A Formula for the Estimation of 24-Hour Urinary Creatinine Excretion: A Derivation and Validation Study.

OBJECTIVE: Twenty-four-hour urinary creatinine (Cr) excretion (24h-uCr) is the basis of Cr clearance and urinary protein-Cr ratio, and it is related to frailty, worsening kidney function, and mortality in patients with chronic kidney disease. Although subjects with lower estimated glomerular filtration rate (eGFR) tend to have lower 24h-uCr, previous formulae for the estimation of 24h-uCr did not include Cr as a predictor. METHODS: This retrospective study included patients admitted to the Department of Nephrology at our hospital (derivation cohort and validation cohort: patients admitted between April 2016 and March 2020). The prediction formula of 24h-uCr was calculated using a multivariate linear regression model with the bootstrap method. Age, height, weight, sex, Cr, and cystatin C were used as predictors. RESULTS: The derivation and validation cohorts included 187 and 63 patients, respectively. The characteristics of the derivation and validation cohorts were as follows: age 73 (61-79.5) years and 70 (58.5-79) years; males, 61.5% and 60.3%; eGFRCr 27.0 (13.7-48.6) mL/min/1.73 m2 and 26.3 (14.0-51.5) mL/min/1.73 m2; and 24-hour urinary protein excretion 0.79 (0.17-2.12) g/day and 1.08 (0.26-2.55) g/day, respectively. Seven prediction formulae were derived. In all models, the Pearson's correlation coefficient was relatively high and statistically significant. However, previous models tended to overestimate the 24h-uCr. Furthermore, the predicted 24h-uCr calculated by the models that do not include Cr as a predictor fluctuates depending on the eGFRCr. CONCLUSION: The best formula for predicting 24h-uCr (mg/day) in a wide range of eGFR populations is a Cr-containing formula: [-9.04 × age (years) + 8.03 × weight (kg) + 0.66 × height (cm) + 188.59 (if male) - 32.11 × Cr (mg/dL) + 779.14].

Sleep debt and prevalence of proteinuria in subjects with short sleep duration on weekdays: a cross-sectional study.

STUDY OBJECTIVE: Short sleep duration is a risk factor of chronic kidney disease, along with cardiovascular diseases and all-cause mortality. Several studies reported that many people sleep longer on weekends than on weekdays, suggesting that they should be compensated for their sleep debt on weekdays on the weekends. Few studies have reported the clinical impact of sleep debt on the kidney. METHODS: This cross-sectional study included 5799 employees of Osaka University who visited its Health Care Center for their annual health examinations and answered ≤ 6 h of sleep duration on weekdays. The independent variable was the sleep debt index defined as a gap in self-reported sleep duration (≤ 5, 5-6, 6-7, 7-8, 8-9, and ≥ 9 h) between weekdays and weekends, which was categorized into ≤ 0, + 1, + 2, + 3 and ≥+4. An association between the sleep debt index and a prevalence of proteinuria defined as dipstick proteinuria of ≥ 1 + was assessed using logistic regression models adjusting for clinically relevant factors. RESULTS: More than four-fifths of the subjects had a positive sleep debt index (≤ 0, + 1, + 2, + 3, and ≥+4 recorded for 19%, 36%, 28%, 11%, and 6%, respectively). The multivariable-adjusted logistic regression models showed the sleep debt index ≥ 3 + was significantly associated with the prevalence of proteinuria (sleep debt index ≤ 0, adjusted odds ratio 1.13 [0.77, 1.65]; + 1, 1.00 [reference]; + 2, 1.29 [0.93, 1.79]; + 3, 1.54 [1.02, 2.33]; ≥ + 4, 1.87 [1.15, 3.05]). CONCLUSIONS: Sleep debt was associated with the prevalence of proteinuria in a dose-dependent manner.

Tolvaptan promotes urinary excretion of sodium and urea: a retrospective cohort study.

BACKGROUND: Tolvaptan (TLV) promotes aquaresis; however, little is known about its effect on solute excretion in chronic kidney disease (CKD). METHODS: We retrospectively studied CKD patients with decompensated heart failure (HF) or those with autosomal dominant polycystic kidney disease (ADPKD) receiving TLV. Patients with an increased urine volume of more than twice of daily variance were defined as "responders" in HF. We compared the ability of the urinary osmolality (U-OSM) change and urinary creatinine concentration ([U-Cr]) change to discriminate "responders". The fractional excretion of sodium (FeNa) and urea nitrogen (FeUN), and blood urea nitrogen (BUN) were monitored. RESULTS: In 30 responders among 53 HF patients, TLV increased FeUN significantly from 36.1 to 44.2% after starting TLV, but not FeNa. Since U-OSM is determined partially by urinary UN concentration, the decrease of [U-Cr] after treatment outperformed the U-OSM decrement to discriminate responders, as shown in receiver operating characteristic curve analysis and significantly higher net reclassification index. In 13 ADPKD patients, TLV increased FeUN (34.8, 47.3%, p = 0.02), and significant decrease of BUN by 2.3 (95% confidence interval 0.4-4.2) mg/dL was observed even 3 months after the intervention. Systolic blood pressure decreased significantly by 14.2 (95% confidence interval 4.0-24.4) mmHg along with the increase in FeNa, leading to reduced dosage of antihypertensives in 6 patients. CONCLUSION: TLV promotes the excretion of sodium and urea. The change in [U-Cr] is useful for early discrimination of responders. Hypotension should be carefully monitored during high-dose TLV therapy.

Alcohol consumption and incidence of proteinuria: a retrospective cohort study.

BACKGROUND: Previous studies report conflicting results of a dose-dependent association between alcohol consumption and incidence of chronic kidney disease. Only a few studies have assessed the clinical impact of > 45-65 g/day of critically high alcohol consumption. METHODS: This retrospective cohort study included 88,647 males and 88,925 females with dipstick urinary protein ≤ ± and estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2 at their first annual health examinations between April 2008 and March 2010 in Japan. The exposure was the self-reported alcohol consumption. The outcome was proteinuria defined as dipstick urinary protein ≥ 1 + or ≥ 2 +. RESULTS: During median 1.8 years (interquartile range 1.0-2.1) of the observational period, 5416 (6.1%) males and 3262 (3.7%) females developed proteinuria defined as dipstick urinary protein ≥ 1 +. In males, a U-shape association between alcohol consumption and proteinuria was observed in a multivariable-adjusted Poisson regression model [incidence rate ratio (95% confidence interval) of rare, occasional, and daily drinkers with ≤ 19, 20-39, 40-59, and ≥ 60 g/day: 1.00 (reference), 0.86 (0.79-0.94), 0.70 (0.64-0.78), 0.82 (0.75-0.90), 1.00 (0.90-1.11), and 1.00 (0.85-1.17), respectively], whereas a J-shape association was observed in females [1.00 (reference), 0.81 (0.75-0.87), 0.74 (0.64-0.85), 0.93 (0.78-1.11), 1.09 (0.83-1.44), and 1.45 (1.02-2.08), respectively]. Similar associations with dipstick urinary protein ≥ 2 + were shown in males and females. CONCLUSIONS: Moderate alcohol consumption was associated with lower risk of proteinuria in both males and females. Females with ≥ 60 g/day of high alcohol consumption were at higher risk of proteinuria, whereas males were not. Females were more vulnerable to high alcohol consumption, than males.

Accuracy of CT Colonography for Detection of Polypoid and Nonpolypoid Neoplasia by Gastroenterologists and Radiologists: A Nationwide Multicenter Study in Japan.

OBJECTIVES: The objective of this study was to assess prospectively the diagnostic accuracy of computer-assisted computed tomographic colonography (CTC) in the detection of polypoid (pedunculated or sessile) and nonpolypoid neoplasms and compare the accuracy between gastroenterologists and radiologists. METHODS: This nationwide multicenter prospective controlled trial recruited 1,257 participants with average or high risk of colorectal cancer at 14 Japanese institutions. Participants had CTC and colonoscopy on the same day. CTC images were interpreted independently by trained gastroenterologists and radiologists. The main outcome was the accuracy of CTC in the detection of neoplasms ≥6 mm in diameter, with colonoscopy results as the reference standard. Detection sensitivities of polypoid vs. nonpolypoid lesions were also evaluated. RESULTS: Of the 1,257 participants, 1,177 were included in the final analysis: 42 (3.6%) were at average risk of colorectal cancer, 456 (38.7%) were at elevated risk, and 679 (57.7%) had recent positive immunochemical fecal occult blood tests. The overall per-participant sensitivity, specificity, and positive and negative predictive values for neoplasms ≥6 mm in diameter were 0.90, 0.93, 0.83, and 0.96, respectively, among gastroenterologists and 0.86, 0.90, 0.76, and 0.95 among radiologists (P<0.05 for gastroenterologists vs. radiologists). The sensitivity and specificity for neoplasms ≥10 mm in diameter were 0.93 and 0.99 among gastroenterologists and 0.91 and 0.98 among radiologists (not significant for gastroenterologists vs. radiologists). The CTC interpretation time by radiologists was shorter than that by gastroenterologists (9.97 vs. 15.8 min, P<0.05). Sensitivities for pedunculated and sessile lesions exceeded those for flat elevated lesions ≥10 mm in diameter in both groups (gastroenterologists 0.95, 0.92, and 0.68; radiologists: 0.94, 0.87, and 0.61; P<0.05 for polypoid vs. nonpolypoid), although not significant (P>0.05) for gastroenterologists vs. radiologists. CONCLUSIONS: CTC interpretation by gastroenterologists and radiologists was accurate for detection of polypoid neoplasms, but less so for nonpolypoid neoplasms. Gastroenterologists had a higher accuracy in the detection of neoplasms ≥6 mm than did radiologists, although their interpretation time was longer than that of radiologists.

[Relationship between visceral fat and development of colorectal neoplasms using computed tomographic colonography and adipocytokine levels].

We evaluated the relationship between colorectal neoplasms and visceral obesity using computed tomographic colonography and adipocytokine levels. We included 123 patients and classified them into four groups as per computed tomographic colonography: no lesion (NL; n=40), adenomatous polyp (polyp; n=41), early colorectal cancer (eCRC; n=21), and advanced CRC (aCRC; n=21). We also measured the patients' serum metabolic markers and adipocytokine levels. The visceral adiposity index in the polyp and eCRC groups was significantly higher than that in the NL group. Visceral obesity is an important risk factor for the development of colonic polyps. Computed tomographic colonography could be a useful examination technique not only for diagnosis of colorectal neoplasms but also for simultaneous evaluation of visceral obesity.

S100A expression and interleukin-10 polymorphisms are associated with ulcerative colitis and diarrhea predominant irritable bowel syndrome.

BACKGROUND: Both ulcerative colitis (UC) and diarrhea-predominant irritable bowel syndrome (IBS-D) are associated with alterations in enteric serotonin (5-HT) signaling. AIMS: The purpose of this study was to compare the rectal and sigmoid colonic mucosal expression of S100A proteins and functional polymorphisms of the 5-HT transporter (5HTT) and interleukin-10 genes in patients with IBS-D or UC with healthy controls. METHODS: mRNA expression of S100 proteins was measured in sigmoid and rectal biopsies and in rectal epithelium isolated by laser-captured microdissection. Leucocyte DNA was analyzed by PCR-based reaction fragment length polymorphisms and direct sequencing. Clinical symptoms were assessed by the self-rating depression scale and by the gastrointestinal symptom rating scale. RESULTS: Fifty patients with IBS-D, 56 with UC and 50 healthy controls were studied. Colonic mucosal expression of S100A8 and S100A9 in UC was significantly higher than in IBS or controls and correlated with the UC disease activity index (r = 0.65, p < 0.001). S100A10 expression in the rectal epithelium of the IBS patients was significantly higher (0.643 vs. 0.402, p = 0.01) than in controls and correlated with the SDS scores (r = 0.41, p = 0.002). The frequency of IL10-819 CC genotype was significantly higher in IBS-D (10.7 vs. 0 %, p = 0.047) and UC (16 vs. 0 %, p = 0.007) than that in controls. CONCLUSION: Overexpression of S100A10 in the rectum may play a role in IBS as it is involved in modulating 5-HT1B receptors. The IL10-819 CC is a candidate genotype for both IBS and UC in Japanese.

Severe leukocytopenia due to copper deficiency induced by zinc supplementation in a patient on peritoneal dialysis: a case report.

Zinc deficiency is one cause of anemia. However, it has been reported that some patients who were treated with zinc supplementation to resolve this anemia subsequently experienced copper deficiency, which lead to continued anemia, as well as leukocytopenia and other symptoms. However, only two patients with copper deficiency induced by zinc supplementation undergoing peritoneal dialysis have been reported. Here, we report the case of a 59 year-old man with copper deficiency after zinc supplementation undergoing peritoneal dialysis (PD). He took meals only once a day and drank about 750 mL/day of wine every day. He had been receiving zinc supplementation for 4 months. He was diagnosed with severe leukocytopenia and worsening anemia at a planned outpatient visit; in addition, his copper levels had markedly decreased. Thus, zinc supplementation was discontinued, and the patient was instructed to take cocoa for copper supplementation. Because of severe leukocytopenia, he was admitted to our hospital, and granulocyte colony-stimulating factor was administered. Red blood cell transfusions were performed for anemia. After discontinuing zinc supplementation, his white blood cell count and hemoglobin levels improved.To avoid Cu deficiency, patients' dietary history should be checked in detail and Cu should be monitored carefully when Zn is supplemented in patients undergoing PD.

Alcohol Consumption and a Decline in Glomerular Filtration Rate: The Japan Specific Health Checkups Study.

Previous studies have reported conflicting results on the clinical impact of alcohol consumption on the glomerular filtration rate (GFR). This retrospective cohort study aimed to assess the dose-dependent association between alcohol consumption and the slope of the estimated GFR (eGFR) in 304,929 participants aged 40-74 years who underwent annual health checkups in Japan between April 2008 and March 2011. The association between the baseline alcohol consumption and eGFR slope during the median observational period of 1.9 years was assessed using linear mixed-effects models with the random intercept and random slope of time adjusting for clinically relevant factors. In men, rare drinkers and daily drinkers with alcohol consumptions of ≥60 g/day had a significantly larger decline in eGFR than occasional drinkers (difference in multivariable-adjusted eGFR slope with 95% confidence interval (mL/min/1.73 m2/year) of rare, occasional, and daily drinkers with ≤19, 20-39, 40-59, and ≥60 g/day: -0.33 [-0.57, -0.09], 0.00 [reference], -0.06 [-0.39, 0.26], -0.16 [-0.43, 0.12], -0.08 [-0.47, 0.30], and -0.79 [-1.40, -0.17], respectively). In women, only rare drinkers were associated with lower eGFR slopes than occasional drinkers. In conclusion, alcohol consumption was associated with the eGFR slope in an inverse U-shaped fashion in men but not in women.

Analysis of small-bowel capsule endoscopy reading by using Quickview mode: training assistants for reading may produce a high diagnostic yield and save time for physicians.

GOAL: The aim was to investigate the clinical utility of RAPID Access 6.5 Quickview software and to evaluate whether preview of the capsule endoscopy video by a trained nurse could detect significant lesions accurately compared with endoscopists. BACKGROUND: As reading capsule endoscopy is time consuming, one possible cost-effective strategy could be the use of trained nonphysicians or newly available software to preread and identify potentially important capsule images. STUDY: The 100 capsule images of a variety of significant lesions from 87 patients were investigated. The minimum percentages for settings of sensitivity that could pick up the selected images and the detection rate for significant lesions by a well-trained nurse, two endoscopists with limited experience in reading, and one well-trained physician were examined. RESULTS: The frequency of the selected lesions picked up by Quickview mode using percentages for sensitivity settings of 5%, 15%, 25%, and 35% were 61%, 74%, 93%, and 98%, respectively. The percentages for sensitivity significantly correlated (r=0.78, P<0.001) with the reading time. The detection rate by the nurse or the well-trained physician was significantly higher than that by the physician with limited capsule experience (87% and 84.1% vs. 62.7%; P<0.01). The clinical use of Quickview at 25% did not significantly improve the detection rate. CONCLUSIONS: Quickview mode can reduce reading time but has an unacceptably miss rate for potentially important lesions. Use of a trained nonphysician assistant can reduce physician's time and improve diagnostic yield.

Tolvaptan Reduces Extracellular Fluid per Amount of Body Fluid Reduction Less Markedly than Conventional Diuretics.

Objective Tolvaptan, a vasopressin V2 receptor antagonist, is a water diuretic, removing electrolyte-free water from the kidneys and affecting the water balance between the intracellular and extracellular fluid. We previously reported that tolvaptan efficiently reduced the intracellular fluid volume, suggesting its utility for treating cellular edema. Furthermore, tolvaptan is known for its low incidence of worsening the renal function, with conventional diuretics use associated with worsening of the renal function Methods In this retrospective observational study, five chronic kidney disease (CKD) patients with fluid retention were assessed by the bioelectrical impedance (BIA) method twice (before and after tolvaptan therapy). Tolvaptan was used with conventional diuretics. The post/pre ratio of extracellular water (ECW)/total body water (TBW) in the tolvaptan group was compared with that in 18 CKD patients undergoing body fluid reduction with conventional diuretics alone (conventional diuretics groups), taking the reduced amount of body fluid into consideration. Results Removing body fluid, either by tolvaptan or by conventional diuretics alone, decreased the ECW/TBW ratio. Of note, the reduction in extracellular fluid was milder in the tolvaptan group than in the conventional diuretics group. Conclusion Tolvaptan reduces the extracellular fluid per amount of body fluid reduction less markedly than conventional diuretics.

Occupational sedentary behavior and prediction of proteinuria in young to middle-aged adults: a retrospective cohort study.

BACKGROUND: Although sedentary behavior is a risk factor of cardiometabolic diseases and mortality, little information is available about a clinical impact of occupational sedentary behavior on chronic kidney disease (CKD). METHODS: The present retrospective cohort study included 10,212 workers of a national university in Japan who underwent annual health checkups between April 2006 and March 2013. Main exposure of interest was self-reported occupational sedentary behavior at the baseline visit. The outcome was the incidence of proteinuria defined as dipstick urinary protein of 1 + or more. The association between sedentary workers and the incidence of proteinuria was assessed using Cox proportional hazards models adjusting for clinically relevant factors, including television viewing time, the major home sedentary behavior. RESULTS: During median 4.8 years (interquartile range 2.1-7.9) of the observational period, the incidence of proteinuria was observed in 597 (12.0%) males and 697 (13.3%) females. In males, sedentary workers were identified as a significant predictor of proteinuria (multivariable-adjusted hazard ratio of non-sedentary and sedentary workers: 1.00 [reference] and 1.35 [1.11-1.63]), along with longer television viewing time (< 30 min, 30-60 min, 1-2 h, 2-3 h, and > 3 h/day: 1.15 [0.93-1.42], 1.00 [reference], 1.24 [1.00-1.53], 1.41 [1.03-1.93], and 1.77 [1.13-2.76]), whereas not daily exercise time. In females, neither sedentary workers nor television viewing time was associated with the incidence of proteinuria. CONCLUSIONS: In conclusion, male sedentary workers were at high risk of proteinuria. Occupational sedentary behavior may be a potentially modifiable target for the prevention of CKD.

Long-term outcome after double-balloon endoscopy in patients with obscure gastrointestinal bleeding.

BACKGROUND AND AIMS: There are limited data concerning the clinical outcome of patients with obscure gastrointestinal bleeding (OGIB) after double-balloon endoscopy (DBE). The aim of the present study was to evaluate the long-term outcome of patients with OGIB after DBE. PATIENTS AND METHODS: Eighty-seven consecutive patients with OGIB (47 men and 40 women; mean age 65.3 years) underwent DBE between July 2006 and December 2009. The criteria for assessment included documented iron deficiency anemia/occult or obscure small intestinal bleeding, and overt small intestinal bleeding. They were followed for a mean period of 41.4 months after DBE, and were divided into two groups according to their outcome, that is a good clinical course group (GC group) and a poor clinical course group (PC group). The clinical characteristics associated with rebleeding after DBE were analyzed by comparison of these two groups. RESULTS: The source of bleeding was identified in 40 patients (46.0%) and endoscopic treatment was required in 21 of them (52.5%). The most frequent source of bleeding was ulcers/erosions (18.4%). During the follow-up period, 39 patients (44.8%) experienced bleeding and/or persistent iron deficiency anemia after DBE, while 48 patients did not. There were no significant differences of clinical characteristics between the two groups. However, there were more patients with diverticular bleeding in the GC group than the PC group, and there were significantly more patients with treatable small intestinal tumors/polyps in the GC group. There were also more patients with normal DBE findings in the GC group. CONCLUSION: This study demonstrated that the rebleeding rate after DBE varies depending on the source of bleeding.

Lactate predicts the 28-day survival rate in patients with septic shock treated with the combination of PMX-DHP and rTM.

We have previously reported that combination therapy with polymyxin-B direct hemoperfusion (PMX-DHP) and recombinant thrombomodulin (rTM) is effective in patients with septic shock accompanied by disseminated intravascular coagulation (DIC). Two previous studies reporting the favorable effect of early initiation of PMX-DHP for septic shock did not focus on the combination therapy of PMX-DHP and rTM. This retrospective study included 47 consecutive patients who underwent the combination therapy of PMX-DHP and rTM for septic shock with DIC from August 2011 to August 2016. Main exposure was early or late initiation of PMX-DHP. PMX-DHP initiated within 12 hours after catecholamine administration was designated as early group (N = 25) and later than 12 hours as late group (N = 22). Main outcome was 28-day survival rate. The patient characteristics were age median 73 (IQR 68-78) years, 26 men (55%), APACHE II score 32.7 ± 7.7 and lactate 26.0 (18.0-41.0) mg/dL. The 28-day survival rate after PMX-DHP initiation was 76.6% and was not significantly different in the two groups. In the early group, APACHE II score was lower (P = .02), and lactate was higher (P = .005) than in the late group. Lactate was the only predictor of 28-day mortality [odds ratio (95%CI) per 1 mg/dL, 1.08 (1.03-1.19); P = .037] in multivariate logistic regression analysis adjusted with age, sex, APACHE II score, lactate and timing of PMX-DHP initiation. Late PMX-DHP initiation did not lead to statistically worse 28-day survival rate in this combination therapy. The combination therapy of PMX-DHP and rTM may improve the therapeutic effect of PMX-DHP and modify the effect of early PMX-DHP on the prognosis. Lactate may be an appropriate indicator rather than time after catecholamine administration if we discuss when to start PMX-DHP in this combination therapy.

Frequency of Breakfast, Lunch, and Dinner and Incidence of Proteinuria: A Retrospective Cohort Study.

Although multiple studies have revealed a close association of skipping breakfast with cardiometabolic diseases, few studies have reported its association with chronic kidney disease (CKD). Furthermore, there is scant reporting on the clinical impacts that skipping lunch and dinner has on cardiometabolic diseases and CKD. This retrospective cohort study, including 5439 female and 4674 male workers of a national university in Japan who underwent annual health checkups between January 2005 and March 2013, aimed to assess an association of frequencies of breakfast, lunch, and dinner with incidence of proteinuria (dipstick urinary protein ≥1+). The incidence of proteinuria was observed in 763 (14.0%) females and 617 (13.2%) males during the median 4.3 and 5.9 years of the observational period, respectively. In females, skipping breakfast as well as skipping dinner, but not lunch, were associated with the incidence of proteinuria (adjusted hazard ratios of breakfast frequency of "every day", "sometimes", and "rarely": 1.00 (reference), 1.35 (1.09-1.66), and 1.54 (1.22-1.94), respectively; those of dinner frequency of "every day" and "≤sometimes": 1.00 (reference) and 1.31 (1.00-1.72), respectively). However, no association was observed in male workers. Skipping breakfast and skipping dinner were identified as risk factors of proteinuria in females, but not in males.

Body mass index modifies the association between frequency of alcohol consumption and incidence of hypertension in men but not in women: a retrospective cohort study.

Alcohol consumption is one of the major modifiable risk factors of hypertension. The aim of the present retrospective study was to assess the clinical impact of obesity on the association between alcohol consumption and the incidence of hypertension. The present study included 5116 male and 6077 female university employees with a median age of 32 (interquartile range 27-39) who underwent annual health checkups between January 2005 and March 2013. Self-reported drinking frequency was recorded at their first checkup and categorized into rarely and 1-3, 4-6, and 7 days/week. During the median observational period of 4.9 years (interquartile range 2.1-8.3), hypertension, defined as systolic/diastolic blood pressure of ≥140/90 mmHg and/or self-reported treatment for hypertension, was observed in 1067 (20.9%) men and 384 (6.3%) women. Poisson regression models adjusted for clinically relevant factors revealed a dose-dependent association between drinking frequency and the incidence of hypertension in men (adjusted incidence rate ratio [95% confidence interval] of men who drank rarely, 1-3, 4-6, and 7 days/week was 1.00 [reference], 1.12 [0.97-1.30], 1.42 [1.19-1.70], and 1.35 [1.14-1.59], respectively; Ptrend < 0.001). However, this association was not observed in women. The dose-dependent association was significant in nonobese men (body mass index (BMI) < 25 kg/m2), but not in obese men (BMI ≥25 kg/m2) (P for interaction between drinking frequency and BMI = 0.072). The present study provides clinically useful evidence to identify the drinkers who may reap the health benefits of abstinence from alcohol consumption.

Severe Colitis Associated with both Epstein-Barr Virus and Cytomegalovirus Reactivation in a Patient with Severe Aplastic Anemia.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are members of the herpesvirus family and common causes of viral infection in humans. CMV infection of the gastrointestinal tract occurs mainly in immunocompromised individuals, on the other hand EBV infection and reactivation involving the gastrointestinal tract is very rare. A 56-year-old man was diagnosed with severe aplastic anemia and treated with antithymocyte globulin (ATG) and cyclosporine (CSP). After 2 years of ATG/CSP therapy, he suddenly started passing bloody diarrhea and developed a high fever despite CSP treatment. Endoscopic features included severe edema and multiple superficial ulcers; the patient was initially diagnosed with severe colitis resembling inflammatory bowel disease (IBD). However, his symptoms did not resolve with steroid treatment. Immunohistochemical analysis of samples obtained from a second colonoscopy showed cells positive for CMV, and in situ hybridization revealed EBV-encoded small RNA-1-positive cells. Additionally, the patient's serum was positive for C7-HRP, and both blood and colon tissues were positive for EBV DNA, which was detected using PCR analysis. We finally diagnosed the patient with colitis associated with reactivation of both CMV and EBV. The patient remains diarrhea-free after 1.5 years with scheduled globulin treatment and after cessation of immunosuppressive drug therapy. To our knowledge, this is the first reported case of an immunodeficient patient with severe hemorrhagic colitis that was associated with reactivation of both EBV and CMV, and whose endoscopic findings mimicked IBD.

Effect of mental processing on low back load while lifting an object.

STUDY DESIGN: Biomechanical study using a 3D motion analysis system conducted in a laboratory setting. OBJECTIVE: To determine the effect of mental processing on low back load during lifting. SUMMARY OF BACKGROUND DATA: In addition to ergonomic factors such as frequent lifting, work-related psychosocial factors are significant in the onset of disabling back pain. Although the ergonomic effects on low back load while lifting have been investigated and are widely accepted in the workplace, few studies have investigated the effect of psychosocial factors on low back load while lifting. METHODS: Thirteen healthy subjects lifted a box from the ground in 4 different lifting tasks in randomized order: (1) squat posture with knees flexed; (2) stoop posture with knees extended; (3) squat posture with mental processing using arithmetic tasks; and (4) stoop posture with mental processing using arithmetic tasks. We used a 3D motion analysis system and 4 force plates to record kinematic and kinetic data. We calculated dynamic triaxial low back joint moments and low back compression force as index parameters of low back load under these experimental conditions. RESULTS: Mental processing significantly increased peak low back compression force and low back extension moment, but not lateral flexion or rotation moment, while lifting in both lifting postures. Also, mental processing increased trunk bending angles in the squat posture. Although a tendency for decreased pelvic forward tilt was observed, mental processing did not significantly decrease forward pelvic tilt in the stoop posture. CONCLUSION: Mental processing during lifting tasks seems to affect both trunk and pelvis angles in the sagittal plane for squat and stoop postures, resulting in increased low back load. The present findings might help explain the effect of ergonomic demands of lifting tasks as well as psychosocial factors responsible for the onset of disabling back pain. LEVEL OF EVIDENCE: 2.

Usefulness of endoscopic brushing and magnified endoscopy with narrow band imaging (ME-NBI) to detect intestinal phenotype in columnar-lined esophagus.

BACKGROUND: Barrett's esophagus with specialized intestinal metaplasia (SIM), which is at high risk of progressing to esophageal adenocarcinoma, has been identified by obtaining biopsy specimens randomly. Magnified endoscopy with narrow band imaging (ME-NBI) is reported to be useful for detecting SIM or the intestinal phenotype. We aimed to evaluate the usefulness of endoscopic brushing followed by ME-NBI for the detection of the intestinal phenotype. METHODS: Biopsy and brushing samples were taken following endoscopic observation by ME-NBI. Total RNA was extracted from the whole sample and microdissected samples, and quantitative reverse transcription-polymerase chain reaction (PCR) analysis of SHH, CDX2, and mucin mRNA expression was performed. RESULTS: Fifty patients (32 men, 18 women, average age 67.3 years) with metaplastic columnar epithelium of the lower esophagus were studied. MUC2 (85 vs. 65 %) and CDX2 (95 vs. 75 %) were detected more frequently in the brushing samples than in the biopsy samples. MUC2 expression levels were significantly higher in the brushing samples than those in the biopsy samples. CDX2 and MUC2 expression levels in the brushing samples were significantly higher in the mucosa with tubular/villous pattern observed by ME-NBI than the levels in mucosae with other patterns. CONCLUSIONS: Endoscopic brushing in mucosa of columnar epithelium with a tubular/villous pattern visualized by ME-NBI is useful to detect the intestinal phenotype.

H. pylori eradication did not improve dysregulation of specific oncogenic miRNAs in intestinal metaplastic glands.

BACKGROUND: Many microRNAs (miRNAs) are differentially expressed in Helicobacter pylori-infected gastric mucosa and in gastric cancer tissue. AIM: We aimed to compare the effect of H. pylori eradication on gastric mucosal miRNAs in subjects in a high-risk group for gastric cancer compared to controls. METHODS: Patients with a recent history of endoscopic resection for early gastric cancer and sex- and age-matched non-cancer controls were enrolled. The expression of 21 miRNAs was examined using gastric mucosal biopsy specimens and microdissected gastric glands from the lesser and greater curvatures of the gastric corpus both before and one year after H. pylori eradication. RESULTS: Twenty patients and 14 controls were enrolled. The expression of oncogenic miRNAs (miR-17/92 and the miR-106b-93-25 cluster, miR-21, miR-194, and miR-196) was significantly higher in the gastric mucosa of the cancer group than in the controls. H. pylori eradication resulted in a significant fall in the expression of oncogenic miRNAs only in the controls, whereas miR-223 expression was decreased and let-7d expression was increased in both groups. miR-196 was expressed only in intestinal metaplastic glands. The expression of oncogenic miRNAs was significantly higher in the intestinal metaplastic glands than in the non-intestinal metaplastic glands irrespective of H. pylori eradication. In neither group did H. pylori eradication significantly change any miRNA expression in the intestinal metaplastic glands. CONCLUSION: Dysregulation of specific miRNAs is present in H. pylori-induced corpus gastritis. H. pylori eradication improved miRNA dysregulation, but not in intestinal metaplastic glands or in the gastric mucosa of patients in a high-risk group for gastric cancer.