Sarcopenia is associated with longer hospital stay and multiorgan dysfunction in alcoholic hepatitis.

INTRODUCTION: Excessive alcohol consumption has steadily risen to become the third leading cause of preventable death in the USA. One consequence of heavy alcohol use recently under considerable investigation is alcoholic hepatitis. Although many risk factors for developing alcoholic hepatitis have been documented, our aim in this study was to examine the potential association between sarcopenia and severity, mortality, 30 days readmission rate, complication, infections and length of hospital stay in alcoholic hepatitis patients. METHODS: A retrospective analysis was performed at a large, academic hospital in 194 alcoholic hepatitis patients aged 18-60 who had cross-sectional computed tomography imaging and met our clinical definition of alcoholic hepatitis. The fifth percentile of the psoas muscle index was used as a cutoff for sarcopenia. RESULTS: One hundred ninety-four patients met the criteria for alcoholic hepatitis and had cross-sectional imaging. Higher Model for End-Stage Liver disease score was found in the sarcopenia group when compared to the non-sarcopenia group (mean Model for End-Stage Liver disease 21.5 and 24.2, respectively, P = 0.03). Sarcopenia also correlated with significantly longer hospital stay; the average length of stay in the sarcopenia group was 17.2 days while the non-sarcopenia patients had an average of 12.4 days. We found higher risk of developing pneumonia, sepsis and hepatic encephalopathy in sarcopenic patients. CONCLUSION: Alcoholic hepatitis patients with sarcopenia have significantly worse outcomes when compared with the patients without sarcopenia, including a severe form of alcoholic hepatitis, longer hospital stays, higher risk of developing pneumonia, sepsis and hepatic encephalopathy.

Update on Vaccinating the Patient With Inflammatory Bowel Disease.

PURPOSE OF REVIEW: Patients with inflammatory bowel disease (IBD) are at increased risk of infectious diseases independent of their immunosuppression status, and yet, studies suggest that this population is not receiving standard vaccinations at the same rate as the general population. This review seeks to understand why IBD patients may not be receiving recommended immunizations and to provide guidelines on vaccinating this vulnerable population. RECENT FINDINGS: Inactive vaccines are recommended for patients with IBD regardless of immunosuppression status due to the increased risk for many vaccine-preventable illnesses. Certain live vaccines can be administered to the immunocompromised patient with IBD. Additionally, many patients with IBD will be immunosuppressed some time in their disease course, further increasing their risk for infection. Despite this understanding, patients with IBD have poor vaccination rates. Inadequate knowledge, limited time with patients, and lack of consensus as to who is responsible for identifying and administering vaccinations are some of the most important barriers to vaccinating the patient with IBD. In this review, we discuss guidelines for vaccinating both the immunocompetent and immunosuppressed patient with IBD as well as provide vaccine-specific recommendations. The evidence suggests that patients with IBD are not receiving recommended vaccinations because of misconceptions on the part of patients as well as a paucity of knowledge by their health care team. Educational programs can be successfully implemented to increase knowledge about appropriate vaccinations and can ultimately increase vaccine uptake among patients with IBD. In the end, gastroenterologists and primary care physicians must work together with their patients with IBD to ensure that recommended vaccinations are administered.

Decade-long trends in the magnitude, treatment, and outcomes of patients aged 30 to 54 years hospitalized with ST-segment elevation and non-ST-segment elevation myocardial infarction.

Although acute myocardial infarction (AMI) occurs primarily in the elderly, this disease also affects young adults. Few studies have, however, presented data on relatively young patients hospitalized with AMI. The objectives of this population-based study were to examine recent trends in the magnitude, clinical characteristics, management, and in-hospital and long-term outcomes associated with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) in patients aged 30 to 54 years. We reviewed the medical records of 955 residents of the Worcester (Massachusetts) metropolitan area aged 30 to 54 years who were hospitalized for an initial STEMI or NSTEMI in 6 biennial periods from 1999 to 2009 at 11 greater Worcester medical centers. From 1999 to 2009, the proportion of young adults hospitalized with an STEMI decreased from approximately 2/3 to 2/5 of all patients with an initial AMI. Patients with STEMI were less likely to have a history of heart failure, hypertension, hyperlipidemia, and kidney disease than those with NSTEMI. Both groups received similar effective medical therapies during their acute hospitalization. In-hospital clinical complications and mortality were low and no significant differences in these end points were observed between patients with STEMI and NSTEMI or with regard to 1-year postdischarge death rates (1.9% vs 2.8%). The present results demonstrate recent decreases in the proportion of relatively young patients diagnosed with an initial STEMI. Patients with STEMI and NSTEMI had similar in-hospital outcomes and long-term survival. Trends in these and other important outcomes warrant continued monitoring.

Polypectomy is adequate treatment for adenoma-like dysplastic lesions (DALMs) in Crohn's disease.

BACKGROUND: The purpose of this study was to reevaluate the clinical and pathologic features and outcomes in patients with Crohn's disease with an adenoma-like dysplasia-associated lesion or mass (DALMs) to determine if polypectomy is adequate treatment. METHODS: The clinical, endoscopic and pathologic features, and outcomes of 50 patients with Crohn's disease, each with ≥1 adenoma-like DALM were evaluated. The median length of follow-up was 39 months (range: 0.5-156 months). RESULTS: Of the 50 patients with Crohn's disease (male to female ratio, 30:20; median age: 53 years; median duration of disease: 83 months), 11 had ileal disease, 26 had colonic disease, and 13 had both ileal and colonic disease. Approximately 43% of polyps occurred within areas of previous or concurrent colitis, whereas 57% occurred in areas not previously involved by colitis. Most polyps had tubular architecture and contained low-grade dysplasia. Of the patients who had polypectomy followed by surveillance, 45% developed new adenoma-like DALMs, but none developed flat dysplasia and only 1 had adenocarcinoma at the time of resection, which was within 3 months of polypectomy. There were no differences in the clinical or pathologic features or outcomes in patients who had adenoma-like DALMs within versus outside areas of previous or concurrent colitis, except that the former showed a higher risk of developing new polyps within areas of colitis and near the site of the original polyp compared with the latter. CONCLUSIONS: Patients with Crohn's disease who develop an adenoma-like DALM, regardless of its location in relationship to previous or concurrent colitis, may be treated safely with polypectomy and continued surveillance.

Plasminogen activator inhibitor-1 is increased in colonic epithelial cells from patients with colitis-associated cancer.

BACKGROUND: Patients with long-term ulcerative colitis are at risk for developing colorectal cancer. METHODS: Archival formalin-fixed paraffin-embedded tissue from ulcerative colitis patients who underwent a colectomy for high-grade dysplasia or carcinoma was examined for changes in expression of plasminogen activator inhibitor-1 (PAI-1) as well as other mediators of inflammation-associated cancer. Epithelia from areas of colons that showed histologic evidence of carcinoma, high-grade dysplasia, and epithelia that were not dysplastic or malignant but did contain evidence of prior inflammation (quiescent colitis) was microdissected using laser capture microscopy. mRNA was extracted from the microdissected tissue and PCR array analysis was performed. To extend our findings, PAI-1 protein levels were determined using immunohistochemistry. RESULTS: The mRNA expression of PAI-1 is increased 6-fold (p=0.02) when comparing the carcinoma group to the quiescent colitis group; increases were also observed in NFKB2, REL, SRC, and VEGFA. The protein levels of PAI-1 are increased by 50% (p<0.001) in high-grade dysplasia and by 60% (p<0.001) in carcinoma when compared to the quiescent colitis group. CONCLUSIONS: The increase in PAI-1 in high-grade dysplasia and carcinoma suggests a functional role for PAI-1 in malignant transformation in colitis-associated cancer. PAI-1 could also prove a useful diagnostic marker to identify patients at risk for neoplasia and it may be a useful therapeutic target to treat colitis-associated cancer.

ASCA IgG and CBir antibodies are associated with the development of Crohn's disease and fistulae following ileal pouch-anal anastomosis.

BACKGROUND: For ulcerative colitis (UC) patients undergoing ileal pouch-anal anastomosis (IPAA), postoperative complications include chronic pouchitis and development of Crohn's disease (CD) of the pouch. AIMS: The aim of this study was to determine if serologic markers obtained postoperatively are associated with the development of complications in UC patients after IPAA. METHODS: A retrospective chart review was conducted of UC patients with IPAA were tested for expression of serologic markers. Complications abstracted from medical records included postoperative fistula, CD of the pouch, chronic pouchitis, and diversion or excision of the pouch. RESULTS: 142 patients were enrolled, 44 of whom developed complications. Positive serologic profiles for ASCA IgG and anti-CBir1 markers were found to be associated with the development of any complication, (P = 0.017 and P = 0.002, respectively). A positive anti-CBir1 test was also found to be associated with CD of the pouch and/or fistula formation (P < 0.001). Similarly, both ASCA IgG and anti-CBir1 titers were significantly associated with postoperative IPAA complications (P = 0.034 and P = 0.001, respectively), and anti-CBir1 titers were associated with CD of the pouch and/or fistula formation (P < 0.001). Complications developed after a median follow-up of 216 months (range 1-264). CONCLUSIONS: ASCA IgG and anti-CBir1 markers were associated with the development of complications after IPAA, specifically fistulae and/or CD of the pouch. The ability to identify patients at high risk for adverse outcomes may allow for early aggressive therapy, which may decrease the rate of pouch failure. A prospective study of patients with preoperative serology is ongoing.

Truncated neurokinin-1 receptor is increased in colonic epithelial cells from patients with colitis-associated cancer.

Patients with chronic ulcerative colitis (UC) are at high risk for developing colorectal cancer. In this study, archival formalin-fixed paraffin-embedded colonic tissue from patients with UC who developed carcinoma (CA) or high-grade dysplasia (HGD) was examined for changes in expression of the proinflammatory and mitogenic neurokinin-1 receptor (NK-1R). Laser capture microscopy was used to microdissect epithelia from areas of colons that showed histologic evidence of CA, HGD, and epithelia that were not dysplastic or cancerous but did contain evidence of prior inflammation (quiescent colitis). mRNA was extracted from the dissected tissue, and PCR array analysis was performed on extracted mRNA. Two antibodies were necessary to separately estimate the protein levels of the truncated (tr-NK-1R) and full-length (fl-NK-1R) receptors by immunohistochemistry. mRNA expression of tr-NK-1R increased 14-fold (P = 0.02) when comparing the HGD and CA groups. In contrast, the fl-NK-1R transcript showed no significant differences among groups. The protein levels of the total NK-1R increased by 40% (P = 0.02) in HGD and 80% (P = 0.0007) in CA compared with quiescent colitis. There were no significant changes in protein levels of the fl-NK-1R. We conclude that the increase in total NK-1R protein in HGD and CA is attributable to an increase in tr-NK-1R, suggesting there may be a functional role for tr-NK-1R in malignant transformation in colitis-associated cancer. The tr-NK-1R could prove useful as a diagnostic marker to identify patients at risk for neoplasia and may serve as a useful therapeutic target in the treatment of colitis-associated cancer.

Vaccinating the inflammatory bowel disease patient: deficiencies in gastroenterologists knowledge.

BACKGROUND: Current therapy for inflammatory bowel disease (IBD) patients often involves agents that suppress the immune system, placing patients at an increased risk for developing infections, of which several are potentially vaccine preventable. Many IBD patients are not being vaccinated appropriately. The aims of this study were to assess gastroenterologist's knowledge regarding vaccinating the IBD patient, eliciting the barriers that prevent vaccinations, and defining the gastroenterologist's role in vaccinations. METHODS: One thousand gastroenterologists, randomly selected from the membership of the American College of Gastroenterology, were asked to complete a 19 question electronic survey regarding the suitable vaccines for the immunocompetent and immunosuppressed IBD patient and the barriers to recommending the vaccines. The perceived role of the gastroenterologist versus the primary care physician (PCP) was also assessed. RESULTS: In all, 108 responses were analyzed; 68 (62%) gastroenterologists managed 40+ IBD patients, with 65 (52%) asking their patients about immunization history most or all of the time. The majority believed that the PCP should determine which vaccinations to give (64%) and to administer the vaccines (83%). Overall, 66%-88% of gastroenterologists correctly recommended the inactivated vaccines for their IBD patients not on immunosuppressive therapies while 20%-30% incorrectly recommended administering the live vaccines to their immunosuppressed patients. CONCLUSIONS: Gastroenterologist knowledge of the appropriate immunizations to recommend to the IBD patient is poor and may be the primary reason why the majority of gastroenterologists believe that the PCP should be responsible for vaccinations. Educational programs on vaccinations directed to gastroenterologists who prescribe immunosuppressive agents are needed.

Preoperative infliximab is not associated with an increased risk of short-term postoperative complications after restorative proctocolectomy and ileal pouch-anal anastomosis.

INTRODUCTION: Considerable controversy exists over whether the preoperative use of infliximab (IFX) for refractory ulcerative colitis (UC) increases the risk for surgical complications after restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA). The aim of this study was to assess the association between preoperative IFX use and short-term surgical complications in a single-surgeon cohort at a tertiary care academic center. METHODS: UC patients who underwent IPAA from September 2005 through May 2009 were retrospectively identified. Twenty-nine patients treated with IFX within 12 weeks of surgery and 52 non-IFX control subjects were identified. Short-term postoperative outcomes were compared between groups occurring within 30 days of loop ileostomy closure. RESULTS: Patients were similar with respect to demographics, co-morbidities, rate of emergency surgery, hand-sewn anastomosis, and preoperative use of cyclosporine, azathioprine, and high-dose steroids. IFX patients were more likely to have received a laparoscopic hand-assisted IPAA, low-, medium-, and any-dose steroids, 6-mercaptopurine (6-MP), methotrexate, and to have failed medical therapy. There was no short-term mortality. Overall postoperative and infectious complications were similar between IFX and non-IFX groups. Multivariate regression models revealed no independent predictors for postoperative complications when including IFX [odds ratio (OR) 0.78, p = 0.67], laparoscopic hand-assisted IPAA, 6-MP, methotrexate, steroids, failure of medical therapy, and body mass index. CONCLUSIONS: Preoperative IFX use was not associated with an increased risk of short-term postoperative complications after IPAA.

Systemic Toll-like receptor ligands modify B-cell responses in human inflammatory bowel disease.

BACKGROUND: Bacteria have a central, although poorly understood, role in inflammatory bowel disease (IBD). Host-bacteria interactions primarily take place in the gastrointestinal tract, but cells may also encounter translocated bacteria in the bloodstream. IBD is associated with activated, circulating Toll-like receptor (TLR)2 and TLR4-expressing B cells suggesting that blood-borne microbial TLR ligands modulate B cell responses. METHODS: Serum levels of lipopolysaccharide (LPS)/endotoxin and high mobility group box 1 (HMGB1), an endogenous TLR ligand, were quantified in Crohn's disease (CD) and ulcerative colitis (UC). Responses of purified B cells to LPS and HMGB1 were correlated with levels of systemic TLR ligands and clinical parameters of disease. RESULTS: While IBD patients have increased levels of blood LPS, the net effect of endotoxemia has unexpected characteristics illustrating that LPS has both pro- and antiinflammatory roles through TLR4+ B cells. Experimental treatment of B cells demonstrates that the antiinflammatory effect of LPS is due to its hypo-acylation of lipid A suggesting an increased prevalence of systemic, hypo-acylated LPS in CD. In contrast, high levels of LPS are associated with disease activity in UC. HMGB1 activates B cells through TLR2 and CD36. Serum levels of HMGB1 correlate with spontaneous IL-8 production by B cells suggesting that blood-borne TLR2 ligands increase B-cell activation in vivo. CONCLUSIONS: Systemic TLR ligands modulate B cells towards either proinflammatory or antiinflammatory activity depending on the predominant ligand(s). Further, the circulating B cell may represent an important proxy for quantifying the LPS lipid A acylation burden in patients with IBD.

Variation in the detection of serrated polyps in an average risk colorectal cancer screening cohort.

OBJECTIVES: Serrated polyps are precursors in an alternative pathway to colon cancer. These polyps are frequently sessile or flat, located in the proximal colon, and may be overlooked during colonoscopy. Histological criteria to classify these polyps have only recently been described. This study assessed the variation of serrated polyp detection among endoscopists and pathologists in an average risk-screening cohort and trends in detection over time. METHODS: Endoscopy and pathology reports were reviewed from all average risk-screening colonoscopies at an urban academic medical center from 2006 through 2008. Polyps were classified as adenoma (tubular, tubulovillous, or villous), serrated polyp (hyperplastic polyp (HP), sessile serrated adenoma (SSA), or dysplastic serrated polyp (DSP)), adenocarcinoma, or other. Differences in polyp detection among endoscopists and pathologists were tested with χ(2)-tests. Potential predictors of polyp detection were modeled with Poisson regression. RESULTS: Included in the study were 4,335 polyps from 7,192 colonoscopies. Detection prevalence (patients with at least one polyp per 100 colonoscopies) was 22.2 for adenomas, 11.7 for HP, 0.6 for SSA, and 0.2 for DSP. Detection prevalence of proximal SSAs increased from 0.2 in 2006 to 4.4 in 2008 (P<0.001). Detection prevalences among endoscopists differed significantly for adenomas, HP, and SSA. Classification rates among pathologists differed significantly for HP and SSA, but not for adenoma or DSP. On multivariate analysis, endoscopist was a significant predictor of adenoma, HP, and SSA. Pathologist was a significant predictor of HP, SSA, and DSP, but not adenoma. CONCLUSIONS: This study describes the detection of colorectal polyps in an average risk-screening cohort at an urban academic medical center. Detection of proximal SSAs increased during the study period. Detection of adenoma, HP, and SSA differed significantly by endoscopist. Classification of HP and SSA differed significantly by pathologist. Endoscopy and pathology practices should consider educational interventions to improve serrated polyp detection and standardize classification.