[Pre-Operative Factors Affecting Trifecta Achievement in the Initial Series of Robot-Assisted Partial Nephrectomy].

We investigated pre-operative factors affecting trifecta achievement in robot-assisted partial nephrectomy (RAPN). We retrospectively analyzed 81 patients who underwent RAPN from December 2016 to September 2021 with final malignant pathologies. Trifecta was defined as negative resection margin (RM),warm ischemic time (WIT) less than 25 minutes, and no severe perioperative complications (Clavien-Dindo＜III). Factors affecting trifecta achievement were analyzed using sex, age, body mass index, RENAL nephrometry score (low or moderate/high complexity), surgical approach (transabdominal or retroperitoneal), tumor diameter and surgical experiences of each surgeon. Negative RM, WIT less than 25 minutes, and no severe complications were obtained in 75 (93%), 65 (80%), and 79 patients (98%), respectively. The trifecta was achieved in 60 patients (74%). In multivariate regression analysis, surgical experience (OR:0.92, 95% CI : 0.86-0.99) was significantly associated with trifecta achievement. Receiver operating characteristic curve analysis identified 9 cases as the optimal cut-off values for the predication of trifecta achievement (AUC＝0.69,p ＝0.11). The achievement of WIT less than 25 minutes (65 vs 90%, p＜0.01) and trifecta (58 vs 84%,p ＜0.05) were significantly lower in surgical experiences less than 9 cases than in 9 or greater. We conclude that surgical experience in RAPN is an important factor affecting WIT and trifecta achievement in the initial series.

Growth Hormone Stops Excessive Inflammation After Partial Hepatectomy, Allowing Liver Regeneration and Survival Through Induction of H2-Bl/HLA-G.

BACKGROUND AND AIMS: Growth hormone (GH) is important for liver regeneration after partial hepatectomy (PHx). We investigated this process in C57BL/6 mice that express different forms of the GH receptor (GHR) with deletions in key signaling domains. APPROACH AND RESULTS: PHx was performed on C57BL/6 mice lacking GHR (Ghr-/- ), disabled for all GH-dependent Janus kinase 2 signaling (Box1-/- ), or lacking only GH-dependent signal transducer and activator of transcription 5 (STAT5) signaling (Ghr391-/- ), and wild-type littermates. C57BL/6 Ghr-/- mice showed striking mortality within 48 hours after PHx, whereas Box1-/- or Ghr391-/- mice survived with normal liver regeneration. Ghr-/- mortality was associated with increased apoptosis and elevated natural killer/natural killer T cell and macrophage cell markers. We identified H2-Bl, a key immunotolerance protein, which is up-regulated by PHx through a GH-mediated, Janus kinase 2-independent, SRC family kinase-dependent pathway. GH treatment was confirmed to up-regulate expression of the human homolog of H2-Bl (human leukocyte antigen G [HLA-G]) in primary human hepatocytes and in the serum of GH-deficient patients. We find that injury-associated innate immune attack by natural killer/natural killer T cell and macrophage cells are instrumental in the failure of liver regeneration, and this can be overcome in Ghr-/- mice by adenoviral delivery of H2-Bl or by infusion of HLA-G protein. Further, H2-Bl knockdown in wild-type C57BL/6 mice showed elevated markers of inflammation after PHx, whereas Ghr-/- backcrossed on a strain with high endogenous H2-Bl expression showed a high rate of survival following PHx. CONCLUSIONS: GH induction of H2-Bl expression is crucial for reducing innate immune-mediated apoptosis and promoting survival after PHx in C57BL/6 mice. Treatment with HLA-G may lead to improved clinical outcomes following liver surgery or transplantation.

[Clinical Significance of Preoperative Image Classification Systems in Robot-Assisted Laparoscopic Partial Nephrectomy].

Robot-assisted laparoscopic partial nephrectomy (RAPN) is being used in Japan as a less invasive procedure. RENAL nephrometry (RN) score, Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) Classification and Simplified PADUA Renal (SPARE) nephrometry system are tumor-specific morphometry scoring systems used for predicting the difficulty of partial nephrectomy. Adherent perinephric fat (APF) is one of the patient-specific factors related to the difficulty of partial nephrectomy. Mayo Adhesive Probability (MAP) score measures the difficulty of partial nephrectomy due to APF. Whether these scoring systems were associated with perioperative outcome of RAPN was retrospectively analyzed in 57 patients who underwent RAPN by two experienced surgeons at our hospital from December 2016 to March 2020. Forty-five patients were male and 12 were female. The right side was resected in 25 and the left side in 32 patients. The approach was transperitoneal in 42 and retroperitoneal in 15 patients. There were significant correlations among RN, PADUA and SPARE scores, while MAP score was independent from the other scores. Warm ischemic time was significantly correlated with RN (r＝0.46, p＜0.001), PADUA (r＝0.45, p＜0.001) and SPARE scores (r＝0.44, p＜0.001). Time for console was significantly correlated with MAP score (r＝0.28, p＝0.035). In conclusion, RN and MAP scores might be useful parameters to predict warm ischemic time and time for console during RAPN, respectively.

[Comparison of Perioperative Outcomes between Open and Robot-Assisted Laparoscopic Radical Cystectomy].

We compared the perioperative outcomes of open (ORC) and robot-assisted laparoscopic radical cystectomy (RARC) for patients with bladder cancer. We retrospectively investigated the intraoperative and 90-day postoperative complications of ORC and RARC performed from March 2014 to September 2021 based on the medical records. Perioperative complications were categorized according to the Clavien- Dindo classification. We used the propensity score matching to adjust for the inherent bias of the different patient characteristics at baseline including gender, age, preoperative chemotherapy, and pathological T classification. Surgery time of RARC was significantly shorter than that of ORC, and blood transfusion was significantly less frequent in RARC than in ORC (3% vs 81%, p＜0.01). The rate of overall complications of Grade III/IV was lower in RARC (8%) than in ORC (25%) (P＝0.09). The prevalence of perioperative urinary tract infection, ileus, and abscess/infectious cyst was similar in ORC and RARC. In patients who underwent RARC, the complication rate was similar in extracorporeal and intracorporeal urinary diversion. Compared to ORC, RARC is more beneficial to reduce blood loss and severe complications.

[Treatment Outcome of Ureteral Reconstruction Surgery].

We retrospectively reviewed the surgical outcome of ureteral reconstruction that was performed in Asahikawa Medical University Hospital between 2005 and 2021. A total of 14 patients (3 males, 11 females; 15 ureters) were included in this analysis. The median age was 57 years old. The reason for ureteral reconstruction was ureteral injury or stenosis due to pelvic surgery in 9 patients, transurethral lithotripsy for ureteral stone in 3, ureteral invasion of sigmoid colon cancer in one and ovarian cancer in one. The site of ureteral reconstruction was proximal ureter in 2, middle in 3 and distal in 10. The surgical procedure was ureteroneocystostomy with Boari flap in 8 patients (57%), ureteroureterostomy in 4 (21%), transureteroureterostomy in one (7%), and transureteroureterostomy combined with Boari flap for bilateral ureteral stenosis in the remaining patient (7%). Postoperatively, vesicoureteral reflux, ileus and surgical site infection were observed in 3, 2 and 1 patient, respectively. No patient required nephrostomy or ureteral catheter, or any additional procedure after the surgery. There was no episode of febrile urinary tract infection after the surgery. The mean estimated glomerular filtration rate was, respectivery 75.8 and 78.5 ml/min/1.73 m2 before surgery and at 1-101 months (median of 18) after the surgery. In conclusion, satisfactory outcome was achieved after ureteral reconstruction surgery. We emphasize the importance of selecting the most appropriate procedure for ureteral reconstruction in each patient to prevent renal function deterioration and urinary tract infection.

Trivalent inactivated influenza vaccine effective against influenza A(H3N2) variant viruses in children during the 2014/15 season, Japan.

The 2014/15 influenza season in Japan was characterised by predominant influenza A(H3N2) activity; 99% of influenza A viruses detected were A(H3N2). Subclade 3C.2a viruses were the major epidemic A(H3N2) viruses, and were genetically distinct from A/New York/39/2012(H3N2) of 2014/15 vaccine strain in Japan, which was classified as clade 3C.1. We assessed vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children aged 6 months to 15 years by test-negative case-control design based on influenza rapid diagnostic test. Between November 2014 and March 2015, a total of 3,752 children were enrolled: 1,633 tested positive for influenza A and 42 for influenza B, and 2,077 tested negative. Adjusted VE was 38% (95% confidence intervals (CI): 28 to 46) against influenza virus infection overall, 37% (95% CI: 27 to 45) against influenza A, and 47% (95% CI: -2 to 73) against influenza B. However, IIV was not statistically significantly effective against influenza A in infants aged 6 to 11 months or adolescents aged 13 to 15 years. VE in preventing hospitalisation for influenza A infection was 55% (95% CI: 42 to 64). Trivalent IIV that included A/New York/39/2012(H3N2) was effective against drifted influenza A(H3N2) virus, although vaccine mismatch resulted in low VE.

Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance.

Insulin resistance is often associated with obesity and can precipitate type 2 diabetes. To date, most known approaches that improve insulin resistance must be preceded by the amelioration of obesity and hepatosteatosis. Here, we show that this provision is not mandatory; insulin resistance and hyperglycemia are improved by the modification of hepatic fatty acid composition, even in the presence of persistent obesity and hepatosteatosis. Mice deficient for Elovl6, the gene encoding the elongase that catalyzes the conversion of palmitate to stearate, were generated and shown to become obese and develop hepatosteatosis when fed a high-fat diet or mated to leptin-deficient ob/ob mice. However, they showed marked protection from hyperinsulinemia, hyperglycemia and hyperleptinemia. Amelioration of insulin resistance was associated with restoration of hepatic insulin receptor substrate-2 and suppression of hepatic protein kinase C epsilon activity resulting in restoration of Akt phosphorylation. Collectively, these data show that hepatic fatty acid composition is a new determinant for insulin sensitivity that acts independently of cellular energy balance and stress. Inhibition of this elongase could be a new therapeutic approach for ameliorating insulin resistance, diabetes and cardiovascular risks, even in the presence of a continuing state of obesity.

Risk factors for failure of long-term dutasteride add-on treatment to alpha-adrenergic antagonist for patients with lower urinary tract symptoms and benign prostatic enlargement.

PURPOSE: To identify the clinical factors resulting in the failure of dutasteride add-on treatment to alpha-adrenergic antagonist for patients with lower urinary tract symptoms and benign prostatic enlargement (BPE). METHODS: We retrospectively surveyed the patient cohort who had been enrolled in the study of dutasteride add-on treatment to alpha-adrenergic antagonist from December 2009 to November 2011. Treatment failure was defined as receiving surgery for BPE or requiring intermittent catheterization or permanent bladder catheter for urinary retention or huge postvoid residual urine. Clinical parameters before dutasteride treatment were compared between the successful and failed group. RESULTS: Of 92 patients, 23 (25%) were defined as treatment failure at 7-109 months (mean: 38 months) after dutasteride add-on treatment. In the failed group, the patient' age was younger (71.6 ± 6.8 vs 75.4 ± 8.4, p = 0.033), prostatic volume (PV) was larger (76 ± 41 vs 49 ± 26 ml, p = 0.005), voiding efficiency was lower (54 ± 27 vs 68 ± 24%, p = 0.045) and bladder outlet obstruction index was higher (73 ± 30 vs 48 ± 30, p = 0.015). The cox proportional-hazards model indicated that only intravesical prostatic protrusion (IPP) was associated with treatment failure. Non-failure rate at 3 years after dutasteride add-on treatment was 89% with patients of IPP < 13 mm versus 51% with those of IPP ≥ 13 mm (p < 0.001). CONCLUSION: IPP ≥ 13 mm is the risk factor resulting in the failure of dutasteride add-on treatment to alpha-adrenergic antagonist. This kind of information should be provided to the patients early in the clinical practice so that they could consider the necessity of BPE surgery in the long run.

Dutasteride add-on treatment to tadalafil for patients with benign prostatic enlargement is similarly effective as dutasteride add-on treatment to alpha blocker: a propensity-score matching analysis.

PURPOSE: To investigate the efficacy of dutasteride add-on treatment to tadalafil in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic enlargement (BPE). METHODS: A prospective study was conducted in patients with BPE who had not been satisfied with tadalafil monotherapy for more than 3 months. Inclusion criteria were prostate volume (PV) ≥ 30 ml and IPSS ≥ 8 or QOL index ≥ 3 under administration of tadalafil without anticholinergic agent. Before and 24 weeks after dutasteride add-on treatment to tadalafil, we assessed IPSS, overactive bladder symptom score (OABSS), serum PSA and testosterone, and uroflowmetry (UFM) to compare these parameters before and after dutasteride add-on treatment. Using a propensity-score matching analysis, the efficacy of dutasteride add-on treatment to tadalafil was compared with the previous study of dutasteride add-on treatment to alpha blocker. RESULTS: Of 52 patients who were enrolled in this study, 48 patients completed the study (mean age: 72 ± 5 years old). Dutasteride add-on treatment to tadalafil significantly improved IPSS (from 16.4 ± 5.2 to 13.3 ± 6.4) and IPSS-QOL (from 4.0 ± 1.2 to 3.3 ± 1.1), and reduced PV from 55 ± 26 to 39 ± 22 ml. Propensity-score matching identified 42 matched pairs of patients. The improvement rate of IPSS and reduction rate of PV were similar between patients treated with dutasteride add-on treatment to tadalafil and dutasteride add-on treatment to alpha blocker. The logistic regression analysis showed that PV at baseline and reduction rate of PV after treatment were associated with the effective symptomatic outcome. CONCLUSIONS: The dutasteride add-on is a reasonable treatment option for male patients with LUTS who are not satisfied with tadalafil monotherapy.

Deterioration of bladder compliance after botulinum toxin A injection and discontinuation of medication for overactive bladder.

Introduction: We report a case of deterioration of bladder compliance after botulinum toxin type A injection and discontinuation of medication for overactive bladder. Case presentation: A female patient with overactive bladder in her sixties had been visiting our outpatient clinic regularly for 4 years. She had received posterolateral spondylus fusion twice, which resulted in a compression fracture. She had been receiving a combination therapy of anticholinergics and ß3-adrenoceptor agonist for the management of overactive bladder. She received botulinum toxin type A injection for refractory overactive bladder and discontinued medical treatment for overactive bladder. Three months after botulinum toxin type A injection, cystometry revealed the deterioration of bladder compliance. Renal dysfunction, hydronephrosis, and vesicoureteral reflux were shown. Renal function and hydronephrosis were improved after restarting anticholinergics and ß3-adrenoceptor agonist therapy and inserting a temporary transurethral catheter. Conclusion: Deterioration of bladder compliance may occur after botulinum toxin type A injection and discontinuation of overactive bladder medication in some patients with underlying neurological disease.

Granuphilin is activated by SREBP-1c and involved in impaired insulin secretion in diabetic mice.

Granuphilin is a crucial component of the docking machinery of insulin-containing vesicles to the plasma membrane. Here, we show that the granuphilin promoter is a target of SREBP-1c, a transcription factor that controls fatty acid synthesis, and MafA, a beta cell differentiation factor. Potassium-stimulated insulin secretion (KSIS) was suppressed in islets with adenoviral-mediated overexpression of granuphilin and enhanced in islets with knockdown of granuphilin (in which granuphilin had been knocked down). SREBP-1c and granuphilin were activated in islets from beta cell-specific SREBP-1c transgenic mice, as well as in several diabetic mouse models and normal islets treated with palmitate, accompanied by a corresponding reduction in insulin secretion. Knockdown- or knockout-mediated ablation of granuphilin or SREBP-1c restored KSIS in these islets. Collectively, our data provide evidence that activation of the SREBP-1c/granuphilin pathway is a potential mechanism for impaired insulin secretion in diabetes, contributing to beta cell lipotoxicity.

Uroflowmetry pattern in detrusor underactivity and bladder outlet obstruction in male patients with lower urinary tract symptoms.

OBJECTIVES: To investigate if uroflowmetry (UFM) curve patterns could differentiate between detrusor underactivity (DU) and bladder outlet obstruction (BOO). METHODS: A hundred consecutive data sets of male patients who were evaluated using UFM and invasive urodynamics (pressure flow study) were retrospectively collected. DU and BOO were diagnosed according to the bladder contractility index and BOO index. The UFM curve with two or more notches was defined as sawtooth pattern, and the interrupted pattern was defined if several curves with interruptions reducing to zero were noted. We also compared other UFM parameters including maximum and average flow rates (Qmax and Qave), voiding time, time to Qmax, the slope to first peak flow, the number of notches on the curve (sawtooth pattern), the number of curves (interrupted pattern), and the maximum drop on the sawtooth pattern. RESULTS: Twenty-five and forty-nine patients were categorized in the BOO group and the DU group, respectively. The incidence of sawtooth pattern was significantly higher in the DU group (57%) than in the BOO group (32%), while the incidence of interrupted pattern was not different between the two groups (36% in the BOO group and 49% in the DU group). There were significant differences in age (area under the curve = 0.75), prostatic volume (0.67), the slope to first peak flow (0.58), the number of notches on the curve (0.61), and the maximum drop (0.76) between the two groups. CONCLUSIONS: The sawtooth UFM pattern is more common in patients with DU than in those with BOO. New parameters on UFM curve patterns could be helpful to evaluate DU and BOO without invasive urodynamics.

Thyroid-related hormones as potential markers of hypoxia/ischemia.

This study aimed to investigate the usefulness of the thyroid-related hormones as markers of acute systemic hypoxia/ischemia to identify deaths caused by asphyxiation due to neck compression in human autopsy cases. The following deaths from pathophysiological conditions were examined: mechanical asphyxia and acute/subacute blunt head injury; acute/subacute non-head blunt injury; sharp instrument injury as the hemorrhagic shock condition; drowning as alveolar injury; burn; and death due to cardiac dysfunction. Blood samples were collected from the left and right cardiac chambers and iliac veins, and serum triiodothyronine (T3), thyroxine (T4), thyroglobulin (Tg), and thyroid-stimulating hormone (TSH) levels were measured using electrochemiluminescence immunoassays. Two types of thyroid cell lines were used to confirm independent thyroid function under the condition of hypoxia (3% O2). The human thyroid carcinoma cell line (HOTHC) cell line derived from human anaplastic thyroid carcinoma and the UD-PTC (sample of the second resection papillary thyroid carcinoma) cell line derived from human thyroid papillary adenoma, which forms Tg retention follicles, were used to examine the secretion levels of T3, T4, and Tg hormones. The results showed a strong correlation between T3 and T4 levels in all blood sampling sites, while the TSH and Tg levels were not correlated with the other markers. Serum T3 and T4 levels were higher in cases of mechanical asphyxia and acute/subacute blunt head injury, representing hypoxic and ischemic conditions of the brain as compared to those in other causes of death. In the thyroid gland cell line, T4, T3, and Tg levels were stimulated after exposure to hypoxia for 10-30 min. These findings suggest that systemic advanced hypoxia/ischemia may cause a rapid and TSH-independent release of T3 and T4 thyroid hormones in autopsy cases. These findings demonstrate that increased thyroid-related hormone (T3 and T4) levels in the pathophysiological field may indicate systemic hypoxia/ischemia.

Role of growth hormone signaling pathways in the development of atherosclerosis.

OBJECTIVE: The direct actions of growth hormone (GH) in the development of atherosclerosis are unclear. The goal of this study was to characterize GH-induced changes in expression of signaling pathway elements and other proteins that may be related to atherosclerosis. METHODS: Human umbilical vein endothelial cells (HUVEC) and THP-1, a human acute monocytic leukemia cell line, were stimulated by exposure to 10-9 M or 10-8 M human GH with or without pretreatment with a mitogen-activated protein kinase kinase (MEK) 1 inhibitor. Levels of transcripts encoding vascular cell adhesion molecule (VCAM) -1, E-selectin, monocyte chemotactic protein (MCP-1), interleukin (IL) -6, and IL-8 were investigated by reverse transcription (RT) -PCR. For the quantitative adhesion assay, THP-1 cells or human primary monocytes were fluorescently labeled with 3'-O-acetyl-2',7'-bis(carboxyethyl) -4 diacetoxymethyl ester (BCECF/AM). HUVEC treated with human GH were co-incubated with BCECF-labeled THP-1 cells. One hour later, the number of BCECF-labeled THP-1 cells was assessed. An equivalent experiment was performed using BCECF-labeled primary monocytes, and the number of monocytes adhering to HUVEC was counted. RESULTS: Treatment with hGH increased the levels of E-selectin- and VCAM-1-encoding mRNAs in HUVEC. This effect was attenuated by pretreatment with a MEK1 inhibitor. Furthermore, hGH treatment increased adhesion of BCECF-labeled THP-1 cells or primary monocytes to HUVEC, and this effect was attenuated by pretreatment with a MEK1 inhibitor. CONCLUSIONS: VCAM-1 and E-selectin expression was stimulated by GH via the mitogen-activated protein kinase pathway, resulting in augmented adhesion of THP-1 cells and monocytes to HUVEC. These data suggested that GH directly stimulates the development of atherosclerosis.

Nuclear SREBP-1a causes loss of pancreatic beta-cells and impaired insulin secretion.

Transgenic mice expressing nuclear sterol regulatory element-binding protein-1a under the control of the insulin promoter were generated to determine the role of SREBP-1a in pancreatic beta-cells. Only low expressors could be established, which exhibited mild hyperglycemia, impaired glucose tolerance, and reduced plasma insulin levels compared to C57BL/6 controls. The islets isolated from the transgenic mice were fewer and smaller, and had decreased insulin content and unaltered glucagon staining. Both glucose- and potassium-stimulated insulin secretions were decreased. The transgenic islets consistently expressed genes for fatty acids and cholesterol synthesis, resulting in accumulation of triglycerides but not cholesterol. PDX-1, BetaEpsilonTauAlpha2, MafA, and IRS-2 were suppressed, partially explaining the loss and dysfunction of beta-cell mass. The transgenic mice on a high fat/high sucrose diet still exhibited impaired insulin secretion and continuous beta-cell growth defect. Therefore, nuclear SREBP-1a, even at a low level, strongly disrupts beta-cell mass and function.

Blood pressure-lowering effects of angiotensin receptor antagonist monotherapy and in combination with other anti-hypertensive drugs in primary care settings in Japan.

Combination therapy with multiple anti-hypertensives is required to achieve target blood pressure (BP) control and is recommended as the first-line therapy in hypertension. Although angiotensin receptor blockers (ARBs) may be combined with other anti-hypertensives, it is unclear how the effects of ARBs are influenced by co-administered anti-hypertensives. We investigated the effect of olmesartan medoxomil (OLM) when it is given alone (monotherapy) or concomitantly with other anti-hypertensives in 6507 OLM-naive Japanese in "real world" clinical practice. After a 12-week treatment, BP was significantly reduced from baseline in both the monotherapy group and the combination therapy group (P < 0.0001). The BP-lowering efficacy after treatment and achievement rates of target BP were similar in both groups. In the combination therapy group, no significant difference of achieved BP level was detected between patients taking Calcium channel blockers and any other class of anti-hypertensive drugs. This study suggests that ARBs such as OLM-elicits BP-lowering efficacy as either a first- or second-line agent and its effects are minimally influenced by co-administered anti-hypertensives.

Postmarketing surveillance on clinical use of edoxaban in patients with nonvalvular atrial fibrillation (ETNA-AF-Japan): Three-month interim analysis results.

BACKGROUND: Direct oral anticoagulants are the first-line drugs for anticoagulation therapy in nonvalvular atrial fibrillation (NVAF). However, a real-world, large-scale, clinical study on edoxaban has not been performed. Our ongoing postmarketing surveillance, ETNA-AF-Japan (Edoxaban Treatment in routiNe clinical prActice in patients with non-valvular Atrial Fibrillation; UMIN000017011), was designed to collect such data. METHODS: Enrollment started on 13 April 2015 and ended on 30 September 2017. Eligible patients were those diagnosed with NVAF who were to receive edoxaban for the first time and provided written consent for study participation. Baseline patient characteristics and adverse events (AEs) were collected. RESULTS: A total of 11 569 patients were enrolled. Data for 8157 patients in the first 3 months were analyzed. Mean age, body weight, creatinine clearance (CLcr), and CHADS 2 score were 74.2 ± 10.0 years, 60.0 ± 12.6 kg, 64.0 ± 25.6 mL/min, and 2.2 ± 1.3, respectively. Female patients, and patients with age ≥75 years, body weight ≤60 kg, and CLcr <30 mL/min constituted 40.7%, 52.4%, 54.6%, and 4.7%, respectively. Patients with paroxysmal, persistent, and permanent AF constituted 46.1%, 38.7%, and 15.1%, respectively. Most patients (85.3%) received dosages according to the prescribing information, and 90.8% continued the medication for 3 months. Bleeding AEs occurred in 3.29%, including major bleeding in 0.29%. CONCLUSIONS: The majority (90.8%) of patients continued medication and no significant safety concerns related to edoxaban were reported during the first 3 months of treatment. Clearer safety and efficacy profiles of edoxaban await data analyses after the 2-year follow-up period.

Early antihypertensive efficacy of olmesartan medoxomil.

The authors assessed the early antihypertensive efficacy of olmesartan medoxomil (OM) in a 12-week prospective observational study. Of 2221 patients with untreated hypertension who received OM (mainly 10 or 20 mg), 331 patients whose blood pressure (BP) was measured at 1 week after initiation of treatment were defined as the "early BP determination group,'' whereas the remaining 1890 patients were defined as the ;;standard BP determination group.'' Baseline characteristics, doses of OM, concomitant drugs used, and BP during treatment did not differ between the 2 groups. The achievement rate of BP target (<140/90 mm Hg) was 28.4% at 1 week in the early BP determination group and 28.3% at 2 weeks in the standard BP determination group (P=NS). Rates of adverse drug reactions in the 2 groups were similar. The present study suggests that OM is safe and effective in reducing BP at an early time point of treatment.

Abdominal Irradiation Ameliorates Obesity in ob/ob Mice.

Leptin-deficient ob/ob mice are a murine model for obesity, insulin resistance, and diabetes. Here we report that non-lethal abdominal irradiation (a single fraction of 850 cGy) to ob/ob mice retarded rapid gain of body weight, leading to amelioration of obesity without marked changes in food intake. This effect was observed only in ob/ob mice and not in lean controls. Reduction of body weight was accompanied by decreased adipose tissue weight without any marked change in the size of adipocytes, indicating prevention of hyperplasia rather than hypertrophy. Gene expression of the radiation-inducible cdk-inhibitor, p21, and the adipocytokines, tumor necrosis factor alpha and interleukin-1beta, were induced as expected; but genes involved in adipogenesis such as peroxisome proliferator-activated receptor gamma and adipsin were not affected in the irradiated adipose tissue. Inversely, hepatic lipid content was elevated with concomitant increases in the expression of lipogenic enzymes such as fatty acid synthase (FAS), and sterol regulatory element-binding protein 1c. Despite the decreased adiposity, there was no improvement in hyperglycemia and hyperinsulinemia after the irradiation. In conclusion, abdominal irradiation to ob/ob mice affected the progression of obesity and altered the energy metabolism between organs through a novel mechanism, implicating a new approach or factor for understanding and treatment of obesity.