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1.
Cureus ; 16(5): e60850, 2024 May.
Article in English | MEDLINE | ID: mdl-38910605

ABSTRACT

Destructive thyroiditis and secondary adrenal insufficiency are major endocrinological immune-related adverse events of immune checkpoint inhibitors (ICIs). However, the timing at which each event occurs most frequently after drug administration varies, and cases where multiple events occur simultaneously are rare. We encountered a patient who concurrently suffered from thyrotoxicosis and adrenal insufficiency. An 80-year-old woman with a history of type 2 diabetes mellitus (DM) was diagnosed with stage IVA squamous cell carcinoma of the lungs. Treatment with a combination of nivolumab and ipilimumab was initiated. Although she tested positive for thyroglobulin antibody and transient subclinical hyperthyroidism was observed after two courses, treatment with ICIs was continued. Four months later, treatment was discontinued due to drug-induced lung disease. One month after the last administration, the patient became unconscious and was admitted to another hospital, diagnosed with diabetic ketoacidosis, urinary tract infection, and sepsis. After acute-phase treatment, she was transferred to our hospital due to persistent fever and tachycardia. Thyrotoxicosis and adrenal insufficiency were observed, with high levels of free thyroxine, low thyroid-stimulating hormone (TSH), and cortisol levels. Treatment with extracellular fluids, potassium iodide, beta-blockers, and hydrocortisone was initiated, and the patient's condition improved. No other pituitary hormone deficiencies were observed. She was diagnosed with painless thyroiditis and secondary adrenal insufficiency based on the positive thyroglobulin antibody, negative TSH receptor antibody, decreased Doppler flow in thyroid ultrasonography, low adrenocorticotrophic hormone (ACTH), and low response of ACTH and cortisol to corticotropin-releasing hormone loading test. MRI revealed no abnormalities. We report a case of thyrotoxicosis and secondary adrenal insufficiency five months after the first administration of nivolumab and ipilimumab. Careful follow-up and early detection of endocrine disorders are critical in patients treated with a combination of ICIs.

2.
BMC Endocr Disord ; 24(1): 71, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769570

ABSTRACT

BACKGROUND: Although vaccination against coronavirus disease (COVID-19) has several side effects, hypopituitarism due to hypophysitis has rarely been reported. CASE PRESENTATION: An 83-year-old healthy woman, who had received her fourth COVID-19 vaccine dose 2 days before admission, presented to the emergency department with difficulty moving. On examination, impaired consciousness (Glasgow Coma Scale: 14) and fever were observed. Computed tomography and magnetic resonance imaging of the head revealed swelling from the sella turcica to the suprasellar region. Her morning serum cortisol level was low (4.4 µg/dL) and adrenocorticotropic hormone level was normal (21.6 pg/mL). Central hypothyroidism was also suspected (thyroid stimulating hormone, 0.46 µIU/mL; free triiodothyronine, 1.86 pg/mL; free thyroxine, 0.48 ng/dL). Secondary adrenocortical insufficiency, growth hormone deficiency, delayed gonadotropin response, and elevated prolactin levels were also observed. After administration of prednisolone and levothyroxine, her consciousness recovered. On the 7th day of admission, the patient developed polyuria, and arginine vasopressin deficiency was diagnosed using a hypertonic saline test. On the 15th day, the posterior pituitary gland showed a loss of high signal intensity and the polyuria resolved spontaneously. On the 134th day, the corticotropin-releasing hormone loading test showed a normal response; however, the thyrotropin-releasing hormone stimulation test showed a low response. The patient's disease course was stable with continued thyroid and adrenal corticosteroid supplementation. CONCLUSIONS: Herein, we report a rare case of anterior hypopituitarism and arginine vasopressin deficiency secondary to hypophysitis following COVID-19 vaccination.


Subject(s)
COVID-19 Vaccines , COVID-19 , Hypopituitarism , Humans , Female , Hypopituitarism/etiology , Aged, 80 and over , COVID-19 Vaccines/adverse effects , COVID-19/complications , Hypophysitis/chemically induced , Hypophysitis/etiology , Arginine Vasopressin/deficiency , Adrenal Insufficiency/etiology , Vaccination/adverse effects , SARS-CoV-2
3.
Gerontology ; 70(5): 517-525, 2024.
Article in English | MEDLINE | ID: mdl-38286122

ABSTRACT

INTRODUCTION: Frailty is a crucial health issue among older adults. Growth differentiation factor 15 (GDF15) is associated with inflammation, oxidative stress, insulin resistance, and mitochondrial dysfunction, which are possible pathogeneses of frailty. However, few longitudinal studies have investigated the association between GDF15 and the incidence of frailty. Therefore, we investigated whether high serum GDF15 levels are associated with the incidence of frailty. METHODS: A total of 175 older adults (mean age: 77 ± 6 years; 63% women) with cardiometabolic diseases and no frailty out of the two criteria at baseline participated. Individuals with severe renal impairment or severe cognitive impairment were excluded. Serum GDF15 levels were measured at baseline. Patients were asked to assess frailty status at baseline and annually during follow-up using the modified version of the Cardiovascular Health Study (mCHS) and the Kihon Checklist (KCL). We examined the association between GDF15 tertiles and each frailty measure during follow-up (median 38-39 months). In the multivariate Cox regression analysis, with the GDF15 tertile groups as the explanatory variables, hazard ratios (HRs) and 95% confidence intervals (CIs) for incident frailty were calculated after adjusting for covariates and using the lowest tertile group as the reference. RESULTS: During the follow-up period, 25.6% and 34.0% of patients developed frailty, as defined by the mCHS and KCL, respectively. The highest GDF15 tertile group had a significantly higher incidence of mCHS- or KCL-defined frailty than the lowest GDF15 tertile group. Multivariate Cox regression analysis revealed that the adjusted HRs for incident mCHS- and KCL-defined frailty in the highest GDF15 tertile group were 3.9 (95% CI: 1.3-12.0) and 2.7 (95% CI: 1.1-6.9), respectively. CONCLUSION: High serum GDF15 levels predicted the incidence of frailty among older adults with cardiometabolic diseases and could be an effective marker of the risk for frailty in interventions aimed at preventing frailty, such as exercise and nutrition.


Subject(s)
Cardiovascular Diseases , Frail Elderly , Frailty , Growth Differentiation Factor 15 , Humans , Growth Differentiation Factor 15/blood , Female , Male , Aged , Frailty/blood , Frailty/epidemiology , Incidence , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Frail Elderly/statistics & numerical data , Biomarkers/blood , Proportional Hazards Models , Longitudinal Studies
4.
Geriatr Gerontol Int ; 24 Suppl 1: 150-155, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37872859

ABSTRACT

AIM: This longitudinal study aimed to determine whether categorization by the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) is associated with risk of frailty onset, disability, and mortality. METHODS: We analyzed longitudinal data from outpatients aged 65 years and older evaluated for the DASC-8 at the Frailty Clinic. The outcomes during the 3-year follow-up period were (Study A) frailty onset (Kihon Checklist ≥8) and (Study B) disability (new certification of nursing care needs) or mortality. Multivariate Cox regression analyses were performed to examine independent associations between the DASC-8 category and outcomes, and hazard ratios and 95% confidence intervals (CIs) were calculated after adjustment for age, sex, and the presence or absence of diabetes, hypertension, and dyslipidemia. RESULTS: (Study A) Out of the 216 patients without frailty in Categories I or II at baseline, 40 (20.4%) and 11 (55.0%) developed frailty, respectively. The adjusted hazard ratio was 3.62 (95% CI: 1.69-7.76, P < 0.001). (Study B) Out of the 350 patients who did not require long-term care at baseline, disability or death occurred for 20 (7.3%) in Category I, 14 (23.0%) in Category II, and 9 (56.3%) in Category III. The adjusted hazard ratios were 2.40 (Category I vs. II; 95% CI: 1.13-5.11, P = 0.023) and 5.43 (Category I vs. III; 95% CI: 2.23-13.3, P < 0.001). CONCLUSION: Categorization according to DASC-8 is associated with the risk of frailty, disability, and mortality in older patients. Geriatr Gerontol Int 2024; 24: 150-155.


Subject(s)
Delivery of Health Care, Integrated , Dementia , Frailty , Humans , Aged , Frailty/diagnosis , Activities of Daily Living , Longitudinal Studies , Independent Living , Cognition , Dementia/diagnosis , Frail Elderly , Geriatric Assessment
5.
BMC Geriatr ; 23(1): 765, 2023 11 22.
Article in English | MEDLINE | ID: mdl-37993771

ABSTRACT

BACKGROUND: Older patients with diabetes mellitus are more susceptible to frailty. Although some imaging markers of appendicular skeletal muscle mass obtained using dual-energy X-ray absorptiometry or computed tomography (CT) imaging can reflect frailty status, the association between imaging indices obtained by abdominal CT scans and frailty in older inpatients has not been reported. METHODS: A total of 151 older inpatients with diabetes mellitus (median age, 79 years; men, 42%) who underwent abdominal CT scans close to the admission date were studied to examine the associations between abdominal CT indices and frailty. Two frailty definitions were used: the modified Cardiovascular Health Study (mCHS) criteria and Kihon Checklist (KCL) criteria. Using the imaging analysis software SYNAPSE VINCENT®, we compared the cross-sectional areas (CSA) of four truncal muscles (erector spinae, iliopsoas, rectus abdominis, and abdominal oblique muscles) and the liver-to-spleen ratio (L/S), the ratio of the CT values of the liver and spleen between frail and non-frail patients. The muscle areas that showed the strongest associations with frailty were also investigated in relation to grip strength and walking speed. Finally, multivariate binominal logistic regression analyses were performed to assess the independent associations of CSA of muscle and L/S with the prevalence of frailty. RESULTS: The prevalence of frailty defined by the mCHS and KCL criteria was 55% and 52%, respectively. The CSA of the erector spinae muscle was most significantly associated with frailty, and was significantly smaller in both sexes of mCHS-defined frail patients and in men with KCL-defined frailty. The CSA of erector spinae muscle was also positively correlated with grip strength and walking speed. In contrast, the L/S was higher in men with KCL-defined frailty. Multivariate logistic regression analyses revealed that the CSA of the erector spinae muscle was independently associated with mCHS-defined frailty in women, and the L/S was associated with KCL-defined frailty in men. CONCLUSIONS: The CSA of erector spinae muscle and low liver fat content could be indices of frailty in older patients with diabetes.


Subject(s)
Diabetes Mellitus , Frailty , Male , Humans , Female , Aged , Frailty/diagnostic imaging , Frailty/epidemiology , Cross-Sectional Studies , Spleen , Muscle, Skeletal/diagnostic imaging , Liver
6.
Front Aging Neurosci ; 14: 912972, 2022.
Article in English | MEDLINE | ID: mdl-35966786

ABSTRACT

Diffusion tensor imaging (DTI) can be used for the early detection of abnormal changes in the integrity of cerebral white matter tracts, and we have previously reported that these changes are associated with indices of early atherosclerotic lesions. Although these changes have been demonstrated to be associated with the incidence of frailty in older adults, no studies have investigated this relationship in patients at high risk for vascular disease. In this longitudinal study, we followed outpatients with cardiometabolic diseases for a maximum of 6 years (median, 3 years) and evaluated the association of baseline DTI data of seven white matter tracts with the incidence of frailty. The modified version of the Cardiovascular Health Study criteria and the Kihon Checklist were used as indices of frailty; fractional anisotropy (FA) and mean diffusivity (MD) were used as indices of white matter changes. Patients who developed frailty based on both indices had low FA and high MD in many of the tracts tested, with the most significant difference found in the MD of the anterior thalamic radiation (ATR). Cox proportional hazard model analysis revealed a significantly high risk of frailty defined by both indices in the groups with high MD values in the left ATR. Similar results were found in patients with diabetes mellitus but not in those without diabetes mellitus. Therefore, abnormalities in the integrity of the left ATR could be associated with the progression of frailty in older adults with cardiometabolic disease, particularly those with diabetes mellitus.

7.
Nihon Ronen Igakkai Zasshi ; 59(2): 225-232, 2022.
Article in Japanese | MEDLINE | ID: mdl-35650056

ABSTRACT

The patient was an 84-year-old man who had been on insulin therapy for type 2 diabetes mellitus for 55 years. He had undergone bile duct stenting to avoid obstruction due to adenocarcinoma of the bile duct. The patient had suffered from fever and anorexia for two weeks, and had subsequently stopped insulin therapy. Since he showed signs of impaired consciousness, he was taken to the emergency room, and was diagnosed with a hyperosmotic hyperglycemic state (HHS) based on the following laboratory findings: blood glucose, 632 mg/dL; plasma osmolality, 391 mOsm/kg·H2O; and serum Na, 163 mEq/L, with urine ketone bodies±and sepsis (Klebsiella pneumoniae). He was therefore admitted to the hospital. His blood glucose and serum Na levels slowly improved following the administration of fluids, insulin, and antibiotics. The patient's consciousness disturbance also improved. However, on the third day after admission, dysphagia was newly observed when the patient resumed eating, and swallowing endoscopy revealed a delayed gag reflex and pharyngeal retention of saliva. Cranial magnetic resonance imaging showed a high-intensity area in the central pontine, which was considered to be caused by osmotic demyelination syndrome (ODS). The patient's oral intake ability recovered with swallowing rehabilitation. ODS is a rare complication of HHS. We report a case of HHS with ODS, in which the patient's chief complaint was dysphagia, which should be distinguished from other diseases.


Subject(s)
Deglutition Disorders , Demyelinating Diseases , Diabetes Mellitus, Type 2 , Hyperglycemic Hyperosmolar Nonketotic Coma , Aged , Aged, 80 and over , Blood Glucose , Deglutition Disorders/complications , Demyelinating Diseases/complications , Diabetes Mellitus, Type 2/complications , Humans , Hyperglycemic Hyperosmolar Nonketotic Coma/complications , Insulin , Male , Syndrome
8.
J Endocr Soc ; 6(7): bvac082, 2022 Jul 01.
Article in English | MEDLINE | ID: mdl-35702602

ABSTRACT

The discovery of bioactive peptides is an important research target that enables the elucidation of the pathophysiology of human diseases and provides seeds for drug discovery. Using a large number of native peptides previously identified using plasma peptidomics technology, we sequentially synthesized selected sequences and subjected them to functional screening using human cultured cells. A 15-amino-acid residue proangiotensinogen-derived peptide, designated ANGT_HUMAN[448-462], elicited cellular responses and bound to cultured human cells. Synthetic fluorescent-labeled and biotinylated ANGT_HUMAN[448-462] peptides were rendered to bind to cell- and tissue-derived proteins and peptide-cell protein complexes were retrieved and analyzed using liquid chromatography-tandem mass spectrometry, revealing the ß-subunit of ATP synthase as its cell-surface binding protein. Because ATP synthase mediates the effects of anorexigenic peptides, the ability of ANGT_HUMAN[448-462] to modulate eating behavior in mice was investigated. Both intraperitoneal and intracerebroventricular injections of low doses of ANGT_HUMAN[448-462] suppressed spontaneous food and water intake throughout the dark phase of the diurnal cycle without affecting locomotor activity. Immunoreactive ANGT_HUMAN[448-462], distributed throughout human tissues and in human-derived cells, is mostly co-localized with angiotensin II and is occasionally present separately from angiotensin II. In this study, an anorexigenic peptide, ANGT_HUMAN[448-462], was identified by exploring cell surface target proteins of the human native peptides identified using plasma peptidomics.

9.
BMC Geriatr ; 22(1): 255, 2022 03 28.
Article in English | MEDLINE | ID: mdl-35346081

ABSTRACT

BACKGROUND: Dementia is an important health issue for older people and requires early intervention in the mild cognitive impairment (MCI) stage to manage risk factors. Both dynapenia (DP) and abdominal obesity (AO) are associated with inflammation and oxidative stress, which may be involved in the pathogenesis of cognitive impairment. Therefore, in this cross-sectional study, we aimed to evaluate the association between MCI and dynapenic abdominal obesity (DAO), a combination of DP and AO. METHODS: A total of 417 older outpatients with cardiometabolic diseases without severe cognitive impairment were studied to compare cognitive function in four groups: control, DP, AO, and DAO groups. DAO was defined as the combination of DP (handgrip strength of < 28 kg and < 18 kg in men and women, respectively) and AO (waist circumference of ≥ 85 cm and ≥ 90 cm in men and women, respectively). MCI was defined as a score of ≤ 25 in the Japanese version of the Montreal Cognitive Assessment. Multiple regression analyses were performed to examine if MCI was independently associated with DAO, low handgrip strength, or high waist circumference. RESULTS: The DAO group obtained the lowest cognitive test scores and had the highest prevalence of MCI. Furthermore, after adjusting for covariates, the logistic regression analysis showed that patients in the DAO group were at an increased risk of MCI (odds ratio [OR] = 3.98, 95% confidence interval [CI]: 1.15-13.77). Further logistic regression analyses revealed that both low handgrip strength (OR = 2.19, 95% CI: 1.11-4.29) and high waist circumference (OR = 2.03, 95% CI: 1.03-3.99) were associated with MCI. CONCLUSIONS: DAO, which can be easily diagnosed by a combination of handgrip strength and waist circumference, was associated with MCI in patents with cardiometabolic metabolic disease. This study suggests that screening for MCI in DAO patients could be important for early intervention of dementia prevention.


Subject(s)
Cardiovascular Diseases , Cognitive Dysfunction , Aged , Cardiovascular Diseases/epidemiology , Cognitive Dysfunction/complications , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/epidemiology , Cross-Sectional Studies , Female , Hand Strength , Humans , Male , Obesity, Abdominal/complications , Obesity, Abdominal/diagnosis , Obesity, Abdominal/epidemiology
10.
Front Aging Neurosci ; 13: 712385, 2021.
Article in English | MEDLINE | ID: mdl-34489681

ABSTRACT

White matter abnormalities may reflect cerebral microvessel disease. Diffusion tensor imaging (DTI) can help detect early changes in white matter integrity in each tract. However, studies investigating the relationship between subclinical atherosclerosis markers and white matter alterations in DTI findings are limited. This study aimed to examine associations between cardiovascular risk factors and indices of subclinical atherosclerosis-ankle brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and carotid artery intima-media thickness (IMT)-and altered white matter integrity in older patients. A total of 224 patients (aged ≥65 years) with cardiometabolic disease who underwent magnetic resonance imaging (MRI) and either plethysmography or cervical ultrasound at the start of the 3-year observational study period were included in this study. We measured fractional anisotropy (FA) and mean diffusivity (MD), which are indices of white matter integrity in seven white matter tracts. In a univariate analysis, lower ABI and higher baPWV values were associated with FA or MD abnormalities in several tracts, whereas IMT was scarcely associated with such change. In addition, high blood pressure and glycoalbumin/glycohemoglobin ratio (GA/HbA1c) and low body mass index (BMI) and triglyceride (TG) levels were associated with FA or MD abnormalities. In a multivariate analysis adjusted for age, sex, BMI, diastolic blood pressure, TG, and GA/HbA1c, the associations between ABI and FA or MD remained in all of either side of the following tracts: anterior thalamic radiation, forceps minor, inferior frontooccipital fasciculus (p < 0.001 for all) and superior longitudinal fasciculus (SLF; p < 0.05), whereas most of those between baPWV and FA or MD disappeared except for SLF (p < 0.05). These results indicate that low ABI could be an indicator of white matter abnormalities.

11.
Nihon Ronen Igakkai Zasshi ; 58(2): 297-302, 2021.
Article in Japanese | MEDLINE | ID: mdl-34039807

ABSTRACT

An 87-year-old woman diagnosed with dementia with Lewy bodies (DLB) 2 years earlier was referred to our institution because of difficulty walking. She was diagnosed with urinary tract infection and admitted to our hospital. During hospitalisation, she became delirious, which prompted the administration of haloperidol. Afterwards, an altered level of consciousness was noted, measuring 300 on the Japan coma scale. A blood test revealed hyperammonaemia without liver damage. Urine culture detected the presence of Corynebacterium urealyticum. Therefore, we diagnosed this case as one of hyperammonaemia due to urinary tract infection caused by urease-producing bacteria. Soon after the insertion of a urethral catheter, the ammonia level decreased, and the consciousness level improved. In this case, the patient took medication to preserve her bladder function, which is frequently associated with DLB. We suspected that the drug caused urinary retention, resulting in hyperammonaemia. Hyperammonaemia due to these bacteria should be considered in DLB patients with an impaired consciousness, especially in those using regulators of the urinary bladder function.


Subject(s)
Hyperammonemia , Lewy Body Disease , Urinary Tract Infections , Aged, 80 and over , Bacteria , Corynebacterium , Female , Humans , Hyperammonemia/etiology , Japan , Lewy Body Disease/complications , Urease , Urinary Tract Infections/complications
12.
Sci Rep ; 11(1): 1047, 2021 01 13.
Article in English | MEDLINE | ID: mdl-33441610

ABSTRACT

Identification of low-abundance, low-molecular-weight native peptides using non-tryptic plasma has long remained an unmet challenge, leaving potential bioactive/biomarker peptides undiscovered. We have succeeded in efficiently removing high-abundance plasma proteins to enrich and comprehensively identify low-molecular-weight native peptides using mass spectrometry. Native peptide sequences were chemically synthesized and subsequent functional analyses resulted in the discovery of three novel bioactive polypeptides derived from an epidermal differentiation marker protein, suprabasin. SBSN_HUMAN[279-295] potently suppressed food/water intake and induced locomotor activity when injected intraperitoneally, while SBSN_HUMAN[225-237] and SBSN_HUMAN[243-259] stimulated the expression of proinflammatory cytokines via activation of NF-κB signaling in vascular cells. SBSN_HUMAN[225-237] and SBSN_HUMAN[279-295] immunoreactivities were present in almost all human organs analyzed, while immunoreactive SBSN_HUMAN[243-259] was abundant in the liver and pancreas. Human macrophages expressed the three suprabasin-derived peptides. This study illustrates a new approach for discovering unknown bioactive peptides in plasma via the generation of peptide libraries using a novel peptidomic strategy.


Subject(s)
Antigens, Differentiation/metabolism , Neoplasm Proteins/metabolism , Peptides/blood , Animals , Apoptosis/drug effects , Appetite/drug effects , Cells, Cultured , Chromatography, High Pressure Liquid , Cytokines/metabolism , Fluorescent Antibody Technique , Humans , Mice , Mitosis/drug effects , Muscle, Smooth, Vascular/drug effects , NF-kappa B/metabolism , Peptides/pharmacology
13.
J Diabetes Investig ; 12(4): 633-640, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32750745

ABSTRACT

AIMS/INTRODUCTION: Older adults with diabetes mellitus are susceptible to sarcopenia. Diffusion tensor imaging studies have also shown that patients with diabetes have altered white matter integrity. However, the relationship between these structural changes in white matter and sarcopenia remains poorly understood. MATERIALS AND METHODS: The study included 284 older patients (aged ≥65 years) who visited the Tokyo Metropolitan Geriatric Hospital Frailty Clinic. We used diffusion tensor imaging to measure fractional anisotropy (FA) and mean diffusivity (MD) to evaluate changes in white matter integrity. We investigated the associations between sarcopenia, or its diagnostic components, and FA or MD in seven white matter tracts considered to be associated with sarcopenia according to the patients' diabetes status. RESULTS: We found significantly low FA or high MD values in the bilateral anterior thalamic radiations (ATR) and right inferior fronto-occipital fasciculus (IFOF) of patients with Asian Working Group for Sarcopenia 2019-defined sarcopenia, in all patients and those with diabetes. Using binominal regression analyses, we associated low FA values in the left ATR and right IFOF with sarcopenia in all patients and those with diabetes, after adjusting for age, gender, HbA1c, blood pressure, cognitive function, physical activity, depression, nutritional status, and inflammation. CONCLUSIONS: White matter alterations in left ATR and right IFOF are associated with the prevalence of sarcopenia in patients with diabetes. Specific changes to the left ATR and right IFOF tracts could play critical roles in the occurrence of sarcopenia in patients with diabetes.


Subject(s)
Diabetes Complications/diagnostic imaging , Sarcopenia/diagnostic imaging , White Matter/diagnostic imaging , Aged , Aged, 80 and over , Cohort Studies , Diabetes Complications/epidemiology , Diffusion Tensor Imaging , Female , Humans , Male , Prevalence , Sarcopenia/epidemiology , Tokyo/epidemiology
14.
Geriatr Gerontol Int ; 20(12): 1157-1163, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33067921

ABSTRACT

AIM: We examined whether the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) is useful for screening frailty and as a comprehensive geriatric assessment (CGA). METHODS: Outpatients (N = 431; 269 women; Mage = 78.9 ± 6.8 years) with cardiometabolic disease from a frailty clinic participated. Frailty status was assessed using modified Cardiovascular Health Study criteria, the Clinical Frailty Scale and the Kihon Checklist. Cognition, higher-level activities of daily living, sarcopenia, physical activities, depression, nutrition, medication adherence, social network and quality of life were assessed as CGA components. We examined the association of DASC-8 category with frailty or CGA components using multiple logistic regression analyses, adjusted for age and sex. RESULTS: Most participants (n = 310, 71.9%) were in Category I, 90 (20.9%) were in Category II and 31 (7.1%) were in Category III. There were no significant differences in sex, body mass index, or past medical history, except regarding age or cerebral infarction. Logistic regression analyses showed that, for all definitions of frailty, the odds ratios of frailty significantly increased as category progressed. Cognitive function, higher-level activities of daily living, handgrip strength, gait speed, physical activities, medication adherence, social network and quality of life decreased as the category increased. Although depressive tendency increased in Category II, there was no significant difference in muscle mass or prevalence of sarcopenia among the categories. Malnutrition was observed in Category III. CONCLUSIONS: DASC-8 category was associated with frailty and several CGA components in older patients with cardiometabolic disease. Geriatr Gerontol Int 2020; 20: 1157-1163.


Subject(s)
Delivery of Health Care, Integrated , Dementia , Frailty , Activities of Daily Living , Aged , Cross-Sectional Studies , Female , Frail Elderly , Frailty/diagnosis , Frailty/epidemiology , Geriatric Assessment , Hand Strength , Humans , Quality of Life
15.
Geriatr Gerontol Int ; 20(10): 980-987, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32886834

ABSTRACT

AIMS: Sarcopenia is a serious problem because of its poor prognosis. Growth differentiation factor 15 (GDF15) is associated with mitochondrial dysfunction, inflammation, insulin resistance and oxidative stress, which may play crucial roles for the development of sarcopenia. We aimed to examine whether serum GDF15 level is associated with muscle mass, strength and lower extremity function in older patients with cardiometabolic disease. METHODS: Serum GDF15 levels were measured in 257 patients with cardiometabolic diseases (including 133 patients with diabetes) who had visited the frailty clinic, using a latex turbidimetric immunoassay. Appendicular skeletal muscle index, handgrip strength, timed-up-and-go test and gait speed were evaluated. Power, speed, balance and total scores based on the sit-to-stand test were calculated to assess lower extremity function. RESULTS: The highest tertile of serum GDF15 was independently associated with low handgrip strength, low gait speed, long timed-up-and-go time and scores of lower extremity function but not an appendicular skeletal muscle index in multiple logistic regression analyses after adjustment for covariates. Patients in the highest tertile of GDF15 were at the risk of having three to nine times lower grip strength, three times lower gait speed, five to six times lower mobility and five to 11 times reduction in lower extremity function as compared with those in the lowest GDF15 tertile dependent on the models. CONCLUSIONS: Elevated serum GDF15 level was independently associated with low muscle strength and lower extremity function in older patients with cardiometabolic disease. Serum GDF15 could be one of the biomarkers for muscle weakness and low physical performance. Geriatr Gerontol Int 2020; 20: 980-987.


Subject(s)
Cardiovascular Diseases/blood , Diabetes Mellitus/blood , Growth Differentiation Factor 15/blood , Lower Extremity/physiopathology , Muscle Strength/physiology , Sarcopenia/blood , Aged , Aged, 80 and over , Biomarkers/blood , Cardiovascular Diseases/physiopathology , Diabetes Mellitus/physiopathology , Female , Frailty , Hand Strength , Humans , Male , Muscle, Skeletal/physiopathology , Sarcopenia/physiopathology , Time and Motion Studies , Walking Speed/physiology
16.
Case Rep Endocrinol ; 2020: 2808101, 2020.
Article in English | MEDLINE | ID: mdl-32158565

ABSTRACT

A 47-year-old woman with a history of diabetes mellitus (DM) and obesity was admitted to our hospital for glucose control. She was detected to have hypertension (HT) and diagnosed with primary aldosteronism (PA) based on the high level of aldosterone to renin ratio and the results of the upright furosemide-loading test according to the criteria of the Japanese Society of Hypertension (JSH) guidelines. Computed tomography revealed left renal tumor and adrenocortical adenoma. She underwent left nephrectomy and adrenalectomy. The pathological findings were clear-cell renal cell carcinoma (RCC) and nonfunctional adrenocortical adenoma. Her nonneoplastic adrenal tissue histologically revealed CYP11B2-positive multiple adrenocortical micronodules (MNs) and concomitant paradoxical hyperplasia of the zona glomerulosa. Therefore, MNs were thought to be responsible for PA in this patient. After surgery, HT was improved, and the result of upright furosemide-loading test after 12 months of surgery did not fulfill the criteria of PA according to the JSH guidelines. However, the adrenocorticotrophic hormone stimulation test was positive; considering the possibility of slight aldosterone overproduction from the right adrenal gland, the administration of spironolactone was started. Herein, we report a rare case of RCC in conjunction with PA histologically associated with MNs.

19.
Am J Pathol ; 186(6): 1481-98, 2016 06.
Article in English | MEDLINE | ID: mdl-27085138

ABSTRACT

The persistence of proinflammatory macrophages, which are recruited to the granulation tissue, impairs the healing of diabetic wounds. Herein, we examined the role of vascular endothelial growth factor receptor type 1 (VEGFR1) signaling in streptozotocin (STZ)-induced diabetic wound healing. Angiogenesis, lymphangiogenesis, and the healing of full-thickness skin wounds were impaired in STZ-treated wild-type (WT) mice compared with vehicle-treated WT mice, with attenuated recruitment of VEGFR1-positive macrophages expressing vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D to the wound granulation tissue. These phenomena were even more prevalent in STZ-treated VEGFR1 tyrosine kinase knockout mice (VEGFR1 TK(-/-) mice). STZ-treated WT mice, but not STZ-treated VEGFR1 TK(-/-) mice, showed accelerated wound healing when treated with placenta growth factor. Compared with that of STZ-treated WT mice, the wound granulation tissue of STZ-treated VEGFR1 TK(-/-) mice contained more VEGFR1-positive cells expressing IL-1ß [a classic (M1) activated macrophage marker] and fewer VEGFR1-positive cells expressing the mannose receptor [CD206; an alternatively activated (M2) macrophage marker]. Treatment of STZ-treated VEGFR1 TK(-/-) mice with an IL-1ß-neutralizing antibody restored impaired wound healing and angiogenesis/lymphangiogenesis and induced macrophages in the wound granulation tissue to switch to an M2 phenotype. Taken together, these results suggest that VEGFR1 signaling plays a role in regulating the balance between macrophage phenotypes in STZ-induced diabetic wounds, prevents impaired diabetic wound healing, and promotes angiogenesis/lymphangiogenesis.


Subject(s)
Diabetes Mellitus, Experimental/metabolism , Interleukin-1beta/biosynthesis , Macrophages/metabolism , Signal Transduction , Vascular Endothelial Growth Factor Receptor-1/metabolism , Wound Healing/physiology , Animals , Cell Line , Diabetes Mellitus, Experimental/immunology , Diabetes Mellitus, Experimental/pathology , Flow Cytometry , Fluorescent Antibody Technique , Humans , Interleukin-1beta/immunology , Lymphangiogenesis/physiology , Macrophages/immunology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Neovascularization, Physiologic/physiology , Real-Time Polymerase Chain Reaction , Signal Transduction/physiology , Vascular Endothelial Growth Factor Receptor-1/immunology
20.
Cardiovasc Res ; 107(4): 509-21, 2015 Sep 01.
Article in English | MEDLINE | ID: mdl-25935870

ABSTRACT

AIMS: Thromboxane A2 (TXA2) induces platelet adhesion through thromboxane prostanoid (TP) receptor. Platelets contain many pro-angiogenic factors and are recruited to the site of vascular injury. However, the cellular and molecular mechanisms of platelet-dependent angiogenesis, especially the involvement of TP signalling, have not been fully elucidated. The present study hypothesized that TP-dependent platelet adhesion would contribute to angiogenesis in a mouse hindlimb ischaemic model. METHODS AND RESULTS: Blood flow recovery was suppressed by the TXA2 receptor antagonist (S-1452) and the TXA2 synthase inhibitor (OKY-046) compared with control mice. TP knockout mice (TP(-/-)) showed delayed blood flow recovery from ischaemia and impaired angiogenesis compared with wild-type (WT) mice and prostacyclin receptor knockout mice (IP(-/-)). Selective platelet adhesion to ischaemic endothelial cells (ECs) via P-selectin was identified in WT and IP(-/-), but not in TP(-/-), via in vivo microscopy. IF analysis showed that P-selectin glycoprotein ligand-1 (PSGL-1) co-localized with endothelial CD31 in ischaemic muscle in WT and IP(-/-) but not diminished in TP(-/-). Platelet-rich plasma levels of stromal cell-derived factor-1 and VEGF were increased after ischaemia in WT, and suppressed by antibody against P-selectin in WT but not in TP(-/-). Furthermore, the blood flow recovery was suppressed by neutralizing antibodies against VEGF or C-X-C chemokine receptor type 4 in WT and IP(-/-) but not in TP(-/-). CONCLUSION: These results indicated that TP signalling facilitates ischaemia-induced angiogenesis via P-selectin-mediated platelet adhesion to PSGL-1 on the ECs at ischaemic sites and the supply of pro-angiogenic factors by the adherent platelets.


Subject(s)
Blood Platelets/drug effects , Endothelial Cells/metabolism , Myocardial Ischemia/metabolism , Platelet Adhesiveness/drug effects , Thromboxane A2/pharmacology , Animals , Blood Platelets/cytology , Male , Membrane Glycoproteins/metabolism , Mice, Knockout , Platelet Adhesiveness/genetics , Receptors, Thromboxane A2, Prostaglandin H2/drug effects , Signal Transduction/drug effects
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