoscopy. Radial EBUS with mini-probes and guiding sheaths provides accurate diagnosis of peripheral pulmonary lesions. Combining EBUS guided procedures with rapid on site cytology (ROSE) increases diagnostic yield even more. Electromagnetic navigation technology (EMN) is also widely used for diagnosis of peripheral lesions. Future development will certainly lead to new improvements in technology and creation of new sophisticated tools for research in respiratory endoscopy. Broncho-microscopy, alveoloscopy, optical coherence tomography are some of the new research techniques emerging for rapid technological development.

The role of autofluorescence bronchoscopy in monitoring a tumorous lesion in the bronchial mucosa: a case report.

INTRODUCTION: Autofluorescence bronchoscopy (AFB) is a diagnostic procedure that is included in all diagnostic algorithms discovering precancerous lesions in the large airways. CASE REPORT: We presented a 71-year-old patient submitted to exploration due to prolonged cough. Both noninvasive and invasive pulmonary diagnostic management was carried out. On bronchoscopy, an endobronchial mass was detected in the apical bronchus. A positive endoscopy finding indicated AFB which disclosed a fluorescence alteration of the tumor mucosa and the former bronchoscopy site. Histopathological analysis of the catheter biopsy obtained samples from the right upper lobe confirmed fibrinous purulent pneumonia in organization. The applied treatment resulted in regression of both symptoms and the lesion in the right upper lobe. Due to a positive AFB finding, the patient was regularly observed over the following three years, having had three control AFB to monitor the initial finding. CONCLUSION: AFB may be utilized in the routine of everyday practice to assess the spread of the disease, as well as in the postsurgical and long-term follow-up of operated patients. The procedure may also be applied to enable an easier and more reliable observation of patients with suspicious endobronchial lesions, smokers with altered fluorescence of the bronchial mucosa, and chronic patients.

Autofluorescence imaging videobronchoscopy improves assessment of tumor margins and affects therapeutic strategy in central lung cancer.

OBJECTIVE: Autofluorescence imaging (AFI) videobronchoscopy is a new endoscopic tool that improves visualization of neoplastic changes in the bronchial mucosa. The major aim of our study was to determine sensitivity and specificity of the technique in the assessment of tumor extent (margins). The secondary objective was to evaluate the possible effect of AFI on the change in therapeutic decisions of lung cancer treatment. METHODS: In this prospective trial, we enrolled 104 patients in whom we performed 624 targeted biopsies, 3 from the pathologically altered mucosa (red-brownish or magenta colored) and 3 from randomly picked normal areas. We were using the Olympus BF-F260 videobronchoscope and EVIS LUCERA system. White light videobronchoscopy (WLB) preceded AFI examination and biopsy collection. All biopsy specimens were examined by a pathologist blinded to bronchoscopy findings, and where applicable surgically resected specimens were examined. RESULTS: In 14.4% of the patients, AFI revealed a greater extent of the tumor than WLB, and in 11.5% that finding led to change in therapeutic decision (lesser or greater resection or avoidance of surgery). We found a significant correlation between tumor extent determined by AFI and changes in therapeutic decisions (P < 0.01). Sensitivity, specificity, positive predictive value and negative predictive value for AFI in the assessment of tumor extension were 93%, 92%, 92% and 93%, respectively. Corresponding results for WLB were 84%, 79%, 77% and 85%, respectively. Relative sensitivity of AFI is 1.11. CONCLUSIONS: Our results confirm that AFI videobronchoscopy significantly improves the assessment of central lung cancer extension and influences the therapeutic strategy. This technique has greater sensitivity and specificity, in assessment of tumor margins, than WLB alone.

Narrow band imaging videobronchoscopy improves assessment of lung cancer extension and influences therapeutic strategy.

OBJECTIVE: Narrow band imaging (NBI) videobronchoscopy is a new technique aimed at lung cancer detection. This study investigated its sensitivity and specificity for evaluation of lung cancer extension and its possible influence on therapeutic decision, compared with white light videobronchoscopy. METHODS: In this prospective study, we evaluated 106 patients with suspected lung cancer. All patients were examined using EVIS LUCERA videoendoscopy system. In every patient, at least three biopsies were taken from places visualized as pathologic, surrounding primary tumor, and three biopsies from places that appeared normal. The overall number of biopsies performed in 106 patients was 636. RESULTS: The specificity and sensitivity of NBI in revealing greater lung cancer extension were 85.6% and 95%, respectively; positive and negative predictive values were 84% and 95.6%, respectively. Specificity and sensitivity were significantly better when compared with white light bronchoscopy alone (P < 0.01). NBI led to the change in therapeutic decision in 14 patients. There was statistically significant correlation between NBI assessment of tumor extension and change in therapeutic decision (P < 0.000). CONCLUSIONS: NBI showed significantly better specificity and sensitivity in the assessment of lung cancer extension. NBI proved that it might have potential influence on therapeutic decision, making it more accurate. The procedure is safe and easily deployed in everyday practice.

Autofluorescence videobronchoscopy (AFI) for the assessment of tumor extension in lung cancer.

The major objective of our study was to determine the specificity and sensitivity of AFI videobronchoscopy vs. white light videobronchoscopy, in the assessment of lung cancer extent. Secondary objective was to investigate whether or not AFI can reveal greater extension of the tumor, and can it influence therapy making decision. Autofluorescence videobronchoscopy systems are new technology for visualization of bronchial mucosa, and the proper indications for such systems will be determined in the near future. In this prospective trial we have enrolled 27 patients with suspected lung cancer in whom we performed 108 diagnostic biopsies and 54 control biopsies. All patients underwent WL videobronchoscopy followed by Auto Fluorescence Imaging (AFI) examination of tracheobronchial tree. We were using videobronchoscope BF-F260 and EVIS LUCERA SPECTRUM processor unit. Overall specificity for AFI in the diagnostics of lung cancer was found to be 85%, sensitivity was 90%, positive predictive value (PPV) 78%, and negative predictive value (NPV) 94%. Specificity, sensitivity, PPV, and NPV for WL videobronchoscopy in lung cancer diagnostics were 54%, 64%, 51%, and 69%, respectively. Relative sensitivity ratio of AFI over WL videobronchoscopy, which is calculated to be 1.41, confirmed superiority of AFI in lung cancer diagnostics. We confirmed significant correlation between the greater extension of the tumor (assessed with AFI) and the therapeutical decision in lung cancer treatment (p = 0.01). Influence of AFI on therapeutical decision was significant (p = 0.034). AFI videobronchoscopy system yields significantly higher sensitivity and specificity for the assessment of lung cancer extent than WLB videobronchoscopy alone. It had shown to be able to influence therapeutic option for lung cancer treatment. Further studies are needed to evaluate and validate these results.