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.     

Clinical implications of additional posterior fractures in combined anterior-posterior pelvic ring fractures in elderly patients

ObjectivesHistorically, pelvic ring fractures (PRF) are considered to occur predominantly in the anterior ring and therfore to be mechanically stable. Combined anterior and posterior (A + P) PRF are expected to be less mechanically stable and therefore to be associated with higher levels of pain and reduced mobility compared to isolated anterior fractures. The current study investigates the clinical relevance of combined A + P PRF in elderly patients.MethodsA prospective multicentre cohort study was conducted in patients >70 years of age with anterior PRF after low-energy trauma diagnosed on conventional radiographs. All patients underwent an additional CT-scan. Patients were divided into two groups; isolated anterior or combined A + P fractures. Patients were treated conservatively with adequate analgesia for at least one week. If patients could not be mobilised after conservative treatment, surgical fixation was performed. Numerical Rating Scale (NRS) pain scores, dependence on walking aids and Activities of Daily Living scores (ADL) were measured at 2–4 weeks, and 3, 6 and 12 months after fracture.Results102 patients (age 81.1 ± 7.6 years) were included. Isolated anterior fractures were diagnosed in 25 (24.5%) and A + P fractures in 77 (75.5%) patients. Baseline characteristics did not differ between the two groups. Most patients were successfully treated conservatively and 5 (4.9%) underwent percutaneous trans-iliac, trans-sacral screw fixation after failure of conservative treatment. At 2–4 weeks post trauma, patients with A + P fractures had similar median pain scores (3 (range 0–8) vs. 5 (0–10), p = 0.19) and ADL scores (85 (25–100) vs. 78.6 (5–100), p = 0.67), but were more dependent on walking aids (92.8% vs. 72.2%; p = 0.02) compared to patients with isolated anterior fractures. There were no significant differences at 3 months. At one year follow-up the median NRS pain and ADL scores for both fracture groups were 0 and 100, respectively. Mortality was 10.8%, and additional loss to follow-up was 17.6%.ConclusionsThe vast majority of elderly patients with PRF have combined A + P fractures. The clinical implications of additional posterior pelvic ring fractures in elderly patients appears to be limited.     

长臂单轴椎弓根螺钉在单纯性胸腰椎压缩性骨折复位固定中的应用及对肌肉损伤的影响

目的分析长臂单轴椎弓根螺钉经 Wiltse入路在单纯性胸腰椎压缩性骨折中的应用效果及对肌肉损伤的影响。方法选取自 2018年 1月至 2020年 8月周口市中心医院收治的单纯性胸腰椎压缩性骨折病人 87例，根据复位固定术式不同，分为观察组 38例、对照组 49例，其中观察组采取长臂单轴椎弓根螺钉经 Wiltse入路，对照组采取 AF系统经传统后正中入路。记录两组病人围术期指标、手术前后血清肌肉损伤指标［肌酸激酶( CK)、肌红蛋白( Mb)］变化；采用疼痛视觉模拟评分( VAS)评价病人不同时间节点疼痛水平；经胸腰椎正侧位片检查获取伤椎原始高度( H0)、术前及术后 1周伤椎椎体前缘高度( H1H2)，计算术前、术后 1周伤椎相对高度( H1/H0、H2/H0)及伤椎复位率，并测量矢状位 Cobb角变化；随访 3个月，采用 Oswestry功能障、碍指数( ODI)评价功能障碍情况，并统计手术相关并发症。结果观察组手术时长、术中失血量、术后引流量及首次下床活动时间均明显短于或低于对照组( P<0.05)。术后 3d，两组血清 CK、Mb水平均较术前升高( P<0.05)，且观察组血清 CK、Mb水平     

Comparison between Antegrade versus Retrograde Ureteral Stent Placement for Malignant Ureteral Obstruction

PurposeTo compare the technical success of antegrade uteral stent (AUS) and retrograde ureteral stent (RUS) placements in patients with malignant ureteral obstruction (MUO) and to determine the predictors of technical failure of RUS.Materials and MethodsThis study retrospectively included 61 AUS placements (44 patients) performed under fluoroscopic guidance and 76 RUS placements (55 patients) performed under cystoscopic guidance in patients with MUO from January 2019 to December 2020. Technical success rates of the 2 techniques were compared using inverse probability of treatment weighting (IPTW) analysis. Logistic regression was used to identify predictive factors for technical failures.ResultsTechnical success was achieved in 98.4% of the AUS group and 47.4% of the RUS group. After stabilized IPTW, the technical success rate was higher in the AUS group than in the RUS group (adjusted risk difference, 49.4%; 95% confidence interval [CI], 35.4%–63.1%). The independent predictors for technical failure of the RUS procedure were age of ≥65 years (odds ratio [OR], 5.56; 95% CI, 1.73–21.27), ureteral orifice invasion (OR, 4.21; 95% CI, 1.46–13.46), and extrinsic cancer (OR, 15.58; 95% CI, 2.92–111.81).ConclusionsThe technical success rate of AUS placement was higher than that of RUS placement in patients with MUO. RUS failure was associated with age of ≥65 years, cancer with ureteral orifice invasion, and extrinsic ureteral obstruction.     

Focal hole versus screw stimulation to prevent false negative results in detecting pedicle breaches during spinal instrumentation

ObjectiveWe describe a stimulus-evoked EMG approach to minimize false negative results in detecting pedicle breaches during lumbosacral spinal instrumentation.MethodsIn 36 patients receiving 176 lumbosacral pedicle screws, EMG threshold to nerve root activation was determined using a focal probe inserted into the pilot hole at a depth, customized to the individual patients, suitable to position the stimulating tip at the point closest to the tested nerve root. Threshold to screw stimulation was also determined.ResultsMean EMG thresholds in 161 correctly fashioned pedicle instrumentations were 7.5 mA ± 2.46 after focal hole stimulation and 21.8 mA ± 6.8 after screw stimulation. Direct comparison between both thresholds in individual pedicles showed that screw stimulation was always biased by an unpredictable leakage of the stimulating current ranging from 10 to 90%. False negative results were never observed with hole stimulation but this was not true with screw stimulation.ConclusionsFocal hole stimulation, unlike screw stimulation, approaches absolute EMG threshold as shown by the lower normal limit (2.6 mA; p < 0.05) that borders the upper limit of threshold to direct activation of the exposed root.SignificanceThe technique provides an early warning of a possible pedicle breakthrough before insertion of the more harmful, larger and threaded screw.     

The detection and management of complications following the treatment of liver metastases

While once considered as incurable systemic disease, treatment options for liver metastases have increased over the last 30 years and safety has improved dramatically, such that for a selected group of patients the hope of cure can now be offered with radical treatment, and low morbidity interventions can be offered which prolong survival, even in patients with more widely disseminated disease. Advances have been made in selection and surgical technique for liver resection and several adjuncts to resection now exist in the form of portal vein embolization, thermal ablation and targeted drug or radiotherapy delivery options. A natural consequence of these developments has been the delivery of services within fewer specialist units, with the result that later complications of therapy may present to local hospitals, rather than directly to the specialist centres. This article will describe the current common liver-directed therapies and outline the presentation and management of their complications.     

Effects of pomegranate supplement on menopausal symptoms and quality of life in menopausal women: A double-blind randomized placebo-controlled trial

BackgroundMenopausal symptoms have negative effects on the aspects of quality of life and impose a high cost on the health system. In traditional Persian medicine, pomegranate is recommended to alleviate menopausal symptoms.Material and methodsA randomized double-blind placebo-controlled trial was performed among 78 healthy women. Participants were interviewed three times: Before receiving the supplement/placebo, after completing the treatment, and after 3 weeks with no intervention. They filled out the demographic information sheet, modified-Kupperman index, and Menopause-Specific Quality of Life (MENQOL) questionnaires.ResultsThe mean scores of the modified-Kupperman index and MENQOL characteristics before and after the treatment and after the follow-up period were significantly different between pomegranate and placebo groups in both modified-Kupperman and MENQOL scores (p < 0.001).ConclusionThis study demonstrated that 4 weeks' treatment with the pomegranate supplement significantly ameliorates the irritating symptoms of menopause and improves the quality of life in menopausal women even after 4 weeks' medicine deprivation.     

Depression in a Patient With Alzheimer Disease

This is a case study of a 73-year-old woman recently diagnosed with Alzheimer disease living in an assisted living facility who presented to an outpatient behavioral health clinic with her son for evaluation and treatment of depression. This article highlights the presentation of depression (a diagnosis) versus apathy (a symptom of Alzheimer disease) and the need to assess for co-occurring mood disorders that warrant pharmacologic intervention as well as treatment for cognitive decline in Alzheimer disease.