mTOR regulates memory CD8 T-cell differentiation.

Memory CD8 T cells are a critical component of protective immunity, and inducing effective memory T-cell responses is a major goal of vaccines against chronic infections and tumours. Considerable effort has gone into designing vaccine regimens that will increase the magnitude of the memory response, but there has been minimal emphasis on developing strategies to improve the functional qualities of memory T cells. Here we show that mTOR (mammalian target of rapamycin, also known as FRAP1) is a major regulator of memory CD8 T-cell differentiation, and in contrast to what we expected, the immunosuppressive drug rapamycin has immunostimulatory effects on the generation of memory CD8 T cells. Treatment of mice with rapamycin following acute lymphocytic choriomeningitis virus infection enhanced not only the quantity but also the quality of virus-specific CD8 T cells. Similar effects were seen after immunization of mice with a vaccine based on non-replicating virus-like particles. In addition, rapamycin treatment also enhanced memory T-cell responses in non-human primates following vaccination with modified vaccinia virus Ankara. Rapamycin was effective during both the expansion and contraction phases of the T-cell response; during the expansion phase it increased the number of memory precursors, and during the contraction phase (effector to memory transition) it accelerated the memory T-cell differentiation program. Experiments using RNA interference to inhibit expression of mTOR, raptor (also known as 4932417H02Rik) or FKBP12 (also known as FKBP1A) in antigen-specific CD8 T cells showed that mTOR acts intrinsically through the mTORC1 (mTOR complex 1) pathway to regulate memory T-cell differentiation. Thus these studies identify a molecular pathway regulating memory formation and provide an effective strategy for improving the functional qualities of vaccine- or infection-induced memory T cells.

Surgical management of Crohn's disease.

INTRODUCTION: Crohn's disease is an inflammatory bowel disease that can affect the entire gastrointestinal tract. It is chronic and incurable, and the mainstay of therapy is medical management with surgical intervention as complications arise. Surgery is required in approximately 70% of patients with Crohn's disease. Because repeat interventions are often needed, these patients may benefit from bowel-sparing techniques and minimally invasive approaches. Various bowel-sparing techniques, including strictureplasty, can be applied to reduce the risk of short-bowel syndrome. METHODS: A review of the available literature using the PubMed search engine was undertaken to compile data on the surgical treatment of Crohn's disease. RESULTS AND CONCLUSION: Data support the use of laparoscopy in treating Crohn's disease, although the potential technical challenges in these settings mandate appropriate prerequisite surgical expertise.

Improving quality of surgical care and outcomes: factors impacting surgical site infection after colorectal resection.

Surgical site infections (SSIs) result in patient morbidity and increased costs. The purpose of this study was to determine reasons underlying SSI to enable interventions addressing identified factors. Combining data from the American College of Surgeons National Surgical Quality Improvement Project with medical record extraction, we evaluated 365 patients who underwent colon resection from January 2009 to December 2012 at a single institution. Of the 365 patients, 84 (23%) developed SSI. On univariate analysis, significant risk factors included disseminated cancer, ileostomy, patient temperature less than 36°C for greater than 60 minutes, and higher glucose level. The median number of cases per surgeon was 36, and a case volume below the median was associated with a higher risk of SSI. On multivariate analysis, significant risks associated with SSI included disseminated cancer (odds ratio [OR], 4.31; P < .001); surgery performed by a surgeon with less than 36 cases (OR, 2.19; P = .008); higher glucose level (OR, 1.06; P = .017); and transfusion of five units or more of blood (OR, 3.26; P = .029). In this study we found both modifiable and unmodifiable factors associated with increased SSI. Identifying modifiable risk factors enables targeting specific areas to improve the quality of care and patient outcomes.