Sex differences in the association between urate metabolism and kidney outcomes in patients with chronic kidney disease.

BACKGROUND: The association between serum uric acid (SUA) concentration and kidney outcomes in patients with chronic kidney disease (CKD) is controversial. Furthermore, there are no reports regarding the association of clearance of uric acid (CUA) with kidney outcomes. We aimed to determine whether SUA or CUA was associated with kidney outcomes in patients with CKD stratified by sex. METHODS: The present prospective study was conducted in 815 patients (523 men and 292 women) with CKD. The participants were divided into quartiles (Q1-Q4) of SUA or CUA for each sex. Endpoints were defined as a composite of doubling of serum creatinine (SCr), end-stage kidney disease (ESKD), or death (outcome 1) and a composite of doubling of SCr or ESKD (outcome 2). RESULTS: During a median follow-up of 2.5 years, outcomes 1 and 2 occurred in 363 and 321 patients, respectively. Multivariable-adjusted Cox analyses showed that in men, the hazard ratios (95% confidence intervals) for outcome 1 of Q1, Q2, and Q3 of CUA were 2.08 (1.18-3.70), 2.03 (1.22-3.39), and 1.85 (1.17-2.95), respectively, compared with Q4. Additionally, there were similar associations between lower CUA quartiles and outcome 2 in men. However, no associations between SUA and either outcome were observed in men. Conversely, in women, neither SUA nor CUA was associated with an outcome. CONCLUSION: In CKD, lower CUA was independently associated with poor kidney outcomes only in men, and in both sexes, there was no association of SUA with kidney outcomes.

Medical leadership training varies substantially between UK medical schools: Report of the leadership in undergraduate medical education national survey (LUMENS).

BACKGROUND: Doctors are increasingly expected to demonstrate medical leadership and management (MLM) skills. The Faculty of Medical Leadership and Management (FMLM) has published an indicative undergraduate curriculum to guide the development of MLM content at UK medical schools. METHOD: Students from 30 medical schools were surveyed to determine their understanding of MLM teaching at their school. Timetables for 21 schools were searched for MLM-related keywords. Student-reported teaching and timetabled teaching were coded according to predefined themes. Aggregated demographic and postgraduate performance data were obtained through collaboration with the Medical Student Investigators Collaborative (msico.org). RESULTS: Whilst 88% of medical students see MLM teaching as relevant, only 18% believe it is well integrated into their curriculum. MLM content represented ∼2% of timetabled teaching in each 5-year undergraduate medical course. Most of this teaching was dedicated to teamwork, performance/reflection and communication skills. There was minimal association between how much of a topic students believed they were taught, and how much they were actually taught. We found no association between the volume of MLM teaching and performance in postgraduate examinations, trainee career destinations or fitness to practice referrals. CONCLUSION: Our findings demonstrate limited and variable teaching of MLM content. Delivery was independent of broader teaching and assessment factors.

[A Case of Rectal Cancer in Which Total Pelvic Organ Excision Could Be Avoided by TNT Therapy and Robotic Surgery].

The patient is a 50s year old man. He visited his local doctor with complaints of anal pain and bloody stools, and a rectal examination revealed a tumor on the anterior wall of the rectal canal. CT imaging showed tumors invading the prostate, urethra, and anorectal muscles, and a 3 mm-sized nodule was found in the lungs. The patient was diagnosed as cT4bN1M1a, Stage Ⅳ, and total neoadjuvant chemotherapy was planned as preoperative treatment. The 5 Gy×5 times radiation therapy followed by 5 courses of CAPOX plus BEV as preoperative chemotherapy and CAPOX. CAPOX was administered. After completion of treatment, the colonoscopy showed PR, and MRI showed clear boundary between the prostate and tumor but invasion into the anorectal muscles; CT showed no lung metastasis, and preoperative diagnosis was ycT4bN0M0, ycStage Ⅱ. Robotic-assisted rectal amputation and left lateral lymph node dissection were performed under general anesthesia. Pathologically, the patient was diagnosed as ycT4bN0M0, Stage Ⅱ, and the efficacy was determined as TRG 1(AJCC). Vertical dissection was negative and radical resection was possible.

[A Case of Rectal Cancer with Enlarged Lateral Lymph Nodes Treated with Total Neoadjuvant Therapy and Robotic Surgery].

A 70s woman with advanced rectal cancer(AV 3 cm, type 2)was diagnosed as cT3N2M1a, Stage Ⅳ(UICC, TNM 8th) and underwent total neoadjuvant therapy(TNT)consisted of preoperative 5 Gy×5 short course RT followed by 5 courses of CAPOX plus BEV and CAPOX. Post-treatment endoscopy revealed nearCR, MRI failed to identify the primary tumor, and the mesenteric and lateral lymph node enlargement had disappeared. The patient underwent robot-assisted low anterior resection, bilateral lymph node dissection, and temporary ileal colostomy. Postoperative pathological findings were ypT0N0M0, Stage 0, and the efficacy evaluation was TRG 0(AJCC)with no residual tumor including lateral lymph nodes. The patient was discharged on the 16th day without any postoperative complications and is currently alive 6 months postoperatively without recurrence.

[A Case of Locally Advanced Sigmoid Colon Cancer Invading the Urinary Bladder Treated with Neoadjuvant Chemotherapy and Robot Assisted Urinary Bladder-Conserving Surgery].

We report a case of 72s male with locally advanced sigmoid colon cancer. Colonoscopy revealed an advanced sigmoid colon cancer(AV 15 cm, type 2, semi-peripheral, deeper than T3). He was diagnosed as cT4bN2M0, cStage Ⅲc(Japanese Classification of Colorectal, appendiceal, and, Carcinoma, 9th edition), and was given chemotherapy as preoperative treatment. He was treated with CAPOX plus BEV as neoadjuvant chemotherapy. Preoperative diagnosis was ycT4bN0M0, ycStage Ⅱc. The robot assisted high anterior resection and partial bladder resection were performed. The bladder was sutured under robotic assistance. The residual bladder capacity was 100 mL. Postoperative diagnosis was ypT0N0M0, ypStage 0, TRG 0 (AJCC). We experienced a case of neoadjuvant chemotherapy for rectosigmoid colon cancer with bladder invasion, which resulted in pCR.

[A Case of Pathological Complete Response for MSI-High Locally Advanced Unresectable Transverse Colon Cancer Treated with Nivolumab plus Ipilimumab Combination Therapy].

74-year-old woman was diagnosed with locally advanced unresectable transverse colon cancer. She started CAPOX therapy as first-line therapy after ileostomy. After second course, MSI-high was detected, so nivolumab plus ipilimumab combination therapy was started as second-line therapy. After 4 courses of combination therapy, she was judged to be in partial response and surgery was performed. Histopathological diagnosis of the surgical specimen showed complete response, and she is still alive without recurrence 15 months after surgery.

[A Case of Response to Pembrolizmab in Unresectable MSI-High Transverse Colon Cancer].

A 80s man was diagnosed circulated type 2 colon cancer at the transverse colon, and pathological findings was adenocarcinoma( por1). Genomic findings were microsatellite instability-high(MSI-H), all RAS wild type and BRAFV600E mutated. Contrast-enhanced CT showed an enlarged lymph nodes(#221, #222, #223, #214)along the middle colic and superior mesenteric artery. Clinical diagnosis was a locally advanced unresectable transverse colon cancer, cT4aN3M1a(LYM), cStage Ⅳa. Drug therapy with pembrolizumab was prescribed. Six months later, contrast-enhanced CT and PET demonstrated remarkable shrinkage of the primary tumor and lymph nodes except 2 peri-colic enlarged lymph nodes. Primary lesion turned almost undetectable, however the biopsy demonstrated residual tumor. Two months later, CT showed that the residual lymph nodes had also disappeared.

Immune response to cytosolic DNA via intercellular receptor modulation in oral keratinocytes and fibroblasts.

OBJECTIVE: Double-strand (ds) DNA-enveloped viruses can cause oral infection. Our aim is to investigate whether oral mucosal cells participate in immune response against cytosolic dsDNA invasion. METHODS: We examined the response to transfected herpes simplex virus (HSV) dsDNA via intracellular receptors in oral keratinocytes (RT7) and fibroblasts (GT1), and the effect of TNF-α on those responses. RESULTS: Transfected dsDNA increased CXCL10 expression via NF-κB activation in both cell types, while those responses were inhibited by knockdown of RIG-I, an RNA sensor. Although IFI16, a DNA sensor, was expressed in the nuclei of both types, its knockdown decreased transfected dsDNA-induced CXCL10 expression in GT1 but not RT7 cells. IFI16 in GT1 cells was translocated into cytoplasm from nuclei, which was attributed to immune response to cytosolic dsDNA. TNF-α enhanced transfected dsDNA-induced CXCL10, and knockdown of IFI16 decreased TNF-α and dsDNA-driven CXCL10 expression in both RT7 and GT1 cells. Finally, the combination of TNF-α and transfected dsDNA resulted in translocation of IFI16 from nuclei to cytoplasm in RT7 cells. CONCLUSION: RIG-I and IFI16 in oral mucosal cells may play important roles in host immune response against DNA viral infection, while TNF-α contributes to development of an antiviral system via those intracellular receptors.

Low plasma renin activity is independently associated with kidney disease progression in patients with type 2 diabetes and overt nephropathy, including those with impaired kidney function: a 2-year prospective study.

Plasma renin activity (PRA) is lower in patients with diabetic nephropathy (DN) than in healthy individuals. However, the association, if any, between PRA and renal outcomes in patients with DN remains uncertain. In a 2-year prospective observational study, we aimed to investigate the association of PRA with the decline in kidney function in patients with DN. We studied 97 patients with DN who were categorized according to tertile (T1-T3) of PRA. The annual changes in estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2/year) were determined from the slope of the linear regression curve for eGFR. The secondary endpoint was defined as a composite of the doubling of serum creatinine or end-stage renal disease. Results showed that kidney function rapidly declined with lower tertiles of PRA (median value [interquartile range] of the annual eGFR changes: -8.8 [-18.5 to -4.2] for T1, -8.0 [-14.3 to -3.2] for T2, and -3.1 [-6.3 to -2.0] for T3; p for trend <0.01). Multivariable linear regression analyses showed that, compared with T3, T1 was associated with a larger annual change in eGFR (coefficient, -4.410; 95% confidence interval [CI], -7.910 to -0.909 for T1). Composite renal events occurred in 46 participants. In multivariable Cox analysis, the lower tertiles of PRA (T1 and T2) were associated with higher incidences of the composite renal outcome (T2: hazard ratio [HR], 4.78; 95% CI, 1.64-13.89; T1: HR, 4.85; 95% CI 1.61-14.65) than T3. In conclusion, low PRA is independently associated with poor renal outcomes in patients with DN.

Enteral tube feeding for people with severe dementia.

BACKGROUND: The balance of benefits and harms associated with enteral tube feeding for people with severe dementia is not clear. An increasing number of guidelines highlight the lack of evidenced benefit and potential risks of enteral tube feeding. In some areas of the world, the use of enteral tube feeding is decreasing, and in other areas it is increasing. OBJECTIVES: To assess the effectiveness and safety of enteral tube feeding for people with severe dementia who develop problems with eating and swallowing or who have reduced food and fluid intake. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE, Embase, four other databases and two trials registers on 14 April 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs), or controlled non-randomised studies. Our population of interest was adults of any age with a diagnosis of primary degenerative dementia of any cause, with severe cognitive and functional impairment, and poor nutritional intake. Eligible studies evaluated the effectiveness and complications of enteral tube feeding via a nasogastric or gastrostomy tube, or via jejunal post-pyloric feeding, in comparison with standard care or enhanced standard care, such as an intervention to promote oral intake. Our primary outcomes were survival time, quality of life, and pressure ulcers. DATA COLLECTION AND ANALYSIS: Three review authors screened citations and two review authors assessed full texts of potentially eligible studies against inclusion criteria. One review author extracted data, which were then checked independently by a second review author. We used the 'Risk Of Bias In Non-randomised Studies of Interventions' (ROBINS-I) tool to assess the risk of bias in the included studies. Risk of confounding was assessed against a pre-agreed list of key potential confounding variables. Our primary outcomes were survival time, quality of life, and pressure ulcers. Results were not suitable for meta-analysis, so we presented them narratively. We presented results separately for studies of percutaneous endoscopic gastrostomy (PEG) feeding, nasogastric tube feeding and studies using mixed or unspecified enteral tube feeding methods. We used GRADE methods to assess the overall certainty of the evidence related to each outcome for each study. MAIN RESULTS: We found no eligible RCTs. We included fourteen controlled, non-randomised studies. All the included studies compared outcomes between groups of people who had been assigned to enteral tube feeding or oral feeding by prior decision of a healthcare professional. Some studies controlled for a range of confounding factors, but there were high or very high risks of bias due to confounding in all studies, and high or critical risks of selection bias in some studies. Four studies with 36,816 participants assessed the effect of PEG feeding on survival time. None found any evidence of effects on survival time (low-certainty evidence). Three of four studies using mixed or unspecified enteral tube feeding methods in 310 participants (227 enteral tube feeding, 83 no enteral tube feeding) found them to be associated with longer survival time. The fourth study (1386 participants: 135 enteral tube feeding, 1251 no enteral tube feeding) found no evidence of an effect. The certainty of this body of evidence is very low. One study of PEG feeding (4421 participants: 1585 PEG, 2836 no enteral tube feeding) found PEG feeding increased the risk of pressure ulcers (moderate-certainty evidence). Two of three studies reported an increase in the number of pressure ulcers in those receiving mixed or unspecified enteral tube feeding (234 participants: 88 enteral tube feeding, 146 no enteral tube feeding). The third study found no effect (very-low certainty evidence).  Two studies of nasogastric tube feeding did not report data on survival time or pressure ulcers. None of the included studies assessed quality of life. Only one study, using mixed methods of enteral tube feeding, reported on pain and comfort, finding no difference between groups. In the same study, a higher proportion of carers reported very heavy burden in the enteral tube feeding group compared to no enteral tube feeding. Two studies assessed the effect of nasogastric tube feeding on mortality (236 participants: 144 nasogastric group, 92 no enteral tube feeding). One study of 67 participants (14 nasogastric, 53 no enteral tube feeding) found nasogastric feeding was associated with increased mortality risk. The second study found no difference in mortality between groups. The certainty of this evidence is very low. Results on mortality for those using PEG or mixed methods of enteral tube feeding were mixed and the certainty of evidence was very low. There was some evidence from two studies for enteral tube feeding improving nutritional parameters, but this was very low-certainty evidence. Five studies reported a variety of harm-related outcomes with inconsistent results. The balance of evidence suggested increased risk of pneumonia with enteral tube feeding. None of the included studies assessed behavioural and psychological symptoms of dementia. AUTHORS' CONCLUSIONS: We found no evidence that tube feeding improves survival; improves quality of life; reduces pain; reduces mortality; decreases behavioural and psychological symptoms of dementia; leads to better nourishment; improves family or carer outcomes such as depression, anxiety, carer burden, or satisfaction with care; and no indication of harm. We found some evidence that there is a clinically significant risk of pressure ulcers from enteral tube feeding. Future research should focus on better reporting and matching of control and intervention groups, and clearly defined interventions, measuring all the outcomes referred to here.

Association between urinary salt excretion and albuminuria in Japanese patients with chronic kidney disease: the Fukuoka kidney disease registry study.

BACKGROUND: Several large population-based studies have demonstrated that urinary salt excretion (USALT) is associated with albuminuria. However, this relationship has not been assessed in a large cohort study of patients with chronic kidney disease (CKD). Thus, the present study aimed to elucidate whether USALT was independently associated with albuminuria in a large cohort of patients with CKD. METHODS: This cross-sectional study was conducted in 4075 patients with CKD not on dialysis. USALT (g/day) was estimated from spot urine. Patients were divided into quartiles (Q1-Q4) according to estimated USALT. Multivariable regression models were used to determine whether USALT was independently related to urinary albumin-to-creatinine ratio (UACR) or the presence of macroalbuminuria. RESULTS: In multivariable linear regression analyses, 1-g/day increment in USALT was significantly associated with log UACR [coefficient 0.098, 95% confidence interval (CI) 0.075-0.121]. In addition, compared with the first USALT quartile, the third and fourth quartiles exhibited significant associations with log UACR (Q3: coefficient 0.305, 95% CI 0.154-0.456; Q4: coefficient 0.601, 95% CI 0.447-0.756). Furthermore, multivariable logistic regression analyses showed that USALT (1-g/day increment) was significantly associated with the presence of macroalbuminuria [odds ratio (OR) 1.11, 95% CI 1.07-1.14]; the third and fourth USALT quartiles exhibited significantly greater risks of macroalbuminuria, compared with the first quartile (Q3: OR 1.33, 95% CI 1.09-1.62; Q4: OR 1.89, 95% CI 1.54-2.32). CONCLUSIONS: This significant association of USALT with UACR and macroalbuminuria suggests that higher USALT may cause increased albuminuria, thereby contributing to kidney disease progression.

Association of aortic valve calcification with carotid artery lesions and peripheral artery disease in patients with chronic kidney disease: a cross-sectional study.

BACKGROUND: Patients with chronic kidney disease (CKD) reportedly have a high prevalence of aortic valve calcification (AVC). In population-based studies, AVC is considered a manifestation of systemic atherosclerosis. The association of AVC with atherosclerotic lesions has not been fully investigated in predialysis patients. The present study was performed to determine whether carotid artery lesions and peripheral artery disease (PAD) are associated with AVC in patients with CKD not on dialysis. METHODS: In total, 749 patients were included in this cross-sectional study. AVC was evaluated using echocardiography. Carotid artery lesions including carotid artery plaque (CAP) and PAD were simultaneously examined in each patient. A logistic regression analysis was applied to determine the factors associated with AVC. RESULTS: AVC, CAP, and PAD were found in 201, 583, and 123 patients, respectively. In the multivariable analyses adjusted for covariates including the estimated glomerular filtration rate and makers of mineral metabolism (serum calcium, serum phosphorus, parathyroid hormone, 1,25-dihydroxyvitamin D, and fibroblast growth factor 23), AVC was significantly associated with the presence of CAP [odds ratio (OR), 3.37; 95% confidence interval (CI), 1.43-7.95], the presence of PAD (OR, 1.76; 95% CI, 1.10-2.81), the CAP score (per 1.0-point increase) (OR, 1.06; 95% CI, 1.02-1.11), and the ankle-brachial blood pressure index (per 0.1-point increase) (OR, 0.83; 95% CI, 0.72-0.95). CONCLUSIONS: AVC was associated with atherosclerotic lesions independent of kidney function and mineral metabolism. We consider that this association between AVC and atherosclerosis might reflect the burden of shared atherosclerotic risk factors.

Blood urea nitrogen is independently associated with renal outcomes in Japanese patients with stage 3-5 chronic kidney disease: a prospective observational study.

BACKGROUND: Blood urea nitrogen (BUN) is one of the substances that affects the calculated serum osmolality (cSosm). A previous study demonstrated that BUN and cSosm were independently associated with the development of chronic kidney disease (CKD) in patients with preserved kidney function. In advanced CKD stages, there is a concomitant increase in cSosm and BUN levels. However, it remains unclear whether BUN or cSosm levels are related to renal outcomes in patients with moderate to severe kidney dysfunction. The aim of this study was to clarify whether the BUN or cSosm level is associated with kidney disease progression in patients with advanced CKD. METHODS: In this prospective study, we enrolled 459 patients with CKD (stages 3-5). The composite renal endpoint was end-stage renal disease (ESRD) or death, and ESRD alone was added as an alternative outcome. A Cox proportional hazards model was utilized to determine the risk factors for a poor renal outcome. We adjusted for covariates including estimated glomerular filtration rate (eGFR). The cSosm (mOsm/kg) was calculated using the following formula: (2 × sodium) + (BUN/2.8) + (glucose/18). RESULTS: During a median follow-up of 25.8 months, the renal endpoint was observed in 210 patients. Multivariable Cox analysis determined the hazard ratio (HR) [95% confidence interval (CI)] for the composite renal outcome in the second, third, and fourth BUN quartiles were 1.36 (0.72-2.58), 1.87 (0.95-3.66), and 2.66 (1.23-5.76) (P for trend < 0.01), respectively compared with the first BUN quartile. Conversely, by multivariable Cox analysis, the HRs (95% CIs) for poor outcomes in the second, third, and fourth cSosm quartiles, compared with the first cSosm quartile, were 1.13 (0.69-1.87), 0.95 (0.58-1.55), and 1.26 (0.78-2.03), respectively (P for trend = 0.39). In addition, with regard to the renal outcome of ESRD alone, higher BUN quartiles had a significantly increased risk for the outcome, but cSosm levels were not associated with the outcome. CONCLUSIONS: Higher BUN levels, but not cSosm levels, were associated with adverse renal outcomes independent of the eGFR, suggesting that BUN may be a useful marker for predicting kidney disease progression.

High neutrophil/lymphocyte ratio is associated with poor renal outcomes in Japanese patients with chronic kidney disease.

BACKGROUND: Several studies have shown that the neutrophil/lymphocyte ratio (NLR) is a marker that reflects the state of systemic inflammation. A high NLR was reported to be associated with cardiovascular events and mortality. However, little is known about the association between NLR and kidney disease progression in patients with chronic kidney disease (CKD). Therefore, the aim of the present study was to determine whether NLR is associated with renal outcomes in CKD patients. METHODS: This prospective observational study included 350 consecutive patients with stage 1-4 CKD treated between June 2009 and November 2016. Data were collected until June 2017. The endpoint was the composite of end-stage renal disease requiring dialysis or death. Subjects were divided into two groups according to high and low NLR levels. A Cox proportional hazards model was used to determine the risk factors for composite outcomes. RESULTS: The composite endpoint was observed in 83 patients during the median follow-up period of 31.8 months: 29 in the low NLR group and 54 in the high NLR group. Multivariable analysis showed that the high NLR group had a significant increase in the hazard ratio (HR) for composite outcomes (HR 1.67, 95% confidence interval 1.02-2.77) compared with the low NLR group. CONCLUSION: The present study demonstrated that a high NLR was associated with poor renal outcomes, suggesting that NLR may be a useful marker for prognostic prediction in patients with CKD.

Candida albicans ß-Glucan-Containing Particles Increase HO-1 Expression in Oral Keratinocytes via a Reactive Oxygen Species/p38 Mitogen-Activated Protein Kinase/Nrf2 Pathway.

Oral keratinocytes provide the first line of host defense against oral candidiasis. We speculated that interactions of fungal cell wall components with oral keratinocytes regulate the stress response against Candida infection and examined the expression of genes induced by heat-killed Candida albicans in oral immortalized keratinocytes using a cDNA microarray technique. Of 24,000 genes revealed by that analysis, we focused on HO-1, a stress-inducible gene, as its expression was increased by both heat-killed and live C. albicans In histological findings, HO-1 expression in the superficial layers of the oral epithelium following Candida infection was elevated compared to that in healthy epithelium. We then investigated fungal cell wall components involved in induction of HO-1 expression and found that ß-glucan-containing particles (ß-GPs) increased its expression. Furthermore, ß-glucan was observed on the surface of both heat-killed C. albicans and Candida cells that had invaded the oral epithelium. Fungal ß-GPs also promoted induction of intracellular reactive oxygen species (ROS), NADPH oxidase activation, and p38 mitogen-activated protein kinase (MAPK) phosphorylation, while those specific inhibitors inhibited the HO-1 expression induced by fungal ß-GPs. Moreover, fungal ß-GPs induced Nrf2 translocation into nuclei via p38 MAPK signaling, while the HO-1 expression induced by fungal ß-GPs was inhibited by Nrf2-specific small interfering RNA (siRNA). Finally, knockdown of cells by HO-1- and Nrf2-specific siRNAs resulted in increased ß-GP-mediated ROS production compared to that in the control cells. Our results show that the HO-1 induced by fungal ß-GPs via ROS/p38 MAPK/Nrf2 from oral keratinocytes may have important roles in host defense against the stress caused by Candida infection in the oral epithelium.

Comparison of Prognostic Values of Daytime and Night-Time Systolic Blood Pressures on Renal Outcomes in Patients With Chronic Kidney Disease.

BACKGROUND: Differences in the predictive value of daytime systolic blood pressure (SBP) and night-time SBP by ambulatory blood pressure monitoring on renal outcomes have not been fully investigated in chronic kidney disease (CKD) patients. This study compared the prognostic value between daytime and night-time SBP on renal outcomes in CKD.Methods and Results:This prospective observational study included 421 patients. The composite renal endpoint was endstage renal disease (ESRD) or death. Cox models were used to determine associations of daytime and night-time SBP with renal outcomes. There were 150 renal events (ESRD, 130; death, 20). Multivariable Cox analyses demonstrated that hazard ratios (HRs) [95% confidence interval (CI)] for composite renal outcomes of every 10-mmHg increase in daytime and night-time SBP levels were 1.13 (1.02-1.26) (P=0.02) and 1.15 (1.05-1.27) (P<0.01), respectively. In addition, compared with the 1st daytime or night-time SBP quartile, HRs (95% CI) for outcomes in the 2nd, 3rd, and 4th quartiles were: daytime SBP, 1.25 (0.70-2.25), 1.09 (0.61-1.94), and 1.58 (0.88-2.85; P=0.13) (P for trend=0.16); night-time SBP, 1.09 (0.61-1.96), 1.31 (0.76-2.28), and 1.82 (1.00-3.30; P=0.049) (P for trend=0.03), respectively. CONCLUSIONS: Night-time SBP appeared superior to daytime SBP for predicting renal outcomes in this population of patients.

Purification, gene cloning, and characterization of γ-butyrobetainyl CoA synthetase from Agrobacterium sp. 525a.

The report is the first of purification, overproduction, and characterization of a unique γ-butyrobetainyl CoA synthetase from soil-isolated Agrobacterium sp. 525a. The primary structure of the enzyme shares 70-95% identity with those of ATP-dependent microbial acyl-CoA synthetases of the Rhizobiaceae family. As distinctive characteristics of the enzyme of this study, ADP was released in the catalytic reaction process, whereas many acyl CoA synthetases are annotated as an AMP-forming enzyme. The apparent Km values for γ-butyrobetaine, CoA, and ATP were, respectively, 0.69, 0.02, and 0.24 mM.

Expression and function of RIG-I in oral keratinocytes and fibroblasts.

BACKGROUND: Innate immune response by oral mucosal cells may be the first line of host defense against viral infection. Retinoic acid-inducible gene-I (RIG-I) recognizes viral dsRNA in the cytoplasm, and RIG-I-mediated signaling regulates antiviral type I IFN, and inflammatory chemokine production. Here, we tested the hypothesis that oral mucosal cell participation in host defense against viral infection via RIG-I. METHODS: RIG-I expression was detected in immortalized oral keratinocytes (RT7), oral fibroblasts (GT1) using and RT-PCR and immunohistochemistry. RT7 and GT1 were exposed to dsRNA virus mimic Poly I:C-LMW/LyoVec (PLV). Expression of IFN-ß and CXCL10 via RIG-I was examined by Real-time RT-PCR and ELISA. Phosphorylation of IRF3 and STAT1 were detected by western blotting. RESULTS: RT7 and GT1 constitutively expressed RIG-I in the cytoplasm. Furthermore, PLV increased IFN-ß and CXCL10 productions in both RT7 and GT1 via RIG-I concurrent with phosphorylation of IRF3 and STAT1. PLV-induced CXCL10 production was attenuated by neutralization of IFN-ß and blocking of IFN-α/ß receptor (IFNAR), indicating primal IFN-ß production via the RIG-I-IRF3 axis, which eventually induces CXCL10 production via the IFNAR -STAT1 axis. CONCLUSION: We propose that RIG-I in oral keratinocytes and fibroblasts may cumulatively develop host-defense mechanisms against viral infection in oral mucosa.

[Tolerability of XELOX in postoperative adjuvant chemotherapy for colorectal cancer].

A regimen of capecitabine plus oxaliplatin(XELOX)has become one of the standard postoperative adjuvant chemotherapies for colon cancer. However, few tolerability studies have been conducted in Japan. In this study, we retrospectively examined treatment continuation and the adverse events that occurred during 8 courses of postoperative adjuvant chemotherapy with XELOX in 21 patients with colorectal cancer who had undergone curative resection. The completion rate for 8 courses of treatment with XELOX was 71.4%, while the median relative dose intensities of capecitabine and oxaliplatin were 85.0% and 75.0%, respectively. Although the incidence of subsequent Grade 3 or higher hand-foot syndrome was 14.3%, the rate of peripheral neuropathy was 0%. Our hospital had a high rate of XELOX treatment continuation, suggesting that XELOX adjuvant chemotherapy would be well tolerated in clinical practice as well.

[Chemotherapy for gastric cancer patients over 75 years of age].

PURPOSE: The efficacy of chemotherapy for advanced or recurrent gastric cancer in patients who were aged over 75 years was investigated. MATERIALS AND METHODS: Progression free survival (PFS) and overall survival (OS) of advanced gastric cancer patients who received first-line chemotherapy with TS-1 plus cisplatin or TS-1 in our hospital from 2009 to 2013 were determined. The patients were divided into two groups: H and L. H group patients were aged over 75 years, and L group patients were aged less than 75 years. RESULTS: Median PFS and median OS of patients in the H and L groups who received TS-1 plus cisplatin chemotherapy were not significantly different. PFS was 77[range, 13-211] days and 139[range, 53-211]days for the H and L groups, respectively(p=0.141), while OS was 523[range, 22-1,030] days and 402 [range, 322-623] days, respectively (p=0.620). Similarly, median PFS and median OS of patients who received TS-1 chemotherapy were not significantly different between the H and L groups. PFS was 103[range, 51-156]days and 152.5[range, 85-278]days for the H and L groups, respectively (p=0.230), while OS was 414 [range, 224-714]days and 605[range, 452-1,077] days, respectively ( p=0.1337). CONCLUSION: PFS and OS were not significantly different in younger patients with advanced gastric cancer who received TS-1 plus cisplatin or TS-1 chemotherapy compared to that in similarly treated elderly patients with advanced gastric cancer.