Hepatitis B virus and hepatitis C virus affect mitochondrial function through different metabolic pathways, explaining virus-specific clinical features of chronic hepatitis.

BACKGROUND: Hepatitis C virus (HCV) and hepatitis B virus (HBV) cause chronic hepatitis with important clinical differences. HCV causes hepatic steatosis and insulin resistance, while HBV confers increased risk of liver cancer. We hypothesised these differences may be due to virus-specific effects on mitochondrial function. METHODS: Seahorse technology was utilised to investigate effects of virus infection on mitochondrial function. Cell based assays were used to measure mitochondrial membrane potential and quantify pyruvate and lactate. Mass spectrometry was performed on mitochondria isolated from HBV expressing, HCV infected and control cells cultured with isotope-labelled amino acids, to identify proteins with different abundance. Altered expression of key mitochondrial proteins was confirmed by real time PCR and western blot. RESULTS: Reduced mitochondrial function and ATP production were observed with HCV infection and HBV expression. HCV impairs glycolysis and reduces expression of genes regulating fatty acid oxidation, promoting lipid accumulation. HBV causes lactate accumulation by increasing expression of lactate dehydrogenase A, which converts pyruvate to lactate. In HBV expressing cells there was marked enrichment of pyruvate dehydrogenase kinase, inhibiting conversion of pyruvate to acetyl-CoA and thereby reducing its availability for mitochondrial oxidative phosphorylation. CONCLUSIONS: HCV and HBV impair mitochondrial function and reduce ATP production. HCV reduces acetyl-CoA availability for energy production by impairing fatty acid oxidation, causing lipid accumulation and hepatic steatosis. HBV has no effect on fatty oxidation but reduces acetyl-CoA availability by disrupting pyruvate metabolism. This promotes lactic acidosis and oxidative stress, increasing the risk of disease progression and liver cancer.

Unicompartmental Knee Arthroplasty Patients Have Lower Joint Awareness and Higher Function at 5 Years Compared to Total Knee Arthroplasties: A Matched Comparison.

BACKGROUND: The purpose of this study was to evaluate postoperative outcomes at minimum 5-year follow-up in patients following unicompartmental knee arthroplasty (UKA) compared to a matched cohort of total knee arthroplasty (TKA) patients. METHODS: Patients who had primarily medial compartment osteoarthritis (OA) who met criteria for medial UKA underwent TKA or medial UKA between 2014 and 2015 at a single institution, matched for age, sex, and body mass index. There were 127 UKAs in 120 patients and 118 TKAs in 116 patients included with minimum 5-year follow-up (range, 6 to 8). Mean age was 69 years (range, 59 to 79) and 71 years (range, 62 to 80) in the UKA and TKA groups, respectively (P = .049). RESULTS: Patients who underwent UKA had significantly higher mean (±SD) Forgotten Joint Scores (87 ± 20 versus 59 ± 34, P < .001); higher Knee Society Scores (88 ± 14 versus 75 ± 21, P < .001); and lower Numeric Pain Rating Scores (0.8 ± 1.6 versus 1.9 ± 2.2, P < .001). Survivorship free from all-cause revision was 96% (95% CI = 93%-99%) and 99% (95% CI = 97%-100%) at 5 years for TKA and UKA, respectively (P = .52). There were 8 both component revisions in the TKA group within 5 years from the date of surgery and 2 UKA conversions to TKA after 5-year follow-up. CONCLUSION: Patients who have medial compartment OA and underwent UKA had significantly lower joint awareness, decreased pain, improved function, and higher satisfaction compared to matched TKA patients at minimum 5-year follow-up while maintaining excellent survivorship.

A systematic review of patient-reported outcome measures in paediatric endocrinology.

CONTEXT: Patient reported outcome measures (PROMs) are useful tools in paediatric endocrinology to gauge health status in children, especially since they are often unable to clearly communicate it themselves. We aimed to systematically search and appraise all available PROMs relevant to paediatric endocrinology and provide a curated resource for health professionals to utilise. EVIDENCE ACQUISITION: We identified PROMs in paediatric endocrinology by systematically searching the Cochrane Library, MEDLINE, World Health Organisation International Clinical Trials Registry Platform, and the Cumulative Index to Nursing and Allied Health Literature on May 20, 2022. Additional studies were located through hand searching and content area expert contributions. We assessed the quality of each PROM using the COSMIN risk of bias checklist. EVIDENCE SYNTHESIS: We identified 5003 papers in the initial search. After applying exclusion criteria we included seven PROMs in the review. Six PROMs were specific to Type I Diabetes and one to Hypothyroidism. We gave all studies an overall COSMIN score of 'inadequate' due to poorly detailed PROM development. CONCLUSION: The scope and quality of PROMs in paediatric endocrinology is limited. Further research and development of PROM tools are required in paediatric endocrinology to allow for improved patient care.

High Satisfaction and Activity Levels After Total Hip Arthroplasty in Patients Under Age 21.

BACKGROUND: With improved materials and bearing surfaces, the use of total hip arthroplasty (THA) in young patients is increasing. Functional outcomes and activity level are particularly relevant in this higher-demand patient population. There is a paucity of data on patient-reported outcomes and activity levels after THA in extremely young (<21 years old) patients. METHODS: We identified 196 patients (222 hips) who underwent THA at age <21 years at our institution from 1982 to 2018. After applying exclusion criteria, 113 of 160 (70.6%) patients (129 hips) were available for follow-up. Patient activity levels and functional outcomes were evaluated using the UCLA activity score, Forgotten Joint Score (FJS), Hip Disability and Osteoarthritis Outcome Score for Joint Replacement, and a validated 5-question satisfaction survey. Survivorship and reasons for revision were recorded. RESULTS: The mean age at surgery was 17.0 ± 2.8 years, and the mean follow-up was 13.2 years (range 2-38 years). The most common indications for THA were osteonecrosis (34%) and juvenile idiopathic arthritis (30%). The mean UCLA activity score was 5.9 ± 2.0, and 64% of patients reported a score ≥6. The mean FJS was 57.9 ± 31.0. The mean Hip Disability and Osteoarthritis Outcome Score for Joint Replacement score was 84.6 ± 16.6. Ninety percent of patients reported that they were very or somewhat satisfied with their surgery. At final follow-up, 27 of 129 (20.9%) hips had undergone revision surgery. CONCLUSION: THA performed in patients under 21 years of age with end-stage hip disease allows for high levels of activity and satisfaction postoperatively, with most patients being able to participate in moderate recreational activities. These data may be useful for surgeons in planning for and counseling extremely young patients indicated for THA.

Post-concussion Vulnerability to Transient Global Amnesia.

Few studies have investigated transient global amnesia (TGA) in the context of a concussion and the concussion sequelae following TGA. Here we review the case of a 43-year-old male with onset of transient global anterograde and retrograde amnesia 22 days after a sustained concussion. The patient's head CT, MRI of brain, and EEG were reported normal, and the patient regained full cognitive function 8 h after the TGA episode, with no recollection of the conspiring events. Following the TGA episode, the patient experienced notable worsening of concussive symptoms, including headache, head pressure, anxiety, neck pain, feeling slowed down, fogginess, not feeling right, difficulty remembering, and fatigue. The patient remained symptomatic for 32 days after the TGA episode. We suggest that a lingering window of post-concussion cerebral vulnerability, which may extend beyond clinical recovery, could lead to increased susceptibility to acute cognitive deficits, such as TGA.

Corneal inflammatory events with daily silicone hydrogel lens wear.

PURPOSE: This study aimed to determine the probability and risk factors for developing a corneal inflammatory event (CIE) during daily wear of lotrafilcon A silicone hydrogel contact lenses. METHODS: Eligible participants (n = 218) were fit with lotrafilcon A lenses for daily wear and followed up for 12 months. Participants were randomized to either a polyhexamethylene biguanide-preserved multipurpose solution or a one-step peroxide disinfection system. The main exposures of interest were bacterial contamination of lenses, cases, lid margins, and ocular surface. Kaplan-Meier (KM) plots were used to estimate the cumulative unadjusted probability of remaining free from a CIE, and multivariate Cox proportional hazards regression was used to model the hazard of experiencing a CIE. RESULTS: The KM unadjusted cumulative probability of remaining free from a CIE for both lens care groups combined was 92.3% (95% confidence interval [CI], 88.1 to 96.5%). There was one participant with microbial keratitis, five participants with asymptomatic infiltrates, and seven participants with contact lens peripheral ulcers, providing KM survival estimates of 92.8% (95% CI, 88.6 to 96.9%) and 98.1% (95% CI, 95.8 to 100.0%) for remaining free from noninfectious and symptomatic CIEs, respectively. The presence of substantial (>100 colony-forming units) coagulase-negative staphylococci bioburden on lid margins was associated with about a five-fold increased risk for the development of a CIE (p = 0.04). CONCLUSIONS: The probability of experiencing a CIE during daily wear of lotrafilcon A contact lenses is low, and symptomatic CIEs are rare. Patient factors, such as high levels of bacterial bioburden on lid margins, contribute to the development of noninfectious CIEs during daily wear of silicone hydrogel lenses.