Building a Successful and Sustainable Academic Career in Gastroenterology.

Starting a new job as an academic gastroenterologist can be very exciting and anxiety provoking at the same time. This is particularly true when the junior faculty member is faced with the unique challenges of practicing medicine in today's world while still attempting to maintain work-life balance and avoid professional burnout. In discussions with several junior colleagues in the specialty over the years, it became clear that there is a relative lack of structured guidance in the literature regarding helping them navigate these turbulent waters in their early careers and setting them up for professional success in the long term. Although there is no guaranteed single formula or recipe for academic success, in this review, we attempt to outline in a stepwise fashion the critical components that we believe are important for junior faculty to consider as they embark on this journey. The significance and value of each step from job selection through promotion and mentorship is discussed in detail based on insights gleaned from experience and the published literature. The importance of citizenship, networking, mission and community-based activities, and work-life balance is highlighted as well. The concept of appreciating and enjoying the "journey," rather than focusing solely on the destination, is emphasized in this paper. We truly believe that these are critical core concepts for junior faculty to grasp that will allow them to derive immense professional gratification in the long run while building successful professional careers along the way.

Nausea: a review of pathophysiology and therapeutics.

The sensation of nausea is a common occurrence with diverse causes and a significant disease burden. Nausea is considered to function as a protective mechanism, warning the organism to avoid potential toxic ingestion. Less adaptive circumstances are also associated with nausea, including post-operative nausea, chemotherapy-induced nausea, and motion sickness. A common definition of nausea identifies the symptom as a precursor to the act of vomiting. The interaction, though present, does not appear to be a simple relationship. Nausea is unfortunately the 'neglected symptom', with current accepted therapy generally directed at improving gastrointestinal motility or acting to relieve emesis. Improved understanding of the pathophysiological basis of nausea has important implications for exploiting novel mechanisms or developing novel therapies for nausea relief.

Patients with irritable bowel syndrome-diarrhea have lower disease-specific quality of life than irritable bowel syndrome-constipation.

AIM: To determine effect of irritable bowel syndrome (IBS) subtype on IBS-specific quality of life (QOL) questionnaire and its subscales. METHODS: We studied IBS patients visiting our functional gastroenterology disorder clinic at a tertiary care center of Unites States. IBS and IBS subtype were diagnosed using Rome-III questionnaire. QOL was assessed using IBS-QOL questionnaire. IBS-QOL assesses quality of life along eight subscales: dysphoria, interference with activities, body image, health worry, food avoidance, social reactions, sexual health, and effect on relationships. IBS-QOL and its subscales were both scored on a range of 0-100 with higher scores suggestive of better QOL. Results of overall IBS-QOL scores and subscale scores are expressed as means with 95%CI. We compared mean IBS-QOL score and its subscales among various IBS-subtypes. Analysis of variance (ANOVA) was used to compare the mean difference between more than two groups after controlling for age and gender. A post-hoc analysis using Bonferroni correction was used only when P value for ANOVA was less than 0.05. RESULTS: Of 542 patients screened, 243 had IBS as per Rome-III criteria. IBS-mixed (IBS-M) was the most common IBS subtype (121 patients, 49.8%) followed by IBS- diarrhea (IBS-D) (56 patients, 23.1%), IBS-constipation (IBS-C) (54 patients, 22.2%) and IBS-unspecified (IBS-U) (12 patients, 4.9%). Overall IBS-QOL scores were significantly different among various IBS-subtypes (P = 0.01). IBS-QOL of patients with IBS-D (61.6, 95%CI: 54.0-69.1) and IBS-M (63.0, 95%CI: 58.1-68.0) was significantly lower than patients with IBS-C (74.5, 95%CI: 66.9-82.1) (P = 0.03 and 0.02 respectively). IBS-D patients scored significantly lower than IBS-C on food avoidance (45.0, 95%CI: 34.8-55.2 vs 61.1, 95%CI: 50.8-71.3, P = 0.04) and interference with activity (59.6, 95%CI: 51.4-67.7 vs 82.3, 95%CI: 74.1-90.6, P < 0.001). IBS-M patients had more interference in their activities (61.6, 95%CI: 56.3-66.9 vs 82.3, 95%CI: 74.1-90.6, P = 0.001) and greater impact on their relationships (73.3, 95%CI: 68.4-78.2 vs 84.7, 95%CI: 77.2-92.2, P = 0.02) than IBS-C patients. Patients with IBS-M also scored significantly lower than IBS-C on food avoidance (47.2, 95%CI: 40.7-53.7 vs 61.1, 95%CI: 50.8-71.3, P = 0.04) and social reaction (66.1, 95%CI: 61.1-71.1 vs 80.0, 95%CI: 72.1-87.7, P = 0.005). CONCLUSION: IBS-D and IBS-M patients have lower IBS-QOL than IBS-C patients. Clinicians should recognize food avoidance, effects on daily activities and relationship problems in these patients.

Vitamin D receptor pathway is required for probiotic protection in colitis.

Low expression of vitamin D receptor (VDR) and dysfunction of vitamin D/VDR signaling are reported in patients with inflammatory bowel disease (IBD); therefore, restoration of VDR function to control inflammation in IBD is desirable. Probiotics have been used in the treatment of IBD. However, the role of probiotics in the modulation of VDR signaling to effectively reduce inflammation is unknown. We identified a novel role of probiotics in activating VDR activity, thus inhibiting inflammation, using cell models and VDR knockout mice. We found that the probiotics Lactobacillus rhamnosus strain GG (LGG) and Lactobacillus plantarum (LP) increased VDR protein expression in both mouse and human intestinal epithelial cells. Using the VDR luciferase reporter vector, we detected increased transcriptional activity of VDR after probiotic treatment. Probiotics increased the expression of the VDR target genes, such as antimicrobial peptide cathelicidin, at the transcriptional level. Furthermore, the role of probiotics in regulating VDR signaling was tested in vivo using a Salmonella-colitis model in VDR knockout mice. Probiotic treatment conferred physiological and histologic protection from Salmonella-induced colitis in VDR(+/+) mice, whereas probiotics had no effects in the VDR(-/-) mice. Probiotic treatment also enhanced numbers of Paneth cells, which secrete AMPs for host defense. These data indicate that the VDR pathway is required for probiotic protection in colitis. Understanding how probiotics enhance VDR signaling and inhibit inflammation will allow probiotics to be used effectively, resulting in innovative approaches to the prevention and treatment of chronic inflammation.

Sustained improvement in health-related quality of life measures in patients with inflammatory bowel disease receiving prolonged anti-tumor necrosis factor therapy.

OBJECTIVE: The aim of this study was to determine whether the effects of prolonged therapy (≥1 year) with anti-tumor necrosis factor (TNF) agents were sustained on the health-related quality of life (HRQoL) in patients with inflammatory bowel disease (IBD). METHODS: A cross-sectional survey of patients with IBD who were treated with anti-TNF agents was performed. Results of the validated HRQoL measures (inflammatory bowel disease questionnaire [IBDQ], EuroQoL-5 dimensions [EQ-5D], health status visual analogue scale [VAS] and the Zung self-rating depression scale) were recorded and compared between patients treated with anti-TNF agents for <1 year and ≥1 year. RESULTS: A total of 41 patients were finally enrolled in the study. Among them, 11 (26.8%) had received anti-TNF therapy for less than one year with a median duration of 7 months (range 3-11 months), while the other 30 (73.2%) had been treated for ≥1 year with a median duration of 42 months (range 12-104 months). Crohn's disease was the most common type in both groups. None of the mean IBDQ, EQ-5D and EQ-5D plus VAS, or Zung self-rating depression scale scores differed significantly between the two groups of patients. CONCLUSIONS: Improvements in HRQoL for IBD patients on anti-TNF therapy were sustained for longer than one year. HRQoL measures for IBD patients treated with anti-TNF therapy for <1 year do not differ significantly from those treated for ≥1 year, but a trend towards improved HRQoL measures with prolonged therapy can be obtained.

Probiotics, nuclear receptor signaling, and anti-inflammatory pathways.

There is increased investigation of the human microbiome as it relates to health and disease. Dysbiosis is implicated in various clinical conditions including inflammatory bowel disease (IBD). Probiotics have been explored as a potential treatment for IBD and other diseases. The mechanism of action for probiotics has yet to be fully elucidated. This paper discusses novel mechanisms of action for probiotics involving anti-inflammatory signaling pathways. We highlight recent progress in probiotics and nuclear receptor signaling, such as peroxisome-proliferator-activated receptor gamma (PPARγ) and vitamin D receptor (VDR). We also discuss future areas of investigation.

Treatment of refractory/recurrent C. difficile-associated disease by donated stool transplanted via colonoscopy: a case series of 12 patients.

PURPOSE AND OBJECTIVE: Over the past 20 years, Clostridium difficile has emerged as an important microbial cause of nosocomial diarrhea. Recurrence is common and management of recurrent disease is not standardized. In this case series, we describe 12 patients with refractory/recurrent C. difficile-associated disease (CDAD) treated at our institution by transplantation of donated stool via colonoscopy. METHODS: This is a retrospective study of 12 consecutive patients with refractory/recurrent C. difficile infection evidenced by recurrent symptoms and a history of a positive fecal C. difficile toxin assay that were treated by transplantation of donated stool administered during colonoscopy. RESULTS: Our cohort comprised 9 women and 3 men with a mean age of 66 years (range 30 to 86 y). Nine of the 12 patients had diverticulosis. Patients were symptomatically ill for 79 to 1532 days (mean 351 d, median 209 d) before fecal transplantation. The index infection for which antibiotics was prescribed varied widely along with the inciting antibiotic. All 12 patients (100%) experienced an immediate and durable clinical response to fecal transplantation. There were no adverse side effects from fecal transplantation. CONCLUSIONS: Fecal transplantation via colonoscopy is a safe, effective treatment regimen for refractory/recurrent CDAD. Our 12 patients had an immediate and durable response rate of 100%. Fecal transplantation is a promising treatment for refractory/recurrent C. difficile infection. Its use and efficacy should be pursued in prospective controlled trials.

The "vertical response time": barriers to ambulance response in an urban area.

BACKGROUND: Ambulance response time is typically reported as the time interval from call dispatch to arrival on-scene. However, the often unmeasured "vertical response time" from arrival on-scene to arrival at the patient's side may be substantial, particularly in urban areas with high-rise buildings or other barriers to access. OBJECTIVES: To measure the time interval from arrival on-scene to the patient in a large metropolitan area and to identify barriers to emergency medical services arrival. METHODS: This was a prospective observational study of response times for high-priority call types in the New York City 9-1-1 emergency medical services system. Research assistants riding with paramedics enrolled a convenience sample of calls between 2001 and 2003. RESULTS: A total of 449 paramedic calls were included, with a median time from call dispatch to arrival on-scene of 5.2 minutes. The median on-scene to patient arrival interval was 2.1 minutes, leading to an actual response interval (dispatch to patient) of 7.6 minutes. The median on-scene to patient interval was 2.8 minutes for residential buildings, 2.7 minutes for office complexes, 1.3 minutes for private homes (less than four stories), and 0.5 minutes for outdoor calls. Overall, for all calls, the on-scene to patient interval accounted for 28% of the actual response interval. When an on-scene escort provided assistance in locating and reaching the patient, the on-scene to patient interval decreased from 2.3 to 1.9 minutes. The total dispatch to patient arrival interval was less than 4 minutes in 8.7%, less than 6 minutes in 28.5%, and less than 8 minutes in 55.7% of calls. CONCLUSIONS: The time from arrival on-scene to the patient's side is an important component of overall response time in large urban areas, particularly in multistory buildings.