Imaging in Therapy Response Assessment and Surveillance of Lung Cancer: Evidenced-based Review With Focus on the Utility of 18F-FDG PET/CT

This review covers the state-of-the-art imaging in therapy assessment and surveillance of lung cancer with focus on the utility of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT). We review different qualitative and quantitative response assessment criteria in lung cancer, common pitfalls and atypical patterns of response to immunotherapy, and imaging features of common immune-related adverse events. In addition, the currently recommended imaging workup in surveillance of asymptomatic patients with non–small-cell and small-cell lung cancer and future developments will be discussed.     

Immune Checkpoint Inhibitors in Thoracic Malignancies: Review of the Existing Evidence by an IASLC Expert Panel and Recommendations

In the past 10 years, a deeper understanding of the immune landscape of cancers, including immune evasion processes, has allowed the development of a new class of agents. The reactivation of host antitumor immune response offers the potential for long-term survival benefit in a portion of patients with thoracic malignancies.The advent of programmed cell death protein 1/programmed death ligand-1 immune checkpoint inhibitors (ICIs), both as single agents and in combination with chemotherapy, and more recently, the combination of ICI, anti–programmed cell death protein 1, and anticytotoxic T-lymphocyte antigen 4 antibody, have led to breakthrough therapeutic advances for patients with advanced NSCLC, and to a lesser extent, patients with SCLC. Encouraging activity has recently emerged in pretreated patients with thymic carcinoma (TC). Conversely, in malignant pleural mesothelioma, pivotal positive signs of activity have not been fully confirmed in randomized trials. The additive effects of chemoradiation and immunotherapy suggested intriguing potential for therapeutic synergy with combination strategies. This has led to the introduction of ICI consolidation therapy in stage III NSCLC, creating a platform for future therapeutic developments in earlier-stage disease. Despite the definitive clinical benefit observed with ICI, primary and acquired resistance represent well-known biological phenomena, which may affect the therapeutic efficacy of these agents.The development of innovative strategies to overcome ICI resistance, standardization of new patterns of ICI progression, identification of predictive biomarkers of response, optimal treatment duration, and characterization of ICI efficacy in special populations, represent crucial issues to be adequately addressed, with the aim of improving the therapeutic benefit of ICI in patients with thoracic malignancies.In this article, an international panel of experts in the field of thoracic malignancies discussed these topics, evaluating currently available scientific evidence, with the final aim of providing clinical recommendations, which may guide oncologists in their current practice and elucidate future treatment strategies and research priorities.     

Circulating MicroRNAs and Extracellular Vesicle–Containing MicroRNAs as Response Biomarkers of Anti–programmed Cell Death Protein 1 or Programmed Death-Ligand 1 Therapy in NSCLC

IntroductionAnti–programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) antibody therapy is a standard treatment for advanced NSCLC, and PD-L1 immunohistochemistry is used as a predictive biomarker for therapeutic response. However, because not all patients with NSCLC with high PD-L1 respond, and some patients with low PD-L1 expression exhibit durable benefit, more accurate predictive biomarkers are needed. Circulating microRNA (miRNA) and miRNA packaged in extracellular vesicles (EVs) are believed to play a role in intercellular communication among immune cells and between immune cells and tumor cells and may represent a good source of mechanism-related biomarkers.MethodsPretreatment plasma of patients with advanced NSCLC treated with single-agent anti–PD-1 or anti–PD-L1 antibody was used in this study. Plasma EVs were isolated using size-exclusion chromatography. Whole plasma and EV-containing RNAs were extracted. The miRNA profile was analyzed with a next-generation sequencing platform.ResultsSamples from 14 responders (patients who exhibited partial response or stable disease ≥6 mo) and 15 nonresponders (patients who exhibited progressive disease as per Response Evaluation Criteria in Solid Tumors) were analyzed. In total, 32 miRNAs (p = 0.0030–0.0495) from whole plasma and seven EV-associated miRNAs (p = 0.041–0.0457) exhibited significant concentration differences between responders and nonresponders. The results of some of these circulating miRNAs were validated in a separate cohort with eight responders and 13 nonresponders. The tumor PD-L1 level was also assessed using immunohistochemistry for patients involved in both cohorts.ConclusionsSpecific circulating miRNAs in whole plasma and plasma EVs are differentially expressed between responders and nonresponders and have potential as predictive biomarkers for anti–PD-1/PD-L1 treatment response.     

Temporary hemodialysis catheters as a long-term vascular access in chronic hemodialysis patients

The objective was to review our experience with temporary, precurved, jugular catheters used for long-term vascular access in chronic hemodialysis patients. Thirty chronic hemodialysis patients, 14 men and 16 women, with an average age of 65.3 +/- 13.5 years (30-90 years), treated by dialysis for 1 month to 30 years (average +/- SD, 6.3 +/- 8.1 years), had single lumen, 'temporary' precurved non-tunneled jugular catheters placed into the right jugular vein as permanent vascular access, with 4% trisodium citrate as a locking solution and mupirocin at the exit site. Hemodialysis catheters were used for vascular access on average for 9.1 +/- 6.5 months, (1-22.7 months), and for a total of 271.7 months (8151 days). Average catheter functioning time was 3.1 +/- 1.9 months (0.5-10 months). The total number of side-effects was 55 (6.7/1000 catheter days), including 26 cases of thrombosis (3.2/1000 catheter days), 9 ruptures of the catheter (1.1/1000 catheter days), 15 catheter malfunctions (1.8/1000 catheter days), 2 exit site infections (0.2/1000 catheter days), 2 bacteremias (0.2/1000 catheter days), 1 avulsion of the catheter (0.1/1000 catheter days), and 2 catheters were removed because an AV fistula was successfully used. In 21 patients single-needle hemodialysis was performed, mean blood flow 251 +/- 16 mL/min (250-300), mean Kt/V 0.96 +/- 0.16 (0.72-1.27) and in 9 patients double-needle hemodialysis was performed (catheter and peripheral vein) with mean blood flow 252 +/- 14 mL/min (200-300), mean Kt/V 1.63 +/- 0.25 (1.21-1.96). 'Temporary' jugular single lumen non-tunneled hemodialysis catheters, with 4% citrate as locking solution and mupirocin ointment at the exit site provided good long-term vascular access with acceptable functioning time and low infection rate. The main reasons for catheter exchange or removal were malfunction and mechanical damage of the catheter.     

The Gastrointestinal Tract Is an Alternative Route for SARS-CoV-2 Infection in a Nonhuman Primate Model

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Hydrochlorothiazide-induced hepatotoxicity: A rare case of DILI

Thiazide diuretics are prescribed daily and rarely hepatotoxic. We report the case of 86-year-old woman who was admitted in hospital for jaundice after taking hydrochlorothiazide. All differential diagnoses have been eliminated. The liver biopsy was compatible with drug-induced hepatitis. Clinical and biological manifestations improved after discontinuation of the treatment. The reported case is compared to three other cases in the literature.     

Calcium, phosphorus, cardiovascular events and all-cause mortality in hemodialysis patients: a single-center retrospective cohort study to reassess the validity of the Japanese Society for Dialysis Therapy guidelines

Mineral and bone disorders frequently cause cardiovascular complications and mortality in hemodialysis patients, but few observational studies of Japanese patients have investigated this matter. A retrospective cohort study of 99 patients (53 males, 46 females; mean age: 65 +/- 12 year; 38% with diabetes mellitus) on maintenance hemodialysis in our dialysis center was conducted. Mean serum Ca, P and intact parathyroid hormone (iPTH) levels were 9.2 +/- 0.9 mg/dL, 6.1 +/- 1.7 mg/dL, and 233 +/- 333 pg/mL, respectively. The cutoff values for each of these three parameter were defined according to the target ranges recommended by the Japanese Society for Dialysis Therapy (JSDT) guidelines (Ca: 8.4-10.0 mg/dL; P: 3.5-6.0 mg/dL; iPTH: 60-180 pg/mL). During a 45-month follow up, patients with all parameters outside the target ranges showed the highest incidence of cardiovascular events and all-cause deaths (16.6 and 29.2 per 1000 person-years, respectively). The relative risks of cardiovascular events and all-cause deaths were analyzed by multivariate Cox regression models. The hazard ratio (HR) for cardiovascular events was significantly lower for patients who achieved serum Ca and P objectives compared with others (HR: 2.12; 95% CI: 1.04-4.34; P < 0.05), and similar differences were observed for all-cause deaths (HR: 3.10; 95% CI: 1.13-8.53; P < 0.05). However, the relationship between iPTH levels and each of the endpoints was less pronounced. The results of this study provide support for the JSDT guidelines, which give priority to the control of serum Ca and P levels over the control of parathyroid function.     

维持性透析患者低血压状态相关因素分析

目的：探讨维持性血液透析（MHD）患者慢性低血压状态的发生的影响因素。方法：收集近3年来进行透析的252例MHD患者慢性低血压状态发生情况,回顾性分析患者进入透析时的基础状态指标,包括一般情况、病史资料、体检情况、实验室指标等,并寻找与慢性低血压发生的相关因素。结果：本组MHD患者中并发慢性低血压状态的发生率为23．02％,低血压组与未发生低血压组相比,两组在年龄、糖尿病史、冠心病史、身体质量指数、左室功能、白蛋白水平、血脂、C反应蛋白等方面的差异有显著性意义,多元分析表明高龄、糖尿病、低蛋白血症、C反应蛋白是MHD患者并发慢性低血压状态的主要危险因素。结论：高龄、糖脂代谢紊乱、营养不良和炎症状态与MHD患者慢性低血压状态有关,可作为透析低血压状态的早期预测因素。     

Loss of Amino Acids Into Dialysate During Hemodialysis Using Hydrophilic and Nonhydrophilic Polyester–Polymer Alloy and Polyacrylonitrile Membrane Dialyzers

During hemodialysis, amino acid loss through the dialysate remained a significant problem and was not clear in some dialyzers; therefore, we investigated amino acid loss with hydrophilic and nonhydrophilic polyester–polymer alloy membranes and polyacrylonitrile membranes. Nine maintenance hemodialysis patients were studied to assess amino acid loss during hemodialysis with the three membranes. Total amino acid losses were 85.7 ± 27.2 mg/L, 83.3 ± 16.1 mg/L, and 72.1 ± 22.5 mg/L with the hydrophilic, nonhydrophilic polyester–polymer alloy, and polyacrylonitrile membranes, respectively. Amino acid losses were greater with the hydrophilic membrane compared with the polyacrylonitrile membrane for ornithine (2.0 ± 0.6 vs. 1.4 ± 0.4 mg/L, P = 0.025), phenylalanine (2.4 ± 0.9 vs. 1.8 ± 0.8 mg/L, P = 0.012), and tryptophan (0.6 ± 0.2 vs. 0.4 ± 0.2 mg/L, P = 0.023). Amino acid losses were greater with the nonhydrophilic membrane than with the polyacrylonitrile membrane for ornithine (2.0 ± 0.4 vs. 1.4 ± 0.4 mg/L, P = 0.017), phenylalanine (2.3 ± 0.5 vs. 1.8 ± 0.8 mg/L, P = 0.018), tryptophan (0.7 ± 0.2 vs. 0.4 ± 0.2 mg/L, P = 0.003), and cystine (3.2 ± 0.7 vs. 2.0 ± 0.7 mg/L, P = 0.005). In conclusion, greater losses of ornithine, phenylalanine, tryptophan, and cystine were observed with polyester–polymer alloy than with polyacrylonitrile membranes during hemodialysis. Constant attention should be paid to the amino acid loss profile to improve nutritional control in hemodialysis patients.