We performed targeted next-generation sequencing of 62 genes, previously described as being mutated in T-cell lymphomas, in 15 formalin-fixed paraffin-embedded samples from patients with primary ...cutaneous CD4+ small/medium T-cell lymphoproliferative disorder.
The dramatic cell shape changes during cytokinesis require the interplay between microtubules and the actomyosin contractile ring, and addition of membrane to the plasma membrane. Numerous ...membrane-trafficking components localize to the central spindle during cytokinesis, but it is still unclear how this machinery is targeted there and how membrane trafficking is coordinated with cleavage furrow ingression. Here we use an arf6 null mutant to show that the endosomal GTPase ARF6 is required for cytokinesis in Drosophila spermatocytes. ARF6 is enriched on recycling endosomes at the central spindle, but it is required neither for central spindle nor actomyosin contractile ring assembly, nor for targeting of recycling endosomes to the central spindle. However, in arf6 mutants the cleavage furrow regresses because of a failure in rapid membrane addition to the plasma membrane. We propose that ARF6 promotes rapid recycling of endosomal membrane stores during cytokinesis, which is critical for rapid cleavage furrow ingression.
Gene profiling using a customized NanoString platform can be applied to routine mycosis fungoides (MF) samples, revealing their specific molecular features. This study shows that MF samples carry a ...signature derived from individual molecular features found in consecutive biopsies.
Merkel cell carcinoma (MCC) is an aggressive malignant neuroendocrine tumour. There are two subsets of MCC, one related to Merkel cell polyomavirus (MCPyV) and the other to ultraviolet radiation ...(UVR). MCPyV-positive and MCPyV-negative MCCs have been considered to be different tumours, as the former harbour few DNA mutations and are not related to UVR, and the latter usually arise in sun-exposed areas and may be found in conjunction with other keratinocytic tumours, mostly squamous cell carcinomas. Two viral oncoproteins, large T antigen (LT; coded by MCPyV_gp3) and small T antigen (sT; coded by MCPyV_gp4), promote different carcinogenic pathways.
To determine which genes are differentially expressed in MCPyV-positive and MCPyV-negative MCC; to describe the mutational burden and the most frequently mutated genes in both MCC subtypes; and to identify the clinical and molecular factors that may be related to patient survival.
Ninety-two patients with a diagnosis of MCC were identified from the medical databases of participating centres. To study gene expression, a customized panel of 172 genes was developed. Gene expression profiling was performed with nCounter technology. For mutational studies, a customized panel of 26 genes was designed. Somatic single nucleotide variants (SNVs) were identified following the GATK Best Practices workflow for somatic mutations.
The expression of LT enabled the series to be divided into two groups (LT positive, n = 55; LT negative, n = 37). Genes differentially expressed in LT-negative patients were related to epithelial differentiation, especially SOX9, or proliferation and the cell cycle (MYC, CDK6), among others. Congruently, LT displayed lower expression in SOX9-positive patients, and differentially expressed genes in SOX9-positive patients were related to epithelial/squamous differentiation. In LT-positive patients, the mean SNV frequency was 4.3; in LT-negative patients it was 10 (P = 0.03). On multivariate survival analysis, the expression of SNAI1 hazard ratio (HR) 1.046, 95% confidence interval (CI) 1.007-1.086; P = 0.02 and CDK6 (HR 1.049, 95% CI 1.020-1.080; P = 0.001) were identified as risk factors.
Tumours with weak LT expression tend to co-express genes related to squamous differentiation and the cell cycle, and to have a higher mutational burden. These findings are congruent with those of earlier studies.
Abstract
Context
Patients with obesity have an overactivated renin-angiotensin-aldosterone system (RAAS) that is associated with essential hypertension. However, the influence of obesity in primary ...aldosteronism (PA) is unknown.
Objective
We analyzed the effect of obesity on the characteristics of PA, and the association between obesity and RAAS components.
Methods
A retrospective study was conducted of the Spanish PA Registry (SPAIN-ALDO Registry), which included patients with PA seen at 20 tertiary centers between 2018 and 2022. Differences between patients with and without obesity were analyzed.
Results
A total of 415 patients were included; 189 (45.5%) with obesity. Median age was 55 years (range, 47.3-65.2 years) and 240 (58.4%) were male. Compared to those without obesity, patients with obesity had higher rates of diabetes mellitus, chronic kidney disease, obstructive apnea syndrome, left ventricular hypertrophy, prior cardiovascular events, higher means of systolic blood pressure, and required more antihypertensive drugs. Patients with PA and obesity also had higher values of serum glucose, glycated hemoglobin A1c, creatinine, uric acid, and triglycerides, and lower levels of high-density lipoprotein cholesterol. Levels of blood aldosterone (PAC) and renin were similar between patients with and without obesity. Body mass index was not correlated with PAC nor renin. The rates of adrenal lesions on imaging studies, as well as the rates of unilateral disease assessed by adrenal vein sampling or I-6β-iodomethyl-19-norcholesterol scintigraphy, were similar between groups.
Conclusion
Obesity in PA patients involves a worse cardiometabolic profile, and need for more antihypertensive drugs but similar PAC and renin levels, and rates of adrenal lesions and lateral disease than patients without obesity. However, obesity implicates a lower rate of hypertension cure after adrenalectomy.
Objective
The aim of this study was to evaluate the rate of adrenal venous sampling (AVS) performance in patients with primary aldosteronism (PA), the main reasons for its non-performance, and the ...success and complications rate of this procedure in Spain. Moreover, the concordance between CT/MRI and AVS for PA subtyping was evaluated.
Methods
A retrospective multicenter study of PA patient follow-up in 20 Spanish tertiary hospitals between 2018–2021 was performed (SPAIN-ALDO Register).
Results
Of the 440 patients with PA included in the study, 153 underwent AVS (34.8%). The main reasons for not performing AVS were: patient rejection to the procedure, low catheterization rate in the center and unilateral disease based on CT/MRI. The overall success rate was 44.4% (the left adrenal vein was properly canulated in 77.8% and the right adrenal vein in 48.4%). Only 3 patients experienced minor complications. In the 45 patients with unilateral disease according to AVS, CT/MRI indicated bilateral disease or normal adrenal glands in 17. In the 23 patients with bilateral disease, CT/MRI indicated unilateral disease in 14. However, no significant differences were observed in biochemical response (
P
= 0.051) and hypertension resolution (
P
= 0.150) between patients who underwent surgery based on CT/MRI results and those who underwent surgery based on AVS results.
Conclusion
In our setting, AVS is still an underused technique in patients with PA. The low experience and success rate in AVS partially justify these results. More training for providers and patients needs to be done to include appropriate well performed AVS in the diagnosis algorithm of PA.
Purpose
To evaluate the prevalence, risk factors and evolution of diabetes mellitus (DM) after targeted treatment in patients with primary aldosteronism (PA).
Methods
A retrospective multicenter ...study of PA patients in follow-up at 27 Spanish tertiary hospitals (SPAIN-ALDO Register).
Results
Overall, 646 patients with PA were included. At diagnosis, 21.2% (n = 137) had DM and 67% of them had HbA1c levels < 7%. In multivariate analysis, family history of DM (OR 4.00 1.68–9.53), the coexistence of dyslipidemia (OR 3.57 1.51–8.43) and advanced age (OR 1.04 per year of increase 1.00–1.09) were identified as independent predictive factors of DM. Diabetic patients were on beta blockers (46.7% (n = 64) vs. 27.5% (n = 140), P < 0.001) and diuretics (51.1% (n = 70) vs. 33.2% (n = 169), p < 0.001) more frequently than non-diabetics. After a median follow-up of 22 months IQR 7.5–63.0, 6.9% of patients developed DM, with no difference between those undergoing adrenalectomy and those treated medically (HR 1.07 0.49–2.36, p = 0.866). There was also no significant difference in the evolution of glycemic control between DM patients who underwent surgery and those medically treated (p > 0.05).
Conclusion
DM affects about one quarter of patients with PA and the risk factors for its development are common to those of the general population. Medical and surgical treatment provides similar benefit in glycemic control in patients with PA and DM.
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