Background Bevacizumab is an antiangiogenic recombinant humanized monoclonal antibody that inhibits tumor growth. FKB238, a bevacizumab biosimilar, has analytical pharmacokinetic and safety profiles similar to those of bevacizumab. Objective This phase III trial (NCT02810457) compared the efficacy and safety of FKB238 with that of bevacizumab in patients with advanced/recurrent non-squamous non-small-cell lung cancer (non-sq-NSCLC). Methods This global, multicenter, double-blind, parallel, randomized, comparative clinical trial enrolled and randomized patients with advanced/recurrent non-sq-NSCLC to receive intravenous infusions of either FKB238 15 mg/kg or bevacizumab 15 mg/kg. All patients received intravenous infusions of paclitaxel 200 mg/m 2 and carboplatin (area under the curve 6.0) immediately prior to investigational products for 4-6 cycles. FKB238 and bevacizumab were administered on day 1 of each 21-day cycle until objective progressive disease by RECIST version 1.1 or other discontinuation criteria were met. The primary efficacy endpoint was overall response rate (ORR), including complete and partial response and based on blinded independent central review assessment. Other efficacy determinations included progression-free survival (PFS), overall survival (OS), and immunogenicity. Adverse events and severity were reported. ResultsThe ORR for the intent-to-treat (ITT) population (N = 731) was 51.6% in the FKB238 arm (N = 364) and 53.7% in the bevacizumab arm (N = 367). The FKB238:bevacizumab ORR ratio (ITT population) was 0.96 (90% confidence interval [CI] 0.86-1.08), and the difference in ORR (per-protocol set) between FKB238 and bevacizumab was − 0.02 (95% CI − 0.09 to 0.06). Both CIs fell within the prespecified equivalence margins. Estimated median PFS was 7.72 and 7.62 months in the FKB238 and bevacizumab arms, respectively (hazard ratio 0.97; 95% CI 0.82-1.16). Treatment-emergent adverse events (TEAEs) were reported for 94.2% and 95.1% of patients in the FKB238 and bevacizumab arms, respectively. Grade 3 or higher TEAEs were reported for 53.6% and 55.5% of patients in the FKB238 and bevacizumab arms, respectively. Serious TEAEs were reported for 25.1% and 26.0% of patients treated with FKB238 and bevacizumab, respectively. Conclusions Efficacy equivalence was demonstrated between the two drugs, and safety profiles were similar. There were no meaningful differences in efficacy and safety between FKB238 or bevacizumab in patients with non-sq-NSCLC. Trial registration number NCT02810457.

AimTo assess the prognostic value of lactate level for mortality in patients with pulmonary embolism (PE) and Pulmonary Embolism Severity Index (PESI) I-III and its independence of gas-analysis parameters and acid-base status.MethodsThis prospective observational study was conducted at the University Clinical Hospital Mostar from 2013 to 2017. On the first day after PE diagnosis, 1.5 mL of arterial blood was collected from 103 patients with PE. Partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood, blood pH value, concentration of bicarbonates in arterial blood (HCO3-), base deficit, and oxygen saturation were analyzed. Lactate levels were assessed using blood samples taken from the cubital vein. Logistic regression analysis was used to assess the predictive value of gas-analysis variables, lactate level, PESI score, age, and sex for in-hospital death due to PE.ResultsThe mortality in the group of PE patients was 19.1% (18 of 103 patients). Lactate level was an independent predictor of mortality (P = 0.002, odds ratio 0.06). HCO3- was also found to be a significant predictor (P = 0.022, odds ratio 2.4). Lactates were independent of other variables. Other gas-analysis parameters were not significant predictors of mortality.ConclusionIn PE patients at low-intermediate risk of mortality (PESI I-III), lactate level was associated with a short-term mortality, independently of other gas-analytic parameters.Oxford Centre for Evidence-based Medicine level of evidence: 2.

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Tuberculosis (TB) is one of the oldest, the most expanded and the most lethal diseases in human history. Although Koch’s discovery of the TB causative agent (1882) represented a great progress in the fight against this infectious disease, it took a significant amount of time to reduce morbidity and mortality in the world. In Bosnia and Herzegovina (B&H) it was necessary to implement actions in the form of education where the popularization of measures of recognition, treatment and preventing the disease was done. After the Annexation of B&H to Austro-Hungarian (1908) began an organized fight against TB. Dr. S. Kukric was a particularly prominent individual, putting his effort by working in clinics, through his lectures and numerous popular research papers on tuberculosis. He was followed by many colleagues working inexhaustibly while facing the high incidence of TB and the difficult social situation in B&H. Although this disease is old, at the end of the 20th century a new TB appeared, with new challenges and new, even grater problems. Significant achievement and great progress in the treatment and control of TB infection was achieved by implementing the direct observed short course treatment (DOTS from 2006.) Still, there is a too high incidence of TB that becomes again a serious threat, together with new problems and difficult economic and social situation. Nowadays in Federation of B&H the guidelines of World Health Organization on reinforcing the DOTS strategy are being daily implemented, including multidrug-resistant (MDR) TB and infection control.