Temporal trends in clinical features of patients with primary aldosteronism over 20 years.

Primary aldosteronism (PA) accounts for approximately 5-10% of hypertension cases. Over the past 20 years, the reported incidence of PA has increased due to widespread screening for secondary hypertension and imaging studies. We aimed to evaluate the temporal trends in the clinical characteristics and subtypes of PA. A total of 1064 patients with PA in two tertiary hospitals between 2000 and 2021 were categorized into three groups according to the year of diagnosis: 2000-2009, 2010-2015, and 2016-2021. The clinical characteristics of the patients over the three time periods were compared using a trend analysis. The age at diagnosis and sex of patients with PA did not change over 20 years. The proportion of patients with bilateral hyperaldosteronism (BHA) increased (11%, 25%, and 40%, P for trend <0.001). The proportion of hypokalemia (87%, 61%, and 40%) and plasma aldosterone concentration (36.0, 30.8, and 26.6 ng/dL) decreased (all P for trend <0.001). There was a trend toward an increased proportion of incidentally detected patients compared to clinically symptomatic patients (36%, 55%, and 61%, P for trend <0.001). The concordance rate of imaging and adrenal venous sampling results decreased (91%, 70%, and 57% P for trend <0.001). However, the proportion of patients with resistant hypertension and comorbidities did not differ. In conclusion, among patients with PA, patients with BHA and incidental detection have increased over 20 years, and more patients are likely to present with milder clinical symptoms and biochemical profiles.

Preoperative prediction of metastatic pheochromocytoma and paraganglioma using clinical, genetic, and biochemical markers: A cohort study.

BACKGROUND: The prevalence of metastatic pheochromocytoma and paraganglioma (PPGL) is approximately 15%-20%. Although there are indicators to assess metastatic risks, none of them predict metastasis reliably. Therefore, we aimed to develop and validate a scoring system using clinical, genetic, and biochemical risk factors to preoperatively predict the metastatic risk of PPGL. METHODS: In the cross-sectional cohort (n = 180), clinical, genetic, and biochemical risk factors for metastasis were identified using multivariate logistic regression analysis, and a novel scoring system was developed. The scoring system was validated and compared with the age, size of tumor, extra-adrenal location, and secretory type (ASES) score in the longitudinal cohort (n = 114). RESULTS: In the cross-sectional cohort, pseudohypoxia group-related gene variants (SDHB, SDHD, or VHL), methoxytyramine >0.16 nmol/L, and tumor size >6.0 cm were independently associated with metastasis after multivariate logistic regression. Using them, the gene variant, methoxytyramine, and size of tumor (GMS) score were developed. In the longitudinal cohort, Harrell's concordance index of the GMS score (0.873, 95% confidence interval [CI]: 0.738-0.941) was higher than that of the ASES score (0.713, 95% CI: 0.567-0.814, p = 0.007). In the longitudinal cohort, a GMS score ≥2 was significantly associated with a higher risk of metastasis (hazard ratio = 25.07, 95% CI: 5.65-111.20). A GMS score ≥2 (p < 0.001), but not ASES score ≥2 (p = 0.090), was associated with shorter progression-free survival. CONCLUSION: The GMS scoring system, which integrates gene variant, methoxytyramine level, and tumor size, provides a valuable preoperative approach to assess metastatic risk in PPGL.

So Shiho Tang Reduces Inflammation in Lipopolysaccharide-Induced RAW 264.7 Macrophages and Dextran Sodium Sulfate-Induced Colitis Mice.

So Shiho Tang (SSHT) is a traditional herbal medicine commonly used in Asian countries. This study evaluated the anti-inflammatory effect of SSHT and the associated mechanism using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and murine dextran sodium sulfate (DSS)-induced ulcerative colitis models. Pre-treatment of RAW 264.7 macrophages with SSHT significantly reduced LPS-induced inflammation by decreasing nitrite production and regulating the mitogen-activated protein kinase pathway. Meanwhile, in mice, DSS-induced colitis symptoms, including colon shortening and body weight loss, were attenuated by SSHT. Moreover, representative compounds of SSHT, including glycyrrhizic acid, ginsenoside Rb1, baicalin, saikosaponin A, and saikosaponin B2, were quantified, and their effects on nitrite production were measured. A potential anti-inflammatory effect was detected in LPS-induced RAW 264.7 cells. Our findings suggest that SSHT is a promising anti-inflammatory agent. Its representative components, including saikosaponin B2, ginsenoside Rb1, and baicalin, may represent the key active compounds responsible for eliciting the anti-inflammatory effects and can, therefore, serve as quality control markers in SSHT preparations.

Inflamed immune phenotype predicts favorable clinical outcomes of immune checkpoint inhibitor therapy across multiple cancer types.

BACKGROUND: The inflamed immune phenotype (IIP), defined by enrichment of tumor-infiltrating lymphocytes (TILs) within intratumoral areas, is a promising tumor-agnostic biomarker of response to immune checkpoint inhibitor (ICI) therapy. However, it is challenging to define the IIP in an objective and reproducible manner during manual histopathologic examination. Here, we investigate artificial intelligence (AI)-based immune phenotypes capable of predicting ICI clinical outcomes in multiple solid tumor types. METHODS: Lunit SCOPE IO is a deep learning model which determines the immune phenotype of the tumor microenvironment based on TIL analysis. We evaluated the correlation between the IIP and ICI treatment outcomes in terms of objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) in a cohort of 1,806 ICI-treated patients representing over 27 solid tumor types retrospectively collected from multiple institutions. RESULTS: We observed an overall IIP prevalence of 35.2% and significantly more favorable ORRs (26.3% vs 15.8%), PFS (median 5.3 vs 3.1 months, HR 0.68, 95% CI 0.61 to 0.76), and OS (median 25.3 vs 13.6 months, HR 0.66, 95% CI 0.57 to 0.75) after ICI therapy in IIP compared with non-IIP patients, respectively (p<0.001 for all comparisons). On subgroup analysis, the IIP was generally prognostic of favorable PFS across major patient subgroups, with the exception of the microsatellite unstable/mismatch repair deficient subgroup. CONCLUSION: The AI-based IIP may represent a practical, affordable, clinically actionable, and tumor-agnostic biomarker prognostic of ICI therapy response across diverse tumor types.

Hidden Direct Bandgap of Bi2O2Se by Se Vacancy and Enhanced Direct Bandgap of Bismuth Oxide Overlayer.

The Bi2O2Se surfaces are well-known to possess 50% Se vacancies, yet they have shown no in-gap states within the indirect bandgap (∼0.8 eV). We have found that the hidden in-gap states arising from the Se vacancies in a 2 × 1 pattern induce a reduced direct bandgap (∼0.5 eV). Such a reduced direct bandgap is responsible for the high electron mobility of Bi2O2Se. Moreover, the Bi oxide overlayers of the Bi thin films, formed through air exposure and annealing, unexpectedly exhibit a large direct bandgap (∼2.1 eV). The simplified fabrication of Bi oxide overlayers provides promise for improving Bi2O2Se electronic devices and enhancing photocatalytic activity.

Impact of Hyperglycemia on Complication and Mortality after Transarterial Chemoembolization for Hepatocellular Carcinoma.

BACKGRUOUND: Current guidelines regarding periprocedural glycemic control to prevent complications after nonsurgical invasive procedures are insufficient. Transarterial chemoembolization (TACE) is a widely used treatment for unresectable hepatocellular carcinoma. We aimed to investigate the association between diabetes mellitus (DM) per se and the degree of hyperglycemia with postprocedural complications after TACE. METHODS: A total of 22,159 TACE procedures performed at Seoul National University Hospital from 2005 to 2018 were retrospectively analyzed. The associations between DM, preprocedural glycosylated hemoglobin (HbA1c), and periprocedural average glucose with postprocedural adverse outcomes were evaluated. The primary outcome was occurrence of postprocedural bacteremia. Secondary outcomes were acute kidney injury (AKI), delayed discharge and death within 14 days. Periprocedural glucose was averaged over 3 days: the day of, before, and after the TACE procedures. Propensity score matching was applied for procedures between patients with or without DM. RESULTS: Periprocedural average glucose was significantly associated with bacteremia (adjusted odds ratio per 50 mg/dL of glucose, 1.233; 95% confidence interval, 1.071 to 1.420; P=0.004), AKI, delayed discharge, and death within 14 days. DM per se was only associated with bacteremia and AKI. Preprocedural HbA1c was associated with delayed discharge. Average glucose levels above 202 and 181 mg/dL were associated with a significantly higher risk of bacteremia and AKI, respectively, than glucose levels of 126 mg/dL or lower. CONCLUSION: Periprocedural average glucose, but not HbA1c, was associated with adverse outcomes after TACE, which is a nonsurgical invasive procedure. This suggests the importance of periprocedural glycemic control to reduce postprocedural complications.

Subtype-specific Body Composition and Metabolic Risk in Patients With Primary Aldosteronism.

BACKGROUND: Primary aldosteronism (PA) is associated with increased metabolic risks. However, controversy exists as to which subtype of PA has a higher metabolic risk between bilateral and lateralized PA. This study aimed to assess the body composition of 2 PA subtypes, bilateral PA and lateralized PA, according to sex and autonomous cortisol secretion (ACS) and their contribution to comorbidities. DESIGN AND METHODS: A total of 400 patients with PA (females, n = 210) and 1:10 age- and sex-matched healthy controls (n = 4000) were enrolled. The skeletal muscle area (SMA), subcutaneous fat area, and visceral fat area (VFA) at the third lumbar spine were calculated using abdominal computed tomography-based body composition analysis. RESULTS: Patients with bilateral PA had higher body mass index (BMI) in both sexes (all P < .05). Hemoglobin A1c level and the prevalence of diabetes were higher in female patients with bilateral PA than in those with lateralized PA (all P < .05). The VFA/BMI ratio was significantly higher in bilateral PA patients than in lateralized PA patients (5.77 ± 2.69 vs 4.56 ± 2.35 in men; 4.03 ± 2.58 vs 2.53 ± 2.05 in women, all P < .001). PA patients with ACS showed decreased SMA compared to those without ACS. Compared with healthy controls, all patients with bilateral PA and female patients with lateralized PA showed significantly higher VFA and VFA/BMI. CONCLUSIONS: Patients with bilateral PA were more obese and had higher VFA levels than those with lateralized PA. Despite a milder form of PA, this metabolically unfavorable visceral fat distribution may lead to a higher metabolic risk in patients with bilateral PA.

Correlation of Histopathologic Subtypes of Primary Aldosteronism with Clinical Phenotypes and Postsurgical Outcomes.

CONTEXT: Clinical implications of unilateral primary aldosteronism (PA) histopathology remain to be determined in various ethnic populations. OBJECTIVE: We examined the histopathology of unilateral PA using CYP11B2 immunostaining in relation to clinical phenotypes and postsurgical outcomes. METHODS: Patients consecutively operated for unilateral PA from 2010 to 2020 at 3 tertiary hospitals in South Korea were retrospectively enrolled. Adrenals with solitary aldosterone-producing adenomas and/or dominant aldosterone-producing nodules were classified as the classical and the others as the nonclassical groups. The classical group was subdivided into mixed or solitary group according to whether other aldosterone-producing lesions coexist or not. RESULTS: Of the 240 cases, 124 were solitary, 86 mixed, and 30 nonclassical. Baseline serum potassium concentration was lower in the solitary group than the mixed or nonclassical group. Plasma aldosterone concentration after saline loading was the highest in the solitary group (median 31.65 ng/dL), followed by the mixed group (median 25.40 ng/dL), and the lowest in the nonclassical group (median 14.20 ng/dL). Solitary and mixed groups showed higher lateralization indices and lower contralateral indices than the nonclassical group. The contralateral index was lower in the solitary group than the mixed group. At 6 to 12 months after adrenalectomy, fewer antihypertensive medications were required for the solitary and mixed groups than the nonclassical group. CONCLUSION: The solitary group, followed by the mixed group, was associated with more severe hyperaldosteronism and more suppressed aldosterone production from the contralateral side than the nonclassical group. Histopathologic phenotypes were related to the clinical manifestations and may suggest postoperative prognosis.

Multiplexed Serum Steroid Profiling Reveals Metabolic Signatures of Subtypes in Congenital Adrenal Hyperplasia.

Context: Altered metabolic signatures on steroidogenesis may characterize individual subtypes of congenital adrenal hyperplasia (CAH), but conventional diagnostic approaches are limited to differentiate subtypes. Objective: We explored metabolic characterizations and identified multiple diagnostic biomarkers specific to individual subtypes of CAH. Methods: Liquid chromatography-mass spectrometry-based profiling of 33 adrenal steroids was developed and applied to serum samples obtained from 67 CAH patients and 38 healthy volunteers. Results: Within- and between-run precisions were 95.4% to 108.3% and 94.1% to 110.0%, respectively, while all accuracies were <12% and the correlation coefficients (r2) were > 0.910. Metabolic ratios corresponding to 21-hydroxylase characterized 21-hydroxylase deficiency (21-OHD; n = 63) from healthy controls (area under the curve = 1.0, P < 1 × 10-18 for all) and other patients with CAH in addition to significantly increased serum 17α-hydroxyprogesterone (P < 1 × 10-16) and 21-deoxycortisol (P < 1 × 10-15) levels. Higher levels of mineralocorticoids, such as corticosterone (B) and 18-hydroxyB, were observed in 17α-hydroxylase deficiency (17α-OHD; N = 3), while metabolic ratio of dehydroepiandrosterone sulfate to pregnenolone sulfate was remarkably decreased against all subjects. A patient with 11ß-hydroxylase deficiency (11ß-OHD) demonstrated significantly elevated 11-deoxycortisol and its metabolite tetrahydroxy-11-deoxyF, with reduced metabolic ratios of 11ß-hydroxytestosterone/testosterone and 11ß-hydroxyandrostenedione/androstenedione. The steroid profiles resulted in significantly decreased cortisol metabolism in both 21-OHD and 17α-OHD but not in 11ß-OHD. Conclusion: The metabolic signatures with specific steroids and their corresponding metabolic ratios may reveal individual CAH subtypes. Further investigations with more substantial sample sizes should be explored to enhance the clinical validity.

A machine learning-assisted system to predict thyrotoxicosis using patients' heart rate monitoring data: a retrospective cohort study.

Previous studies have shown a correlation between resting heart rate (HR) measured by wearable devices and serum free thyroxine concentration in patients with thyroid dysfunction. We have developed a machine learning (ML)-assisted system that uses HR data collected from wearable devices to predict the occurrence of thyrotoxicosis in patients. HR monitoring data were collected using a wearable device for a period of 4 months in 175 patients with thyroid dysfunction. During this period, 3 or 4 thyroid function tests (TFTs) were performed on each patient at intervals of at least one month. The HR data collected during the 10 days prior to each TFT were paired with the corresponding TFT results, resulting in a total of 662 pairs of data. Our ML-assisted system predicted thyrotoxicosis of a patient at a given time point based on HR data and their HR-TFT data pair at another time point. Our ML-assisted system divided the 662 cases into either thyrotoxicosis and non-thyrotoxicosis and the performance was calculated based on the TFT results. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of our system for predicting thyrotoxicosis were 86.14%, 85.92%, 52.41%, and 97.18%, respectively. When subclinical thyrotoxicosis was excluded from the analysis, the sensitivity, specificity, PPV, and NPV of our system for predicting thyrotoxicosis were 86.14%, 98.28%, 94.57%, and 95.32%, respectively. Our ML-assisted system used the change in mean, relative standard deviation, skewness, and kurtosis of HR while sleeping, and the Jensen-Shannon divergence of sleep HR and TFT distribution as major parameters for predicting thyrotoxicosis. Our ML-assisted system has demonstrated reasonably accurate predictions of thyrotoxicosis in patients with thyroid dysfunction, and the accuracy could be further improved by gathering more data. This predictive system has the potential to monitor the thyroid function status of patients with thyroid dysfunction by collecting heart rate data, and to determine the optimal timing for blood tests and treatment intervention.

Evaluation of the lead and chromium removal capabilities of Bacillus subtilis-induced food waste compost-based biomedia.

Food waste compost (FWC) is a sustainable recycling approach employed in soil media, offering extensive advantages to urban areas by promoting resource circulation and effectively managing water pollution. To improve value, Bacillus subtilis (B. subtilis)-induced FWC-based biomedia (BIBMFWCs) was produced via a secondary treatment involving selective meso-thermophilic stages. During the production of BIBMFWCs, physicochemical properties were found to have favorable characteristics for the efficient removal of metal ions. The produced organic-carbonate complex structure demonstrated the synergistic effect involving simultaneous sorption/precipitation mechanisms for the removal of Pb(II) and Cr(III). Also, the dose of B. subtilis has an impact on the pseudo-second-order (PSO) and intra-particle diffusion (IPD) reaction, leading to distinct removal capacities for Pb(II) and Cr(III) [24.26-24.74 mg g-1 in Pb(II) and 12.7-23.93 mg g-1 in Cr(III)]. Furthermore, B. subtilis, an inducing mediator for microbial metabolites, exhibits the potential to facilitate the removal of Pb(II) and Cr(III) through biological modification of raw materials, which are transformed, facilitating the presence of hydroxyl groups, immobilizing metal ions, and enabling ion exchange via biogenic carbonate formation processes. Finally, the developed BIBMFWCs could be used as a nature-based solution (NBS) material without in-situ pH control.

Comparing zero-profile and conventional cage and plate in anterior cervical discectomy and fusion using finite-element modeling.

Conventional cage and plate (CCP) implants usually used in ACDF surgery, do have limitations such as the development of postoperative dysphagia, adjacent segment degeneration, and soft tissue injury. To reduce the risk of these complications, zero-profile stand-alone cage were developed. We used finite-element modeling to compare the total von Mises stress applied to the bone, disc, endplate, cage and screw when using CCP and ZPSC implants. A 3-dimensional FE (Finite element) analysis was performed to investigate the effects of the CCP implant and ZPSC on the C3 ~ T1 vertebrae. We confirmed that the maximum von Mises stress applied with ZPSC implants was more than 2 times greater in the endplate than that applied with CCP implants. The 3D analysis of the ZPSC model von Mises stress measurements of screw shows areas of higher stress in red. Although using ZPSC implants in ACDF reduces CCP implant-related sequalae such as dysphagia, we have shown that greater von Mises stress is applied to the endplate, and screw when using ZPSC implants. This may explain the higher subsidence rate associated with ZPSC implant use in ACDF. When selecting an implant in ACDF, surgeons should consider patient characteristics and the advantages and disadvantages of each implant type.

Biomechanical Effects of Different Sitting Postures and Physiologic Movements on the Lumbar Spine: A Finite Element Study.

This study used the finite element method(FEM) to investigate how pressure on the lumbar spine changes during dynamic movements in different postures: standing, erect sitting on a chair, slumped sitting on a chair, and sitting on the floor. Three load modes (flexion, lateral bending, and axial rotation) were applied to the FEM, simulating movements of the lumbar spine. Results showed no significant difference in pressure distribution on the annulus fiber and nucleus pulposus, representing intradiscal pressure, as well as on the cortical bone during movements between standing and erect sitting postures. However, both slumped sitting on a chair and sitting on the floor postures significantly increased pressure on the nucleus pulposus, annulus fibrosus, and cortical bone in all three movements when compared to standing or erect sitting on a chair. Notably, sitting on the floor resulted in even higher pressure on the nucleus pulposus and annulus fibers compared to slumped sitting on a chair. The decreased lumbar lordosis while sitting on the floor led to the highest increase in pressure on the annulus fiber and nucleus pulposus in the lumbar spine. In conclusion, maintaining an erect sitting position with increased lumbar lordosis during seated activities can effectively reduce intradiscal pressure and cortical bone stress associated with degenerative disc diseases and spinal deformities.

Serum steroid profile captures metabolic phenotypes in adults with classic congenital adrenal hyperplasia.

OBJECTIVES: Adult patients with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency have an increased risk of metabolic diseases. We aimed to investigate whether liquid chromatography-mass spectrometry (LC-MS)-based serum steroid profiling reveals metabolic phenotypes in adults with classic CAH. DESIGN AND METHODS: This study prospectively enrolled 63 adult patients with CAH and 38 healthy volunteers. The levels of the 24 steroids were quantified in the morning serum using LC-MS. Unsupervised clustering algorithms were applied to the serum steroid profiles to identify unique patterns associated with metabolic syndrome. RESULTS: Serum steroid profiles of patients with CAH were clearly delineated from those of healthy controls with a higher degree of interindividual heterogeneity. The unsupervised clustering algorithm divided CAH patients into two clusters based on serum steroid profile. Cluster 2 showed higher serum levels of glucocorticoids and androgens than cluster 1. The prevalence of metabolic syndrome was significantly higher in cluster 2 than in cluster 1 (37.8 % vs. 5.6 %, P = 0.011). Other clinical characteristics, including age, sex, body mass index, CAH subtypes, and glucocorticoid dose, did not differ between the two clusters. The multivariate logistic regression model of selective 15 steroids could discriminate metabolic syndrome in patients with CAH with an area under the receiver operating characteristic curve of 0.832 (95 % confidence interval:0.732-0.933). CONCLUSIONS: Serum steroid profiles can be valuable biomarkers for estimating metabolic risk in adult patients with CAH.

Incidence and Clinicopathological Features of Differentiated High-Grade Thyroid Carcinomas: An Institutional Experience.

Differentiated high-grade thyroid carcinoma (DHGTC) is a new entity in the 2022 WHO classification. We aimed to investigate the incidence and clinicopathological features of differentiated HG thyroid carcinoma (DHGTC) and compare the clinicopathological parameters of DHGTC, DTC without HG features, and poorly differentiated thyroid carcinoma (PDTC). A total of 1069 DTCs including papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs) were included in this study. Consecutive 22 PDTCs were also included for comparative purposes. There were a total of 14 (1.3%) cases of DHGTCs, with 13 HGPTCs (1.2% of PTCs) and one HGFTC (6.7% of FTCs). Compared to DTCs without HG features, DHGTCs were associated with larger tumor size, presence of blood vessel invasion, gross extrathyroidal extension, distant metastasis at the time of diagnosis, higher American Joint Committee on Cancer stage, high American Thyroid Association risk, and TERT promoter mutations. DHGTC and PDTC showed a significantly shorter recurrence-free survival (RFS) than DTC without HG features. Multivariate Cox regression analysis revealed that blood vessel invasion, lateral node metastasis, TERT promoter mutations, and HG features were independent prognostic factors (all p < 0.05). When tumor necrosis and increased mitotic count were evaluated separately, tumor necrosis, but not increased mitotic counts, was found to be an independent prognostic factor (p = 0.006). This study confirmed that DHGTC is significantly associated with aggressive clinicopathological features and poor clinical outcomes, similar to PDTC. Although the incidence is low, careful microscopic examination of HG features in DTC is required.

Freestanding Oxide Membranes for Epitaxial Ferroelectric Heterojunctions.

Since facile routes to fabricate freestanding oxide membranes were previously established, tremendous efforts have been made to further improve their crystallinity, and fascinating physical properties have been also reported in heterointegrated freestanding membranes. Here, we demonstrate our synthetic recipe to manufacture highly crystalline perovskite SrRuO3 freestanding membranes using new infinite-layer perovskite SrCuO2 sacrificial layers. To accomplish this, SrRuO3/SrCuO2 bilayer thin films are epitaxially grown on SrTiO3 (001) substrates, and the topmost SrRuO3 layer is chemically exfoliated by etching the SrCuO2 template layer. The as-exfoliated SrRuO3 membranes are mechanically transferred to various nonoxide substrates for the subsequent BaTiO3 film growth. Finally, freestanding heteroepitaxial junctions of ferroelectric BaTiO3 and metallic SrRuO3 are realized, exhibiting robust ferroelectricity. Intriguingly, the enhancement of piezoelectric responses is identified in freestanding BaTiO3/SrRuO3 heterojunctions with mixed ferroelectric domain states. Our approaches will offer more opportunities to develop heteroepitaxial freestanding oxide membranes with high crystallinity and enhanced functionality.

Rare or Overlooked Cases of Acute Acalculous Cholecystitis in Young Patients with Central Nervous System Lesion.

This case series presents two cases of acute acalculous cholecystitis (AAC)-a rare condition-in young women with central nervous system (CNS) lesions. Both patients had significant neurologic deficits and no well-known risk factors or presence of comorbidities (such as diabetes or a history of cardiovascular or cerebrovascular disease). Early diagnosis is important in cases of AAC owing to its high mortality rate; however, due to neurological deficits in our cases, accurate medical and physical examinations were limited, thereby leading to a delay in the diagnosis. The first case was of a 33-year-old woman with multiple fractures and hypovolemic shock due to a traumatic accident; she was diagnosed with hypoxic brain injury. The second case was of a 32-year-old woman with bipolar disorder and early-onset cerebellar ataxia who developed symptoms of impaired cognition and psychosis; she was later diagnosed with autoimmune encephalopathy. In the first case, the duration between symptom onset and diagnosis was 1 day, but in the second case, it was 4 days from diagnosis based on the occurrence of high fever. We emphasize that if a young woman presents with high fever, the possibility of AAC should be considered, particularly if a CNS lesion is present because it may pose difficulty in the evaluation of typical symptoms of AAC. Careful attention is thus required in such cases.

Serum and hair steroid profiles in patients with nonfunctioning pituitary adenoma undergoing surgery: A prospective observational study.

Patients who undergo transsphenoidal surgery (TSS) experience perioperative hormonal changes, but there are few studies on the perioperative changes of serum and hair steroid profiles. This study investigated the perioperative changes in steroid metabolic signatures in patients with nonfunctioning pituitary adenoma (NFPA) who underwent transsphenoidal surgery (TSS). A total of 55 participants who underwent TSS for NFPA at a single center between July 2017 and October 2018 were enrolled. Fifteen serum steroids and their metabolic ratios were profiled using gas chromatography-mass spectrometry (GC-MS) before and 1 day, 1 week, and 3 months after TSS. Five steroids from hair samples collected 1 day and 3 months after TSS were also quantitatively compared. Serum cortisol and its A-ring reductive metabolites, as well as 6ß-hydroxycortisol, increased dramatically 1 day after TSS and then gradually decreased. Seven serum steroids, including adrenal androgens and mineralocorticoids, and hair cortisone levels were significantly lower in patients with preoperative adrenocorticotropic hormone (ACTH) deficiency (N = 7) than in those without ACTH deficiency (N = 48). Serum levels of dehydroepiandrosterone (DHEA) levels 1 week after TSS predicted ACTH deficiency 3 months after TSS, with 100 % sensitivity and 86 % specificity. A significant positive correlation between the preoperative serum and hair DHEA levels (r = 0.356, P = 0.008) was observed. These findings suggest that the levels of DHEA in both the serum and hair could be an early marker of ACTH deficiency after TSS. In addition, hair cortisone may be a useful preoperative indicator of chronic ACTH deficiency.

Effect of olmesartan and amlodipine on serum angiotensin-(1-7) levels and kidney and vascular function in patients with type 2 diabetes and hypertension.

BACKGROUND: Recent studies suggest that angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) [Ang-(1-7)] might have beneficial effects on the cardiovascular system. We investigated the effects of olmesartan on the changes in serum ACE2 and Ang-(1-7) levels as well as kidney and vascular function in patients with type 2 diabetes and hypertension. METHODS: This was a prospective, randomized, active comparator-controlled trial. Eighty participants with type 2 diabetes and hypertension were randomized to receive 20 mg of olmesartan (N = 40) or 5 mg of amlodipine (N = 40) once daily. The primary endpoint was changes of serum Ang-(1-7) from baseline to week 24. RESULTS: Both olmesartan and amlodipine treatment for 24 weeks decreased systolic and diastolic blood pressures significantly by > 18 mmHg and > 8 mmHg, respectively. Serum Ang-(1-7) levels were more significantly increased by olmesartan treatment (25.8 ± 34.5 pg/mL → 46.2 ± 59.4 pg/mL) than by amlodipine treatment (29.2 ± 38.9 pg/mL → 31.7 ± 26.0 pg/mL), resulting in significant between-group differences (P = 0.01). Serum ACE2 levels showed a similar pattern (6.31 ± 0.42 ng/mL → 6.74 ± 0.39 ng/mL by olmesartan treatment vs. 6.43 ± 0.23 ng/mL → 6.61 ± 0.42 ng/mL by amlodipine treatment; P < 0.05). The reduction in albuminuria was significantly associated with the increases in ACE2 and Ang-(1-7) levels (r = - 0.252 and r = - 0.299, respectively). The change in Ang-(1-7) levels was positively associated with improved microvascular function (r = 0.241, P < 0.05). Multivariate regression analyses showed that increases in serum Ang-(1-7) levels were an independent predictor of a reduction in albuminuria. CONCLUSIONS: These findings suggest that the beneficial effects of olmesartan on albuminuria may be mediated by increased ACE2 and Ang-(1-7) levels. These novel biomarkers may be therapeutic targets for the prevention and treatment of diabetic kidney disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT05189015.

Ultrahigh dielectric permittivity in oxide ceramics by hydrogenation.

Boosting dielectric permittivity representing electrical polarizability of dielectric materials has been considered a keystone for achieving scientific breakthroughs as well as technological advances in various multifunctional devices. Here, we demonstrate sizable enhancements of low-frequency dielectric responses in oxygen-deficient oxide ceramics through specific treatments under humid environments. Ultrahigh dielectric permittivity (~5.2 × 106 at 1 Hz) is achieved by hydrogenation, when Ni-substituted BaTiO3 ceramics are exposed to high humidity. Intriguingly, thermal annealing can restore the dielectric on-state (exhibiting huge polarizability in the treated ceramics) to the initial dielectric off-state (displaying low polarizability of ~103 in the pristine ceramics after sintering). The conversion between these two dielectric states via the ambient environment-mediated treatments and the successive application of external stimuli allows us to realize reversible control of dielectric relaxation characteristics in oxide ceramics. Conceptually, our findings are of practical interest for applications to highly efficient dielectric-based humidity sensors.