Concomitant aortic valve replacement, mitral valve replacement, and coronary artery bypass grafting for aortic stenosis and mitral regurgitation in a patient with relapsing polychondritis.

Relapsing polychondritis is a rare multi-system disease characterized by inflammation in cartilaginous structures and other connective tissues. Cardiovascular complications occur in 10-51% of the patients. We report a case of concomitant aortic valve replacement, mitral valve replacement, and coronary artery bypass grafting in a patient with relapsing polychondritis. A 71-year-old female with relapsing polychondritis on prednisolone (5 mg/day) for 15 years presented at our hospital for further evaluation of valvular disease. Severe aortic stenosis and severe mitral regurgitation were diagnosed. We performed aortic and mitral valve replacement. During surgery, we found connective tissue surrounding the intima of the sinus of Valsalva and stenosis of the right coronary artery ostium, which was not noted on preoperative coronary angiography. We removed the tissue and performed bypass grafting to the right coronary artery. Postoperative recovery was uneventful, and she was discharged 27 days after surgery.

Correction to: Concomitant aortic valve replacement, mitral valve replacement, and coronary artery bypass grafting for aortic stenosis and mitral regurgitation in a patient with relapsing polychondritis.

In the original publication of the article, the figures were published in wrong order.

Interplay between prior knowledge and communication mode on teaching effectiveness: Interpersonal neural synchronization as a neural marker.

Teacher-student interaction allows students to combine prior knowledge with new information to develop new knowledge. It is widely understood that both communication mode and students' knowledge state contribute to the teaching effectiveness (i.e., higher students' scores), but the nature of the interplay of these factors and the underlying neural mechanism remain unknown. In the current study, we manipulated the communication modes (face-to-face [FTF] communication mode/computer-mediated communication [CMC] mode) and prior knowledge states (with vs. without) when teacher-student dyads participated in a teaching task. Using functional near-infrared spectroscopy, the brain activities of both the teacher and student in the dyads were recorded simultaneously. After teaching, perceived teacher-student interaction and teaching effectiveness were assessed. The behavioral results demonstrated that, during teaching with prior knowledge, FTF communication improved students' academic performance, as compared with CMC. Conversely, no such effect was found for teaching without prior knowledge. Accordingly, higher task-related interpersonal neural synchronization (INS) in the left prefrontal cortex (PFC) was found in the FTF teaching condition with prior knowledge. Such INS mediated the relationship between perceived interaction and students' test scores. Furthermore, the cumulative INS in the left PFC could predict the teaching effectiveness early in the teaching process (around 25-35 s into the teaching task) only in FTF teaching with prior knowledge. These findings provide insight into how the interplay between the communication mode and students' knowledge state affects teaching effectiveness. Moreover, our findings suggest that INS could be a possible neuromarker for dynamic evaluation of teacher-student interaction and teaching effectiveness.

Mitral valve repair versus replacement with preservation of the entire subvalvular apparatus.

OBJECTIVE: This study aimed to evaluate the outcomes of mitral valve (MV) repair versus MV replacement with preservation of the entire subvalvular apparatus. METHODS: We retrospectively searched our dedicated in-hospital database for patients who underwent MV surgery between 2012 and 2017. RESULTS: A total of 82 patients were divided into a group that underwent MV replacement (n = 35) and a group that underwent MV repair (n = 47). Patients undergoing MV replacement were significantly older (p < 0.01). Mortality at 30 days was not significantly different [MV replacement: n = 1 (2.9%), MV repair: n = 0 (0%); p = 0.43]. The single case of 30-day mortality after MV replacement was due to acute aortic dissection. The total cohort did not show significant differences in long-term survival (p = 0.07). There were no cardiac-related deaths in this cohort. Postoperative left ventricular end-diastolic diameter (MV replacement: 45.4 ± 6.2 mm, MV repair: 45.6 ± 5.8 mm; p = 0.89), left ventricular end-systolic diameter (MV replacement: 29.6 ± 7.1 mm, MV repair: 29.4 ± 5.2 mm; p = 0.89), and ejection fraction (MV replacement: 59.2 ± 11.4%, MV repair: 62.0 ± 6.8%; p = 0.17) were not significantly different. CONCLUSIONS: This study found that MV replacement had operative mortality, long-term survival, and complication rates similar to those of MV repair. There were no cardiac-related deaths in this cohort. MV replacement with preservation of the entire subvalvular apparatus does not seem to be inferior to MV repair.

Protective effect of eicosapentaenoic acid on insulin resistance in hyperlipidemic patients and on the postoperative course of cardiac surgery patients: the possible involvement of adiponectin.

Accumulated studies have shown that ω-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) have protective roles against inflammatory responses such as hyperlipidemia, diabetes mellitus (DM) and cardiovascular diseases. Here we examined the effects of administering EPA to hyperlipidemic patients and other patients undergoing cardiac surgery to determine whether this treatment would increase plasma EPA levels and to clarify the association between EPA treatment and adiponectin production in hyperlipidemic patients. We also assessed the effect of preoperative EPA administration on postoperative adverse events such as postoperative atrial fibrillation (POAF) and postoperative infection in the cardiac surgery patients. The EPA administration significantly increased the serum EPA concentrations in both patient populations (p＜0.001). In the hyperlipidemic patients, the EPA administration significantly increased plasma adiponectin levels (p＜0.05), accompanied by a decrease in insulin resistance designated by the HOMA-IR (homeostasis model assessment of insulin resistance) score (p＜0.05) and Hs-CRP (high sensitivity C-reactive protein) value (p＜0.05). In the cardiac surgery patients, no significant effect of EPA on cardiac adverse events such as POAF was observed. However, our results clearly demonstrated that both the neutrophil-to-lymphocyte ratio and the 2nd-line antibiotic requirement in the EPA group were significantly decreased compared to the untreated control group (p＜0.05). We suggest that EPA administration may exert anti-inflammatory effects in patients with hyperlipidemia and in those undergoing cardiac surgery, possibly through an increase in plasma adiponectin levels.

Feasibility of cisplatin/5-fluorouracil and panitumumab in Japanese patients with squamous cell carcinoma of the head and neck.

OBJECTIVE: In Japan, cisplatin/5-fluorouracil 80/800 (cisplatin 80 mg/m2, 5-fluorouracil 800 mg/m2) is widely used to treat recurrent/metastatic squamous cell carcinoma of the head and neck, whereas cisplatin/5-fluorouracil 100/1000 (1000 mg/m2/24 h by continuous intravenous infusion on Days 1-4 plus cisplatin 100 mg/m2 on Day 1 in 3-week cycles) is the standard treatment in Europe and North America. METHODS: We prospectively evaluated the feasibility of cisplatin/5-fluorouracil 100/1000 in Japanese patients enrolled in the global Phase 3 study of panitumumab 9 mg/kg combined with cisplatin/5-fluorouracil 100/1000 (Arm 1) versus cisplatin/5-fluorouracil 100/1000 alone (Arm 2). RESULTS: Twenty Japanese patients were enrolled and received treatment (Arm 1, n=13; Arm 2, n=7). Grade 3/4 adverse events included neutropenia, hypomagnesemia, stomatitis, hyponatremia, paronychia, febrile neutropenia, decreased appetite and hypokalemia. There were no fatal adverse events. Median overall survival was not estimable in Arm 1 and 15.4 months in Arm 2. Median progression-free survival was 6.9 months in Arm 1 and 5.7 months in Arm 2. The median number of infusions (cycles) of cisplatin was 5 in Arm 1 and 4 in Arm 2; the median number of infusions (cycles) of 5-fluorouracil was 6 in both arms. The mean administered dose for cisplatin was 93.6 mg/m2 in Arm 1 and 97.2 mg/m2 in Arm 2, and 3732.6 and 3880 mg/m2 in Arm 1 and Arm 2, respectively, for 5-fluorouracil. CONCLUSIONS: These results suggested that cisplatin/5-fluorouracil 100/1000 was feasible for recurrent/metastatic squamous cell carcinoma of the head and neck in Japanese patients.

[Coronary Artery Bypass Grafting (CABG) and simultaneous cardiac resynchronization therapy in a patient with left ventricular noncompaction repeating heart failure].

Noncompaction of the left ventricular myocardium (NCLV) is a rare congenital cardiomyopathy resulting from an arrest in normal endomyocardial embryogenesis, and has been known as a disease of infants. However, some cases of NCLV in adults have been recently reported. We experienced an adult NCLV case repeating heart failure, and controlled it by surgery. The patient was 75-year-old man with NCLV and he had repeated heart failure and hospitalization. His heart failure had been barely control by infusion of human atrial natriuretic peptide (hANP). Coronary angiography revealed double vessel disease( #2 100%, #6 90).We performed coronary artery bypass grafting(CABG) with intraoperative cardiac resynchronization therapy. The heart failure was dramatically improved and the patient was discharged on foot 32 days after operation. However, careful observation of cardiac function is vital because of the possibility of progression to heart failure of NCLV.

Dopaminergic control of long-term depression/long-term potentiation threshold in prefrontal cortex.

Long-term memory in the prefrontal cortex is a necessary component of adaptive executive control and is strongly modulated by dopamine. However, the functional significance of this dopaminergic modulation remains elusive. In vitro experimental results on dopamine-dependent shaping of prefrontal long-term plasticity often appear inconsistent and, altogether, draw a complicated picture. It is also generally difficult to relate these findings to in vivo observations given strong differences between the two experimental conditions. This study presents a unified view of the functional role of dopamine in the prefrontal cortex by framing it within the Bienenstock-Cooper-Munro theory of cortical plasticity. We investigate dopaminergic modulation of long-term plasticity through a multicompartment Hodgkin-Huxley model of a prefrontal pyramidal neuron. Long-term synaptic plasticity in the model is governed by a calcium- and dopamine-dependent learning rule, in which dopamine exerts its action via D1 and D2 dopamine receptors in a concentration-dependent manner. Our results support a novel function of dopamine in the prefrontal cortex, namely that it controls the synaptic modification threshold between long-term depression and potentiation in pyramidal neurons. The proposed theoretical framework explains a wide range of experimental results and provides a link between in vitro and in vivo studies of dopaminergic plasticity modulation. It also suggests that dopamine may constitute a new player in metaplastic and homeostatic processes in the prefrontal cortex.

[Combined surgical and endovascular treatment( hybrid-procedure) of thoracoabdominal dissecting aneurysm].

A 50-year-old man was admitted because of enlargement in diameter of the descending thoracoabdominal aorta. Seven years previously, he had undergone Bentall operation and graft replacement of the aortic arch due to an acute dissecting aneurysm, and he had also received graft replacement of the descending aorta due to a rupture of dissecting aneurysm 2 years before. The surgical stress of conventional repair under left lateral thoracotomy and laparotomy was considered to be excessive, and the 3-dimensional computed tomography (3D-CT) image revealed the reconstruction of intercostals artery was difficult. Hence, extra-anatomic bypasses were created to perfuse the visceral and renal vessels, and endovascular thoracic stent-grafts were deployed into the false lumen, because of the severe narrowing of the true lumen( hybrid-procedure). The postoperative course was uneventful and the patient was discharged on postoperative 30 days. Hybrid-procedure of aortic aneurysm is feasible, and may be an alternative to standard open procedures in high-risk patients and emergency cases.

Phase 1 study of ganitumab (AMG 479), a fully human monoclonal antibody against the insulin-like growth factor receptor type I (IGF1R), in Japanese patients with advanced solid tumors.

PURPOSE: This study was to investigate the safety and tolerability of ganitumab in Japanese patients with advanced solid tumors. METHODS: Patients were enrolled into 1 of 3 dose cohorts (6, 12, or 20 mg/kg) of single-agent ganitumab administered intravenously every 2 weeks. Dose-limiting toxicity (DLT) was assessed for the first 28 days. The primary objectives were to assess the safety, tolerability, and pharmacokinetics (PK) of ganitumab in Japanese patients with advanced solid tumors. An exploratory pharmacodynamic analysis was done to investigate the relationship between exposure and changes in the level of circulating factors in IGF1R pathway (IGFBP-3 and total IGF-1). RESULTS: Nineteen patients with ECOG performance status 0-1 (6 in cohort 1 and 3, 7 in cohort 2) received at least 1 dose of ganitumab. Median age was 58.0 years. Tumor types included: breast (4), gastric (3), rectal (2), NSCLC (2), thymic (2), and other cancers (6). No DLTs were observed. The most common grade ≥3 adverse events were neutropenia (21 %), leukopenia (16 %) and lymphopenia (11 %). There was a trend of dose-dependency on severity of thrombocytopenia, but not on that of neutropenia. No neutralizing anti-ganitumab antibodies were detected during this study. Dose-linearity on PK of ganitumab was indicated in the dose range. Tumor response was assessed for 19 patients. Stable disease as best response was reported in 7 patients. CONCLUSIONS: Ganitumab up to 20 mg/kg was tolerable in Japanese patients with advanced solid tumors. The safety and PK profiles were similar to those previously observed in non-Japanese patients.

Tumor KRAS status predicts responsiveness to panitumumab in Japanese patients with metastatic colorectal cancer.

OBJECTIVE: Mutation status of the KRAS gene in tumors has been shown to be a predictive biomarker of response to anti-epidermal growth factor receptor antibody therapy in patients with metastatic colorectal cancer. This retrospective analysis examined the association between efficacy and safety of the fully human anti-epidermal growth factor receptor antibody panitumumab and KRAS mutation status in Japanese metastatic colorectal cancer patients using data from two clinical trials with adherence to good clinical practices. METHODS: An exploratory, integrated analysis of data from KRAS evaluable patients enrolled in a Phase 1 study (Study 20040192) and a Phase 2 study (Study 20050216) was performed. Paraffin-embedded tumor samples were analyzed for KRAS status. Primary efficacy endpoint of this analysis was objective tumor response per modified response evaluation criteria in solid tumors; a key secondary endpoint was progression-free survival. Safety endpoints included incidence of adverse events. RESULTS: Tumor samples with known KRAS status were available from 8 of 13 (62%) metastatic colorectal cancer patients in the Phase 1 study and 16 of 53 patients (30%) in the Phase 2 study. Overall, 14 (58%) patients had wild-type KRAS tumors and 10 (42%) patients had mutated KRAS tumors. Four (17%) patients had a partial response; all responders had tumors with wild-type KRAS. Results of all secondary efficacy endpoints also favored patients with wild-type KRAS. Treatment-related adverse events were predominantly mild to moderate and skin related, and were similar between patients with tumors with wild-type and mutated KRAS in this small patient population. CONCLUSIONS: Mutated KRAS status in tumors of Japanese patients with metastatic colorectal cancer is associated with lack of response to panitumumab therapy.

Safety and pharmacokinetics of panitumumab in Japanese patients with advanced solid tumors.

BACKGROUND: Panitumumab is a fully human, monoclonal antibody against the epidermal growth factor receptor. Previous studies in non-Japanese patients with solid tumors showed that panitumumab exhibited nonlinear pharmacokinetics, was well tolerated (skin toxicities were the most common treatment-related adverse events), and had antitumor activity in some patients. This open-label, phase 1 study investigated panitumumab safety and pharmacokinetics in Japanese patients. METHODS: Japanese patients with advanced solid tumors were enrolled into one of three sequential panitumumab dose cohorts (cohort 1, 2.5 mg/kg weekly; cohort 2, 6.0 mg/kg every 2 weeks; and cohort 3, 9.0 mg/kg every 3 weeks) and received panitumumab until disease progression or drug intolerability. Safety endpoints included the incidence of adverse events, changes in laboratory values, and the appearance of anti-panitumumab antibodies. Serial pharmacokinetic samples were collected after the first and third doses of panitumumab. Tumors were assessed at week 8 and every 8 weeks thereafter. RESULTS: Eighteen patients (6 per cohort) were enrolled. No dose-limiting toxicities, investigator-reported infusion reactions, or deaths occurred. Seven patients had grade-3/4 adverse events; fatigue and anorexia were most common. The most common skin toxicities were rash and acneiform dermatitis. No neutralizing anti-panitumumab antibodies were detected. Panitumumab exhibited nonlinear pharmacokinetics, and antitumor activity was observed in 31% (4/13) of the patients with colorectal cancer. CONCLUSION: In Japanese patients with solid tumors, panitumumab was well tolerated, demonstrated pharmacokinetic and safety profiles similar to those observed previously in non-Japanese patients, and exhibited encouraging antitumor activity in patients with colorectal cancer.

Preoperative oral administration of pentoxifylline ameliorates respiratory index after cardiopulmonary bypass through decreased production of IL-6.

Activation of inflammatory response during cardiopulmonary bypass (CPB) may lead to considerable post-operative mortality. Recently, pentoxifylline (PTX), a methylxanthine derivative, has been reported to be effective in inhibiting proinflammatory cytokine production. This study aimed to determine whether or not PTX prevented CPB-induced systemic inflammatory response syndrome (SIRS) in patients undergoing cardiovascular surgery. Thirty adult patients were randomly separated into 2 experimental groups and 1 control group of 10 patients each. The experimental group received peroral PTX administration (Group 1: 600 mg/day, Group 2: 900 mg/day), while the control group did not. In Group 1 and Group 2, PTX administration was started on preoperative day 5 and continued for 5 days. Serum levels of PTX and IL-6 were measured just before and at 4 h after CPB using HPLC and ELISA, respectively. Respiratory index (RI) before and at 4 h after CPB was calculated, and serum levels of C-reactive protein (CRP) and fibrinogen on postoperative day 1 were also determined. There were no significant differences in age, body weight, sex, surgical procedures, CPB time, haemodynamics or risk factors among the 3 groups. Serum IL-6 level and RI index after CPB in Group 2 were significantly decreased compared with those in Group 1 and the control group. These results, therefore, suggested that preoperative daily administration of 900 mg/day PTX contributed to the attenuation of CPB-induced SIRS and had a beneficial effect on the postoperative course after cardiovascular surgery.

Staged repair of a thoracoabdominal aortic aneurysm with mesenteric ischemia using the reversed elephant trunk technique.

Improvements in surgical techniques, and adjuncts for spinal cord protection and perioperative care have resulted in decreased morbidity and mortality in repair of thoracoabdominal aortic aneurysm (TAAA). However the surgical treatment of TAAA of extent II is still associated with high mortality, especially in patients with preoperative co-morbidities. We report a successful staged repair of extent II TAAA using the reversed elephant trunk technique for a patient with ischemic colitis.