Characteristics, Treatment, and Outcomes of Real-World Talazoparib-Treated Patients With Germline BRCA-Mutated Advanced HER2-Negative Breast Cancer.

BACKGROUND: Talazoparib is a poly (adenosine diphosphate-ribose) polymerase inhibitor approved for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative, locally advanced or metastatic breast cancer (LA/mBC), with approval based on the EMBRACA trial. To date, there are no published data on talazoparib use in the real-world United States (USA) setting. PATIENTS AND METHODS: Characteristics, treatment patterns, and clinical outcomes of real-world US patients with gBRCAm HER2-negative LA/mBC treated with talazoparib monotherapy were collected via retrospective chart review and summarized using descriptive statistics. RESULTS: Among 84 eligible patients, 35.7% had hormone receptor-positive tumors and 64.3% had triple-negative LA/mBC (TNBC). At talazoparib initiation, 29.8% had ECOG PS of ≥2 and 19.0% had brain metastasis. Mutations in gBRCA1 or 2 were detected among 64.3% and 35.7% of patients, respectively. Talazoparib was given as 1st-line therapy in 14.3% of patients, 2nd-line in 40.5%, and 3rd- or 4th-line in 45.2%. Median time to talazoparib treatment failure was 8.5 months (95% CI, 8.0-9.7), median progression-free survival was 8.7 months (95% CI, 8.0-9.9), the median time from initiation to chemotherapy was 12.2 months (95% CI, 10.5-20.1), and the overall response rate was 63.1%. No differences in clinical outcomes were observed between patients with HR-positive/HER2-negative LA/mBC and patients with TNBC by using unadjusted statistical comparisons. Brain metastasis and ECOG PS ≥2 at talazoparib initiation were associated with treatment failure and progression or mortality. CONCLUSION: Overall, talazoparib clinical outcomes in this real-world population are consistent with findings from EMBRACA.

Fungi: Friend or Foe? A Mycobiome Evaluation in Children With Autism and Gastrointestinal Symptoms.

ABSTRACT: Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD + GI), 10 children with ASD but no GI symptoms (ASD - GI), and 20 from typically developing (TD) children in this pilot study. Fecal mycobiome taxa were analyzed by Internal Transcribed Spacer sequencing. GI symptoms (GI Severity Index [GSI]), behavioral symptoms (Social Responsiveness Scale -2 [SRS-2]), inflammation and fungal immunity (fecal calprotectin and serum dectin-1 [ELISA]) were evaluated. We observed no changes in the abundance of total fungal species (alpha diversity) between groups. Samples with identifiable Candida spp. were present in 4 of 19 (21%) ASD + GI, in 5 of 9 (56%) ASD - GI, and in 4 of 16 (25%) TD children (overall P = 0.18). The presence of Candida spp. did not correlate with behavioral or GI symptoms (P = 0.38, P = 0.5, respectively). Fecal calprotectin was normal in all but one child. Finally, there was no significance in serum dectin-1 levels, suggesting no increased fungal immunity in children with ASD. Our data suggest that fungi are present at normal levels in the stool of children with ASD and are not associated with gut inflammation.

Resistin levels decrease as insulin resistance increases in a Mexican-American cohort.

AIMS: Links between resistin, insulin resistance (IR), and resistin-stimulated cytokine signaling remain unknown in Mexican-Americans. A Mexican-American cohort was examined to determine (1) relationships between circulating resistin and IR, (2) resistin's associations with cytokines and demographic and anthropometric variables, and (3) similar measurements with other adipokines. METHODS: For cross sectional analyses, 953 adults (367 males and 586 females) in the Cameron County Hispanic Cohort (CCHC) were stratified into three groups: normal glucose tolerance, prediabetes, and diabetes mellitus. Differences in resistin and other adipokine levels were examined using linear regression via unadjusted model (Model 1), model adjusted for cytokines (Model 2), and model further adjusted for demographic and anthropometric variables (Model 3). RESULTS: HOMA-IR increased with worsening glucose tolerance (p < 0.0001). In all models, resistin significantly decreased as glucose tolerance deteriorated. Model 3 resistin was positively associated with IL-1ß (p = 0.0252) and IL-8 (p < 0.0001), inversely associated with TNF-α (p = 0.0352), but nonsignificantly associated with IL-6 (p = 0.8671). Model 3 leptin was significantly lower in diabetes mellitus compared to other groups (p < 0.005) and positively associated with female sex (p < 0.0001), age (p = 0.024), and BMI (p < 0.0001), without significant cytokine associations. Adiponectin displayed no significant associations with glucose tolerance, but was significantly associated with sex, BMI, and lipids (Model 3). CONCLUSIONS: Resistin unexpectedly decreased as IR increased while supporting evidence of a resistin-stimulated cytokine pathway in this Mexican-American cohort. Leptin fell with elevated IR after adjusting for cytokines, demographic and anthropometric variables. Adiponectin nonsignificantly decreased as IR increased while showing significant associations with sex, BMI, and lipids.

The beneficial effect of providing kidney transplantation information on transplantation status differs between for-profit and nonprofit dialysis centers.

Informing end-stage kidney disease patients about kidney transplantation options increases the likelihood of kidney transplant waiting list (WL) enrollment and live donor kidney transplant (LDKT) receipt. Patients in for-profit dialysis centers have lower rates of WL enrollment and LDKT receipt. This study examined if the ownership status of dialysis centers modified the association between informing patients about transplantation options and patients' transplantation status. Multilevel analysis using mixed-effect multinomial logistic regression was performed using the United States Renal Data System (USRDS) data (January 2005 to December 2017). The study showed that informing patients improved the odds of WL enrollment and LDKT receipt. However, the effect of informing patients on transplantation status was less pronounced at for-profit as compared with nonprofit centers (Nonprofit: WL enrollment OR: 2.23 [95% CI: 2.07-2.40], and LDKT receipt OR: 3.35 [95% CI: 2.65-4.25]. For-profit: WL enrollment OR: 1.73 [95% CI: 1.66-1.79], and LDKT receipt OR: 2.35 [95% CI: 2.08-2.66]), although the odds of informing patients was higher for for-profit centers, and type of patients informed were similar across both types of centers. Information provided by for-profit centers was potentially less effective than those provided by nonprofit centers. Standardized guidelines for transplantation information provision are needed in order to ensure similar informational quality across centers.

Regional Intervention of Stroke Care to Increase Thrombolytic Therapy for Acute Ischemic Stroke.

Background and Purpose- The aims of this study were to investigate the effect of an intervention to unblind data on r-tPA (recombinant tissue-type plasminogen activator) administration and sharing data with chief executive officers of participating hospitals, on r-tPA administration rates postintervention and on potential healthcare cost savings implemented at 26 Southeast Texas Regional Advisory Council hospitals. Methods- Retrospective analysis of prospective data on thrombolytic therapy from 26 Southeast Texas Regional Advisory Council hospitals, collected between April 2014 and June 2016. The control (blinded) period (Q2-2014 to Q2-2015) was followed by unblinding (Q3-2015). Results- Intervention was associated with 21.1% increase in r-tPA administration rates, with 38.5% increase in r-tPA administration with door-to-needle time ≤60 minutes. An absolute increase in r-tPA administration of 2.1% was seen with an average lifetime cost savings of $3.6 million. Conclusions- Transparent regional data sharing was associated with improved r-tPA administration and healthcare cost savings.