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Context There are inconsistent results and insufficient evidence as to whether an association exists between the size and aldosterone-producing ability of aldosterone-producing adenomas. Objective We further investigated this possible association retrospectively. Methods A total of 142 cases of primary aldosteronism diagnosed as unilateral by adrenal venous sampling at 2 referral centers between 2009 and 2019 were included. We classified these individuals into small and large tumor groups using a diameter of 14 mm as a cutoff. This size was the median diameter of the tumor on the affected side of the adrenal gland. We compared plasma aldosterone concentration (PAC), plasma renin activity (PRA), PAC to PRA ratio, PAC from a saline infusion test (SIT), urinary aldosterone secretion (uAld), and serum potassium as indices of aldosterone-producing ability between the 2 groups. In some cases, we conducted histopathological evaluations and detection of the KCNJ5 mutation. Results PAC, PAC to PRA ratio, PAC from SIT, and uAld were higher and serum potassium was lower in the large tumor group. PAC, PAC from SIT, uAld, and serum potassium significantly correlated with tumor diameter. PRA was not associated with tumor diameter. Clear cell–dominant cases were more common in the large tumor group, while cases showing a strong expression of CYP11B2 were not significantly different between the groups. KCNJ5 mutations tended to be more common in the large tumor group. Conclusion The higher aldosterone-producing ability in larger adenomas can be used to infer the responsible lesion and disease type.

Regional assessments of ice elevation change provide insight into the processes controlling an ice sheet's geometric response to climate forcing. In Southwest Greenland's land terminating sector (SWLTS), it is presumed that ice surface elevation changes result solely from changing surface mass balance (SMB). Here we test this assumption by developing a multi-decadal (1985–2017) record of elevation change from digital elevation models (DEMs) and comparing it to regional climate model output and available records of ice speed. The SWLTS thinned by >12 m on average over the full 32-year period, but the change was highly variable in time and space. Thinning was amplified in the central region of the SWLTS, relative to the north and south. During 1985–2007, the north and south regions demonstrated net thickening while the central region thinned. Regional differences in elevation change are inconsistent with SMB anomalies, indicating that enhanced ice flow in the north and south contributed to thickening during this early time interval. While clear validation in the south is prevented by incomplete velocity data, historical surface speeds in the north were elevated. These findings support the interpretation that changing ice flow can influence ice surface elevation in the slow-moving SWLTS.

Basal sliding in the ablation zone of the Greenland Ice Sheet is closely associated with water from surface melt introduced to the bed in summer, yet melting of basal ice also generates subglacial water year-round. Assessments of basal melt rely on modeling with results strongly dependent upon assumptions with poor observational constraints. Here we use surface and borehole measurements to investigate the generation and fate of basal meltwater in the ablation zone of Isunnguata Sermia basin, western Greenland. The observational data are used to constrain estimates of the heat and water balances, providing insights into subglacial hydrology during the winter months when surface melt is minimal or nonexistent. Despite relatively slow ice flow speeds during winter, the basal meltwater generation from sliding friction remains manyfold greater than that due to geothermal heat flux. A steady acceleration of ice flow over the winter period at our borehole sites can cause the rate of basal water generation to increase by up to 20 %. Borehole measurements show high but steady basal water pressure rather than monotonically increasing pressure. Ice and groundwater sinks for water do not likely have sufficient capacity to accommodate the meltwater generated in winter. Analysis of basal cavity dynamics suggests that cavity opening associated with flow acceleration likely accommodates only a portion of the basal meltwater, implying that a residual is routed to the terminus through a poorly connected drainage system. A forcing from cavity expansion at high pressure may explain observations of winter acceleration in western Greenland.

In patients with primary aldosteronism (PA), multiple adrenocortical nodules may be present on the surgical side. The aim of this study was to clarify the pathological diagnosis and the node-by-node diagnostic capability of segmental adrenal venous sampling (sAVS).Retrospective study.A total of 162 patients who underwent adrenalectomy following sAVS were studied.Multiple nodules on the surgical side were extracted while referring to contrast-enhanced computed tomography images. We also performed a detailed histopathological analysis of the resected specimens from patients undergoing sAVS, which included immunohistochemistry for CYP11B2.In 11 (6.8%) patients, two to three nodules were detected on the surgical side. All patients were diagnosed by sAVS with at least one aldosterone-producing adenoma (APA) for localized aldosterone elevation in tributaries. Seven patients showed a lateralization index value of ≥ 4 after ACTH stimulation. Histopathologically and clinically, two patients had two or three CYP11B2-positive APAs, and the other nine patients both APAs and non-APAs. The positive predictive value of the most suspected APA, i.e., the drainer that showed the highest aldosterone level by sAVS, was 11/11 (100%, 95% confidence interval [CI]: 71.5-100%), while that for the second and third suspected APA was 3/7 (42.9%, 95% CI: 9.9-81.6%), and they were significantly different (p=0.01). Further, the positive predictive value of non-APA was 4/4 (100%, 95% CI: 39.8-100%).The sAVS could correctly diagnose the aldosterone production in multiple ipsilateral adrenal nodules. This article is protected by copyright. All rights reserved.

Introduction Hypertension is one of the most common clinical features of patients with overt and subclinical hypercortisolism. Although previous studies have shown the coexistence of autonomous cortisol and aldosterone secretion, it is unclear whether aldosterone plays a role in hypertension among patients with hypercortisolism. Therefore, we examined the associations of plasma aldosterone concentrations (PACs) with hypertension among patients with overt and subclinical hypercortisolism. Methods This single-center retrospective cohort study included patients with adrenal tumor and serum cortisol levels after 1-mg dexamethasone suppression test >1.8 µg/dL (50 nmol/L). Using multivariable regression models adjusting for baseline characteristics, we investigated the association of PACs with systolic blood pressure and postoperative improvement of hypertension after the adrenalectomy. Results Among 89 patients enrolled in this study (median age, 51 years), 21 showed clinical signs of Cushing syndrome (overt hypercortisolism) and 68 did not show clinical presentations (subclinical hypercortisolism). We found that higher PACs were significantly associated with elevated systolic blood pressure among patients with subclinical hypercortisolism (adjusted difference [95% CI] = +0.59 [0.19-0.99], P = 0.008) but not among those with overt hypercortisolism. Among 33 patients with subclinical hypercortisolism and hypertension who underwent adrenalectomy, the postoperative improvement of hypertension was significantly associated with higher PACs at baseline (adjusted risk difference [95% CI] = +1.45% [0.35-2.55], P = 0.01). Conclusion These findings indicate that aldosterone may contribute to hypertension among patients with subclinical hypercortisolism. Further multi-institutional and population-based studies are required to validate our findings and examine the clinical effectiveness of the intervention targeting aldosterone for such patients.

Human speech is often accompanied by body gestures including arm and hand gestures. We present a method that reenacts a high-quality video with gestures matching a target speech audio. The key idea of our method is to split and re-assemble clips from a reference video through a novel video motion graph encoding valid transitions between clips. To seamlessly connect different clips in the reenactment, we propose a pose-aware video blending network which synthesizes video frames around the stitched frames between two clips. Moreover, we developed an audio-based gesture searching algorithm to find the optimal order of the reenacted frames. Our system generates reenactments that are consistent with both the audio rhythms and the speech content. We evaluate our synthesized video quality quantitatively, qualitatively, and with user studies, demonstrating that our method produces videos of much higher quality and consistency with the target audio compared to previous work and baselines., 15 pages, 10 figures. Accepted by CVPR 2022

In patients with primary aldosteronism diagnosed with unilateral lesions through adrenal venous sampling, excess aldosterone occasionally persists after adrenalectomy. We investigated whether aldosterone values from unresected adrenals would be associated with postoperative outcomes. Overall, 102 primary aldosteronism patients, who underwent segmental adrenal venous sampling and unilateral adrenalectomy, were assessed for biochemical success (as outlined in the PASO [Primary Aldosteronism Surgical Outcomes] Study) at 1 year after surgery by using the saline infusion test. We divided patients into the biochemical complete or incomplete success group. Eighty-seven and 15 patients had complete and incomplete biochemical success, respectively. The biochemical incomplete group, compared with the biochemical complete group, had higher maximum aldosterone in tributary veins (11 000 versus 7030 pg/mL, P =0.006), maximum aldosterone/cortisol in tributary veins (18.05 versus 9.13, P P =0.011), and aldosterone/cortisol in the central vein (13.67 versus 8.08, P

Background Pheochromocytoma and paraganglioma caused by succinate dehydrogenase gene mutations is called hereditary pheochromocytoma/paraganglioma syndrome. In particular, succinate dehydrogenase subunit B mutations are important because they are strongly associated with the malignant behavior of pheochromocytoma and paraganglioma . This is a case report of a family of hereditary pheochromocytoma/paraganglioma syndrome carrying a novel mutation in succinate dehydrogenase subunit B. Case presentation A 19-year-old Japanese woman, whose father died of metastatic paraganglioma, was diagnosed with abdominal paraganglioma, and underwent total resection. Succinate dehydrogenase subunit B genetic testing detected a splice-site mutation, c.424-2delA, in her germline and paraganglioma tissue. Afterwards, the same succinate dehydrogenase subunit B mutation was detected in her father’s paraganglioma tissues. In silico analysis predicted the mutation as “disease causing.” She is under close follow-up, and no recurrence or metastasis has been observed for 4 years since surgery. Conclusions We detected a novel succinate dehydrogenase subunit B mutation, c.424-2delA, in a Japanese family afflicted with hereditary pheochromocytoma/paraganglioma syndrome and found the mutation to be responsible for hereditary pheochromocytoma/paraganglioma syndrome. This case emphasizes the importance of performing genetic testing for patients with pheochromocytoma and paraganglioma suspected of harboring the succinate dehydrogenase subunit B mutation (that is, metastatic, extra-adrenal, multiple, early onset, and family history of pheochromocytoma and paraganglioma) and offer surveillance screening to mutation carriers.

Steroid administration to patients with urea cycle disorders can cause hyperammonemia. We encountered a 36-year-old woman with neuromyelitis optica (NMO) complicated by ornithine transcarbamylase (OTC) deficiency. By reducing the doses of steroids and adequate infusion management, we were able to administer pulse steroid therapy without any severe complications. This case indicates the safety of steroid treatment in patients with urea cycle disorders.

This report presents a case of left adrenal aldosterone-producing adenoma (APA) diagnosed by segmental adrenal venous sampling in a patient with primary aldosteronism and a rare venous anomaly in which the left inferior phrenic vein (LIPV) and adrenal central vein entered the left renal vein separately. The outflow of tumor blood into the LIPV and the specimen from the LIPV that showed much higher aldosterone level than that from the adrenal central vein and tributaries were useful for proving the aldosterone hypersecretion from the APA. Sampling from the LIPV could be of diagnostic value for left APA.

Aims/Introduction Renal dysfunction might quickly progress in patients with type 2 diabetes mellitus, when accompanied by hypertension. However, whether primary aldosteronism (PA), which autonomously over‐secretes aldosterone, causes additional renal damage in patients with type 2 diabetes mellitus is unclear. We evaluated the impact of PA on renal function in patients with type 2 diabetes mellitus. Materials and Methods A retrospective review of all patients with type 2 diabetes mellitus who visited Yokohama Rosai Hospital’s (Yokohama Japan) outpatient department between April 2017 and March 2018 was carried out. Records of patients with PA who underwent PA treatment by adrenalectomy or mineralocorticoid receptor antagonists (PA group) and those without PA (non‐PA group) were extracted, and renal function was compared between the two groups. Untreated PA patients were excluded, as their renal function might be overestimated as a result of glomerular hyperfiltration. Results There were 83 patients in the PA group and 1,580 patients in the non‐PA group. The PA group had significantly lower estimated glomerular filtration rates than the non‐PA group (66.3 [52.4–78.2] vs 70.5 [56.0–85.6] mL/min/1.73 m2, P = 0.047). Multiple regression analysis showed that PA was a factor for decreased estimated glomerular filtration rate, independent of age, sex, glycated hemoglobin, diuretic use and hypertension (P = 0.025). PA induced a 3.7‐mL/min/1.73 m2 (95% confidence interval 0.47–6.9) decrease in estimated glomerular filtration rate, equivalent to that induced by 4.4 years of aging. Conclusions Our results show that in patients with type 2 diabetes mellitus, PA is an independent risk factor for renal dysfunction. To prevent the progression of renal failure, PA should not be overlooked., In this retrospective study, primary aldosteronism was an independent risk factor for renal dysfunction in patients with type 2 diabetes. To prevent the progression of renal failure, primary aldosteronism should not be overlooked, and should be promptly diagnosed and treated.

[Purpose] The aim of this study was to assess the usefulness of computed tomography for outcome prediction in patients with putaminal hemorrhage at admission to a convalescent rehabilitation ward. [Participants and Methods] Patients admitted to our convalescent rehabilitation ward after transfer from acute care hospitals were included in this study. Multiple regression analyses were performed using the score in the motor component of the Functional Independence Measure at discharge as the target value. Hemorrhage volume assessed with computed tomography during acute care and age were set as the explanatory variables. The motor component of the Functional Independence Measure score at admission and the time (days) from onset were also recorded. Correlation analyses between all the possible pairs of explanatory variables were then performed. [Results] Hemorrhage volume and age were both significant contributors to the motor component of the Functional Independence Measure score at discharge. However, the contribution of hemorrhage volume disappeared when the time from onset and motor component of the Functional Independence Measure score at admission were added. Hemorrhage volume significantly correlated with the time from onset and motor component of the Functional Independence Measure score at admission. [Conclusion] The present findings suggest that computed tomography may be useful for outcome prediction from the acute stage in stroke patients with putaminal hemorrhage. However, because of multicollinearity, its predictive power was reduced when the patients were transferred to a convalescent rehabilitation ward.

We herein report a case of Carney complex (CNC) complicated with primary pigmented nodular adrenocortical disease (PPNAD) after unilateral adrenalectomy. A 44-year-old woman was admitted to our hospital for PPNAD surgery. She had previously undergone surgery for cardiac myxoma and had a PRKAR1A mutation with no family history of CNC. She had Cushing's signs, but her metabolic abnormalities were mild. Adrenal insufficiency due to poor medication adherence was a concern, so she underwent unilateral adrenalectomy. Cushing's signs improved postoperatively and without recurrence for five years. Treatment plans for PPNAD should be determined based on the patient's condition, medication adherence, and wishes.

PURPOSE: We aimed to analyze the prevalence and radiological characteristics of duplicated right adrenal veins (DRAVs) and evaluate the diagnostic impact of adrenal venous sampling (AVS) in primary aldosteronism. METHODS: DRAVs were retrospectively identified among patients who underwent segmental AVS between April 2017 and March 2020. DRAVs were defined as main or accessory according to the drainage area. The diameter, position, hormone levels, and treatment plan based on AVS were compared between main and accessory RAVs, using the Wilcoxon rank-sum test. RESULTS: Fourteen of 432 patients (3.2%) were diagnosed with DRAVs. On venography, the mean diameters of the main and accessory side were 3±0.63 mm and 2.1±0.41 mm, respectively, and were significantly different (p < 0.001). The mean relative position in craniocaudal direction of main and accessory veins from the adrenal caudal edge on computed tomography was 65.5%±16.0%, and 48.1%±16.8%, respectively, which was significantly different (p = 0.007). The left–right positions and hormone levels were not significantly different. Based on conventional AVS, the treatment plan between DRAVs was not changed in six of eight patients, but changed from surgery to medication in two patients with right aldosterone-producing adenoma (APA)/microadenoma based on segmental AVS findings. CONCLUSION: DRAVs, in which the main RAV was thicker and more cranially located than the accessory RAV were rare. Depending on blood sampled from either of DRAVs, the diagnosis made through conventional AVS might change treatment approach from surgery to medication, especially with right APA. Hence, their identification is important to make an accurate subtyping by AVS.

Primary aldosteronism (PA) usually accompanies suppressed plasma renin activity (PRA) through a negative feedback mechanism. While some cases of PA with unsuppressed PRA were reported, there have been no studies about the characteristics of PA with unsuppressed PRA; thus, these characteristics were examined herein. Nine patients with unsuppressed PRA and 86 patients with suppressed PRA were examined. All patients underwent segmental adrenal venous sampling (sAVS) and adrenalectomy, and were pathologically confirmed to have cytochrome P450 11B2 (CYP11B2)-positive aldosterone-producing adenoma according to international histopathology consensus criteria. Unsuppressed and suppressed PRA were defined as PRA levels of > 1.0 and ≤ 1.0 ng/mL/hr, respectively, in multiple blood samples obtained in the resting position. The unsuppressed PRA group had higher morning cortisol levels (12.6 [8.5, 13.5] vs. 8.5 [7.1, 11.0] μg/dL, P = 0.03) and higher cortisol levels after a 1 mg dexamethasone suppression test (DST) (2.2 [1.6, 2.5] vs. 1.3 [1.0, 1.9] μ g/dL, P = 0.004) than the suppressed PRA group. The unsuppressed PRA group also showed higher aldosterone levels on the non-surgical side during sAVS (P = 0.02 before adrenocorticotropic hormone (ACTH) stimulation, P = 0.002 after ACTH stimulation), a higher intensity of CYP17 expression in the resected adrenal gland (P = 0.02), and a lower clinical complete success rate 1 year after surgery (P = 0.04) compared with those in the suppressed PRA group. These findings suggest that PA should not be ruled out by unsuppressed PRA among patients with hypertension, particularly when their cortisol levels remain unsuppressed in the 1 mg DST. Meanwhile, it should be acknowledged that patients with unsuppressed PRA have higher aldosterone levels on the non-surgical side, and a lower likelihood of postoperative complete clinical success is to be expected.

We propose Neural State Machine , a novel data-driven framework to guide characters to achieve goal-driven actions with precise scene interactions. Even a seemingly simple task such as sitting on a chair is notoriously hard to model with supervised learning. This difficulty is because such a task involves complex planning with periodic and non-periodic motions reacting to the scene geometry to precisely position and orient the character. Our proposed deep auto-regressive framework enables modeling of multi-modal scene interaction behaviors purely from data. Given high-level instructions such as the goal location and the action to be launched there, our system computes a series of movements and transitions to reach the goal in the desired state. To allow characters to adapt to a wide range of geometry such as different shapes of furniture and obstacles, we incorporate an efficient data augmentation scheme to randomly switch the 3D geometry while maintaining the context of the original motion. To increase the precision to reach the goal during runtime, we introduce a control scheme that combines egocentric inference and goal-centric inference. We demonstrate the versatility of our model with various scene interaction tasks such as sitting on a chair, avoiding obstacles, opening and entering through a door, and picking and carrying objects generated in real-time just from a single model.

Adrenal Cushing's syndrome (CS) is caused by cortisol-producing adrenal adenoma and is frequently accompanied by glucose metabolism disorders, which are characterized by increased insulin resistance and insufficient β-cell compensation. However, considering the rarity of CS, few studies have assessed whether the glucose metabolism disorders could be ameliorated by surgical treatment. In this case series, we evaluated glucose metabolism before and after surgery in 11 patients (10 women and 1 man) who underwent unilateral adrenalectomy for overt adrenal CS between 2005 and 2016. Patients with pre-diagnosed diabetes mellitus (DM) were excluded. Pre- and post-operative 75-g oral glucose tolerance tests were performed. Cortisol secretion decreased significantly after surgery (median 24-h urinary free cortisol: 582.0 μg/day [interquartile range: 321.0-743.0 μg/day] to 31.3 μg/day [23.6-40.6 μg/day], p = 0.001). The results of the OGTT generally improved after surgery (normal glucose tolerance/impaired glucose tolerance/DM: 2/8/1 to 8/3/0), with significant decreases in the immunoreactive insulin and glucose levels. We also found a decrease in the median homeostatic model assessment of insulin resistance (2.4 [1.4-2.8] to 1.0 [0.6-1.1], p = 0.002), and increases in the median Matsuda index (3.0 [2.3-4.5] to 8.2 [6.3-11.4], p < 0.001), median insulinogenic index (0.70 [0.22-1.51] to 1.22 [0.78-1.64], p = 0.08), and median disposition index (609.1 [237.8-1,095.2] to 1,286.0 [1,034.6-1,857.6], p = 0.002). These findings indicate that adrenalectomy for adrenal CS without overt DM may help ameliorate glucose metabolism disorders, and improve both insulin resistance and insulin secretion.

Pheochromocytoma (PCC) is rare catecholamine-producing endocrine tumor that metastasizes in approximately 10% of cases. As a functional imaging of PCC, 123I-metaiodobenzylguanidine (MIBG) scintigraphy was established, and some cases of PCC exhibit negative accumulation on MIBG scintigraphy, indicating a high risk of metastasis. Additionally, germline genetic variants of PCC are evident in approximately 30% of cases, although the genotype-phenotype correlation in PCC, especially the association between genetic mutations and MIBG scintigraphy, remains unclear. A 33-year-old man was admitted to our hospital for further examination for hypertension. He was diagnosed with sporadic PCC, and left adrenalectomy was performed. The adrenal tumor was negative on MIBG scintigraphy. Histology of the tumor revealed a moderately differentiated PCC. Target gene testing revealed a mutation in RET (c.2071G > A). This mutation has been reported to be a tumor-developing gene involved in the pathogenesis of PCC. Moreover, the RET mutation is the only gene mutation reported in a previous study of PCC with negative results on MIBG scintigraphy, except for the SDHB gene mutation, which is a common mutation in metastatic PCC. Correctively, the present RET gene mutation may be associated to MIBG-scintigraphy negative PCC and its pathophysiology. Clinicians should follow such cases more cautiously in clinical practice.

On the Kamchatka Peninsula in the Russian Far East, 405 glaciers with an estimated total mass of 49 Gt were reported in the 1970s. These have been retreating at an accelerated rate since the start of the 21st century. Because glacier studies in this region are scarce, ice loss and its influence on sea level rise and regional environments is poorly understood. In this study, we analyzed satellite data to quantify glacier mass change from 2000 to 2016 in six major glacier-covered regions on the peninsula. The mean rate of the glacier mass change over the study period was −0.46 ± 0.01 m w.e. a−1 (total mass change was −4.9 ± 0.1 Gt, −304.2 ± 9.1 Mt a−1), which is slightly lower than other regions in mid-latitude and subarctic zones. The mass loss accelerated from >−0.33 ± 0.02 m w.e. a−1 in the period 2000–2006/2010 to −1 in 2006/2010–2015/16. The increase in mass loss is attributed to a rise in average decadal summer temperatures observed in the region (+0.68°C from 1987–99 to 2000–13). Moreover, a recent trend in Pacific decadal oscillation suggests future acceleration of mass loss due to a decline in winter precipitation.

Basal sliding in the ablation zone of the Greenland Ice Sheet is closely associated with water from surface melt introduced to the bed in summer, yet melting of basal ice also generates subglacial water year-round. Assessments of basal melt rely on modelling with results strongly dependent upon assumptions with poor observational constraint. Here we use surface and borehole measurements to investigate the generation and fate of basal meltwater in the ablation zone of Isunnguata Sermia basin, Western Greenland. The observational data are used to constrain estimates of the heat and water balances, providing insights into subglacial hydrology during the winter months when surface melt is minimal or non-existent. Despite relatively slow ice flow speeds during winter, the basal meltwater generation from sliding friction remains many fold greater than that due to geothermal heat flux. A steady acceleration of ice flow over the winter period at our borehole sites can cause the rate of basal water generation to increase by up to 20 %. Borehole measurements show high but steady basal water pressure, rather than monotonically increasing pressure. Ice and groundwater sinks for water do not likely have sufficient capacity to accommodate the meltwater generated in winter. Analysis of basal cavity dynamics suggests that cavity opening associated with flow acceleration likely accommodates only a portion of the basal meltwater, implying a residual is routed to the terminus through a poorly connected drainage system. A forcing from cavity expansion at high pressure may explain observations of winter acceleration in Western Greenland.

BACKGROUND Diabetic kidney disease (DKD) is one of the main complications of type 2 diabetes mellitus (T2DM). DKD is a known risk factor for end-stage renal disease, cardiovascular disease, and all-cause death. Effective intervention for early-stage DKD is vital to slowing down the progression of kidney disease and improve prognoses. Mobile health (mHealth) is reportedly effective in supporting patients’ self-care and improving glycemic control, but the impact of mHealth on DKD has yet to be shown. OBJECTIVE The purpose of this study is to evaluate the efficacy of standard therapy with the addition of a self-management support system, DialBetesPlus, in patients with DKD and microalbuminuria. METHODS This study is a prospective, randomized, open-label, multicenter clinical trial. The target population consists of 160 patients diagnosed with T2DM accompanied by microalbuminuria. We randomly assigned the patients to 2 groups—the intervention group using DialBetesPlus in addition to conventional therapy and the control group using conventional therapy alone. DialBetesPlus is a smartphone application that supports patients’ self-management of T2DM. The study period was 12 months, with a follow-up survey at 18 months. The primary outcome was a change in albuminuria levels at 12 months. Secondary outcomes included changes in physical parameters, blood test results (glycemic control, renal function, and lipid metabolism), lifestyle habits, self-management scores, medication therapy, and quality of life. RESULTS The study was approved in April 2018. We began recruiting patients in July 2018 and completed recruiting in August 2019. The final 18-month follow-up was conducted in March 2021. We recruited 159 patients and randomly allocated 70 into the intervention group and 61 into the control group, with 28 exclusions due to withdrawal of consent, refusal to continue, or ineligibility. The first results are expected to be available in 2021. CONCLUSIONS This is the first randomized controlled trial assessing the efficacy of mHealth on early-stage DKD. We expect that albuminuria levels will decrease significantly in the intervention group due to improved glycemic control with ameliorated self-care behaviors. CLINICALTRIAL UMIN-CTR UMIN000033261; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000037924 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/31061

Segmental selective adrenal venous sampling (sAVS) elucidates an intraadrenal aldosterone activity map (IAMap), which allows us to design a novel surgical treatment strategy for patients with primary aldosteronism. We evaluated the usefulness of sAVS by analyzing 278 patients with whom we had prospectively used IAMap using the criteria of sAVS for surgical indication between 2009 and 2015. We evaluated its diagnostic accuracy using pathological and postsurgical biochemical and clinical outcomes. One hundred twenty and 158 patients were diagnosed with unilateral and bilateral disease, respectively, through sAVS. The concordance of lateralization diagnosis with computed tomography imaging was 66.6%. Among the unilateral patients, we performed partial adrenalectomy in 68 patients whose IAMap showed focal aldosterone hypersecretion from computed tomography-detectable tumor in the affected adrenal gland. All of them achieved complete biochemical success 1 year after surgery. Furthermore, 25 of 158 bilateral disease patients underwent surgical resection because they were preoperatively diagnosed as bilateral aldosterone-producing adenomas by IAMap. These cases showed complete or partial biochemical success (28.0% and 72.0%, respectively); 36.0% showed complete clinical success. Pathological studies demonstrated that all 145 resected specimens possessed aldosterone-producing adenoma or multiple nodules (132 and 13 cases, respectively), and none showed diffuse hyperplasia. IAMap accurately diagnosed both bilateral and unilateral aldosterone-producing adenomas and diffuse hyperplasia before surgery. sAVS allows a novel surgical strategy for selected PA patients with favorable outcomes.

Background: Hypertension is one of the most common and distinguishing clinical features of patients with overt Cushing’s syndrome (CS) and subclinical Cushing’s syndrome (SCS). Although hypertension can be triggered by excess cortisol levels, it is unclear whether the cortisol is sufficient to explain the hypertension among these diseases (particularly SCS in which cortisol is slightly elevated) indicating the potential contribution of aldosterone to the elevated blood pressure. In this study, we aimed to examine the aldosterone biosynthesis among patients with CS or SCS. Methods: We conducted the prospective study enrolling 90 patients (21 CS and 69 SCS) from 2016 to 2019 at Yokohama Rosai Hospital. We diagnosed patients with CS when they showed clinical features of CS and serum cortisol levels (F) after 1 mg dexamethasone (1-mg DST) was >5 μg/dl. SCS was defined as F after 1-mg DST was >1.8 μg/dl. For patients who are considered to be appropriate for adrenalectomy, we performed the segment-selective ACTH-loading adrenal venous sampling (AVS) to find the laterality of cortisol producing adenoma (CPA). The resolution of hypertension was assessed 1-year after the adrenalectomy. Results: The median [interquartile range] age was 51 [46–62] years and males were 28%. Hypertension was observed in 21 (100%) CS and 58 (84%) SCS patients. Median F after 1mg-DST were 16.4 [14.3–18.7] mg/dl and 5.1 [3.4–7.5] mg/dl among CS and SCS patients, respectively. Median plasma renin activity among CS and SCS patients were 0.7 [0.4–1.3] ng/ml/h and 0.5 [0.2–0.9] ng/ml/h, respectively. Median plasma aldosterone concentrations (PAC) among CS and SCS patients were 8.3 [7.2–9.8] ng/dl and 9.3 [7.2–17.0] ng/dl at baseline, rising to 24.7 [18.6–32.3] ng/dl and 32.9 [25.8–48.3] ng/dl after ACTH stimulation. During the AVS, all SCS cases with hypertension showed the aldosterone excess (i.e. effluent aldosterone concentrations ≥1400 ng/dl after ACTH stimulation) in at least one adrenal segmental tributary vein. All CS cases showed the hypertension resolution after the resection of CPA except one case showing aldosterone excess on the opposite side of CPA. Among 39 SCS cases who underwent adrenalectomy, hypertension remained in 10 cases, and all of them showed aldosterone excess on the opposite side of CPA. Conclusion: We found that aldosterone was likely to be elevated (or hyper-responsive to ACTH) among CS or SCS patients with hypertension. The proportion of the hypertension resolution after the CPA resection was lower when patients showed aldosterone excess on the opposite side of CPA. These findings indicate that elevated aldosterone may contribute to the high prevalence of hypertension and its resolution rate after adrenalectomy for patients with CPA. Further studies are needed to examine the clinical effectiveness of the intervention targeting aldosterone among patients with CS and SCS.

Background and Aim: Glycated albumin (GA) reflects a short-term glycemic control (about 2 weeks) in comparison to glycated hemoglobin (HbA1c) which reflects a long-term glycemic control. Thus, if the dietary, exercise, or medication therapy before the educational admission is effective, a rapid improvement in GA can be observed. However, the impact of the improvement in GA on the subsequent glycemic control is not well understood. This retrospective study analyzed the association between the change of GA before educational admission and glycemic control one year after the discharge of patients with type 2 diabetes mellitus (T2DM). Method: We analyzed data from 114 T2DM patients who were admitted to our hospital from 2011 to 2016. The GA data within 30 days before admission and on the day of admission were available for all patients. The change of GA per day (ΔGA/day) was calculated as [(GA on admission) - (GA before admission)/number of days between the two measurements of GA]. Patients with renal dysfunction (eGFR < 30 mL/min/1.73 m2) or insulin deficiency [fasting C-peptide (CPR) < 0.5 ng/mL or two-hour postprandial CPR < 1.0 ng/mL] were excluded. Patients achieving an HbA1c of < 7.0 % at one year after discharge were defined as achievers, and the rest were defined as non-achievers. Multiple baseline factors including the ΔGA/day between the two groups were compared. Results: Of the 114 patients, 68 were achievers and 46 were non-achievers. GA significantly declined during before and just after the admission to hospital (median [interquartile range]: 26.0 [22.2 - 32.7] to 25.0 [21.4 - 29.8] %, p < 0.001). The range of the ΔGA/day was between -1.14 and 0.28, with a median value of -0.08 [-0.26 - 0.002]. The age, body mass index, and HbA1c levels at admission were not significantly different between the two groups. The increase in CPR after the glucagon loading test was higher in the achievers than in the non-achievers (1.85 [1.32 - 2.87] vs 1.21 [0.53 - 1.92] ng/ml, p = 0.004). The ΔGA/day was lower in the achievers than in the non-achievers (-0.14 [-0.39 - -0.006] vs -0.04 [-0.13 - 0.03], p = 0.002). A logistic regression analysis demonstrated that the ΔGA/day was the factor associated with achieving an HbA1c of < 7.0% at one year after discharge (Odds ratio: 0.037, 95 % confidence interval: 0.004 - 0.267, p < 0.001). In the receiver operating characteristic curve analysis, the ΔGA/day had an area under the curve of 0.67 in the achievement group and the cutoff value was set as -0.146 for predicting the achievement, with a sensitivity of 0.50 and a specificity of 0.85. Conclusion: Our results suggest that the change in GA before the educational admission can predict the glycemic control one year after the discharge of T2DM patients.