Reduced tonicity stimulates an inflammatory response in nucleus pulposus tissue that can be limited by a COX‐2‐specific inhibitor

In intervertebral disc herniation with nucleus pulposus (NP) extrusion, the elicited inflammatory response is considered a key pain mechanism. However, inflammatory cytokines are reported in extruded herniated tissue, even before monocyte infiltration, suggesting that the tissue itself initiates the inflammation. Since herniated tissue swells, we investigated whether this simple mechanobiological stimulus alone could provoke an inflammatory response that could cause pain. Furthermore, we investigated whether sustained‐release cyclooxygenase‐2 (COX2) inhibitor would be beneficial in such conditions. Healthy bovine NP explants were allowed to swell freely or confined. The swelling explants were treated with Celecoxib, applied either as a bolus or in sustained‐release. Swelling explants produced elevated levels of interleukin‐6 (IL‐6) and prostaglandin E₂ (PGE₂) for 28 days, while confined explants did not. Both a high concentration bolus and 10 times lower concentration in sustained release completely inhibited PGE₂ production, but did not affect IL‐6 production. Swelling of NP tissue, without the inflammatory system response, can trigger cytokine production and Celecoxib, even in bolus form, may be useful for pain control in extruded disc herniation. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1724–1731, 2015.     

A pleasant dilemma to have: to treat the HCV patient on the waiting list or to treat post‐liver transplantation?

New and relatively well‐tolerated medications to treat hepatitis C virus (HCV) infection have presented an opportunity for hepatologists to eliminate HCV in liver transplant (LT) candidates prior to transplantation. While concern for causing decompensated liver disease in the sickest subset of pre‐transplant patients makes some clinicians reluctant to offer treatment, we believe that several advantages of early HCV eradication appear to shift the debate in favor of using anti‐HCV agents before LT. There are encouraging safety data for new HCV medications in cirrhotic patients, and given the limited supply of donor livers available, delaying or possibly preventing the need for LT by treating HCV can offer significant benefit. Post‐LT, making immunosuppression management easier as well as avoiding both extrahepatic manifestations of HCV (e.g., diabetes mellitus and kidney disease) and the dilemma of distinguishing post‐transplant viral recurrence from allograft rejection makes earlier treatment of HCV especially appealing to clinicians. Furthermore, retrospective data have demonstrated a mortality benefit among HCV patients who are free of the virus at the time of LT. This article explores arguments for and against treating HCV in patients on the transplant list.     

丙型肝炎肝硬化合并脾功能亢进腹腔镜下脾全切除术后行抗病毒治疗的疗效观察

目的观察丙型肝炎肝硬化合并脾功能亢进患者在行手助腹腔镜下脾全切除术后采用聚乙二醇干扰素(Peg-IFNα-2α)联合利巴韦林抗病毒治疗的疗效。方法 46例丙型肝炎肝硬化(基因型为Ib型)合并脾亢患者,行手助腹腔镜下脾全切除术,待脾亢改善3个月后,予以Peg-IFNα-2α135μg或180μg皮下注射,每周1次,联合利巴韦林800~1 200 mg/d抗病毒治疗,疗程48周。抗病毒期间,第1、2、4、6、8、12周随访,之后每4周随访1次,停药后继续观察24周。治疗及随访期间观察HCV RNA水平、血常规、肝功能及抗病毒期间的不良反应。结果丙型肝炎肝硬化(基因型为Ib型)合并脾亢患者行手助腹腔镜下脾全切除术后,给予Peg-IFNα-2α联合利巴韦林抗病毒治疗后的持续病毒学应答率(SVR)为67.39%(31/46)。结论丙型肝炎肝硬化合并脾功能亢进患者,行手助腹腔镜下脾全切除术改善脾亢后予以PegIFNα-2α联合利巴韦林抗病毒治疗后有较好的SVR,从而延缓了丙型肝硬化患者肝硬化的进展。     

丙戊酸镁缓释片单用与和喹硫平伍用治疗老年躁狂发作的对照研究

目的：探讨喹硫平合并丙戊酸镁缓释片治疗老年双相情感障碍躁狂发作的临床疗效和安全性。方法选择2013年5月至2014年5月在解放军第261医院,住院符合国际疾病分类-10（ICD-10）双相情感障碍躁狂发作诊断的46例患者,年龄60-78岁。46例符合ICD-10躁狂发作的老年患者随机分为喹硫平合并丙戊酸镁缓释片组（研究组）和单用丙戊酸镁缓释片组（对照组）。治疗6周,应用贝克？拉范森躁狂量表（BRMS）评定疗效,治疗意外症状量表（副反应量表,TESS）评定不良反应。结果治疗过程中每组BRMS总分都有显著下降（P＜0.05）,治疗2周后研究组总分及因子分言语/吵闹、睡眠与对照组比较,差异存在统计学意义（P＜0.05）。治疗6周后,研究组与对照组临床总有效率差异无统计学意义（P＞0.05）。两组均无严重的药物不良反应,两组TESS评分差异无统计学意义（P＞0.05）。结论喹硫平和丙戊酸镁缓释片伍用治疗老年躁狂发作疗效较好,安全性较好,特别是在治疗初期（2周末）能更好的控制兴奋症状和改善睡眠。     

Hepatitis C cure improved patient‐reported outcomes in patients with and without liver fibrosis in a prospective study at a large urban medical center

Patient‐reported outcomes (PROs) are important measures of quality of life. Direct‐acting antiviral (DAA) drugs for hepatitis C virus (HCV) improved PROs in clinical trials. We prospectively evaluated the impact of DAA‐based HCV cure on PROs and liver‐related outcomes in real‐world patients at a large urban medical center. The short form (SF)‐36 and three additional validated instruments were used. F3‐4 fibrosis was defined as > 9.6 kPa by transient elastography (TE); S2‐3 steatosis was defined as > 270 dB/m by TE‐controlled attenuation parameter (CAP). Data were analysed by paired and unpaired t tests. Patients (n = 16) who did not achieve a sustained virologic response at 12 weeks (SVR12) were excluded. The study achieved its primary endpoint and showed a significant 30% improvement in the SF‐36 vitality score, measured baseline to SVR12: 63 versus 82, P < .001 (n = 111). Scores in 24 of 25 PRO domains improved at SVR12 (P < .05). Nearly all gains exceeded 5%, indicating their clinical significance. Transaminase values and liver stiffness improved (decreased) significantly, baseline to SVR12 (P < .005), but steatosis was unchanged (P = .58). Patients with baseline F0‐2 fibrosis and those with F3‐F4 fibrosis both improved in 22 domains. Patients with baseline S0‐S1 steatosis improved in more domains (23) than patients with S2‐S3 steatosis (19). At baseline, patients with F3‐F4 fibrosis and patients with S2‐3 steatosis had worse scores in certain PRO domains than patients with F0‐2 fibrosis or S0‐S1 steatosis, but this difference resolved by SVR12. HCV cure led to meaningful gains in PROs, and these findings may encourage patients to seek treatment.     

Transient elastography in DAA era. Relation between post‐SVR LSM and histology

The natural history of HCV chronic infection has drastically changed after direct‐acting antiviral treatment. Due to the high sustained virological response (SVR) achieved, noninvasive estimation of liver fibrosis regression has become a major key point. The present study tries to evaluate the relation between liver histology and liver stiffness measurement (LSM) by transient elastography (TE) after SVR.