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.

Modulation of hippocampus-prefrontal cortex synaptic transmission and disruption of executive cognitive functions by MK-801.

Noncompetitive N-methyl-d-aspartate receptor antagonists such as phencyclidine and MK-801 are known to impair cognitive function in rodents and humans, and serve as a useful tool to study the cellular basis for pathogenesis of schizophrenia cognitive symptoms. In the present study, we tested in rats the effect of MK-801 on ventral hippocampus (HPC)-medial prefrontal cortex (mPFC) synaptic transmission and the performance in 2 cognitive tasks. We found that single injection of MK-801 (0.1 mg/kg) induced gradual and long-lasting increases of the HPC-mPFC response, which shares the common expression mechanisms with long-term potentiation (LTP). But unlike LTP, its induction required no enhanced or synchronized synaptic inputs, suggesting aberrant characteristics. In parallel, rats injected with MK-801 showed impairments of mPFC-dependent cognitive flexibility and HPC-mPFC pathway-dependent spatial working memory. The effects of MK-801 on HPC-mPFC responses and spatial working memory decayed in parallel within 24 h. Moreover, the therapeutically important subtype 2/3 metabotropic glutamate receptor agonist LY379268, which blocked MK-801-induced potentiation, ameliorated the MK-801-induced impairment of spatial working memory. Our results show a novel form of use-independent long-lasting potentiation in HPC-mPFC pathway induced by MK-801, which is associated with impairment of HPC-mPFC projection-dependent cognitive function.

Inhibition of dopamine transporter activity impairs synaptic depression in rat prefrontal cortex through over-stimulation of D1 receptors.

In rat prefrontal cortex (PFC), long-term depression induced by low-frequency single stimuli has never been studied. Combined with the well-documented involvement of dopamine transporters (DATs) in the regulation of PFC-dependent cognitive processes, it is important to test whether this form of plasticity can be modulated by DAT activity in the PFC. Here, we show first that prolonged 3-Hz stimuli successfully induced synaptic depression in rat PFC slices whose induction depended on endogenous stimulation of D1-like and D2-like receptors and the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). This depression was found to be significantly impaired by selective inhibition of the DAT by GBR12909 (1-200 nM) or GBR12935 (100 nM). The excess amount of extracellular dopamine caused by DAT inhibition acted critically on D1-like receptors to impair depression. Furthermore, this impairment by GBR12 909 was cancelled by the allosteric-positive mGluR5 modulator CDPPB, the drug known to reverse hyperdopaminergia-induced abnormal PFC activity, and the associated cognitive disturbances. Finally, these induction, impairment, and restoration of synaptic depression were correlated by an inverted-U shape manner with the phosphorylation level of ERK1/2. We suggest that abnormal increases of the extracellular dopamine level by DAT inhibition impair synaptic depression in the PFC through over-stimulation of D1-like receptors.

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.

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.

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.

Post-stress Social Interaction and 3-Cyano-N-(1,3-Diphenyl-1H-Pyrazol-5-yl) Benzamide Treatment Attenuate Depressive-like Behavior Induced by Repeated Social Defeat Stress.

Persistent stress increases the probability for developing depression significantly thereafter. Repeated social defeat stress is a widely used model to investigate depressive-like behavior in preclinical models. Hence, the repeated social defeat stress model provided an ideal animal model, through which the hypotheses of prevention and treatment can be investigated. We have successfully induced depressive-like behavior for male C57BL/6J mice with this model. Here, we reported that certain level of during-stress social interactions with single female or multiple male peer(s) exerted a positive role in preventing the development of depressive-like behavior induced by repeated social defeat stress. Our data suggested that the stress-susceptible mice may benefit from positive social interaction, which reduces the chance for depressive-like behavior development. Since numerous studies indicate that the metabotropic glutamate receptor 5 (mGluR5) plays an important role in various cognitive functions, we further investigate the treatment effect of 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) on the depressive-like behavior induced by repeated social defeat stress. Most importantly, robust anti-depressant effects have been achieved through modulating the mGluR5 function. We found that single oral dose administration of CDPPB (20 mg/kg), to some extent, alleviated the social avoidance behaviors for the stress-susceptible mice. Our data implies that the CDPPB, a positive allosteric modulator of mGluR5, is a promising anti-depressant candidate with limited side effect.

[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.

[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.

Modulation of cortical activity by spherical blur and its correlation with retinal defocus.

Cortical activity, as recorded via electroencephalography, has been linked to the refractive error of an individual. It is however unclear which optical metric modulates this response. Here, we measured simultaneously the brain activity and the retinal defocus of a visual stimulus perceived through several values of spherical blur. We found that, contrary to the existing literature on the topic, the cortical response as a function of the overcorrections follows a sigmoidal shape rather than the classical bell shape, with the inflection point corresponding to the subjective refraction and to the stimulus being in focus on the retina. However, surprisingly, the amplitude of the cortical response does not seem to be a good indicator of how much the stimulus is in or out of focus on the retina. Nonetheless, the defocus is not equivalent to the retinal image quality, nor is an absolute predictor of the visual performance of an individual. Simulations of the retinal image quality seem to be a powerful tool to predict the modulation of the cortical response with the refractive error.

Early postnatal stress alters extracellular signal-regulated kinase signaling in the corticolimbic system modulating emotional circuitry in adult rats.

The present study elucidated whether early life stress alters the extracellular signal-regulated kinase (ERK) pathway that underlies fear retrieval and fear extinction based on a contextual fear conditioning paradigm, using a juvenile stress model. Levels of phospho-ERK (pERK), the active form of ERK, increased after fear retrieval in the hippocampal CA1 region but not in the medial prefrontal cortex (mPFC). ERK activation in the CA1 following fear retrieval was not observed in adult rats who received aversive footshock (FS) stimuli during the second postnatal period (2wFS), which exhibited low levels of freezing. In fear extinction, pERK levels in the CA1 were increased by repeated extinction trials, but they were not altered after extinction retrieval. In contrast, pERK levels in the mPFC did not change during extinction training, but were enhanced after extinction retrieval. These findings were compatible in part with electrophysiological data showing that synaptic transmission in the CA1 field and mPFC was enhanced during extinction training and extinction retrieval, respectively. ERK activation in the CA1 and mPFC associated with extinction processes did not occur in rats that received FS stimuli during the third postnatal period (3wFS), which exhibited sustained freezing behavior. The repressed ERK signaling and extinction deficit observed in the 3wFS group were ameliorated by treatment with the partial N-methyl-D-aspartate receptor agonist D-cycloserine. These findings suggest that early postnatal stress induced the downregulation of ERK signaling in distinct brain regions through region-specific regulation, which may lead to increased behavioral abnormalities or emotional vulnerabilities in adulthood.

Phase-dependent synaptic changes in the hippocampal CA1 field underlying extinction processes in freely moving rats.

Recent studies focus on the functional significance of a novel form of synaptic plasticity, low-frequency stimulation (LFS)-induced synaptic potentiation in the hippocampal CA1 area. In the present study, we elucidated dynamic changes in synaptic function in the CA1 field during extinction processes associated with context-dependent fear memory in freely moving rats, with a focus on LFS-induced synaptic plasticity. Synaptic transmission in the CA1 field was transiently depressed during each extinction trial, but synaptic efficacy was gradually enhanced by repeated extinction trials, accompanied by decreases in freezing. On the day following the extinction training, synaptic transmission did not show further changes during extinction retrieval, suggesting that the hippocampal synaptic transmission that underlies extinction processes changes in a phase-dependent manner. The synaptic potentiation produced by extinction training was mimicked by synaptic changes induced by LFS (0.5 Hz) in the group that previously received footshock conditioning. Furthermore, the expression of freezing during re-exposure to footshock box was significantly reduced in the LFS application group in a manner similar to the extinction group. These results suggest that LFS-induced synaptic plasticity may be associated with the extinction processes that underlie context-dependent fear memory. This hypothesis was supported by the fact that synaptic potentiation induced by extinction training did not occur in a juvenile stress model that exhibited extinction deficits. Given the similarity between these electrophysiological and behavioral data, LFS-induced synaptic plasticity may be related to extinction learning, with some aspects of neuronal oscillations, during the acquisition and/or consolidation of extinction memory.

Maternal deprivation induces deficits in temporal memory and cognitive flexibility and exaggerates synaptic plasticity in the rat medial prefrontal cortex.

Early life adverse events can lead to structural and functional impairments in the prefrontal cortex (PFC). Here, we investigated whether maternal deprivation (MD) alters PFC-dependent executive functions, neurons and astrocytes number and synaptic plasticity in adult male Long-Evans rats. The deprivation protocol consisted of a daily separation of newborn Long-Evans pups from their mothers and littermates 3h/day postnatal day 1-14. Cognitive performances were assessed in adulthood using the temporal order memory task (TMT) and the attentional set-shifting task (ASST) that principally implicates the PFC and the Morris water maze task (WMT) that does not essentially rely on the PFC. The neurons and astrocytes of the prelimbic (PrL) area of the medial PFC (mPFC) were immunolabelled respectively with anti-NeuN and anti-GFAP antibodies and quantified by stereology. The field potentials evoked by electrical stimulation of ventral hippocampus (ventral HPC) were recorded in vivo in the PrL area. In adulthood, MD produced cognitive deficits in two PFC-dependent tasks, the TMT and ASST, but not in the WMT. In parallel, MD induced in the prelimbic area of the medial PFC an upregulation of long-term potentiation (LTP), without any change in the number of neurons and astrocytes. We provide evidence that MD leads in adults to an alteration of the cognitive abilities dependent on the PFC, and to an exaggerated synaptic plasticity in this region. We suggest that this latter phenomenon may contribute to the impairments in the cognitive tasks.

Long-term memory, synaptic plasticity and dopamine in rodent medial prefrontal cortex: Role in executive functions.

Mnemonic functions, supporting rodent behavior in complex tasks, include both long-term and (short-term) working memory components. While working memory is thought to rely on persistent activity states in an active neural network, long-term memory and synaptic plasticity contribute to the formation of the underlying synaptic structure, determining the range of possible states. Whereas, the implication of working memory in executive functions, mediated by the prefrontal cortex (PFC) in primates and rodents, has been extensively studied, the contribution of long-term memory component to these tasks received little attention. This review summarizes available experimental data and theoretical work concerning cellular mechanisms of synaptic plasticity in the medial region of rodent PFC and the link between plasticity, memory and behavior in PFC-dependent tasks. A special attention is devoted to unique properties of dopaminergic modulation of prefrontal synaptic plasticity and its contribution to executive functions.

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.

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.

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.

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.

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.

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.