bluuebunny/crossref_metadata_2025 huggingface dataset:
PREVALENCE OF PATIENT WITH TREATMENT-RESISTANT HYPERTENSION AND SCREENING RATE FOR PRIMARY HYPERALDOSTERONISM IN THAI AMBULATORY CARE SETTING
Authors: Suksiriworaboot Tanawin , Yacharad Arun , Sunthornyothin Yongkasem Vorasettakarnkij Sarat , Chattranukulchai Pairoj
Published: June 2023

Objective:

Patients with treatment-resistant hypertension (TRH) have significantly higher mortality outcomes when compared with controlled hypertension. Primary hyperaldosteronism (PA) is one of the common treatable causes of this condition. Although the practice guidelines recommend testing for PA among those with TRH, the screening rates in Thailand's ambulatory care setting are unknown.

Design and method:

This is a single-center cross-sectional study. All hypertensive adults followed at ambulatory clinics of a tertiary care hospital between January 2020, and May 2022 were screened. Patients who met one of two following criteria were diagnosed as TRH: 1) uncontrolled blood pressure (BP) despite the use of 3 antihypertensive drug classes, including diuretics 2) concurrent use of greater than or equal to 4 antihypertensive drug classes, regardless of BP control. Patients without data of consecutive office BP records at least one month apart or lack of laboratory results were excluded. Hypokalemia was defined as a low serum potassium level identified on at least 2 visits.

Results:

Among 2,047 patients diagnosed with hypertension, the prevalence of TRH was 9.4% (192 patients) with a mean (±SD) age of 74 (±10) years, 59% were women, and the mean number of antihypertensive agents was 3.8±0.7. The screening rate for PA in TRH and non-TRH groups were 3.1% and 0.8%, respectively (p = 0.001). Among those with TRH, the screened PA group significantly had more prevalence of hypokalemia than the non-screened group (33.3% vs 2.7%, p<0.001). From subgroup analysis of all patients with hypokalemia and without hypokalemia, the testing rates for PA were 18.2% and 0.6%, respectively (p<0.001). The average duration from first hypokalemia detection to receiving testing for PA was 19 months. Five of the 20 patients received screening were diagnosed with PA and had better BP control after receiving appropriate treatment.

Conclusions:

This is the first study in Thailand to examine a PA screening rate in a real-life, ambulatory care setting. The low screening rate reflects the unawareness and inertia of physicians to adhere to guideline-recommended practices. Initiatives to encourage PA screening should be more emphasized and barriers that caused low screening rate should be further explored.
POOR ACHIEVEMENT OF THE TARGET BLOOD PRESSURE LEVELS ASSOCIATED WITH DIASTOLIC HEART FAILURE IN PATIENTS WITH RESISTANT HYPERTENSION
Authors: Rekovets Oksana , Sirenko Yuriy , Torbas Olena , Kushnir Svitlana , Primak Galina
Published: June 2023

Objective:

Aim of this study was to assess the impact of not achievement of the target blood pressure levels on the presence of the diastolic heart failure in patient with resistant hypertension (RH).

Design and method:

The study included patients with arterial hypertension who received 3 and more AH drugs and had BP > 140/90 mm Hg and were admitted to the department of secondary hypertension. In all patients we performed the following examinations: anthropometry, office blood pressure, electrocardiography (ECG), echocardiography, ABPM, sleep apnea determination, blood biochemical analysis, determination of levels of TTH, T3, T4, blood renin, blood aldosterone levels, blood cortisol level and metanephrine in the urine.

Results:

The study included 1146 patients with RH who received 3 or more antihypertensive drugs with the level of office blood pressure at admission > = 140/90 mm Hg. The mean age was 57,9 ± 0,37 years. The average body weight is 87,7 ± 0,61 kg, body mass index - 31,0 ± 0,19 kg/m2. Baseline office SBP/DBP - 174,6 ± 0,64/100,5 ± 0,38 mmHg. Half of the patients (51.4%) received 3 antihypertensive drugs, four drugs - 37.1%, five drugs - 9.1%, and six drugs - 2.4% respectively. Our data showed that after correction of the therapy only 31% of patients who received 3 or more antihypertensive drugs had true resistant hypertension. Fixed combinations were taken by 71.9% of patients. Patients who did not achieve target BP had significantly higher cortisol level (155.0 ± 44.0 vs 35.9 ± 20.8 ng/l) and the highest left ventricular mass index (147.5 ± 3.46 vs 135.3  ± 1.74 g/m2), obesity (42.9 vs 37.5 %), kidney function abnormalities (2.7 vs 0.8 %), and also we noted the higher prevalence of the diastolic heart failure in comparison with patients who achieved target BP (16.9 vs 8.5 %).

Conclusions:

Not achievement of the target blood pressure levels was associated with the presence of the diastolic heart failure in patients with resistant hypertension
RENAL DENERVATION REDUCES RETINAL ARTERIAL REMODELING IN PATIENTS WITH TREATMENT RESISTANT HYPERTENSION AND TYPE 2 DIABETES MELLITUS
Authors: Bosch Agnes , Schmid Axel , Kannenkeril Dennis , Ott Christian , Harazny Joanna , Striepe Kristina , Guenes-Altan Merve , Schiffer Mario , Uder Michael , Schmieder Roland E.
Published: June 2023

Objective:

Renal denervation has been shown to be a safe and effective method to lower blood pressure (BP) in patients with uncontrolled treatment resistant hypertension (TRH). Patients with TRH and T2DM typically show hypertrophic arteriolar remodeling, which is associated with the development of early target end-organ damage. By using the retinal vasculature as a mirror of vascular remodeling in the systemic circulation, arteriolar remodeling can be non-invasively assessed with Scanning Laser Doppler Flowmetry (SLDF). In this analysis we assessed the impact of RDN on retinal arteriolar remodeling in patients with TRH and T2DM.

Design and method:

Retinal arteriolar remodeling was assessed using SLDF together with office and 24-hour ambulatory BP before and 6 as well as 12 months after renal denervation in 22 patients with TRH and T2DM. All patients participated in the investigator initiated study program “Renal Denervation in Treatment Resistant Hypertension” (NCT01687725). SLDF allows confocal measurement of the retinal arteriolar parameters, such as outer (OD) and inner (ID) diameter. Based on ID and OD the following parameters of arteriolar remodeling are derived: retinal arteriolar wall thickness (WT), wall-to-lumen ratio (WLR), and retinal arteriolar crosssectional area (CA).

Results:

Retinal arteriolar parameters were analysed in 18 male and 4 female patients with 6.5 antihypertensive medications on average. There was a significant reduction of systolic and diastolic 24-hour ambulatory as well office BP 6 as well as 12 months after RDN (table 1). In 77.3% of the patients number of antihypertensive medications was reduced. We found a reduction of hypertrophic retinal arteriolar remodeling and also a reduction of WLR 12 months after RDN (table 1). Of note, no significant changes of retinal arteriolar remodeling were found 6 months after RDN.

Conclusions:

In very high-risk patients with TRH and T2DM endovascular RDN reduced retinal arteriolar remodeling and retinal wall-to-lumen ratio, a prognostic marker of further end-organ damage. Whereas BP-changes already occurred 6 months after RDN, changes in retinal arteriolar remodelling were observed 12 months after RDN. We conclude that after RDN reversal of arteriolar remodeling happens slowly and requires long-term effective BP control.
RENAL SYMPATHETIC DENERVATION AND NEURO-HORMONAL EVALUATION BY SELECTIVE VENOUS CATHETERIZATION: THE RESIDENCY STUDY
Authors: Bagordo Domenico , Rossitto Giacomo , Crimì Filippo , Ceolotto Giulio , Antonelli Giorgia , Battistel Michele , Barbiero Giulio , Tarantini Giuseppe , Basso Daniela , Rossi Gian Paolo
Published: June 2023

Objective:

Renal denervation (RD) is effective in reducing blood pressure (BP) in hypertensive patients, but the pathophysiologic mechanisms underlying the variable individual response are unclear and early markers of procedural success are lacking. The aim of the study was to evaluate intra-/peri-operative effects of RD on the renin-angiotensin-aldosterone system (RAAS) either as determinants and markers of efficacy.

Design and method:

Patients with resistant hypertension and eGFR>45 ml/min underwent radiofrequency-RD (Medtronic Symplicity-Spyral) with simultaneous sampling of the renal veins (RV), left adrenal vein and pre-renal inferior vena cava (IVC). Samples were collected before (t0) and 15’ after RD from each sequentially-approached side. Additional peripheral blood samples collected on the morning before RD and 3h, 24h and 7 days after the procedure were tested for renin, aldosterone and cortisol. During this timeframe, antihypertensive therapy remained unchanged.

Results:

Ten patients were recruited (61±11yo; 30%F; BP = 149/84 ±11/12 mmHg on 4 (range 3-6) antihypertensive drugs). Peripheral renin concentration showed no significant changes during/immediately after RD and up to 7 days after, in spite of the observed BP reduction (136/78 ±17/15 mmHg; p<0.05). Similarly, RV renin was unaffected by ipsilateral RD compared to the corresponding t0 values (p = 0.899). Aldosterone and cortisol increased in the adrenal vein during RD (p<0.001), but their IVC-corrected ratio and their peripheral plasma concentrations at follow-up did not, likely reflecting a self-limiting stress reaction.

Conclusions:

These results do not suggest any direct blunting effect of RD on RAAS, and do not support the contention of monitoring acute RAAS changes as proxies for procedural effectiveness.
RENAL DENERVATION IN PATIENTS WITH RESISTANT HYPERTENSION: FOLLOW UP 2011-2021 OF THE SERIES OF THE ESH CENTER OF EXCELLENCE IN TURIN
Authors: Fasano Chiara , Ponsa Lara , Fanelli Elvira , Rabbia Franco , Rossato Denis , Pappaccogli Marco , Eula Elisabetta , Mangeruga Martina , Bertello Chiara , Veglio Franco
Published: June 2023

Objective:

Renal denervation (DRN) is one of the invasive therapeutic approaches of resistant arterial hypertension. The aim of this study was to re-evaluate patients undergoing DRN, in terms of safety and efficacy.

Design and method:

A retrospective evaluation of patients undergoing DRN between 01/01/2011 and 31/12/2021 in the Arterial Hypertension Center of Turin.

Results:

The series included 14 subjects, of which 8 (57%) were female and with an average age 54±10 years. The number of antihypertensive drugs before renal denervation was 5.7±1.0 and at baseline the blood pressure was 188/113±22±18 mmHg. 28% of subjects had a history of ischemic heart disease and 27% of previous stroke and/or transient ischemic event. 9 subjects were denervated with Symplicity device, 1 with Vessix, 4 with Symplicity Spyral. The mean duration of follow-up was 5.2 years. From a safety point of view, there were no short-term or long-term complications. In terms of efficacy, the number of responders at 6 months, defined as a reduction of at least 10 mmHg in systolic blood pressure (PAS) at 24h Blood Pressure Monitoring, was 9 subjects (64%). Two subjects reported systolic blood pressure values below 135 mmHg.

Regarding the type of device used, 75% of subjects treated with Spiral devices were responders, compared with 60% of subjects treated with other catheters. Among the non-responders, 2 presented events one year after the DRN. Only 1 responder had high level of renin at baseline.

Conclusions:

The data relating to the case studies of the Arterial Hypertension Center of Turin highlight the safety of the renal denervation procedure and a blood pressure response in 60% of patients. The latest generation catheters seems to be more effective. However, the small number of cases did not allow to identify predictive factors of response to DRN.
EXERCISE THERAPY IN PATIENTS WITH ARTERIAL HYPERTENSION: A SYSTEMATIC REVIEW WITH META-ANALYSIS
Authors: Vanparys Joris , Decorte Elise , Cornelissen Veronique
Published: June 2023

Objective:

High grade evidence supports exercise as a key therapy in the prevention and management of hypertension. Yet, the lack of a meta-analysis on the effects of exercise on ambulatory blood pressure monitoring (ABPM) in patients with hypertension was identified as an important research gap in the 2022 consensus document from the European Association of Preventive Cardiology and the ESC council on Hypertension. Therefore, we performed a meta-analysis to investigate the effects of exercise on blood pressures measured by means of ABPM, in patients with arterial hypertension or high-normal blood pressure (BP).

Design and method:

A systematic literature search was performed in three databases from inception to October 2021. Randomized controlled trials involving exercise training of at least 4 weeks, in adults with a high-normal BP or arterial hypertension, were included. Trials had to report data on daytime, nighttime or 24-h ambulatory systolic blood pressure (SBP) and/or diastolic blood pressure (DBP). Primary outcomes were changes in 24h, daytime and nighttime ABP. Pooled effect sizes are reported as weighted mean with 95% confidence intervals (CI).

Results:

We included 24 trials, involving 23 aerobic training interventions and 4 resistance exercise interventions. A total of 1668 participants were included: 942 in exercise groups, 726 as controls.

Table 1: Pooled effect size, 95% CI and p-value of different exercise types on 24h, daytime and nighttime BP:

Only 67 participants and 35 controls were included in resistance exercise protocols. In this subpopulation, results for 24h, daytime or nighttime BP were insignificant (p>0.05).

Funnel plots for 24h, daytime and nighttime BP did not show any significant publication bias.

Conclusions:

Exercise therapy reduces 24h BP in patients with arterial hypertension or high normal blood pressure. The effect is more pronounced on daytime than on nighttime BP. The results of this meta-analysis are mostly driven by trials examining aerobic exercise. More trials are needed on the effect of resistance exercise on ABPM.
WARBURG EFFECT CHARACTERIZES THE SKELETAL MUSCLE IN FABRY DISEASE: EXPERIMENTAL EVIDENCE AND CLINICAL IMPLICATIONS
Authors: Gambardella Jessica , Fiordelisi Antonella , Cerasuolo Federica Andrea , Buonaiuto Antonietta , Avvisato Roberta , Viti Alessandro , Sommella Eduardo , Merciai Fabrizio , Salviati Emanuela , Campiglia Pietro , D’Argenio Valeria , Parisi Silvia , Bianco Antonio , Spinelli Letizia , Riccio Eleonora , Pisani Antonio , Ciccarelli Michele , Santulli Gaetano , Sorriento Daniela , Iaccarino Guido
Published: June 2023

Objective:

Skeletal muscle (SM) pain and fatigue are common in Fabry disease (FD), and strongly impact the patient's quality of life. Still, the SM in FD is poorly investigated. Although energetic alterations are reported in cells from FD patients, they have never been related to fatigue and pain. Given the pivotal relevance of energetics for SM health, we undertook the investigation of the SM.

Design and method:

We consistently observed a reduced tolerance to aerobic activity and lactate accumulation in FD-humanized mouse model and patients. Accordingly, in sedentary mouse FD SM we detected an increase in fast/glycolytic-fibers, mirrored by an upregulation of glycolytic enzymes and glucose-transporters

Results:

In fibroblasts derived from FD patients, we confirmed a high glycolytic-rate and accordingly, metabolomic/lipidomic-analysis revealed that lipids are underutilized as energetic fuel in FD-patients. In the quest for a tentative mechanism, we explored analogies with genetic myopathies, that show altered expression of energetic metabolism. Specifically, we explored HIF-1 upregulation and found it increased in FD mice and patients. Consistent with our previous screening of miRNAs associated with metabolic stress in FD, we observed a significant upregulation of miR-17 in FD patients and mice. Of note, miR-17 has been associated with cellular metabolic remodeling and HIF-1 up-regulation in different contexts. In our experimental setting, a specific antagomir targeting miR-17 was able to inhibit HIF-1 accumulation and revert metabolic-remodeling in FD-cells.

Conclusions:

Our findings unveil an anaerobic glycolytic-switch under normoxia, known as Warburg Effect, which is induced by miR-17-mediated-upregulation of HIF-1. The miR-17/HIF-1 pathway can be a new therapeutic target in FD, and Exercise-testing and blood lactate may become a new diagnostic and monitoring-tool in FD.
EXERCISE RELATED HYPOTENSIVE EFFECT IN A CARDIAC REHABILITATION PROGRAM AS A POSSIBLE PROGNOSTIC MARKER OF CARDIOVASCULAR RISK
Authors: Carvalho Simão Almeida , Costa Carlos , Fernandes Andreia , Adrega Tiago , Albuquerque Nelson , Briosa Ana , Gome Ana , Bastos Mesquita
Published: June 2023

Objective:

There are some studies that analyze the correlation between the magnitude of the hypotensive effect after exercise and the long-term cardiovascular benefit. However, this same effect in a cardiac rehabilitation program (CRP) is unknown.

The aim was meausuring the benefit of this effect in patients undergoing a cardiac rehabilitation program.

Design and method:

We analyzed 19 patients who completed a CRP for 3 months (2 weekly sessions of cardiovascular and resistance exercise), in the period between September 2021 and September 2022, after an Acute Coronary Syndrome or hospitalization for Decompensated Heart Failure.

In each rehabilitation session, the blood pressure values were evaluated before the beginning of the exercise and after (1st minute and 5th minute of recovery).

The effect was compared in two different moments of the program - 1st and 12th session - having defined as main “outcome” a magnitude of higher systolic blood pressure drop in the 12th compared to the 1st session.

After completion of the CRP, all patients included in the study were given two validated questionnaires to assess insomnia (“Insomnia Severity Index – ISI”) and the impact of the current illness on quality of life (EQ-5D).

Results:

Regarding the patients included, the clinical and sociodemographic characteristics are described in table 1.

Comparing males and females, using a T-student analysis, there was a statistically significant difference in relation to a greater systolic hypotensive effect in the male group compared to the female group (91.7% vs 40.0%, p < 0.05) – table 2.

Regarding the analysis of the impact on quality of life, the total number of patients with improvement in the hypotensive effect of systolic blood pressure showed statistically significant lower values in the questionnaire (EQ5D) – 6.8±1.3 vs 9.0±1.0 (p<0.05) and higher in the score of insomnia 10.7 ± 9.0 vs. 3.9 ± 4.1 - table 2.

Conclusions:

The systolic hypotensive effect of exercise, observed in the rehabilitation program of the current study, is associated with better rates of insomnia and impact on quality of life. The authors intend to confirm this hypothesis in the longitudinal evaluation of future events.
EXPRESSION OF MICRO-RNA 221 AND 223 IN ISCHEMIC STROKE DUE HYPERTENSIVE EMERGENCY
Authors: Martin Jose F Vilela , Andrade Days Oliveira De , Cosenso-Martin Luciana N , Yugar-Toledo Juan C , Silva-Souza Doroteia
Published: June 2023

Objective:

Hypertensive crisis can account for damage on target organs characterizing hypertensive emergencies (HE). Ischemic Stroke (IS) is among these injuries. Expression of microRNAs (miRNAs) is considered the possible factors related to HE. This study evaluated the association of expression of miRNAs 221 and 223 in patients suffering ischemic stroke due to HE.

Design and method:

Thirty and four patients with IS due to hypertensive emergency (IS-HE), 33 individuals with IS without HE (IS), 31 controlled hypertensive (CHT) and 33 normotensive (NT) individuals were studied. The expression of miRNAs 221 and 223 was performed by RT-q PCR (real-time quantitative polymerase chain reaction).

Results:

Systolic and diastolic blood pressure were significantly higher in the IS-HE compared to IS, CHT and NT groups (162/99 mmHg vs 140/87, 128/69 and 129/82 mmHg, respectively; p <0.05). The miRNA-221 expression was higher in the IS-HE group compared to the IS, CHT and NT groups (4.23 vs 2.44, 1.35 and 1.05, respectively; p<0.0001). There was overexpression of miR-223 in the IS-HE and IS groups compared to CHT and NT groups (1.56 and 1.73 vs 0.13 and 0.66; p < 0.001).

Conclusions:

This study provides evidence of the miRNAs participation in the pathophysiology of ischemic stroke due hypertensive emergency, thus assuring that the increased expression of miR-221 and miR-223 determines a greater chance of the individual presenting IS due HE. The miRNAs 221 and 223 are related to endothelial damage; thus, their overexpression shows the participation of endothelial dysfunction in cases of acute blood pressure elevation.

FAPESP 2016/08203-6.
DIFFERENCES IN SYMPATHETIC OUTFLOW PROFILES AMONG CANDIDATES TO RENAL DENERVATION
Authors: Sciarrone Paolo , D’alesio Giacomo , Borrelli Chiara , Navari Alessandro , Filidei Francesco , Carrasco Adrian , Mazzoni Alberto , Oddo Calogero M. , Emdin Michele , Passino Claudio , Taddei Stefano , Masi Stefano , Bacca Alessandra V. , Giannoni Alberto
Published: June 2023

Objective:

Renal denervation (RDN) is increasingly used to reduce sympathetic outflow and improve blood pressure (BP) control in patients with resistant or difficult-to-treat arterial hypertension. However, the BP response to the procedure is variable, and factors influencing this variability remain largely unknown. Sympathetic outflow recorded before the procedure might predict the BP response to RDN, although results from different studies remain conflicting. These discrepancies might depend on the limited characterization of the sympathetic outflow before RDN, making its better definition an important goal to refine the patient selection.

Design and method:

We prospectively enrolled patients with difficult-to-treat arterial hypertension undergoing RDN. Patients underwent an extensive clinical evaluation, and the muscle sympathetic nerve activity (MSNA) in resting conditions and during respiratory maneuvers (controlled inspiratory apneas, evaluation of chemoreflex sensitivity to hypoxia and hypercapnia with the rebreathing technique) was recorded through microneurography. Sympathetic burst frequency, incidence, amplitude, duration and integral, as well as inter-burst interval, were calculated with a semi-automated in-house software.

Results:

Table 1 reports the clinical characteristics of the 10 patients that were enrolled and underwent MSNA recording before RDN. Only in 6 patients the MSNA signal was clearly interpretable and, of these, 5 subjects (Figure 1) completed the whole battery of the respiratory stimuli (2 patients couldn’t perform chemoreflex testing due to panic attack and loss of neural signal). Apnea increased the burst frequency and incidence in all patients, although the magnitude of the changes from the resting acquisition was variable. The MSNA responses to the other respiratory maneuvers were jeopardized. Burst duration remained stable, whereas an increased MSNA could be observed (subjects 1 and 3) in terms of risen burst integral and reduced inter-burst interval compared to baseline. The sympathetic response to inspiratory apneas seems mediated by chemoreflex responses in these patients. The other subjects did not show such variations.

Conclusions:

Respiratory maneuvers are feasible during MSNA acquisitions and unveil different patterns of sympathetic responses in patients with hypertension undergoing RDN. Such differences might be missed at rest but could represent novel predictors of the BP response to the procedure.
SACUBITRIL/VALSARTAN ON CLINICAL, LABORATORY, AND ECHOCARDIOGRAPHIC VARIABLES IN HONDURANS WITH HEART FAILURE WITH REDUCED LEFT VENTRICULAR EJECTION FRACTION. FIVE YEARS EXPERIENCE
Authors: Alvarenga Francisco Somoza , Martinez Juan Fernando Toledo , Cano Jose Francisco Somoza , Handal Ramses Amaya
Published: June 2023

Objective:

This study aimed to describe the response to sacubitril/valsartan in a group of Hondurans with heart failure and reduced Left Ventricular Ejection Fraction (LVEF) between January 2018 and December 2022.

Design and method:

This observational, descriptive, retrospective cohort study was conducted on 216 adult patients with heart failure and reduced Left Ventricular Ejection Fraction (LVEF) who received treatment with angiotensin-receptor antagonist/neprilysin inhibitors (sacubitril/valsartan) in two medical center in Honduras. The study participants included the patients with LVEF < 40% treated with sacubitril/valsartan for at least one year. The patients also received optimal medical therapy for HFrEF according to the American Heart Association -guidelines.

Results:

This study was conducted on 216 patients with HFrEF treated with SAC/VAL. The median age of the patients was 71 years. The sociodemographic and clinical variables have been presented in Table 1.

Treatment with SAC/VAL was done at three dosages (24/26 mg, 49/51 mg, and 97/103 mg) twice a day. For most of the patients, the treatment was started with 24/26 mg and the dose was progressively titrated to the maximum tolerated dose. 60% completed the follow-up at the optimal dose of 97/103 mg.

All the patients had at least one underlying comorbidity. The main comorbidity was hypertension (92.4%) followed by dyslipidemia (61.9%)

At the beginning of the study, 64.8%, 29.5% and 5.7% of the patients were in NYHA functional classes IV, III, and II, respectively. Following six months of treatment with SAC/VAL, 58.1% of the patients were in the functional class II, 28.6% were in class III, 9.5% were in class IV and 3.8% were in class I. Based on the results, 82.9% of the patients (n = 180) presented improvement, 16.2% (n = 34) had unchanged functional classes, and 1% showed worse baseline conditions (Figure 1).

The results revealed the improvement of LVEF in 94.3% of the cases after treatment with SAC/VAL, while 3.8% presented no changes in this regard.

Conclusions:

The study population had sociodemographic and clinical similarities with the Latin American Cohort in the PARADIGM-HF trial with the significant improvement of the LVEF and functional class.
CIRCULATING BIOACTIVES RESULTING FROM TOTUM-854 ABSORPTION IN HUMANS PROTECTS PRIMARY HUMAN ENDOTHELIAL CELLS AGAINST LIPOTOXICITY: LESSONS FROM AN ORIGINAL EX VIVO CLINICAL TRIAL
Authors: Wauquier Fabien , Ripoche Doriane , Boutin-Wittrant Line , Otero Yolanda F. , Joubioux Florian Le , Maugard Thierry , Roux Veronique , Macian Nicolas , Pickering Gisele , Bargetto Maxime , Sapone Veronique , Cazaubiel Murielle , Peltier Sebastien , Sirvent Pascal , Wittrant Yohann
Published: June 2023

Objective:

TOTUM-854 is a patented plant blend extract characterized for its polyphenol-rich content that supports hypertension prevention in preclinical studies. However, clinically validated approaches and further investigations on the mode of action at the cellular level especially in humans are required for optimized care management. In this study, we designed an ex-vivo clinical innovative approach considering the circulating metabolites produced by the digestive tract following the ingestion of TOTUM-854 in humans.

Design and method:

Human serum was collected in healthy subjects before and following acute intake of 3.71g of TOTUM-854. Availability of circulating metabolites was confirmed and characterized by UPLC-MS. Human serum enriched with metabolites deriving from TOTUM-854 absorption was further incubated with human endothelial cells (HUVEC), pretreated or not with palmitate (200 μM). In such lipotoxic environment, HUVEC behavior was monitored to determine whether and how TOTUM-854 metabolites may improve vascular response in humans.

Results:

In the presence of the human metabolites from TOTUM-854, HUVECs were protected from an induced lipotoxic stress. No effect on cell toxicity was detected in the presence of enriched sera. HUVEC protection was characterized by (1) decreased ACE-1 activity (-32% p<0.0001); (2) the inhibition of oxidative stress with decreased ROS (-12% observed by DCFDA, and by DHE fluorescent microscopy) as well as decreased Nox2 gene expression (-6,7 fold change vs palmitate, p<0.01); (3) the inhibition of inflammatory response, with a decrease in IL-1↓ release (-37% compared to palmitate, p<0.001) and decreased MCP-1 et VCAM-1 gene expression (-93% p<0.001 and -77% p<0.001 respectively). All together, these data provide new biochemical mechanisms for a protective role of TOTUM-854 in human endothelial cells.

Conclusions:

Using a pioneering clinical ex vivo approach considering the circulating and bioavailable actives, we give clues on the role of metabolites produced following TOTUM-854 intake in humans in vascular protection.
ACUPUNCTURE IN ARTERIAL HYPERTENSION: EVALUATION OF ITS EFFICACY WITH BOTH OFFICE AND AMBULATORY BLOOD PRESSURE MEASUREMENTS
Authors: Migliarese Cristina , Maloberti Alessandro , Gatto Roberto , Algeri Michela , Gualini Elena , Biolcati Marco , Ruzzenenti Giacomo , Giannattasio Cristina
Published: June 2023

Objective:

A possible alternative to pharmacological antihypertensive therapies in grade 1 low risk hypertensive patients or in those experienced drugs adverse effects could be acupuncture.

Design and method:

We focused on its possible effects on BP both as Office BP (OBP) and as Ambulatory BP Monitoring (ABPM) evaluating it before starting a 6 weeks twice weekly (total 12 session) acupuncture cycle and after 2 months from its completion.

In this prospective study we treated with acupuncture 45 patients: 24 of them presents high-normal BP values and low cardiovascular risk while 21 patients were on anti-hypertensive drug with slightly uncontrolled BP values (from 140 to 145 mmHg for Systolic BP – SBP – and/or from 90 to 95 mmHg for Diastolic BP – DBP).

Results:

Regarding SBP, a significant reduction have been observed for office values (from 134.2±15.7 to 125.1±12.2, p = 0.03), and for ABPM 24h (from 131.1±10.7 to 126.0±10.1, p = 0.01) and day-time values (from 134.7±10.5 to 127.1±18.4, p = 0.02). For DBP, only ABPM 24h and day-time values showed significant changes (from 85.3±9.1 to 82.1±7.5, p = 0.03; and from 88.5±9.3 to 85.7±7.8, p = 0.02). Within session SBP decrease was -5.8 mmHg (-3.75%) during the first session while it falls to -2.1 mmHg (-1.25%) and stands firmly under 2 mmHg for all the next session. At the last session SBP reduction was -1.9 mmHg (-1.6%).

Conclusions:

We found a significant reduction in office, 24h and day-time ABPM SBP determined by a 6-weeks twice weekly acupuncture cycle that lasts at least for the first two months after its completion.
PSYCHIATRIC SEQUELAE OF CALCIUM CHANNEL BLOCKERS – PRELIMINARY RESULTS FROM A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Fürtig Marc-Alexander , Kovalenko Yana , Kreutz Reinhold , Riemer Thomas Günther
Published: June 2023

Objective:

L-type Calcium Channel Blockers (CCB) are widely used in the treatment of hypertension and other cardiovascular diseases. The risk of adverse events such as hypotension and edema for dihydropyridine-CCB (DHP), and bradycardia, atrioventricular block, and constipation for non-dihydropyridine-CCB (non-DHP) is well known. In addition, CCB have also been suspected of causing psychiatric adverse events (PAE). In our study, we evaluate the risk of PAE during CCB therapy.

Design and method:

We conducted a systematic search in literature databases and clinical trial registries to identify placebo-controlled randomized controlled trials (RCT) that reported frequencies of PAE during CCB therapy. We extracted data on frequencies of PAE and reviewed them, taking into account the total number of exposed patients. We separately calculated odds ratios (OR) with a 95% confidence interval (CI) for PAE in users of DHP or non-DHP CCB.

Results:

We retrieved 86 eligible placebo-controlled studies, encompassing 14,585 patients exposed to CCB. Main indications for CCB use were hypertension (64 studies) and angina pectoris (11 studies). PAE were reported in 1,425 patients, with fatigue, depression, agitation, and insomnia accounting for most of cases (299, 272, 113, and 105 respectively). Meta-analyses were possible for eight symptoms in DHP studies and for two symptoms in non-DHP studies, with a total of 73 RCT contributing data. We found no significant differences between the risk of PAE during DHP (anxiety (OR = 0.85; CI = 0.47–1.54; p = 0.58), depression (OR = 0.87; CI = 0.73–1.03; p = 0.11), unusual dreams (OR = 0.92; CI = 0.47–1.80; p = 0.80), fatigue (OR = 1.15; CI = 0.91–1.46; p = 0.24), insomnia (OR = 0.90; CI = 0.62–1.29; p = 0.55), nervousness (OR = 1.18; CI = 0.87–1.59; p = 0.29), sleep disorders (OR = 1.26; CI = 0.68–2.33; p = 0.47), and somnolence (OR = 1.15; CI = 0.77–1.71; p = 0.49) or non-DHP (fatigue (OR = 1.32; CI = 0.76–2.27; p = 0.32) and insomnia (OR = 0.94; CI = 0.31–2.86; p = 0.92)) compared to placebo.

Conclusions:

PAE are occasionally reported during CCB therapy but not more frequently than during placebo. Therefore, CCB do not impose a risk of psychiatric sequelae and can be considered safe regarding mental health.
LOSARTAN/AMLODIPINE IN ARTERIAL STIFFNESS SHOWS DOMINANT EFFICACY IN REDUCING 24 HOURS BRACHIAL AND CENTRAL BP COMPARED WITH LOSARTAN/HYDROCHLOROTHIAZID OR IN NORMAL ARTERY
Authors: Cho Eun Joo , Lee Hae Young , Sung Ki Chul , Park Sungha , Sohn Il-Suk , Park Chang Gyu , Choi Dong-Ju , Ha Jong Won , Ahn Young Keun , Shin Jinho , Hong Soon-Jun , Kim Soon Kil , Chung Wook-Jin , Yoo Byung Su , Hong Taek Jong , Youn Ho Joong , Cho Myeong-Chan , Chae Shung Chull , Kim Young Jo , Kim Chong-Jin
Published: June 2023

Objective:

The aim of this research was to compare the efficacy between 20 weeks treatments of losartan/amlodipine(L/A) versus losartan/hydrochlorothiazide(L/H) combination therapy in reducing 24 hours brachial and central blood pressure (BP) according to the severity of baseline arterial stiffness measured by 24 hours pulse wave velocity (PWV).

Design and method:

The K-central research was a prospective, randomized, double-blind, multicenter trial including 231 hypertensive patients (mean age = 59.2±12.2 years). Patients take losartan 50 mg monotherapy for 4 weeks, followed by additional amlodipine 5 mg (L/A) or hydrochlorothiazide 12.5 mg (L/H) for 20 weeks after randomization. The patients who did not achieve the BP goal after 4 weeks’ randomization receive an increased dose of losartan 100 mg for the L/A group and increased doses of losartan 100 mg and hydrochlorothiazide 25 mg for L/H group. The 24 hours brachial BP, central BP, and PWV were measured using an oscillometric device (Mobil-O-Graph 24-hour PWA monitor, I.E.M. Gmbh, Stolberg, Germany) at baseline and after 20 weeks’ treatment.

Results:

The main results of this research are presented in the table and figure.

Conclusions:

We concluded that L/A combination therapy in subjects with advanced arterial stiffness shows dominant efficacy in reducing 24 hours mean brachial and central BP compared with in subjects without arterial stiffness or with L/H combination therapy.
Positive Predictive Values and Outcomes for Uninformative Cell-Free DNA Tests: An Italian Multicentric Cytogenetic and Cytogenomic Audit of DiagnOstic Testing (ICARO Study)
Authors: Grati Francesca Romana , Bestetti Ilaria , de Siero Daria , Malvestiti Francesca , Villa Nicoletta , Sala Elena , Crosti Francesca , Parisi Valentina , Nardone Anna Maria , Di Giacomo Gianluca , Pettinari Antonella , Tortora Giada , Montaldi Annamaria , Calò Annapaola , Saccilotto Donatella , Zanchetti Sara , Celli Paola , Guerneri Silvana , Silipigni Rosamaria , Cardarelli Laura , Lippi Elisabetta , Cavani Simona , Malacarne Michela , Genesio Rita , Beltrami Nicola , Pittalis Maria Carla , Desiderio Laura , Gentile Mattia , Ficarella Romina , Recalcati Maria Paola , Catusi Ilaria , Garzo Maria , Miele Lorena , Corti Cecilia , Ghezzo Sara , Bertini Veronica , Cambi Francesca , Valetto Angelo , Facchinetti Barbara , Bernardini Laura , Capalbo Anna , Balducci Federica , Pelo Elisabetta , Minuti Barbara , Pescucci Chiara , Giuliani Costanza , Renieri Alessandra , Longo Ilaria , Tita Rossella , Castello Giuseppe , Casalone Rosario , Righi Rossana , Raso Barbara , Civolani Alessandro , Muzi Maria Cristina , di Natale Manuela , Varriale Luigia , Gasperini Daniela , Nuzzi Maria Cristina , Cellamare Angelo , Casieri Paola , Busuito Rosa , Ceccarini Caterina , Cesarano Carla , Privitera Orsola , Melani Daniela , Menozzi Cristina , Falcinelli Cristina , Calabrese Olga , Battaglia Paola , Tanzariello Antonella , Stampalija Tamara , Ardisia Carmela , Gasparini Paolo , Benn Peter , Novelli Antonio
Published: June 2023

(Abstracted from Prenat Diagn 2022;42:1575–1586

Methods for diagnosis of genetic abnormalities have recently undergone substantial improvement. Noninvasive prenatal testing (NIPT) is performed early in pregnancy, typically at the end of the first trimester using cell-free DNA (cfDNA) to identify 3 commonly occurring trisomies (13, 18, and 21).
The Impact of Paternal Age on New Mutations and Disease in the Next Generation
Authors: Wood Katherine A. , Goriely Anne
Published: June 2023

(Abstracted from Fertil Steril 2022;118(6):1001–1012

Previous research has long established a link between genetic disorders and advanced maternal age. Newer research has shown an additional and independent link between advanced paternal age and difficulty conceiving, complications during pregnancy, and increased possibility of many conditions including spontaneous dominant disorders, congenital abnormalities, neurodevelopmental conditions, and malignancies.
Outcomes of a Career Development Award (Pre-K) Mock Review Program for Postdoctoral Fellows and Early-Career Faculty
Authors: Castillo-Mancilla Jose R. , Erlandson Kristine M. , Hecker Emily R. , Komaie Goldie , Shomaker Lauren B. , Cicutto Lisa , Mankin Galit , Maclean Paul
Published: June 2023

Purpose

Securing research funding for early-career investigators remains challenging. The authors present the results of a presubmission career development award (Pre-K) review program for postdoctoral fellows and early-career faculty.

Method

The Pre-K program is designed to help mentored postdoctoral fellows and early-career faculty write successful career development awards by assigning expert reviewers to score each application and provide written and oral critiques before a mock study section. Applicants and mentors attend the review and can ask questions directly to reviewers about their application. Quarterly, annual, and alumni surveys are sent to applicants who participated in the Pre-K program to assess satisfaction, confirm grant submission and status (i.e., funded and unfunded), and understand the long-term career impact of the program.

Results

A total of 212 applicants (136 [64%] female; 19 [9%] from underrepresented in medicine groups) participated in the program between 2014 and 2021. Outcome data from 194 grants were available. Among these grants, 71 were awarded (37% success rate). Among underrepresented in medicine applicants, 7 of 18 submitted grants were funded (39% success rate). Of 183 Pre-K participants sent the alumni survey, 123 (67%) responded. Academic degrees included 64 PhDs (52%), 46 MDs (37%), and 14 MDs/PhDs (11%). One hundred nine respondents (90%) were employed in an academic institution, and 106 (86%) devoted more than 50% of their time to research. One hundred twelve (91%) reported receipt of an award (87 [78%] federal and 59 [53%] intramural funding), the most common being National Institutes of Health K/Career Development Awards. Pre-K was rated as very useful to their careers by 102 respondents (83%).

Conclusions

A Pre-K mock review program can assist early-career investigators in securing funding and launching their research career. Continued investment in the next generation of clinical and translational researchers should remain an institutional priority.
All-cause mortality in moderate and severe COVID-19 patients with myocardial injury receiving versus not receiving azvudine: a propensity score-matched analysis
Authors: Chen Ru , Guo Yi , Deng Shan , Wang Jian , Gao Meng , Han Hongli , Wang Lin , Jiang Hongwei , Huang Kai
Published: June 2023

Background and purpose:

Omicron is currently the dominant strain of severe acute respiratory syndrome coronavirus 2, but little is known about the characteristics and management of omicron related myocardial injury, particularly the potential benefit of the antiviral agent azvudine.

Methods:

Patients with confirmed and suspected coronavirus disease 2019 (COVID-19) admitted to Wuhan Union Hospital from December 7, 2022, to December 30, 2022, were included in this study. Cox regression was conducted to identify risk factors for all-cause mortality. A propensity score-matched analysis was performed at a 1:1 ratio with a caliper of 0.1 pooled standard deviations of relevant confounders.

Results:

The final analysis included a total of 332 patients (167 confirmed cases and 165 suspected cases), 42.77% (142/332) of the patients aged over 80 years and 68.67% (228/332) of them were men, 158 of the patients were treated with azvudine. In the matched cohort, a total of 60 (30.30%, 60/198) patients deceased, 40 (20.20%, 40/198) of the patients received noninvasive ventilation and 22 (11.11%, 22/198) received invasive ventilation, 34 (17.17%, 34/198) of the cases were admitted to intensive care unit (ICU). The rate of shock, multiple organ damages and arrhythmia were 11.62% (23/198), 20.20% (40/198), and 12.12% (24/198), respectively. There was no significant difference on these clinical outcomes in patients treated with azvudine or not. Azvudine reduced early mortality (within 14 days from admission) (hazard ratio: 0.37, 95% confidence interval: 0.18–0.77) even after adjusting for other treatments including glucocorticoids, immunoglobin and anticoagulant therapy, but not the final in-hospital mortality of patients.

Conclusions:

Patients with COVID-19-related myocardial injury had a high mortality of about 30.30% (60/198). Azvudine improved the early survival of the patients but not final mortality.
Comprehensive quantitative sensory testing shows altered sensory function in women with chronic pelvic pain: results from the Translational Research in Pelvic Pain (TRiPP) Study
Authors: Coxon Lydia , Vollert Jan , Perro Danielle , Lunde Claire E. , Ferreira-Gomes Joana , Charrua Ana , Abreu-Mendes Pedro , Krassowski Michal , Birch Judy , Meijlink Jane , Hummelshoj Lone , Hoffmann Anja , Aziz Qasim , Arendt-Nielsen Lars , Pogatzki-Zahn Esther , Evans Emma , Demetriou Lysia , McMahon Stephen B. , Missmer Stacey A. , Becker Christian M. , Zondervan Krina T. , Horne Andrew W. , Cruz Francisco , Sieberg Christine B. , Treede Rolf-Detlef , Nagel Jens , Vincent Katy
Published: June 2023

Chronic pelvic pain (CPP), despite its high prevalence, is still relatively poorly understood mechanistically. This study, as part of the Translational Research in Pelvic Pain (TRiPP) project, has used a full quantitative sensory testing (QST) paradigm to profile n = 85 women with and without CPP (endometriosis or bladder pain specifically). We used the foot as a control site and abdomen as the test site. Across 5 diagnostically determined subgroups, we found features which are common across different aetiologies, eg, gain of function in pressure pain threshold (PPT) when assessing responses from the lower abdomen or pelvis (referred pain site). However, disease-specific phenotypes were also identified, eg, greater mechanical allodynia in endometriosis, despite there being large heterogeneities within diagnostic groups. The most common QST sensory phenotype was mechanical hyperalgesia (>50% across all the groups). A “healthy’ sensory phenotype was seen in <7% of CPP participants. Specific QST measures correlated with sensory symptoms assessed by the painDETECT questionnaire (pressure-evoked pain [painDETECT] and PPT [QST] [r = 0.47, P < 0.001]; mechanical hyperalgesia (painDETECT) and mechanical pain sensitivity [MPS from QST] [r = 0.38, P = 0.009]). The data suggest that participants with CPP are sensitive to both deep tissue and cutaneous inputs, suggesting that central mechanisms may be important in this cohort. We also see phenotypes such as thermal hyperalgesia, which may be the result of peripheral mechanisms, such as irritable nociceptors. This highlights the importance of stratifying patients into clinically meaningful phenotypes, which may have implications for the development of better therapeutic strategies for CPP.
Pelvic Girdle Pain in Pregnancy: A Review
Authors: Sward Lindsey , Manning Nirvana , Murchison Amanda B. , Ghahremani Taylor , McCaulley Jill A. , Magann Everett F.
Published: June 2023

Importance

Pelvic girdle pain is often thought to be a recent phenomenon, but this condition was described as early as 400 BC by Hippocrates. Despite being identified for years, confusion continues about the definition and management of this ailment affecting many pregnancies.

Objectives

The purpose of the review is to assess the incidence, etiology, pathophysiology, risk factors, diagnosis, management, and pregnancy outcomes/recovery of current pregnancies, and outcomes of future pregnancies complicated by pelvic girdle pain.

Evidence Acquisition

Electronic databases (PubMed and Embase) were searched from 1980 to 2021 with the only limitation being that the articles were in English. Studies were selected that examined associations between pelvic pain/pelvic girdle pain and pregnancy.

Results

There were 343 articles identified. After reviewing the abstracts, 88 were used in this review. Pelvic girdle pain is a common condition of pregnancy, affecting a reported 20% of pregnant women. The pathophysiology is poorly understood and likely multifactorial, involving both hormonal and biomechanical changes that occur during pregnancy. Several risk factors have been identified. This diagnosis is most commonly made based on symptoms related to pelvic pain during pregnancy. Treatment should be multimodal, including pelvic girdle support, stabilizing exercises, analgesia, and potentially complementary therapies. The effects on future pregnancies are uncertain, although some limited information suggests an increased risk of recurrent PGP in subsequent pregnancies.

Conclusions

Pelvic girdle pain in pregnancy is a common condition that is often overlooked as a normal part of pregnancy but has a significant impact on quality of life during, after, and in subsequent pregnancies. Multimodal therapies are available and are largely low cost and noninvasive.

Relevance

Our aim is to increase the awareness of pelvic girdle pain in pregnancy as a common but often underdiagnosed and undertreated condition.

Target Audience

Obstetricians and gynecologist, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to describe the diagnosis, etiology, and pathophysiology of pelvic girdle pain; identify risk factors and appropriate management; and predict reoccurrence in a subsequent pregnancy.
Pharmacologic Interventions to Minimize Fluid Absorption at the Time of Hysteroscopy: A Systematic Review and Meta-analysis
Authors: Désilets Jade , Zakhari Andrew , Chagnon Miguel , Ekmekjian Taline , Nguyen Dong Bach , Smith Jessica Papillon , Mansour Fady W. , Krishnamurthy Srinivasan
Published: June 2023

(Abstracted from Obstet Gynecol 2023;141:285–298

With a range of both therapeutic and diagnostic indications, hysteroscopy is one of the gynecological procedures most commonly performed. Although both effective and generally safe, this intervention does carry a small risk of fluid overload, fluid absorption, and electrolyte imbalance (which can on rare occurrence be fatal).
Perioperative Opioid Dispensing and Persistent Use After Benign Hysterectomy: A Systematic Review and Meta-analysis
Authors: Hessami Kamran , Welch Jennifer , Frost Anja , AlAshqar Abdelrahman , Arian Sara E. , Gough Ethan , Borahay Mostafa A.
Published: June 2023

(Abstracted from Am J Obstet Gynecol 2022; doi: 10.1016/j.ajog.2022.12.015

Between 1999 and 2019, the opioid epidemic claimed the lives of nearly 250,000 individuals in the United States. Many patients first opioid prescription is dispensed in a surgical setting, and hysterectomy is the second most common surgical procedure in women.