Screening and management of hypertensive patients with chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. A pilot survey based on questionnaire.

OBJECTIVE: Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear. METHODS: A survey was conducted in 2023 by the European Society of Hypertension (ESH) to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate preexisting CKD management quality. RESULTS: Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 [75.0%]). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had preexisting CKD, with 10% of them (5-30%) previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates SGLT2 inhibitors (27.5% [20-40%] vs. 15% [10-25], P  = 0.003), GLP1-RA (10% [10-20%] vs. 5% [5-10%], P  = 0.003) and mineralocorticoid receptor antagonists (20% [10-30%] vs. 15% [10-20%], P  = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across countries. CONCLUSIONS: Our estimation indicates deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across countries. This information can be used to build specific programs to improve care in hypertensives with CKD.

2-Deoxy-D-glucose inhibits lymphocytic choriomeningitis virus propagation by targeting glycoprotein N-glycosylation.

BACKGROUND: Increased glucose uptake and utilization via aerobic glycolysis are among the most prominent hallmarks of tumor cell metabolism. Accumulating evidence suggests that similar metabolic changes are also triggered in many virus-infected cells. Viral propagation, like highly proliferative tumor cells, increases the demand for energy and macromolecular synthesis, leading to high bioenergetic and biosynthetic requirements. Although significant progress has been made in understanding the metabolic changes induced by viruses, the interaction between host cell metabolism and arenavirus infection remains unclear. Our study sheds light on these processes during lymphocytic choriomeningitis virus (LCMV) infection, a model representative of the Arenaviridae family. METHODS: The impact of LCMV on glucose metabolism in MRC-5 cells was studied using reverse transcription-quantitative PCR and biochemical assays. A focus-forming assay and western blot analysis were used to determine the effects of glucose deficiency and glycolysis inhibition on the production of infectious LCMV particles. RESULTS: Despite changes in the expression of glucose transporters and glycolytic enzymes, LCMV infection did not result in increased glucose uptake or lactate excretion. Accordingly, depriving LCMV-infected cells of extracellular glucose or inhibiting lactate production had no impact on viral propagation. However, treatment with the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) profoundly reduced the production of infectious LCMV particles. This effect of 2-DG was further shown to be the result of suppressed N-linked glycosylation of the viral glycoprotein. CONCLUSIONS: Although our results showed that the LCMV life cycle is not dependent on glucose supply or utilization, they did confirm the importance of N-glycosylation of LCMV GP-C. 2-DG potently reduces LCMV propagation not by disrupting glycolytic flux but by inhibiting N-linked protein glycosylation. These findings highlight the potential for developing new, targeted antiviral therapies that could be relevant to a wider range of arenaviruses.

Revisiting the Warburg Effect with Focus on Lactate.

Rewired metabolism is acknowledged as one of the drivers of tumor growth. As a result, aerobic glycolysis, or the Warburg effect, is a feature of many cancers. Increased glucose uptake and glycolysis provide intermediates for anabolic reactions necessary for cancer cell proliferation while contributing sufficient energy. However, the accompanying increased lactate production, seemingly wasting glucose carbon, was originally explained only by the need to regenerate NAD+ for successive rounds of glycolysis by the lactate dehydrogenase (LDH) reaction in the cytosol. After the discovery of a mitochondrial LDH isoform, lactate oxidation entered the picture, and lactate was recognized as an important oxidative fuel. It has also been revealed that lactate serves a variety of signaling functions and helps cells adapt to the new environment. Here, we discuss recent findings on lactate metabolism and signaling in cancer while attempting to explain why the Warburg effect is adopted by cancer cells.

Hypertension outcomes of adrenalectomy for unilateral primary aldosteronism.

PURPOSE: To evaluate laboratory and clinical results after unilateral adrenalectomy in patients with primary aldosteronism (PHA). METHODS: A cross-sectional analysis was performed using data from patients who underwent transperitoneal laparoscopic adrenalectomy for PHA, between January 2008 and December 2019. Surgical indications were based on adrenal venous sampling without ACTH stimulation. Analyses included patient demographics; preoperative clinical, pharmacological, laboratory, and radiological data; and postoperative results assessed after a median of 4 months. Antihypertensive drug use was quantified by estimating the daily defined dose (DDD) of antihypertensive medication, thus enabling standardized comparison of dosage between the drug classes. Statistical assessments included univariable and multivariable logistic regression analysis. RESULTS: This study enrolled 87 patients. The patients were taking 5.4 DDD of antihypertensive medication before surgery, and 3.0 DDD after surgery. Complete biochemical success of surgery was reached 67 patients (77%), 19 patients (22%) had partial biochemical success. Complete clinical success with normalization of blood pressure and withdrawal of all antihypertensive drugs was achieved in 19 patients (22%). 57 patients (65%) exhibited a reduction of DDD after surgery and/or improvement of blood pressure-partial clinical success. Thus, in 76 (87%) of all enrolled patients, surgery had an overall positive effect on hypertension control. Multivariable logistic regression showed that complete clinical success was independently associated with female gender and baseline sum of antihypertensive drugs DDD < 4. CONCLUSION: A majority of patients undergoing unilateral adrenalectomy for PHA achieved markedly improved hypertension control, despite almost halving their antihypertensive medication. Almost a quarter of patients were cured and able to cease using all antihypertensive drugs.

Effect of sertraline in paroxysmal hypertension.

OBJECTIVE: Paroxysmal hypertension or pseudopheochromocytoma is quite a common problem in clinical practice. The optimal treatment for this condition has not been established. This study sought to investigate whether sertraline (a selective serotonin reuptake inhibitor) reduces the symptoms. METHODS: We enrolled 64 patients referred to our department between April 2008 and October 2014 for symptomatic paroxysmal hypertension. Patients received sertraline, 50 mg once daily, in addition to their current medication. The effect of the treatment was assessed during their next clinical visit at least 3 months later. RESULTS: Of the 64 patients, 57 (89%) also had sustained arterial hypertension. Mean office baseline blood pressure (BP) was 147.6/83.8 mmHg and patients used a mean of 3.1 antihypertensive drugs. Five patients did not start using sertraline and three were lost to follow-up. Of the 56 patients who started using sertraline and who came for check up, clinical improvement was observed in 42 (75%) patients - symptoms of paroxysmal hypertension fully subsided in 28 (50%) and were partially reduced in 14 (25%) . Side effects or intolerance leading to discontinuation of treatment occurred in 7 patients (12.5%). Mean office BP in patients using sertraline decreased by 12.8/7.4 mmHg (P<0.001 for both). CONCLUSIONS: Sertraline effectively removed or reduced symptoms of paroxysmal hypertension in the majority of patients who used this treatment.

Real time 3-dimensional transesophageal echocardiography is more specific than 2-dimensional TEE in the assessment of left atrial appendage thrombosis.

BACKGROUND: In patients indicated for detection of intraatrial thrombus (T), 2-dimensional transesophageal echocardiography (2DTEE) is routinely used but differentiation between T and trabeculae or artifacts in the left atrial appendage (LAA) is often difficult. AIMS: To compare the diagnostic value of real time 3D-transesophageal echocardiography (RT3DTEE) and 2DTEE in the assessment of LAA thrombosis. PATIENTS AND METHODS: One hundred and ten consecutive patients (73M, aged 64+-13) were examined by 2DTEE. In terms of possible T, individual pts were diagnosed as negative (N2), uncertain trabecular finding (U2), other/artifacts (O2), and clearly positive (T2). The RT3DTEE was then applied and the categorization repeated (N3,U3,O3 and T3, resp.). Finally, the operator decided whether the RT3DTEE. A: had an additional diagnostic value, and/or B: changed the definite diagnosis of thrombosis. RESULTS: N2:71; U2:17; O2:19; T2:3; N3:97; U3:1; O3:12; T3:0. Ad A/ RT3DTEE enabled us to refine or change the diagnosis in 26/110 cases. 17 pts were switched from group U2 to N3, 7:O2-N3 and 2:T2-N3. 12 pts from O2 and 1 pt from T2 remained unclarified. Ad B/ Diagnoses were changed in 6 patients after RT3DTEE. A very suspicious T2 was found in 3 patients. In 1, the finding was requalified definitely as musculi pectinati. In the second patient, the finding was re-categorized as just a spontaneous echocontrast without T. In another 4 patients, T in LAA was definitely excluded after RT3DTEE (1 patient switched from U2 to N3, 3 from O2 to N3). In another 13, the findings remained unclear, mostly because of poor quality image. No real thrombus was found in this study. CONCLUSION: RT3DTEE provides additional information, which may be helpful in the differentiation of thrombus from other findings. It is particularly useful in the identification of muscular trabeculae in the left atrial appendage.