Systemic sclerosis (SSc) is a chronic, severe autoimmune disease characterized by progressive fibrosis of the skin and internal organs. Pulmonary (arterial) hypertension (P(A)H) is a common complication and leading cause of death. This review highlights preclinical and clinical advances of recent years that contribute to our understanding of pathomechanisms, risk stratification, treatment and potential targets in SSc-P(A)H. As SSc-PH emerges from a complex interplay of immune dysregulation, endothelial injury, metabolic reprogramming and fibroproliferative remodeling, an integrated approach to early detection, combining refined cardiac imaging metrics, circulating and omics-based biomarkers, and clinical stratifiers such as age and timing of symptom onset, is increasingly feasible. Recent literature highlights mechanistic targets for therapy and also practical tools for sharpening screening algorithms to reduce unnecessary right heart catheterization. Exercise testing and detailed right heart phenotyping yield promise for early disease diagnosis. Four randomized controlled trials in PAH provide (indirect) evidence on efficacy and safety of activin signaling inhibitor, Sotatercept in SSc-PAH. Recent years have brought major preclinical and clinical advances improving diagnosis and management of SSc-P(A)H. Large-scale multi-omics analyses, and novel treatment targets offer further advances in the field.
Isolated diastolic hypertension can precede combined systolic-diastolic hypertension, suggesting isolated diastolic hypertension may be a risk factor for adverse cardiovascular outcomes. Little is known about the prevalence of hypertensive subtypes (isolated diastolic, isolated systolic, or combined systolic-diastolic hypertension) in the years after first pregnancy, and whether these differ after hypertensive disorder of pregnancy. This is a secondary analysis (conducted 2023-2024) of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study. Nulliparas were enrolled at 8 US clinical sites from 2010 to 2013; participants who completed the Heart Health Study visit 2 to 7 years after pregnancy were eligible. Blood pressures were elevated at the visit if systolic was ≥130 mm Hg and diastolic ≥80 mm Hg. Multinomial logistic regression relative risk models were adjusted for age, body mass index, race, and time from pregnancy to visit. Four thousand three hundred two participants were included. Mean age at Heart Health Study visit was 30.7 years (SD, 5.6 years); 812 (19%) had elevated blood pressure. Isolated diastolic hypertension was most prevalent (n=627; 15%). Compared with normotensive pregnancy, hypertensive disorders of pregnancy were associated with combined systolic-diastolic (adjusted risk ratio, 3.09 [95% CI, 2.21-4.31]) and isolated diastolic hypertension (adjusted risk ratio, 1.65 [95% CI, 1.36-2.00]). Isolated diastolic hypertension is the most prevalent hypertensive subtype after first pregnancy. Women with hypertensive disorders of pregnancy had increased risk of combined systolic-diastolic and isolated diastolic hypertension. Given the high prevalence of isolated diastolic hypertension found in this cohort, postpartum women represent a subgroup with opportunity for cardiovascular risk reduction. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02231398.
Nighttime blood pressure (BP) is a stronger predictor of cardiovascular events than daytime BP. However, the global prevalence of nocturnal hypertension across different populations has not been previously described. This review estimates the global prevalence of nocturnal hypertension, offering insights to guide clinical practice, healthcare planning and future research. For this systematic review and meta-analysis, we searched PubMed, EMBASE, CINAHL, and Scopus and included studies reporting the prevalence of nocturnal hypertension and non-dipping BP in adults, including studies published up to 12 December 2024. Study selection, data extraction, and risk of bias assessment were conducted independently by two reviewers, with discrepancies resolved by consensus. There were no language restrictions. Random-effects meta-analyses were used to estimate pooled prevalence across study populations. The review was pre-registered with PROSPERO (CRD42025625712). A total of 449 studies were included. The prevalence of nocturnal hypertension was 45% (95% confidence interval (CI): 39-51, I2=97.4%) in the general population and was higher among individuals with hypertension (57%, 95%CI: 54-60, I2=84.7%), and high-risk patients including diabetes mellitus (56%, 95%CI: 38-72, I2=97.1%), obstructive sleep apnoea (60%, 95%CI: 42-78, I2=93.0%), chronic kidney disease (64%, 95%CI: 53-73, I2=95.2%). The prevalence of isolated nocturnal hypertension in the general population was 23% (95%CI: 14-34; I2= 93.8%), while the prevalence of non-dipping was 39% (95%CI: 34-45, I2=95.4%) in the general population and was higher among individuals with hypertension (48%, 95%CI: 46-50, I2=90.5%) and in high-risk populations, including patients with diabetes mellitus (52%, 95%CI: 44-59, I2=89.9%), obstructive sleep apnoea (63%, 95%CI: 47-76, I2=89.8%), and chronic kidney disease (58%, 95%CI: 54-61, I2=90.3%). Substantial heterogeneity was observed across studies, and pooled prevalence estimates should be interpreted in the context of population and methodological differences. Nocturnal hypertension is common across populations and particularly prevalent among individuals with hypertension and high-risk conditions such as diabetes and chronic kidney disease. Despite available diagnostic tools and effective treatments to lower nighttime BP, it remains substantially underdiagnosed. Evidence demonstrating that targeted reduction of nocturnal BP improves long-term cardiovascular outcomes is still limited. Future work should focus on establishing the clinical effectiveness of screening, diagnosis, and treatment of nocturnal hypertension.
Hypertension is the main risk factor for cardiovascular-related morbidities and mortalities. Nurses play a pivotal role in hypertension care, encompassing screening, detection, management, patient education and self-management counselling. This study assessed nurses' knowledge of hypertension care and associated factors in the Northern Region of Ghana. Tamale Metropolis of the Northern Region of Ghana. A descriptive cross-sectional study was conducted among nurses. Using a census approach, 410 eligible nurses working in hypertension care across the study hospitals were invited to participate. Of these, 266 consented and completed a self-reported validated questionnaire. The IBM Statistical Package for the Social Sciences programme version 30 was used to process the data and perform descriptive and inferential statistics. The mean hypertension care knowledge score was 51.47% ± 11.76%. About 4% had good knowledge, 57.1% average knowledge, and 38.7% had poor knowledge. While nurses demonstrated good knowledge of accurate blood pressure measurement (82.4%), their knowledge of hypertension diagnosis (35.1%) and management (48.8%) was poor. The following were significantly associated with overall knowledge of hypertension care: hospital of practice (p = 0.021), age (p = 0.007), nursing category (p = 0.002), qualification (p = 0.001), years of practice in the present unit (p = 0.021) and hypertension in-service training (p = 0.027). This study revealed significant gaps in nurses' knowledge of hypertension care and highlighted the need for continuous professional development to bridge knowledge gaps and sustain clinical competence. The study provided evidence on nurses' knowledge of hypertension care in Ghana, which can inform the development of tailored interventions to improve management and patient outcomes.
The SPHInX study is the first-ever randomized controlled trial (RCT) seeking to inform an area of equipoise regarding the efficacy of oral anticoagulation as adjunct therapy in systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH). The SPHInX study was an Australian multicenter, double-blind Phase III RCT of 1:1 oral apixaban 2.5 mg twice daily versus placebo over 3 years, as additional therapy in patients with SSc-PAH. The primary end-point was time to clinical worsening (TtCW), or death. A sample size of 85 per arm was required to show a two-fold reduction in TtCW. Participants experiencing clinical worsening events continued in the study, allowing for assessment of exploratory endpoints (including physical function and quality of life measures) up until 3 years of treatment. Among 11 SSc-PAH participants assigned apixaban treatment and 14 participants assigned placebo, apixaban demonstrated no benefit compared to placebo for TtCW from commencement until 30 days after discontinuation of study drug, Cox proportional hazard ratio 0.92 (95% confidence interval 0.32-2.66), p = 0.88. There was no difference between treatment groups in event-free survival, all-cause mortality, or exploratory endpoints. New iron deficiency anemia occurred in 9 (81.8%) apixaban treated participants compared to 4 (28.6%) controls. Although strict selection criteria in a complex disease meant recruitment was insufficient for the primary efficacy endpoint, the SPHInX RCT showed no signal for benefit with anticoagulation as adjunct therapy, with a high frequency of iron deficiency anemia suggesting that even at low doses, risk may outweigh benefit with anticoagulation in SSc-PAH. Trial Registration: Australian New Zealand Clinical Trials Registry Registration Number: ACTRN12614000418673 (http://www.ANZCTR.org.au/ACTRN12614000418673.aspx).
Hypertension is the leading global risk factor for mortality, causing over 10 million deaths annually. In sub-Saharan Africa, hypertension prevalence is high, particularly in rural areas, where it is less likely to be diagnosed, treated or controlled effectively. This results in a high burden of complications, including heart failure, stroke and kidney disease. Community-centred approaches using community health workers (CHWs), risk-based approaches and simplified treatment regimens have shown promise in improving hypertension management. However, there is limited evidence on the effectiveness of such approaches in rural sub-Saharan Africa.The primary aim of this study is to assess the feasibility of a community-centred intervention for hypertension management in rural Kenya and The Gambia. The objectives are to evaluate the intervention's adoption, fidelity, reach and dose; understand the mechanisms of action and contextual factors affecting its implementation; assess acceptability from the perspectives of patients, healthcare providers and policymakers; estimate the costs associated with the intervention; and evaluate study procedures to inform the design of a future full-scale trial. We will conduct a mixed-methods, non-randomised, single-arm feasibility study, designed in accordance with the Consolidated Standards of Reporting Trials (CONSORT) framework and checklist for feasibility and pilot studies, including best practice guidance for non-randomised feasibility studies. The study will be conducted in two rural sites: Kilifi, Kenya and Kiang West, The Gambia. The intervention was codesigned with stakeholders and includes community-based hypertension screening by CHWs, risk stratification and hypertension-mediated organ damage assessment at primary healthcare facilities, followed by treatment initiation using single-pill combination (SPC) antihypertensive therapy for eligible individuals. Training will be provided to all healthcare providers involved in the study. We will screen 500 participants aged 30-80 years at their residence (250 from each country), and we expect that about 45% will be referred for additional assessments and of these 25% (or 10% of the total sample) will be prescribed treatment with SPC. Data collection to evaluate the intervention and its implementation will involve quantitative measures of feasibility and clinical outcomes; observations to assess fidelity and costing measures; and qualitative interviews and focus group discussions with patients, healthcare providers and policymakers to understand the acceptability and contextual influences on intervention implementation. Ethics approval was obtained from the Kenyan National Committee for Science, Technology and Innovation (ref: 415561), the Gambia Government/Medical Research Council Joint Ethics Committee (ref: 31372) and the London School of Hygiene and Tropical Medicine Ethics Committee (ref: 31372). Study findings will be disseminated through peer-reviewed publications, conferences, policy briefs, community engagement forums and accessible summaries shared via the Improving Hypertension Control in Rural sub-Saharan Africa and partner newsletters. This study is registered with the ISRCTN- The UK's Clinical Study Registry (ISRCTN81228019), and Pan African Clinical Trials Registry (PACTR202504839027548).
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, potentially curable form of pulmonary hypertension, with limited data in pregnancy. We describe a 37-year-old woman with progressive dyspnea, back pain, and cough, whose evaluation revealed severe right ventricular enlargement, high pulmonary pressures, and extensive V/Q mismatches, confirming CTEPH. She underwent successful pulmonary thromboendarterectomy with marked hemodynamic recovery. An unrecognized early pregnancy, later confirmed after spontaneous miscarriage at 14 weeks, complicated the course. This case underscores the diagnostic challenges of CTEPH in women of reproductive age and highlights the impact of pregnancy-related hemodynamic stress on disease presentation.
Sympathetic nervous system over-activity is associated with liver disease progression and development of portal hypertension, influencing systemic inflammation. This study examined the role of the sympathetic-signalling alpha 2a adrenergic receptor (ADRA2a) and its antagonism on hepatic stellate cell (HSC) activation, as a key event in fibrosis progression in experimental metabolic dysfunction-associated steatohepatitis (MASH) and portal pressure elevation in a cirrhotic-rat model. An established bile duct ligation (BDL)-induced cirrhosis model (n=14) assessed ADRA2a's influence on portal hypertension by acute treatment with two different ADRA2a antagonists (BRL44408 and Yohimbine). Human (h)HSCs were incubated with either an ADRA2a agonist (guanfacine) or antagonist (BRL44408), to determine whether ADRA2a modulation altered HSC activation. We also investigated ADRA2a expression in patients with MASH fibrosis (n=15) and conducted a longer-term Yohimbine treatment study in a diet-induced MASH rodent model (n=24). BRL44408 reduced portal pressure in BDL rats (12±3 vs. 18 ± 4 mmHg; p<0.0001) whilst preserving mean arterial pressure (102±16 vs. 93±13mmHg, p=0.13), associated with (i) restored eNOS phosphorylation towards control levels and reduced Caveolin-1 (p<0.05); (ii) reduced hepatic inflammation, and Kuppfer cell activation (p<0.001). Moreover, Guanfacine stimulation of hHSC increased their contractility, which was attenuated by BRL44408 (p<0.001). In MASH patients with fibrosis and in MASH rats, hepatic ADRA2a mRNA expression was increased. In MASH rats, Yohimbine treatment reduced fibrosis (collagen-proportionate-area); p < 0.01. Our study shows that ADRA2a expression is increased in two experimental models of liver disease and in patients with MASH fibrosis and is implicated in the pathogenesis of portal hypertension and fibrogenesis. These data suggest that ADRA2a antagonism could be a potential target for treating portal hypertension and fibrosis progression. Managing fibrosis progression and portal hypertension remain challenges in liver disease, with for example less than 60% responding to current beta blocker therapy despite clear evidence for increased sympathetic activation as liver disease advances. We show that ADRA2a receptors may represent an important pathway for stellate cell activation and also influence other mechanisms that regulate rise in portal pressure. The results provide an alternative approach to beta blockade therapy for portal hypertension with their implicit drop in cardiac output and liver blood flow, which provide challenges in patients with advanced disease. The data from this study in two different rodent models supports considerations for a clinical translational study of ADRAa antagonism in portal hypertension, and for further mechanisms to be elaborated on the effects of ADRA2a antagonism in MASLD.
Hypertension remains a major global health challenge, with suboptimal treatment and blood pressure (BP) control rates and apparent or confirmed resistant hypertension (RHT) affecting approximately 10-20% of treated patients. Increasing evidence suggests that the gut microbiota may contribute to BP regulation through interconnected metabolic, immune-inflammatory, intestinal barrier, gut-brain, and gut-kidney pathways. Short-chain fatty acids (SCFAs) may support vasodilation, renal sodium handling, epithelial barrier integrity, and anti-inflammatory signaling through receptor- and tissue-specific mechanisms, whereas trimethylamine N-oxide (TMAO) has been associated with adverse vascular and cardio-renal phenotypes but may function either as a pathogenic mediator or as a biomarker of altered microbial-host metabolism or impaired renal clearance. Beyond the SCFA-TMAO axis, bile acid metabolism, tryptophan/indole derivatives, phenylacetylglutamine, uremic toxins, and the nitrate-nitrite-nitric oxide pathway provide additional mechanistic links between microbial ecology and BP phenotypes. This review synthesizes mechanistic, pharmacological, clinical, and translational evidence on microbiota-hypertension interactions, with particular emphasis on drug-microbiota bidirectionality. We propose a three-layer framework in which bacterial enzymatic transformation, host metabolic regulation, and epithelial transport/barrier functions jointly shape antihypertensive drug exposure and response. Human interventional evidence remains preliminary: colon-targeted acetylated and butyrylated high-amylose maize starch increased circulating SCFAs and reduced 24-hour systolic BP by approximately 5-6 mmHg in a small, short-duration trial of untreated essential hypertension, whereas probiotics and prebiotics generally show modest BP reductions of approximately 1-3 mmHg systolic and 1-2 mmHg diastolic in meta-analyses. These findings support microbiota-informed hypertension research and risk stratification, but clinical implementation, particularly in well-defined RHT populations, remains investigational.
The global demographic shift has highlighted the co-occurrence of hypertension (HTN) and physical frailty, both of which severely impact the health outcomes and quality of life of middle-aged and older adults. This relationship remains underexplored in India's rapidly aging population. We conducted a cross-sectional analysis using data from Longitudinal Aging Study in India (Wave 1), comprising a nationally representative sample of 66,606 participants. Physical frailty was assessed using a modified Fried phenotype. Multivariable logistic regression and the Karlson-Holm-Breen method were utilised to evaluate associations and quantify the mediating effect of additional comorbidities. The weighted prevalence of physical frailty among participants with HTN was 19.26% (95% CI: 18.43, 20.11). Multivariable analysis revealed that advanced age, lack of education, non-working status, underweight BMI, and presence of additional comorbidities were significantly associated with higher odds of frailty in HTN patients. Mediation analysis showed that additional comorbidities accounted for 21.31% of the total effect of HTN on frailty for all HTN cases, and 38.36% for previously diagnosed cases. Treating HTN in isolation might be insufficient for addressing functional decline. Healthcare policies and clinical practices must adopt comprehensive geriatric assessments that target patients' entire comorbid profiles, while prioritising interventions that address the modifiable risk factors. As the world’s population ages, managing conditions like high blood pressure (hypertension) and physical frailty (weakness and fatigue) is a major health challenge. We wanted to understand how these two conditions are linked in middle-aged and older adults living in India.We conducted data analysis of 66,606 adults who were aged 45 and above from a large national survey titled as Longitudinal Ageing Study in India. We looked at people with hypertension and checked how many of them were also physically frail.We discovered that nearly one in five middle-aged and older adults with hypertension were physically frail. People were more likely to be frail if they were aged over 75, had no formal education, were not working, were underweight, or had other health conditions.Upon advanced analysis, we observed that having other diseases alongside hypertension strongly overlapped with the presence of physical frailty.Managing hypertension on its own may not be enough to support middle-aged and older adults who face frailty. Doctors and healthcare policies need to look at the patient’s overall health, including all their other medical conditions. By focusing on improving nutrition, education, and overall disease management, we can better support middle-aged and older adults experiencing frailty.
The role of microRNA in primary hypertension remains unclear. This study examined the expression of microRNA-16, -21, -27a, -27b, -133a, and -145 in untreated hypertensive children, their response to aerobic exercise, and correlations with blood pressure and related parameters. A pre-post study, observational, hypothesis generating study included 56 hypertensive (SG - study group) and 59 healthy children (CG - control group). Plasma microRNA levels and clinical, biochemical, blood pressure, vascular, and hypertension-mediated organ damage (HMOD) parameters were assessed before and after one session of standardized aerobic exercise. The baseline relative microRNA-27b (p < 0.001) and microRNA-133a (p = 0.018) expressions were significantly lower in the SG; similarly, after an exercise bout. After an exercise bout, the expression of microRNA-27b, -133a, and -145 increased in CG, whereas only the expression of microRNA-145 increased in SG. In SG, microRNA-16, -21, -27a, and -145 correlated positively with pre-exercise blood pressure. There were no correlations between the analyzed microRNA particles and parameters of HMOD. ROC analysis identified the best prognostic profile for relative microRNA-27b expression as a potential biomarker of the absence of primary hypertension. Multivariate analysis revealed the relative microRNA-16 expression as the only significant predictor of elevated diastolic blood pressure. MicroRNA-27b, as well as microRNA-133a, are underexpressed in children with PH. These particles may represent potential markers of hypertension in children and may also be associated with a lower burden of hypertension-related alterations. MicroRNA-16 may serve as a marker of diastolic hypertension.
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While higher dietary quality scores for several established dietary indices has been consistently associated with lower risk of cardiovascular disease (CVD) and total mortality in the general population, limited evidence exists regarding their potential benefits among individuals with established hypertension. To examine the associations of dietary quality scores of multiple established dietary patterns with the risks of incident CVD and all-cause death among adults with hypertension, and to evaluate whether different dietary constructs exhibit heterogeneous prognostic relevance in this high-risk population. We analyzed 83,248 UK Biobank participants with hypertension and no prior CVD at baseline. Diet quality was assessed using repeated 24-hour recall questionnaires and scored according to five dietary indices: the Dietary Approaches to Stop Hypertension (DASH) score, the Alternative Healthy Eating Index-2010 (AHEI-2010), the Alternate Mediterranean Diet (AMED) score, the healthful Plant-Based Diet Index (hPDI), and the Empirical Dietary Inflammatory Pattern (EDIP). Each score was categorized into quintiles for analysis. The primary outcomes include a composite of nonfatal CVD events and cardiovascular death and all-cause mortality. Subgroup and interaction analyses were conducted across predefined clinical strata. During 1,230,983 person-years of follow-up, 4,889 primary CVD events were documented. After adjustment for demographic and cardiovascular risk factors, compared with the lowest quintile, the highest quintile of the DASH score was associated with significantly lower CVD risk (HR 0.85 [95% CI: 0.77-0.93]), as was the reversed EDIP score (HR 0.89 [0.81-0.97]). The AHEI-2010 score also showed a significant association (HR 0.91 [0.83-1.00]), while the AMED scores (HR 1.02 [0.93-1.11]) and hPDI (HR 0.95 [0.86-1.03]) were not significantly associated with CVD risk. All five dietary scores were inversely associated with all-cause mortality (Q5 vs Q1 HRs: 0.78-0.85; all P < 0.01), with the strongest association again observed for the DASH score. Food group-based analysis showed that higher intake of vegetables, whole grains, nuts and legumes, fruits, and dairy was significantly associated with lower CVD or mortality risk, whereas greater consumption of sugar-sweetened beverages and meats was significantly associated with higher risk (all P < 0.05). Among adults with hypertension, higher dietary quality scores of healthy dietary patterns, especially the DASH diet and reversed EDIP, were associated with lower risks of CVD and all-cause mortality.
Understanding how family history and genetic factors-particularly apolipoprotein L1 (APOL1) renal risk variants (RRVs)-contribute to kidney disease risk among Black individuals continues to evolve. In a cohort of prospectively enrolled Black adults who underwent APOL1 genotyping and completed surveys at a Midwestern U.S. academic hospital (01/24/2019-03/21/2025; NCT05656261), we examined APOL1 RRV distribution in relation to family history, baseline clinical factors, and 3-month renal function change. Among 220 eligible participants, 17% (37/220) carried APOL1 high-risk genotypes (two RRVs). Family history of hypertension alone was reported by 37% (81/220), kidney disease alone by 3% (6/220), and both by 49% (109/220). High-risk genotypes were more common among those with both hypertension and kidney disease in their family (18%) versus those without either (12%). High-risk APOL1 genotype prevalence rose with increasing antihypertensive medication use (24% among those prescribed ≥4 agents) and was higher among individuals with lower race-free estimated glomerular filtration rate (eGFR) or albuminuria. Among 173 participants with eGFR values at 3-months, high-risk genotypes were more frequent among those with eGFR decline versus improvement (23% vs. 12%). APOL1 high-risk genotypes were more common among individuals with a family history of hypertension and/or kidney disease, greater medication burden, lower kidney function, and early eGFR decline. The partial overlap between genetic and familial risk underscores the complex interplay of inherited, clinical, and environmental factors. Continued study and integrative strategies are needed to refine kidney disease risk stratification, enhance early identification, and guide prevention and treatment in at-risk populations.
Lung transplant provides a durable long-term option for group III pulmonary hypertension patients. Historically, bilateral lung transplant is the preferred option due to superior long-term survival. This benefit manifests itself after 2 years posttransplantation. Recipient medical urgency and organ availability may blunt the benefits of bilateral lung transplant over single lung transplant, necessitating alternative transplant strategies. We report a patient with group III pulmonary hypertension with clinical deterioration while awaiting double lungs who underwent salvage single lung transplant. The patient demonstrated excellent graft function with pulmonary hypertension resolution, highlighting the beneficial potential role of single lung transplant in this patient group.
Chronic Thromboembolic Pulmonary Hypertension (CTEPH), classified as group 4 pulmonary hypertension (PH), is a progressive disease caused by unresolved pulmonary artery thrombi that undergo organization and fibrosis, leading to increased pulmonary vascular resistance, right heart failure, and death. Over the past decade, the understanding, diagnosis, and management of CTEPH have undergone profound transformation. This review aims to summarize and discuss recent advances in CTEPH, focusing on pathophysiological mechanisms, diagnostic innovations, therapeutic evolution, and future directions. Current evidence establishes CTEPH as a complex, multifactorial disease involving genetic susceptibility, endothelial dysfunction, inflammation, and aberrant vascular remodeling-far beyond simple mechanical obstruction. In diagnosis, novel imaging modalities including ultra-high-resolution CT, dual-energy CT, computational fluid dynamics, and artificial intelligence have significantly enhanced the sensitivity, objectivity, and functional assessment of pulmonary vascular lesions. Therapeutically, a "three-pillar" paradigm is now firmly established, with pulmonary endarterectomy (PEA) as the curative cornerstone, complemented by balloon pulmonary angioplasty (BPA) and targeted pharmacotherapy (e.g., riociguat). This paradigm is increasingly evolving toward multimodal combination strategies, including preoperative bridging therapy and management of residual PH after intervention. Despite these advances, critical challenges remain: precise identification of operable patients, optimization of surgical and interventional techniques, development of novel targeted therapies, and construction of individualized prognostic models integrating multiomics and artificial intelligence. By addressing these core issues, this review provides a comprehensive, clinically oriented perspective on the current state and future trajectory of CTEPH research and multidisciplinary management, while also discussing emerging precision medicine approaches (e.g., multi-omics and artificial intelligence) that remain investigational.
Bilateral nephroblastoma, also known as Wilms tumor, represents a rare yet critical pediatric renal malignancy. Hypertensive emergencies with seizures are exceptional. We report the case of an 18-month-old girl who presented with status epilepticus secondary to malignant hypertension (180/120 mmHg) associated with a two-week history of abdominal distension. Clinical examination revealed bilateral lumbar masses, and computed tomography confirmed the presence of bilateral renal tumors, the largest measuring 102 × 80 × 100 mm. Neoadjuvant chemotherapy resulted in a partial response, with tumor size reduced to 69 × 60 × 63 mm, pending nephron-sparing surgery. Rapid diagnosis is crucial, as seizures presenting as the initial manifestation are rare and may delay recognition of the underlying abdominal pathology. Early imaging in cases of pediatric hypertension can prevent severe complications and improve outcomes, allowing renal preservation with survival rates exceeding 85%. Wilms tumor should be suspected in hypertensive toddlers presenting with abdominal signs, and prompt ultrasound evaluation is essential to avoid diagnostic delay and associated complications.
Federally Qualified Health Centers (FQHCs) serve as critical safety net providers for over 30 million patients annually, operating with diverse payer mixes that create unique financial and operational challenges. This study examined associations between payer mix patterns and clinical quality outcomes in FQHCs, comparing relationships between 2019 and 2022 to capture COVID-19-related coverage transitions. Using Resource Dependence Theory, we conducted a repeated cross-sectional analysis of Uniform Data System data from 1,190 FQHCs in 2019 and 1,150 FQHCs in 2022, examining eight clinical quality measures before (2019) and after (2022) the pandemic-driven coverage shifts. Multiple linear regression models with state-clustered robust standard errors assessed associations between payer mix proportions (Medicaid, Medicare, uninsured, with private insurance as reference) and quality performance, controlling for organizational characteristics. Results revealed complex, evolving relationships between payer mix and quality. In 2019, a 10 percentage point (pp) increase in Medicaid proportion was associated with lower performance on tobacco screening (-1.64 pp, p =.004), statin therapy (-1.43 pp, p = .014), and colorectal screening (-1.91 pp, p = .010). By 2022, tobacco screening associations reversed, with Medicaid (0.94 pp, p = .023) and uninsured (1.35 pp, p = .009) populations showing better performance than the privately insured. For outcome measures, higher proportions of Medicaid and uninsured patients were consistently associated with more patients with uncontrolled diabetes across both years, while higher Medicare proportions were associated with fewer patients with uncontrolled diabetes. Larger FQHCs showed better performance on process measures, while rural location was associated with lower cervical cancer screening rates but better hypertension control. These findings suggest that payer mix associations with quality are neither uniform nor stable over time, challenging assumptions about resource munificence and organizational performance in safety net settings. Policymakers should consider the dynamic nature of payer mix associations when designing payment models and quality improvement initiatives for FQHCs.
Immunoglobulin M nephropathy (IgMN) is a pathological term defining glomerulonephritis with IgM deposition. The clinical significance is still a matter of debate. The aim was to evaluate children with IgM nephropathy (IgMN) in terms of clinical and pathological features, along with treatment responses and outcomes. The children with idiopathic nephrotic syndrome (INS) who underwent kidney biopsy at our center (n=41) were evaluated retrospectively. Twenty-one children with IgMN were included. The female to male ratio was 0.9, the median age was 3.5 years in the study group. The mean disease duration and follow-up periods were 11.8 and 11.3years, respectively. At admission, 14% of the patients had hypertension, and 19% had microscopic hematuria. Steroid-dependent nephrotic syndrome (SDNS) was observed in 62% of the patients at admission and 81% at last visit. The patients with IgM (≥2+) depositions had more SDNS than those with IgM (1+). The most common light microscopic diagnosis was mesangial proliferative glomerulonephritis (MesPGN) (47.6%). Focal segmental glomerulosclerosis (FSGS) elevated significantly from 14% at initial biopsy to 57% at follow-up biopsies. Patients who progressed to FSGS mostly had C3 co-deposition, high IgM intensity (≥2+), diagnosis of MesPGN, and SDNS clinic. The most frequently used adjuvant agent was cyclosporine-A (n=19) with mean duration of 68 months. It provided lower relapse rates. Rituximab (n=4) showed 75% remission rate. None of the patients had needed renal replacement treatment. Two patients who were steroid-resistant at admission had FSGS in their first biopsies, acted as multi-drug resistance at follow-up, and ended up in Stage-2 chronic kidney disease (CKD). This study shows IgMN is mainly presented with SDNS clinic and MesPGN pathology. Evolution to FSGS may be related to steroid resistance, MesPGN, high IgM intensity, and C3 co-deposition.
Primary liver cancer (PLC) is a highly malignant disease, with an increasing incidence among the elderly population. However, there is a lack of systematic evaluation regarding its progression, recurrence, and prognostic factors. This study aims to investigate the clinicopathologic characteristics of elderly patients with PLC and to establish predictive models for overall survival and recurrence risk in this population. A retrospective analysis was conducted on 460 elderly PLC patients admitted to Longyou County People's Hospital from January 2018 to December 2019. According to pathological types, patients were classified into hepatocellular carcinoma group (HCC, n=395), intrahepatic cholangiocarcinoma group (ICC, n=49), and combined hepatocellular-cholangiocarcinoma group (CHC, n=16). Based on clinical outcomes, patients were further grouped as survivors (n=228) and non-survivors (n=232), or recurrence (n=223) and non-recurrence (n=237) groups. To validate the predictive models, 210 elderly patients with PLC from the same hospital, admitted between January 2020 and December 2020, were included as a verification cohort. Demographic and clinical data collected included age, sex, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-fetoprotein (AFP), tumor number, and tumor size. Univariate analysis was performed using the chi-square (χ2) test. Then, multivariate logistic regression analysis was performed to identify independent risk factors and establish predictive models for mortality and recurrence. A Random Forest model was also constructed for comparison. Model performance was assessed using the area under the receiver operating characteristic (ROC) curve (AUC) for discrimination, and the Hosmer-Lemeshow test for calibration. HCC predominated among male patients (P<0.05), with significantly higher AFP expression in males (P<0.05). Multivariate analysis identified age ≥80 years, AFP>400 ng/ml, multifocal tumors, tumor size >2 cm as independent predictors of mortality (all P<0.05). Additionally, hypertension, smoking, alcohol consumption, AFP>400 ng/ml, and tumor multiplicity were identified as independent predictors of postoperative recurrence (P<0.05). The constructed predictive models demonstrated good performance in both the training and validation cohorts. Comparative analysis showed similar predictive efficacy between logistic regression and Random Forest models (AUC for mortality prediction: 0.846/0.852 vs. 0.842/0.858, respectively; AUC for recurrence prediction: 0.756/0.762 vs. 0.761/0.764, respectively). The Hosmer-Lemeshow test suggested adequate model calibration (P>0.05). HCC is the most common form of PLC among elderly patients and is closely associated with metabolic and lifestyle factors. Advanced age, elevated AFP, multilocality, and larger tumor size increase mortality risk, while smoking and alcohol consumption further elevate recurrence risk. Early identification of high-risk patients, individualized intervention, and close postoperative follow-up focusing on modifiable risk factors are recommended to improve patient outcomes.