RESUMEN
Induced pluripotent stem cells (iPSC) have a great potential, but their clinical application depends on finding strategies to abolish their tumorigenic potential. The use of Oct4, Sox2, Klf4, c-Myc and Nanog to generate iPSC demonstrated the already known importance of these genes to maintain stemness. Therefore, the presence of these genes is responsible for iPSC-derived teratomas. Similar to iPSC, P19 teratocarcinoma cell line also has characteristics of embryonic carcinoma cells and the ability to differentiate into many cell types. We separately silenced the transcription factors Oct4, Sox2, Klf4, c-Myc and Nanog in P19 cells and measured the impact of this silencing in vivo. All silenced cells generated tumors when injected in immunosuppressed mice, but silencing of Oct4, Sox2 and Klf4 generated mainly teratomas with mesoderm tissue. Our results suggest that downregulation of these transcription factors is not enough to avoid the formation of teratomas, but their silencing affect their differentiation potential.
Asunto(s)
Silenciador del Gen , Teratoma/genética , Factores de Transcripción/genética , Animales , Carcinogénesis/genética , Carcinogénesis/patología , Línea Celular , Proliferación Celular , Femenino , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Proteína Homeótica Nanog/genética , Factor 3 de Transcripción de Unión a Octámeros/genética , Proteínas Proto-Oncogénicas c-myc/genética , Factores de Transcripción SOXB1/genética , Teratoma/patologíaRESUMEN
OBJECTIVE: This study aimed to verify the prognostic impact of pleural invasion according to the revised TNM classification, seventh edition. METHODS: The study consisted of 1488 patients with surgically resected non-small cell carcinoma. The degree (pl0-3) and location of pleural invasion were examined using hematoxylin and eosin- and elastica van Gieson-stained slides, and outcome was compared with stratification by several clinicopathological factors. RESULTS: The 5-year overall survival rates of 1008, 260, 85 and 135 patients with pl0, pl1, pl2 and pl3 tumours were 80, 60, 55 and 52%, respectively. Overall survival differed significantly between patients with pl0 tumours and those with pl1 tumours (P < 0.0001). The difference was significant for patients with 1<≤ 2 cm (P = 0.004), 2<≤ 3 cm (P = 0.003) and 3<≤ 5 cm (P = 0.02) tumours. The overall survival of pl0 patients was also significantly better in patients with adenocarcinoma (P < 0.0001) than squamous cell carcinoma (P = 0.043). The overall survival of pl0 patients was significantly better in patients without lymph node metastasis (P < 0.0001) than in those with lymph node metastasis. The 5-year overall survival rates of patients with interlobar, lateral, mediastinal and diaphragmatic pl3 tumours were 65, 51, 51 and 40%, respectively. Overall survival did not differ significantly among these four groups. CONCLUSIONS: Outcome differs between patients with pl0 tumours and those with pl1-3 tumours, particularly among patients with 1<≤ 2 cm, 2 <≤ 3 cm and 3<≤ 5 cm tumours, adenocarcinoma histology and no lymph node metastasis. The location of pl3 pleural invasion did not affect outcome significantly.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Neoplasias Pleurales/secundario , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Neumonectomía , Valor Predictivo de las Pruebas , Pronóstico , Coloración y Etiquetado/métodosRESUMEN
The BacT/Alert system has been used for detecting the presence of bacteria in various clinical settings as well as in blood services, but it is associated with a relatively high incidence of false-positive results. We analyzed the results of our quality control sterility testing of blood products by BacT/Alert 3D to understand the mechanism of false-positive results. Anaerobic and aerobic bottles were inoculated with 10 mL of samples and cultured in BacT/Alert 3D for 10 days. Positive-reaction cases were classified as true positive if any bacterium was identified or false positive if the identification test had a negative result. The detection algorithm and the bottle graph pattern of the positive reaction cases were investigated. Among the 43,374 samples, 25 true positives (0.06%) and 29 false positives (0.07%) were observed. Although the detection algorithm of all true positives and 25 of 29 false positives was accelerating production of CO2, a steep rise in the bottle graph was observed only in the true positives, and it was not observed in either of the false positives. Four of 29 false positives were dependent on high baseline scatter reflections. Furthermore, evaluating the bottle graph pattern of Streptococcus pneumoniae, a bacterium known to autolyze, we confirmed that no viable bacterium was detected even if a steep rise was observed. In conclusion, the bottle graph pattern of positive reactions allows the differentiation between true positives and false positives. In case of a steep rise without bacterium detection, the bacterium might have autolyzed. Moreover, positive reactions with high baseline scatter reflections, despite immediate loading of bottles after sampling, are potentially false positive. IMPORTANCE In clinical settings, false-positive results are treated as positive until bacterial identification. It may result in the discarding of blood products in blood centers or affect clinical decisions in hospitals or testing facilities. Moreover, the management of these samples is usually time- and labor-consuming. The results of our study may help clinicians and laboratory staff in making a more precise evaluation of positive reactions in BacT/Alert.
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Bacterias , Técnicas Bacteriológicas , HumanosRESUMEN
To address whether hospital antimicrobial use influences surgical site infection (SSI), we investigated factors including antimicrobial homogeneity index (AHI), an indicator of prescription diversity, with a retrospective study during 120 months for patients undergoing lung, breast, and general surgery (n = 4,510). We analyzed the odds ratios of background factors for SSI and the correlation between AHI and drug susceptibility in isolates of SSI. A total of 243 cases of SSI (5.4%) occurred. Factors that significantly contributed for SSI were operative time [odds ratio (OR), 1.78; 95% confidence interval (CI), 1.33-2.39; P < 0.001], American Society of Anesthesiologists' score (OR, 1.68, 95% CI, 1.23-2.28; P < 0.001), endoscopic use (OR, 0.10, 95% CI, 0.04-0.24; P < 0.001), lung and breast surgery versus general surgery (OR, 0.12, 95% CI, 0.06-0.22; P < 0.001), increased AHI (OR, 0.72, 95% CI, 0.55-0.95; P = 0.020), and older age (OR, 2.08, 95% CI, 1.39-3.11; P < 0.001). AHI showed a positive correlation coefficient (CC, P < 0.05) with susceptibility to ampicillin (CC = +0.327), cefotaxime (CC = +0.142), imipenem/cilastatin (CC = +0.101), and sulbactam/cefoperazone (CC = +0.145). AHI, which has been described to help prevent drug resistance, was associated with increased susceptibility in microbes of SSI. This finding in part may explain that increase in AHI reduced SSI.
Asunto(s)
Antiinfecciosos/administración & dosificación , Infección de la Herida Quirúrgica/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacterias/efectos de los fármacos , Mama/cirugía , Humanos , Modelos Logísticos , Pulmón/cirugía , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Pautas de la Práctica en Medicina , Estudios Retrospectivos , Infecciones Estafilocócicas/epidemiología , Infección de la Herida Quirúrgica/epidemiologíaRESUMEN
BACKGROUND: While thoracic surgeons occasionally encounter pulmonary thromboembolism, the use of unfractionated heparin may cause adverse effects. METHODS: We assessed a series of 323 consecutive pulmonary operations performed during 4 years from 2008 to 2011. All patients were given elastic stockings and intermittent pneumatic compression. During the first 2 years (2008-2009), none of the 169 patients received unfractionated heparin. In the second 2-year period (2010-2011), 135/154 patients received subcutaneous unfractionated heparin, either 5000 units (n = 37) or 2500 units (n = 93) twice daily for 3 days, or continuous intravenous unfractionated heparin (n = 5). The epidural catheters were withdrawn 6 h or more after unfractionated heparin use. Among patients without postoperative unfractionated heparin, 8 (42.1%) had a bleeding risk and 5 (26.3%) had limited operative time. RESULTS: One (0.6%) patient developed pulmonary thromboembolism during 2008-2009, but none had this complication during 2010-2011. The adverse outcome of intrathoracic bleeding occurred in one (2.7%) of the patients given 5000 units of unfractionated heparin, but no epidural hematomas occurred in these patients. CONCLUSION: Patients undergoing thoracic surgery at low risk of bleeding may receive unfractionated heparin to prevent pulmonary thromboembolism while avoiding epidural complications.
Asunto(s)
Anticoagulantes/administración & dosificación , Heparina/administración & dosificación , Embolia Pulmonar/prevención & control , Procedimientos Quirúrgicos Pulmonares/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Esquema de Medicación , Femenino , Hemorragia/inducido químicamente , Heparina/efectos adversos , Humanos , Infusiones Intravenosas , Inyecciones Subcutáneas , Aparatos de Compresión Neumática Intermitente , Masculino , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiología , Medición de Riesgo , Factores de Riesgo , Medias de Compresión , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Crystal-storing histiocytosis is a rare clinical entity characterized by an increase in the number of abnormal histiocytes accompanied by accumulation of crystallized immunoglobulins. We describe the case of an 80-year-old man who presented with crystal-storing histiocytosis of the lung 13 years after receiving a diagnosis of gastric non-Hodgkin lymphoma (NHL ; clinical stage, Lugano IA). After wedge resection of the left upper lobe, the histological findings showed crystal-storing histiocytosis with CD68(+), some small to medium lymphoid cells with CD79a(+) with κ(+(weekly)) and λ(-), and some plasma cells with CD138(+), and rearrangement of the immunoglobulin heavy chain. Based on the nonrecurrent gastric NHL, small B-cell population, and failure to detect the same clone by polymerase chain reaction analysis, our case was classified as pulmonary localized crystal-storing histiocytosis without underlying lymphoproliferative or plasma cell disorder. The findings of minor B-cell populations harboring a heavy chain rearrangement with slight light-chain restriction (κ > λ) may be related to the pathogenesis of crystallogenesis and crystal-storing histiocytosis. Moreover, surgical treatment may be an effective therapeutic option for solitary crystal-storing histiocytosis.
Asunto(s)
Histiocitosis/complicaciones , Histiocitosis/cirugía , Linfoma no Hodgkin/complicaciones , Nódulo Pulmonar Solitario/complicaciones , Nódulo Pulmonar Solitario/cirugía , Neoplasias Gástricas/complicaciones , Anciano de 80 o más Años , Fluorodesoxiglucosa F18 , Reordenamiento Génico , Histiocitos/metabolismo , Histiocitos/patología , Histiocitosis/diagnóstico , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Inmunoglobulinas/química , Inmunoglobulinas/metabolismo , Inmunohistoquímica , Pulmón/patología , Linfoma no Hodgkin/diagnóstico , Masculino , Tomografía de Emisión de Positrones , Nódulo Pulmonar Solitario/diagnóstico , Neoplasias Gástricas/diagnóstico , Resultado del TratamientoRESUMEN
In pulmonary surgery, methicillin-resistant Staphylococcus aureus (MRSA)-positive patients present an issue of perioperative antimicrobials. During 1996 to 2009 in a total of 1,080 pulmonary operations, MRSA was detected before 20 operations. Perioperatively, we followed the Sanford Guide using vancomycin (VCM) or arbekacin (ABK) in MRSA-positive cases at high risk (n = 14), including 1 with clinical infection and 13 with colonization. We used 1-day cefazolin (CEZ) in MRSApositive cases at low risk (n = 6). We defined the outcome as surgical site infection (SSI) that included death from infection. The 14 high-risk cases received a median of 3 days of VCM or ABK, of which 1 (7%) developed SSI. Of the cases given CEZ, we noted SSI in 1 of 6 low-risk cases (17%). Thus, MRSA-positive pulmonary surgery patients at large may receive 3-day VCM or ABK.