A Large Population Histology Study Showing the Lack of Association between ALT Elevation and Significant Fibrosis in Chronic Hepatitis B

OBJECTIVE: We determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. METHODS: From 1994 to 2008, liver biopsy was performed on 319 treatment-naive CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis. RESULTS: 211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5%) HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading >/= 7 or fibrosis score >/= 3). There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women) and patients with a normal ALT but exceeding the Prati criteria (p = 0.024). Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively). HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively). An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345) and -negative (p = 0.544) disease. There was no significant difference in fibrosis staging among ALT 1-2 x upper limit of normal (ULN) and > x 2 ULN for both HBeAg-positive (p = 0.098) and -negative (p = 0.838) disease. CONCLUSION: An elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold.published_or_final_versio

Contribution of glibenclamide-sensitive, ATP-dependent K+ channel activation to acetophenone analogues-mediated in vitro pulmonary artery relaxation of rat

Compared to the currently available therapeutic drugs for peripheral vascular diseases, agents that are selective for relaxing pulmonary circulation are scarce. The present study was undertaken, using isometric tension change measurement and whole-cell patch-clamp electrophysiology methods, to evaluate the vascular relaxation effect and the underlying mechanisms involved of two naturally found alkaloids: paeonol (2-hydroxy-4-methoxy-acetophenone), acetovanillone (4-hydroxy-3-methoxy-acetophenone) and the non-substituted analogue acetophenone on pulmonary artery of Sprague-Dawley rats. Cumulative administration (3 μM–1 mM) of acetophenone analogues resulted in a concentration-dependent relaxation of phenylephrine (1 μM) pre-contracted pulmonary artery. A relative order of inhibitory potency, estimated by comparing the concentration at which a 50% relaxation of phenylephrine-induced contraction observed was: acetovanillone > paeonol > acetophenone. Endothelial denudation and inhibition of nitric oxide synthase (with 20 μM NG-nitro-l-arginine methyl-ester) only moderately suppressed (17.6 ± 4.2%) acetovanillone- but not paeonol- or acetophenone-mediated maximum relaxation. Glibenclamide (3 μM, an ATP-sensitive K+ (IKATP) channel blocker) markedly attenuated all acetophenone analogues-mediated endothelium-independent relaxation. Neither cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL 12330A, 10 μM), iberiotoxin (300 nM), 4-aminopyridine (3 mM), (±)-propranolol (1 μM, a non-selective β-adrenoceptor blocker) nor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (3 μM, a guanylate cyclase inhibitor) altered endothelium-independent relaxation. In electrophysiological experiments using single pulmonary artery smooth muscle cells, acetovanillone, paeonol, acetophenone and cromakalim activated glibenclamide-sensitive, IKATP channels. In conclusion, our results demonstrate that acetophenone analogues caused pulmonary artery relaxation through opening of IKATP channels. In addition, acetovanillone-mediated pulmonary artery relaxation is partly depended on nitric oxide released from endothelium

Neurosensory Rehabilitation and Olfactory Network Recovery in Covid-19-related Olfactory Dysfunction

Non-conductive olfactory dysfunction (OD) is an important extra-pulmonary manifestation of coronavirus disease 2019 (COVID-19). Olfactory bulb (OB) volume loss and olfactory network functional connectivity (FC) defects were identified in two patients suffering from prolonged COVID-19-related OD. One patient received olfactory treatment (OT) by the combination of oral vitamin A and smell training via the novel electronic portable aromatic rehabilitation (EPAR) diffusers. After four-weeks of OT, clinical recuperation of smell was correlated with interval increase of bilateral OB volumes [right: 22.5 mm3 to 49.5 mm3 (120%), left: 37.5 mm3 to 42 mm3 (12%)] and improvement of mean olfactory FC [0.09 to 0.15 (66.6%)]

One-year mortality in displaced intracapsular hip fractures and associated risk: a report of Chinese-based fragility fracture registry

Abstract Background The purpose of this registry-based retrospective study was to investigate the risk factors related to one-year mortality in displaced intracapsular fragility hip fracture patients. Methods Patients were screened from the Fragility Fracture Registry. Inclusion criterion was displaced intracapsular hip fracture patients with atypical or pathological fractures excluded. One-year mortality was investigated against risk factors including age, gender, past medical history, pre-fracture mobility (PFM), pre-operation ASA grade, delayed surgery over 48 h, post-surgical complications, and length of stay at acute orthopedic ward (LOS). Results A total of 1050 patients were included for further analysis. Gross one-year mortality was 14.9%. One-year mortality was significantly higher in patients who received non-operative treatment and those who received surgery but delayed over 48 h after admission (both p <  0.001). Male gender (OR = 2.708), advanced age (OR = 1.359), higher risk ASA grades (III to V) (OR = 1.990), past history of gastrointestinal disease (OR = 1.671), and renal impairment (OR = 1.984) were related to higher one-year mortality. The mortality of patients in PFM grade 3 and LOS group 3 was significantly higher (OR = 2.240 and 1.722, respectively). Conclusions Higher age, male gender, past gastrointestinal disease and renal impairment, ASA grade over 3, indoor confined pre-fracture ambulatory, and stay at hospital over 15 days were risk factors related to higher one-year mortality in surgically treated displaced intracapsular hip fracture patients. A multi-disciplinary approach is advised to patients identified with these risks factors and co-managed by orthopedic surgeons, geriatricians, and fracture liaison nurses

Mitochondrial diseases in Hong Kong: prevalence, clinical characteristics and genetic landscape

Abstract Objective To determine the prevalence of mitochondrial diseases (MD) in Hong Kong (HK) and to evaluate the clinical characteristics and genetic landscape of MD patients in the region. Methods This study retrospectively reviewed the phenotypic and molecular characteristics of MD patients from participating public hospitals in HK between January 1985 to October 2020. Molecularly and/or enzymatically confirmed MD cases of any age were recruited via the Clinical Analysis and Reporting System (CDARS) using relevant keywords and/or International Classification of Disease (ICD) codes under the HK Hospital Authority or through the personal recollection of treating clinicians among the investigators. Results A total of 119 MD patients were recruited and analyzed in the study. The point prevalence of MD in HK was 1.02 in 100,000 people (95% confidence interval 0.81–1.28 in 100,000). 110 patients had molecularly proven MD and the other nine were diagnosed by OXPHOS enzymology analysis or mitochondrial DNA depletion analysis with unknown molecular basis. Pathogenic variants in the mitochondrial genome (72 patients) were more prevalent than those in the nuclear genome (38 patients) in our cohort. The most commonly involved organ system at disease onset was the neurological system, in which developmental delay, seizures or epilepsy, and stroke-like episodes were the most frequently reported presentations. The mortality rate in our cohort was 37%. Conclusion This study is a territory-wide overview of the clinical and genetic characteristics of MD patients in a Chinese population, providing the first available prevalence rate of MD in Hong Kong. The findings of this study aim to facilitate future in-depth evaluation of MD and lay the foundation to establish a local MD registry