Huimin Zhang

Glucocorticoid-remediable aldosteronism (GRA) is an autosomal-dominant inherited aldosteronism that is often accompanied by early-onset hypertension. GRA is caused by the unequal crossover of the 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes. As a result of chimeric gene duplication, aldosterone is ectopically synthesized in the adrenal zona fasciculata under the control of adrenocorticotropic hormone (ACTH). Here, we describe a Chinese pedigree with three affected subjects. Both the uncle and nephew were hospitalized in our hospital due to early-onset hypertension (onset +). Captopril failed to suppress aldosterone secretion. This family had a strong paternal history of hypertension. Thirteen members underwent gene testing, and three of them were found to be GRA positive. Through long-extension PCR (XL-PCR) and direct sequencing, we identified the CYP11B1/CYP11B2 chimeric gene, and with unequal crossover breakpoints located between intron 2 of CYP11B1 and exon 3 of CYP11B2 in the three patients. Low-dose dexamethasone was effective. This is the first family report of GRA in northern China. Moreover, a case of GRA combined with a CACNA1H gene mutation is reported for the first time. We found that dihydropyridine calcium channel blockers (CCBs) combined with aldosterone receptor antagonists exerted good therapeutic effects in controlling blood pressure in GRA patients for whom glucocorticoid therapy was not an option.

Objective: Evidence-based studies on endovascular approaches for childhood Takayasu arteritis(c-TA) are limited. This study presented the real-world scenario of largest cohort up-to-date for c-TA patients undergoing interventions and their post-interventional outcomes. Design and method: Patients with c-TA satisfying the 1990 ACR or 2010 EULAR/PRINTO/PReS criteria were recruited from January 2002 to December 2017. Data on clinical, laboratory, imaging features, treatment and post-interventional outcomes were collected. Statistical analysis was performed based on data distribution. Complication-free survival and Re-intervention-free survival were projected by Kaplan-Meier methods and compared by Log-rank tests. Associated factors for intervention (or stenting) and predictors for post-interventional complications (or re-interventions) were assessed via Logistic regression and COX regression models, respectively. Results: Among 101 patients enrolled, 69(68.3%) underwent 121 interventions (Angioplasty 95; Stenting 26) during a median 3.1 years of follow-up. Compared with the medical treatment group, the intervention group appeared with fewer male population(18.8% vs 39.3%, OR = 0.2, p = 0.017) and more type IV disease(47.8% vs. 17.9%, OR = 10.60, p = 0.002). Male sex also indicated the risk for re-intervention(HR = 4.72, p = 0.016). Retinopathy(OR = 4.8, p = 0.027), time of delay in diagnosis per year(OR = 1.76, p = 0.016) and descending thoracic aorta involvement(OR = 10.19, p = 0.003) associated with stent insertion. Hypertension secondary to renal artery(59.4%) or mid-aorta(14.5%) stenosis, heart failure(21.7%), claudication(21.7%) served as leading clinical hints for interventions. Anti-inflammatory and anti-platelet therapies covered 89.9% and 91.3% patients, respectively. The technical success rate was 96.7%. Over median 2.88 years since intervention, 36 lesions occurred complications in 28 patients and 22 lesions in 17 patients, majorly on renal artery or mid-aorta. The 5-year complication-free and re-intervention survivals were 50.7% and 65.8%, separately. Dual antiplatelet therapy(HR = 0.28, p = 0.011), concurrent surgery(HR = 14.84, p = 0.002), retinopathy secondary to hypertension(HR = 3.54, p = 0.004), and pulmonary artery hypertension(HR = 3.0, p = 0.024) were independent predictors for complications. Conclusions: Over two-thirds c-TA patients require interventions and the 5-year complication-free survival is 50.7%. Male sex, retinopathy, and pulmonary artery hypertension alert unfavorable outcomes. Dual anti-platelet therapy appears to protect c-TA patients from post-interventional complications. Endovascular approaches can be a choice for mid-aorta and/or renal artery lesions caused by c-TA.

Background: Pheochromocytoma and paraganglioma is a rare disease with a prevalence of 0.2–0.6% in hypertensive patients from outpatient. Case summary: A 21-year-old man complained of blood pressure elevation over one year and persistent hyperhidrosis near 5 years. In local hospital, a mass in the pericardial space with abundant blood flow was observed via echocardiography and confirmed under minimally invasive thoracotomy. With suspicion of malignant cardiac mass, the patient was recommended to transfer for further diagnosis and treatment. Combining evaluation for blood and urinary catecholamine levels, somatostatin receptor imaging, and iodine-131 metaiodobenzylguanidine scintigraphy, he was confirmed with the diagnosis of cardiac paraganglioma with blood supply from the right coronary artery identified via angiography. The cardiac tumour was then surgically resected and confirmed with a pathological diagnosis of paraganglioma. Subsequent genetic test suggested succinate dehydrogenase complex iron sulfur subunit B (SDHB) gene mutation. At 5-month follow-up, the patient was recovered with normal levels of blood catecholamines and catecholamine metabolites. Discussion: Cardiac paraganglioma should be considered and evaluated in hypertensive patients with cardiac mass, even in non-typical population. Given a potential risk of developing malignancies, close follow-up is significant in patients with SDHB gene mutations.

Objective: Evidence‐based studies on endovascular approaches for childhood Takayasu arteritis (TAK) are limited. Our objective was to present the largest current real‐world scenario for patients with childhood TAK undergoing interventions and their postinterventional outcomes.Methods: Data were collected for patients with childhood TAK admitted from 2002 to 2017. Complication/reintervention‐free survival was projected by Kaplan‐Meier methods. Associated factors for intervention and predictors for postinterventional complications/reinterventions were assessed via regression models.Results: Among 101 patients enrolled, 69 (68.3%) underwent 121 interventions (angioplasty 95, stenting 26) during a 3.1‐year follow‐up. Compared with the nonintervention group, the intervention group independently associated with a male population (odds ratio [OR] 0.27, P = 0.035) and type IV disease (OR 17.92, P = 0.001). Male sex also marginally indicated a risk for reintervention (hazard ratio [HR] 3.22, P = 0.05). Baseline retinopathy, delay in diagnosis, and descending thoracic aorta involvement were associated with stent insertion (P < 0.05). Hypertension secondary to renal artery stenosis (RAS; 59.4%) or mid‐aorta stenosis (MAS; 14.5%), heart failure (21.7%), and claudication (21.7%) were leading clinical hints for interventions. The technical success rate was 96.7%. During a median 2.88‐year of follow‐up after intervention, 36 lesions occurred with complications in 28 patients, and 22 lesions in 17 patients, particularly on the renal artery or mid‐aorta. The 5‐year complication‐free and reintervention‐free survivals were 50.7% and 65.8%, respectively. Peri‐interventional dual antiplatelet therapy (DAPT; HR 0.31), concurrent surgery (HR 26.5), and technical failure (HR 3.65) were independent predictors for complications (P < 0.05). Male sex (HR 2.52), retinopathy secondary to hypertension (HR 3.41), and pulmonary artery hypertension (PAH; HR 3.64) were baseline indicators for complications (P < 0.05).Conclusion: Over two‐thirds of patients with childhood TAK require interventions, and the 5‐year complication‐free survival is 50.7%. Male sex, retinopathy, and PAH at baseline indicate the possibility of unfavorable outcomes. Interventions on MAS or RAS in childhood TAK raise specific concerns. DAPT peri‐intervention appears to protect patients with childhood TAK from postinterventional complications.

Objective The present study aimed to evaluate the value of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) aiding in diagnosing and evaluating disease activity in Takayasu arteritis (TA) patients with atypical clinical manifestations. Methods A retrospective study of 22 TA patients was conducted. All the participants were classified into two groups. Group one including 12 patients, who did not fulfill American College of Rheumatology (ACR) criteria, were diagnosed by modified Ishikawa criteria. Group two involving ten patients, who did not satisfy the modified Ishikawa criteria or ACR criteria, were clinically diagnosed as TA after panel discussion by a combination of clinical data, excluding other diagnoses. PET/CT results were analyzed using quantitative and qualitative metrics. Disease activity was evaluated using the US National Institutes of Health (NIH) criteria. Results In group one, nine patients in active stage and two patients in inactive stage had active FDG uptake. One patient in inactive stage had inactive PET/CT results. In group two, five patients in active stage had active FDG uptake and five patients in inactive stage had inactive FDG uptake with SUVmax values of several vascular lesions slightly lower than livermean in each person. The sensitivity of PET/CT scans for evaluating disease activity was 100.0%, specificity was 75.0%, positive predictive value was 87.5%, and negative predictive value was 100.0% compared to NIH criteria. Conclusions PET/CT plays a unique role in diagnosing these TA with atypical manifestation and assisting in evaluating disease activity. Key Points • Diagnosis of these TA patients with atypical manifestations may be difficult. • PET/CT plays a unique role in diagnosing these TA patients and assisting in evaluating disease activity.

Following publication of the original article [1], the authors reported an error.

Childhood Takayasu’s arteritis (c-TA) is scarcely reported but is characterized by devastating morbidity and mortality. This study aims to investigate the clinical course of c-TA and prognostic factors associated with rehospitalization and events including vascular complications, flares, and death. An ambispective study of 101 c-TA patients satisfying the American College of Rheumatology (ACR) criteria and/or the European League against Rheumatism (EULAR)/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS) criteria was conducted from January 2002 to December 2017. Data on demographic, clinical, laboratory, imaging, and therapeutic features were collected. Event-free survival, complication-free survival, flare-free survival, rehospitalization-free survival, and associated prognostic factors were assessed by Kaplan-Meier survival curve and propensity score analysis. The median age at c-TA onset was 14 (interquartile range (IQR) 12–16) years and 76.2% were female. Hypertension (70.3%), blood pressure discrepancy (55.4%), bruits (51.5%), and pulse deficits (37.6%) were core presentations. Major vascular involvement included the renal artery (62.4%), abdominal aorta (42.6%), subclavian artery (43.6%), and carotid artery (42.6%). Glucocorticoids (78.2%), antihypertensive drugs (72.3%), antiplatelet agents (72.3%), and revascularization (57.4%) were made up the majority administered. At a median 2.4 (IQR 0.7–6.1) years of follow-up, events, rehospitalization, vascular complications, flares and death were observed in 44.6%, 37.6%, 44.6%, 26.7%, and 3%, respectively. The 5-year event-free survival, rehospitalization-free survival, vascular complication-free survival, and flare-free survival were 42.8%, 55.8%, 45.9%, and 62.3%, respectively. Body mass index (BMI) (hazard ratio (HR) = 0.49, 95% confidence interval (CI) 0.30–0.81, p = 0.005), stroke (HR = 7.37, 95% CI 2.35–23.1, p = 0.001), and revascularization (HR = 0.51, 95% CI 0.27–0.94, p = 0.032) were independent prognostic predictors of events. Predictors for rehospitalization include age at admission (HR = 0.81, 95% CI 0.69–0.94, p = 0.006), renal artery involvement (HR = 0.49, 95% CI 0.25–0.96, p = 0.037), and elevated C-reactive protein (CRP; HR = 2.50, 95% CI 1.24–5.00, p = 0.01). BMI level (p = 0.024) and renal artery involvement (p = 0.015) were also associated with vascular complications, while revascularization (p = 0.002) independently correlated with re-flares. This large ambispective study of c-TA revealed an early 3% mortality at the first year and around 50% morbidity within 5 years after diagnosis. Hypertension, renal artery involvement, and revascularization based on anti-inflammation, antihypertension, and antiplatelet medications dominated c-TA with indications for optimistic prognosis. Patients with initial lower BMI level, a younger age at admission, stroke, and elevated CRP have a high risk of poor outcomes, requiring close c-TA monitoring and more aggressive management. NCT03199183 , unique protocol ID: 2016-ZX43. June 26, 2017

The objective of this study was to explore the presentation and management of hypertension secondary to Takayasu arteritis (TA) in a large cohort, single center in China. We retrospectively analyzed 381 TA patients with hypertension hospitalized in Fuwai hospital between Jan. 2004 and Feb. 2014. Diagnosis of hypertension was according to clinic blood pressure or the central blood pressure measured during angiography. Renal artery stenosis was the most common cause (264, 69.3%), followed by the thoracic descending aorta stenosis (98, 25.7%), abdominal aorta stenosis (78, 20.5%), and severe aortic regurgitation (45, 11.8%). More than two kinds of pathologies were found in 98 (25.7%) patients. The mean age of hypertension onset was 25.0 ± 14.3 years. The mean blood pressure of upper extremity in patients without bilateral subclavian artery stenosis (321, 84.3%) was 176.0 ± 29.4 mmHg/97.2 ± 23.0 mmHg, while in 60 (15.7%) patients with bilateral subclavian artery stenosis, the mean central blood pressure was 192.7 ± 30.8 mmHg/102.4 ± 121.1 mmHg. A total of 305 were followed for 38.4 ± 36.7 months, and the rate of blood pressure control, improvement, and failure was 50.8, 41.0, and 8.2%, respectively. Immunosuppressive therapy (OR 2.402, 95% confidence interval 1.253–4.603, P = 0.008) and the pathogenesis of hypertension (P = 0.010) were associated with prognosis of hypertension. The pathogenesis of hypertension due to TA is very complex and multifactorial. Renal artery stenosis is most frequently observed, followed by stenosis of the thoracic descending aorta, abdominal aorta, and severe aortic regurgitation. Immunosuppressive therapy and identifying the pathogenesis of hypertension is of great importance in patients with TA.

Hypoxemia sometimes occurs in the emergency room in the patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI), even in those with administration of conventional high-flow oxygen inhalation. The objective of the present study was to evaluate the effectiveness of non-invasive ventilation (NIV) in improving blood oxygen content and hemorheology in patients with AMI and hypoxemia. This prospective study enrolled 50 consecutive eligible patients with AMI (aged 72.3 ± 9.5 years), who had undergone PCI and been administered high-flow oxygen but still had hypoxemia. Blood was taken before NIV and at 0.5, 1, and 2 h after NIV. Blood gases, hemorheological variables including erythrocyte deformability, erythrocyte aggregation, erythrocyte osmotic fragility, membrane fluidity, and oxidative stress level were measured. Blood PaO2 increased to normal by 1 h after NIV. Assessed hemorheological variables had all improved and plasma malondialdehyde concentration decreased significantly after 2 h of NIV. Our data suggest that NIV can help to improve blood oxygen content, hemorheological status, and minimize plasma lipid peroxidation injury in hypoxemic patients with AMI who have undergone PCI.