An Analysis of Stroke Risk Factors by HIV Serostatus in Uganda: Implications for Stroke Prevention in Sub-Saharan Africa

ObjectiveHIV infection is an important stroke risk factor in sub-Saharan Africa.  However, data on stroke risk factors in the era of antiretroviral therapy (ART) are sparse. We aimed to determine if stroke risk factors differed by HIV serostatus in Uganda.MethodsWe conducted a matched cohort study, enrolling persons living with HIV (PWH) with acute stroke, matched by sex and stroke type to HIV uninfected (HIV-) individuals. We collected data on stroke risk factors and fitted logistic regression models for analysis.ResultsWe enrolled 262 participants:105 PWH and 157 HIV-. The median ART duration was 5 years, and the median CD4 cell count was 214 cells/uL. PWH with ischemic stroke had higher odds of hypertriglyceridemia (AOR 1.63; 95% CI 1.04, 2.55, p=0.03), alcohol consumption (AOR 2.84; 95% CI 1.32, 6.14, p=0.008), and depression (AOR 5.64; 95%CI 1.32, 24.02, p=0.02) while HIV- persons with ischemic stroke were more likely to be > 55 years of age (AOR 0.43; 95%CI 0.20-0.95, p=0.037), have an irregular heart rhythm (AOR 0.31; 95%CI 0.10-0.98, p=0.047) and report low fruit consumption (AOR 0.39; 95%CI 0.18-0.83, p=0.014).  Among all participants with hemorrhagic stroke (n=78) we found no differences in the prevalence of risk factors between PWH and HIV-.ConclusionsPWH with ischemic stroke in Uganda present at a younger age, and with a combination of traditional and psychosocial risk factors. By contrast, HIV- persons more commonly present with arrhythmia. A differential approach to stroke prevention might be needed in these populations.     

Incidence,early case fatality and determinants of stroke in Iran: Golestan Cohort Study

Objectives: While few studies investigated the incidence of stroke in Iran, no Iranian cohort has estimated the standardized-incidence rate and early fatality of first-ever-stroke subtypes along with associated factors. Methods: Golestan Cohort Study is a prospective study launched in northeastern Iran in 2004, including 50,045 individuals aged 40-75 at baseline. Age-standardized incidence rate of first-ever-stroke was calculated per 100,000 person-years, according to World Standard Population. The 28-day case fatality was calculated by dividing the number of fatal first-ever-stroke during the first 28 days by total events. Cox proportional hazard models were conducted to assess incidence and fatality risk factors. We used Population Attributable Fractions to estimate the incidence and early fatality proportions reduced by ideal risk factor control. Results: 1,135 first-ever-strokes were observed during 8.6 (median) years follow-up. First-ever-stroke standardized incidence rate was estimated 185.2 (95% CI: 173.2-197.2) per 100,000 person-years. The 28-day case fatality was 44.1% (95% CI: 40.4-48.2). Hypertension and pre-stroke physical activity were the strongest risk factors associated with first-ever-stroke incidence (Hazard ratio: 2.83; 2.47-3.23) and 28-day case fatality (Hazard ratio: 0.59; 0.44-0.78), respectively. Remarkably, opium consumption was strongly associated with hemorrhagic stroke incidence (Hazard ratio: 1.52; 1.04-2.23) and ischemic stroke fatality (Hazard ratio: 1.44; 1.01-2.09). Overall, modifiable risk factors contributed to 83% and 61% of first-ever-stroke incidence and early fatality, respectively. Conclusion: Efficient risk factor control can considerably reduce stroke occurrence and fatality in our study. Establishing awareness campaigns and 24-hour stroke units seem necessary for improving the stroke management in this area.     

Use of cyproheptadine hydrochloride (HCl) to reduce neuromuscular hypertonicity in stroke survivors: A Randomized Trial: Reducing Hypertonicity in Stroke

ObjectivesThe goal of this study was to examine how the administration and dosing of the anti-serotonergic medication cyproheptadine hydrochloride (HCl) affects involuntary muscle hypertonicity of the spastic and paretic hands of stroke survivors.Materials and MethodsA randomized, double-blinded, placebo-controlled longitudinal intervention study was performed as a component of a larger clinical trial. 94 stroke survivors with chronic, severe hand impairment, rated as levels 2 or 3 on the Chedoke-McMaster Stroke Assessment Stage of Hand (CMSA-H), were block randomized to groups receiving doses of cyproheptadine HCl or matched doses of placebo. Doses were increased from 4 mg BID to 8 mg TID over 3 weeks. Outcomes were assessed at baseline and after each of the three weeks of intervention. Primary outcome measure was grip termination time; other measures included muscle strength, spasticity, coactivation of the long finger flexors, and recording of potential adverse effects such as sleepiness and depression.Results89 participants (receiving cyproheptadine HCl: 44, receiving placebo: 45) completed the study. The Cyproheptadine group displayed significant reduction in grip termination time, in comparison with the Placebo group (p<0.05). Significant change in the Cyproheptadine group (45% time reduction) was observed after only one week at the 4mg BID dosage. The effect was pronounced for those participants in the Cyproheptadine group with more severe hand impairment (CMSA-H level 2) at baseline. Conversely, no significant effect of Group * Session interaction was observed for spasticity (p=0.6) or coactivation (p=0.53). There were no significant changes in strength (p=0.234) or depression (p=0.441) during the trial.ConclusionsUse of cyproheptadine HCl was associated with a significant reduction in relaxation time of finger flexor muscles, without adversely affecting voluntary strength, although spasticity and coactivation were unchanged. Decreasing the duration of involuntary flexor activity can facilitate object release and repeated prehensile task performance.RegistrationClinical Trial number: NCT02418949     

早期妊娠稽留流产患者术后转归的临床观察

目的：　观察一系列保护女性生育能力的干预措施应用在早期妊娠稽留流产患者手术治疗后的效果及在此类人群中获益情况。方法：　对293例早期妊娠稽留流产的手术治疗患者给予围手术期规范处理及全程贯彻流产后关爱（post-abortion care,PAC）服务,观察术中出血、子宫穿孔等并发症发生情况,随访其术后恢复、再生育及意外妊娠情况。结果：　通过规范围手术期操作,手术治疗术中并发症发生率极低,临床效果肯定,术后有生育意愿者术后6个月内再次妊娠占比为20.22%,1年内再次妊娠占比为46.45%。通过围手术期优质PAC服务,术后患者避孕意识明显提高,1年内无生育计划者意外妊娠率为1.82%。结论：　围手术期规范手术操作、提供优质PAC服务,降低了术中并发症的发生率,提高了早期妊娠稽留流产患者再次妊娠率,减少了意外妊娠,保护了女性生育能力。     

吉西他滨低剂量延时输注的研究进展

吉西他滨（gemcitabine,GEM）为抗嘧啶核苷酸代谢类药物。目前,GEM的标准给药方式为1 000~1 250 mg·m^-2,30 min静脉快速输注。但是,药理学研究表明,GEM延时输注可使细胞内有活性的GEM三磷酸盐达到最佳的蓄积速度,提示GEM延时输注在药动学方面要优于30 min快速输注。故本文对GEM低剂量延时输注的相关研究进行综述,以期为临床用药提供相关依据。     

Killed but metabolically active Pseudomonas aeruginosa-based vaccine induces protective humoral- and cell-mediated immunity against Pseudomonas aeruginosa pulmonary infections

Pseudomonas aeruginosa (Pa) is a significant cause of morbidity and mortality, especially in cystic fibrosis patients. Its eradication is difficult due to a wide phenotypic adaptability and an increase of its resistance to antibiotics. After the failure of several recombinant vaccines which mainly triggered humoral response, live-attenuated vaccines received attention thanks to their ability to elicit a broad immunity with both humoral- and cell-mediated responses, essential to fight this pathogen. In this study, we developed an innovative and safer live-attenuated Pa vaccine based on a Killed But Metabolically Active (KBMA) attenuation method. KBMA Pa has been further rationally designed to overexpress beneficial effectors like the type 3 secretion system apparatus. We demonstrated that KBMA Pa elicits a high and broad humoral response in mice against several antigens of particular interest such as OprF and PcrV proteins. Moreover, we assessed cytokines in the serum of immunized mice and showed that KBMA Pa elicits Th1, Th2 and especially Th17 pathways of cell-mediated immune responses. Th17 pathway involvement was also confirmed after specific stimulation of helper T cells in immunized mice. Finally, we showed that this vaccine is safe and has a protective effect in a murine acute pulmonary infectious challenge. In conclusion, KBMA Pa is a new platform with high potential for the development of a vaccine against Pa.     

Dexmedetomidine promotes liver regeneration in mice after 70% partial hepatectomy by suppressing NLRP3 inflammasome not TLR4/NFκB

Inflammasome activation is mediated by NOD-like receptors (NLRs) that play important role in cellular proliferation. NLRP3 senses the widest array of stimuli. But its role in the liver regeneration after partial hepatectomy (PHx) is still unknown. Dexmedetomidine (Dex) has been documented to protect the liver against ischemia-reperfusion injury via the suppression of the TLR4/NF-κB pathway, which is important for NLRP3 inflammasome activation and liver regeneration. We tested whether Dex contributes to liver regeneration, and investigated its consequent effect on inflammasome activation. In vitro, L02 human liver cells were treated with Dex at different concentrations. The 70% PHx was performed in C57 BL/6 mice as PHx group, and sham-operated animals as Sham group, Dex-treated animals were assigned into two groups: Dex + PHx, which received single intraperitoneal injections of Dex (25 μg/kg) before PHx 30 mins; Dex + PHx + Dex, which received additional Dex (25 μg/kg) after PHx for 3 days. Dex significantly inhibited the proliferation of Lo2 cells in vitro and decreased the expression of TLR4/NFκB. In vivo, Dex + PHx exhibited promoted effect on liver regeneration and liver function recovery via inhibiting NLRP3 inflammasome activation. Dex + PH + Dex inhibited the liver regeneration, which may be associated with suppressed expression levels of TLR4/NFκB pathway. Though Dex pretreatment contributed to liver regeneration and function recovery via inflammation suppression, excessive inflammation suppression accompanied with TLR4 suppression could be related to the diminished liver regeneration, suggesting that TLR4/NFκB played important role in liver regeneration and Dex + PHx might be a useful therapeutic strategy to promote liver regeneration in clinical.     

系统性红斑狼疮患者外周血CD3+CD56+NKT水平与Th1/Th2细胞表达的相关性

目的 探讨系统性红斑狼疮（SLE）患者外周血CD3+CD56+NKT水平与相关机制的关系。方法 选取2019年8月～2020年12月重庆市九龙坡区中医院收治的112例SLE患者（SLE组）,按SLEDAI评分分为非活动期72例,活动期40例,另选取同期健康自愿者50例（健康组）。采集受试者血采用流式细胞技术测定CD3+CD56+NKT水平,采用酶联免疫法测定血清中相关细胞因子,分析各指标与病情的相关性。结果 SLE组外周血CD3+CD56+NKT细胞计数及占比均较健康组明显减小,差异有统计学意义（P＜0.05）;SLE活动期组外周血CD3+CD56+NKT细胞计数及占比、IFN-γ、IFN-γ/IL-4明显低于非活动期组,SLEDAI评分、24 h UPQ、IL-4明显高于非活动期组,差异有统计学意义（均P＜0.05）;Pearson相关分析结果显示,CD3+CD56+NKT细胞与SLE患者SLEDAI评分、24 hUPQ及IL-4呈负相关（r=-0.573、-0.682、-0.374,P＜0.05）,而与IFN-γ无显著相关性（r=0.016,P＞0.05）。结论 CD3+CD56+NKT细胞参与了SLE免疫调节过程,其表达水平与患者SLEDAI评分呈显著负相关,CD3+CD56+NKT细胞可能通过分泌Th1/Th2细胞相关因子发挥SLE免疫调节作用,值得临床借鉴。     

沙库巴曲缬沙坦治疗急性失代偿射血分数降低心力衰竭患者的有效性和安全性

探讨沙库巴曲缬沙坦（S/V）治疗射血分数降低急性失代偿心力衰竭（ADHF）患者的有效性和安全性。方法 连续纳入2018年5月～2019年10月重庆4个研究中心心血管内科射血分数降低的ADHF患者,根据临床处方信息患者被分为S/V组和血管紧张素转换酶抑制剂（ACEI）/血管紧张素受体阻滞剂（ARB）组（ACEI/ARB组）。住院期间和出院后医生根据患者的一般情况和血压滴定药物剂量,随访至出院后12个月。主要有效性终点是心源性死亡和心衰（HF）住院发生率,次要有效性终点是全因死亡和全因住院发生率。安全性终点肾功能损伤、高钾血症、咳嗽、血管神经性水肿和症状性低血压发生率。结果 筛选期共纳入758例,根据入排标准排除127例,631例纳入倾向性评分,最后502例患者纳入数据分析,S/V组和ACEI/ARB组各251例。S/V组和ACEI/ARB组患者主要疗效性终点心血管死亡和HF住院发生率分别为235%和32.3%（HR:0.687; 95% CI:0.493～0.958; P=0.027）,其中心血管死亡发生率分别为48%和10.4%（HR:0.444; 95% CI: 0.235～0.840; P=0.017）,HF再住院发生率分别为18.7%和21.9%（HR:0.845; 95% CI:0.573～1.247; P=0.398）;次要疗效终点全因死亡和全因住院发生率分别为35.1%和38.2%（HR:0.891; 95% CI:0.668～1.191; P=0.4.37）,其中全因死亡发生率分别为4.8%和11.6%（HR:0.396; 95% CI:0.214～0.731; P=00005）,全因住院发生率分别为30.3%和26.7%（HR, 1.168; 95% CI:0.841～1.622; P=0.352）。安全性终点两组无显著差异。结论 与ACEI/ARB相比,S/V治疗可降低射血分数降低的ADHF患者1年心源性死亡和心衰住院复合终点,并且其安全性相当。     

消化内镜专科护士培训中应用目标反馈教学的效果研究

目的　探讨目标反馈教学在消化内镜专科护士培训中的应用效果。方法　以参加重庆市消化内镜专科护士培训的68名学员为研究对象,将2019年的30名学员作为观察组,采用目标反馈教学法进行培训;2018年的38名学员作为对照组,采用传统培训方法。培训结束后,从理论成绩、技能操作成绩及综合成绩3个方面评价并比较两组学员的培训效果,同时针对学员的满意度进行问卷调查。采用SPSS 25.0进行t检验、卡方检验和Mann-Whitney U检验。结果　观察组学员的技能操作成绩（84.90±4.92）、综合成绩（86.30±4.62）高于对照组（82.39±4.10）（83.86±5.10）,差异有统计学意义（P<0.05）;理论成绩差异不大,无统计学意义[（85.80±5.63）vs.（83.68±4.51）,P>0.05]。学员对新的培训方法满意度较高。结论　目标反馈教学能很好地提高消化内镜专科护士的操作技能和综合能力,提高培训效果,确保专科护士对培训的满意度。