Leigh syndrome (LS) is an inherited mitochondrial encephalopathy associated with gene mutations of oxidative phosphorylation pathway that result in early disability and death in affected young children. Currently, LS is incurable and unresponsive to many treatments, although some case reports indicate that supplements can improve the condition. Many novel therapies are being continuously tested in pre-clinical studies. In this review, we summarize the genetic basis of LS, current treatment, pre-clinical studies in animal models and the management of other mitochondrial diseases. Future therapeutical strategies and challenges are also discussed.
Background Respiratory function would be impaired during general anesthesia period. Researchers devoted their energies to finding effective strategies for protecting respiratory function. Low tidal volume, positive end-expiratory pressure (PEEP), and lung recruitment maneuvers (LRMs) were recommended for patients under mechanical ventilation. However, based on the current evidence, there was no consensus on whether LRMs should be routinely used for anesthetized patients with healthy lungs, and the benefits of them remained to be determined. Materials and methods To evaluate the benefits of LRMs on patients undergoing surgery with general anesthesia, we searched relevant studies in PubMed, EMBASE, Ovid Medline and the Cochrane Library up to June 30, 2018. The primary outcome was postoperative pulmonary complications (PPCs). Results Twelve trials involving 2756 anesthetized patients were included. The results of our study showed a significant benefit of LRMs for reducing the incidence of PPCs (RR = 0.67; 95%CI, 0.49 to 0.90; P<0.05; Chi 2 = 32.94, p for heterogeneity = 0.0005, I 2 = 67%). After subgroup analyses, we found LRMs combining with lung protective ventilation strategy and sustained recruitment maneuvers were associated with reducing the occurrence of PPCs. The results also revealed that the use of LRMs improved PaO 2 /FiO 2 in non-obese patients, but with extremely high heterogeneity (I 2 = 95%). Conclusion According to the findings from contemporary meta-analysis, LRMs combining with lung protective ventilation strategy may have an association with decreasing in the incidence of PPCs and improvement of oxygenation on non-obese patients. However, the conclusions must be interpreted cautiously as the outcome may be influenced dramatically due to varied LRMs and ventilation patterns.
Lung ischemia and reperfusion injury (LIRI) were mediated by several processes including over-production of reactive oxygen species (ROS) and inflammatory activation. ROS generated by nicotinamide adenine dinucletide phosphate (NADPH) oxidase (Nox) may play a pivotal role in pathophysiological changes in a range of disease. However, it was poorly understood in LIRI. Thus, the purpose of our study was to explore whether GKT137831, as a special dual inhibitor of Nox1 and 4, could alleviate LIRI in mice model and explore the minimal dose. According to the protocol, this study was divided into two parts. The first part was to determine the minimal dose of Nox1/4 inhibitor in attenuating LIRI via histopathology and apoptosis analysis. Eighteen C57BL/6J male wild-type mice were randomly divided in to sham, 2.5Nox+sham, 5.0Nox+sham, IR, 2.5Nox+IR and 5.0Nox+IR groups. According to the different group, mice were pretreated with corresponding dose of Nox1/4 inhibitors or normal saline. After LIRI, the results showed 5.0mg/kg Nox1/4 inhibitor could be considered as the minimal dose to alleviate injury by decreasing of lung injury score and the number of TUNEL-positive cells. The second part was to further verify the benefit of 5.0mg/kg Nox1/4 inhibitor in lung protective effects. Thirty-seven C57BL/6J male wild-type mice were divided in to sham, IR and 5.0Nox+IR groups randomly. The results showed that expressions of inflammatory, autophagy cytokines were markedly elevated and PH value was declined after LIRI. However, 5.0 mg/kg Nox1/4 inhibitor significantly attenuated cytokine production as reflected by immunohistochemistry, western blotting and Q-PCR analysis. In conclusion, our findings suggested that 5.0mg/kg Nox1/4 inhibitor contributed to protect lung tissue damage after LIRI via the suppression of inflammatory and autophagy activation.
<b><i>Background:</i></b> Lung recruitment maneuvers (LRMs) may reduce mortality and improve oxygenation in patients with acute respiratory distress syndrome (ARDS). However, the existing literature provides controversial conclusions. <b><i>Objectives:</i></b> To determine whether LRMs have benefits on ARDS patients. <b><i>Searching Methods:</i></b> We searched relevant studies in PubMed, EMBASE, Medline, and the Cochrane Library up to May 2018. We considered for inclusion all prospective and randomized controlled trials which compared LRMs and non-LRM in adult patients with ARDS. We collected data about in-hospital mortality, 28-day mortality, the length of ICU and hospital stay, PaO<sub>2</sub>/FiO<sub>2</sub>, and FiO<sub>2</sub>. <b><i>Main Results:</i></b> Ten trials including 3,025 patients were analyzed. No significant difference was found in the hospital and 28-day mortality, as well as the length of ICU stay and oxygen requirement, even undergoing subgroup analysis. However, the results of this meta-analysis showed a significant benefit of LRMs for shortening the length of hospital stay (mean difference, MD = –1.75; 95% CI, –3.40 to –0.09; <i>p</i> = 0.04; <i>p</i> for heterogeneity = 0.3, <i>I</i><sup>2</sup> = 18%) and improving PaO<sub>2</sub>/FiO<sub>2</sub> ratio on the third day (MD = 52.72; 95% CI, 18.77–86.67; <i>p</i> = 0.002), but with extremely high heterogeneity (<i>p</i> for heterogeneity <0.0001, <i>I</i><sup>2</sup> = 99%). <b><i>Conclusion:</i></b> LRMs do not produce significant reduction of mortality in patients with ARDS but may shorten the length of hospital stay and improve oxygenation on the third day. However, the results must be interpreted cautiously as most studies were on multiple intervention exposures.
Study Objective Pain management plays a pivotal role in enhanced recovery after surgery (ERAS). Erector spinae plane block (ESPB) is widely used in many regions to treat perioperative pain, but its benefits are still somewhat controversial. We, therefore, intent to systematically review the available literature on ESPB, to elucidate its effects on opioid-sparing analgesia, and summarize its potential complications. Design Systematic review of randomized controlled trials (RCTs) with meta-analysis. Setting Postoperative opioid consumption for various surgeries. Patients Patients undergoing various surgeries. Intervention We searched relevant studies in PubMed, EMBASE, Medline, and the Cochrane Library up to May 16, 2021. All prospective and RCTs that compared ESPB and sham block or no block were enrolled. Measurements The primary outcomes were postoperative opioid consumption during the first 24 hours. The secondary outcomes were the requirement of rescue analgesia, time to first rescue analgesic and ESPB-related adverse events. Results We included 52 trials that reported postoperative opioid consumption during the first 24 hours. The results presented that compared to control group (ie, no intervention or a sham block), ESPB reduced the accumulated opioid consumption during the first 24 h after surgery [mean difference (MD) of − 12.83 (95% CI: − 17.29 to − 8.38; p < 0.001) mg; I 2 = 100%]. Besides, ESPB could prolong time to first rescue analgesia after surgery [SMD = 5.31; 95% CI 4.01–6.61; p < 0.001; I 2 = 97%]. The number of patients who received rescue analgesia after surgery in the ESPB group was less than that in the control group (OR 0.13; 95% CI 0.09, 0.21; p < 0.001; I 2 = 54%), and the incidence of PONV was lower in the ESPB group (OR 0.51; 95% CI 0.43, 0.62; p < 0.001; I 2 = 19%). Conclusion ESPB is an effective technique on pain management with few complications.
Flexible ureteroscopy is a common therapy for patients with renal calculi. In recent years, the prevalence of single-use flexible ureteroscope (FURS) use has been on the rise. Thus, several trials have been conducted to compare the efficacy between single-use and reusable FURS. The aim of this meta-analysis was to systematically assess the effectiveness and safety of single-use vs. reusable FURS in treating renal stones.PubMed, Web of Science, Cochrane Library and EMBASE were researched to identify relevant studies up to September 2019. Article selection was performed through the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. The Newcastle-Ottawa Scale was applied to assess the methodological quality of non-randomized controlled trials, and the methodological quality of randomized controlled trials was evaluated using the Jadad scale. A total of five studies with 772 patients were included in the meta-analysis, including two randomized controlled trials, two single-centre prospective studies, and one prospective case-control trial. The pooled results showed that single-use FURS was associated with a higher stone-free rate (SFR) (OR: 1.50; 95% CI, 1.06-2.12; P=0.02) than reusable FURS.
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