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A 59-year-old male patient presented with left chest discomfort on admission. His medical history included encephalitis in childhood and his smoking history was 20 cigarettes per day for 40 years. A physical examination showed an anemic and edematous face with weak respiratory sounds in the left lung. The patient had elevated calcium levels and decreased hemoglobin and potassium. His parathyroid hormone-related protein level was elevated. Thoracic radiography showed cardiomegaly and computed tomography revealed a left lung mass with invasion of the heart and pleural effusion. Magnetic resonance imaging showed endocardial invasion of the tumor mass. Gallium-68 imaging revealed positive accumulation in the region surrounding the heart. No diagnoses were possible upon frequent cytology of his sputum and pleural effusion. The patient died from congestive heart failure with anoxia 38 days after admission. An autopsy revealed tumoral mass occlusion in the left main bronchus and tumoral invasion of the left atrium, left ventricle, and aorta.

A 94-year-old female patient presented with anorexia and left axillar lymphadenopathy on admission. Her past history was angina pectoris at 83 years of age and total gastrectomy due to gastric cancer at 87 years. The family history revealed that her son had had a malignant lymphoma, the histopathological diagnosis of which was diffuse large B-cell lymphoma. A physical examination showed both cervical, axillar, and inguinal lymphadenopathy without tenderness. She had elevated lactate dehydrogenase, ferritin, and soluble interleukin-2 receptor (sIL-2R). Whole-body computed tomography confirmed the cervical, axillary, and inguinal lymphadenopathy. Gallium-68 imaging revealed positive accumulation in these superficial lymph nodes. A right inguinal lymph node biopsy showed features of Epstein-Barr virus-associated lymphoproliferative disorder. Immunohistological studies on this lymph node biopsy showed CD20-positive large cells, CD3-positive small cells, and CD30-partly-positive large cells. In situ hybridization showed Epstein-Barr virus-positive, LMP-partly-positive, and EBNA2-negative cells. She refused chemotherapy as her son had died from hematemesis during chemotherapy. She received intravenous hyperalimentation for 1 month after admission. No palpable lymph nodes were identified by physical examination or computed tomography 3 months after admission, and regression of lactate dehydrogenase, ferritin, and sIL-2R was observed. She recovered from anorexia and was discharged. She died from pneumonia 10 months later after initial symptoms of anorexia. The autopsy showed no superficial lymphadenopathy.

Background: Corynebacterium striatum (C. striatum) is a gram-positive, anaerobic bacillus found both environmentally and in human skin and nasal mucosa flora. It is reportedly the etiologic agent of community-acquired and nosocomial diseases and is significantly associated with bacteremia and medical endovascular devices. This is the rare case of mitral valve native valve endocarditis (NVE) caused by C. striatum occurring in a young adult without underlying structural heart disease or indwelling cardiovascular medical devices successfully treated with multidisciplinary therapy., Case Presentation: The patient was a 28-year-old female with no medical history. She was transferred our hospital due to sudden onset of vertigo and vomit. A computed tomography on day 2 revealed the hydrocephalus due to the cerebellar infarction, and she underwent posterior fossa decompression for cerebellar infarction. An angiography on day 8 revealed a left vertebral artery dissection, which was suspected be the etiology. Afterwards, a sudden fever of 39 degrees developed on day 38. She was diagnosed with aspiration pneumonia and treated with ampicillin/sulbactam but was still febrile at the time of transfer for rehabilitation. Treatment continued with levofloxacin, the patient had no fever decline, and she was readmitted to our hospital. Readmission blood cultures (3/3 sets) revealed C. striatum, and an echocardiogram revealed an 11 mm long mitral valve vegetation, leading to NVE diagnosis. On the sixth illness day, cardiac failure symptoms manifested. Echocardiography revealed mitral valve rupture. She was transferred again on the 11th day of illness, during which time her mitral valve was replaced. C. striatum was detected in the vegetation. Following surgery, she returned to our hospital, and vancomycin administration continued. The patient was discharged after 31 total days of postoperative antimicrobial therapy. The patient experienced no exacerbations thereafter., Conclusions: We report the rare case of C. striatum mitral valve NVE in a young adult without structural heart disease or indwelling cardiovascular devices., Clinical Trial Number: Not applicable., (© 2024. The Author(s).)

Aim: Whether serum concentration of procalcitonin (PCT), brain natriuretic peptide (BNP) and albumin (Alb) have an association with the outcome of hospitalized older patients is unclear. We investigated clinical outcomes and any predictive factors in hospitalized Japanese older patients with a risk of infection., Methods: In the retrospective study, 820 Japanese patients were followed up for 30 days or until death. During the observation period, 656 patients survived and 164 patients died. The predictive factors of death were analyzed according to demographic and clinical variables., Results: The survival rate was decreased as the serum PCT increased from <0.5 to ≥10 ng/mL, as was also the case with BNP from <300 to ≥300 pg./mL, whereas low Alb (<2.5 g/dL) showed a lower survival rate than high Alb (≥2.5 g/dL; P < 0.01). Using the Cox regression model, the multivariable-adjusted hazard ratios (95% confidence interval) were as follows: PCT 0.5-2 versus <0.5 ng/mL: 1.61(1.04-2.49), PCT 2-10 versus <0.5 ng/mL: 1.91(1.15-3.16), PCT ≥10 versus <0.5 ng/mL: 2.90(1.84-4.59), high BNP 1.26 (0.89-1.76) and low Alb 0.68 (0.52-0.87). The mortality rate increased as the number of scores (PCT + BNP + Alb) increased., Conclusions: Concentration-dependent high PCT, high BNP and low Alb were positive risk factors associated with poor prognosis in hospitalized older patients with a risk of infection. Geriatr Gerontol Int 2024; 24: 571-576., (© 2024 Japan Geriatrics Society.)

Viral hepatitis represents a major danger to public health, and is a globally leading cause of death. The five liver-specific viruses: Hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, and hepatitis E virus, each have their own unique epidemiology, structural biology, transmission, endemic patterns, risk of liver complications, and response to antiviral therapies. There remain few options for treatment, in spite of the increasing prevalence of viral-hepatitis-caused liver disease. Furthermore, chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality, even though effective treatments are available that could reduce or prevent most patients' complications. In 2016, the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030, along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis. Today, treatment is sufficiently able to prevent the disease from reaching advanced phases. However, future therapies must be extremely safe, and should ideally limit the period of treatment necessary. A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis. This review aims to summarize the current state of knowledge on each type of viral hepatitis, together with major innovations., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: This study aimed to evaluate the effects of orthogeriatric co-management of hip fractures at a regional core hospital., Methods: This study included patients with proximal hip fracture. Patients were divided into two groups, conventional multidisciplinary group I including patients attending the hospital between April 2015 and March 2016 and orthogeriatric group II including patients attending the hospital between April 2016 and March 2017, which were compared retrospectively. In the control group, the conventional multidisciplinary team treated patients as whole-body controls. In the intervention group, the newly recruited geriatricians performed physical examinations, laboratory tests, radioactive imaging, and physiological tests. Furthermore, they consulted ward pharmacists, rigorously conducted positive polypharmacy interventions , and evaluated the type and number of mediated drugs on admission., Results: The number of medicated drugs significantly decreased from 6.03 ± 4.3 on admission to 5.50 ± 3.59 on discharge in group II, whereas group I did not show a significant decrease. Despite the more number of hospitalized patients in group II (166 patients) than in group I (126 patients), the recovery rate from postoperative urinary retention increased significantly from 57.8% (19/30) in group I to 84.3% (32/59) in group II (p = 0.049), while the incidence of aspiration pneumonia decreased from 7.1% (9/126) in group I to 2.49% (4/166) in group II (p = 0.08). The patients received six or more prescribed drugs on admission, and the number remained constant. However, the number of medicated drugs on discharge showed a marginally significant decrease from 6.03 ± 4.3 in group I to 5.50 ± 3.59 in group II (p < 0.05)., Conclusions: Compared to the conventional multidisciplinary group, the orthogeriatric team contributed to reducing the number of multi-effect drugs and perioperative complications without negatively affecting mortality despite the increased number of patients. The in-hospital mortality rate did not change between the groups. The orthogeriatric program succeeded in preventing and treating perioperative complications., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Introduction: Disasters and accidents have occurred with increasing frequency in recent years. Primary disasters have the potential to result in mass casualty events involving crush syndrome (CS) and other serious injuries. Prehospital providers and emergency clinicians stand on the front lines of these patients' evaluation and treatment. However, the bulk of our current knowledge, derived from historical data, has remained unchanged for over ten years. In addition, no evidence-based treatment has been established to date., Objective: This narrative review aims to provide a focused overview of, and update on, CS for both prehospital providers and emergency clinicians., Discussion: CS is a severe systemic manifestation of trauma and ischemia involving soft tissue, principally skeletal muscle, due to prolonged crushing of tissues. Among earthquake survivors, the reported incidence of CS is 2-15%, and mortality is reported to be up to 48%. Patients with CS can develop cardiac failure, kidney dysfunction, shock, systemic inflammation, and sepsis. In addition, late presentations include life-threatening systemic effects such as hypovolemic shock, hyperkalemia, metabolic acidosis, and disseminated intravascular coagulation. Immediately beginning treatment is the single most important factor in reducing the mortality of disaster-situation CS. In order to reduce complications from CS, early, aggressive resuscitation is recommended in prehospital settings, ideally even before extrication. However, in large-scale natural disasters, it is difficult to diagnose CS, and to reach and start treatments such as continuous administration of massive amounts of fluid, diuresis, and hemodialysis, on time. This may lead to delayed diagnosis of, and high on-site mortality from, CS. To overcome these challenges, new diagnostic and therapeutic modalities in the CS animal model have recently been advanced., Conclusions: Patient outcomes can be optimized by ensuring that prehospital providers and emergency clinicians maintain a comprehensive understanding of CS. The field is poised to undergo significant advances in coming years, given recent developments in what is considered possible both technologically and surgically; this only serves to further emphasize the importance of the field, and the need for ongoing research., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Pneumonia in elderly patients who require nursing care is becoming more and more common among the aging populations of developed countries, and treatment is an important topic worldwide. A simpler prognostic indicator would be expected to improve the treatment of pneumonia. This single-center, prospective cohort study aimed to compare the usefulness of B-type natriuretic peptide (BNP), procalcitonin (PCT), and the A-DROP score, which have been reported to correlate with pneumonia prognoses, such as aspiration pneumonia (AP)., Methods: We included patients who were admitted to the Kanazawa Medical University Himi Municipal Hospital with a diagnosis of either nursing- and healthcare-associated pneumonia (NHCAP) or AP between January 1, 2012 and July 31, 2019. We collected demographic, clinical, and laboratory characteristics and outcome data from electronic medical records, and calculated A-DROP scores. The primary outcome was 30-day mortality. We evaluated correlations with the primary outcome using the chi-square test, Fisher exact test, t -test, Cox-regression analysis, and receiver operating characteristic curve analysis., Results: Of the 1,215 patients with pneumonia, 297 were eligible for the study, of whom 37 (12%) died whin 30 days. After univariate analysis, we performed Cox proportional-hazards analysis for BNP, PCT, A-DROP score, albumin, C-reactive protein, and disseminated intravascular coagulation, which were significantly correlated with the primary outcome in univariate analysis. As a result, only BNP showed a significant correlation (P=0.008, 95% CI: 1.30-6.06). No significant correlation was obtained in PCT (P=0.529) and A-DROP score (P=0.107). Furthermore, we generated receiver operating characteristic curve to estimate the prognostic cut-off values of BNP for the primary outcome of NHCAP and AP. The optimal cut-off value of BNP for predicting death was 179.3 pg/mL (sensitivity 62.2%, specificity 76.2%, negative likelihood ratio 0.50%, positive likelihood ratio 2.61%). And, BNP yielded the highest area under the curve (0.72) in comparison with PCT (0.67) and A-DROP score (0.69)., Conclusions: BNP may be a more clinically useful prognostic factor for NHCAP and AP than PCT or A-DROP score, and should be considered as a routine test at the beginning of these treatments., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4151/coif). The authors have no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Amebic liver abscesses (ALAs) are the most commonly encountered extraintestinal manifestation of human invasive amebiasis, which results from Entamoeba histolytica ( E. histolytica ) spreading extraintestinally. Amebiasis can be complicated by liver abscess in 9% of cases, and ALAs led to almost 50000 fatalities worldwide in 2010. Although there have been fewer and fewer cases in the past several years, ALAs remain an important public health problem in endemic areas. E. histolytica causes both amebic colitis and liver abscess by breaching the host's innate defenses and invading the intestinal mucosa. Trophozoites often enter the circulatory system, where they are filtered in the liver and produce abscesses, and develop into severe invasive diseases such as ALAs. The clinical presentation can appear to be colitis, including upper-right abdominal pain accompanied by a fever in ALA cases. Proper diagnosis requires nonspecific liver imaging as well as detecting anti- E. histolytica antibodies; however, these antibodies cannot be used to distinguish between a previous infection and an acute infection. Therefore, diagnostics primarily aim to use PCR or enzyme-linked immunosorbent assay to detect E. histolytica . ALAs can be treated medically, and percutaneous catheter drainage is only necessary in approximately 15% of cases. The indicated treatment is to administer an amebicidal drug (such as tinidazole or metronidazole) and paromomycin or other luminal cysticidal agent for clinical disease. Prognosis is good with almost universal recovery. Establishing which diagnostic methods are most efficacious will necessitate further analysis of similar clinical cases., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozin's osmotic diuresis mechanism, patients' serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (β1=-0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/e' tended to decrease (β1=-0.382, p=0.13, LRA). Compared to the baseline, E/e' was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/e' group (E/e'≥10, n=34), E/e' decreased significantly (β1=-0.63, p<0.05, LRA). ΔE/e' was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/e' in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: Hospitalized elderly patients are often at risk of life-threatening infectious diseases such as pneumonia and urinary tract infection, thus diagnostic tools for bacterial infections are demanded. We developed a new predictive tool consolidating modified CURB-65, procalcitonin (PCT) and albumin (Alb)., Method: This is a retrospective study. Modified CURB-65 (mCURB-65) score, PCT, Alb, and various cardiovascular/respiratory/renal functions were measured. Survival analyses were conducted to assess 30-days mortality of elderly patients using mCURB-65 score, PCT and Alb. The consolidated scores were compared with the number of patients died., Results: There were 445 elderly patients included. Kaplan-Meier survival curves showed significant differences between the high and low groups of mCURB-65, PCT and Alb (log-rank test, P < .001). Cox proportional regression showed that the hazard ratios (95% confidence intervals) for high mCURB-65, high Alb, and high PCT were all significant, 1.95 (1.24-3.05), 0.50 (0.32-0.77), and 2.09 (1.32-3.31), respectively. The consolidated scores showed tendency of increase with proportion of the number of patients died., Conclusions: The consolidated score consisted of mCURB-65, PCT and Alb can be a useful tool to predict short-term mortality of the hospitalized elderly patients with infectious disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Tsukamurella species are obligate aerobic, gram-positive, weak acid-fast, nonmotile bacilli. They are found in various environments, such as soil, water, sludge, and petroleum reservoir wastewater, and belong to the order Actinomycetales . In 2016, there was a reclassification of species within the genus Tsukamurella , merging the species Tsukamurella tyrosinosolvens ( T. tyrosinosolvens ) and Tsukamurella carboxydivorans . Tsukamurella species are clinically considered to be a rare opportunistic pathogen, because most reported cases have been related to bacteremia and intravascular prosthetic devices and immunosuppression. To date, it has been isolated only from human specimens, and has always been associated with clinical disease; human infections are very rare. Reported infections have included pneumonia, brain abscesses, catheter-related bloodstream infections, ocular infections, bacteremia, and sepsis presenting with septic pulmonary emboli in patients who are immunocompromised. To date, there is no commercially available test for identification. On the other hand, sequence-based identification, including matrix-assisted laser desorption ionization time-of-flight mass spectrometry, is an alternative method for identifying clinical isolates that are either slow growers or difficult to identify through biochemical profiling. The golden standards for diagnosis and optimal management still remain to be determined. However, newer molecular biological techniques can provide accurate identification, and contribute to the appropriate selection of definitive therapy for infections caused by this organism. Combinations of several antimicrobial agents have been proposed for treatment, though the length of treatment for infections has yet to be determined, and should be individualized according to clinical response. Immunocompromised patients often experience severe cases due to infection, and life-threatening T. tyrosinosolvens events associated with dissemination and/or failure of source control have occurred. Favorable prognoses can be achieved through earlier identification of the cause of infection, as well as successful management, including appropriate antibiotic therapy together with source control. Further analyses of similar cases are required to establish the most adequate diagnostic methods and treatment regimens for infections., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

We assessed risk factors for postoperative urinary retention (UR) in elderly males with femoral bone fractures: 169 Japanese males (mean age 81.95 ± 1.19 years) who had undergone hip surgery at a municipal hospital (Toyama, Japan). A multiple logistic regression analysis was used to test possible risk factors for UR: age, body mass index, serum albumin, cognitive impairment, activities of daily living (ADL), and history of diabetes mellitus (DM). UR occurred in 24 (14.2%) of the 169 patients. A multivariate logistic regression analysis with age adjustment showed that ADL (odds ratio [OR] 3.88; 95% confidence interval [CI]: 1.2-12.5, p=0.023) was significantly associated with the development of UR, and a history of DM showed marginal significance for UR occurrence (OR 0.36, 95%CI: 0.11-10, p=0.064). These results suggests that ADL is a risk factor for UR development in elderly males who have undergone surgery for femoral neck or trochanter fractures., Competing Interests: No potential conflict of interest relevant to this article was reported.

Forward genetics is a powerful approach based on chromosomal mapping of phenotypes and has successfully led to the discovery of many mouse mutations in genes responsible for various phenotypes. Although crossing between genetically remote strains can produce F 2 and backcross mice for chromosomal mapping, the phenotypes are often affected by background effects from the partner strains in genetic crosses. Genetic crosses between substrains might be useful in genetic mapping to avoid genetic background effects. In this study, we investigated single nucleotide polymorphisms (SNPs) available for genetic mapping using substrains of C57BL/6 and BALB/c mice. In C57BL/6 mice, 114 SNP markers were developed and assigned to locations on all chromosomes for full utilization for genetic mapping using genetic crosses between the C57BL/6J and C57BL/6N substrains. Moreover, genetic differences were identified in the 114 SNP markers among the seven C57BL/6 substrains from five production breeders. In addition, 106 SNPs were detected on all chromosomes of BALB/cAJcl and BALB/cByJJcl substrains. These SNPs could be used for genotyping in BALB/cJ, BALB/cAJcl, BALB/cAnNCrlCrlj, and BALB/cCrSlc mice, and they are particularly useful for genetic mapping using crosses between BALB/cByJJcl and other BALB/c substrains. The SNPs characterized in this study can be utilized for genetic mapping to identify the causative mutations of the phenotypes induced by N-ethyl-N-nitrosourea mutagenesis and the SNPs responsible for phenotypic differences between the substrains of C57BL/6 and BALB/c mice.

Laboratory mouse strains have mosaic genomes derived from at least three major subspecies that are distributed in Eurasia. Here, we describe genomic variations in ten inbred strains: Mus musculus musculus-derived BLG2/Ms, NJL/Ms, CHD/Ms, SWN/Ms, and KJR/Ms; M. m. domesticus-derived PGN2/Ms and BFM/Ms; M. m. castaneus-derived HMI/Ms; and JF1/Ms and MSM/Ms, which were derived from a hybrid between M. m. musculus and M. m. castaneus. These strains were established by Prof. Moriwaki in the 1980s and are collectively named the "Mishima Battery". These strains show large phenotypic variations in body size and in many physiological traits. We resequenced the genomes of the Mishima Battery strains and performed a comparative genomic analysis with dbSNP data. More than 81 million nucleotide coordinates were identified as variant sites due to the large genetic distances among the mouse subspecies; 8,062,070 new SNP sites were detected in this study, and these may underlie the large phenotypic diversity observed in the Mishima Battery. The new information was collected in a reconstructed genome database, termed MoG+ that includes new application software and viewers. MoG+ intuitively visualizes nucleotide variants in genes and intergenic regions, and amino acid substitutions across the three mouse subspecies. We report statistical data from the resequencing and comparative genomic analyses and newly collected phenotype data of the Mishima Battery, and provide a brief description of the functions of MoG+, which provides a searchable and unique data resource of the numerous genomic variations across the three mouse subspecies. The data in MoG+ will be invaluable for research into phenotype-genotype links in diverse mouse strains., (© 2021. The Author(s).)

The presence of preexisting brain lesions due to previous stroke and cerebral small vessel disease has been reported to influence stroke related disability or rehabilitation outcomes. However, there is no data about the impact of such lesions on the recovery period after pusher behavior (PB). This retrospective cohort study aimed to determine the influence of preexisting brain lesions on PB recovery time. Nineteen patients who were suffering from PB were included in the study. The presence of preexisting brain lesions, including previous stroke, silent brain infarcts, microbleed, white matter hyperintensity, and enlarged perivascular spaces were assessed using medical history reports, radiological reports, and magnetic resonance imaging data. The lesion score, ranging from 0 to 5, was calculated based on each preexisting brain lesion. The time to recovery from PB was assessed using the Scale for Contraversive Pushing. Based on the median value of the lesion score, we divided patients into those with a lesion score < 2 and those with a lesion score ≥ 2. A Kaplan Meier survival analysis was performed between these two groups. A multivariable Cox proportional hazards analysis was also performed using the side with hemiparesis and the score of preexisting brain lesions as covariates to determine the hazard ratio. The results showed that the group with a lesion score ≥ 2 had significantly delayed recovery from PB and the hazard ratio of preexisting brain lesions score was 0.458 (95% confidence interval: 0.221, 0.949), while the side of hemiparesis was not identified a significant covariate. Our results indicated that patients with PB having higher score of preexisting brain abnormalities might require a longer time to recover, and this might be useful in planning inpatient rehabilitation and treatment goals for patients with PB., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Abstract: Adrenocorticotropic hormone (ACTH) and cortisol reportedly play a role in glycemic control in patients with type 2 diabetes mellitus (T2DM); however, the underlying mechanism remains controversial. We retrospectively investigated the effect of tofogliflozin on serum ACTH and cortisol levels in elderly patients with T2DM.Patients received 20 mg tofogliflozin daily for 3 months. Serum ACTH and cortisol levels were measured at baseline, as well as after 1 month and 3 months of tofogliflozin therapy.Serum ACTH levels were significantly reduced 3 months after tofogliflozin treatment (P < .01). Additionally, serum cortisol levels were reduced 3 months after tofogliflozin treatment, demonstrating borderline significance (P = .05). The higher body mass index (BMI; ≥25 kg/m2) group showed higher ACTH and cortisol levels than the lower BMI (<25 kg/m2) group, with borderline significance (P = .05). Renin levels were significantly increased 1 month after treatment (P < .05), maintaining serum aldosterone levels in parallel with the extracellular fluid.Our findings suggested that tofogliflozin decreased both serum ACTH and cortisol levels, with higher levels observed in the high BMI group. Tofogliflozin increased serum renin levels while maintaining serum aldosterone and extracellular fluid levels. Collectively, tofogliflozin could affect the hypothalamic-pituitary-adrenal pathway in patients with T2DM, especially in the low BMI group., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Heart failure (HF) is a clinical syndrome that results from a structural or functional cardiac disorder that reduces the ability of the ventricle of the heart to fill with, or eject, blood. It is a multifaceted clinical condition that affects up to 2% of the population in the developed world, and is linked to significant morbidity and mortality; it is therefore considered a major concern for public health. Regarding the mechanism of HF, three neurohumoral factors - the renin-angiotensin-aldosterone system, the sympathetic nervous system, and natriuretic peptides - are related to the pathology of chronic HF (CHF), and the targets of treatment. Angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor), namely sacubitril/valsartan (SAC/VAL), has been introduced as a treatment for CHF. SAC/VAL is an efficacious, safe, and cost-effective therapy that improves quality of life and longevity in patients with HF with reduced ejection fraction (HFrEF), and reduces hospital admissions. An in-hospital initiation strategy offers a potential new avenue to improve the clinical uptake of SAC/VAL. In the last five years, SAC/VAL has been established as a cornerstone component of comprehensive disease-modifying medical therapy in the management of chronic HFrEF. On the other hand, further work, with carefully designed and controlled preclinical studies, is necessary for understanding the molecular mechanisms, effects, and confirmation of issues such as long-term safety in both human and animal models., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: Early and simple detection of high-risk groups is crucial for minimizing severe coronavirus disease 2019 (COVID-19)-related deaths. Soluble interleukin 2 receptors (sIL2R) have been suspected as being prognostic markers for infectious diseases. This study validated the usefulness of sIL2R as a marker for deaths related to COVID-19., Methods: This retrospective observational study enrolled participants who showed positive results for severe acute respiratory syndrome coronavirus 2 RNA admitted to the current hospital between 01 April and 30 September 2020. Of the 102 patients enrolled in this study, sIL2R levels were measured in 87 patients. For comparisons between survival and non-survival groups, potential confounding variables were entered into univariate models, and variables showing significant correlations (p < 0.05) in those models were added to a multivariate model., Results: Being aged ≥60 years and sIL2R levels ≥1060 U/ml were significantly associated with mortality on univariate analyses; only sIL2R levels significantly correlated with mortality on multivariate logistic regression analysis. Further, sequential sIL2R levels in three patients were increased at progression or death., Conclusion: SIL2R on admission and sequential monitoring of sIL2R might reflect disease severity., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

BACKGROUND The etiology of syndrome of inappropriate antidiuretic hormone secretion (SIADH) is highly variable. With little evidence, much of the guidance and recommendations available for management are based on clinical judgement. Although percutaneous balloon kyphoplasty can effectively relieve the severe pain associated with osteoporotic vertebral compression fractures that do not respond to conventional treatments, the effect of balloon kyphoplasty on SIADH associated with vertebral compression fracture remains unknown. CASE REPORT A 72-year-old woman was admitted to our hospital due to severe pain associated with lumbar compression fracture and pain-related SIADH. Since her pain could not be relieved by analgesics, she underwent percutaneous balloon kyphoplasty, a minimally invasive procedure intended to relieve pain. After the surgery, the patient's pain almost completely disappeared and her sodium level was gradually corrected within 3 days without any adverse events. CONCLUSIONS Percutaneous balloon kyphoplasty is a novel treatment option for SIADH associated with vertebral compression fracture. In the case presented here, it rapidly reduced pain and disability and also improved severe pain-associated SIADH without adverse effects. It may offer an alternative to pain regimens consisting of drugs, such as duloxetine, pregabalin, and opioids, that may exacerbate SIADH and hyponatremia. This case suggests treatment for new-onset or worsening hyponatremia in patients with vertebral compression fracture.

Online databases are crucial infrastructures to facilitate the wide effective and efficient use of mouse mutant resources in life sciences. The number and types of mouse resources have been rapidly growing due to the development of genetic modification technology with associated information of genomic sequence and phenotypes. Therefore, data integration technologies to improve the findability, accessibility, interoperability, and reusability of mouse strain data becomes essential for mouse strain repositories. In 2020, the RIKEN BioResource Research Center released an integrated database of bioresources including, experimental mouse strains, Arabidopsis thaliana as a laboratory plant, cell lines, microorganisms, and genetic materials using Resource Description Framework-related technologies. The integrated database shows multiple advanced features for the dissemination of bioresource information. The current version of our online catalog of mouse strains which functions as a part of the integrated database of bioresources is available from search bars on the page of the Center ( https://brc.riken.jp ) and the Experimental Animal Division ( https://mus.brc.riken.jp/ ) websites. The BioResource Research Center also released a genomic variation database of mouse strains established in Japan and Western Europe, MoG + ( https://molossinus.brc.riken.jp/mogplus/ ), and a database for phenotype-phenotype associations across the mouse phenome using data from the International Mouse Phenotyping Platform. In this review, we describe features of current version of databases related to mouse strain resources in RIKEN BioResource Research Center and discuss future views.

Background: Abdominal compartment syndrome (ACS) is defined as a sustained raised level of intra-abdominal pressure more than 20 mmHg with or without abdominal perfusion pressure less than 60 mmHg and the development of new end-organ failure. Abdominal surgery, major trauma, volvulus, ileus, distended abdomen, fecal impaction, acute pancreatitis, liver dysfunction, sepsis, shock, obesity, and age have all been reported as risk factors. Herein, we report the severest known case of ACS due to extremely elongated sigmoid colon and rectum plus fecal impaction caused by disuse syndrome and diabetic neuropathy, together with a brief review of the literature., Case Presentation: A 48-year-old Asian man suffering from shock was transported by ambulance to our hospital. His medical history included hypoglycemic encephalopathy sequelae, disuse syndrome, type 2 diabetic neuropathy, and constipation. He recovered consciousness in the ambulance, and his physical examination as well as laboratory findings were normal. X-ray and dynamic computed tomography revealed a thickened gut wall, and an extremely dilated sigmoid colon and rectum filled with a massive amount of stool as well as gas, compressing other intra-abdominal organs. We diagnosed the patient with transient vasovagal syncope, together with ACS, due to extremely elongated sigmoid colon and rectum plus fecal impaction, caused by anorectal disturbance derived from disuse syndrome and diabetic neuropathy. We first repeated stool extraction for bowel decompression and he subsequently became symptom-free, after which we performed a colostomy on the 28th hospital day. The postoperative course was uncomplicated, and he was discharged on the 44th hospital day., Conclusions: Clinicians need to keep ACS in mind as a differential diagnosis and perform careful and detailed examination when encountering patients presenting with symptoms or risk factors of ACS. In addition, they need to precisely diagnose ACS and perform optimal treatment without delay.

Background: The main purpose of this study is to exhaustively explore risk factors, including age, gender, and several clinical indices, for mortality in elderly patients with femoral neck fracture and to evaluate some of them using survival analyses., Methods: This was a retrospective study tracking 1 year for vital prognosis. Data were collected at post-operation from medical records of the cases. Survival analysis was conducted to investigate the risk factors for death, including albumin, urinary retention, activity of daily living (ADL), and cognitive disorder., Results: We recruited 318 patients with a history of hip surgery carried out at Toyama Municipal Hospital, in which 39 patients died for 1 year after discharge. The results showed a significant decrease in survival rate in low albumin, positive urinary retention, and low ADL (P < 0.01, by log-rank test). The hazard ratios (95% confidence interval) of albumin, urinary retention, ADL, and cognitive disorder were 0.36 (0.19 - 0.69), 0.4 (0.2 - 0.8), 0.29 (0.15 - 0.58) and 0.65 (0.32 - 1.29), respectively., Conclusions: This study demonstrated that albumin, urinary retention and ADL were the important risk factors for mortality, and suggested that the postoperative management of albumin, urinary retention and ADL is important, especially in elderly female patients receiving surgery of femoral neck and trochanteric fractures., Competing Interests: None to declare., (Copyright 2020, Higashikawa et al.)

Background: Patients with type 2 diabetes mellitus (T2DM) are at increased risk for impairment in heart failure and diastolic relaxation while preserving ejection fraction (EF). Recently, several sodium glucose cotransporter-2 (SGLT2) inhibitors have demonstrated to decrease cardiovascular disease (CVD) events in elderly diabetic patients, although gender difference in the effect of SGLT2 inhibitors is unknown. The objective of the present study was to evaluate gender difference in the effect of tofogliflozin, one of the SGLT2 inhibitors, on CVD function in patients with diabetes mellitus., Methods: This was a retrospective study. Patients received 20 mg of tofogliflozin daily for 3 months. EF, ratio of early filling to atrial filling (E/A), a change in mitral inflow E and mitral e' annular velocities (E/e'), left atrial dimension (LAD) and maximal diameter of inferior vena cava (IVC max ), including various physiological parameters were measured between baseline, 1 month and 3 months after administration of tofogliflozin. Interaction between gender and time after administration was evaluated using mixed effect model., Results: The results showed significant decrease in E/e' (P < 0.01) and significant interaction between time and gender in E/A (P < 0.01), following administration of tofogliflozin for 3 months. EF was constantly higher significantly in women (P < 0.01)., Conclusion: It is concluded that 3-month administration of tofogliflozin decreased E/e' with gender difference in EF and E/A., Competing Interests: None to declare., (Copyright 2020, Higashikawa et al.)

Background: Patients with type 2 diabetes mellitus (T2DM) are at increased risk for impairments in diastolic relaxation and heart failure with preserved ejection fraction (EF). Recent clinical data suggest that several sodium glucose transporter-2 (SGLT2) inhibitors are found to reduce cardiovascular disease (CVD) events in elderly diabetic patients, but the effect of tofogliflozin, one of the SGLT2 inhibitors, on CVD is unknown. We retrospectively investigated the effect of tofogliflozin on cardiac function in elderly patients with T2DM., Methods: Patients received 20 mg of tofogliflozin daily for 1 month. EF, ratio of early filling to atrial filling (E/A), a change in mitral inflow E and mitral e' annular velocities (E/e'), left atrial dimension (LAD) and maximal diameter of inferior vena cava (IVC max ) were measured between baseline and 1 month after the administration of tofogliflozin., Results: Body weight, systolic and diastolic blood pressures significantly decreased, while renin and aldosterone level significantly increased after 1 month of tofogliflozin treatment. Most of the physiological parameters and the level of serum electrolyte did not change significantly. E/A, E/e' and LAD significantly decreased, while no significant changes were observed in EF and IVC max . The interactions of E/e' between time, gender and age were not significant., Conclusion: The present study suggested that tofogliflozin improved left ventricular diastolic function irrespective of gender and age, while preserving IVC, renal function and electrolyte balance., Competing Interests: The authors declare no conflict of interest., (Copyright 2020, Higashikawa et al.)

Aspiration pneumonia (AP) has been recognized as one of the most common postoperative complications after hip surgery in elderly. The objective of the present study was to evaluate risk for postoperative complications of AP in elderly patients with femoral neck fractures.We recruited 426 patients (age 84.9 ± 7.4 years) with a history of hip surgery carried out at Toyama Municipal Hospital. AP occurred in 18 out of 426 cases (4.23%). Statistical test has found significant differences in age, gender, serum albumin level, and cognitive impairment, between AP and non-AP groups. Subsequently multiple logistic regression analysis was conducted to investigate the risk factors for AP, including age, gender, serum albumin, cognitive impairment, and activities of daily living (ADL). Adjusted odds ratio showed significant differences in age, gender, and serum albumin, whereas no significant differences were found in cognitive impairment and ADL.This study suggested that serum albumin seemed to be a risk factor for AP but were necessary to assess under adjustment of confounding factors, including age and gender. Monitoring serum albumin level seemed to be important for the postoperative management of AP, especially in elderly patients receiving surgery of femoral neck and trochanteric fractures.

Urinary retention (UR) has been recognized as one of the most common postoperative complications after hip surgery in elderly. The objective of the present study was to evaluate risk for postoperative complications of UR in elderly female patients with femoral neck fractures.We recruited 221 female patients (age 85.3 ± 7.0 years) with a history of hip surgery carried out at Toyama Municipal Hospital. UR occurred in 34 out of 221 cases (15.4%). Multiple logistic regression analysis was conducted to investigate the risk factors for UR, including age, body mass index (BMI), serum albumin, cognitive impairment, and activities of daily living (ADL).The results showed significant association of UR with cognitive impairment (P = .005, odds ratio [OR] 4.11, 95% confidence interval [CI] 1.53-11.03), and ADL (P = .029, OR 2.61, 95% CI 1.11-6.18), under adjustment with age and BMI.This study demonstrated that cognitive function and ADL were the important risk factors for UR, suggested that the postoperative management of UR is important with taking account of neurofunctional assistance and nursing care in daily living, especially in elderly female patients receiving surgery of femoral neck and trochanteric fractures.

Objective: To assess the effect of 12 months of treatment with tofogliflozin on electrolytes and dehydration in Japanese patients with type 2 diabetes mellitus (T2DM)., Methods: This retrospective study involved mainly elderly patients with T2DM who had received tofogliflozin for 12 months. Data on glycated haemoglobin (HbA1c), serum electrolytes (sodium, potassium, chloride), haematocrit, estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN)/creatinine ratio were retrieved and analysed., Results: Data from 69 patients (77% of whom were ≥65 years) showed that there was a significant reduction in HbA1c over the 12-month treatment period with tofogliflozin. However, the drug had no significant effect on levels of haematocrit, electrolytes, eGFR or BUN/creatinine ratio., Conclusion: This retrospective analysis of data from mainly elderly Japanese patients with T2DM showed that 12-month administration of tofogliflozin exhibited glucose-lowering capabilities with accompanying low risk of electrolyte abnormalities and dehydration.

Background: Adult onset Still's disease is a systemic auto-inflammatory condition of unknown etiology characterized by intermittent spiking high fever, an evanescent salmon-pink or erythematous maculopapular skin rash, arthralgia or arthritis, and leukocytosis. Recently, a high level of interleukin-18 has been reported as a new characteristic marker. On the other hand no reports have been published on high interleukin-18 as a marker in older patients. We report a case of adult onset Still's disease in an older patient successfully treated with steroids in which interleukin-18 was a useful marker of disease activity., Case Presentation: A 66-year-old Asian woman presented to our hospital with fever and arthralgia. We diagnosed adult onset Still's disease based on Yamaguchi criteria and a history of a high spiking fever, salmon-colored rash, and bilateral pain to shoulders, knees, and wrists. In this case, a high serum level of interleukin-18 was a diagnostic parameter. Administration of 40 mg of prednisolone followed by subcutaneous administration of 200 mg cyclosporine daily resulted in a dramatic resolution of our patient's febrile episodes 2 months after admission. Prednisolone was tapered to 5 mg/day every 2 weeks and cyclosporine 200 mg/day was continued. Her serum interleukin-18 level was prominently decreased, and she was discharged 3 months after treatment., Conclusions: Serum interleukin-18 level may be a good diagnostic biomarker to monitor adult onset Still's disease activity in older patients, measuring levels in both the acute and convalescent phases.

Aim This study was performed to investigate serum procalcitonin (PCT) and albumin (Alb) as prognostic biomarkers in elderly patients at risk of bacterial infection. Methods Serum PCT was measured in 270 hospitalized patients (mean age, 77.4 years) with suspected bacterial infection. The PCT-negative (<0.5 ng/mL) and PCT-positive (≥0.5 ng/mL) groups comprised 155 and 115 patients, respectively. Logistic regression analysis was performed with various clinical laboratory test values as independent variables and PCT positivity/negativity as the dependent variable. Results C-reactive protein (CRP) was the only independent variable significantly associated with PCT positivity/negativity. In the survival analysis, the 30-day in-hospital death rate was significantly higher in the PCT-positive than -negative group. Within the Alb-positive group (>2.5 g/dL), no significant difference in survival was observed between the PCT-positive and -negative groups. However, within the Alb-negative group (≤2.5 g/dL), the survival rate was significantly lower in the PCT-positive than -negative group. PCT was strongly associated with CRP and Alb, and having both PCT positivity and Alb negativity was a prognostic factor for elderly people at risk of bacterial infection. Conclusions Combined measurement of PCT with Alb is expected to be a valuable tool to assess prognosis in elderly people at risk of bacterial infection.

Objectives: To validate a B-type natriuretic peptide (BNP) as a prognostic marker in pneumonia patients., Design: A prospective cohort study., Setting: Kanazawa Medical University Himi Municipal (a 250-bed community hospital in Himi-shi, Toyama-ken, Japan)., Participants: All patients diagnosed with pneumonia by the physician and admitted to our hospital between 1 January 2012 and 31 March 2015 whose BNP levels had been determined in the first 24 h of admission. A total of 673 patients were enrolled. Of these, BNP levels were measured for a total of 369 patients on admission., Intervention: After enrolment, baseline, demographic, clinical and laboratory characteristics including levels of suspected prognostic markers for pneumonia proposed in previous papers, were collected. All patients were followed up until discharge. During analysis, they were divided into categories as follows: community-acquired pneumonia (CAP), aspiration pneumonia (AP), healthcare-associated pneumonia (HCAP) and pneumonia with acute heart failure (PAHF). A univariate and multivariable Cox-regression analysis were applied to each parameter to identify predictors of death. Three cut-off points, namely 40, 100 and 200 pg/mL, as well as the mean, were applied when comparing BNP levels., Main Outcome Measures: 30-day mortality., Results: Of the 369 patients finally included, 137 were diagnosed with CAP, 122 with AP, 74 with HCAP, and 36 with PAHF. In the univariate analysis, BNP levels (mean, cut-off points 100 pg/mL and 200 pg/mL, p<0.01, respectively) were associated with death in CAP, and similar situation was found for BNP (cut-off points 200 pg/mL, p<0.05) in AP, but not for HCAP, or PAHF. In multivariable Cox-regression analysis, BNP remained an independent mortality predictor (HR 10.01, 95% CI 1.32 to 75.7, p=0.03) in CAP., Conclusions: BNP levels may be a useful single prognostic marker for CAP. Further research for validation is warranted., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Here we describe recent advances in our understanding of the natural history of the house mouse, Mus musculus, with a focus on the genetic characteristics of the home territories and how this relates to prehistoric eastward movements from the predicted source areas. Recent studies of mitochondrial and nuclear gene sequences provide insight into the ancient divergence of the three subspecies groups, M. m. castaneus (CAS), M. m. domesticus (DOM), and M. m. musculus (MUS), with inferred natural habits (homelands) in central (Iran, Afghanistan, Pakistan, and India), western (western Iran), and northern (central Asia) areas, respectively. Our mitochondrial DNA and nuclear gene analyses indicate that only one local lineage of CAS extended its range via historical rapid expansion at two different times to Southeast Asia and East Asia, including Japan and southern Sakhalin. This is suggestive of a rapid range expansion of CAS out of its homeland, perhaps associated with the spread of agricultural practices in Asia. The subspecies group MUS now occurs in a large portion of northern Eurasia from eastern Europe in the West to the Japanese Islands in the East, including Uzbekistan, Kazakhstan, southern Siberia, northern China, and Korea, showing divergent patterns in terms of Mus musculus genetics, particularly in relation to nuclear gene sequences, allozymes (e.g., hemoglobin), morphological characteristics, and cytogenetic C-banding patterns. In this review article, we explain the complex spatial patterns of MUS. We postulate that two historical dispersal events took place, from two different source areas, and tentatively assign the taxon names "musculus" and "wagneri" to the two populations, which are associated with distinct genetic modules.

Background: Leptospirosis is an important but largely under-recognized public health problem in the tropics. Establishment of highly sensitive and specific laboratory diagnosis is essential to reveal the magnitude of problem and to improve treatment. This study aimed to evaluate the diagnostic accuracy of a recombinant LigA protein based IgM ELISA during outbreaks in the clinical-setting of a highly endemic country., Methodology/principal Findings: A prospective study was conducted from October 2011 to September 2013 at a national referral hospital for infectious diseases in Manila, Philippines. Patients who were hospitalized with clinically suspected leptospirosis were enrolled. Plasma and urine were collected on admission and/or at discharge and tested using the LigA-IgM ELISA and a whole cell-based IgM ELISA. Sensitivity and specificity of these tests were evaluated with cases diagnosed by microscopic agglutination test (MAT), culture and LAMP as the composite reference standard and blood bank donors as healthy controls: the mean+3 standard deviation optical density value of healthy controls was used as the cut-off limit (0.062 for the LigA-IgM ELISA and 0.691 for the whole cell-based IgM ELISA). Of 304 patients enrolled in the study, 270 (89.1%) were male and the median age was 30.5 years; 167 (54.9%) were laboratory confirmed. The sensitivity and ROC curve AUC for the LigA-IgM ELISA was significantly greater than the whole cell-based IgM ELISA (69.5% vs. 54.3%, p<0.01; 0.90 vs. 0.82, p<0.01) on admission, but not at discharge. The specificity of LigA-IgM ELISA and whole cell-based IgM ELISA were not significantly different (98% vs. 97%). Among 158 MAT negative patients, 53 and 28 were positive by LigA- and whole cell-based IgM ELISA, respectively; if the laboratory confirmation was re-defined by LigA-IgM ELISA and LAMP, the clinical findings were more characteristic of leptospirosis than the diagnosis based on MAT/culture/LAMP., Conclusions/significance: The newly developed LigA-IgM ELISA is more sensitive than the whole cell-based IgM based ELISA. Although the final diagnosis must be validated by more specific tests, LigA-IgM ELISA could be a useful diagnostic test in a real clinical-setting, where diagnosis is needed in the early phase of infection.