Safety and effectiveness of low-dose amikacin in nontuberculous mycobacterial pulmonary disease treated in Toronto, Canada

Amikacin; NTM lung disease; Nontuberculous mycobacteriaAmikacina; Malaltia pulmonar per micobacteri no tuberculós; Micobacteri no tuberculósAmikacina; Enfermedad pulmonar por micobacteria no tuberculosa; Micobacteria no tuberculosaBACKGROUND: Treatment guidelines suggest either a low-dose or high-dose approach when prescribing amikacin for nontuberculous mycobacterial pulmonary disease (NTM PD), but data supporting the low-dose approach are limited. The purpose of this study was to describe the safety and efficacy of the use of a low-dose of intravenous amikacin in a cohort of patients with NTM PD. METHODS: We retrospectively reviewed all patients with NTM PD who received amikacin at our institution between July 1, 2003 and February 28, 2017. Demographics, clinical, microbiological and radiological data, indication and dose of amikacin, and adverse drug effects were recorded. RESULTS: A total of 107 patients received a regimen containing amikacin for a median (IQR) of 7 (4-11) months. Seventy (65.4%) were female and the mean age (SD) was 58.3 (14.9) years. Amikacin was started at a median dose of 9.9 (2.5) mg/kg/day. Ototoxicity was observed in 30/77 (39%) patients and it was related to female sex (OR 4.96, 95%CI 1.24-19.87), and total dose of amikacin per bodyweight (OR 1.62, 95%CI 1.08-2.43). Patients of East Asian ethnicity were less likely to develop ototoxicity (0.24, 95%CI 0.06-0.95). Out of 96 patients who received amikacin for more than 3 months, 65 (67.7%) experienced symptom improvement and 30/62 (49.2%) converted their sputum to culture negative within a year. CONCLUSIONS: Patients with NTM PD treated with low-dose intravenous amikacin frequently developed ototoxicity, which was associated with female sex, and total dose of amikacin per bodyweight. Physicians should carefully consider dose, treatment duration, and long term prognosis in balancing risks and benefits of intravenous amikacin in NTM PD

Safety and effectiveness of low-dose amikacin in nontuberculous mycobacterial pulmonary disease treated in Toronto

Treatment guidelines suggest either a low-dose or high-dose approach when prescribing amikacin for nontuberculous mycobacterial pulmonary disease (NTM PD), but data supporting the low-dose approach are limited. The purpose of this study was to describe the safety and efficacy of the use of a low-dose of intravenous amikacin in a cohort of patients with NTM PD. We retrospectively reviewed all patients with NTM PD who received amikacin at our institution between July 1, 2003 and February 28, 2017. Demographics, clinical, microbiological and radiological data, indication and dose of amikacin, and adverse drug effects were recorded. A total of 107 patients received a regimen containing amikacin for a median (IQR) of 7 (4-11) months. Seventy (65.4%) were female and the mean age (SD) was 58.3 (14.9) years. Amikacin was started at a median dose of 9.9 (2.5) mg/kg/day. Ototoxicity was observed in 30/77 (39%) patients and it was related to female sex (OR 4.96, 95%CI 1.24-19.87), and total dose of amikacin per bodyweight (OR 1.62, 95%CI 1.08-2.43). Patients of East Asian ethnicity were less likely to develop ototoxicity (0.24, 95%CI 0.06-0.95). Out of 96 patients who received amikacin for more than 3 months, 65 (67.7%) experienced symptom improvement and 30/62 (49.2%) converted their sputum to culture negative within a year. Patients with NTM PD treated with low-dose intravenous amikacin frequently developed ototoxicity, which was associated with female sex, and total dose of amikacin per bodyweight. Physicians should carefully consider dose, treatment duration, and long term prognosis in balancing risks and benefits of intravenous amikacin in NTM PD

Development of Primary Percutaneous Coronary Intervention as a National Reperfusion Strategy for Patients with ST-Elevation Myocardial Infarction and Assessment of Its Use in Egypt

Objective: Early treatment of acute ischemia of the heart by performing immediate percutaneous coronary intervention (PCI) to restore blood flow in patients with the clinical presentation of an acute coronary syndrome and more specifically with ST-elevation myocardial infarction (STEMI) can save lives. This study aims to identify the mean time (door to balloon time and first contact to balloon time) to primary PCI for STEMI patients and to assess the percentage of primary PCI and its success rate in Egypt. Methods: A registry study of patients presenting to cardiac centers in Egypt was designed, where patients’ basic characteristics, the treatment strategy, and the door to balloon time and the first contact to balloon time were assessed. Results: One thousand six hundred fifty STEMI patients with a mean age of 57 years were included in the study. Immediate transfer for primary PCI was the most used treatment strategy, representing 74.6% of all treatment strategies used. The door to balloon time and the first contact to balloon time were 50 and 60 minutes, respectively, with a primary PCI success rate of 65.1%. Conclusion: The registry study results showed a marked improvement by implementation of the best treatment strategy with respect to the time factor to achieve a better outcome for STEMI patients in Egypt

Sperm DNA fragmentation: A new guideline for clinicians

Sperm DNA integrity is crucial for fertilization and development of healthy offspring. The spermatozoon undergoes extensive molecular remodeling of its nucleus during later phases of spermatogenesis, which imparts compaction and protects the genetic content. Testicular (defective maturation and abortive apoptosis) and post-testicular (oxidative stress) mechanisms are implicated in the etiology of sperm DNA fragmentation (SDF), which affects both natural and assisted reproduction. Several clinical and environmental factors are known to negatively impact sperm DNA integrity. An increasing number of reports emphasizes the direct relationship between sperm DNA damage and male infertility. Currently, several assays are available to assess sperm DNA damage, however, routine assessment of SDF in clinical practice is not recommended by professional organizations

Greenlight laser (XPSTM) 180W prostatectomy for treatment of benign prostate hyperplasia in patients with uncorrectable bleeding tendency

ABSTRACTObjectives Safety of GreenLight™ laser prostatectomy (GL-LP) in patients with ongoing blood thinners has been proven. Yet, the possibility of drug manipulation makes it a less challenging situation compared to treating patients with uncorrectable bleeding tendency. Herein, we aim at evaluating the outcomes of XPS™-180 W GL-LP for treatment of BPH in patients who had uncorrectable bleeding tendency due to hepatic dysfunction.Methods A prospectively maintained database for all patients who underwent GL-LP for symptomatic BPH was reviewed. Patients were divided into two groups based on the degree of hepatic dysfunction using Fib-4 index: Group 1 (indexed patients; low-risk Fib-4) and Group 2 (non-indexed patients; intermediate-high-risk Fib-4) included those who had chronic liver disease associated with either thrombocytopenia and/or hypoprothrombinemia. Primary outcome was the difference in perioperative bleeding complications between the two groups. Other outcome measures included all perioperative findings and complications as well-functional outcome measures.Results The study included 140 patients (93 indexed patients and 47 non-indexed). There were no significant differences between both groups in operative time, laser time and energy, auxiliary procedures, catheter time, hospital stay, and hemoglobin deficit. The need for blood transfusion was significantly more in group 2 (two patients (4.3%) versus no patients in group 1, P = 0.045). Perioperative and late postoperative complications were comparable for both groups (P = 0.634 and 0.858, respectively). There were no significant differences in the postoperative uroflow, symptoms score, and PSA reduction between the two groups (P = 0.57, 0.87, and 0.05, respectively).Conclusions XPS™-180 W GL-LP is a safe and effective technique for treatment of BPH in patients with uncorrectable bleeding tendency due to hepatic dysfunction

Relative Importance of Different Elements of Mitochondrial Oxidative Phosphorylation in Maintaining the Barrier Integrity of Retinal Endothelial Cells: Implications for Vascular-Associated Retinal Diseases

Purpose: Mitochondrial dysfunction is central to breaking the barrier integrity of retinal endothelial cells (RECs) in various blinding eye diseases such as diabetic retinopathy and retinopathy of prematurity. Therefore, we aimed to investigate the role of different mitochondrial constituents, specifically those of oxidative phosphorylation (OxPhos), in maintaining the barrier function of RECs. Methods: Electric cell-substrate impedance sensing (ECIS) technology was used to assess in real time the role of different mitochondrial components in the total impedance (Z) of human RECs (HRECs) and its components: capacitance (C) and the total resistance (R). HRECs were treated with specific mitochondrial inhibitors that target different steps in OxPhos: rotenone for complex I, oligomycin for complex V (ATP synthase), and FCCP for uncoupling OxPhos. Furthermore, data were modeled to investigate the effects of these inhibitors on the three parameters that govern the total resistance of cells: Cell–cell interactions (Rb), cell–matrix interactions (α), and cell membrane permeability (Cm). Results: Rotenone (1 µM) produced the greatest reduction in Z, followed by FCCP (1 µM), whereas no reduction in Z was observed after oligomycin (1 µM) treatment. We then further deconvoluted the effects of these inhibitors on the Rb, α, and Cm parameters. Rotenone (1 µM) completely abolished the resistance contribution of Rb, as the Rb became zero immediately after the treatment. Secondly, FCCP (1 µM) eliminated the resistance contribution of Rb only after 2.5 h and increased Cm without a significant effect on α. Lastly, of all the inhibitors used, oligomycin had the lowest impact on Rb, as evidenced by the fact that this value became similar to that of the control group at the end of the experiment without noticeable effects on Cm or α. Conclusion: Our study demonstrates the differential roles of complex I, complex V, and OxPhos coupling in maintaining the barrier functionality of HRECs. We specifically showed that complex I is the most important component in regulating HREC barrier integrity. These observed differences are significant since they could serve as the basis for future pharmacological and gene expression studies aiming to improve the activity of complex I and thereby provide avenues for therapeutic modalities in endothelial-associated retinal diseases

Intramedullary Kirschner wire fixation of displaced distal forearm fractures in children

Abstract Aim of the work This study was designed to highlight internal fixation by intramedullary K-wires for displaced distal forearm fractures among children and analyze the results of this technique. We hypothesize that physis-sparing intramedullary fixation prevents displacement with a lower complication rate. Methods This prospective case series involving 47 patients was conducted between February 2018 and December 2019. All patients with open physis presented with recent displaced distal forearm fractures were included, and all of them were treated with an intramedullary k-wire fixation for both bones with the assessment of the union rate, union time, suspected complication, radiographic evaluation, and functional outcome. Results The study population consisted of 31 boys (66%) and 16 girls (34%). The mean age of the patients was 10.68 ± 2.728 years (range, 7–15 years). All fractures were united in a median of 6 weeks (range, 4–8 weeks), The functional outcome after 12 months was normal in 42 patients (89.4%), whereas, in five patients (10.6%), the functional parameters were minimally reduced. The median preoperative angulation improved from 36° (range, 24°–52°) preoperatively to 4° (range, 0°–10°) on immediate postoperative radiographs. After 12 months, the median angulation was 2° (range, 0°–7°) (p < 0.001). The angulation of the distal radius immediately after surgery and at the final follow-up was statistically correlated with the functional outcome (p < 0.001 and 0.002, respectively). Conclusion This technique provides a good result with less susceptibility to re-displacement and low complication rates. Level of evidence Level IV

Safety and effectiveness of low-dose amikacin in nontuberculous mycobacterial pulmonary disease treated in Toronto

Treatment guidelines suggest either a low-dose or high-dose approach when prescribing amikacin for nontuberculous mycobacterial pulmonary disease (NTM PD), but data supporting the low-dose approach are limited. The purpose of this study was to describe the safety and efficacy of the use of a low-dose of intravenous amikacin in a cohort of patients with NTM PD. We retrospectively reviewed all patients with NTM PD who received amikacin at our institution between July 1, 2003 and February 28, 2017. Demographics, clinical, microbiological and radiological data, indication and dose of amikacin, and adverse drug effects were recorded. A total of 107 patients received a regimen containing amikacin for a median (IQR) of 7 (4-11) months. Seventy (65.4%) were female and the mean age (SD) was 58.3 (14.9) years. Amikacin was started at a median dose of 9.9 (2.5) mg/kg/day. Ototoxicity was observed in 30/77 (39%) patients and it was related to female sex (OR 4.96, 95%CI 1.24-19.87), and total dose of amikacin per bodyweight (OR 1.62, 95%CI 1.08-2.43). Patients of East Asian ethnicity were less likely to develop ototoxicity (0.24, 95%CI 0.06-0.95). Out of 96 patients who received amikacin for more than 3 months, 65 (67.7%) experienced symptom improvement and 30/62 (49.2%) converted their sputum to culture negative within a year. Patients with NTM PD treated with low-dose intravenous amikacin frequently developed ototoxicity, which was associated with female sex, and total dose of amikacin per bodyweight. Physicians should carefully consider dose, treatment duration, and long term prognosis in balancing risks and benefits of intravenous amikacin in NTM PD