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。     

Early tracheostomy and active exercise programmes in adult intensive care patients with severe burns

BackgroundTracheostomy is a strategy often employed in patients requiring prolonged intubation in ICU settings. Evidence suggests that earlier tracheostomy and early active exercise are associated with better patient centered outcomes. Severe burn patients often require prolonged ventilatory support due to their critical condition, complex sedation management and multiple operating room visits. It is still unclear the optimal timing for tracheostomy in this population.MethodsWe conducted a service evaluation where we compared Early Tracheostomy (≤10 days) with Late Tracheostomy (>10 days) in 41 severely burned patients that required prolonged respiratory support.ResultsEarly Tracheostomy cohort was associated with fewer days of mechanical ventilation (16 vs 33, p = 0.001), shorter hospital length of stay (65 vs 88 days, p = 0.018), earlier first day of active exercise (day 8 vs day 25, p < 0.0001) and higher Functional Assessment for Burns scores upon discharge (32 vs 28, p = 0.016).ConclusionEarly tracheostomy in patients with severe burns is associated with earlier active exercise, fewer days of ventilation, shorter length of hospital stay and better physical functional independence upon discharge from hospital.     

全息影像术中导航在泌尿外科腹腔镜和机器人手术中的应用价值

目的探讨全息影像术中导航在泌尿外科腹腔镜和机器人手术中的应用价值。方法回顾性分析2019年1—12月北京和睦家医院等19家医疗中心收治的86例患者的病例资料,临床诊断包括肾肿瘤78例,膀胱癌2例,肾上腺肿瘤2例,肾囊肿1例,前列腺癌1例,汗腺癌淋巴结转移1例,根治性膀胱切除术后盆腔转移瘤1例。其中,32例接受标准腹腔镜手术,分别为肾部分切除术(LPN)27例,根治性前列腺切除术1例,根治性膀胱切除术2例,肾上腺肿瘤切除术2例;54例接受达芬奇机器人手术,分别为肾部分切除术(RAPN)51例,腹膜后淋巴结清扫术1例,双侧肾囊肿去顶减压术1例,盆腔转移肿瘤切除术1例。两种术式的肾部分切除术患者中41例有可统计的临床数据,其中RAPN 23例,LPN 18例。男26例,女15例;中位年龄53.5(24~76)岁;中位R.E.N.A.L评分7.8(4~11)分。专业工程师根据86例术前增强CT检查图像和诊断报告重建全息影像。术前,全息影像可帮助术者对供应肿瘤或手术切除部位的动静脉血管、淋巴结和神经的立体空间结构及相互关系有更直观的认识,协助术前手术规划。在术中将全息影像与腹腔镜监视器中的术野图像进行实时追踪和融合,实现术中导航。结果本组86例手术均顺利完成。术中通过人工调整全息影像,可提示重要血管如肾动脉和肾静脉在体内的投影位置,帮助术者定位血管、淋巴结和其他重要解剖结构的位置,便于精准分离。本研究采用标准腹腔镜手术和达芬奇机器人手术的肾部分切除术患者中共41例有可统计的临床数据。41例中位手术时间140(50~225)min,其中RAPN为140(50~215)min,LPN为160(80~225)min;中位热缺血时间23(14~60)min,其中RAPN为21(17~40)min,LPN为25(14~60)min;中位出血量80(5~1200)ml,其中RAPN为150(30~1200)ml,LPN为50(5~1200)ml。术中无周围重要脏器损伤。2例LPN患者出现ClavienⅡ级并发症,1例出血1200 ml给予输血,另一例血肿未予处理,自行吸收。此2例分别为前、后肾门肿瘤,R.E.N.A.L评分均为11分。结论全息影像术中导航可协助术者在腹腔镜和机器人手术中对重要的解剖结构进行定位、识别,在减少术中组织和器官损伤、降低手术并发症和提高手术成功率方面有重要的应用价值。     

Subtalar Arthroereisis Implantation in Acquired Neuropathic Pes Planus: A Preliminary Report Detailing a Minimally Invasive Approach to Healing Medial Column Ulcerations

Ulcerations under the medial column in patients with acquired neuropathic pes planus may be intractable to conservative techniques such as regular debridement, offloading, bracing, and accommodative shoes. When surgery becomes necessary for these patients, the foot and ankle surgeon has the option of exostectomy, medial column beaming, medial column fusion, and external fixation, among others. In the case of a flexible midfoot collapse, the option of arthroereisis for indirect medial column support may be warranted. In this preliminary report, the authors detail a technique of Achilles tendon lengthening, arthroereisis implantation, and advanced cellular tissue product application in an attempt at wound coverage and prevention of recurrence. Three patients presenting with intractable medial column ulcerations of ∼1 year's duration underwent this procedure, and within 7 weeks (range 5 to 7), all medial column ulcerations healed. These patients remained healed at last follow-up (average 29 months; range 8 to 44). This preliminary report provides evidence for a minimally invasive procedure aimed at offloading, healing, and preventing recurrence of medial column ulcerations in patients with flexible neuropathic pes planus.     

Primary cilia mediate sonic hedgehog signaling to regulate neuronal‐like differentiation of bone mesenchymal stem cells for resveratrol induction in vitro

Mesenchymal stem cells (MSCs) can differentiate into neuronal‐like cell types under specific conditions. The classical antioxidant inducers such as β‐mercaptoethanol (BME), butylated hydroxyanisol (BHA), and dimethylsulfoxide (DMSO) are limited in clinical because of toxicity. Resveratrol, a safer, natural antioxidant, can stimulate osteoblastic differentiation of MSCs. However, its effect of inducing MSCs to differentiate into neuronal‐like cells is less well studied, and its differentiated mechanisms are not well understood. Sonic hedgehog (Shh) signaling, mediated by the primary cilia, is crucial for embryonic development and tissue differentiation, but relatively little is known about the role of Shh signaling and primary cilia in neuronal‐like differentiation of MSCs. Here we show that primary cilia, harboring patched 1 (Ptc1), are present in growth‐arrested MSCs and that smoothened (Smo) and Gli1 are present in cytoplasm of MSCs, which are important components of the Shh signaling pathway. After resveratrol induction, MSCs acquire neuronal‐like cell morphologies and phenotypes, Smo translocates to the primary cilia, Gli1 enters the nucleus, and expressions of Smo and Gli1 proteins increase, which can be inhibited by cyclopamine, a Smo antagonist. Meanwhile, Smo agonist (SAG) attains similar effects compared with the resveratrol group. These data indicate that resveratrol can induce MSCs to differentiate into neuronal‐like cells and activate Shh signaling pathway in the primary cilia. Moreover, the primary cilia and Shh signaling are essential for resveratrol inducing neuronal‐like differentiation of MSCs. Our finding is important for understanding the neuronal‐like differentiation mechanism of MSCs for resveratrol and promoting its clinical therapeutic utility. © 2014 Wiley Periodicals, Inc.     

HIF-1α and HIF-2α are critically involved in hypoxia-induced lipid accumulation in hepatocytes through reducing PGC-1α-mediated fatty acid β-oxidation

During periods of cellular hypoxia, hepatocytes adapt to consume less oxygen by shifting energy production from mitochondrial fatty acid β-oxidation to glycolysis. One of the earliest responses to pathologic hypoxia is the activation of the hypoxia-inducible factor (HIF). In the present study, we examined whether HIF-1 and HIF-2 were involved in the regulation of fatty acid synthesis and β-oxidation. We showed that hypoxia induced fat accumulation in the livers of mice and in HepG2 cells. These hypoxia-induced changes in fatty acid metabolism were mediated by suppressing fatty acid β-oxidation, without significantly influencing fatty acid synthesis. Exposing hepatocytes to 1% O₂ reduced the mRNA expression of carnitine palmitoyltransferase 1 (CPT-1), which catalyzes the rate-limiting step in the mitochondrial import of fatty acids for β-oxidation. Moreover, hypoxia exposure reduced proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein levels, which plays an important role in regulation of β-oxidation. Exposure of HIF-1α or HIF-2α deficient hepatocytes to hypoxia abrogated the reduction in PGC-1α and CPT-1 expression and cellular lipid accumulation observed in normal hepatocytes exposed to hypoxia. These results suggest that both HIF-1α and HIF-2α are involved in hypoxia-induced lipid accumulation in hepatocytes via reducing PGC-1α mediated fatty acid β-oxidation.     

住院患者退药现象分析及改进方法

目的了解患者退药的具体原因,有针对性地实行应对措施,以减少退药现象。方法采用回顾性研究方法,对医院2013年7月25日至8月10日收治的495例住院患者退药单的退药情况进行统计及分析。结果日平均退药率为2.20%,退药原因为出院（43.64%）,调整用药（17.98%）,医生原因（10.91%）,手术原因（9.90%）;退药较多的科室为普外科、妇产科、骨科、中医科,分别占10.30%,8.89%,8.08%,8.08%;退药种类中营养及补液类药物最多（28.31%）,其次为抗感染药物（20.48%）。结论退药现象由医院信息管理系统、医生、患者等多方面因素造成,只有医患共同努力,医院提高信息技术水平,才能减少退药情况的发生,提高医疗服务质量。     

A Two-site Pilot Randomized 3 Day Trial of High Dose Left Prefrontal Repetitive Transcranial Magnetic Stimulation (rTMS) for Suicidal Inpatients

BackgroundSuicide attempts and completed suicides are common, yet there are no proven acute medication or device treatments for treating a suicidal crisis. Repeated daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) for 4–6 weeks is a new FDA-approved treatment for acute depression. Some open-label rTMS studies have found rapid reductions in suicidality.DesignThis study tests whether a high dose of rTMS to suicidal inpatients is feasible and safe, and also whether this higher dosing might rapidly improve suicidal thinking. This prospective, 2-site, randomized, active sham-controlled (1:1 randomization) design incorporated 9 sessions of rTMS over 3 days as adjunctive to usual inpatient suicidality treatment. The setting was two inpatient military hospital wards (one VA, the other DOD).PatientsResearch staff screened approximately 377 inpatients, yielding 41 adults admitted for suicidal crisis. Because of the funding source, all patients also had either post-traumatic stress disorder, mild traumatic brain injury, or both.TMS methodsRepetitive TMS (rTMS) was delivered to the left prefrontal cortex with a figure-eight solid core coil at 120% motor threshold, 10 Hertz (Hz), 5 second (s) train duration, 10 s intertrain interval for 30 minutes (6000 pulses) 3 times daily for 3 days (total 9 sessions; 54,000 stimuli). Sham rTMS used a similar coil that contained a metal insert blocking the magnetic field and utilized electrodes on the scalp, which delivered a matched somatosensory sensation.Main outcome measurePrimary outcomes were the daily change in severity of suicidal thinking as measured by the Beck Scale of Suicidal Ideation (SSI) administered at baseline and then daily, as well as subjective visual analog scale measures before and after each TMS session. Mixed model repeated measures (MMRM) analysis was performed on modified intent to treat (mITT) and completer populations.ResultsThis intense schedule of rTMS with suicidal inpatients was feasible and safe. Minimal side effects occurred, none differing by arm, and the 3-day retention rate was 88%. No one died of suicide within the 6 month followup. From the mITT analyses, SSI scores declined rapidly over the 3 days for both groups (sham change −15.3 points, active change −15.4 points), with a trend for more rapid decline on the first day with active rTMS (sham change −6.4 points, active −10.7 points, P = 0.12). This decline was more pronounced in the completers subgroup [sham change −5.9 (95% CI: −10.1, −1.7), active −13 points (95% CI: −18.7, −7.4); P = 0.054]. Subjective ratings of ‘being bothered by thoughts of suicide’ declined non-significantly more with active rTMS than with sham at the end of 9 sessions of treatment in the mITT analysis [sham change −31.9 (95% CI: −41.7, −22.0), active change −42.5 (95% CI: −53.8, −31.2); P = 0.17]. There was a significant decrease in the completers sample [sham change −24.9 (95% CI: −34.4, −15.3), active change −43.8 (95% CI: −57.2, −30.3); P = 0.028].ConclusionsDelivering high doses of left prefrontal rTMS over three days (54,000 stimuli) to suicidal inpatients is possible and safe, with few side effects and no worsening of suicidal thinking. The suggestions of a rapid anti-suicide effect (day 1 SSI data, Visual Analogue Scale data over the 3 days) need to be tested for replication in a larger sample.Trial registrationClinicalTrials.gov Identifier: NCT01212848, TMS for suicidal ideation.     

Infant 7-valent pneumococcal conjugate vaccine immunization alters young adulthood CD4T cell subsets in allergic airway disease mouse model

7-Valent pneumococcal conjugate vaccine (PCV7) immunization in adulthood can inhibit allergic asthma in mouse model. The aim of this study is to investigate the effects of infant PCV7 immunization on young adulthood CD4⁺T cell subsets in a murine allergic airway disease (AAD) model. Our study indicated that infant PCV7 immunization can inhibit young adulthood airway inflammation and airway hyperresponsiveness (AHR) by inducing the production of Foxp3⁺Treg, Th1 cells and their cytokines IL-10 and IFN-γ, inhibiting the production of Th2, Th17 cells and their cytokines IL-13 and IL-17A in BALB/c mice model. These results suggested that infant PCV7 immunization may serve as an effective measure to prevent young adulthood mice AAD.