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Daily low-dose carboplatin plus concurrent thoracic radiotherapy is the standard treatment for elderly patients with unresectable clinical stage (c-Stage) III non-small cell lung cancer (NSCLC) in Japan. However, a phase I study by Omori et al. suggests that weekly carboplatin and nab-paclitaxel plus concurrent thoracic radiotherapy have comparable efficacy outcomes with more manageable adverse events. In December 2020, we initiated a randomized controlled trial in Japan to confirm whether the weekly carboplatin plus nab-paclitaxel regimen is noninferior to the daily low-dose carboplatin regimen for concurrent chemoradiotherapy in elderly patients with unresectable c-Stage III NSCLC. We plan to enroll 166 patients from 50 institutions in 3.5 years. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, response rate, proportion of patients starting maintenance durvalumab therapy, adverse events, site of progression, Functional Assessment of Cancer Therapy-Trial Outcome Index deterioration and Instrumental Activities of Daily Living deterioration.

The attention on mismatch repair-deficient (dMMR) gastric cancer has increased in this era of anti-PD-1 blockade therapy; however, the prevalence and molecular genetics of patients with dMMR gastric cancer have not been completely investigated.

Immunohistochemistry of MMR proteins (MLH1, MSH2, MSH6 and PMS2) was performed on formalin-fixed paraffin-embedded sections prepared from resected primary gastric cancers of 513 consecutive patients. Genetic and/or epigenetic alterations of the MMR genes were also investigated.

Loss of expression of one or more MMR proteins was observed in 58 patients (11.3%); 54 patients showed loss of MLH1/PMS2, 3 patients showed loss of MLH1/PMS2/MSH6 and 1 patient showed loss of PMS2 alone. Among these 58 patients, 55 showed hypermethylation of the promoter region of MLH1. Genetic testing revealed that the remaining three patients had Lynch syndrome (n=1) or Lynch-like syndrome (n=2). A total of 15 patients (25.9% of all patients with dMMR gastric cancer and 2.9% of all patients with gastric cancer), including 11 patients with stage I-III dMMR gastric cancer who had recurrence and 4 patients with stage IV dMMR gastric cancer, are potential candidates for the use of anti-PD-1 blockades.

This is the first study to investigate the frequency and molecular genetic mechanisms of dMMR gastric cancer comprehensively, focusing on the benefit of using PD-1 blockades. Our observations will be beneficial in the clinical practice of metastatic gastric cancer.

This is the first study to investigate the frequency and molecular genetic mechanisms of dMMR gastric cancer comprehensively, focusing on the benefit of using PD-1 blockades. Our observations will be beneficial in the clinical practice of metastatic gastric cancer.

Patients with chronic kidney disease (CKD) are more prone to severe infection. Vaccination is a key strategy to reduce this risk. Some studies suggest vaccine efficacy may be reduced in patients with CKD, despite preserved maintenance of long-term responses to some pathogens and vaccines. Here, we investigated immune responses to two vaccines in patients with CKD in order to identify predictors of immunological responsiveness.

Individuals >65 years old, with or without non-dialysis CKD (n=36 and 29, respectively), were vaccinated with a non-adjuvanted seasonal influenza vaccine (T-dependent) and Pneumovax23 (PPV23, T-independent). Humoral responses were measured at baseline, day 28 and 6 months. Lymphocyte subset and plasmacell/blast analyses were performed using flow cytometry. CMV serotyping was assessed by ELISA.

Only modest responsiveness was observed to both vaccines, independent of CKD status (25% adequate response in controls versus 12-18% in CKD group). Unexpectedly, previous immunization with PPV23 (median 10-year interval) and CMV seropositivity were associated with poor PPV23 responsiveness in both study groups (p<0.001 and 0.003 respectively, multi-variable linear regression model). Patients with CKD displayed expanded circulating populations of Th2 and Tregs, which were unrelated to vaccine responses. Despite fewer circulating B cells, patients with CKD were able to mount a similar day 7 plasmacell/blast response to controls.

Patients with non-dialysis CKD can respond similarly to vaccines as age and sex matched healthy individuals. CKD patients display an immune signature that is independent of vaccine responsiveness. Prior PPV23 immunization and CMV infection may influence responsiveness to vaccination.

Patients with non-dialysis CKD can respond similarly to vaccines as age and sex matched healthy individuals. CKD patients display an immune signature that is independent of vaccine responsiveness. Prior PPV23 immunization and CMV infection may influence responsiveness to vaccination.The diamondback moth, Plutella xylostella L., is a worldwide crop pest that is difficult to control because of its ability to develop resistance to many insecticides. To provide a reference for resistance management of P. xylostella in China, the present study used a leaf-dip bioassay to monitor the resistance of P. xylostella to nine insecticides in eight regions of China. The results showed that P. xylostella had developed a high level of resistance to beta-cypermethrin (resistance ratio [RR] > 112), and moderate (RR 100 were found in Midu (Yunnan Province) and Jinghai (Tianjin). In most regions, the resistance to spinetoram and chlorfenapyr and Bacillus thuringiensis (Bt) was low. No resistance was detected to diafenthiuron. Overall, P. xylostella resistance to insecticides was higher in Midu than in other regions. The data in this study should help guide the selection of insecticides for management of P. xylostella in China.

Is there an evolution in the risk of operated cryptorchidism in France and does local geographical environment appear as an important trigger for this defect?

We observed an increase of the risk of operated cryptorchidism in boys under the age of 7 years during the period 2002-2014 and a strong spatial heterogeneity, with the detection of spatial clusters suggesting environmental factors.

Epidemiologic data on cryptorchidism are scarce and its etiology is poorly understood. As part of the testicular dysgenesis syndrome, cryptorchidism is suspected to be a male genital developmental disorder caused by endocrine disruptor chemical (EDC) exposure during the prenatal period.

This was a retrospective and descriptive study using data from the French national hospital discharge database, in the 2002-2014 study period. We built an indicator to reflect incident cases of operated cryptorchidism in boys under the age of 7 years in metropolitan France, with an algorithm using specific codes for diseases (ICD-10 cctual or potential competing financial interest.

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N/A.The Chicago Classification of esophageal motility disorders improved the differentiation of achalasia subtypes and tailored treatment. Heller myotomy (HM) and pneumatic dilation are two established treatments for achalasia. Peroral endoscopic myotomy (POEM) has become a third definitive option and is on the rise. Using the National Inpatient Sample (NIS) database, we evaluated patients hospitalized with achalasia and associated surgical and endoscopic interventions from 2013 to 2017 and compared patients undergoing HM versus POEM. The NIS database was queried to include patients with achalasia. Patients who underwent HM, POEM (only 2017 due to lack of distinct procedure code in 2013), pneumatic dilation, or esophagectomy were identified. Adverse events during the hospitalization were also queried using diagnosis codes. From 2013 to 2017, patients hospitalized with achalasia increased from 16 850 to 19 485. There were reductions in the number of esophageal dilations (10.6-5.4%, P  64 (P = 0.004), Charlson comorbidity index (P  less then  0.001), disease severity (P  less then  0.001), and likelihood of mortality (P  less then  0.001). There were no differences in length of stay, mortality, or total costs between the HM and POEM groups. Patients hospitalized with achlasia increased from 2013 to 2017, possibly due to the growth and accessibility of high-resolution esophageal manometry. Cell Cycle inhibitor As expertise in POEM increases, the number of POEM performed is anticipated to rise with possible further reductions in other treatment modalities for achalasia.Two frequently encountered but underrecognized challenges for causal inference in studying the long-term health effects of disasters among survivors include (a) time-varying effects of disasters on a time-to-event outcome and (b) selection bias due to selective attrition. We review approaches to overcome these challenges and show application of the approaches to a real-world longitudinal data of older adults who were directly impacted by the 2011 earthquake and tsunami (n=4,857). To illustrate the problem of time-varying effects of disasters, we examined the association between degree of damage due to the tsunami and all-cause mortality. We compared results from Cox regression assuming proportional hazards versus adjusted parametric survival curves allowing for time-varying hazard ratios. To illustrate the problem of selection bias, we examined the association between proximity to the coast (a proxy for housing damage from the tsunami) and depressive symptoms. We corrected for selection bias due to attrition in the two post-disaster follow-up surveys (conducted in 2013 and 2016) using multivariable adjustment, inverse probability censoring weighting, and survivor average causal effect estimation. Our results demonstrate that the analytic approaches ignoring time-varying effects on mortality and selection bias due to selective attrition may underestimate the long-term health effects of disasters.

Treatment guidelines for patients with atrial fibrillation (AF) suggest that patients should be managed with an antiarrhythmic drug (AAD) before undergoing catheter ablation (CA). This study evaluated whether pulmonary vein isolation employing cryoballoon CA is superior to AAD therapy for the prevention of atrial arrhythmia (AA) recurrence in rhythm control naive patients with paroxysmal AF (PAF).

A total of 218 treatment naive patients with symptomatic PAF were randomized (1  1) to cryoballoon CA (Arctic Front Advance, Medtronic) or AAD (Class I or III) and followed for 12 months. The primary endpoint was ≥1 episode of recurrent AA (AF, atrial flutter, or atrial tachycardia) >30 s after a prespecified 90-day blanking period. Secondary endpoints included the rate of serious adverse events (SAEs) and recurrence of symptomatic palpitations (evaluated via patient diaries). Freedom from AA was achieved in 82.2% of subjects in the cryoballoon arm and 67.6% of subjects in the AAD arm (HR = 0.48, P = 0.01). There were no group differences in the time-to-first (HR = 0.76, P = 0.28) or overall incidence [incidence rate ratio (IRR)=0.79, P = 0.28] of SAEs. The incidence rate of symptomatic palpitations was lower in the cryoballoon (7.61 days/year) compared with the AAD arm (18.96 days/year; IRR = 0.40, P < 0.001).

Cryoballoon CA was superior to AAD therapy, significantly reducing AA recurrence in treatment naive patients with PAF. Additionally, cryoballoon CA was associated with lower symptom recurrence and a similar rate of SAEs compared with AAD therapy.

Cryoballoon CA was superior to AAD therapy, significantly reducing AA recurrence in treatment naive patients with PAF. Additionally, cryoballoon CA was associated with lower symptom recurrence and a similar rate of SAEs compared with AAD therapy.