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Background: Cardiopulmonary exercise testing (CPET) variables represent central and peripheral factors and combined factors in the pathology of patients with cardiac disease. The difference in end-tidal oxygen partial pressure from resting to anaerobic threshold (ΔPETO 2 ) may represent predominantly peripheral factors. This study aimed to verify the prognostic significance of ΔPETO 2 for major adverse cardiac and cerebrovascular events (MACCE) in cardiac patients, including comparison with the minute ventilation-carbon dioxide production relationship (VE/VCO 2 slope), and peak oxygen uptake (VO 2 )., Methods: In total, 185 patients with cardiac disease who underwent CPET were consecutively enroled in this retrospective study. The primary endpoint was 3-year MACCE. The ability of ΔPETO 2 , VE/VCO 2 slope, and peak VO 2 to predict MACCE was examined., Results: Optimal cut-off values for predicting MACCE were 2.0 mmHg for ΔPETO 2 (area under the curve [AUC]: 0.829), 29.8 for VE/VCO 2 slope (AUC: 0.734), and 19.0 mL/min/kg for peak VO 2 (AUC: 0.755). The AUC of ΔPETO 2 was higher than those of VE/VCO 2 slope and peak VO 2 . The MACCE-free survival rate was significantly lower in the ΔPETO 2  ≤ 2.0 group versus the ΔPETO 2  > 2.0 group (44.4% vs. 91.2%, p < 0.001). ΔPETO 2  ≤ 2.0 was an independent predictor of MACCE after adjustment for age and VE/VCO 2 slope (hazard ratio [HR], 7.28; p < 0.001) and after adjustment for age and peak VO 2 (HR, 6.52; p < 0.001)., Conclusion: ΔPETO 2 was a strong predictor of MACCE independent of and superior to VE/VCO 2 slope and peak VO 2 in patients with cardiac disease., (© 2023 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Patients with heart disease have a low anaerobic threshold (AT), and the determinants of AT may differ, depending on the severity of renal dysfunction. This study aimed to verify the determinants of AT for each stage of renal function in patients with heart disease. We consecutively enrolled 250 patients with heart disease who underwent cardiopulmonary exercise testing in our institution. The patients were divided into 3 groups by their estimated glomerular filtration rate (eGFR): <45, 45 to 59, and ≥60 ml/min/1.73 m 2 . A multivariate linear regression analysis was performed to evaluate the independent determinants of AT for each group. In total, 201 patients were analyzed. AT decreased with the deterioration of renal function (eGFR <45, 10.9 ± 2.1 vs eGFR 45 to 59, 12.4 ± 2.5 vs eGFR ≥60, 14.0 ± 2.6 ml/min/kg, p <0.001). In the eGFR <45 group, left ventricular ejection fraction and hemoglobin were significantly associated with AT (β = 0.427, p = 0.006 and β = 0.488, p = 0.002, respectively). In the eGFR 45 to 59 and ≥60 groups, ΔP ET O 2 (end-tidal oxygen partial pressure from rest to AT) showed a significant association with AT (β = 0.576, p <0.001 and β = 0.308, p = 0.003, respectively). The determinants of AT depended on the stage of renal dysfunction in patients with heart disease. In conclusion, in the eGFR <45 group, the determinants of AT were left ventricular ejection fraction and hemoglobin, whereas in the eGFR 45 to 59 and eGFR ≥60 groups, the determinant of AT was ΔP ET O 2 ., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Context: Adrenocorticotropin (ACTH) loading is used to increase the success rate of adrenal vein sampling (AVS)., Objective: We aimed to determine the effect of intraprocedural cortisol measurement (ICM) on ACTH-stimulated AVS (AS-AVS) owing to a lack of reliable data on this topic., Methods: This multicenter, retrospective, observational study took place in 28 tertiary centers in Japan. Among 4057 patients enrolled, 2396 received both basal AVS (B-AVS) and AS-AVS and were divided into 2 groups according to whether ICM was used. The effect of ICM on AS-AVS was measured., Results: In patients who underwent both AVS procedures, the ICM group had significantly higher success rates for both B-AVS and AS-AVS than the non-ICM group did. However, the probability of failure of AS-AVS after a successful B-AVS and the probability of success of AS-AVS after a failed B-AVS were not significantly different in the 2 groups. For subtype diagnosis, propensity-score matching revealed no significant difference between the 2 groups, and the discrepancy rate between B-AVS and AS-AVS for subtype diagnosis was also not significantly different., Conclusion: ICM significantly increased the success rate of B-AVS and AS-AVS in protocols in which both AVS procedures were performed and had no effect on subtype diagnosis. However, in protocols in which both AVS procedures were performed, the results suggest ICM may not be necessary when performing AS-AVS if ICM is used only when B-AVS is performed. Our study suggests that ICM during AVS plays an important role and should be recommended., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Identifying the causes of low peak oxygen uptake (peak V̇ O 2 ) in heart disease patients with renal dysfunction is necessary for prognostic improvement strategies. The purpose of this study was to verify the determinants of peak V̇ O 2 for each stage of renal function in heart disease patients, focusing on end-tidal oxygen partial pressure ( PETO 2 )., Methods: Two hundred fifty heart disease patients who underwent cardiopulmonary exercise testing (CPET) in our institution were consecutively enrolled. Patients were divided into three groups by their estimated glomerular filtration rate (eGFR): < 45, 45-59 and ≥ 60 mL/min/1.73 m 2 . Patient characteristics and CPET parameters including Δ 2 (rest-anaerobic threshold) were compared between the groups. The relationship between Δ PETO PETO 2 and peak V̇ O 2 was also investigated for each group., Results: In total, 201 patients were analyzed. Δ PETO 2 decreased with the deterioration of renal function (eGFR < 45, 0.1 mmHg vs. eGFR 45-59, 2.4 mmHg vs. eGFR ≥ 60, 5.2 mmHg, p < 0.001). In the eGFR < 45 group, left ventricular ejection fraction (LVEF) and hemoglobin (Hb) were significantly associated with peak V̇ O 2 β = 0.518, p < 0.001 and β = 0.567, p < 0.001, respectively), whereas Δ PETO 2 was not. In the eGFR 45-59 group, age, Hb, and Δ PETO 2 showed a significant association with peak V̇ O 2 ( β = -0.354, p = 0.006; β = 0.258, p = 0.007; β = 0.501, p < 0.001; respectively). In the univariate analysis, eGFR 45-59 group showed the highest coefficient of determination of Δ PETO 2 to peak V̇ O 2 ( R 2 = 0.247, p < 0.001)., Conclusions: The determinants of peak V̇ O 2 in heart disease patients depended on the stage of renal function. The determinants of peak V̇ O 2 in patients with eGFR < 45 were LVEF and Hb, while Δ PETO 2 was the strongest predictor of peak V̇ O 2 in patients with eGFR 45-59., Competing Interests: The author declares no conflict of interest. Kazuhiro P. Izawa is serving as one of the guest editor of this journal. We declare that Kazuhiro P. Izawa had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Brian Tomlinson., (Copyright: © 2022 The Author(s). Published by IMR Press.)

This study aimed to clarify the effects of gardening on hemodynamic response, rating of perceived exertion (RPE) during exercise, and body weight in patients in whom phase 2 cardiac rehabilitation (CR) was interrupted due to the Coronavirus disease 2019 (COVID-19) pandemic. Among 76 outpatients participating in consecutive phase 2 CR in both periods from March to April and June to July 2020, which were before and after CR interruption, respectively, at Sanda City Hospital were enrolled. The inclusion criterion was outpatients whose CR was interrupted due to COVID-19. Patients under the age of 65 were excluded. We compared the data of hemodynamic response and RPE during exercise on the last day before interruption and the first day after interruption when aerobic exercise was performed at the same exercise intensity in the gardener group and the non-gardener group. Forty-one patients were enrolled in the final analysis. After CR interruption, the gardener group did not show any significant difference in all items, whereas the non-gardener group experienced significant increase in HR (Peak) (p = 0.004) and worsening of the Borg scale scores for both dyspnea and lower extremity fatigue (p = 0.039 and p = 0.009, respectively). Older phase 2 CR patients engaged in gardening did not show any deterioration in hemodynamic response or RPE during exercise, despite CR interruption and refraining from going outside. Gardening may be recommended as one of the activities that can maintain or improve physical function in older phase 2 CR patients during the COVID-19 pandemic., (© 2021. Springer Japan KK, part of Springer Nature.)

The anaerobic threshold (AT), obtained during cardiopulmonary exercise testing (CPET), is an important prognostic measure and can be used to develop an exercise prescription in patients after a myocardial infarction (post-MI). The purpose of this study was to examine the central and peripheral determinants of AT in post-MI patients end-tidal oxygen partial pressure (PETO 2 ) measures. We performed cardiopulmonary exercise testing (CPET) on 148 consecutively enrolled post-MI patients to determine PETO 2 measured at the AT (AT PETO 2 ) and ΔPETO 2 (difference between resting PETO 2 and AT PETO 2 ). We subsequently investigated the relationship between these measures of PETO 2 and the individual AT for each patient. Multivariate linear regression analysis indicated that AT PETO 2 and ΔPETO 2 were independently and significantly associated with the AT (β = -0.344, p < 0.001 and β = 0.228, p < 0.001, respectively). Furthermore, the independent factors of AT PETO 2 were left ventricular ejection fraction (p = 0.005), resting ventilatory equivalent for carbon dioxide (p = 0.002), and resting dead-space gas volume to tidal volume ratio (p < 0.001). However, the independent factors for ΔPETO 2 were history of diabetes (p = 0.047), estimated glomerular filtration rate (p = 0.001), and resting systolic blood pressure (p = 0.017). These findings suggested that AT PETO 2 was associated with central determinants; whereas, and ΔPETO 2 was associated with peripheral determinants, The AT PETO 2 and ΔPETO 2 provide variable insight regarding the cause of exercise intolerance and can be used to determine appropriate therapies., (© 2021. Springer Japan KK, part of Springer Nature.)

This study aimed to clarify the effects of the interruption of cardiac rehabilitation (CR) and refraining from going outside due to the COVID-19 pandemic on hemodynamic response and rating of perceived exertion (RPE) during exercise including differences by age in phase 2 CR outpatients. Among 76 outpatients participating in consecutive phase 2 CR in both periods from March to April and June to July 2020, which were before and after CR interruption, respectively, at Sanda City Hospital were enrolled. The inclusion criterion was outpatients whose CR was interrupted due to COVID-19. We compared the data of hemodynamic response and RPE during exercise on the last day before interruption and the first day after interruption when aerobic exercise was performed at the same exercise intensity in the  < 75 years group and  ≥ 75 years group. Fifty-three patients were enrolled in the final analysis. Post-CR interruption, peak heart rate increased significantly (p = 0.009) in the  < 75 years group, whereas in the  ≥ 75 years group, weight and body mass index decreased significantly (p = 0.009, 0.011, respectively) and Borg scale scores for both dyspnea and lower extremities fatigue worsened significantly (both, p < 0.001). CR interruption and refraining from going outside due to the COVID-19 pandemic affected the hemodynamic response, RPE during exercise and body weight in phase 2 CR outpatients. In particular, patients aged  ≥ 75 years appeared to be placed at an increased risk of frailty.

Aim: Worsening renal function (WRF) induced by acute myocardial infarction (AMI) is a strong predictor of cardiovascular events and mortality. Peak oxygen uptake may contribute to prognosis in AMI patients with WRF, however, the impact of WRF on peak oxygen uptake is unclear., Methods: Among 154 patients with AMI who underwent emergency percutaneous coronary intervention and participated in phase II cardiac rehabilitation, those who underwent cardiopulmonary exercise testing were consecutively enrolled. WRF was defined as a ≥20% decrease in estimated glomerular filtration rate (eGFR [ml/min/1.73 m 2 ]) from admission to that at cardiopulmonary exercise testing. The association of WRF with peak oxygen uptake was evaluated by multivariate regression analysis. The non-WRF group was divided into two subgroups according to eGFR <60/≥60 at cardiopulmonary exercise testing, and eGFR at cardiopulmonary exercise testing and peak oxygen uptake of all three groups were compared., Results: Ninety-four patients were enrolled in the final analysis. Multiple linear regression analysis showed that WRF was associated with peak oxygen uptake (p = .003). Comparing the non-WRF group with eGFR at cardiopulmonary exercise testing <60 and the WRF group, although eGFR at cardiopulmonary exercise testing was similar (p = 1.000), peak oxygen uptake in the WRF group was significantly lower (p = .026)., Conclusion: WRF, not eGFR at cardiopulmonary exercise testing was significantly associated with peak oxygen uptake in patients with AMI. This result suggests that when considering the relationship between renal function and peak oxygen uptake, WRF must be taken into account., (© 2021 Asian Pacific Society of Nephrology.)

Left ventricular hypertrophy (LVH) is often seen in patients with primary aldosteronism (PA), and the prevalence of LVH is reportedly higher among patients with PA than patients with essential hypertension. However, the correlation between aldosterone levels and LVH is undefined, and how aldosterone affects LVH in patients with PA remains unclear. We, therefore, retrospectively assessed a large PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) to reveal the factors associated with LVH in patients with PA without suspected autonomous cortisol secretion. In the 1186 patients with PA studied, the basal plasma aldosterone concentration, plasma renin activity, and the aldosterone-to-renin ratio did not significantly correlate with left ventricular LV mass index (LVMI) in single or multiple regression analyses. However, the plasma aldosterone concentration after the captopril challenge test or saline-infusion test, which are associated with autonomous aldosterone secretion, correlated significantly with LVMI, even after adjusting for patients' backgrounds, including age and blood pressure. In addition, hypokalemia and the unilateral subtype also correlated with LVMI. Longitudinal subanalysis of medically or surgically treated patients with PA showed significant reductions in LVMI in both the surgery (63.0±18.1 to 55.3±19.5 g/m 2.7 , P <0.001) and drug treatment (56.8±14.1 to 52.1±13.5 g/m 2.7 , P <0.001) groups. Our results suggest the autonomous aldosterone secretion level, not the basal aldosterone level itself, is relevant to LVH in patients with PA. In addition, the elevated LVMI seen in patients with PA is at least partially reversible with surgical or medical treatment.

Objectives: We investigated the clinical significance of ACTH stimulation during adrenal venous sampling (AVS) by surgical outcome of primary aldosteronism (PA)., Design: Multicenter retrospective study by Japan PA study., Method: We allocated 314 patients with both basal and ACTH-stimulated AVS data who underwent adrenalectomy to three groups: basal lateralization index (LI) ≥2 with ACTH-stimulated LI ≥4 on the ipsilateral side (Unilateral (U) to U group, n = 245); basal LI <2 with ACTH-stimulated LI ≥4 (Bilateral (B) to U group, n = 15); and basal LI ≥2 with ACTH-stimulated LI <4 (U to B group, n = 54). We compared surgical outcomes among the groups using the Primary Aldosteronism Surgical Outcome (PASO) criteria., Results: Compared with U to U group, U to B group had poor clinical and biochemical outcomes and low rates of adrenal adenoma as pathological findings (P = 0.044, 0.006, and 0.048, respectively), although there were no significant differences between U to U and B to U groups. All patients in U to B group with clinical and biochemical benefits, however, had adrenal adenoma as pathological findings and could be well differentiated from those with poor surgical outcomes via basal LI (>8.3), but not ACTH-stimulated LI. These results were similar even when we defined each group based on a cut-off value of 4 for basal LI., Conclusions: Although PA patients in U to B group had worse surgical outcomes than did those in U to U group, basal LI could discriminate among patients with better surgical outcomes in U to B group.

Primary aldosteronism (PA) is a common curable cause of hypertension. Adrenal venous sampling (AVS) is recommended for subtype diagnosis but is a difficult procedure. Recently, an increased prevalence of PA was reported, creating a greater demand for treatment of the condition in clinical facilities. The aim of the present study was to identify the historical changes over time and the differences between facilities in the success rate and subtype diagnosis of PA. The database of the PA registry developed by the Japan PA Study (JPAS) was used. A total of 2599 patients with PA who underwent AVS were evaluated. The overall success rate of AVS was 88%. The bilateral subtype was the dominant subtype, comprising 69% of cases. During the period 2004-2011 to 2011-2017, there were significant changes in the total number of AVS procedures (from 562 to 1732), ratio of ACTH administration with AVS (75 to 97%), success rate (79 to 90%), and proportion with bilateral subtype diagnosis (53 to 72%). There were also significant inter-facility differences in the number of AVS procedures (6 to 322), success rate (59 to 97%), and proportion with the bilateral subtype (44 to 86%). The principal enrolled department was Endocrinology (86%), and the ratio of unilateral PA was significantly higher in this department than in others (32% vs. 25%). In conclusion, the number of AVS procedures performed, the success rate, and the proportion with the bilateral subtype increased over time after normalizing the centre difference. Significant differences were observed between the centres.

Chronic-phase worsening renal function (WRF) in patients with acute myocardial infarction (AMI) has been associated with poor prognosis. However, there is no consensus on either the method of prevention or the cause. The aim of this study was to determine factors predictive of chronic-phase WRF from the viewpoint of circulatory dynamics response to exercise during hospitalization of AMI patients without renal dysfunction on admission. We studied 186 consecutively AMI patients who underwent the 200-m walk test. Chronic-phase WRF was defined as a 20% decrease in estimated glomerular filtration rate (eGFR) from baseline to 8-10 months after AMI onset. Heart rate (HR) and systolic blood pressure recorded during the 200-m walk test were evaluated as circulatory dynamics responses. In total, 94 patients were enrolled. Multiple linear regression analysis showed that ΔHR (peak-rest) associated significantly with ΔeGFR ( β = 0.427, p = 0.018). The receiver operating characteristic curve of ΔHR to predict chronic-phase WRF showed an area under the curve of 0.77, with a cut-off value of 22.0 bpm having a 95% sensitivity and 55% specificity. Among circulatory dynamics responses during exercise in the acute phase after AMI, ΔHR was an independent predictor of chronic-phase WRF.

Primary aldosteronism causes renal structural damage after glomerular hyperfiltration, and primary aldosteronism-specific treatment leads to an acute fall in estimated glomerular filtration rate (eGFR). We investigated whether this change affected the long-term eGFR slope in a retrospective cohort from the multicenter Japan Primary Aldosteronism Study. We allocated patients with primary aldosteronism to the adrenalectomy (n=202) and MR (mineralocorticoid receptor) antagonist (n=303) groups based on their treatment history and analyzed the association between the initial eGFR fall and long-term eGFR slope. The increased age, low serum potassium levels, high eGFR, and high plasma aldosterone levels were independent predictors for a large initial eGFR fall in both groups. Our analysis of tertiles based on the initial eGFR fall revealed that in the MR antagonist group, patients with a small initial eGFR fall had a significantly steeper long-term eGFR slope than those with a large initial fall (tertile 1 versus 2, P=0.025; tertile 1 versus 3, P=0.017). These associations were not identified in the adrenalectomy group. Thus, the smaller the acute fall in eGFR by initiation of MR antagonists, the greater was the rate of long-term eGFR decline. While the acute fall in eGFR induced by primary aldosteronism-specific treatment is occasionally a clinical concern, our findings highlight the favorable implications of the acute fall with respect to long-term renal outcomes.

Context: Aldosterone-producing adenomas are a curable subtype of primary aldosteronism (PA); however, hypertension persists in some patients after adrenalectomy., Objective: To identify factors associated with, and develop prediction models for, blood pressure (BP) normalization or improvement after adrenalectomy., Design: Retrospective analysis of patients treated between 2006 and 2018, with a 6-month follow-up., Setting: A nationwide, 29-center Japanese registry encompassing 15 university hospitals and 14 city hospitals., Patients: We categorized 574 participants in the Japan Primary Aldosteronism Study, who were diagnosed with PA and underwent adrenalectomy, as BP normalized or improved, on the basis of their presentations at 6 months postsurgery., Main Outcome Measure: The rate of complete, partial, and absent clinical success. Predictive factors related to BP outcomes after PA surgery were also evaluated., Results: Complete clinical success was achieved in 32.6% and partial clinical success was achieved in 53.0% of the patients at 6 months postsurgery. The following five variables were independent predictors for BP normalization: ≤7 years of hypertension, body mass index ≤25 kg/m 2 , no more than one antihypertensive medication, absence of medical history of diabetes, and female sex. The area under the receiver operator characteristic curve was 0.797 in the BP normalization model., Conclusion: We established models that predicted postoperative BP normalization in patients with PA. These should be useful for shared decision-making regarding adrenalectomy for PA., (Copyright © 2019 Endocrine Society.)

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension. Adrenal vein sampling (AVS) is an established method for finding patients with the unilateral subtype of PA, for which adrenalectomy is an applicable treatment. In this study, we analyzed a large database of patients with PA who underwent adrenal vein sampling, to investigate the sex differences in the impact of age at diagnosis on the subtype and cause of PA. In 2122 patients, women with the unilateral subtype were younger than men with the same subtype and women with the bilateral subtype. Younger age and older age were associated with unilateral PA in women and men, respectively. After stratification by tertiles of age, there was a trend of decreased and increased incidence of unilateral PA with aging in women and men, respectively. Male sex was a predictor of unilateral PA in middle-aged and older patients but not in younger patients. We also found that obesity, a known factor associated with idiopathic hyperaldosteronism, was positively associated with bilateral PA in younger patients but not in older patients. These findings suggest that the proportion of operable patients with unilateral PA differs depending on the combination of sex and age, and that other than obesity, the cause of PA is also associated with the bilateral subtype in older patients.

Objectives: Because of the influence on the renin-angiotensin-aldosterone system, it is recommended to avoid, if possible, the use of angiotensin-converting-enzyme inhibitors, angiotensin II type 1 receptor blockers, diuretics, β-blockers, and mineralocorticoid receptor antagonists during the diagnostic period of primary aldosteronism. A laterality index more than 4 in adrenocorticotropic hormone (ACTH)-stimulated adrenal venous sampling (ACTH-AVS) is a widely used classification of the unilateral subtype that can benefit from adrenalectomy. Here, we revealed clinical features of patients taking drugs that could affect the primary aldosteronism diagnosis (DAPD) and investigated whether the classification with laterality index more than 4 in ACTH-AVS is applicable to these patients., Patients and Methods: Using a large database of primary aldosteronism patients in Japan, we analyzed 2122 patients with successful ACTH-AVS., Results: Patients who received any DAPD (n = 209) showed higher prevalence of comorbidity burdens and took more antihypertensive drugs compared with patients without DAPD. In patients taking DAPD, those with laterality index more than 4 had a higher prevalence of hypokalemia, a higher aldosterone-to-renin ratio and a higher prevalence of adrenal mass than those with laterality index of 4 or less. Adrenalectomy was performed in 76% patients with laterality index more than 4 and 20% with laterality index of 4 or less. Patients who underwent adrenalectomy showed biochemical cure in 89% with laterality index more than 4 and 50% with laterality index of 4 or less (P = 0.001). Multivariate regression analysis showed that laterality index more than 4 was an independent predictor of a biochemical cure. Biochemical cure rate in patients with laterality index more than 4 was consistently high, irrespective of the potential effect of individual DAPD on laterality index., Conclusion: Our findings suggest that in primary aldosteronism patients to whom DAPD were administrated due to severe clinical features, laterality index more than 4 in ACTH-AVS could accurately predict a biochemical cure after adrenalectomy.

Objectives: Current clinical guidelines of primary aldosteronism recommend adrenalectomy (AdX) for unilateral primary aldosteronism based on the studies showing the potential superiority of AdX over the medical treatment. However, since most medically treated cases consisted of bilateral primary aldosteronism and all surgically treated cases consisted of unilateral primary aldosteronism, the different subtype of primary aldosteronism could be a bias for their effects. This study compared the effects of AdX and medical therapy in patients with unilateral primary aldosteronism confirmed by adrenal vein sampling., Methods: Of the 339 patients with unilateral primary aldosteronism in the Japan Primary Pldosteronism Study data base, unilateral AdX and treatment with mineral corticoid receptor antagonists (MRAs) was done in 276 patients (AdX group) and in 63 patients (MRAs group), respectively. The effects were compared by the clinical (improvement of blood pressure) and biochemical outcomes (improvement of hypokalemia)., Results: At baseline, use of potassium replacement, plasma aldosterone concentration, aldosterone-to-renin ratio, estimated glomerular filtration rate, and prevalence of adrenal mass on imaging were higher in the AdX group than in the MRAs group. At 6 months after commencement of specific treatment for primary aldosteronism, clinical outcome and biochemical outcome in the AdX group were superior than those in the MRAs group. The difference of the outcome between the two groups were the case even after adjusting for the different clinical backgrounds in the two groups before the specific treatment., Conclusion: Our study provides evidence that AdX is the first choice of treatment in the patients with unilateral primary aldosteronism in terms of clinical and biochemical outcome.

Context: In patients with primary aldosteronism (PA), it remains unclear whether aldosterone-producing adenomas are likely to develop in the left or right adrenal gland., Objective: To investigate left-right differences of PA laterality diagnoses via CT imaging and adrenal vein sampling (AVS)., Design: Retrospective, observational study., Patients: From the Japan Primary Aldosteronism Study, 1493 patients with PA were enrolled who underwent CT and ACTH-stimulated AVS., Measurements: Left or right adrenal nodular lesion distribution and laterality observed on CT scans and from AVS were noted., Results: Both on CT scans and AVS, unilateral results were observed more frequently on the left side than on the right side (25.1% vs 15.4% and 17.3% vs 13.5%, respectively; P < 0.01for both diagnostic techniques). There was no significant difference in the concordance rate for CT and AVS between patients with left and right unilateral nodular lesions observed on CT scans (44.1% and 50.9%, respectively; P = 0.15). In patients with nodules <20 mm, the concordance rate was significantly greater on the right side than the left side (45.8% vs 56.4%; P = 0.03). In patients with bilateral results of AVS, unilateral nodular lesions were detected more frequently on the left side than the right side (17.8% vs 9.4%; P < 0.01)., Conclusion: These results suggest aldosterone-producing adenomas and nonfunctioning tumors are more likely to develop on the left side in patients with PA and that misdiagnosis of CT-based lateralization may occur more frequently on the left side.

Background: Adrenal venous sampling (AVS) is essential for identifying a surgically curable form of primary aldosteronism. Adrenocorticotropic hormone (ACTH) infusion or bolus has been reported to improve the success rate of AVS, although the effects on lateralization and its outcomes in unilateral primary aldosteronism are unclear., Methods: The success rate and lateralization indices were examined in a cohort of 2197 Japanese patients with primary aldosteronism from 28 centres who underwent AVS. Outcomes were analysed in 267 patients with aldosterone-producing adenomas (APAs)., Results: ACTH loading during AVS improved the success rate from 67 to 89%, while lateralization indices decreased from 62 to 28%. Bolus, bolus along with continuous infusion or continuous infusion of ACTH did not affect both indices. The absence of clinical success (i.e. unchanged or increased blood pressure) was 33% and absence of biochemical success (persistent hypokalaemia or persistently raised aldosterone-to-renin ratio, or both) was 15%. The clinical and biochemical success rates did not differ between the three groups [lateralization index >2 in basal condition (LIb) and lateralization index >4 after ACTH loading (lateralization indices), and LIb >2 + lateralization indices<4, LIb<2+lateralization indices>4]. The three groups (LIb>4+lateralization indices>4, LIb>4+lateralization indices<4 and LIb<4+lateralization indices>4) did not show any significant differences of clinical and biochemical outcome., Conclusion: ACTH loading during AVS improved the success rate but decreased laterality. ACTH did not affect the clinical and biochemical outcomes in APA patients. These data showed that the use of ACTH during AVS was helpful for improving the success rate, but did not contribute to better outcomes.

Objective: To investigate the prevalence and causes of diabetes in patients with primary aldosteronism (PA) in a multi-institutional cohort study in Japan., Research Design and Methods: The prevalence of diabetes was determined in 2,210 patients with PA (diagnosed or glycated hemoglobin [HbA 1c ] ≥6.5% [≥48 mmol/mol]; NGSP) and compared with that of the Japanese general population according to age and sex. In 1,386 patients with PA and clear laterality (unilateral or bilateral), the effects of plasma aldosterone concentration (PAC), hypokalemia (<3.5 mEq/L), suspected subclinical hypercortisolism (SH; serum cortisol ≥1.8 µg/dL after 1-mg dexamethasone suppression test), and PA laterality on the prevalence of diabetes or prediabetes (5.7% ≤ HbA 1c <6.5% [39 mmol/mol ≤ HbA 1c <48 mmol/mol]) were examined., Results: Of the 2,210 patients with PA, 477 (21.6%) had diabetes. This prevalence is higher than that in the general population (12.1%) or in 10-year cohorts aged 30-69 years. Logistic regression or χ 2 test revealed a significant contribution of suspected SH to diabetes. Despite more active PA profiles (e.g., higher PAC and lower potassium concentrations) in unilateral than bilateral PA, BMI and HbA 1c values were significantly higher in bilateral PA. PA laterality had no effect on the prevalence of diabetes; however, the prevalence of prediabetes was significantly higher in bilateral than unilateral PA., Conclusions: Individuals with PA have a high prevalence of diabetes, which is associated mainly with SH. The prevalence of prediabetes is greater for bilateral than unilateral PA, suggesting a unique metabolic cause of bilateral PA., (© 2019 by the American Diabetes Association.)

Context: Recently, the relationship between primary aldosteronism (PA) and various metabolic disorders, including obesity, diabetes mellitus, and dyslipidemia, has been discussed. However, in PA, aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) have different etiologies., Objective: Our objectives were to clarify differences in obesity and metabolic disorders between APA and IHA and to gain insight in the pathogenesis of IHA., Design, Setting, and Participants: This is a retrospective cross-sectional study. We assessed the PA database established by the multicenter Japan Primary Aldosteronism Study. For comparative analysis, data were also collected from 274 patients with essential hypertension (EHT)., Main Outcome Measures: We compared prevalences of obesity and metabolic disorders between patients with APA and patients with IHA. Comparisons with sex-, age-, and blood pressure-matched patients with EHT were also performed. Correlations between metabolic parameters and plasma aldosterone concentrations (PACs) in each subtype were analyzed., Results: Analysis of 516 patients with APA and 1015 patients with IHA revealed PACs were significantly higher in patients with APA than patients with IHA. By contrast, after we adjusted for clinical backgrounds, the prevalence of obesity was significantly higher in patients with IHA than in patients with APA or EHT. Although the prevalences of diabetes mellitus and dyslipidemia did not significantly differ between patients with IHA and patients with APA, triglyceride and HbA1c were significantly higher in patients with IHA than in patients with APA. There was no significant correlation between metabolic parameters and PACs in either subtype., Conclusions: Patients with IHA tend to be obese despite lower PACs than in patients with APA. The present results suggest that obesity-related factors contribute to the pathogenesis of IHA.

Objectives: A subtype prediction score for primary aldosteronism has not yet been developed and validated using a large dataset. This study aimed to develop and validate a new subtype prediction score and to compare it with existing scores using a large multicenter database., Methods: In total, 1936 patients with primary aldosteronism were randomly assigned to the development and validation datasets, constituting 1290 and 646 patients, respectively. Three prediction scores were generated with or without confirmatory tests, using logistic regression analysis. In the validation dataset, new and existing prediction scores were compared using receiver operating characteristic curve, net reclassification improvement, and integrated discrimination improvement analyses., Results: The new prediction score is simply calculated using serum potassium levels [>3.9 mmol/l (four points); 3.5-3.9 mmol/l (three points)], the absence of adrenal nodules during computed tomography (three points), a baseline plasma aldosterone concentration of <210.0 pg/ml (two points), a baseline aldosterone/renin ratio of less than 620 (two points), and female sex (one point). Using the validation dataset, we found that a new subtype prediction score of at least 8 had a positive predictive value of 93.5% for bilateral hyperaldosteronism. The new prediction score for bilateral hyperaldosteronism was better than the existing prediction scores in the receiver operating characteristic curve and net reclassification improvement analyses., Conclusion: The new prediction score has clear advantages over the existing prediction scores in terms of diagnostic accuracy, feasibility, and the potential for generalization in a large population. These data will help healthcare professionals to better select patients who require adrenal venous sampling.

Context: Primary aldosteronism (PA) in the elderly has increased in importance in association with population aging., Objective: To investigate the characteristics and outcomes of elderly patients with PA undergoing adrenalectomy., Patients and Methods: Using a database of patients with PA who underwent adrenal venous sampling (AVS), we compared elderly patients (≥65 years old) with nonelderly patients (<65 years old) in terms of characteristics, subtype classification in ACTH-stimulated AVS, and outcomes after adrenalectomy., Results: The elderly group had a higher prevalence of comorbidities than the nonelderly group. The proportion of the unilateral subtype [defined as a lateralization index (LI) >4] was comparable between the age groups. In patients who received adrenalectomy, biochemical cure was comparable between the groups, whereas persistent hypertension was more common in the elderly group. The prevalences of hyperkalemia and renal impairment (chronic kidney disease stage 3b or higher) were higher in the elderly group. Multiple regression analysis showed that the duration of hypertension predicted persistent hypertension and hyperkalemia and that preoperative estimated glomerular filtration rate predicted renal impairment in the elderly group. LI >4 in AVS was an independent predictor of biochemical cure after adrenalectomy in the elderly group but not in the nonelderly group. Age was negatively associated with biochemical cure in patients with LI ≤4., Conclusion: Adrenalectomy contributes to biochemical improvement in elderly patients if determined in accordance with AVS. The treatment strategy should be determined considering the high postoperative incidence of persistent hypertension and hyperkalemia in elderly patients with a long history of hypertension or renal impairment in those with reduced renal function.

Objectives: The aim of this study was to investigate the impact of adrenal venous sampling (AVS) lateralization cutoffs on surgical outcomes., Patients and Methods: Cosyntropin-stimulated AVS was used to guide surgical management of 377 patients with primary aldosteronism (PA) who were evaluated 6 months after surgery., Main Outcome Measures: The proportion of patients that achieved clinical benefit and complete biochemical success based on the AVS aldosterone lateralization index (LI) was determined., Results: Clinical benefit was achieved in 29 of 47 patients with an LI between 2 and 4, in 66 of 101 with an LI between 4 and 10, and in 158 of 203 with an LI > 10 ( P < 0.01 for trend). Complete biochemical success was achieved in 27 of 42 with an LI between 2 and 4, in 60 of 76 with an LI between 4 and 10, and in 127 of 155 with an LI > 10 ( P = 0.024 for trend). After adjustment for confounders and using those patients with an LI between 2 and 4 as a reference, a clinical benefit was associated only with those with an LI > 10 (OR, 2.30; 95% CI, 1.03 to 5.16), whereas complete biochemical success was associated with those with an LI between 4 and 10 (OR, 2.83; 95% CI, 1.14 to 7.01) or LI > 10 (OR, 3.55; 95% CI, 1.47 to 8.55)., Conclusions: Difference of clinical outcome was relatively small when strict LI diagnostic threshold was used; biochemical cure was sufficiently achieved when an LI > 4 was used. Our study by standardized outcome measures validated that an LI > 4 may be appropriate for determining unilateral disease in PA.

A fundamental quest of modern astronomy is to locate the earliest galaxies and study how they influenced the intergalactic medium a few hundred million years after the Big Bang 1-3 . The abundance of star-forming galaxies is known to decline 4,5 from redshifts of about 6 to 10, but a key question is the extent of star formation at even earlier times, corresponding to the period when the first galaxies might have emerged. Here we report spectroscopic observations of MACS1149-JD1 6 , a gravitationally lensed galaxy observed when the Universe was less than four per cent of its present age. We detect an emission line of doubly ionized oxygen at a redshift of 9.1096 ± 0.0006, with an uncertainty of one standard deviation. This precisely determined redshift indicates that the red rest-frame optical colour arises from a dominant stellar component that formed about 250 million years after the Big Bang, corresponding to a redshift of about 15. Our results indicate that it may be possible to detect such early episodes of star formation in similar galaxies with future telescopes.

Context: The current Endocrine Society Guideline suggests that patients aged <35 years with marked primary aldosteronism (PA) and unilateral adrenal lesions on adrenal computed tomography (CT) scan may not need adrenal vein sampling (AVS) before proceeding to unilateral adrenalectomy. This suggestion is, however, based on the data from only one report in the literature., Objective: We sought to determine the accuracy of CT findings in young PA patients who had unilateral adrenal disease on CT with hypokalaemia and elevation of aldosterone., Design and Patients: We retrospectively studied 358 PA patients (n = 30, aged <35 years; n = 39, aged 35-40 years; n = 289, aged ≥40 years) with hypokalaemia and elevation of aldosterone and unilateral disease on CT who had successful AVS., Main Outcome Measure: Accuracy of CT findings is determined by AVS findings and/or surgical outcomes in patients aged <35 years., Results: Concordance of the diagnosis between CT and AVS was 90% (27/30) in patients aged <35 years, 79% (31/39) in patients aged 35-40 years and 69% (198/289) in those aged ≥40 years (trend for P < .01). Surgical benefit was confirmed in three patients aged <35 years and in three patients aged 35-40 years with the available surgical data who had discordance between CT and AVS findings. Collectively, the diagnostic accuracy of CT findings was 100% (30/30) if aged <35 years and 87% (34/39) if aged 35-40 years., Conclusion: Primary aldosteronism patients aged <35 years with hypokalaemia and elevation of aldosterone and unilateral disease on adrenal CT could be spared AVS., (© 2018 John Wiley & Sons Ltd.)

Context: The number of centers with established adrenal venous sampling (AVS) programs for the subtype diagnosis of primary aldosteronism (PA) is limited., Objective: Aim was to develop an algorithm for AVS based on subtype prediction by computed tomography (CT) and serum potassium., Design: A multi-institutional retrospective cohort study in Japan., Patients: A total of 1591 patients with PA were classified into four groups according to CT findings and potassium status. Subtype diagnosis of PA was determined by AVS., Main Outcome Measure: Prediction value of the combination of CT findings and potassium status for subtype diagnosis., Results: The percentages of unilateral hyperaldosteronism on AVS were higher in patients with unilateral disease on CT than those with bilateral normal results on CT (50.8% vs 14.6%, P < 0.01), and these percentages were higher in those with hypokalemia than those with normokalemia (58.4% vs 11.5%, P < 0.01). The prevalence and odds ratio for unilateral hyperaldosteronism on AVS were as follows: bilateral normal on CT with normokalemia, 6.2% (reference); unilateral disease on CT with normokalemia, 23.8% and 4.8 [95% confidence interval (CI), 3.1 to 7.2]; bilateral normal on CT with hypokalemia, 38.1% and 9.4 (95% CI, 6.2 to 14.1), and unilateral disease on CT with hypokalemia, 70.6% and 36.4 (95% CI, 24.7 to 53.5)., Conclusions: Patients with PA with bilateral normal results on CT and normokalemia likely have a low prior probability of a lateralized form of AVS and could be treated medically, whereas those with unilateral disease on CT and hypokalemia have a high probability of a lateralized form of AVS.

There have been several clinical studies examining the factors associated with cardiovascular disease (CVD) in patients with primary aldosteronism (PA); however, their results have left it unclear whether CVD is affected by the plasma aldosterone concentration or hypokalemia. We assessed the PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) and compared the prevalence of CVD among patients with PA with that among age-, sex-, and blood pressure-matched essential hypertension patients and participants with hypertension in a general population cohort. We also performed binary logistic regression analysis to determine which parameters significantly increased the odds ratio for CVD. Of the 2582 patients with PA studied, the prevalence of CVD, including stroke (cerebral infarction, cerebral hemorrhage, or subarachnoid hemorrhage), ischemic heart disease (myocardial infarction or angina pectoris), and heart failure, was 9.4% (stroke, 7.4%; ischemic heart disease, 2.1%; and heart failure, 0.6%). The prevalence of CVD, especially stroke, was higher among the patients with PA than those with essential hypertension/hypertension. Hypokalemia (K + ≤3.5 mEq/L) and the unilateral subtype significantly increased adjusted odds ratios for CVD. Although aldosterone levels were not linearly related to the adjusted odds ratio for CVD, patients with plasma aldosterone concentrations ≥125 pg/mL had significantly higher adjusted odds ratios for CVD than those with plasma aldosterone concentrations <125 pg/mL. Thus, patients with PA seem to be at a higher risk of developing CVD than patients with essential hypertension. Moreover, patients with PA presenting with hypokalemia, the unilateral subtype, or plasma aldosterone concentration ≥125 pg/mL are at a greater risk of CVD and have a greater need for PA-specific treatments than others., (© 2018 American Heart Association, Inc.)

Subtype diagnosis of primary aldosteronism (PA) by adrenal vein sampling (AVS) is recommended as a mandatory step for indicating adrenal surgery. It is a technically demanding procedure, especially in the right adrenal vein. The aim of the study was to predict the subtype diagnosis in the absence of values from the right AVS. From the databases of nine centers (WAVES-J), 308 patients with PA who underwent successful AVS were studied. Based on the ipsilateral ratio (IR) (aldosterone/cortisol ratio of the left adrenal vein [A/C left AV ] / aldosterone/cortisol ratio of the inferior vena cava [A/C IVC ]), the patients were divided into two groups: the patients with IR ≥ 1.0 (n = 262) and those with IR < 1.0 (n = 46). In patients with IR > 1.0, the A/C left AV was significantly higher in patients with the left unilateral subtype than in patients with the bilateral subtype. Receiver operating characteristic (ROC) curve analysis revealed that an A/C left AV cutoff >68 showed 70.8% sensitivity and 93.5% specificity for the left unilateral subtype. On the other hand, in patients with IR < 1.0, the A/C left AV was significantly lower in patients with the right unilateral subtype. ROC analysis revealed that an A/C left AV cutoff <9 showed 86.7% sensitivity and 75.0% specificity for the right unilateral subtype. Hence, the combination of the IR and A/C ratio in the left adrenal vein is useful for predicting the subtype. The present results provide important information for patients with PA in whom AVS was unsuccessful in the right adrenal vein.

Objective: Although corticotropin is a representative secretagogue of aldosterone, the utility of the cosyntropin stimulation test (C-ST) in diagnosing primary aldosteronism (PA) has not been elucidated. Aim of the study was to evaluate the clinical utility of C-ST for confirmatory testing and subtype classification of PA., Design, Setting and Patients: In this retrospective study, we identified patients with hypertension and positive case-detection results for PA who underwent C-ST and saline infusion testing (SIT) between 2006 and 2013 at eight referral centres in Japan. PA and essential hypertension (EH) were distinguished based on SIT results. PA subtype classification was determined by adrenal venous sampling (AVS). Plasma aldosterone concentration (PAC) was measured before and 30 and 60 min after intravenous cosyntropin administration. The ability of C-ST to distinguish PA from EH and to distinguish unilateral from bilateral disease was assessed by the area under the receiver operating characteristic curve., Results: Of 205 patients with hypertension and positive case-detection results, 139 (68%) had PA based on SIT results. Eighteen patients in whom AVS was unsuccessful were excluded from analysis. The baseline PAC before C-ST was significantly higher (P < 0·01) in patients with PA than in those with EH. However, the degree of difference in PAC between patients with PA and EH was not enhanced by the administration of cosyntropin. In addition, the administration of cosyntropin did not improve the distinction between bilateral and unilateral PA subtypes., Conclusions: C-ST has no utility as a confirmatory and subtype testing of PA when the diagnosis of PA is based on the positive results in SIT., (© 2016 John Wiley & Sons Ltd.)

We present a new method for measuring camera vibrations such as camera shake and shutter shock. This method successfully detects the vibration trajectory and transient waveforms from the camera image itself. We employ a time-varying pattern as the camera test chart over the conventional static pattern. This pattern is implemented using a specially developed blinking light-emitting-diode array. We describe the theoretical framework and pattern analysis of the camera image for measuring camera vibrations. Our verification experiments show that our method has a detection accuracy and sensitivity of 0.1 pixels, and is robust against image distortion. Measurement results of camera vibrations in commercial cameras are also demonstrated.

Context: In adrenal vein sampling (AVS) for patients with primary aldosteronism, the contralateral ratio of aldosterone/cortisol (A/C) between the nondominant adrenal vein and the inferior vena cava is one of the best criteria for determining lateralized aldosterone secretion. Despite successful cannulation in some patients, the A/C ratios in the adrenal veins are bilaterally lower than that in the inferior vena cava (bilateral aldosterone suppression; BAS)., Objectives: To investigate the prevalence of BAS in AVS and how to resolve this condition., Design and Setting: Retrospective study involving nine referral centres., Patients: Four hundred and ninety-one patients who were confirmed as having primary aldosteronism and had an AVS between January 2006 and December 2013., Measurements: The prevalence of BAS before and after ACTH stimulation was compared. In addition, we investigated other methods for overcoming BAS., Results: In 304 patients with successful AVS before ACTH stimulation, BAS was observed in 29 (9·5%). BAS was resolved after ACTH stimulation in 22 patients. In 276 patients with successful AVS both before and after ACTH stimulation, the frequency of BAS was significantly reduced after ACTH (8·7% vs 2·5%, P < 0·01). In a few patients, BAS was also resolved by adding a sampling point at the common trunk of the left adrenal vein and by an alternative drainage vein from the adrenal tumour., Conclusions: BAS sometimes occurs in AVS without ACTH stimulation. ACTH stimulation significantly reduces BAS with a single AVS procedure., (© 2016 John Wiley & Sons Ltd.)

The physical properties and elemental abundances of the interstellar medium in galaxies during cosmic reionization are important for understanding the role of galaxies in this process. We report the Atacama Large Millimeter/submillimeter Array detection of an oxygen emission line at a wavelength of 88 micrometers from a galaxy at an epoch about 700 million years after the Big Bang. The oxygen abundance of this galaxy is estimated at about one-tenth that of the Sun. The nondetection of far-infrared continuum emission indicates a deficiency of interstellar dust in the galaxy. A carbon emission line at a wavelength of 158 micrometers is also not detected, implying an unusually small amount of neutral gas. These properties might allow ionizing photons to escape into the intergalactic medium., (Copyright © 2016, American Association for the Advancement of Science.)

Context: Adrenal vein sampling (AVS) is essential for identifying a surgically curable form of primary aldosteronism (PA), but accurate placement of the sampling catheter is technically challenging. Intraprocedural cortisol measurement can confirm the catheter's position, thereby increasing the AVS success rate., Objective and Methods: We developed a quick cortisol assay (QCA) that uses immunochromatography and gold nanoparticles and can be performed either semiquantitatively or quantitatively. The assay was evaluated in two studies. In a single-center study, PA patients were assigned to undergo AVS incorporating the semiquantitative QCA (n = 30), the quantitative QCA (n = 30), or without the QCA (n = 30), and the rates of successful AVS were determined. In a prospective multicenter randomized, controlled study, the success rates of AVS performed with (n = 148) or without (n = 145) the semiquantitative QCA were determined., Results: Cortisol concentrations were measured during AVS in 6 minutes or less in the radiology suite, without additional technical assistance, and significantly correlated with a conventional reference assay (R(2) = 0.994; P < .001). In the single-center study, the differences in the AVS success rates associated with semiquantitative and quantitative QCAs were not significant (both 93%); however, the success rates were significantly higher than the rate of successful AVS performed without using the QCA (63%; P < .001). The success rate of AVS performed in the multicenter study was 94% for the semiquantitative QCA, which was significantly higher than the rate for the patients without QCA (60%; P < .001)., Conclusions: Our novel QCA was rapidly and easily performed at the point of care and improved the rate of successful AVS.

Adrenal venous sampling is considered to be the most reliable diagnostic procedure to lateralize aldosterone excess in primary aldosteronism (PA). However, normative criteria have not been established partially because of a lack of data in non-PA hypertensive patients. The aim of the study was to investigate aldosterone concentration and its gradient in the adrenal vein of non-PA hypertensive patients. We retrospectively studied the results of cosyntropin-stimulated adrenal venous sampling in 40 hypertensive patients who showed positive screening testing but negative results in 2 confirmatory tests/captopril challenge test and saline infusion test. Plasma aldosterone concentration, aldosterone/cortisol ratio, its higher/lower ratio (lateralization index) in the adrenal vein with cosyntropin stimulation were measured. Median plasma aldosterone concentration in the adrenal vein was 25 819 pg/mL (range, 5154-69 920) in the higher side and 12 953 (range, 1866-36 190) pg/mL in the lower side (P<0.001). There was a significant gradient in aldosterone/cortisol ratio between the higher and the lower sides (27.2 [5.4-66.0] versus 17.3 [4.0-59.0] pg/mL per μg/dL;P<0.001) with lateralization index ranging from 1.01 to 3.87. The aldosterone lateralization gradient was between 1 to 2 in 32 patients and 2 to 4 in 8 patients. None of the patients showed lateralization index ≥4. The present study demonstrated that plasma aldosterone concentration in the adrenal veins showed significant variation and lateralization gradient even in non-PA hypertensive patients. Adrenal venous sampling aldosterone lateralization gradients between 2 and 4 should be interpreted with caution in patients with PA because these gradients can be found even in patients with negative confirmatory testing for PA., (© 2016 American Heart Association, Inc.)

Context: Although adrenal vein sampling (AVS) is the standard method for subtype diagnosis in primary aldosteronism (PA), protocol details including the sampling position in the adrenal vein are not standardized., Objective: To establish the optimum sampling position in the left adrenal vein based on postoperative outcome in PA patients., Design and Setting: Retrospective study in nine referral centres., Participants: Of 496 consecutive PA patients who underwent AVS between 2006 and 2013, 217 with successful AVS under cosyntropin stimulation, and with concomitant data from two positions: proximal (common trunk) and distal (central vein) to the junction with the inferior phrenic vein, were included., Main Outcome Measures: Discordant rate of subtype diagnosis between common trunk and central vein, and postoperative outcomes in patients with discordant results., Results: Subtype diagnosis using common trunk and central vein was discordant in 10 (4·6%) of the 217 patients (κ = 0·87, P < 0·05). Of these 10 patients, eight with left unilateral subtype and two with bilateral subtype using common trunk data showed bilateral subtype and unilateral subtype, respectively, using central vein data. Five patients with left unilateral subtype and one with bilateral subtype by common trunk data underwent unilateral adrenalectomy. All six patients were cured of PA after adrenalectomy, resulting in false-negative rates of 17% (1/6) by common trunk data, and 83% (5/6) by central vein data., Conclusion: In view of its better potential diagnostic accuracy, technical ease, lower cost and lower risk of vein rupture, blood sampling from the common trunk of the left adrenal vein may be preferable as the standard method of AVS in patients with PA, although additional studies in a larger number of cases are required., (© 2015 John Wiley & Sons Ltd.)

Objectives: Adrenal vein sampling (AVS) is the standard criterion for the subtype diagnosis in primary aldosteronism (PA). Although lateralized index (LI) ≥4 after cosyntropin stimulation is the commonly recommended cut-off for unilateral aldosterone hypersecretion, many of the referral centres in the world use LI cut-off of <4 without sufficient evidence for its diagnostic accuracy., Aim: The aim of the study was to establish the diagnostic significance of contralateral (CL) aldosterone suppression for the subtype diagnosis in patients with LI <4 in AVS., Design and Patients: A retrospective multicentre study was conducted in Japan. Of 124 PA patients subjected to unilateral adrenalectomy after successful AVS with cosyntropin administration, 29 patients with LI < 4 were included in the study. The patients were divided into Group A with CL suppression (n = 16) and Group B (n = 13) without CL suppression. Three outcome indices were assessed after 6 months postoperatively: normalization/significant improvement of hypertension, normalization of the aldosterone to renin ratio (ARR) and normalization of hypokalaemia., Results: The normalization/significant improvement of hypertension was 81% in Group A and 54% in Group B (P = 0·2). The normalization of ARR was 100% in Group A and 46% in Group B (P = 0·004). Hypokalaemia was normalized in all patients of both groups. The overall cure rate of PA based on meeting all the three criteria was 81% in Group A and 31% in Group B (P = 0·01)., Conclusions: In patients with PA, where the LI is <4 on AVS, CL suppression of aldosterone is an accurate predictor of a unilateral source of aldosterone excess. CL suppression data should be interpreted in conjunction with computed tomographic adrenal imaging findings to guide surgical management., (© 2015 John Wiley & Sons Ltd.)

A 77-year-old man developed pulmonary tumor thrombotic microangiopathy (PTTM) 2 days after undergoing transurethral resection for urothelial carcinoma (G3) of the urinary bladder and died of respiratory failure 6 days later. Histological findings demonstrated marked intimal fibrocellular proliferation, fibrin thrombi, and both cancer cells and fibrin thrombi in the arteries of the lungs, findings consistent with PTTM. Prominent stenosis in arteries smaller than 300 μm was also seen. The Ki-67 labeling index of primary and metastasized cancer cells was 62.4 % and 70.2 %, respectively. The membranes of metastasized cancer cells expressed E-cadherin, similar to membranes in the urinary bladder. An aggressive PTTM course is affected by intimal fibrocellular proliferation and the high cell proliferation of cancer cells. Furthermore, prominent stenosis in small arteries and membranous staining of E-cadherin of metastasized cells suggest that cancer cells formed clusters by maintaining adhesion molecules and migrated into the arteries of the lungs, where they easily caused damage to the endothelium of small arteries, in contrast to dispersed cancer cells.

Lyman-alpha emitters are thought to be young, low-mass galaxies with ages of approximately 10(8) yr (refs 1, 2). An overdensity of them in one region of the sky (the SSA 22 field) traces out a filamentary structure in the early Universe at a redshift of z approximately 3.1 (equivalent to 15 per cent of the age of the Universe) and is believed to mark a forming protocluster. Galaxies that are bright at (sub)millimetre wavelengths are undergoing violent episodes of star formation, and there is evidence that they are preferentially associated with high-redshift radio galaxies, so the question of whether they are also associated with the most significant large-scale structure growing at high redshift (as outlined by Lyman-alpha emitters) naturally arises. Here we report an imaging survey of 1,100-microm emission in the SSA 22 region. We find an enhancement of submillimetre galaxies near the core of the protocluster, and a large-scale correlation between the submillimetre galaxies and the low-mass Lyman-alpha emitters, suggesting synchronous formation of the two very different types of star-forming galaxy within the same structure at high redshift. These results are in general agreement with our understanding of the formation of cosmic structure.

When galaxy formation started in the history of the Universe remains unclear. Studies of the cosmic microwave background indicate that the Universe, after initial cooling (following the Big Bang), was reheated and reionized by hot stars in newborn galaxies at a redshift in the range 6 < z < 14 (ref. 1). Though several candidate galaxies at redshift z > 7 have been identified photometrically, galaxies with spectroscopically confirmed redshifts have been confined to z < 6.6 (refs 4-8). Here we report a spectroscopic redshift of z = 6.96 (corresponding to just 750 Myr after the Big Bang) for a galaxy whose spectrum clearly shows Lyman-alpha emission at 9,682 A, indicating active star formation at a rate of approximately 10M(o) yr(-1), where M(o) is the mass of the Sun. This demonstrates that galaxy formation was under way when the Universe was only approximately 6 per cent of its present age. The number density of galaxies at z approximately 7 seems to be only 18-36 per cent of the density at z = 6.6.

Acute pulmonary thromboembolism (APTE) and deep venous thrombosis (DVT) are categorized into venous thromboembolism. APTE is one of the most critical post-operative complications because of its high mortality. Meanwhile, DVT is responsible for more than 80-95% of APTE cases. APTE occurred in 6 patients and DVT in 3 patients in the post-operative period during the past eleven years at our hospital. The median age of these patients, 5 men and 4 women, was 62 years (45-77). In many cases, the course of APTE showed a rapid progression. Four of the six patients with APTE died, and two of these four patients died within a few hours following the onset. Once it occurs, it is often lethal. Therefore, the prevention of thromboembolism is most important. In this study, we examined these 6 APTE cases and 3 DVT cases and discussed low dose heparin and intermittent sequential pneumatic compression (ISPC), prophylaxis against APTE in the post-operative period. We have been using ISPC for the high-risk group of thromboembolism in the post-operative period since 1999. In addition to using ISPC, we have been administering low dose heparin since November 2001. These 3 cases of DVT occurred regardless of adoption of ISPC. However, there were no cases of APTE after adoption of ISPC, and no cases of DVT or APTE after adoption of ISPC and administration of low dose heparin.