METHODS: We conducted a retrospective review of childhood primary sclerosing cholangitis-inflammatory bowel disease from three tertiary centers in Singapore and Malaysia.
RESULTS: Of 24 patients (boys, 58%; median age at diagnosis: 6.3 years) with primary sclerosing cholangitis-inflammatory bowel disease (ulcerative colitis, n = 21; Crohn's disease, n = 1; undifferentiated, n = 2), 63% (n = 15) were diagnosed during follow-up for colitis, and 21% (n = 5) presented with acute or chronic hepatitis, 17% (n = 4) presented simultaneously. Disease phenotype of liver involvement showed 79% had sclerosing cholangitis-autoimmune hepatitis overlap, 54% large duct disease, and 46% small duct disease. All patients received immunosuppression therapy. At final review after a median [±S.D.] duration follow-up of 4.7 [±3.8] years, 12.5% patients had normal liver enzymes, 75% persistent disease, and 12.5% liver failure. The proportion of patients with liver cirrhosis increased from 13% at diagnosis to 29%; 21% had portal hypertension, and 17% had liver dysfunction. One patient required liver transplant. Transplant-free survival was 95%. For colitis, 95% had pancolitis, 27% rectal sparing, and 11% backwash ileitis at initial presentation. At final review, 67% patients had quiescent bowel disease with immunosuppression. One patient who had UC with pancolitis which was diagnosed at 3 years old developed colorectal cancer at 22 years of age. All patients survived.
CONCLUSIONS: Liver disease in primary sclerosing cholangitis-inflammatory bowel disease in Asian children has variable severity. With immunosuppression, two-thirds of patients have quiescent bowel disease but the majority have persistent cholangitis and progressive liver disease.
METHODS: This prospective study included a derivation cohort before validation in multiple international cohorts. The derivation cohort was a cross-sectional, multicentre study of patients aged 18 years or older, scheduled to have a liver biopsy for suspicion of NAFLD at seven tertiary care liver centres in England. This was a prespecified secondary outcome of a study for which the primary endpoints have already been reported. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and controlled attenuation parameter (CAP) measured by FibroScan device were combined with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or AST:ALT ratio. To identify those patients with NASH, an elevated NAS, and significant fibrosis, the best fitting multivariable logistic regression model was identified and internally validated using boot-strapping. Score calibration and discrimination performance were determined in both the derivation dataset in England, and seven independent international (France, USA, China, Malaysia, Turkey) histologically confirmed cohorts of patients with NAFLD (external validation cohorts). This study is registered with ClinicalTrials.gov, number NCT01985009.
FINDINGS: Between March 20, 2014, and Jan 17, 2017, 350 patients with suspected NAFLD attending liver clinics in England were prospectively enrolled in the derivation cohort. The most predictive model combined LSM, CAP, and AST, and was designated FAST (FibroScan-AST). Performance was satisfactory in the derivation dataset (C-statistic 0·80, 95% CI 0·76-0·85) and was well calibrated. In external validation cohorts, calibration of the score was satisfactory and discrimination was good across the full range of validation cohorts (C-statistic range 0·74-0·95, 0·85; 95% CI 0·83-0·87 in the pooled external validation patients' cohort; n=1026). Cutoff was 0·35 for sensitivity of 0·90 or greater and 0·67 for specificity of 0·90 or greater in the derivation cohort, leading to a positive predictive value (PPV) of 0·83 (84/101) and a negative predictive value (NPV) of 0·85 (93/110). In the external validation cohorts, PPV ranged from 0·33 to 0·81 and NPV from 0·73 to 1·0.
INTERPRETATION: The FAST score provides an efficient way to non-invasively identify patients at risk of progressive NASH for clinical trials or treatments when they become available, and thereby reduce unnecessary liver biopsy in patients unlikely to have significant disease.
FUNDING: Echosens and UK National Institute for Health Research.
METHODS: Non-interventional multicenter historical cohort study of intravitreal ranibizumab use for nAMD in routine clinical practice between April 2010 and April 2013. Eligible patients were diagnosed with nAMD, received at least one intravitreal ranibizumab injection during the study period, and had been observed for a minimum of 1 year (up to 3 years). Reimbursement scenarios were defined as self-paid, partially-reimbursed, and fully-reimbursed.
RESULTS: More than three-fourths (n = 2521) of the analysis population was partially-reimbursed for ranibizumab, while 16.4% (n = 532) was fully-reimbursed, and 5.8% was self-paid (n = 188). The average annual ranibizumab injection frequency was 4.1 injections in the partially-reimbursed, 4.7 in the fully-reimbursed and 2.6 in the self-paid populations. The average clinical monitoring frequency was estimated to be 6.7 visits/year, with similar frequencies observed across reimbursement categories. On average, patients experienced VA reduction of -0.7 letters and a decrease in CRT of -44.4 μm. The greatest mean CRT change was observed in the self-paid group, with -92.6 μm.
CONCLUSIONS: UNCOVER included a large, heterogeneous ranibizumab-treated nAMD population in real-world settings. Patients in all reimbursement scenarios attained vision stability on average, indicating control of disease activity.
METHODS: All the patients with end-stage heart failure (ESHF) and implanted LVAD who underwent LSG from2013 to January 2017 were studied.
RESULTS: Seven patients with end stage heart failure (ESHF) and implanted LVAD were included. The median age and median preoperative BMI were 39 years (range: 26-62) and 43.6 kg/m2 (range 36.7-56.7), respectively. The median interval between LVAD implantation and LSG was 38 months (range 15-48). The median length of hospital stay was 9 days (rang: 6-23) out of which 4 patients had planned postoperative ICU admission. Thirty-day complications were noted in 5 patients (3 major and 2 minor) without any perioperative mortality. The median duration of follow-up was 24 months (range 2-30). At the last available follow-up, the median BMI, %EWL, and %TWL were 37 kg/m2, 47%, and 16%, respectively. The median LVEF before LSG and at the last follow-up point (before heart transplant) was 19% (range 15-20) and 22% (range, 16-35), respectively. In addition, the median NYHA class improved from 3 to 2 after LSG. Three patients underwent successful heart transplantations.
CONCLUSION: Patients with morbid obesity, ESHF, and implanted LVAD constitute a high-risk cohort. Our results with 7 patients and result from other studies (19 patients) suggested that bariatric surgery may be a reasonable option for LVAD patients with severe obesity. Bariatric surgery appears to provide significant weight loss in these patients and may improve candidacy for heart transplantation.
PURPOSE: Information regarding mediators of differences in bone mineral density (BMD) among Asian ethnicities are limited. Since the majority of hip fractures are predicted to be from Asia, differences in BMD in Asian ethnicities require further exploration. We compared BMD among the Chinese, Malay, or Indian ethnicities in Singapore, aiming to identify potential mediators for the observed differences.
METHODS: BMD of 1201 women aged 45-69 years was measured by dual-energy X-ray absorptiometry. We examined the associations between ethnicity and BMD at both sites, before and after adjusting for potential mediators measured using standardized questionnaires and validated performance tests.
RESULTS: Chinese women had significantly lower femoral neck BMD than Malay and Indian women. Of the more than 20 variables examined, age, body mass index, and height accounted for almost all the observed ethnic differences in femoral neck BMD between Chinese and Malays. However, Indian women still retained 0.047 g/cm2 (95% CI, 0.024, 0.071) higher femoral neck BMD after adjustment, suggesting that additional factors may contribute to the increased BMD in Indians. Although no crude ethnic differences in lumbar spine BMD were observed, adjusted regression model unmasked ethnic differences, wherein Chinese women had 0.061(95% CI, - 0.095, 0.026) and 0.065 (95% CI, - 0.091, 0.038) g/cm2 higher lumbar spine BMD compared to Malay and Indian women, respectively.
CONCLUSION: BMD in middle-aged Asian women differ by ethnicity and site. Particular attention should be paid to underweight women of Chinese ethnic origin, who may be at highest risk of osteoporosis at the femoral neck and hence hip fractures.
METHODS: Detailed phenotyping and next-generation sequencing (panel and exome).
RESULTS: Our analysis revealed 224 pathogenic/likely pathogenic variants (54 (24%) of which are novel) in 123 genes with established or tentative links to skeletal dysplasia. In addition, we propose 5 genes as candidate disease genes with suggestive biological links (WNT3A, SUCO, RIN1, DIP2C, and PAN2). Phenotypically, we note that our cohort spans 36 established phenotypic categories by the International Skeletal Dysplasia Nosology, as well as 18 novel skeletal dysplasia phenotypes that could not be classified under these categories, e.g., the novel C3orf17-related skeletal dysplasia. We also describe novel phenotypic aspects of well-known disease genes, e.g., PGAP3-related Toriello-Carey syndrome-like phenotype. We note a strong founder effect for many genes in our cohort, which allowed us to calculate a minimum disease burden for the autosomal recessive forms of skeletal dysplasia in our population (7.16E-04), which is much higher than the global average.
CONCLUSION: By expanding the phenotypic, allelic, and locus heterogeneity of skeletal dysplasia in humans, we hope our study will improve the diagnostic rate of patients with these conditions.
CONCLUSION: An 8-week duration of treatment with LDV/SOF is highly effective in properly selected patients; greater use of this regimen is recommended. (Hepatology 2017;65:1094-1103).
OBJECTIVE: This study aimed to investigate the effectiveness and safety of sulfonylurea therapy in Chinese NDM patients during infancy before genetic testing results were available.
METHODS: The medical records of NDM patients with their follow-up details were reviewed and molecular genetic analysis was performed. Sulfonylurea transfer regimens were applied in patients diagnosed after May 2010, and glycemic status and side effects were evaluated in each patient.
RESULTS: There were 23 NDM patients from 22 unrelated families, 10 had KCNJ11 mutations, 3 harbored ABCC8 mutations, 1 had INS mutations, 4 had chromosome 6q24 abnormalities, 1 had a deletion at chromosome 1p36.23p36.12, and 4 had no genetic abnormality identified. Sixteen NDM infants were treated with glyburide at an average age of 49 days (range 14-120 days) before genetic confirmation. A total of 11 of 16 (69%) were able to successfully switch to glyburide with a more stable glucose profile. The responsive glyburide dose was 0.51 ± 0.16 mg/kg/d (0.3-0.8 mg/kg/d), while the maintenance dose was 0.30 ± 0.07 mg/kg/d (0.2-0.4 mg/kg/d). No serious adverse events were reported.
CONCLUSIONS: Molecular genetic diagnosis is recommended in all patients with NDM. However, if genetic testing results are delayed, sulfonylurea therapy should be considered before such results are received, even in infants with newly diagnosed NDM.