Systemic Deletion of ARRDC4 Improves Cardiac Reserve and Exercise Capacity in Diabetes.

BACKGROUND: Exercise intolerance is an independent predictor of poor prognosis in diabetes. The underlying mechanism of the association between hyperglycemia and exercise intolerance remains undefined. We recently demonstrated that the interaction between ARRDC4 (arrestin domain-containing protein 4) and GLUT1 (glucose transporter 1) regulates cardiac metabolism. METHODS: To determine whether this mechanism broadly impacts diabetic complications, we investigated the role of ARRDC4 in the pathogenesis of diabetic cardiac/skeletal myopathy using cellular and animal models. RESULTS: High glucose promoted translocation of MondoA into the nucleus, which upregulated Arrdc4 transcriptional expression, increased lysosomal GLUT1 trafficking, and blocked glucose transport in cardiomyocytes, forming a feedback mechanism. This role of ARRDC4 was confirmed in human muscular cells from type 2 diabetic patients. Prolonged hyperglycemia upregulated myocardial Arrdc4 expression in multiple types of mouse models of diabetes. We analyzed hyperglycemia-induced cardiac and skeletal muscle abnormalities in insulin-deficient mice. Hyperglycemia increased advanced glycation end-products and elicited oxidative and endoplasmic reticulum stress leading to apoptosis in the heart and peripheral muscle. Deletion of Arrdc4 augmented tissue glucose transport and mitochondrial respiration, protecting the heart and muscle from tissue damage. Stress hemodynamic analysis and treadmill exhaustion test uncovered that Arrdc4-knockout mice had greater cardiac inotropic/chronotropic reserve with higher exercise endurance than wild-type animals under diabetes. While multiple organs were involved in the mechanism, cardiac-specific overexpression using an adenoassociated virus suggests that high levels of myocardial ARRDC4 have the potential to contribute to exercise intolerance by interfering with cardiac metabolism through its interaction with GLUT1 in diabetes. Importantly, the ARRDC4 mutation mouse line exhibited greater exercise tolerance, showing the potential therapeutic impact on diabetic cardiomyopathy by disrupting the interaction between ARRDC4 and GLUT1. CONCLUSIONS: ARRDC4 regulates hyperglycemia-induced toxicities toward cardiac and skeletal muscle, revealing a new molecular framework that connects hyperglycemia to cardiac/skeletal myopathy to exercise intolerance.

Remimazolam for general anesthesia in a patient with aortic stenosis and severe obesity undergoing transcatheter aortic valve implantation.

INTRODUCTION: There is currently limited research on the clinical use of remimazolam in severely obese patients. In this report, we describe the anesthesia management of transcatheter aortic valve implantation (TAVI) in a severely obese patient using remimazolam. CASE DESCRIPTION: A 76-year-old woman (height 1.54 m; total body weight 104 kg; body mass index 43.9 kg/m2) was scheduled for TAVI via the femoral artery approach for aortic valve stenosis. Preoperative echocardiography showed an aortic valve peak flow of 4.0 m/s and an effective orifice area of 0.75 cm2. Anesthesia induction was performed with a bolus dose of 100 µg fentanyl, 15 mg remimazolam, 60 mg rocuronium, and a continuous infusion of remifentanil at 0.4 mg/h. Intraoperatively, remimazolam was administered at a rate of 35 mg/h. General anesthesia management was completed without any complications, although the patient required temporary catecholamine and inhalation anesthesia assistance due to hemodynamic changes. CONCLUSION: Owing to its pharmacological advantages, remimazolam may be an option for anesthesia induction and maintenance in severely obese patients with unstable circulation.

Fluttering cord-like thrombus in the aortic arch.

BACKGROUND: The optimal treatment for aortic thrombus remains to be determined, but surgical treatment is indicated when there is a risk for thromboembolism. CASE PRESENTATION: A 47-year-old male presented with weakness in his left arm upon awakening. Contrast-enhanced computed tomography and transesophageal echocardiography revealed a mobile pedunculated object suggestive of a thrombus arising from the ascending aorta and extending to the left common carotid artery. It was removed under hypothermic circulatory arrest and direct cannulation of the left carotid artery to avoid carotid thromboembolism. Histopathological examination revealed that the object was a thrombus. The patient had an uneventful postoperative course and was discharged 9 days after surgery. CONCLUSION: When a thrombus in the aortic arch extends to the neck arteries, direct cannulation of the neck arteries with selective cerebral perfusion via cervical incision is a useful technique.

Long-term outcomes following surgical repair of coronary artery fistula in adults.

BACKGROUND AND AIM OF THE STUDY: Coronary artery fistula (CAF) is a relatively rare cardiac anomaly. We investigated long-term outcomes following surgical repair of CAF in adults. METHODS: We retrospectively investigated 13 consecutive patients undergoing surgical repair of CAF in our institution between 2008 and 2019 (67.3 ± 10.4 years old, 38% male). CAF types were coronary artery-pulmonary artery fistula (77%), coronary artery-coronary sinus fistula (15%), and both (8%). CAFs originated from the left coronary artery (38%), right coronary artery (8%), and bilateral coronary arteries (38%). Pulmonary and systemic flow (Qp/Qs) was measured in seven patients (54%), with a mean value of 1.52. Seven patients underwent surgery for CAFs alone, and others simultaneously underwent surgery for comorbid cardiac diseases. RESULTS: All procedures were conducted under cardiopulmonary bypass. Surgical procedures were direct epicardial ligation of fistula (92%), direct closure of CAF through pulmonary artery incision (38%), direct closure of CAF through coronary sinus incision (8%), or patch closure of CAF through coronary artery incision (8%). Myocardial perfusion scintigraphy showed asymptomatic myocardial ischemia in the right coronary area after surgery in one patient. There were no deaths perioperatively or during follow-up (mean: 66.6 months). There were no coronary or other CAF-related events. CONCLUSIONS: Several anatomical variations in CAF were observed which coexist with cardiac disease. Long-term outcomes following surgical repair were satisfactory, and the concurrent intervention of CAFs during surgery for comorbid cardiac disease is useful to prevent future complications related CAFs in adults.

Impact of dialysis in patients undergoing bioprosthetic aortic valve replacement.

OBJECTIVES: To determine the incidence of bioprosthetic structural valve deterioration in dialysis patients undergoing aortic valve replacement compared to that in patients without dialysis. METHODS: This single-centre retrospective observational study included 1159 patients who underwent aortic valve replacement using bioprosthetic valves for aortic stenosis and/or regurgitation at our institution between 2007 and 2017 [patients with dialysis (group D, n = 134, 12%) or without dialysis (group N, n = 1025, 88%)]. To adjust for potential differences between groups in terms of initial preoperative characteristics or selection bias, a propensity score analysis was conducted. The final sample that was used in the comparison included 258 patients, as follows: 129 patients with dialysis (group D) and 129 patients without dialysis (group N). The cumulative incidences of all-cause death, cardiac death and moderate or severe structural valve deterioration were estimated using the Kaplan-Meier method. RESULTS: Operative mortality was significantly higher in group D than group N (9% vs 0%, P = 0.001). Kaplan-Meier analysis revealed that in group D, the incidence was significantly higher for all-cause death (P < 0.001, 50% vs 18% at 5 years), cardiac death (P = 0.001, 18% vs 5% at 5 years) and moderate or severe structural valve deterioration (P < 0.001, 29% vs 5% at 5 years) compared with group N. CONCLUSIONS: The incidence of structural valve deterioration in dialysis patients undergoing aortic valve replacement was higher than that in patients without dialysis. Bioprosthetic valves should be carefully selected in dialysis patients undergoing aortic valve replacement.

Communicating Syringomyelia.

BACKGROUND: Communicating syringomyelia can develop in association with hydrocephalus, with communication between syringomyelia and the fourth ventricle a representative neuroimaging finding. CASE DESCRIPTION: A 51-year-old woman presented with slowly progressive bladder dysfunction and scoliosis. She had a nonfunctioning cerebrospinal fluid shunt that had been placed after birth for neonatal hydrocephalus. Tetraventricular enlargement and a holocord syrinx were noted in neuroimaging findings, while phase contrast magnetic resonance imaging and ventriculography revealed communication between the syrinx and fourth ventricle via a dilated central canal. Placement of a de novo ventriculoperitoneal shunt led to collapse of the syringomyelia, though apparent improvement of clinical symptoms was not obtained. CONCLUSIONS: Communicating syringomyelia can develop as a late complication in patients with shunted hydrocephalus. In the majority of reported cases, shunt revision has been shown to be effective, though some cases require posterior fossa decompression and exploration.

The Impact of Post-Graduate Year of Primary Surgeon on Technical Performance Score in Tetralogy of Fallot Repair.

BACKGROUND: The aim of this study was to assess the impact of surgeon years of experience on clinical outcomes of tetralogy of Fallot (TOF) repair using technical performance score (TPS), and to investigate the possibility of safe operations by surgical trainees.Methods and Results:We assessed the cases of 159 consecutive patients who underwent TOF repair between 2001 and 2015. Thirteen different primary surgeons performed operations with 41 different first assistants. The primary surgeon and first assistant mean postgraduate years were 19.1±5.1 years (range, 5.7-31.6 years) and 11.2±6.3 years (range, 3.2-36.3 years), respectively. TPS was assigned using pre-discharge echocardiography based on original criteria. Logistic regression analysis was used to examine the factors associated with TPS. TPS could be scored for all patients, 16 of whom were graded as having optimal (10%), 119 as adequate (75%), and 24 as having inadequate (15%) TPS. None of the preoperative and perioperative variables affected TPS. Although neither the primary surgeon nor the first assistant postgraduate years was associated with TPS independently, total primary surgeon and first assistant postgraduate years correlated with TPS (OR, 1.07; 95% CI: 1.01-1.13, P=0.031). CONCLUSIONS: Primary surgeon postgraduate years was not associated with TPS for TOF repair. TOF repair can be performed adequately and safely by surgical trainees under the support of highly experienced supervisors.

Changes in Cognitive Function Scores After Cerebrospinal Fluid Tap Testing in Patients with Suspected Idiopathic Normal-Pressure Hydrocephalus.

BACKGROUND: In patients suspected of having idiopathic normal-pressure hydrocephalus (iNPH), improvement in impaired cognition is common after a diagnostic cerebrospinal fluid tap test (CSFTT). Measures used to evaluate cognitive function before and after a CSFTT include the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Trail Making Test (TMT). However, the time point at which cognitive function should be reevaluated after a CSFTT remains controversial. OBJECTIVE: To investigate differences in cognitive function 1 day and 1 week after a CSFTT (versus baseline) in patients with suspected iNPH. METHODS: This retrospective study, conducted between October 2012 and January 2017, involved 39 patients with suspected iNPH. We analyzed their MMSE, FAB, and TMT scores on tests conducted before and 1 day and 1 week after the CSFTT. RESULTS: Changes in MMSE scores were negligible 1 day after the CSFTT but began to appear 1 week later. Changes in FAB scores were observed from 1 day to 1 week after the CSFTT. Although no statistically significant differences in TMT scores were observed at either time point, the execution time for the test tended to be shorter on the day after the CSFTT. Changes in cognitive function were not associated with demographic or morphological parameters. More severe impairments at baseline, however, were associated with greater changes in cognitive function. CONCLUSIONS: Performing several reevaluations using each test may enable more accurate assessment of cognitive function in patients with suspected iNPH. Our results highlight the need for long-term follow-up, regardless of the severity of cognitive impairment.

Investigation and clinical applications of muscle strength change in cerebrospinal fluid tap test in cases of idiopathic normal pressure hydrocephalus: A retrospective study.

The cerebrospinal fluid tap test (CSFTT) is widely used to diagnose idiopathic normal pressure hydrocephalus (iNPH) and predict the therapeutic effectiveness of shunting. However, the ability to walk cannot be quantified for patients who are unable to walk. Therefore, we examined whether the iNPH diagnostic aid is possible using dynamometry, even for patients who are unable to walk. In this study, 45 patients underwent grip strength assessment, quadriceps strength assessment, 10-m walk test, and 3-m Timed Up and Go test before and after CSFTT. Our investigation of physical functions indicated that the CSFTT-positive group demonstrated significant improvements in grip and bilateral quadriceps muscle strength. The results of the receiver operating characteristic analysis indicated that leg muscle strength measurement reliability was high and that the area under the curve was 0.754-0.811. Our investigation of the clinically effective cutoff point for the rate of change indicated that it was 13.6% for right quadriceps muscle strength and 15.3% for left quadriceps muscle strength. Comparing CSFTT results in cases of iNPH with the observed rate of change in muscle strength can aid in the diagnosis of iNPH.

Mechanical ventilatory assistance may reduce dyspnea during walking especially in patients with impaired cardiopulmonary function early after cardiovascular surgery.

BACKGROUND: To determine which patients effectively respond to ventilatory assistance (VA) and to examine the factors influencing patient response in patients who underwent cardiovascular (CV) surgery. METHODS: We conducted the first walking session after surgery either with or without VA in a randomized order. The patients walked with 3cmH2O of inspiratory pressure support. We measured dyspnea and leg fatigue during initial walking either with or without VA by using a modified Borg scale. Ventilatory parameters were measured by mechanical ventilation before and immediately after walking. Lung function and maximal inspiratory pressure (MIP) were measured and chest radiographs were analyzed by the same cardiac surgeon on the same day as walking. RESULTS: From the total of 74 patients who underwent CV surgery, 56 patients were successively enrolled in the study. Thirty-five out of 56 patients had dyspnea and 18 patients (30% of the total patients) effectively responded to VA (responders). Minute ventilation/estimated maximum voluntary ventilation immediately after walking significantly decreased with VA, and MIP was lower in responders than in non-responders after surgery. The responders revealed greater pulmonary edema scores than non-responders. CONCLUSIONS: The findings of the present study suggest that VA may possibly facilitate successful mobilization early after CV surgery, especially in patients with impaired cardiopulmonary function.

[Perioperative management after non-cardiac surgery in patients with chronic kidney disease].

The number of patients with chronic kidney disease (CKD) continues to increase all over the world for the past ten years. It follows that we have more CKD patients with various complications who need perioperative management in Japan. Previous studies revealed that impaired renal function in preoperative period was the independent predictor of postoperative renal dysfunction. Safe comprehensive anesthetic management is required in order not to aggravate the preoperative CKD. In this review, we will take up some recent topics and novel concept in association with noncardiac surgery for the perioperative management of CKD patients.

Combination therapy of voriconazole and terbinafine for disseminated fusariosis: case report and literature review.

Fusarium spp. cause a broad spectrum of infection and are relatively resistant to most antifungal agents, leading to unfavorable prognosis, especially in immunocompromised patients. Several reports have shown synergism among amphotericin B, voriconazole (VRC), terbinafine (TRB), and other antifungal agents in vitro, but the most efficacious combination remains to be elucidated. We report the first case of disseminated Fusarium solani infection successfully treated by combination therapy of VRC and TRB accompanied by surgical resection of endocardial lesions. We also review 15 case reports of combination antifungal therapy for fusariosis and 6 case reports of Fusarium endocarditis.

[Successful treatment of the intracranial hemorrhage after the cardiac surgery for infective endocarditis].

We report an extremely rare case of a successful treatment of the intracranial hemorrhage after the cardiac surgery for infective endocarditis(IE). A 34-year-old woman was admitted to our hospital with a diagnosis of active IE due to Staphylococcus aureus, complicated with cerebral infarctions. Preoperative echocardiography showed mobile vegetations on both leaflets of the mitral valve with 15 and 6 mm diameters. Mitral valve repair was performed on hospital day 10. There were mobile vegetations on the A2 and P3. Five days after the cardiac surgery, brain magnetic resonance imaging(MRI) and angiography demonstrated intracranial hemorrhage due to the rupture of the intracranial aneurysm, which was urgently clipped. No neurological sequel has been noted since the successful treatment.

Development of a surgical procedure for biointegration of a newly designed orthodontic onplant.

AIM: An onplant is an orthodontic anchorage device fixed to the bone surface with osseointegration. Compared with implants, the onplant has fewer limitations regarding placement and is less invasive. The purpose of this study was to clarify the effect of bone-surface treatment and the fixing method of a newly designed smaller-sized onplant and establish a prospective surgical procedure for placement of the onplant. METHODS: Thirty-eight onplants were placed in six beagle dogs. The bone surface was planed where the cortical bone was thick and reducible (bone-planed). Where the cortical bone was thin and uneven, a filling was inserted in the space between the onplant and bone (filled). The onplant was fixed to the bone in one of two ways: using a membrane that covered the onplant and fixing the membrane with titanium pins (membrane-fixed) or fixing the onplant directly to the bone using the same titanium pins (pin-fixed). RESULTS: Twelve weeks later, all the onplants were osseointegrated. The bone-planed group showed significantly (P < .05) larger shear stress than the filled groups. In the bone-planed group, the pin-fixed group showed significantly (P < .05) larger shear stress than the membrane-fixed group. The shear stresses were considered strong enough to function in orthodontic treatment. CONCLUSION: The effect of the bone-surface treatment and the onplant-fixing method on the shear stress was clarified, and the findings in the present study may be useful for the improvement of surgical procedures for orthodontic onplants.

Ocular Circulation and Chronic Ocular Ischemic Syndrome before and after Carotid Artery Revascularization Surgery.

Background. We evaluated the effect of carotid revascularization surgery on ocular circulation and chronic ocular ischemic syndrome (OIS). Methods. We examined ninety patients with carotid artery stenosis (more than 50% stenosis) at its origin treated with carotid endarterectomy (N = 56) or carotid artery stenting (N = 34). Twenty-five patients (28%) complained of chronic OIS. Ocular circulation was examined before and after revascularization surgery using ophthalmic artery (OphAr) and central retinal artery (CRA) color Doppler flow imaging. Results. (1) Ocular circulation: preoperatively, the average OphAr peak systolic flow velocity (Vs) was 0.05 m/sec, and the average CRA Vs was 0.07 m/sec. At 1 week after surgery, the average OphAr Vs significantly increased to 0.32 (P < 0.05), and the average CRA Vs significantly increased to 0.11 m/sec (P < 0.05). These significant improvements were sustained throughout the three months of the followup. (2) OIS: during the follow-up period (mean: 3.6 years), 15 patients (60%) showed visual acuity improvement, and no patients complained of amaurosis fugax or worsening of the chronic OIS. Conclusion. Carotid revascularization surgery was effective in improving the ocular circulation, and it was also useful for the chronic OIS due to the carotid artery stenosis.

Diagnostic value of adenosine-induced left ventricular diastolic dysfunction for detecting coronary artery restenosis in patients undergoing stent implantation by Stress ECG-gated myocardial perfusion SPECT. A pilot study.

BACKGROUND: Usefulness of diastolic dysfunction after adenosine stress for detecting coronary stenosis has not been defined. The diagnostic accuracy of a combination of myocardial perfusion and diastolic function, as defined by prolongation of time to peak-filling rate (TTPF)/R-R and myocardial perfusion alone for the detection of coronary restenosis, was evaluated. METHODS AND RESULTS: We used rest (201)Tl/ adenosine stress (99m)Tc-tetrofosmin myocardial perfusion singlephoton emission computed tomography (SPECT) in 70 patients. Patients were divided into the following 4 groups: 20 patients with normal SPECT without stent (Control group), 20 patients showing normal SPECT without coronary restenosis (Group 1), 16 patients showing significant coronary restenosis and myocardial ischemia (Group 2a) and 14 patients showing significant coronary restenosis without myocardial ischemia (Group 2b). The TTPF, which was calculated by quantitative gated SPECT (QGS)/R-R, was not different between after stress and at rest in Control group (0.18±0.02 vs 0.19±0.04, P=NS). The TTPF/R-R after stress was significantly lower than that at rest in Group 1 (0.17±0.02 vs 0.18±0.03, P<0.05), but TTPF/R-R after stress was significantly higher than that at rest in Groups 2a and 2b (0.22±0.03 vs 0.16±0.03, P<0.001 in Group 2a and 0.19±0.02 vs 0.16±0.02, P<0.001 in Group 2b, respectively). Diagnostic accuracy improved from 72% to 92% when prolongation of TTPF/R-R was taken into account (P<0.001). CONCLUSIONS: Diastolic dysfunction after stress was an accurate marker for detecting significant restenosis following stent implantation.

Whole-heart magnetic resonance imaging of isolated subpulmonary stenosis accompanied by hypertrophic cardiomyopathy.

Isolated subvalvular pulmonary stenosis (ISPS) is a rare condition, and it is often accompanied by hypertrophic cardiomyopathy. However, diagnosis of ISPS is obscure because of difficulty in comprehension of three-dimensional cardiac anatomy. Whole-heart magnetic resonance imaging (MRI) is a new, totally non-invasive technique which allows not only depiction of the coronary artery system, but also three-dimensional comprehension of the cardiac structure. We describe a patient with ISPS associated with hypertrophic cardiomyopathy, in whom whole-heart MRI was useful to detect and evaluate the cause of ISPS.