Toshihiko Takada

Diversity of Intestinal Clostridium coccoides Group in the Japanese Population, as Demonstrated by Reverse Transcription-Quantitative PCR

We used sensitive rRNA-targeted reverse transcription-quantitative PCR (RT-qPCR) to quantify the Clostridium coccoides group, which is a major anaerobic population in the human intestine. For this purpose, the C. coccoides group was classified into 3 subgroups and 19 species for expediency in accordance with the existing database, and specific primers were newly developed to evaluate them. Population levels of the C. coccoides group in human feces determined by RT-qPCR were equivalent to those determined by fluorescence in situ hybridization. RT-qPCR analysis of fecal samples from 96 volunteers (32 young children, 32 adults and 32 elderly) by using the 22 new primer sets together with the C. coccoides group-specific primer setm revealed that (i) total counts obtained as the sum of the 3 subgroups and 19 species were equivalent to the results obtained by using the C. coccoides group-specific primer set; (ii) total C. coccoides-group counts in the elderly were significantly lower than those in young children and adults; (iii) genus Blautia was the most common subgroup in the human intestinal C. coccoides-group populations at all age populations tested; (iv) the prevalences of Fusicatenibacter saccharivorans and genus Dorea were significantly higher in adults than in young children and the elderly; and (v) the prevalences of C. scindens and C. hylemonae, both of which produce secondary bile acid in the human intestine, were significantly higher in the elderly than in young children and adults. Hierarchical clustering and principal component analysis showed clear separation of the bacterial components between adult and elderly populations. Taken together, these data suggest that aging plays an important role in the diversity of C. coccoides-group populations in human intestinal microbiota; changes in this diversity likely influence the health of the host.

The role of digital rectal examination for diagnosis of acute appendicitis: A systematic review and meta-analysis

Background Digital rectal examination (DRE) has been traditionally recommended to evaluate acute appendicitis, although several reports indicate its lack of utility for this diagnosis. No meta-analysis has examined DRE for diagnosis of acute appendicitis. Objectives To assess the role of DRE for diagnosis of acute appendicitis. Data Sources Cochrane Library, PubMed, and SCOPUS from the earliest available date of indexing through November 23, 2014, with no language restrictions. Study Selection Clinical studies assessing DRE as an index test for diagnosis of acute appendicitis. Data Extraction and Synthesis Two independent reviewers extracted study data and assessed the quality, using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Bivariate random-effects models were used for the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) as point estimates with 95% confidence intervals (CI). Main Outcomes and Measures The main outcome measure was the diagnostic performance of DRE for diagnosis of acute appendicitis. Results We identified 19 studies with a total of 7511 patients. The pooled sensitivity and specificity were 0.49 (95% CI 0.42–0.56) and 0.61 (95% CI 0.53–0.67), respectively. The positive and negative likelihood ratios were 1.24 (95% CI 0.97–1.58) and 0.85 (95% CI 0.70–1.02), respectively. The DOR was 1.46 (0.95–2.26). Conclusion and Relevance Acute appendicitis cannot be ruled in or out through the result of DRE. Reconsideration is needed for the traditional teaching that rectal examination should be performed routinely in all patients with suspected appendicitis.

Predictors for benign paroxysmal positional vertigo with positive Dix–Hallpike test

Objective Patient medical history is important for making a diagnosis of causes of dizziness, but there have been no studies on the diagnostic value of individual items in the history. This study was performed to identify and validate useful questions for suspecting a diagnosis of benign paroxysmal positional vertigo (BPPV). Methods Construction and validation of a disease prediction model was performed at the outpatient clinic in the Department of General Medicine of Chiba University Hospital. Patients with dizziness were enrolled (145 patients for construction of the disease prediction model and 61 patients for its validation). This study targeted BPPV of the posterior semicircular canals only with a positive Dix–Hallpike test (DHT + BPPV) to avoid diagnostic ambiguity. Binomial logistic regression analysis was performed to identify the items that were useful for diagnosis or exclusion of DHT + BPPV. Results Twelve patients from the derivation set and six patients from the validation set had DHT + BPPV. Binomial logistic regression analysis selected a “duration of dizziness ≤15 seconds” and “onset when turning over in bed” as independent predictors of DHT + BPPV with an odds ratio (95% confidence interval) of 4.36 (1.18–16.19) and 10.17 (2.49–41.63), respectively. Affirmative answers to both questions yielded a likelihood ratio of 6.81 (5.11–9.10) for diagnosis of DHT + BPPV, while negative answers to both had a likelihood ratio of 0.19 (0.08–0.47). Conclusion A “duration of dizziness ≤15 seconds” and “onset when turning over in bed” were the two most important questions among various historical features of BPPV.

Limitations of using imaging diagnosis for psoas abscess in its early stage.

Objective Patients diagnosed with psoas abscess have a high mortality rate. The major cause of its poor prognosis is delayed treatment. Therefore, making a correct diagnosis rapidly is important. Both computed tomography (CT) and magnetic resonance imaging (MRI) are considered to be the gold standards as imaging modalities that have a high sensitivity for detecting psoas abscess. There have been few reports regarding the limitations of these methods, but psoas abscess in its early stage may go undetected by CT and MRI. Methods Detection of psoas abscess by CT and MRI was investigated in the present study through a retrospective review of 15 patients in whom psoas abscess was diagnosed during a course of ten years at our hospital. Results In all patients, psoas abscess was diagnosed by at least a plain CT, enhanced CT, and/or plain MRI. The interval between the onset of symptoms and diagnosis was 20.9±17.9 days (mean ± standard deviation). In three patients, repeat imaging identified a psoas abscess, whereas initial imaging failed to detect it. The overall sensitivity of plain CT, enhanced CT, and plain MRI for psoas abscess was 78%, 86%, and 88%, respectively. From six days after the onset of symptoms, the sensitivity of each modality was 100%, while the sensitivity from day one to five days was only 33%, 50%, and 50%, respectively. Conclusion Although CT and MRI are considered to be gold standard modalities for diagnosing psoas abscess, both methods can fail to notice this condition in its early stage.

Microscale spatial analysis provides evidence for adhesive monopolization of dietary nutrients by specific intestinal bacteria

Each species of intestinal bacteria requires a nutritional source to maintain its population in the intestine. Dietary factors are considered to be major nutrients; however, evidence directly explaining the in situ utilization of dietary factors is limited. Microscale bacterial distribution would provide clues to understand bacterial lifestyle and nutrient utilization. However, the detailed bacterial localization around dietary factors in the intestine remains uninvestigated. Therefore, we explored microscale habitats in the murine intestine by using histology and fluorescent in situ hybridization, focusing on dietary factors. This approach successfully revealed several types of bacterial colonization. In particular, bifidobacterial colonization and adhesion on granular starch was frequently and commonly observed in the jejunum and distal colon. To identify the bacterial composition of areas around starch granules and areas without starch, laser microdissection and next-generation sequencing-based 16S rRNA microbial profiling was performed. It was found that Bifidobacteriaceae were significantly enriched by 4.7 fold in peri-starch areas compared to ex-starch areas. This family solely consisted of Bifidobacterium pseudolongum. In contrast, there was no significant enrichment among the other major families. This murine intestinal B. pseudolongum had starch-degrading activity, confirmed by isolation from the mouse feces and in vitro analysis. Collectively, our results demonstrate the significance of starch granules as a major habitat and potential nutritional niche for murine intestinal B. pseudolongum. Moreover, our results suggest that colonizing bifidobacteria effectively utilize starch from the closest location and maintain the location. This may be a bacterial strategy to monopolize solid dietary nutrients. We believe that our analytical approach could possibly be applied to other nutritional factors, and can be a powerful tool to investigate in vivo relationships between bacteria and environmental factors in the intestine.

Recurrent Back Pain of Eosinophilic Esophagitis

A 66-year-old man presented with 5 episodes per week of recurrent severe back pain for 2 weeks. At an emergency clinic, laboratory tests, electrocardiography, contrastenhanced thoracoabdominal computed tomography, and upper gastrointestinal endoscopy had revealed nothing remarkable. His history included aspirin-induced asthma, hypertension, and hyperlipidemia. Current medications were oral candesartan, amlodipine, and simvastatin, as well as inhaled beclomethasone dipropionate. He complained of spontaneous midline back pain at Th 4-7 that worsened over 30 minutes and resolved after 2 hours. It was not aggravated by movement, suggesting referred visceral pain. The pattern of pain and the test results excluded angina pectoris, gallstones, chronic pancreatitis, and peptic ulcer, while the duration, repeatability, and site of pain suggested esophageal spasm. Review of the computed tomography revealed mid to distal esophageal wall thickening (Figure). Endoscopy performed at our hospital identified slight linear furrows at this site, while biopsy revealed epithelial infiltration of eosinophils ( 15 per high power field) in all 4 specimens. The eosinophil count was 605/mL, with no organopathy to suggest hypereosinophilic syndrome. Among diseases associated with eosinophilic infiltration of the esophagus, eosinophilic gastroenteritis and Crohn disease were excluded in this patient, because upper and lower gastrointestinal endoscopy with random biopsy at a total of 10 sites identified no abnormalities outside the esophagus. Pathological examination showed no evidence of esophageal infection, and his symptoms did not suggest celiac disease or vasculitis.

Association between daily salt intake of 3-year-old children and that of their mothers: A cross-sectional study

This study investigated the association between the daily salt intake of 3‐year‐old children and that of their mothers. A total of 641 children were studied. The daily salt intake of the children and their mothers was estimated by morning and spot urine methods, respectively. In the multivariable analysis, a 1 g higher maternal daily salt intake was associated with a 0.14 g (95% confidence interval [CI], 0.07‐0.22, P < .001) higher salt intake of her children. In the secondary analysis, the odds ratios for excess salt intake of children were 1.61 (95% CI, 1.01‐2.55, P = .045) and 1.81 (95% CI, 1.12‐2.91, P = .015) for 9.7‐11.5 g and 11.5 g or more of maternal daily salt intake, respectively. Our findings could help to convince mothers of the importance of appropriate salt intake, not only for themselves but also for their children.

Effects of self-monitoring of daily salt intake estimated by a simple electrical device for salt reduction: a cluster randomized trial

Recently, a simple device for self-monitoring of daily salt intake was developed, and it is recommended by The Japanese Society of Hypertension. This study aimed to investigate the effects of this device on salt reduction and on lowering blood pressure. In this single blinded, cluster randomized controlled trial, families were randomly assigned to either an intervention or a control group. Participants in both groups attended lectures about salt reduction, but only the intervention group used the self-monitoring device to estimate their daily salt intake. The main outcome measure was the difference in the estimated daily salt intake by spot urine between the two groups after 4 weeks. The secondary outcome was the difference in blood pressure. A total of 105 families (158 participants) were randomized. The mean daily salt intake was 9.04 (SD 1.77) g/day in the control group and 9.37 (SD 2.13) g/day in the intervention group at baseline. After 4 weeks, the mean daily salt intake was 8.97 (SD 1.97) g/day in the control group and 8.60 (SD 2.25) g/day in the intervention group; the mean difference between the two groups was −0.50 g/day (95% confidence interval (CI) −0.95, −0.05; P = 0.030). The mean difference in systolic blood pressure was −4.4 mm Hg (95% CI −8.7, −0.1; P = 0.044). This is the first randomized controlled trial to demonstrate the effectiveness of a device for self-monitoring of salt intake with a significant reduction in daily salt intake and systolic blood pressure.

Development and validation of a prediction model for functional decline in older medical inpatients

OBJECTIVE To prevent functional decline in older inpatients, identification of high-risk patients is crucial. The aim of this study was to develop and validate a prediction model to assess the risk of functional decline in older medical inpatients. METHODS In this retrospective cohort study, patients ≥65 years admitted acutely to medical wards were included. The healthcare database of 246 acute care hospitals (n = 229,913) was used for derivation, and two acute care hospitals (n = 1767 and 5443, respectively) were used for validation. Data were collected using a national administrative claims and discharge database. Functional decline was defined as a decline of the Katz score at discharge compared with on admission. RESULTS About 6% of patients in the derivation cohort and 9% and 2% in each validation cohort developed functional decline. A model with 7 items, age, body mass index, living in a nursing home, ambulance use, need for assistance in walking, dementia, and bedsore, was developed. On internal validation, it demonstrated a c-statistic of 0.77 (95% confidence interval (CI) = 0.767-0.771) and good fit on the calibration plot. On external validation, the c-statistics were 0.79 (95% CI = 0.77-0.81) and 0.75 (95% CI = 0.73-0.77) for each cohort, respectively. Calibration plots showed good fit in one cohort and overestimation in the other one. CONCLUSIONS A prediction model for functional decline in older medical inpatients was derived and validated. It is expected that use of the model would lead to early identification of high-risk patients and introducing early intervention.

Diagnostic utility of appetite loss in addition to existing prediction models for community-acquired pneumonia in the elderly: a prospective diagnostic study in acute care hospitals in Japan

Objective Diagnosis of community-acquired pneumonia (CAP) in the elderly is often delayed because of atypical presentation and non-specific symptoms, such as appetite loss, falls and disturbance in consciousness. The aim of this study was to investigate the external validity of existing prediction models and the added value of the non-specific symptoms for the diagnosis of CAP in elderly patients. Design Prospective cohort study. Setting General medicine departments of three teaching hospitals in Japan. Participants A total of 109 elderly patients who consulted for upper respiratory symptoms between 1 October 2014 and 30 September 2016. Main outcome measures The reference standard for CAP was chest radiograph evaluated by two certified radiologists. The existing models were externally validated for diagnostic performance by calibration plot and discrimination. To evaluate the additional value of the non-specific symptoms to the existing prediction models, we developed an extended logistic regression model. Calibration, discrimination, category-free net reclassification improvement (NRI) and decision curve analysis (DCA) were investigated in the extended model. Results Among the existing models, the model by van Vugt demonstrated the best performance, with an area under the curve of 0.75(95% CI 0.63 to 0.88); calibration plot showed good fit despite a significant Hosmer-Lemeshow test (p=0.017). Among the non-specific symptoms, appetite loss had positive likelihood ratio of 3.2 (2.0–5.3), negative likelihood ratio of 0.4 (0.2–0.7) and OR of 7.7 (3.0–19.7). Addition of appetite loss to the model by van Vugt led to improved calibration at p=0.48, NRI of 0.53 (p=0.019) and higher net benefit by DCA. Conclusions Information on appetite loss improved the performance of an existing model for the diagnosis of CAP in the elderly.