Myocardial deformation assessment in patients with precapillary pulmonary hypertension: A cardiac magnetic resonance study

PurposeThe purpose of this study was to investigate right atrial and ventricular strain parameters on cardiac magnetic resonance (CMR) in patients with precapillary pulmonary hypertension (PPH) and whether they can aid in the assessment of PPH prognosis.Materials and methodsAdult patients with groups 1 and 4 PPH were invited to participate in the study. Age- and sex-matched healthy volunteers were also recruited as controls. At baseline, patients underwent clinical examination, N-terminal pro-B-type natriuretic peptide measurement and CMR with feature tracking post-processing (CMR-FT). Healthy controls underwent only CMR-FT. The study's primary endpoint was clinical failure, defined as death, hospitalization or demonstrable clinical deterioration during follow-up. Patients who were unable to perform 6-minute walking test due to musculoskeletal disorders were excluded from the study.ResultsThirty-six patients (8 men, 28 women; mean age, 50.6 ± 13.8 [SD] years [range: 18.6–78.5 years]) and 12 healthy control subjects (5 mean, 7 women; mean age, 40.6 ± 13.5 [SD] years [range: 23.1–64.4 years]) were recruited. Right ventricular global longitudinal strain (GLS) was significantly impaired in PPH patients (?20.2 ± 5.3 [SD] % [range: ?28.8 to ?9.1%] vs. ?28.4 ± 3.1% [?33.7 to ?22.7%] respectively, P < 0.001). The right atrial GLS was significantly impaired in PPH compared to healthy controls (?19.9 ± 4.5% [range: ?28.6 to ?3.6%] vs. ?26.5 ± 4.2% [range: ?32.8 to ?15.8%] respectively) (P < 0.001). Clinical failure occurred in 19 (19/36, 53%) of patients. Right ventricular GLS predicted clinical failure most reliably among CMR parameters (?22.6 ± 3.8 [SD] % [range: ?27.6 to ?12.7%] for patients without clinical failure vs. ?18 ± 5.6 [SD] % [range: ?28.8 to ?9.1%] for patients with clinical failure; hazard ratio [HR] = 1.85; P = 0.007; area under the AUC curve = 0.75). Lower absolute right atrial GLS was significantly associated with clinical failure (?22.7 ± 3.0 [SD] % [range: ?28.6 to ?17.7%] for patients without clinical failure vs. ?16.9 ± 5.8 [SD] % [range: ?24.2 to ?3.6%] for patients with clinical failure) (HR = 1.53; P = 0.035).ConclusionCMR feature tracking-derived myocardial strain parameters of both the right atrium and ventricle can assist clinicians in the prognosis of PPH.     

左卡尼汀联合重组人促红素注射液治疗规律透析慢性肾功能衰竭合并贫血患者的临床效果

目的探究左卡尼汀联合重组人促红素注射液治疗规律透析慢性肾功能衰竭合并贫血患者的临床效果。方法选择2017年1月至2020年1月收治的100例规律透析慢性肾功能衰竭合并贫血患者,以计算机随机化法将其分为对照组和试验组,每组50例。对照组给予重组人促红素注射液治疗,试验组给予左卡尼汀与重组人促红素注射液联合治疗。比较两组患者的治疗效果。结果试验组的治疗总有效率为96.00%,高于对照组的80.00%(P<0.05);治疗后,两组患者的MCHC、MCH、MCV、SF、Hb、RBC水平均高于治疗前,且试验组高于对照组(P<0.05);两组患者的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论规律透析慢性肾功能衰竭合并贫血患者接受左卡尼汀与重组人促红素注射液联合治疗,可获得较好的效果,改善贫血相关生化指标水平,且不良反应发生率低,安全有效。     

Acute total hip arthroplasty for older patients with acetabular fractures: A meta-analysis

ObjectiveMultiple treatment options for acetabular fractures in geriatric patients exist. However, no large-scale studies have reported the outcomes of acute total hip arthroplasty (THA) in this patient population. We systematically evaluated all available evidence to characterize clinical outcomes, complications, and revisions of acute THA for acetabular fractures in geriatric patients.MethodsMeta-analysis of 21 studies of 430 acetabular fractures with mean follow-up of 44 months (range, 17−97 months). Two independent researchers searched and evaluated the databases of Ovid, Embase, and United States National Library of Medicine using a Boolean search string up to December 2019. Population demographics and complications, including presence of heterotopic ossification (HO), dislocation, infection, revision rate, neurological deficits, and venous thromboembolic event (VTE), were recorded and analyzed.ResultsWeighted mean Harris Hip Score was 83.3 points, and 20% of the patients had reported complications. The most common complication was HO, with a rate of 19.5%. Brooker grade III and IV HO rates were lower at 6.8%. Hip dislocation occurred at a rate of 6.1%, 4.1% of patients developed VTE, deep infection occurred in 3.8%, and neurological complications occurred in 1.9%. Although the revision rate was described in most studies, we were unable to perform a survival analysis because the time to each revision was described in only a few studies. The revision rate was 4.3%.ConclusionsAcute THA is a viable option for treatment of acetabular fracture and can result in acceptable clinical outcomes and survivorship rates in older patients but with an associated complication rate of approximately 20%. Considering the limited treatment options, THA might be a viable alternative for appropriately selected patients.     

Phase II Study of Panitumumab Monotherapy in Chemotherapy‐Naïve Frail or Elderly Patients with Unresectable RAS Wild‐Type Colorectal Cancer: OGSG 1602

Lessons Learned

• Panitumumab monotherapy showed favorable efficacy and feasibility in the treatment of frail or elderly patients with RAS wild‐type unresectable colorectal cancer.
• It is especially effective for left‐sided tumors; therefore, panitumumab as first‐line treatment could be an additional therapeutic option for frail elderly patients, particularly in those who are unsuitable for upfront oxaliplatin‐based or irinotecan‐based combination regimens.

BackgroundFirst‐line panitumumab monotherapy is expected to be well tolerated and improve survival in patients ineligible for intensive chemotherapy. However, its safety and efficacy in chemotherapy‐naïve frail or elderly patients with unresectable RAS wild‐type (WT) colorectal cancer (CRC) have not been studied. The aim of this phase II trial was to evaluate the efficacy and safety of panitumumab as first‐line treatment.MethodsWe conducted a multicenter phase II study on patients aged ≥76 years or ≥65 years considered unsuitable for intensive chemotherapy. Panitumumab 6 mg/kg of intravenous infusion was administered every 2 weeks. The primary endpoint was disease control rate (DCR). Secondary endpoints included progression‐free survival (PFS), overall survival (OS), response rate (RR), time to treatment failure (TTF), and incidence of grade 3 or 4 toxicities.ResultsThirty‐six patients (median age: 81 [range, 67–88] years) were enrolled between February 2017 and August 2018. Two patients were excluded from the analysis of efficacy: one from lack of image examination at baseline and the other from lack of a measurable lesion. Thirty‐three (91.6%) patients had a performance status (PS) of 0 or 1, whereas two (5.6%) patients and one (2.8%) patient had a PS of 2 and 3, respectively. Twenty‐eight patients (77.8%) had left‐sided CRC, whereas eight (22.2%) had right‐sided CRC. The RR was 50.0% (95% confidence interval [CI], 32.4–67.6), including three patients (8.8%) who had complete responses. A total of 26.5% had stable diseases, resulting in a DCR of 76.5% (90% CI, 61.5–87.7). The RR of patients with left‐ and right‐sided tumors was 65.4% (95% CI, 44.3–82.8) and 0.0% (95% CI, 0.0–36.9), respectively. Major grade 3 or 4 nonhematologic toxicities were rash (n = 6, 16.7%), hypomagnesemia (n = 4, 11.1%), fatigue (n = 3, 8.3%), paronychia (n = 2, 5.6%), and hyponatremia (n = 2, 5.6%). The only grade 3 hematologic toxicity was neutropenia (n = 1, 2.8%).ConclusionPanitumumab monotherapy showed favorable efficacy and feasibility in frail or elderly patients with RAS WT unresectable CRC. Survival analysis including OS, PFS, and TTF is currently in progress.     

内囊预警综合征的临床特征和预后

目的 分析内囊预警综合征（capsular warning syndrome，CWS）的临床特点、影像学特征及治疗预后，
以提高对此病的认识。
方法 回顾性分析战略支援部队特色医学中心神经内科2013年1月-2018年12月收住院治疗的CWS的
临床资料、影像学特征及治疗预后情况。
结果 共12例患者，男性8例（66.67%），中位年龄为60岁。高脂血症9例（75.0%），高血压8例
（66.67%），糖尿病4例（33.33%），肿瘤病史3例（25.0%）。纯运动性卒中4例（33.33%），运动伴有构
音障碍者4例（33.33%），运动及感觉性障碍3例（25.00%），纯感觉障碍1例（8.33%）。影像学示豆纹
动脉供血区新发脑梗死6例（50%）。所有患者给予口服双联抗血小板治疗，其中3例症状复发患者又
给予静脉溶栓和静脉抗血小板治疗。3个月随访，所有患者均未再出现症状发作，10例mRS评分为0
分，2例mRS评分分别为4分及3分。
结论 CWS主要表现为运动障碍，发作刻板，常见原因为动脉粥样硬化性。在本组病例中发现双重
抗血小板治疗有效，静脉溶栓效果不肯定。     

Diffusion-weighted MRI and PET/CT reproducibility in epithelial ovarian cancers during neoadjuvant chemotherapy

PurposeTo investigate the reproducibility of diffusion-weighted (DW) MRI and ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG)-Positron emission tomography/CT (PET/CT) in monitoring response to neoadjuvant chemotherapy in epithelial ovarian cancer.Materials and methodsTen women (median age, 67 years; range: 41.8–77.3 years) with stage IIIC-IV epithelial ovarian cancers were included in this prospective trial (NCT02792959) between 2014 and 2016. All underwent initial laparoscopic staging, four cycles of carboplatine-paclitaxel-based chemotherapy and interval debulking surgery. PET/CT and DW-MRI were performed at baseline (C0), after one cycle (C1) and before surgery (C4). Two nuclear physicians and two radiologists assessed five anatomic sites for the presence of ≥ 1 lesion. Target lesions in each site were defined and their apparent diffusion coefficient (ADC), maximal standardized uptake value (SUV-max), SUV-mean, SUL-peak, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were monitored (i.e., 10 patients × 5 sites × 3 time-points). Their relative early and late changes were calculated. Intra/inter-observer reproducibilities of qualitative and quantitative analysis were estimated with Kappa and intra-class correlation coefficients (ICCs).ResultsFor both modalities, inter- and intra-observer agreement percentages were excellent for initial staging but declined later for DW-MRI, leading to lower Kappa values for inter- and intra-observer variability (0.949 and 1 at C0, vs. 0.633 and 0.643 at C4, respectively) while Kappa values remained > 0.8 for PET/CT. Inter- and intra-observer ICCs were > 0.75 for SUV-max, SUL-peak, SUV-mean and their change regardless the time-point. ADC showed lower ICCs (range: 0.013–0.811). ANOVA found significant influences of the evaluation time, the measurement used (ADC, SUV-max, SUV-mean, SUV-max, SUL-peak, MTV or TLG) and their interaction on ICC values (P = 0.0023, P< 0.0001 and P =0.0028, respectively).ConclusionWhile both modalities demonstrated high reproducibility at baseline, only SUV-max, SUL-peak, SUV-mean and their changes maintained high reproducibility during chemotherapy.     

Predicting osimertinib‐treatment outcomes through EGFR mutant‐fraction monitoring in the circulating tumor DNA of EGFR T790M‐positive patients with non‐small cell lung cancer (WJOG8815L)

The WJOG8815L phase II clinical study involves patients with non‐small cell lung cancer (NSCLC) that harbored the EGFR T790M mutation, which confers resistance to EGFR tyrosine kinase inhibitors (TKIs). The purpose of this study was to assess the predictive value of monitoring EGFR genomic alterations in circulating tumor DNA (ctDNA) from patients with NSCLC that undergo treatment with the third‐generation EGFR‐TKI osimertinib. Plasma samples of 52 patients harboring the EGFR T790M mutation were obtained pretreatment (Pre), on day 1 of treatment cycle 4 (C4) or cycle 9 (C9), and at diagnosis of disease progression or treatment discontinuation (PD/stop). CtDNA was screened for EGFR‐TKI‐sensitizing mutations, the EGFR T790M mutation, and other genomic alterations using the cobas EGFR Mutation Test v2 (cobas), droplet digital PCR (ddPCR), and targeted deep sequencing. Analysis of the sensitizing—and T790M—EGFR mutant fractions (MFs) was used to determine tumor mutational burden. Both MFs were found to decrease during treatment, whereas rebound of the sensitizing EGFR MF was observed at PD/stop, suggesting that osimertinib targeted both T790M mutation‐positive tumors and tumors with sensitizing EGFR mutations. Significant differences in the response rates and progression‐free survival were observed between the sensitizing EGFR MF‐high and sensitizing EGFR MF‐low groups (cutoff: median) at C4. In conclusion, ctDNA monitoring for sensitizing EGFR mutations at C4 is suitable for predicting the treatment outcomes in NSCLC patients receiving osimertinib (Clinical Trial Registration No.: UMIN000022076).

Abbreviations

CIs

confidence intervals

ctDNA

circulating tumor DNA

ddPCR

droplet digital PCR

EGFR

epidermal growth factor receptor

MFs

mutant fractions

NGS

next‐generation sequencing

NSCLC

non‐small cell lung cancer

ORR

overall response rate

OS

overall survival

PD

progressive disease

PFS

progression‐free survival

PR

partial response

SD

stable disease

TKI

tyrosine kinase inhibitor