Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

A Snapshot of the Guidelines on Vesicoureteral Reflux in Children

The main goal in the management of patients with vesicoureteral reflux (VUR) is the preservation of kidney function by minimizing the risk of pyelonephritis. By defining and analyzing the risk factors for each patient depending on age, sex, grade of reflux, lower urinary tract dysfunction, anatomic abnormalities, and kidney status, it is possible to identify those patients with a potential risk of upper urinary tract infection and resulting renal scarring. This paper gives a brief overview of the European Association of Urology guidelines for the management and treatment of VUR in children. These guidelines are based on the best currently available knowledge and evidence.     

Long-term anticoagulant therapy in patients with coronary artery disease.

Secondary prevention of coronary events in coronary artery disease (CAD) patients with aspirin is generally accepted because of ease of administration, predictable safety, and proven efficacy. The use of long-term anticoagulant therapy with heparins, vitamin-K antagonists (VKAs), or thrombin inhibitors is, however, more controversial. During the last 40 years, several trials have been conducted in order to evaluate the role of anticoagulant therapy in patients with CAD as a protection against subsequent death and thrombo-embolic complications. The conducted trials are heterogeneous in many ways, concerning comparative medications, patient populations, endpoints and follow-up, which makes a standardized recommendation on the basis of these studies difficult. This review is an overview of the largest and best studies on this topic and discusses the scientific background for a possible use of VKA or an alternative anticoagulant treatment in CAD patients, looking at both the beneficial effects and the risk of bleeding.     

Practical guidelines for physicians in the management of febrile seizures

Recent studies have shown that adequate medication can prevent the recurrence of febrile seizures (FS). It has also been clarified that the vast majority of, though not all, FS patients follow a benign course. Then, questions arise as to whether or not FS should be prevented, particularly in light of the risks of side effects from drugs. Which kinds of FS can be prevented, if necessary? The guidelines presented here are aimed primarily at helping general practitioners in considering how to manage FS most appropriately. The guidelines stress that judgements should be individualized, while referring to a few specific ‘warning factors’. The guidelines follow a ‘laissez-faire’ principle for the majority of FS cases, whereas intermittent therapy with diazepam and continuous medication with either phenobarbital or valproate are indicated in other limited cases meeting respective definite criteria.     

阿司匹林间歇疗法在脑卒中二级预防中的临床价值

目的观察阿司匹林间歇疗法与常规疗法在脑卒中二级预防中临床价值的差异。方法收集250例脑卒中恢复期患者,按随机单盲开放对照原则分为间歇疗法组(间歇组)(每8周内停药1周)和常规疗法组(单规组)各125例,均给予阿司匹林100mg Qd治疗2年。结果(1)2组脑卒中再发率无明显差异;(2)2组患者的血小板聚集率和凝血功能无明显差异;(3)间歇组上消化道出血、腹痛、腹泻等不良反应发生率较常规组明显下降(P<0.01)。结论阿司匹林间歇疗法较常规疗法能有效减低了长期治疗导致的消化道不良反应,同时有效降低脑卒中的再发率,在脑卒中二级预防中具有重要的临床应用价值。     

糖尿病酮症酸中毒诱因调查及防治对策

目的 :探讨糖尿病酮症酸中毒 (DKA)诱发因素的防治对策 ;方法 :采用计数方法间接确定住院的 57例DKA各种诱因的发生率 ,两组间进行对比分析 ,找寻诱因产生的根源 ;结果 :感染为诱因者 3 5例 ( 61 .4% ) ,用药不当 8例 ( 1 4 .0 % ) ,医源性因素 6例 ( 1 0 .5% ) ;感染诱因中呼吸道感染 2 3例 ( 65.7% ) ;病程一年以上者感染诱发率高于病程一年以下者 (P <0 .0 5) ,医源性诱因 1 0 0 %发生在病程一年以下且无糖尿病病史的 2型糖尿病 ;结论 :感染是DKA的首要诱发因素 ,严格控制血糖是减少感染发生率的必要手段 ,要避免用药不当这个主要诱因有赖于加强卫生宣教 ,取得患者在治疗上的配合 ;糖尿病的早期诊断可防止医源性诱因的发生     

气流喷砂对牙面粗糙度的影响

目的　探讨使用气流喷砂技术对牙面粗糙度的影响。方法　光波干涉显微镜观察 2 4颗离体牙在使用气流喷砂后牙面粗糙度的变化 ,并研究磨光糊剂磨光对减轻其粗糙度的作用。结果　气流喷砂和超声洁治一样都会使牙面糊糙度显著增加 (P <0 .0 1 ) ,进一步磨光可使牙面粗糙度显著下降 (P <0 .0 1 )。结论　临床上使用气流喷砂后 ,需进一步磨光来增加牙面光洁度     

Febrile seizures - treatment and outcome

Assessment of treatment strategies in febrile seizures should be based on short- and long-term outcomes, with and without acute, intermittent, or chronic medical intervention, as well as short- and long-term side effects. Febrile seizures are a benign condition with a normal neurological, motor, intellectual, and cognitive long-term outcome and have a low risk of later epilepsy in most cases. Even many complex febrile seizures have a benign outcome. Prophylaxis may or may not reduce the recurrence rate, but does not appear to improve the long-term outcome as compared to acute treatment of seizures in progress. All agree that chronic prophylaxis with anti-epileptic agents is justified only in highly selected cases, if at all. Treatment with benzodiazepines during febrile episodes appears to effectively reduce the recurrence rate, provided adequate doses are given and compliance problems minimized. A selective approach to intermittent diazepam prophylaxis seems rational, as the recurrence risk and response to treatment are highly variable. An attractive alternative is acute treatment at seizure onset with rectal diazepam in solution given by the parents at home in order to prevent prolonged recurrent seizures. This regimen has the potential of moving the first line of anti-convulsant defence close to the child. It appears to be effective, inexpensive, feasible even for non-professionals, has few side effects and is well accepted by the parents. A reasonable policy would be to treat simple febrile seizures solely with acute rectal diazepam in solution and reserve intermittent diazepam prophylaxis for selected cases including those with multiple or prolonged recurrences, several risk factors for recurrent febrile seizures and other special situations.     

A microbiologist''s guide to travellers abroad: do as I say not as I do

Clinical microbiologists do not normally prescribe prophylactic antibiotics for travellers' diarrhoea, and when questioned at a Hospital Infection Society (HIS) meeting only 2% admitted doing so. During a HIS visit to India, 5 (28%) members took daily ciprofloxacin prophylaxis and none of them developed diarrhoea.