High Shear Stress Reduces ERG Causing Endothelial-Mesenchymal Transition and Pulmonary Arterial Hypertension.

Pathological high shear stress (HSS, 100 dyn/cm 2 ) is generated in distal pulmonary arteries (PA) (100-500 µm) in congenital heart defects and in progressive PA hypertension (PAH) with inward remodeling and luminal narrowing. Human PA endothelial cells (PAEC) were subjected to HSS versus physiologic laminar shear stress (LSS, 15 dyn/cm 2 ). Endothelial-mesenchymal transition (EndMT), a feature of PAH not previously attributed to HSS, was observed. H3K27ac peaks containing motifs for an ETS-family transcription factor (ERG) were reduced, as was ERG-Krüppel-like factors (KLF)2/4 interaction and ERG expression. Reducing ERG by siRNA in PAEC during LSS caused EndMT; transfection of ERG in PAEC under HSS prevented EndMT. An aorto-caval shunt was preformed in mice to induce HSS and progressive PAH. Elevated PA pressure, EndMT and vascular remodeling were reduced by an adeno-associated vector that selectively replenished ERG in PAEC. Agents maintaining ERG in PAEC should overcome the adverse effect of HSS on progressive PAH.

Incidences and circumstances of falls among women following total hip arthroplasty on long-term follow-up.

BACKGROUND: Patients who undergo total hip arthroplasty have an increased risk of falls during the first postoperative year. However, it is unclear whether patients after total hip arthroplasty will continue to be at high risk of falls more than 1 year postoperatively. To better understand whether the risk of falls changes after a 1-year period, we investigated the incidences and circumstances of falls in women patients for 5 years after total hip arthroplasty. METHODS: This longitudinal prospective cohort study analyzed 65 women with severe hip osteoarthritis who underwent total hip arthroplasty. The incidences and circumstances of falls before total hip arthroplasty and at 1, 2, and 5 years postoperatively were investigated. We assessed the Harris Hip Score and evaluated hip pain and ambulatory ability using a self-administered questionnaire. RESULTS: The incidences of at least one fall were 30.8%, 26.2%, 23.1%, and 30.8% before and 1, 2, and 5 years after surgery, respectively. Among the circumstances of falls from pre-surgery to 5 years post-surgery, there was a significant difference in the direction of falls; however, there were no significant differences in the location, time, cause, and type of injury. Most falls occurred indoors by tripping or loss of balance during the daytime. Among the participants who had falls almost half sustained injuries, and approximately 10% of falls resulted in fractures each year. Although self-reported hip pain, ambulation, and the Harris Hip Score significantly improved in women after total hip arthroplasty compared to pre-surgery, there was no significant difference in the incidences of falls from 1 to 5 years post-surgery. CONCLUSION: Women who underwent total hip arthroplasty continued to have an increased risk of falls and fall-induced injuries for 5 years postoperatively. Preventive measures against falling to reduce fall-induced injuries in the long term are required for women after total hip arthroplasty.

Proton magnetic resonance spectroscopy assessment of neonatal brain metabolism during cardiopulmonary bypass surgery.

Here, we report on the development and performance of a robust 3-T single-voxel proton magnetic resonance spectroscopy (1 H MRS) experimental protocol and data analysis pipeline for quantifying brain metabolism during cardiopulmonary bypass (CPB) surgery in a neonatal porcine model, with the overall goal of elucidating primary mechanisms of brain injury associated with these procedures. The specific aims were to assess which metabolic processes can be reliably interrogated by 1 H MRS on a 3-T clinical scanner and to provide an initial assessment of brain metabolism during deep hypothermia cardiac arrest (DHCA) surgery and recovery. Fourteen neonatal pigs underwent CPB surgery while placed in a 3-T MRI scanner for 18, 28, and 37°C DHCA studies under hyperglycemic, euglycemic, and hypoglycemic conditions. Total imaging times, including baseline measurements, circulatory arrest (CA), and recovery averaged 3 h/animal, during which 30-40 single-voxel 1 H MRS spectra (sLASER pulse sequence, TR/TE = 2000/30 ms, 64 or 128 averages) were acquired from a 2.2-cc right midbrain voxel. 1 H MRS at 3 T was able to reliably quantify (1) anaerobic metabolism via depletion of brain glucose and the associated build-up of lactate during CA, (2) phosphocreatine (PCr) to creatine (Cr) conversion during CA and subsequent recovery upon reperfusion, (3) a robust increase in the glutamine-to-glutamate (Gln/Glu) ratio during the post-CA recovery period, and (4) a broadening of the water peak during CA. In vivo 1 H MRS at 3 T can reliably quantify subtle metabolic brain changes previously deemed challenging to interrogate, including brain glucose concentrations even under hypoglycemic conditions, ATP usage via the conversion of PCr to Cr, and differential changes in Glu and Gln. Observed metabolic changes during CPB surgery of a neonatal porcine model provide new insights into possible mechanisms for prevention of neuronal injury.

Effects of foam rolling on hip pain in patients with hip osteoarthritis: a retrospective propensity-matched cohort study.

BACKGROUND: Foam rolling is a self-applied massage using a foam roller that has gained popularity for treatment of muscle soreness. However, its efficacy for improving hip pain in patients with hip osteoarthritis remains unclear. OBJECTIVE: To investigate the effects of foam rolling on hip pain in patients with hip osteoarthritis. METHODS: In this retrospective propensity-matched cohort study, medical records of outpatients between January 2017 and March 2019 were reviewed. Of these, 115 patients with hip osteoarthritis were divided into foam rolling or non-foam rolling groups based on home exercises. Both groups were propensity-score matched (1:1) for age, sex, body mass index, Kellgren and Lawrence grade, and visual analog scale (VAS) of hip pain at baseline. The primary outcome was the hip pain-VAS. Effects of interventions on the hip pain-VAS were examined using a split-plot design variance analysis. RESULTS: After matching, both groups comprised 37 patients each. No significant differences were observed in baseline characteristics and outcome measurements between the matched groups. A statistically significant interaction was seen between the effects of time and group for hip pain-VAS (F [1, 72] = 31.874, interaction: P < .001, η2 = 0.307). Hip pain-VAS was improved more effectively in the foam rolling group than those in the non-foam rolling group (P < .001). Thirty-four (92%) patients in the foam rolling group, compared to 15 (41%) in the non-foam rolling group, showed a ≥ 32% (minimal clinically important difference) improvement in hip pain-VAS. CONCLUSION: These results suggested that foam rolling was an effective intervention for improving hip pain in patients with hip osteoarthritis.

Loss of antibodies to hepatitis E virus in organ transplant patients with hepatitis E.

AIM: Studies regarding changes in antibodies to hepatitis E virus (HEV) after HEV infection in organ transplant patients are limited. This study aimed to clarify HEV infection trends in organ transplant patients who contracted HEV using data from a previous Japanese nationwide survey. METHODS: This study was undertaken from 2012 to 2019. Among 4518 liver, heart, and kidney transplant patients, anti-HEV immunoglobulin G (IgG) antibodies were positive in 164; data were collected from 106 of these patients, who consented to participate in the study. In total, 32 liver transplant patients, seven heart transplant patients, and 67 kidney transplant patients from 16 institutions in Japan were examined for IgG, IgM, and IgM antibodies to HEV and the presence of HEV RNA in the serum. The χ2 -test was used to determine the relationship between the early and late postinfection groups in patients with anti-HEV IgG positive-to-negative conversion rates. The Mann-Whitney U-test was used to compare clinical factors. RESULTS: Anti-HEV IgG positive-to-negative conversion occurred in 25 (23.6%) of 106 organ transplant patients. Of eight patients with hepatitis E who tested positive for HEV RNA, one (14.0%) had anti-HEV IgG positive-to-negative conversion. Twenty-four (24.5%) of 98 patients negative for HEV RNA had anti-HEV IgG positive-to-negative conversion. CONCLUSIONS: This study revealed, for the first time, the changes in HEV antibodies in organ transplant patients. Loss of anti-HEV IgG could often occur unexpectedly in organ transplant patients with previous HEV infection.

Survival Outcomes of Two-Stage Intracardiac Repair in Large Ventricular Septal Defect and Trisomy 18.

BACKGROUND: Surgical management has not been encouraged in patients with trisomy 18 (T18) and congenital heart diseases due to poor survival. This study aimed to investigate (1) the appropriateness of palliative surgeries followed by intracardiac repair (ICR) (i.e., two-stage ICR) for patients with a large ventricular septal defect (VSD) and T18, and (2) its impact on their long-term outcomes. METHODS: Medical charts of patients with VSD and T18 who underwent two-stage ICR at the Japanese Red Cross Medical Center between January 2005 and December 2019 were retrospectively reviewed. Demographic data, timing, and types of palliative surgeries, information related to ICR, peri- and postoperative clinical information, postoperative survival, and cause of death were collected. The long-term prognosis of patients treated with two-stage ICR was compared with that of patients treated with primary ICR and palliative surgery without ICR. RESULTS: Overall, 18 (2 male, 16 female) patients underwent two-stage ICR. Pulmonary artery banding was the initial palliative surgery in all patients after a median duration of 19.5 (range 6-194) days of life. The median age and the mean body weight at the time of ICR were 18.2 (7.6-50.7) months and 6.0 ± 1.0 kg, respectively. The mean pulmonary artery pressure and pulmonary vascular resistance index before ICR were 19.1 ± 7.3 mmHg and 3.4 ± 2.0 U m2, respectively. Overall, 17/18 (94%) patients were discharged after ICR. Fourteen (78%) patients were alive during data collection. None of the patients died of cardiac insufficiency, and the median duration of survival was 46.3 (14.3-186.4) months since birth. Most patients required cardiac medications rather than pulmonary vasodilators at the last follow-up. During the study period, three patients underwent primary ICR, and 46 underwent palliative surgery without ICR. Of those who underwent primary ICR, two died in the hospital on the first and 48th day following ICR, and the third died 179 days after the ICR. The Log-rank test revealed a significantly longer survival for the patients treated with two-stage ICR compared with those treated with palliative surgery without ICR (P = 0.003). CONCLUSION: Two-stage ICR improves the long-term survival of patients with VSDs and T18. This safe surgical strategy can also prevent pulmonary hypertension in such patients.

Complete resection of a giant calcifying fibrous tumor of myocardial origin.

A calcifying fibrous tumor (CFT) is a rare, benign tumor that commonly develops in the internal viscera. It is histologically characterized by hyalinized collagenous tissue with calcifications and lymphoplasmacytic infiltrates. There have been few reports of CFTs occurring in the heart. and the therapeutic approach of such cases has not been well established; however, complete surgical resection appears to be the best treatment option for cardiac CFT, since this lesion can cause cardiac symptoms and recurrence has been recently noted. To our knowledge, this report describes the largest cardiac CFT for which complete surgical resection was successfully performed.

Plantar pressure distribution during standing in women with end-stage hip osteoarthritis.

BACKGROUND: Patients with hip osteoarthritis (OA) experience abnormal movement patterns and reduced loading of the affected leg. The plantar contacts the ground and receives force from the ground. Plantar pressure distribution may differ in patients with hip OA compared to healthy adults and may influence physical functioning in these patients. RESEARCH QUESTION: We investigated whether plantar pressure distribution during standing differed between patients with hip OA and healthy adults. We also analyzed the relationship between plantar pressure distribution and walking ability and the factors affecting plantar pressure distribution. METHODS: Maximum plantar pressure distribution during standing for 20 seconds was investigated in patients with hip OA (n = 62; OA group) and in healthy adults (n = 53; Control group). Statistical comparisons between these groups were made using Fisher's exact test and residual analysis. In the OA group, leg length discrepancy, range of hip extension, leg loading, knee extensor strength, and 10 m walking time were assessed; multiple linear regression and logistic regression analyses were used to examine the relationships between these factors and maximum plantar pressure distribution. RESULTS: Maximum plantar pressure distribution was different between the OA and control groups. In the OA group, maximum plantar pressure distribution was one of the significant predictors of 10 m walking time. Additionally, leg length discrepancy was a significant predictor of maximum plantar pressure distribution in this group. SIGNIFICANCE: During standing, the proportion of patients for whom the maximum plantar pressure region was the heel tended to be lower in the group with hip OA compared to the healthy adults. Plantar pressure distribution may have an importance for evaluating walking ability in patients with hip OA. Correcting leg length discrepancy and loading under the heel could adjust plantar pressure distribution in patients with hip OA.

Therapeutic targeting of mitochondrial ROS ameliorates murine model of volume overload cardiomyopathy.

Concomitant heart failure is associated with poor clinical outcome in dialysis patients. The arteriovenous shunt, created as vascular access for hemodialysis, increases ventricular volume-overload, predisposing patients to developing cardiac dysfunction. The integral function of mitochondrial respiration is critically important for the heart to cope with hemodynamic overload. The involvement, however, of mitochondrial activity or reactive oxygen species (ROS) in the pathogenesis of ventricular-overload-induced heart failure has not been fully elucidated. We herein report that disorganization of mitochondrial respiration increases mitochondrial ROS production in the volume-overloaded heart, leading to ventricular dysfunction. We adopted the murine arteriovenous fistula (AVF) model, which replicates the cardinal features of volume-overload-induced ventricular dysfunction. Enzymatic assays of cardiac mitochondria revealed that the activities of citrate synthase and NADH-quinone reductase (complex Ⅰ) were preserved in the AVF heart. In contrast, the activity of NADH oxidase supercomplex was significantly compromised, resulting in elevated ROS production. Importantly, the antioxidant N-acetylcysteine prevented the development of ventricular dilatation and cardiac dysfunction, suggesting a pathogenic role for ROS in dialysis-related cardiomyopathy. A cardioprotective effect was also observed in metformin-treated mice, illuminating its potential use in the management of heart failure complicating diabetic patients on dialysis.

Experiences With Aggressive Cardiac Rehabilitation in Pediatric Patients Receiving Mechanical Circulatory Supports.

Although some patients with fulminant myocarditis can be rescued owing to the improvements in mechanical circulatory support therapy, there are few reports providing evidence of cardiac rehabilitation during mechanical circulatory supports, particularly among pediatric patients. We treated two pediatric patients who underwent aggressive cardiac rehabilitation during mechanical support. Five days after the initiation of extracorporeal membrane oxygenation therapy aggressive cardiac rehabilitation was started in a 10-year-old girl with fulminant myocarditis. After explantation of the device, she was discharged on postoperative day 23. A 6-year-old girl with fulminant myocarditis started receiving cardiac rehabilitation two days after the initiation of an extracorporeal left ventricular assist device, despite having hemiplegia due to a recent broad stroke. She achieved an exercise capacity of supported walking for 280 meters after 127 days of cardiac rehabilitation and then went abroad to undergo heart transplantation when she was in the best physical condition possible. Early initiation of cardiac rehabilitation may be safe and effective for successful pediatric mechanical circulatory support therapy; this acts as a bridge to explantation or heart transplantation.

[DeBakey type 2 Aortic Dissection Failed to Diagnose by Enhanced Computed Tomography;Report of a Case].

An 81-year-old woman presented with dyspnea and chest pain. A plain chest X-ray revealed widening of the mediastinum and a contrast-enhanced chest computed tomography showed dilatation of the ascending aorta without any specific findings of aortic dissection. Transesophageal echocardiography revealed severe aortic regurgitation (AR). We planned an aortic valve replacement on the 34th day after admission because of the severe AR. During the operation, we found an entry in the intima of the ascending aorta 5 mm above the aortic valve and she was diagnosed with DeBakey type II aortic dissection. Therefore, we decided to perform Bentall's operation and the operation was successful.

Hybrid stenting therapy for dysphagia aortica with Rokitansky's diverticulum concomitant with thoracic aortic aneurysm.

An 87-year old man with a past medical history of a descending aortic aneurysm for 20 years presented with progressive dysphagia and aspiration pneumonia. Computed tomography angiography demonstrated the impending rupture of the thoracic aortic aneurysm (TAA) and endoscopic examinations revealed the extrinsic compression of the middle oesophagus with Rokitansky's diverticulum proximal to the compression area. He underwent urgent thoracic endovascular aortic aneurysm repair, followed by oesophageal stenting. The patient's symptoms immediately improved, and the postoperative period was uneventful. This report is the first to describe a hybrid stenting therapy for dysphagia aortica with Rokitansky's diverticulum concomitant with a TAA.

A rare case of axillobifemoral bypass graft infection caused by Helicobacter cinaedi.

Helicobacter cinaedi infection is rarely encountered in nonimmunocompromised patients. We report the case of an 85-year-old man who presented with axillobifemoral bypass graft infection caused by Helicobacter cinaedi. The patient was not immunocompromised. We successfully treated him by iliac stenting of the native iliac artery, with near-total removal of the infected graft. At present, 48 months later, the patient is doing well at home, with no evidence of infection. To the best of our knowledge, this is the first report of infection of a prosthetic graft caused by Helicobacter cinaedi.

[Bridge to recovery with ventricular assist device support for eosinophilic myocarditis].

A 39-year-old man initially presented with cough, fever, and shortness of breath. His symptom got worse gradually, and he was admitted to a nearby hospital. Echocardiography revealed a dilated left ventricle and severe left ventricular dysfunction. Despite inotropic and intra-aortic balloon pumping (IABP) support, the patient developed cardiogenic shock with fever of unknown origin, followed by multi-organ failure. A left-ventricular assist device (LVAD) was implanted. Pathologic evaluation showed an extensive eosinophil-rich inflammatory infiltrate, and consistent with the diagnosis of eosinophilic myocarditis. After high-dose steroid administration, the cardiac function improved and explantation of the LVAD was successfully performed. The patient was discharged and remains well at the 24-month follow-up.

Coronary artery aneurysm occurring very late after drug-eluting stent implantation.

An 82-year old woman presented with chest pain and was diagnosed as having acute myocardial infarction. Coronary angiography (CAG) showed 90% stenosis in the proximal left anterior descending artery (LAD). The patient underwent percutaneous coronary intervention using a sirolimus-eluting stent (SES). A repeat CAG performed 6 months after SES implantation revealed no problems. Eight years later, the patient presented with recurrent angina. CAG showed severe stenosis of the SES with a large aneurysm. We performed off-pump coronary artery bypass grafting without ligation or plication of the LAD, but with the application of fibrin glue to the coronary artery aneurysm. The postoperative course was uneventful. The mechanism responsible for the occurrence of coronary artery aneurysms occurring late after drug-eluting stent implantation remains unclear, and the treatment strategy remains controversial. Herein, we discuss a surgical treatment for this rare entity.

Conservative therapy as a primary treatment for spontaneous isolated dissection of the superior mesenteric artery.

BACKGROUND: Spontaneous isolated dissection of the superior mesenteric artery (SIDSMA) is a rare and potentially fatal disease. Several therapeutic options are available, including conservative therapy, endovascular repair, and open surgery. Herein, we report our experiences in the treatment of SIDSMA. METHODS: Between February 2009 and June 2013, 17 patients were diagnosed as having SIDSMA. We retrospectively reviewed and analyzed their clinical characteristics, medical history, risk factors, symptoms, diagnostic imaging modality, treatment, and outcome. The lesions were categorized according to the modified Sakamoto's classification. If no evidence of bowel necrosis or arterial rupture was present in the patients with symptomatic SIDSMA, we first performed conservative therapy, even if the patients had abdominal pain. RESULTS: The subjects included 15 men and 2 women, with a median age of 62.8 years. Eight patients were symptomatic and 9 were asymptomatic. Conservative therapy included the use of antithrombotic agents in 3 patients but not in 5 patients. During the follow-up period (mean, 21.1 months), all the patients were discharged without any significant complications, and none of the patients showed the progression of the dissection on follow-up computed tomography angiography examinations. CONCLUSIONS: Conservative therapy without antithrombotic agents should be the primary treatment for SIDSMA. Endovascular repair for SIDSMA is associated with several risks, thus the procedure might occasionally be useful and necessary.

Stanford type A aortic dissection after urgent prosthetic valve replacement: case reports.

Occurrence of acute aortic dissection after aortic valve replacement is rare, however, it is associated with high mortality and morbidity rates. We report two Asian cases in which acute aortic dissection occurred after urgent aortic valve replacement for infective endocarditis. Successful graft replacement was carried out with preservation of the prosthetic valves in both cases. Our experience with these cases suggests that, even in urgent or emergent situations, surgical intervention for associated aortic dilatation should be considered when aortic valve replacement is performed.

[Concomitant off-pump coronary artery bypass and left lower lobectomy for lung cancer;report of a case].

A 58-year-old man had an abnormal shadow in the left lower lobe on his computed tomography, and also had stenosis of the coronary arteries. Preoperative coronary angiography revealed severe stenosis of right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex branch(LCx). The diagnosis of lung cancer was made by transbronchial lung biopsy. Initially, we scheduled to undergo surgery of both the heart and lung in 2stage operation. However, before surgery, the infection of cavity was caused by tumor growing, so we performed the surgery in 1stage operation. Off-pump coronary artery bypass and left lower lobectomy with lymph node dissection was concomitantly performed. The postoperative course was uneventful. He was discharged after confirming the patent bypass grafting on the 13th postoperative day. Histopathological diagnosis was squamous cell carcinoma without lymph node metastasis. Lung cancer and ischemic heart disease can be surgically treated simultaneously, benefitting selected patients.