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BACKGROUND: The supraglottic airway device (SGD) was introduced as a breakthrough in airway management. The Fastrach emerged as the first commercially available intubating SGD, drawing extensive investigation. I-gel is a more recent device that has gained popularity, can be used as an intubating SGD, and replaced Fastrach in many institutions. However, there is uncertainty regarding the comparison between these devices in terms of efficacy for intubation and ventilation, and safety in an airway rescue situation. METHODS: PubMed, EMBASE, Scopus, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing I-gel and Fastrach SGD in adult patients undergoing intubation. The primary outcome was the first-pass success rate for tracheal intubation. Secondary outcomes were tracheal intubation time, SGD insertion time and success, and complications. We computed risk ratios (RRs) to assess binary end points and weighted mean differences (WMDs) for continuous outcomes, with corresponding 95% confidence intervals (CIs) for the primary outcome and its subgroup analysis ( P < .05 was considered statistically significant) and 99% CI after Bonferroni correction for the secondary outcomes ( P < .01 was considered statistically significant). RESULTS: This study included a total of 14 RCTs encompassing 1340 patients. The results indicated a significant difference in the first-pass success rate favoring Fastrach (RR, 0.81; 95% CI, 0.67–0.98; P = .03; I² = 91%). In the subgroup analysis, when a flexible scope was utilized through I-gel, providers achieved a better tracheal intubation first-pass success rate (RR, 1.05; 95% CI, 1.01–1.11; P = .03; I² = 0%), compared with the Fastrach. Overall intubation success rates (RR, 0.92; 99% CI, 0.82–1.04; P = .08, I² = 92%) and time (WMD - 1.03 seconds; 99% CI, -4.75 to 2.69; P = .48; I² = 84%) showed no significant difference irrespective of the device used. There was no significant difference regarding device insertion time by the providers (WMD -6.48 seconds; 99% CI, -13.23 to 0.27; P = .01; I 2 = 98%). Success rates of the providers’ initial SGD insertion and complications such as sore throat (RR, 1.01; 99% CI, 0.65–1.57; P = .95, I² = 33%) and blood presence post-SGD removal (RR, 0.89; 99% CI, 0.42–1.86; P = .68, I² = 0%) showed no significant difference. CONCLUSIONS: Based on our findings, a higher first-pass success rate was observed with the use of Fastrach when compared to I-gel. However, the use of I-gel might result in a better intubation success rate with the flexible scope-guided intubation. There are no significant differences in performance in terms of the success rate for intubation overall, time for device insertion, or time to intubation or complications regardless of the device used.

Background We wished to explore possible sexual dimorphism in mechanisms sensitizing or activating meningeal nociceptors that can promote the headache phase of migraine. Methods Male and female C57BL6J mice received either supradural orexin B and an inflammatory mediator cocktail (IM) with migraine-like pain behaviors and photophobia recorded. Expression of orexin 2 receptor (OX2R) in trigeminal ganglion (TG) and phosphorylated extracellular signal-regulated kinases (ERK) levels in trigeminal nucleus caudalis (TNC) were evaluated. Orexin B-induced excitability of TG cells was assessed with patch-clamp electrophysiology. Intranasal delivery of CRISPR/Cas9 plasmids was used to edit the expression of OX2R in the TG. Results Supradural orexin B induced migraine-like pain behaviors, photophobia and increased TNC ERK phosphorylation exclusively in males. Blockade of orexin signaling with supradural suvorexant, a dual orexin receptor antagonist, prevented, but did not reverse, migraine-like pain in males induced by supradural IM cocktail. OX2R expression was higher in male TG and orexin B increased TG neuron excitability in males. Intranasal OX2R CRISPR/Cas9 reduced TG receptor expression and orexin B-induced TNC ERK phosphorylation and prevented migraine-like pain induced by supradural orexin B in males. Conclusions Our studies reveal a male-specific mechanism of TG nociceptor sensitization and migraine-like pain behavior mediated by orexin B/OX2R signaling. Sexually dimorphic mechanisms of trigeminal nociceptor sensitization and activation offer opportunities to improve patient outcomes by considering patient sex and may influence clinical trial design and interpretation.

Purpose To assess the efficacy and safety of dexmedetomidine as an adjuvant to intra‐articular (IA) injections of local anesthetics (LA) in adult patients undergoing knee arthroscopy. Methods We searched MEDLINE, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing IA dexmedetomidine plus LA versus LA alone for knee arthroscopy in adults. We used the DerSimonian and Laird random‐effects model for all outcomes and conducted a sensitivity analysis with the leave‐one‐out method, as well as a subgroup analysis for the type of LA. We used R version 4.1.2 for all statistical analyses. Results We included 16 RCTs encompassing 799 patients, of whom 49.8% received IA dexmedetomidine. In the pooled analysis, time to first analgesia rescue was prolonged in almost 4 hours with the use of dexmedetomidine (mean difference [MD] 229 minutes; P < .001). We found statistically significant differences favoring dexmedetomidine in pain scores at rest and movement throughout the first 2, 6, 12, and 24 hours postoperatively ( P < .001). Although the MD ranged from –0.3 to –0.9 cm, corresponding to a 3% to 9% reduction in pain scores, this change is not clinically significant compared with the minimal clinically important difference (MCID). Additionally, the intervention group showed a statistically significant reduction in cumulative opioid consumption over 24 hours (MD –4.5 mg; P < .001). However, this reduction did not meet the threshold for the MCID. There was no difference between groups on the incidence of hypotension ( P = .190), bradycardia ( P = .430), and postoperative nausea and vomiting ( P = .550). Conclusions Adding dexmedetomidine to LA in IA injections for knee arthroscopy significantly extended analgesia duration. Additionally, it lowered pain scores and opioid use, although these effects did not reach the MCID. Furthermore, this addition did not increase the risk of adverse events. Level of Evidence Level II, meta‐analysis of Level I and II studies.

Abstract Sex and gender—biological and social constructs—significantly impact the prevalence of protective and risk factors, influencing the burden of Alzheimer's disease (AD; amyloid beta and tau) and other pathologies (e.g., cerebrovascular disease) which ultimately shape cognitive trajectories. Understanding the interplay of these factors is central to understanding resilience and resistance mechanisms explaining maintained cognitive function and reduced pathology accumulation in aging and AD. In this narrative review, the ADDRESS! Special Interest Group (Alzheimer's Association) adopted a multidisciplinary approach to provide the foundations and recommendations for future research into sex‐ and gender‐specific drivers of resilience, including a sex/gender‐oriented review of risk factors, genetics, AD and non‐AD pathologies, brain structure and function, and animal research. We urge the field to adopt a sex/gender‐aware approach to resilience to advance our understanding of the intricate interplay of biological and social determinants and consider sex/gender‐specific resilience throughout disease stages. Highlights Sex differences in resilience to cognitive decline vary by age and cognitive status. Initial evidence supports sex‐specific distinctions in brain pathology. Findings suggest sex differences in the impact of pathology on cognition. There is a sex‐specific change in resilience in the transition to clinical stages. Gender and sex factors warrant study: modifiable, immune, inflammatory, and vascular.

Abstract Background and Aims Biological sex has been associated to a more rapid rate of chronic kidney disease progression (ie, speed of kidney function loss) in male than female [1]. Testosterone can increase oxidative stress, activate the renin angiotensin system, and aggravate renal fibrosis, whereas estrogens inhibit these pathological processes in the diseased kidney [2]. Several factors such as lower disease awareness and surveillance rates as well as disparities in health-care access result in late initiation or lack of kidney replacement therapy among females [3-5]. The impact of sex in the clinical presentation and outcomes of patients with anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) with glomerulonephritis (AAV-GN) has not been studied, particularly in patients with severe kidney involvement at presentation (eGFR&lt;15 mL/min/1.73 m2). Method A retrospective cohort study on MPO- or PR3-ANCA positive patients with AAV (MPA or GPA) and eGFR&lt;15 ml/min/1.73 m2 or ESKD at presentation. Clinical presentation and outcomes (renal recovery, dialysis at presentation, and ESKD) were analyzed according with sex. Results We analyzed 166 patients with biopsy proven active AAV-GN and eGFR &lt;15 mL/min/1.73 m2 at the time of diagnosis (Fig. 1): 78 (47%) were females and 88 (53%) were males. Arterial hypertension was more frequently present in males (85.2% vs. 70.5%, p = 0.022). Median serum creatinine (SCr) was higher in males when compared with females (5.2 [IQR 4.2-7.4] vs. 3.6 [IQR 2.8-5.1] mg/dL, p &lt; 0.001) but there were no differences in eGFR at presentation. When analyzing only the 71 (24 females and 47 males) patients that started dialysis within 4 weeks, infections at 12 months were more common in females (75.0% vs. 36.2%, p = 0.017). The rate of dialysis initiation or progression to ESKD was not different between males (15, 62.5%) versus females (29, 61.7%) being on dialysis at 12 months. By multivariable logistic regression, factors related with dialysis initiation within 4 weeks in our cohort were SCr (OR1.478, [95% CI 1.231-1.776], p &lt; 0.001), alveolar hemorrhage (OR 2.726, [95% CI 1.099-6.763], p = 0.031) and PR3-ANCA (OR3.155, [95% CI 1.485-6.702], p = 0.003) adjusted to sex). Patients who remained on dialysis at 12 months more often had higher SCr at diagnosis (IRR 1.098 [95% CI, 1.026–1.175], p = 0.007), severe chronicity changes on kidney biopsies (IRR 2.469 [95% CI,1.205–5.061], p = 0.014), higher chronicity score (IRR 1.178 [95%CI, 1.062-1.308], p = 0.002) and lower hemoglobin (IRR 0.824 [95%CI, 0.683-0.994], p = 0.043). Minimal chronicity changes were protective for the achievement of this endpoint (IRR 0.228 [95% CI, 0.070-0.741], p = 0.014). Multivariable Cox regression showed that patients with higher SCr at diagnosis and moderate/severe chronicity changes on biopsy were at higher risk to evolve to ESKD at 12 months compared to patients with lower chronicity grades, even when adjusted to sex. Conclusion In our cohort, male patients presented with higher SCr, and dialysis was started within 4 weeks more frequently. However, this did not result in different outcomes in terms of kidney recovery, overall dialysis rates, and progression to ESKD in patients with AAV-GN and eGFR&lt;15 mL/min/1.73 m2 between groups.

Abstract Chronic conditions associated with aging have proven difficult to prevent or treat. Senescence is a cell fate defined by loss of proliferative capacity and the development of a pro‐inflammatory senescence‐associated secretory phenotype comprised of cytokines/chemokines, proteases, and other factors that promotes age‐related diseases. Specifically, an increase in senescent peripheral blood mononuclear cells (PBMCs), including T cells, is associated with conditions like frailty, rheumatoid arthritis, and bone loss. However, it is unknown if the percentage of senescent PBMCs associated with age‐associated orthopedic decline could be used for potential diagnostic or prognostic use in orthopedics. Here, we report senescent cell detection using the fluorescent compound C 12 FDG to quantify PBMCs senescence across a large cohort of healthy and osteoarthritic patients. There is an increase in the percent of circulating C 12 FDG + PBMCs that is commensurate with increases in age and senescence‐related serum biomarkers. Interestingly, C 12 FDG + PBMCs and T cells also were found to be elevated in patients with mild to moderate osteoarthritis, a progressive joint disease that is strongly associated with inflammation. The percent of C 12 FDG + PBMCs and age‐related serum biomarkers were decreased in a small subgroup of study participants taking the senolytic drug fisetin. These results demonstrate quantifiable measurements in a large group of participants that could create a composite score of healthy aging sensitive enough to detect changes following senolytic therapy and may predict age‐related orthopedic decline. Detection of peripheral senescence in PBMCs and subsets using C 12 FDG may be clinically useful for quantifying cellular senescence and determining how and if it plays a pathological role in osteoarthritic progression.

Abstract Background Unlike cigarette smoking, environmental tobacco smoke (ETS) has not been as well described as an environmental risk for Multiple sclerosis (MS) nor as a risk factor for disease progression. Objective We systematically reviewed the association between ETS and the risk of onset and/or progression of MS. Methods We systematically screened MedLine/PubMed, Science Direct, LILACs, and SciELO searching for publications between January 1st, 2010, and July 5, 2021, with the following keywords: “multiple sclerosis and smoking”; “multiple sclerosis and passive smoking”; “multiple sclerosis and secondhand smoking”. Results Fifteen articles were included in this review, which consisted of systematic reviews with meta-analysis (N = 2), systematic reviews (N = 2), and observational studies (N = 11). Both meta-analyses reported an impact of ETS on MS onset among secondhand smokers. One of the systematic reviews selected two observational studies showing the association between ETS and MS development, and one study that did not find a significant association between ETS and the risk of MS development. The other systematic review identified selected eight articles showing a relationship between ETS and MS. Seven observational studies reported higher odds of MS onset when associated with ETS. Four observational studies did not show a relationship between ETS and MS onset or progression. Conclusion Most articles showed a positive association between ETS exposure and the risk of developing MS. On the other hand, an association between ETS and a higher risk for MS progression could not be established.