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Patients with type 2 diabetes mellitus are frequently hospitalized for heart failure. The ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e'), measured by echocardiography, is a simple and convenient indicator of diastolic dysfunction. Various large clinical trials have reported that sodium glucose transporter-2 inhibitor therapy reduced cardiovascular events and hospitalizations in heart failure patients. We examined the effect of tofogliflozin on various physiological and cardiac function. A retrospective analysis was performed on elderly patients aged 65 years or older with type 2 diabetes mellitus attending Himi Municipal Hospital who were taking oral tofogliflozin 20 mg/day. Measurement of physiological and hormonal variables, blood sampling, and echocardiographic evaluations at 0, 1, 3, and 6 months were performed on those with ejection fraction (EF) of 40% or greater at the time of treatment. Statistical analysis was performed using t-tests and mixed-effects models, with brain natriuretic peptide less than or not less than 100 pg/mL, estimated glomerular filtration rate (eGFR) less than or not less than 50 mL/min/1.73 m2, and diuretics administered or not. Hypoglycemic effects were observed at 0, 1, 3, and 6 months. At each time point, EF was retained and E/e' was significantly reduced. On the other hand, most physiological parameters and laboratory results showed no clinical abnormalities. Mixed-effects models showed time-dependent reduction of E/e' in high/low brain natriuretic peptide, high/low eGFR, with or without diuretics between baseline and at 6 months. The interaction with time was significant in high/low eGFR. Tofogliflozin was shown to improve E/e', a measure of diastolic function, while maintaining EF, with hypoglycemic effects and no clinical side effects., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

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.)

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.)

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.)

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.)

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.

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: 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.)

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/)