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BACKGROUND: Lymphedema is an intractable disease that can be caused by injury to lymphatic vessels, such as by surgical treatments for cancer. It can lead to impaired joint mobility in the extremities and reduced quality of life. Chronic inflammation due to infiltration of various immune cells in an area of lymphedema is thought to lead to local fibrosis, but the molecular pathogenesis of lymphedema remains unclear. Development of effective therapies requires elucidation of the immunological mechanisms involved in the progression of lymphedema. The complement system is part of the innate immune system which has a central role in the elimination of invading microbes and acts as a scavenger of altered host cells, such as apoptotic and necrotic cells and cellular debris. Complement-targeted therapies have recently been clinically applied to various diseases caused by complement overactivation. In this context, we aimed to determine whether complement activation is involved in the development of lymphedema. RESULTS: Our mouse tail lymphedema models showed increased expression of C3, and that the classical or lectin pathway was locally activated. Complement activation was suggested to be involved in the progression of lymphedema. In comparison of the C3 knockout (KO) mouse lymphedema model and wild-type mice, there was no difference in the degree of edema at three weeks postoperatively, but the C3 KO mice had a significant increase of TUNEL+ necrotic cells and CD4+ T cells. Infiltration of macrophages and granulocytes was not significantly elevated in C3 KO or C5 KO mice compared with in wild-type mice. Impaired opsonization and decreased migration of macrophages and granulocytes due to C3 deficiency should therefore induce the accumulation of dead cells and may lead to increased infiltration of CD4+ T cells. CONCLUSIONS: Vigilance for exacerbation of lymphedema is necessary when surgical treatments have the potential to injure lymphatic vessels in patients undergoing complement-targeted therapies or with complement deficiency. Future studies should aim to elucidate the molecular mechanism of CD4+ T cell infiltration by accumulated dead cells.

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OBJECTIVE: Factors such as age, vital signs, renal function, Killip class, cardiac arrest, elevated cardiac biomarker levels, and ST deviation predict survival in patients with acute myocardial infarction (AMI). However, the existing risk assessment tools lack comprehensive consideration of catheter-related factors, and short-term prognostic predictors are unknown. This study aimed to clarify in-hospital prognostic predictors in hospitalized patients with AMI. METHODS: Five hundred and thirty-six patients who underwent percutaneous coronary intervention (PCI) for AMI were divided into non-survivor (n = 36) and survivor (n = 500) groups. Coronary risk factors, laboratory findings, angiographic findings, and clinical courses were compared between the two groups. Multiple logistic regression was used to analyze in-hospital death in pre- and post-PCI phases. RESULTS: In the pre-PCI phase, multiple logistic regression analysis revealed several predictors of in-hospital death, including systolic blood pressure [odds ratio (OR) = 0.985, p = 0.023)], Killip class ≥2 (OR = 14.051, p <0.001), and chronic kidney disease (OR = 4.859, p = 0.040). In the post-PCI phase, multiple logistic regression analysis revealed additional predictors of in-hospital death, including Killip class ≥2 (OR = 5.982, p = 0.039), presence of lesions in the left main trunk (OR = 51.381, p = 0.044), utilization of intra-aortic balloon pumps and percutaneous cardiopulmonary support (OR = 6.141, p = 0.016), and presence of multi-vessel disease (OR = 6.323, p = 0.022). CONCLUSION: Predictors of in-hospital death in AMI extend beyond conventional risk factors to include culprit lesions, mechanical support, and multi-vessel disease that manifest post-PCI.

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A 79-year-old man presented with impaired consciousness, fever with a body temperature of 41.1°C, and an electrocardiogram showing significant ST segment elevation in leads V1-6, coved-type ST elevation in leads V1-3, and partial right bundle branch block. Echocardiography revealed notable left ventricle dysfunction with apex-based akinesis. Coronary angiography confirmed severe obstructive lesions but left ventriculography displayed the distinct apical ballooning of takotsubo cardiomyopathy (TC). This case highlights the presence of atypical electrocardiographic patterns in TC influenced by comorbidities, supporting the diagnosis of TC despite concurrent obstructive coronary artery disease.

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Background The close relationship between earlobe creases (ELC) and the presence of coronary artery disease (CAD) has been reported. In addition, this study aimed to determine associations between ELC and the presence, extent, and severity of coronary atherosclerosis assessed by coronary angiography in non-elderly and elderly patients. Methods We assessed 1,086 consecutive patients with suspected CAD by coronary angiography. We defined severe CAD as Gensini scores > 20. Multiple logistic regression analysis was adjusted for age, sex, hypertension, diabetes mellitus, smoking status, lipid profiles, and body mass index (BMI) to assess the presence or absence of CAD, multivessel disease, and severe CAD in elderly (age ≥ 60 years) and non-elderly (age < 60 years) patients. Results ELC was a significantly positive determinant of CAD (odds ratio (OR) = 3.074, p < 0.001), multivessel disease (OR = 3.101, p < 0.001), and severe CAD (OR = 2.823, p < 0.001) in all patients. ELC was also a predictor of CAD, multivessel disease, and severe CAD not only in patients aged ≥ 60 years (OR = 3.095, p < 0.001; OR = 3.071, p < 0.001; OR = 2.761, p < 0.001, respectively) but also in those aged < 60 years (OR = 2.749, p = 0.035; OR = 2.634, p = 0.038; OR = 2.766, p = 0.006, respectively). Conclusions ELC was independently associated with the presence of CAD, multivessel disease, and severe CAD in both elderly and non-elderly patients who were assessed by coronary angiography.

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Background: Surgery for zygomatic complex fractures primarily aims to obtain facial symmetry. We investigated facial symmetry specific to lower eyelid bulges following zygomatic complex fractures approached through the lower eyelid. Methods: Forty-one consecutive patients underwent treatment of zygomatic complex fractures by swinging eyelid approach or subciliary approach. In both approaches, the periosteum was incised 2 mm caudal to the inferior orbital rim and the orbicularis retaining ligament (ORL) was released. The orbital rim periosteum was interruptedly sutured and reconstruction of the orbital septum or ORL was not performed at the time of closure. In cases with a lower eyelid bulge on the nonfractured side, in a frontal photograph 6 months after the operation, the degree of loss of the lower eyelid bulge on the fractured side was classified as either "none," "mild," or "severe." Results: Lower eyelid bulge was present on the nonfractured side in 19 of 41 patients, all of whom were over 50 years old. Loss of lower eyelid bulge was observed on the fractured side in all cases: 15 cases following the swinging eyelid approach (mild/severe; 6/9) and four cases following the subciliary approach (mild/severe; 2/2). Conclusions: In reconstruction after zygomatic complex fractures, lower eyelid bulges were lost in both the swinging eyelid and subciliary approaches in patients over 50 years old. The cause was thought to be an ORL release or an unintended septal reset-like effect.

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ABSTRACT: We introduce the application of mandibular reconstruction with the superficial circumflex iliac artery (SCIA)-based iliac bone flap. Until now, iliac bone flaps based on the SCIA have been used in relatively small bony and plane defects, such as in the orbital floor, maxilla, distal phalanx, and calcaneus. This flap has minimal donor-site morbidity compared with the conventional deep circumflex iliac artery flap, and it can be harvested simultaneously with tumor resection in most reconstructions, including those in the head and neck. A great advantage of the SCIA-based iliac bone flap is the thin and reliable large skin paddle that can be used for intraoral and lip defects. Although there are remaining problems to overcome, such as the blood circulation to the bone, this flap may be an option in mandibular reconstruction where there are large soft tissue defects, or where there is complicated peripheral arteriosclerosis or arterial abnormality.

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The patient was a 49-year-old woman. She had worked at a child welfare facility where she sustained a wound to the left side of her upper eyelid after it was scratched by a child facility resident's finger. One month had passed since the injury when she visited our hospital. The initial treatment was not appropriate, and her left eyelid could not be lifted at all. A secondary surgery was performed 2 months after the injury when the scar contracture was most strong. Such corrective surgery for posttraumatic eyelid is typically scheduled after at least 6 months when the scar tissue softens from the viewpoint of wound healing. However, this case indicated the importance of determining the appropriate timing of surgery in consideration of the patient's background and the scientific basis. Reports of sharp traumatic ptosis are rare, and this is the first reported case of traumatic ptosis resulting from a scratch caused by human hand.

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This study examines the incidence of iatrogenic atrial septal defect (iASD) after the MitraClip procedure and its influence on echocardiographic and clinical outcomes. We examined 96 patients who underwent a successful MitraClip procedure and who also had baseline and 1-year postprocedure transthoracic echocardiograms. At 1-year follow-up, iASD were observed in 24% of cases. Compared with the patients without iASD, the patients with iASD had a larger right atrium and greater severity of tricuspid regurgitation (TR) at baseline. After the MitraClip procedure, mitral regurgitation lessened significantly in both groups. Although right atrial area and right ventricular diameters increased significantly in patients with iASD (25.3 ± 8.0 to 28.3 ± 9.5 cm2, 39.7 ± 7.1 to 42.2 ± 8.1 mm, p <0.05 for both comparisons), these variables did not change in patients without iASD. In addition, patients with iASD had worse TR at follow-up. The incidence of stroke was comparable between the 2 groups during 1-year follow-up (4.3% vs 4.1%). However, patients with iASD had a markedly higher re-hospitalization rate for heart failure (26% vs 2.7%, p <0.05). In conclusion, iASD occurred in 24% of patients who underwent the MitraClip therapy and the presence of iASD was associated with right-sided heart enlargement, worse TR, and a higher re-hospitalization rate for heart failure.

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PURPOSE: The purpose of this study was to evaluate left ventricular (LV) deformation and LV dyssynchrony in patients with Wolff-Parkinson-White (WPW) syndrome and to identify the factors that affect the efficacy of radiofrequency catheter ablation (RFCA). METHODS: Thirty patients (26 men, mean age 40 ± 12 years) with WPW syndrome were prospectively recruited for this study. They underwent 2-dimensional transthoracic echocardiography with speckle tracking analysis before RFCA and again within 48 hours after RFCA. Control group consisted of 15 age and sex-matched healthy volunteers. RESULTS: The patients had significantly lower LV ejection fraction (LVEF), global longitudinal strain (Sl ), and global circumferential strain (Sc ) compared with healthy controls (64% ± 8% vs 68% ± 5%, P = .049; -17.6% ± 3.2% vs -19.9% ± 3.3%, P = .037, -15.2% ± 2.5% vs -19.4% ± 2.5%, P < .0001, respectively). Patients had a significantly higher dyssynchrony index relative to healthy controls (58.4 ± 49.0 ms vs 36.4 ± 31.1 ms, P = .031). After RFCA, there was a significant increase in LVEF and global Sc (68% ± 8% vs 64% ± 8%, P = .005; -17.3% ± 2.0% vs -15.2% ± 2.5%, P < .0001, respectively), along with a significant decrease in the dyssynchrony index (36.9 ± 36.3 ms vs 58.4 ± ms, P < .001) relative to the baseline values. Logistic regression revealed that the baseline dyssynchrony index was a predictor of LVEF improvement after RFCA (odds ratio: 1.060, P = .038). CONCLUSION: In WPW syndrome, impaired LV circumferential deformation can be restored by RFCA with concomitant improvement in LV dyssynchrony and LVEF.

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Low sodium levels are strongly associated with poor prognosis in acute heart failure (AHF); however, the prognostic impact of the sodium level trajectory overtime has not been determined. A secondary analysis of the AQUAMARINE study in which patients with AHF and renal impairment were randomized to receive either tolvaptan or conventional treatment was performed. Sodium levels were evaluated at the baseline and at 6, 12, 24, and 48 h. We defined 'sodium dipping' as sodium level falling below the baseline level at any time point. The primary endpoint was the combined event of all-cause death and heart failure rehospitalization during follow-up. The analysis included 184 patients with a median follow-up of 21.1 months. Sodium levels more steeply increased during the 48 h in patients without events as compared to sodium levels in patients with events (P = 0.018 in linear-mixed effect model). The sodium dipping group (n = 100; 54.3%) demonstrated significantly less urine output, less body weight reduction, and poorer diuretic response within 48 h compared to the non-dipping group. The sodium dipping group was also significantly associated with a low combined-event-free survival after adjustment for other prognostic factors (HR 1.97; 95% CI 1.06-3.38; P = 0.033). The trajectory of sodium levels during the acute phase is associated with the prognosis of patients with AHF independently of the baseline sodium level.

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The effect of percutaneous mitral valve repair using the MitraClip system on tricuspid regurgitation (TR) has not been well investigated. We retrospectively analyzed 102 consecutive patients who underwent the successful MitraClip procedure, and who also had a preprocedural and 1-year follow-up transthoracic echocardiography. TR severity was graded by standard guideline-recommended criteria. At 1 year after the MitraClip procedure, the degree of TR regressed (at least 1 grade) in 23% of the patients, was unchanged in 62% of the patients, and progressed in 16% of the patients. Compared with patients in the other groups, the patients with TR regression had a greater severity of TR at baseline. The TR regression group showed a significant reduction in the systolic pulmonary artery pressure (sPAP) (49 ± 13 to 37 ± 11 mm Hg, p <0.05), a right-sided cardiac reverse remodeling (right ventricular diameter: 41 ± 7 to 39 ± 7 mm, tricuspid annular diameter: 48 ± 8 to 46 ± 9 mm, both p <0.05), and an increase in the right ventricular fractional area change (38 ± 7 to 40 ± 7%, p <0.05). In the multivariate analysis, the decrease in sPAP was the only independent parameter change associated with TR regression. In conclusion, TR regression was observed in 23% of the patients after the successful MitraClip procedures, and favorable echocardiographic parameter changes were detected in this group. Only a reduction in sPAP was independently associated with TR regression.

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BACKGROUND: Poor response to diuretics is associated with worse prognosis in patients with acute heart failure (AHF). We hypothesized that treatment with tolvaptan improves diuretic response in patients with AHF. METHODS: We performed a secondary analysis of the AQUAMARINE open-label randomized study in which a total of 217 AHF patients with renal impairment (eGFR < 60 mL/min/1.73 m2) were randomized to either tolvaptan or conventional treatment. We evaluated diuretic response to 40 mg furosemide or its equivalent based on two different parameters: change in body weight and net fluid loss within 48 h. RESULTS: The mean time from patient presentation to randomization was 2.9 h. Patients with a better diuretic response showed greater relief of dyspnea and less worsening of renal function. Tolvaptan patients showed a significantly better diuretic response measured by diuretic response based both body weight [-1.16 (IQR -3.00 to -0.57) kg/40 mg vs. -0.51 (IQR -1.13 to -0.20) kg/40 mg; P < 0.001] and net fluid loss [2125.0 (IQR 1370.0-3856.3) mL/40 mg vs. 1296.3 (IQR 725.2-1726.5) mL/40 mg; P < 0.001]. Higher diastolic blood pressure and use of tolvaptan were independent predictors of a better diuretic response. CONCLUSIONS: Better diuretic response was associated with greater dyspnea relief and less WRF. Early treatment with tolvaptan significantly improved diuretic response in AHF patients with renal dysfunction.

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BACKGROUND: Longitudinal motion of the mitral annulus is an index that reflects left ventricular (LV) function. The aim of this study was to evaluate and compare the effects of transcatheter mitral valve (MV) repair and open heart surgery for mitral regurgitation (MR) on mitral annular motion (MAM). METHODS: We retrospectively analyzed in total 115 patients who underwent isolated transcatheter MV repair using MitraClip (n=50) or surgical MV interventions (n=65, 50 repairs and 15 replacements) for MR. MAM was assessed by two-dimensional B-mode echocardiography in the four- and two-chamber views. MAM was measured before and within 1 month after the mitral procedure. RESULTS: Compared with patients undergoing MV surgery, patients undergoing the MitraClip procedure were older and had more comorbidities. MR grade improved significantly in both groups after MV intervention. MAM decreased significantly in the surgery group (12.0±3.1 to 8.1±2.2 mm, P<.01), whereas MAM did not change in the MitraClip group (8.8±2.6 to 8.6±2.5 mm, P=.59). In multivariate analysis, mitral surgery was associated with a decrease in MAM when compared to the MitraClip procedure. Furthermore, LV ejection fraction (EF) decreased to a greater degree in patients undergoing surgery than those undergoing MitraClip placement (MV surgery; -10.1±7.6% vs MitraClip; -3.0±10.5%, P<.01). CONCLUSIONS: MitraClip therapy does not adversely influence MAM and is associated with less postprocedural EF reduction compared to surgical intervention. Our results suggest that patients with reduced LV systolic function may benefit from the MitraClip procedure compared to mitral surgery.

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A 55-year-old female with a history of hypertension was admitted for dyspnea, epigastralgia and nausea. A chest X-ray showed pulmonary congestion. Transthoracic echocardiography (TTE) revealed severe left ventricular dysfunction with akinesis of the infero-posterior wall and Doppler color-flow mode showed mild aortic regurgitation (AR). Noninvasive positive pressure ventilation, intravenous heparin and diuretics were administered. Follow-up TTE revealed a dissection flap as well as momentary and wide AR only during isovolumetric relaxation. Contrast-enhanced computed tomography of the chest revealed Stanford type A aortic dissection. A momentary and wide AR in echocardiograms might serve as an important and useful indicator of aortic dissection in patients with acute myocardial infarction and congestive heart failure.

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Eosinophilic myocarditis may be accompanied by Churg-Strauss syndrome (CSS). We report a case of CSS that was accompanied by myocardial changes in the early stage. A 71-year-old woman complained of mild chest pain at rest, but routine echocardiography did not reveal any endocardial abnormalities. Four months later, the patient was hospitalized due to congestive heart failure with neuropathy of both upper extremities. A diagnosis of eosinophilic myocarditis was made based on the patient's laboratory results and the presence of mural thrombus. This case illustrates that, although early eosinophilic myocarditis is an important differential diagnosis in patients with chest pain, it may be difficult to identify in without an apparent mural thrombus.

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BACKGROUND: Renal dysfunction is a common comorbidity in acute heart failure (AHF) patients. The prognostic significance of early treatment with tolvaptan in AHF patients complicated with renal dysfunction has not been elucidated. METHODS: Post hoc analysis was performed on a randomized clinical study for prespecified prognostic endpoints and prespecified subgroups. 217 AHF patients with renal dysfunction (eGFR 15 to 60mL/min/1.73m(2)) were randomized within 6h from hospitalization to either tolvaptan treatment for 2days or conventional treatment. The primary outcome was the combined endpoint of all-cause death and HF readmission. RESULTS: During follow-up (636days, median) 99 patients experienced combined endpoint and 53 patients died. There was no significant difference in event-free survival rate for either the combined events (Log-rank: P=0.197) or all-cause death (Log-rank: P=0.894) between tolvaptan and conventional groups. In prespecified subgroup analysis, in patients whose BUN/creatinine ratio was above the median (>20), tolvaptan significantly reduced the risk of combined events (HR: 0.52, 95% CI: 0.30-0.91, P=0.021) with a significant interaction (P value for interaction=0.045). Likewise, in patients whose eGFR was 30mL/min/1.73m(2) or above, tolvaptan reduced the risk of combined events (HR: 0.54, 95% CI: 0.32-0.90, P=0.017) with a significant interaction (P value for interaction=0.015). CONCLUSION: Short-term use of tolvaptan in acute-phase in AHF with renal dysfunction showed a neutral effect on prognosis. Patients with relatively preserved renal function and relatively high BUN/creatinine ratios are potentially favorable subgroups for treatment with tolvaptan.

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BACKGROUND: More efficacious and/or safer decongestive therapy is clearly needed in acute heart failure (AHF) patients complicated by renal dysfunction. We tested the hypothesis that adding tolvaptan, an oral vasopressin-2 receptor antagonist, to conventional therapy with loop diuretics would be more effective treatment in this population. METHODS AND RESULTS: A multicenter, open-label, randomized control trial was performed, and 217 AHF patients with renal dysfunction (estimated glomerular filtration rate 15-60 mL • min(-1) • 1.73 m(-2)) were randomized 1:1 to treatment with tolvaptan (n=108) or conventional treatment (n=109). The primary end point was 48-hour urine volume. The tolvaptan group showed more diuresis than the conventional treatment group (6464.4 vs 4999.2 mL; P <.001) despite significantly lower amounts of loop diuretic use (80 mg vs 120 mg; P <.001). Dyspnea relief was achieved significantly more frequently in the tolvaptan group at all time points within 48 hours except 6 hours after enrollment. The rate of worsening of renal function (≥0.3 mg/dL increase from baseline) was similar between the tolvaptan and conventional treatment groups (24.1% vs 27.8%, respectively; P =.642). CONCLUSIONS: Adding tolvaptan to conventional treatment achieved more diuresis and relieved dyspnea symptoms in AHF patients with renal dysfunction. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index/htm/ Unique identifier: UMIN000007109.

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PURPOSE: Over half of all admitted acute decompensated heart failure (ADHF) patients have renal failure. Although diuretics represent the mainstay of treatment strategy even in this population, there are unmet needs for safer and more effective treatment. Tolvaptan is a vasopressin-2 receptor antagonist, and we hypothesized that adding tolvaptan to standard diuretic therapy would be more effective in ADHF patients with renal function impairment. METHODS: The Answering question on tolvaptan's efficacy for patients with acute decompensated heart failure and renal failure (AQUAMARINE) is a multicenter, randomized controlled clinical trial, which will enroll 220 patients from 17 hospitals in Japan. ADHF patients whose estimated glomerular filtration rate is above 15 and below 60 mL/min/1.72 m(2) will be randomly assigned within 6 h after admission to usual care with furosemide or tolvaptan add-on therapy. Primary endpoint is achieved urine output within 48 h. Secondary endpoints include dyspnea relief measured by 7-points Likert scale, incidence of worsening renal function, dose of furosemide used within 48 h, and changes of brain natriuretic peptide. CONCLUSION: This study is the first multicenter study in Japan to evaluate clinical effectiveness of tolvaptan add-on therapy in ADHF patients with renal failure. The results of this study address the treatment strategy of this high-risk population (UMIN Clinical Trial Registry Number: UMIN000007109).

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