Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

Effects of the Cerebral Aneurysm Treatment Method on Coil Packing Density and Its Relationship with the Ostium Area

PurposeTo test the following hypotheses: (a) balloon or stent assistance increases coil packing density (CPD) in the endovascular treatment of intracranial aneurysms, and (b) CPD correlates to ostium area (OA) and aneurysm volume (AV).Materials and MethodsThis retrospective study included 60 aneurysms (54 ruptured and 6 unruptured) treated with simple coiling (SC) (n = 18), balloon-assisted coiling (BAC) (n = 7), or stent-assisted coiling (SAC) (n = 35) at the authors’ institution between August 2017 and December 2019. AV and OA measurements were obtained from 3-dimensional digital subtraction angiography images using commercial software. Coil sizes were retrieved from patient files, and coil volume (CV) measurements were obtained from https://www.angiocalc.com/. Analysis of covariance, multivariate covariance analysis, and Pearson correlation analyses were performed.ResultsThe median value for AV, CV, CPD, and OA was 63.4 mm³ (range, 5.5–1,771.4 mm³), 23.13 mm³ (range, 2.03–296.95 mm³), 33.29% (range, 13.41%–81.02%), and 10.7 mm² (range, 2.7–49.9 mm²), respectively. Multivariate analysis showed that the CPD values were not significantly different among the treatment groups, although OA significantly differed between the SC and SAC groups (P < .05). Pearson correlations showed that similar to AV, OA was negatively correlated with CPD (r = ?0.321, P < .05).ConclusionsThe CPD value in cerebral aneurysms treated with BAC or SAC did not differ from that in aneurysms treated with SC.     

免疫抑制儿童感染新型冠状病毒Omicron变异株病毒清除时间的回顾性队列研究

背景：儿童新型冠状（新冠）病毒Omicron变异株流行期间，免疫抑制状态儿童新冠病毒清除时间定量分析研究较少。 目的：探讨新冠病毒Omicron株感染后免疫抑制和非免疫抑制儿童病毒清除的时间差别，为公共卫生政策制定和精准疫情防控措施提供临床数据。 设计：回顾性队列研究。 方法：以新冠病毒Omicron变异株感染住院患儿为队列人群，分为免疫抑制组和非免疫抑制组，免疫抑制分为绝对免疫抑制、相对免疫抑制和实施免疫抑制疗法，以免疫抑制组病例的性别、年龄和新冠病毒感染的分型与非免疫抑制组行1∶3匹配。以鼻咽拭子新冠病毒PCR检测拷贝数阈（Ct）值≥35为队列终点。 主要结局指标：新冠病毒清除时间。 结果：2022年4月12日至2022年5月12日在上海市新冠病毒感染定点收治医院符合本文共同纳入和排除标准的连续病例728例。免疫抑制组33例，其中绝对免疫抑制8例，相对免疫抑制23例，接受免疫抑制疗法2例（不包括绝对和相对免疫抑制患儿）。非免疫抑制组匹配后99例。2组临床症状、新冠病毒感染治疗和疫苗接种次数差异均无统计学意义。免疫抑制组和非免疫抑制组新冠病毒清除时间分别为（16.5±6.8）和（10.3±4.4）d，差异有统计学意义。免疫抑制组和非免疫抑制组新冠病毒感染轻型病例病毒清除时间分别为（14.0 ± 8.3）和（9.7 ± 3.1）d，普通型病例病毒清除时间分别为（18.3 ± 4.9）和（11.2 ± 5.9）d，差异均有统计学意义。2组单日病毒清除率在第9~14天时差异有统计学意义（P为0.005~0.039）。2组普通型病例单日病毒清除率在第10~15天时差异有统计学意义。免疫抑制组新冠病毒感染2周后核酸检测再次呈阳性3例（9%），临床分型均较前轻，3例均未接种新冠疫苗。 结论：Omicron株感染的免疫抑制患儿病毒清除时间较非免疫抑制患儿显著延长，主要反映在第9~14天，免疫抑制患儿病毒复阳风险高，提示需要更长的隔离时间和转阴后严格的病毒监测。     

Pulmonary metastases in urogenital cancers: Surgical treatment and outcomes

IntroductionMetastasis is remaining one of the major problems in cancer treatment. Like many other malignancies, urogenital tumors originating from kidney, prostate, testes, and bladder tend to metastasize to the lungs.The aim of this retrospective study is to evaluate the operative results and prognosis of pulmonary metastasectomy in patients with primary urogenital tumors.MethodsThis study was approved by the local ethical committee. We retrospectively analyzed the surgical and oncological results of patients who underwent lung resections for urogenital cancer metastases in our department between 2002 and 2018. Demographic data and clinicopathological features were extracted from the medical records. Survival outcomes according to cancer subtypes and early postoperative results of VATS and thoracotomy were analyzed.Results22 out of 126 patients referred for pulmonary metastasectomy to our department had metastases from urogenital tumors. These patients consisted of 17 males and five females. Their metastasis originated from renal cell carcinoma (RCC; n = 9), bladder tumor (n = 7), testis tumors (n = 4), and prostate cancer (n = 2). There was no intraoperative complication. Postoperative complications were seen in 2 patients.ConclusionsAlthough pulmonary metastasectomy in various types of tumors is well known and documented, the data is limited for metastases of urogenital cancers in the literature. Despite the limitations of this study, we aim to document our promising results of pulmonary metastasectomy in patients with primary urogenital tumors and wanted to emphasize the role of minimally invasive approaches.     

Functional outcomes and complications after treatment of distal radius fracture in patients sixty years and over: A systematic review and network meta-analysis

AimThis network meta-analysis aims to compare functional outcomes and complications between conservative treatment and surgery for distal radius fractures in patients aged 60 years and over.MethodsWe searched the PubMed, EMBASE, and Web of Science databases for randomized controlled trials (RCTs) assessing the effect of conservative treatment and surgery for distal radius fractures in patients aged 60 years and over. Primary outcomes included grip strength and overall complications. Secondary outcomes included Disabilities of the Arm, Shoulder, and Hand (DASH) scores, Patient-Rated Wrist Evaluation (PRWE) scores, wrist range of motion and forearm rotation, and radiographic assessment. All continuous outcomes were assessed using standardized mean differences (SMDs) with 95% confidence intervals (CIs), and binary outcomes were assessed using odds ratio (OR) with 95% CIs. The surface under the cumulative ranking curve (SUCRA) was used to determine a hierarchy of treatments. Cluster analysis was performed for grouping treatments based on the SUCRA values of primary outcomes.ResultsFourteen RCTs were included to compare conservative treatment, volar lockedplate (VLP), K-wires fixation, and external-fixation. VLP outperformed conservative treatment for 1-year and minimum 2-year grip strength (SMD; 0.28 [0.07 to 0.48] and 0.27 [0.02 to 0.53], respectively). VLP yielded the optimal grip strength at 1-year and minimum 2-year follow-up (SUCRA; 89.8% and 86.7%, respectively). In a subgroup analysis of patients aged 60 to 80 years old, VLP outperformed conservative treatment in DASH and PRWE scores (SMD, 0.33 [0.10, 0.56] and 0.23 [0.01, 0.45], respectively). In addition, VLP had the fewest complications (SUCRA = 84.3%). Cluster analysis suggested that VLP and K-wire fixation were more effective treatment groups.ConclusionEvidence to date demonstrates that VLP provides measurable benefits in grip strength and fewer complications to those 60 years of age and over, and that benefit is not reflected in current practice guidelines. There is a subgroup of patients where K-wire fixation outcomes are similar to those of VLP; defining this subgroup may yield substantial societal benefits.