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MITOL/MARCH5 is an E3 ubiquitin ligase that plays a crucial role in the control of mitochondrial quality and function. However, the significance of MITOL in cardiomyocytes under physiological and pathological conditions remains unclear. First, to determine the significance of MITOL in unstressed hearts, we assessed the cellular changes with the reduction of MITOL expression by siRNA in neonatal rat primary ventricular cardiomyocytes (NRVMs). MITOL knockdown in NRVMs induced cell death via ferroptosis, a newly defined non-apoptotic programmed cell death, even under no stress conditions. This phenomenon was observed only in NRVMs, not in other cell types. MITOL knockdown markedly reduced mitochondria-localized GPX4, a key enzyme associated with ferroptosis, promoting accumulation of lipid peroxides in mitochondria. In contrast, the activation of GPX4 in MITOL knockdown cells suppressed lipid peroxidation and cell death. MITOL knockdown reduced the glutathione/oxidized glutathione (GSH/GSSG) ratio that regulated GPX4 expression. Indeed, the administration of GSH or N-acetylcysteine improved the expression of GPX4 and viability in MITOL-knockdown NRVMs. MITOL-knockdown increased the expression of the glutathione-degrading enzyme, ChaC glutathione-specific γ-glutamylcyclotransferase 1 (Chac1). The knockdown of Chac1 restored the GSH/GSSG ratio, GPX4 expression, and viability in MITOL-knockdown NRVMs. Further, in cultured cardiomyocytes stressed with DOX, both MITOL and GPX4 were reduced, whereas forced-expression of MITOL suppressed DOX-induced ferroptosis by maintaining GPX4 content. Additionally, MITOL knockdown worsened vulnerability to DOX, which was almost completely rescued by treatment with ferrostatin-1, a ferroptosis inhibitor. In vivo, cardiac-specific depletion of MITOL did not produce obvious abnormality, but enhanced susceptibility to DOX toxicity. Finally, administration of ferrostatin-1 suppressed exacerbation of DOX-induced myocardial damage in MITOL-knockout hearts. The present study demonstrates that MITOL determines the cell fate of cardiomyocytes via the ferroptosis process and plays a key role in regulating vulnerability to DOX treatment. (288/300).
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Cardiomiopatías/inducido químicamente , Doxorrubicina/farmacología , Glutatión/metabolismo , Proteínas Mitocondriales/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Muerte Celular/efectos de los fármacos , Células Cultivadas , Doxorrubicina/efectos adversos , Ferroptosis/efectos de los fármacos , Células HEK293 , Humanos , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Mitocondriales/genética , Miocitos Cardíacos/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Ratas , Ubiquitina-Proteína Ligasas/genética , gamma-Glutamilciclotransferasa/genética , gamma-Glutamilciclotransferasa/metabolismoRESUMEN
In recent years, endovascular treatment has become the first-line revascularisation method for aortoiliac artery occlusive disease. Rarely, aortoiliac artery occlusive disease may be associated with stenosis of the external iliac artery (EIA) that suggested pseudo-stenosis. We describe a case of aortoiliac artery occlusive disease with EIA stenosis without calcification or atheroma. Stent grafts were inserted from the abdominal aorta to the bilateral common iliac arteries. Pre-operative computed tomography and intravascular ultrasound findings confirmed the absence of calcification or atheroma in both EIA, suggesting that the EIA had developed pseudo-stenosis. Following endovascular treatment, the EIA diameter recovered only with balloon dilation after inflow improvement. Consideration is necessary when placing an easy stent graft in the narrow EIA during endovascular treatment for aortoiliac artery occlusive disease with EIA stenosis to avoid a potential stent graft diameter mismatch.
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Ruptured phyllodes tumors, though extremely rare, can necessitate emergency surgery in certain cases, particularly those with active bleeding. A 51-year-old woman presented to our hospital with a newly identified mass in her right breast that developed over the past two months. The tumor had ruptured through the paramammary nipple. While initially diagnosed with a phyllodes tumor and scheduled for elective surgery, she experienced active bleeding from the ruptured tumor, leading to a drop in hemoglobin levels. An emergency right simple mastectomy was performed to control the bleeding. Postoperatively, no complications or recurrences were observed. Phyllodes tumors, which are characterized by rapid growth, may present with active bleeding following rupture and may require emergency surgery.
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BACKGROUND: Letrozole, an aromatase inhibitor, is used to treat breast cancer in postmenopausal women. Tumor lysis syndrome (TLS) is a complication that can trigger multiple organ failure caused by the release of intracellular nucleic acids, phosphate, and potassium into the blood due to rapid tumor cell disintegration induced by drug therapy. TLS is uncommon in solid tumors and occurs primarily in patients receiving chemotherapy. Herein, we report a rare occurrence of TLS that developed in a patient with locally advanced breast cancer following treatment with letrozole. CASE PRESENTATION: An 80-year-old woman with increased bleeding from a fist-sized left-sided breast mass presented to our hospital. Histological examination led to a diagnosis of invasive ductal carcinoma of the luminal type. The patient refused chemotherapy and was administered hormonal therapy with letrozole. Seven days after letrozole initiation, she complained of anorexia and diarrhea. Blood test results revealed elevated blood urea nitrogen (BUN) and creatinine (Cr) levels, and she was admitted to our hospital for intravenous infusions. On the second day after admission, marked elevations of LDH, BUN, Cr, potassium, calcium, and uric acid levels were observed. Furthermore, metabolic acidosis and prolonged coagulation capacity were observed. We suspected TLS and discontinued letrozole, and the patient was treated with hydration, febuxostat, and maintenance hemodialysis. On the third day after admission, her respiratory status worsened because of acute respiratory distress syndrome associated with hypercytokinemia, and she was intubated. On the fourth day after admission, her general condition did not improve, and she died. CONCLUSIONS: Although TLS typically occurs after chemotherapy initiation, the findings from the present case confirm that this syndrome can also occur after hormonal therapy initiation and should be treated with caution.
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IgG4-related mastitis is an extremely rare IgG4-related sclerosing disease involving the breast that must be differentiated from breast cancer. There is currently no consensus regarding the optimal treatment strategies. Here, we report a case of IgG4-related mastitis followed up without excision or steroid therapy. Although the association between IgG4-related mastitis and breast cancer remains unclear, regular follow-up imaging and measurement of serum concentrations of disease activity markers may allow for follow-up without excision or steroid therapy.
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The accurate diagnosis and therapeutic strategies of thyroglossal duct cysts (TGDCs) are challenging for surgeons if the opening with exudate is far from the hyoid bone. A 7-year-old boy presented with a right supraclavicular mass and persistent pus. Ultrasonography and magnetic resonance imaging revealed the fistula to the hyoid bone. Suspecting a TGDC, we combined the stepladder incision technique and the Sistrunk procedure. The first skin incision cut through the opening in a spindle shape, and the second incision was made in the skin just above the hyoid bone. This combined technique allowed en bloc resection of the TGDC and the hyoid bone to the base of the tongue. Cervical masses are commonly encountered in surgical clinics, and even distant openings off the midline must be considered in the differential diagnosis of TGDCs. This treatment strategy is essential for preventing the recurrence of TGDCs and ensures optimal cosmetic outcomes.
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BACKGROUND: Open thoracic surgery (with infected lesion removal, prosthetic graft replacement, and pedicled tissue flap) has remained the main treatment for infected thoracic aortic aneurysms to date. Recent reports have highlighted good prognostic outcomes with thoracic endovascular aortic repair. However, thoracic endovascular aortic repair for infected thoracic aortic aneurysms is associated with an exacerbation of infection due to residual infected tissues. We discuss the control of refractory infections following endovascular treatment of infected thoracic aortic aneurysms. CASE PRESENTATION: An 81-year-old man, with a history of insulin-dependent diabetes mellitus and pancreaticoduodenectomy, presented to our emergency department with a fever. Blood tests revealed a markedly elevated leukocyte count, and contrast-enhanced computed tomography suggested a descending thoracic aortic pseudoaneurysm. We diagnosed the patient with an infected descending thoracic aortic aneurysm, and performed urgent thoracic endovascular aortic repair; he was started on an intravenous antibiotic treatment. Postoperatively, blood tests revealed a decreased leukocyte count and the patient remained afebrile. However, computed tomography revealed temporal enlargement of the abscess cavity; therefore, an abscess debridement and stent graft wrapping with pedicled latissimus dorsi muscle flaps were performed, which successfully controlled the infection. Six weeks after abscess debridement, the patient was switched to an oral antibiotic therapy. There was no evidence of recurrence of infection 8 months after the surgery. CONCLUSIONS: A combined abscess debridement and pedicled tissue flap approach is useful for patients with poor surgical tolerance in whom infection control is difficult after thoracic endovascular aortic repair for infected thoracic aortic aneurysms. Pedicled latissimus dorsi muscle flaps are useful when using the omentum for pedicled tissue flap is difficult.
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Aneurisma de la Aorta Torácica , Implantación de Prótesis Vascular , Músculos Superficiales de la Espalda , Masculino , Humanos , Anciano de 80 o más Años , Reparación Endovascular de Aneurismas , Implantación de Prótesis Vascular/métodos , Absceso/cirugía , Desbridamiento , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico , Prótesis Vascular , Stents , Resultado del TratamientoRESUMEN
Axillary artery injury secondary to shoulder dislocation with humerus fracture is rare. Rupture of the axillary artery during open reduction is extremely rare. Here, we report about a rare case of a ruptured axillary artery during an open reduction for shoulder dislocation with humerus fracture. A 58-year-old man with left shoulder pain because of a fall after alcohol consumption was diagnosed as having left shoulder dislocation with a humerus fracture. He underwent open reduction surgery. During the procedure, bleeding was observed, and further examination through angiography revealed an ruptured axillary artery. To address this urgent situation, stent grafts were promptly deployed retrogradely from the brachial artery. The postoperative course was uneventful, except for brachial plexus palsy. In the emergent setting, endovascular repair is an efficient alternative to conventional open surgery for controlling bleeding when a ruptured axillary artery occur during open reduction for shoulder dislocation.
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INTRODUCTION: Fetal intestinal volvulus without malrotation is extremely rare, and early prenatal diagnosis is challenging because the signs and symptoms are non-specific. However, without proper management, it can cause massive bowel necrosis. PRESENTATION OF CASE: A woman experienced a dilated fetal bowel at 34 weeks of pregnancy and noticed a decrease in fetal movements at 36 weeks; however, she did not visit a hospital. Her newborn developed severe abdominal distension and was diagnosed with neonatal abdominal compartment syndrome with respiratory distress immediately after emergency caesarean section at 36 weeks and 5 days of pregnancy. The neonate underwent emergency exploratory laparotomy. This revealed a volvulus of the small bowel with extensive necrosis and no findings of congenital malrotation. While the patient required massive necrotic bowel resection, 80 cm of the small intestine was preserved. DISCUSSION: Fetal intestinal volvulus without malrotation can cause abdominal compartment syndrome with rapid respiratory distress. Therefore, it should be considered in the differential diagnosis of fetal intestinal dilatation. Volvulus exacerbation risk increases from 30 weeks of pregnancy to late preterm delivery. However, the time lag between the mother's awareness of decreased fetal movement and caesarean section makes early diagnosis challenging, resulting in a life-threatening condition for the neonate. CONCLUSION: When a fetal ultrasound examination shows intestinal dilatation between gestational week 30 and late preterm, the mother must be fully informed about the possibility that the foetus has intestinal volvulus and the potential risk of massive fetal intestinal necrosis.
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A 70-year-old woman with hypertension and dyslipidemia presented with slow communication and difficulty walking 90 days after 6 courses of postoperative chemotherapy following right breast cancer surgery. What is your diagnosis?