Usefulness of bicarbonate-based Impella purge solution in a patient with heparin-induced thrombocytopenia: the first case report of long-term management in Japan.

Percutaneous mechanical circulatory support utilizing micro-axial flow pumps, such as the Impella group of devices, has become a life-saving technique in the treatment of refractory cardiogenic shock, with ever-increasing success rates. A 30-year-old man presented with acute decompensated heart failure and a severely reduced left ventricular ejection fraction (17%). Despite initial treatment with inotropic drugs and intra-aortic balloon pump support, his hemodynamic status remained unstable. Transition to Impella CP mechanical circulatory support was made on day 6 owing to persistently low systolic blood pressure. A significant decline in platelet count prompted suspicion of heparin-induced thrombocytopenia (HIT), later confirmed by positive platelet-activated anti-platelet factor 4/heparin antibody and a 4Ts score of 6 points. Argatroban was initially used as the purge solution, but owing to complications, a switch to Impella 5.0 and a bicarbonate-based purge solution (BBPS) was performed. Despite additional veno-arterial extracorporeal membrane oxygenation support on day 24, the patient, aiming for ventricular assist device treatment and heart transplantation, died from infection and multiple organ failure. Remarkably, the Impella CP continued functioning normally until the patient's demise, indicating stable Impella pump performance using BBPS. This case highlights the usefulness of BBPS as an alternative to conventional Impella heparin purge solution when HIT occurs.

Evaluation of plasma and urine pharmacokinetics of tranexamic acid for equine medication control.

This study aimed to evaluate the pharmacokinetics (PK) of tranexamic acid (TXA) in horses and estimate its irrelevant plasma and urine concentrations using the pharmacokinetic/pharmacodynamic (PK/PD) approach by applying the Pierre-Louis Toutain model. TXA was intravenously administered to eight thoroughbred mares, and plasma and urine TXA concentrations were quantified by liquid chromatography/tandem mass spectrometry. The quantified data were used to calculate the PK parameters of TXA in horses. The plasma elimination curves were best-fitted to a three-compartment model. Using the Toutain model approach, irrelevant plasma and urine TXA concentrations were estimated to be 0.0206 and 0.997 µg/mL, respectively. The typical values of clearance, steady-state volume of distribution, and steady-state urine-to-plasma ratio were 0.080 L/kg/h, 0.86 L/kg, and 49.0, respectively. The obtained irrelevant concentrations will be useful for establishing relevant regulatory screening limits for effective control of TXA use in horse racing and equestrian sports.

Impact of Early Ambulation on the Prognosis of Coronary Artery Bypass Grafting Patients.

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.

Impact of an improved driveline management for HeartMate II and HeartMate 3 left ventricular assist devices.

BACKGROUND: We evaluated the impact of a standardized driveline care strategy, including a subfascial-tunneling method and dressing protocol, on the incidence of driveline infection (DLI). METHODS: DLI data from all HeartMate II (HMII) and HeartMate 3 (HM3) patients (including exchange devices) were retrospectively collected between 2013 and 2021. The driveline subfascial-tunneling method was altered in three steps (A: right direct; B: left triple, C: right triple), and the shower protocol was changed in two steps (A: with/without cover, B: with cover). Disinfection was individually tailored after changing the shower protocol. Complications associated with morbidity and mortality were evaluated for each modification. RESULTS: During the study period, 80 devices were implanted (HMII, n = 54; HM3, n = 26). The 8-year incidence of DLI was 15% (n = 8) in HMII patients and 0% in HM3 patients (p = 0.039). DLI was not associated with hospital mortality. The modified dressing protocol and tunneling method was associated with a significantly better DLI incidence rate in comparison to the previous one: Protocol-A (n = 17), Protocol-B (n = 63), 35% vs 3% (p = 0.0009), Method-A (n = 13), Method-B (n = 42), Method-C (n = 25), 46% vs 5% vs 0% (p = 0.0001). The rete of freedom form DLI at 1, 2, and 3 years had also significant difference between groups: Protocol-A and Protocol-B, 80%, 54%, 54% vs 96%, 96%, 96%, respectively (p < 0.0001), Method-A, Method-B and Method-C, 76%, 44%, 44%, vs 94%, 94%, 94% vs 100%, 100%, respectively (p < 0.0001). CONCLUSIONS: A standardized triple driveline tunneling strategy and waterproof dressing protocol reduced driveline infection in HM3 patients to 0%.

Efficacy and safety of twice-daily tramadol hydrochloride bilayer sustained-release tablets with an immediate release component for postherpetic neuralgia: Results of a Phase III, randomized, double-blind, placebo-controlled, treatment-withdrawal study.

BACKGROUND: We investigated the efficacy and safety of twice-daily bilayer sustained-release tramadol hydrochloride tablets (35% immediate-release; 65% sustained-release) in patients with postherpetic neuralgia. METHODS: This was a Phase III treatment-withdrawal study with 1-4-week dose-escalation, 1-week fixed-dose, and 4-week randomized, double-blind, placebo-controlled withdrawal periods performed at 43 medical institutions in Japan. Patients aged ≥20 years, ≥3 months after the onset of herpes zoster with localized, persistent pain despite fixed-dose analgesics for ≥2 weeks before enrollment were eligible. Patients started tramadol at 100 mg/day and its dose escalated to a maximum of 400 mg/day to achieve a reduction in their Numeric Rating Scale (NRS) for pain of ≥2 points. Eligible patients were randomized to continue tramadol or switched to placebo for 4 weeks (double-blind period). Patients were withdrawn due to inadequate analgesia (NRS deteriorated on ≥2 consecutive days) or their request. RESULTS: Overall, 252 patients started tramadol and 173 were randomized (tramadol: 85; placebo: 88). Tramadol was superior to placebo for the primary endpoint (time from randomization to an inadequate analgesic effect) with log-rank test p = 0.0005. The hazard ratio was 0.353 (95% confidence interval 0.190-0.657) in favor of tramadol and fewer patients in the tramadol group experienced inadequate analgesic effects (16.9% vs. 39.8%). Adverse events in ≥10% of patients in the open-label period were constipation (43.8%), nausea (34.9%), somnolence (18.5%), and dizziness (11.6%). The frequencies of adverse events in the double-blind period were similar in both groups. CONCLUSION: Sustained-release tramadol tablets with an immediate-release component are effective and well tolerated for managing postherpetic neuralgia.

Generic approach for the discovery of drug metabolites in horses based on data-dependent acquisition by liquid chromatography high-resolution mass spectrometry and its applications to pharmacokinetic study of daprodustat.

In drug metabolism studies in horses, non-targeted analysis by means of liquid chromatography coupled with high-resolution mass spectrometry with data-dependent acquisition (DDA) has recently become increasingly popular for rapid identification of potential biomarkers in post-administration biological samples. However, the most commonly encountered problem is the presence of highly abundant interfering components that co-elute with the target substances, especially if the concentrations of these substances are relatively low. In this study, we evaluated the possibility of expanding DDA coverage for the identification of drug metabolites by applying intelligently generated exclusion lists (ELs) consisting of a set of chemical backgrounds and endogenous substances. Daprodustat was used as a model compound because of its relatively lower administration dose (100 mg) compared to other hypoxia-inducible factor stabilizers and the high demand in the detection sensitivity of its metabolites at the anticipated lower concentrations. It was found that the entire DDA process could efficiently identify both major and minor metabolites (flagged beyond the pre-set DDA threshold) in a single run after applying the ELs to exclude 67.7-99.0% of the interfering peaks, resulting in a much higher chance of triggering DDA to cover the analytes of interest. This approach successfully identified 21 metabolites of daprodustat and then established the metabolic pathway. It was concluded that the use of this generic intelligent "DDA + EL" approach for non-targeted analysis is a powerful tool for the discovery of unknown metabolites, even in complex plasma and urine matrices in the context of doping control.

Rhabdomyolysis with Multiple Electrolyte Imbalances under Proton Pump Inhibitor Treatment after Total Thyroidectomy.

A 90-year-old man presented with muscle weakness, difficulty concentrating, and dysphagia. About eighteen months prior to presentation, lansoprazole had been initiated to prevent stress ulcers; he also had a history of total thyroidectomy due to papillary thyroid cancer ten years prior. Laboratory findings were as follows: K 2.4 mEq/L, Ca 3.7 mg/dL, Mg 1.3 mg/dL, CK 5386 U/L, and intact PTH (iPTH) 14 pg/mL. Rhabdomyolysis with multiple electrolyte imbalances under proton pump inhibitor (PPI) treatment was diagnosed. We initiated intravenous hydration and electrolyte supplementation with discontinuation of PPI. After discontinuing PPI, the patient's serum magnesium, potassium, and calcium levels normalised with oral vitamin D and calcium supplementation. PPIs can cause hypocalcaemia and hypokalaemia via hypomagnesemia; hypocalcaemia is also a common postoperative complication of thyroidectomy. Careful monitoring of electrolyte levels is required in patients with long-term PPI treatment, especially in post-thyroidectomy cases.

Is Hybrid Repair for an Entire Shaggy Aorta Feasible?

OBJECTIVE: This paper reviewed clinical experiences to evaluate the feasibility of a surgical strategy for an entire shaggy aorta. METHODS: Fifty-two (52) surgeries (47 men, average age 72±7 years) were performed for an entire shaggy aorta at the current institution from 2002-2017. Open surgery was performed in 30 cases, including total arch replacement in 12, extended aortic arch replacement via L-shaped thoracotomy in 10 and median sternotomy combined with left thoracotomy in two, and thoracoabdominal aortic replacement in six. Hybrid procedures were performed in 22 cases: type I hybrid arch repair in six, type II hybrid arch repair in seven and type III hybrid arch repair in nine. RESULTS: Hospital mortality was significantly higher with a hybrid repair: surgical, one case (3%); hybrid, six cases (27%), (p=0.0125). Stroke occurred at relatively high rates in both groups: surgical, seven cases (23%); hybrid, six cases (27%) (p=0.75). Spinal cord injury was significantly higher in hybrid repair: surgical, one case (3%); hybrid, seven cases (32%), (p=0.004). Open surgery revealed a better long-term survival rate than the hybrid procedure at 5 and 10 years: surgical, 82%, 65.7%; hybrid, 53%, 35.1%, respectively (p=0.0452). The rate of freedom from aortic events was significantly better with open surgery than a hybrid procedure at 5 and 10 years: surgical, 96%, 85%; hybrid, 83%, 41.3%, respectively (p=0.0082). CONCLUSIONS: Surgery for an entire shaggy aorta was frequently associated with embolic complications such as stroke, paraplegia, renal failure, and bowel necrosis. However, open surgical repair may produce better early and late outcomes and freedom from aortic events compared with hybrid repair.

Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older (EWTOPIA 75): A Randomized, Controlled Trial.

BACKGROUND: Evidence regarding the primary prevention of coronary artery disease events by low-density lipoprotein cholesterol (LDL-C) lowering therapy in older individuals, aged ≥75 years, is insufficient. This trial tested whether LDL-C-lowering therapy with ezetimibe is useful for the primary prevention of cardiovascular events in older patients. METHODS: This multicenter, prospective, randomized, open-label, blinded end-point evaluation conducted at 363 medical institutions in Japan examined the preventive efficacy of ezetimibe for patients aged ≥75 years, with elevated LDL-C without history of coronary artery disease. Patients, who all received dietary counseling, were randomly assigned (1:1) to receive ezetimibe (10 mg once daily) versus usual care with randomization stratified by site, age, sex, and baseline LDL-C. The primary outcome was a composite of sudden cardiac death, myocardial infarction, coronary revascularization, or stroke. RESULTS: Overall, 3796 patients were enrolled between May 2009 and December 2014, and 1898 each were randomly assigned to ezetimibe versus control. Median follow-up was 4.1 years. After exclusion of 182 ezetimibe patients and 203 control patients because of lack of appropriate informed consent and other protocol violations, 1716 (90.4%) and 1695 (89.3%) patients were included in the primary analysis, respectively. Ezetimibe reduced the incidence of the primary outcome (hazard ratio [HR], 0.66; 95% CI, 0.50-0.86; P=0.002). Regarding the secondary outcomes, the incidences of composite cardiac events (HR, 0.60; 95% CI, 0.37-0.98; P=0.039) and coronary revascularization (HR, 0.38; 95% CI, 0.18-0.79; P=0.007) were lower in the ezetimibe group than in the control group; however, there was no difference in the incidence of stroke, all-cause mortality, or adverse events between trial groups. CONCLUSIONS: LDL-C-lowering therapy with ezetimibe prevented cardiovascular events, suggesting the importance of LDL-C lowering for primary prevention in individuals aged ≥75 years with elevated LDL-C. Given the open-label nature of the trial, its premature termination and issues with follow-up, the magnitude of benefit observed should be interpreted with caution. Clinical Registration: URL: https://www.umin.ac.jp. Unique identifier: UMIN000001988.

Associations of Hospital Discharge Services With Potentially Avoidable Readmissions Within 30 Days Among Older Adults After Rehabilitation in Acute Care Hospitals in Tokyo, Japan.

OBJECTIVE: To examine the associations of 3 major hospital discharge services covered under health insurance (discharge planning, rehabilitation discharge instruction, and coordination with community care) with potentially avoidable readmissions (PARs) within 30 days in older adults after rehabilitation in acute care hospitals in Tokyo, Japan. DESIGN: Retrospective cohort study using a large-scale medical claims database of all Tokyo residents aged ≥75 years. SETTING: Acute care hospitals. PARTICIPANTS: Patients who underwent rehabilitation and were discharged to home (N=31,247; mean age in years ± SD, 84.1±5.7) between October 2013 and July 2014. INTERVENTIONS: None. MAIN OUTCOME MEASURE: 30-day PAR. RESULTS: Among the patients, 883 (2.9%) experienced 30-day PAR. A multivariable logistic generalized estimating equation model (with a logit link function and binominal sampling distribution) that adjusted for patient characteristics and clustering within hospitals showed that the discharge services were not significantly associated with 30-day PAR. The odds ratios were 0.962 (95% confidence interval [CI], 0.805-1.151) for discharge planning, 1.060 (95% CI, 0.916-1.227) for rehabilitation discharge instruction, and 1.118 (95% CI, 0.817-1.529) for coordination with community care. In contrast, the odds of 30-day PAR among patients with home medical care services were 1.431 times higher than those of patients without these services (P<.001), and the odds of 30-day PAR among patients with a higher number (median or higher) of rehabilitation units were 2.031 times higher than those of patients with a lower number (below median) (P<.001). Also, the odds of 30-day PAR among patients with a higher Hospital Frailty Risk Score (median or higher) were 1.252 times higher than those of patients with a lower score (below median) (P=.001). CONCLUSIONS: The insurance-covered discharge services were not associated with 30-day PAR, and the development of comprehensive transitional care programs through the integration of existing discharge services may help to reduce such readmissions.

Spinal cord injury following aortic arch replacement.

PURPOSE: Postoperative spinal cord injury is a devastating complication after aortic arch replacement. The purpose of this study was to determine the predictors of this complication. METHODS: A group of 254 consecutive patients undergoing aortic arch replacement via median sternotomy, with (n = 78) or without (n = 176) extended replacement of the upper descending aorta, were included in a risk analysis. The frozen elephant trunk technique was used in 46 patients. The patients' atherothrombotic lesions (extensive intimal thickening of > 4 mm) were identified from computed tomography images. RESULTS: Complete paraplegia (n = 7) and incomplete paraparesis (n = 4) occurred immediately after the operation (permanent spinal cord injury rate, 1.97%; transient spinal cord injury rate, 2.36%). A multivariable logistic regression analysis identified the use of the frozen elephant trunk technique (odds ratio 36.3), previous repair of thoracoabdominal aorta or descending aorta (odds ratio 29.4), proximal atherothrombotic aorta (odds ratio 9.6), chronic obstructive lung disease (odds ratio 7.1) and old age (odds ratio 1.1) as predictors of spinal cord injury (p < 0.0001, area under curve 0.93). CONCLUSIONS: Spinal cord injury occurs with a non-negligible incidence following aortic arch replacement. The full objective assessment of the morphology of the whole aorta and the recognition of the risk factors are mandatory.

Exclusion Technique for Entire Shaggy Aorta Followed by One-Stage Repair of the Aortic Arch and Descending Aorta.

OBJECTIVE: A shaggy aorta is defined as a very extensive atheromatous disease with diffuse ulcers in combination with fragile and mobile debris, and actual thrombus. Multiple embolisation - resulting in permanent neurological deficits, paraplegia and a large area of mesenteric embolisation - attributed to cholesterol atheromatic mobile plaque caused by shaggy aorta needs to be prevented. METHODS: Complete exclusion of the shaggy aorta from the distal aortic arch to the end of the descending aorta was presented in two cases: a 71-year-old male and a 51-year-old male. Successful one-stage repair of the extended aortic arch and descending aorta was performed using an isolated selective cerebral perfusion technique via sternotomy and left anterior thoracotomy. RESULTS: There were no neurological or embolic events in the present cases. Contrast-enhanced computed tomography showed good reconstruction of the aortic arch and descending aorta. The patients are still being followed up in the outpatient clinic and have shown no atheromatic embolisation for the past 6 years. CONCLUSIONS: The exclusion technique for an entire shaggy aorta followed by one-stage repair of the aortic arch and descending aorta is a durable and feasible operation for preventing atheromatous embolisation.

Development and exacerbation of pulmonary nontuberculous mycobacterial infection in patients with systemic autoimmune rheumatic diseases.

Objectives: To examine the development and exacerbation of pulmonary nontuberculous mycobacterial (NTM) infection in patients with systemic autoimmune rheumatic diseases (SARD).Methods: We conducted a case-control study. Seventeen of 7013 patients with SARD fulfilling the criteria for pulmonary NTM infection were enrolled in the NTM group. The control group was matched for age, sex, and SARD at a ratio of 2:1.Results: Eight patients with rheumatoid arthritis, four with systemic vasculitis, three with Sjögren's syndrome, and one each with dermatomyositis and systemic lupus erythematosus were included in the NTM group. Mycobacterium avium was detected in 12 (71%) patients, M. chelonae in 2, and M. intracellulare, M. abscessus, and M. kansasii in 1 patient each. Preexisting lung disease was more common in the NTM group than in the control group (88% versus 38%, p = .0009), particularly bronchiectasis (65% versus 29%, p = .033). The body mass index and serum albumin level were significantly lower in the NTM group than in the control group. Six patients (35%) experienced NTM exacerbation during observation. Clinical immune status at the time of NTM diagnosis, as indicated by the peripheral blood leukocyte/lymphocyte count and serum immunoglobulin G level, was unremarkable and comparable between patients with and without exacerbation, as were the treatments for SARD.Conclusions: In patients with SARD, pulmonary NTM infection may develop and exacerbate without clinically apparent immunosuppression.

Meat intake and incidence of cardiovascular disease in Japanese patients with type 2 diabetes: analysis of the Japan Diabetes Complications Study (JDCS).

PURPOSE: Excessive meat intake has been researched as a major cause of cardiovascular disease (CVD) among healthy adults, but data on this topic in Asian patients with diabetes are sparse. The quantity and variety of available meats vary widely between Asian and Western countries. As part of a nationwide cohort study we investigated the relationship between meat intake and incidence of CVD in Japanese patients with type 2 diabetes aged 40-70 years with HbA1c ≥ 6.5%. METHODS: Analyzed were 1353 responders to a baseline dietary survey assessed by the Food Frequency Questionnaire based on food groups. Primary outcome was the 8-year risk of a CVD event, including coronary heart disease (CHD) and stroke. Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders. RESULTS: Mean meat intake in quartiles ranged from 9.9 to 97.7 g/day. After adjusting for confounders, HRs of CHD in the 2nd, 3rd, and 4th quartiles for meat intake compared with the 1st quartile were 2.84 (95% confidence interval 1.29-6.24, p = 0.01), 3.02 (1.36-6.70, p < 0.01), and 2.99 (1.35-6.65, p = 0.01), respectively. In two groups according to meat intake, patients consuming ≥ 20 g/day of meat had a 2.94-fold higher risk of CHD than those consuming < 20 g/day (p < 0.01). There was no significant association of stroke with meat intake. CONCLUSIONS: An elevated incidence of CHD in Japanese patients with type 2 diabetes was associated with high meat intake.

Patterns of Co-Occurrence of Chronic Disease Among Older Adults in Tokyo, Japan.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Clinical characteristics of bullous pemphigoid in elderly patients with type 2 diabetes mellitus: The association with the use of dipeptidyl peptidase-4 inhibitors].

AIM: Bullous pemphigoid (BP) is an autoimmune skin disorder characterized by the production of autoantibodies. Several recent reports have described the occurrence of BP in diabetic patients treated with dipeptidyl peptidase-4 (DPP-4) inhibitors. However, the clinical features of BP in diabetic patients, particularly in those treated with DPP-4 inhibitors, have not yet been examined. The aim of this study was to clarify clinical characteristics of BP in elderly type 2 diabetic patients. METHODS: We found cases of BP in 15 elderly type 2 diabetic patients (11 men, 4 women) and 20 non-diabetic patients (8 men, 12 women) from September, 2012 to September, 2016. These patients had all been treated with corticosteroid therapy. We investigated the participants' basic clinical characteristics and the course of BP treatment. The differences in variables between the two groups were analyzed using Wilcoxon's test and the chi-square test. RESULTS: The mean age of type 2 diabetes patients with BP was 81.1±5.5 years. The mean HbA1c was 7.3±1.6%. A total of 87% of diabetic patients had been treated with DPP-4 inhibitors for 11.7 months prior to the BP onset. The diabetic patients had a lower prevalence of neurogenerative disease, severe ADL disabilities, and dementia than the non-diabetic patients. Furthermore, the diabetic patients with BP tended to be younger and more frequently male than those without diabetes. After stopping the DPP-4 inhibitors, the skin lesions were successfully treated with systemic corticosteroid therapy, and glycemic control was achieved using intensive insulin therapy. DPP-4 inhibitors were used in all cases where the aniti-BP180NC16a antibody showed negative conversion. CONCLUSION: BP in patients with type 2 diabetes had different clinical features from that in non-diabetic patients, suggesting an association between BP and the use of DPP-4 inhibitors.

A retrospective comparison of induction with thiopental/guaifenesin and propofol/ketamine in Thoroughbred racehorses anesthetized with sevoflurane and medetomidine during arthroscopic surgery.

This study compares clinical characteristics between induction with thiopental/guaifenesin and propofol/ketamine in Thoroughbred racehorses anesthetized with sevoflurane and medetomidine. Clinical records of 214 horses that underwent arthroscopic surgery between 2015 and 2016 were retrospectively retrieved. Horses were premedicated with medetomidine and midazolam to sedate at the adequate level for smooth induction, and then induced with either thiopental (4.0 mg/kg) and guaifenesin (100 mg/kg) in Group TG (n=91) or propofol (1.0 mg/kg) and ketamine (1.0 mg/kg) in Group PK (n=123). Anesthesia was maintained using sevoflurane with constant rate infusion of medetomidine. Quality of induction/recovery, sevoflurane requirement, cardiovascular function and recovery characteristics were evaluated. Anesthetic induction scores (median, range) for Group TG (5, 2-5) and Group PK (5, 2-5) were not significantly different. There were no significant differences in end-tidal sevoflurane concentration (mean ± standard deviation) between Group TG and Group PK (both 2.4 ± 0.2%). Dobutamine infusion rate (µg/kg/min) required for keeping mean arterial blood pressure (MAP) above 70 mmHg in Group PK (0.43, 0.10-1.40) was significantly lower than in Group TG (0.67, 0.08-1.56). Recovery score in Group PK (5, 2-5) was significantly higher than in Group TG (4, 2-5). Both propofol/ketamine and thiopental/guaifenesin provided a smooth induction of anesthesia. Moreover, induction with propofol/ketamine resulted in lower dobutamine requirements for keeping MAP above 70 mmHg during maintenance, and better quality of recovery. Induction with propofol/ketamine would be preferable to thiopental/guaifenesin in Thoroughbred racehorses anesthetized with sevoflurane and medetomidine during arthroscopic surgery.

Deficient ganglioside synthesis restores responsiveness to leptin and melanocortin signaling in obese KKAy mice.

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.

Strategy of Cardiovascular Surgery for Patients With Dementia as Evaluated by Mini-Mental State Examination.

BACKGROUND: The strategy for cardiovascular surgery in dementia patients is controversial, so we aimed to investigate whether preoperative dementia and its severity might affect the outcomes of cardiovascular surgery by evaluating with the Mini-Mental State Examination (MMSE). Methods and Results: The study group comprised 490 patients undergoing cardiovascular surgery. Their preoperative cognitive status was evaluated using the MMSE, and analysis was performed to compare the patients with MMSE score <24 (dementia group, n=51) or MMSE score 24-30 (non-dementia group, n=439). Furthermore, the effect of the severity of dementia was analyzed with a cut-off MMSE score of 19/20. Risk factors for surgical outcomes were explored using multivariate logistic regression analysis. Hospital mortality was 11.8% in the dementia group and 2.1% in the non-dementia group (P=0.002). Regarding the postoperative morbidities, the incidence of cerebrovascular disorder (P=0.001), pneumonia (P=0.039), delirium (P=0.004), and infection (P=0.006) was more frequent in dementia group. Among the patients with MMSE <20, hospital mortality was as high as 25%, and the rate of delirium was 58%. Multivariate logistic regression analysis revealed that MMSE score <24 (P=0.003), lower serum albumin (P=0.023) and aortic surgery (P=0.036) were independent risk factors for hospital death. CONCLUSIONS: Preoperative dementia affects the outcomes of cardiovascular surgery with regard to hospital death and delirium. The surgical indication for patients with MMSE <20 might be difficult, but surgery with an appropriate strategy should be considered for patients with MMSE <24.