RESUMEN
Renal inflammation is a final common pathway of chronic kidney disease (CKD), and its progression can be used to effectively gauge the degree of renal dysfunction. Inflammatory mechanisms contribute to glomerulosclerosis and tubulointerstitial fibrosis, which are hallmarks of CKD leading to end-stage renal disease. Receptor-interacting protein kinase 2 (RIP2) is largely committed to nucleotide-binding oligomerization domain signaling as a direct effector and transmits nuclear factor-κB (NF-κB)-mediated proinflammatory cytokine production. In the present study, we hypothesized that if inflammation via RIP2 and NF-κB signaling plays an important role in renal failure, then the anti-inflammatory effect of RIP2 inhibitors should be effective in improving CKD. To determine its pharmacologic potency, we investigated the renoprotective properties of the novel RIP2 inhibitor AS3334034 [7-methoxy-6-(2-methylpropane-2-sulfonyl)-N-(4-methyl-1H-pyrazol-3-yl)quinolin-4-amine] in uninephrectomized adriamycin-induced CKD rats. Six weeks' repeated administration of AS3334034 (10 mg/kg, once daily) significantly reduced urinary protein excretion and prevented the development of glomerulosclerosis and tubulointerstitial fibrosis. In addition, AS3334034 showed beneficial effects on renal function, as demonstrated by a decrease in levels of plasma creatinine and blood urea nitrogen and attenuation of a decline in creatinine clearance. Furthermore, AS3334034 significantly attenuated inflammation, renal apoptosis, and glomerular podocyte loss. These results suggest that the RIP2 inhibitor AS3334034 suppresses the progression of chronic renal failure via an anti-inflammatory effect and is therefore potentially useful in treating patients with CKD. SIGNIFICANCE STATEMENT: The receptor-interacting protein kinase 2 (RIP2) inhibitor AS3334034 suppresses the progression of chronic renal failure via an anti-inflammatory effect, suggesting that the nucleotide-binding oligomerization domain-RIP2 axis might play a crucial role in the pathogenesis of inflammatory kidney diseases. AS3334034 is expected to be potentially useful in the treatment of patients with chronic kidney disease.
Asunto(s)
Doxorrubicina/farmacología , Riñón/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor/antagonistas & inhibidores , Proteína Serina-Treonina Quinasa 2 de Interacción con Receptor/metabolismo , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Progresión de la Enfermedad , Inflamación/sangre , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Riñón/metabolismo , Pruebas de Función Renal/métodos , Masculino , FN-kappa B/metabolismo , Ratas , Ratas Wistar , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Vascular adhesion protein-1 (VAP-1) is a promising therapeutic target for the treatment of diabetic nephropathy. Here, we conducted structural optimization of the glycine amide derivative 1, which we previously reported as a novel VAP-1 inhibitor, to improve stability in dog and monkey plasma, and aqueous solubility. By chemical modification of the right part in the glycine amide derivative, we identified the carbamimidoylcarbamate derivative 20c, which showed stability in dog and monkey plasma while maintaining VAP-1 inhibitory activity. We also found that conversion of the pyrimidine ring in 20c into saturated rings was effective for improving aqueous solubility. This led to the identification of 28a and 35 as moderate VAP-1 inhibitors with excellent aqueous solubility. Further optimization led to the identification of 2-fluoro-3-{3-[(6-methylpyridin-3-yl)oxy]azetidin-1-yl}benzyl carbamimidoylcarbamate (40b), which showed similar human VAP-1 inhibitory activity to 1 with improved aqueous solubility. 40b showed more potent ex vivo efficacy than 1, with rat plasma VAP-1 inhibitory activity of 92% at 1h after oral administration at 0.3mg/kg. In our pharmacokinetic study, 40b showed good oral bioavailability in rats, dogs, and monkeys, which may be due to its improved stability in dog and monkey plasma.
Asunto(s)
Amina Oxidasa (conteniendo Cobre)/antagonistas & inhibidores , Carbamatos/farmacología , Moléculas de Adhesión Celular/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Administración Oral , Amina Oxidasa (conteniendo Cobre)/sangre , Amina Oxidasa (conteniendo Cobre)/metabolismo , Animales , Carbamatos/administración & dosificación , Carbamatos/química , Moléculas de Adhesión Celular/sangre , Moléculas de Adhesión Celular/metabolismo , Perros , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Inyecciones Intravenosas , Macaca fascicularis , Masculino , Estructura Molecular , Ratas , Ratas Sprague-Dawley , Relación Estructura-ActividadRESUMEN
Vascular adhesion protein-1 (VAP-1) is a promising therapeutic target for the treatment of diabetic nephropathy. Here, we conducted optimization studies of our lead compound 1, which we previously reported as a novel VAP-1 inhibitor, to enhance the inhibition of human VAP-1 and to reduce CYP3A4 and CYP2C19 inhibition. As a result, we identified 3-chloro-4-{4-[5-(3-{[glycyl(methyl)amino]methyl}phenyl)pyrimidin-2-yl]piperazin-1-yl}benzoic acid (17h) as a novel orally active VAP-1 inhibitor, with 14-fold increased human VAP-1 inhibitory activity compared to 1, without CYP3A4 and CYP2C19 inhibition. Oral administration of 17h significantly inhibited the progression of proteinuria in streptozotocin (STZ) induced diabetic rats at 0.3 and 1mg/kg, suggesting that this compound has potential to be a therapeutic agent for the treatment of diabetic nephropathy.
Asunto(s)
Amina Oxidasa (conteniendo Cobre)/antagonistas & inhibidores , Moléculas de Adhesión Celular/antagonistas & inhibidores , Inhibidores del Citocromo P-450 CYP2C19/farmacología , Inhibidores del Citocromo P-450 CYP3A/farmacología , Glicina/análogos & derivados , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Glicina/síntesis química , Glicina/química , Glicina/farmacología , Glicina/uso terapéutico , Humanos , Simulación del Acoplamiento Molecular , Espectroscopía de Protones por Resonancia Magnética , Ratas , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Vascular Adhesion Protein-1 (VAP-1) is a promising therapeutic target for the treatment of several inflammatory-related diseases including diabetic microvascular complication. We identified glycine amide derivative 3 as a novel structure with moderate VAP-1 inhibitory activity. Structure-activity relationship studies of glycine amide derivatives revealed that the tertiary amide moiety is important for stability in rat blood and that the position of substituents on the left phenyl ring plays an important role in VAP-1 inhibitory activity. We also found that low TPSA values and weak basicity are both important for high PAMPA values for glycine amide derivatives. These findings led to the identification of a series of orally active compounds with enhanced VAP-1 inhibitory activity. Of these compounds, 4g exhibited the most potent ex vivo efficacy, with plasma VAP-1 inhibitory activity of 60% after oral administration at 1mg/kg.
Asunto(s)
Acetamidas/farmacología , Amina Oxidasa (conteniendo Cobre)/antagonistas & inhibidores , Moléculas de Adhesión Celular/antagonistas & inhibidores , Glicina/análogos & derivados , Glicina/farmacología , Acetamidas/síntesis química , Acetamidas/farmacocinética , Animales , Células CHO , Cricetulus , Estabilidad de Medicamentos , Pruebas de Enzimas , Glicina/síntesis química , Glicina/farmacocinética , Humanos , Simulación del Acoplamiento Molecular , Ratas , Relación Estructura-ActividadRESUMEN
PURPOSE: Guidelines for the treatment of postoperative recurrent lung cancer in octogenarians do not exist. In this study, we investigated the prognosis of patients with recurrence after the resection of lung cancer and discuss the management of recurrent tumors in octogenarians. METHODS: This study clinicopathologically evaluated 135 octogenarians who underwent resections for lung cancer at a single institution between 1992 and 2010. We retrospectively reviewed the clinical records of 37 patients with confirmed recurrence. The overall survival of the patients and the treatments used for postoperative recurrence were evaluated. RESULTS: Among 37 patients, six underwent intensive treatment, 14 underwent palliative treatment and 17 received supportive care only. The overall survival rates of the patients in the antitumor treatment groups tended to be associated with a better prognoses than those of the patients in the supportive care only group, but they did not exhibit significantly better prognoses at 1 year (p = 0.202). However, among the patients with a good performance status, the intensive treatment group tended to exhibit prolonged survival. Of the 37 patients with recurrent tumors, five (14%) died of other diseases. CONCLUSIONS: Antitumor treatment of postoperative recurrent lung cancer in octogenarians may not always improve the survival rate. However, carefully selecting patients for intensive therapy, such as those with a good performance status, may lead to longer survival rates after postoperative recurrence in octogenarians.
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Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/terapia , Anciano de 80 o más Años , Quimioterapia Adyuvante , Humanos , Neoplasias Pulmonares/mortalidad , Terapia Molecular Dirigida , Recurrencia Local de Neoplasia , Neumonectomía , Pronóstico , Radioterapia Adyuvante , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
Novel thiazole derivatives were synthesized and evaluated as vascular adhesion protein-1 (VAP-1) inhibitors. Although we previously identified a compound (2) with potent VAP-1 inhibitory activity in rats, the human activity was relatively weak. Here, to improve the human VAP-1 inhibitory activity of compound 2, we first evaluated the structure-activity relationships of guanidine bioisosteres as simple small molecules and identified a 1H-benzimidazol-2-amine (5) with potent activity compared to phenylguanidine (1). Based on the structure of compound 5, we synthesized a highly potent VAP-1 inhibitor (37b; human IC50=0.019 µM, rat IC50=0.0051 µM). Orally administered compound 37b also markedly inhibited ocular permeability in streptozotocin-induced diabetic rats after oral administration, suggesting it is a promising compound for the treatment of diabetic macular edema.
Asunto(s)
Amina Oxidasa (conteniendo Cobre)/antagonistas & inhibidores , Moléculas de Adhesión Celular/antagonistas & inhibidores , Retinopatía Diabética/tratamiento farmacológico , Edema Macular/tratamiento farmacológico , Tiazoles/química , Tiazoles/farmacología , Amina Oxidasa (conteniendo Cobre)/metabolismo , Aminas/química , Aminas/farmacocinética , Aminas/farmacología , Animales , Moléculas de Adhesión Celular/metabolismo , Diabetes Mellitus Experimental/complicaciones , Retinopatía Diabética/metabolismo , Humanos , Edema Macular/metabolismo , Masculino , Modelos Moleculares , Simulación del Acoplamiento Molecular , Ratas , Ratas Sprague-Dawley , Tiazoles/farmacocinéticaRESUMEN
Vascular adhesion protein-1 (VAP-1), an amine oxidase that is also known as a semicarbazide-sensitive amine oxidase (SSAO), is present in particularly high levels in human plasma, and is considered a potential therapeutic target for various inflammatory diseases, including diabetes complications such as macular edema. In our VAP-1 inhibitor program, structural modifications following high-throughput screening (HTS) of our compound library resulted in the discovery that thiazole derivative 10, which includes a guanidine group, shows potent human VAP-1 inhibitory activity (IC(50) of 230 nM; rat IC(50) of 14 nM). Moreover, compound 10 exhibited significant inhibitory effects on ocular permeability in STZ-induced diabetic rats.
Asunto(s)
Amina Oxidasa (conteniendo Cobre)/antagonistas & inhibidores , Moléculas de Adhesión Celular/antagonistas & inhibidores , Inhibidores Enzimáticos/síntesis química , Guanidinas/síntesis química , Tiazoles/química , Amina Oxidasa (conteniendo Cobre)/metabolismo , Animales , Sitios de Unión , Moléculas de Adhesión Celular/metabolismo , Complicaciones de la Diabetes , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Inhibidores Enzimáticos/farmacocinética , Inhibidores Enzimáticos/uso terapéutico , Guanidinas/farmacocinética , Guanidinas/uso terapéutico , Semivida , Humanos , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Masculino , Simulación del Acoplamiento Molecular , Permeabilidad/efectos de los fármacos , Estructura Terciaria de Proteína , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad , Tiazoles/síntesis química , Tiazoles/farmacocinética , Tiazoles/uso terapéuticoRESUMEN
Novel thiazole derivatives were synthesized and evaluated as vascular adhesion protein-1 (VAP-1) inhibitors. Although our previous compound 1 showed potent VAP-1 inhibitory activity, the activity differed between humans and rats. This issue was overcome by a hybrid design using human VAP-1 specific inhibitor 2, which was found by high-throughput screening (HTS), a docking study of a human VAP-1 homology model, and an analysis of sequence information for humans and rats. As a result, we identified compound 35c, which showed strong VAP-1 inhibitory activity (human IC(50) of 20 nM; rat IC(50) of 72 nM) and significant inhibitory effects in the ex vivo test.
Asunto(s)
Amina Oxidasa (conteniendo Cobre)/antagonistas & inhibidores , Moléculas de Adhesión Celular/antagonistas & inhibidores , Retinopatía Diabética/tratamiento farmacológico , Edema Macular/tratamiento farmacológico , Tiazoles/farmacología , Amina Oxidasa (conteniendo Cobre)/sangre , Animales , Moléculas de Adhesión Celular/sangre , Relación Dosis-Respuesta a Droga , Humanos , Modelos Moleculares , Estructura Molecular , Ratas , Ratas Wistar , Relación Estructura-Actividad , Tiazoles/síntesis química , Tiazoles/químicaRESUMEN
PURPOSE: This study was undertaken to assess the mortality, complication, and major morbidity rates of surgical treatment for superior sulcus tumors (SSTs), and to estimate the significance of prognostic factors. METHODS: We retrospectively reviewed the hospital records of 50 consecutive patients undergoing surgical treatment for SSTs between 1992 and 2007. The significance of risk factors for an adverse outcome was investigated. RESULTS: Both the thirty-day and in-hospital mortality rates were 0 %. Complications developed in 18.0 % (9/50) of the patients. The overall 5-year survival was 32.7 %. Pathological T4 and N1 or more were the risk factors predicting an adverse outcome. Survival was not significantly influenced by the preoperative symptoms, the histological type, the invaded organ or the curability. CONCLUSION: Surgical treatment for SSTs is associated with acceptable overall morbidity and mortality rates. However, special care must be taken for the patients with pathological T4 and N1 or higher tumors. Preoperative chemoradiotherapy followed by surgical treatment has become a logical strategy for SSTs. Preoperative chemoradiotherapy for SSTs may yield better results than surgery alone.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Quimioradioterapia Adyuvante , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Complicaciones Posoperatorias/epidemiología , Cuidados Preoperatorios , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: To assess the mortality, complications and major morbidity of pneumonectomy for non-small cell lung cancer (NSCLC) and to establish the importance of various prognostic factors. METHODS: We reviewed retrospectively the hospital records of 71 consecutive patients who underwent pneumonectomy for NSCLC between 1992 and 2007 to evaluate the significance of risk factors for an adverse outcome. Patients were divided into two period groups according to the period when they were treated: early (1992-1999; n = 47) and late (2000-2007; n = 24). RESULTS: Both the 30-day and the in-hospital mortality rates were 4.2 % (3/71). Complications developed in 31.3 % (22/71) and overall 5-year survival was 23.1 %. Pathological stage III or more, T3 or more, and N2 or more were risk factors of an adverse outcome. Survival was not significantly influenced by histological type, the side of surgery, or curability. The 5-year survival rates for the early and late periods were 19.6 and 32.9 %, respectively. There were more patients with clinical N2 or 3 disease in the early period than in the late period (66.0 vs. 33.3 %). CONCLUSIONS: Pneumonectomy is associated with acceptable overall morbidity and mortality; however, patients with pathological stage III or more, T3 or more, and N2 or more disease require special consideration. Pneumonectomy should be performed only in selected patients.
Asunto(s)
Neoplasias Pulmonares/cirugía , Neumonectomía/efectos adversos , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonectomía/estadística & datos numéricos , Pronóstico , Estudios RetrospectivosRESUMEN
The Ewing's sarcoma family of tumors has been reported to originate in a variety of sites, most commonly in the extremities. We herein describe a rare case of primary pulmonary Ewing's sarcoma in a patient with a family history of sarcoma. The patient was a 42-year-old male, who presented with hemoptysis. Chest radiographs revealed a pulmonary mass in the right lower lobe. Clinical and radiological examinations (computed tomography and positron emission tomography) revealed that the lesion was a primary lesion. The lesion was resected by right lower lobectomy. The tumor was located in the pulmonary parenchyma, and there was no evidence of an extrapulmonary involvement by the tumor. Histologically, the tumor was composed of uniform cells with round nuclei and scant cytoplasm which were arranged in cohesive lobules with rare pseudorosette formation. Immunohistochemically, the tumor cells were positive for CD99, and negative for epithelial markers, neuroendocrine markers, myogenic markers and lymphoma markers. This diagnosis was further supported by the cytogenic and reverse transcriptase-polymerase chain reaction findings of EWS/FLI-1 fusion transcripts. This demonstrated the presence of a very rare primary pulmonary Ewing's sarcoma. The patient was treated with chemotherapy after the operation because Ewing's sarcoma is an aggressive neoplasm. The patient has had no recurrent disease for 6 months after the operation.
Asunto(s)
Neoplasias Pulmonares/diagnóstico , Sarcoma de Ewing/diagnóstico , Adulto , Hemoptisis/etiología , Humanos , Neoplasias Pulmonares/complicaciones , Masculino , Sarcoma de Ewing/complicacionesRESUMEN
We report a case of reconstruction of radiation ulcer on the chest wall and sternum osteomyelitis using a rectus abdominis musculocutaneous flap. A case of 67-year-old woman, Halsted operation was performed for right breast cancer, 23 years ago. After 4 years, transcatheter arterial injection and radiation therapy was performed to treat recurrence of parasternal lymph nodes. Since then, she had been without recurrence of the tumor, but suffered from repeated scabbing of parasternal skin. In 2009, she suffered from pain, redness and purulent discharge of the wound, and diagnosed with sternum osteomyelitis. She was admitted to our hospital and underwent debridement of sternum, and the resection of surrounding skin. Sixteen days later, reconstruction using a rectus abdominis musculocutaneous flap was performed. Twenty months after the operation, she is well without any evidence of recurrence.
Asunto(s)
Osteomielitis/cirugía , Esternón , Colgajos Quirúrgicos , Toracoplastia/métodos , Anciano , Neoplasias de la Mama/radioterapia , Femenino , Humanos , Osteomielitis/etiología , Traumatismos por Radiación/complicaciones , Radiodermatitis/complicaciones , Recto del AbdomenRESUMEN
BACKGROUND: The prognosis of patients with bone metastasis from primary lung cancer is poor, and the effective treatment for bone metastasis had not been established. We report a case of more than 6 years survival after a surgical resection of rib metastasis. CASE: A 56-years-old woman underwent right lower lobectomy and mediastinal lymph node dissection for lung cancer (well differentiated adenocarcinoma, pT1N0M0, stage IA) in another hospital in July 1995. In May 2003, the patient suffered right lateral chest pain and the chest computed tomography (CT) showed an osteolytic mass of right 5th rib. Percutaneous ultrasound-guided fine-needle aspiration cytology revealed adenocarcinoma and the tumor was diagnosed as bone metastasis from primary lung cancer. A chest wall resection for bone metastasis of right 5th rib was carried out and she underwent adjuvant chemotherapy. She is presently alive and well without recurrence more than 6 years after chest wall resection. CONCLUSION: A resection of bone metastasis from lung cancer may offer the possibility of a long-term survival in selected patients.
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Adenocarcinoma/patología , Neoplasias Óseas/secundario , Neoplasias Óseas/cirugía , Neoplasias Pulmonares/patología , Costillas , Neoplasias Óseas/mortalidad , Femenino , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: We investigated acute adverse events in patients with brain metastases (BMs) of anaplastic lymphoma kinase-rearranged (ALKr) non-small cell lung cancer (NSCLC) treated with both cranial radiotherapy and tyrosine kinase inhibitors (TKIs) of ALK. PATIENTS AND METHODS: Acute AEs were retrospectively investigated in patients with BMs of ALKr-NSCLC who received both whole-brain radiotherapy (WBRT) and ALK-TKI. For comparison, they were also assessed in patients with epidermal growth factor receptor (EGFR)-mutated NSCLC and wild-type with neither ALK rearrangement nor EGFR mutation treated with WBRT. RESULTS: Two ALKr cases were consequently eligible. Grade 3 otitis media unexpectedly occurred in both cases, while there was one case out of 11 and one case out of 18 of grade 2 otitis media among the EGFR-mutated cases and wild-type cases (p=0.013), respectively. CONCLUSION: Concurrent treatment with WBRT and ALK-TKI may be associated with acute severe ear toxicity in patients with BMs of ALKr-NSCLC.
Asunto(s)
Adenocarcinoma del Pulmón/terapia , Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Quinasa de Linfoma Anaplásico/genética , Neoplasias Encefálicas/terapia , Quimioradioterapia/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Reordenamiento Génico , Radiodermatitis/etiología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adulto , Anciano , Antineoplásicos/efectos adversos , Biomarcadores de Tumor , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Irradiación Craneana/efectos adversos , Crizotinib/efectos adversos , Receptores ErbB/genética , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Estudios RetrospectivosRESUMEN
While percent time within therapeutic range (%TTR) of international normalized ratio of prothrombin time (PT-INR) represents the quality of anticoagulation therapy with warfarin, it is often maintained less than 50% in patients with non-valvular atrial fibrillation (NVAF). We aimed to study if implementation of a multi-disciplinary ambulatory anticoagulation service (MAAS) may improve %TTR. Collaborating with cardiologists at Kanto Rosai Hospital, we conducted a MAAS for NVAF patients receiving warfarin from April 2013 to December 2015. Patients who agreed to utilize the service in addition to their appointments with cardiologists visited pharmacists to have counseling about diet, concomitant medications, and lifestyle. According to a protocol, pharmacists made dose adjustment proposals to cardiologists, if necessary. Upon approval by cardiologists, dose modifications were made. We retrospectively reviewed medical records of the patients who participated in the MAAS before and during the service. The study protocol was approved by the institutional review board. We identified 78 eligible patients (44 males and 34 females, aged 51 to 91 years). Their median %TTR increased significantly (p<0.05) from 57% during the pre-MAAS period to 77% during the MAAS period. In addition, the median percent time below therapeutic range (%TBTR) decreased significantly (p<0.05) from 35% during the baseline period to 11% during the MAAS period. The present study indicates that MAAS improves the quality of anticoagulation therapy with warfarin in ambulatory patients with NVAF. Further prospective, randomized studies with a greater number of patients are required to confirm the results of the present study.
Asunto(s)
Atención Ambulatoria , Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Comunicación Interdisciplinaria , Grupo de Atención al Paciente , Mejoramiento de la Calidad , Calidad de la Atención de Salud , Warfarina/uso terapéutico , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/sangre , Femenino , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Tiempo de Protrombina , Estudios RetrospectivosRESUMEN
OBJECTIVES: Platinum-based combination chemotherapy is the standard postoperative adjuvant treatment for pathological stage II/III non-small cell lung cancer (NSCLC). Oral S-1 therapy has good efficacy and relatively low toxicity for the treatment of advanced NSCLC. We investigated whether long-term S-1 monotherapy is also useful as an adjuvant therapy after surgery in patients with NSCLC. PATIENTS AND METHODS: We conducted a phase II randomized open-label multi-institutional study in patients with pathological stage II/IIIA NSCLC (7th TNM classification) who underwent complete resection from 2009 to 2013. The primary endpoint, the 2-year disease-free survival (DFS) rate, was evaluated using the Bayesian method. Eligible patients were randomly assigned to two arms: oral S-1 monotherapy (S-1 arm) and S-1 plus cisplatin combination therapy followed by S-1 (S-1 plus cisplatin arm) both for a total of 1 year. RESULTS: A total of 70 and 71 patients were enrolled in S-1 arm and S-1 plus cisplatin arm, respectively. The 2-year DFS rates were 52% (95% confidence interval [CI], 0.40-0.63) and 61% (95% CI, 0.48-0.70) for S-1 arm and S-1 plus cisplatin arm, respectively. Both arms met the primary endpoint. Neither DFS nor OS was significantly different between the arms (log-rank test: P = 0.1695 and P = 0.8684, respectively). The main G3/4 adverse events were loss of appetite and anemia (S-1 vs. S-1 plus cisplatin: 4.3% vs. 11.6% and 0% vs. 5.8%, respectively). The treatment completion rate did not differ between the two arms (S-1 vs. S-1 plus cisplatin: 45.7%, 95% CI, 41.9-66.3% vs. 43.5% 95% CI, 44.0-68.4%). CONCLUSIONS: Long-term adjuvant chemotherapy with S-1 was a feasible and promising treatment for patients with completely resected NSCLC, regardless of cisplatin addition. S-1 monotherapy should be investigated further, based on its low toxicity and practical convenience.
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Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Ácido Oxónico/uso terapéutico , Tegafur/uso terapéutico , Anciano , Quimioterapia Adyuvante , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neumonectomía , Periodo PosoperatorioRESUMEN
INTRODUCTION: Pulmonary dirofilariasis is a rare pulmonary parasitic infection by the nematode Dirofilaria immitis. It is characterized by an asymptomatic pulmonary nodule usually seen on chest X-ray. The differential diagnosis of pulmonary dirofilariasis includes other pulmonary diseases, primary lung carcinoma and metastatic lung tumor. CASE PRESENTATION: Pulmonary dirofilariasis was diagnosed in a woman who presented with interstitial pneumonia. Growth of the pulmonary nodule was detected subsequent to hemoptysis. The histological diagnosis was made based on a wedge resection performed under video-associated thoracic surgery (VATS). CONCLUSION: Pulmonary dirofilariasis often varies in its clinical course. The diagnosis is best made using wedge resection under VATS.
RESUMEN
Hemangioma of the rib is a rare benign vascular tumor. This benign disease induces osteolytic changes, and must be distinguished from a malignant bone tumor or metastatic tumor. Definitive diagnosis is achieved by excision biopsy or histological examination after surgical resection in many cases. We here in present a rare case of hemangioma of the rib.
RESUMEN
Pulmonary epithelial hemangioendothelioma is a rare low to intermediate malignant vascular tumor originating from vascular endothelial cells. The therapy for this disease, if possible, is surgical resection. However, there is no standard treatment for patients with multiple unresectable lesions. We present the case of a 42-year-old woman treated with a natural clinical course of hemangioendothelioma for four years without therapy. The nodules have increased in number and size extremely slowly, and the patient is alive and asymptomatic four years after diagnosis.
RESUMEN
Catamenial pneumothorax (CP) is a rare entity of spontaneous, recurring pneumothorax in females. Although it has been known to be associated with thoracic endometriosis, varying clinical course and the lack of consistent intraoperative findings have led to conflicting etiological theories. We herein discuss the etiology, clinical course, and surgical treatment of three patients with CP. Three females (aged 40 years, 28 years, and 34 years) had recurrent right-sided spontaneous pneumothoraces that coincided with their menses. They had undergone video-assisted thoracoscopic surgery (VATS) previously. Blueberry spots in the right diaphragm were detected in all three cases. Two patients had recurrence, postoperatively. The other patient, who received luteinizing hormone-releasing hormone analog therapy for an abdominal endometriosis in the perioperative period and postoperative chemical pleurodesis to prevent recurrence, has been free of recurrence for 15 months, postoperatively. However, pelvic endometriosis was detected in this patient only. Therefore, CP should be suspected in ovulating females with spontaneous pneumothorax, even in the absence of any symptoms associated with pelvic endometriosis. In addition, while performing VATS, careful inspection of the diaphragmatic surface is important. In complicated cases, hormonal suppression therapy and chemical pleurodesis might also be helpful adjunct modalities.