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Cummings posted an update 1 year, 6 months ago
Children living with HIV are reaching adulthood and transitioning to adult clinics. This study aimed to describe clinical and immunovirological status after transition in patients with perinatal HIV.
Patients participating in the Spanish multicenter pediatric HIV cohort (CoRISpe) transferred to adult care (FARO cohort) from 1997 to 2016 were included. Clinical and immunovirological data were collected from 12 years old to the last follow-up moment after transition (up to December 2017). We used mixed-effect models to analyze changes in CD4 counts or viral suppression and multivariate analysis for risk factors for virological failure (VF) and immune status after transition. Transition years were classified into 5-year periods.
Three hundred thirty-two youths were included. The median age at transition was 18 years (interquartile range 16.3-18.9) and 58.1% women. The median follow-up time after transition was 6.6 years (interquartile range 4.6-9.8), and 11 patients (3.3%) died. The immunovirological status at transition improved over the last periods. Globally, VF decreased from 27.7% at transition to 14.4% at 3 years post-transition (P < 0.001), but no changes were observed in the last 2 transition periods. There were no significant differences in CD4 over the transition period. Risk factors for VF after transition were female sex, being born abroad and VF at transition, and for lower CD4 after transition were Romani heritage, younger age at transition, lower CD4 nadir, and CD4 at transition.
After transition, virological suppression improved in the early transition periods, and immunological status remained stable. Nevertheless, some patients had higher risk of worse outcomes. BEZ235 purchase Identifying these patients may aid during transition.
After transition, virological suppression improved in the early transition periods, and immunological status remained stable. Nevertheless, some patients had higher risk of worse outcomes. Identifying these patients may aid during transition.Meningiomas are a central nervous system tumor primarily afflicting adults, with less then 1% of cases diagnosed during childhood or adolescence. Somatic variation in NF2 may be found in ∼50% of meningiomas, with other genetic drivers (eg, SMO, AKT1, TRAF7) contributing to NF2 wild-type tumors. NF2 is an upstream negative regulator of YAP signaling and loss of the NF2 protein product, Merlin, results in YAP overexpression and target gene transcription. This mechanism of dysregulation is described in NF2-driven meningiomas, but further work is necessary to understand the NF2-independent mechanism of tumorigenesis. Amid our institutional patient-centric comprehensive molecular profiling study, we identified an individual with meningioma harboring a YAP1-FAM118B fusion, previously reported only in supratentorial ependymoma. The tumor histopathology was remarkable, characterized by prominent islands of calcifying fibrous nodules within an overall collagen-rich matrix. To gain insight into this finding, we subsequently evaluated the genetic landscape of 11 additional pediatric and adolescent/young adulthood meningioma patients within the Children’s Brain Tumor Tissue Consortium. A second individual harboring a YAP1-FAM118B gene fusion was identified within this database. Transcriptomic profiling suggested that YAP1-fusion meningiomas are biologically distinct from NF2-driven meningiomas. Similar to other meningiomas, however, YAP1-fusion meningiomas demonstrated overexpression of EGFR and MET. DNA methylation profiling further distinguished YAP1-fusion meningiomas from those observed in ependymomas. In summary, we expand the genetic spectrum of somatic alteration associated with NF2 wild-type meningioma to include the YAP1-FAM118B fusion and provide support for aberrant signaling pathways potentially targetable by therapeutic intervention.Currently, there is no consensus on the optimal tumor response score (TRS) system to assess regression in pancreatic cancers resected after neoadjuvant therapy. We developed a novel TRS (Royal North Shore [RNS] system) based on estimating the percentage of tumor bed occupied by viable cancer and categorized into 3 tiers grade 1 (≤10%), grade 2 (11% to 75%), and grade 3 (>75%). We assessed 147 resected carcinomas with this and other TRS systems (College of American Pathologists [CAP], MD Anderson Cancer Center [MDACC], and Evans). The 3-tiered RNS system predicted median survival after surgery for grades 1, 2, and 3 of 54, 23, and 9 months, respectively (P less then 0.05). The CAP, MDACC, and Evans systems also predicted survival (P less then 0.05) but less consistently. The median survival for MDACC and CAP grade 0 (complete regression) was less than MDACC grade 1 and CAP grades 1 and 2. There was no difference in survival between CAP grades 2 and 3 (P=0.960), Evans grades 1 and 2a (P=0.395), and Evans grades 2a and 2b (P=0.587). Interobserver concordance was weak for CAP (κ=0.431), moderate for MDACC (κ=0.691), minimal for Evans (κ=0.307), and moderate to strong for RNS (κ=0.632 to 0.84). Of age, sex, size, stage, grade, perineural and vascular invasion, extrapancreatic extension, margin status, and RNS score, only RNS score, vascular invasion, and extrapancreatic extension predicted survival in univariate analysis. Only extrapancreatic extension (P=0.034) and RNS score (P less then 0.0001) remained significant in multivariate analysis. We conclude that the RNS system is a reproducible and powerful predictor of survival after resection for pancreatic cancers treated with neoadjuvant therapy and should be investigated in larger cohorts.
Opioid-related disparities are magnified among Alaska Native and American Indian (ANAI) people. Yet, no outcome studies on medication for addiction treatment, an effective treatment in other populations, among ANAI people exist. The objective of this study was to identify variables associated with buprenorphine/naloxone retention among ANAI people with opioid use disorder (OUD).
The sample was 240 ANAI adults in Anchorage, Alaska who received buprenorphine/naloxone treatment for an OUD. We gathered data from the electronic health record from January 1, 2015 to December 31, 2019. We used survival analysis to explore possible predictors (demographic variables, psychiatric comorbidity, medical severity, previous opioid prescriptions, previous injury, alcohol use disorder, and co-occurring substance use of length of treatment retention (in days) while accounting for right censoring.
We found that 63% of the 240 patients were retained in buprenorphine/naloxone treatment at 90 days, 51% at 6 months, and 40% at 1 year, slightly lower than the general US population.