Hemorrhagic varices around the pancreatojejunostomy site due to left-sided portal hypertension after pancreaticoduodenectomy: A case report.

Pancreaticoduodenectomy (PD) with combined portal vein resection sometimes causes left-sided portal hypertension, which can be a problem. An appropriate treatment strategy for hemorrhagic ectopic varices due to left-sided portal hypertension after PD has not yet been determined. We report a case of repeated variceal rupture around the pancreatojejunostomy site. A 65-year-old woman with a history of PD for pancreatic head cancer was admitted with a chief complaint of bloody stools. She was diagnosed with pancreatojejunostomy variceal rupture, and an endoscopic cyanoacrylate injection was performed. As rebleeding occurred 2 weeks after the first treatment, endoscopic cyanoacrylate injection was repeated, and hemostasis was achieved. Additionally, she had esophageal, colonic, and gastrojejunostomy varices, and the future risk of these variceal ruptures was considered very high. Hence, a splenectomy was performed to prevent rebleeding or other variceal ruptures. Endoscopic cyanoacrylate injection is a useful treatment for hemorrhagic varices around the pancreatojejunostomy site. It is also necessary to understand portal vein hemodynamics and provide appropriate additional treatment in cases of recurrent variceal rupture due to left-sided portal hypertension after PD.

Toll-like receptor 4 mutation mitigates gut microbiota-mediated hypertensive kidney injury.

Hypertension-associated dysbiosis is linked to several clinical complications, including inflammation and possible kidney dysfunction. Inflammation and TLR4 activation during hypertension result from gut dysbiosis-related impairment of intestinal integrity. However, the contribution of TLR4 in kidney dysfunction during hypertension-induced gut dysbiosis is unclear. We designed this study to address this knowledge gap by utilizing TLR4 normal (TLR4N) and TLR4 mutant (TLR4M) mice. These mice were infused with high doses of Angiotensin-II for four weeks to induce hypertension. Results suggest that Ang-II significantly increased renal arterial resistive index (RI), decreased renal vascularity, and renal function (GFR) in TLR4N mice compared to TLR4M. 16 S rRNA sequencing analysis of gut microbiome revealed that Ang-II-induced hypertension resulted in alteration of Firmicutes: Bacteroidetes ratio in the gut of both TLR4N and TLR4M mice; however, it was not comparably rather differentially. Additionally, Ang-II-hypertension decreased the expression of tight junction proteins and increased gut permeability, which were more prominent in TLR4N mice than in TLR4M mice. Concomitant with gut hyperpermeability, an increased bacterial component translocation to the kidney was observed in TLR4N mice treated with Ang-II compared to TLR4N plus saline. Interestingly, microbiota translocation was mitigated in Ang-II-hypertensive TLR4M mice. Furthermore, Ang-II altered the expression of inflammatory (IL-1ß, IL-6) and anti-inflammatory IL-10) markers, and extracellular matrix proteins, including MMP-2, -9, -14, and TIMP-2 in the kidney of TLR4N mice, which were blunted in TLR4M mice. Our data demonstrate that ablation of TLR4 attenuates hypertension-induced gut dysbiosis resulting in preventing gut hyperpermeability, bacterial translocation, mitigation of renal inflammation and alleviation of kidney dysfunction.

TG2 participates in pulmonary vascular remodelling by regulating the senescence of pulmonary artery smooth muscle cells.

Pulmonary hypertension (PH) is a severe cardiovascular disease characterised by pulmonary vascular remodelling. The pivotal role of cellular senescence in vascular remodelling has been acknowledged. Transglutaminase type 2 (TG2), a calcium-dependent enzyme, is intricately linked to both cellular senescence and PH. However, the precise mechanisms underlying the involvement of TG2 in PH remain unclear. In this study, we explored the expression of TG2 and the cellular senescence marker p16INK4a in the pulmonary vasculature of mice with PH induced by hypoxia combined with SU5416. Our findings revealed upregulation of both TG2 and p16INK4a expression in the pulmonary vasculature of PH mice. Additionally, a notable increase in TG2 expression was observed in senescent pulmonary artery smooth muscle cells (PASMC). To delve deeper, we employed proteomic sequencing to reveal seven genes associated with cellular senescence, with a subsequent focus on MAPK14. Our investigation revealed that TG2 regulates senescence in PASMC by modulating the phosphorylation levels of MAPK14. Additionally, in the context of hypoxia combined with SU5416, our observations revealed a noteworthy reduction in both pulmonary vascular remodelling and senescent manifestations in smooth muscle-specific TG2 knockout mice compared with their wild-type counterparts. In summary, our findings indicate that TG2 deficiency lowers the senescence levels of PASMC by inhibiting the activity of MAPK14. This inhibition of senescence in the pulmonary vasculature of PH mice helps to decelerate the progression of pulmonary vascular remodelling and consequently hinders the onset and development of PH.

Urinary complement factor D is increased in primary malignant hypertension: a single-center, cross-sectional study.

Kidney injury is one of the detrimental consequences of primary malignant hypertension (pMHTN). There is a paucity of non-invasive biomarkers to enhance diagnosis and elucidate the underlying mechanisms. This study aims to explore urine protein biomarkers for pMHTN associated renal damage. In the discovery phase, urine samples were collected from 8 pMHTN, 19 disease controls (DCs), and 5 healthy controls (HCs). In-gel digestion combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was used for identification of proteins associated with pMHTN. In the validation phase, the differentially expressed proteins were validated by ELISA assay in cohort with 10 pMHTN patients, 37 DCs, and 30 HCs. Compared to DCs and HCs, a specific band between 15 and 25 kDa was found in 7 out of 8 patients with pMHTN. Further LC-MS/MS analysis revealed 5 differentially expressed proteins. ELISA validation demonstrated that urinary complement factor D (CFD) was significantly up regulated in pMHTN. By receiver operating characteristic curve analysis, urinary CFD/Cr showed moderate potential in discriminating pMHTN from DCs (the area under curve: 0.822, 95% CI 0.618-0.962). Urinary CFD may be a potential biomarker for pMHTN with its elevation indicative of the activation of the alternative complement pathway in pMHTN.

Effect of caspase inhibitors on hemodynamics and inflammatory factors in ARDS model rats.

To study the effects of caspase inhibitors on hemodynamics and inflammatory factors in acute respiratory distress syndrome (ARDS) model rats. Sixty healthy male Wistar rats were randomly divided into three groups, namely, the control group, ARDS group and ARDS + Caspase inhibitor group, with 20 rats in each group. The control group was intraperitoneally injected with 2 mL/kg saline, and the ARDS model group was established by intraperitoneally injecting 4 mg/kg Lipopolysaccharide (LPS), ARDS + Caspase inhibitor group was adminstered 20 mg/kg caspase inhibitor after intraperitoneal LPS injection. Changes in pulmonary arterial pressure (PAP) and mean arterial pressure (MAP) at 6 and 12 h before and after administration were recorded. Moreover, arterial blood gas was evaluated with a blood gas analyzer and changes in the partial pressure of O2 (PaO2), partial pressure of CO2 (PaCO2), partial pressure of O2/fraction of inspired O2 (PaO2/FiO2) were evaluated. In addition, the lung wet/dry weight (W/D) ratio and inflammatory factor levels in lung tissue were determined. Finally, pathological sections were used to determine the pulmonary artery media thickness (MT), MT percentage (MT%), and the degree of muscle vascularization. The pulmonary arterial pressure of rats was determined at several time points. Compared with the control group, the model group had a significantly increased pulmonary arterial pressure at each time point (P < 0.01), and the mean arterial pressure significantly increased at 6 h (P < 0.05). Compared with that of rats in the model group, the pulmonary arterial pressure of rats in drug administration group was significantly reduced at each time point after administration (P < 0.01), and the mean arterial pressure was significantly reduced at 6 h (P < 0.05). The arterial blood gas analysis showed that compared with those in the control group, PaO2, PaCO2 and PaO2/FiO2 in the model group were significantly reduced (P < 0.01), and PaO2, PaCO2 and PaO2/FiO2 were significantly increased after caspase inhibitor treatment (P < 0.05 or 0.01). The levels of the inflammatory mediators tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in the model group were significantly higher than those in the control group (P < 0.01), and they were significantly decreased after caspase inhibitor treatment (P < 0.01). In the model group, pulmonary artery MT, MT% and the degree of muscle vascularization were significantly increased (P < 0.05 or 0.01), and pulmonary artery MT and the degree of muscle vascularization were significantly reduced after caspase inhibitor treatment (P < 0.05 or 0.01). Apoptosis Repressor with a Caspase Recuitment Domain (ARC) can alleviate the occurrence and development of pulmonary hypertension (PH) by affecting hemodynamics and reducing inflammation.

Investigation into the role of H2-Ab1 in vascular remodeling in pulmonary arterial hypertension via Bioinformatics.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disease of vascular remodeling characterized by persistent pulmonary arterial pressure elevation, which can lead to right heart failure and premature death. Given the complex pathogenesis and poor prognosis of PAH, the identification and investigation of biomarkers become increasingly critical for advancing further understanding of the disease. METHODS: PAH-related datasets, GSE49114, GSE180169 and GSE154959, were downloaded from the publicly available GEO database. By performing WGCNA on the GSE49114 dataset, a total of 906 PAH-related key module genes were screened out. By carrying out differential analysis on the GSE180169 dataset, a total of 576 differentially expressed genes were identified. Additionally, the GSE154959 single-cell sequencing dataset was also subjected to differential analysis, leading to the identification of 34 DEGs within endothelial cells. By taking intersection of the above three groups of DEGs, five PAH-related hub genes were screened out, namely Plvap, Cyp4b1, Foxf1, H2-Ab1, and H2-Eb1, among which H2-Ab1 was selected for subsequent experiments. RESULTS: A SuHx mouse model was prepared using the SU5416/hypoxia method, and the successful construction of the model was evaluated through Hematoxylin-Eosin staining, hemodynamic detection, fulton index, and Western Blot (WB). The results of WB and qRT-PCR demonstrated a significant upregulation of H2-Ab1 expression in SuHx mice. Consistent with the results of bioinformatics analysis, a time-dependent increase was observed in H2-Ab1 expression in hypoxia-treated mouse pulmonary artery endothelial cells (PAECs). To investigate whether H2-Ab1 affects the development and progression of PAH, we knocked down H2-Ab1 expression in PAECs, and found that its knockdown inhibited the viability, adhesion, migration, and angiogenesis, while concurrently promoted the apoptosis of PAECs. CONCLUSION: H2-Ab1 could regulate the proliferation, apoptosis, adhesion, migration, and angiogenesis of PAECs.

IL-33 Signaling Inhibition Leads to a Preeclampsia-Like Phenotype in Pregnant Rats.

PROBLEM: Preeclampsia (PE) is a hypertensive pregnancy disorder that is a leading cause of maternal and fetal morbidity and mortality characterized by maternal vascular dysfunction, oxidative stress, chronic immune activation, and excessive inflammation. No cure exists beyond delivery of the fetal-placental unit and the mechanisms driving pathophysiology are not fully understood. However, aberrant immune responses have been extensively characterized in clinical studies and shown to mediate PE pathophysiology in animal studies. One pathway that may mediate aberrant immune responses in PE is deficiencies in the IL-33 signaling pathway. In this study, we aim to investigate the impact of IL-33 signaling inhibition on cNK, TH17, and TReg populations, vascular function, and maternal blood pressure during pregnancy. METHOD OF STUDY: In this study, IL-33 signaling was inhibited using two different methods: intraperitoneal administration of recombinant ST2 (which acts as a decoy receptor for IL-33) and administration of a specific IL-33 neutralizing antibody. Maternal blood pressure, uterine artery resistance index, renal and placental oxidative stress, cNK, TH17, and TReg populations, various cytokines, and pre-proendothelin-1 levels were measured. RESULTS: IL-33 signaling inhibition increased maternal blood pressure, uterine artery resistance, placental and renal oxidative stress. IL-33 signaling inhibition also increased placental cNK and TH17 and renal TH17 cells while decreasing placental TReg populations. IL-33 neutralization increased circulating cNK and TH17s and decreased circulating TRegs in addition to increasing pre-proendothelin-1 levels. CONCLUSIONS: Data presented in this study demonstrate a role for IL-33 signaling in controlling vascular function and maternal blood pressure during pregnancy possibly by mediating innate and adaptive immune inflammatory responses, identifying the IL-33 signaling pathway as a potential therapeutic target for managing preeclampsia.

Intra-operative hypertension as a predictor of surgical outcomes in microvascular decompression surgery for trigeminal neuralgia.

PURPOSE: The trigeminocardiac reflex (TCR) has traditionally been characterized by a sudden decrease in heart rate, asystole, or hypotension during the manipulation of the trigeminal nerve (MTN) or its branches. While this classical TCR is well-documented, there is limited literature on alternative forms of TCR, such as the development of intraoperative hypertension (HTN) or tachycardia, and the underlying pathogenesis. Furthermore, a gap exists in understanding the correlation between intraoperative blood pressure readings and postoperative outcomes, particularly regarding pain relief in patients with trigeminal neuralgia (TN). Our study aims to examine intraoperative blood pressure trends during microvascular decompression (MVD) for TN and assess their impact on postoperative outcomes. METHODS: We selected 90 patients who underwent MVD for TN treatment. Blood pressure and heart rate were recorded both preoperatively and during the procedure, specifically during the MTN period, using an arterial line. The Barrow Neurological Institute (BNI) Pain Scale was calculated for all patients both pre- and post-operatively to evaluate pain relief after surgery. RESULTS: The mean age of the patients was 61.0 ± 12.35 years, with 64.4% being females. Classical TCR (hypotension) was observed in only 2.2% of patients, whereas 80% of patients developed hypertension (≥ 140/90) during MTN. The mean preoperative systolic blood pressure was 128 ± 22.25, and the mean intraoperative systolic blood pressure during MTN was 153.1 ± 20.2. An analysis of covariance, utilizing either preoperative BNI or duration of symptoms as covariate variables, revealed a statistically significant association between intraoperative HTN and postoperative BNI. A linear regression model demonstrated that intraoperative HTN following MTN significantly predicted a lower postoperative BNI score (p = 0.006). CONCLUSIONS: Intraoperative HTN during MTN, an observed yet underexplored phenomenon, demonstrated a correlation with improved postoperative outcomes. Furthermore, it is recommended to conduct additional investigations into potential neurovascular conflicts in patients not manifesting intraoperative HTN following MTN. A comprehensive understanding of TCR, encompassing its various forms, is vital for optimizing surgical management. This study underscores the imperative for further research to unravel the mechanisms linking intraoperative HTN to surgical outcomes in TN patients.

Improving hypertension control in Nigeria: early policy implications from the Hypertension Treatment in Nigeria program.

Hypertension poses a significant health burden globally. In Nigeria, hypertension prevalence is on the rise, with low rates of awareness, treatment, and control. This policy brief explores the critical gaps addressed by the Hypertension Treatment in Nigeria (HTN) Program, highlighting its strengths, initial outcomes, and scalability in primary care settings. The HTN Program employs an integrated, multilevel care model based on the World Health Organization's HEARTS technical package, including patient registration and empanelment, team-based care, training and supervision, a standardized treatment protocol, a health information management system, and a drug revolving fund to improve medication accessibility. By December 2023, hypertension treatment and control rates reached surpassing 90% and 50%, respectively, thus underscoring the program's impact. The HTN Program serves as a model for delivering integrated hypertension care in primary care. Results should be leveraged for political commitment and financing to evaluate and manage non-communicable diseases such as hypertension in primary care through federal and state primary health development agencies. Furthermore, incorporating metrics related to hypertension control and treatment into the Integrated Supportive Management Information System can enhance routine monitoring and evaluation.

Endoscopic variceal ligation combined with sclerotherapy for management of gastroesophageal variceal bleeding in pediatric patients: a single-center retrospective study.

Objectives: Portal hypertension (PH) frequently gives rise to severe and life-threatening complications, including hemorrhage accompanied by the rupture of esophageal and gastric varices. In contrast to the guidelines for the management of PH in adults, the optimal endoscopic management of variceal bleeding for secondary prophylaxis in children remains unclear. The present study evaluated the efficacy and safety of endoscopic variceal ligation (EVL) and endoscopic sclerotherapy (EST) to control gastroesophageal variceal bleeding in children. Methods: This retrospective study included children with gastroesophageal variceal bleeding who underwent EST or EVL at Xinhua Hospital, Shanghai Jiaotong University School of Medicine, between February 2013 and March 2020. Short-term hemostasis rate and long-term rebleeding rate were evaluated. Adverse events related to the procedures, such as esophageal ulcer, esophageal stricture, abnormal embolization, pneumonia and perforation, were also recorded. Results: EVL (n = 8) and EST (n = 13) were performed successfully in all pediatric patients diagnosed with moderate to severe esophageal varices concurrent with gastric varices. Hemostasis was achieved during episodes of upper gastrointestinal bleeding. The mean volume of each single aliquot of cyanoacrylate injected was 0.3 ± 0.1 ml (range: 0.1-0.5 ml). Varices were eradicated in six (75%) of the eight patients who underwent EVL after a median 2 (range: 1-4) procedures and a median time of 3.40 months (range: 1.10-13.33 months). Eleven (52.4%) of the 21 patients developed rebleeding events, with the mean duration of hemostasis being 11.1 ± 11.6 months (range 1.0-39.2 months). No treatment-related complications, for example, distal embolism, occurred except for abdominal pain in one patient (4.8%). Conclusions: EST, alone or in combination with EVL, is an effective and safe method of managing gastroesophageal variceal hemorrhage in children undergoing secondary prophylaxis.

The Role of Serum Erythropoietin (EPO) and Vascular Endothelial Growth Factor (VEGF) in Pulse Wave Velocity (PWV) Among Hypertensive Patients: A Cross-Sectional Study.

Background and objective While hypertension (HTN) is a major health-related threat globally, it is often an under-reported clinical condition as most of the stage I hypertensive patients do not present with any symptoms. The relationship between endogenous oxygen-sensing protein [erythropoietin (EPO) and vascular endothelial growth factor (VEGF)] levels and vascular stress in hypertensive patients is not fully understood as the mechanistic pathway by which these oxygen-sensing proteins alter the vascular physiology and cause hypertension is still a matter of debate. In light of this, we explored the role of these two proteins in the development of vascular stress including increased pulse wave velocity (PWV). We aimed to examine the correlation between oxygen-sensing proteins and vascular stress markers including PWV in hypertensive patients. Materials and methods We conducted a cross-sectional study involving age-matched participants classified into three groups (group 1: normotensive persons, n=36; group 2: stage I hypertensive patients, n=36; and group 3, stage II hypertensive patients, n=36). Adiposity-related parameters such as waist circumference (WC), hip circumference (HC), BMI, and waist-hip ratio (WHR) were measured. BP was recorded manually in resting posture by using a sphygmomanometer. PWV, which predicts the progression of BP and the development of HTN, was recorded using a periscope, which works based on the oscillometric method. Vascular stress-induced oxidative stress parameters [serum malondialdehyde (MDA) and serum nitric oxide (NO)] were also estimated by using a UV spectrophotometer. Quantitative estimations of oxygen-sensing proteins (serum EPO and serum VEGF) were done by using the ELISA kit method. The results were expressed as mean ± standard deviation (SD). The correlation between the variables was done using Spearman's correlation. A p-value <0.05 was considered statistically significant. Results Adiposity indices and vascular stiffness parameters were found to be significantly (p <0.05) increased in group 2 and group 3 compared to group 1. The levels of serum MDA were found to be significantly (p<0.05) increased in group 2 and group 3 than group 1, whereas the levels of serum NO were significantly (p<0.05) decreased in group 3 and group 2 than group 1. A significant (p<0.05) positive correlation was observed between the PWV and EPO (r=0.492) while a significant (p<0.05) negative correlation was observed between PWV and VEGF (r=-0.406) among the study population. Conclusion The results are indicative of the influence of vascular stress in stage I and II hypertensive patients. Furthermore, the relationship between oxygen-sensing proteins and vascular stress in hypertensive patients has also been established.

Critical Insights Into Neonatal Hypertension: A Comprehensive Review of Current Understanding and Management Strategies.

Hemodynamic adaptation to the extrauterine environment results in rapid blood pressure (BP) fluctuations during the neonatal period, particularly in premature infants. BP levels in neonates are influenced by several factors, including gestational age, birth weight, and maternal health. Diagnosing neonatal hypertension (HTN) typically requires a thorough diagnostic evaluation. Common etiologies include renal parenchymal disease, umbilical catheter-related thrombosis, and chronic lung disease. Despite the prevalence of HTN-associated factors and risk factors in neonates, management can be challenging. Fortunately, most cases of neonatal HTN resolve over time. This review explores these concepts and highlights the evidentiary gaps that need to be addressed.

Association between lifestyle factors and hypertension control in Indonesian primary healthcare settings: A cross-sectional study.

Introduction: A healthy lifestyle influences hypertension control. However, studies investigating the effects of lifestyle on hypertension remain elusive. This study aimed to analyse the association between lifestyle factors and hypertension control among patients with hypertension. Methods: This cross-sectional exploratory study was conducted from June to December 2022 among 265 patients with hypertension from the Pusat Kesehatan Masyarakat. The status of hypertension control was assessed by checking the serial blood pressure. The physical activity (PA) level, sleep quality, stress level and eating pattern were measured using the Global Physical Activity Questionnaire; Pittsburgh Sleep Quality Index; Depression Anxiety Stress Scale-21; and 24-Hour Food Recall Questionnaire, Adolescent Food Habits Checklist and Emotional Eating Scale, respectively. Stepwise binary logistic regression and a generalised linear model were used for the statistical analysis. Results: Approximately 72.2% of the participants had uncontrolled hypertension. The majority showed a low PA level (46%), normal stress level (94.7%), good sleep quality (80%), low caloric intake (95.5%), neutral food habit (55.5%) and low emotional eating (93.2%). Sex (P=0.030), age (P=0.018), PA level (P=0.011), sleep quality (P=0.032) and stress level (P=0.030) significantly influenced hypertension control. Specifically, moderate (odds ratio [OR]=5.868, 95% confidence interval [CI]=3.024-11.798, P=0.000) and vigorous PA levels (OR=2.188, 95% CI=1.026-4.678, P=0.042) were significantly associated with hypertension control. Conclusion: Moderate and vigorous PA levels are lifestyle factors that may play a role in controlling hypertension.

Development and validation of a video-based intervention on self-care practices for patients with hypertension in Malaysian primary care settings.

Introduction: Self-care practices among patients with hypertension have been shown to improve blood pressure control. Video-based interventions (VBIs) are helpful in enhancing patients' selfcare practices. However, validated VBIs in the Malay language for patients in primary care settings are scarce. This study aimed to develop and validate a VBI series in the Malay language to educate patients with hypertension on self-care practices in primary care settings. Methods: This study was conducted in three phases: (1) pre-production, (2) production and (3) post-production. The pre-production phase involved designing the storyboard and scripts, which underwent content validation by content experts and subsequently by patients with hypertension. Once the storyboards and scripts achieved acceptable consensus, the videos were recorded (production phase). The post-production phase included video editing and face validation among patients with hypertension. Statistical analysis included the calculation of the item-level content validation index (I-CVI) and item-level face validation index (I-FVI) during content and face validation, respectively. Results: The storyboards and scripts for five videos were developed. The I-CVI of all videos was 1.0 after two rounds of content validation among six content experts. The I-CVI of all videos was 1.0 among five patients with hypertension. Five videos were recorded and edited, achieving an I-FVI of 1.0 during face validation among 10 patients. Conclusion: A VBI series consisting of five videos was developed and validated for use among patients with hypertension in primary care settings to improve their knowledge of self-care practices.

Rapid Plaque Progression Is Independently Associated With Hyperglycemia and Low HDL Cholesterol in Patients With Stable Coronary Artery Disease: A PARADIGM Study.

BACKGROUND: We assessed whether combinations of cardiometabolic risk factors independently predict coronary plaque progression (PP) and major adverse cardiovascular events in patients with stable coronary artery disease. METHODS: Patients with known or suspected stable coronary artery disease (60.9±9.3 years, 55.4% male) undergoing serial coronary computed tomography angiographies (≥2 years apart), with clinical characterization and follow-up (N=1200), were analyzed from the PARADIGM study (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging). Plaque volumes measured in coronary segments (≥2 mm in diameter) were summed to provide whole heart plaque volume (mm3) and percent atheroma volume (plaque volume/vessel volume×100; %) per patient at baseline and follow-up. Rapid PP was defined as a percent atheroma volume increase of ≥1.0%/y. Major adverse cardiovascular events included nonfatal myocardial infarction, death, and unplanned coronary revascularization. RESULTS: In an interscan period of 3.2 years (interquartile range, 1.9), rapid PP occurred in 341 patients (28%). At multivariable analysis, the combination of cardiometabolic risk factors defined as metabolic syndrome predicted rapid PP (odds ratio, 1.51 [95% CI, 1.12-2.03]; P=0.007) together with older age, smoking habits, and baseline percent atheroma volume. Among single cardiometabolic variables, high fasting plasma glucose (diabetes or fasting plasma glucose >100 mg/dL) and low HDL-C (high-density lipoprotein cholesterol; <40 mg/dL in males and <50 mg/dL in females) were independently associated with rapid PP, in particular when combined (odds ratio, 2.37 [95% CI, 1.56-3.61]; P<0.001). In a follow-up of 8.23 years (interquartile range, 5.92-9.53), major adverse cardiovascular events occurred in 201 patients (17%). At multivariable Cox analysis, the combination of high fasting plasma glucose with high systemic blood pressure (treated hypertension or systemic blood pressure >130/85 mm Hg) was an independent predictor of events (hazard ratio, 1.79 [95% CI, 1.10-2.90]; P=0.018) together with family history, baseline percent atheroma volume, and rapid PP. CONCLUSIONS: In patients with stable coronary artery disease, the combination of hyperglycemia with low HDL-C is associated with rapid PP independently of other risk factors, baseline plaque burden, and treatment. The combination of hyperglycemia with high systemic blood pressure independently predicts the worse outcome beyond PP. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02803411.

Placental biophysical model for prediction of early onset fetal growth restriction in first and second trimester of pregnancy: A prospective cohort study.

INTRODUCTION: To assess the placental biometry, placental biomarkers and uterine artery Doppler in each trimester of pregnancy for prediction of early-onset fetal growth restriction (EO FGR). METHODS: In this prospective cohort study placental biometry; biomarkers PAPP-A, sFLT-1, and PlGF along with the uterine artery blood flow evaluation was done serially at 11-14, 20-24 and 28-32 weeks of gestation. The above parameters were compared between women with early onset FGR and controls. RESULTS: Out of 1008 fully followed cases, the small for gestational age fetuses were 227/1008 (22.5 %), and EO FGR were 84/1008(8.3 %).The placental length, volume, and PlGF levels were significantly lower, whereas the uterine artery PI(Ut PI) was significantly higher at all time points among cases. The sFLT-1 level showed a significant increase among cases, whereas it decreased among controls from the first to the second trimester. The detection rate using PV/UtA PI was 60 % in the first trimester and 66.7 % in the second trimester at 30 % FPR. CONCLUSION: The PV/Ut PI in first and the second trimester was a good marker for the prediction of pregnancies at increased risk of developing EO FGR.

Activation of angiotensin-converting enzyme 2 promotes hippocampal neurogenesis via activation of Wnt/ß-catenin signaling in hypertension.

Hypertension-induced brain renin-angiotensin system (RAS) activation and neuroinflammation are hallmark neuropathological features of neurodegenerative diseases. Previous studies from our lab have shown that inhibition of ACE/Ang II/AT1R axis (by AT1R blockers or ACE inhibitors) reduced neuroinflammation and accompanied neurodegeneration via up-regulating adult hippocampal neurogenesis. Apart from this conventional axis, another axis of RAS also exists i.e., ACE2/Ang (1-7)/MasR axis, reported as an anti-hypertensive and anti-inflammatory. However, the role of this axis has not been explored in hypertension-induced glial activation and hippocampal neurogenesis in rat models of hypertension. Hence, in the present study, we examined the effect of ACE2 activator, Diminazene aceturate (DIZE) at 2 different doses of 10 mg/kg (non-antihypertensive) and 15 mg/kg (antihypertensive dose) in renovascular hypertensive rats to explore whether their effect on glial activation, neuroinflammation, and neurogenesis is either influenced by blood-pressure. The results of our study revealed that hypertension induced significant glial activation (astrocyte and microglial), neuroinflammation, and impaired hippocampal neurogenesis. However, ACE2 activation by DIZE, even at the low dose prevented these hypertension-induced changes in the brain. Mechanistically, ACE2 activation inhibited Ang II levels, TRAF6-NFκB mediated inflammatory signaling, NOX4-mediated ROS generation, and mitochondrial dysfunction by upregulating ACE2/Ang (1-7)/MasR signaling. Moreover, DIZE-induced activation of the ACE2/Ang (1-7)/MasR axis upregulated Wnt/ß-catenin signaling, promoting hippocampal neurogenesis during the hypertensive state. Therefore, our study demonstrates that ACE2 activation can effectively prevent glial activation and enhance hippocampal neurogenesis in hypertensive conditions, regardless of its blood pressure-lowering effects.

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OBJECTIVES: To investigate the protective effects of 2-methoxyestradiol (2ME) against hypoxic pulmonary hypertension (HPH) in neonatal rats. METHODS: Ninety-six Wistar neonatal rats were randomly divided into a normoxia group, a hypoxia group, and a hypoxia + 2ME group, with each group further subdivided into 3-day, 7-day, 14-day, and 21-day subgroups, containing eight rats each. The hypoxia and hypoxia + 2ME groups received daily subcutaneous injections of saline and 2ME (240 µg/kg), respectively, while the normoxia group was raised in a normoxic environment with daily saline injections. Right ventricular systolic pressure (RVSP) was measured using the direct pressure method. Pulmonary vascular morphology was assessed using hematoxylin and eosin staining, with metrics including the percentage of medial thickness of small pulmonary arteries relative to the external diameter (MT%) and the cross-sectional area of the media of small pulmonary arteries relative to the total cross-sectional area (MA%). Immunohistochemistry was used to detect the expression levels of hypoxia-inducible factor-1α (HIF-1α) and proliferating cell nuclear antigen (PCNA) proteins, while real-time quantitative PCR was used to to assess HIF-1α and PCNA mRNA levels. RESULTS: Compared to the normoxia group, the hypoxia and hypoxia + 2ME groups showed increased RVSP and upregulated HIF-1α and PCNA protein and mRNA expression levels at 3, 7, 14, and 21 days after hypoxia (P<0.05). Furthermore, at 7, 14, and 21 days after hypoxia, the hypoxia group showed increased MT% and MA% (P<0.05). In comparison to the hypoxia group, the hypoxia + 2ME group exhibited reduced RVSP and downregulated HIF-1α and PCNA protein and mRNA expression levels, along with decreased MT% and MA% at 7, 14, and 21 days after hypoxia (P<0.05). CONCLUSIONS: 2ME may protect against HPH in neonatal rats by inhibiting the expression of HIF-1α and PCNA and reducing pulmonary vascular remodeling. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 757-764.

Paediatric idiopathic intracranial hypertension: Epidemiology, clinical features and treatment outcomes in a tertiary care centre in Western Australia.

AIM: This retrospective study aims to analyse the epidemiology, clinical and neuroimaging features, treatment modalities, and outcomes of paediatric idiopathic intracranial hypertension (IIH) in a tertiary care centre in Australia. METHODS: Using the International Classification of Diseases Diagnostic Criteria for IIH, we identified and analysed a cohort of children diagnosed with IIH over a 5-year period (2017-2022). Data on patient demographics, symptomatology, examination findings, investigative results, treatments and outcomes were collected from medical records and electronic health records. RESULTS: A total of 45 cases were analysed. The pre-pubertal group saw a male predominance and the post-pubertal a female one. Increased body mass index was an associated comorbidity in majority of patients. Headaches (89%) and visual symptoms (56%) were the most common symptoms, with tinnitus also seen in 20% of patients. Papilledema was detected in 91% of the cases examined. The commonest neuroimaging features were optic nerve sheath distention (78%) and empty sella (49%). Acetazolamide was the primary treatment, with most patients responding well. Only a minority required surgical intervention. Long-term resolution of headaches was achieved in 89% of patients. CONCLUSIONS: The incidence of paediatric IIH in the West Australian population appears relatively high. It presents with subtle symptoms, emphasising the need for increased awareness among health-care providers. Younger children may represent a distinct subgroup with unique clinical features. Timely diagnosis and aggressive medical management lead to favourable outcomes. However, weight loss interventions showed limited effectiveness. This study underscores the importance of early recognition and management of paediatric IIH to optimise patient outcomes.