bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPARATIVE EFFECT OF ATENOLOL AND NEBIVOLOL ON REVERSE REMODELING OF INTRAMURAL CORONARY ARTERIOLES IN THE SPONTANEOUSLY HYPERTENSIVE RAT MODEL
Authors: Ciuceis Carolina De , Bonomini Francesca , Rosei Claudia Agabiti , Lemoli Matteo , Giugno Lorena , Rossini Claudia , Lonati Claudio , Chiarini Giulia , Malerba Paolo , Famà Francesca , Muiesan Maria Lorenza , Rizzoni Damiano , Rezzani Rita
Published: June 2023

Objective:

Arterial hypertension is an established major risk factor for ischemic heart disease. Functional and structural abnormalities at the level of the microcirculation may play a crucial role in coronary microvascular dysfunction. Indeed, coronary flow reserve is often reduced at angiography in hypertensive patients independently on the presence of left ventricular hypertrophy (Mancini M. et al. Microcirculation 2017). The aim of this study was to assess the effect of the beta-blocker Atenolol and the selective third-generation beta1-adrenergic antagonist Nebivolol on markers of remodeling and endothelial dysfunction in coronary microvascular. Nebivolol has been demonstrated to possess direct vasodilator and antioxidant properties which may improve endothelial dysfunction and reduce smooth muscle cell proliferation.

Design and method:

For this purpose, we used three groups of SHR rats: Hypertensive untreated group (SHR); SHR plus Atenolol 50 mg/kg/day by oral gavaging for 8 weeks (SHR + ATE); SHR plus Nebivolol 20 mg/kg/day by oral gavaging for 8 weeks (SHR + NEB). Protein expression levels of vasoactive factors, oxidative stress and remodeling markers in coronary microcirculation were determined by immunohistochemical analysis of Endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS) and transforming growth factor-beta1 (TGF-beta1).

Results:

No differences were observed in structural parameters of mesenteric arteries among groups. SHR + NEB showed a significant reduction in ET-1, iNOS, and TGF-beta1 staining in coronary small arteries comparing to SHR and SHR + ATE.

Conclusions:

In comparison to atenolol, nebivolol may provide additional benefit beyond blood pressure reduction and beta-receptor blockade since show greater activity in the modulation of protein involved in vasodilation and oxidative stress protection.
RETINAL ARTERIOLAR REMODELING IN PRIMARY ALDOSTERONISM: A STUDY WITH ADAPTIVE OPTICS
Authors: Rosei Claudia Agabiti , Ciuceis Carolina De , Rossini Claudia , Petelca Alina , Dusi Margherita , Chiarini Giulia , Malerba Paolo , Porteri Enzo , Salvetti Massimo , Rizzoni Damiano , Muiesan Maria Lorenza
Published: June 2023

Objective:

Primary aldosteronism (PA) represents the most frequent form of secondary hypertension. In previous studies an hypertrophic remodeling, with smooth muscle cell growth and an increase in media to lumen ratio (MLR), has been shown in patients with primary aldosteronism (Rizzoni D et al. Hypertension 1996;28:785–790.). To date, Adaptive Optics (AO) is one of the most innovative and non-invasive methods for studying the wall-to-lumen ratio of retinal arterioles (WLR), which directly correlates with the MLR of subcutaneous small arteries (De Ciuceis C et al. J Hypertens. 2018;36(5):1154-1163.).

Design and method:

Therefore, the aim of this study was to evaluate microvascular structure of retinal arterioles by Adaptive Optics in PA patients, before and after pharmacological or surgical treatment, compared to essential hypertensive patients (EH). Eleven patients with PA before treatment have been matched with 11 patients with EH and 11 patients with treated PA in follow up. All patients underwent assessment of retinal microcirculation morphology with AO (RTX-1, Imagine Eyes; Orsay, FR) in order to calculate WLR and wall cross sectional area (WCSA).

Results:

A total of 33 patients was enrolled in the study. PA patients at the baseline showed a significant higher WLR compared to EH and to PA in follow-up (Figure 1; 0.31±0.03 vs 0.27±0.04 vs 0.275±0.03 respectively; p = 0.01). Otherwise, differences between WCSA turned out to be less relevant with no significant differences among the three groups (4500.85±879.9 vs 4195.96±553.3 vs 4278.52±836.6 respectively; p = ns).

Conclusions:

Our data confirm with a non-invasive technique the presence of a more evident retinal arterioles remodeling in PA patients compared to EH patients, as suggested by the increased WLR, and an improvement in WLR after PA surgical or pharmacological treatment. Further studies in a larger population are needed in order to confirm these data.
MIR204 POTENTIALLY PROMOTES NON-ALCOHOLIC FATTY LIVER DISEASE BY INHIBITION OF CPT1A IN MOUSE HEPATOCYTES
Authors: Kim Seonhee , Kim Minsoo , Piao Shuyu , Giang Huong Vu , Choi Su-Jeong , Kim Cuk-Seong
Published: June 2023

Objective:

Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic metabolism dysfunction. However, the mechanistic role of miR204 in the development of NAFLD is unknown. We investigated the functional significance of miR204 in the evolution of NAFLD.

Design and method:

NAFLD was induced in isocitrate dehydrogenase (IDH2) knockout (KO) mice by feeding them with a high-fat diet (HFD). Blood parameters and hepatic fat accumulation were evaluated in IDH2 KO mice and wild-type (WT) mice. A miR204 inhibitor was subcutaneously injected into mice using an osmotic pump. The expression of miR204 was analyzed by quantitative PCR (qPCR).

Results:

IDH2 KO mice fed a normal diet (ND) or HFD showed significantly increased body weight, epididymal fat-pad weight, cholesterol, triglyceride, and macrophage marker (CD68), and inflammatory cytokine [tumor necrosis factor-a (TNF-a), interleukin (IL)-6 and IL-1b] expression compared to WT mice fed a ND or HFD. Moreover, the expression of miR204 was significantly increased in mice with IDH2 deficiency. miR204 regulates carnitine palmitoyltransferase 1a (cpt1a) synthesis, which inhibits fatty acid b-oxidation. Inhibition of miR204 prevents the disassembly of two fatty acid-related genes—peroxisomal acyl-coenzyme A oxidase 1 (ACOX-1) and peroxisome proliferator-activated receptor alpha (PPARa)—by activating CPT1a expression, which decreases inflammatory cytokines, epididymal fat pad weight, cholesterol, low-density lipoprotein (LDL), and triglycerides.

Conclusions:

miR204 promotes the pathogenesis of HFD-induced NAFLD by regulating hepatic metabolism and inflammation.
RELATIONSHIP OF HYPERURACEMIA WITH METABOLIC DISORDERS IN PATIENTS WITH ARTERIAL HYPERTENSION
Authors: Duysewnbaeva Aziza , Srojidinova Nigora , Saidakbarova Feruza
Published: June 2023

Objective:

To study the prevalence of hyperuremia and to study its role in development of metabolic disorders in patients with arterial hypertension (AH).

Design and method:

The study analyzed 188 case histories of patients with AH grades 1-3 (ESC/ESH, 2018). 109 women and 79 men were studied. Mean age 62.8±10.2 years. Hyperuricemia was established with an increase in the level of uric acid > 7 mg / dl in men, > 5.7 mg / dl in women.

Results:

Results: For analysis, patients were divided into 2 groups: the first group consisted of patients with hyperuricemia (n = 103), the second - patients with normal levels of uric acid (n = 85). The average level of uric acid in the 1st group was 7.44±1.33 mg/dl, and in the 2nd group - 5.06±0.98 mg/dl, p<0.00001. The compared groups were similar in terms of age, office SBP and DBP. Age: 62.7±10.51 vs 62.8±10.01 years, p = 0.95; SBP - 136.82±22.09 mm Hg. vs 132.98±24.4 mmHg, p = 0.26; DBP - 85.17±10.27 mm Hg. vs 84.27±10.71 mmHg, p = 0.56. The groups also did not differ in BMI and WC: BMI-32.96±5.84 kg/m2 vs 31.24±5.00 kg/m2 p = 0.44; OT-105.44±13.75 cm vs 102.76±12.06 cm, p = 0.16. It should be noted that patients with hyperuricemia had a significantly high level of MAU: 63.24±104.06 vs 39.33±36.42 mg/l, p = 0.044. Patients with hyperuricemia had more pronounced dyslipidemia. Thus, total cholesterol was significantly high in group 1: 198.31±49.41 mg/dl vs 181.75±49.1 mg/dl, p = 0.04, LDL cholesterol 111.83±42.46 mg/dl dl vs 100.56±37.99 mg/dl, p = 0.04. TG and HDL-C did not differ between the groups. TG: 223.39±130.76 vs 189.69±122.18 p = 0.057. HDL-C: 41.92±13.54 mg/dl vs 43.30±12.87 mg/dl, p = 0.48. In the group of patients with hyperuricemia, there was a significantly high level of glucose compared with patients with normal levels of uric acid: 9.71±04.35 mmol/l vs 6.51±3.06 mmol/l, p = 0.0001. The creatinine level was also high in patients with hyperuricemia: 98.45±36.75 μmol/l vs 85.06±17.21 μmol/l, p = 0.003.

Conclusions:

Hyperuricemia should be considered as an additional cardiovascular risk in hypertensive patients. Hyperuricemia is associated with severe dyslipidemia and elevated levels of glycemia and creatinine in hypertensive patients.
LEVELS OF THE ADIPOKINE CHEMERIN HELP TO PREDICT PREECLAMPSIA AND ITS COMPLICATIONS
Authors: Tan Lunbo , Neuman Rugina I. , Schoenmakers Sam , Danser A.H. Jan , Verdonk Koen
Published: June 2023

Objective:

The adipokine chemerin is increased in preeclampsia (PE). Here, we evaluated its potential as a biomarker to predict PE or fetal complications.

Design and method:

We measured chemerin in 523 women with suspected or confirmed PE, as a secondary analysis of a prospective cohort study that evaluated the use of the sFlt-1 (soluble Fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio. The concordance (c)-statistic was used to evaluate the predictive value of chemerin or the sFlt-1/PlGF ratio on top of the traditional clinical risk factors (TCF) model involving gestational age, parity, proteinuria, and mean arterial pressure (MAP).

Results:

At the time of biomarker measurement, women had a median gestational age of 35.6 weeks (range 31.7-38.0). Serum chemerin was elevated (P<0.001) in women with confirmed PE (n = 152) or gestational hypertension (n = 95) vs. women without hypertensive disease of pregnancy (n = 276; 252±129 and 236±113 vs. 198±83 ng/mL). Moreover, serum chemerin levels were higher (P<0.001) in pregnancies with fetal growth restriction or fetal death (n = 78) vs. those without fetal complications (n = 361; 289±172 vs. 210±95 ng/mL). To predict PE, the TCF model yielded a C-index of 0.90, while adding chemerin or the sFlt-1/PlGF ratio to the model raised this to 0.95, with no further increase occurring when adding both at the same time. To predict fetal complications, the C-index was 0.76 for the TCF model only. This increased to 0.78 and 0.80 when adding chemerin and the ratio, respectively, and to 0.82 when adding both.

Conclusions:

Chemerin levels are elevated in women with PE and gestational hypertension, and chemerin levels might be used to predict PE and fetal complications.
SAFETY, FEASIBILITY, AND ACCEPTABILITY OF TELEMEDICINE FOR HYPERTENSION IN PRIMARY CARE: A PROOF-OF-CONCEPT AND PILOT RANDOMIZED CONTROLLED TRIAL (SATE-HT)
Authors: Lee Eric Kam-Pui , Wang Shuqi , Leung Maria , Leung Shuk-Yun , Han Jinghao , Leung Will , Hui Elsie , Mihailidou Anastasia , Tsoi Kelvin Kam-Fai , Wong Martin Chi-Sang , Wong Samuel
Published: June 2023

Objective:

Hypertension (HT) continues to be a leading cause of cardiovascular death and an enormous burden on the healthcare system. Although telemedicine may provide improved blood pressure (BP) monitoring and control, it remains unclear whether it could replace face-to-face consultations in patients with optimal BP control. We hypothesized that an automatic drug refill coupled with a telemedicine system tailored to patients with optimal BP would lead to non-inferior BP control

Design and method:

In this pilot, multicenter, randomized control trial (RCT), participants receiving anti-HT medications were randomly assigned (1:1) to either the telemedicine or usual care group. Patients in the telemedicine group measured and transmitted their home BP readings to the clinic. The medications were refilled without consultation when optimal control (BP <135/85 mmHg) was confirmed. The primary outcome of this trial was the feasibility of using the telemedicine app. Office and ambulatory BP readings were compared between the two groups at the study endpoint. Acceptability was assessed through interviews with the telemedicine study participants.

Results:

Overall, 49 participants were recruited in 6 months and retention rate was 98%. Participants from both groups had similar BP control (daytime systolic BP: 128.2 versus 126.9 mmHg [telemedicine vs. usual care], p = 0.41) and no adverse events. Participants in the telemedicine group had fewer general outpatient clinic attendances (0.8 vs. 2, p<0.001). Interviewees reported that the system was convenient, timesaving, cost saving, and educational.

Conclusions:

The system could be safely used. However, the results must be verified in an adequately powered RCT.
RELATIONSHIP OF T704C AGT GENE POLYMORPHISM WITH RESISTANT ARTERIAL HYPERTENSION IN UZBEK POPULATION
Authors: Abdullaeva Guzal , Masharipov Shukhrat , Khamidullaeva Gulnoz , Yusupova Khafiza , Zakirova Darya , Abdullaev Alisher , Radjapova Guliruh
Published: June 2023

Objective:

to study the association of T704C polymorphism of AGT gene with resistant arterial hypertension (AH) in Uzbek population.

Design and method:

Study included 178 patients with AH I–III degree of both sexes. The mean age of patients was 57.15 ± 11.01 years, duration of AH was 9.55 ± 5.75 years. Genotyping of the T704C polymorphism of the AGT gene was performed using real-time PCR using gene-specific primers of allele-specific probes. Relative risk (RR) was calculated using genetic models. Calculations were performed using the online program “Calculator for calculating statistics in case-control studies”. The results of all studies were considered statistically significant at p<0.05.

Results:

Patients were divided into two groups: 1 - patients with resistant AH (cases, n = 61) and 2 - patients with controlled hypertension (controls, n = 117). TT genotype - determined in 16.4%, TC genotype - in 32.8%, CC genotype - 50.8%, 2 = 16.279, p = 0.000. The allelic distribution showed the predominance of C allele: C allele - 67.2%, T allele - 32.8%, ⇙2 = 27.557, p = 0.000. In group 2, C allele in 52.6%, T allele in 47.4%, respectively, ⇙2 = 1.034, p = 0.309. The ratio of TT:TC:CC- genotypes was as follows: 20.5%: 53.8%: 25.6%, ⇙2 = 33.923, p = 0.000. An analysis revealed an association of the C allele T704C of the AGT gene polymorphism with resistant AH. 61 patients with resistant AH of group 1, the C allele was more common than in patients with of group 2 (67.2%; ⇙2 = 7.05; P = 0.008; OR = 1.85, 95% CI 1.17-2.92) and 32.8% had T allele. Accumulation of CC genotype among patients of group 1 (50.8%; ⇙2 = 11.59; P = 0.003; OR = 3.00, 95% CI 1.56-5.75), while TC genotype was found in 32, 8% of cases and TT genotype in 16.4% of cases. Whereas in the 2nd group, the CC genotype was less common - in 25.6% of cases than the TCgenotype (53.8%) cases.

Conclusions:

The results obtained indicate a significantly greater accumulation of the C-allele of T704C polymorphism of the AGT gene among patients with resistant hypertension. The C allele and CC genotype T704C of AGT gene polymorphism are associated with resistant hypertension in the Uzbek population.
EFFECTS OF TRIATHLON TRAINING ON HEMODYNAMIC RESPONSES AND VASCULAR FUNCTION: THE ATHLAS STUDY
Authors: Piscitello Tessy Cuffaro , Azzi Julien , Dupont Anne Charlotte , Salvi Paolo , Labat Carlos , Mandry Damien , Poussel Mathias , Mejri Menel , Benetos Athanase , Joly Laure
Published: June 2023

Objective:

Regular and moderate endurance exercise has beneficial effects on the cardiovascular system. Triathlon is a rigorous endurance multisport that requires a higher level of training. Chronic consequences on cardiovascular system of such a high cardiovascular demand have not yet been highlighted. In this study, we assessed the effect of triathlon training and racing on the cardiovascular system in experienced triathletes.

Design and method:

ATHLAS is a prospective controlled study comparing 34 male recreational long-distance triathletes aged 19 to 39 years (Tri) with 29 healthy insufficiently active of the same age (Ctrl). All volunteers completed three visits throughout an annual sports season: at baseline during the off-season (in winter), at peak of physical performance during races period (in spring/summer), and during active rest in post-season (in autumn). At each visit, peripheral blood pressure was measured, and applanation tonometry was performed to evaluate arterial stiffness by carotid-femoral pulse wave velocity (cfPWV) and myocardial perfusion using the subendocardial viability ratio (SEVR).

Results:

At baseline, Tri had higher systolic blood pressure (SBP) and pulse pressure (PP) than Ctrl (respectively, 131.1±8.9 vs 125.7±10.4 mmHg; and 56.5±12.8 vs 48.9±6.5 mmHg, p<0.05) but lower cfPWV (6.29 ±0.15 vs 6.95 ±0.16 m/sec, p<0.01). SEVR was increased in Tri indicating better myocardial perfusion (mean difference of 34.42%, p = 0.03). At peak of performance in Tri, SBP and PP were decreased (respectively, mean difference of 3.63 mmHg, and 3.36 mmHg, p<0.05), and returning to baseline levels in active rest. Tri cfPWV and SEVR were not influenced by training phases. In Ctrl group, SBP, PP and cfPWV exhibited seasonal variation with lower levels in spring/summer (p< 0.05).

Conclusions:

Triathlon training and racing have beneficial effects on arterial stiffness and myocardial perfusion regardless of time of season. In triathletes, increased SBP despite lower arterial stiffness (cfPWV) reflects adaptation of the athlete's heart with a high cardiac output. These results will require further study to determine whether high blood pressure could lead to negative cardiovascular impact in the long term.
ELEVATED PLATELET REACTIVITY IN PATIENTS WITH UNCONTROLLED HYPERTENSION: THE EFFECT OF CHA2DS2-VASC SCORE
Authors: Marketou Maria , Spatharaki Paraskevi , Nioti Eleni , Kalomoirakis Petros , Karagounis Thomas , Alifrangie Aggeliki , Zacharis Evaggelos , Fragiadak Kostas , Plevritaki Anthoula , Kampanieris Emmanouil , Kassotakis Spyridon , Pateromichelakis Themis , Maragkoudakis Spyros , Kalpadaki Christina , Kochiadakis George
Published: June 2023

Objective:

Hypertension is associated with vascular and endothelial dysfunction that may result in a greater propensity for reactive platelets to cause thrombosis.

Purpose: The aim of this study was to evaluate multiple platelet activation pathways in hypertensive patients with different level of blood pressure control and cardiovascular risk factors.

Design and method:

Thirty nine uncontrolled (office SBP > 140 mmHg and ambulatory daytime SBP >135 mmHg, 27 males, aged 58 ± 9 years) and 32 well controlled (office SBP < 140 mmHg and ambulatory daytime SBP < 135 mmHg, 21 males, aged 58 ± 8 years) essential hypertensive patients were included in the study. Twenty four healthy individuals (12 males, aged 53 ± 10 years) were served as control group. Blood samples were obtained before and 48 hours after the procedure and platelet aggregation was tested in platelet rich plasma after activation with arachidonic acid (AA), adenosine diphosphate ADP), collagen (Col), epinephrine (Epi) and ristocetin (Risto), by using AggRAM Platelet Aggregation Analyzer.

Results:

Hypertensive patients showed elevated platelet reactivity in all platelet activation pathways compared to normotensive group (AA: 88.8 ± 6.8% versus 79.5 ± 7.3%, ADP: 86.8±9.1% versus 71.5±7.7%, Col: 86.5 ± 5.7% versus 73.9 ± 6.7%, Epi: 92.6±5.4% versus 80.5 ± 5.7%, Risto: 93.8 ± 6.8% versus 79.9 ± 6.3%, p <0.05 for all). Col, Epi and Risto platelet activation pathway showed a statistically significant increase in patients with uncontrolled hypertension compared to the group with well controlled hypertension (AA: 88.8 ± 6.1% versus 89.1 ± 4.1%, ADP: 89.8 ± 4.1% versus 87.5±4.7%, Col: 87.5±4.7% versus 81.9 ± 6.7%, Epi: 93.6 ± 4.4% versus 80.1 ± 5.7%, Risto: 94.8 ± 3.8% versus 80.9 ± 4.3%,). Notably, strong correlations were found between the Col platelet pathway activation and Risto platelet pathway activation and CHA2DS2-VASc score (r = 0.57, p <0.001 and r = 0.61, p <0.001, respectively) in hypertensive patients.

Conclusions:

Patients with uncontrolled hypertension showed elevated platelet reactivity. Patients with high CHA2DS2-VASc even without atrial fibrillation carry also a higher risk of thrombosis as indicated by the increased platelet aggregation under certain pathways of activation.
ISTO STUDY - INTENSIV-INTERMEDIATE STATIN THERAPY OBSERVATIONAL STUDY
Authors: Joaquim Meireles-Brandao , R. Meireles-Brandao Lucia , Rui Coelho , Francisco Rocha-Goncalves
Published: June 2023

Objective:

lifestyle changes are frequently insufficient to reduce cardiovascular risk (CVR) in patients with dislipidemia. This study aims to characterize the long-term evolution of lipid profile and CVR of patients under primary prevention.

Design and method:

A retrospective study was performed of outpatients at a Portuguese cardiovascular risk clinic with > 2 CVRF, followed >2 years between 1995 and 2015 (Fig. 1). Intermediate-intensity statin therapy had initiated early, in accordance with the clinićs practice. After written informed consent was obtained, sociodemographic and clinical charecteristics were collected from medical charts, at baseline and last visit. Changes in lipid profile and CV risk scores (FRS, ASCVD, SCORE) were estimated. Associations between HDL-C or LDL-C changes and gender, age, observation times and treatments were assessed through bivariate analysis and multiple linear regression models.

Results:

Out of 516 participants with mean follow-up of 11.4 +/- 4.3 years, 56.6% were female and and received intermediate-intensity statins. Lipid profile showed statistically significant improvment, including median changes in LDL-C and HDL-C of - 77.0 mg/dl and +19 mg/dl, respectively. CVR also showed statistically significant improvements according to all scores. Statin therapy resulted in a mean HDL-C ncrease of 7.4 mg/dl (independently of gender and other treatments) and a mean LDL-C reduction of 51.8 mg/dl (irrespective of age and other treatments).

Conclusions:

Results from this long-term real-life study indicate that primary prevention, specifically early and continuous therapy with intermediate-intensity statins as an add-on to lifestyle interventions, was important in obtaining consistent and adequate metabolic correction in patients with additional risk factors.
SELF-MONITORING OF BLOOD PRESSURE AND FEEDBACK USING APP IN TREATMENT OF UNCONTROLLED HYPERTENSION: SMART APP STUDY
Authors: Choi Dong-Ju , Park Sungji , Yoon Minjae , Jo Sangho , Kim Eungju , Kim Soojoong
Published: June 2023

Objective:

Self-monitoring of blood pressure (SMBP) is a reliable method used to assess blood pressure (BP) accurately. However, patients do not often know how to respond to the measured BP value. We developed a mobile application-based feedback for tailored recommendations and aimed to evaluate whether this feedback is superior to SMBP alone in terms of BP reduction and drug compliance improvement in patients with hypertension.

Design and method:

Self-Monitoring of and Feed-back using APP in TReatment of UnconTrolled Blood Pressure (SMART-BP) is a prospective, randomized, open-label, multicenter trial to evaluate the efficacy of SMBP-App compared with SMBP alone. In the SMBP alone group, the patients performed home BP measurement and receive the standard care, whereas in the SMBP-App group, the patients received additional recommendations from the application using feedback algorithm in response to the obtained BP value. The primary endpoints were mean home BP and adherence of antihypertensive medication. Follow-up visits were scheduled at 12 and 24 weeks after randomization.

Results:

Among total 173 patients (88 for SBMP-app and 85 for SMBP alone) with full-analysis set, 53% were men, and the mean age was 59.8 years. Baseline characteristics including BP were not significantly different between two groups. At 6 months, mean reduction in home systolic BP was significantly higher in SMBP-App group than SBMP alone group (-20.0±13.5 vs. -14.9±12.9, = 0.012). Also, SMBP-app group showed higher drug adherence value and proportion of adherence over 95% than in SMBP alone group (95.2% vs. 90.4%, P = 0.004; 72/88 vs. 46/85, P = 0.010). Reduction in home systolic BP at 3 months and office systolic BP at 3 months were also higher in SBMP-App, similar with primary end point.

Conclusions:

SMBP-App is superior to SMBP alone in terms of blood pressure reduction and improved drug adherence in patients with hypertension.
Intrauterine Insemination After Human Chorionic Gonadotropin Trigger or Luteinizing Hormone Surge
Authors: Potapragada Nivedita R. , Babayev Elnur , Strom Danielle , Beestrum Molly , Schauer Jacob M. , Jungheim Emily S.
Published: June 2023

OBJECTIVE:

To assess the odds of pregnancy after intrauterine insemination (IUI) timed by ultrasound monitoring and human chorionic gonadotropin (hCG) administration compared with monitoring luteinizing hormone (LH) levels.

DATA SOURCES:

We searched PubMed (MEDLINE), EMBASE (Elsevier), Scopus (Elsevier), Web of Science (Clarivate Analytics), ClinicalTrials.gov (National Institutes of Health), and the Cochrane Library (Wiley) from the inception until October 1, 2022. No language limitations were applied.

METHODS OF STUDY SELECTION:

After deduplication, 3,607 unique citations were subjected to blinded independent review by three investigators. Thirteen studies (five retrospective cohort, four cross-sectional, two randomized controlled trials, and two randomized crossover studies) that enrolled women undergoing natural cycle, oral medication (clomid or letrozole), or both for IUI were included in the final random-effects model meta-analysis. Methodologic quality of included studies was assessed with the Downs and Black checklist.

TABULATION, INTEGRATION, AND RESULTS:

Data extraction was compiled by two authors, including publication information, hCG and LH monitoring guidelines, and pregnancy outcomes. No significant difference in odds of pregnancy between hCG administration and endogenous LH monitoring was observed (odds ratio [OR] 0.92, 95% CI 0.69–1.22, P=.53). Subgroup analysis of the five studies that included natural cycle IUI outcomes also showed no significant difference in odds of pregnancy between the two methods (OR 0.88, 95% CI 0.46–1.69, P=.61). Finally, a subgroup analysis of 10 studies that included women who underwent ovarian stimulation with oral medications (clomid or letrozole) did not demonstrate a difference in odds of pregnancy between ultrasonography with hCG trigger and LH-timed IUI (OR 0.88, 95% CI 0.66–1.16, P=.32). Statistically significant heterogeneity was noted between studies.

CONCLUSION:

This meta-analysis showed no difference between pregnancy outcomes between at-home LH monitoring and timed IUI.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42021230520.
Evaluation of a New Model for Human Chorionic Gonadotropin Rise in Pregnancies of Unknown Viability
Authors: Bollig Kassie J. , Finlinson Alex , Barnhart Kurt T. , Coutifaris Christos , Schust Danny J.
Published: June 2023

OBJECTIVE:

To evaluate the performance of a new human chorionic gonadotropin (hCG) threshold model to classify pregnancies as viable or nonviable using a longitudinal cohort of individuals with pregnancy of unknown viability. The secondary objective was to compare the new model with three established models.

METHODS:

This is a single-center, retrospective cohort study of individuals seen at the University of Missouri from January 1, 2015, until March 1, 2020, who had at least two consecutive quantitative hCG serum levels with an initial level greater than 2 milli-international units/mL and 5,000 milli-international units/mL or less, with the first interval between laboratory draws no greater than 7 days. Prevalence of correct classification of viable intrauterine pregnancies, ectopic pregnancies, and early pregnancy losses was evaluated with a new proposed hCG threshold model and compared with three established models describing minimum expected rates of hCG rise for a viable intrauterine pregnancy.

RESULTS:

Of an initial cohort of 1,295 individuals, 688 patients met inclusion criteria. One hundred sixty-seven individuals (24.3%) had a viable intrauterine pregnancy; 463 (67.3%) had an early pregnancy loss; and 58 (8.4%) had an ectopic pregnancy. A new model based on the total additive percent rise of hCG at 4 and 6 days after initial hCG (70% or greater and 200% or greater rise, respectively) was created. The new model was able to correctly identify 100% of viable intrauterine pregnancies while minimizing incorrect classification of early pregnancy losses and ectopic pregnancies as normal pregnancies. At 4 days after initial hCG, 14 ectopic pregnancies (24.1%) and 44 early pregnancy losses (9.5%) were incorrectly classified as potentially normal pregnancies. At 6 days after initial hCG, only seven ectopic pregnancies (12.1%) and 25 early pregnancy losses (5.6%) were incorrectly classified as potentially normal pregnancies. In established models, up to nine intrauterine pregnancies (5.4%) were misclassified as abnormal pregnancies and up to 26 ectopic pregnancies (44.8%) and 58 early pregnancy losses (12.5%) were incorrectly classified as potentially normal pregnancies.

CONCLUSION:

The proposed new hCG threshold model optimizes a balance between identifying potentially viable intrauterine pregnancies and minimizing misdiagnosis of ectopic pregnancies and early pregnancy losses. External validation in other cohorts is needed before widespread clinical use.
Alteration of the fecal microbiome in patients with cholecystectomy: potential relationship with postcholecystectomy diarrhea – before and after study
Authors: Noh Choong-Kyun , Jung Woohyun , Yang Min Jae , Kim Wook Hwan , Hwang Jae Chul
Published: June 2023

Background:

Bile acid (BA) is a crucial determinant of the gut microbiome, and cholecystectomy can alter the physiology of BA. Physiological changes in BA resulting from cholecystectomy can also influence the gut microbiome. We aimed to identify the specific taxa associated with perioperative symptoms, including postcholecystectomy diarrhea (PCD), and to evaluate the effect of cholecystectomy on the microbiome by investigating the fecal microbiome of patients with gallstones.

Methods:

We analyzed the fecal samples of 39 patients with gallstones (GS group) and 26 healthy controls (HC group) to evaluate their gut microbiome. We also collected fecal samples from GS group 3 months postcholecystectomy. Symptoms of patients were evaluated before and after cholecystectomy. Further, 16S ribosomal RNA amplification and sequencing were performed to determine the metagenomic profile of fecal samples.

Results:

The microbiome composition of GS differed from that of HC; however, the alpha diversity was not different. No significant microbiome alterations were observed before and after cholecystectomy. Moreover, GS group showed a significantly lower Firmicutes to Bacteroidetes ratio before and after cholecystectomy than the HC group (6.2, P<0.05). The inter-microbiome relationship was lower in GS than in HC and tended to recover 3 months after surgery. Furthermore, ~28.1% (n=9) of patients developed PCD after surgery. The most prominent species among PCD (+) patients was Phocaeicola vulgatus. Compared with the preoperative state, Sutterellaceae, Phocaeicola, and Bacteroidals were the most dominant taxa among PCD (+) patients.

Conclusion:

GS group showed a different microbiome from that of HC; however, their microbiomes were not different 3 months after cholecystectomy. Our data revealed taxa-associated PCD, highlighting the possibility of symptom relief by restoring the gut microbiome.
Bridging the Digital Health Divide
Authors: Ahmed Naheed , Brown Jason , Parau Codrin , McCullers Asli , Sanghavi Kavya , Littlejohn Robin , Wesley Deliya B.
Published: June 2023

Objective:

The objectives of this study were to (1) examine demographic differences between patient portal users and nonusers; and (2) examine health literacy, patient self-efficacy, and technology usage and attitudes between patient portal users and nonusers.

Methods:

Data were collected from Amazon Mechanical Turk (MTurk) workers from December 2021 to January 2022. MTurk workers completed an online survey, which asked about their health, access to technology, health literacy, patient self-efficacy, media and technology attitudes, and patient portal use for those with an account. A total of 489 MTurk workers completed the survey. Data were analyzed using latent class analysis (LCA) and multivariate logistic regression models.

Results:

Latent class analysis models revealed some qualitative differences between users and nonusers of patient portals in relation to neighborhood type, education, income, disability status, comorbidity of any type, insurance type, and the presence or absence of primary care providers. These results were partially confirmed by logistic regression models, which showed that participants with insurance, a primary care provider, or a disability or comorbid condition were more likely to have a patient portal account.

Conclusions:

Our study findings suggest that access to health care, along with ongoing patient health needs, influence the usage of patient portal platforms. Patients with health insurance have the opportunity to access health care services, including establishing a relationship with a primary care provider. This relationship can be critical to a patient ever creating a patient portal account and actively engaging in their care, including communicating with their care team.
Decoding the Mastectomy SKIN Score: An Evaluation of Its Predictive Performance in Immediate Breast Reconstruction
Authors: Hassan Abbas M. , Nguyen Huan T. , Elias Alexandra M. , Nelson Jonas A. , Coert J. Henk , Mehrara Babak J. , Butler Charles E. , Selber Jesse C.
Published: June 2023

Background:

The skin ischemia and necrosis (SKIN) score was introduced to standardize the assessment of mastectomy skin flap necrosis (MSFN) severity and the need for reoperation. The authors evaluated the association between the SKIN score and the long-term postoperative outcomes of MSFN after mastectomy and immediate breast reconstruction.

Methods:

The authors conducted a retrospective cohort study of consecutive patients who developed MSFN after mastectomy and immediate breast reconstruction from January of 2001 to January of 2021. The primary outcome was breast-related complications after MSFN. Secondary outcomes were 30-day readmission, operating room (OR) débridement, and reoperation. Study outcomes were correlated with the SKIN composite score.

Results:

The authors identified 299 reconstructions in 273 consecutive patients with mean follow-up time of 111.8 ± 3.9 months. Most patients had a composite SKIN score of B2 (25.0%, n = 13), followed by D2 (17.3%) and C2 (15.4%). We found no significant difference in rates of OR débridement (P = 0.347), 30-day readmission (P = 0.167), any complication (P = 0.492), or reoperation for a complication (P = 0.189) based on the SKIN composite score. The composite skin score was a poor predictor of reoperation, with an area under the curve of 0.56. A subgroup analysis in patients who underwent implant-based reconstruction revealed no difference in rates of OR débridement (P = 0.986), 30-day readmission (P = 0.530), any complication (P = 0.492), or reoperation for a complication (P = 0.655) based on the SKIN composite score.

Conclusions:

The SKIN score was a poor predictor for postoperative MSFN outcomes and reoperation. An individualized risk-assessment tool that incorporates the anatomic appearance of the breast, imaging data, and patient-level risk factors is needed.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, IV.
PrEP initiation, persistence, and adherence during pregnancy through the postpartum period: a prospective analysis in Kenya
Authors: Pintye Jillian , Kinuthia John , Abuna Felix , Anderson Peter L. , Dettinger Julia C. , Gomez Laurén , Haberer Jessica E. , Marwa Mary , Mwongeli Nancy , Omondi Pascal. , Ochieng Ben , Stern Joshua , Watoyi Salphine , Baeten Jared M. , John-Stewart Grace
Published: June 2023

Objective:

We evaluated PrEP initiation, persistence, and adherence measured via tenofovir-diphosphate (TFV-DP) concentrations in dried blood spots (DBS) among women offered PrEP during pregnancy.

Methods:

We prospectively analyzed data from participants in the PrIMA Study (NCT03070600) who were offered PrEP during the 2nd trimester and followed through 9-months postpartum. At follow-up visits (monthly in pregnancy; 6 weeks, 6 months, 9 months postpartum), self-reported PrEP use was assessed, and DBS were collected for quantifying TFV-DP concentrations.

Results:

In total, 2949 participants were included in the analysis. At enrollment, median age was 24 years (IQR 21–29), gestational age 24 weeks (IQR 20–28), and 4% had a known partner living with HIV. Overall, 405 (14%) participants initiated PrEP in pregnancy with higher frequency among those with risk factors for HIV acquisition, including >2 lifetime sexual partners, syphilis during pregnancy, forced sex, and intimate partner violence (p < 0.05). At 9-months postpartum, 58% of PrEP initiators persisted with PrEP use, of which 54% self-reported not missing any PrEP pills in the last 30 days. Among DBS randomly selected from visits where participants persisted with PrEP (n = 427), 50% had quantifiable TFV-DP. Quantifiable TFV-DP was twice as likely in pregnancy than postpartum (aRR=1.90, 95% CI 1.40–2.57, p < 0.001). Having a partner known to be living with HIV was the strongest predictor of PrEP initiation, persistence, and quantifiable TFV-DP (p < 0.001).

Conclusions:

PrEP persistence and adherence waned postpartum, though over half of PrEP initiators persisted through 9-months postpartum. Interventions should prioritize increasing knowledge of partner HIV status and sustaining adherence in the postpartum period.
Prognostic Role of Dynamic CZT Imaging in Heart Failure With Preserved Ejection Fraction
Authors: Kopeva Kristina V. , Mochula Andrey V. , Maltseva Alina N. , Soldenko Mikhail V. , Grakova Elena V. , Zavadovsky Konstantin V.
Published: June 2023

Objective

The objective of the study was to evaluate the prognostic role of myocardial flow reserve (MFR) and myocardial blood flow (MBF) estimates obtained with dynamic cadmium-zinc-telluride (CZT) imaging in the development and progression of heart failure with preserved ejection fraction (HFpEF) in patients with nonobstructive coronary artery disease (CAD) during a 12-month follow-up period.

Patients and Methods

A total of 112 patients (70 men; median age of 62.5 [57.0; 69.0] years) with nonobstructive coronary artery disease were enrolled in the study. Dynamic CZT-SPECT, echocardiography, and coronary CT angiography studies were performed baseline.

Results

Distribution of patients was performed by adverse events: group 1 comprised patients with adverse outcomes (n = 25), and group 2 comprised those without it (n = 87). Based on receiver operating characteristic analysis, the levels of MFR ≤1.62 (area under the curve [AUС], 0.884; Р < 0.001), stress-MBF ≤1.35 mL/min per gram (AUС, 0.750; Р < 0.001), and NT-proBNP ≥760.5 pg/mL (AUС, 0.764; Р = 0.001) were identified as cutoff values to predict adverse outcomes. Univariate analysis revealed that type 2 diabetes mellitus (P = 0.044), the levels of MFR ≤1.62 (P = 0.014), stress-MBF ≤1.35 mL/min per gram (P = 0.012), NT-proBNP ≥760.5 pg/mL (P = 0.018), and diastolic dysfunction (P = 0.009) were potential risk factors for the development and progression of HFpEF. Multivariate analysis demonstrated that the values of NT-proBNP ≥760.5 pg/mL (odds ratio, 1.87; 95% confidence interval, 1.17–3.62; P = 0.027) and MFR ≤1.62 (odds ratio, 2.801; 95% confidence interval, 1.19–6.55; P = 0.018) were independent predictors of adverse outcomes.

Conclusions

Our data suggest that reduced MFR ≤1.62 obtained with dynamic CZT imaging and overexpression of NT-proBNP ≥760.5 pg/mL can individuate patients at high risk of development and progression of HFpEF during a 12-month follow-up period, independently of baseline clinical parameters and imaging variables.
Prostate-Specific Membrane Antigen Uptake Heterogeneity in Mixed Ductal-Acinar Adenocarcinoma of the Prostate
Authors: Zhao Qian , Dong Aisheng , Bai Yushu , Zuo Changjing
Published: June 2023

Prostate-specific membrane antigen (PSMA) PET findings of mixed ductal-acinar adenocarcinoma of the prostate are rarely reported. We describe 18F-PSMA-1007 PET/CT and delayed pelvic 18F-PSMA-1007 PET/MRI findings in a case of prostatic mixed ductal-acinar adenocarcinoma with multiple lymph node and bone metastases. The primary tumor showed heterogeneous PSMA uptake. The metastases in the right ilium and acetabulum showed intense PSMA uptake, but the pelvic lymph node and left iliac bone metastases showed no significant PSMA uptake. Knowledge of the intraprimary and intermetastatic heterogeneity of PSMA uptake in mixed ductal-acinar adenocarcinoma of the prostate may be helpful for accurate interpretation.
A clinical metagenomic study of biopsies from Mexican endophthalmitis patients reveals the presence of complex bacterial communities and a diversity of resistance genes
Authors: Vences-Guzmán Miguel Ángel , Jiménez-Rodríguez Martín , Lozano Luis , Rojas-Juárez Sergio , Ramírez-Estudillo Juan Abel , Hernández-Vázquez Ángeles Yahel , Pita Ortiz Ingrid Yazmín , Ramírez-Ceballos Karol Guadalupe , Medina-Medina Silvia , Sohlenkamp Christian
Published: June 2023

Infectious endophthalmitis is a severe ophthalmic emergency. It is known that this infection can be caused by bacteria and fungi. For efficient treatment, the administration of antimicrobial drugs to which the microbes are susceptible is essential. The aim of this study was to identify microorganisms in biopsies of Mexican endophthalmitis patients using metagenomic next-generation sequencing and determine which antibiotic resistance genes were present in the biopsy samples. In this prospective case study, 19 endophthalmitis patients were recruited. Samples of vitreous or aqueous humor were extracted for DNA extraction for metagenomic next-generation sequencing. Analysis of the sequencing results revealed the presence of a wide variety of bacteria in the biopsies. The resistome analysis showed that homologs of antibiotic resistance genes were present in several biopsy samples. Genes possibly conferring resistance to ceftazidime and vancomycin were detected in addition to a variety of genes encoding efflux pumps. Our findings contrast with the widespread opinion that only one or a few bacterial strains are present in the infected tissues of endophthalmitis patients. These diverse communities might host many of the resistance genes that were detected, which can further complicate the infections.
Effect of dextransucrase antibodies on biofilm formation and certain cariogenic activities in Streptococcus mutans
Authors: Rather Shabeer Ahmad , Majeed Abid , Singh Lakhvinder , Bhatia Alka , Sharma Sukesh Chander , Mahmood Akhtar
Published: June 2023

Introduction. Dextransucrase produced by

Streptococcus mutans

plays a vital role in the formation of dental caries by synthesizing exopolysaccharides from sucrose, which helps in the attachment of microbes to the tooth surface, causing caries. Exploring antibody production against

S. mutans

antigens could be an effective method to protect against dental caries.

Hypothesis. Dextransucrase antibodies may help in the prevention of caries formation by inhibiting essential cariogenic factors.

Aims. The aim of this study was to investigate the effects of dextransucrase antibodies on biofilm formation and certain associated cariogenic factors of

S. mutans

.

Methodology. Dextransucrase was purified from culture of

S. mutans

. The antisera against the enzyme were raised in rabbits. The effect of dextransucrase antibodies on biofilm formation was studied using scanning electron microscopy, fluorescence microscopy and quantitative real-time polymerase chain reaction. The effects of the antibodies on associated cariogenic factors were examined using established methods. The cross-reactivity of antibodies with human lung, liver, heart, thyroid and kidney tissues was evaluated by immunohistochemistry.

Results. Our findings showed impaired biofilm formation in

S. mutans

in the presence of dextransucrase antibodies. Genes associated with biofilm formation such as gtfB, gtfC, brpA, relA, Smu.630 and vicK were downregulated (50–97 %) by dextransucrase antibodies in

S. mutans

. The adherence of

S. mutans

to glass surface was reduced by 58 % and hydrophobicity was reduced by 55.2 % in the presence of the antibodies compared to the controls. Immunohistochemistry studies revealed no cross-reactivity of human tissues with dextransucrase antibodies.

Conclusions. These findings suggest that antibodies raised against dextransucrase exhibit a profound inhibitory effect on biofilm formation and vital cariogenic factors of

S. mutans

, which supports the contention that dextransucrase could be a promising antigen to study for its anticariogenic potential.
Hippocampal Theta Phase Precession Supports Memory Formation and Retrieval of Naturalistic Experience in Humans
Authors: Zheng Jie , Yebra Mar , Schjetnan Andrea G.P. , Mosher Clayton , Kalia Suneil K. , Chung Jeffrey M. , Reed Chrystal M. , Valiante Taufik A. , Mamelak Adam N. , Kreiman Gabriel , Rutishauser Ueli
Published: June 2023

Linking different experiences together is a key aspect of episodic memory. A potential neural mechanism for linking sequential events over time is phase precession, which causes neurons to fire progressively earlier in time relative to theta-frequency local field potential oscillations. However, no direct link between phase precession and behaviorally assessed memory encoding or retrieval success has been established. We recorded the activity of single neurons and local field potentials in the human medial temporal lobe (MTL) while participants encoded and retrieved memories of movie clips. Transient brief theta bouts and theta phase precession were observed following cognitive boundaries during movie watching as well as following stimulus onset during memory retrieval. Phase precession was dynamic, with different neurons exhibiting phase precession in different task periods. The strength of phase precession provided information about memory encoding and retrieval success that was not available in firing rates, thereby linking the temporal code established by phase precession to behaviorally assessed memory strength. These data reveal phase precession during non spatial memory in humans and provide direct neural evidence for a functional role of phase precession in episodic memory.