Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Comparison of outcomes of mixed unicompartmental knee arthroplasty and total knee arthroplasty in the treatment of medial osteoarthritis of the knee / 中国骨伤

OBJECTIVE@#To evaluate outcomes of mixed unicompartmental knee arthroplasty(UKA) and total knee arthroplasty(TKA) in the treatment of medial osteoarthritis(OA) of the knee.@*METHODS@#Retrospective analysis of 156 patients, 44 males and 112 females, aged from 50 to 75 years old with an average of(58.76±4.97) years old, who underwent knee arthroplasty from October 2017 to October 2019. The patients were divided into two groups:81 cases(81 knees) underwent TKA, including 23 males and 58 females, aged from 51 to 75 years old with an average of (58.60±5.01) years old, and 75 case (75 knees) underwent UKA with mixed phase 3 Oxford, including 21 males and 54 females, aged from 50 to 72 years old with an average of (58.92±4.95) years old. The two groups were compared regarding to the clinical outcomes, assessed using surgical information and complications, American Knee Society score(AKSS) clinical score and functional score. Radiographs were assessed using hip-knee-ankle angle(HKA), tibial component valgus/varus angle(TCVA), tibial component posterior slope angle(TCPSA), femoral component valgus/varus angle(FCVA), femoral component posterior slope angle(FCPSA), looking for bearing dislocation, prosthesis loosening, progression of OA in lateral compartment.@*RESULTS@#Intraoperative bleeding, operative time and hospital days were significantly better in the UKA group than in the TKA group (P<0.05), and there were no postoperative complications in either group. Patients in both groups were enrolled with an average follow-up time of (38.01±8.90) months, ranged from 24 to 54 months. AKSS functional, AKSS clinical, HKA in both groups significantly improved at the final follow-up compared with those before operation. At the final follow-up, the UKA group was significantly better than the TKA group in AKSS functional and AKSS clinical, whereas HKA in the TKA group was better. At the final follow-up. TCVA and FCVA between the two groups were not significantly different, while TCPSA and FCPSA in the UKA group were significantly greater than the TKA group. No signs of progression of OA to the lateral compartment were observed.@*CONCLUSION@#Mixed phase 3 Oxford UKA in medial unicompartmental knee osteoarthritis was considerably better than TKA for less blood loss, shorter operation time, shorter hospital stay, rapid postoperative recovery, helping achieve satisfactory function, provided satisfactory outcome.

Are vaccines effective and safe for the prevention of COVID-19 infections? A living systematic review

@#Introduction. In the attempt to control the spread of the disease and the pandemic, numerous COVID-19 vaccines are in development. A review of the evidence on their efficacy and safety are critical. Methods. A search for trials was done using the COVID-19 Living OVerview of Evidence (L·OVE) platform. We also searched for relevant authorization documents and trial reports for COVID-19 vaccines of the US-Food and Drug Authority (US-FDA), the European Medicines Agency (EMA), the United Kingdom Medicines and Health Products Regulatory Agency (MHRA), and the WHO website. We included studies that fulfilled the following inclusion criteria: population – humans; intervention – COVID-19 vaccines; comparison – control or placebo; outcomes – efficacy and adverse events; methods – phase 3 randomized trials. Two reviewers independently screened the reports, assessed the methodological quality, and extracted the data on the trial characteristics and results on vaccine efficacy and safety. The date of last search was March 11, 2021. Results. Interim results of trials investigating five vaccines were identified and included in the review. All five vaccines demonstrated satisfactory vaccine efficacy (VE) against symptomatic COVID-19 infection among adults in the short term with moderate certainty of evidence: BNT162b2, VE 95% (95% CI 90.3, 97.6); mRNA-1273, VE 93.6% (95% CI 88.6, 96.5); ChAdOx1, VE 66.7% (95% CI 57.4, 74.0), Gam-COVID-Vac, VE 91.1% (95% CI 83.6, 95.1); and Ad26.CoV2.S, VE 67.2% (95% CI 59.3, 73.7). Data on the efficacy against severe COVID-19 infection and asymptomatic COVID-19 infection are still inconclusive, except for Ad26.CoV2.S, which demonstrated good efficacy in preventing moderate and/or severe COVID-19 infection and acceptable protection against asymptomatic COVID-19 infection 28 days after vaccination (moderate certainty of evidence). Efficacy data on preventing death from COVID-19 infection are still inconclusive. Very limited phase 3 trial data is available to inform vaccine efficacy against the different variants of SARS-CoV-2. Vaccination with these five vaccines was associated with higher adverse reactions compared to control. These adverse events, due to reactions to the vaccines, were mild to moderate and of short duration. Available evidence on vaccine efficacy and safety is limited, mainly due to the short follow up and the small sample size of specific populations. Conclusion. BNT162b2, mRNA-1273, ChAdOx1, Gam-COVID-Vac and Ad26.CoV.S vaccines demonstrated satisfactory vaccine efficacy against symptomatic COVID-19 infection among adults in the short term with moderate certainty of evidence. Data on the efficacy against severe COVID-19 infection, asymptomatic COVID-19 infection, and death from COVID-19 infection are still inconclusive. Long-term efficacy and safety data, and data on the efficacy against variant strains of SARS-CoV-2 are still lacking.

Conducción anestésica de un paciente con bloqueo de rama izquierda agudo / Anesthetic approach of a patient with acute left-branch block

Introducción: El bloqueo de rama izquierda del haz de His dependiente de la frecuencia cardíaca no es una entidad común en la práctica clínica del anestesiólogo, sino que se presenta como consecuencia de enfermedades cardiacas o no que ocurren por lentitud de la frecuencia ventricular sobre todo, con enfermedad de las arterias coronarias planteadas solo como diagnóstico después de haberlas descartado. Objetivo: Describir el manejo clínico-anestésico de una paciente que presentó bloqueo de rama izquierda del haz de His para cirugía torácica electiva por tumor de mediastino. Desarrollo: Se presenta un caso clínico de una paciente con bloqueo de rama izquierda dependiente de la frecuencia cardiaca que se anunció para cirugía del tórax, sin historia previa de coronariopatía. La cirugía trascurrió sin complicaciones y con buenos resultados. Conclusiones: el bloque de rama izquierda dependiente de la frecuencia cardiaca es una entidad rara y un diagnóstico excluyente de otras entidades cardiovasculares o no como la isquemia miocárdica. Un adecuado manejo intraoperatorio del paciente proporciona excelentes resultados sin traducción clínica ni complicaciones(AU)

Introduction: Rate-dependent left bundle branch block is not a rare entity for the clinical practice in anesthesiology, but appears as a consequence of heart diseases or not always due to slowness in atrial frequency above all, with coronary artery diseases diagnosed only after their being ruled out. Objective: To describe the clinical-anesthetic management of a patient who presented left bundle branch block for elective thoracic surgery due to mediastinal tumor. Findings: We present a clinical case of a female patient with rate-dependent left bundle branch block who was announced for thoracic surgery, without a previous history of coronary artery disease. The surgery proceeded without complications and with positive outcome. Conclusions: Rate-dependent left-branch block is a rare entity and a diagnosis ruling out other cardiovascular entities or not, such as myocardial ischemia. An adequate intraoperative management of the patient provides excellent outcome without clinical translation or complications(AU)

Efficacy and Safety of Teriflunomide in Chinese Patients with Relapsing Forms of Multiple Sclerosis: A Subgroup Analysis of the Phase 3 TOWER Study / 中华医学杂志(英文版)

Background@#Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study.@*Methods@#TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54).@*Results@#Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning.@*Conclusions@#Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China.@*Trial Registration@#ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.

Effect of accuracy of phase 3 Oxford prosthesis positioning on short-term effectiveness of unicompartmental knee arthroplasty / 中国修复重建外科杂志

Objective: To investigate the effect of accuracy of phase 3 Oxford prosthesis positioning on short-term effectiveness of unicompartmental knee arthroplasty (UKA). Methods: The clinical data of 26 patients (26 knees) who were treated with UKA between September 2015 and November 2015 was retrospectively analyzed. The single-peg Oxford prosthesis was implanted in 15 patients (single-peg group), and twin-peg Oxford prosthesis was implanted in 11 patients (twin-peg group). There was no significant difference in gender, age, body mass index, Kellgren-Lawrence grading, and preoperative Hospital for Special Surgery (HSS) scores between 2 groups ( P>0.05). HSS, knee society score (KSS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and Oxford knee score (OKS) were used to evaluate the knee function. Radiographic criteria for Oxford UKA was used to evaluate the prosthesis position. The reason and treatment of bearing dislocations were recorded. Results: All patients were followed up with mean follow-up time of 26.2 months in single-peg group (range, 24-27 months) and 25.2 months in twin-peg group (range, 24-26 months). The bearing dislocation occurred in 2 cases of twin-peg group during follow-up. At last follow-up, there was no significant difference in HSS, WOMAC, OKS, and KSS scores between 2 groups ( P>0.05). There was no significant difference in radiographic scores of femoral component, tibial component, and overall components between 2 groups ( P>0.05). No significant correlation was found between radiographic scores and postoperative functional outcome in 2 groups ( P>0.05). Conclusion: Within a safe range, the accuracy of phase 3 Oxford prosthesis positioning has limited influence on the short-term functional outcome.

Characteristics of phase 3-like activity and rebound excitation triggered by hexamethonium and atropine administration in the ovine small bowel.

Administration of hexamethonium (Hx) and atropine inhibits myoelectric and motor activity and then evokes a stimulatory effect called rebound excitation (RE) in the ovine small bowel. RE has not been precisely characterized so far and it is possible that it is composed of different types of motility. This study was thus devoted to characterizing these excitatory changes in the myoelectric and motor activity of the small bowel, particularly in the duodenum in conscious sheep. These alterations occurred in response to different intravenous doses of Hx and atropine administered alone or in combinations during various phases of the migrating myoelectric or motor complex (MMC) in the fasted and non-fasted sheep. Initially two basic types of excitatory response to the cholinergic blockade were found. In the course of chronic experiments different doses of Hx and atropine evoked phase 3-like activity (unorganized phase 3 of the MMC or its fragments) alternating with the less regular RE and the duration of these changes was related to the drug dose. In the non-fasted sheep these changes were less pronounced than in the fasted animals. When the drug was given during phase 1 of the MMC, RE did not occur or was greatly reduced. Administration of Hx and atropine in the course of phase 2a and phase 2b of the MMC produced roughly similar effects. Hx triggered stronger phase 3-like activity and RE than atropine. Combinations of Hx and atropine induced an additive effect, more evident in the fasted animals. These actions of Hx and atropine, thus, appear to involve at least partly the same intramural pathways. It is concluded that Hx and atropine evoke phase 3-like activity alternating with RE as the secondary stimulatory response in conscious sheep and both these types of the intestinal motility represent two distinct motility patterns.

Oxford Phase 3 Unicompartmental Knee Arthroplasty: Minimum 5-year Follow-up Results

PURPOSE: We wanted to evaluate the postoperative clinical results, the complications and the survival rate of Oxford phase 3 unicompartmental knee arthroplasty (UKA), based on a prospective analysis and the follow-up study. MATERIALS AND METHODS: We operated on 142 patients, 180 cases of UKA using the Oxford phase 3 prosthesis from January 2002 to December 2002. Clinical assessments were made using the Knee Society score rating system. Among those, 152 cases (121 patients) were able to be followed up for at least 5 years after the operation. The mean patient age at the time of surgery was 61.1 years and the mean duration of follow-up was 5.5 years. RESULTS: For these 152 knees, the mean preoperative knee and function scores were 53.5 and 55.8, respectively, and they were improved to 88.7 and 83.1, respectively, at the last follow-up. The mean range of knee motion recovered to 133.1degrees and the mean tibiofemoral angle was changed to 4.9degrees of valgus. When we asked patients about their level of satisfaction, 88% of the patients said they were 'very satisfied' or 'satisfied'. There were 7 postoperative complications and the survival rate of the implant at 5 years was 96.8%. CONCLUSION: The Oxford phase 3 UKA was satisfactory for improving the clinical results, the subjective satisfaction of the patients and the survival rate of the implant.