bluuebunny/crossref_metadata_2025 huggingface dataset:
COST-EFFECTIVENESS OF SINGLE-PILL AND SEPARATE-PILL ADMINISTRATION OF ANTIHYPERTENSIVE TRIPLE-COMBINATION THERAPY: A POPULATION-BASED MICROSIMULATION STUDY
Authors: Morabito Gabriella , Rea Federico , Gregorio Caterina , Ieva Francesca , Barbati Giulia , Corrao Giovanni , Mancia Giuseppe
Published: May 2024

Objective:

To evaluate the lifetime cost-effectiveness profile of the perindopril/amlodipine/indapamide single-pill combination (SPC) compared with the combination of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic as a SPC of two drugs plus the third drug separately from the Italian payer perspective.

Design and method:

A cost-effectiveness analysis was conducted employing multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged >=40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug prescription until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty.

Results:

Compared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61–1.14), with a reduction in total cost of –€12 (95% CI –9,719 to 8,131), making it the dominant strategy (ICER of –14, 95% CI –€15,871 to €7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to €1,850 (95% CI 17 to 7,813) and €2,027 (95% CI 19 to 8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (€3,848, 95% CI 574 to 10,640 vs. €3,710, 95% CI 263 to 11,955). This was the case for all strata of age, sex, and clinical status.

Conclusions:

The SPC was projected to increase survival and reduce costs compared with the two-pill combination. This is likely explained by an improvement in drug compliance. As three-drug SPC is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system.
FOLLOW-UP OF SURVIVAL PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION
Authors: Rekovets Oksana , Sirenko Yuriy , Torbas Olena , Primak Galina , Granich Volodymyr , Kushnir Svitlana
Published: May 2024

Objective:

Resistant arterial hypertension (RAH) contributes to high mortality worldwide.

Aim of the study: to assess 7-year follow-up survival and development of a composite end point (CEP) in patients with RAH.

Design and method:

The analysis includes 50 patients with RAH who were discharged from hospital. After 7 years discharge from the hospital, the patients underwent office BP measurement. Adverse events or death were reported as the composite endpoint (CEP). The average age of patients as of 2016 was 57.89 ± 11.81 y.o. 16% had type 2 diabetes (n=8).

Results:

After 7 years, in 32% (n=16) developed CEP, and 10% (n=5) of them died. The BMI increased from 30.87 ± 6.30 to 33.80 ± 6.90 kg/m2 (p<0.05). 20% had smoke (n=10), but 8% (n=4) (quit smoking after developing CEP). After 7 years, 48.88% of patients (n=22) controlled office blood pressure below 140/90 mmHg and 51.11% did not (n=23). Among patients who reached the target office BP (130.73 ± 6.61/81.59 ± 4.13 mmHg), there was a decrease in the number of drugs from 3.76 ± 0.19 to 2.85 ± 0.14, p<0.05. 45% (n=10) from the group took fixed combinations. Among patients who did not reach target office BP (148.04 ± 7.49/92.17 ± 4.66 mmHg), there was also a decrease in the number of drugs from 3.52 ± 0.18 to 2.50 ± 0.13, p<0.05 – patients decision. After regression analysis the main factors that were associated with the occurrence of CEP in patients with RAH were: the presence of diabetes (β= 5,237, p= 0,032) smoking (β=4,326, p= 0,037), increased body weight (β =3,423, p=0,024), failure to achieve target blood pressure levels (β =4,152, p=0,041)

Conclusions:

Mortality among patients with RAH were 10% during 7 years. The total composite endpoint were 32%. Did not reach the target office BP in patients with RAH the factors for the development of combined end point was diabetes mellitus, smoking and weight gain.
AN EXPLORATORY STUDY OF SERUM PROTEOMICS COMPARING SUBJECTS WITH TREATMENT-RESISTANT HYPERTENSION TO CONTROLLED HYPERTENSION
Authors: Elsadig Mohamed , Hameed Mohammed Awais , Grammatopoulos Dimitris , Dasgupta Indranil , Gill Paramjit , Medvecky Matej
Published: May 2024

Objective:

The mechanism of treatment-resistant hypertension (TRH) is not fully understood yet. However, studies suggest the involvement of vascular endothelial dysfunction and systemic inflammation as contributors to the pathogenesis. This study aims to identify any measurable differences in protein abundance between two groups of hypertensive adults, controlled hypertension (CH) and TRH, using proteomics analysis techniques.

Design and method:

The study samples were obtained from an existing observational cohort study involving CH and TRH groups; venous blood samples were previously stored at -80°C, and appropriate consenting and ethical approval was obtained. TRH was defined blood pressure (BP) of 140/90 mmHg or more, on 3 or more antihypertensive agents or controlled BP (less than140/90 mmHg) after taking 4 or more antihypertensive agents. The study was conducted in two phases: the discovery phase, where 60 samples of matched group's (CH, n=30, TRH n=30) Peripheral venous serum samples were initially depleted from the highly abundant proteins before undergoing trypsin digestion, this was followed by Liquid Chromatography Mass Spectrometry analysis. The validation phase included 140 candidates (CH n=81, TRH n=59). Results were statistically analysed using an independent T-test, P valve <0.05 was considered to be statistically significant. Gen Ontology (GO) description is used for the functional description of the proteins.

Results:

Full results analysis is still undergoing by the time this abstract is being submitted, however, 12 different proteins were found to be significantly different in their expression between the two groups: Alpha 1B glycoprotein, Leucine-rich alpha 2 glycoproteins, Inter alpha trypsin inhibitor heavy chain H3, Lumican, Complement component C9, Complement factor D, Contactin-1, Lysozyme C, Phospholipid transfer protein, and Vascular cell adhesion protein 1.Initial GO analysis suggests above proteins are involved in vascular integrity, endothelial function and inflammatory response.

Conclusions:

There are significant differences in the proteins expression between patients with TRH and CH. This may allow better understanding of TRH, and treatment strategies.
SOCIAL DETERMINANTS OF HEALTH, BLOOD PRESSURE CLASSIFICATION, AND INCIDENT STROKE IN COMMUNITY-DWELLING ADULTS: A PROSPECTIVE COHORT STUDY
Authors: Chen Chaolei , Feng Yingqing
Published: May 2024

Objective:

To determine whether the association of blood pressure (BP) categories, defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) BP guideline, with stroke differ among Chinese adults with low or high burden of unfavorable social determinants of health (SDOH).

Design and method:

Analyses were conducted in the prospective sub-cohort of the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project, started in 1, July 2017 and followed stroke events until 31, June 2023. Participants were divided into groups with low and high burden of unfavorable SDOH, which consisted of educational attainment, economic stability, health care access, social support, and neighborhood relationship. Within each group, participants were categorized as having normal BP (systolic BP [SBP] <120 mm Hg and diastolic BP [DBP] <80 mm Hg), elevated BP (SBP 120-129 mm Hg and DBP <80 mm Hg), stage 1 hypertension (SBP 130-139 mm Hg or DBP 80-89 mm Hg), and stage 2 hypertension (SBP no less than 140 mm Hg or DBP no less than 90 mm Hg). The association between BP categories and stroke were examined within each SDOH group, separately, using multivariable-adjusted Cox proportional hazards models.

Results:

Of the 96,686 adults included in this study (mean [SD] age, 53.8 [10.1] years; 59,080 [61.1%] women), 64,823 (67.0%) were categorized as having high burden of unfavorable SDOH. Over a median follow-up of 5.0 years, 4,673 (4.8%) new-onset stroke events occurred. In the group of low burden of SDOH, hazard ratios (95% CI) for stroke for elevated BP, stage 1 hypertension, and stage 2 hypertension vs normal BP were 1.09 (0.86-1.37), 1.14 (0.94-1.37), and 1.59 (1.33-1.90), respectively. In the group of high burden of SDOH, hazard ratios for stroke events for elevated BP, stage 1 hypertension, and stage 2 hypertension vs normal BP were 1.20 (1.04-1.38), 1.45 (1.29-1.62), and 1.71 (1.53-1.91), respectively. Results were similar after excluding those taking antihypertensive medications.

Conclusions:

Lower BP categories were closely associated with increased risk of stroke in the context of high burden of SDOH. Early counseling and surveillance of high BP should be emphasized within socioeconomically disadvantaged populations.
ASSOCIATION OF SEVERE SLEEP APNOEA IN PRIMARY ALDOSTERONISM
Authors: Tanaka Yasushi
Published: May 2024

Objective:

It is well known that sleep apnoea and primary aldosteronism are related. However, it is unclear whether aldosterone excess contributes to the severity of sleep apnoea. We investigated factors correlated with sleep apnoea in patients with primary aldosteronism: the endocrine system, including aldosterone, cardiac function, renal function, and blood pressure.

Design and method:

We performed a 3% oxygen saturation index with a pulse oximeter in 50 patients (54% male, 49 ± 7.3 years) diagnosed with primary aldosteronism scheduled for adrenal vein sampling in 2017-2020. 3% oxygen saturation index results were classified as mild (less than 5), moderate (5-15), or severe(15 and above) sleep apnoea. In addition, we compared aldosterone (radioimmunoassay), renin activity, aldosterone/renin activity, brain natriuretic peptide, estimated glomerular filtration rate and blood pressure at the initial visit in the severe group and other groups.

Results:

The severe group did not have higher aldosterone than the mild (192.7 ± 114.7 vs 238.9 ± 128.8 pg/mL, P=0.640) and moderate (192.7 ± 114.7 vs 187.5 ± 85.5 pg/mL, P=0.995) groups, and the same results were obtained for renin activity and aldosterone/renin activity. In other parameters, estimated glomerular filtration rate was not significantly different between groups, but systolic blood pressure at the initial visit in the severe group was significantly higher than in the mild (175.3±25.7 vs 144.8±18.7 mmHg, P=0.003) and moderate (175.3±25.7 vs 143.0±18.5 mmHg, P=0.003) groups. Similarly, brain natriuretic peptide in the severe group was significantly higher than in the mild (53.5±90.0 vs 12.7±8.3 pg/mL, P=0.020) and moderate (53.5±90.0 vs 10.7±11.2, P=0.014) groups.

Conclusions:

Our results showed that aldosterone excess did not contribute to the severity of sleep apnoea. However, severe sleep apnoea was significantly associated with elevated systolic blood pressure and brain natriuretic peptide.
HYPERTENSION AND VASCULAR RIGIDITY MEASUREMENTS IN ABORIGINAL AND NON-ABORIGINE POPULATIONS OF NORTHERN ARGENTINE DURING 2023
Authors: Romano José René , Olga Yegros , Anair Fernandez
Published: May 2024

Objective:

Valuate central aortic pressure and blood pressure in 2 populations in the city of formosa in the year 2023, differences between them, degree of control. It has that one of such populations has its own socio-cultural characteristics.a prospective observational type study was carried out

Design and method:

taking the central blood and aortic pressure with standardized measurements with a tel or graph tensiometer, The data was taken during 3 months of 2023 in 2 institutions one a primary care center in an aboriginal(a) neighborhood of the toba race and another in the central hospital, both public institutions, have a prior diagnosis of hta. the data was analyzed in the statistix 7.0

Results:

study 75 patients, 30 a and 45 non-aborigine (na), the age was 56 in na and 50 in a, the sex of the patients was 25% men (m) in na and 53% h in a. the systolic pressure was 1/2 of 146 in no a and 117 in a, the diastolic pressure 89 in na and 67 in a, the pwv 9.2 in na and 7.3 in a, the increase index 29 in na and 15 in a.

Conclusions:

found in similar populations, lower values of vop, ta and increase index in the aboriginal population studyed. we should study more population to see if the data are correct and then see the cause
INFLUENCE OF STATINS ON ARTERIAL STIFFNESS AND BLOOD PRESSURE CONTROL IN PATIENTS WITH SEVERE ARTERIAL HYPERTENSION
Authors: Radchenko Ganna , Sirenko Yuriy
Published: May 2024

Objective:

In some studies, there was well established a statin influence on arterial stiffness. It was suggested statins could decrease the blood pressure too. Pulse wave velocity (PWV), a gold standard for arterial stiffness measurement, depends on blood pressure (BP). The aim of study was to evaluate the influence of statins on PWV changes in dependency on normalization of the 24-h BP.

Design and method:

In study, there were included 46 patients (mean age 55.6 ±1.07, f/male 47.8/52.2%) with systolic (SBP)/diastolic (DBP) BP >/=180/110 mmHg, who were treated in specialized unit. Baseline and at the 6th month of combination therapy (mean medicines - 3.8±1.2), we provided office/ambulatory BP and PWV measurements.

Results:

At 6th month, only 39.1% had 24-h BP <130/80. PWV changes under treatment are present in tab. In statin treatment group we noted significant PWV lowering in spite of BP control. In patients without statins, PWV decreased significantly only in subgroup with achieved the target 24-h BP. In statin group 66.7% achieved target 24-h BP compared to 33.3% in statin (-) group (p=0.048).

Conclusions:

The statin therapy is able to improve the arterial stiffness (independently to BP control) and helps to achieve the target BP.
EFFECT OF ANTI-PCSK9 ANTIBODIES ON ARTERY STRUCTURE AND FUNCTION: THE NIGUARDA HOSPITAL COHORT
Authors: Maloberti Alessandro , Toscani Giorgio , Busti Andrea , Tognola Chiara , Intravaia Rita Cristina Mi , De Censi Lorenzo , Galasso Michele , Daus Franesca , Giani Valentina , Gualini Elena , Garofani Ilaria , Riccio Alfonso , Biolcati Marco , Fabbri Saverio , Algeri Michela , Merlini Piera , Giannattasio Cristina , Morelli Marco
Published: May 2024

Objective:

PCSK9 inhibitors antibodies (PCSK9-i) are a valid option to reduce LDL cholesterol in patients who failed to reach therapeutic target with maximized lipid-lowering therapies or in patient with statins intolerances. These antibodies reduce the frequency of new cardiovascular events, however if this effect is due only to LDL reduction or also to an improvement in arterial function and structure is yet to be proved. Our study aim was to evaluate aortic stiffness (Pulse Wave Velocity - PWV), carotid's Intima-Media Thickness (IMT) and endothelial function (brachial Flow Mediated Dilatation - FMD) in patients treated with Alirocumab and Evolocumab.

Design and method:

This is a monocentric prospective longitudinal study on patients who received PCSK9-i administrations at the Niguarda Hospital's cardiovascular rehabilitation and prevention unit. They underwent 3 evaluations of PWV, FMD and IMT (T0 the same day of the first injection, T1 after 6 months and T2 after 12 months of therapy).

Results:

39 patients concluded the 12 months period. The group average age is 66.8 ± 7.6 years, most of them were male (64.1%). LDL cholesterol average levels were significantly reduced by the therapy (128.3 ± 27.7 vs 44.7 ± 29.3 mg/dL, p<0.001), however, there were no significant changes in PWV (10.2 ± 3.0 vs 10.6 ± 2.5 m/s, p=0.404), FMD (8.6 ± 7.0 vs 8.9 ± 7.4%, p=0.560) and IMT (768.7 ± 175.4 vs 733.5 ± 147.2 μm, p=0.270) values.

Conclusions:

It was not possible to prove a significant effect of PCSK9-i on vascular properties, however, the stability of these indexes may suggest a deceleration of the atherosclerotic disease which it could have worsen in this population, especially considering the risk factors of our patients.
ANALYSING THE RELATIONSHIP BETWEEN SFLT-1/PLGF RATIO AND PREMATURE BIRTH
Authors: Rodríguez Claudia Martín , Morales Eduardo Martínez , González Esther Rubio , Sánchez Paula López , Testillano Lucía Martín , Pujol Javier Relea , García Irene García , Sánchez Paola Carolina Villegas , García M Mercedes Pérez , Fernández M Isabel Galán , Arroyo Ana María Huerta , Briales Paula Sánchez , Vidas María Marques , Recio María De Valdenebro , Sánchez Ana Muñoz , Menéndez Estefanya Lisset García , Marín Darío Janeiro , Salazar María Luisa Serrano , Carratalá Rosario Llópez , Pérez Jose María Portolés
Published: May 2024

Objective:

To analyse the relationship between sFlt-1/PlGF ratio and the occurrence of premature birth (<37 week)

Design and method:

An observational, retrospective, cross-sectional study that includes pregnant women who under sFlt-1/PlGF ratio determination since January until September 2022 in a tertiary hospital. Baseline characteristics and data related with the pregnancy, birth and the development of hypertensive disorders of pregnancy (HDP) were included. A multivariate logistic regression was applied to identify risk factors.

Results:

Out of 109 recruited patients, 104 were analyzed (5 were excluded due to the lost of follow-up). The mean age was 33.9 years (SD 5.0), 52.5% were primiparous and 4.8% were twin pregnancies. 7.7% had pre-pregnancy hypertension and 15.4% had a prior HDP. Additional data are specified in Table 1.

During pregnancy, a total of 64.4% women developed HDP; 45.2% presented pre-eclampsia (PE) / eclampsia; 4.8% had chronic hypertension and 14.4% had gestational hypertension.

The mean week of birth presentation was 37.9 (SD 2.4).18.3% were preterm births (<37 week). Among patients with PE, 30.6% had a preterm birth compared with 7.3% of preterm births in cases without PE (p-value 0.002).

Fifty-four percent women obtained a pathological sFlt-1/PlGF ratio (>38). 30.4% of patients with a pathological ratio underwent preterm birth, whereas only 4.2% with a normal ratio developed preterm birth (p-value 0.001). 73.7% of preterm births had a ratio >65, and 26.3% had a ratio between 26-65. No differences in neonate weight (p- value 0.058) between women with a pathological ratio (2.9 kg, SD 90.1) and a normal one (3.1 kg, SD 82.4)

In multivariate analysis, excluding twin pregnancies, patients with a pathological ratio had a higher risk of preterm birth, OR 5.2 (CI95% [1.0-28.0]), regardless of patient's age or the presence or not of preeclampsia.

Conclusions:

The sFlt-1/PlGF ratio could be a valuable tool to predict the risk of preterm birth, as patients with a pathological ratio had higher risk of preterm birth, regardless women's age or the presence of preeclampsia. More studies are necessary to establish thisratio in clinical practice for this purpose.
GENDER DIFFERENCES IN THE IMPACT OF VENTRICULAR-ARTERIAL COUPLING ON LEFT VENTRICULAR FUNCTION IN PATIENTS WITH HYPERTENSION
Authors: Joo Seungjae , An Soyeon , Boo Kiyoung , Lee Jaegeun , Choi Joonhyouk , Kim Songyi
Published: May 2024

Objective:

Increased arterial stiffness elevates aortic load, which can have adverse impacts on left ventricular (LV) function and contribute to the onset of heart failure. This impact is known to be more pronounced in women. Optimal coordination between ventricular contraction and the arterial system is required to maintain efficient cardiac function. This study aimed to investigate gender differences in the impact of ventricular-arterial coupling (VAC) on LV function in patients with hypertension at rest and after handgrip exercise.

Design and method:

Echocardiographic indexes of LV volumes, systolic function, and diastolic function were obtained in the usual way. Effective arterial elastance (EA) and index (EAI) were calculated from stroke volume measured using LV outflow waveform. Effective LV end-systolic elastance (ELV) and index (ELVI) were obtained using the single-beat method. Central aortic pressure waveform was recorded using the applanation tonometry. Characteristic impedance (Zc) of aortic root and reflection magnitude (RM) was calculated after Fourier transformation of both aortic pressure and flow waveforms.

Results:

Sixty-four patients (31 women and 33 men) with hypertension were enrolled. Women showed higher ELVI (1.33±0.34 vs. 1.10±0.29 mmHg/ml/m2, P=0.004) and EAI (1.14±0.25 vs. 0.93±0.26 mmHg/ml/m2, P=0.001), but VAC was not different (women: 0.88±0.17 vs. men: 0.85±0.11, P=0.431). Zc and RM were not different between women and men. After handgrip exercise, an increase in ELVI (P=0.021) and a decrease in VAC (P=0.035) were observed specifically in men, with no corresponding changes noted in women. In women, VAC was significantly associated with E’ velocity (beta -0.344, P=0.029) and left ventricular global longitudinal strain (beta 0.470, P=0.012) after adjustment, but in men, no association was found.

Conclusions:

Hypertensive women demonstrated greater stiffness in both the left ventricle and arterial systems, along with impaired LV contractile reserve in response to handgrip exercise, as compared to men. The ventricular-arterial mismatch had a notable impact on LV diastolic and systolic dysfunction only in women, but not in men.
EFFECTS OF VITAMIN D ON CAROTID STRUCTURE AND FUNCTION IN A RAT MODEL OF POLYCYSTIC OVARY SYNDROME
Authors: Horváth Eszter Mária , Benkö Rita , Süli Anita , Kiss Stella Tímea , Bányai Bálint , Vezér Márton , Kim Dongwoog , Várbíró Szabolcs , Szekeres Mária
Published: May 2024

Objective:

Polycystic ovary syndrome (PCOS) is a common gynecological disorder of endocrine origin that can be associated with increased cardiovascular morbidity and vitamin D deficiency. The effects of vitamin D deficiency on cardio-metabolic risk in PCOS have been shown in previous studies. In the present experiments, we investigated the effect of vitamin D supplementation in light of optimal vitamin D intake on rat carotid artery function in a rat model of PCOS.

Our aim was to investigate the effects of vitamin D supplementation and hyperandrogenism on functional and morphological changes of the carotid artery.

Design and method:

Adolescent female Wistar rats were provided with normal (C: 1000 IU/day/kg/week) or increased (D: 3000 IU/day/kg/week) vitamin D intake for 8 weeks. In half of these animals hyperandrogenism was induced by testosterone treatment (T and T+D: daily cutaneous testosterone: 3.3 mg/100 g) (N=8 in all 4 groups). After 8 weeks, carotid arteries were isolated and phenylephrine (Phe)-induced contraction and acetylcholine (Ach)-induced relaxation of the vascular rings were examined by myography. Wall thickness and intima-media ratio were determined in hematoxylin-eosin stained tissue sections, vessel wall connective tissue fiber density in resorcin-fuchsin stained sections, and vessel smooth muscle densitometry by -αsmooth muscle actin immunostaining.

Results:

The hyperandrogenic state induced a decreased contractility as a response to Phe (10-6 M Phe expressed in the % of K+-induced contraction: T: 62±22% p<0.001 vs. C: 116±33%; D: 101±39%), that was reversible by Vitamin D treatment (T+D: 95±16%, ns.). Endothelium-mediated relaxation did not differ between groups. Hyperandrogenic state significantly increased vessel wall thickness (T: 74.81 ±4.48 μm, p<0.05 vs. C: 57.92±2.96 μm; D: 53.21±10.8 μm), which was prevented by Vitamin D (58.99±8.75 μm, ns.) whereas intima-media ratio did not change. No significant differences were found for smooth muscle actin and connective tissue fiber density.

Conclusions:

Our results suggest that the hyperandrogenism increased vessel wall thickness and, in comparison to media thickness the alpha1-adrenerg sensitivity decreased, leading to a limited capacity of regulation. The morphological remodeling of the vascular wall induced by testosterone treatment did not cause significant endothelial functional changes yet.
LONG-TERM IMPACT OF PREVIOUS GESTATIONAL HYPERTENSIVE DISORDERS ON BLOOD PRESSURE PROFILE AND HEART STRUCTURE
Authors: Verardino Renata , Macedo Thiago , Rodrigues Sara , Baptista Fernanda , Pulcinelli Rossana , Bortolotto Luiz
Published: May 2024

Objective:

To evaluate subclinical cardiac repercussions and blood pressure (BP) profile by noninvasive methods in women with previous severe preeclampsia (PE).

Design and method:

Cross-sectional study was carried out in a tertiary hospital. Women were evaluated 2 to 5 years after delivery and divided into 3 groups: isolated preeclampsia (IPE=30), superimposed preeclampsia and/or chronic hypertension (Sup/CH) =60 and normal gestation (NG) =30. Variables analyzed: age, body mass index (BMI), office systolic blood pressure (SBP), diastolic BP (DBP), 24-hours ambulatory blood pressure monitoring (ABPM-24h), central pressure (BPc) by Sphigmocor®; and echocardiographic variables (ViviDI-GE®).

Results:

Table

∗ = p <0,05, Sup/CH vs. NG; # = IPE vs. NG; & = Sup/CH vs. IPE

Conclusions:

Women with previous gestational hypertensive disorders, either Sup/CH or isolated PE, had elevated BP values (office, ABPM and central) and cardiac repercussions, 2 to 5 years after delivery compared to previous normal gestation.
BENEFICIAL ROLE OF DIETARY CHANGES IN MENOPAUSE: IMPACT ON CARDIOVASCULAR RISK
Authors: Tikhonoff Valerie , Ciaghi Gioele , Poncina Gianluca , Lievore Nicole , Zandi Pouya
Published: May 2024

Objective:

The changing hormonal milieu in post-menopausal women (PMW) predisposes them to increase cardiovascular (CV) risk, due to a constellation of risk factors, such as visceral obesity, atherogenic dyslipidemia and arterial hypertension. Our ongoing study aims to evaluate the impact of dietary changes in CV risk in PMW.

Design and method:

For 1 year, 65 PMW with BMI 24-39 Kg/m2 and at least another CV risk factor were followed. Anthropometric parameters, plicometry and blood pressure (BP) were taken. Questionnaires on medical history, physical activity, and food frequency (FFQ) were administered. Balanced low-calorie dietary plan with quantitative advice were released. Repeated measures ANOVA at 1 year were performed.

Results:

We observed at 1 year significant reductions (p<0.01) in weight (δ=-4.5 Kg), BMI (δ=-1.7 Kg/m2), waist (δ=-4.3cm) and hips (δ=-3.1cm) circumferences, subscapular (δ=-5.8mm), suprailiac (δ=-3.3mm) and triceps (δ=-5.5mm) skinfolds, adipose area of the arm (AFA) (δ=-7.3cm2), and fat mass (δ=-4.5kg) without variation of the lean mass (δ=-0.1 kg, p=0.48). All those reductions were followed by change in the obesity prevalence (-21.1%), in the fat mass distribution with 10% reduction in abdominal and truncular obesity and 5.2% reduction on waist-to-height ratio, and in systolic (δ=-8.8 mmHg) and diastolic (δ=-4.3 mmHg) BP. Significant positive correlations (p<0.0001) were observed between weight reduction and the following variables: waist (r=0.61) and hip (r=0.77) circumferences, subscapularis (r=0.56) and triceps (r=0.66) skinfolds, and AFA (r=0.73). Significant reductions (p<0.05) were observed in daily caloric intake (δ=-99.8Kcal/day), due to the reduction in fat intake (36.6->33.6%), specially saturated fatty acids (12->10.8%) and cholesterol (δ=-23.1mg/day), with maintenance of the average level of physical activity and in agreement with a significant reductions in consumption of animal meats, visible fat, processed meats, olive oil, sweets and baked goods detected by FFQ.

Conclusions:

The study underlines the medium-term utility of a 1 year balanced low-calorie diet in PMW with elevated CV risk factors with a clear reduction in CV risk.
Risk of Recurrent Severe Maternal Morbidity: A Population-Based Study
Authors: Ukah Ugochinyere Vivian , Platt Robert W. , Auger Nathalie , Lisonkova Sarka , Ray Joel G. , Malhamé Isabelle , Ayoub Aimina , El-Chaâr Darine , Dayan Natalie
Published: May 2024

(Abstracted from Am J Obstet Gynecol 2023;229:545.e1–545.e11

Severe maternal morbidity (SMM) is a composite outcome that encompasses life-threatening maternal complications and eclampsia around the time of delivery and up to 42 days after birth. It is associated with a higher incidence of cardiovascular disease and all-cause mortality long-term, beyond the postpartum period, as well as prolonged hospitalization.
Genetic Causes of Sporadic and Recurrent Miscarriage
Authors: Melo Pedro , Dhillon-Smith Rima , Islam Md Asiful , Devall Adam , Coomarasamy Arri
Published: May 2024

(Abstracted from Fertil Steril 2023;120:940–944

Early pregnancy loss, or miscarriage, is a relatively common occurrence. Of these losses, 80% occur in the first 12 weeks of gestation and 50% of them are diagnosed with chromosomal abnormalities.
Cryocompression to Reduce Peripheral Neuropathy in Gynecologic Cancer: A Randomized Controlled Trial
Authors: Anastasio Mary Katherine , Unnithan Shakthi , Scott Amelia , Hayes Taylor , Shah Suma , Moss Haley A. , Erkanli Alaattin , Havrilesky Laura J.
Published: May 2024

(Abstracted from Obstet Gynecol 2024;143:53–66

Between 30% and 40% of patients treated with neurotoxic chemotherapy, including taxanes and platinum drugs commonly used to treat gynecologic malignancies, experience peripheral neuropathy. Symptoms of these neuropathies include numbness, tingling, and pain in the hands and feet and often result in chemotherapy dose delay, reduction, or discontinuation along with a lower quality of life.
Machine Learning–Driven Analysis of Individualized Treatment Effects Comparing Buprenorphine and Naltrexone in Opioid Use Disorder Relapse Prevention
Authors: Afshar Majid , Graham Linck Emma J. , Spicer Alexandra B. , Rotrosen John , Salisbury-Afshar Elizabeth M. , Sinha Pratik , Semler Matthew W. , Churpek Matthew M.
Published: May 2024

Objective

A trial comparing extended-release naltrexone and sublingual buprenorphine-naloxone demonstrated higher relapse rates in individuals randomized to extended-release naltrexone. The effectiveness of treatment might vary based on patient characteristics. We hypothesized that causal machine learning would identify individualized treatment effects for each medication.

Methods

This is a secondary analysis of a multicenter randomized trial that compared the effectiveness of extended-release naltrexone versus buprenorphine-naloxone for preventing relapse of opioid misuse. Three machine learning models were derived using all trial participants with 50% randomly selected for training (n = 285) and the remaining 50% for validation. Individualized treatment effect was measured by the Qini value and c-for-benefit, with the absence of relapse denoting treatment success. Patients were grouped into quartiles by predicted individualized treatment effect to examine differences in characteristics and the observed treatment effects.

Results

The best-performing model had a Qini value of 4.45 (95% confidence interval, 1.02–7.83) and a c-for-benefit of 0.63 (95% confidence interval, 0.53–0.68). The quartile most likely to benefit from buprenorphine-naloxone had a 35% absolute benefit from this treatment, and at study entry, they had a high median opioid withdrawal score (P < 0.001), used cocaine on more days over the prior 30 days than other quartiles (P < 0.001), and had highest proportions with alcohol and cocaine use disorder (P ≤ 0.02). Quartile 4 individuals were predicted to be most likely to benefit from extended-release naltrexone, with the greatest proportion having heroin drug preference (P = 0.02) and all experiencing homelessness (P < 0.001).

Conclusions

Causal machine learning identified differing individualized treatment effects between medications based on characteristics associated with preventing relapse.
Changes in the Term Neonatal Electroencephalogram with General Anesthesia: A Systematic Review with Narrative Synthesis
Authors: Corlette Sebastian J. , Walker Suellen M. , Cornelissen Laura , Brasher Christopher , Bower Janeen , Davidson Andrew J.
Published: May 2024

Background

Although effects of general anesthesia on neuronal activity in the human neonatal brain are incompletely understood, electroencephalography provides some insight and may identify age-dependent differences.

Methods

A systematic search (MEDLINE, Embase, PubMed, and Cochrane Library to November 2023) retrieved English language publications reporting electroencephalography during general anesthesia for cardiac or noncardiac surgery in term neonates (37 to 44 weeks postmenstrual age). Data were extracted, and risk of bias (ROBINS-I Cochrane tool) and quality of evidence (Grading of Recommendations Assessment, Development, and Evaluation [GRADE] checklist) were assessed.

Results

From 1,155 abstracts, 9 publications (140 neonates; 55% male) fulfilled eligibility criteria. Data were limited, and study quality was very low. The occurrence of discontinuity, a characteristic pattern of alternating higher and lower amplitude electroencephalography segments, was reported with general anesthesia (94 of 119 neonates, 6 publications) and with hypothermia (23 of 23 neonates, 2 publications). Decreased power in the delta (0.5 to 4 Hz) frequency range was also reported with increasing anesthetic dose (22 neonates; 3 publications).

Conclusion

Although evidence gaps were identified, both increasing sevoflurane concentration and decreasing temperature are associated with increasing discontinuity.

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The Role of the Glymphatic System in Perioperative Neurocognitive Disorders
Authors: Roy Bhaswati , Kumar Rajesh , Sarovich Stephanie-Dee , Vacas Susana
Published: May 2024

Background:

The glymphatic system plays a crucial role in clearing metabolic waste from the central nervous system and is most active during sleep. Patients with obstructive sleep apnea (OSA) have a dysfunctional glymphatic system that correlates with disease severity. In addition, these patients have worse outcomes after surgery. The status of the glymphatic system during the perioperative period is unclear and can be examined with magnetic resonance imaging (MRI)-based diffusion tensor imaging (DTI). This study assessed perioperative glymphatic system changes in OSA surgical patients and possible relationships with perioperative neurocognitive disorders.

Methods:

DTI data from 13 OSA patients having laparoscopic abdominal surgery with general anesthesia were acquired and analyzed using a 3.0-T MRI scanner. Diffusivity maps in the x-axis (D
xx
), y-axis (D
yy
), z-axis (D
zz
), x-y axis (Dxy), y-z axis (Dyz), and x-z axis (Dxz) were calculated. Diffusion values for the projection and association fibers were extracted, and DTI analysis along the perivascular space (ALPS) was performed. The patients’ cognition was assessed using the Montreal Cognitive Assessment tool. Evaluations were carried out within 5 days before surgery and within the first 48 hours after surgery.

Results:

The ALPS index decreased after surgery, and this correlated with a decrease in general cognition scores and specific memory domains, including visuospatial and delayed recall.

Conclusions:

The glymphatic system in OSA patients is worsened after surgery and this may contribute to an increased risk for long-term postoperative cognitive disorders. This study suggest that the glymphatic system might play a role in the pathophysiology of perioperative neurocognitive disorders and be a potential therapeutic target.
Association of Fluid Balance and Hemoglobin Decline With Neurological Outcome After Aneurysmal Subarachnoid Hemorrhage*
Authors: Truckenmueller Peter , Wolf Stefan , Wasilewski David , Vajkoczy Peter , Früh Anton ,   for the Earlydrain Study Group
Published: May 2024

OBJECTIVES:

To explore the relationship between fluid balance and hemoglobin decline with secondary infarctions and neurologic outcome in aneurysmal subarachnoid hemorrhage (aSAH) patients.

DESIGN:

Secondary analysis of the Earlydrain trial, a prospective randomized controlled study investigating prophylactic lumbar drain use in aSAH patients.

SETTING:

Patients with aSAH treated in ICUs at 19 tertiary hospitals in Germany, Switzerland, and Canada.

PATIENTS:

From January 2011 to January 2016, 287 patients were enrolled in the Earlydrain trial. Only files with complete information on both daily hemoglobin and balance values were used, leaving 237 patients for analysis.

INTERVENTIONS:

Investigation of fluid balance management and hemoglobin levels during the initial 8 days post-aSAH to establish thresholds for unfavorable outcomes and assess their impact on secondary infarctions and 6-month neurologic outcome on the modified Rankin Scale (mRS).

MEASUREMENTS AND MAIN RESULTS:

Patients with unfavorable outcome after 6 months (mRS > 2) showed greater hemoglobin decline and increased cumulative fluid balance. A significant inverse relationship existed between fluid balance and hemoglobin decline. Thresholds for unfavorable outcome were 10.4 g/dL hemoglobin and 4894 mL cumulative fluid balance in the first 8 days. In multivariable analysis, fluid balance, but not fluid intake, remained significantly associated with unfavorable outcome, while the influence of hemoglobin lessened. Fluid balance but not hemoglobin related to secondary infarctions, with the effect being significant after inverse probability of treatment weighting. Transfusion was associated with unfavorable outcomes.

CONCLUSIONS:

Increased fluid balance influences hemoglobin decline through hemodilution. Fluid overload, rather than a slight decrease in hemoglobin levels, appears to be the primary factor contributing to poor outcomes in aSAH patients. The results suggest aiming for euvolemia and that a modest hemoglobin decline may be tolerated. It may be advisable to adopt a restrictive approach to transfusions, as they can potentially have a negative effect on outcome.
Emerging therapies in Ewing sarcoma
Authors: Strauss Sandra J. , Berlanga Pablo , McCabe Martin G.
Published: May 2024

Purpose of review

There is an unmet need to improve outcomes for patients for Ewing sarcoma, a rare, aggressive sarcoma with a peak incidence in adolescents and young adults (AYA). Current therapy at diagnosis involves multiagent chemotherapy and local therapy, but despite intensification of treatment, those with metastases at diagnosis and recurrent disease have poor outcomes.

Recent findings

Improved understanding of Ewing sarcoma biology has identified novel targets with promising activity in Ewing sarcoma patients, including tyrosine kinase inhibitors that are now undergoing evaluation as combination and maintenance therapy. Other emerging therapies include those that target the EWSR1::FLI1 fusion oncoprotein, and act on DNA damage, cell cycle and apoptotic pathways. Immunotherapeutic approaches, particularly CAR-T-cell therapy directed at GD2, also hold promise. Recent collaborative clinical trials that have defined an international standard of care for patients with newly diagnosed Ewing sarcoma and novel platform studies with adaptive designs offer unique opportunities to investigate these therapies inclusive of all ages.

Close international collaboration between clinicians and biologists will allow us to prioritize promising emerging therapies and develop biomarkers to facilitate their incorporation into standard of care and more rapidly translate into benefit for Ewing sarcoma patients.
Low MBOAT7 expression, a genetic risk for MASH, promotes a profibrotic pathway involving hepatocyte TAZ upregulation
Authors: Moore Mary P. , Wang Xiaobo , Kennelly John Paul , Shi Hongxue , Ishino Yuki , Kano Kuniyuki , Aoki Junken , Cherubini Alessandro , Ronzoni Luisa , Guo Xiuqing , Chalasani Naga P. , Khalid Shareef , Saleheen Danish , Mitsche Matthew A. , Rotter Jerome I. , Yates Katherine P. , Valenti Luca , Kono Nozomu , Tontonoz Peter , Tabas Ira
Published: May 2024

Background and Aims:

The common genetic variant rs641738 C>T is a risk factor for metabolic dysfunction–associated steatotic liver disease and metabolic dysfunction–associated steatohepatitis (MASH), including liver fibrosis, and is associated with decreased expression of the phospholipid-remodeling enzyme MBOAT7 (LPIAT1). However, whether restoring MBOAT7 expression in established metabolic dysfunction–associated steatotic liver disease dampens the progression to liver fibrosis and, importantly, the mechanism through which decreased MBOAT7 expression exacerbates MASH fibrosis remain unclear.

Approach and Results:

We first showed that hepatocyte MBOAT7 restoration in mice with diet-induced steatohepatitis slows the progression to liver fibrosis. Conversely, when hepatocyte-MBOAT7 was silenced in mice with established hepatosteatosis, liver fibrosis but not hepatosteatosis was exacerbated. Mechanistic studies revealed that hepatocyte-MBOAT7 restoration in MASH mice lowered hepatocyte-TAZ (WWTR1), which is known to promote MASH fibrosis. Conversely, hepatocyte-MBOAT7 silencing enhanced TAZ upregulation in MASH. Finally, we discovered that changes in hepatocyte phospholipids due to MBOAT7 loss-of-function promote a cholesterol trafficking pathway that upregulates TAZ and the TAZ-induced profibrotic factor Indian hedgehog (IHH). As evidence for relevance in humans, we found that the livers of individuals with MASH carrying the rs641738-T allele had higher hepatocyte nuclear TAZ, indicating higher TAZ activity and increased IHH mRNA.

Conclusions:

This study provides evidence for a novel mechanism linking MBOAT7-LoF to MASH fibrosis, adds new insight into an established genetic locus for MASH, and, given the druggability of hepatocyte TAZ for MASH fibrosis, suggests a personalized medicine approach for subjects at increased risk for MASH fibrosis due to inheritance of variants that lower MBOAT7.
Autologous Platelet-rich Fibrin as a Three-dimensional Structural Scaffold in the Healing of Contracted Orbital Sockets
Authors: Bhattacharjee Kasturi , Venkatraman Vatsalya , Soni Deepak , Gaikwad Sonali
Published: May 2024

Purpose:

Evaluation of platelet-rich fibrin as an adjuvant in surface healing of contracted orbital sockets.

Methods:

Prospective, interventional, and comparative study of 25 patients with moderate to severe contracted sockets conducted over 2 years (February 2020–February 2022). Group 1 underwent a dermis-fat graft with fornix forming sutures supplemented by a platelet-rich fibrin membrane, while group 2 received a dermis-fat graft with fornix forming sutures only. Patients over 18 years were evaluated as per prefixed inclusion and exclusion criteria. Assessments were conducted at 1, 3, and 12 months postsurgery, focusing on wound evaluation, socket epithelialization, postoperative pain, prosthesis rehabilitation, and complications, if any. Wound evaluation and pain intensity were assessed utilizing the wound evaluation score and visual analog scale, respectively. Socket epithelization was documented clinically at every visit.

Results:

The study showed a mean age of 38.8 ± 8.8 years, with a 2:1 male-to-female ratio. Group 1 consistently scored higher on wound evaluation score than group 2 at all follow-up points. In group 1, 81.8% achieved a maximum wound evaluation score at 4 weeks and 100% at 3 and 12 months, compared to group 2’s 42.8%, 50%, and 57.1%, respectively (p < 0.05). Postoperative contracture occurred in 3 group 2 patients at the final follow-up, with 6 showing unsatisfactory appearance. Group 1 demonstrated significantly lower pain intensity on postoperative day 1 (p = 0.03), and greater epithelization at 4 weeks.

Conclusion:

platelet-rich fibrin appears to be an effective solution for enhancing wound healing during socket reconstruction, attributed to its sustained release of growth factors and mesenchymal stem cells.
Unravelling the molecular landscape of endometrial cancer subtypes: insights from multiomics analysis
Authors: Shen Yufei , Tian Yan , Ding Jiashan , Chen Zhuo , Zhao Rong , Lu Yingnan , Li Lucia , Zhang Hui , Wu Haiyue , Li Xi , Zhang Yu
Published: May 2024

Background:

Endometrial cancer (EC) as one of the most common gynecologic malignancies is increasing in incidence during the past 10 years. Genome-Wide Association Studies (GWAS) extended to metabolic and protein phenotypes inspired us to employ multiomics methods to analyze the causal relationships of plasma metabolites and proteins with EC to advance our understanding of EC biology and pave the way for more targeted approaches to its diagnosis and treatment by comparing the molecular profiles of different EC subtypes.

Methods:

Two-sample mendelian randomization (MR) was performed to investigate the effects of plasma metabolites and proteins on risks of different subtypes of EC (endometrioid and nonendometrioid). Pathway analysis, transcriptomic analysis, and network analysis were further employed to illustrate gene-protein-metabolites interactions underlying the pathogenesis of distinct EC histological types.

Results:

The authors identified 66 causal relationships between plasma metabolites and endometrioid EC, and 132 causal relationships between plasma proteins and endometrioid EC. Additionally, 40 causal relationships between plasma metabolites and nonendometrioid EC, and 125 causal relationships between plasma proteins and nonendometrioid EC were observed. Substantial differences were observed between endometrioid and nonendometrioid histological types of EC at both the metabolite and protein levels. The authors identified seven overlapping proteins (RGMA, NRXN2, EVA1C, SLC14A1, SLC6A14, SCUBE1, FGF8) in endometrioid subtype and six overlapping proteins (IL32, GRB7, L1CAM, CCL25, GGT2, PSG5) in nonendometrioid subtype and conducted network analysis of above proteins and metabolites to identify coregulated nodes.

Conclusions:

Our findings observed substantial differences between endometrioid and nonendometrioid EC at the metabolite and protein levels, providing novel insights into gene-protein-metabolites interactions that could influence future EC treatments.
6-Mercaptopurine-Associated Sinusoidal Obstructive Syndrome During Interim Maintenance I: A Case Report
Authors: Voelz Katie , Miller Gwendolyn , Lee-Miller Cathy
Published: May 2024

Thiopurine-methyltransferase (TPMT) and nudix-hydrolase-15 (NUDT15) are enzymes relevant to the metabolism of thiopurine medications, used to treat immunologic disorders and malignancies. Standard dosing administered in the setting of TPMT/NUDT15 dysfunction can cause excessive cytotoxic metabolites and life-threatening complications. We describe an adolescent with high-risk B-cell acute lymphoblastic leukemia (ALL) whose TPMT/NUDT15 status was unknown due to lack of insurance approval for genetic testing. He subsequently developed myelosuppression and severe veno-occlusive disease (VOD) after receiving 6-mercaptopurine (6-MP). Our patient provides an example of a very rare 6-MP-related toxicity and the potential benefit of TPMT/NUDT15 screening before initiating thiopurine therapy.
Randomized, Assessor-Blinded Trial Comparing Highly Purified Human Menotropin and Recombinant Follicle-Stimulating Hormone in High Responders Undergoing Intracytoplasmic Sperm Injection
Authors: Witz Craig A. , Daftary Gaurang S. , Doody Kevin J. , Park John K. , Seifu Yodit , Yankov Vladimir I. , Heiser Patrick W. ,   On Behalf of the Menopur in GnRH Antagonist Cycles With Single Embryo Transfer–High Responder (MEGASET-HR) Trial Group
Published: May 2024

(Abstracted from Fertil Steril 2020;114:321–330

There exists considerable variation in patient’s response to gonadotropin stimulation when undergoing assisted reproductive technologies (ARTs). Serum anti-Müllerian hormone (AMH) level has been shown to be a robust predictor of ovarian response and is used to guide gonadotropin dosing.