The Efficacy of Mirabegron for the Relief of Ureteral Stent-Related Symptoms

To investigate the efficacy of mirabegron for lower urinary tract symptoms in patients with an indwelling ureteral stent after ureterorenoscopic lithotripsy. This was a prospective follow-up study of 76 patients with stent-related symptoms (SRSs). Patients with upper urinary calculi who were pre-stented for > 2 weeks before lithotripsy were examined for the presence of SRSs by tests including the International Prostate Symptom Score (IPSS), OAB Symptom Score (OABSS), and urinary bother and pain measured by a Visual Analogue Scale (VAS) before lithotripsy. Mirabegron (50 mg/day) was prescribed post-lithotripsy for 2 weeks. SRSs were assessed at the time of stent removal. The IPSS scores improved significantly from 16.2 to 14.3 (p<0.001) and the IPSS-QoL scores decreased significantly from 5.0 to 4.6 (p=0.012). The OABSS scores improved significantly from 7.7 to 6.8 (p=0.006), and the urinary urgency scores (OABSS-Q3) decreased significantly from 3.24 to 2.68 (p<0.001). The number of nocturia episodes decreased significantly from 2.5 to 2.2 (p=0.045). Urinary bother and pain assessed by the VAS declined from 4.2 and 3.1 to 3.8 (p=0.15) and 2.5 (p=0.075), respectively. Mirabegron significantly improved SRSs and the number of nocturia episodes due to a ureteral stent

Synthetic magnetic resonance imaging for primary prostate cancer evaluation:Diagnostic potential of a non-contrast-enhanced bi-parametric approach enhanced with relaxometry measurements

PURPOSE: Bi-parametric magnetic resonance imaging (bpMRI) with diffusion-weighted images has wide utility in diagnosing clinically significant prostate cancer (csPCa). However, bpMRI yields more false-negatives for PI-RADS category 3 lesions than multiparametric (mp)MRI with dynamic-contrast-enhanced (DCE)-MRI. We investigated the utility of synthetic MRI with relaxometry maps for bpMRI-based diagnosis of csPCa. METHODS: One hundred and five treatment-naïve patients who underwent mpMRI and synthetic MRI before prostate biopsy for suspected PCa between August 2019 and December 2020 were prospectively included. Three experts and three basic prostate radiologists evaluated the diagnostic performance of conventional bpMRI and synthetic bpMRI for csPCa. PI-RADS version 2.1 category 3 lesions were identified by consensus, and relaxometry measurements (T1-value, T2-value, and proton density [PD]) were performed. The diagnostic performance of relaxometry measurements for PI-RADS category 3 lesions in peripheral zone was compared with that of DCE-MRI. Histopathological evaluation results were used as the reference standard. Statistical analysis was performed using the areas under the receiver operating characteristic curve (AUC) and McNemar test. RESULTS: In 102 patients without significant MRI artefacts, the diagnostic performance of conventional bpMRI was not significantly different from that of synthetic bpMRI for all readers (p = 0.11–0.79). The AUCs of the combination of T1-value, T2-value, and PD (T1 + T2 + PD) for csPCa in peripheral zone for PI-RADS category 3 lesions were 0.85 for expert and 0.86 for basic radiologists, with no significant difference between T1 + T2 + PD and DCE-MRI for both expert and basic radiologists (p = 0.29–0.45). CONCLUSION: Synthetic MRI with relaxometry maps shows promise for contrast media-free evaluation of csPCa

Human Adrenocortical Remodeling Leading to Aldosterone-Producing Cell Cluster Generation

Background. The immunohistochemical detection of aldosterone synthase (CYP11B2) and steroid 11β-hydroxylase (CYP11B1) has enabled the identification of aldosterone-producing cell clusters (APCCs) in the subcapsular portion of the human adult adrenal cortex. We hypothesized that adrenals have layered zonation in early postnatal stages and are remodeled to possess APCCs over time. Purposes. To investigate changes in human adrenocortical zonation with age. Methods. We retrospectively analyzed adrenal tissues prepared from 33 autopsied patients aged between 0 and 50 years. They were immunostained for CYP11B2 and CYP11B1. The percentage of APCC areas over the whole adrenal area (AA/WAA, %) and the number of APCCs (NOA, APCCs/mm2) were calculated by four examiners. Average values were used in statistical analyses. Results. Adrenals under 11 years old had layered zona glomerulosa (ZG) and zona fasciculata (ZF) without apparent APCCs. Some adrenals had an unstained (CYP11B2/CYP11B1-negative) layer between ZG and ZF, resembling the rat undifferentiated cell zone. Average AA/WAA and NOA correlated with age, suggesting that APCC development is associated with aging. Possible APCC-to-APA transitional lesions were incidentally identified in two adult adrenals. Conclusions. The adrenal cortex with layered zonation remodels to possess APCCs over time. APCC generation may be associated with hypertension in adults

Transumbilical laparo-endoscopic single site surgery for adrenal cortical adenoma inducing primary aldosteronism: initial experience

<p>Abstract</p> <p>Background</p> <p>We have started using laparo-endoscopic single-site surgery (LESS) in urologic surgery, although its use has not gained momentum due to its level of difficulty. We here report our initial experience with transumbilical LESS for adrenal cortical adenoma by using a single port with a multichannel cannula (SILS port) and bent laparoscopic instrumentation.</p> <p>Findings</p> <p>A multichannel port (SILS port), bent laparoscopic instrument (Roticulator Endo Mini-Shears) and Opti4 laparoscopic electrodes were used in all cases. The intraperitoneal space was approached through the umbilicus. The SILS port was placed through a 2 cm incision at the inner edge of the umbilicus. A 5 mm flexible laparoscope was introduced to keep the laparoscope outside, and surgical specimens were extracted using an Endocatch bag. In addition, as a case control study, we compared perioperative data of LESS adrenalectomy (LESS-A) with that of conventional laparoscopic adrenalectomy (LA). We performed transumbilical LESS-A for adrenal cortical adenoma in 12 cases, beginning in December, 2009. All procedures were successfully completed, with only one incision through the umbilicus, and without conversion to a standard laparoscopic approach. Mean operative time for LESS-A was 121.2 ± 7.8 min, which was slightly longer than LA (110.2 ± 7.3 min). For right adrenal tumors, we used a miniport (2 mm port) in addition to a SILS port, and were able to successfully perform adrenalectomy "with no visible scaring". Tumor laterality and patient BMI did not affect surgical morbidity in these procedures. Moreover, there was no significant difference between LESS-A and LA in blood loss, analgesic requirement, hospital stay, and scar satisfaction.</p> <p>Conclusions</p> <p>The transumbilical approach in LESS for adrenalectomy is safe and feasible and also improves cosmetic outcome compared with standard laparoscopic procedures. Improvements in surgical devices may aid the further development of this approach.</p

CNVs in Three Psychiatric Disorders

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25–0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD

SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

To discover susceptibility genes of late-onset Alzheimer’s disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values ,261025 were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P=7.3361027 in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P=1.7761029) and rs3781834 (P=1.0461028). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P=1.7161025) and rs744373 near BIN1 (P = 1.3961024). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations