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Comment on https://www.jmir.org/2024/1/e54985

People with serious mental illness are at great risk of suicide, but little is known about the suicide rates among this population. We aimed to quantify the suicide rates among people with serious mental illness (bipolar disorder, major depression, or schizophrenia). PubMed and Web of Science were searched to identify studies published from 1 January 1975 to 10 December 2020. We assessed English-language studies for the suicide rates among people with serious mental illness. Random-effects meta-analysis was used. Changes in follow-up time and the suicide rates were presented by a locally weighted scatter-plot smoothing (LOESS) curve. Suicide rate ratio was estimated for assessments of difference in suicide rate by sex. Of 5014 identified studies, 41 were included in this analysis. The pooled suicide rate was 312.8 per 100 000 person-years (95% CI 230.3-406.8). Europe was reported to have the highest pooled suicide rate of 335.2 per 100 000 person-years (95% CI 261.5-417.6). Major depression had the highest suicide rate of 534.3 per 100 000 person-years (95% CI 30.4-1448.7). There is a downward trend in suicide rate estimates over follow-up time. Excess risk of suicide in males was found [1.90 (95% CI 1.60-2.25)]. The most common suicide method was poisoning [21.9 per 100 000 person-years (95% CI 3.7-50.4)]. The suicide rates among people with serious mental illness were high, highlighting the requirements for increasing psychological assessment and monitoring. Further study should focus on region and age differences in suicide among this population.

A novel Lycopodium alkaloid, lycocasine A (1), and seven known Lycopodium alkaloids (2–8), were isolated from Lycopodiastrum casuarinoides. Their structures were determined through NMR, HRESIMS, and X-ray diffraction analysis. Compound 1 features an unprecedented 5/6/6 tricyclic skeleton, highlighted by a 5-aza-tricyclic[6,3,1,02,6]dodecane motif. In bioactivity assays, compound 1 demonstrated weak inhibitory activity against acid-sensing ion channel 1a.

Currently, the optimal volume of pericapsular nerve group (PENG) block for analgesia after total hip arthroplasty (THA) has not been clarified. In this trial, we investigated whether a high-volume PENG block has a superior analgesic effect than a conventional PENG block for primary THA. Forty patients receiving primary THA under spinal anesthesia were enrolled and randomly divided into the high-volume PENG group (40 mL of 0.375% ropivacaine) and the conventional-volume PENG group (20 mL of 0.375% ropivacaine). Dexamethasone (5 mg) was added to the local anesthetic in both groups. A blinded researcher performed pain scores and lower limb sensory and motor block assessments at 3, 6, and 24 h after surgery. The time of first walking, time of first opioid consumption, total opioid consumption within 48 h, nerve block, opioid-related complications, and length of hospital stay were recorded. The primary outcome was the dynamic pain scores at 6 h post-surgery. Thirty-seven patients were included in the final analysis, among whom 18 were in the high-volume group and 19 in the conventional-volume group. There were no significant differences between the two groups in dynamic pain scores at 6h after surgery [median and interquartile range (p25, p75) 5(4,6) vs 4 (4,5)] and other secondary outcomes. The high-volume PENG block is not superior to conventional-volume PENG block in improving post-operative analgesia in patients undergoing primary THA and does not increase the risk of quadriceps weakness. Chinese Clinical Trial Registry (ChiCTR, https://www.chictr.org.cn). Clinical trial registration number: ChiCTR2300077281.

Background The adverse prognostic impact of diabetes on hypertrophic cardiomyopathy (HCM) is poorly understood. We sought to explore the underlying mechanisms in terms of structural and functional remodelling in HCM patients with coexisting diabetes (HCM-DM). Methods A total of 45 HCM-DM patients were retrospectively included. Isolated HCM controls (HCM patients without diabetes) were matched to HCM-DM patients in terms of maximal wall thickness, age, and gender distribution. Left ventricular (LV) and atrial (LA) performance were evaluated using cardiac magnetic resonance feature tracking strain analyses. The associations between diabetes and LV/LA impairment were investigated by univariable and multivariable linear regression. Results Compared with the isolated HCM controls, the HCM-DM patients had smaller end-diastolic volume and stroke volume, lower ejection fraction, larger mass/volume ratio and impaired strains in all three directions (all P  < 0.05). In terms of the LA parameters, HCM-DM patients presented impaired LA reservoir and conduit strain/strain rate (all P  < 0.05). Among all HCM patients, comorbidity with diabetes was independently associated with a low LV ejection fraction (β = − 6.05, P  < 0.001) and impaired global longitudinal strain (β = 1.40, P  = 0.007). Moreover, compared with the isolated HCM controls, HCM-DM patients presented with more myocardial fibrosis according to late gadolinium enhancement, which was an independent predictor of impaired LV global radial strain (β = − 45.81, P  = 0.008), LV global circumferential strain (β = 18.25, P  = 0.003), LA reservoir strain (β = − 59.20, P  < 0.001) and strain rate (β = − 2.90, P  = 0.002). Conclusions Diabetes has adverse effects on LV and LA function in HCM patients, which may be important contributors to severe manifestations and outcomes in those patients. The present study strengthened the evidence of the prevention and management of diabetes in HCM patients.

The strategies concerning modification of the complex immune pathological inflammatory environment during acute spinal cord injury remain oversimplified and superficial. Inspired by the acidic microenvironment at acute injury sites, a functional pH-responsive immunoregulation-assisted neural regeneration strategy was constructed. With the capability of directly responding to the acidic microenvironment at focal areas followed by triggered release of the IL-4 plasmid-loaded liposomes within a few hours to suppress the release of inflammatory cytokines and promote neural differentiation of mesenchymal stem cells in vitro, the microenvironment-responsive immunoregulatory electrospun fibers were implanted into acute spinal cord injury rats. Together with sustained release of nerve growth factor (NGF) achieved by microsol core-shell structure, the immunological fiber scaffolds were revealed to bring significantly shifted immune cells subtype to down-regulate the acute inflammation response, reduce scar tissue formation, promote angiogenesis as well as neural differentiation at the injury site, and enhance functional recovery in vivo. Overall, this strategy provided a delivery system through microenvironment-responsive immunological regulation effect so as to break through the current dilemma from the contradiction between immune response and nerve regeneration, providing an alternative for the treatment of acute spinal cord injury. Inflammatory responses determine the pathological course of spinal cord injury. Here, the authors report on pH responsive fibers for triggered release of IL-4 plasmid liposomes and sustained release of nerve growth factor to regulate the immune response and promote nerve regeneration to enhance functional recovery.

Background Few studies have compared the efficacy and safety of omadacycline with other treatments for acute bacterial skin and skin structure infections (ABSSSI). Therefore, updated meta-analyses on this topic is necessary. Methods We conducted a network meta-analysis (NMA) of randomized controlled trials (RCTs) to compare omadacycline with other anti-MRSA antibiotics. A systematic search of seven databases was undertaken to identify eligible RCTs enrolling adults with ABSSSI. Two reviewers independently assessed the quality of the included studies and three reviewers independently extracted data from all manuscripts. All meta-analyses were performed using R software. Results Our NMA included 39 RCTs with a total of 20,862 patients with ABSSSI. Eighteen anti-MRSA antibiotics were analyzed in the NMA. In terms of early clinical response, omadacycline was comparable to oxazolidinones like linezolid, tedizolid, and contezolid. Across various populations, including the intention-to-treat (ITT), modified ITT, and clinically evaluable populations, omadacycline showed higher or comparable clinical success rates, although these results were of borderline statistical significance. The results showed that omadacycline ranked first in efficacy among 18 antibiotics, based on surface under the cumulative ranking curve values. Additionally, omadacycline had significantly fewer serious adverse events than telavancin and demonstrated a safety profile comparable to other antibiotics. Conclusions Our findings indicate that omadacycline is a promising treatment option for ABSSSI, demonstrating efficacy that is comparable to or potentially superior to many other anti-MRSA agents, along with a favorable safety profile. However, these results should be interpreted with caution due to the study’s inherent limitations.

Background To systematically review and assess the efficacy and safety of hydroxychloroquine (HCQ) for treating primary Sjogren’s syndrome (pSS). Methods Five electronic databases (Pubmed, EMBASE, Web of science, Ovid, Cochrane Library) were searched for randomized controlled trials and retrospective or prospective studies published in English that reported the effect of HCQ on pSS. The subjective symptoms (sicca symptoms, fatigue and pain) and the objective indexes (erythrocyte sedimentation rate and Schirmer test) were assessed as main outcome measures. A meta-analysis and descriptive study on the efficacy and safety of HCQ were conducted. The estimate of the effect of HCQ treatment was expressed as a proportion together with 95% confidence interval, and plotted on a forest plot. Results Four trials with totals of 215 SS patients, including two randomized controlled trials, one double blind crossover trial and one retrospective open-label study, were analyzed in this review. For dry mouth and dry eyes, the effectiveness of HCQ treatment was essentially the same as placebo treatment. For fatigue, the effectiveness of HCQ was lower than placebo. The efficacy of HCQ in treating pain associated with pSS was superior to that of the placebo. There was no significant difference between HCQ-treated groups and controls in terms of Schirmer test results, but HCQ could reduce the erythrocyte sedimentation rate compare with placebo. A descriptive safety assessment showed that gastrointestinal adverse effects were the most common adverse effects associated with HCQ. Conclusions This systematic review showed that there is no significant difference between HCQ and placebo in the treatment of dry mouth and dry eye in pSS. Well-designed, randomized, controlled trials are needed to provide higher-quality evidence to confirm our findings, and future studies should focus on some other index or extraglandular measures, such as cutaneous manifestations, to further explore the therapeutic effect of HCQ in pSS.

Non-alcoholic steatohepatitis (NASH) is a common chronic liver disease worldwide, with no effective therapies available. Discovering lead compounds from herb medicine might be a valuable strategy for the treatment of NASH. Here, we discovered Alisol B, a natural compound isolated from Alisma orientalis (Sam.), that attenuated hepatic steatosis, inflammation, and fibrosis in high-fat diet plus carbon tetrachloride (DIO+CCl4)-induced and choline-deficient and amino acid-defined (CDA)-diet-induced NASH mice. RNA-seq showed Alisol B significantly suppressed CD36 expression and regulated retinol metabolism in NASH mice. In mouse primary hepatocytes, Alisol B decreased palmitate-induced lipid accumulation and lipotoxicity, which were dependent on CD36 suppression. Further study revealed that Alisol B enhanced the gene expression of RARα with no direct RARα agonistic activity. The upregulation of RARα by Alisol B reduced HNF4α and PPARγ expression and further decreased CD36 expression. This effect was fully abrogated after RARα knockdown, suggesting Alisol B suppressed CD36 via regulating RARα-HNF4α-PPARγ cascade. Moreover, the hepatic gene expression of RARα was obviously decreased in murine NASH models, whereas Alisol B significantly increased RARα expression and decreased CD36 expression, along with the downregulation of HNF4α and PPARγ. Therefore, this study showed the unrecognized therapeutic effects of Alisol B against NASH with a novel mechanism by regulating RARα-PPARγ-CD36 cascade and highlighted Alisol B as a promising lead compound for the treatment of NASH.