Background Nafamostat, a serine protease inhibitor, has been used for the treatment of disseminated intravascular coagulation and pancreatitis. In vitro studies and clinical reports suggest its beneficial effect in the treatment of COVID-19 pneumonia. Methods This phase 2 open-label, randomised, multicentre, controlled trial evaluated nafamostat (4.8 mg/kg/day) plus standard-of-care (SOC) in hospitalised patients with COVID-19 pneumonia (i.e., those requiring nasal high-flow oxygen therapy and/or non-invasive mechanical ventilation). The primary outcome was the time to clinical improvement. Key secondary outcomes included the time to recovery, rates of recovery and National Early Warning Score (NEWS). The trial is registered with ClinicalTrials.gov Identifier: NCT04623021. Findings A total of 104 patients, mean age 58.6 years were enrolled in 13 clinical centres in Russia between 25/9/2020 and 14/11/2020 and randomised to nafamostat plus SOC (n=53) or SOC alone (n=51). There was no significant difference in time to clinical improvement (primary endpoint) between the nafamostat and SOC groups (median 11 [interquartile range (IQR) 9 to 14) vs 11 [IQR 9 to 14] days; Rate Ratio [RR; the ratio for clinical improvement], 1.00; 95% CI, 0.65 to 1.57; p=0.953). In 36 patients with baseline NEWS ≥7, nafamostat was superior to SOC alone in median time to clinical improvement (11 vs 14 days; RR, 2.89; 95% CI, 1.17 to 7.14; p=0.012). Patients receiving nafamostat in this subgroup had a significantly higher recovery rate compared with SOC alone (61.1% (11/18) vs 11.1 % (2/18) by Day 11, p=0.002). The 28-day mortality was 1.9% (1/52) for nafamostat and 8.0% (4/50) for SOC (95% CI, -17.0 to 3.4; p=0.155). No case of COVID-19 related serious adverse events leading to death was recorded in the patients receiving nafamostat. Interpretation Our study found no significant difference in time to clinical improvement between the nafamostat and SOC groups, but a shorter median time to clinical improvement in a small group of high-risk COVID-19 patients requiring oxygen treatment. To assess the efficacy further, a larger Phase 3 clinical trial is warranted. Funding Korea Research Institute of Bioscience and Biotechnology [2020M3A9H5108928] and Chong Kun Dang (CKD) Pharm (Seoul, Korea).
Introduction. The development of laser technologies in medicine and their introduction into everyday clinical practice determine the trend of using this type of energy in the treatment of patients with lower urinary tract symptoms caused by benign prostatic hyperplasia (BPH). In the last decade, holmium laser enucleation (HoLEP) of the prostate has been claiming to be «the gold standard» in the BPH treatment. The advantages of HoLEP over alternative technologies (transurethral resection, bipolar enucleation) in the BPH treatment have been demonstrated in randomized trials. These advantages include the reduction of the patient's hospital stay, safety of manipulation and high quality of life for the patient after surgery. The use of electrical energy in resection techniques for the BPH treatment in most cases is limited by the prostate volume (80 cm3). A better understanding of the effect of laser radiation and its clinical efficacy has led to increased interest and widespread adoption of laser systems. The constant search and improvement of existing approaches encourages urologists and surgical equipment companies to research new laser systems. One type of improvement is a software update for laser pulse modulation that has been developed to improve the efficiency of laser equipment. For the further development of new laser technologies and widespread use in routine clinical practice, it is necessary to compare them with standard methods of BPH surgical treatment with an assessment of the effectiveness, as well as the pros and cons of the compared methods.Purpose of the study. To evaluate the results of laser endoscopic treatment of patients with prostatic hyperplasia.Materials and methods. The study included 50 patients with prostatic hyperplasia who underwent two different types of surgery — HoLEP (group I; n = 25) and HoLEP with MOSES (HoLEP-M) technology (group II; n = 25). Inclusion criteria were: the presence of moderate or severe obstructive symptoms of the lower urinary tract, prostate volume > 40 cm3, maximum urine flow (Q-max) < 12 ml/sec. Exclusion criteria were: the presence of cystostomy drainage, an oncological process of the urinary system, an active inflammatory process of the genitourinary system, previous surgical interventions on the urinary system. I-PSS, QoL and IIEF questionnaires data, the level of prostate-specific antigen (PSA), the maximum flow of the urine stream (Q-max) and the post-void residual volume were assessed at baseline and 3 months after the operation. The main indicators of the compared methods, the number and nature of complications were studied.Results. Both methods of laser enucleation allow achieving a good functional result with a minimum number of complications. When comparing both methods in the group II of patients who underwent HoLEP-M, there was a statistically significant difference in terms of characteristics: the time of enucleation in group I (HoLEP) — 46.7 ± 15.0 min (31 - 80) vs group II (HoLEP-M) — 38.9 ± 7.6 min (30 - 60) (p = 0.03), but this did not affect the total time of surgery (p = 0.21), the level of haemoglobin postoperative changes in group I (HoLEP) — 7.5 ± 5.4 g/l (2 - 18) vs group II (HoLEP-M) — 5.0 ± 2.9 g/l (2 - 13) (p = 0.04) and irrigation time in the postoperative period, group I (HoLEP) — 17.6 ± 3.6 h (11 - 26) vs group II — 14.0 ± 4.3 h (5 - 21) (p < 0.001). Thus, the results of the study suggest that the HoLEP with the modified pulse MOSES technology has advantages over the standard HoLEP technique. HoLEP-M allows you to perform the enucleation stage faster, with better hemostasis and minimizes the effect of the laser on the surrounding tissues. Complications above level 2 were not observed in both groups according to the Clavien-Dindo scale.Conclusion. HOLEP-M is a safe method of surgical treatment of prostatic hyperplasia from the point of view of surgical safety, efficacy, as well as the duration of the patient's recovery period and can serve as an alternative to the HoLEP standard technique.
RationaleThere are few treatment options for severe COVID-19 pneumonia. Opaganib is an oral treatment under investigation.ObjectiveEvaluate opaganib treatment in hospitalized patients with severe COVID-19 pneumonia.MethodsA randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 60 sites worldwide from August 2020 to July 2021.Patients received either opaganib (n=230; 500mg twice daily) or matching placebo (n=233) for 14 days.Main Outcome MeasurementsPrimary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28- and 42-days.Main ResultsPre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FiO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FiO2levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n=117) compared to placebo (n=134). The proportion of patients with ≤60% FIO2 at baseline that no longer required supplemental oxygen (≥24 hours) by day 14 of opaganib treatment increased (76.9% vs 63.4%: p-value =0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs 17.91%; p-value=0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs 16.7%; p-value=0.019) by day 42. No new safety concerns observed.ConclusionsPost-hoc analysis supports opaganib benefit in COVID-19 severe pneumonia patients that require lower supplemental oxygen (≤60% FiO2). Further studies are warranted.Trial registration numberNCT04467840
AIM: was to conduct a comparative assessment of copulative function and the severity of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) who underwent laser and bipolar transurethral enucleation of the prostate and who treated conservatively. MATERIALS AND METHODS: 143 BPH patients aged 50 to 80 years (mean age 65 years) with complaints of copulatory and urinary disorders were under observation. All patients were divided into two groups. The 1st (main) group included 102 patients who underwent surgical treatment: transurethral laser enucleation of the prostate (n = 55) and transurethral bipolar enucleation of the prostate (n = 47). Patients of the 2nd group (n = 41) received conservative treatment. Control examinations were performed before treatment, 4, 12 and 24 weeks after it. RESULTS: All 102 patients of group 1, regardless of the type of surgery, noted retrograde ejaculation four weeks after surgery. In the majority of patients of the 1st group during these periods weakening of orgasm was noted, in a significant number deterioration of erection and decreased libido were noted. Upon further observation, by the 12th week after the operation, restoration of all components of the copulatory function was noted, with the exception of ejaculation. By the 24th week of observation, only in 2 patients of the 1st group the normal mechanism of ejaculation was restored. Surgical treatment of patients in group 1, regardless of the method of surgery, led to a significant decrease in the severity of LUTS, an increase in the maximum urine flow rate, a decrease in the volume of the prostate gland and the amount of residual urine. There were no significant differences in the dynamics of these indicators depending on the method of transurethral enucleation. The patients of the 2nd group also had an improvement in clinical parameters, but it was much less pronounced than in the 1st group. CONCLUSION: Laser and bipolar transurethral enucleation of the prostate are effective surgical techniques that significantly improve the outflow of urine from the bladder, reduce the severity of LUTS and improve the sexual function of patients. Surgery is well tolerated by patients. At the same time, almost all patients operated on by these methods develop retrograde ejaculation.
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