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Holgersen Skaarup posted an update 6 months, 2 weeks ago
6/50 (12%) cases (5 N0 and 1 N+) were amplified for MDM2 without matching to molecular phenotypes. Of 50, 14 (37%) cases expressed PD-L1 at 1% cut-off; 3/50 (9%) at >50% cut-off; of these, 2 cases on side of neoplasia among inflammatory cells. Only one out of six (17%) cases amplified for MDM2 showed expression (>50% cut-off) of PD-L1. MDM2 amplification was independent to all documented profiles (k test=0.3) and was prevalent in recurrent UC.
MDM2 amplification has been seen in both PD-L1 positive and negative muscle-invasive bladder UC independently from the TCGA molecular phenotypes. MDM2 and PD-L1 might be assessed in order to predict a better response to combo/single targeted therapies.
MDM2 amplification has been seen in both PD-L1 positive and negative muscle-invasive bladder UC independently from the TCGA molecular phenotypes. MDM2 and PD-L1 might be assessed in order to predict a better response to combo/single targeted therapies.Essential thrombocythaemia (ET) is driven by somatic mutations involving the JAK2, CALR and MPL genes. Approximately 10% of patients lack driver mutations and are referred as ‘triple-negative’ ET (TN-ET). The diagnosis of TN-ET, however, relies on bone marrow examination that is not always performed in routine practice, and thus in the real-world setting, there are a group of cases with suspected TN-myeloproliferativeneoplasm.In this real-world cohort, patients with suspected TN-ET were initially rescreened for JAK2, CALR and MPL and then targeted next-generation sequencing (NGS) was applied.The 35 patients with suspected TN-ET had a median age at diagnosis of 43 years (range 16-79) and a follow-up of 10 years (range 2-28). The median platelet count was 758×109/L (range 479-2903). Thrombosis prior to and following diagnosis was noted in 20% and 17% of patients. Six patients were JAK2V617F and two patients were CALR positive on repeat screening. NGS results showed that 24 of 27 patients harboured no mutations. Selleck Nutlin-3 Four mutations were noted in three patients.There was no evidence of clonality for the majority of patients with suspected TN-ET with targeted NGS analysis. Detection of driver mutations in those who were previously screened suggests that regular rescreening is required. This study also questions the diagnosis of TN-ET without the existence of a clonal marker.
The effects of preventive interventions on cardiovascular autonomic neuropathy (CAN) remain unclear. We examined the effect of intensively treating traditional risk factors for CAN, including hyperglycemia, hypertension, and dyslipidemia, in individuals with type 2 diabetes (T2D) and high cardiovascular risk participating in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.
CAN was defined as heart rate variability indices below the fifth percentile of the normal distribution. Of 10,251 ACCORD participants, 71% (
= 7,275) had a CAN evaluation at study entry and at least once after randomization. The effects of intensive interventions on CAN were analyzed among these subjects through generalized linear mixed models.
As compared with standard intervention, intensive glucose treatment reduced CAN risk by 16% (odds ratio 0.84, 95% CI 0.75-0.94,
= 0.003)-an effect driven by individuals without cardiovascular disease (CVD) at baseline (OR 0.73, 95% CI 0.63-0.85,
< 0.0001) rather than those with CVD (OR 1.10, 95% CI 0.91-1.34,
= 0.34) (
= 0.001). Intensive blood pressure (BP) intervention decreased CAN risk by 25% (OR 0.75, 95% CI 0.63-0.89,
= 0.001), especially in patients ≥65 years old (OR 0.66, 95% CI 0.49-0.88,
= 0.005) (
= 0.05). Fenofibrate did not have a significant effect on CAN (OR 0.91, 95% CI 0.78-1.07,
= 0.26).
These data confirm a beneficial effect of intensive glycemic therapy and demonstrate, for the first time, a similar benefit of intensive BP control on CAN in T2D. A negative CVD history identifies T2D patients who especially benefit from intensive glycemic control for CAN prevention.
These data confirm a beneficial effect of intensive glycemic therapy and demonstrate, for the first time, a similar benefit of intensive BP control on CAN in T2D. A negative CVD history identifies T2D patients who especially benefit from intensive glycemic control for CAN prevention.
To assess the diagnostic utility of corneal confocal microscopy (CCM) for diabetic peripheral neuropathy (DPN) and the risk factors for corneal nerve loss.
A total of 490 participants, including 72 healthy control subjects, 149 with type 1 diabetes, and 269 with type 2 diabetes, underwent detailed assessment of peripheral neuropathy and CCM in relation to risk factors.
Corneal nerve fiber density (CNFD) (
< 0.0001 and
< 0.0001), corneal nerve fiber branch density (CNBD) (
< 0.0001 and
< 0.0001), and corneal nerve fiber length (CNFL) (
< 0.0001 and
= 0.02) were significantly lower in patients with type 1 and type 2 diabetes compared with control subjects. CNFD (
< 0.0001), CNBD (
< 0.0001), and CNFL (
< 0.0001) were lower in type 1 diabetes compared with type 2 diabetes. Receiver operating characteristic curve analysis for the diagnosis of DPN demonstrated a good area under the curve for CNFD of 0.81, CNBD of 0.74, and CNFL of 0.73. Multivariable regression analysis showed a significant association among reduced CNFL with age (β = -0.27,
= 0.007), HbA
(β = -1.1;
= 0.01), and weight (β = -0.14;
= 0.03) in patients with type 2 diabetes and with duration of diabetes (β = -0.13;
= 0.02), LDL cholesterol (β = 1.8,
= 0.04), and triglycerides (β = -2.87;
= 0.009) in patients with type 1 diabetes.
CCM identifies more severe corneal nerve loss in patients with type 1 diabetes compared with type 2 diabetes and shows good diagnostic accuracy for DPN. Furthermore, the risk factors for a reduction in corneal nerve fiber length differ between type 1 and type 2 diabetes.
CCM identifies more severe corneal nerve loss in patients with type 1 diabetes compared with type 2 diabetes and shows good diagnostic accuracy for DPN. Furthermore, the risk factors for a reduction in corneal nerve fiber length differ between type 1 and type 2 diabetes.