Long-term outcomes in patients with mucinous, medullary, tubular, and invasive ductal carcinomas after lumpectomy

BACKGROUND: Mucinous, medullary, and tubular carcinomas are uncommon types of breast cancer whose rarity does not permit large single-institution studies or randomized trials to define optimal treatments. In this study, we evaluated the long-term outcomes of breast-conserving therapy (BCT) for these subtypes of breast cancer and compared them with those for invasive ductal carcinoma. METHODS: In our institutional database of patients who received BCT from 1965 to 1999, 1,643 patients with stage I to II mucinous (61), medullary (37), tubular (60), and invasive ductal (1,485) histologies were identified. The clinical and pathologic features of the 4 groups were evaluated and compared with respect to local-regional recurrence rates, disease-free survival, and overall survival (OS). RESULTS: No statistically significant differences were found in the local-regional failure rate among the 4 groups (10.6-year median follow-up). Only patients with tubular carcinoma had better 5- and 10-year OS rates (P = .013). In multivariable analysis, factors associated with improved OS included age at or below 50 years, negative nodal status, use of chemotherapy or hormonal therapy, and tubular histology. CONCLUSIONS: BCT for mucinous, medullary, or tubular carcinoma resulted in similar local-regional failure rates to that for invasive ductal carcinoma. Tubular carcinoma patients had the most favorable OS. BCT is an appropriate treatment strategy for early-stage mucinous, medullary, and tubular carcinomas.     

Outcomes after identical and compatible orthotopic liver transplantation for fulminant hepatic failure: a single center experience in UK

To analyze the outcomes between identical and compatible liver transplantation (OLT) for fulminant hepatic failure (FHF) from September 1984 to November 2005. The patients were divided in three groups; group 1 (identical), group 2 (compatible) and group 3 (incompatible), according to the donor-recipient blood type matching. We analyzed several outcomes regarding mortality, patient and graft survival, incidence of acute graft rejection during the first postoperative month (30 days), incidence of biliary complications and indications of re-transplantation. We also analyzed the relationship of Coomb's positive test with postoperative hemolysis to all the above mentioned factors. During the study period, 168 males and 112 females underwent their first OLT for FHF, with 37.1% overall mortality and 42.1% overall graft failure rate. The results between group 1 (203 patients) and group 2 (73 patients) were comparable. A statistically significant difference was recorded in 1 year and overall graft survival between group 1 and group 2 (P = 0.049 and log-rank = 0.035 respectively). Coomb's positive test did not influence the outcomes. OLT in FHF can be safely carried out whether the donor organs are identical or compatible. Hemolysis (Coomb's positive test) after identical or compatible OLT does not influence the outcomes.     

高迁移率族蛋白B1诱导小鼠腹腔巨噬细胞凋亡的受体机制

目的 了解高迁移率族蛋白B1(HMGB1)对小鼠腹腔巨噬细胞凋亡的影响及其受体机制.方法 分离培养小鼠腹腔巨噬细胞,在巨噬细胞中加入不同的刺激物,分为HMGB1组:加入10 μg/ml的HMGB1;HMGB1+抗晚期糖基化终末产物受体(RAGE)组:先加入RAGE多克隆抗体5μg/ml孵育2 h后,再加入HMGB1;HMGB1+重组鼠(rm)RAGE/Fc组:将10 μg/ml的HMGB1与10μg/ml的rmRAGE/Fc混合作用2 h后,再加入巨噬细胞;对照组:加入磷酸盐缓冲液.采用流式细胞仪检测细胞表面RAGE的表达强度.激光共聚焦显微镜观察细胞凋亡情况,流式细胞仪检测细胞凋亡率.结果 HMGB1组RAGE阳性细胞率(54±12)%明显高于对照组[(13±5)%,P＜0.01],其荧光强度(126±10)也显著高于对照组(34±8,P＜0.01).HMGB1+rmRAGE/Fc组、HMGB1+抗RAGE组凋亡细胞明显多于对照组,而HMGB1组晚期凋亡及坏死细胞明显多于其他3组.HMGB1组细胞凋亡率(39.5±2.3)%高于HMGB1+rmRAGE/Fc组[(17.3±3.6)%]、HMGB1+抗RAGE组[(14.8±4.8)%]及对照组[(5.4±2.3)%,P＜0.01].结论 HMGB1可诱导RAGE表达上调,RAGE是HMGB1诱导巨噬细胞凋亡的主要受体之一.     

Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice

The hypothesis of this study was that sustained activity of the Nod-like receptor protein (NLRP)-3 inflammasome in wounds of diabetic humans and mice contributes to the persistent inflammatory response and impaired healing characteristic of these wounds. Macrophages (Mp) isolated from wounds on diabetic humans and db/db mice exhibited sustained inflammasome activity associated with low level of expression of endogenous inflammasome inhibitors. Soluble factors in the biochemical milieu of these wounds are sufficient to activate the inflammasome, as wound-conditioned medium activates caspase-1 and induces release of interleukin (IL)-1β and IL-18 in cultured Mp via a reactive oxygen species–mediated pathway. Importantly, inhibiting inflammasome activity in wounds of db/db mice using topical application of pharmacological inhibitors improved healing of these wounds, induced a switch from proinflammatory to healing-associated Mp phenotypes, and increased levels of prohealing growth factors. Furthermore, data generated from bone marrow–transfer experiments from NLRP-3 or caspase-1 knockout to db/db mice indicated that blocking inflammasome activity in bone marrow cells is sufficient to improve healing. Our findings indicate that sustained inflammasome activity in wound Mp contributes to impaired early healing responses of diabetic wounds and that the inflammasome may represent a new therapeutic target for improving healing in diabetic individuals.     

Mangiferin Stimulates Carbohydrate Oxidation and Protects Against Metabolic Disorders Induced by High-Fat Diets

Excessive dietary fat intake causes systemic metabolic toxicity, manifested in weight gain, hyperglycemia, and insulin resistance. In addition, carbohydrate utilization as a fuel is substantially inhibited. Correction or reversal of these effects during high-fat diet (HFD) intake is of exceptional interest in light of widespread occurrence of diet-associated metabolic disorders in global human populations. Here we report that mangiferin (MGF), a natural compound (the predominant constituent of Mangifera indica extract from the plant that produces mango), protected against HFD-induced weight gain, increased aerobic mitochondrial capacity and thermogenesis, and improved glucose and insulin profiles. To obtain mechanistic insight into the basis for these effects, we determined that mice exposed to an HFD combined with MGF exhibited a substantial shift in respiratory quotient from fatty acid toward carbohydrate utilization. MGF treatment significantly increased glucose oxidation in muscle of HFD-fed mice without changing fatty acid oxidation. These results indicate that MGF redirects fuel utilization toward carbohydrates. In cultured C2C12 myotubes, MGF increased glucose and pyruvate oxidation and ATP production without affecting fatty acid oxidation, confirming in vivo and ex vivo effects. Furthermore, MGF inhibited anaerobic metabolism of pyruvate to lactate but enhanced pyruvate oxidation. A key target of MGF appears to be pyruvate dehydrogenase, determined to be activated by MGF in a variety of assays. These findings underscore the therapeutic potential of activation of carbohydrate utilization in correction of metabolic syndrome and highlight the potential of MGF to serve as a model compound that can elicit fuel-switching effects.     

Enhanced Recovery Pathway for Urgent Colectomy

Background

Enhanced recovery protocols have been proven to decrease complications and hospital stay following elective colorectal surgery. However, these principles have not yet been reported for urgent surgery procedures. We aimed to assess our initial experience with urgent colectomies performed within an established enhanced recovery pathway.

Methods

In a prospective cohort study, all patients undergoing colonic resection between April 2012 and March 2013 were treated according to a standardized enhanced recovery protocol. Urgent surgeries were compared with the elective procedures with regards to baseline characteristics, compliance with enhanced recovery items, and clinical outcome.

Results

Patients (N = 28) requiring urgent colonic resection were included and compared with patients undergoing elective colectomy (N = 63). Overall compliance with the protocol was 57 % for the urgent compared with 77 % for the elective procedures (p = 0.006). The pre-operative compliance was 64 versus 96 % (p < 0.001), the intra-operative compliance was 77 versus 86 % (p = 0.145), and the post-operative compliance was 49 versus 67 % (p = 0.015), for the urgent and elective resections, respectively. Overall, 18 urgent patients (64 %) and 32 elective patients (51 %) developed postoperative complications (p = 0.261). Median postoperative length of stay was 8 days in the urgent setting compared with 5 days in the elective setting (p = 0.006).

Conclusions

Many of the intra-operative and post-operative enhanced recovery items can also be applied to urgent colectomy, entailing outcomes that approach the results achieved in the elective setting.     

Combined liver–kidney transplantation versus liver transplant alone based on KDIGO stratification of estimated glomerular filtration rate: data from the United Kingdom Transplant registry – a retrospective cohort study

Patient selection for combined liver–kidney transplantation (CLKT) is a current issue on the background of organ shortage. This study aimed to compare outcomes and post‐transplant renal function for patients receiving CLKT and liver transplantation alone (LTA) based on native renal function using estimated glomerular filtration rate (eGFR) stratification. Using the UK National transplant database (NHSBT) 6035 patients receiving a LTA (N = 5912; 98%) or CLKT (N = 123; 2%) [2001–2013] were analysed, and stratified by KDIGO stages of eGFR at transplant (eGFR group‐strata). There was no difference in patient/graft survival between LTA and CLKT in eGFR group‐strata (P > 0.05). Of 377 patients undergoing renal replacement therapy (RRT) at time of transplantation, 305 (81%) and 72 (19%) patients received LTA and CLKT respectively. A significantly greater proportion of CLKT patients had severe end‐stage renal disease (eGFR < 30 ml/min/1.73 m²) at 1 year post‐transplant compared to LTA (9.5% vs. 5.7%, P = 0.001). Patient and graft survival benefit for patients on RRT at transplantation was favouring CLKT versus LTA (P = 0.038 and P = 0.018, respectively) but the renal function of the long‐term survivors was not superior following CLKT. The data does not support CLKT approach based on eGFR alone, and the advantage of CLKT appear to benefit only those who are on established RRT at the time of transplant.     

指侧方静脉动脉化再植末节断指

目的：探讨指侧方静脉动脉化再植末节断指的疗效。方法2007年3月至2012年4月,收治末节断指患者34例,均在正常指动脉多次吻合失败后行静脉动脉化。20例采用指侧方静脉动脉化再植,将近端指动脉与远端指侧方静脉吻合（A组）;14例采用指腹静脉动脉化再植,用近端指动脉与远端指腹静脉吻合（B组）。结果 A组患者末节断指全部成活,创面均Ⅰ期愈合;B组中有4例坏死。本组中有27例随访6～14个月（A组18例,B组9例）。 A组再植末节断指指腹饱满,指体无明显萎缩,B组指体轻度萎缩;A组指甲长度（15.6±2.7） mm,长于B组（11.9±2.2） mm;A组DIPJ活动度（62±4）°,大于B组（45±3）°;A组两点分辨觉（4.6±0.3） mm,小于B组（7.4±0.6） mm;A组再植断指感觉测定为S（3.49±0.33）,高于B组S（2.47±0.44）;手指各关节活动度参照TAM标准：A组优良率94.4%,B组优良率87.5%,两组优良率比较差异无统计学意义（P=0.534）。结论指侧方静脉动脉化是正常供血失败后的末节断指再植的有效方法。     

A simple scoring system to evaluate the effects of cold ischemia on marginal liver donors

BACKGROUND: Exactly what constitutes a marginal donor remains ill defined. The authors set out to create a scoring system that objectively classifies a donor as marginal or nonmarginal and to define what the maximum acceptable preservation period is for the marginal liver to minimize early graft dysfunction. METHODS: The authors performed an analysis on data collected prospectively of 397 cadaveric liver transplants. Both univariate and multivariate analyses were performed on donor, recipient, and perioperative factors with relation to early allograft dysfunction. A score was developed that classified donors into marginal and nonmarginal populations, and the influence of cold ischemia was determined for each group. RESULTS: Multivariate analysis-determined donor age and steatosis (moderate to severe) were independent predictors of deranged function. This enabled the authors to produce a scoring system to differentiate marginal donors with respect to risk of early allograft dysfunction as follows: Formula=(20.06xsteatosis)+(0.44xdonor age), cutoff 23.1. In the marginal group, the cutoff value of cold ischemia time was 12.6 hr. CONCLUSIONS: The authors developed a scoring system that classified an organ as marginal or nonmarginal depending on the donor age and degree of steatosis. Marginal livers have a strong risk of developing early allograft dysfunction with increasing cold ischemia times and should be transplanted within 12 hr. Cold ischemia time was not found to be an important factor in the development of early allograft dysfunction in nonmarginal donors.