The demographics of autoimmune hepatitis in human immunodeficiency virus-infected patients: a United States cross-sectional study.

Introduction: Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver with increasing global prevalence. However, no epidemiological data exist for AIH in human immunodeficiency virus (HIV)-infected patients. Aim: To determine the demographics and comorbid conditions associated with AIH among HIV-infected individuals in the United States. Material and methods: The United States National Inpatient Sample database was used to identify HIV hospital encounters in 2012-2014. The encounters were then classified into 2 groups based on a concomitant primary diagnosis of AIH. Primary outcomes included the demographics and comorbid conditions of AIH among HIV-infected patients. Secondary outcomes assessed the independent predictors of AIH. Results: A total of 48,3310 patients with an HIV diagnosis were included. The estimated AIH prevalence was 52.8/100,000 HIV hospital encounters. The female gender was more likely to have AIH with an odds ratio (OR) of 1.82; 95% confidence interval (CI) 1.42-2.32, p < 0.0001. The age intervals of 35-50 and 51-65 years had higher odds of AIH 110 (43.1%) and 115 (45.1%) with OR = 1.30; 95% CI: 1.02-1.67, p = 0.03 and OR = 1.34; 95% CI: 1.05-1.71, p = 0.02, respectively. African American and Hispanic races were more commonly affected. Moreover, HIV-infected patients with AIH had a higher risk of having elevated transaminases, long-term steroid use, rheumatoid arthritis, and ulcerative colitis. Conclusions: This study illustrates that the estimated prevalence of AIH in HIV-infected patients in the United States is 52.8/100,000. AIH in HIV-positive individuals has a predilection for the female gender and African American and Hispanic races, and shows a higher correlation with rheumatoid arthritis and ulcerative colitis.

Physical therapy assessment and whole-body magnetic resonance imaging findings in children with glycogen storage disease type IIIa: A clinical study and review of the literature.

INTRODUCTION: Early recognized manifestations of GSD III include hypoglycemia, hepatomegaly, and elevated liver enzymes. Motor symptoms such as fatigue, muscle weakness, functional impairments, and muscle wasting are typically reported in the 3rd to 4th decade of life. OBJECTIVE: In this study, we investigated the early musculoskeletal findings in children with GSD IIIa, compared to a cohort of adults with GSD IIIa. METHODS: We utilized a comprehensive number of physical therapy outcome measures to cross-sectionally assess strength and gross motor function including the modified Medical Research Council (mMRC) scale, grip and lateral/key pinch, Gross Motor Function Measure (GMFM), Gait, Stairs, Gowers, Chair (GSGC) test, 6 Minute Walk Test (6MWT), and Bruininks-Oseretsky Test of Motor Proficiency Ed. 2 (BOT-2). We also assessed laboratory biomarkers (AST, ALT, CK and urine Glc4) and conducted whole-body magnetic resonance imaging (WBMRI) to evaluate for proton density fat fraction (PDFF) in children with GSD IIIa. Nerve Conduction Studies and Electromyography results were analyzed where available and a thorough literature review was conducted. RESULTS: There were a total of 22 individuals with GSD IIIa evaluated in our study, 17 pediatric patients and 5 adult patients. These pediatric patients demonstrated weakness on manual muscle testing, decreased grip and lateral/key pinch strength, and decreased functional ability compared to non-disease peers on the GMFM, 6MWT, BOT-2, and GSGC. Additionally, all laboratory biomarkers analyzed and PDFF obtained from WBMRI were increased in comparison to non-diseased peers. In comparison to the pediatric cohort, adults demonstrated worse overall performance on functional assessments demonstrating the expected progression of disease phenotype with age. CONCLUSION: These results demonstrate the presence of early musculoskeletal involvement in children with GSD IIIa, most evident on physical therapy assessments, in addition to the more commonly reported hepatic symptoms. Muscular weakness in both children and adults was most significant in proximal and trunk musculature, and intrinsic musculature of the hands. These findings indicate the importance of early assessment of patients with GSD IIIa for detection of muscular weakness and development of treatment approaches that target both the liver and muscle.

Quantitative whole-body magnetic resonance imaging in children with Pompe disease: Clinical tools to evaluate severity of muscle disease.

OBJECTIVE: Since the introduction of enzyme replacement therapy (ERT) with alglucosidase alfa, there has been increased survival in patients with Pompe disease. It is essential to characterize and quantify the burden of disease in these patients. Here, we report a measure of muscle fat infiltration in children with infantile and pediatric late-onset Pompe disease (IPD and LOPD, respectively) to better understand the extent of muscle involvement. METHODS: Eleven pediatric patients with Pompe disease (five IPD, six LOPD), ages 7-17 years, received whole-body magnetic resonance imaging (WBMRI), muscle strength testing using the modified Medical Research Council (mMRC) scale, functional assessment using gait, stairs, gowers, chair (GSGC), and urine glucose tetrasaccharide (Glc4) testing. The intramuscular fat seen on WBMRI was quantified using proton density fat fraction (PDFF) and correlated to appropriate muscle strength and functional tests, and urine Glc4. RESULTS: Patients with IPD, although younger, had higher mean PDFF values than LOPD patients (11.61% vs 8.52%). Significant correlation existed between PDFF and the GSGC assessment (r = .9273, P = .0003). Moderate correlation existed between PDFF and mMRC (r = -.667, P = .0831), and PDFF and urine Glc4 (r = .6121, P = .0667). Anterior tibialis was in the top quartile of muscle involvement for patients with LOPD. CONCLUSION: In the past, physical therapy assessments alone have been used to track disease progression. Here, we show the clinical utility of WBMRI in quantifying muscle involvement in children with Pompe disease, especially regarding the novel involvement of anterior tibialis in children with LOPD, to better assess baseline muscle burden and mapping disease progression in children treated with ERT.

Higher dosing of alglucosidase alfa improves outcomes in children with Pompe disease: a clinical study and review of the literature.

PURPOSE: Enzyme replacement therapy (ERT) with recombinant human acid-α glucosidase (rhGAA) at standard dose of 20 mg/kg every other week is insufficient to halt the long-term progression of myopathy in Pompe disease. METHODS: We conducted a retrospective study on infantile-onset Pompe disease (IPD) and late-onset Pompe disease (LOPD) patients with onset before age 5 years, ≥12 months of treatment with standard dose ERT, and rhGAA immunogenic tolerance prior to dose escalation. Long-term follow-up of up to 18 years was obtained. We obtained physical therapy, lingual strength, biochemical, and pulmonary assessments as dose was escalated. RESULTS: Eleven patients with IPD (n = 7) or LOPD (n = 4) were treated with higher doses of up to 40 mg/kg weekly. There were improvements in gross motor function measure in 9/10 patients, in lingual strength in 6/6 patients, and in pulmonary function in 4/11. Significant reductions in urinary glucose tetrasaccharide, creatine kinase, aspartate aminotransferase, and alanine aminotransferase were observed at 40 mg/kg weekly compared with lower doses (p < 0.05). No safety or immunogenicity concerns were observed at higher doses. CONCLUSION: Higher rhGAA doses are safe, improve gross motor outcomes, lingual strength, pulmonary function measures, and biochemical markers in early-onset Pompe disease, and should be considered in patients with clinical and functional decline.

Whole-body magnetic resonance imaging in late-onset Pompe disease: Clinical utility and correlation with functional measures.

Whole-body magnetic resonance imaging (WBMRI) has clinical utility in measuring the amount of fatty infiltration in late-onset Pompe disease (LOPD). Muscle strength and function testing also provide valuable insight to the progression of myopathy seen in these patients. The main purpose of this study was to determine how closely muscle strength and functional testing correlate to the amount of fatty infiltration seen on WBMRI. LOPD patients were followed longitudinally and WBMRI, muscle strength testing using the modified Medical Research Council (mMRC) scale, muscle function testing using the Gait, Stairs, Gowers, Chair (GSGC) score, and labs including urinary glucose tetrasaccharide (Glc4) were performed at each visit. The amount of fat seen on WBMRI was quantified using proton density fat fraction (PDFF) and correlated to appropriate muscle strength and functional tests. Nineteen patients with LOPD aged 10 to 67 years were followed for a 1 to 2 year duration. There was a small increase of 1.26% (±2.57%) in overall PDFF per year in patients on ERT. Muscle strength (mMRC) and functional testing (GSGC) correlated highly with PDFF (r = -.7596, P < .0001 and r = .8267, P < .0001, respectively). Time to carry out individual tasks of the GSGC also correlated highly with PDFF of the muscles involved. Glc4 levels were normal on most visits (27/39) despite varying severity of muscle weakness in patients. Muscle strength and GSGC scores correlate highly with PDFF values from WBMRI. They may be used in assessing severity of muscle disease and to follow LOPD patients over time.

Thyroid Screening During Early Pregnancy and the Need for Trimester Specific Reference Ranges: A Cross-Sectional Study in Lahore, Pakistan.

Background Derangements in thyroid hormone levels can cause multiple complications in the mother and the foetus. Thyroid stimulating hormone (TSH) and free thyroxine (free T4 or FT4) levels are used to screen for maternal thyroid dysfunction; these should be compared with population based trimester-specific reference ranges. Our goal was: to determine the prevalence of various thyroid derangements, in early pregnancy, according to the current reference ranges available; to determine the need for trimester specific reference ranges for the local population. Methods A multi-centric, cross sectional population survey was conducted in Lahore, Pakistan. Serum TSH and FT4 levels were measured at the hormone lab of the Pathology department of Combined Military Hospital (CMH) Lahore. The results were entered and analysed using Statistical Package for the Social Sciences (SPSS) version 23.  Results In the 293 women sampled, mean FT4 and TSH levels were 15.03 (±5.62) pmol/L and 2.53 (±6.82) mIU/L respectively. According to the laboratory specific reference ranges, the prevalence of overt hyperthyroidism was 4.10%, (mean TSH= 0.03mIU/L); subclinical hyperthyroidism was 16.38%, (mean TSH= 0.17mIU/L); normal 70.65%, (mean TSH = 1.29mIU/L); subclinical hypothyroidism 4.44%, (mean TSH= 15.11mIU/L); overt hypothyroidism 4.44%, (mean TSH = 20.60mIU/L). Conclusion Our study showed a significant prevalence of thyroid dysfunction in the first trimester of pregnancy, and therefore highlights the need for more rigorous thyroid screening of women, in early pregnancy. There is a need to monitor these women in order to reduce maternal and foetal complications. Trimester specific reference ranges for thyroid hormones need to be developed in Pakistan.

Suppurative Granulomatous Cholecystitis in a Pediatric Chronic Carrier with Salmonella enterica serotype Typhi: A Case Report and Review of Literature.

Bacterial infection of Salmonella enterica serotype Typhi is rare in the United States but endemic in many developing countries. Approximately 3-5% of patients become chronic asymptomatic carriers. We describe an atypical presentation of S. enterica serotype Typhi infection in a 10-year-old male, whose cholecystechtomy and bile culture revealed chronic carrier status despite negative stool tests and the absence of gallstones. The gallbladder showed marked thickening of the wall with an intense suppurative granulomatous reaction.