Comparative Analysis of Real-World Efficacy and Safety of Hypoxia-Inducible Factor Prolyl-Hydroxylase Inhibitors in Kidney Transplant Recipients Versus Nontransplant Individuals: A Single-Center Study.

OBJECTIVES: To compare the efficacy and safety of hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHis), a novel agent for management of anemia in chronic kidney disease (CKD), between transplant recipients and nontransplant individuals. METHODS: A retrospective analysis was conducted on nondialysis-dependent CKD stage 3 to 5 patients treated with the HIF-PHi roxadustat or daprodustat at a single institution. Patients were categorized as kidney transplant recipients (KTRs) and non-KTRs. Efficacy outcomes (hemoglobin and creatinine levels) and safety profiles (rate of adverse events [AEs], descriptions, and discontinuations due to AEs) were assessed 3 months before and 6 months after HIF-PHi initiation within and then between the groups. RESULTS: The study comprised 82 patients (KTR: 43, non-KTR: 39). Median ages significantly differed between the KTR (52.7 years) and non-KTR (82.9 years) groups (P < .001). Roxadustat was predominantly used in the KTR group (88.4%), while daprodustat was used in the non-KTR group (94.9%, P < .001). Both groups exhibited significant increases in Hb levels at 1, 3, and 6 months post-HIF-PHi initiation (P for trend, <.001), with a relative increase in Hb level at 6 months of 16% for KTRs and 13% for non-KTRs. Creatinine levels showed no significant changes over 6 months. Although no difference was observed in drug discontinuation due to AEs, the KTR group experienced a significantly higher rate of thrombotic events (18.6 vs 2.6%, P = .049). CONCLUSIONS: HIF-PHis demonstrate comparable efficacy for managing anemia in CKD, regardless of transplant status. However, heightened vigilance for thrombosis events is necessary during follow-up for KTRs.

Selective recognition between aromatics and aliphatics by cage-shaped borates supported by a machine learning approach.

Selective recognition between hydrocarbon moieties is a longstanding issue. Although we developed a π-pocket Lewis acid catalyst with high selectivity for aromatic aldehydes over aliphatic ones, a general strategy for catalyst design remains elusive. As an approach that transfers the molecular recognition based on multiple cooperative non-covalent interactions within the π-pocket to a rational catalyst design, herein, we demonstrate Lewis acid catalysts showing improved selectivity through the support of an ensemble algorithm with random forest, Ada Boost, and XG Boost as a machine learning (ML) approach. Using 7963 explanatory variables extracted from model hetero-Diels-Alder reactions, the ensemble algorithm predicted the chemoselectivity of unlearned catalysts. Experiments confirmed the prediction. The proposed catalyst shows the highest selective recognition, reminiscing enzymatic catalytic activity. Additionally, a SHapley Additive exPlanations (SHAP) method suggested that the selectivity originates from the polarizability and three-dimensional size of the catalyst. This insight leads to rational design guidelines for Lewis acid catalysts with dispersion forces.

Association between occurrence of multiple white and flat elevated gastric lesions and oral proton pump inhibitor intake.

BACKGROUND/AIMS: Multiple white and flat elevated lesions (MWFL) that develop from the gastric corpus to the fornix may be strongly associated with oral antacid intake. Therefore, this study aimed to determine the association between the occurrence of MWFL and oral proton pump inhibitor (PPI) intake and clarify the endoscopic and clinicopathological characteristics of MWFL. METHODS: The study included 163 patients. The history of oral drug intake was collected, and serum gastrin levels and anti-Helicobacter pylori immunoglobulin G antibody titers were measured. Upper gastrointestinal endoscopy was performed. The primary study endpoint was the association between MWFL and oral PPI intake. RESULTS: In the univariate analyses, MWFL were observed in 35 (49.3%) of 71 patients who received oral PPIs and 10 (10.9%) of 92 patients who did not receive oral PPIs. The occurrence of MWFL was significantly higher among patients who received PPIs than in those who did not (p<0.001). Moreover, the occurrence of MWFL was significantly higher in patients with hypergastrinemia (p=0.005). In the multivariate analyses, oral PPI intake was the only significant independent factor associated with the presence of MWFL (p=0.001; odds ratio, 5.78; 95% confidence interval, 2.06-16.2). CONCLUSION: Our findings suggest that oral PPI intake is associated with the presence of MWFL (UMINCTR 000030144).

Neuropathological hallmarks in autopsied cases with mitochondrial diseases caused by the mitochondrial 3243A>G mutation.

The mitochondrial (m.) 3243A>G mutation is known to be associated with various mitochondrial diseases including mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Their clinical symptoms have been estimated to occur with an increased mitochondrial DNA (mtDNA) heteroplasmy and reduced activity of oxidative phosphorylation (OXPHOS) complexes, but their trends in the central nervous system remain unknown. Six autopsied mutant cases and three disease control cases without the mutation were enrolled in this study. The mutant cases had a disease duration of 1-27 years. Five of six mutant cases were compatible with MELAS. In the mutant cases, cortical lesions including a laminar necrosis were frequently observed in the parietal, lateral temporal, and occipital lobes; less frequently in the frontal lobe including precentral gyrus; and not at all in the medial temporal lobe. The mtDNA heteroplasmy in brain tissue samples of the mutant cases was strikingly high, ranging from 53.8% to 85.2%. The medial temporal lobe was preserved despite an inhospitable environment having high levels of mtDNA heteroplasmy and lactic acid. OXPHOS complex I was widely decreased in the mutant cases. The swelling of smooth muscle cells in the vessels on the leptomeninges, with immunoreactivity (IR) against mitochondria antibody, and a decreased nuclear/cytoplasmic ratio of choroidal epithelial cells were observed in all mutant cases but in none without the mutation. Common neuropathological findings such as cortical laminar necrosis and basal ganglia calcification were not always observed in the mutant cases. A high level of mtDNA heteroplasmy was observed throughout the brain in spite of heterogeneous cortical lesions. A lack of medial temporal lesion, mitochondrial vasculopathy in vessels on the leptomeninges, and an increased cytoplasmic size of epithelial cells in the choroid plexus could be neuropathological hallmarks helpful in the diagnosis of mitochondrial diseases.

Short-term effects of transcatheter aortic valve replacement on blood pressure and cardiac function in elderly patients with severe aortic stenosis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a standard treatment for elderly and high-risk patients with aortic valve stenosis (AS); however, its short-term effects on blood pressure (BP) and cardiac function are not clear. Therefore, we aimed to determine the short-term effects of TAVR in elderly patients (>75 years), who reflect the clinical situation in Japan. METHOD AND RESULTS: Twenty-eight consecutive elderly patients with severe AS and hypertension who underwent TAVR under general anesthesia were retrospectively investigated. All patients had hypertension that was well controlled with antihypertensive drugs. Serum brain natriuretic peptide level and peak velocity in the aortic valve were significantly reduced. TAVR induces an increase in BP that requires additional antihypertensive agents. There was no correlation between the change rate of SBP and stroke volume index (SVI), but there was a positive correlation between the rate of change in pulse pressure (PP) and SVI. This tendency was particularly observed in patients with low brachial-ankle pulse wave velocity (baPWV). CONCLUSION: We observed post-TAVR hypertension and required additional antihypertensive drugs. The increases in SVI and PP after TAVR resulted in post-TAVR hypertension. Moreover, post-TAVR hypertension is less likely to occur in elderly patients with a high baPWV, which indicates advanced arteriosclerosis.

Nature of a white opaque substance visualized by magnifying endoscopy in colorectal hyperplastic polyps.

Background and study aims A white opaque substance (WOS) has been observed in the epithelia of gastric, duodenal, and colorectal epithelial adenomas and carcinomas, using magnifying endoscopy (ME). The WOS has been reported to be derived from a dense accumulation of minute lipid droplets in the epithelium. This study aimed to investigate whether the WOS in colorectal hyperplastic polyps was derived from lipid droplets accumulated in the epithelium, as observed in the case of gastric, duodenal, and colorectal epithelial neoplasms. Patients and methods We analyzed 30 consecutive patients who were positive for the WOS, as visualized in colorectal hyperplastic polyps by ME with narrow-band imaging and 30 consecutive patients who were negative for the WOS. Biopsy specimens obtained from the polyps were immunostained with anti-adipophilin antibody to determine the correlation between the presence of the WOS and that of lipid droplets in the epithelium. Results In all patients, the epithelial cells were histologically positive for adipophilin. However, the area of adipophilin-positive epithelial cells in the WOS-positive group was significantly larger than that in the WOS-negative group ( P  < 0.001). The density of the WOS was strongly and positively correlated with the area of adipophilin-positive cells. Conclusions This study reveals that the WOS visualized in the superficial layers of colorectal hyperplastic polyps is produced by a dense accumulation of minute lipid droplets in the epithelia of the polyps.

Erratum: Nature of a white opaque substance visualized by magnifying endoscopy in colorectal hyperplastic polyps.

[This corrects the article DOI: 10.1055/a-1452-9669.].

Gastric metaplasia of the duodenal mucosa in Crohn's disease: novel histological and endoscopic findings.

Background and study aims Upper gastrointestinal endoscopy and biopsy are useful for differential diagnosis of Crohn's disease (CD) of the large intestine and ulcerative colitis (UC). We aimed to identify novel histopathological and endoscopic findings in the upper gastrointestinal tract in patients with CD who did not have Helicobacter pylori infection. Patients and methods Upper gastrointestinal endoscopy was performed on patients with CD and UC. Mucosal lesions detected were subsequently observed using magnifying endoscopy with narrow-band imaging (M-NBI), following which biopsy was performed. When no mucosal lesion was detected on conventional endoscopy, M-NBI and biopsy were performed on four sites: the gastric body, gastric antrum, duodenal bulb, and second portion of the duodenum. Results The prevalences of gastric metaplasia (GM) were 48 % (24/50) and 16 % (8/50) in the CD and UC groups, showing a significant difference ( P  = 0.001). In 23 of 24 patients with histologically proven GM in the CD group, mucosal lesions were detected using conventional white-light imaging (C-WLI). In 22 of 24 patients with histologically proven GM in the CD group, disappearance of normal villous structure and the presence of curved marginal crypt epithelium were noted using magnifying endoscopic findings characteristic of GM (M-GM). A combination of C-WLI and M-NBI yielded a significantly increased specificity ( P  = 0.004) and accuracy ( P  = 0.039). Conclusions The prevalence of GM in the duodenal mucosa was significantly higher in patients with CD than in controls. The identified endoscopic findings may be useful as novel indicators for the histological diagnosis of GM in the duodenum.

Rapid Optimization of Reaction Conditions Based on Comprehensive Reaction Analysis Using a Continuous Flow Microwave Reactor.

Generally, the flow method has the advantage of a precise control over the reaction parameters and a facile modification of the reaction conditions, while a continuous flow microwave reactor allows for the quick optimization of reaction conditions owing to the rapid uniform heating. In this study, we developed a "9+4+1 method" to optimize reaction conditions based on comprehensive reaction analysis using a flow microwave reactor. The proposed method is expected to contribute to the synthesis of various fine and bulk chemicals by reducing cost and wastage, and by conserving time.

Estimation of Outlet Temperature of a Flow Reactor Heated by Microwave Irradiation.

Flow reactors heated by microwave irradiation attract attention. The reactors are suitable for difficult synthesis processes due to rapid heating and cooling, and easy pressurization. In order to predict the quality of the product, it is appropriate to estimate the outlet conditions of the reactor. In this paper, the outlet temperature of the flow direction is estimated by using the flow condition and dynamic thermal energy balance of the reactor.

Correction: Different transferability of incompatibility (Inc) P-7 plasmid pCAR1 and IncP-1 plasmid pBP136 in stirring liquid conditions.

[This corrects the article DOI: 10.1371/journal.pone.0186248.].

Different transferability of incompatibility (Inc) P-7 plasmid pCAR1 and IncP-1 plasmid pBP136 in stirring liquid conditions.

Self-transmissible plasmids are classified into two types based on their sex pili: short and rigid pili, and long and flexible pili. The transferability of two plasmids with different types of sex pili, pBP136 and pCAR1, was compared in stirring liquid conditions with different cell density. The most probable number method to count transconjugants could detect differences in the transfer frequency with higher resolution in comparison with the conventional CFU counting method. Both plasmids showed higher transfer frequency in high stirring rates than static liquid conditions when the donor and recipient density was 106-107 CFU mL-1. The probability of donor-initiated plasmid transfer was investigated by a single-cell-level analysis using a cell sorter. The probability was >36-fold higher for pBP136 than for pCAR1; thus, the simulated transfer frequency of pBP136 was much higher than that of pCAR1 in stirring liquid conditions. Nevertheless, the transfer frequency of pCAR1 was as high as that of pBP136 when the donor and recipient cell density was 106 CFU mL-1. This fact indicates that the lower probability of the donor pCAR1 to initiate transfer could be overcome by its high tolerance to the shearing force between donor and recipient cells under higher stirring liquid conditions. Our findings can explain the different survival strategies of these two types of plasmids based on their preferences of transfer conditions.

Impact of age on left ventricular geometry and diastolic function in elderly patients with treated hypertension.

PURPOSE: Left ventricular (LV) remodelling is observed in numerous patients with hypertension and is a principal cause of heart failure in elderly patients. The aim of this study was to determine the relationships between age and structural/functional LV remodelling observed in elderly hypertensive patients. METHODS: A total of 557 elderly hypertensive patients (mean age: 74.0 ± 8.6 years) with preserved LV systolic function underwent echocardiography and 24-hour blood pressure (BP) measurement. RESULTS: Overall, 41.1% of patients had LV hypertrophy, 77.9% had increased relative wall thickness (RWT) defined as RWT >0.42, and 31.8% had both. Logistic analysis of the entire study population showed that increased RWT was associated with both 24-hour systolic BP (odds ratio (OR) 1.38, 95% confidence interval (CI) 1.12 to 1.70) and age (OR 1.32, 95%CI 1.08 to 1.61), whereas increased RWT was associated only with age (OR 1.61, 95%CI 1.23 to 2.11) after excluding patients with LV hypertrophy. Univariate and multivariate linear regression analyses of all patients showed that LV diastolic echocardiographic parameters were consistently associated with age (p ≤ .001) alone, even considering LV structural changes. CONCLUSIONS: Age was independently correlated with LV concentric/functional changes regardless of LV hypertrophy, suggesting that ageing is independently involved in the progression of LV remodelling.

Two Case Reports of Group B Streptococcal Infective Endocarditis Complicated by Embolism.

Streptococcus agalactiae (Group B streptococcus, GBS) is the major pathogen encountered in the perinatal period, although the incidence of GBS infection has recently increased among non-pregnant adults. Nevertheless, GBS infective endocarditis (IE) is uncommon and often accompanies aortic embolism. We experienced two cases of GBS IE. In Case 1, mobile vegetation of the aortic valve caused an infective cerebral aneurysm. In Case 2, the patient experienced an acute aortic embolic episode. Generally, early surgery for large mobile sites of vegetation is recommended as a class IIb therapy in the guidelines. GBS IE often exhibits a severe clinical course and specificity of vegetation. Therefore, early surgery should be considered in such cases.

Primary aldosteronism due to unilateral adrenal microadenoma in an elderly patient: efficacy of selective adrenal venous sampling.

We encountered a case of drug-resistant hypertension and hypokalemia. Laboratory data suggested primary aldosteronism (PA). Computed tomography imaging appeared normal for a long duration with a left-sided nodule appearing far later; adrenal scintigraphy was first normal, and the second test showed right-sided uptake. However, a repeat selective adrenal venous sampling (SAVS) indicated a left-sided lateralization of the hypersecretion of aldosterone. Left adrenectomy was performed, and his clinical symptoms improved. The histopathological findings demonstrated the aldosterone-producing microadenoma with secondary micronodules. In conclusion, SAVS should be performed to determine the laterality of PA with obscure CT imaging.

Aortic valve stenosis associated with Bazin's disease.

Bazin's disease was first reported in 1861, and is described as erythema induratum or nodular vasculitis. The condition is seen occasionally in middle-aged women on the skin of the calf, and a relationship to a tuberculosis infection has been proposed. In the present patient, valvular lesions occurred simultaneously with Bazin's disease, with granulomatous changes being demonstrated by the aortic valve pathology.

Workplace hypertension is associated with obesity and family history of hypertension.

Job strain, which is a risk for hypertension and increased left ventricular mass, is thought to cause masked hypertension during work even if blood pressure (BP) is normal at health examinations. To study the prevalence of and factors related to workplace hypertension, 265 public officials (mean age, 41.4+/-10.7 years) measured their own BP at their workplace using semiautomated BP measurement devices. Factors related to workplace hypertension were assessed with multiple regression analysis. Workplace hypertension, defined as a BP no less than 140/90 mmHg, was observed in 23% of subjects (n=61). Compared with subjects without workplace hypertension (n=204), subjects with workplace hypertension were older (48.5+/-10.0 vs. 39.3+/-10.0 years), more likely to be men (69% vs. 46%), and had a higher body mass index (BMI) (23.4+/-2.7 vs. 21.6+/-3.2 kg/m(2)), higher cholesterol levels (214+/-33 vs. 194+/-36 mg/dl), and a higher Brinkman index (134+/-228 vs. 59+/-148). Subjects with workplace hypertension had higher BPs at checkup than did those without it (125+/-11/79+/-9 vs. 110+/-11/68+/-9 mmHg). The increases in BPs at the workplace were independently and significantly correlated with BMI, and a family history of hypertension. BP no less than 130/ 85 mmHg at health checkup was a good detector of workplace hypertension (sensitivity, 49%; specificity, 91%), suggesting that subjects with high-normal BPs at health checkup might have workplace hypertension. In conclusion, workplace hypertension was found to be associated with age, BMI, a family history of hypertension, and high-normal BPs at health checkup.