Management of patients with hypertension and chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. On behalf of the European Society of Hypertension Working Group on Hypertension and the Kidney.

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.

What is the context? Hypertension is a strong independent risk factor for development of chronic kidney disease (CKD) and progression of CKD to ESKD. Improved adherence to the guidelines in the treatment of CKD is believed to provide further reduction of cardiorenal events. European Society of Hypertension Excellence Centres (ESH-ECs) have been developed in Europe to provide excellency regarding management of patients with hypertension and implement guidelines. Numerous deficits regarding general practitioner CKD screening, use of nephroprotective drugs and referral to nephrologists prior to referral to ESH-ECs have been reported. In contrast, real-life management of these patients among ESH-ECs is unknown. Before implementation of strategies to improve guideline adherence in Europe, we aimed to investigate how patients with CKD are managed among the ESH-ECs.What is the study about? In this study, a survey was conducted in 2023 by the ESH to assess management of CKD patients referred to ESH-ECs. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed among their centres.What are the results? RAAS blockers are initiated in 90% of ESH-ECs in CKD patients, but the initiation of MRA and SGLT2i is less frequently done. Hyperkalemia is the main barrier for initiation or adequate dosing of RAAS blockade, and its most reported management was RAAS blockers dosage reduction. These findings will be crucial to implement strategies in order to improve management of patients with CKD and guideline adherence among ESH-ECs.

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.

Percutaneous balloon-assisted ultrasound-guided direct thrombin embolization of superficial femoral artery pseudoaneurysm: a case series and literature review.

BACKGROUND: Superficial femoral artery (SFA) pseudoaneurysms, a rare but potentially life-threatening complication, that can arise after vascular interventions or trauma. This case series explores the efficacy and safety of a minimally invasive treatment modality, percutaneous ultrasound-guided thrombin injection (PUGTI) combined with balloon occlusion, in three patients with SFA pseudoaneurysms. CASE PRESENTATION: Three patients (age: 71-82 years; 3 female) with SFA pseudoaneurysms underwent PUGTI with balloon occlusion. The procedure involved direct thrombin injection under ultrasound guidance while occluding the parent artery using a balloon catheter. Follow-up was conducted at 1 week and 1 month post-procedure to assess technical success, complications, and recurrence. CONCLUSION: PUGTI combined with balloon occlusion appears to be a safe and effective treatment for SFA pseudoaneurysms, particularly for larger pseudoaneurysms. The procedure is associated with a high technical success rate. Balloon occlusion may offer a safer alternative to direct thrombin injection without occlusion, as it potentially minimizes the risk of complications such as distal thromboembolism.

Predictive Factors for Neutralizing Antibody Levels Nine Months after Full Vaccination with BNT162b2: Results of a Machine Learning Analysis.

Vaccination against SARS-CoV-2 with BNT162b2 mRNA vaccine plays a critical role in COVID-19 prevention. Although BNT162b2 is highly effective against COVID-19, a time-dependent decrease in neutralizing antibodies (NAbs) is observed. The aim of this study was to identify the individual features that may predict NAbs levels after vaccination. Machine learning techniques were applied to data from 302 subjects. Principal component analysis (PCA), factor analysis of mixed data (FAMD), k-means clustering, and random forest were used. PCA and FAMD showed that younger subjects had higher levels of neutralizing antibodies than older subjects. The effect of age is strongest near the vaccination date and appears to decrease with time. Obesity was associated with lower antibody response. Gender had no effect on NAbs at nine months, but there was a modest association at earlier time points. Participants with autoimmune disease had lower inhibitory levels than participants without autoimmune disease. K-Means clustering showed the natural grouping of subjects into five categories in which the characteristics of some individuals predominated. Random forest allowed the characteristics to be ordered by importance. Older age, higher body mass index, and the presence of autoimmune diseases had negative effects on the development of NAbs against SARS-CoV-2, nine months after full vaccination.

Age-Dependent Invasion of Pseudorabies Virus into Porcine Central Nervous System via Maxillary Nerve.

Pseudorabies virus (PRV) is the causative agent for Aujeszky's disease, a disease that mainly affects pigs and incidentally other domestic and wild animals. While PRV is almost always fatal, causing neurological disease independently of the age in non-porcine species, the development of neurological manifestation in its host species, the pig, highly depends on the age. In this study, an attempt was made to investigate the effect of nerve development on the outcome of virus infection and the effect of virus infection on the structure of nerves in piglets of various ages. For that reason, 42 pigs at the age of one (n = 14), three (n = 14) and five (n = 14) weeks were inoculated with 107 TCID50 of PRV Kaplan strain and euthanized at one- or four-days post inoculation (DPI). The tissues of the trigeminal nervous pathway were collected and examined for virus replication (titration) in cell cultures for nerve morphology by light and transmission electron microscopy, and for viral antigen visualization by immunohistochemistry. The results showed that as the age of the pig increases, virus titers and clinical manifestations reduced, while, at the same time, myelin and axon development ceased. Following infection, the nerve structure was disrupted at all ages examined, being more prominent in one-week-old pigs compared to five-week-old pigs. In conclusion, the age-dependent PRV neuroinvasion in pigs seems to correlate with the morphological changes of neurons.

Sustained but Declining Humoral Immunity Against SARS-CoV-2 at 9 Months Postvaccination With BNT162b2: A Prospective Evaluation in 309 Healthy Individuals.

The sustainability of coronavirus 19 (COVID-19) vaccine-induced immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to be determined to inform public health decisions on vaccination programs and prevention measures against COVID-19. The aim of the present study was to prospectively evaluate the kinetics of neutralizing antibodies (NAbs) and anti-S-receptor binding domain (RBD IgGs) against SARS-CoV-2 after full vaccination with the BNT162b2 mRNA vaccine for up to 9 months in healthy individuals (NCT04743388). The assessments were performed at the following time points after the second vaccination: 2 weeks, 1 month, 3 months, 6 months, and 9 months. The measurements were performed with the GenScript's cPassTM SARS-CoV-2 NAbs Detection Kit (GenScript, Inc.; Piscataway, NJ) and the Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics GmbH; Mannheim, Germany). Three hundred nine participants with a median age of 48 years were included. A gradual decline in both NAbs and anti-S-RBD IgGs became evident from 2 weeks to 9 months postvaccination. Both NAbs and anti-S-RBD IgGs levels were significantly lower at 9 months compared with the previous timepoints. Interestingly, age was found to exert a statistically significant effect on NAbs elimination only during the first-trimester postvaccination, as older age was associated with a more rapid clearance of NAbs. Furthermore, simulation studies predicted that the median NAb value would fall from 66% at 9 months to 59% and 45% at 12 and 18 months postvaccination, respectively. This finding may reflect a declining degree of immune protection against COVID-19 and advocates for the administration of booster vaccine shots especially in areas with emerging outbreaks.

Generation of optically synchronized pump-signal beams for ultrafast OPCPA via the optical Kerr effect.

In recent years, multi-petawatt laser installations have achieved unprecedented peak powers, opening new horizons to laser-matter interaction studies. Ultra-broadband and extreme temporal contrast pulse requirements make optical parametric chirped pulse amplification (OPCPA) in the few-picosecond regime the key technology in these systems. To guarantee high fidelity output, however, OPCPA requires excellent synchronization between pump and signal pulses. Here, we propose a new highly versatile architecture for the generation of optically synchronized pump-signal pairs based on the Kerr shutter effect. We obtained >550µJ pump pulses of 12 ps duration at 532 nm optically synchronized with a typical ultrashort CPA source at 800 nm. As a proof-of-principle demonstration, our system was also used for amplification of ∼20µJ ultra-broadband pulses based on an OPCPA setup.

Comparison of multi-pass and regenerative strategies for energetic high-gain amplifiers based on Yb:CaF2.

Yb-doped materials, due to their high saturation fluence and consequently their low gain, represent a challenging choice for high-energy amplifiers. In this Letter, we study two original amplifier designs adapted to a large number of passes capable of operating in the 100 mJ energy range at repetition rates up to 100 Hz using Yb:CaF2 crystals as active media. Amplification geometries based on double-head active-mirror configurations are presented. We confront two alternative strategies suitable for amplification of large beams: regenerative and geometrical multi-pass amplifiers. This Letter consists of finding the pivot point, allowing us to discriminate the specific interest of each strategy. We present compensation methods of the thermal lens adapted to each amplifier configuration with and without cavity, and we demonstrate that despite similar laser heads and pumping conditions, the thermal lens impacts differently the optimal performance for multi-pass or regenerative strategy. We perform amplification up to 66 mJ pulses at 10 Hz with the regenerative amplifier and 52 mJ at 100 Hz with the multi-pass amplifier.

Improvement in the temporal contrast in the tens of ps range of the multi-PW Apollon laser front-end.

We demonstrate the impact of the optics roughness in Öffner stretchers used in chirped pulse amplification laser chains and how it is possible to improve the temporal contrast ratio in the temporal range of 10-100 ps by adequately choosing the optical quality of the key components. Experimental demonstration has been realized in the front-end source of the multi-petawatt (PW) laser facility Apollon, resulting in an enhancement of the contrast ratio by two to three orders of magnitude.

Portal Hypertensive Biliopathy in Adult Patients: Findings and Interventional Radiologic Treatment-A Single-Center Experience.

The aim of this study was to evaluate the morphologic appearance, the clinical scenario, and the outcomes of patients with portal hypertensive biliopathy (PHB), particularly in the symptomatic subgroup treated with interventional radiology (IR) procedures. The outcome of 20 patients with PHB were retrospectively reviewed over a 5-year period. In all cases, the extrahepatic portal vein occlusion (EHPVO) and the compensatory cavernomatosis was the cause of PHB. Eight out of 20 patients had severe symptoms (jaundice and bleeding). Five out of these eight patients were successfully treated with IR procedures. PHB is a rare but serious complication of PH from EHPVO. IR treatments are highly effective in controlling symptoms. Moreover, IR procedures, as drainage and transjugular intrahepatic portosystemic shunt placement, are the first-line treatment in cases of life-threatening bleeding from ruptures of the varices.

Computed Tomography-Colonography With Intravenous Contrast Medium and Urographic Phase for the Evaluation of Pelvic Deep Infiltrating Endometriosis of Intestinal and Urinary Tract.

OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of a specific protocol of computed tomography-colonography with intravenous contrast medium and urographic phase, which combined simultaneously the study of the intestinal and urinary tract, in the preoperative evaluation of women with deep infiltrating endometriosis (DIE) of anterior and posterior pelvic compartments. METHODS: We retrospectively analyzed 73 women who underwent 74 computed tomography-colonography with intravenous contrast medium and urographic phase examinations for strong clinical suspicion of DIE. All the women had surgical confirmation. RESULTS: Computed tomography-colonography with intravenous contrast medium and urographic phase in detecting DIE rectosigmoid involvement had a sensitivity of 82.3% and a specificity of 66.7%, while in detecting DIE urinary tract involvement had a sensitivity of 45.9% and a specificity of 78.4%. CONCLUSIONS: Computed tomography-colonography with intravenous contrast medium and urographic phase is a useful technique for the preoperative planning of selected women with DIE, in particular, for the detection of sigmoid colon and bladder lesions especially when performed with a dose reduction protocol.

Orthostatic hypertension: From pathophysiology to clinical applications and therapeutic considerations.

Orthostatic hypertension (OHT), that is, sustained increase in blood pressure after standing, is an increasingly recognized cardiovascular disorder having been examined in much fewer studies compared with orthostatic hypotension (OH). However, in both OHT and OH, dysfunction of the autonomous nervous system is considered to be the primary pathophysiological disturbance, while significant associations with essential hypertension have been observed. Although in many studies OHT has been related to subclinical or clinical target organ damage, there is also evidence denying such an association. Because OHT is defined variably across different studies, the comparison of relevant outcomes is at least problematic. Since evidence about OHT treatment is exclusively based on limited non-randomized studies, no specific recommendations have been developed. Therefore, both the prognostic role and the clinical significance of OHT remain largely undefined. The aim of the present review is to summarize the available evidence regarding the definition, diagnosis, pathophysiology, prognostic role and treatment of OHT and highlight potential clinical implications of this underestimated condition.

Reviewing the epigenetics of schizophrenia.

BACKGROUND: Epigenetic research in mental health has grown exponentially during the last decade and holds what some claim are "revolutionary" potentials for the development of new interdisciplinary models of mental ill health. Schizophrenia is the most appropriate diagnosis against which to assess progress in this regard. METHOD: Papers on epigenetics and schizophrenia identified in a systematic literature search are subject to a conceptually-driven narrative review that assesses the relations between schizophrenia and epigenetics; considers some issues associated with empirical studies; and thereby identifies key assumptions guiding this research. FINDINGS: The revolutionary potentials of epigenetics are thus far not being realised due to various influences, including a preponderance of hypotheses that begin from a primarily biological question; the "condensation" of environmental influences and their effective reduction to their molecular consequences; and a frequent reliance upon animal studies that effectively preclude some important influences already established as relevant to this diagnosis. CONCLUSION: Epigenetic research in schizophrenia (and mental health generally) could benefit from being more thoroughly interdisciplinary, from testing hypotheses that foreground social as well as biological influences, and from reconsidering its reliance upon psychiatric diagnoses.

The Role of Angiogenesis Inhibitors in Hypertension: Following "Ariadne's Thread".

Arterial hypertension (HT) is one of the most frequently recorded comorbidities among patients under antiangiogenic therapy. Inhibitors of vascular endothelial growth factor and vascular endothelial growth factor receptors are most commonly involved in new onset or exacerbation of pre-existing controlled HT. From the pathophysiology point of view, data support that reduced nitric oxide release and sodium and fluid retention, microvascular rarefaction, elevated vasoconstrictor levels, and globular injury might contribute to HT. The purpose of this review was to present recent evidence regarding the incidence of HT induced by antiangiogenic agents, to analyze the pathophysiological mechanisms, and to summarize current recommendations for the management of elevated blood pressure in this field.

Novel Application of the Two-Period Microtracer Approach to Determine Absolute Oral Bioavailability and Fraction Absorbed of Ertugliflozin.

Ertugliflozin, a sodium glucose cotransporter-2 inhibitor, is approved in the United States for treatment of type 2 diabetes mellitus. A novel two-period study design with 14 C microtracer dosing in each period was used to determine absolute oral bioavailability (F) and fraction absorbed (Fa ) of ertugliflozin. Eight healthy adult men received 100-µg i.v. 14 C-ertugliflozin (400 nCi) dose 1 h after a 15-mg oral unlabeled ertugliflozin dose (period 1), followed by 100 µg 14 C-ertugliflozin orally along with 15 mg oral unlabeled ertugliflozin (period 2). Unlabeled ertugliflozin plasma concentrations were determined using high-performance liquid-chromatography tandem mass spectrometry (HPLC-MS/MS). 14 C-ertugliflozin plasma concentrations were determined using HPLC-accelerator mass spectrometry (AMS) and 14 C urine concentrations were determined using AMS. F ((area under the curve (AUC)p.o. /14 C-AUCi.v. )*(14 C-Dosei.v. /Dosep.o. )) and Fa ((14 C_Total_Urinep.o. /14 C_Total_Urinei.v. )* (14 C-Dosei.v. /14 C-Dosep.o. )) were estimated. Estimates of F and Fa were 105% and 111%, respectively. Oral absorption of ertugliflozin was complete under fasted conditions and F was ∼100%. Ertugliflozin was well tolerated.

Human Immunodeficiency Virus Infection And Hypertension. Is There a Connection?

Data support that hypertension (HTN) is prevalent among human immunodeficiency virus (HIV) patients contributing to increased risk of cardiovascular disease. Immunodeficiency and prolonged antiretroviral treatment along with common risk factors including older age, male gender, and high body mass index might conduce to greater incidence of HTN. The purpose of this review was to summarize recent evidence of the increased cardiovascular risk in these patents linking HIV infection to HTN.

Air pollution and arterial hypertension. A new risk factor is in the air.

Air pollution is one of the greatest environmental threats and has been implicated for several adverse cardiovascular effects including arterial hypertension (HTN). However, the exact relationship between air pollution exposure and HTN is still unclear. Air contamination provokes oxidative stress, systemic inflammation, and autonomic nervous system imbalance that subsequently induce endothelial dysfunction and vasoconstriction leading to increased blood pressure. The aim of this review was to describe the potential mechanisms by which air pollution contributes to HTN and to summarize the consequences of short- and long-term exposure.

Comparison of transvaginal sonography and computed tomography-colonography with contrast media and urographic phase for diagnosing deep infiltrating endometriosis of the posterior compartment of the pelvis: a pilot study.

PURPOSE: To compare the diagnostic accuracy of transvaginal sonography (TVS) and computed tomography-colonography with contrast media and urographic phase (CTCU) in the preoperative detection of deep infiltrating endometriosis (DIE). MATERIALS AND METHODS: Forty-seven patients with clinical suspicion of DIE underwent preoperative TVS and CTCU. Imaging data were compared with histopathologic analysis. Sensitivity, specificity, positive and negative predictive values and test accuracies of the two modalities were calculated. RESULTS: For diagnosing intestinal DIE, TVS and CTCU had a sensitivity of 98 and 71%, specificity of 33 and 50%, positive predictive value of 91 and 91%, negative predictive value of 67 and 20%, accuracy of 89 and 68%, respectively. For diagnosing ureteral DIE, TVS and CTCU had a sensitivity of 10 and 60%, specificity of 94.8 and 70.2% on the right; sensitivity of 28.5 and 57.1%, specificity of 96.3 and 76.9% on the left, respectively. CONCLUSION: TVS should be regarded as an accurate, radiation-free first-line diagnostic modality for patients with suspicion of posterior endometriosis. CTCU should be regarded as a complementary imaging modality, particularly for sigmoid or ureteral endometriosis.