Reassessment of postural stimulation testing as a simple tool to identify a subgroup of patients with unilateral primary aldosteronism

Context Adrenal vein sampling (AVS) represents the current diagnostic gold standard for differentiation between unilateral and bilateral primary aldosteronism (PA). Postural stimulation testing (PST) has been used to provide additional diagnostic information. Objective To evaluate diagnostic utility of PST in the differential diagnosis of PA. Design Cohort study. Setting Single tertiary reference center. Patients We analyzed 106 PST performed between 2008 and 2020. Diagnosis of PA and cause of PA were determined according to the Endocrine Society Clinical Practice Guideline, taking into account results of saline infusion testing, AVS, preoperative imaging and outcome after medical or surgical treatment. Main Outcome Measures The suggested cut-offs for the diagnosis of unilateral PA were revisited and optimized for high specificity using receiver operating characteristics (ROC)-analysis. Results 106 patients had confirmed PA (unilateral PA: n=55, bilateral PA: n=29, AVS unsuccessful/declined by patients: n=22). Based on decreased aldosterone plasma concentration of ≥ 28% after 4 hours in the upright position, the PST showed a sensitivity of 36.4% at a specificity of 100% to identify unilateral disease (AUC=0.72, 95% CI=0.62-0.83, p=0.001). In patients with valid testing (drop of cortisol ≥ 10% after 4 hours, n=53) sensitivity of PST rose to 51.4% at a specificity of 100% (AUC=0.77, 95% CI=0.65-0.90, p=0.001). Conclusion The high specificity of 100% for the detection of unilateral PA in patients with decreased aldosterone by at least 28% after 4 hours, makes PST a simple, non-invasive contribution to subtype differentiation in PA.

Microtubules and Dynein Regulate Human Neutrophil Nuclear Volume and Hypersegmentation During H. pylori Infection

Neutrophils (also called polymorphonuclear leukocytes, PMNs) are heterogeneous and can exhibit considerable phenotypic and functional plasticity. In keeping with this, we discovered previously that Helicobacter pylori infection induces N1-like subtype differentiation of human PMNs that is notable for profound nuclear hypersegmentation. Herein, we utilized biochemical approaches and confocal and super-resolution microscopy to gain insight into the underlying molecular mechanisms. Sensitivity to inhibition by nocodazole and taxol indicated that microtubule dynamics were required to induce and sustain hypersegmentation, and super-resolution Stimulated Emission Depletion (STED) imaging demonstrated that microtubules were significantly more abundant and longer in hypersegmented cells. Dynein activity was also required, and enrichment of this motor protein at the nuclear periphery was enhanced following H. pylori infection. In contrast, centrosome splitting did not occur, and lamin B receptor abundance and ER morphology were unchanged. Finally, analysis of STED image stacks using Imaris software revealed that nuclear volume increased markedly prior to the onset of hypersegmentation and that nuclear size was differentially modulated by nocodazole and taxol in the presence and absence of infection. Taken together, our data define a new mechanism of hypersegmentation that is mediated by microtubules and dynein and as such advance understanding of processes that regulate nuclear morphology.

Recent Development toward the Next Clinical Practice of Primary Aldosteronism: A Literature Review

For the last seven decades, primary aldosteronism (PA) has been gradually recognized as a leading cause of secondary hypertension harboring increased risks of cardiovascular incidents compared to essential hypertension. Clinically, PA consists of two major subtypes, surgically curable and uncurable phenotypes, determined as unilateral or bilateral PA by adrenal venous sampling. In order to further optimize the treatment, surgery or medications, diagnostic procedures from screening to subtype differentiation is indispensable, while in the general clinical practice, the work-up rate is extremely low even in the patients with refractory hypertension because of the time-consuming and labor-intensive nature of the procedures. Therefore, a novel tool to simplify the diagnostic flow has been recently in enormous demand. In this review, we focus on recent progress in the following clinically important topics of PA: prevalence of PA and its subtypes, newly revealed histopathological classification of aldosterone-producing lesions, novel diagnostic biomarkers and prediction scores. More effective strategy to diagnose PA based on better understanding of its epidemiology and pathology should lead to early detection of PA and could decrease the cardiovascular and renal complications of the patients.

Liq_ccRCC: Identification of Clear Cell Renal Cell Carcinoma Based on the Integration of Clinical Liquid Indices

Currently, preoperative diagnosis and differentiation of renal clear cell carcinoma and other subtypes remain a serious challenge for doctors. The liquid biopsy technique and artificial intelligence have inspired the pursuit of distinguishing clear cell renal cell carcinoma using clinically available test data. In this work, a method called liq_ccRCC based on the integration of clinical blood and urine indices through machine learning approaches was successfully designed to achieve this goal. Clinically available biochemical blood data and urine indices were collected from 306 patients with renal cell carcinoma. Finally, the integration of 18 top-ranked clinical liquid indices (13 blood samples and 5 urine samples) was proven to be able to distinguish renal clear cell carcinoma from other subtypes of renal carcinoma by cross-valuation with an AUC of 0.9372. The successful introduction of this identification method suggests that subtype differentiation of renal cell carcinoma can be accomplished based on clinical liquid test data, which is noninvasive and easy to perform. It has huge potential to be developed as a promising innovation strategy for preoperative subtype differentiation of renal cell carcinoma with the advantages of convenience and real-time testing. liq_ccRCC is available online for the free test of readers at http://lishuyan.lzu.edu.cn/liq_ccRCC.