Peginterferon Alfa-2b or Alfa-2a with Ribavirin for Treatment of Hepatitis C Infection

Background Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared. Methods At 118 sites, patients who had HCV genotype 1 infection and who had not previously been treated were randomly assigned to undergo 48 weeks of treatment with one of three regimens: peginterferon alfa-2b at a standard dose of 1.5 μg per kilogram of body weight per week or a low dose of 1.0 μg per kilogram per week, plus ribavirin at a dose of 800 to 1400 mg per day, or peginterferon alfa-2a at a dose of 180 μg per week plus ribavirin at a dose of 1000 to 1200 mg per day. We compared the rate of sustained virologic response and the safety and adverse-event profiles between the peginterferon alfa-2b regimens and between the standard-dose peginterferon alfa- 2b regimen and the peginterferon alfa-2a regimen. Results Among 3070 patients, rates of sustained virologic response were similar among the regimens: 39.8% with standard-dose peginterferon alfa-2b, 38.0% with low-dose peginterferon alfa-2b, and 40.9% with peginterferon alfa-2a (P=0.20 for standarddose vs. low-dose peginterferon alfa-2b; P=0.57 for standard-dose peginterferon alfa-2b vs. peginterferon alfa-2a). Estimated differences in response rates were 1.8% (95% confidence interval [CI], −2.3 to 6.0) between standard-dose and low-dose peginterferon alfa-2b and −1.1% (95% CI, −5.3 to 3.0) between standard-dose peginterferon alfa-2b and peginterferon alfa-2a. Relapse rates were 23.5% (95% CI, 19.9 to 27.2) for standard-dose peginterferon alfa-2b, 20.0% (95% CI, 16.4 to 23.6) for lowdose peginterferon alfa-2b, and 31.5% (95% CI, 27.9 to 35.2) for peginterferon alfa- 2a. The safety profile was similar among the three groups; serious adverse events were observed in 8.6 to 11.7% of patients. Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12, a sustained virologic response was achieved in 86.2% and 78.7%, respectively. Conclusions In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon– ribavirin regimens or between the two doses of peginterferon alfa-2b. (ClinicalTrials. gov number, NCT00081770.

Divergent elbow dislocation with radial shaft fracture, distal ulnar deformation, and distal radioulnar joint instability: an unclassifiable Monteggia variant

Originally described by Monteggia and later classified by Bado, elbow dislocations with concurrent radial and ulnar shaft fractures with distal radioulnar joint (DRUJ) disruption are considered operative cases with high-energy injurious etiologies. Here, we present an unclassifiable Monteggia variant fracture suffered through a high axial load mechanism in a 47-year-old female. The fracture pattern initially exhibited included a divergent elbow dislocation, a radial shaft fracture, plastic deformation of the distal ulna, and DRUJ instability. Here we describe the pattern in detail, along with definitive treatment and clinical outcome at 1 year follow-up

Patella fracture fixation with a non-locked anterior plating technique: A biomechanical study.

OBJECTIVES: The purpose of this study was to compare the biomechanical attributes of patella fracture fixation with either anterior plating utilizing two parallel, longitudinal 2.0 mm plates technique versus a cannulated screw tension band technique. METHODS: Five matched pairs (ten specimens) of fresh frozen cadavers were utilized. A transverse patella fracture (OTA 34C1.1) was fixed using either two 4.0 mm cannulated screw anterior tension band (CATB) or with two 2.0 mm stainless steel non-locking plates along the anterior cortex secured with 2.4 mm cortical screws traversing the fracture site. Specimens underwent 1000 cycles of simulated active knee range of motion before load to failure destructive testing. RESULTS: During cyclic loading there were no failures in the plate fixation group, and 2 out of 5 specimens catastrophically failed in the CATB group (p = 0.22). Average fracture displacement at the end of fatigue testing was 0.96 mm in the plate fixation group and 2.72 mm in the CATB group (p = 0.18). The specimens that withstood cyclic testing underwent a destructive load. Mean load to failure for the plate fixation specimens was 1286 N, which was not significantly different from the CATB group mean of 1175 N (p = 0.48). The mechanism of failure in the plate fixation cohort was uniformly via a secondary vertical patella fracture around the plates in all five specimens. In the CATB group, the mechanism of failure was via wire elongation and backing out of the screws. CONCLUSIONS: Patella fixation with anterior plating technique statistically performed equivalent to cannulated screw anterior tension band in ultimate load to failure strength and fatigue endurance under cyclical loading. No failures were observed cyclic simulated active range of motion in the anterior plate group. There was a trend towards improved fatigue endurance in the plate fixation group, however this did not reach statistical significance. We believe plate fixation technique represents a low-profile implant option for treatment of transverse patella fractures, which may allow for early active range of motion, and these data support biomechanical equivalency to standard of care

The Role of Computed Tomography in Surgical Planning for Trimalleolar Fracture. A Survey of OTA Members.

OBJECTIVE: Does the additional information provided by computed tomography (CT) alter surgeons\u27 treatment plans for trimalleolar ankle fracture? DESIGN: Prospective. SETTING: Electronic survey. PATIENTS/PARTICIPANTS: Members of the OTA. INTERVENTION: Compare management of trimalleolar ankle fracture before and after CT. MAIN OUTCOME MEASUREMENTS: Compare types of fixation used, indication for fixation, and approach need for fixation before and after CT. RESULTS: Overall, OTA members\u27 operative technique changed in 430 of the 1710 (25.1%) cases after review of the CT images. Of the 430 observations in which the operative technique was altered, the surgeon had initially stated that they would not have requested a CT in 51.2% incidences. When analyzing if CT affected whether or not operative fixation was indicated, a total of 16.3% responses changed. Surgeons were significantly more likely to change from no fixation to fixation (11.5%) than vice versa (4.8%) after reviewing CT imaging. A total of 17.8% of responses changed operative approach after reviewing the CT; 11.7% changed to open reduction internal fixation, whereas 6.1% changed away from open reduction internal fixation. CONCLUSION: A consensus on the ideal treatment of trimalleolar fractures remains elusive, evidenced by a high variation in treatment preference, both before and after CT review. Our results demonstrate with the additional information delineated on CT, a surgeons\u27 operative plan, technique, and approach often change. With greater than 25% of respondents changing their treatment strategy after seeing CT imaging, radiographs alone limited surgeon understanding of fracture pattern. Because of difficulty understanding the posterior fracture fragment, we recommend preoperative CT on all trimalleolar fractures. LEVEL OF EVIDENCE: Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence

Serum Troponin I Assessments in 5- to 30-Year-Olds After BNT162b2 Vaccination.

INTRODUCTION: Rare myocarditis and pericarditis cases have occurred in coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine recipients. Troponin levels, a potential marker of myocardial injury, were assessed in healthy participants before and after BNT162b2 vaccination. METHODS: Vaccine-experienced 12- to 30-year-olds in phase 3 crossover C4591031 Substudy B (NCT04955626) who had two or three prior BNT162b2 30-μg doses were randomized to receive BNT162b2 30 μg followed by placebo, or placebo followed by BNT162b2 30 µg, 1 month apart. A participant subset, previously unvaccinated against COVID-19, in the phase 3 C4591007 study (NCT04816643) received up to three vaccinations (BNT162b2 10 μg or placebo [5- to 11-year-olds]) or open-label BNT162b2 30 μg (12- to 15-year-olds). Blood samples collected pre-vaccination, 4 days post-vaccination, and 1-month post-vaccination (C4591031 Substudy B only) were analyzed. Frequencies of elevated troponin I levels (male, > 35 ng/l; female, > 17 ng/l) were assessed. RESULTS: Percentages of 12- to 30-year-olds (n = 1485) in C4591031 Substudy B with elevated troponin levels following BNT162b2 or placebo receipt were 0.5% and 0.8% before vaccination, 0.7% and 1.0% at day 4, and 0.7% and 0.5% at 1 month, respectively. In Study C4591007 (n = 1265), elevated troponin I levels were observed in 0.2, 0.4, and 0.2% of 5- to 11-year-old BNT162b2 recipients at baseline and 4 days post-dose 2 and 3, respectively; corresponding values in 12- to 15-year-olds were 0.4, 0.4, and 0.7%. No 5- to 11-year-old placebo recipients had elevated troponin levels. No myocarditis or pericarditis cases or deaths were reported. CONCLUSIONS: Among 5- to  < 30-year-olds in both studies, troponin levels were rarely elevated (≤ 1.0%) and similar before and post-vaccination; troponin levels were also similar between BNT162b2 and placebo in 12- to 30-year-old and 5- to 11-year-old recipients in the respective studies. No myocarditis or pericarditis cases were reported. These findings did not provide evidence that BNT162b2 causes troponin elevations. No utility of routine measurement of troponin levels in asymptomatic BNT162b2 recipients was identified

Safety and immunogenicity of two RNA-based covid-19 vaccine candidates

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide. Multiple vaccine candidates are under development, but no vaccine is currently available. Interim safety and immunogenicity data about the vaccine candidate BNT162b1 in younger adults have been reported previously from trials in Germany and the United States. METHODS: In an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted in the United States, we randomly assigned healthy adults 18 to 55 years of age and those 65 to 85 years of age to receive either placebo or one of two lipid nanoparticle-formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor-binding domain; or BNT162b2, which encodes a membrane-anchored SARS-CoV-2 full-length spike, stabilized in the prefusion conformation. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. Trial groups were defined according to vaccine candidate, age of the participants, and vaccine dose level (10 μg, 20 μg, 30 μg, and 100 μg). In all groups but one, participants received two doses, with a 21-day interval between doses; in one group (100 μg of BNT162b1), participants received one dose. RESULTS: A total of 195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1, particularly in older adults. In both younger and older adults, the two vaccine candidates elicited similar dose-dependent SARS-CoV-2-neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples. CONCLUSIONS: The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults, added to earlier interim safety and immunogenicity data regarding BNT162b1 in younger adults from trials in Germany and the United States, support the selection of BNT162b2 for advancement to a pivotal phase 2-3 safety and efficacy evaluation