Nimisha K. Parekh

Elevated troponin I levels in acute liver failure: Is myocardial injury an integral part of acute liver failure?

Although rare instances of cardiac injury or arrhythmias have been reported in acute liver failure (ALF), overall, the heart is considered to be spared in this condition. Troponin I, a sensitive and specific marker of myocardial injury, may be elevated in patients with sepsis and acute stroke without underlying acute coronary syndrome, indicating unrecognized cardiac injury in these settings. We sought to determine whether subclinical cardiac injury might also occur in acute liver failure. Serum troponin I levels were measured in 187 patients enrolled in the US Acute Liver Failure Study Group registry, and correlated with clinical variables and outcomes. Diagnoses were representative of the larger group of >1000 patients thus far enrolled and included 80 with acetaminophen‐related injury, 26 with viral hepatitis, 19 with ischemic injury, and 62 others. Overall, 74% of patients had elevated troponin I levels (>0.1 ng/ml). Patients with elevated troponin I levels were more likely to have advanced hepatic coma (grades III or IV) or to die (for troponin I levels >0.1 ng/ml, odds ratio 3.88 and 4.69 for advanced coma or death, respectively). Conclusion: In acute liver failure, subclinical myocardial injury appears to occur more commonly than has been recognized, and its pathogenesis in the context of acute liver failure is unclear. Elevated troponin levels are associated with a significant increase in morbidity and mortality. Measurement of troponin I levels may be helpful in patients with acute liver failure, to detect unrecognized myocardial damage and as a marker of unfavorable outcome. (HEPATOLOGY 2007;45:1489–1495.)

1041 Intravenous Cyclosporin in Severe Steroid-Refractory Ulcerative Colitis: Long-Term Follow-Up

OBJECTIVE:Intravenous (IV) cyclosporin (CSA) is an alternative to surgery for patients (pts) with severe ulcerative colitis (UC). We previously published open-label 5-year data, and now present long-term follow-up on the same pts. METHODS:The original 42 pts with IV steroid-refractory severe UC treated with IV CSA from 1991 to 1995 were identified using the University of Chicago IBD registry. Additional information on clinical course, medication use, surgeries and adverse events were collected from electronic and paper charts. Pts who initially received CSA but eventually went to colectomy were referred to as “surgical” pts; those who have avoided colectomy were referred to as “non-surgical” pts. RESULTS:The mean duration of IV CSA was 10.3 days (+/5.4), at a mean CSA level of 379 (+/-126) ng/ mL (HLPC). Initial response was seen in 36 of 42 pts (86%); 11 patients subsequently underwent colectomy at a median of 18 weeks (range 3-79). Twenty-five (60%) of the original 42 pts avoided colectomy in the short-term at a mean follow-up of 23 months. Nineteen of these 25 (76%) pts have continued to avoid colectomy at a median of 81 months. Overall, 45% of the initial pts remained colectomy-free at a mean 75 months (+/44.7). Surgery was avoided in 56% of pts receiving 6-mercaptopurine (6MP) or azathioprine (aza) vs. 27% of those who did not (p=0.014). The rate of 6MP/aza use was higher in nonsurgical pts (79% vs. 40%, p= 0.08). Life analysis predicted 15.5 year “noncolectomy survival” rates of 39% overall; rates were highest in those with 6MP/aza (49% vs. 17%, p= 0.036; Figure 1). Six of 8 pts who repeated IV CSA subsequently underwent colectomy at a median 8.3 months (range 0.1-37) after last IV CSA, despite 6MP/aza in all (mean duration 38.27 months +/31.05). CONCLUSION:Intravenous cyclosporin was successful in avoiding surgery in 45% of severe, IV steroidrefractory UC pts; predicted long-term success is highest in those who received 6MP/aza.

National Trends and In-Hospital Outcomes of Adult Patients With Inflammatory Bowel Disease Receiving Parenteral Nutrition Support

BACKGROUND Patients with inflammatory bowel disease (IBD), including Crohns disease (CD) and ulcerative colitis (UC), are susceptible to protein-calorie malnutrition secondary to decreased oral intake, malabsorption, and increased metabolic expenditure. In this study, we seek to assess the national frequencies of parenteral nutrition (PN) use among hospitalized patients with IBD and to determine their in-hospital outcomes. METHODS We analyzed the Nationwide Inpatient Sample from 1988-2006 to determine the frequency of PN usage among patients with UC or CD and to determine their in-hospital outcomes. A multivariate analysis was performed to identify factors predictive of increased inpatient mortality in this population. RESULTS From 1988-2006, the annual incidence of PN use among hospitalized patients with CD was 4.29 per 100,000 and among those with UC was 3.80 per 100,000, with trends being relatively stable through the indexed period. The mean length of hospitalization among patients with UC receiving PN was longer compared with patients with CD. Factors predictive of an increased risk for mortality include the following: age >50 years, acute kidney injury, hospital-acquired pneumonia, Clostridium difficile colitis, prolonged postoperative ileus requiring PN use, pulmonary embolism, malnutrition, and patients with UC relative to CD. CONCLUSION Traditionally, patients with CD are at a higher risk for developing malnutrition than patients with UC; however, there is a 2-fold higher risk for inpatient mortality and a longer length of hospitalization among patients with UC compared with those with CD. This pattern suggests that the use of PN, particularly among patients with UC, serves as a surrogate marker of higher disease acuity and severity.

Coping Strategies Used by Adult Patients with Inflammatory Bowel Disease.

Objectives Symptoms of and treatments for inflammatory bowel disease (IBD) have a significant impact on patients’ quality of life (QOL) and result in an increased prevalence of depression and anxiety disorders. Little is known about the type of coping strategies used by adult patients with IBD to better cope with their chronic illness, however. The objectives of this study were to identify the types of coping styles and their impact on the QOL of patients with IBD. Methods The first 150 consecutive participants with IBD were recruited at five major tertiary hospitals and given an anonymous survey consisting of demographic information, the Jalowiec Coping Scale, and the Shortened Inflammatory Bowel Disease Questionnaire. Results The cohort was 51.3% men and included 150 participants with a mean age of 39.3 years. The primary coping mechanisms used were confrontive (46.7%), evasiveness (30.0%), optimistic (18.7%), and fatalistic (4.6%) coping. Participants rated confrontive (62.0%), optimistic (26.6%), and evasive (11.4%) coping styles as the most effective. Those who reported an increased frequency of flares scored lower on QOL (P <0.05) and more often used evasive and fatalistic coping styles (P < 0.05) compared with other coping strategies; however, after controlling for disease activity, QOL was significantly better for those who primarily used adaptive coping styles compared with those who used maladaptive styles (P <0.001). Conclusions We demonstrated that confrontive, evasive, and optimistic styles of coping are most widely used among patients with IBD. Despite controlling for disease activity, we demonstrated that those who used adaptive coping styles had a higher QOL compared with those who used maladapative coping styles. Future research on coping is warranted to assess coping styles on therapeutic compliance and disease perception.

Human placenta-derived cells (PDA-001) for the treatment of moderate-to-severe Crohn's disease: A phase 1b/2a study

Background:PDA-001 (cenplacel-L), a preparation of placenta-derived mesenchymal-like adherent cells with immunomodulatory effects, previously demonstrated safety and tolerability in an open-label Crohns disease (CD) study. The current phase 1b/2a study evaluated the safety and efficacy of PDA-001 in subjects with moderate-to-severe CD. Methods:Subjects had active inflammation on colonoscopy or elevated fecal calprotectin and inadequate response to conventional therapy. Concomitant therapy with stable doses of immunomodulators and/or biologics was permitted. Subjects received 8 units of PDA-001 (1.5 × 108 cells per unit) in the phase 1b open-label study. In the phase 2a double-blind study, subjects were randomly assigned placebo, 1 unit, or 4 units of PDA-001 (2 infusions 1 wk apart). The primary endpoint was induction of clinical response (≥100 points and/or 25% decrease in Crohns Disease Activity Index) at 4 and 6 weeks. Results:Fifty subjects were enrolled (safety analysis, 50 subjects; efficacy analysis, 48 subjects). Four subjects received 8 units of PDA-001 (phase 1b study); 46 subjects were subsequently randomized to 1 or 4 units of PDA-001 or placebo (phase 2a study). The primary endpoint was achieved in 10/28 (36%) of PDA-001 subjects compared with placebo (0%, P = 0.026). Clinical remission was achieved in 4/28 (14%) of PDA-001 subjects compared with placebo (0%, P = 0.3). One treatment-related serious adverse event occurred (systemic hypersensitivity reaction at 8 units). In the phase 2a study, serious adverse events occurred in 9/28 (32%) of PDA-001 subjects and 1/16 (7%) of placebo subjects. Conclusions:A 2-infusion regimen of PDA-001 induced clinical response in subjects with moderate-to-severe CD. Additional studies are warranted.

Case of intestinal tuberculosis mimicking Crohn's disease.

Summary Background: Intestinal tuberculosis can closely mimic Crohn’s disease and colon cancer. Presented here is a case of intestinal tuberculosis that closely mimicked both. Case Report: A 23 year old Hispanic female presented with several months of weight loss, recurrent fever, and emesis. The patient did not have pulmonary symptoms or radiographic evidence of tuberculosis. Colonoscopy evaluation with biopsy of the affected bowel segments were thought to be consistent with either colon cancer or Crohn’s Disease. Acid fast bacilli staining and histological analysis did not display evidence of tuberculosis on two separate occasions. The patient developed colonic obstruction acutely during the course of treatment requiring resection of the affected bowel segment. Acid fast staining of the resected lymph nodes was positive and submucosal caseating granulomas were identified histologically, consistent with intestinal tuberculosis. Conclusions: Intestinal tuberculosis remains a diagnostic challenge. Consideration of the disease should be maintained in equivocal cases.

Effects of caregiver burden on quality of life and coping strategies utilized by caregivers of adult patients with inflammatory bowel disease

Background While previous studies have evaluated caregivers’ quality of life (QOL), burnout, and stress amongst across a variety of chronic illnesses, few such studies have been related to inflammatory bowel disease (IBD). Methods Caregivers accompanying adult patients with IBD at 6 tertiary centers were enrolled. They completed self-administered surveys related to QOL and burden, including the QOL scale, Zarit Burden Interview (ZBI), and Brief COPE. Results Of the 200 consecutive caregivers asked to participate, 162 (81.0%) enrolled and completed the survey. A total of 43.8% caregivers reported having a high level of burden as measured by the ZBI. Factors predictive of a high burden included female gender, younger age of caregiver, household income <

Patterns of Internet use by gastroenterologists in the management and education of patients with inflammatory bowel disease.

30,000, having more than one dependent in the household, caring for a patient with active disease and higher disease severity, and a personal history of psychiatric illness. Over one third of the caregivers reported a maladaptive coping pattern. The caregiver factors predictive of maladaptive coping skills included male gender, lack of involvement in a support group, a personal history of psychiatric illness, and living in a different household from the patient. Conclusions A large proportion of caregivers of IBD patients experience a high level of caregiver burden and reduced QOL. Participation in religious/spiritual activities and support groups appeared to reduce perceived caregiver burden and improve QOL. This study suggests there is an unmet need to address the caregiver burden of adult IBD patients.

Evaluation of an ongoing psychoeducational inflammatory bowel disease support group in an adult outpatient setting.

Aims To define the patterns of Internet use among physicians who treat inflammatory bowel disease (IBD) and physicians’ perceptions of their patients’ Internet use. Methods An online survey about physician and patient use of the Internet was created and e-mailed to gastroenterologists nationwide. Surveys were distributed and collected via an online database and a subsequent statistical analysis was performed. Results Of the 1000 e-mail invitations sent to practicing gastroenterologists in the United States, 223 participants (22.3%) completed the survey. A total of 183 (82.1%) physicians reported using an Internet-based reference to assist them in deriving management strategies for their patients with IBD, with the most commonly utilized resource being UpToDate followed by PubMed and the Crohn’s and Colitis Foundation of America Web site. Although nearly 80% of gastroenterologists believed that using the Internet helped them facilitate clinical discussions, 183 participants (82.1%) believed that inaccurate information found online could sometimes result in increased clinic time because physicians must spend more time dispelling misleading information. Conclusions Despite a study design biased toward selecting gastroenterologists who commonly used the Internet, we demonstrated that only 60% of the providers routinely refer their patients to the Internet. This underscores the fact that it is important to have a centralized “physician-certified” online resource to which physicians could readily refer their patients to navigate through various disease-specific resources without concern that their patients are receiving unreliable or misleading information.

Strategies for overcoming anti-tumor necrosis factor drug antibodies in inflammatory bowel disease: Case series and review of literature

Previous studies assessing efficacy of support groups for patients with inflammatory bowel disease showed mixed results in terms of attendance and overall effectiveness. In this study, researchers evaluated the use of an ongoing open psychoeducational support group for adult patients with inflammatory bowel disease in an outpatient tertiary setting. The sample consisted of 18 adults who have attended more than 2 meetings of the support group. Topics addressed in the support group include complementary medicine, diet and nutrition, the psychological impact of inflammatory bowel disease, medication and side effects, and insurance/disability. Participants were asked to complete the Client Satisfaction Questionnaire, Multidimensional Support Scale, 11 general demographic questions, and a brief open-ended qualitative questionnaire developed by the researchers. Results demonstrated that participants reported very high satisfaction with the support group and rated the adequacy of peer support from others with inflammatory bowel disease higher than support from family/friends and professionals. A majority of group members reported joining the group for mutual support and education; this expectation was met through the psychoeducational structure of the group. This study demonstrates the potential for success of an ongoing psychoeducational inflammatory bowel disease support group for adult patients and their caregivers.