A Dimorphic Diagnosis of a Pleomorphic Disease: An Unusual Cause of Hypercalcemia.

BACKGROUND: Histoplasmosis is a rare cause of 1, 25-dihydroxy vitamin-D-mediated hypercalcemia. In this study, we report 2 cases of hypercalcemia secondary to histoplasmosis seen at Mayo Clinic, Rochester and a review of cases reported in the literature. METHODS: We conducted a PubMed search using the keywords "hypercalcemia" and "histoplasmosis." Fourteen cases of hypercalcemia secondary to histoplasmosis were reported between 1977 and 2020. We identified an additional 2 patients from our institution. RESULTS: We reviewed a total of 16 cases. The median age at presentation was 58.5 years (interquartile range, 41.5-68.75 years), and 13 of 16 patients (81.2%) were men. Serum parathyroid hormone level was available in 13 of 16 (81.25%) patients, of whom 11 patients (84.6%) had a low level, 1 patient (7.6%) had a normal level, and 1 patient (7.6%) had an elevated level. 1, 25-dihydroxy vitamin D level was reported in 9 of 16 (56.25%) patients. Of these, 5 patients (55.5%) had levels within normal limits, and 4 patients (44.4%) had levels above normal. Serum angiotensin-converting enzyme level was evaluated in 4 of 16 patients (25%), and it was elevated in all 4 (100%) cases. Four patients received corticosteroids before a diagnosis of histoplasmosis was made, which resulted in rapidly progressive disease and death in 2 patients. CONCLUSIONS: In patients with granulomatous disorder and hypercalcemia, it is crucial to rule out infectious etiologies before initiating steroids. Histoplasmosis can cause nonparathyroid hormone-mediated hypercalcemia and, if not suspected, may have catastrophic implications.

Fishing for a Diagnosis, the Impact of Delayed Diagnosis on the Course of Mycobacterium marinum Infection: 21 Years of Experience at a Tertiary Care Hospital.

BACKGROUND: Mycobacterium marinum is a common but underreported mycobacterial infection. We conducted a large retrospective study to determine risk factors and describe the therapeutic interventions and outcomes in patients with uncomplicated and complicated M. marinum infection. METHODS: Culture-confirmed M. marinum infection cases were identified from the Mayo Clinic Clinical Mycology Laboratory from January 1998 to December 2018. Complicated M. marinum infection was defined as the presence of tenosynovitis, septic arthritis, or osteomyelitis. Differences in complicated vs uncomplicated M. marinum infections were analyzed using statistical comparisons. RESULTS: Twelve cases had a complicated M. marinum infection. Patients with a complicated infection were older (64.3 ±â€…11.1 vs 55.8 ±â€…14.5; P = .03), had longer duration of symptoms (5 vs 3 months; P = .011), and had more surgical debridements (1 vs 0; P < .001). Length of treatment and number of drugs used were not statistically significant. Complicated M. marinum cases received more medications (2 vs 1; P = .263) and were treated longer (5.7 vs 3.5 months; P = .067). Antibiotic susceptibilities were performed in 59% of the patients. All isolates were susceptible to clarithromycin. From the tetracyclines, doxycycline had a better susceptibility pattern. CONCLUSIONS: M. marinum infection is an important cause of skin and soft tissue infection. Poor water exposure documentation, unusual clinical presentation, and empiric antibiotic treatment before definitive M. marinum diagnosis often contribute to a delayed diagnosis. Complicated M. marinum cases had longer duration of symptoms and more surgical debridements. No difference in the number of drugs used or clinical outcome was observed.

Prospective randomized controlled study on the effects of Saccharomyces boulardii CNCM I-745 and amoxicillin-clavulanate or the combination on the gut microbiota of healthy volunteers.

Probiotics are believed to be beneficial in maintaining a healthy gut microbiota whereas antibiotics are known to induce dysbiosis. This study aimed to examine the effects of the probiotic Saccharomyces boulardii CNCM I-745 (SB), the antibiotic Amoxicillin-Clavulanate (AC) and the combination on the microbiota and symptoms of healthy humans. Healthy subjects were randomized to one of 4 study groups: SB for 14 days, AC for 7 days, SB plus AC, Control (no treatment). Participants gave stool samples and completed gastro-intestinal symptom questionnaires. Microbiota changes in stool specimens were analyzed using 16s rRNA gene pyrosequencing (bTEFAP). Only one subject withdrew prematurely due to adverse events. Subjects treated by S boulardii + AC had fewer adverse events and tolerated the study regimen better than those receiving the AC alone. Control subjects had a stable microbiota throughout the study period. Significant microbiota changes were noted in the AC alone group during antibiotic treatment. AC associated changes included reduced prevalence of the genus Roseburia and increases in Escherichia, Parabacteroides, and Enterobacter. Microbiota alterations reverted toward baseline, but were not yet completely restored 2 weeks after antibiotherapy. No significant shifts in bacterial genera were noted in the SB alone group. Adding SB to AC led to less pronounced microbiota shifts including less overgrowth of Escherichia and to a reduction in antibiotic-associated diarrhea scores. Antibiotic treatment is associated with marked microbiota changes with both reductions and increases in different genera. S. boulardii treatment can mitigate some antibiotic-induced microbiota changes (dysbiosis) and can also reduce antibiotic-associated diarrhea.

Systematic Analysis and Critical Appraisal of the Quality of the Scientific Evidence and Conflicts of Interest in Practice Guidelines (2005-2013) for Barrett's Esophagus.

BACKGROUND: Barrett's esophagus (BE) is a condition that has a small but important risk of progressing to esophageal cancer. To date, no study has assessed the strength of evidence supporting the recommendations for BE. We sought to assess the overall quality of the recommendations and strength of the BE using the AGREE II instrument. METHODS: A PubMed search was performed to identify guidelines published pertaining to BE. Every guideline was reviewed using the AGREE II format to assess the methodological rigor and validity of the guideline. Additionally, guidelines were reviewed for the level of evidence used to support recommendations, conflicts of interest (COI), and differences in recommendations. Statistical analysis was performed using Stata (version 12). RESULTS: In total, 234 manuscripts were identified of which 8 guidelines published between 2005 and 2013 pertained to BE. Seventy-five percentage (6/8) graded the evidence used to formulate recommendations. Of the 126 recommendations with supporting evidence, 6 % were supported by level A evidence, 49 % level B evidence, and 45 % level C evidence. Using the AGREE II format, the highest overall assessment grade was the BSG BE guideline (6.5 ± 0.6) followed by the AGA (5.5 ± 0.6). The highest rated domains were scope and purpose (mean 77 range 24-96) and clarity of presentation (mean 75), while the lowest rated domains were editorial independence (mean 32 range 0-92) and applicability of the guideline (mean 35 range 7-90). There was significant variability in recommendations regarding who to screen for BE and surveillance intervals. Finally, only 50 % of the guidelines disclosed if COI were present and 75 % (3/4) reported potentially relevant COI. CONCLUSIONS: Majority of the BE guideline fail to meet the AGREE II domains, and most of the recommendations are level B or C quality evidence. Further interventions are necessary to improve the overall quality of the guidelines.

Poor Documentation of Inflammatory Bowel Disease Quality Measures in Academic, Community, and Private Practice.

BACKGROUND & AIMS: Quality measures are used to standardize health care and monitor quality of care. In 2011, the American Gastroenterological Association established quality measures for inflammatory bowel disease (IBD), but there has been limited documentation of compliance from different practice settings. METHODS: We reviewed charts from 367 consecutive patients with IBD seen at academic practices, 217 patients seen at community practices, and 199 patients seen at private practices for compliance with 8 outpatient measures. Records were assessed for IBD history, medications, comorbidities, and hospitalizations. We also determined the number of patient visits to gastroenterologists in the past year, whether patients had a primary care physician at the same institution, and whether they were seen by a specialist in IBD or in conjunction with a trainee, and reviewed physician demographics. A univariate and multivariate statistical analysis was performed to determine which factors were associated with compliance of all core measures. RESULTS: Screening for tobacco abuse was the most frequently assessed core measure (89.6% of patients; n = 701 of 783), followed by location of IBD (80.3%; n = 629 of 783), and assessment for corticosteroid-sparing therapy (70.8%; n = 275 of 388). The least-frequently evaluated measures were pneumococcal immunization (16.7% of patients; n = 131 of 783), bone loss (25%; n = 126 of 505), and influenza immunization (28.7%; n = 225 of 783). Only 5.8% of patients (46 of 783) had all applicable core measures documented (24 in academic practice, none in clinical practice, and 22 in private practice). In the multivariate model, year of graduation from fellowship (odds ratio [OR], 2.184; 95% confidence interval [CI], 1.522-3.134; P < .001), year of graduation from medical school (OR, 0.500; 95% CI, 0.352-0.709; P < .001), and total number of comorbidities (OR, 1.089; 95% CI, 1.016-1.168; P = .016) were associated with compliance with all core measures. CONCLUSIONS: We found poor documentation of IBD quality measures in academic, clinical, and private gastroenterology practices. Interventions are necessary to improve reporting of quality measures.

Prevalence of abnormal liver function tests in celiac disease and the effect of a gluten-free diet in the US population.

OBJECTIVES: Guidelines recommend routine screening of liver function tests (LFTs) in patients diagnosed with celiac disease (CD). However, little is known about the prevalence of liver disorders in CD outside of Europe. Our aims were to estimate the prevalence of LFT abnormalities in CD and to evaluate the effect of a gluten-free diet (GFD) on LFTs. METHODS: Adult patients with biopsy-proven CD were identified from a prospectively maintained database and matched with healthy controls. LFT levels for women and men were defined as abnormal based on the Third National Health and Nutrition Examination Survey (NHANES III) criteria. Data on demographics, coexisting liver diseases, and laboratory work-ups including aspartate transaminase (AST) and alanine transaminase (ALT) values at the time of diagnosis and on a GFD were recorded. Subsequently, data from this cohort were compared with data from 7,789 individuals participating in the National Health and Nutrition Examination Survey, 2009-2010. Univariate logistic regression, Wilcoxon signed-ranks, Student's t-test, χ(2), and Fischer's exact test were used for statistical analysis. RESULTS: In 463 CD patients with ALT or AST levels at the time of CD diagnosis, 40.6% had elevated LFTs compared with 24.2% of treated CD patients (P<0.001) and 16.6% of matched controls (P<0.001). Similarly, 36.7% of CD patients on the NHANES database had abnormal ALT values compared with 19.3% of non-celiac patients (P=0.03). Approximately, 78.6% of CD patients with elevated LFTs at diagnosis normalized LFTs on a GFD after a mean duration of 1.5±1.5 years. CONCLUSIONS: Forty percent of individuals will have elevated LFTs at CD diagnosis; however, the majority will normalize with standard CD therapy. LFTs should be checked in all patients with CD and coexisting liver disorder should be considered in patients whose LFTs have not improved within a year on a GFD.

The present and the future in the diagnosis and management of celiac disease.

Celiac disease is an autoimmune enteropathy caused by gluten in genetically predisposed individuals. In celiac disease, adaptive and innate immune activation results in intestinal damage and a wide range of clinical manifestations. In the past, celiac disease was thought to result in signs and symptoms solely related to the gastrointestinal tract. Now, more than half of the adult population presents with extra-intestinal manifestations that can also be expected to improve on a gluten-free diet. For this reason, it is recommended that physicians have a low threshold of suspicion for celiac disease. Current knowledge of the immune pathogenesis of this autoimmune disease has served as a catalyst for the development of novel diagnostic tools and therapeutics. Over the years, highly sensitive and specific serological assays, in addition to genetic markers, have been found to target specific steps in the cascade pathway of celiac disease. Also the advent of the gluten challenge has enabled experts to design diagnostic algorithms and monitor clinical responses in clinical trials. The gluten challenge has provided substantial benefit in the advance of novel therapeutics as an adjuvant treatment to the gluten free diet. Generally, a strict gluten-free diet is highly burdensome to patients and can be limited in its efficacy. Alternative therapies-including gluten modification, modulation of intestinal permeability and immune response-could be central to the future treatment of celiac disease.