HIV-1-specific cytotoxic T lymphocyte (CTL) responses against immunodominant optimal epitopes slow the progression of AIDS in China

To assess the immunodominance patterns of HIV-1-specific cytotoxic T lymphocyte (CTL) responses and the contribution of these responses against the peptides scanning optimal epitopes in chronic infection, we test the HIV-1-specific CTL responses against a panel of 413 overlapping peptides spanning HIV-1 Asian B sequence, including 147 peptides corresponding to optimal clade B epitopes in 49 chronically HIV-1 infected individuals by interferon-gamma Elispot assay. A large variation in the recognition of peptides restricted by the same HLA class I allele is presented. Some epitopes are targeted frequently by individuals while other epitopes restricted by the same allele are rarely recognized in our research. HLA-B35 and HLA-A03 rather than other HLA alleles contribute greatly to total virus-specific CTL responses. Furthermore, there is a significant inverse correlation between the total contribution of HIV-1-specific CTL responses restricted by different HLA alleles to virus-specific immune responses and viral load in the individuals during advanced infection (P=0.002, r=-0.549). The peptides targeted by individuals have significantly lower entropy compared with those not targeted but restricted by the same HLA class I alleles (P<0.05) in 49 individuals infected by HIV-1, especially the advanced infection subgroup (P=0.044). These data demonstrate that the consistent immunodominance patterns of HIV-1-specific CTL responses of Chinese HIV-1 infected individuals and an inverse correlation between the relative contribution of responses restricted by HLA alleles and viral load, which indicates the important protective effect of optimal epitopes against slow disease progression even in advanced infection.     

Diabetes enhances lipopolysaccharide-induced cardiac toxicity in the mouse model

Diabetic patients have a higher rate of mortality from sepsis than do their nondiabetic septic counterparts. The hypothesis in this study is that chronic diabetes may make cardiovascular systems more sensitive to septicemia. To test this hypothesis, the authors investigated the effect of diabetes on endotoxin-induced cardiac toxicity. Diabetes was induced in FVB mice by injecting a single dose (150 mg/kg) of streptozotocin. Two months after streptozotocin treatment, the diabetic mice were treated with lipopolysaccharide by intraperitoneal injection at 2 mg/kg. Cardiac toxicity was evaluated by measuring levels of serum cardiac enzymes and cardiac morphology at 1 h, 4.5 h, and 24 h after lipopolysaccharide treatment. Serum and cardiac tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay methods at 1 h and 4.5 h after lipopolysaccharide treatment. Lipopolysaccharide treatment did not significantly affect the diabetic manifestations, including decreased body weight gain and increased glycated hemoglobin and serum triglyceride levels. However, diabetes significantly enhanced lipopolysaccharide-induced cardiac toxicity, which was demonstrated by significant increases in the levels of cardiac enzymes such as creatine phosphokinase and troponin T, abnormal morphological changes examined under light microscope with hematoxylin and eosin staining, and oxidative damage to proteins detected by 3-nitrotyrosine staining. Lipopolysaccharide treatment significantly increased serum and cardiac TNF-α and IL-6 concentrations. Diabetes did not alter the effect of lipopolysaccharide on serum and cardiac TNF-α elevation, but it significantly enhanced lipopolysaccharide-induced cardiac IL-6 production. These results suggest that diabetes significantly enhances endotoxin-induced cardiac toxicity, possibly through mechanisms that involve inflammatory/acute-phase cytokines.     

A case of primary small cell carcinoma arising from the common bile duct]

Small cell carcinoma is usually seen in the lung, but rarely involves the gastrointestinal tract including biliary tract. A 65 year-old man was admitted because of obstructive jaundice. A smooth-surfaced round intraluminal mass with proximal bile duct dilatation was seen in the proximal common bile duct on endoscopic retrograde cholangiogram. Under the diagnosis of bile duct cancer, pylorus-preserving pancreatoduodenectomy was done. Pathology revealed a 2 cm sized small cell carcinoma in the proximal common bile duct and distal common hepatic duct. On immunohistochemical stain, the tumor cells were positive for neuroendocrine markers CD56 and synaptophysin. After surgery, the patient received 5 cycles of adjuvant chemotherapy with VIP (etoposide, ifosfamide, and cisplatin) regimen. However, the patient died of liver metastasis 12 months after the diagnosis. We report a case of extrapulmonary small cell carcinoma arising from the common bile duct.     

Development of web-based diabetic patient management system using short message service (SMS)

We developed a blood glucose management system using the Internet and short message service (SMS) which can lessen the social economic burden and materialize an individualized diabetes mellitus management. A total of 185 diabetic patients participated in this study and their mean age was 42.4 years old (8-79 year-old). Participants sent their self-measured blood glucose levels, medication and its dosages, amount of meal, and degree of exercise to their health providers in this specialized web-based diabetes management system for 3 months. The health providers consisting of endocrinology specialists, dietitians, and nurses sent recommendations for individualized diabetes management according to the data on the web. Laboratory tests including lipid profiles and glycated hemoglobin (HbA1c), and a survey of satisfaction about this system were performed before and after the study period. The mean HbA1c improved from 7.5 +/- 1.5 to 7.0 +/- 1.1% after using the management program (P = 0.003). The mean serum triglyceride and HDL-cholesterol levels turned for the better also. HbA1c improved from 8.4 +/- 1.2 to 7.5 +/- 1.0% after applying this program to patients with the HbA1c of 7% or higher at baseline (P = 0.010). We propose this web-based diabetic patient management system as a new tool for communication between health care providers and patients.     

Minimally invasive surgery for gastroesophageal reflux disease]

Gastroesophageal reflux disease (GERD) is a chronic disease deteriorating patient's quality of life. With the advent of proton pump inhibitors, treatment failures have decreased considerably. However, surgical therapy offers the potential for cure in more than 90% of patients with GERD. Specific indications for antireflux surgery are: incomplete response to medical therapy, frequent recurrences despite the medical treatment, laryngopharyngeal, and/or respiratory symptoms, and complications of GERD, such as esophageal stricture, erosive esophagitis, esophageal ulcer, and/or Barrett's esophagus. The introduction of laparoscopic surgery in early ninties had a profound impact on many surgical fields, including the treatment of GERD. In this review, laparoscopic Nissen fundoplication is described and controversial topics, such as total vs. partial fundoplication, and the natural history of Barrett's esophagus after antireflux surgery are addressed.     

肺静脉电隔离术后房性心律失常风暴现象的机制及对策

目的回顾分析阵发心房颤动(房颤)肺静脉电隔离术后早期房颤频繁复发并加重的病例,研讨此现象发生的机制和治疗对策。方法对连续54例药物治疗无效的阵发性房颤患者行肺静脉电隔离术,观察术后两周内的房颤复发情况。结果消融术后两周内10例(18.5%)有房颤早期复发或合并快速房性心律失常发作,其中4例(7.4%)出现肺静脉电隔离术后房性心律失常风暴现象。此4例患者联合使用抗心律失常药物两周左右心律逐渐恢复正常,继续服药至3个月,停药后房性心律失常风暴患者仅有1例仍有房颤发作,行二次肺静脉电隔离消融术,术后无房颤发作。结论消融术后早期房颤发作较常见,少数患者短期内房颤发作更加频繁,表现为房性心律失常风暴现象。其可能为多种因素联合作用所致,联合抗心律失常药物治疗有效,不必急于短时间内二次消融。     

Prospective evaluation of the efficacy of peroral endoscopic myotomy in patients with achalasia

Peroral endoscopic myotomy (POEM) is an endoscopic alternative to surgical myotomy in patients with achalasia. This study aimed to evaluate the efficacy and clinical outcomes of POEM.A total of 20 patients with achalasia who underwent POEM between October 2016 and November 2017 were prospectively recruited. The intraoperative esophagogastric junction distensibility index (mm²/mm Hg) was measured pre- and post-myotomy using an endoluminal functional lumen imaging probe. Clinical response was defined as Eckardt score ≤3. Health-related quality of life was measured by the 36-item short-form health survey score.POEM was successfully completed in all cases. The median procedure time was 68.5 minutes (range 50.0–120.0), and the median myotomy length was 13 cm (range 11–18). Major adverse events were encountered in 2 cases. Overall, clinical responses were observed in all patients during a median follow-up of 11.9 months (range 1.2–26.2). Postoperative esophagogastric junction distensibility index was significantly higher than baseline (from 1.3 [range 0.8–6.9] to 6.3 [range 25–19.2], P < .001). The median Eckardt scores were decreased after POEM (5 [range 2–11] to 1 [range 0–3], P < .001), and the 36-item short-form health survey score was also improved significantly after POEM (67.5 [range 34.5–93.9] to 85.7 [range 53.4–93.3], P = .004).POEM is an effective treatment for achalasia, based on the improvement of both symptoms and objective measures.Clinicaltrial.gov {"type":"clinical-trial","attrs":{"text":"NCT 02989883","term_id":"NCT02989883"}}NCT 02989883     

Interstitial lung disease in patients with polymyositis, dermatomyositis and amyopathic dermatomyositis

OBJECTIVE: To assess the prevalence, characteristics and prognostic factors of interstitial lung disease (ILD) in Korean patients with polymyositis (PM), dermatomyositis (DM) and amyopathic dermatomyositis (ADM). METHODS: We reviewed the medical records of 72 consecutive PM and DM patients, including six patients with ADM, who were seen at the Rheumatology Clinic of Seoul National University Hospital between 1984 and 2003. RESULTS: Twenty-nine PM/DM patients (40.3%) developed ILD. Anti-Jo-1 antibody and arthralgia were associated with the presence of ILD (P = 0.022 and P = 0.041, respectively), whereas dysphagia was more frequently found in patients without ILD (P = 0.041). Lung biopsies revealed diffuse alveolar damage (DAD) (n = 2), usual interstitial pneumonia (UIP) with DAD (n = 2), UIP (n = 1), and non-specific interstitial pneumonia (n = 2). Of the 29 patients, 11 (37.9%) died. The mean survival time in ILD patients was significantly shorter than in those without ILD (13.8+/-1.8 vs 19.2+/-0.9 yr, P = 0.017). Poor survival in ILD patients was associated with a Hamman-Rich-like presentation (P = 0.0000), ADM features (P = 0.0001) and an initial forced vital capacity (FVC) < or =60% (P = 0.024). CONCLUSIONS: ILD was observed in 40.3% of Korean PM/DM patients and was associated with poor survival. A Hamman-Rich-like presentation, ADM features and an initial FVC < or =60% were associated with poor survival in ILD.