Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology.

Intestinal epithelial cell (IEC) damage by T cells contributes to graft-versus-host disease, inflammatory bowel disease and immune checkpoint blockade-mediated colitis. But little is known about the target cell-intrinsic features that affect disease severity. Here we identified disruption of oxidative phosphorylation and an increase in succinate levels in the IECs from several distinct in vivo models of T cell-mediated colitis. Metabolic flux studies, complemented by imaging and protein analyses, identified disruption of IEC-intrinsic succinate dehydrogenase A (SDHA), a component of mitochondrial complex II, in causing these metabolic alterations. The relevance of IEC-intrinsic SDHA in mediating disease severity was confirmed by complementary chemical and genetic experimental approaches and validated in human clinical samples. These data identify a critical role for the alteration of the IEC-specific mitochondrial complex II component SDHA in the regulation of the severity of T cell-mediated intestinal diseases.

Current process and outcomes of the surgical management of LUTS due to benign prostatic enlargement: how consistent are we? - results from the multi-institutional audit of surgical management of BPE (AuSuM BPE) in the United Kingdom.

OBJECTIVE: In view of changing landscape of surgical treatment for LUTS secondary to BPE, this audit was undertaken to assess key aspects of the processes and outcomes of the current interventional treatments for BPE, across different units in the UK. MATERIALS AND METHOD: A multi-institutional snapshot audit was conducted for patients undergoing interventions for LUTS/BPE over 8-week period. Using Delphi process two-part proforma was designed to capture data. RESULTS: 529 patients were included across 20 NHS trusts in England and Wales. Median age was 73 years. Indications for surgery were acute retention (47%) and LUTS (45%). 80% of patients had prior medical therapy. TURP formed the commonest procedure. 27% patients had <23 hour hospital stay. Immediate (21%) and delayed (18%) complications were Clavien-Dindo <2 category. High proportion of patients reported residual symptoms. Type and indication of surgery were significant predictor of complications, length of stay and failure of TWOC outcomes, on multivariate analyses. There were variations in departmental processes, 50% centres used PROMs. CONCLUSION: Monopolar TURP still remains the commonest intervention for BPE. Most departments are adopting newer technologies. The audit identified opportunities for development of consistent, effective and patient centric practices as well as need for large-scale focused studies.

Criteria versus guidelines: Are we doing the best for our paediatric patients?

The National Institute for Health and Care Excellence guidance for the provision of cochlear implants (NICE Technology Appraisal Guidance 166. Cochlear implants for children and adults with severe to profound deafness. 2009. National Health Service National Institute for Health and Clinical Excellence.) are used to develop candidacy criteria by public health funding bodies within the UK. Often the guidance is interpreted as strict 'criteria' whereby clinicians adhere to specific audiometric thresholds without accounting for the acceptable range of performance on individual tests or a child's functional development. In this paper four clinical paediatric case studies are described from two cochlear implant centres which serve to illustrate difficulties in applying NICE guidance as strict criteria. These are presented in the context of recommending more flexible interpretation based on the content of the current guidance along with considerations of circumstances where NICE guidance might be adapted to optimise use of cochlear implant technology within a national framework.

Research and comprehensive cancer control coalitions.

The goal of cancer control research is "to generate basic knowledge about how to monitor and change individual and collective behavior and to ensure that knowledge is translated into practice and policy rapidly, effectively, and efficiently" (Division of Cancer Control and Population Sciences in Cancer control framework and synthese rationale, 2010). Research activities span the cancer control continuum from prevention to early detection and diagnosis through treatment and survivorship (Division of Cancer Control and Population Sciences in Cancer control framework and synthese rationale, 2010). While significant advancements have been made in understanding, preventing and treating cancer in the past few decades, these benefits have yielded disproportionate results in cancer morbidity and mortality across various socioeconomic and racial/ethnic subgroups (Ozols et al in J Clin Oncol, 25(1):146-1622, 2007). It has been a high priority since the beginning of the Comprehensive Cancer Control (CCC) movement to utilize research in the development and implementation of cancer plans in the states, tribes and tribal organizations, territories and US Pacific Island Jurisdictions. Nevertheless, dissemination and implementation of research in coalition activities has been challenging for many programs. Lessons learned from programs and coalitions in the implementation and evaluation of CCC activities, as well as resources provided by national partners, can assist coalitions with the translation of research into practice.

Client-directed interventions to increase community demand for breast, cervical, and colorectal cancer screening a systematic review.

Most major medical organizations recommend routine screening for breast, cervical, and colorectal cancers. Screening can lead to early detection of these cancers, resulting in reduced mortality. Yet not all people who should be screened are screened, either regularly or, in some cases, ever. This report presents the results of systematic reviews of effectiveness, applicability, economic efficiency, barriers to implementation, and other harms or benefits of interventions designed to increase screening for breast, cervical, and colorectal cancers by increasing community demand for these services. Evidence from these reviews indicates that screening for breast cancer (mammography) and cervical cancer (Pap test) has been effectively increased by use of client reminders, small media, and one-on-one education. Screening for colorectal cancer by fecal occult blood test has been increased effectively by use of client reminders and small media. Additional research is needed to determine whether client incentives, group education, and mass media are effective in increasing use of any of the three screening tests; whether one-on-one education increases screening for colorectal cancer; and whether any demand-enhancing interventions are effective in increasing the use of other colorectal cancer screening procedures (i.e., flexible sigmoidoscopy, colonoscopy, double contrast barium enema). Specific areas for further research are also suggested in this report.

Client-directed interventions to increase community access to breast, cervical, and colorectal cancer screening a systematic review.

Most major medical organizations recommend routine screening for breast, cervical, and colorectal cancers. Screening can lead to early detection of these cancers, resulting in reduced mortality. Yet not all people who should be screened are screened, either regularly or, in some cases, ever. This report presents the results of systematic reviews of effectiveness, applicability, economic efficiency, barriers to implementation, and other harms or benefits of interventions designed to increase screening for breast, cervical, and colorectal cancers by increasing community access to these services. Evidence from these reviews indicates that screening for breast cancer (by mammography) has been increased effectively by reducing structural barriers and by reducing out-of pocket client costs, and that screening for colorectal cancer (by fecal occult blood test) has been increased effectively by reducing structural barriers. Additional research is needed to determine whether screening for cervical cancer (by Pap test) can be increased by reducing structural barriers and by reducing out-of-pocket costs, whether screening for colorectal cancer (fecal occult blood test) can be increased by reducing out-of-pocket costs, and whether these interventions are effective in increasing the use of other colorectal cancer screening procedures (i.e., flexible sigmoidoscopy, colonoscopy, double contrast barium enema). Specific areas for further research are also suggested in this report.