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1.
Cureus ; 16(7): e63567, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39087191

RESUMEN

Syncope is a common clinical entity with variable presentations and often an elusive causal mechanism, even after extensive evaluation. In any case, global cerebral hypoperfusion, resulting from the inability of the circulatory system to maintain blood pressure (BP) at the level necessary to supply blood to the brain efficiently, is the final pathway for syncope. Steno-occlusive carotid artery disease, even if bilateral, does not usually cause syncope. However, the patient presented here had repeated syncope attacks and underwent a thorough examination for suspected cardiac disease, but no abnormality was found. Since there was severe stenosis in the right unilateral internal carotid artery (ICA), but no stenosis in the left ICA or vertebrobasilar artery (VBA), and transient left mild hemiparesis associated with syncope, carotid revascularization surgery for the right ICA was performed, and the repeated syncope attacks completely disappeared after the surgery. The patient's condition improved markedly, and no further episodes of syncope have been reported. We report the relationship between carotid artery stenosis and syncope and discuss its pathomechanism.

2.
Clin Ophthalmol ; 18: 1999-2007, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39005589

RESUMEN

Purpose: To report the outcomes of different therapies in patients with conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma. Patients and Methods: This retrospective study included patients diagnosed with conjunctival MALT lymphoma between August 2000 and April 2022. Patients were classified into three groups according to their treatment: an observation group, a radiation therapy (RT) group, and a rituximab group (rituximab with or without chemotherapy). We analyzed overall survival (OS), overall, local, and systemic relapse-free survival (RFS), and adverse events after treatment. Results: This study included 15 patients (22 eyes). The 10-year OS was 100%. The 2-, 5-, and 10-year overall RFS rates were 80.1%, 41.2%, and 41.2% in all patients, respectively. The 2- and 5-year local RFS rates in the observation group were 100% and 0%, respectively. The 2-, 5-, and 10-year local RFS rates were 87%, 87%, and 87% in the RT group and 83%, 67%, and 67% in the rituximab group, respectively. The 2- and 5-year systemic RFS rates in the observation group were both 100%, and the 2-, 5-, and 10-year systemic RFS rates were 92%, 55%, and 55% in the RT group, and 100%, 60%, and 60% in the rituximab group, respectively. After RT, 53.3% of the eyes developed cataracts and 75% of these were treated with cataract surgery. In addition, 53.3% of the eyes developed dry eyes and were treated with eye drops. Rituximab with or without chemotherapy resulted in some systemic adverse events, but these improved following symptomatic therapies. Conclusion: RT resulted in good local control of conjunctival MALT lymphoma; however, systemic relapse may occur during long-term follow-up. Local and/or systemic relapse may also occur during long-term follow-up in patients treated by observation or rituximab with or without chemotherapy. Patients with conjunctival MALT lymphoma should be followed-up carefully for as long as possible after treatment.

3.
Leukemia ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38987275

RESUMEN

Selinexor, a first-in-class exportin1 (XPO1) inhibitor, is an attractive anti-tumor agent because of its unique mechanisms of action; however, its dose-dependent toxicity and lack of biomarkers preclude its wide use in clinical applications. To identify key molecules/pathways regulating selinexor sensitivity, we performed genome-wide CRISPR/Cas9 dropout screens using two B-ALL lines. We identified, for the first time, that paralogous DDX19A and DDX19B RNA helicases modulate selinexor sensitivity by regulating MCL1 mRNA nuclear export. While single depletion of either DDX19A or DDX19B barely altered MCL1 protein levels, depletion of both significantly attenuated MCL1 mRNA nuclear export, reducing MCL1 protein levels. Importantly, combining selinexor treatment with depletion of either DDX19A or DDX19B markedly induced intrinsic apoptosis of leukemia cells, an effect rescued by MCL1 overexpression. Analysis of Depmap datasets indicated that a subset of T-ALL lines expresses minimal DDX19B mRNA levels. Moreover, we found that either selinexor treatment or DDX19A depletion effectively induced apoptosis of T-ALL lines expressing low DDX19B levels. We conclude that XPO1 and DDX19A/B coordinately regulate cellular MCL1 levels and propose that DDX19A/B could serve as biomarkers for selinexor treatment. Moreover, pharmacological targeting of DDX19 paralogs may represent a potential strategy to induce intrinsic apoptosis in leukemia cells.

4.
CEN Case Rep ; 2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38825653

RESUMEN

Peritoneal dialysis (PD)-associated peritonitis is a common complication of PD. Enteric peritonitis is defined as peritonitis arising from an intestinal or intra-abdominal organ source. The delay in the diagnosis or treatment of enteric peritonitis has been reported to increase mortality. Therefore, the early consideration of enteric peritonitis, particularly in cases of culture-negative peritonitis, is imperative. A 67-year-old Japanese man who had been undergoing PD for 3 years, was admitted to our hospital with a diagnosis of PD-associated peritonitis. A month previously, he experienced a bleeding gastric ulcer, which led to severe anemia (hemoglobin 6.3 mg/dL), followed by thrombocytosis. On admission, peritoneal fluid analysis showed a high white blood cell count (WBC: 8,570 /µL), with neutrophils predominating (74.5%). Cultures of both his dialysis effluent and blood were negative. After admission, the WBC count of the dialysis effluent gradually decreased alongside antibiotic therapy, but the patient's abdominal pain did not improve. After 4 days, enhanced computed tomography showed superior mesenteric artery (SMA) thrombosis and intestinal necrosis. Therefore, emergency intestinal resection and PD catheter removal were performed, and then antithrombosis therapy was initiated. Because the patient's abdominal pain was improved and platelet count and D-dimer concentration were reduced by these treatments, he was discharged from the hospital after 47 days. Thus, we report a rare case of culture-negative PD-associated peritonitis, which was caused by SMA thrombosis and intestinal necrosis. It is likely that combination of severe calcification of SMA and prolonged thrombocytosis secondary to the severe anemia contributed to the thrombosis.

5.
Sci Rep ; 14(1): 10251, 2024 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-38704512

RESUMEN

Mesenchymal stem cells (MSCs) exert their anti-inflammatory and anti-fibrotic effects by secreting various humoral factors. Interferon-gamma (IFN-γ) can enhance these effects of MSCs, and enhancement of regulatory T (Treg) cell induction is thought to be an underlying mechanism. However, the extent to which Treg cell induction by MSCs pretreated with IFN-γ (IFN-γ MSCs) ameliorates renal fibrosis remains unknown. In this study, we investigated the effects of Treg cell induction by IFN-γ MSCs on renal inflammation and fibrosis using an siRNA knockdown system. Administration of IFN-γ MSCs induced Treg cells and inhibited infiltration of inflammatory cells in ischemia reperfusion injury (IRI) rats more drastically than control MSCs without IFN-γ pretreatment. In addition, administration of IFN-γ MSCs more significantly attenuated renal fibrosis compared with control MSCs. Indoleamine 2,3-dioxygenase (IDO) expression levels in conditioned medium from MSCs were enhanced by IFN-γ pretreatment. Moreover, IDO1 knockdown in IFN-γ MSCs reduced their anti-inflammatory and anti-fibrotic effects in IRI rats by reducing Treg cell induction. Our findings suggest that the increase of Treg cells induced by enhanced secretion of IDO by IFN-γ MSCs played a pivotal role in their anti-fibrotic effects. Administration of IFN-γ MSCs may potentially be a useful therapy to prevent renal fibrosis progression.


Asunto(s)
Fibrosis , Indolamina-Pirrol 2,3,-Dioxigenasa , Interferón gamma , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Linfocitos T Reguladores , Animales , Interferón gamma/metabolismo , Linfocitos T Reguladores/inmunología , Células Madre Mesenquimatosas/metabolismo , Ratas , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Masculino , Trasplante de Células Madre Mesenquimatosas/métodos , Riñón/patología , Riñón/efectos de los fármacos , Daño por Reperfusión/inmunología , Enfermedades Renales/terapia , Enfermedades Renales/patología , Ratas Sprague-Dawley
6.
Clin Exp Nephrol ; 28(7): 647-655, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38416340

RESUMEN

BACKGROUND: This study aims to compare patency rates of the 0- and 30-s (sec) balloon dilation time in hemodialysis (HD) patients with restenosis after percutaneous transluminal angioplasty (PTA). METHODS: The patients who underwent PTA within 6 months for failed arteriovenous fistula at the forearm were randomly assigned the 0-s or 30-s dilation time group. Effect of dilation time on the 3- and 6-month patency rates after PTA was examined. RESULTS: Fifty patients were enrolled in this study. The 3-month patency rate in the 30-s dilation group was better than that in the 0-s dilation group (P = 0.0050), while the 6-month patency rates did not show a significant difference between the two groups (P = 0.28). Cox's proportional hazard model revealed that 30-s of inflation time (hazard ratio 0.027; P = 0.0072), diameter of the proximal (hazard ratio 0.32; P = 0.031), and dilation pressure (hazard ratio 0.63; P = 0.014) were associated with better 3-month patency. Dilation pressure between previous and present PTA did not differ in the 0-s (P = 0.15) and 30-s dilation groups (P = 0.16). The 6-month patency rate of the present PTA in the 30-s dilation group was higher than that of the previous PTA (P = 0.015). The visual analog scale did not differ between the two groups (P = 0.51). CONCLUSION: The presenting data suggest that 30-s dilation potentially results in a better 3-month patency rate than 0-s dilation in HD patients with restenosis after PTA.


Asunto(s)
Angioplastia de Balón , Derivación Arteriovenosa Quirúrgica , Oclusión de Injerto Vascular , Diálisis Renal , Grado de Desobstrucción Vascular , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Derivación Arteriovenosa Quirúrgica/efectos adversos , Factores de Tiempo , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/fisiopatología , Oclusión de Injerto Vascular/terapia , Modelos de Riesgos Proporcionales , Resultado del Tratamiento , Recurrencia , Adulto , Antebrazo/irrigación sanguínea
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