Role of High-sensitivity C-reactive Protein in Future Cardiovascular Events in Hemodialysis Patients.

BACKGROUND/AIM: The pathogenesis of cardio-vascular disease (CVD) in hemodialysis (HD) patients involves inflammation and oxidative stress. High-sensitivity C-reactive protein (hs-CRP) is an established inflammatory biomarker associated with CVD. Several studies have suggested that the inflammatory biomarker pentraxin-3 (PTX-3) and the oxidative stress-related biomarker soluble lectin-like low-density lipoprotein receptor-1 (sLOX-1) are novel biomarkers for CVD in non-HD populations. This study aimed to clarify the association of these established and novel biomarkers with future cardiovascular (CV) events in HD patients. PATIENTS AND METHODS: This was a single-center prospective cohort study that included 255 HD patients. The primary outcome was the composite of nonfatal and fatal CV events. The event-free survival rate between the two groups according to the median plasma level of each biomarker at baseline was evaluated using the Kaplan-Meier method. The risk for CV events at elevated levels of each biomarker was estimated using Cox proportional hazard model. RESULTS: We observed 44 CV events during the median follow-up period of 743 days. The event-free survival rate significantly differed between the two groups in hs-CRP but not in PTX-3 or sLOX-1. The unadjusted hazard ratio (HR) for CV events in patients with hs-CRP levels above the median was 2.63 [95% confidence interval (CI)=1.37-5.02]. The HR remained significant after adjusting for age, sex, history of CVD, and diabetes (HR=2.30; 95%CI=1.20-4.43). CONCLUSION: In HD patients, hs-CRP may have a predictable role for future CV events, whereas PTX-3 and sLOX-1 do not.

Relationship Between Cardiovascular Events and Serum Lipid and Plasma Fatty Acid Profile in Maintenance Hemodialysis Patients With Diabetic Mellitus.

BACKGROUND/AIM: Cardiovascular disease (CVD) is a frequent complication in hemodialysis (HD) patients, especially when the underlying disease is diabetes mellitus (DM). In this study, we investigated cardiovascular events and lipid and fatty acid profile in maintenance HD patients with diabetic kidney disease (DKD). PATIENTS AND METHODS: The subjects were 123 patients undergoing HD at Oyokyo Kidney Research Institute Hirosaki Hospital, who were considered to have DKD as the underlying cause of dialysis induction. Among these patients, the lipid and fatty acid profile were examined in two groups, CVD group (n=53) and non-CVD group (n=70), according to the presence or absence of a history of cardiovascular events (coronary artery disease, stroke, arteriosclerosis obliterans, valvular disease, and aortic disease). For serum lipid profile, the levels of total-cholesterol (T-C), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C) were measured, and for fatty acid balance, 24 fractions of fatty acid composition in plasma total lipids were measured. These markers were compared between the CVD and non-CVD groups. RESULTS: The levels of T-C and TG were significantly lower in the CVD group compared with the non-CVD group (147.7±36.9 mg/dl vs. 159.2±35.6 mg/dl, p<0.05, 120.2±65.7 mg/dl vs. 143.8±124.4 mg/dl, p<0.05). In the plasma fatty acid composition, alpha-linolenic acid (ALA) and docosapentaenoic acid (DPA) were significantly lower in the CVD group compared with the non-CVD group (0.74±0.26 wt% vs. 0.84±0.31 wt%, p<0.05; 0.61±0.21 wt% vs. 0.70±0.30 wt%, p<0.05). CONCLUSION: Abnormal fatty acid balance, especially low levels of ALA and DPA, rather than serum lipids, are more likely the factors associated with cardiovascular events in maintenance HD patients with underlying DKD.

Evaluation of simulation-based ultrasound education using a bladder simulator for medical students in Japan: a prospective observational study.

PURPOSE: This study aimed to investigate the usefulness of ultrasound education for medical students using a bladder simulator. METHODS: This prospective observational study included volunteer fifth- and sixth-year medical students. An intravesical urine volume measurement simulator and a pocket-sized hand-held ultrasound device were used. The ultrasound education comprised pre-learning, briefing, simulation, debriefing, and learning summary. The simulation consisted of two tests: bladder simulator cube evaluation and scenario-based clinical application. A self-rated confidence score of 0-10 points along with reasons for the scores was recorded before and after the ultrasound education. RESULTS: Twelve participants (median age, 23 years; female, 75%) met the inclusion criteria and were examined. Participants' bladder simulator cube evaluation and scenario-based clinical application test results were good, and the educational difficulty level was appropriate. The mean confidence scores for main unit operation, probe control, image acquisition, image evaluation and clinical application before the ultrasound education were 1.0, 1.8, 1.3, 0.8 and 0.1 points, respectively. The mean confidence scores after the ultrasound education were 5.8, 5.9, 5.4, 5.5 and 5.1, respectively, with significant increases for all items (p < 0.01). The positive impression categories that affected confidence scores after ultrasound education were related to device operation, image acquisition, image evaluation, clinical application and learning. CONCLUSION: Ultrasound education using a bladder simulator increases confidence scores by imparting competencies related to device operation, image acquisition, image evaluation and clinical application, and it improves students' learning impression. This is a useful method for introductory ultrasound education for medical students.

Pseudo-fever caused by predictive electronic thermometers: A case report.

A 33-year-old man was referred to our hospital with chief complaints of fever, dizziness, and headache. Although he had recurring fever and dizziness for 7 months, neurological examination, magnetic resonance imaging, computed tomography, electrocardiograms, and blood tests were normal. He was diagnosed with functional hyperthermia, cervical vertigo, and tension headache and was treated with oral medication and physical therapy. After treatment, the dizziness and headache resolved; however, the fever and anxiety did not. During follow-up, he noticed differing results from different electronic thermometers. The physician decided to use an accurate analog thermometer, a gallium thermometer, in combination with the other thermometers. The results differed significantly among the thermometers, and the electronic thermometer readings were found to be inappropriately high. The physician made a diagnosis of pseudo-fever, and the patient recognized that the gallium thermometer's results were the most accurate reflection of his physical condition, resolving his anxiety.

Functional hyperthermia caused by obstructive sleep apnea syndrome: A case report.

A 47-year-old farm worker with diabetes mellitus, dyslipidemia, and hyperuricemia was referred to our hospital for a 3-month history of fever and malaise. He had no respiratory tract or abdominal symptoms, skin rashes, or joint pain. There was no change to his regular medication or pesticide exposure. Blood tests and echocardiography revealed no abnormalities. Whole-body computed tomography revealed a fatty liver; however, non-alcoholic steatohepatitis was excluded. We diagnosed the patient with functional hyperthermia. He had a history of snoring and weight gain, and we suspected the obstructive sleep apnea syndrome to be a stressor. Polysomnography revealed severe obstructive sleep apnea syndrome with an apnea-hypopnea index of 44.5. Continuous positive airway pressure was introduced; the axillary temperature decreased gradually and malaise was resolved. Functional hyperthermia should be considered a cause of fever with a negative inflammatory response. Obstructive sleep apnea syndrome can be a stressor for functional hyperthermia, which can be improved by interventions.

Non-convulsive epilepsy with acute-onset and short-lasting repeated fatigue attacks: A case of 30-year-old man.

A 30-year-old man was referred to our department because of repeated acute-onset and short-lasting fatigue attacks, which occurred from 3 months before the referral. He had no abnormal findings in blood tests, electrocardiogram (including 24- h monitoring), or head MRI (including angiography). His vital signs were unremarkable, and his physical examination revealed no abnormal findings. Detailed history-taking with closed-ended questions revealed the occurrence of tingling sensation from the right fingers as the aura before his attacks. Electroencephalography was performed, which revealed focal epilepsy. Levetiracetam resolved his symptoms. Physicians could consider non-convulsive epilepsy as a potential cause of repeated acute-onset and short-lasting fatigue attacks of unknown etiology after underlying conditions, such as metabolic diseases, have been ruled out.

Clinical diagnosis of seasonal influenza by physicians: a retrospective observational study.

OBJECTIVE: To elucidate the diagnostic accuracy of pretest probability of influenza (%) by physicians and the factors affecting the clinical diagnosis. DESIGN: Retrospective, single-centre observational study. SETTING: A community primary care clinic in Japan. PARTICIPANTS: The participants were recruited from a database of studies conducted during the influenza season from December 2017 to April 2019. PRIMARY OUTCOME MEASURE: Sensitivity and specificity of the physician's clinical diagnosis of influenza recorded in the medical record as pretest probability. RESULTS: A total of 335 patients (median age, 31 years; male, 66.6%) were analysed in this study. The area under the curve (AUC) of the physician's pretest probability was 0.77. At a cut-off value of 30%, the sensitivity and negative likelihood ratio were 92.0% (95% CI 86.7 to 95.7) and 0.19 (95% CI 0.11 to 0.33), respectively. At a cut-off value of 80%, the specificity and positive likelihood ratio were 90.8% (95% CI 85.4 to 94.6) and 4.01 (95% CI 2.41 to 6.66), respectively. The AUCs of patients who had and had not taken any medications before visiting the clinic were 0.77 (95% CI 0.69 to 0.85) and 0.78 (95% CI 0.71 to 0.84), respectively. The AUCs of patients with type A and B influenza were 0.78 (95% CI 0.72 to 0.84) and 0.76 (95% CI 0.70 to 0.82), respectively. The AUCs of vaccinated and unvaccinated patients were 0.80 (95% CI 0.72 to 0.88) and 0.76 (95% CI 0.63 to 0.89), respectively. The AUC for patients less than 12 hours after onset was 0.69 (95% CI 0.51 to 0.88), and that for patients aged younger than 6 years was 0.69 (95% CI 0.49 to 0.88). CONCLUSIONS: The physician's pretest probability of influenza (%) may be useful for both definitive and exclusionary diagnoses within the limits of our study.

Factors associated with children's seasonal influenza diagnosis by their guardians: a prospective observational study in Japan.

Introduction Children's influenza diagnosis by their guardians has been reported to be highly accurate, but clinical factors that improve the reliability of a guardian's diagnosis are unclear. Aim To determine the accuracy of guardians' influenza diagnosis of their children, investigate clinical factors that improve the diagnostic accuracy, and determine the additional clinical value of the guardian's diagnosis. Methods A prospective observational study was conducted at a primary care clinic in Japan from December 2017 to April 2019. Pre-examination checklists completed by guardians accompanying children aged Results A total of 112 patient pairs of child (median age, 6 years) and guardian (mother, 81.2%; father, 16.1%; grandmother, 1.8%; other, 0.9%) were included in the analysis. The AUC for guardians' influenza diagnosis was higher in mothers (0.72), as well as pairs with children with a history of influenza (0.72), guardians who were aware of the influenza epidemic (0.71), and unvaccinated children (0.76), than in other guardians. After multivariate analysis, the AUC increased significantly from 0.79 to 0.85. Discussion Guardians' influenza diagnosis for their children was highly accurate. We identified factors that improve the accuracy of the guardians' diagnosis and demonstrated that the guardians' diagnosis can support physicians' diagnostic accuracy.

A case of juvenile myoclonic epilepsy in which a disease-specific question led to the diagnosis.

A 17-year-old female patient presented to our hospital with repeated transient loss of consciousness lasting less than 10 min. After regaining consciousness, she experienced no disorientation, confusion, tongue-biting, or incontinence. Physical findings, blood tests, electrocardiogram, and echocardiogram showed no obvious abnormalities. On being asked whether she had experienced sudden rapid body movements, she answered "yes." Therefore, we suspected juvenile myoclonic epilepsy (JME) and obtained an electroencephalogram, which showed diffuse bilateral bursts of spike-and-wave complexes, confirming the diagnosis. In adolescent patients with transient loss of consciousness, myoclonic jerks should be actively confirmed for the diagnosis of JME.

A case of Raynaud's phenomenon of toes induced by whole-body warm stimulation.

Raynaud's phenomenon, induced by cold stimulation and emotional stress, is also induced by whole-body warm stimulation. A 74-year-old man was referred to our department because of nocturnal toe pain from 2 years prior and immediate color change of the toes from 1 year prior when submerging himself into a warm bath. Physical examination and blood tests revealed no abnormal findings suggestive of secondary Raynaud's phenomenon. Two years later, the signs and symptoms persisted. When physicians confirm Reynaud's phenomenon, they should check for the possibility of secondary Reynaud's phenomenon. Additional research on Reynaud's phenomenon induced by warm stimulation is needed.

Severe edema and blood blisters of the lower extremities caused by sitagliptin, a dipeptidyl peptidase-4 inhibitor.

Severe edema and blood blisters can occur as adverse events associated with sitagliptin. A history of dipeptidyl peptidase-4 inhibitors should be considered when examining patients with edema and blood blisters of uncertain cause.

ß­glucan vaccine adjuvant approach for cancer treatment through immune enhancement (B­VACCIEN) in specific immunocompromised populations (Review).

The incidence of cancer, which is the second leading cause of mortality globally, continues to increase, although continued efforts are being made to identify effective treatments with fewer side­effects. Previous studies have reported that chronic microinflammation, which occurs in diseases, including diabetes, along with weakened immune systems, may ultimately lead to cancer development. Chemotherapy, radiotherapy and surgery are the mainstream approaches to treatment; however, they all lead to immune system weakness, which in turn increases the metastatic spread. The aim of the present review was to provide evidence of a biological response modifier ß­glucan [ß­glucan vaccine adjuvant approach to treating cancer via immune enhancement (B­VACCIEN)] and its beneficial effects, including vaccine­adjuvant potential, balancing metabolic parameters (including blood glucose and lipid levels), increasing peripheral blood cell cytotoxicity against cancer and alleviating chemotherapy side effects in animal models. This suggests its value as a potential strategy to provide long­term prophylaxis in immunocompromised individuals or genetically prone to cancer.

Diagnostic accuracy of pocket-sized ultrasound for aspiration pneumonia in elderly patients without heart failure: A prospective observational study.

AIM: To investigate the diagnostic accuracy of pocket-sized ultrasound (PsUS) for aspiration pneumonia in elderly patients without heart failure. METHODS: This prospective observational study included patients with aspiration pneumonia. PsUS was performed in six areas (bilateral chest, four dorsal areas) by an independent examiner, blinded to the computed tomography (CT) results as a reference standard. Patients with heart failure were excluded. RESULTS: PsUS findings of 34 patients (median age, 87.5 years) and 204 areas were analyzed. Three or more B-lines (comet tail artifacts) were strongly suggestive (positive likelihood ratio [LR+] 17.302) of consolidation on CT (CT-consolidation, subpleural hypoechoic area with tissue-like echostructure) or pleural change on CT. Consolidation on US (US-consolidation) was suggestive of CT-consolidation or pleural changes on CT (LR+ 6.453). Pleural effusion on US was strongly suggestive (LR+ 10.989) of CT-consolidation or pleural change on CT. Absence of either three or more B-lines, US-consolidation, or US pleural effusion could not rule out CT-consolidation or pleural change on CT (negative likelihood ratio [LR-] 0.482-0.683). However, absence of all three findings could rule out abnormal CT findings (LR- 0.230). Chest radiograph findings proved difficult to confirm or exclude CT-consolidation or pleural changes on CT (LR+ 1.584, LR- 0.489); when combined with PsUS findings, LR- improved to 0.124. CONCLUSIONS: Three or more B-lines or US-consolidation on PsUS in elderly patients with aspiration pneumonia without heart failure suggested CT-consolidation or pleural changes on CT. When both PsUS and chest radiograph findings were negative, CT-consolidation and pleural change could be excluded. Geriatr Gerontol Int 2021; 21: 1118-1124.

[Danaparoid Sodium Controlled Chronic Disseminated Intravascular Coagulation Associated with Chronic Aortic Dissection and Patent False Lumen for a Long Term:Report of a Case].

The management of chronic disseminated intravascular coagulation( DIC) caused by aortic dissection has not yet been established. We report the successful treatment of a case of aortic dissection with a patent false lumen using danaparoid sodium for acute exacerbation of chronic DIC. 2,000 U danaparoid sodium per day has been stabilizing the coagulative and fibrinolytic parameters and has been relieving bleeding tendencies with no side effects for a long term.

An undiagnosed patient with skin rash, polyarthritis, and edema responding to low-dose colchicine: A case report.

A 54-year-old man was referred to our hospital with painful rashes on the extremities. He also developed polyarthritis and pitting pedal edema. Blood tests showed no specific autoantibodies and were negative for human leukocyte antigens B51, B15, and B27. Lower extremity venous ultrasonography and computed tomography angiography showed no vascular disorders. Skin biopsy showed no evidence of thrombosis or vasculitis. Direct fluorescence antibody analysis showed no antibody or complement deposition. Joint ultrasonography showed mild synovial thickening and/or synovial effusion in the extremities. Non-steroidal anti-inflammatory drugs and topical steroids were administered, followed by oral steroids. However, the signs and symptoms did not improve. Oral steroids were discontinued, and colchicine (0.5 mg/day) was administered. Thereafter, the symptoms of arthritis improved, and no skin rash developed. In potentially inflammatory conditions with skin rash, edema, and polyarthritis that are difficult to diagnose, low-dose colchicine administration may be considered for prompt relief of symptoms.

Vestibular migraine without headache treated with lomerizine: A 35-year-old woman undiagnosed for 10 years.

A 35-year-old woman presented with recurrent vertigo without headache, which had persisted for 10 years. Detailed medical history revealed that she experienced hearing loss, tinnitus, nausea, photophobia, phonophobia, and slight discomfort in the head during vertigo attacks, which often led to absence from work. Based on the diagnostic criteria of the International Classification of Headache Disorders, third edition, she was diagnosed with vestibular migraine and was prescribed lomerizine, as prophylaxis. Her symptoms markedly improved, enabling her to go to work. Accurate diagnosis and treatment are important for improving the quality of life of patients, since vestibular migraine is commonly underdiagnosed.

Initial assessment of femoral proximal fracture and acute hip arthritis using pocket-sized ultrasound: a prospective observational study in a primary care setting in Japan.

BACKGROUND: Acute hip pain caused by femoral proximal fractures or acute hip arthritis requires imaging for accurate diagnosis. Although pocket-sized ultrasound (PsUS) offers several advantages over other imaging modalities, there is limited information regarding its use in diagnosing femoral proximal fractures or acute hip arthritis. Thus, we aimed to validate the diagnostic accuracy of PsUS for both disorders. METHODS: In this prospective observational study, outpatients with acute hip pain were diagnosed according to a fixed procedure of the PsUS probe handling. We verified the diagnostic accuracy of PsUS findings (cortical discontinuity and joint fluid retention) and compared it with that of radiography, computed tomography, and magnetic resonance imaging. RESULTS: Our study included 52 outpatients (mean age, 78.0 years; female, 88.5%). Of 26 patients diagnosed with femoral proximal fractures, 14 had femoral neck fractures and 12 had femoral trochanteric fractures. The sensitivity and specificity for identifying cortical discontinuity in femoral proximal fractures were 0.96 and 0.92, respectively. The sensitivity for identifying either cortical discontinuity or joint fluid retention in femoral proximal fractures or acute hip arthritis was 0.97. CONCLUSIONS: Negative PsUS findings of cortical discontinuity and joint fluid retention in the hip are useful for ruling out femoral proximal fractures and acute hip arthritis. PsUS and radiography have comparable diagnostic accuracies, and PsUS could aid in the initial assessment of acute hip pain among the elderly in primary care settings.

Factors associated with seasonal influenza self-diagnosis: a prospective observational study in Japan.

This prospective observational study, conducted at a community clinic in Japan during the influenza season, from December 2017 to April 2018 aimed to investigate the accuracy of factors used for influenza self-diagnosis. Data were collected from pre-examination checklists issued to patients with suspected influenza and electronic medical records. Receiver operating characteristic (ROC) curve analysis was performed using a rapid influenza diagnostic test as the reference standard, and 2 × 2 contingency tables were analysed at each cut-off point. We analysed data from 290 patients (72.8% males, median age: 38 years, interquartile range: 26-50 years). The area under the ROC curve (AUC) for patients who were aware of other patients presumed to have influenza within close proximity was 0.74 (95% confidence interval (CI): 0.66-0.82). The AUCs for patients with a history of influenza, unvaccinated status, cough, or nasal discharge were 0.68 (95% CI: 0.60-0.75), 0.66 (95% CI: 0.59-0.73), 0.67 (95% CI: 0.59-0.75), and 0.70 (95% CI: 0.62-0.78), respectively. The sensitivity, specificity and positive likelihood ratio at a 90% cut-off point was 19.5% (95% CI: 13.5-26.6%), 94.1% (95% CI: 88.7-97.4%) and 3.31 (95% CI: 1.57-6.98). The sensitivity, specificity and negative likelihood ratio at a 10% cut-off point was 95.5% (95% CI: 90.9-98.2%), 9.6% (95% CI: 5.2-15.8%) and 0.48 (95% CI: 0.20-1.16). After multivariate logistic regression analysis, the AUC increased significantly from 0.77 (95% CI: 0.70-0.83) to 0.81 (95% CI: 0.76-0.86) when self-diagnosis-related information was added to basic clinical information. We identified factors that improve the accuracy and validity of influenza self-diagnosis. Appropriate self-diagnosis could contribute to the containment efforts during influenza epidemics and reduce its social and economic burden.

Self-diagnosis of seasonal influenza in a rural primary care setting in Japan: A cross sectional observational study.

OBJECTIVE: To elucidate the accuracy and optimal cut-off point of self-diagnosis and clinical symptoms of seasonal influenza compared with rapid influenza diagnostic tests as the reference standard, we conducted a cross sectional observational study at a rural clinic in Japan. METHODS: Data during three influenza seasons (December 2013 to April 2016) were retrospectively collected from the medical records and pre-examination sheets of 111 patients aged >11 years (mean age 48.1 years, men 53.2%) who were suspected of influenza infection and underwent rapid influenza diagnostic testing. Patients' characteristics (age, sex, and past medical history of influenza infection), clinical signs (axillary temperature, pulse rate, cough, joint and muscle pain, and history of fever [acute or sudden, gradual, and absence of fever]), duration from the onset of symptoms, severity of feeling sick compared with a common cold (severe, similar, and mild), self-reported likelihood of influenza (%), and results of rapid influenza diagnostic tests. RESULTS: At the optimal cut-off point (30%) for estimation of self-diagnosis of seasonal influenza, the positive likelihood ratio (LR+) was 1.46 (95% confidence interval 1.07 to 2.00) and negative likelihood ratio (LR-) was 0.57 (0.35 to 0.93). At a 10% cut-off point, LR-was 0.33 (0.12 to 0.96). At an 80% cut-off point, LR+ was 2.75 (0.75 to 10.07). As for clinical signs, the combination of acute or sudden onset fever and cough had LR+ of 3.27 (1.68 to 6.35). Absence of cough showed LR-of 0.15 (0.04 to 0.61). CONCLUSIONS: Self-diagnosis of influenza using the optimal cut-off point (30%) was not found useful for ruling in or ruling out an influenza diagnosis. However, it could be useful when patients self-report extremely high (80%) or low (10%) probability of having influenza. Clinically useful signs were the combination of history of fever and cough, and absence of cough.