The Degree of Blood Supply and Infection Control Needed to Treat Diabetic Chronic Limb-Threatening Ischemia with Forefoot Osteomyelitis.

BACKGROUND: Diabetic foot ulcers combined with ischemia and infection can be difficult to treat. Few studies have quantified the level of blood supply and infection control required to treat such complex diabetic foot ulcers. We aimed to propose an index for ischemia and infection control in diabetic chronic limb-threatening ischemia (CLTI) with forefoot osteomyelitis. METHODS: We retrospectively evaluated 30 patients with diabetic CLTI combined with forefoot osteomyelitis who were treated surgically from January 2009 to December 2016. After 44 surgeries, we compared patient background (age, sex, hemodialysis), infection status (preoperative and 1- and 2-week postoperative C-reactive protein [CRP] levels), surgical bone margin (with or without osteomyelitis), vascular supply (skin perfusion pressure), ulcer size (wound grade 0-3 using the Society for Vascular Surgery Wound, Ischemia, and foot Infection classification), and time to wound healing between patients with healing ulcers and those with nonhealing ulcers. RESULTS: Preoperative CRP levels and the ratio of ulcers classified as wound grade 3 were significantly lower and skin perfusion pressure was significantly higher in the healing group than in the nonhealing group (P < .05). No other significant differences were found between groups. CONCLUSIONS: This study demonstrates that debridement should be performed first to control infection if the preoperative CRP level is greater than 40 mg/L. Skin perfusion pressure of 55 mm Hg is strongly associated with successful treatment. We believe that this research could improve the likelihood of salvaging limbs in patients with diabetes with CLTI.

Determinants and impact of physical impairment in patient-reported outcomes among older patients with type 2 diabetes mellitus in Japan.

OBJECTIVE: To investigate the predictive factors associated with physical impairment among older patients with type 2 diabetes mellitus (T2DM) in Japan and to examine the potential impact of physical impairment on patient-reported health outcomes in this population. METHODS: A cross-sectional analysis was conducted using patient-reported data from the 2012-2014 Japan National Health and Wellness Survey. Physical impairment was measured using the Physical Component Summary (PCS) score of the Short-Form 36-Item Health Survey (SF-36) three-component model (using Japanese norms). Older T2DM patients (≥65 years old; n = 1511) were dichotomized into physically impaired (PCS ≤ 25th percentile; n = 378) and non-physically impaired (PCS > 25th percentile; n = 1133). Work productivity (absenteeism, presenteeism and overall work impairment), activity impairment and healthcare resource utilization were compared between these groups. RESULTS: Age, female sex, low and high body mass index (BMI), diabetes-related complications, cardiovascular events, unawareness of having hypoglycemic events in the past 3 months, and lack of regular exercise were significant factors associated with physical impairment in multivariable analysis. The physically impaired group reported significantly more regular outpatient visits (13.48 vs. 10.16, respectively, p < .001), 1% or greater absenteeism (16.7% vs. 4.1%, p = .005), greater presenteeism (27.8% vs. 12.2%, p = .001), overall work impairment (30.0% vs. 13.0%, p = .001) and overall activity impairment (39.5% vs. 17.2%, p < .001) than the non-physically-impaired group after adjusting for covariates. CONCLUSIONS: This study identified age, BMI, diabetes-related comorbidities, history of cardiovascular events and lack of exercise as key predictors associated with physical impairment in older patients with T2DM in Japan, which predicted low work productivity as well as activity impairment. This study provides support that physical impairment in patients with T2DM may lead to low work productivity and activity impairment.Supplemental data for this article is available online at https://doi.org/10.1080/03007995.2020.1846170.

Epidemic Myalgia Associated with Human Parechovirus Type 3 Infection.

A 42-year-old man was hospitalized due to a fever, orchiodynia, and extremely severe myalgia predominantly in the extremities, which made it difficult for him to stand or walk. He had a history of contact with his son who had acute upper respiratory infection. Based on the characteristic clinical symptoms and detection of the partial sequence of human parechovirus type 3 (HPeV3) in throat swabs as well as stool and serum samples, he was diagnosed with epidemic myalgia associated with HPeV3 infection. Because HPeV3 infection is widespread among children in Japan, HPeV3-associated myalgia should be considered when adult patients manifest such distinguishing clinical characteristics.

Diabetes care providers' manual for disaster diabetes care.

To ensure that experiences and lessons learned from the unprecedented 2011 Great East Japan Earthquake are used to improve future disaster planning, the Japan Diabetes Society (JDS) launched the "Research and Survey Committee for Establishing Disaster Diabetes Care Systems Based on Relevant Findings from the Great East Japan Earthquake" under the supervision of the Chairman of the JDS. The Committee conducted a questionnaire survey among patients with diabetes, physicians, disaster medical assistance teams (DMATs), nurses, pharmacists, and nutritionists in disaster areas about the events they saw happening, the situations they found difficult to handle, and the needs that they felt required to be met during the 2011 Great East Japan Earthquake. A total of 3,481 completed questionnaires were received. Based on these and other experiences and lessons reported following the 2011 Great East Japan Earthquake and the 2004 Niigata-Chuetsu Earthquakes, the current "Manual for Disaster Diabetes Care" has been developed by the members of the Committee and other invited authors from relevant specialties. To our knowledge, the current Manual is the world's first to focus on emergency diabetes care, with this digest English version translated from the Japanese original. It is sincerely hoped that patients with diabetes and healthcare providers around the world will find this manual helpful in promoting disaster preparedness and implementing disaster relief.

Diabetes Care Providers' Manual for Disaster Diabetes Care.

To ensure that experiences and lessons learned from the unprecedented 2011 Great East Japan Earthquake are used to improve future disaster planning, the Japan Diabetes Society (JDS) launched the "Research and Survey Committee for Establishing Disaster Diabetes Care Systems Based on Relevant Findings from the Great East Japan Earthquake" under the supervision of the Chairman of the JDS. The Committee conducted a questionnaire survey among patients with diabetes, physicians, disaster medical assistance teams (DMATs), nurses, pharmacists, and nutritionists in disaster areas about the events they saw happening, the situations they found difficult to handle, and the needs that they felt required to be met during the 2011 Great East Japan Earthquake. A total of 3,481 completed questionnaires were received. Based on these and other experiences and lessons reported following the 2011 Great East Japan Earthquake and the 2004 Niigata-Chuetsu Earthquakes, the current "Manual for Disaster Diabetes Care" has been developed by the members of the Committee and other invited authors from relevant specialties. To our knowledge, the current Manual is the world's first to focus on emergency diabetes care, with this digest English version translated from the Japanese original. It is sincerely hoped that patients with diabetes and healthcare providers around the world will find this manual helpful in promoting disaster preparedness and implementing disaster relief.

A case of pulmonary tuberculosis diagnosed in a patient with manifestations of haemophagocytic lymphohistiocytosis.

An 80-year-old woman was admitted with continuous fever, hepatic dysfunction and cytopaenia. The presence of hepatosplenomegaly, hyperferritinaemia, hypofibrinogenaemia and phagocytosis by macrophages in the bone marrow was consistent with a diagnosis of haemophagocytic lymphohistiocytosis (HLH). We suspected that HLH was induced by pre-existing tuberculosis, and antitubercular agents were started. Positive nucleic acid amplification and sputum culture for Mycobacterium tuberculosis resulted in a diagnosis of pulmonary tuberculosis. The patient improved with three months of treatment. In this patient, manifestations of HLH preceded those of pulmonary tuberculosis. A diagnosis of HLH should increase suspicion of disseminated tuberculosis and thus contribute to early detection.

A case of pernicious anemia requiring differential diagnosis of autoimmune hemolytic anemia complication.

An 80-year-old female was admitted to our hospital due to malaise. The initial diagnosis on admission was pernicious anemia (PA), Hashimoto thyroiditis and autoimmune atrophic gastritis. Autoimmune hemolytic anemia was suspected because direct antiglobulin test (DAT) was positive. Treatment with vitamin B12 improved anemia, with the disappearance of hemolysis. In some cases, PA patients with positive DAT may have hemolysis without the involvement of the autoimmune mechanism. Therefore, it is important to carefully assess PA patients with hemolysis and positive DAT for the prevention of unnecessary administration of steroid therapy.

Surgical treatment strategy for diabetic forefoot osteomyelitis.

The aim of this study was to propose an appropriate surgical treatment for diabetic forefoot osteomyelitis (DFO) involving ischemia or moderate to severe soft tissue infection. The records of 28 patients with osteomyelitis from 2009 to 2015 were retrospectively studied. All patients had undergone surgery based on preoperative magnetic resonance imaging examinations and histopathological or culture analyses confirming the surgical bone margin. The appropriate surgical margin, crucial factors for early healing, and prognosis after complete resection of osteomyelitis were examined. After healing, patients were followed up to assess prognosis (range 32-1,910 days, median 546 days). The healing rate of nonischemic cases of DFO with negative surgical margins was 100% and that of ischemic cases was 84.6%; the ambulatory rates for both types of cases were 100%. No wound (and/or osteomyelitis) recurrence was observed. Nine new cases of DFO developed in six patients (21.4%; eight were due to vascular stenosis, and one was due to biomechanical changes in the foot. After complete resection of osteomyelitis, preoperative and postoperative C-reactive protein levels and the size of the ulcer were significant predictors of early healing (p < 0.05, 0.01, and 0.05, respectively). The appropriate surgical margin should be set in the area of bone marrow edema, based on magnetic resonance imaging examinations after revascularization. In cases with high preoperative or postoperative C-reactive protein levels, long-term antibiotic therapy is recommended, and surgery should be planned after the C-reactive protein levels decrease, except in emergencies.

Atherogenic phenotype remains in elderly diabetic patients.

AIM: It is known that plasma low-density lipoprotein cholesterol (LDL-C) levels tend to decrease with age. Thus, most elderly diabetic patients often show normal LDL-C levels. Therefore, the present study was carried out to examine whether elderly diabetic patients show "the atherogenic phenotype" even if their LDL-C is not elevated. METHODS: The study participants consisted of 236 patients. They were separated into four groups according to their age (below 64 years and above 65 years) and an association of type 2 diabetes. A total of 88 middle-aged diabetic, 34 middle-aged non-diabetic, 64 elderly diabetic and 50 elderly non-diabetic participants were enrolled. LDL-C, small dense LDL-C (sLDL-C) were investigated. ANOVA were used for comparison of LDL-C, sLDL-C and the sLDL-C/LDL-C ratio between the four groups. Multivariate regression analysis was carried out in order to find the independent factors associated with the sLDL-C/LDL-C ratio. RESULTS: Among the four groups, the LDL-C of the elderly diabetic group showed lower LDL-C levels compared with that of middle-aged diabetic group, although the difference was not significant (128.6 ± 38.7 vs 138.4 ± 35.8 mg/dL). In contrast, sLDL-C and the sLDL-C/LDL-C ratio in the elderly diabetic group were both higher than those of the elderly non-diabetic group (47.0 ± 24.2 mg/dL and 0.36 ± 0.14 mg/dL, vs 21.4 ± 16.7 mg/dL and 0.19 ± 0.11 mg/dL, P < 0.05). Multivariate regression analysis showed that age, sex, the presence of diabetes mellitus and plasma triglyceride were the independent factors determining the sLDL-C/LDL-C ratio. DISCUSSION: It is concluded from the present data that the atherogenic phenotype remains in elderly diabetic patients even if their LDL-C is not elevated.

The dual role of scavenger receptor class A in development of diabetes in autoimmune NOD mice.

Human type 1 diabetes is an autoimmune disease that results from the autoreactive destruction of pancreatic ß cells by T cells. Antigen presenting cells including dendritic cells and macrophages are required to activate and suppress antigen-specific T cells. It has been suggested that antigen uptake from live cells by dendritic cells via scavenger receptor class A (SR-A) may be important. However, the role of SR-A in autoimmune disease is unknown. In this study, SR-A-/- nonobese diabetic (NOD) mice showed significant attenuation of insulitis, lower levels of insulin autoantibodies, and suppression of diabetes development compared with NOD mice. We also found that diabetes progression in SR-A-/- NOD mice treated with low-dose polyinosinic-polycytidylic acid (poly(I:C)) was significantly accelerated compared with that in disease-resistant NOD mice treated with low-dose poly(I:C). In addition, injection of high-dose poly(I: C) to mimic an acute RNA virus infection significantly accelerated diabetes development in young SR-A-/- NOD mice compared with untreated SR-A-/- NOD mice. Pathogenic cells including CD4+CD25+ activated T cells were increased more in SR-A-/- NOD mice treated with poly(I:C) than in untreated SR-A-/- NOD mice. These results suggested that viral infection might accelerate diabetes development even in diabetes-resistant subjects. In conclusion, our studies demonstrated that diabetes progression was suppressed in SR-A-/- NOD mice and that acceleration of diabetes development could be induced in young mice by poly(I:C) treatment even in SR-A-/- NOD mice. These results suggest that SR-A on antigen presenting cells such as dendritic cells may play an unfavorable role in the steady state and a protective role in a mild infection. Our findings imply that SR-A may be an important target for improving therapeutic strategies for type 1 diabetes.

[Concept and clinical characteristics of diabetes mellitus in the elderly].

Both decreased insulin secretion and insulin resistance are two major factors of impaired glucose tolerance (IGT) in the elderly. Up to now, decreased lean body mass and relatively increased fat mass, so-called sarcopenia or sarcopenic obesity, contribute to insulin resistance in the elderly. However, recent reports indicate that muscle mitochondrial function is reduced in aging, and this age-associated decline in mitochondrial function contributes to insulin resistance in the elderly. In addition, exercise intervention to IGT in the elderly is more effective to reduce in the incidence of type 2 diabetes than in younger people. Exercise seems to improve insulin resistance through mitochondrial function by activating AMP-activated protein kinase(AMPK) and PPARgamma coactivator-1alpha (PGC-1alpha). Because cognitive impairment is a most crucial factor plunging into frailty in diabetic elderly, diabetic control would be very important in preventing cognitive decline as well as vascular events. However, comprehensive management of diabetes, including dyslipidemia and hypertension, might contribute to the prevention of declines in cognitive function in older diabetic patients.

A warning index used in prescreening for Alzheimer's disease, based on self-reported cognitive deficits and vascular risk factors for dementia in elderly patients with type 2 diabetes.

Background/Aims. Diabetes might increase the risk of Alzheimer's disease (AD). For detecting dementia, it is typical to obtain informants' perceptions of cognitive deficits, but such interviews are usually difficult in routine care. We aimed to develop a model for predicting mild to moderate AD using a self-reported questionnaire and by evaluating vascular risk factors for dementia in elderly subjects with diabetes. Methods. We recruited 286 diabetic and 155 nondiabetic elderly subjects. There were 25 patients with AD and 261 cognitively normal individuals versus 30 with AD and 125 normal subjects, respectively. Each participant answered subjective questions on memory deficits and daily functioning. Information on vascular risk factors was obtained from clinical charts, and multivariate logistic regression was used to develop a model for predicting AD. Results. The predicted probabilities used in screening for AD in diabetic subjects constituted age, education, lower diastolic blood pressure, subjective complaints of memory dysfunction noticeable by others, and impaired medication, shopping, and travel outside a familiar locality. Receiver operating characteristic analysis revealed a satisfactory discrimination for AD specific for diabetic elderly subjects, with 95.2% sensitivity and 90.6% specificity. Conclusion. This is the first useful index that can prescreen for AD in elderly subjects with diabetes.

A case of an elderly patient with slowly progressive type 1 diabetes who developed severe nonocclusive mesenteric ischemia without predisposing events.

A 72-year-old woman with slowly progressive type 1 diabetes (SPIDDM) was admitted to our hospital because of increasing abdominal pain and diarrhea. The patient was diagnosed with nonocclusive mesenteric ischemia (NOMI), and a subtotal colonectomy was performed successfully. The resected sample revealed transmural gangrenous necrosis of the colon and rectum. This case is interesting because the severe NOMI occurred in a SPIDDM patient without common predisposing events such as hypoperfusion. Prolonged generation of reactive oxygen species in SPIDDM, together with the decline in adaptive response to oxidative stress with aging, might be an exacerbating factor for ischemic injury in the elderly.

Long-term multiple risk factor interventions in Japanese elderly diabetic patients: the Japanese Elderly Diabetes Intervention Trial--study design, baseline characteristics and effects of intervention.

AIM: To evaluate long-term, multiple risk factor intervention on physical, psychological and mental prognosis, and development of complications and cardiovascular disease in elderly type 2 diabetes patients. METHODS: Our randomized, controlled, multicenter, prospective intervention trial included 1173 elderly type 2 diabetes patients who were enrolled from 39 Japanese institutions and randomized to an intensive or conservative treatment group. Glycemic control, dyslipidemia, hypertension, obesity, diabetic complications and atherosclerotic disease were measured annually. Instrumental activity of daily living, cognitive impairment, depressive symptoms and diabetes burden were assessed at baseline and 3 years. RESULTS: There was no significant difference in clinical or cognitive parameters at baseline between the two groups. The prevalence of low activities of daily living, depressive symptoms and cognitive impairment was 13%, 28% and 4%, respectively, and was similar in the two groups. A small, but significant difference in HbA1c between the two groups was observed at 1 year after the start of intervention (7.9% vs 8.1%, P < 0.05), although this significant difference was not observed after the second year. With the exception of coronary revascularization, there was no significant difference in fatal or non-fatal events between the two groups. Composite events were also similar in the two groups. CONCLUSIONS: This study showed no significant differences in fatal or non-fatal events between intensive and conventional treatment. The present study might clarify whether treatment of risk factors influences function and quality of life in elderly diabetic patients.

Non-high-density lipoprotein cholesterol: an important predictor of stroke and diabetes-related mortality in Japanese elderly diabetic patients.

AIMS: To evaluate the association of low-density lipoprotein, high-density lipoprotein and non-high-density lipoprotein cholesterol with the risk of stroke, diabetes-related vascular events and mortality in elderly diabetes patients. METHODS: This study was carried out as a post-hoc landmark analysis of a randomized, controlled, multicenter, prospective intervention trial. We included 1173 elderly type 2 diabetes patients (aged ≥ 65 years) from 39 Japanese institutions who were enrolled in the Japanese elderly diabetes intervention trial study and who could be followed up for 1 year. A landmark survival analysis was carried out in which follow up was set to start 1 year after the initial time of entry. RESULTS: During 6 years of follow up, there were 38 cardiovascular events, 50 strokes, 21 diabetes-related deaths and 113 diabetes-related events. High low-density lipoprotein cholesterol was associated with incident cardiovascular events, and high glycated hemoglobin was associated with strokes. After adjustment for possible covariables, non-high-density lipoprotein cholesterol showed a significant association with increased risk of stroke, diabetes-related mortality and total events. The adjusted hazard ratios (95% confidence intervals) of non-high-density lipoprotein cholesterol were 1.010 (1.001-1.018, P = 0.029) for stroke, 1.019 (1.007-1.031, P < 0.001) for diabetes-related death and 1.008 (1.002-1.014; P < 0.001) for total diabetes-related events. CONCLUSIONS: Higher non-high-density lipoprotein cholesterol was associated with an increased risk of stroke, diabetes-related mortality and total events in elderly diabetes patients.