Overview of CF lung pathophysiology

Defects of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein affect the homeostasis of chloride, bicarbonate, sodium, and water in the airway surface liquid, influencing the mucus composition and viscosity, which induces a severe condition of infection and inflammation along the whole life of CF patients. The introduction of CFTR modulators, novel drugs directly intervening to rescue the function of CFTR protein, opens a new era of experimental research. The review summarizes the most recent advancements to understand the characteristics of the infective and inflammatory pathology of CF lungs.     

The usefulness of measuring n-butyric acid concentration as a new indicator of blood decomposition in forensic autopsy

In forensic medicine, although various alcohols have been reported as indicators of decomposition in collected blood, no studies have examined short-chain fatty acids as indicators. In this study, the blood n-butyric acid concentration was quantified, and the association between n-butyric acid and decomposition was investigated to determine whether the detection of n-butyric acid could be a new indicator of decomposition. Among the forensic autopsies performed from 2016 to 2018 in our laboratory, the cases were divided into decomposed (n = 20) and non-decomposed (n = 20) groups based on macroscopic findings. Blood samples collected at the time of autopsy were derivatized with 3-nitrophenylhydrazine hydrochloride after solid-phase extraction. The n-butyric acid concentration was measured using liquid chromatography–tandem mass spectrometry. In addition, ethanol and n-propanol were measured using a gas chromatography-flame ionization detector. There was a significant difference (p < 0.01) in the concentrations of n-butyric acid between the decomposed and non-decomposed groups (0.343 ± 0.259 [0.030–0.973] and 0.003 ± 0.002 [0.001–0.007] mg/mL, respectively). In the decomposed group, n-butyric acid was detected at high concentrations, even in cases where n-propanol was low. These results suggest that n-butyric acid is more likely to be an indicator of blood decomposition than n-propanol.     

Circulating tumor DNA analysis in breast cancer: Is it ready for prime-time?

Precision Medicine is becoming the new paradigm in healthcare as it enables better resources allocation, treatment optimization with a potential side-effects reduction and consequent impact on quality of life and survival. This revolution is being catalyzed by liquid biopsy technologies, which provide prognostic and predictive information for advanced cancer patients, without the analytical and procedural drawbacks of tissue-biopsy. In particular, circulating tumor DNA (ctDNA) is gaining momentum as a clinically feasible option capable to capture both spatial and temporal tumor heterogeneity.Several techniques are currently available for ctDNA extraction and analysis, each with its preferential case scenarios and preanalytical implications which must be taken into consideration to effectively support clinical decision-making and to better highlight its clinical utility.Aim of this review is to summarize both analytical developments and clinical evidences to offer a comprehensive update on the deployment of ctDNA in breast cancer’s (BC) characterization and treatment.     

Monitoring Therapeutic Response and Resistance: Analysis of Circulating Tumor DNA in Patients With ALK+ Lung Cancer

IntroductionDespite initial effectiveness of ALK receptor tyrosine kinase inhibitors (TKIs) in patients with ALK+ NSCLC, therapeutic resistance will ultimately develop. Serial tracking of genetic alterations detected in circulating tumor DNA (ctDNA) can be an informative strategy to identify response and resistance. This study evaluated the utility of analyzing ctDNA as a function of response to ensartinib, a potent second-generation ALK TKI.MethodsPre-treatment plasma was collected from 76 patients with ALK+ NSCLC who were ALK TKI–naive or had received prior ALK TKI, and analyzed for specific genetic alterations. Longitudinal plasma samples were analyzed from a subset (n = 11) of patients. Analysis of pre-treatment tumor biopsy specimens from 22 patients was compared with plasma.ResultsDisease-associated genetic alterations were detected in 74% (56 of 76) of patients, the most common being EML4-ALK. Concordance of ALK fusion between plasma and tissue was 91% (20 of 22 blood and tissue samples). Twenty-four ALK kinase domain mutations were detected in 15 patients, all had previously received an ALK TKI; G1269A was the most prevalent (4 of 24). Patients with a detectable EML4-ALK variant 1 (V1) fusion had improved response (9 of 17 patients; 53%) to ensartinib compared to patients with EML4-ALK V3 fusion (one of seven patients; 14%). Serial changes in ALK alterations were observed during therapy.ConclusionsClinical utility of ctDNA was shown, both at pre-treatment by identifying a potential subgroup of ALK+ NSCLC patients who may derive more benefit from ensartinib and longitudinally by tracking resistance. Prospective application of this technology may translate to improved outcomes for NSCLC patients treated with ALK TKIs.     

Duration of Targeted Therapy in Patients With Advanced Non–small-cell Lung Cancer Identified by Circulating Tumor DNA Analysis

BackgroundOutcomes of therapy targeting molecular driver alterations detected in advanced non–small-cell lung (NSCLC) using circulating tumor DNA (ctDNA) have not been widely reported in patients who are targeted therapy-naive.Patients and MethodsWe performed a multicenter retrospective review of patients with unresectable stage IIIB to IV NSCLC who received matched therapy after a targetable driver alteration was identified using a commercial ctDNA assay through usual clinical care. Eligible patients must not have received targeted therapy prior to ctDNA testing (prior chemotherapy or immunotherapy was permitted). Kaplan-Meier analysis was used to estimate the median duration of targeted therapy. Patients still on targeted therapy were censored at last follow-up.ResultsSeventy-six patients met inclusion criteria. The median age of diagnosis of NSCLC was 64.5 years (range, 31-87 years), 67% were female, 74% were never-smokers, and 97% had adenocarcinoma histology. Twenty-one (28%) patients received systemic treatment prior to targeted therapy, including chemotherapy (n = 17), immunotherapy (n = 5), and/or a biologic (n = 4). Thirty-three (43%) patients remain on targeted therapy at the time of data analysis. The median time on targeted therapy was similar to what has been reported for tissue-detected oncogenic driver mutations in the targeted therapy-naive setting.ConclusionsPatients with ctDNA-detected drivers had durable time on targeted therapy. These treatment outcomes data compliment previous studies that have shown enhanced targetable biomarker discovery rates and high tissue concordance of ctDNA testing when incorporated at initial diagnosis of NSCLC. Identification of NSCLC driver mutations using well-validated ctDNA assays can be used for clinical decision-making and targeted therapy assignment.     

结直肠癌早期筛查进展

目的 总结中美权威机构推荐的结直肠癌筛查手段。方法 在美国预防医学工作组（USPSTF）、美国纽约州卫生部、国家消化系统疾病临床医学研究中心等权威机构网站检索 “结直肠癌”、“筛查”等关键词。根据权威机构推荐的早期筛查方法，进一步在NCBI数据库中检索获得技术实施方法、优缺点等信息。结果 比较了结肠镜、结肠CT、钡灌肠造影、粪便隐血试验、粪便免疫化学试验、粪便DNA检测和液体活检的敏感性、特异性及优缺点。结论 内镜及影像技术不断完善。各种非侵入性、高敏感性、高特异性的生物标志物不断涌现，并需及早开展临床试验，以满足大规模人群筛查的需求。     

复方黄柏液涂剂联合吲哚美辛栓治疗PPH术后肛门下坠

目的:观察复方黄柏液涂剂灌肠联合吲哚美辛栓纳肛治疗吻合器痔上黏膜环切术(Procedure for Prolapse and Hemorrhoids,PPH)术后肛门下坠的临床效果。方法:收集40例PPH术后1个月后出现肛门下坠患者并随机分为两组,治疗组20例,给予复方黄柏液涂剂灌肠联合吲哚美辛栓纳肛;对照组20例,单独给予吲哚美辛栓纳肛。7天为1个疗程,连续治疗2个疗程,观察治疗后的症状积分及治疗有效率。结果:两组患者治疗前肛门下坠评分比较,差异无统计学意义(P> 0.05);两组患者经过2个疗程的治疗,治疗前与治疗后的症状积分均有改善(P <0.05),2个疗程后治疗组的肛门下坠评分低于对照组(P <0.05)。治疗组总有效率为94.7%(18/19),低于对照组的78.9%(15/19),差异有统计学意义(P <0.05)。结论:复方黄柏液涂剂灌肠联合吲哚美辛栓治疗PPH术后肛门下坠比单独使用吲哚美辛栓效果明显,尤其是对肛门坠胀不适疼痛不明显者。