COVID-19 convalescent plasma: current status,lessons from the past and future perspectives

When the COVID-19 pandemic hit, blood transfusion services worldwide started collection of convalescent plasma as early as possible, as exemplified by the response in Norway. There were challenges related to donor selection, donor safety, testing for relevant antibodies and indications for and dosing of the convalescent plasma. As more knowledge became available, the product quality was more standardised. Multiple case reports, observational studies and some randomized studies were published during the pandemic, as well as laboratory studies reporting different approaches to antibody testing. The results were conflicting and the importance of convalescent plasma was disputed.Even though there has been strong international collaboration with involvement of many key organisations, we may better prepare for the next pandemic. An even stronger, more formalised collaboration between these organisations could provide more clear evidence of the importance of convalescent plasma, based on the principles of passive immunisation.     

PKP术中不同注入量高粘度骨水泥治疗骨质疏松性腰椎骨折的疗效分析

目的探讨经皮椎体后凸成形术（PKP）术中不同注入量高粘度骨水泥治疗骨质疏松性腰椎骨折（OLVF）的疗效及安全性。 方法前瞻性收集2016年9月至2018年9月本院OLVF患者150例，男84例，女66例，年龄（60±8）岁。依据随机数字表分为高量组、中量组、低量组，每组50例，高量组、中量组、低量组PKP术中高粘度骨水泥注入量分别为5.0~7.0 ml、3~4.9 ml、<3.0 ml，比较三组疗效及安全性。 结果150例患者获得满意随访，随访时间（19±7）个月。高量组、中量组、低量组手术时间、术中出血量比较，差异无统计学意义（P>0.05）；高量组和中量组术后3、6个月椎体前缘高度[（27.3±3.1）mm、（26.0±2.7）mm和（26.9±3.0）mm、（25.7±2.8）mm]明显高于低量组[（23.8±2.8）mm、（21.3±2.5）mm]，高量组和中量组术后3、6个月Cobb角及疼痛视觉模拟评分法（VAS）、Oswestry功能障碍指数问卷表（ODI）评分[（40.2±4.7）°、（41.5±4.8）°、（2.6±0.4）分、（1.6±0.3）分、（25.8±3.5）分、（26.9±3.5）分和（40.9±4.8）°、（42.1±4.8）°、（2.6±0.4）分、（1.6±0.3）分、（26.2±3.5）分、（27.2±3.7）分]明显低于低量组[（46.3±5.3）°、（47.8±5.6）°、（3.3±0.4）分、（2.3±0.4）分、（33.3±4.1）分、（34.3±4.2）分]，差异有统计学意义（F=25.371、18.914、29.334、22.457、34.276、30.217、29.364、20.071，均P<0.001）；高量组骨水泥渗漏率（28.00%）明显高于中量组和低量组（8.00%和4.00%），差异有统计学意义（χ²=10.241，P=0.005）。 结论PKP术中不同注入量高粘度骨水泥治疗OLVF的疗效及安全性存在一定的差异，其中注入中量（3~4.9 ml）高粘度骨水泥可获得良好的疗效及安全性，值得临床推广。     

Therapeutic plasma exchange in pediatric patients with acute demyelinating syndromes of the central nervous system: A single-center experience

BackgroundTherapeutic plasma exchange (TPE) is an extracorporeal treatment that can be used in adult and pediatric patients with acute demyelinating syndromes of the central nervous system. In this study, the efficacy and safety of TPE was evaluated in 10 pediatric patients who underwent TPE that were unresponsive to corticosteroid treatment.MethodsRecords of 10 pediatric patients who underwent TPE in our pediatric intensive care unit (PICU) between May 2017 and June 2020 were used. Expanded Disability Status Scale (EDSS), Gait Scale (GS), and Visual Outcome Scale (VOS) were applied to the patients before and after TPE.ResultsOf the 10 patients who underwent TPE, five were diagnosed with multiple sclerosis (MS), three with transverse myelitis (TM), and two with acute disseminated encephalomyelitis (ADEM). The median age of the patients was 13.3 years (IQR 8-15), and the median day from symptom onset to onset of TPE was 12.5 days (IQR 7-28). A total of 104 TPE sessions were performed successfully. While no complications were encountered in three patients during the sessions, the most common complication was hypofibrinogenemia. The decrease in EDSS and GS scores was found to be consistent with the clinical response of the patients. There was no statistically significant decrease in the VOS.ConclusionsWith this study, we can say that TPE is a feasible, effective, and safe treatment modality in children with acute demyelinating syndromes of the central nervous system.     

Pharmacokinetics and Early Tumor Response to Conventional Transarterial Chemoembolization with Sorafenib and Doxorubicin in a VX2 Rabbit Tumor Model

PurposeTo investigate the pharmacokinetics (PK) and early effects of conventional transarterial chemoembolization (TACE) using sorafenib and doxorubicin on tumor necrosis, hypoxia markers, and angiogenesis in a rabbit VX2 liver tumor model.Materials and MethodsVX2 tumor-laden New Zealand White rabbits (N = 16) were divided into 2 groups: 1 group was treated with hepatic arterial administration of ethiodized oil and doxorubicin emulsion (DOX-TACE), and the other group was treated with ethiodized oil, sorafenib, and doxorubicin emulsion (SORA-DOX-TACE). Animals were killed within 3 days of the procedure. Levels of sorafenib and doxorubicin were measured in blood, tumor, and adjacent liver using mass spectrometry. Tumor necrosis was determined by histopathological examination. Intratumoral hypoxia-inducible factor (HIF) 1α, vascular endothelial growth factor (VEGF), and microvessel density (MVD) were determined by immunohistochemistry.ResultsThe median intratumoral concentration of sorafenib in the SORA-DOX-TACE group was 17.7 μg/mL (interquartile range [IQR], 7.42–33.5 μg/mL), and its maximal plasma concentration (C_max) was 0.164 μg/mL (IQR, 0.0798–0.528 μg/mL). The intratumoral concentration and C_max of doxorubicin were similar between the groups: 4.08 μg/mL (IQR, 3.18–4.79 μg/mL) and 0.677 μg/mL (IQR, 0.315–1.23 μg/mL), respectively, in the DOX-TACE group and 1.68 μg/mL (IQR, 0.795–4.08 μg/mL) and 0.298 μg/mL (IQR, 0.241–0.64 μg/mL), respectively, in the SORA-DOX-TACE group. HIF-1α expression was increased in the SORA-DOX-TACE group than in the DOX-TACE group. Tumor volume, tumor necrosis, VEGF expression, and MVD were similar between the 2 groups.ConclusionsThe addition of sorafenib to DOX-TACE delivered to VX2 liver tumors resulted in high intratumoral and low systemic concentrations of sorafenib without altering the PK of doxorubicin.     

Microwave Ablation as Bridging to Liver Transplant for Patients with Hepatocellular Carcinoma: A Single-Center Retrospective Analysis

PurposeTo evaluate the efficacy and safety of microwave (MW) ablation as first-line locoregional therapy (LRT) for bridging patients with hepatocellular carcinoma (HCC) to liver transplant.Materials and MethodsThis retrospective study evaluated 88 patients who received percutaneous MW ablation for 141 tumors as first-line LRT for HCC and who were listed for liver transplantation at a single medical center between 2011 and 2019. The overall survival (OS) rate statuses after liver transplant, waitlist retention, and disease progression were evaluated using the Kaplan-Meier techniques.ResultsAmong the 88 patients (72 men and 16 women; mean age, 60 years; Model for End-Stage Liver Disease score, 11.2) who were listed for transplant, the median waitlist time was 9.4 months (interquartile range, 5.5–18.9). Seventy-one (80.7%) patients received transplant after a median waitlist time of 8.5 months. Seventeen (19.3%) patients were removed from the waitlist; of these, 4 (4.5%) were removed because of tumors outside of the Milan criteria (HCC-specific dropout). No difference in tumor size or alpha-fetoprotein was observed in the transplanted versus nontransplanted patients at the time of ablation (2.1 vs 2.1 cm and 34.4 vs 34.7 ng/mL for transplanted vs nontransplanted, respectively; P > .05). Five (5.1%) of the 88 patients experienced adverse events after ablation; however, they all recovered. There were no cases of tract seeding. The local tumor progression (LTP) rate was 7.2%. The OS status after liver transplant at 5 years was 76.7%, and the disease-specific survival after LTP was 89.6%, with a median follow-up of 61 months for all patients.ConclusionsMW ablation appears to be safe and effective for bridging patients with HCC to liver transplant without waitlist removal from seeding, adverse events, or LTP.     

Barrett’s esophagus: Review of natural history and comparative efficacy of endoscopic and surgical therapies

Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Progression to cancer typically occurs in a stepwise fashion through worsening dysplasia and ultimately, invasive neoplasia. Established EAC with deep involvement of the esophageal wall and/or metastatic disease is invariably associated with poor long-term survival rates. This guides the rationale of surveillance of Barrett’s in an attempt to treat lesions at an earlier, and potentially curative stage. The last two decades have seen a paradigm shift in management of Barrett’s with rapid expansion in the role of endoscopic eradication therapy (EET) for management of dysplastic and early neoplastic BE, and there have been substantial changes to international consensus guidelines for management of early BE based on evolving evidence. This review aims to assist the physician in the therapeutic decision-making process with patients by comprehensive review and summary of literature surrounding natural history of Barrett’s by histological stage, and the effectiveness of interventions in attenuating the risk posed by its natural history. Key findings were as follows. Non-dysplastic Barrett’s is associated with extremely low risk of progression, and interventions cannot be justified. The annual risk of cancer progression in low grade dysplasia is between 1%-3%; EET can be offered though evidence for its benefit remains confined to highly select settings. High-grade dysplasia progresses to cancer in 5%-10% per year; EET is similarly effective to and less morbid than surgery and should be routinely performed for this indication. Risk of nodal metastases in intramucosal cancer is 2%-4%, which is comparable to operative mortality rate, so EET is usually preferred. Submucosal cancer is associated with nodal metastases in 14%-41% hence surgery remains standard of care, except for select situations.