Monitoring of the Healthy Neonatal Transition Period with Serial Lung Ultrasound.

Ultrasound has been used to observe lung aeration and fluid clearance during the neonatal transition period, but there is no consensus regarding the optimal timing of lung ultrasound. We aimed to monitor the trend of the serial lung ultrasound score (LUS) and extended LUS (eLUS) throughout the neonatal transition period (≤1, 2, 4, 8, 24, and 48 h after birth), assess any correlation to the clinical presentation (using the Silverman Andersen Respiratory Severity Score (RSS)), and determine the optimal time of the ultrasound. We found both LUS and eLUS decreased significantly after 2 h of life and had similar statistical differences among the serial time points. Although both scores had a positive, moderate correlation to the RSS overall (Pearson correlation 0.499 [p < 0.001] between LUS and RSS, 0.504 [p < 0.001] between eLUS and RSS), the correlation was poor within 1 h of life (Pearson correlation 0.15 [p = 0.389] between LUS and RSS, 0.099 [p = 0.573] between eLUS and RSS). For better clinical correlation, the first lung ultrasound for the neonate may be performed at 2 h of life. Further research is warranted to explore the clinical value and limitations of earlier (≤1 h of life) lung ultrasound examinations.

Markers of Kidney Tubular Function Deteriorate While Those of Kidney Tubule Health Improve in Primary Aldosteronism After Targeted Treatments.

Background Targeted treatment with mineralocorticoid receptor antagonists (MRAs) or adrenalectomy in patients with primary aldosteronism (PA) causes a decline in estimated glomerular filtration rate; however, the associated simultaneous changes in biomarkers of kidney tubule health still remain unclear. Methods and Results We matched 104 patients with newly diagnosed unilateral PA who underwent adrenalectomy with 104 patients with unilateral PA who were treated with MRAs, 104 patients with bilateral PA treated with MRAs, and 104 patients with essential hypertension who served as controls. Functional biomarkers were measured before the targeted treatment and 1 year after treatment, including serum markers of kidney function (cystatin C, creatinine), urinary markers of proximal renal tubular damage (L-FABP [liver-type fatty-acid binding protein], KIM-1 [kidney injury molecule-1]), serum markers of kidney tubular reserve and mineral metabolism (intact parathyroid hormone), and proteinuria. Compared with the patients with essential hypertension, the patients with PA had higher pretreatment serum intact parathyroid hormone and urinary creatinine-corrected parameters, including L-FABP, KIM-1, and albumin. The patients with essential hypertension and with PA had similar cystatin C levels. After treatment with MRAs or adrenalectomy of unilateral PA and MRAs of bilateral PA, the patients with PA had increased serum cystatin C and decreased urinary L-FABP/creatinine, KIM-1/creatinine, creatinine-based estimated glomerular filtration rate, intact parathyroid hormone, and proteinuria (all P<0.05). In multivariable regression models, a higher urinary L-FABP/creatinine ratio and older age were significantly correlated with the occurrence of kidney failure (estimated glomerular filtration rate dip ≥30%) in the patients with PA after targeted treatment. Conclusions Compared with the matched patients with essential hypertension, the incident patients with PA at diagnosis had higher levels of several biomarkers, including markers of kidney damage, tubular reserve/mineral metabolism, and proteinuria. Functional kidney failure in the patients with PA after treatment could be predicted by a higher baseline urinary L-FABP/creatinine ratio and older age. After targeted treatments in the patients with bilateral or unilateral PA, these biomarkers of kidney tubule health were restored, but creatinine-based estimated glomerular filtration rate declined, which may therefore reflect hemodynamic changes rather than intrinsic damage to kidney tubular cells.

The Imposter Dance of Alternating QRS Complexes.

This case report describes a patient in their late 50s with acute onset chest pain with diaphoresis.

Cortisol-producing adenoma-related somatic mutations in unilateral primary aldosteronism with concurrent autonomous cortisol secretion: their prevalence and clinical characteristics.

Objective: Concurrent autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) is being reported more frequently. Several somatic mutations including PRKACA, GNAS, and CTNNB1 were identified in cortisol-producing adenomas (CPAs). The presence of these mutations in unilateral PA (uPA) patients concurrent with ACS (uPA/ACS) is not well known. This study aimed to investigate the prevalence of these mutations and their clinical vs pathological characteristics in uPA/ACS. Design: This is a retrospective cohort study. Methods: Totally 98 uPA patients from the Taiwan Primary Aldosteronism Investigation registry having overnight 1-mg dexamethasone suppression test (DST) and adrenalectomy from 2016 to 2018 were enrolled. Their adrenal tumors were tested for PRKACA, GNAS, and CTNNB1 mutations. Results: 11 patients had CPA-related mutations (7 PRKACA and 4 GNAS). The patients carrying these mutations had higher post-DST cortisol (5.6 vs 2.6 µg/dL, P = 0.003) and larger adenoma (2.2 ± 0.3 vs 1.9 ± 0.7 cm, P = 0.025). Adenomas with these mutations had a higher prevalence of non-classical uPA (72.7% vs 26.3%, P = 0.014). Numerically, slightly more complete clinical success of uPA patients with these mutations was noticed after adrenalectomy, although it was statistically non-significant. Post-DST cortisol levels, adenoma size >1.9 cm, and the interaction of adenoma size >1.9 cm with potassium level were found to be associated with the presence of these mutations. Conclusion: Our study showed that CPA-related mutations were detected in 36.7% of uPA/ACS adenomas. The presence of these mutations was associated with higher post-DST cortisol levels, larger adenoma sizes, and a high percentage of non-classical uPA. However, these mutations did not significantly affect the clinical and biochemical outcomes after adrenalectomy of uPA/ACS patients but they showed a better trend.

Synergistic Effects of Inflammation and Atherogenic Dyslipidemia on Subclinical Carotid Atherosclerosis Assessed by Ultrasound in Patients with Familial Hypercholesterolemia and Their Family Members.

Low-density lipoprotein cholesterol (LDL-C) and total to high-density lipoprotein cholesterol (TC/HDL-C) ratio are both common risk factors for atherosclerotic cardiovascular diseases (ASCVDs). However, whether high-sensitivity C-reactive protein (hsCRP) has synergistic or attenuated effects on atherogenic dyslipidemia remains unclear. We investigated subclinical carotid atherosclerosis in patients with familial hypercholesterolemia (FH) and their family members. A total of 100 families with 761 participants were prospectively studied. Participants were categorized into four groups according to atherogenic dyslipidemia and inflammatory biomarkers. The group with LDL-C ≥ 160 mg/dL (or TC/HDL-C ratio ≥ 5) combined with hsCRP ≥ 2 mg/L have a thicker carotid intima-media thickness (CIMT) in different common carotid artery (CCA) areas and a higher percentage of high plaque scores compared with other subgroups. Multivariate logistic regression analysis revealed a significantly higher adjusted odds ratio (aOR) for thicker CIMT of 3.56 (95% CI: 1.56-8.16) was noted in those with concurrent LDL-C ≥ 160 mg/dL and hsCRP ≥ 2 mg/L compared with the group with concurrent LDL-C < 160 mg/dL and hsCRP < 2 mg/L. Our results demonstrated that systemic inflammation, in terms of higher hsCRP levels ≥ 2 mg/L, synergistically contributed to atherogenic dyslipidemia of higher LDL-C or a higher TC/HDL-C ratio on subclinical atherosclerosis.

Transtubular potassium gradient predicts kidney function impairment after adrenalectomy in primary aldosteronism.

BACKGROUND: In primary aldosteronism (PA), kidney function impairment could be concealed by relative hyperfiltration and emerge after adrenalectomy. We hypothesized transtubular gradient potassium gradient (TTKG), a kidney aldosterone bioactivity indicator, could correlate to end organ damage and forecast kidney function impairment after adrenalectomy. METHODS: In the present prospective study, we enrolled lateralized PA patients who underwent adrenalectomy and were followed up 12 months after operation in the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry from 2010 to 2018. The clinical outcome was kidney function impairment, defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 at 12 months after adrenalectomy. End organ damage is determined by microalbuminuria and left ventricular mass. RESULTS: In total, 323 patients [mean, 50.8 ± 10.9 years old; female 178 (55.1%)] were enrolled. Comparing pre-operation and post-operation data, systolic blood pressure, serum aldosterone, urinary albumin to creatinine ratio and eGFR decreased. TTKG ⩾ 4.9 correlated with pre-operative urinary albumin to creatinine ratio >50 mg/g [odds ratio (OR) = 2.42; p = 0.034] and left ventricular mass (B = 20.10; p = 0.018). Multivariate logistic regression analysis demonstrated that TTKG ⩾ 4.9 could predict concealed chronic kidney disease (OR = 5.42; p = 0.011) and clinical success (OR = 2.90, p = 0.017) at 12 months after adrenalectomy. CONCLUSIONS: TTKG could predict concealed kidney function impairment and cure of hypertension in PA patients after adrenalectomy. TTKG more than 4.9 as an adverse surrogate of aldosterone and hypokalaemia correlated with pre-operative end organ damage in terms of high proteinuria and cardiac hypertrophy.

Influence of Different Treatment Strategies on New-Onset Atrial Fibrillation Among Patients With Primary Aldosteronism: A Nationwide Longitudinal Cohort-Based Study.

Background Primary aldosteronism (PA) is associated with higher atrial fibrillation prevalence and other cardiovascular complications. However, the effect of target treatment to prevent new-onset atrial fibrillation (NOAF) remains unclear. This study investigated incidence of NOAF under different treatment strategies in patients with PA. Methods and Results We analyzed longitudinal data for patients with PA without atrial fibrillation history from 1997 to 2009 within the National Health Insurance Research Database in Taiwan. Patients with essential hypertension matched by propensity score were enrolled as controls. The primary outcome measurement was NOAF, and secondary outcome measurements were mortality, major cardiac and cardiac/cerebrovascular events, and a combined end point of NOAF and mortality. We identified 2202 patients with PA (534 adrenalectomy, 1668 mineralocorticoid receptor antagonist [MRA] therapy) and 8808 essential hypertension controls with mean follow-up of 4.4 years. In primary outcome measurement, patients with PA who underwent adrenalectomy had a lower incidence of NOAF (adjusted hazard ratio; 0.28, P=0.011) than controls. In contrast, the patients with PA who received MRA therapy had comparable risk of NOAF (adjusted hazard ratio, 1.20; P=0.224). In secondary outcome measurement, patients with PA who underwent adrenalectomy had a lower rate of mortality and combined end point of NOAF and mortality than controls. Patients with PA who received MRA therapy had a higher risk of mortality, major cardiac and cardiac/cerebrovascular events, and combined NOAF with mortality than the essential hypertension controls. Conclusions Compared with patients with essential hypertension, patients with PA who underwent adrenalectomy had a lower incidence of NOAF. However, this finding was not observed in patients with PA who received MRA therapy with a lower dose. Differences between the 2 strategies may reduce with a higher dose of MRA therapy.

Surgery decreases the long-term incident stroke risk in patients with primary aldosteronism.

BACKGROUND: Hypertension with hyperaldosteronism could be associated with stroke attributable to endothelial injury. Whether the detrimental effect of aldosterone on stroke among primary aldosteronism patients could be mitigated by administration of mineralocorticoid receptor antagonist or by reduction of aldosterone level via adrenalectomy is still inconclusive. METHODS: Primary aldosteronism and essential hypertensive patients were enrolled in the Taiwan National Health Insurance from 1997 to 2009. We used a validated algorithm to enroll primary aldosteronism patients. We conducted a competing risk analysis, using a time-varying Cox proportional hazard model. RESULTS: We enrolled 3,167 primary aldosteronism patients with a subgroup of 1,047 aldosterone-producing adenoma patients, and matched these with essential hypertensive controls in a 1:4 ratio. The risk of incident stroke, both ischemic and hemorrhagic, was statistically higher in primary aldosteronism patients than in their essential hypertensive control. The differences in stroke incidences between primary aldosteronism and essential hypertensive patients significantly increased as the hypertensive period lengthened. Primary aldosteronism patients who received mineralocorticoid receptor antagonist treatment had higher risk of all stroke (competing hazard ratio = 1.83, P < .001) compared with their essential hypertensive controls. In light of this, aldosterone-producing adenoma patients had a lower risk of incident stroke after adrenalectomy (competing for hazard ratio = 0.75), but a higher cumulative risk of incident stroke after mineralocorticoid receptor antagonist only (competing for hazard ratio = 1.76) than their matched essential hypertensive patients. CONCLUSION: We observed an increased stroke risk among primary aldosteronism patients than among their matched essential hypertensive controls. A prolonged duration of hypertension was proportionate to the raised risk of stroke. Our findings emphasize the importance of aldosterone-producing adenoma benefitting from adrenalectomy in attenuating the cerebrovascular event.

Incidental Congestive Heart Failure in Patients With Aldosterone-Producing Adenomas.

Background Previous studies show that patients with primary aldosteronism are associated with higher risk of congestive heart failure (CHF). However, the effect of target treatment to the incidental CHF has not been elucidated. We aimed to investigate the risk of new-onset CHF in patients with aldosterone-producing adenomas (APAs) and explore the effect of adrenalectomy on new onset of CHF. Methods and Results From 1997 to 2009, 688 APA were identified and matched with essential hypertension controls. The risks of developing incidental CHF (hazard ratio, 0.49; 95% CI, 0.31-0.75; P=0.001) and mortality (hazard ratio, 0.29; 95% CI, 0.20-0.44; P<0.001) were significantly lower in the APA group after targeted treatment. A total of 605 patients with APAs who underwent adrenalectomy lowered the risks of CHF (subdistribution hazard ratio, 0.55; 95% CI, 0.34-0.90; P=0.017) and mortality (adjusted hazard ratio, 0.27; 95% CI, 0.16-0.44; P<0.001) compared with essential hypertension controls. Conclusions In conclusion, for patients with APAs, adrenalectomy can be associated with lower risk of incidental CHF and all-cause mortality in a long-term follow-up.

Plasma Aldosterone After Seated Saline Infusion Test Outperforms Captopril Test at Predicting Clinical Outcomes After Adrenalectomy for Primary Aldosteronism.

OBJECTIVE: The saline infusion test (SIT) and the captopril test (CT) are widely used as confirmatory tests for primary aldosteronism (PA). We hypothesized that post-SIT and post-CT plasma aldosterone concentrations (PAC) indicate the severity of aldosterone-producing adenoma (APA) and might predict clinical outcome. METHODS: We recruited 216 patients with APA in the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry who received both seated SIT and CT as confirmatory tests. The data of 143 patients who underwent adrenalectomy with complete follow-up after diagnosis were included in the final analysis. We determined the proportion of patients achieving clinical success in accordance with the Primary Aldosteronism Surgical Outcome consensus. Logistic regression analysis was conducted to identify preoperative factors associated with cure of hypertension. RESULTS: Complete clinical success was achieved in 48 (33.6%) patients and partial clinical success in 59 (41.2%) patients; absent clinical success was seen in 36 (25.2%) of 143 patients. Post-SIT PAC but not post-CT PAC was independently associated with clinical outcome. Higher levels of post-SIT PAC had a higher likelihood of clinical benefit (complete plus partial clinical success; odds ratio = 1.04 per ng/dl increase, 95% confidence interval = 1.01, 1.06; P = 0.004). Patients with post-SIT PAC > 25 ng/dl were more likely to have a favorable clinical outcome after adrenalectomy. This cutoff value translated into a positive predictive value of 86.0%. CONCLUSIONS: We suggest that post-SIT PAC is a better predictor than post-CT PAC for clinical success in PA post adrenalectomy.

Adrenalectomy Improves the Long-Term Risk of End-Stage Renal Disease and Mortality of Primary Aldosteronism.

OBJECTIVE: Primary aldosteronism (PA) is a common cause of secondary hypertension, and the long-term effect of excess aldosterone on kidney function is unknown. PATIENTS AND METHODS: We used a longitudinal population database from the Taiwan National Health Insurance system and applied a validated algorithm to identify patients with PA diagnosed between 1997 and 2009. RESULTS: There were 2699 patients with PA recruited, of whom 761 patients with an aldosterone-producing adenoma (APA) were identified. The incidence rate of end-stage renal disease (ESRD) was 3% in patients with PA after targeted treatments and 5.2 years of follow-up, which was comparable to the rate in controls with essential hypertension (EH). However, after taking mortality as a competing risk, we found a significantly lower incidence of ESRD when comparing patients with PA vs EH [subdistribution hazard ratio (sHR), 0.38; P = 0.007] and patients with APA vs EH (sHR 0.55; P = 0.021) after adrenalectomy; however, we did not see similar results in groups with mineralocorticoid receptor antagonist (MRA)‒treated PA vs EH. There was also a significantly lower incidence of mortality in groups with PA and APA who underwent adrenalectomy than among EH controls (P < 0.001). CONCLUSION: Regarding incident ESRD, patients with PA were comparable to their EH counterparts after treatment. After adrenalectomy, patients with APA had better long-term outcomes regarding progression to ESRD and mortality than hypertensive controls, but MRA treatments did not significantly affect outcome.

Reconstruction of reference error in high overlapping density subaperture stitching interferometry.

The vibration modulated stitching interferometry acquires many subaperture phases timely forming the high overlapping density subapertures for asphere phase stitching. The large number of overlapping subapertures had been proven effective in suppressing the reference error. In this research, we propose a pixel-by-pixel reference calibration method by using the averaged difference between the stitched phase and compensated phase within the overlapping subapertures. The measurement for both tested optics and calibration of the reference optics are accomplished in a single phase stitching process. The requirement for a high-quality reference optics or dedicated reference calibration procedure for subaperture stitching interferometry is therefore significantly eliminated. Both the simulation and experimental results shows the feasibility of the proposed method for high frequency reference error and most of the form error in the third order Zernike aberrations.

Identification of a novel LDLR disease-causing variant using capture-based next-generation sequencing screening of familial hypercholesterolemia patients in Taiwan.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is an autosomal dominant disorder with paramount health impacts. However, less than 1% FH patients in Taiwan were formally diagnosed, partly due to the lack of reliable cost-effective genetic testing. We aimed at using a next-generation sequencing (NGS) platform as the clinical genetic testing method for FH. METHODS: We designed probes to capture the whole LDLR gene and all coding sequences of APOB and PCSK9, and then sequenced with Illumina MiSeq platform (2 × 300 bps). The entire pipeline was tested on 13 DNA samples with known causative variants (including 3 large duplications and 2 large deletions). Then we enrolled a new cohort of 28 unrelated FH patients with Dutch Lipid Clinic Network score ≥5. Relatives were included in the cascade screening. RESULTS: From the 13 DNA samples, we correctly identify all the variants, including big duplications and deletions. From the new cohort, we identified the causative variants in 21 of the 28 unrelated probands; five of them carrying a novel splice site variant c.1186+2T>G in LDLR. Among the family members, the concentration of LDL cholesterol was 7.82 ±â€¯2.13 mmol/l in LDLR c.1186+2T>G carrier group (n = 26), and was significantly higher than 3.18 ± 1.36 mmol/l in the non-carrier group (n = 25). CONCLUSIONS: This is the first capture-based NGS testing for FH to cover the whole LDLR genomic region, and therefore making reliable structural variation detection. This panel can comprehensively detect disease-causing variants in LDLR, APOB, and PCSK9 for FH patients.

Risk of Fracture in Primary Aldosteronism: A Population-Based Cohort Study.

Primary aldosteronism (PA) is associated with increased urinary calcium excretion and osteoporosis prevalence. We studied the long-term effect of hyperaldosterone on fracture risk and possible risk mitigation via treatments, by comparing PA patients and their essential hypertension (EH) counterparts extracted by propensity score match. We used a longitudinal population database from the Taiwan National Health Insurance, and used a validated algorithm to identify PA patients diagnosed in 1997-2010. Our sample included 2533 PA patients, including 921 patients with aldosterone-producing adenoma (APA). Our methods for assessing excessive fracture risk included multivariable Cox regression and the competing risk regression. The incidence rate of fracture at any site was 14.4 per 1000 person-years for PA, and 11.2 per 1000 person-years for APA. In contrast, the incidence rate of fracture at any site was 8.3 per 1000 person-years in EH controls for PA, and 6.5 per 1000 person-years in EH controls for APA. Mineralocorticoid receptor antagonist (MRA) treatment might be associated with higher risk of osteoporotic fracture in the whole female PA cohort (subdistribution hazard ratio [SHR] = 2.12, p = 0.008) as well as female APA patients (SHR = 1.15, p = 0.049). As to fracture at any site, MRA treatment was also associated with higher risk; the SHR was 1.88 (p < 0.001) in the whole female PA cohort, and 2.17 (p = 0.019) in female APA patients. PA is tightly associated with higher risk of bone fracture, even in the case where the competing risk of death was controlled. Particularly, female PA patients treated with MRA were confronted with significantly higher risk in bone fracture than their EH controls. © 2017 American Society for Bone and Mineral Research.

Clinical and Imaging Outcomes up to 1 Year Following Balloon Angioplasty for Isolated Penile Artery Stenoses in Patients With Erectile Dysfunction: The PERFECT-2 Study.

PURPOSE: To assess the angiographic and clinical outcomes in patients with erectile dysfunction and isolated penile artery stenoses treated by balloon angioplasty. METHODS: In this prospective study, 22 patients (mean age 61.0±7.6 years, range 50-79) with erectile dysfunction and 34 isolated penile artery stenoses (mean 74.9%±9.1%) were enrolled and underwent balloon angioplasty. The mean International Index for Erectile Function-5 (IIEF-5) score at baseline was 10.3±4.5. The mean lesion length was 11.1±9.0 mm (mean reference vessel diameter 1.7±0.4 mm). The primary endpoint was in-segment restenosis ≥50% by pelvic computed tomography angiography (CTA) at 8 months. The 1-year sustained clinical success (IIEF-5 score ≥22 or a ≥4-point change in the IIEF-5 score and no later decline by ≥4) was the secondary outcome measure. RESULTS: Procedural success was achieved in 31 (91%) of 34 stenotic lesions; there was 1 flow-limiting dissection and 2 arteries with >30% residual stenosis. At 8 months, 14 of 34 lesions in 13 of 22 patients had CTA-documented binary restenosis. At 1 year, sustained clinical success was achieved in 11 of 22 patients. Of the 9 patients not developing binary restenosis, 8 achieved sustained clinical success. CONCLUSION: Our findings establish the safety and efficacy of penile artery angioplasty for patients with erectile dysfunction and isolated penile artery stenoses. They also highlight the unmet need for a more enduring treatment strategy for penile artery stenotic disease.

The Emerging Roles of Coronary Computed Tomographic Angiography: Acute Chest Pain Evaluation and Screening for Asymptomatic Individuals.

UNLABELLED: Coronary computed tomographic angiography (CCTA) has been widely available since 2004. After that, the diagnostic accuracy of CCTA has been extensively validated with invasive coronary angiography for detection of coronary arterial stenosis. In this paper, we reviewed the updated evidence of the role of CCTA in both scenarios including acute chest pain and screening in asymptomatic adults. Several large-scale studies have been conducted to evaluate the diagnostic value of CCTA in the context of acute chest pain patients. CCTA could play a role in delivering more efficient care. For risk stratification of asymptomatic patients using CCTA, latest studies have revealed incremental benefits. Future studies evaluating the totality of plaque characteristics may be useful for determining the role of noncalcified plaque for risk stratification in asymptomatic individuals. KEY WORDS: Acute chest pain • Computed tomography • Coronary artery disease • Health screening • Stable angina.

Measurement improvement by high overlapping density subaperture stitching interferometry.

The vibration-modulated subaperture stitching interferometer acquires the interferogram on the fly dynamically. With its highly improved measurement throughput, we applied the device for high overlapping density subaperture stitching interferometry to acquire hundreds of overlapping subapertures in a single phase stitching measurement. The averaging effect of the high overlapping density stitching interferometer is discussed. In the experiment, the proposed high overlapping density stitching interferometer is also proved to reduce measurement uncertainty and improve measurement quality effectively.