Objectives: Lamivudin has been approved for the treatment of chronic hepatitis B but experience with lamivudin treatment for acute severe hepatitis B is still limited. Fulminant hepatitis develops in 1% of patients with acute hepatitis B. Severe acute hepatitis B in immunocompetent patients may progress to fulminant hepatitis and death. Aim: To evaluate the efficasy of lamivudine for the treatment of acute severe hepatitis B virus infection in imunocompetent adults in Clinic for infectious diseases Banja Luka. Patients and methods: In the period of 2006-2024 years, 12 immunocompetent patients (4 women, 8 men, age 24-77 years) with severe acute hepatitis B were treated with lamivudin. All 12 patients fulfil at least two of the criteria for severe acute hepatitis B infection: 1. hepatic encephalopathy; 2. total bilirubin 210 micromole per litre; and severe coagulopathy (international normalized ratio-INR was 4.5 ± 6.4 or prothrombin time-PT < 40%). All patients had evidence of severe hepatocyte lysis. Nine patients had rapid increase of total bilirubin and contemporary decrease of alanine aminotransferase level, which escalate risk of development of fulminant hepatitis B. All patients received lamivudin at a dose 100 mg per day. Results: Ten patients responded well to the treatment and their biochemical parameters improved rapidly. Within 1-6 months, the HBsAg was undetectable in 10 out of 12 investigated patients. Protective anti-HBs antibodies developed in 10 of them in 1-6 months. The corticosteroid therapy was short-term in 2 of 12 patients. Two patient developed fulminant hepatitis B and died after the lamivudine therapy was initiated. Lamivudine treatment was well tolerated in all patients. Conclusion: Lamivudin induces a prompt clinical, biochemical and serological response in immunocompetent patients with severe acute hepatitis B. Early treatment with lamivudine probably decreases the risk of progression to fulminant hepatitis in patients with severe acute hepatitis B.

Aim: To assess Red blood cell Distribution Width (RDW) and platelet indices values in patients with type 2 diabetes mellitus (T2DM) and to verify its association with kidney dysfunction (KD). Patients and Methods: A cross-sectional study included 149 T2DM subjects divided into two groups with (T2DM – KD; n=52) and without (T2DM-nKD; n=97) presence of kidney dysfunction and 30 healthy subjects. White Blood Cells (WBC) count, C-reactive protein (CRP), fibrinogen, RDW, platelet indices, urea, and creatinine, were measured in all participants. Kidney function was evaluated by the estimated glomerular filtration rate (eGFR) calculated using the simplified Modification of Diet in Renal Disease (MDRD) formula. Results: T2DM-KD subjects showed statistically significantly higher values of the parameters RDW (p<0.01), Mean Platelet Volume - MPV (p<0.01), Platelet Distribution Width-PDW (p<0.01), Platelecrit-PCT (p<0.01), and Platelet Mass Index-PMI (p<0.01) compared to T2DM-nKD subjects, and statistically significantly lower values of the WBC count in T2DM-KD subjects compared to subjects suffering from T2DM without kidney dysfunction (p<0.01). ROC curve analysis revealed that RDW (sensitivity of 80.8%, specificity of 78.3%), MPV (sensitivity of 75%, specificity of 78.4 %), and PDW (sensitivity of 80.8%, specificity of 83.5%) could be used as markers in distinguishing between T2DM subjects with and without kidney dysfunction. Conclusion: This study confirms the reliability of the RDW,MPV, and PDW as simple, low cost and useful markers in distinguishing between T2DM subjects with and without kidney dysfunction.

Abstract Guidewire loss is a rare complication of central venous catheterization. A 65-year-old male was hospitalized in a high-dependency unit for exacerbation of chronic obstructive pulmonary disease, pneumonia, erythrocytosis, and clinical signs of heart failure. Upon admission, after an unsuccessful right jugular approach, a left jugular central venous catheter was placed. The next day, chest radiography revealed the catheter located in the left parasternal region, with suspected retention of the guidewire, visually confirmed by the presence of its proximal end inside the catheter. The left parasternal location of the catheter and the typical projection of the guidewire in the coronary sinus, later confirmed by echocardiography, raised suspicion of a persistent left superior vena cava (PLSVC). Agitated saline injected into the left antecubital vein confirmed bubble entry from the coronary sinus into the right atrium. After clamping the guidewire, the catheter was carefully retrieved along with the guidewire without any complications. This is the first reported case of guidewire retention in PLSVC and coronary sinus. It underscores the potential causes of guidewire loss and advocates preventive measures to avoid this potentially fatal complication.

In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole genome sequencing (WGS). We now introduce MRD-EDGE, a machine learning-guided WGS ctDNA single nucleotide variant (SNV) and copy number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGESNV uses deep learning and a ctDNA-specific feature space to increase SNV signal-to-noise enrichment in WGS by ~300X compared to previous WGS error suppression. MRD-EDGECNV also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1 Gb to 200 Mb, vastly expanding its applicability within solid tumors. We harness the improved performance to identify MRD following surgery in multiple cancer types, track changes in TF in response to neoadjuvant immunotherapy in lung cancer and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal-to-noise enrichment in MRD-EDGESNV enables plasma-only (non tumor-informed) disease monitoring in advanced melanoma and lung cancer, yielding clinically informative TF monitoring for patients on immune checkpoint inhibition (ICI).

PURPOSE The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with various solid tumors with germline or somatic BRCA1/2 mutations treated with talazoparib are reported. METHODS Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. Patients with germline BRCA-mutated human epidermal growth factor receptor 2–negative locally advanced or metastatic breast cancer were not eligible for this study. Primary end point was disease control (DC) determined by investigator assessment of objective response (OR) or stable disease (SD) of at least 16 weeks duration (SD16+). The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power = 0.82; α = .10). Secondary end points were OR, progression-free survival, overall survival, duration of response, duration of SD, and safety. RESULTS Twenty-eight patients (20 cancer types) with BRCA1/2 mutations were enrolled from December 2019 to September 2021 and collapsed into a single histology pooled cohort for analysis. All patients were evaluable for efficacy. One complete response, nine partial response, and six SD16+ were observed for DC and OR rates of 57% (one-sided 90% CI, 43 to 100) and 36% (95% CI, 19 to 56), respectively. The null hypothesis of a 15% DC rate was rejected (P < .001). Patients with OR had the following tumor types: breast (2), nonmelanoma skin, mesothelioma, stomach, uterus, non–small cell lung cancer, ovary, hepatocellular carcinoma, and pancreas. Thirteen patients had at least one grade 3-5 adverse event (AE) or serious AE at least possibly related to talazoparib. All were consistent with the drug label except bilirubin increase and hyponatremia (both grade 3 AEs). CONCLUSION Talazoparib demonstrated antitumor activity in patients with advanced solid tumors and BRCA1/2 mutations, including cancer types for which poly ADP-ribose polymerase inhibitors are not yet US Food and Drug Administration–approved.

Abstract This paper presents an artificial neural network (ANN) based method for overhead lines magnetic flux density estimation. The considered method enables magnetic flux density estimation for arbitrary configurations and load conditions for single-circuit, multi-circuit, and also overhead lines that share a common corridor. The presented method is based on the ANN model that has been developed using the training dataset that is produced by a specifically designed algorithm. This paper aims to demonstrate a systematic and comprehensive ANN-based method for simple and effective overhead lines magnetic flux density estimation. The presented method is extensively validated by utilizing experimental field measurements as well as the most commonly used calculation method (Biot - Savart law based method). In order to facilitate extensive validation of the considered method, numerous magnetic flux density measurements are conducted in the vicinity of different overhead line configurations. The validation results demonstrate that the used method provides satisfactory results. Thus, it could be reliably used for new overhead lines’ design optimization, as well as for legally prescribed magnetic flux density level evaluation for existing overhead lines.

Propranolol hydrochloride, a non-cardio-selective beta blocker, is used to treat several conditions in children, including hypertension, arrhythmias, hyperthyroidism, hemangiomas, etc. Commercial liquid formulations are available in Europe and the US, but they have disadvantages, such as limited stability, bitter taste, and the need for multiple daily doses due to the drug’s short half-life. Considering these limitations, controlled-release solid formulations, such as microparticles, may offer a better solution for pediatric administration. The main objective of this study was to formulate an encapsulation system for propranolol hydrochloride, based on sodium alginate and other polysaccharide polymers, to control and prolong its release. Microparticles were prepared using the ionotropic gelation method, which involves instilling a polymer solution into a solution of gelling ions via the extrusion technique. Physicochemical characterization was conducted by assessing the entrapment efficiency, drug loading, swelling index, microparticle size, rheological properties, and surface tension. In order to improve the characteristics of the tested microparticles, selected formulations were coated with chitosan. Further experimental work included differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) analysis, and SEM imaging. This in vitro release study showed that chitosan-coated microparticles demonstrate favorable properties, suggesting a novel approach to formulating pediatric dosage forms, although further optimization is necessary.