Hip Displacement in Cerebral Palsy: The Role of Surveillance

IntroductionHip displacement is common in cerebral palsy (CP) and is related to the severity of neurological and functional impairment. It is a silent, but progressive disease, and can result in significant morbidity and decreased quality of life, if left untreated. The pathophysiology of hip displacement in CP is a combination of hip flexor-adductor muscle spasticity, abductor muscle weakness, and delayed weight-bearing, resulting in proximal femoral deformities and progressive acetabular dysplasia. Due to a lack of symptoms in the early stages of hip displacement, the diagnosis is easily missed. Awareness of this condition and regular surveillance by clinical examination and serial radiographs of the hips are the key to early diagnosis and treatment.Hip surveillance programmesSeveral population-based studies from around the world have demonstrated that universal hip surveillance in children with CP allows early detection of hip displacement and appropriate early intervention, with a resultant decrease in painful dislocations. Global hip surveillance models are based upon the patients’ age, functional level determined by the Gross Motor Function Classification system (GMFCS), gait classification, standardized clinical exam, and radiographic indices such as the migration percentage (MP), as critical indicators of progressive hip displacement.ConclusionDespite 25 years of evidence showing the efficacy of established hip surveillance programmes, there is poor awareness among healthcare professionals in India about the importance of regular hip surveillance in children with CP. There is a need for professional organizations to develop evidence-based guidelines for hip surveillance which are relevant to the Indian context.     

Efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) created using covered stents of different diameters: A systematic review and meta-analysis

PurposeThe purpose of this study was to make a systematic review and meta-analysis to determine the stent diameter (8 mm vs. 10 mm) that conveys better safety and clinical efficacy for transjugular intrahepatic portosystemic shunt (TIPS).Materials and methodsFour databases were used to identify clinical trials published from inception until March 2020. Data were extracted to estimate and compare one-year and three-year overall survivals, hepatic encephalopathy, variceal rebleeding, and shunt dysfunction rates between patients with 8 mm covered stents and those with 10 mm covered stents.ResultsFive eligible studies were selected, which included 489 patients (316 men, 173 women). The 8 mm covered stent group had higher efficacy regarding one-year or three-year overall survival (odds ratio [OR], 2.88; P = 0.003) and (OR, 1.81; P = 0.04) and lower hepatic encephalopathy (OR, 0.69; P = 0.04) compared with 10 mm covered stent group. There were no significant differences in variceal rebleeding rate (OR 0.80; P = 0.67). However, shunt dysfunction was lower in 10 mm covered stent group (OR, 2.26; P = 0.003).ConclusionsOur results suggest that the use of 8 mm covered stents should be preferred to that of 10 mm covered stents for TIPS placement when portal pressure is frequently monitored.     

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.     

A candidate multi-epitope vaccine against porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae induces robust humoral and cellular response in mice

Porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (M. hyopneumoniae, Mhp) are two of the most common pathogens involved in the porcine respiratory disease complex (PRDC) resulting in significant economic losses worldwide. Vaccination is the most effective approach to disease prevention. Since PRRSV and Mhp co-infections are very common, an efficient dual vaccine against these pathogens is required for the global swine industry. Compared with traditional vaccines, multi-epitope vaccines have several advantages, they are comparatively easy to produce and construct, are chemically stable, and do not have an infectious potential. In this study, to develop a safe and effective vaccine, B cell and T cell epitopes of PRRSV-GP5, PRRSV-M, Mhp-P46, and Mhp-P65 protein had been screened to construct a recombinant epitope protein rEP-PM that has good hydrophilicity, strong antigenicity, and high surface accessibility, and each epitope is independent and complete. After immunization in mice, rEP-PM could induce the production of high levels of antibodies, and it had good immunoreactivity with anti-rEP-PM, anti-PRRSV, and anti-Mhp antibodies. The anti-rEP-PM antibody specifically recognizes proteins from PRRSV and Mhp. Moreover, rEP-PM induced a Th1-dominant cellular immune response in mice. Our results showed that the rEP-PM protein could be a potential candidate for the development of a safe and effective multi-epitope peptide combined vaccine to control PRRSV and Mhp infections.     

Prospective characterization of incident hepatic steatosis in pediatric and adolescent patients after total pancreatectomy with islet autotransplantation

BackgroundHepatic steatosis has been described as a common finding in adults following total pancreatectomy with islet autotransplantation (TPIAT) but it is unknown if this occurs in children and adolescents.ObjectivesTo define the frequency of post-TPIAT hepatic steatosis in a sample of children and adolescents and to identify clinical predictors of incident steatosis post-TPIAT.MethodsIn this prospective study, consecutive participants at least 1-month post-TPIAT underwent a liver MRI with proton density fat fraction (PDFF) and blood draw at our pediatric academic medical center between April 2021 and January 2022. Comparison clinical pre-TPIAT liver MRI or ultrasound and insulin use and graft function data were extracted from the medical record. T-tests were used for the comparison of means across continuous variables between participants with and without post-TPIAT steatosis.ResultsA total of 20 participants (mean: 13 ± 4 years; 12 female) were evaluated. Mean liver PDFF at research MRI was 7.4 ± 6.2% (range: 2–25%). Seven participants (35%) had categorical hepatic steatosis (PDFF>5%) post-TPIAT, five of whom had pre-TPIAT steatosis, reflecting a 13% (2/15; 95% CI: 2–40%) incidence of post-TPIAT steatosis. Participant characteristics were not significantly different between subgroups with and without post-TPIAT steatosis. Mean PDFF at research MRI was not different between graft function subgroups (7.5% optimal/good vs. 7.3% marginal/failure; p = .96).ConclusionOur study shows a moderate prevalence but low incidence of hepatic steatosis in a small sample of children and adolescents post-TPIAT. This study raises questions about a causal relationship between TPIAT and hepatic steatosis.     

健脾生血片治疗慢性心力衰竭伴贫血的临床效果

目的:探索健脾生血片治疗慢性心力衰竭伴贫血的疗效、安全性和作用机制。方法:选取2016年5月至2017年2月同济医院收治的慢性心力衰竭贫血患者144例,按照随机数字表法分为观察组和对照组,每组72例。观察组给予健脾生血片治疗,3片/次,3次/d,疗程3个月;对照组给予生血宝合剂治疗,15 m L/次,3次/d,3个月为1个疗程。比较2组患者治疗前与治疗后血红蛋白、红细胞计数、网织红细胞、血清铁、转铁蛋白饱和度、血清铁蛋白、血清铁调素(Hepcidin)、血清IL-1β、血清肿瘤坏死因子-α(TNF-α)、血清C反应蛋白(CRP)、左室射血分数(LVEF)、6 min步行距离、明尼苏达心力衰竭生命质量量表(MLHFQ)和不良事件。并随访2组心血管事件次数,住院次数与全因死亡率。结果:观察组72例患者完成了前3个月的治疗,随访期间脱失2例;对照组治疗期间1例患者退出研究,随访期间脱失4例。2组一般资料比较,差异无统计学意义(P 0. 05),具有可比性。观察组贫血有效率98. 6%,对照组有效率11. 3%,差异有统计学意义(P0. 05)。治疗后观察组红细胞计数和网织红细胞、均显著高于对照组(P 0. 05)。观察组血清铁、转铁蛋白饱和度水平均高于对照组,差异有统计学意义(P 0. 05),但血清铁调素水平显著低于对照组,差异有统计学意义(P 0. 05),血清铁蛋白水平2组差异无统计学意义(P 0. 05)。观察组IL-1β、血清TNF-α、血清CRP均显著低于对照组,差异有统计学意义(P 0. 05)。观察组LVEF、6 min步行距离、明尼苏达心力衰竭生命质量量表(MLHFQ)均显著高于对照组,差异有统计学意义(P 0. 05)。2组不良事件总发生率比较,差异无统计学意义(P 0. 05),但对照组4例患者出现血清肌酐、尿素氮水平异常,发生率高于观察组,差异有统计学意义(P 0. 05)。经1年随访,观察组心血管事件人均发生次数显著少于对照组(P 0. 05),但2组住院次数和全因死亡率比较,差异无统计学意义(P 0. 05)。结论:健脾生血片可有效治疗心力衰竭伴贫血,减少心血管发生次数,并且安全性良好,其作用机制与提供准确足量铁元素、抑制铁调素表达,抑制慢性炎性反应有关。