Notes

Caspase-11 cleaves gasdermin N pertaining to non-canonical inflammasome signalling.
OBJECTIVE There is concern whether established parenting programs for children's conduct problems meet the needs of families with severe and complex mental health problems. For example, many children with conduct problems show comorbid ADHD or emotional problems, or have parents who are depressed, but families with such complex mental health problems typically seen in real life are often underrepresented in evaluation trials. We tested whether children with more severe conduct problems, and those with more complex mental health problems, benefit less from the Incredible Years parenting program, using individual participant data meta-analysis of randomized trials in Europe. METHOD In 1,696 families from 13 trials (child age 2-11; 37% girls; 58% low income; 30% ethnic minority; 98% mothers), we used moderator analysis within a multilevel model to test whether initial conduct problem severity, comorbid ADHD or emotional problems and maternal depression diminished intervention effects for children's conduct problems RESULTS The Incredible Years program reduced children's conduct problems overall (Cohen's d = -0.35), but more so in children with more severe conduct problems. There was no evidence that children's comorbid ADHD and emotional problems changed the intervention benefits. Children of mothers with more depressive symptoms benefited more. CONCLUSION Children with more severe conduct problems derive greater, rather than lesser, benefits from a high-quality group parenting program, and comorbid ADHD and emotional problems do not reduce effects; maternal depression, rather than being linked to less child change, were associated with greater reductions in children's conduct problems. BACKGROUND Although sorafenib as a standard of care for advanced hepatocellular carcinoma (HCC) prolongs overall survival (OS), its efficacy is limited due to its unsatisfactory objective response and marginal survival benefit. To counter these limitations, we designed a single-arm, phase II trial with liver-directed concurrent chemoradiotherapy (LD-CCRT) and sequential sorafenib treatment in patients with advanced HCC. METHOD We enrolled advanced HCC patients diagnosed between 2014 and 2017 who were ineligible for curative treatment. During the first and last 5 days of 5-week radiotherapy, concurrent hepatic arterial infusion with 5-fluorouracil (500 mg/day) and leucovorin (50 mg/day) through an implanted port was administered 4 weeks after initiation of LD-CCRT and sequential sorafenib treatment (400 mg, twice daily). The primary endpoint was OS. This trial has been registered at clinicaltrials.gov. RESULT Among the enrolled patients (n=47), objective response rates 4 weeks after LD-CCRT and during up-to-sorafenib maintenance were 44.7% and 53.2%, respectively. Overall, nine patients (19.1%) underwent curative resection or transplantation after down-staging. The median radiation dose was 60 Gy. The median OS was 24.6 months for the entire cohort and 13.0 months for the subgroup with tumor invasion into the main portal trunk or its first branch, whereas the median progression-free survival (PFS) for the cohort and subgroup was 6.8 and 5.6 months, respectively. The most frequent treatment-related adverse events were diarrhea (36.2%) and hand-foot skin reaction (34%), which were manageable with conservative treatment. CONCLUSION LD-CCRT and sequential sorafenib treatment provided favorable OS and PFS with good tolerability. Tumor reduction using an initial LD-CCRT enabled down-staging, subsequent curative treatment, and long-term survival in about 20% of the patients with advanced HCC. However, further randomized trials are required to confirm these results. PURPOSE Brain metastases are a common sequelae of breast cancer. Survival varies widely based on diagnosis-specific prognostic factors (PF). We previously published a prognostic index (Graded Prognostic Assessment [GPA]) for patients with breast cancer with brain metastases (BCBM), based on cohort A (1985-2007, n = 642), then updated it, reporting the effect of tumor subtype in cohort B (1993-2010, n = 400). The purpose of this study is to update the Breast GPA with a larger contemporary cohort (C) and compare treatment and survival across the 3 cohorts. METHODS AND MATERIALS A multi-institutional (19), multinational (3), retrospective database of 2473 patients with breast cancer with newly diagnosed brain metastases (BCBM) diagnosed from January 1, 2006, to December 31, 2017, was created and compared with prior cohorts. Associations of PF and treatment with survival were analyzed. Kaplan-Meier survival estimates were compared with log-rank tests. PF were weighted and the Breast GPA was updated such that a GPcal trials. Furthermore, these data suggest human epidermal receptor 2-targeted therapies improve clinical outcomes in some patients with BCBM. PURPOSE We sought to evaluate the feasibility and tolerability of a novel APBI regimen delivered in a single fraction postoperatively. METHODS AND MATERIALS We enrolled 50 patients with low-risk, hormone-sensitive breast cancer from 2015-2018 on a prospective phase I/II trial to receive single-fraction high-gradient partial breast irradiation (SFHGPBI) 2-8 weeks after lumpectomy for node-negative, invasive or in-situ breast cancer. The high gradient was achieved by prescribing 20 Gy to the surgical bed and 5 Gy to the breast tissue within 1 cm of the surgical bed simultaneously in one fraction using external beam. RESULTS The median age was 65 (range, 52-84). Ten patients (20%) had small volume DCIS while the remainder had stage I disease. At a median follow-up of 25 months, we evaluated toxicity, patient and physician-reported cosmesis, patient-reported quality of life (QOL), and initial tumor control. There was no CTCAEv4.0 grade 3+ toxicity. Only 34% of patients experienced grade 1 erythema. Good-to-excellllent, with longer follow-up required to confirm efficacy. Sodium dichloroacetate inhibitor BACKGROUND Radiation therapy (RT), a standard Breast Cancer (BC) treatment modality, is associated with a small increased risk of in-field second primary malignancy (SPM). SPM rates following RT in BRCA mutation carriers, have rarely been reported. An elevated risk of SPM would impact the safety of breast conservation for early BC or prophylactic radiation as a method of prevention. We analyzed a population of BRCA carriers irradiated for BC to determine if there is an elevated rate of SPM. METHODS BC patients treated with breast/chestwall RT +/- regional lymph nodes between 1991-2012 at a single institution who were BRCA 1/2 carriers were retrospectively identified. Only those with >5 years of follow up with adequate demographic, tumor, and radiation data were included. SPMs were recorded and previously delivered RT doses to the organ/site of malignancy were determined. RESULTS 230 women, of whom 80% carried an Ashkenazi Jewish founder mutation, met entry criteria with 3D-RT delivered to 266 breasts/chest walls including regional nodes in 110 (41%).
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