Diabetes mellitus is associated with an increased prevalence and incidence of geriatric syndrome: functional disabilities, depression, fall, urinary incontinence, malnutrition and cognitive ...impairment. Geriatric syndrome not only leads to frailty, loss of independence and low quality of life, but also becomes a major obstacle in the treatment and care of diabetic people. The risk factors or contributing factors of geriatric symptoms are micro‐ and macrovascular complications, age‐rated comorbid disease and aging per se. Comprehensive geriatric assessment of geriatric syndrome, including basic activities of daily living, instrumental activities of daily living, gait and balance, visual acuity, the Mini‐Mental State Examination, depression scores, history and risk of fall, urination and nutrition, should be performed as part of the care of elderly diabetic patients, in particular old‐old patients. Because geriatric syndromes are multifactorial and share risk factors, diabetic people with any geriatric symptoms should be treated with a common concentric strategy, such as supervised exercise therapy including muscle‐strengthening training, psychological support, social support for adherence, and good glycemic control with avoidance of hypoglycemia.
Multimorbidity, the co-occurrence of 2 or more disorders in a patient, can complicate treatment planning and affect health outcomes. Improvements in prevention and management strategies for patients ...with 3 or more or more co-occurring chronic diseases requires an understanding of the epidemiology of common 3-way disease patterns and their interactions. Our study aimed to describe these common 3-way disease patterns and examine the factors associated with the co-occurrence of 3 or more diseases in elderly Japanese patients.
We included all Japanese citizens aged 75 or older living in Tokyo who used medical care between September 2013 and August 2014 (N = 1,311,116) in our analysis. The 15 most common 3-way patterns of 22 target diseases according to sex and age were identified from among all possible combinations by using an anonymized medical claims database. We examined the associations of sociodemographic characteristics and health care use with the presence of 1 or 2 co-occurring diseases and 3 or more co-occurring diseases by using multinomial logistic regression.
Approximately 65% of patients had 3 or more co-occurring diseases. The most common 3-way pattern was hypertension, coronary heart disease, and peptic ulcer disease in men (12.4%) and hypertension, dyslipidemia, and peptic ulcer disease in women (12.8%). The prevalence of 3 or more diseases was positively associated with men, patients aged 85 to 90, the use of home medical care services, the number of outpatient facilities visited, and hospital admissions.
The common 3-way disease patterns and multimorbidity factors identified in our study may facilitate the recognition of high-risk patients and support the development of clinical guidelines for multimorbidity.
Background: The effect of delayed ambulation on the outcome of coronary artery bypass grafting (CABG) remains to be clarified.Methods and Results: The long-term and in-hospital outcomes of 887 ...patients who underwent isolated CABG (455 off-pump cases, 135 urgent cases) were evaluated, with a focus on the timing of first ambulation. In-hospital mortality cases were excluded. Early ambulation (first ambulation within 3 days after operation) was achieved in 339 (38%) patients. In the multivariable logistic regression analysis, longer operation time and urgent case, EuroSCORE II, re-thoracotomy, and respiratory time were associated with delayed (≥4 days) ambulation. Delayed ambulation was associated with a high incidence of postoperative complications, such as pneumonia, and stroke (P<0.01). Following discharge, 22.2% of patients experienced major cardiac events and 13.8% died during the follow-up period (median follow-up 60 months). Cox hazards analysis revealed that delayed ambulation was associated with long-term adverse events (hazard ratio 1.04 per day, P<0.001). With adjustment for preoperative factors, the estimated future risk of adverse events was found to be increased day-by-day during the delay until initial ambulation.Conclusions: In isolated CABG patients, delayed ambulation was associated with poor outcomes, even in the long-term period. The results support the current guideline recommending early ambulation protocol after cardiac surgery.
Phosphodiesterases (PDEs) are enzymes that hydrolyze and inactivate 3′, 5′-cyclic adenosine monophosphate (cAMP) and/or 3′, 5′-cyclic guanosine monophosphate (cGMP). The regulation of intracellular ...signaling pathways mediated by cyclic nucleotides is imperative to synaptic plasticity and memory in animals. Because PDEs play an important role in this regulation, PDE inhibitors are considered as candidate compounds for treating cognitive and memory disorders. In the present study, we tested whether cilostazol, a selective PDE3 inhibitor, prevents the cognitive deterioration that occurs during the course of normal aging in mice. Ten months of cilostazol administration (1.5%) in 13-month-old mice improved spatial memory when tested at 23 months of age. First, it prevented the decline in the ability of these aged mice to recognize a change in an object's location in the object recognition task. Second, spatial memory of these cilostazol-treated aged mice in the Morris water maze was comparable to that of untreated middle-aged mice (13 months old). Cilostazol administration had no effect on the emotional states and physical ability of aged mice. Thus, long-term cilostazol administration prevented hippocampus-dependent memory decline in aged mice, allowing them to achieve a level of cognitive performance similar to middle-aged mice and without negative behavioral side effects. Considering its well-established safety in other medical contexts, cilostazol may be a potential therapeutic candidate drug for staving off cognitive decline in the aging human population.
•Serum cilostazol concentration in mice was at the clinically effective level in humans.•Cilostazol improved spatial memory in mice when tested at 23-months of age.•Memory of cilostazol-treated aged mice was similar to middle-aged untreated mice.•Cilostazol had no effect on emotional state or physical ability of aged mice.•Long-term cilostazol administration may prevent cognitive decline in aging humans.
We investigated predictors of failure of mitral valve repair (MVr) using expanded polytetrafluoroethylene (ePTFE) and its durability in the long term in a single institution.
Four hundred twenty-one ...consecutive patients with primary mitral valve disease underwent MVr using artificial chordae (group A, n = 304) and suture repair (group S, n = 117) at our institution from January 2002 to April 2020. A comparison study was performed to examine the long-term outcomes, reoperation rate, and risk factors for reoperation.
One hospital death and 5 late deaths occurred in group S, and 20 late deaths occurred in group A. The reoperation rates were similar: group A, n = 8 (2.6%); and group S, n = 6 (5%). The major cause of reoperation was ruptured ePTFE (CV-4, n = 1; CV-5, n = 6) in group A, and suture rupture in group S. Reoperation was performed after a median of 88 months for ruptured ePTFE, and 26 months for group S. The rate of ePTFE rupture was 1.8% with CV-5 and 0.2% with CV-4. Risk factors for reoperation included postoperative arrhythmia, urgent operation, no annular ring, ruptured ePTFE, and suture rupture. The rates of freedom from reoperation and actuarial mitral valve survival rates at 5, 10, and 15 years were 99%, 95%, and 93% and 96%, 91%, and 89%, respectively, in group A; and 96%, 91%, and 91% and 95%, 94%, and 94%, respectively, in group S.
The long-term surgical outcomes of MVr using both techniques were feasible. Over the long term, the ePTFE rupture rate of CV-5 was higher than that of CV-4.
GM3, a precursor for synthesis of a- and b-series gangliosides, is elevated in adipocytes of obese model animals and in sera of obese human patients with type 2 diabetes and/or dyslipidemia. GM3 ...synthase (GM3S)-KO C57BL/6 mice display enhanced insulin sensitivity and reduced development of high-fat diet-induced insulin resistance. However, the pathophysiological roles of GM3 and related gangliosides in the central control of feeding and metabolism remain unclear. We found that a mouse model (KKAy GM3S KO) generated by KO of the GM3S gene in the yellow obese strain, KKAy, displayed significant amelioration of obese phenotype. Whereas KKAy mice were hyperphagic and developed severe obesity, KKAy GM3S KO mice had significantly lower body weight and food intake, and greater glucose and insulin tolerance. The hypothalamic response to intraperitoneal administration of leptin was greatly reduced in KKAy mice, but was retained in KKAy GM3S KO mice. In studies of a cultured mouse hypothalamic neuronal cell line, enhanced leptin-dependent phosphorylation of ERK was observed in GM3S-deficient cells. Furthermore, KKAy GM3S KO mice did show altered coat color, suggesting that GM3S is also involved in melanocortin signaling. Our findings, taken together, indicate that GM3-related gangliosides play key roles in leptin and melanocortin signaling.
To elucidate the disease-flare process in rheumatoid arthritis (RA) after discontinuing biological disease-modifying antirheumatic drugs (bDMARDs), we first focused on RA-flare prediction after ...achieving stringent remission criteria. Patients with RA who maintained a simplified disease activity index ≤ 3.3 for ≥ 3 months during November 2014-January 2018 in our medical centre in Tokyo, Japan, were eligible. The primary endpoint was flare (disease activity score 28-erythrocyte sedimentation rate ≥ 3.2 with increase from baseline > 0.6) within 2 years after bDMARD discontinuation. Comprehensive clinical assessments, ultrasonographic evaluation of 40 joints, and blood sampling for 12 biomarkers were performed every 2-3 months for 2 years unless patients experienced flare. Flare-positive and flare-negative patients were compared using univariate and Kaplan-Meier analyses. Thirty-six patients (80.6% female, median disease duration, 5.2 years; median treatment period with discontinued bDMARD, 2 years; median remission duration, 18 months) were enrolled. Twenty patients (55.6%) experienced RA flare 43-651 (median, 115) days after the first skipped date of bDMARDs. Two patients who withdrew without disease flare were excluded from the comparison. Clinical and ultrasonographic evaluations did not show significant between-group differences; Kaplan-Meier analysis showed that higher baseline soluble tumour necrosis factor receptor 1 (sTNFR1) concentration impacted subsequent disease flare (p = 0.0041); higher baseline interleukin (IL)-2 concentration was exclusively beneficial to patients with lower sTNFR1 (p = 0.0058), resulting in remission maintenance in 83.3% of patients with lower sTNFR1 and higher IL-2. We demonstrated the usefulness of combined biomarker evaluation for predicting sustained remission after bDMARD discontinuation in RA.
Phosphodiesterases (PDEs), which hydrolyze and inactivate 3′, 5′-cyclic adenosine monophosphate (cAMP) and 3′, 5′-cyclic guanosine monophosphate (cGMP), play an important role in synaptic plasticity ...that underlies memory. Recently, several PDE inhibitors were assessed for their possible therapeutic efficacy in treating cognitive disorders. Here, we examined how cilostazol, a selective PDE3 inhibitor, affects brain functions in senescence-accelerated mouse prone 8 (SAMP8), an animal model of age-related cognitive impairment. Long-term administration of cilostazol restored the impaired context-dependent conditioned fear memory of SAMP8 to match that in normal aging control substrain SAMR1. Cilostazol also increased the number of cells containing phosphorylated cAMP-responsive element binding protein (CREB), a downstream component of the cAMP pathway. Finally, cilostazol improves blood-brain barrier (BBB) integrity, demonstrated by reduced extravasation of 2-deoxy-2-18F-fluoro-d-glucose and Evans Blue dye in the brains of SAMP8. This improvement in BBB integrity was associated with an increased amount of zona occludens protein 1 (ZO-1) and occludin proteins, components of tight junctions integral to the BBB. The results suggest that long-term administration of cilostazol exerts its beneficial effects on age-related cognitive impairment through a dual mechanism: by enhancing the cAMP system in the brain and by maintaining or improving BBB integrity.
•Senescence-accelerated mouse prone 8 (SAMP8) was used as an animal model of aging.•Long-term administration of cilostazol restored the impaired fear memory of SAMP8.•Cilostazol administration increased phosphorylation of CREB in hippocampal dentate gyrus.•Cilostazol administration reduced extravasation of 2-deoxy-2-18F-fluoro-d-glucose and Evans Blue dye from SAMP8 brain.•Cilostazol increased the amount of tight junction proteins.
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