Poor Outcomes in Clostridium difficile Enteritis is Associated With Low Vitamin D Levels

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1 Poor Outcomes in Clostridium difficile Enteritis is Associated With Low Vitamin D Levels Wallace Wang, M.D., Sondra Gray, M.D., Cristina Sison, Ph.D., Sushma Arramraju, M.D., Bijo K. John, M.D., Syed Hussain, M.D., Sang Kim, M.D., Preeti Mehta, M.D., Moshe Rubin, M.D. Purpose: The incidence, recurrence, and all-cause mortality rate for Clostridium difficile-associated diarrhea (CDAD) has increased markedly over the past 10 years despite treatment. Low levels of vitamin D are known to impair immune responses to infection and are associated with increased mortality. In a prior study, we found that patients with normal vitamin D levels had higher resolution rates of CDAD than patients with low vitamin D levels. In this study, we compared the role of patient comorbidity as measured by the Charlson Comorbidity Index to vitamin D levels in our cohort of patients, to ascertain whether vitamin D levels were an independent variable affecting the outcome of CDAD or simply a marker of overall comorbidity. Methods: In a prospective cohort study, 62 patients hospitalized at New York Hospital Queens between 2008 and 2009 with manifestations of CDAD and a positive Clostridium difficile toxin assay were studied. All patients received standard antibiotic treatment (metronidazole and/or vancomycin). Vitamin D levels above 21 ng/ml were considered normal. Their status at 30-day follow-up was classified as resolved or recurred/expired. Patients' Charlson Comorbidity Index (CCI) was calculated using their medical history. Logistic regression analysis of variables including vitamin D (total 25-hydroxyvitamin D) level, CCI, age, gender, white blood cell count (WBC), albumin level, and type of residence (nursing facility vs. private home) were then performed. Results: There were 62 patients (43.6% males, 56.4% females) with CDAD in the study. The mean age of subjects was 75 ± 17 years. At 30-day follow-up, 28 (45.2%) expired, 10 (16.1%) had persistent or recurrent diarrhea and 24 (38.7%) resolved. In total, 38 (61.3%) were not resolved. There was no significant association between 30-day resolution status and CCI, gender, WBC, albumin level, or type of residence. Two variables were found to be independent predictors of resolution of CDAD: normal vitamin D levels (p = 0.028) and age < 70 years old (p = 0.024). Subjects with low vitamin D levels were 4.75 times more likely to fail to resolve CDAD than subjects with normal levels of vitamin D. Conclusions: In this study, vitamin D level and age are independent predictors of CDAD resolution in hospitalized patients. Low vitamin D levels and age > 70 years old are associated with increased likelihood of recurrence. Low vitamin D levels are not a marker of co-morbidity or advanced age.

2 Cognitive Changes After Surgery in the Elderly: Does Minimally Invasive Surgery Influence the Incidence of Postoperative Cognitive Changes, Compared to Open Colon Surgery? C. Tan, M.D., 1 F. Kawai, M.D., 1 C. Pan, M.D., 1 J. Ng, 1 S. Cohen, M.D., 2 J. Turner, M.D., 2 M. Chorost, M.D. 1 Background: delirium is a growing concern among the elderly population. It is associated with an increase in morbidity, mortality, increase in hospital stay, and a significant decline in functional status upon discharge. With advances in surgical techniques, laparoscopic procedures are increasingly used as an option for different colon pathologies. However, data regarding significant differences in morbidity, mortality, and cognitive changes associated with postoperative delirium in patients who have undergone laparoscopic, as compared to open colon resection, are not well established. Objective: To compare any significant occurrence of post-operative delirium in laparoscopic versus open colon surgery in the elderly population group. Methods: A prospective non-randomized clinical trial was done on New York Hospital Queens surgical ambulatory unit on non-demented patients aged 65 and above, who were deemed candidates for colon surgery. A pre- and post-operative CANTAB testing was done on these patients. CANTAB is a computer-based cognitive assessment system consisting of a battery of neuropsychological tests, administered to subjects using a touch screen computer. CANTAB examines various areas of cognitive function including general memory and learning, working memory and executive function, visual memory, attention and reaction time, semantic/verbal memory, and decision making/response control. Postoperative testing was done on Day 3. Data from Pre and post-operative Paired Associated Learning (PAL) and Spatial Working Memory (SWM) portion of the CANTAB battery of tests were extracted for analysis to determine the presence of delirium after surgery as evidenced by any worsening of individual scores. A Fisher's exact test was done to compare the presence or absence of delirium on laparoscopic versus open surgical group. Pre- and post-operative blood testing was done to determine changes in inflammatory markers (including IL-10, IL-6, IL-8, MCP-1 and TGF-b). blood testing was done during preoperative evaluation or immediately prior to surgery. blood testing was done within 3 days after surgery. Results: A total of 44 patients were enrolled in the study. 26 patients underwent laparoscopic and 18 underwent open colon surgery. Of the 44 patients, 3 of the laparoscopic group and 3 in the open surgery group did not perform the PAL testing. One in laparoscopic group did not perform the SWM testing. In the PAL testing, 12 out of 23 (52.2%) in the laparoscopic group had worsened scores post operatively. In the open surgery group, 7 of the 15 (46.7%) had worsened scores 1. New York Hospital Queens, Flushing, NY 2. NYU Langone Medical Center, New York, NY

3 post operatively. Fisher's exact test comparing laparoscopic versus open surgery group showed no significant difference (P = ) on post-operative delirium. In the SWM testing, 14 out of 25 (56%) in the laparoscopic group had worsened scores post-operatively. In the open surgery group, 6 out of 18 (33.3%) had worsened scores post operatively. Fisher's exact test comparing laparoscopic versus open surgery group showed no significant difference (P = ) on post-operative delirium (Figure 1). Eleven subjects in the laparoscopic group and 7 in the open surgical group had pre- and post-operative blood testing. Results of pre- and postoperatively inflammatory marker testing and the respective maximum normal values are summarized in Table 1. Conclusion: Compared to open colon surgery, laparoscopic colon surgery did not appear to influence the incidence of post-operative cognitive changes. In the open colon surgery group, there were higher increases in post-operative inflammatory markers, but its significance is unclear. Figure 1. Summary of Findings TOTAL OF 44 PATIENTS ENROLLED LAPAROSCOPIC GROUP (26) OPEN SURGICAL GROUP (18) SWM TESTING (25) PAL TESTING (23) PAL TESTING (15) SWM TESTING (18) 14 OUT OF 25 HAS DELIRIUM (56%) 12 OUT OF 23 HAS DELIRIUM (52.17%) 7 OUT OF 15 HAS DELIRIUM (46.66%) 6 OUT OF 18 HAS DELIRIUM (22.22%) NO DIFFERENCE P VALUE NO DIFFERENCE P VALUE

4 Table 1. Pre- and Post-Operative Inflammatory Markers in Laparoscopic and Open Colon Surgery Inflammatory Markers IL 10 IL 6 IL 8 MCP 1 TGF-alpha TGF-b Laparoscopic N = 11 (Mean/SD) 2.31 / / / / / / / / / / / / Open N = 7 (Mean/SD) 1.41 / / / / / / / / / / / / Max Normal Values (pg/ml)

5 Glycemic Control in Patients with Type 2 Diabetes Mellitus Transitioning From Acute Care Hospital to the Nursing Home M. Oprea, M.D., F. Kawai, M.D., D. Lorber, M.D., S. Pollack, Ph.D., C. Pan, M.D. Background: Studies have found that ~30% of all nursing home (NH) patients have diabetes mellitus (DM). Glycemic control is highly individualized in elderly, especially frail, NH patients and there are no standard guidelines for this population. In general, glycemic control is not optimally managed in NHs, leading to an increased number of hospitalizations (admissions and readmissions) related to DM associated complications (i.e., increased infection risk), and as a result, becoming a burden for the healthcare system. Gaps in transition of care to and from hospital and NH contribute to poor management of DM. In our affiliated NH, we observe a similar phenomenon. It is unclear whether poor glycemic control started at NH or during hospital stay, when patients were acutely ill. Objective: To investigate adequacy of glycemic control in NH patients with DM across health care settings, by comparing their average finger-stick blood sugar (FSBGs) values in 3 different settings: at NH prior to hospitalization, during hospital stay, and upon return to NH. Methods: This is a retrospective analysis of glycemic control in NH patients with type 2 DM transitioning from hospital back to the nursing home. Subjects: DM patients who are residents of Silvercrest Nursing and Rehabilitation Center (SCNHR) and who have been admitted to New York Hospital Queens (NYHQ) during a two-year period from 08/01/2010 to 08/01/2012. Demographic and clinical data were collected, including FSBG values at baseline (from day 14 to 28 preadmission), during the last 2 days of hospital stay (when patients are generally stabilized), and upon return to NH (days post discharge). Average FSBG values from morning (AM) and evening (PM) data were obtained across all settings to detect potential diurnal differences. Because some patients had multiple admissions and readmissions in close sequence, they did not have the required 14-day baseline or stable period; these patients were excluded from the study. Using a mixed model for repeated measures analysis of variance, we analyzed variability of FSBG control in the 3 settings as follows: a) NH pre-hospital vs. NH post-hospital; b) NH pre-hospital vs. hospital; and c) NH post-hospital vs. hospital. We compared overall FSBG average values as well as AM vs. PM values. Results: During the study period, 98 DM patients were identified but only 52 patients were included (after exclusions). The patients' average age was 72.2 years (range 45-96yo); 20 were female and 32 were male. In terms of race/ethnicity, 29 (55%) were African American, 17 (33%) Caucasian, 4 (8%) Hispanic, and 2 (4%) Asian. We found that the average pre-hospital FSBG values were comparable to the average post-hospital FSBG values (Table 1). There were very few episodes of hypoglycemia in all settings. Table 2 shows that hospital average FSBG values were significantly lower than NH FSBG values (both preand post-hospitalization) (P = 0.033). More significant differences were found in PM values compared to AM values (P = 0.008). 5

6 Conclusion: Our findings showed that NH patients with DM have poorer glycemic control at the NH compared to when they were hospitalized. This is true both when patients are at their baseline, prior to hospitalization, and post discharge from the hospital. This implies that there may be gaps in management adherence during transitions of care from hospital to NH. Possible explanations might include: a) inaccurate discharge summaries and medication lists; b) fear of NH physicians to adequately control DM for fear of hypoglycemic episodes; c) difference in diet at different settings; d) lack of medication availability at NH. There appears to be room for improved glycemic control in the NH setting. Future studies can examine more specific factors that may contribute to inadequate glycemic control in NH patients with DM.

7 Colonic Lesions Found During Retrograde Double Balloon Enteroscopy for Obscure Bleeding Following a Negative Colonoscopy Masud Habibullah, M.D., David Tenembaum, M.D., Jose Najul, M.D., Moshe Rubin, M.D. Background: Evaluation of the distal small bowel with Double Balloon Enteroscopy (DBE) requires passage through the colon and intubation of the ileum. Patients referred for obscure bleeding have undergone routine colonoscopy with reportedly negative results. There is limited data on colonic findings during these retrograde DBE procedures. Objectives: To evaluate the detection rate of colonic vascular ectasia, ulcers and polyps at retrograde DBE. Methods: We performed a retrospective cohort study on 134 sequential patients undergoing retrograde DBE. All patients had a negative colonoscopy (excluding diverticulosis and hemorrhoids) and were referred for obscure bleeding. The median days between colonoscopy and DBE were days. The detection rate of vascular ectasia, ulcers and polyps were calculated. Results: 134 patients, ages (mean age) were evaluated. There were 56 women (41.18%) with a median age of 65.5 and 78 men (58.82%) with a median age of DBE detected colonic lesions in 36 patients (28.36%) overall. Of those patients, 28 (20.90%) had polyps, 13 had vascular ectasias (9.70%) and 2 had ulcers (1.49%). Conclusions: Retrograde DBE following reportedly negative colonoscopy detects a significant number of clinically relevant colonic lesions in patients with obscure bleeding. This data suggests that a careful reexamination of the colon at the time of retrograde DBE may be warranted.

8 Minimally Invasive Temporary Loop Ileostomy for Severe Clostridium difficile Colitis: A Case Report Alexander Ramirez Valderrama, M.D., Soni Chousleb, M.D., Joel A. Ricci, M.D., Pierre F. Saldinger, M.D. Introduction: Clostridium difficile (C. diff) infection is a very frequent cause of morbidity and mortality secondary to antibiotic therapy. About 3% to 10% of patients progress to a toxic, severely complicated colitis. Oral therapy with metronidazole or vancomycin as well as vancomycin enemas remain the mainstay of therapy. Total abdominal colectomy is preserved as a last resource in patients that fail medical therapy. Although this approach has been shown to improve survival, outcomes remain poor with associated mortality rates ranging from 35% to 80%. The emergence of an alternative surgical approach via a minimally invasive temporary loop ileostomy with inter-loop vancomycin infusion has been shown to achieve adequate outcomes with less morbidity and mortality than the more radical total colectomy. More importantly, it allows colon preservation and precludes further morbidity. This minimally invasive procedure is fairly quick and simple under experienced hands. Case report: We present a case of a 69-year-old morbidly obese woman with past medical history of peptic ulcer disease, hypertension, osteoarthritis, suicide attempt, depression and folate deficiency that underwent a left knee arthroplasty for treatment of intractable pain from osteoarthritis. She developed C. diff colitis during the immediate post-operative period. An abdominal/pelvis CT scan revealed severe colitis without perforation (Figures 1, 2). Extensive pseudomembranous colitis with necrotic/ischemic mucosal patches was found on sigmoidoscopy (Figures 3, 4). Despite aggressive IV fluid hydration, bowel rest, and antibiotic therapy with oral and IV metronidazole followed by oral and vancomycin enemas, she progressed into a septic state. She underwent an urgent laparoscopic loop ileostomy with intra-operative colonic lavage without complications. The intra-operative antegrade colonic lavage was performed with polyethylene glycol. This was followed by a 10-day course of antegrade colonic instillation of vancomycin via the ileostomy (500 mg every 8 hours). By postoperative day #3, the patient was alert, awake, and oriented with resolved abdominal pain, decreased leukocytosis, and clinically controlled diarrhea. She was tolerating diet with normal bowel movements and no evidence of leukocytosis by post-operative day #6. A control colonoscopy performed once the therapy was completed revealed almost complete resolution of the C. diff colitis (Figures 5, 6). The patient was discharged to a short-term rehabilitation center on post-operative day #11. She underwent ileostomy reversal 3 months later. Conclusion: Laparoscopic loop ileostomy with intra-operative and post-operative colonic lavage is a viable and effective alternative to total abdominal colectomy in the treatment of severe, complicated C. diff colitis. We reproduced the technique recommended by the University of Pittsburg as a measure to preserve the colon and avoid morbidity and mortality associated with extensive surgery and this relentless disease.

9 Poster Presentation Figure 1. CT Scan With Severe Colitis (Transverse View) Figure 2. CT Scan With Severe Colitis (Coronal View)

10 Figure 3. Colonoscopy With Green Membranes Figure 4. Colonoscopy With Severe C. diff Colitis

11 Figure 5. Colonoscopy Control After Loop Ileostomy Figure 6. Colonoscopy Control With Some Residual Membranes