Exocrine Pancreatic Insufficiency Is Common in Celiac Disease: A Systematic Review and Meta-Analysis.

The prevalence of celiac disease (CD) is approximately 1% in the US. Studies have shown possible association between exocrine pancreatic insufficiency (EPI) and CD, with numerous hypothesized biological mechanisms including small bowel mucosal damage causing disruption of enteric-mediated hormonal secretion such as cholecystokinin and loss of enterokinase. The overall prevalence of EPI in CD remains unknown. We performed systematic review and metanalysis and examined the prevalence of EPI in patients who were first diagnosed with CD versus those who had been on treatment with gluten-free diet (GFD). Results  Six studies were included in the analysis totaling 446 CD patients (Avg age 44.1 years; 34% Males). One hundred and forty-four patients had newly diagnosed CD, and 302 patients had known CD with at least 9 months treatment with GFD. Four studies examined newly diagnosed CD patients. The individual rates of EPI in new CD patients ranged from 10.5 to 46.5%. The pooled prevalence of EPI in newly diagnosed CD patients was 26.2% (95% CI 8.43-43.92%, Q = 2.24, I2 = 0%). Five studies examined CD patients on GFD. The rate of EPI ranged from 1.9% to 18.2%. The prevalence of EPI in patients treated with GFD is 8% (95% CI 1.52-14.8%, Q = 4.42, I2 = 9.59%). Patients with newly diagnosed CD are significantly more likely to have EPI compared to those patients treated with GFD (p = 0.031). CD patients on GFD with persistent symptoms have a significantly higher rate of EPI (28.4%) compared to CD patients on GFD who are asymptomatic (3%) (p < 0.001).

Association Between Immunosuppressive Therapy and Outcome of Clostridioides difficile Infection: Systematic Review and Meta-Analysis.

BACKGROUND: Patients with Clostridioides difficile infection (CDI) often have coexisting medical problems requiring immunosuppressive therapy. However, limited data are available on the association between immunosuppressive therapy and CDI outcomes. AIM: To determine the association between immunosuppressive therapy and CDI outcomes. METHODS: PubMed, Embase, and Cochrane Library were searched through February 2021. Two reviewers independently reviewed and included studies that compared adult CDI patients who received immunosuppressive therapy to those who did not. The primary outcome was complicated CDl, including death, surgery, shock, or ICU admission. Raw data or unadjusted odds ratios (ORs) were used to calculate pooled ORs with 95% confidence intervals (CIs). RESULTS: Twenty-two studies with a total of 5759 CDI patients were selected. Immunosuppressive therapy was significantly associated with both primary outcome and death, with pooled ORs of 1.61 (95% CI 1.33-1.96) and 1.73 (95% CI 1.39-2.15) separately. The association between corticosteroids and primary outcome was also significant with OR of 1.73 (95% CI 1.41, 2.12). In subgroup analysis, the factors explaining differences in study results included study quality, patient age, and whether individual studies had adjusted for potential confounders. In a systematic review, most studies suggested a positive association between immunosuppressive therapy and complicated outcomes of CDI in patients comorbid for IBD. CONCLUSIONS: Our systematic review and meta-analysis demonstrate that immunosuppressive therapy is a risk factor for complicated outcomes of CDI.

Chronic Pancreatitis and Bone Disease.

Patients with chronic pancreatitis (CP) may have a higher prevalence of osteoporosis than the general population thereby increasing the risk of bone fracture. The pathophysiology of bone disease in CP is multifactorial. Their risk factors for secondary osteoporosis include increasing age, low body mass index from sitophobia, maldigestion due to exocrine pancreatic insufficiency (EPI) with resulting low vitamin D, as well as smoking and alcohol abuse. An obvious association of bone disease with CP is from EPI with maldigestion of fat-soluble vitamins including vitamin-D, which has a significant role in the process of bone formation. Vitamin-D deficiency may be higher in CP patients vs controls, and it is especially so in CP patients with EPI. Screening for CP-associated osteopathy, including osteopenia and osteoporosis, should be initiated early in the course of CP, as the overall prevalence of bone disease is approximately two-thirds of CP patients. Our initial approach in the treatment of osteoporosis should include correction of maldigestion resulting from EPI with use of pancreatic enzyme replacement therapy (PERT). PERT, which is the treatment for EPI is associated with improvement in Dual energy X-ray absorptiometry (DXA) values and vitamin-D levels compared to those who are not treated. This should improve, in addition to body mass index, vitamin-D deficiency and calcium absorption as well as improve overall nutritional status. Osteopathy is common in CP patients, has significant associated morbidity, should be screened for regularly, and corrected with fat soluble vitamin supplementation and PERT to prevent clinical sequelae. In this article, we review the epidemiology, pathophysiology, and treatment of bone disease in patients with CP.

Preferential usage of rifaximin for the treatment of hydrogen-positive smallintestinal bacterial overgrowth.

OBJECTIVES: Small intestinal bacterial overgrowth (SIBO) is challenging to treat and diagnose and is associated with diagnosis of irritable bowel syndrome (IBS). Although no FDA-approved medications exist for treatment of SIBO, rifaximin has recently received approval to treat diarrhea-predominant IBS and patients with methane-positive SIBO breath tests. The aim of this study is to evaluate patient response to rifaximin for SIBO based on breath test results. MATERIALS AND METHODS: All patients underwent breath testing to evaluate for SIBO during a 42-month period. Patients were defined as having a positive glucose breath test for SIBO based on an increase of ≥ 20 ppm of hydrogen and/or ≥ 10 ppm of methane 90 minutes after ingesting glucose. Patient demographic and symptom data, antibiotic treatment regimens, symptomatic response to therapy, and repeat treatments were recorded. Institutional review board approval was obtained. RESULTS: A total of 53 of 443 patients had positive breath testing for SIBO. Response rates to rifaximin (550 mg three times daily for 14 days) were 47.4% for hydrogen positivity alone and 80% for both hydrogen and methane positivity. CONCLUSIONS: Rifaximin was the most commonly prescribed antibiotic regimen for SIBO therapy. Patients with hydrogen or hydrogen and methane positive breath tests responded well to rifaximin therapy. For patients with hydrogen-positive SIBO, rifaximin may prove a highly effective therapy in providing symptom relief from the effects of SIBO.

Is There an Effect of Cannabis Consumption on Acute Pancreatitis?

BACKGROUND AND AIM: Twenty-percentage of acute pancreatitis (AP) cases is labeled as idiopathic. Cannabis remains the most frequently used illicit drug in the world. The aim of this study was to identify the prevalence of cannabis use among all patients with a first episode of AP, particularly in those labeled as idiopathic etiology, and determine any effect on AP severity. METHODS: Retrospective cohort of all consecutive patients admitted with a first episode of AP at a large tertiary referral hospital from 01/2013 through 12/2014. AP was identified by ICD9 code, or lipase ≥ 3 times the upper limit of normal and abdominal pain consistent with AP. Cannabis users (CU) were identified via history or urine toxicology. RESULTS: Four hundred and sixty patients were included. 54% were men, with a mean age of 48 years (range 17-89 years). Forty-eight patients (10%) were identified as CU. After adjusting for admission SIRS, age, and gender, cannabis use was not found to be an independent risk factor for persistent SIRS, AKI, ARDS, pancreatic necrosis, mortality, ICU admission, length of stay, in-hospital infections, nor recurrent AP. Of note, AKI was least common among non-CU compared to CU (OR 0.4; p = 0.02; CI 0.2-0.9) and non-CU had a higher admission BISAP score (≥ 2) compared to CU (OR 2.5; p = 0.009; CI 1.2-4.9). CONCLUSION: This is the largest study to date examining cannabis use in AP. Cannabis use was found across almost all etiologies of AP with a prevalence of 10% (48 cases), and in 9% (9 cases) of so-called idiopathic AP cases in this cohort, which could account as an association for approximately 2% of all AP cases. Cannabis use did not independently impact AP severity or mortality.

Clostridium difficile Infection and Patient-Specific Antimicrobial Resistance Testing Reveals a High Metronidazole Resistance Rate.

BACKGROUND: Clostridium difficile (CD) infection (CDI) causes marked morbidity and mortality, accounting for large healthcare expenditures annually. Current CDI treatment guidelines focus on clinical markers of patient severity to determine the preferred antibiotic regimen of metronidazole versus vancomycin. The antimicrobial resistance patterns for patients with CD are currently unknown. AIM: The aim of this study was to define the antimicrobial resistance patterns for CD. METHODS: This study included all patients with stools sent for CD testing to a private laboratory (DRG Laboratory, Alpharetta, Georgia) in a 6-month period from across the USA. Patient data was de-identified, with only age, gender, and zip-code available per laboratory protocol. All samples underwent PCR testing followed by hybridization for CD toxin regions A and B. Only patients with CD-positive PCR were analyzed. Antimicrobial resistance testing using stool genomic DNA evaluated presence of imidazole- and vancomycin-resistant genes using multiplex PCR gene detection. RESULTS: Of 2743, 288 (10.5%) stool samples were positive for CD. Six were excluded per protocol. Of 282, 193 (69.4%) were women, and average age was 49.4 ± 18.7 years. Of 282, 62 were PCR positive for toxins A and B, 160 for toxin A positive alone, and 60 for toxin B positive alone. Antimicrobial resistance testing revealed 134/282 (47.5%) patients resistant to imidazole, 17 (6.1%) resistant to vancomycin, and 9 (3.2%) resistant to imidazole and vancomycin. CONCLUSIONS: CD-positive patients with presence of imidazole-resistant genes from stool DNA extract was a common phenomenon, while vancomycin resistance was uncommon. Similar to treatment of other infections, antimicrobial resistance testing should play a role in CDI clinical decision-making algorithms to enable more expedited and cost-effective delivery of patient care.

The association of tissue anti-TNF drug levels with serological and endoscopic disease activity in inflammatory bowel disease: the ATLAS study.

OBJECTIVE: The aim of this study was to assess the correlation between serum and intestinal anti-tumour necrosis factor (TNF) levels, and their relationship to endoscopic disease activity and levels of TNF. DESIGN: Cross-sectional study of 30 patients receiving treatment with infliximab or adalimumab for Crohn's disease or UC. For each patient, a sample of serum was matched to tissue biopsies. Endoscopic and histological disease activity was recorded for each tissue sample. RESULTS: There was a significant positive correlation between anti-TNF in serum and tissue (r=0.3920, p=0.002), especially in uninflamed tissue (r=0.50, p<0.001), but not with those samples that had inflammation (r=0.19, p=0.54). Anti-TNF concentration in tissue correlated with degree of endoscopic inflammation, except for tissue with severe inflammation in which anti-TNF levels were again lower (mean normalised anti-TNF in tissue: uninflamed=0.93, mild=2.17, moderate=13.71, severe=2.2 inflammation (p=0.0042)). The ratio of anti-TNF-to-TNF in tissue was highest in uninflamed areas and lowest in severely inflamed areas. Patients with active mucosal disease had a higher rate of serum to tissue drug level mismatch when compared to those in remission (73.3% vs 33.3%, respectively; p=0.03). CONCLUSIONS: Our data suggest that local tissue inflammation characterised by high levels of TNF serves as a sink for anti-TNF. We further postulate that some patients with high serum anti-TNF levels have active disease because tissue levels of anti-TNF are insufficient to neutralise local TNF production.

Gastric Enterovirus Infection: A Possible Causative Etiology of Gastroparesis.

BACKGROUND: Gastroparesis (GP) is a disabling chronic gastroenterologic disorder with high morbidity that severely impacts patients' quality of life. GP can present acutely after a viral-like gastrointestinal illness resulting in speculation that in some patients, neurologic damage caused by the infection might underlie the pathogenesis of idiopathic gastroparesis (IGP). AIMS: The aim of this study is to document case reports of Enterovirus (EV) infection as a possible cause of IGP. METHODS: Eleven patients referred with a diagnosis of GP underwent workup to exclude known causes of GP. Those with a history of flu-like symptoms or gastroenteritis prior to onset of GP symptoms had gastric biopsies taken during upper endoscopy to assess for the presence of gastric mucosal EV infection. Data on presenting symptoms, extra-intestinal symptoms and conditions, prior nutritional support requirements, upper endoscopy findings, and response to therapy were cataloged. RESULTS: Eleven patients were diagnosed as IGP. Nine had active EV infection on gastric biopsies and were included (7/9 female, mean age 43 years). Eight out of nine received EV treatment with antivirals and/or immune therapies, with a wide degree of variability in treatment regimens. Four out of eight who received EV treatment had symptomatic improvement. One patient had stable symptoms. Three patients are currently undergoing therapy. CONCLUSIONS: Gastric EV infection was frequently detected (82 %) in patients undergoing investigation for IGP. Antiviral and/or immune therapies against EV seem to be favorable, as most of our patients had resolution of their GP symptoms after treatment. This is the first study to identify EV as a possible infectious etiology of IGP.

Comparison of Performance Characteristics of Oval Cup Forceps Versus Serrated Jaw Forceps in Gastric Biopsy.

BACKGROUND: Obtaining quality endoscopic biopsy specimens is vital in making successful histological diagnoses. The influence of forceps cup shape and size on quality of biopsy specimens is unclear. AIM: To identify whether oval cup or two different serrated jaw biopsy forceps could obtain specimens of superior size. Secondary endpoints were tissue adequacy, depth of tissue acquisition, and crush artifact. METHODS: A single-center, prospective, pathologist-masked, randomized controlled trial was performed. In total 136 patients with a clinical indication for esophagogastroduodenoscopy with biopsy were randomized to receive serial biopsies with a large-capacity serrated forceps with jaw diameter 2.2 mm (SER1) and either a large-capacity oval forceps with jaw diameter 2.4 mm (OVL) or large-capacity serrated biopsy forceps with jaw diameter 2.4 mm (SER2) in two parallel groups. RESULTS: SER2 provided significantly larger specimens than did the other forceps (SER2 3.26 ± 1.09 vs. SER1 2.92 ± 0.88 vs. OVL 2.92 ± 0.76; p = 0.026), with an average size difference of 0.34 mm greater with SER2 compared to SER1 and OVL. OVL provided significantly deeper biopsies compared to SER1 and SER2 (p = 0.02), with 31 % of OVL biopsies reaching the submucosa. SER2 had significantly less crush artifact than SER1 and OVL (p < 0.0001). CONCLUSION: Serrated forceps provided larger samples compared to oval jaw forceps of the same size, with SER2 providing the largest specimen size. Oval cup forceps had deeper penetration of epithelium, while the larger jaw diameter serrated jaw forceps had less crush artifact. All three forceps provided specimens adequate for diagnostic purposes.

Type 1 autoimmune pancreatitis: case scenario and review of the disease.

Autoimmune pancreatitis (AIP) is an uncommon disease that represents a diagnostic challenge unless it is considered as a cause of acute pancreatitis, pancreatic exocrine insufficiency and a pancreatic mass. This entity is under diagnosed and successful medical therapy is available. In this paper, we will describe a case of a 59 year-old, Hispanic woman diagnosed with autoimmune pancreatitis, a disease previously believed to affect typically older men. We will review the definition, types, clinical manifestations, radiological features, serology, histopathological findings, treatment strategies and diagnostic criteria of autoimmune pancreatitis.

Concentrations of 6-thioguanine nucleotide correlate with trough levels of infliximab in patients with inflammatory bowel disease on combination therapy.

BACKGROUND & AIMS: In patients with inflammatory bowel diseases, the combination of infliximab and thiopurines (such as 6-thioguanine) is more effective treatment than monotherapy. We assessed the correlation between serum levels of 6-thioguanine (6-TGN) and infliximab levels or antibodies to infliximab (ATI). METHODS: We performed a cross-sectional study of 72 patients receiving maintenance therapy with infliximab and a thiopurine for inflammatory bowel disease at the Crohn's and Colitis Center of the University of Miami, FL. We collected clinical, endoscopic, and biochemical data, and levels of thiopurine metabolites. The primary outcomes were trough level of infliximab and the presence of ATI. RESULTS: Levels of 6-TGN correlated with those of infliximab (ρ, 0.53; P < .0001). The cut-off point of 6-TGN that best predicted a higher level of infliximab was 125 pmol/8 × 10(8) red blood cells (RBCs) (area under receiver operating characteristic, 0.86; P < .001). Patients in the lowest quartile of 6-TGN had infliximab levels that were similar to patients on no thiopurines (4.3 vs. 4.8 mcg/mL, respectively; P = .8). An infliximab level of 8.3 mcg/mL or greater was associated with mucosal healing. Only 8 patients (11%) had detectable ATI. Patients with 6-TGN levels less than 125 pmol/8 × 10(8) RBCs were significantly more likely to have ATI (odds ratio, 1.3; 95% confidence interval, 2.3-72.5; P < .01). CONCLUSIONS: Although 6-TGN levels of greater than 230 pmol/8 × 10(8) RBCs have been associated with improved outcomes in patients on monotherapy, a level of 6-thioguanine of 125 pmol/8 × 10(8) RBCs or greater may be adequate to achieve therapeutic levels of infliximab. In the long term, this may minimize the toxicity for patients on combination therapy.

[Acute respiratory distress syndrome due to Clostridium difficile colitis: a case report and review of the literature]. / Síndrome de distress respiratorio agudo debido a colitis por Clostridium difficile: reporte de caso y revisión de la literatura.

Clostridium difficile is a major cause of antibiotic-associated diarrhea. We report a patient with complicated Clostridium difficile infection (CDI) who developed rapidly progressive acute respiratory distress syndrome (ARDS), for which CDI was the only identifiable source. CDI should be considered in the differential diagnosis for anyone with diarrhea who presents especially in high-risk groups such as the elderly, hospitalized patients, or those who have had a history of CDI.

Real-World Patient Experience With Pancreatic Enzyme Replacement Therapy in the Treatment of Exocrine Pancreatic Insufficiency.

OBJECTIVES: This study aimed to provide patients insights on the management of exocrine pancreatic insufficiency (EPI) with pancreatic enzyme replacement therapy (PERT). MATERIALS AND METHODS: A survey of 75 members of Inspire's Pancreatitis or Pancreatic Cancer Support communities was conducted. Eligibility included having EPI secondary to chronic pancreatitis, pancreatic cancer, pancreatic surgery, or acute pancreatitis, and current/past PERT experience. RESULTS: Patients were 73% female, 57% aged 50 to 69 years, and 85% White, with PERT prescribed by a gastroenterologist/pancreatologist for 64%. Only approximately half of respondents agreed that their healthcare provider provided detailed information about EPI (54%) or how PERT works to treat EPI (56%). Most respondents (83%) reported searching for information about EPI, 56% were taking PERT solely before or after eating, 36% reported taking suboptimal PERT doses, and 39% reported no follow-up. In addition, 24% decreased their PERT dosage without consulting their physician, and 21% reported purposely skipping PERT. CONCLUSIONS: This study reveals potential barriers to effective treatment of EPI with PERT, including lack of patient education, mainly how and when to take PERT, gaps in appropriate dosing, and lack of patient follow-up. Continued focus on patient and provider education is essential to address these gaps and optimize the treatment of EPI.