Fultonyildiz2992

5% of ischaemic strokes in HES were coded as 'non-specific' strokes in CPRD data. Furthermore, 48.2% had same-day recordings, and 56.2% were date-matched within ±1 day.

The completeness and accuracy of stroke recording is improved by the use of linked hospital and primary care records. For studies that have a time-sensitive research question, the use of linked, as opposed to stand-alone, CPRD data is strongly recommended.

The completeness and accuracy of stroke recording is improved by the use of linked hospital and primary care records. For studies that have a time-sensitive research question, the use of linked, as opposed to stand-alone, CPRD data is strongly recommended.

Although chimeric antigen receptor T-cell (CAR-T) therapy development for B-cell malignancies has made significant progress in the last decade, broadening the success to treating T-cell acute lymphoblastic leukemia (T-ALL) has been limited. We conducted two clinical trials to verify the safety and efficacy of GC027, an "off-the-shelf" allogeneic CAR-T product targeting T-cell antigen, CD7. Here, we report 2 patients as case reports with relapsed/refractory T-ALL who were treated with GC027.

Both the trials reported here were open-label and single-arm. A single infusion of GC027 was given to each patient after preconditioning therapy.

Robust expansion of CAR-T cells along with rapid eradication of CD7

T lymphoblasts were observed in the peripheral blood, bone marrow, and cerebrospinal fluid. Both patients achieved complete remission with no detectable minimal residual disease. At data cutoff, 30 September 2020, 1 of the 2 patients remains in ongoing remission for over 1 year after CAR T-cell infusion. Grade 3 cytokine release syndrome (CRS) occurred in both patients and was managed by a novel approach with a ruxolitinib-based CRS management. Acetylcholine Chloride Ruxolitinib showed promising activity in a preclinical study conducted at our center. No graft-versus-host disease was observed.

The two case reports demonstrate that a standalone therapy with this novel CD7-targeted "off-the-shelf" allogeneic CAR-T therapy may provide deep and durable responses in select patients with relapsed/refractory T-ALL. GC027 might have a potential to be a promising new approach for treating refractory/relapsed T-ALL. Further studies are warranted.

The two case reports demonstrate that a standalone therapy with this novel CD7-targeted "off-the-shelf" allogeneic CAR-T therapy may provide deep and durable responses in select patients with relapsed/refractory T-ALL. GC027 might have a potential to be a promising new approach for treating refractory/relapsed T-ALL. Further studies are warranted.

Current diabetes quality measures are agnostic to patient clinical complexity and type of treatment required to achieve it. Our objective was to introduce a patient-centered indicator of appropriate diabetes therapy indicator (ADTI), designed for patients with type 2 diabetes, which is based on hemoglobin A1c (HbA1c) but is also contextualized by patient complexity and treatment intensity.

A draft indicator was iteratively refined by a multidisciplinary Delphi panel using existing quality measures, guidelines, and published literature. ADTI performance was then assessed using OptumLabs Data Warehouse data for 2015. Included adults (n=206 279) with type 2 diabetes were categorized as clinically complex based on comorbidities, then categorized as treated appropriately, overtreated, or undertreated based on a matrix of clinical complexity, HbA1c level, and medications used. Associations between ADTI and emergency department/hospital visits for hypoglycemia and hyperglycemia were assessed by calculating event rates for each treatment intensity subset.

Overall, 7.4% of patients with type 2 diabetes were overtreated and 21.1% were undertreated. Patients with high complexity were more likely to be overtreated (OR 5.60, 95% CI 5.37 to 5.83) and less likely to be undertreated (OR 0.65, 95% CI 0.62 to 0.68) than patients with low complexity. Overtreated patients had higher rates of hypoglycemia than appropriately treated patients (22.0 vs 6.2 per 1000 people/year), whereas undertreated patients had higher rates of hyperglycemia (8.4 vs 1.9 per 1000 people/year).

The ADTI may facilitate timely, patient-centered treatment intensification/deintensification with the goal of achieving safer evidence-based care.

The ADTI may facilitate timely, patient-centered treatment intensification/deintensification with the goal of achieving safer evidence-based care.Fbxw7 is an F-box protein that contributes to regulation of cell proliferation and cell fate determination as well as to tumor suppression in various tissues. In this study, we generated mice with mammary gland-specific ablation of Fbxw7 (Blg-Cre/Fbxw7F/F mice) and found that most neonates born to mutant dams die soon after birth as a result of defective maternal lactation. The mammary gland of mutant dams was markedly atrophic and manifested both excessive cell proliferation and apoptosis in association with the accumulation of Notch1 and p63. Despite the hypoplastic nature of the mutant mammary gland, Blg-Cre/Fbxw7F/F mice spontaneously developed mammary tumors that resembled basal-like carcinoma with marked intratumoral heterogeneity. Additional inactivation of Trp53 in Blg-Cre/Fbxw7F/F mice further promoted onset and development of mammary tumors, suggesting that spontaneous mutation of Trp53 may facilitate transition of hypoplastic mammary lesions to aggressive cancer in mice lacking Fbxw7. RNA-sequencing analysis of epithelial- and mesenchymal-like cell lines from a Blg-Cre/Fbxw7F/F mouse tumor revealed an increased mutation rate and structural alterations in the tumor and differential expression of upstream transcription factors including known targets of Fbxw7. Together, our results implicate Fbxw7 in the regulation of cell differentiation and in tumor suppression in the mammary gland. Loss of Fbxw7 increases mutation rate and chromosome instability, activates signaling pathways governed by transcription factors regulated by Fbxw7, and triggers the development of mammary tumors with prominent heterogeneity. SIGNIFICANCE Mammary gland-specific ablation of Fbxw7 in mice results in defective gland development and spontaneous mammary tumor formation reminiscent of human basal-like carcinoma with intratumoral heterogeneity. GRAPHICAL ABSTRACT http//cancerres.aacrjournals.org/content/canres/80/24/5515/F1.large.jpg.