Unique mechanism of mitral valve prolapse in atrial septal defect: Three-dimensional insights into mitral complex geometry using real-time transesophageal echocardiography.

BACKGROUND: Mitral valve prolapse (MVP) is often identified in patients with atrial septal defect (ASD), which occasionally require surgical intervention at the time of ASD closure or even long after the surgery. Ventricular and valvular geometric characteristics in preoperative ASD patients were evaluated by three-dimensional (3D) transesophageal echocardiography. METHODS AND RESULTS: Mitral valve (MV) complex geometry was quantitatively measured by 3D transesophageal echocardiography in 11 ASD patients (Qp/Qs > 1.5) and 11 controls. The ASD group had a significantly larger indexed prolapse volume and height, with a larger anterior mitral leaflet than controls (0.53 [0.33-0.75] vs 0.057 [0.027-0.11] mL/m2 , P = .0001; 2.89 [2.13-3.50] vs 0.92 [0.48-1.32] mm/m2 , P < .0001; 391.3 [346.4-445.1] vs 295.3 (281.9-330.0) mm2 /m2 , P = .011, respectively). The right ventricular (RV)-to-left ventricular (LV) end-systolic diameter ratio was larger in the ASD group than in the control group (1.34 [0.96-1.45] vs 0.85 [0.75-0.88], P = .004). The indexed inter-papillary muscle distance (IPMD) was significantly shorter in the ASD group than in the control group (7.77 [6.55-8.24] vs 9.71 [8.64-10.8] mm/m2 , P = .011). IPMD was significantly correlated with the RV-LV end-systolic diameter ratio (r = -.70, P = .017). CONCLUSIONS: Inward shift of the LV papillary muscle tips due to RV dilation may be a major mechanism of MV prolapse in ASD. At the same time, positive remodeling of the anterior leaflet was observed in the ASD group, which may compensate for the billowing leaflet geometry to maintain effective coaptation. Three-dimensional assessment of the MV apparatus geometry will help to further understand perioperative mitral regurgitation in patients with ASD.

Predictors of Recurrent In-Stent Restenosis After Paclitaxel-Coated Balloon Angioplasty.

BACKGROUND: Although paclitaxel-coated balloon (PCB) angioplasty is an effective procedure for in-stent restenosis (ISR) after coronary stenting, recurrent ISR after PCB angioplasty still occurs. The aim of this study was to evaluate the predictors of recurrent ISR after PCB angioplasty for ISR.Methods and Results:A total of 157 ISR lesions treated with PCB angioplasty from January 2014 to May 2015 were retrospectively examined. Recurrent ISR was judged on 6-month follow-up angiography. Clinical, angiographic and procedural parameters were evaluated as possible predictors of recurrent ISR. Recurrent ISR occurred in 13.9% of lesions after PCB angioplasty. On multivariate analysis the following independent predictors of recurrent ISR were identified: (1) smaller acute gain after initial ballooning (OR, 3.06; 95% CI: 1.08-8.71; P=0.04); (2) geographic mismatch between PCB position and initial ballooning (OR, 5.59; 95% CI: 1.64-19.1; P=0.006); and (3) use of percutaneous transluminal coronary rotational atherectomy (PTCRA) at primary percutaneous coronary intervention (PCI; OR, 5.53; 95% CI: 1.89-16.2; P=0.002). CONCLUSIONS: Optimal expansion at initial ballooning before PCB angioplasty and careful positioning of PCB are important technical tips to prevent recurrent ISR after PCB angioplasty. Recurrent ISR occurred more frequently in severely calcified lesions that required PTCRA at primary PCI.

Clinical Implications of Additional Pedal Artery Angioplasty in Critical Limb Ischemia Patients With Infrapopliteal and Pedal Artery Disease.

PURPOSE: To evaluate the clinical implications of additional pedal artery angioplasty (PAA) for patients with critical limb ischemia (CLI). METHODS: Twenty-nine patients (mean age 77.8±8.6 years; 21 men) with CLI (32 limbs) presenting with de novo infrapopliteal and pedal artery (Kawarada type 2/3) disease were reviewed. The need for PAA was based on the existence of sufficient wound blush (WB) around the target wounds after conventional above-the-ankle revascularization. Fourteen patients with insufficient WB in 14 limbs received additional PAA, while 15 patients with sufficient WB in 18 limbs did not. The groups were compared for overall survival, limb salvage, and amputation-free survival within 1 year after the procedure. The wound healing rate, time to wound healing, and freedom from reintervention rate were also evaluated. RESULT: The success rate of additional PAA was 93% (13/14). All limbs with successful PAA achieved sufficient WB (13/13). Despite insufficient WB before the additional PAA, overall survival (86% vs 73%, p=0.350), limb salvage (93% vs 83%, p=0.400), amputation-free survival (79% vs 53%, p=0.102), and freedom from reintervention (64% vs 73%, p=0.668) rates were similar in both groups. Furthermore, the wound healing rate (93% vs 60%, p=0.05) was higher and time to wound healing (86.0±18.7 vs 152.0±60.2 days, p=0.05) was shorter in the patients who received PAA. CONCLUSION: Additional PAA might improve the WB and clinical outcomes (especially speed and extent of wound healing) in patients with CLI attributed to infrapopliteal and pedal artery disease.

Clinical evaluation of high mobility group box 1 protein in Legionella pneumophila pneumonia.

High mobility group box 1 (HMGB-1) protein is involved in acute lung injury due to various etiologies. We evaluated HMGB-1 levels in sera and bronchoalveolar fluids in patients with pneumonia caused by Legionella pneumophila. Levels of HMGB-1 in the sera of patients with L. pneumophila pneumonia (32 cases) and control subjects (24 cases) were determined. Serum HMGB-1 levels in Legionella pneumonia were similar to those of the control subjects. No significant correlation between HMGB-1 levels and other biomarkers and the outcome of cases was observed. In contrast, HMGB-1 levels, as well as interferon-γ, in bronchoalveolar (BA) fluids from severe L. pneumophila pneumonia (7 cases) were significantly higher than those in the sera of identical patients. HMGB-1 levels in BA fluids were relatively higher in pneumonia cases with ALI than those without ALI. Our findings suggest that intra-pulmonary HMGB-1 may be involved in the pathophysiology of pneumonia caused by L. pneumophila.

The bending technique of a scoring balloon Aperta NSE leading to successful crossing into stents.

A new scoring balloon Aperta NSE has 3 longitudinal nylon elements mounted on the non-compliant balloon surface. Although a high-pressure balloon is usually used as a post-dilation balloon in an implanted stent, it is difficult to pass into the stents because a balloon gets caught in stents in some cases. Aperta NSE has some grooves at elements; therefore, this balloon is bendable and shaped in an arc. The bent scoring balloon could eliminate interference between the balloon and the stents or lesions. Moreover, the point where the tip of the balloon contacts could change. As a result, it helps to improve crossability of this balloon. The bending technique of a scoring balloon Aperta NSE could lead to successful crossing into stents or complex lesions.

Transcatheter aortic valve implantation with a balloon-expandable prosthesis in a patient with single coronary artery: a case report.

Background: Single coronary artery is a rare coronary artery anomaly with an incidence of <0.03%. The coexistence of coronary artery anomalies with severe aortic stenosis is extremely rare. Due to the singularity of the coronary artery orifice, the most concerning risk of transcatheter aortic valve implantation (TAVI) in such patients is coronary occlusion, which may very well be life-threatening. Case summary: An 83-year-old female complaining of chest pain was referred to our hospital for severe aortic stenosis. The multi-slice computed tomography showed a congenital single coronary artery originating from the right sinus of Valsalva. The left coronary artery branched off of the right coronary artery, and passed between the aorta and main pulmonary artery. The heart team of the hospital decided to perform TAVI via femoral artery with a balloon-expandable prosthesis, with coronary angioplasty devices on standby in case of coronary occlusion. The TAVI procedure was performed successfully without coronary occlusion. Discussion: Although there have been some case reports of TAVI in patients with single coronary artery, little is known about the safety of TAVI in such cases, and which device (such as the balloon-expandable or the self-expandable prosthesis) is preferable. From this particular case, and accumulation of past and various TAVI experience, the balloon-expandable prosthesis can be a safe device choice in carefully selected patients with coronary artery anomalies.

Left atrial appendage orifice dimensions in Japanese atrial fibrillation population measured by multiplane transesophageal echocardiography.

BACKGROUND: Successful implantation of the WATCHMAN device requires an accurate understanding of left atrial appendage (LAA) anatomy and orifice dimensions. Racial differences are observed in LAA size when comparing Asians with non-Asians. METHODS: A total of 170 patients (123 male, 67.4 ± 9.2 years) with paroxysmal or persistent atrial fibrillation (AF) underwent transesophageal echocardiography before catheter ablation or cardioversion (September 2018 to September 2019). As per the recommendations of the WATCHMAN device, the maximal LAA ostial diameters were measured at multiplane angles of 0°, 45°, 90°, and 135°. RESULTS: The majority of patients (121/170, 71%) had an LAA orifice size within 17-25 mm. Fifteen (8.8%) patients had undersized (< 17 mm) and eight (0.5%) had oversized (> 31 mm) LAA. One patient in this population had no LAA. LAA size was significantly larger in patients with persistent AF than in those with paroxysmal AF (23.3 ± 4.2 mm vs. 20.0 ± 3.0 mm, p < 0.001) and in male patients than in female patients (22.4 ± 4.2 vs. 20.9 ± 3.7 mm, p = 0.03). LAA orifice dimension was significantly correlated with CHADS2 score, the left atrial volume (LAV), E/e', and the left ventricular ejection fraction. Persistent AF, body mass index, and LAV were independently associated with LAA orifice dimension in multivariate analysis. CONCLUSION: This study demonstrated the distribution of LAA orifice dimension in the Japanese AF patients. This finding should be used as a reference to understand the racial characteristics of LAA size for the WATCHMAN procedure.

Efficacy and Safety of Sitafloxacin in Treating Low-risk Febrile Neutropenia in Patients with Lung Cancer.

Introduction: Febrile episodes in patients with cancer and chemotherapy-induced neutropenia can be life-threatening and generally require prompt administration of broad-spectrum antimicrobials. However, little evidence exists for treating patients with solid tumors and febrile neutropenia (FN) with oral antimicrobials. Methods: In this prospective study, we aimed to determine the efficacy and safety of sitafloxacin (STFX) for treating FN in lung cancer patients. In this prospective study, low-risk FN patients with lung cancer received STFX. The primary endpoint was response rate, defined as 5 sequential days of absence of fever without adverse events. The study was registered as UMIN000010911. Results: As a result, STFX was administered to 26 patients, all of whom survived during its administration. Of the 26, 14 completed primary endpoint (53.85%). The low response rate was attributed to occurrence of fevers of unknown cause rather than failure of FN treatment. Only two patients received antibacterial agents other than STFX. If response rate omitted absence of fever and been defined only as recovery from FN without changing microbial agents or serious complications, the response rate would have been 91.67%. Adverse events occurred in eight patients, none of which were serious. Conclusions: In conclusion, STFX might be used to treat low-risk FN in patients with lung cancer; however, a more detailed study will be required in future.

Hepatocyte growth factor levels in Legionella pneumonia: a retrospective study.

BACKGROUND: Hepatocyte growth factor (HGF) is known to be involved in the resolution of pulmonary inflammation and repair of acute lung injury. Legionella pneumonia is sometimes complicated by acute lung injury. Our study aimed to determine the role of serum HGF levels in Legionella pneumonia. METHODS: Sera from patients with Legionella pneumonia (42 cases), other bacterial pneumonia (33 cases), pulmonary tuberculosis (19 cases), and normal controls (29 cases) were collected. The serum HGF levels for each serum sample were determined by sandwich ELISA. Clinical and laboratory data were collected by reviewing the medical charts. RESULTS: Serum HGF levels were higher in patients with Legionella pneumonia than in those with other bacterial pneumonia, pulmonary tuberculosis, and controls. The HGF levels were compared with white blood cell counts, C-reactive protein, Alanine amino-transferase, and lactate dehydrogenase (LDH). The HGF levels were correlated to serum LDH levels. Moreover, serum HGF levels were significantly higher in non-survivors than in survivors. CONCLUSIONS: HGF levels increased in severer pneumonia caused by Legionella, suggesting that HGF might play a significant role in the Legionella pneumonia.

Combination chemotherapy with carboplatin and paclitaxel for advanced thymic cancer.

OBJECTIVE: Thymic carcinoma is a rare cancer of the thymus, different from thymoma in respect of its malignant nature, and no standard chemotherapy for this cancer has been established yet. METHODS: We conducted a retrospective review of the efficacy of combination chemotherapy with carboplatin (an area under the curve of 6) and paclitaxel (200 mg/m(2)) in 16 patients with histologically or cytologically proven thymic carcinoma, Masaoka Stage IVa/IVb or post-operative recurrent disease. RESULTS: There were 13 males and 3 females, with a median (range) age of 56 (38-73) years. Squamous cell carcinoma was the most common (n= 12), followed by undifferentiated carcinoma (n= 2) and others (n= 2). Four, nine and three patients had Stage IVa, IVb and post-operative recurrent disease, respectively. Two and four patients showed complete and partial responses, respectively, representing a response rate (95% confidence interval) of 37.5 (15.2-64.6)%. The median (95% confidence interval) progression-free and overall survivals in the 16 patients were 8.6 (1.8-15.3) and 49.4 (30.1-68.8) months, respectively. CONCLUSIONS: Combination therapy with carboplatin and paclitaxel yielded an objective response in about one-third of the patients with advanced thymic carcinoma.

Impact of osteogenic activity on degenerative aortic valve disease in patients with osteoporotic hip fracture.

BACKGROUND: Previous studies have proposed that osteogenic and apoptotic processes of valve interstitial cells contribute to the mineralization and then calcification of the aortic valve. Osteoblast-like cells subsequently mediate calcification of the aortic valve as part of a highly regulated process analogous to skeletal bone formation. The objective of this study was to evaluate the pathogenesis of the sclerotic/calcific changes in the aortic valve from histological and biological findings, and investigate the role of osteoblasts in the calcified pathway of aortic stenosis. METHODS: Preoperative echocardiography in 550 consecutive patients with osteoporotic hip fracture were retrospectively examined (475 females, mean 25th-75th, 89 [85-93] years). One hundred sixteen patients were under medical treatment with anti-osteoporosis drugs. We evaluated the prevalence and degree of degenerative changes in the aortic valve and examined the associations of bone turnover biomarkers N-terminal pro-peptide of type 1 collagen (P1NP) and serum tartrate-resistant acid phosphatase (TRACP-5b) with degenerative calcific changes in the aortic valve. RESULTS: Of 550 patients, 112 patients (20.9%) showed no leaflet calcification; 296 (53.8%), 1 leaflet calcification; and 142 (25.8%), 2 ≥ leaflets calcification. Significant (peak velocity ≥ 3.0m/s) Aortic stenosis was found in 43 patients (7.8%). In patients who were not taking anti-osteoporotic drugs, P1NP was higher in the 2 ≥ leaflets calcification group than in the other groups (p < 0.01). TRACP-5b was not significantly different among the three groups (p = 0.15). CONCLUSIONS: Degenerative changes in the aortic valve were related to bone biomarker activation in osteoporotic hip fracture patients.

Impact of frailty on outcomes in elderly patients with acute myocardial infarction who undergo percutaneous coronary intervention.

AIMS: Frailty is characterized by reduced biological reserves and weakened resistance to stressors, and is common in older adults. This study evaluated the prognostic implications of frailty at hospitalization in elderly patients with acute myocardial infarction (AMI) who undergo percutaneous coronary intervention (PCI). METHODS AND RESULTS: We prospectively analysed 546 AMI patients aged ≥80 years undergoing PCI from 2009 to 2017. Frailty was classified based on impairment in walking (unassisted, assisted, and wheelchair/non-ambulatory), cognition (normal, mildly impaired, moderately to severely impaired), and basic activities of daily living. Impairment in each domain was scored as 0, 1, or 2, and patients were categorized into the following three groups based on total score: no frailty (0), mild frailty (1-2), moderate-to-severe frailty (≥3). The median follow-up period was 589 days. Of the 546 patients, 27.8% were frail (mild or moderate-to-severe), and this proportion significantly increased to 35.5% at discharge (P < 0.001). Compared to non-frail patients, frail patients were older, less likely to be male, and had a higher rate of advanced Killip class. Major bleeding (no frailty, 9.6%; mild frailty, 16.9%; moderate-to-severe frailty, 31.8%; P < 0.001) and in-hospital mortality (no frailty, 8.4%; mild frailty, 15.4%; moderate-to-severe frailty, 27.3%; P < 0.001) increased as frailty worsened. After adjusting for confounders, frailty was independently associated with higher mid-term all-cause mortality (hazard ratio, 1.81; 95% confidence interval, 1.23-2.65; P = 0.002). CONCLUSION: Frailty in AMI patients aged ≥80 years undergoing PCI was associated with major bleeding, in-hospital death, and mid-term mortality.

A long-term survivor keeping in a complete response without treatment after pemetrexed maintenance therapy for advanced non-squamous non-small cell lung cancer.

Pemetrexed has significant efficacy for some non-squamous non-small cell lung cancer cases, as demonstrated in the current case. For those patients, pemetrexed administration should be carefully considered.

[Secondary organizing pneumonia after pneumococcal pneumonia].

A 28-year-old woman was admitted to our hospital complaining of a 7-day chilly sensation with fever. She was given a diagnosis of pneumococcal pneumonia because of infiltration on chest radiography, sputum gram staining and testing positive for a pneumococcal urinary antigen. A 10-day course of antibiotics showed improvements in symptoms and infiltration. However, her X-ray film revealed severe volume loss in the right lung. Organizing pneumonia was diagnosed with lymphocytosis in BALF and Masson bodies upon TBLB examination. Administration of prednisolone obtained rapid improvement of the volume loss. This case was interesting, showing an organizing tendency in the acute-stage pneumococcal pneumonia.

Hypertrophic pulmonary osteoarthropathy due to lung cancer: A case report and literature review.

Hypertrophic pulmonary osteoarthropathy (HPOA) is a rare paraneoplastic syndrome. Our literature review shows the location of arthralgia and existence of edema are referable information for the differential diagnosis in paraneoplastic arthralgia.

[Tuberculosis of the tongue initially suspected of tongue cancer: a case report--including the search for recent 16 cases in Japan].

A 56-year-old man, having no particular past history, was admitted to our hospital, with a 9-month history of painful ulcerated lesion of the tongue and a 6-month history of productive cough. A physical examination revealed swelling of his cervical lymph nodes, and a chest roentgenogram on admission showed cavities in the both upper lung fields and nodular shadows over the both lung fields. He was initially suspected of having both cancer of the tongue and pulmonary tuberculosis, but finally diagnosed as secondary tuberculosis of the tongue due to sputum smear-positive pulmonary tuberculosis by biopsy of the tongue and sputum examination. He was treated with isoniazid, rifampicin, ethambutol and pyrazinamide, and his pain and ulcerated lesion of the tongue rapidly improved. Due to our search for recent 16 cases of tuberculosis of the tongue in Japan, we found that the patients of tuberculosis of the tongue were more likely to have concurrently sputum smear-positive pulmonary tuberculosis. In some cases, the delay in diagnosis was seen. These cases suggest that refractory ulcerated cases of the tongue should be subjected to the biopsy and examination for acid fast bacilli of the tongue with suspicion of tuberculosis of the tongue, and then a chest roentgenogram with suspicion of pulmonary tuberculosis.

[Obesity and hypertension].

Obesity is one of the cardiovascular disease' s risk factors, at the same time to affect the development of hypertension and other risk factors. Recently, physiology or pathophysiology functions of adipocyte have been elucidated. And the mechanism of development hypertension has been investigated from adipocyte standpoints. In particular, knowledge of cytokine by adipocyte and insulin resistance has been clear. On the other hand, as the population of obesity is on the increases by the change of our living habits, hypertensive prevalence increases in particularly middle-aged men. Hypertension with obesity is often refractory, and it is poor prognosis. We have to develop an effective therapy in hypertension with obese subjects and have to spread it.

Radiation-induced sarcoma in a 10-year survivor with stage IV EGFR-mutated lung adenocarcinoma.

A 70-year-old Japanese man with stage IV EGFR-mutated lung adenocarcinoma complained of right mild back pain. The patient had been heavily treated with several cytotoxic or molecular targeted agents for 10 years and received a palliative radiation therapy of 2nd sacral vertebra 5 years ago. Computed tomography showed the abnormal lesion in right iliopsoas muscle. A pathological examination confirmed undifferentiated pleomorphic sarcoma, consistent with the diagnosis of radiation-induced sarcoma (RIS). Since RIS is a rare late-onset complication of radiation therapy, to our knowledge, this is the first report of RIS that was associated with advanced lung cancer and detected after palliative radiation therapy. The careful long-term follow-up is thus necessary even after palliative radiation therapy and we have to be aware of the existence of RIS.

Legionella pneumophila infection induces programmed cell death, caspase activation, and release of high-mobility group box 1 protein in A549 alveolar epithelial cells: inhibition by methyl prednisolone.

BACKGROUND: Legionella pneumophila pneumonia often exacerbates acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Apoptosis of alveolar epithelial cells is considered to play an important role in the pathogenesis of ALI and ARDS. In this study, we investigated the precise mechanism by which A549 alveolar epithelial cells induced by L. pneumophila undergo apoptosis. We also studied the effect of methyl prednisolone on apoptosis in these cells. METHODS: Nuclear deoxyribonucleic acid (DNA) fragmentation and caspase activation in L. pneumophila-infected A549 alveolar epithelial cells were assessed using the terminal deoxyribonucleotidyl transferase-mediated triphosphate (dUTP)-biotin nick end labeling method (TUNEL method) and colorimetric caspase activity assays. The virulent L. pneumophila strain AA100jm and the avirulent dotO mutant were used and compared in this study. In addition, we investigated whether methyl prednisolone has any influence on nuclear DNA fragmentation and caspase activation in A549 alveolar epithelial cells infected with L. pneumophila. RESULTS: The virulent strain of L. pneumophila grew within A549 alveolar epithelial cells and induced subsequent cell death in a dose-dependent manner. The avirulent strain dotO mutant showed no such effect. The virulent strains of L. pneumophila induced DNA fragmentation (shown by TUNEL staining) and activation of caspases 3, 8, 9, and 1 in A549 cells, while the avirulent strain did not. High-mobility group box 1 (HMGB1) protein was released from A549 cells infected with virulent Legionella. Methyl prednisolone (53.4 muM) did not influence the intracellular growth of L. pneumophila within alveolar epithelial cells, but affected DNA fragmentation and caspase activation of infected A549 cells. CONCLUSION: Infection of A549 alveolar epithelial cells with L. pneumophila caused programmed cell death, activation of various caspases, and release of HMGB1. The dot/icm system, a major virulence factor of L. pneumophila, is involved in the effects we measured in alveolar epithelial cells. Methyl prednisolone may modulate the interaction of Legionella and these cells.

Incidence of hypertension in individuals with abdominal obesity in a rural Japanese population: the Tanno and Sobetsu study.

Although abdominal obesity (AO) assessed by waist circumference (WC) is an important component of the metabolic syndrome (MetS), the usefulness of AO as a predictor of hypertension (HT) is not known. In this study, we investigated the incidence of HT in residents of two rural communities in Japan. The subjects were 187 men and 209 women selected from 712 residents who had undergone medical examinations in the towns of Tanno and Sobetsu, Hokkaido, in 1994 and 2002. Participants with HT in 1994 were excluded. Participants with AO were determined according to the WC criteria in the Japanese definition of MetS (> or = 85 cm for men, > or = 90 cm for women). The participants were divided into two groups: a non-AO group and an AO group. We compared the incidence of HT between the two groups and found a significantly higher incidence in the AO group. The results of logistic regression analysis showed that the relative risk of developing HT in individuals with AO was 2.33 (p = 0.017; 95% confidence interval [CI], 1.17-4.63) and that the risk per 1-cm increase in WC from 1994 to 2002 was 1.06 (p = 0.003; 95% CI, 1.02-1.10), both adjusted for several confounding factors. The results of this study suggest that, to prevent HT in Japanese, it is important to manage abdominal obesity and to monitor WC in individuals with or without abdominal obesity.