RESUMEN
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently characterized T-cell malignancy that has raised significant patient safety concerns and led to worldwide impact on the implants used and clinical management of patients undergoing reconstructive or cosmetic breast surgery. Molecular signatures distinguishing BIA-ALCL from other ALCLs have not been fully elucidated and classification of BIA-ALCL as a WHO entity remains provisional. We performed RNA sequencing and gene set enrichment analysis comparing BIA-ALCLs to non-BIA-ALCLs and identified dramatic upregulation of hypoxia signaling genes including the hypoxia-associated biomarker CA9 (carbonic anyhydrase-9). Immunohistochemistry validated CA9 expression in all BIA-ALCLs, with only minimal expression in non-BIA-ALCLs. Growth induction in BIA-ALCL-derived cell lines cultured under hypoxic conditions was proportional to up-regulation of CA9 expression, and RNA sequencing demonstrated induction of the same gene signature observed in BIA-ALCL tissue samples compared to non-BIA-ALCLs. CA9 silencing blocked hypoxia-induced BIA-ALCL cell growth and cell cycle-associated gene expression, whereas CA9 overexpression in BIA-ALCL cells promoted growth in a xenograft mouse model. Furthermore, CA9 was secreted into BIA-ALCL cell line supernatants and was markedly elevated in human BIA-ALCL seroma samples. Finally, serum CA9 concentrations in mice bearing BIA-ALCL xenografts were significantly elevated compared to control serum. Together, these findings characterize BIA-ALCL as a hypoxia-associated neoplasm, likely attributable to the unique microenvironment in which it arises. These data support classification of BIA-ALCL as a distinct entity and uncover opportunities for investigating hypoxia-related proteins such as CA9 as novel biomarkers and therapeutic targets in this disease.
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Implantes de Mama , Neoplasias de la Mama , Linfoma Anaplásico de Células Grandes , Animales , Implantes de Mama/efectos adversos , Femenino , Humanos , Hipoxia/genética , Inmunohistoquímica , Linfoma Anaplásico de Células Grandes/genética , Ratones , Microambiente TumoralRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
FLT3-internal tandem duplication occurs in 20-30% of acute myeloid leukemia and confers an adverse prognosis with its allelic ratio being a key risk stratifier. The US Food and Drug Administration recently approved FLT3 inhibitors midostaurin and gilteritinib in FLT3 mutation-positive acute myeloid leukemia. Historically, FLT3 was tested by fragment analysis, which has become the standard method endorsed by international guidelines. However, next generation sequencing is increasingly used at acute myeloid leukemia diagnosis given its ability to simultaneously evaluate multiple clinically informative markers. As FLT3-internal tandem duplication detection was known to be challenging by next generation sequencing and the results carry profound prognostic and therapeutic implications, it is important to thoroughly examine its performance in FLT3-internal tandem duplication detection and allelic ratio classification. In a comparative study with fragment analysis, we retrospectively reviewed our experience using a custom-designed, hybridization capture-based, targeted next generation sequencing panel. Among 7902 cases, FLT3-internal tandem duplication was detected in 335 with variable sizes (3-231 bp) and insertion sites. Fragment analysis was also performed in 402 cases, demonstrating 100% concordance in FLT3-internal tandem duplication detection. In 136 dual-tested, positive cases, 128/136 (94%) exhibited concordant high/low allelic ratio classifications. The remaining 6% showed borderline low allelic ratio by next generation sequencing. The two methods were concordant in FLT3-tyrosine kinase domain mutation detection at the hotspot D835/I836 targeted by fragment analysis. Furthermore, seven mutations which may benefit from FLT3 inhibitor therapy were detected by next generation sequencing, in regions not covered by fragment analysis. Our study demonstrates that using a hybridization capture-based chemistry and optimized bioinformatics pipeline, next generation sequencing can reliably detect FLT3-internal tandem duplication and classify its allelic ratio for acute myeloid leukemia risk stratification. Next generation sequencing also exhibits superior comprehensiveness in FLT3 mutation detection and may further improve personalized, targeted therapy in acute myeloid leukemia.
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Biomarcadores de Tumor/genética , Análisis Mutacional de ADN , Secuenciación de Nucleótidos de Alto Rendimiento , Leucemia Mieloide Aguda/genética , Mutación , Secuencias Repetidas en Tándem , Tirosina Quinasa 3 Similar a fms/genética , Biología Computacional , Predisposición Genética a la Enfermedad , Humanos , Fenotipo , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
Noninvasive prenatal testing (NIPT) using sequencing of fetal cell-free DNA from maternal plasma has enabled accurate prenatal diagnosis of aneuploidy and become increasingly accepted in clinical practice. We investigated whether NIPT using semiconductor sequencing platform (SSP) could reliably detect subchromosomal deletions/duplications in women carrying high-risk fetuses. We first showed that increasing concentration of abnormal DNA and sequencing depth improved detection. Subsequently, we analyzed plasma from 1,456 pregnant women to develop a method for estimating fetal DNA concentration based on the size distribution of DNA fragments. Finally, we collected plasma from 1,476 pregnant women with fetal structural abnormalities detected on ultrasound who also underwent an invasive diagnostic procedure. We used SSP of maternal plasma DNA to detect subchromosomal abnormalities and validated our results with array comparative genomic hybridization (aCGH). With 3.5 million reads, SSP detected 56 of 78 (71.8%) subchromosomal abnormalities detected by aCGH. With increased sequencing depth up to 10 million reads and restriction of the size of abnormalities to more than 1 Mb, sensitivity improved to 69 of 73 (94.5%). Of 55 false-positive samples, 35 were caused by deletions/duplications present in maternal DNA, indicating the necessity of a validation test to exclude maternal karyotype abnormalities. This study shows that detection of fetal subchromosomal abnormalities is a viable extension of NIPT based on SSP. Although we focused on the application of cell-free DNA sequencing for NIPT, we believe that this method has broader applications for genetic diagnosis, such as analysis of circulating tumor DNA for detection of cancer.
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Aberraciones Cromosómicas/embriología , ADN/sangre , Feto/anomalías , Diagnóstico Prenatal/métodos , Semiconductores , Análisis de Secuencia de ADN/métodos , Sistema Libre de Células , Deleción Cromosómica , Duplicación Cromosómica , Hibridación Genómica Comparativa , Femenino , Humanos , Peso Molecular , EmbarazoRESUMEN
Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting.
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Aneuploidia , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Diagnóstico Prenatal/métodos , Adulto , Trastornos de los Cromosomas/diagnóstico , Cromosomas Humanos Par 13 , Cromosomas Humanos Par 18 , Análisis Costo-Beneficio , Síndrome de Down/diagnóstico , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/instrumentación , Humanos , Cariotipificación , Masculino , Embarazo , Estudios Prospectivos , Estudios Retrospectivos , Semiconductores , Sensibilidad y Especificidad , Trisomía/diagnóstico , Síndrome de la Trisomía 13 , Síndrome de la Trisomía 18Asunto(s)
Implantes de Mama/efectos adversos , Neoplasias de la Mama/cirugía , Linfoma Anaplásico de Células Grandes/clasificación , Linfoma Anaplásico de Células Grandes/genética , Proteínas de Neoplasias/genética , Proteínas de Fusión Oncogénica/genética , Adulto , Anciano , Neoplasias de la Mama/complicaciones , Femenino , Reordenamiento Génico , Humanos , Linfoma Anaplásico de Células Grandes/etiología , Linfoma Anaplásico de Células Grandes/patología , Persona de Mediana EdadRESUMEN
Drawing inspiration from origami structures, a pressure sensor was developed with unique interconnection scaling at its creases crafted on a conductive paper substrate, paving the way for advanced wearable technology. Two screen-printed conductive paper substrates were combined face-to-face, and specific folds were introduced to optimize the sensor structure. The Electrical Contact Resistance (ECR) was systematically analyzed across different fold numbers and crease gaps, revealing a notable trade-off: while increasing the number of folds expanded the sensing area, it also influenced the ECR, reaching a performance plateau. Strategic modifications in the sensor's design, including refining interconnections at the crease, enhanced its sensitivity and stability, culminating in a remarkable sensitivity of 3.75 kPa-1 at subtle pressure levels (0-0.05 kPa). This sensor's real-world applications proved to be transformative, from detecting bruxism and aiding in neck posture correction to remotely sensing trigger finger locking phenomena, highlighting its potential as a pivotal tool in upcoming medical diagnostics and treatments.
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Dispositivos Electrónicos Vestibles , Conductividad Eléctrica , Impedancia EléctricaRESUMEN
Leukemia stem cells (LSCs) are linked to relapse in acute myeloid leukemia (AML). The LSC17 gene expression score robustly captures LSC stemness properties in AML and can be used to predict survival outcomes and response to therapy, enabling risk-adapted, upfront treatment approaches. The LSC17 score was developed and validated in a research setting. To enable widespread use of the LSC17 score in clinical decision making, we established a laboratory-developed test (LDT) for the LSC17 score that can be deployed broadly in clinical molecular diagnostic laboratories. We extensively validated the LSC17 LDT in a College of American Pathologists/Clinical Laboratory Improvements Act (CAP/CLIA)-certified laboratory, determining specimen requirements, a synthetic control, and performance parameters for the assay. Importantly, we correlated values from the LSC17 LDT to clinical outcome in a reference cohort of patients with AML, establishing a median assay value that can be used for clinical risk stratification of individual patients with newly diagnosed AML. The assay was established in a second independent CAP/CLIA-certified laboratory, and its technical performance was validated using an independent cohort of patient samples, demonstrating that the LSC17 LDT can be readily implemented in other settings. This study enables the clinical use of the LSC17 score for upfront risk-adapted management of patients with AML.
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Laboratorios Clínicos , Leucemia Mieloide Aguda , Estudios de Cohortes , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Células Madre Neoplásicas/metabolismo , Medición de RiesgoRESUMEN
OBJECTIVES: Pure erythroid leukemia (PEL) is exceptionally rare in the pediatric setting. Four pediatric PEL cases with t(1;16)(p31;q24) NFIA-CBFA2T3 were reported previously. We present a case of an infant with PEL presenting with erythroblastic sarcoma and harboring a novel t(1;8)(p31.3;q21.3) NFIA-RUNX1T1 fusion detected by RNA sequencing and conventional karyotype. METHODS: Bone marrow (BM) and abdominal mass biopsies from the patient were evaluated with extensive immunohistochemical, flow cytometric, cytogenetic, and molecular studies. RESULTS: The patient was a female infant who presented between 2 and 5 months of age with cytopenias and an enlarging abdominal mass. Blasts in the BM and abdominal mass expressed CD71 and CD117 with focal expression of CD43, E-cadherin, epithelial membrane antigen, and hemoglobin A. They were negative for additional myeloid, lymphoid, and nonhematolymphoid markers. These findings were most consistent with PEL and erythroblastic sarcoma. RNA sequencing revealed the novel NFIA-RUNX1T1 fusion. CONCLUSIONS: Along with the previously reported PELs with NFIA-CBFA2T3 fusions, we describe a subset of PELs that occur in children, that frequently display extramedullary disease, and that harbor rearrangements of NFIA with core binding factor genes. We hypothesize that, together, these cases represent a rare but distinct clinicopathologic group of pediatric PELs with recurrent genetic abnormality.
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Leucemia Eritroblástica Aguda/genética , Factores de Transcripción NFI/genética , Proteína 1 Compañera de Translocación de RUNX1/genética , Femenino , Humanos , Lactante , Leucemia Eritroblástica Aguda/patología , Fusión de Oncogenes/genética , Translocación GenéticaRESUMEN
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and â¼2% to 9% patients develop an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (Richter transformation, DLBCL-RT). Programmed death-1 (PD-1) pathway plays a crucial role in tumor host immunity evasion and its blockade has emerged as an effective anti-cancer immunotherapy. PD-L1 and PD-1 expression has shown predictive value in anti-PD cancer immunotherapy; however, it has not been well documented in CLL/SLL and DLBCL-RT. We evaluated PD-1 and PD-L1 expression by immunohistochemistry in 39 CLL/SLL, 15 DLBCL-RT, and 26 other DLBCL. In CLL/SLL, neoplastic B-cell PD-1 expression was weak and restricted to prolymphocytes/paraimmunoblasts within proliferation centers (PCs) and accentuated PCs of all sizes. Neoplastic B-cell PD-1 expression was highly prevalent and demonstrated increased intensity in DLBCL-RT, but in contrast was only rarely seen in other DLBCL (12/15 vs. 1/26; P<0.0001). An excellent correlation (90% concordance) was observed between neoplastic B-cell PD-1 immunohistochemistry positivity and molecularly defined CLL/SLL clonal relatedness in DLBCL-RT. PD-L1 expression was observed on the neoplastic B cells in rare DLBCL-RT and other DLBCL cases (1/15 vs. 1/26; P>0.05) as well as background histiocytes and dendritic cells. Overall survival of DLBCL-RT was significantly inferior to that of the other DLBCL (median, 16.9 vs. 106.1 mo; P=0.002). Our findings suggest a biological continuum from prolymphocytes/paraimmunoblasts in CLL/SLL PCs to the neoplastic B-cells in DLBCL-RT. The characteristic PD-1 expression in DLBCL-RT makes it a potential surrogate marker for determining clonal relatedness to CLL/SLL, which may have important prognostic and therapeutic implications.
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Linfocitos B/inmunología , Biomarcadores de Tumor/análisis , Transformación Celular Neoplásica/inmunología , Leucemia Linfocítica Crónica de Células B/inmunología , Linfoma de Células B Grandes Difuso/inmunología , Receptor de Muerte Celular Programada 1/análisis , Linfocitos B/patología , Antígeno B7-H1/análisis , Biomarcadores de Tumor/genética , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Evolución Clonal , Análisis Mutacional de ADN , Genes de las Cadenas Pesadas de las Inmunoglobulinas , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/patología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Mutación , Fenotipo , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND AND PURPOSE: To evaluate the significance of multidrug-resistant Acinetobacter baumannii (MDRAB)-related ventilator-associated pneumonia at a medical center in southern Taiwan. METHODS: We retrospectively reviewed the medical records of patients with MDRAB isolated from sputum and described the characteristics of these patients. Patients were divided into 2 groups according to their clinical pulmonary infection scores (CPIS), and their host factors and outcomes compared. RESULTS: In the patient group with significant MDRAB-related lung infection, Acute Physiology and Chronic Health Evaluation II scores were significantly higher than in those patients with lower CPIS scores (<6). However, the clinical outcomes, including the duration of hospitalization after isolation of MDRAB and mortality rate, were not different. CONCLUSION: Our investigation showed that significant lung infections with MDRAB isolation did not result in prolonged hospitalization or increased mortality. The initial clinical severity of the group with significant MDRAB-related lung infection was significantly greater than in the other. We propose that MDRAB-related pneumonia should be regarded as a signal of the clinical severity of the patient rather than as a prognostic factor.
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Acinetobacter baumannii/efectos de los fármacos , Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana Múltiple , Neumonía Asociada al Ventilador/microbiología , APACHE , Infecciones por Acinetobacter/mortalidad , Infecciones por Acinetobacter/fisiopatología , Acinetobacter baumannii/aislamiento & purificación , Anciano , Anciano de 80 o más Años , Infección Hospitalaria/mortalidad , Infección Hospitalaria/fisiopatología , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Neumonía Asociada al Ventilador/mortalidad , Neumonía Asociada al Ventilador/fisiopatología , Pronóstico , Estudios Retrospectivos , Esputo/microbiología , TaiwánRESUMEN
BACKGROUND AND PURPOSE: Actinomycosis is an uncommon and frequently misdiagnosed infection that may present as an acute or indolent process. Even when clinical suspicion is high, the disease is commonly confused with other chronic inflammatory diseases and malignancy. An early diagnosis helps the clinician in deciding treatment and can avoid physical morbidity such as unwarranted surgery. METHODS: We retrospectively evaluated the histopathology and selected clinical information on all cases of actinomycosis that occurred at Kaohsiung Veterans General Hospital in Taiwan from 1993 to 2005. Data on the demographic characteristics, predisposing conditions, clinical presentations, diagnosis and treatment were analyzed. RESULTS: A total 36 cases of actinomycosis were identified and evaluated. The mean age of patients was 52.14 +/- 13.28 years, and the male-to-female ratio was 1:1.1. Only three types of actinomycosis were found in this study: cervicofacial, at an incidence of 31%; thoracic (33%); and pelvic (36%). The clinical manifestations depended upon the region of infection; the most frequent presentations of cervicofacial, thoracic and pelvic actinomycosis were cutaneous soft tissue swelling with drainage sinus formation (55%), hemotypsis (75%) and abnormal vaginal spotting (54%), respectively. The most common initial laboratory abnormalities were normochromic anemia (69%) and leukocytosis (25%). While most patients had no history of a foreign body, all pelvic actinomycotic patients had a history of intrauterine device use. Nineteen patients (53%) had no comorbid conditions and 11 patients (31%) had malignancy. Most patients were initially diagnosed as malignancy (56%). All patients with actinomycosis were diagnosed by histopathologic findings. Twenty two patients (61%) were treated by surgery combined with antibiotics, 11 patients (31%) by surgery only and 3 patients (8%) by antibiotics only. No recurrence or mortality occurred. CONCLUSIONS: Actinomycosis should be included in the differential diagnosis when patients present with chronic drainage sinus, chronic hemoptysis and abnormal vaginal spotting with use of intrauterine devices.
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Actinomicosis/diagnóstico , Actinomicosis/epidemiología , Actinomicosis/fisiopatología , Actinomicosis/terapia , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Causalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Taiwán/epidemiologíaRESUMEN
Janus kinase 2 (JAK2) is located on chromosome 9 at band p24 and JAK2V617F is the most common mutation in Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPN). However, rearrangement of JAK2 is a rare event. We report a case of myeloproliferative neoplasm, unclassifiable (MPN-U) with BCR-JAK2 fusion confirmed by molecular studies. Conventional chromosome analysis (CC) revealed t(9;22)(p24;q11.2) and fluorescence in situ hybridization (FISH) showed a JAK2 gene rearrangement in 88% of interphase nuclei. The BCR-JAK2 fusion was confirmed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) and demonstrated two in-frame 5'BCR/3'JAK2 transcripts with BCR exon 1 juxtaposed to JAK2 exon 15 and exon 17, respectively. Our results, together with literature review, reveal BCR-JAK2 fusions as oncogenic genetic alterations that are associated with myeloid or lymphoid neoplasms and are frequently characterized by eosinophilia. Further, patients with BCR-JAK2 are candidates for JAK2 inhibitor therapy. Given the distinct clinical and pathological characteristics, we believe that hematological neoplasms harboring BCR-JAK2 should be included as an additional distinct entity to the current WHO category of "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR", and testing for a JAK2 fusion should be pursued in neoplasms with a karyotypic 9p24 abnormality.
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Janus Quinasa 2/genética , Trastornos Mieloproliferativos/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Proto-Oncogénicas c-bcr/genética , Adulto , Femenino , Reordenamiento Génico , Humanos , Hibridación Fluorescente in Situ , Cariotipo , Reacción en Cadena de la Polimerasa Multiplex , Translocación GenéticaRESUMEN
A significant fraction of hereditary nonpolyposis colorectal cancer cases with defective mismatch repair (ie, Lynch syndrome) have large genomic deletions or duplications in the mismatch repair genes, hMLH1 and hMSH2, which can be challenging to detect by traditional methods. For this study, we developed and validated a novel Southern blot analysis method that allows for ascertainment of the extent of the dosage alterations on an exon-by-exon basis and compared this method to a second novel technique, multiplex ligation-dependent probe amplification (MLPA). From a total of 254 patients referred for Lynch syndrome testing, 20 of the 118 MLH1 cases and 42 of the 136 MSH2 cases had large genomic alterations, as detected by Southern blot. MLPA and Southern blot results were concordant with the exception of three major discrepancies: one because of a lack of MLPA probes for the region altered, another because of a point mutation near the MLPA probe ligation site, and another that was unexplained. Compared to Southern blot, MLPA has a shorter turn-around time, the analysis is less costly, less time-consuming, and less labor-intensive, and results are generally clear and unambiguous. However, concerns with MLPA include the presence of false-negatives and -positives because of positioning of probes and DNA variants near the probe ligation site. Overall, both Southern blot and MLPA provide important tools for the complete evaluation of patients with Lynch syndrome.
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Southern Blotting/métodos , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Análisis Mutacional de ADN/métodos , Dosificación de Gen , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Proteínas Adaptadoras Transductoras de Señales , Proteínas Portadoras , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , ADN de Neoplasias/genética , Humanos , Homólogo 1 de la Proteína MutL , Proteínas MutLRESUMEN
For patients with chronic lymphocytic leukemia, an important prognostic indicator is the somatic hypermutation status of immunoglobulin heavy chain variable region nucleic acid within the clonal cell population. Current clinical assays for this evaluation rely on Sanger sequencing and are complex, such that availability of testing for patients is limited and costly. However, advances in high-throughput sequencing provide an opportunity to improve complex clinical sequencing applications. Our goal was to determine whether high-throughput sequencing technology could reliably perform the sequencing required for somatic hypermutation analysis and improve clinical testing for chronic lymphocytic leukemia patients. Blood or liquid bone marrow aspirate samples from 50 different patients were evaluated in parallel using a validated clinical assay based on Sanger sequencing and a modified protocol in which the sequencing was performed using an Ion Torrent personal genome machine. In each case, both methods gave identical results with respect to interpreted somatic hypermutation status and dominant immunoglobulin heavy chain variable region gene reported. The personal genome machine-based method had significant advantages over the Sanger-based method for use in clinical laboratories that perform long-read, high-throughput sequencing.
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Leucemia Linfocítica Crónica de Células B/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , MutaciónRESUMEN
OBJECTIVE: To investigate the protective effect of high-pressure carbon monoxide for preservation of ex vivo rabbit heart graft in comparison with the conventional HTK cardioplegic solution preservation. METHODS: Heart grafts isolated from 85 New Zealand rabbits were randomly divided into Naive group (n=5), HTK group (n=40) and CO group (n=40). The grafts underwent no preservation procedures in Naive group, preserved at 4 degrees celsius; in HTK cardioplegic solution in HTK group, and preserved at 4 degrees celsius; in a high-pressure tank (PO2: PCO=3200 hPa: 800 hPa) in CO group with Krebs-Henseleit solution perfusion but without cardioplegic solution. After preservation for 2, 4, 6, 8, 10, 14, 18, and 24 h, 5 grafts from the two preservation groups were perfused for 30 min with a modified Langendorff apparatus and examined for left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), arrhythmia score (AS), myocardial ultrestructure, and cardiac enzyme profiles. RESULTS: After preservation for 6 to 24 h, the cardiac enzyme profiles and systolic and diastolic functions were significantly better in CO group than in HTK group, but these differences were not obvious between the two groups after graft preservation for 2 to 4 h. Significant changes in the myocardial ultrastructures occurred in the isolated hearts after a 24-h preservation in both CO and HTK groups, but the myocardial damages were milder in CO group. CONCLUSION: Preservation using high-pressure carbon monoxide can better protect isolated rabbit heart graft than the conventional HTK preservation approach especially for prolonged graft preservation.
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Monóxido de Carbono , Soluciones Cardiopléjicas , Corazón/fisiología , Conservación de Tejido/métodos , Animales , Glucosa , Trasplante de Corazón , Miocardio/ultraestructura , Conejos , TrometaminaRESUMEN
Despite the existence of a government-run tuberculosis (TB) control program, the current nationwide burden of TB continues to be a public health problem in Taiwan. Intense current and previous efforts into diagnostic, therapeutic, and preventive interventions have focused on TB in adults, but childhood TB has been relatively neglected. Children are particularly vulnerable to severe disease and death following infection, and children with latent infections become reservoirs for future transmission following disease reactivation in adulthood, thus fueling future epidemics. Additional research, understanding, and prevention of childhood TB are urgently needed. This review assesses the epidemiology, diagnosis, treatment, and relevant principles of TB vaccine development and presents efficacy data for the currently licensed vaccines.
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Vacunas contra la Tuberculosis/inmunología , Tuberculosis/epidemiología , Niño , Humanos , Incidencia , Mycobacterium tuberculosis/aislamiento & purificación , Radiografía Torácica , Taiwán/epidemiología , Prueba de Tuberculina , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/prevención & control , VacunaciónRESUMEN
OBJECTIVE: To summarize the experience with surgical treatment of coronary artery disease with severe ischemic mitral valve regurgitation (IMR). METHODS: From January 2006 to December 2009, 45 patients (35 males, 10 females aged 32-74 years) with the diagnosis of coronary artery disease complicated by IMR underwent coronary artery bypass grafting (CABG) combined with mitral valve plasty (MVP, 24 cases) or mitral valve replacement (MVR, 21 cases). RESULTS: Perioperative deaths occurred in 2 cases due to multiple organ failure (MOF). Echocardiography showed a significant reduction of the mitral regurgitation area (from 11.80∓2.45 cm(2) to 2.83∓0.98 cm(2), t=22.80, P=0.00) after CABG combined with mitral valve surgery, with also significantly reduced postoperative left ventricular end diastolic diameter (LVEDD) (from 57.61∓10.06 mm to 51.84∓8.98 mm, t=2.85, P=0.005). No significant difference was detected in the left ventricular ejection fraction after the operation [(52.7∓15.4)% vs (53.2∓13.2)%, t=0.16, P=0.87)]. CONCLUSIONS: CABG combined with mitral valve surgery can improve early postoperative left ventricular function in patients with ischemic coronary heart disease complicated by severe mitral regurgitation, but further follow-up study is still needed for evaluation of the long-term results.
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Enfermedad Coronaria/cirugía , Insuficiencia de la Válvula Mitral/cirugía , Isquemia Miocárdica/cirugía , Adulto , Anciano , Puente de Arteria Coronaria , Enfermedad Coronaria/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia de la Válvula Mitral/complicaciones , Isquemia Miocárdica/complicaciones , Resultado del TratamientoRESUMEN
OBJECTIVE: To analyze the changes in the cardiac function after St. Jude Regent mechanical valve replacement and assess the prosthesis-patient matching. METHODS: From October 2007 to March 2009, 44 patients received implantation of 17 mm St. Jude aortic prostheses in our hospital. The patients were followed up for clinical symptoms, signs, electrocardiogram (ECG), echocardiogram and cardiac functions, and the results were compared with those of randomly selected 44 patients receiving 21 mm St. Jude aortic prostheses. RESULTS: In 17 mm St Jude Medica Regent valve group, 8 patients presented with ECG ST segment changes, 3 complained of chest tightness, 3 had occasional chest pain and discomfort, and 8 had grade II and 4 grade III cardiac function. In 21 mm St Jude Medical Regent valve group, 6 patients had ECG ST segment changes, 2 complained of chest tightness, 2 reported occasional chest pain and discomfort, 11 had grade II and 2 grade III cardiac function. No significant differences were found in these indices between the two groups (P=0.32). Compared with those before operation, the two groups showed significant improvements in the left ventricular end-diastolic diameter, left ventricular posterior wall thickness, left ventricular mass index, and aortic pressure gradient (P<0.05). A significant increase in the left ventricular ejection fraction occurred 6-12 months after operation, but without statistical difference between the two groups (P>0.05). CONCLUSION: For underweight patients (<60 kg) and those with small body surface area (<1.6 cm(2)), 17 mm St. Jude Medical Regent valve prosthesis may produce good therapeutic effect, and some indices are even close to those after placement of 21 mm St. Jude Medical Regent valve prosthesis. No obvious prosthesis-patient mismatch occurs after the placement of the 17 mm valve prosthesis and aortic valve ring expansion is not necessary.
Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Prótesis Valvulares Cardíacas , Adolescente , Adulto , Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Niño , Preescolar , China/epidemiología , Femenino , Estudios de Seguimiento , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento , Ultrasonografía , Adulto JovenRESUMEN
OBJECTIVE: To summarize the experience with surgical treatment of constrictive pericarditis. METHODS: A retrospective analysis of the post-operative clinical data was conducted in 128 surgical patients with chronic constrictive pericarditis. RESULTS: Two early postoperative death occurred in this group due to severe low cardiac output syndrome, with the mortality rate of 1.57%. The postoperative complications included low cardiac output syndrome (13.2%), arrhythmia (7.02%), acute renal insufficiency (3.9%), respiratory insufficiency (3.1%), wound infection (2.3%), postoperative chest bleeding (1.6%) and cerebral infarction (0.78%). Relapse occurred in one case because of incomplete pericardial resection. CONCLUSIONS: Constrictive pericarditis should be confirmed as soon as possible with actively surgery, and the extent of pericardial resection should be decided according to the individual conditions. Complete untethering of the diseased pericardium should be performed with active prevention of postoperative complications.