BNT162b2 mRNA COVID-19 vaccine Reactogenicity: The key role of immunity

We examined the impact of pre-existing SARS-CoV-2-specific cellular immunity on BNT162b2 mRNA COVID-19 vaccine reactogenicity. Of 96 healthcare workers (HCWs), 76% reported any vaccine reaction (first dose: 70%, second dose: 67%), none of which was severe. Following first dose, systemic reactions were significantly more frequent among HCWs with past infection than in infection-naïve individuals, and among HCWs with pre-existing cellular immunity than in those without it. The rate of systemic reactions after second dose was 1.7 and 2.0-times higher than after first dose among infection-naïve HCWs and those without pre-existing cellular immunity, respectively. Levels of SARS-CoV-2-specific T-cells before vaccination were higher in HCWs with systemic reactions after the first dose than in those without them. BNT162b2 vaccine reactogenicity after first dose is attributable to pre-existing cellular immunity elicited by prior COVID-19 or cross-reactivity. Reactogenicity following second dose suggests an immunity-boosting effect. Overall, these data may reduce negative attitudes towards COVID-19 vaccines.Study Registration.The study was registered on clinicaltrials.gov, NCT04402827.     

The Effectiveness and Safety of Platelet-Rich Plasma for Chronic Wounds: A Systematic Review and Meta-analysis

ObjectiveTo evaluate the effectiveness and adverse events of autologous platelet-rich plasma (PRP) in individuals with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers.Patients and MethodsWe searched multiple databases from database inception to June 11, 2020, for randomized controlled trials and observational studies that compared PRP to any other wound care without PRP in adults with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers.ResultsWe included 20 randomized controlled trials and five observational studies. Compared with management without PRP, PRP therapy significantly increased complete wound closure in lower-extremity diabetic ulcers (relative risk, 1.20; 95% CI, 1.09 to 1.32, moderate strength of evidence [SOE]), shortened time to complete wound closure, and reduced wound area and depth (low SOE). No significant changes were found in terms of wound infection, amputation, wound recurrence, or hospitalization. In patients with lower-extremity venous ulcers or pressure ulcers, the SOE was insufficient to estimate an effect on critical outcomes, such as complete wound closure or time to complete wound closure. There was no statistically significant difference in adverse events.ConclusionAutologous PRP may increase complete wound closure, shorten healing time, and reduce wound size in individuals with lower-extremity diabetic ulcers. The evidence is insufficient to estimate an effect on wound healing in individuals with lower-extremity venous ulcers or pressure ulcers.Trial RegistrationPROSPERO Identifier: CRD42020172817     

颊部外周型牙源性角化囊肿2例

外周型牙源性角化囊肿十分罕见，位于颊部软组织内的外周型牙源性角化囊肿更为罕见。本文报道2例颊部软组织内的外周型牙源性角化囊肿，并结合相关文献进行讨论。     

High expression of HVEM is associated with improved prognosis in intrahepatic cholangiocarcinoma

Herpesvirus entry mediator (HVEM) displays dual signals in T-cell activation according to the ligands and intracytoplasmic effectors it interacts with. High HVEM expression may play an immunosuppressive role in several malignancies. The present study investigated the clinical impact of HVEM on intrahepatic cholangiocarcinoma (ICC), including its prognostic value, and association with clinicopathological features and immune status. The clinical data of 102 consecutive patients with ICC who underwent surgical treatment from January 2012 to December 2017 were collected. The expression of HVEM and different types of tumor-infiltrating lymphocytes (TILs) were investigated in ICC tissue samples by immunohistochemical staining. HVEM expression was detected in the tumor tissues of 92 (90.2%) patients with ICC. Patients with high HVEM expression were more likely to have increased peripheral blood lymphocyte (PBL) concentrations (P=0.031), decreased CEA (P=0.036), low TNM stage (P=0.043) and high frequencies of small-duct histological type (P=0.021) and BAP1 retained expression (P=0.010). Survival analysis showed that high HVEM expression was a favorable independent predictor of overall postoperative survival (P=0.034, hazard ratio=0.486, 95% confidence interval=0.249–0.945). In addition, no significant association of HVEM expression with CD4⁺ (P=0.512), CD8⁺ (P=0.750) or CD45RO⁺ (P=0.078) TILs was identified in the ICC tissues. These results indicate that HVEM may serve as a favorable prognostic marker for ICC. Furthermore, co-stimulatory signals from HVEM may play a dominant role in the progression of ICCs, which can be explained by an increase in the number of PBLs rather than a change in the number of TILs. However, the function of the HVEM network in ICC progression is complex and requires further study.     

Inherited peripheral neuropathies: what does a paediatrician need to know?

Collectively, inherited peripheral neuropathies (IPN) are relatively common in children. They have a combined estimated incidence of 1 in 2500 live births. Therefore, it is likely that most paediatricians and many healthcare professionals working in primary care settings will encounter children with IPN during their careers. This article outlines when to suspect an IPN, the common manner of presentation and how to diagnose and classify these conditions in children. It offers advice on the differential diagnosis, the genetic aspects of childhood IPN and the importance of genetic counselling. The modern aspects of diagnosis, which often use next generation sequencing to rapidly diagnose both common and rare IPNs, are considered. The common surveillance measures and treatment modalities together with the basic science developments that underpin future treatments for IPNs are discussed.     

基于“肝阳虚”理论探讨化疗所致周围神经病变的病机与治疗＊

化疗所致周围神经病变（Chemotherapy-induced peripheral neuropathy，CIPN）是临床常见的由化疗药物引起的一系列神经毒性症状，易造成神经功能障碍，四肢感觉弱化、缺失等，严重影响肿瘤患者生活质量及临床疗效。CIPN的发病机制尚不十分明确，目前也没有可广泛用于临床的特效药物治疗。中医药治疗CIPN具有特定的优势，取得了一定成绩，但在理论依据和临床疗效方面仍有一定的局限性。本文通过分析CIPN的临床症状特点，深入剖析其与中医肝阳虚理论之间的关系，探讨CIPN的中医病因病机与用药规律，指导临床治疗CIPN，以期更好地发挥中医药在肿瘤治疗中的减毒增效作用。     

Phosphatidylcholine attenuated docetaxel-induced peripheral neurotoxicity in rats

Docetaxel is a taxane chemotherapeutic agent used in the treatment of breast cancer, prostate cancer and gastric cancer, but several side effects such as peripheral neurotoxicity could occur. The present study was designed to investigate the therapeutic potential of phosphatidylcholine (PC) on docetaxel-induced peripheral neurotoxicity. Rats were randomly divided into three groups and treated for 4 weeks. Behavioral tests were conducted to measure the effects of PC on docetaxel-induced decreases in mechanical & thermal nociceptive threshold. Biochemical tests were conducted to measure the level of oxidative stress on sciatic nerve. Histopathological and immunohistochemical experiments were also conducted to assess neuronal damage and glial activation. PC treatment significantly attenuated docetaxel-induced changes in mechanical & thermal nociceptive response latencies. PC decreased oxidative stress in sciatic nerve by increasing antioxidant levels (glutathione, glutathione peroxidase and superoxide dismutase activity). In immunohistochemical evaluation, PC treatment ameliorated docetaxel-induced neuronal damage and microglial activation in the sciatic nerve and spinal cord. Thus, PC showed protective effects against docetaxel-induced peripheral neurotoxicity. These effects may be attributed to its antioxidant properties and modulation of microglia.     

Suitability of the AUC Ratio as an Indicator of the Pharmacokinetic Advantage in HIPEC

The purpose of this study was to evaluate the area under the concentration-time curve (AUC) ratio as an optimal indicator of the pharmacokinetic advantage during hyperthermic intraperitoneal perioperative chemotherapy. The impact on the AUC ratio on the variables related to the calculation of systemic drug exposure, instillation time, and peripheral drug distribution was evaluated through simulations as well as through a retrospective analysis of studies published in the literature. Both model simulations and the retrospective analysis showed that the 3 variables evaluated had an impact on the AUC ratio value if the complete systemic exposure was not fully considered. However, when that complete systemic exposure was considered, none of these variables affected the AUC ratio value. AUC ratio is not a characteristic parameter of a drug if the calculated systemic drug exposure is not complete. Thus, AUC ratio is not valid for comparing the pharmacokinetic advantage of 2 drugs, and it should not be employed to prove whether a drug can be used in hyperthermic intraperitoneal perioperative chemotherapy safely with regard to toxicity. As an alternative, the study of the absorption rate constant and the bioavailability are proposed as the true and independent parameters that reflect the amount of drug absorbed.     

Comparative analgesic efficacy of pregabalin administered according to either a prevention protocol or an intervention protocol in rats with cisplatin‐induced peripheral neuropathy

Chemotherapy‐induced peripheral neuropathy (CIPN) is a type of peripheral neuropathic pain that may be dose‐limiting in patients administered potentially curative cancer chemotherapy dosing regimens. In cancer survivors, persistent CIPN adversely affects patient quality of life and so adjuvant drugs (anticonvulsants eg pregabalin or antidepressants eg amitriptyline) are recommended for the relief of CIPN. However, most studies in rodent models of CIPN involve administration of single bolus doses of adjuvant drugs to assess pain‐relieving efficacy. Hence this study was designed to assess the efficacy of pregabalin administered to CIPN‐rats according to either a prevention or an intervention protocol. Groups of male Sprague‐Dawley rats received four single intraperitoneal bolus doses of cisplatin at 3 mg/kg at once‐weekly intervals to induce CIPN. For the prevention protocol, oral pregabalin (or vehicle) was administered to CIPN‐rats once‐daily for 21 consecutive days from day 0 to day 20 inclusive. For the intervention protocol, oral pregabalin was administered once‐daily for 21 consecutive days from day 28 to day 48, inclusive. Mechanical allodynia and mechanical hyperalgesia in the bilateral hindpaws were assessed just prior to each dose of cisplatin and at least once weekly until study completion (day 27, prevention protocol; or day 48, intervention protocol). Mechanical allodynia and mechanical hyperalgesia were also determined at the time of peak effect at about 2 hours post pregabalin/vehicle administration, once weekly until study completion. For the prevention protocol in CIPN‐rats, pregabalin alleviated mechanical hyperalgesia but not mechanical allodynia. For the intervention protocol, pregabalin alleviated both mechanical allodynia and mechanical hyperalgesia in the hindpaws.