Glucose Tolerance and the Risk Factors for Transmission in Japanese SARS-CoV-2/WA-1/2020 Epicenter: A Retrospective Study.

Purpose: The severe pathogenic ancient-type COVID-19, SARS-CoV-2/WA-1/2020 was the predominant gene variant in early 2020 in Japan, however, its transmissibility was uncertain. The period before the public commenced using any personal protective equipment (PPE) was evaluating to describe the transmissibility of the SARS-CoV-2/WA-1/2020. We analyzed the secondary attack rate (SAR) among close contacts and the risk factor for SAR. Methods: This retrospective cohort study included a total of 539 patients who were anticipated for the SARS-CoV-2/WA-1/2020 infection at Toho University Medical Center Omori Hospital from February to May 2020. We selected 54 patients with 1) exclude other pathogens infection, 2) include "Three Cs" condition: crowded places between distance< 6 feet, closed spaces indoor and close contact settings involving contact >15min with a person tested positive for SARS-CoV-2/WA-1/2020 without PPE. We evaluated alternative infection risks: the body mass index (BMI) and diabetes (DM) status (non-DM, pre-DM, and DM) as demographic determinants of transmissibility and infectivity of SARS-CoV2/WA-1/2020 cases during the incubation period. Results: The calculated SAR was 79.3%. BMI was significantly associated with the PCR positivity rate, which was significant in the univariate (CI 95%, 1.02-1.51; P = 0.03) and multivariate (CI 95%, 1.02-1.60; P = 0.03) analyses. Comparing the different BMI groups, the highest BMI group (25.5-35.8 kg/m2) had an elevated risk of SAR compared to the lowest BMI group (14.0-22.8 kg/m2), with an odds ratio of 1.41 (95% CI, 1.02-1.59; P = 0.03). There were no significant differences in the risk of SAR among different DM statuses. Conclusion: The transmissibility of SARS-CoV2/WA-1/2020 was high (79.3%) among household members without PPE who had "Three Cs" exposure. Although pre-DM and established DM did not confer a risk for transmissibility, higher BMI was associated with an increased risk of SAR. Trial Registration: UMIN Clinical Trials Registry, UMIN0000 50905.

Beneficial Effect of Heat-Killed Lactic Acid Bacterium Lactobacillus johnsonii No. 1088 on Temporal Gastroesophageal Reflux-Related Symptoms in Healthy Volunteers: A Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Study.

A randomized, placebo-controlled, double-blind, parallel-group clinical study was conducted to examine the effects of ingesting a heat-killed lactic acid bacterium, Lactobacillus johnsonii No. 1088 (LJ88) on temporal gastroesophageal reflux-related symptoms in healthy volunteers. A total of 120 healthy Japanese volunteers of both sexes, aged between 21 and 63 years, whose Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) total score was 8 or greater, but who were not diagnosed with functional dyspepsia according to the Rome IV classification, were enrolled. They were randomly assigned to either the LJ88 or placebo group and instructed to ingest the test food (1 billion heat-killed LJ88 or placebo) once a day for six weeks. Gastroesophageal reflux-related symptoms were evaluated using FSSG scores as a primary endpoint. The Gastrointestinal Symptoms Rating Scale (GSRS), stomach state questionnaire, and serum gastrin concentration were used as secondary endpoints. In the FSSG evaluation, the heartburn score was significantly improved at 6 weeks in the LJ88 group compared to the placebo group. No severe adverse events related to the test food were observed. In conclusion, daily ingestion of heat-killed LJ88 improved temporal heartburn symptoms in non-diseased individuals.

Effect of Chronic Ethanol Consumption on Exogenous Glucose Metabolism in Rats Using [1-13C], [2-13C], and [3-13C]glucose Breath Tests.

The C3 carbon of glucose molecules becomes the C1 carbon of pyruvate molecules during glycolysis, and the C1 and C2 carbons of glucose molecules are metabolized in the tricarboxylic acid (TCA) cycle. Utilizing this position-dependent metabolism of C atoms in glucose molecules, [1-13C], [2-13C], and [3-13C]glucose breath tests are used to evaluate glucose metabolism. However, the effects of chronic ethanol consumption remain incompletely understood. Therefore, we evaluated glucose metabolism in ethanol-fed rats using [1-13C], [2-13C], and [3-13C]glucose breath tests. Ethanol-fed (ERs) and control rats (CRs) (n = 8 each) were used in this study, and ERs were prepared by replacing drinking water with a 16% ethanol solution. We administered 100 mg/kg of [1-13C], [2-13C], or [3-13C]glucose to rats and collected expired air (at 10-min intervals for 180 min). We compared the 13CO2 levels (Δ13CO2, ‰) of breath measured by IR isotope ratio spectrometry and area under the curve (AUC) values of the 13CO2 levels-time curve between ERs and CRs. 13CO2 levels and AUCs after administration of [1-13C]glucose and [2-13C]glucose were lower in ERs than in CRs. Conversely, the AUC for the [3-13C]glucose breath test showed no significant differences between ERs and CRs, although 13CO2 levels during the 110-120 min interval were significantly high in ERs. These findings indicate that chronic ethanol consumption diminishes glucose oxidation without concomitantly reducing glycolysis. Our study demonstrates the utility of 13C-labeled glucose breath tests as noninvasive and repeatable methods for evaluating glucose metabolism in various subjects, including those with alcoholism or diabetes.

Preparation of [1'-13 C]citric acid as a probe in a breath test to evaluate tricarboxylic acid cycle flux.

[1'-13 C]Citric acid (1) was efficiently prepared from dimethyl 1,3-acetonedicarboxylate in two steps as a probe for a breath test. The synthetic method was selected because of the yield and reproducibility. Compound 1 was orally administrated to rats, and the time course of the increase of 13 CO2 /12 CO2 ratios (Δ13 CO2 ) in their breath was successfully followed, indicating the metabolism of 1. Thus, the 13 C-breath test using 1 is a promising method to evaluate tricarboxylic acid (TCA) cycle flux.

Pseudomonas otitidis bacteremia in an immunocompromised patient with cellulitis: case report and literature review.

BACKGROUND: Pseudomonas otitidis belongs to the genus Pseudomonas and causes various infections, including ear, skin, and soft tissue infections. P. otitidis has a unique susceptibility profile, being susceptible to penicillins and cephalosporins but resistant to carbapenems, due to the production of the metallo-ß-lactamase called POM-1. This revealed genetic similarities with Pseudomonas aeruginosa, which can sometimes lead to misidentification. CASE PRESENTATION: We report the case of a 70-year-old Japanese male who developed cellulitis and bacteremia during chemotherapy for multiple myeloma. He was initially treated with meropenem, but blood culture later revealed gram-negative bacilli identified as P. otitidis using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Carbapenem resistance was predicted from previous reports; therefore, we switched to dual therapy with levofloxacin and cefepime, and favorable treatment results were obtained. CONCLUSION: This is the first reported case of P. otitidis cellulitis and bacteremia in an immunocompromised patient. Carbapenems are typically used in immunocompromised patients and P. otitidis is often resistant to it. However, its biochemical properties are similar to those of Pseudomonas aeruginosa; therefore, its accurate identification is critical. In the present study, we rapidly identified P. otitidis using MALDI-TOF MS and switched from carbapenems to an appropriate antimicrobial therapy, resulting in a successful outcome.

Effects of ethanol and sex on propionate metabolism evaluated via a faster 13C-propionate breath test in rats.

BACKGROUND: Alcoholism is regarded as a risk factor for vitamin B12 (VB12) deficiency. Because VB12 serves as a coenzyme of methylmalonyl-CoA mutase, a key enzyme in propionate metabolism, the 13C-propionate breath test (PBT) has been studied as a non-invasive diagnostic modality for VB12 deficiency. However, the conventional PBT requires 2 h, which is inconvenient in clinical practice. We hypothesized that a faster PBT can be used to evaluate propionate metabolism and is more easily adaptable for clinical practice. AIM: To evaluate a faster PBT for assessing the effects of long-term ethanol consumption on propionate metabolism in ethanol-fed rats (ERs). METHODS: ERs were obtained by replacing standard drinking water (for control rats, CRs) with 16% ethanol solution in descendants of F344/DuCrj rats. Faster PBT was performed by administering 13C-propionate aqueous solution to male and female ERs and CRs by inserting a metal tubule from the mouth to the stomach; exhaled gas was collected in a bag to measure its 13CO2/12CO2 isotope ratio via infrared isotope spectrometry. Serum VB12 and alanine transaminase (ALT) levels were measured via chemiluminescence immunoassay and the lactate dehydrogenase-ultraviolet method, respectively. We evaluated statistical differences in mean body weight, change in 13CO2 (Δ13CO2‰), peak Δ13CO2‰, and serum VB12 and ALT, between males and females and between ERs and CRs using the t-test and Mann-Whitney U test for normally and non-normally distributed variables, respectively. RESULTS: Males weighed significantly more than females (P < 0.001); CRs weighed significantly more than ERs (P < 0.008). Δ13CO2 reached a peak (Cmax) at 20 min and 30 min in females and males, respectively, decreasing after 20-30 min without rebound in all groups. Males had significantly higher Cmax and Δ13CO2 at 15-45 min than females (P < 0.05; for all pairs). Propionate metabolism was enhanced in male ERs relative to male CRs, whereas metabolism did not differ markedly between ERs and CRs for females. Males had higher serum VB12 levels than females, without prominent differences between the ER and CR groups. Male CRs had notably higher ALT levels than male ERs. Thus, chronic ethanol consumption may trigger fatty acid production via intestinal bacteria and changes in gut microbiome composition. CONCLUSION: Faster PBT shows that 16% ethanol consumption promotes propionate metabolism without inducing liver injury. This PBT may be used clinically to evaluate gut flora status.

Evaluation of the One-Hour ¹³C-Propionate Breath Test in 49 Patients from a Single Center in Japan to Detect Vitamin B12 Deficiency.

BACKGROUND Given the unavailability of reliable biomarkers for vitamin B12 (VB12) deficiency in clinical settings, the usefulness of the ¹³C-propionate breath test (PBT), utilizing VB12 as a coenzyme of methylmalonyl-CoA in propionate metabolism, as a diagnostic modality for VB12 deficiency has been studied. However, a collection time of 2 h reduces its convenience. Hence, we evaluated the effectiveness of 1-h PBT for detecting VB12 deficiency in 49 patients with suspected VB12 deficiency. MATERIAL AND METHODS We collected 100-200 mL breath gas every 10 min until 1 h after the administration of 1 g of ¹³C-propionate from 49 patients (31 men, 18 women; median age, 70 years) with clinically suspected VB12 deficiency and calculated the ¹³CO2 recovered in the breath per hour as the recovery rate (RR [%dose/h]) from ¹³CO2/¹²CO2 using infrared isotope spectrometry. We compared the RRs between groups: (1) with serum VB12 levels ≥145 pg/mL and <145 pg/mL, (2) with mean corpuscular volume ≤100 fL and >100 fL, and 3) pre- and post-VB12 supplementation. RESULTS The RRs peaked within 30 min. The RRs at 20 min (RR20) and 30 min (RR30) were significantly lower in macrocytotic patients (41.28 vs 50.07, p=0.026 and 37.82 vs 43.93, P=0.003). The RR30 was higher in the supplemented patients (41.93 vs 32.84, P=0.024). There was no significant difference in RRs between the patients with normal and low serum VB12 levels. CONCLUSIONS The 1-h PBT can be a diagnostic modality for VB12 deficiency because 1 h is a sufficient collection time.

Evaluation of a Previously Developed Predictive Model for Infective Endocarditis in 320 Patients Presenting with Fever at 4 Centers in Japan Between January 2018 and December 2020.

BACKGROUND In our previous single-center study, we developed an infective endocarditis (IE) prediction model among patients with undiagnosed fever (UF) based on 5 factors that can be obtained on admission: ambulance transfer, presence of cardiac murmur or pleural effusion, blood neutrophil percentage, and platelet count. The present study aimed to retrospectively evaluate the prediction model for IE in 320 patients presenting with fever at 4 university hospitals in Japan from January 2018 to December 2020. MATERIAL AND METHODS Patients aged ≥20 years admitted to 4 hospitals with I-330 (IE) or R-50-9 (UF) according to the International Statistical Classification of Diseases and Related Health Problems-10 were enrolled. More than 2 physicians at each hospital reviewed the patient diagnoses using the modified Duke criteria, allocating "definite IE" to IE group (n=119) and "non-definite IE" to UF group (n=201). Five factors on admission were analyzed by multivariate logistic regression. The discriminative ability and calibration of the model were evaluated using the area under the curve (AUC) and the shrinkage coefficient, respectively. RESULTS A total of 320 patients were enrolled. The odds ratios (95% confidence intervals) were as follows: ambulance transfer 1.81 (0.91-3.55); cardiac murmur 13.13 (6.69-27.36); pleural effusion 2.34 (0.62-2.42); blood neutrophil percentage 1.09 (1.06-1.14); and platelet count 0.96 (0.93-0.99). The AUC was 0.783 (0.732-0.834) with a shrinkage coefficient of 0.961. CONCLUSIONS The IE prediction model is useful to estimate the probability of IE immediately after admission for fever in patients aged ≥20 years.

Clinical characteristics of older Japanese patients with acute appendicitis: A post hoc analysis.

BACKGROUND: Acute appendicitis (AA) in older patients can look different from AA in younger patients. Although it is crucial that primary care physicians can recognize AA in patients of any age, few Japanese studies have examined the characteristics of older AA patients. To address this, we evaluated the clinical characteristics of older Japanese patients with AA. METHODS: We performed a post hoc analysis of the data from a previous Japanese single-center study. We analyzed the clinical information of both younger (age: 16-64 years) and older patients (age: ≥65 years). RESULTS: A cohort of 236 patients consisting of 219 (92.8%) younger patients and 17 (7.2%) older patients was evaluated. The median ages of the younger and older patients were 34 (interquartile range [IR], 24-45) and 78 years (IR, 74-81), respectively. The prevalence of complicated appendicitis (CA) (older: 41.2% vs. younger: 14.2%), comorbidities (70.6% vs. 13.2%), and thrombocytopenia (17.7% vs. 4.1%), along with serum C-reactive protein (CRP) level (6.7 mg/dl vs. 1.0 mg/dl), was significantly higher in older patients. Significantly fewer older patients had epigastric pain (17.7% vs. 53.0%). Logistic regression evaluating the characteristics of older AA patients showed that CRP >5 mg/dl had a high odds ratio (OR) (5.01; 95% CI, 1.73-14.54), while epigastric pain had a low OR (0.24; 95% CI, 0.06-0.90). CONCLUSION: Our study reveals a higher prevalence of CA and comorbidities in older patients, and suggests that a lack of epigastric pain, thrombocytopenia, and higher serum CRP level are characteristics of older AA patients.

Impact of Helicobacter pylori infection on fluid duodenal microbial community structure and microbial metabolic pathways.

BACKGROUND: The bioactivities of commensal duodenal microbiota greatly influence the biofunction of hosts. We investigated the role of Helicobacter pylori infection in extra-gastroduodenal diseases by determining the impact of H. pylori infection on the duodenal microbiota. We sequenced 16 S rRNA genes in samples aspirated from the descending duodenum of 47 (male, 20; female, 27) individuals who were screened for gastric cancer. Samples were analysed using 16 S rRNA gene amplicon sequencing, and the LEFSe and Kyoto Encyclopaedia of Genes and Genomes methods were used to determine whether the duodenal microflora and microbial biofunctions were affected using H. pylori infection. RESULTS: Thirteen and 34 participants tested positive and negative for H. pylori, respectively. We identified 1,404 bacterial operational taxonomic units from 23 phyla and 253 genera. H. pylori infection changed the relative mean abundance of three phyla (Proteobacteria, Actinobacteria, and TM7) and ten genera (Neisseria, Rothia, TM7-3, Leptotrichia, Lachnospiraceae, Megasphaera, F16, Moryella, Filifactor, and Paludibacter). Microbiota features were significantly influenced in H. pylori-positive participants by 12 taxa mostly classified as Gammaproteobacteria. Microbial functional annotation revealed that H. pylori significantly affected 12 microbial metabolic pathways. CONCLUSIONS: H. pylori disrupted normal bacterial communities in the duodenum and changed the biofunctions of commensal microbiota primarily by upregulating specific metabolic pathways. Such upregulation may be involved in the onset of diseases associated with H. pylori infection.

The metabolic parameters based on volume in PET/CT are associated with clinicopathological N stage of colorectal cancer and can predict prognosis.

BACKGROUND: A combination of positron emission tomography and computed tomography (PET/CT) is an important modality for the diagnosis of carcinoma. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been reported as metabolic parameters in PET/CT since the late 1990s, and they are expected to be useful in diagnosing diverse cancers and as prognostic biomarkers. We evaluated the potential of these parameters in the prognosis of colorectal cancer (CRC) by comparing them with conventional parameters, including the maximum standardized uptake value (SUVmax). We enrolled 84 patients who underwent surgery for CRC without distal metastasis between April 2015 and April 2019. SUVmax, MTV, and TLG were measured by 18F-fluorodeoxyglucose (FDG)-PET/CT. To find an optimal threshold value related to prognosis, the volume of interest in the primary carcinoma was measured at fixed relative and absolute thresholds based on SUVmax (30%, 40%, and 50%; 2.5, 3.0, and 3.5, respectively), tumor-to-liver standardized uptake ratios, TLR (1.0, 1.5, and 2.0), and SUV normalized to lean body mass, SUL (2.0, 2.5, and 3.0). After classifying the patients into two groups according to pathological N stage, the optimal threshold values of all metabolic parameters were compared between groups using a non-parametric comparison test. RESULT: The most suitable thresholds for MTV were a SUVmax of 3.5 and a TLR 2.0. TLG with a SUVmax value of 40% showed the most significant difference. The MTV standard uptake ratio of 2.0 was significantly associated with pathological N stage. CONCLUSION: Our results suggest that an MTV TLR 2.0 on PET/CT reflects pathological N stage in local patients with CRC.

Pseudo-thrombotic Microangiopathy Caused by Acquired Cobalamin Deficiency Due to Unintentional Neglect.

Acquired vitamin B12 (VB12) deficiency is a rare cause of thrombotic microangiopathy (TMA). We experienced an 86-year-old Japanese woman who presented with coma, renal dysfunction, and microangiopathic hemolytic anemia. Although we initially considered thrombotic thrombocytopenic purpura, we eventually diagnosed her to have VB12 deficiency due to inappropriate dietary care based on her low serum VB12 level, social history, and negative parietal cell finding and the presence of intrinsic factor antibody. Because similar cases are expected to increase in today's aging society, our experience underscores the importance of including acquired VB12 deficiency in the differential diagnosis of TMA, even in elderly patients without a history of gastrectomy.

New Assay System Elecsys Anti-p53 to Detect Serum Anti-p53 Antibodies in Esophageal Cancer Patients and Colorectal Cancer Patients: Multi-institutional Study.

BACKGROUND: Several recent studies suggest that serum anti-p53 antibodies (s-p53-Abs) may be combined with other markers to detect esophageal and colorectal cancer. In this study, we assessed the sensitivity and specificity of s-p53-Abs detection of a new electrochemiluminescence immunoassay (ECLIA; Elecsys anti-p53). METHODS: Elecsys anti-p53 assay was used to analyze the level of s-p53-Abs in blood sera from patients with esophageal or colorectal cancer taken before treatment. Control blood sera from healthy volunteers, patients with benign diseases, and patients with autoimmune diseases served as a reference. In addition, squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA21-1) were assessed in patients with esophageal cancer, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were assessed in patients with colorectal cancer. RESULTS: Samples from 281 patients with esophageal cancer, 232 patients with colorectal cancer, and 532 controls were included in the study. The median value of s-p53-Abs in control samples was < 0.02 µg/mL (range < 0.02-29.2 µg/mL). Assuming 98% specificity, the cut-off value was determined as 0.05 µg/mL. s-p53-Abs were detected in 20% (57/281) of patients with esophageal cancer and 18% (42/232) of patients with colorectal cancer. In combination with SCC-Ag and CEA, respectively, s-p53-Abs detected 51% (144/281) of patients with esophageal and 53% (124/232) of patients with colorectal cancer. CONCLUSIONS: The new s-p53-Abs assay Elecsys anti-p53 was useful in detecting esophageal and colorectal cancers with high specificity. Adding s-p53-Abs to conventional markers significantly improved the overall detection rates.

Reactive leukocytosis in older patients with acute colonic diverticulitis: A retrospective study utilizing logistic regression analysis.

AIM: Although various neutrophilic immunosenescence mechanisms have been shown, there are few clinical studies on age-related differences in leukocytosis against acute bacterial infections, including acute colonic diverticulitis. METHODS: We performed a retrospective study of 26 patients ≥65 years old and 211 patients 16-64 years old who were hospitalized for acute colonic diverticulitis at Toho University Medical Center Omori Hospital between 2010 and 2016. We compared patients' characteristics, including sex, immunocompromised status, diverticulitis site, complications, severity, previous diverticulitis, vital signs, leukocyte counts, neutrophil-to-lymphocyte ratio and serum C-reactive protein on admission. To adjust for confounding factors, we performed a logistic regression analysis. RESULTS: Univariate comparisons showed that leukocyte count (older: 10 850 [interquartile range, 9400-12 000]/mm3 vs. younger: 12 600 [interquartile range, 10 500-15 000]/mm3 , P = 0.004) and prevalence of leukocytosis (leukocytes >11 000/mm3 ) were lower in older compared with younger patients. There were significantly more female, left-sided diverticulitis and immunocompromised patients in the older compared with the younger group. Logistic regression showed that leukocyte count, prevalence of female patients, and left-sided diverticulitis were independent predictors for the older patients: Their odds ratios were 0.866 (95% confidence interval [95% CI] 0.753-0.996), 2.631 (95% CI, 1.032-6.707) and 5.810 (95% CI, 2.328-14.497), respectively. CONCLUSION: Caution should be taken when managing older patients with colonic diverticulitis because reactive leukocytosis might be poor, possibly reflecting immunosenescence. Geriatr Gerontol Int 2020; 20: 951-955.

Sex difference in clinical presentation of patients with infectious mononucleosis caused by Epstein-Barr virus.

INTRODUCTION: There are few studies on sex difference in patients with infectious mononucleosis caused by Epstein-Barr virus (EBV-IM). We performed a retrospective study to evaluate the sex difference in clinical presentation of patients with EBV-IM. METHODS: We performed a single-center retrospective study evaluating >14-year-old patients with serologically confirmed EBV-IM during 2006-2017. We compared the patients' age, symptoms, physical findings, and laboratory data between male and female patients. To adjust for confounding factors, we performed a logistic regression analysis based on the results of univariate comparisons. RESULT: Of the 122 eligible patients (56 male and 66 female, ratio: 1:1.2), the median ages were 26 years old (interquartile range [IR], 22-31.5 years old]) and 22 years old (IR, 20-25 years old) for males and females, respectively (p < 0.001). Headache was significantly more prevalent in males (25.0% vs. 10.6%, p = 0.036). Leukocyte count was also significantly higher in males (11,400/mm3 [IR, 7,600-14,100/mm3] vs. 9,400/mm3 [IR, 6,600-11,600/mm3], p = 0.021). The prevalence of periorbital edema (male: 3.6% vs. female: 18.1%, p = 0.012) and severity of transaminase elevation were significantly higher in females. The regression analysis evaluating clinical characteristics of male patients showed that age >30 years old, headache, and leukocyte >11,000/mm3 had high odds ratios. CONCLUSION: Our single-center retrospective study suggests that older age of onset, headache, and leukocytosis are more likely to be characteristics of male patients with EBV-IM. Our study also underscores the importance of periorbital edema as a clue for early diagnosis of EBV-IM, especially in female patients.

Clinical prediction of complicated appendicitis: A case-control study utilizing logistic regression.

BACKGROUND: Since high-quality evidence on conservative treatment of acute appendicitis using antibiotics has increased, differentiation of patients with complicated appendicitis (CA) from those with simple appendicitis (SA) has become increasingly important. Previous studies have revealed that male gender, advanced age, comorbid conditions, prehospital delay, fever, and anorexia are risk factors of perforated appendicitis. Elevated serum C-reactive protein (CRP) level and hyponatremia have also been reported as predictive biomarkers of CA. However, confounding between various factors is problematic because most previous studies were limited to univariate analysis. AIM: To evaluate non-laboratory and laboratory predictive factors of CA using logistic regression analyses. METHODS: We performed an exploratory, single-center, retrospective case-control study that evaluated 198 patients (83.9%) with SA and 38 patients (16.1%) with CA. Diagnoses were confirmed by computed tomography images for all cases. We compared age, sex, onset-to-visit interval, epigastric/periumbilical pain, right lower quadrant pain, nausea/vomiting, diarrhea, anorexia, medical history (of previous non-surgically treated appendicitis, diabetes, hypertension, dyslipidemia, liver cirrhosis, hemodialysis, chronic lung diseases, malignant tumors, immunosuppressant use, and antiplatelet use), vital signs, physical findings, and laboratory data to select the explanatory variates for logistic regression. Based on the univariate comparisons, we performed logistic regression for clinical differentiation between CA and SA using only non-laboratory factors and also including both non-laboratory and laboratory factors. RESULTS: The 236 eligible patients consisted of 198 patients (83.9%) with SA and 38 patients (16.1%) with CA. The median ages were 34 years old [interquartile ranges (IR), 24-45 years] in the SA group and 49 years old (IR, 35-63 years) in the CA group (P < 0.001). The median onset-to-visit interval was 1 d (IR, 0-1) and 1 d (IR, 1-2) in the SA and CA groups, respectively (P < 0.001). Heart rate, body temperature, and serum CRP level in the CA group were significantly higher than in the SA group; glomerular filtration rate and serum sodium were significantly lower in the CA group. Anorexia was significantly more prevalent in the CA group. The regression model including age, onset-to-visit interval, anorexia, tachycardia, and fever as non-laboratory predictive factors of CA (Model 1) showed that age ≥ 65 years old, longer onset-to-visit interval, and anorexia had significantly high odds ratios. The logistic regression for prediction of CA including age, onset-to-visit interval, anorexia, serum CRP level, hyponatremia (serum sodium < 135 mEq/L), and glomerular filtration rate < 60 mL/min/1.73 m2 (Model 2) showed that only elevated CRP levels had significantly high odds ratios. Under the curve values of receiver operating characteristics curves of each regression model were 0.74 for Model 1 and 0.87 for Model 2. CONCLUSION: Our logistic regression analysis on differentiating factors of CA from SA showed that high CRP level was a strong dose-dependent predictor of CA.

Profile of regional fat and fat-free soft tissue accumulation in male athletes.

BACKGROUND: It is unclear whether or not the breakpoint (BP), at which the proportion of each of fat mass (FM) and fat-free soft tissue mass (FFSTM) to body mass (BM) alter, exists in male athletes. We examined the hypothesis that in male athletes, the regional FM and FFSTM-BM relationships have a BP, but the body mass at BP (BMBP) differs among the arms, trunk, and legs. METHODS: By using a dual X-ray absorptiometry, whole-body and regional FMs and FFSTMs in the arms, trunk, and legs were estimated in 198 male athletes (20.8 ± 2.1 years; 1.73 ± 0.07 m; 72.7 ± 14.8 kg). To detect the BP in the relationship between each of FM and FFSTM and BM, a piecewise linear regression analysis was used. If a BP was detected in the corresponding relationship, the significant difference between the regression slopes above and below the BP was examined. RESULTS: The regression analysis indicated that the BMBP existed in the FM- and FFSTM-BM relationships regardless of region and whole body. For the whole body, BMBP was 81.8 kg for FM and 82.2 kg for FFSTM. In regional FM-BM relationships, BMBP was 80.5 kg for arms, 82.6 kg for trunk, and 63.3 kg for legs, and the regression slopes above the BMBP became higher than those below the BP, and vice versa in regional FFSTM-BM relationships (BMBP 104.6 kg for arms, 80.9 kg for trunk, and 79.0 kg for legs). The relative differences in the slopes between below and above BMBP in the regional FM-BM relationships were higher in the arms and trunk than in the legs, and those in the regional FFSTM-BM relationships in the legs than in the trunk. CONCLUSION: Whole-body and regional FM- and FFSTM-BM relationships for male athletes have breakpoints at which the proportion of the tissue masses to BM alters. The BMBP and differences in the distribution of regional FM and FFSTM around the breakpoint are region specific.

A Study of Morphological Changes in Renal Afferent Arterioles Induced by Angiotensin II Type 1 Receptor Blockers in Hypertensive Patients.

BACKGROUND: Renin-angiotensin-aldosterone system blockers are known to reduce hypertrophy of vascular smooth muscle cells (SMCs) in hypertensive cases. However, we have reported marked proliferative changes of renal afferent arteriolar SMCs in rats induced by a long-term administration of angiotensin II type 1 receptor blockers (ARBs) and an angiotensin-converting enzyme inhibitor (ACEI). In this study, we examined the morphological changes of afferent arteriolar walls in human kidneys with or without ARBs/ACEIs. METHODS: Forty-four wedge resections were taken from patients aged 45-74 years from 92 nephrectomized kidneys due to malignancy at Toho University Omori Medical Center between 2013 and 2016. They were divided into the following three groups: 18 hypertensive patients treated with antihypertensive agents including ARBs or ACEIs (the HTARB group), 6 hypertensive patients treated with calcium channel blockers without ARBs/ACEIs (the HTCCB group), and 20 normotensive patients (the normotensive group) as a control. Cases expecting vascular changes such as diabetes were excluded. In each case renal arterioles were measured as the ratio of inner/outer arteriolar diameter, and pathologists estimated morphological abnormal changes, scoring each specimen independently. RESULTS: The ratio in the HTARB group was 0.39 ± 0.05 (mean ± SD), and was significantly the lowest among the three groups (0.46 ± 0.02 in the HTCCB, 0.53 ± 0.02 in the normotensive group; p = 0.0107 vs. HTCCB, p = 0.00001 vs. normotensive). The ratio in the three groups significantly correlated with the estimated glomerular filtration rate (r = 0.4915, p < 0.0007). The afferent arteriolar SMCs in the HTARB group frequently showed marked proliferative and irregular changes. The score of SMC abnormalities estimated regarding the proliferation, irregularity of the arrangement, and size in hilar afferent arteriolar SMCs was highest in the HTARB group and showed statistical significance (p = 0.0088, p = 0.00001, and p = 0.025 versus other two groups). CONCLUSIONS: We consider that these morphological changes in arterioles are induced by ARBs/ACEIs. These changes could induce an important suppression of glomerular hyperfiltration and could lead to glomerular ischemia. However, the clinical consequences of these morphological changes in correlation with ARBs/ACEIs were not sufficiently clear and require further analysis. We should consider renal arteriolar morphological changes when using ARBs/ACEIs.

Clinical differentiation of acute appendicitis and right colonic diverticulitis: A case-control study.

BACKGROUND: Acute right colonic diverticulitis (ARCD) is an important differential diagnosis of acute appendicitis (AA) in Asian countries because of the unusually high prevalence of right colonic diverticula. Due to qualitative improvement and the high penetration rate of computed tomography (CT) scanning in Japan, differentiation of ARCD and AA mainly depends on this modality. But cost, limited availability, and concern for radiation exposure make CT scanning problematic. Differential findings of ARCD from AA are based on several small studies that used univariate comparisons from Korea and Taiwan. Previous studies on clinical and laboratory differences between AA and ARCD are limited. AIM: To determine clinical differences between AA and ARCD for differentiation of these two diagnoses by creating a logistic regression model. METHODS: We performed an exploratory single-center retrospective case-control study evaluating 369 Japanese patients (age ≥ 16 years), 236 (64.0%) with AA and 133 (36.0%) with ARCD, who were hospitalized between 2012 and 2016. Diagnoses were confirmed by CT images. We compared age, sex, onset-to-visit interval, epigastric/periumbilical pain, right lower quadrant (RLQ) pain, nausea/vomiting, diarrhea, anorexia, medical history, body temperature, blood pressure, heart rate, RLQ tenderness, peritoneal signs, leukocyte count, and levels of serum creatinine, serum C-reactive protein (CRP), and serum alanine aminotrans-ferase. We subsequently performed logistic regression analysis for differentiating AA from ARCD based on the results of the univariate analyses. RESULTS: In the AA and ARCD groups, median ages were 35.5 and 41.0 years, respectively (p=0.011); median onset-to-visit intervals were 1 [interquartile range (IQR): 0-1] and 2 (IQR: 1-3) days, respectively (P < 0.001); median leukocyte counts were 12600 and 11500/mm3, respectively (P = 0.002); and median CRP levels were 1.1 (IQR: 0.2-4.1) and 4.9 (IQR: 2.9-8.5) mg/dL, respectively (P < 0.001). In the logistic regression model, odds ratios (ORs) were significantly high in nausea/vomiting (OR: 3.89, 95%CI: 2.04-7.42) and anorexia (OR: 2.13, 95%CI: 1.06-4.28). ORs were significantly lower with a longer onset-to-visit interval (OR: 0.84, 95%CI: 0.72-0.97), RLQ pain (OR: 0.28, 95%CI: 0.11-0.71), history of diverticulitis (OR: 0.034, 95%CI: 0.005-0.20), and CRP level > 3.0 mg/dL (OR: 0.25, 95%CI: 0.14-0.43). The regression model showed good calibration, discrimination, and optimism. CONCLUSION: Clinical findings can differentiate AA and ARCD before imaging studies; nausea/vomiting and anorexia suggest AA, and longer onset-to-visit interval, RLQ pain, previous diverticulitis, and CRP level > 3.0 mg/dL suggest ARCD.

Clinical differentiation of infectious mononucleosis that is caused by Epstein-Barr virus or cytomegalovirus: A single-center case-control study in Japan.

INTRODUCTION: Infectious mononucleosis (IM) is a common viral infection that typically causes fever, pharyngitis, and lymphadenopathy in young patients. The Epstein-Barr virus (EBV) is the most common cause of IM, followed by cytomegalovirus (CMV). Given that serological testing is associated with limitations regarding its accuracy, availability, and time to receive results, clinical differentiation based on symptoms, signs, and basic tests would be useful. We evaluated whether clinical findings could be used to differentiate EBV-IM from CMV-IM. METHODS: In this single-center retrospective case-control study, we evaluated >14-year-old patients with serologically confirmed EBV-IM or CMV-IM during 2006-2017. We compared the patients' symptoms, physical findings, blood counts, and serum biomarkers to create three regression models: model 1 (symptoms and signs), model 2 (model 1 plus sonographic hepatosplenomegaly and blood counts), and model 3 (model 2 plus hepatobiliary biomarkers). RESULTS: Among the 122 patients (72.6%) with EBV-IM and 46 patients (27.4%) with CMV-IM, the median age was 25 years and 82 patients (48.8%) were male. The median age was 10 years older in the CMV-IM group (p < 0.001) and the median interval from onset to visit was 5 days longer in the CMV-IM group (p < 0.001). Logistic regression revealed that EBV-IM was predicted by younger age, short onset-to-visit interval, lymphadenopathy, tonsillar white coat, hepatosplenomegaly, atypical lymphocytosis, and elevations of lactate dehydrogenase and gamma-glutamyl transferase. All regression models had areas under the curve of >0.9. CONCLUSION: History and physical findings, especially when used with atypical lymphocytosis and sonographic hepatosplenomegaly, can help physicians differentiate EBV-IM from CMV-IM.