Arsenic trioxide replacing or reducing chemotherapy in consolidation therapy for acute promyelocytic leukemia (APL2012 trial)

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO–based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA–anthracycline for low-/intermediate-risk patients, or ATRA-ATO–anthracycline versus ATRA–anthracycline–cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of –5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI –0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan–Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA–chemotherapy (https://www.clinicaltrials.gov/, {"type":"clinical-trial","attrs":{"text":"NCT01987297","term_id":"NCT01987297"}}NCT01987297).

The treatment of all-trans retinoic acid (ATRA) combined with anthracycline-based chemotherapy has remarkably improved the prognosis of patients with acute promyelocytic leukemia (APL), achieving over 90% complete remission (CR) and 60 to 80% long-term survival (1–6). For patients relapsed from ATRA-chemotherapy, arsenic trioxide (ATO) was initially used as salvage therapy and showed a satisfactory outcome (7–9). Then, the treatment of newly diagnosed APL with an ATRA-ATO combination therapy was reported in 2004, which demonstrated curative effects in 90% of patients (10–13). The advantage of ATO as the front-line treatment of APL has been further validated by a number of international working groups (14–18). Meanwhile, an exploratory study on ATRA-ATO with or without gemtuzumab ozogamicin (GO, the cytotoxic agent calicheamicin linked an anti-CD33 monoclonal antibody) by the MD Anderson Cancer Center suggested that a deescalating cytotoxic regimen might be feasible for APL patients (14, 19).A large body of evidence has been obtained to show that both ATRA and ATO target the APL-specific PML-RARA oncoprotein and the two agents may exert a synergistic effect in achieving a curative clinical effect in most APL (2, 9). However, in our previous studies, though ATRA-ATO were used as main therapeutic agents for induction, the consolidation was based on chemotherapy rather than ATO, which could cause life-threatening myelosuppression and cardiotoxicity (10, 11). Besides, risk-stratified treatment had not been introduced, leading to probable overtreatment for low- risk (a white blood cell [WBC] count ≤ 10 × 10⁹/L and a platelet count > 40 × 10⁹/L) to intermediate-risk (a WBC count ≤ 10 × 10⁹/L and a platelet count ≤ 40 × 10⁹/L) patients (20). These issues warranted further clinical investigations to address the role of ATRA-ATO in consolidation and to adapt the treatment protocols to distinct clinical risks. In order to optimize the treatment protocols by reducing their relevant toxicities and costs, as well as further improving therapeutic efficacy and tolerance, we proposed a multicenter randomized trial, APL2012, deriving from our previous ATRA-ATO–based therapy taking into consideration of Sanz risk stratification (20). The objective of this study was to examine whether chemotherapy could be replaced or reduced in consolidation therapy by ATO in patients with APL at different risks.     

Intrapartum fetal surveillance: a physiological approach

Continuous utero-placental circulation, and patent umbilical blood vessels ensure an uninterrupted transfer of oxygen and nutrients to the fetus as well as clearance of metabolic waste products. The onset of labour characterized by progressive and strong uterine contractions poses a threat to fetal oxygenation as a result of collapsing the spiral arterioles traversing the myometrium to supply the placental bed, and repetitive compression of the blood vessels within the umbilical cord. Human fetuses are equipped with compensatory mechanisms to cope with transient interruptions of blood supply during labour. The ability to compensate may be blunted in cases of poor fetal reserves, increased metabolic demand (macrosomia or maternal fever), and due to non-hypoxic pathways (e.g. chorioamniontis or fetal hypovolumia-hypotension syndrome). Intrapartum fetal surveillance involves prompt recognition of the features that signal the onset of fetal decompensation on the cardiotocograph (CTG) to ensure a timely intervention to avoid hypoxic-ischaemic encephalopathy (HIE) or perinatal deaths. This article summarises a ‘physiological approach’ to the interpretation of the CTG which, in places, conflicts with other current UK guidance.     

RIPAS阑尾炎评分对可疑急性阑尾炎的诊断价值

目的:研究RIPAS阑尾炎(RIPASA)评分对可疑急性阑尾炎的诊断价值。方法:对2014年1月-2015年1月诊断的可疑急性阑尾炎患者150例分别以Alvarado评分和RIPASA评分进行评估,比较其诊断价值。结果:以7.5分和7分定义为RIPASA和Alvarado评分的最佳界值,RIPASA评分和Alvarado评分诊断急性阑尾炎的敏感度、特异度、阳性预测值、阴性预测值、准确率、阑尾阴性切除率分别为(97.50%、81.42%、85.71%、96.61%、90.30%、14.29%)和(68.75%、87.14%、85.93%、70.93%、73.80%、14.06%);使用RIPASA和Alvarado评分对可疑急性阑尾炎患者评估结果与综合临床诊断结果相关联,且RIPASA评分关联程度明显高于Alvarado评分(P0.05)。结论 :急诊医师使用RIPASA评分对中国大陆地区东方人种可疑急性阑尾炎患者进行辅助诊断优于Alvarado评分。     

Recent progress on the diagnosis of 2019 Novel Coronavirus

Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has become a global pandemic. Therefore, convenient, timely and accurate detection of SARS‐CoV‐2 is urgently needed. Here, we review the types, characteristics and shortcomings of various detection methods, as well as perspectives for the SARS‐CoV‐2 diagnosis. Clinically, nucleic acid‐based methods are sensitive but prone to false‐positive. The antibody‐based method has slightly lower sensitivity but higher accuracy. Therefore, it is suggested to combine the two methods to improve the detection accuracy of COVID‐19.     

Risk of acute pancreatitis with incretin-based therapy: a systematic review and updated meta-analysis of cardiovascular outcomes trials

ABSTRACT

Background

The link of acute pancreatitis (AP) with Incretin based therapies (IBTs) in type 2 diabetes has existed since United States Food and Drug Administration alert in 2010. This issue still remains unresolved due to conflicting results among studies.     

Rationale and design of the Kidney Precision Medicine Project

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Gastrointestinal and hepatic manifestations of COVID-19 infection: Lessons for practitioners

Originating from Wuhan in China, coronavirus disease 2019 (COVID-19) spread globally within months and was declared a pandemic by World Health Organization in March 2020, making it one of the biggest healthcare calamities of our time. As more data on COVID-19 infection became available, what was initially thought to be a simple respiratory illness was found to be more complex. Many extra-pulmonary manifestations are now frequently reported for COVID-19 in available literature, most commonly gastrointestinal and hepatopancreato-biliary manifestations. Due to early scarcity of data, extra pulmonary manifestations were initially overlooked and may have contributed to nosocomial spread of the infection. Practitioners, especially gastroenterologists, who frequently encounter patients with these symptoms, need to be aware of them. This can not only help minimize the nosocomial spread, ensure safety of provider but also help conserve already stretched-thin healthcare resources. A tremendous amount of COVID-19 related literature is getting added to the growing pool every day, making it difficult for providers to follow. The aim of our review is to summarize the available evidence for gastrointestinal and hepatopancreatobiliary manifestations of COVID-19. We here briefly discussed the possible pathophysiologic mechanism for these manifestations and summarized the recommendations put forward by multiple gastrointestinal societies regarding safe and effective clinical practice during the ongoing pandemic.