Colorectal cancer screening in patients with spinal cord injury yields similar results to the general population with an effective bowel preparation: a retrospective chart audit.

STUDY DESIGN: Retrospective chart audit. OBJECTIVES: To compare adequacy of colonoscopy bowel preparation and diagnostic findings between persons with SCI receiving an extended inpatient bowel preparation and the general population. SETTING: Veterans Affairs Puget Sound Healthcare System, Seattle, WA, USA. METHODS: We reviewed an electronic database of all colonoscopies performed at a tertiary Veterans Affairs medical center between 7/12/13 and 15/10/15. Patients with SCI received a multi-day bowel preparation with magnesium citrate, and 8-10 liters of polyethylene glycol-3350 and electrolyte colonic lavage solution (PEG-ELS) over two and one half days. The control population received a standard bowel preparation consisting of magnesium citrate and 4 liters of PEG-ELS over 1 day. RESULTS: Two hundred and fifty-five patients were included in the study, including 85 patients with SCI. Average risk screening was a more common colonoscopy indication in patients with SCI vs. the control population (24 vs. 13% p = 0.03). There was no difference in adequacy of bowel preparation (87 vs. 85%, p = 0.73) or adenoma detection rate (55 vs. 51%, p = 0.59) when comparing patients with SCI with the control population. No difference in polyp histopathology was detected (p = 0.748). CONCLUSIONS: Our study demonstrated that an extended bowel preparation for patients with SCI produces similar bowel preparation results and diagnostic yield when compared to patients without SCI undergoing colonoscopy.

ECM components guide IL-10 producing regulatory T-cell (TR1) induction from effector memory T-cell precursors.

We describe a role for ECM as a biosensor for inflammatory microenvironments that plays a critical role in peripheral immune tolerance. We show that hyaluronan (HA) promotes induction of Foxp3- IL-10-producing regulatory T cells (TR1) from conventional T-cell precursors in both murine and human systems. This is, to our knowledge, the first description of an ECM component inducing regulatory T cells. Intact HA, characteristic of healing tissues, promotes induction of TR1 capable of abrogating disease in an IL-10-dependent mouse colitis model whereas fragmentary HA, typical of inflamed tissues, does not, indicating a decisive role for tissue integrity in this system. The TR1 precursor cells in this system are CD4(+)CD62L(-)FoxP3(-), suggesting that effector memory cells assume a regulatory phenotype when they encounter their cognate antigen in the context of intact HA. Matrix integrity cues might thereby play a central role in maintaining peripheral tolerance. This TR1 induction is mediated by CD44 cross-linking and signaling through p38 and ERK1/2. This induction is suppressed, also in a CD44-dependent manner, by osteopontin, a component of chronically inflamed ECM, indicating that CD44 signaling serves as a nexus for fate decisions regarding TR1 induction. Finally, we demonstrate that TR1 induction signals can be recapitulated using synthetic matrices. These results reveal important roles for the matrix microenvironment in immune regulation and suggest unique strategies for immunomodulation.

The association between pre-operative PSA and prostate cancer-specific mortality in patients with long-term follow-up after radical prostatectomy.

BACKGROUND: The clinical and pathologic predictors of prostate cancer-specific mortality (PCSM) many years after radical prostatectomy (RP) remain to be fully elucidated. We explored the association between pre-operative prostate-specific antigen (PSA) and other pathologic predictors and PCSM in men who have undergone (RP). METHODS: We report on 459 patients with PCSM data after RP who were followed prospectively over a 23-year period between 1987 and 1997. Cox regression and Kaplan-Meier analysis were used to evaluate pre-operative PSA, pathologic Gleason sum, pathologic stage, and surgical margin status as predictors of PCSM. RESULTS: The median PSA was 6.6 ng/ml (± 9.9) and the median follow-up time was 9.4 (± 4.9) years. Fourteen patients (3.1%) died of PC. On multivariate analysis, only PSA (HR: 1.050; P = 0.001) and binary Gleason sum (HR: 3.402; P = 0.043) remained significant predictors of PCSM. The predicted 10-year PCSM was significantly worse in those patients in the highest PSA tertile compared to those in other tertiles [PSA > 9.9: 87% (82-92%) vs. PSA = 4-9.9: 95% (93.0-97.0%) vs. PSA = 0-3.9: 100.0% (100.0-100.0%)]. CONCLUSIONS: We have highlighted the importance of pre-operative PSA in predicting PCSM many years after RP. It is a more significant predictor than Gleason sum and pathologic stage. Thus, PSA may help identify patients with life-threatening PC at a time when their disease is curable with definitive therapy.

Sports Participation and Exercise Restriction in Children with Isolated Bicuspid Aortic Valve.

Our study was to apply the 2015 American Heart Association/American College of Cardiology Athletic Participation Guidelines to a group of otherwise healthy school age children and young adults with bicuspid aortic valve (BAV) and describe the potential competitive sports restriction as they age. We performed a retrospective chart review of children and young adults aged 5 to 22 years with isolated BAV with at least two echocardiograms between 2000 and 2013. Using task force guidelines, exercise restriction was recommended for any of the following: (1) any dilation of the aortic root, (2) any dilation of the ascending aorta, (3) moderate aortic stenosis, (4) severe aortic regurgitation; (5) left ventricular dilation or (6) reduced shortening fraction. Of the 345 patients with isolated BAV, 202 were considered restricted at study entry. The final cohort included 123 children and young adults. Over the course of follow up, 36% (44 of 123) met restriction criteria. The most likely cause for restriction was aortic dilation (34%). Progression of aortic valve disease occurred in a minority of patients (3%). There were no reports of death, dissection or catheter or surgical based intervention. In conclusion, we found that strict adherence to current guidelines would result in restriction of more than 1/3 of school age children and young adults with BAV from some form of competitive athletics during school age years. Strict application of the current guidelines in this age group may lead to over-restriction of youths from competitive sports.

A safe and effective multi-day colonoscopy bowel preparation for individuals with spinal cord injuries.

CONTEXT/OBJECTIVE: Colonoscopy with polypectomy is associated with a reduced risk of colorectal cancer (CRC), but poor bowel cleansing limits the diagnostic yield of the procedure. Patients with spinal cord injury (SCI) frequently have suboptimal bowel cleansing with standard pre-colonoscopy bowel preparation regimens. We aimed to assess the safety, tolerability, and efficacy of a multi-day inpatient bowel preparation regimen in a population of patients with SCI. DESIGN: Retrospective case series. SETTING: VA Puget Sound SCI Center. PARTICIPANTS: All patients with SCI (n = 53) who underwent inpatient colonoscopy at the VA Puget Sound from July 12, 2013 to February 12, 2015. OUTCOME MEASURES: Patient characteristics, tolerance of full bowel preparation, pre- and post-bowel preparation electrolyte values, adverse events, and adequacy of bowel cleansing were abstracted. RESULTS: Sixty-eight percent of patients had a cervical level of injury and the majority were either American Spinal Injury Association Impairment Scale A (41%) or D (43%). The full bowel preparation was tolerated by 91% of inpatients. In those with pre- and post-bowel preparation laboratory testing, there were small, but statistically significant decreases in serum calcium and phosphate. No patient had symptoms associated with electrolyte abnormalities or required treatment. Five out of 53 inpatients experienced autonomic dysreflexia (AD) during bowel preparation. Eighty-nine percent of patients had adequate bowel cleansing at colonoscopy. CONCLUSIONS: We demonstrate a safe and effective inpatient bowel preparation regimen in a SCI population. The regimen was associated with mild, asymptomatic hypophosphatemia and hypocalcemia. AD was an uncommon event, predominantly occurring in patients who experienced frequent AD episodes at baseline.

The long-term outcomes after radical prostatectomy of patients with pathologic Gleason 8-10 disease.

Background. We explored the long-term clinical outcomes including metastases-free survival and prostate cancer-specific survival (PCSS) in patients with pathologic Gleason 8-10 disease after radical prostatectomy (RP). Methods. We report on 91 patients with PCSS data with a median followup of 8.2 years after RP performed between 1988 and 1997. Cox regression and Kaplan-Meier analysis were used to evaluate year of surgery, pathologic stage, and surgical margin status as predictors of PCSM. Results. Median age was 65 years (IQR: 61-9), and median PSA was 9.7 ng/ml (IQR: 6.1-13.4). Of all patients, 62 (68.9%) had stage T3 disease or higher, and 48 (52.7%) had a positive surgical margin. On multivariate analysis, none of the predictors were statistically significant. Of all patients, the predicted 10-year BCR-free survival, mets-free survival, and PCSS were 59% (CI: 53%-65%), 88% (CI: 84%-92%), and 94% (CI: 91%-97%), respectively. Conclusions. We have demonstrated that cancer control is durable even 10 years after RP in those with pathologic Gleason 8-10 disease. Although 40% will succumb to BCR, only 6% of patients died of their disease. These results support the use of RP for patients with high-risk localized prostate cancer.

Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse.

Hyaluronan (HA) production by dendritic cells (DCs) is known to promote antigen presentation and to augment T-cell activation and proliferation. We hypothesized that pericellular HA can function as intercellular 'glue' directly mediating T cell-DC binding. Using primary human cells, we observed HA-dependent binding between T cells and DCs, which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone (4-MU), an agent which blocks HA synthesis. Furthermore, T cells regulate HA production by DCs via T cell-derived cytokines in a T helper (Th) subset-specific manner, as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production. Similar effects were seen upon the addition of exogenous Th1 cytokines, IL-2, interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). The critical factors which determined the extent of DC-T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA, as T-cell clones which were pre-treated with monensin, added to block cytokine secretion, bound equivalently irrespective of their Th subset. These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA, which in turn affects the extent of DC-T cell binding. We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation. These data point to a pivotal role for HA in DC-T cell interactions at the IS.