[Supra-annular Mitral Valve Replacement Using a Composite Valve for an Infant with Acute Rupture of Chordae Tendineae].

Acute rupture of the chordae tendineae of the mitral valve could lead to severe mitral regurgitation and circulatory collapse in infants. Mitral valve replacement may be often challenging because of the valve-annulus size mismatch in small infants when mitral valve repair cannot be accomplished. We present an infant with acute massive rupture of the chordae tendineae of the mitral valve who successfully underwent supra-annular mitral valve replacement using the short composite valve of an expanded polytetrafluoroethylene( ePTFE) graft and a mechanical valve. His mechanical valve has been functioning without complications such as thrombosis and pulmonary venous obstruction for 20 months after surgery. This technique could be helpful even infants with acute rupture of the chordae tendineae of the mitral valve whose left atrium may not be dilated.

A Case of Successful Biventricular Repair of the Transposition of the Great Arteries with a Coronary Anomaly Associated with an Atrioventricular Septal Defect.

The transposition of the great arteries (TGA) associated with a complete atrioventricular septal defect is a rare and serious congenital cardiac anomaly. In this report, we describe the successful biventricular repair of a TGA with a complete atrioventricular septal defect in an infant. Due to the low body weight of the patient and a complex coronary pattern anomaly, an arterial switch operation was executed, with the Mee procedure and pulmonary arterial banding as initial palliative measures when the infant was 22 days old and weighed 2.5 kg. Subsequently, atrioventricular septal defect repair using the modified one-patch method was performed when the patient was 1.3 years old and weighed 8.8 kg. Remarkably, the postoperative course of the patient demonstrated no notable incidents. To our knowledge, this is the first time a two-stage strategy was applied to repair these complex defects, presenting a promising approach for managing similar cases in future medical practice.

[Successful Thoracic Endovascular Aortic Repair in a Patient with Mid-aortic Syndrome:Report of a Case].

We report a case of thoracic endovascular aortic repair (TEVAR) for mid-aortic syndrome, which is characterized by a segmental narrowing of the aorta, in a 71-year-old man who presented with intermittent claudication. Contrast-enhanced computed tomography (CT) showed segmental stenosis of the descending aorta, for which TEVAR was performed. The ankle-branchial index increased after surgery, and the dorsalis pedis arterial pulses became palpable bilaterally. The patient was discharged on postoperative day 14 without any complication. At present, four years after surgery, he is in good condition with improved renal function, requiring no hospitalization for the treatment of heart failure.

Emergent option in complicated acute type B aortic dissection.

Man in his 30s was diagnosed with type B acute aortic dissection with malperfusion syndrome. Emergent endovascular therapy assisted by intravascular ultrasound was performed due to the unavailability of the neighbourhood cardiovascular surgeons and stored stent grafts. Stenting at the dissected superior mesenteric artery resolved the malperfusion syndrome. Acute aortic dissection complicated by malperfusion syndrome warrants rapid diagnosis and appropriate treatment. Endovascular therapy could be the most promptly accessible and effective strategy in certain situations. Intravascular ultrasound is also crucial for proper wiring and stenting.

The effect of aortic arch replacement on pulse wave velocity after surgery.

OBJECTIVES: The purpose of this study was to investigate the changes in pulse wave velocity (PWV) after aortic arch repair and to evaluate possible perioperative factors associated with an increase in PWV. METHODS: Eighty-nine patients with preoperative and postoperative PWV measurements who underwent surgical treatment for true aortic arch aneurysm were included in the study. The patients were treated by prosthetic graft replacement with or without the frozen elephant trunk technique or by hybrid surgery with a stent graft. Changes in PWV and perioperative factors were evaluated. RESULTS: Fifty-one patients were treated by prosthetic graft replacement; 22 patients were treated with the frozen elephant trunk procedure; and 16 patients were treated by hybrid surgery. A significant increase in PWV was observed in patients undergoing surgical treatment for aortic arch aneurysm regardless of the types of operations performed (all treatments: before, 1797 ± 397.8 cm/s vs after, 2061 ± 600.4 cm/s, P < 0.001; graft replacement: before, 1769 ± 398.1 cm/s vs after, 1895 ± 459.0 cm/s, P = 0.004; frozen elephant trunk procedure: before, 1911 ± 461.9 cm/s vs after 2307 ± 826.9 cm/s, P = 0.005; hybrid surgery: before, 1732 ± 273.3 cm/s vs after, 2254 ± 484.6 cm/s, P < 0.001). Differences in PWV were largest in patients treated with hybrid surgery and lowest in those treated with graft replacement (P = 0.002). In univariate analysis, an increase in PWV was positively correlated with treatment length (r = 0.41; P < 0.001); the use of a postoperative beta blocker was associated with a smaller increase in postoperative PWV (with: 165.0 ± 371.92 cm/s vs without: 439.4 ± 530.38 cm/s, P = 0.005). Multivariate analysis suggested that treatment length (coefficient 3.31, 95% confidence interval 0.056-6.562, P = 0.046) and postoperative beta blocker (coefficient -220.08, 95% confidence interval -401.972 to -38.183, P = 0.018) were factors independently associated with changes in PWV. CONCLUSIONS: There was a significant increase in PWV after aortic arch repair. Treatment length and use of postoperative beta blockers were factors associated with changes in postoperative PWV. Minimizing the treatment length and using postoperative beta blockers may attenuate the effects of prostheses on postoperative PWV.

Prosthetic Graft Dilation at the Aortic Arch in the Era of Hybrid Aortic Surgery.

Objective: This study aims to evaluate the chronological size changes of the prosthetic graft in the aortic arch, which is used as a landing zone for a subsequent stent grafting in hybrid aortic surgery. Materials and Methods: Eighty-five patients who underwent total aortic arch replacement followed by computed tomography follow-up for at least 30 months after the surgery were included in the study. Results: Prosthetic grafts used were Hemashield (Maquet, Rastatt, Germany), J-Graft (Japan Lifeline Inc., Tokyo, Japan) and Triplex (Terumo, Tokyo, Japan). There was an initial increase in diameter compared to package size after implantation (Hemashield, 1.04±0.035 vs. J-Graft, 1.06±0.027 vs. Triplex, 1.04±0.023, p=0.13). Significant difference in graft dilation ratio was observed in Triplex (1.18±0.062) at long-term compared to Hemashield (1.07±0.052, p<0.001) and J-Graft (1.10±0.071, p<0.001). Multivariate analysis showed that age (r=0.002; 95% confidence interval [CI], 0.0001-0.0037; p=0.035), knitted-type prosthesis (r=0.089; 95% CI, 0.0610-0.1163; p<0.0001), and prevalence of cerebral vascular disease (r=0.038; 95% CI, 0.0030-0.0732; p=0.034) were independently associated with graft dilation after surgery. Conclusion: Prosthetic graft selection and appropriate sizing of the stent graft should be considered for each individual undergoing hybrid aortic surgery to maintain sufficient oversizing of the stent graft.

Effect of endoprostheses on pulse wave velocity and its long-term outcomes after thoracic endovascular aortic repair.

BACKGROUND: The purpose of this study was to evaluate the changes in pulse wave velocity and left ventricular dimensions in patients undergoing stent-graft treatment for aortic arch aneurysm. METHODS: From July 2008 to February 2019, 86 patients underwent thoracic endovascular aortic repair of an aortic arch aneurysm. Changes in pulse wave velocity (PWV), echocardiogram findings, and long-term outcomes were compared between endoskeleton type (n = 60) and exoskeleton type stent-graft (n = 26). RESULTS: There was no significant difference in patient demographics except for diabetes which was more observed in endoskeleton type (p = 0.017). There was a significant increase in PWV in exoskeleton type after surgery, which further progressed at a median follow-up of 32 months (before: 2047 cm/s vs. after: 2259 cm/s vs. follow-up: 2486 cm/s, p = 0.010, p = 0.017). No significant difference was observed in endoskeleton type (before: 1980 cm/s vs. after: 2058 cm/s, vs. follow-up: 2042 cm/s, p = 0.25, p = 0.34). Echocardiogram performed at a median period of 46.3 months, revealed a significant increase in left ventricular diastolic volume (LVDV) (before: 107.4 ± 20.6 ml vs. follow-up: 127.7 ± 27.5 ml, p = 0.003) and decrease in e' (before: 5.5 ± 1.78 cm/s vs. follow-up: 4.7 ± 1.72 cm/s, p = 0.012) in exoskeleton type, while no significant change was observed in endoskeleton type (LVDV: before: 102.6 ± 32.3 ml vs. follow-up: 96.9 ± 35.4 ml, p = 0.74; e': before: 4.4 ± 1.21 cm/s vs. follow-up: 4.8 ± 1.40 cm/s, p = 0.68). At the median period of 61.3 months, there was no significant difference in long-term mortality (p = 0.89). However, the endoskeleton type was associated with a lower incidence of a cardiac event (p = 0.034) and cerebrovascular event (p = 0.029). CONCLUSION: Types of endoprosthesis might affect differently on physiological changes and its accommodated risk factors after surgery.

Effects of Obesity on Outcomes of Acute Type A Aortic Dissection Repair in Japan.

Background: The prevalence of obesity among Japanese acute type A aortic dissection (ATAAD) patients and its effect on repair outcomes remain to be elucidated. Methods and Results: The prevalence of obesity (body mass index [BMI] ≥30.0 kg/m2) among 1,059 patients (mean [±SD] age 64.3±12.7 years) who underwent ATAAD repair between 1990 and 2018 was compared with that among the general Japanese population (National Health and Nutrition Survey data). The prevalence of obesity among male patients (17.1% [6/35], 20.0% [18/90], and 14.4% [20/139] for those aged 20-39, 40-49, and 50-59 years, respectively) was significantly higher than that among the age- and sex-matched general population. The 1,059 patients were divided into groups according to weight (normal [BMI <25.0 kg/m2; n=742], overweight [BMI 25.0-29.9 kg/m2; n=248], or obese [BMI ≥30.0 kg/m2; n=69]). Comparing the normal weight, overweight, and obese groups revealed significant differences among the 3 groups in median cardiopulmonary bypass time (143, 167, and 183 min, respectively), ventilation >48 h (44.5%, 60.1%, and 78.3%, respectively), and in-hospital mortality (7.0%, 7.3%, and 17.4%, respectively), but not in 30-day survival. Shock, visceral malperfusion, operation time >360 min, obesity, and coronary malperfusion were identified as predictors of in-hospital mortality. Conclusions: The prevalence of obesity is increased among Japanese male patients with ATAAD aged ≤59 years. Obesity may increase these patients' operative risk; overweight does not.

Epigenetic transcriptional activation of monocyte chemotactic protein 3 contributes to long-lasting neuropathic pain.

A multiplex analysis for profiling the expression of candidate genes along with epigenetic modification may lead to a better understanding of the complex machinery of neuropathic pain. In the present study, we found that partial sciatic nerve ligation most remarkably increased the expression of monocyte chemotactic protein 3 (MCP-3, known as CCL7) a total of 33 541 genes in the spinal cord, which lasted for 4 weeks. This increase in MCP-3 gene transcription was accompanied by the decreased trimethylation of histone H3 at Lys27 at the MCP-3 promoter. The increased MCP-3 expression associated with its epigenetic modification observed in the spinal cord was almost abolished in interleukin 6 knockout mice with partial sciatic nerve ligation. Consistent with these findings, a single intrathecal injection of recombinant proteins of interleukin 6 significantly increased MCP-3 messenger RNA with a decrease in the level of Lys27 trimethylation of histone H3 at the MCP-3 promoter in the spinal cord of mice. Furthermore, deletion of the C-C chemokine receptor type 2 (CCR2) gene, which encodes a receptor for MCP-3, failed to affect the acceleration of MCP-3 expression in the spinal cord after partial sciatic nerve ligation. A robust increase in MCP-3 protein, which lasted for up to 2 weeks after surgery, in the dorsal horn of the spinal cord of mice with partial sciatic nerve ligation was seen mostly in astrocytes, but not microglia or neurons. On the other hand, the increases in both microglia and astrocytes in the spinal cord by partial sciatic nerve ligation were mostly abolished in interleukin 6 knockout mice. Moreover, this increase in microglia was almost abolished by CCR2 gene deletion, whereas the increase in astrocytes was not affected in nerve-ligated mice that lacked the CCR2 gene. We also found that either in vivo or in vitro treatment with MCP-3 caused robust microglia activation. Under these conditions, intrathecal administration of MCP-3 antibody suppressed the increase in microglia within the mouse spinal cord and neuropathic pain-like behaviours after nerve injury. With the use of a functional magnetic resonance imaging analysis, we demonstrated that a single intrathecal injection of MCP-3 induced dramatic increases in signal intensity in pain-related brain regions. These findings suggest that increased MCP-3 expression associated with interleukin 6 dependent epigenetic modification at the MCP-3 promoter after nerve injury, mostly in spinal astrocytes, may serve to facilitate astrocyte-microglia interaction in the spinal cord and could play a critical role in the neuropathic pain-like state.

Sleep disturbances in a neuropathic pain-like condition in the mouse are associated with altered GABAergic transmission in the cingulate cortex.

Insomnia is a common problem for people with chronic pain. Cortical GABAergic neurons are part of the neurobiological substrate that underlies homeostatic sleep regulation. In the present study, we confirmed that sciatic nerve ligation caused thermal hyperalgesia and tactile allodynia in mice. In this experimental model for neuropathic pain, we found an increase in wakefulness and a decrease in non-rapid eye movement sleep under a neuropathic pain-like state. Under these conditions, membrane-bound GABA (γ-aminobutyric acid) transporters (GATs) on activated glial fibrillary acidic protein-positive astrocytes were significantly increased in the cingulate cortex, and extracellular GABA levels in this area after depolarization were rapidly decreased by nerve injury. Furthermore, sleep disturbance induced by sciatic nerve ligation was improved by the intracingulate cortex injection of a GAT-3 inhibitor. These findings provide novel evidence that sciatic nerve ligation decreases extracellular-released GABA in the cingulate cortex of mice. These phenomena may, at least in part, explain the insomnia in patients with neuropathic pain. Neuropathic pain-like stimuli suppress the GABAergic transmission with increased GABA (γ-aminobutyric acid) transporters located on activated astrocytes in the cingulate cortex related to sleep disturbance.

Direct evidence for the ongoing brain activation by enhanced dynorphinergic system in the spinal cord under inflammatory noxious stimuli.

BACKGROUND: Dynorphin A in the spinal cord is considered to contribute to nociceptive stimuli. However, it has not yet been determined whether activation of the spinal dynorphinergic system under nociceptive stimuli plays a role in direct acceleration of the ascending nociceptive pathway. In this study, the authors investigated the role of spinal dynorphinergic transmission in ongoing brain activation under noxious stimuli in mice. METHODS: The changes in prodynorphin messenger RNA expression and dynorphin A (1-17)-like immunoreactivity in the mouse spinal cord were determined after the intraplantar injection of complete Freund's adjuvant in mice. The signal intensity in different brain regions after the intraplantar injection of complete Freund's adjuvant or intrathecal injection of dynorphin A (1-17) was measured by a pharmacological functional magnetic resonance imaging analysis. RESULTS: Complete Freund's adjuvant injection produced pain-associated behaviors and induced a dramatic increase in signal intensity in the mouse cingulate cortex, somatosensory cortex, insular cortex, and thalamic nuclei. These effects were not seen in prodynorphin knockout mice. Prodynorphin messenger RNA expression and dynorphin A (1-17)-like immunoreactivity on the ipsilateral side of the spinal cord were markedly increased in complete Freund's adjuvant-injected mice. Furthermore, intrathecal injection of dynorphin A (1-17) at relatively high doses caused pain-associated behaviors and a remarkable increase in the activities of the cingulate cortex, somatosensory cortex, insular cortex, and medial and lateral thalamic nuclei in mice. CONCLUSIONS: These findings indicate that spinally released dynorphin A (1-17) by noxious stimuli leads to the direct activation of ascending pain transmission.

Efficacy and safety of azathioprine and 6-mercaptopurine in Japanese pediatric patients with ulcerative colitis: a survey of the Japanese Society for Pediatric Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Azathioprine (AZA) and 6-mercaptopurine (6-MP) have recently been used in Japanese pediatric patients with ulcerative colitis. The aims of this study were to evaluate both the therapeutic efficacy and safety of AZA/6-MP in this group of patients. METHODS: Fourteen members of the Japanese Society for Pediatric Inflammatory Bowel Disease reported 35 retrospective cases that received AZA/6-MP and were evaluated for adverse drug effects. In those who tolerated AZA/6-MP, disease activity and corticosteroid doses before and during the first 6 months of therapy were assessed. RESULTS: AZA or 6-MP was safely used in 21 of 35 patients (60%) without adverse drug effects. The disease activity began to decrease from the first month of therapy and the maximum effect was achieved after 3 months. The mean daily prednisolone dose was decreased from 26.9 to 11.6 mg and dose reduction was achieved in 58% of patients after 6 months of therapy. Fourteen of the 35 patients (40%) experienced adverse drug effects, including leukopenia (n = 11), aplastic anemia (n = 1), pancreatitis (n = 1) and liver dysfunction (n = 1). CONCLUSIONS: The majority of Japanese children with ulcerative colitis tolerated AZA/6-MP and experienced favorable effects. However, 40% experienced adverse drug effects, mainly myelosuppression.