The Optimal Primary Treatment for Pediatric Perianal Abscess and Anal Fistula: A Systemic Review and Meta-Analysis

BackgroundPerianal abscesses and anal fistulas are common. The principle of intention-to-treat has not been considered in previous systemic reviews. Thus, the comparison between primary and post-recurrence management was confused, and the recommendation of primary treatment is obscure. The current study aims to identify the optimal initial treatment for pediatric patients.MethodsUsing PRISMA guidelines, studies were identified from MEDLINE, EMBASE, PubMed, Cochrane Library, and Google Scholar without any language or study design restriction. The inclusion criteria include original articles or articles with original data, studies of management for a perianal abscess with or without anal fistula, and patient age of <18 years. Patients with local malignancy, Crohn's disease, or other underlying predisposing conditions were excluded. Studies without analyzing recurrence, case series of <5, and irrelevant articles were excluded in the screening stage. Of the 124 screened articles, 14 articles had no full texts or detailed information. Articles written in a language other than English or Mandarin were translated by Google Translation first and confirmed with native speakers. After the eligibility process, studies that compared identified primary managements were then included in the qualitative synthesis.ResultsThirty-one studies involving 2507 pediatric patients met the inclusion criteria. The study design consisted of two prospective case series of 47 patients and retrospective cohort studies. No randomized control trials were identified. Meta-analyses for recurrence after initial management were performed with a random-effects model. Conservative treatment and drainage revealed no difference (Odds ratio [OR], 1.222; 95% Confidential interval [CI]: 0.615–2.427, p = 0.567). Conservative management had a higher risk of recurrence than surgery without statistical significance (OR 0.278, 95% CI: 0.109–0.707, p = 0.007). Compared with incision/drainage, surgery can prevent recurrence remarkably (OR 4.360, 95% CI: 1.761–10.792, p = 0.001). Subgroup analysis of different approaches within conservative treatment and operation was not performed for lacking information.ConclusionStrong recommendations cannot be made due to the lack of prospective or randomized controlled studies. However, the current study based on real primary management supports initial surgical intervention for pediatric patients with perianal abscesses and anal fistula to prevent recurrence.Level of evidenceType of study: Systemic review; Evidence level: Level II.     

The American Association for Thoracic Surgery (AATS) 2022 Expert Consensus Document: The use of mechanical circulatory support in lung transplantation

ObjectiveThe use of mechanical circulatory support (MCS) in lung transplantation has been steadily increasing over the prior decade, with evolving strategies for incorporating support in the preoperative, intraoperative, and postoperative settings. There is significant practice variability in the use of these techniques, however, and relatively limited data to help establish institutional protocols. The objective of the AATS Clinical Practice Standards Committee (CPSC) expert panel was to review the existing literature and establish recommendations about the use of MCS before, during, and after lung transplantation.MethodsThe AATS CPSC assembled an expert panel of 16 lung transplantation physicians who developed a consensus document of recommendations. The panel was broken into subgroups focused on preoperative, intraoperative, and postoperative support, and each subgroup performed a focused literature review. These subgroups formulated recommendation statements for each subtopic, which were evaluated by the entire group. The statements were then developed via discussion among the panel and refined until consensus was achieved on each statement.ResultsThe expert panel achieved consensus on 36 recommendations for how and when to use MCS in lung transplantation. These recommendations included the use of veno-venous extracorporeal membrane oxygenation (ECMO) as a bridging strategy in the preoperative setting, a preference for central veno-arterial ECMO over traditional cardiopulmonary bypass during the transplantation procedure, and the benefit of supporting selected patients with MCS postoperatively.ConclusionsAchieving optimal results in lung transplantation requires the use of a wide range of strategies. MCS provides an important mechanism for helping these critically ill patients through the peritransplantation period. Despite the complex nature of the decision making process in the treatment of these patients, the expert panel was able to achieve consensus on 36 recommendations. These recommendations should provide guidance for professionals involved in the care of end-stage lung disease patients considered for transplantation.     

Predicting Survival for Chimeric Antigen Receptor T-Cell Therapy: A Validation of Survival Models Using Follow-Up Data From ZUMA-1

ObjectivesSurvival extrapolation for chimeric antigen receptor T-cell therapies is challenging, owing to their unique mechanistic properties that translate to complex hazard functions. Axicabtagene ciloleucel is indicated for the treatment of relapse or refractory diffuse large B-cell lymphoma after 2 or more lines of therapy based on the ZUMA-1 trial. Four data snapshots are available, with minimum follow-up of 12, 24, 36, and 48 months. This analysis explores how survival extrapolations for axicabtagene ciloleucel using ZUMA-1 data can be validated and compared.MethodsThree different parametric modeling approaches were applied: standard parametric, spline-based, and cure-based models. Models were compared using a range of metrics, across the 4 data snapshot, including visual fit, plausibility of long-term estimates, statistical goodness of fit, inspection of hazard plots, point-estimate accuracy, and conditional survival estimates.ResultsStandard and spline-based parametric extrapolations were generally incapable of fitting the ZUMA-1 data well. Cure-based models provided the best fit based on the earliest data snapshot, with extrapolations remaining consistent as data matured. At 48 months, the maximum survival overestimate was 8.3% (Gompertz mixture-cure model) versus the maximum underestimate of 33.5% (Weibull standard parametric model).ConclusionsWhere a plateau in the survival curve is clinically plausible, cure-based models may be helpful in making accurate predictions based on immature data. The ability to reliably extrapolate from maturing data may reduce delays in patient access to potentially lifesaving treatments. Additional research is required to understand how models compare in broader contexts, including different treatments and therapeutic areas.     

Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma

Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.     

Efficacy,immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.     

原发性肺鳞癌中EGFR和ALK基因突变的临床研究北大核心

目的:探讨赣南地区原发性肺鳞癌患者EGFR和ALK基因突变的特点,科学指导此类患者优选靶向用药。方法:入组73例原发性肺鳞癌病例,采用ARMS-PNA技术检测EGFR基因第18、19、20、21外显子突变,应用不平衡法检测其中60例病例的ALK融合基因,回顾性分析EGFR和ALK基因突变患者的临床病理特征。结果:EGFR基因突变8例,阳性率为10.96%(8/73),4例为L858R突变,3例为19del突变,1例为G719X突变。女性患者突变率(66.67%,2/3)明显高于男性患者(8.57%,6/70)(P=0.030),EGFR基因突变在高龄(≥60岁)、进展期(N_(1-3)、Ⅲ+Ⅳ期)患者中相对较高,但差异无统计学意义(P>0.05)。EGFR基因突变与吸烟史、T分期以及肿瘤分布位置均无相关性(P>0.05);ALK融合基因表达2例,阳性率3.33%(2/60),与患者性别、年龄、吸烟史、TNM分期及肿瘤分布类型等各临床病理特征均无相关性(P>0.05);未发现EGFR和ALK基因共存突变病例。结论:赣南地区原发性肺鳞癌患者EGFR和ALK基因突变率相对不高,EGFR基因突变以L858R和19del突变为主,且好发于女性患者,可能是患者病情进展的预测因子之一。     

艾司氯胺酮复合麻醉在小儿瘢痕非插管全身麻醉患者超脉冲点阵二氧化碳激光治疗术中的应用及效果观察

目的探讨艾司氯胺酮+七氟烷+小儿布洛芬肛栓在小儿烧伤后增生性瘢痕非插管全身麻醉患者超脉冲二氧化碳点阵激光(UFCL)治疗术中的应用及效果观察。 方法选取2020年1月至2021年4月就诊于空军军医大学第一附属医院烧伤与皮肤外科门诊89例烧伤后增生性瘢痕患儿纳入本随机对照临床试验。将患儿采用随机数字表法分为氯胺酮+丙泊酚组[共42例，其中男22例，女20例，平均年龄为(44.33±14.87)个月]和复合麻醉镇痛组(艾司氯胺酮+七氟烷+小儿布洛芬肛栓)[共47例，男24例，女23例，平均年龄(44.47±14.65)个月]；在麻醉前和术中监测患儿血流动力学指标以及警觉/镇静(OAA/S)量表评分；在麻醉清醒时(T0)、麻醉清醒后1 h(T1)、麻醉清醒后2 h(T2)应用儿童疼痛行为量表(FLACC)对患儿疼痛程度进行评估；分别于术前和术后6个月应用温哥华瘢痕量表(VSS)对瘢痕进行评分。对数据行独立样本t检验和χ²检验。 结果(1)麻醉前氯胺酮+丙泊酚组血流动力学及OAA/S量表评分[平均动脉压(63.71±3.40)mmHg、心率(107.21±9.45)次/min、呼吸(25.29±2.34)次/min、血氧饱和度(99.00±0.80)%、OAA/S量表评分(4.64±0.49)分]与复合麻醉镇痛组[平均动脉压(63.87±3.57)mmHg、心率(109.34±12.21)次/min、呼吸(26.473.53)次/min、血氧饱和度(98.77±0.91)%、OAA/S量表评分(4.57±0.50)分]比较差异均无统计学意义(t＝-0.213、0.490、-1.840、1.280、0.204，P>0.05)；麻醉后手术中氯胺酮+丙泊酚组[平均动脉压(56.29±2.43)mmHg、心率(94.48±7.01)次/min、呼吸(21.07±3.03)次/min、血氧饱和度(96.12±1.64)%、OAA/S量表评分(2.07±0.71)分]与复合麻醉镇痛组[平均动脉压(62.87±3.56)mmHg、心率(108.791±1.93)次/min、呼吸(26.52±3.48)次/min、血氧饱和度(99.23±0.67)%、OAA/S量表评分(1.45±0.50)分]比较差异有统计学意义(t＝-10.068、-6.794、-7.824、-11.960、4.820，P<0.05)。(2)氯胺酮+丙泊酚组患儿麻醉清醒时[T0：(4.40±1.17)分]麻醉清醒后1 h[T1：(2.05±0.88)分]、麻醉清醒后2 h[T2：(0.43±0.63)分]FLACC评分比复合麻醉镇痛组[(1.32±0.96)、(0.43±0.62)、(0.13±0.34)分]评分高，说明患儿疼痛度高，且数据比较差异均有统计学意义(t＝10.139、13.669、2.794，P<0.05)。(3)术前及术后6个月瘢痕评分：氯胺酮+丙泊酚组[(9.33±1.60)、(4.48±1.11)分]与复合麻醉镇痛组[(8.43±2.04)、(4.26±1.04)分]相比差异均无统计学意义(t＝2.320、0.940, P>0.05)。 结论复合麻醉镇痛措施在小儿烧伤后增生性瘢痕非插管全身麻醉患者(UFCL)治疗术中应用效果较好，可使患儿术中血流动力学平稳，术中镇静良好，术后疼痛度较低，对于激光治疗效果无影响。     

脂质纳米粒-mRNA递送系统及其在嵌合抗原受体T细胞治疗中的应用

尽管嵌合抗原受体（CAR）T细胞治疗在血液系统恶性肿瘤患者中取得了显著的临床疗效，但需要进一步优化。脂质纳米粒（LNP）-信使核糖核酸（mRNA）递送系统作为一种非病毒性基因载体运用于CAR-T细胞治疗研究中，一方面通过LNP将密封蛋白-6 mRNA靶向递送至抗原提呈细胞，从而实现抗原提呈细胞辅助性增强密封蛋白-6靶向的CAR-T细胞的功能，以进一步诱导对实体瘤的清除；另一方面，通过LNP将成纤维细胞激活蛋白（FAP）CARmRNA靶向递送至T细胞，实现体内FAP靶向的CAR-T细胞的制备，以通过阻断心脏纤维化过程达到治疗急性心肌损伤的目的。在CAR-T细胞研究和治疗中，LNP-mRNA递送系统具有不与细胞基因组整合、价格便宜、毒副作用小及可修饰等优点，亦存在蛋白瞬时表达导致调控细胞功能的持久性不足及制备等方面的技术局限性。本文综述了LNP-mRNA递送系统及其在CAR-T细胞治疗中的应用研究。