Salman Nusrat

Adding to the Burden: Gastrointestinal Symptoms and Syndromes in Multiple Sclerosis

Background. Multiple sclerosis (MS) patients often suffer from gastrointestinal (GI) symptoms. However, the full extent and prevalence of such symptoms are not clearly established. Thus, we sought to define the prevalence of GI symptoms and syndromes in those with MS. Methods. 218 MS patients completed self-reported demographic and clinical data questionnaires as well as several standardized surveys probing MS severity and GI health. Results. Nearly two thirds (65.6%) of patients endorsed at least one persistent GI symptom. Constipation (36.6%), dysphagia (21.1%), and fecal incontinence (15.1%) were common. Surprisingly, nearly 30% (28.4%) of the patients reported dyspeptic symptoms. Using validated diagnostic algorithms, patients met criteria for functional dysphagia (14.7%), functional dyspepsia (16.5%), functional constipation (31.7%), and IBS (19.3%), among others. Functional dysphagia, functional dyspepsia, and IBS were significantly more common in those with self-identified mood disorders. Conclusions. Constipation, fecal incontinence, and dysphagia are indeed frequent symptoms seen in MS patients. We also noted a ~30% prevalence of dyspepsia in this population. The mechanisms driving this association are not clear and require further study. However, due to this high prevalence, dyspeptic symptoms should be incorporated into the routine assessment of MS patients and, if found, may warrant collaborative referral with a GI specialist.

Mystery of Hepatitis E Virus: Recent Advances in Its Diagnosis and Management

Mysterious aspects of the long presumed to be well-known hepatitis E virus (HEV) have recently surfaced that distinguish it from other hepatotropic viruses. It is a cause of chronic hepatitis in immunosuppressed patients. It has human to human transmission through blood and mantains high seroprevalence in blood donors. HEV has also been found to occur more frequently in the West in those without a history of travel to endemic countries. It has varied extrahepatic manifestations and has multiple non-human reservoirs including pigs and rats. Considering these recent discoveries, it appears odd that HEV is not sought more frequently when working up acute and chronic hepatitis patients. The disease is particularly severe among pregnant women and has a high attack rate in young adults. What adds to its ambiguity is the absence of a well-established diagnostic criteria for its detection and that there is no specific antiviral drug for hepatitis E, except for isolated cases where ribavirin or pegylated interferon alpha has been used with occasional success. This review paper discusses the recent advances in the knowledge of the virus itself, its epidemiology, diagnostic approach and prevention, and the treatment options available.

Pain and opioid use in chronic pancreatitis.

Objective Opioid therapy for pain in chronic pancreatitis (CP) is associated with tolerance and possibly opioid-induced hyperalgesia. We thus examined opioid use and pain rating in CP patients. Methods Medical records of patients with established CP treated at the University of Pittsburgh Medical Center’s Digestive Disorders Center between April 2008 and December 2009 were retrospectively reviewed. Results Two hundred nineteen unique patients (53% men; age, 50 ± 1 years) were identified. At least moderate pain was initially present in 37% of the patients. Half (51%) of the patients received opioids (average morphine equivalent, 78.1 ± 12.4 mg/d). Pain severity correlated with age (r2 = −0.22), history of alcohol abuse (r2 = 0.14), affective spectrum disorders (r2 = 0.14), presence of coexisting pain syndromes (r2 = 0.24), opioid use (r2 = 0.49), and days with concerns about physical (r2 = 0.55) or mental problems (r2 = 0.35). In contrast, computed tomography–defined pancreatic abnormalities (calcification, pseudocysts, ductal stones, or dilation) did not correlate with pain rating. Regression analysis identified age, days with physical problems, and a coexisting chronic pain syndrome as best independent predictors of pain. Conclusions Chronic pancreatitis etiology, especially alcohol use, and psychosocial factors are important determinants of pain severity in CP. Successful management thus needs to go beyond treatment of changes in pancreatic morphology to effectively improve quality of life and utilization of medical resources.

Reflux and sex: what drives testing, what drives treatment?

Gastroesophageal reflux (GER) affects ∼10–20% of American adults. Although symptoms are equally common in men and women, we hypothesized that sex influences diagnostic and therapeutic approaches in patients with GER. PubMed database between 1997 and October 2011 was searched for English language studies describing symptoms, consultative visits, endoscopic findings, use and results of ambulatory pH study, and surgical therapy for GER. Using data from Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality, we determined the sex distribution for admissions and reflux surgery between 1997 and 2008. Studies on symptoms or consultative visits did not show sex-specific differences. Even though women are less likely to have esophagitis or Barretts esophagus, endoscopic studies enrolled as many women as men, and women were more likely to undergo ambulatory pH studies with a female predominance in studies from the US. Surgical GER treatment is more commonly performed in men. However, studies from the US showed an equal sex distribution, with Nationwide Inpatient Sample data demonstrating an increase in women who accounted for 63% of the annual fundoplications in 2008. Despite less common or severe mucosal disease, women are more likely to undergo invasive diagnostic testing. In the US, women are also more likely to undergo antireflux surgery. These results suggest that healthcare-seeking behavior and socioeconomic factors rather than the biology of disease influence the clinical approaches to reflux disease.

New pharmacological treatment options for irritable bowel syndrome with constipation

Introduction: Constipation predominant irritable bowel syndrome (IBS-C) is a common disorder and accounts for a large number of ambulatory visits. Sensory abnormalities, that is, presence of abdominal pain and discomfort, distinguish IBS-C from chronic idiopathic constipation. Area covered: This review focuses on the pharmacology, efficacy, safety, and future of prucalopride, YKP-10811, DSP-6952, dexloxiglumide, linaclotide, plecanatide, tenapanor, and elobixibat. Expert opinion: It is now well established that treatment focusing only on bowel transit provides incomplete relief to patients with IBS-C. Improved understanding of pathophysiology of IBS-C has led to use of sensory end points like complete spontaneous bowel movements and the FDA combined end point (abdominal pain and complete spontaneous bowel movements) in clinical trials. A number of drugs are in development and provide hope for this challenging group of patients. However, because of recent failures secondary to ineffectiveness and/or adverse events, we cautiously await how clinical data play out in larger studies and in clinical practice.

Pulmonary Mucormycosis: An Emerging Infection

Mucormycosis is a rare, but emerging, life-threatening, rapidly progressive, angioinvasive fungal infection that usually occurs in immunocompromised patients. We present a case of pulmonary mucormycosis in a diabetic patient who was on chronic steroid therapy for ulcerative colitis. Early recognition of this diagnosis, along with aggressive management, is critical to effective therapy and patient survival. The delay in diagnosis of this rapidly progressive infection can result in mortality.

Effective Constipation Treatment Changes More Than Bowel Frequency: A Systematic Review and Meta-Analysis

Background/Aims The marketing of newer agents for treatment of constipation and irritable bowel syndrome with constipation (IBS-C) emphasize improvements in abdominal pain. However, it is not clear whether this observation reflects a unique visceral analgesic effect of these agents or is a general feature of effective laxation. We sought to determine the relationship between improvements in bowel frequency and decreases in abdominal pain in clinical trials of patients with constipation or IBS-C. Methods We searched “PubMed” and “Embase” databanks for clinical trials in patients with constipation or IBS-C, targeting publications that provided detailed data on bowel movement frequency and pain intensity before and after an intervention. We abstracted the results and performed meta-analytic and meta-regression analyses. Results Twenty-seven trials (16 constipation and 11 IBS) met entry criteria. Baseline weekly bowel movement frequency was low with 2.35 (2.07–2.64) with differences between constipation (2.00 [1.62–2.38]) and IBS-C (2.77 [2.40–3.14]; Q = 8.18; P = 0.002). Studies reported moderate pain levels (2.12 [1.81–2.42]) with comparable baseline levels in constipation (2.02 [1.63–2.42]) and IBS-C (2.35 [2.10–2.60]; Q = 1.92; P = 0.167). Treatments increased bowel frequency by 2.17 [1.88–2.47] and lowered pain ratings by 0.58 [0.49–0.68]. Meta-regression demonstrated a significant correlation between treatment-induced increases in bowel frequency and decreased pain ratings. Conclusions Our analysis suggests that reduction of abdominal pain observed in clinical trials of constipation and IBS-C is associated with laxation, and may not require specific drug mechanisms, thus arguing against a unique advantage of newer agents over traditional laxatives in the treatment of constipation and IBS-C.

Fundoplication for gastroesophageal reflux disease: regional variability and factors predicting operative approach.

We have recently shown that the majority of patients undergoing fundoplication in the United States are women. Based on these findings, we hypothesized that nonbiological factors contribute to the decisions on surgical reflux therapy. Using State Inpatient Databases of the Agency for Healthcare Research and Quality, we extracted annual fundoplication rates, sex distribution, age cohorts, racial background, and insurance coverage. To account for potential differences in state populations, the results were normalized and correlated with Census data, adult obesity rates, median income, poverty rates, and physician workforce within the state. Fundoplication rates varied fivefold between states, ranging from 4.1±0.1 per 100,000 in New Jersey to 21.8±0.4 per 100,000 in Oregon. Higher poverty rates and a higher fraction of Caucasians within a state independently predicted higher fundoplication rates. While the majority of operations were performed laparoscopically, surgical approaches also differed between states with rates of laparoscopic ranging from 52.3±1.8% in Oklahoma to 87.4±1.7% in Hawaii. A lower number of pediatric and Medicaid-insured patient and a higher fraction of privately insured patients best predicted higher rates of laparoscopic surgery. Our study shows significant regional variation in surgical reflux management, which cannot be explained by differences in disease mechanisms. Insurance coverage and racial background influenced the likelihood of surgery, suggesting a role of financial incentives.

Celiac Artery Compression Syndrome

Celiac artery compression syndrome is a rare disorder characterized by episodic abdominal pain and weight loss. It is the result of external compression of celiac artery by the median arcuate ligament. We present a case of celiac artery compression syndrome in a 57-year-old male with severe postprandial abdominal pain and 30-pound weight loss. The patient eventually responded well to surgical division of the median arcuate ligament by laparoscopy.

Disorders of gastrointestinal hypomotility

Ingestion and digestion of food as well as expulsion of residual material from our gastrointestinal tract requires normal propulsive, i.e. motor, function. Hypomotility refers to inherited or acquired changes that come with decreased contractile forces or slower transit. It not only often causes symptoms but also may compromise nutritional status or lead to other complications. While severe forms, such as pseudo-obstruction or ileus, may have a tremendous functional impact, the less severe forms of hypomotility may well be more relevant, as they contribute to common disorders, such as functional dyspepsia, gastroparesis, chronic constipation, and irritable bowel syndrome (IBS). Clinical testing can identify changes in contractile activity, defined by lower amplitudes or abnormal patterns, and the related effects on transit. However, such biomarkers show a limited correlation with overall symptom severity as experienced by patients. Similarly, targeting hypomotility with pharmacological interventions often alters gut motor function but does not consistently improve symptoms. Novel diagnostic approaches may change this apparent paradox and enable us to obtain more comprehensive information by integrating data on electrical activity, mechanical forces, patterns, wall stiffness, and motions with information of the flow of luminal contents. New drugs with more selective effects or more specific delivery may improve benefits and limit adverse effects. Lastly, the complex regulation of gastrointestinal motility involves the brain-gut axis as a reciprocal pathway for afferent and efferent signaling. Considering the role of visceral input in emotion and the effects of emotion on visceral activity, understanding and managing hypomotility disorders requires an integrative approach based on the mind-body continuum or biopsychosocial model of diseases.