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Oncologists are increasingly using molecular profiling to inform personalized patient treatment decisions. Despite its promising utility, the integration of genomic testing into diverse clinical health care settings across geographic settings has been understudied.

We used data from the National Survey of Precision Medicine in Cancer Treatment, a nationally representative sample of practicing US oncologists, to assess the availability of six genomic testing resources, including on-site pathology, contracts with outside laboratories, on-site genetic counselors, internal policies or protocols for using genomic and biomarker testing, electronic medical record alerts, and genomic or molecular tumor boards. We used multivariate logistic regression models to examine differences in the availability of each genomic testing resource by practice type and rurality while adjusting for payer mix and patient volume.

A larger proportion of multispecialty group and academic practices had genomic testing resources availr.Metastatic prostate cancer is initially sensitive to androgen receptor inhibition, but eventually becomes castration-resistant prostate cancer (mCRPC). Early use of more intensive therapies targeting androgen receptor and other oncogenic drivers in treatment-naïve primary prostate cancer (PC) may be more effective than that in advanced mCRPC. However, analysis of primary tumors may not reveal targetable metastatic drivers that are subclonal in the primary tumor or acquired at metastatic sites.

PC samples spanning one patient's clinical course diagnostic biopsies, pre- or post-enzalutamide metastatic biopsies, and rapid autopsy samples including a patient-derived xenograft (PDX) were analyzed by targeted exome sequencing followed by phylogenetic analysis.

Left- and right-lobe primary PC tumors appeared to diverge, with the right acquiring additional shared mutations and striking differences in copy number alterations that later appeared in metastatic samples during the treatment course and at autopsy, where RB1 and BRCA2 loss), and suggest that earlier detection and targeting of these truncal alterations may be effective at halting disease progression.Neurotrophic tyrosine receptor kinase (NTRK) gene fusions encode oncogenic, chimeric tropomyosin receptor kinase (TRK) proteins. Larotrectinib, an approved TRK inhibitor, is efficacious in locally advanced or metastatic (adv/met) TRK fusion cancer. We evaluated the time from initial diagnosis to locally advanced or metastatic disease and to initiation of larotrectinib treatment as well as larotrectinib impact on disease course.

Patients were grouped by prior lines of therapy (0, 1-2, and ≥ 3) and pre-larotrectinib duration of adv/met disease (short [< 3.5 months], medium [3.5 to < 15.7 months], and long [≥ 15.7 months]). Overall response rate (ORR), duration of response (DOR), and progression-free survival were assessed.

One hundred sixty-four patients were evaluated. The median time from initial diagnosis to development of locally adv/met stage was 2.1 months; the duration of pre-larotrectinib adv/met disease was 7.3 months (n = 153). In patients with 0, 1-2, and ≥ 3 prior lines of therapy, the medies not generally have a positive prognostic value. Patients on larotrectinib had high, sustained ORR, independent of number of prior therapies or duration of adv/met disease, suggesting that the effect of TRK inhibition in molecularly selected patients is independent of prior treatments or disease course.

Medical education fellowships in emergency medicine (EM) provide training in teaching, assessment, educational program administration, and scholarship. The longitudinal impact of this training is unknown. Our objective was to characterize the career outcomes of medical education fellowship graduates.

We solicited curriculum vitae (CV) from graduates of U.S. EM education fellowships by email. see more We abstracted data from CVs with a standard instrument that included program characteristics, employment history, leadership positions, awards, and scholarly productivity. We calculated and reported descriptive statistics.

A total of 71 of 91 (78%) graduates participated. Thirty-three completed a 1-year fellowship and 38 completed a 2-year fellowship. Nineteen (27%) completed an advanced degree during fellowship. Median (range) graduation year was 2016 (1997-2020). The majority, 63 of 71 (89%), work in an academic setting. Graduates held leadership positions in continuing medical education, graduate medical education, and undergraduate medical education. Forty-eight (68%) served on national medical education committees. The mean±SD number of national medical education awards was 1.27±2.03. The mean±SD number of national medical education presentations was 7.63±10.83. Graduates authored a mean±SD of 3.63±5.81 book chapters and a mean±SD of 4.99±6.17 peer-reviewed medical education research publications. Ten (14%) served on journal editorial boards, 34 (48%) were journal reviewers, and 31 (44%) had received a medical education grant.

EM medical education fellowship graduates are academically productive and hold education leadership positions.

EM medical education fellowship graduates are academically productive and hold education leadership positions.

The primary objective was to survey pediatric emergency medicine (PEM) leaders and fellows regarding point-of-care ultrasound (POCUS) training in PEM fellowship programs, including teaching methods, training requirements, and applications taught. Secondary objectives were to compare fellows' and program leaders' perceptions of fellow POCUS competency and training barriers.

This was a cross-sectional survey of U.S. PEM fellows and fellowship program leaders of the 78 fellowship programs using two online group-specific surveys exploring five domains program demographics; training strategies and requirements; perceived competency; barriers, strengths, and weaknesses of POCUS training; and POCUS satisfaction.

Eighty-three percent (65/78) of programs and 53% (298/558) of fellows responded. All participating PEM fellowship programs included POCUS training in their curriculum. Among the 65 programs, 97% of programs and 92% of programs utilized didactics and supervised scanning shifts as educational techniques,oes conform to many of the expert recommended guidelines; however, there are some discrepancies and perceived barriers to POCUS training remain.

Although most PEM fellowship programs provide POCUS training, there is variation in content and requirements. link2 Training does conform to many of the expert recommended guidelines; however, there are some discrepancies and perceived barriers to POCUS training remain.Affinity of the mineralocorticoid receptor (MR) is similar for aldosterone and the glucocorticoids (GC) cortisol and corticosterone, which circulate at concentrations far exceeding those of aldosterone. 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) inactivation of GC within the immediate vicinity of the MR is credited with prereceptor specificity for aldosterone in cells coexpressing MR and 11βHSD2. 11βHSD2 efficacy is also critical to other recently described 11βHSD2 substrates. The aim of this work was to address doubts that low levels of expression of 11βHSD2 in aldosterone target tissues suffice to prevent the initiation of gene transcription by the MR activated by physiological concentrations of corticosterone. Cell models stably expressing an MR/Gaussia luciferase reporter and various levels of constitutive or induced 11βHSD2 at concentrations lower than those in rat kidney homogenates and microsomes were produced. link3 Aldosterone and corticosterone were equipotent transactivators of the MR reporter gene in cells without 11βHSD2. Rate of conversion of tritiated corticosterone to 11-dehydrocorticosterone increased and corticosterone-induced nuclear translocation of MR decreased, as 11βHSD2 expression increased. The 50% maximal MR activation for the reporter gene stimulation by corticosterone rose with increasing 11βHSD2 expression, shifting the steroid dose-response curve for corticosterone-induced MR transactivation to the right. Several stable cell lines expressing an easily and reproducibly measured MR reporter system and consistent incremental amounts of 11βHSD2 protein were produced and used to document that 11βHSD2 within low physiological levels inactivates relevant concentrations of GC and decreases MR transactivation by GC in a dose-dependent fashion, laying to rest doubts of the efficacy of this enzyme.

Hepatic glycogenosis (HG) has been reported after intravenous (IV) dextrose administration to treat insulin overdose. We describe a case of HG in a patient with type 1 diabetes mellitus (T1DM) due to insulin overdose treated with oral glucose administration.

An adolescent boy with T1DM on a basal bolus insulin regimen presented with abdominal discomfort, nausea, vomiting, and hypoglycemia of a few hours. His glucose was 71 mg/dL, aspartate transaminase (AST) 119 U/L, and alanine transaminase (ALT) 65 U/L. Hypoglycemia was treated with juice, and 12 hours later AST and ALT were 979 U/L and 700 U/L, respectively. Workup for infectious, autoimmune, metabolic, and toxic causes of hepatitis was negative. The transaminases improved by the next day and normalized within 3 weeks. Two weeks after discharge the patient returned with hypoglycemia, nausea, and right-sided abdominal pain of 13 hours. Hypoglycemia persisted despite multiple courses of glucose tablets and juice. Laboratory studies showed glucose of 58 mg/dL, AST of 776 U/L, ALT of 496 U/L, negative toxicology studies, and normal abdominal ultrasound. His serum insulin level was 249.7 mU/L and, C-peptide was less than 0.1 ng/mL, consistent with insulin overdose. He received IV fluids with dextrose, and insulin was held. Transaminases improved by the following day. Repeat serum insulin while on home regimen was normal.

Along with other diagnoses, HG should be considered in patients treated with insulin who present with hypoglycemia and acute hepatitis. HG can occur in cases of insulin overdose treated with repeated oral glucose administration.

Along with other diagnoses, HG should be considered in patients treated with insulin who present with hypoglycemia and acute hepatitis. HG can occur in cases of insulin overdose treated with repeated oral glucose administration.

Dyslipidemia is highly prevalent in youth with type 2 diabetes (T2D), yet the pathogenic components of dyslipidemia in youth with T2D are poorly understood.

To evaluate the genetic determinants of lipid traits in youth with T2D through a genome-wide association study.

We genotyped 206 928 variants and imputed 17 642 824 variants in 1076 youth (mean age 15.0 ± 2.48 years) with T2D from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) and SEARCH for Diabetes in Youth (SEARCH) studies as part of the Progress in Diabetes Genetics in Youth (ProDiGY) consortium. We performed association testing for triglyceride and low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (HDL-c) concentrations adjusted for the genetic relationship matrix within each substudy followed by meta-analyses for each trait.

We identified a novel association between a deletion on chromosome 3 (367817380_AT/A_DeletionRP11-81N13.1) and triglyceride levels at genome-wide level of significance (

= 2.