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Radical cystectomy is the gold standard treatment for muscle invasive bladder cancer, but some patients have medically inoperable disease or refuse cystectomy to preserve their bladder function. Bladder preservation therapy with transurethral resection of the bladder tumor and concurrent chemoradiotherapy, known as trimodal treatment, is regarded to be a curative-intent alternative to radical cystectomy for patients with muscle invasive bladder cancer during the past decade. After the development of immune checkpoint inhibitors, a world-changing breakthrough occurred in the field of metastatic urothelial carcinoma and many clinical trials have been conducted against non-muscle invasive bladder cancer. Interestingly, preclinical and clinical studies against other malignancies have shown that immune checkpoint inhibitors interact with the radiation-induced immune reaction. As half of the patients with muscle invasive bladder cancer are elderly, and some have renal dysfunction, not only as comorbidity but also because of hydronephrosis caused by their tumors, immune checkpoint inhibitors are expected to become part of a new therapeutic approach for combination treatment with radiotherapy. Accordingly, clinical trials testing immune checkpoint inhibitors have been initiated to preserve bladder for muscle invasive bladder cancer patients using radiation and immune checkpoint inhibitors with/without chemotherapy. The objective of this review is to summarize the evidence of trimodal therapy for muscle invasive bladder cancer during the past decade and to discuss the future directions of bladder preservation therapy in immuno-oncology era.

When evaluating deep brain stimulation (DBS) for newer indications, patients may benefit from trial stimulation prior to permanent implantation or for investigatory purposes. Although several case series have evaluated infectious complications among DBS patients who underwent trials with external hardware, outcomes have been inconsistent.

To determine whether a period of lead externalization is associated with an increased risk of infection.

We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses compliant systematic review of all studies that included rates of infection for patients who were externalized prior to DBS implantation. A meta-analysis of proportions was performed to estimate the pooled proportion of infection across studies, and a meta-analysis of relative risks was conducted on those studies that included a control group of nonexternalized patients. Heterogeneity across studies was assessed via I2 index.

Our search retrieved 23 articles, comprising 1354 patientsin the clinical setting.PCB118, a 2,3′,4,4′,5-pentachlorobiphenyl, has been shown to destroy thyroidal ultrastructure and induce thyrocyte autophagy. Previously, we reported that PCB118 promoted autophagosome formation in vivo and in vitro, but more details remain to be revealed. To explore the underlying mechanism by which PCB118 regulates thyrocyte autophagy, Fischer rat thyroid cell line-5 (FRTL-5) cells were exposed to different doses of PCB118 at 0, 0.25, 2.5, and 25 nM for 0-48 h. Western blot analysis of autophagy-related proteins P62, BECLIN1, and LC3 demonstrated that PCB118 induced autophagy formation in dose- and time-dependent manner. Moreover, laser scanning confocal microscopy and flow cytometry showed PCB118 treatment led to time- and dose-dependent increase in intracellular calcium concentration ([Ca2+]i). Additionally, PCB118 promoted store-operated Ca2+ entry (SOCE) channel followed by significant increase of ORAI1 and STIM1 protein levels. On the other hand, PCB118 induced thyroidal autophagy via class III β-tubulin (TUBB3)/death-associated protein kinase 2 (DAPK2)/myosin regulatory light chain (MRLC)/autophagy-related 9A (ATG9A) pathway in FRTL-5 cells. find more Pretreatment with SOCE inhibitor SKF96365 reduced cytosolic Ca2+, ORAI1, STIM1, and BECLIN1 levels as well as LC3 II/LC3 I ratio, while increased P62 expression. SKF96365 also inhibited TUBB3/DAPK2/MRLC/ATG9A pathway in FRTL-5 cells treated by PCB118. Our results provide evidence that PCB118 may induce thyroidal autophagy through TUBB3-related signaling pathway, and these effects are likely to be regulated by calcium influx via SOCE channel.

To determine if there are distinct developmental trajectories of medical responsibility in youth with spina bifida (SB) across ages 8-17 years and to identify condition-related, parental, and family systems predictors of membership in these trajectory groups.

Participants were 140 youth with SB and their parents who participated in four waves of a longitudinal study across 6 years (ages 8-15 years at Time 1). Multi-method (questionnaires and observed family interactions) and multi-respondent assessments were conducted during home visits.

Findings revealed that there were two distinct developmental trajectories that characterized this sample, with one being labeled “high increasing” (two thirds of the sample) and one labeled “low increasing” (one third of the sample). Most predictor variables were significantly associated with trajectory group membership, with the exception of ethnicity, SES, and measures of conflict. When all significant univariate predictors were included in the same model, only intellg with youth with SB to recognize that the transfer of medical responsibility from parent to child cannot be expected to unfold in the same manner for all families of youth with SB.Endoscopic submucosal dissection (ESD) has been developed to overcome the limitations of endoscopic mucosal resection (EMR). Yet, the potential for EMR should not be ignored. This study aimed to compare the efficacy and safety of ESD and EMR in the treatment of superficial esophageal carcinoma (SEC). All relevant articles were retrieved from electronic databases. The primary outcomes included en bloc resection, curative resection, R0 resection, and local recurrence rates. Secondary outcomes included procedure time, rates of perforation, bleeding, and postoperative stricture. Subgroup analyses based on histologic types and lesion sizes were conducted. Twenty-two studies were enrolled. Overall results showed higher en bloc, curative, and R0 resection rate, and lower recurrence rate in ESD compared with EMR. ESD was significantly more time-consuming and induced more perforations than EMR procedure. In subgroup analyses of squamous cell carcinoma (SCC) and Barrett’s esophagus (BE)-associated neoplasia and esophageal adenocarcinoma (EAC) subtypes, ESD also excelled in en bloc, curative, R0 resection and local recurrence rates.