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1.
Diagnostics (Basel) ; 14(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732358

RESUMO

The mortality rate of acute intracerebral hemorrhage (ICH) can reach up to 40%. Although the radiomics of ICH have been linked to hematoma expansion and outcomes, no research to date has explored their correlation with mortality. In this study, we determined the admission non-contrast head CT radiomic correlates of survival in supratentorial ICH, using the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) trial dataset. We extracted 107 original radiomic features from n = 871 admission non-contrast head CT scans. The Cox Proportional Hazards model, Kaplan-Meier Analysis, and logistic regression were used to analyze survival. In our analysis, the "first-order energy" radiomics feature, a metric that quantifies the sum of squared voxel intensities within a region of interest in medical images, emerged as an independent predictor of higher mortality risk (Hazard Ratio of 1.64, p < 0.0001), alongside age, National Institutes of Health Stroke Scale (NIHSS), and baseline International Normalized Ratio (INR). Using a Receiver Operating Characteristic (ROC) analysis, "the first-order energy" was a predictor of mortality at 1-week, 1-month, and 3-month post-ICH (all p < 0.0001), with Area Under the Curves (AUC) of >0.67. Our findings highlight the potential role of admission CT radiomics in predicting ICH survival, specifically, a higher "first-order energy" or very bright hematomas are associated with worse survival outcomes.

2.
J Pancreatol ; 7(1): 10-20, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38524855

RESUMO

Acute pancreatitis is a severe inflammatory disorder with limited treatment options. Improved understanding of disease mechanisms has led to new and potential therapies. Here we summarize what we view as some of the most promising new therapies for treating acute pancreatitis, emphasizing the rationale of specific treatments based on disease mechanisms. Targeted pharmacologic interventions are highlighted. We explore potential treatment benefits and risks concerning reducing acute injury, minimizing complications, and improving long-term outcomes. Mechanisms associated with acute pancreatitis initiation, perpetuation, and reconstitution are highlighted, along with potential therapeutic targets and how these relate to new treatments.

3.
Genes (Basel) ; 14(9)2023 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-37761951

RESUMO

INTRODUCTION: The independent effect of exercise on liver histology in non-alcoholic fatty liver disease (NAFLD) remains unclear. As such, we conducted a systematic review and meta-analysis of the effect of exercise alone on histological endpoints in biopsy-proven NAFLD. MATERIALS AND METHODS: A systematic literature search was conducted to include controlled clinical trials investigating the effect of exercise alone on liver histology in biopsy-proven NAFLD. Meta-analysis was conducted for histological outcomes with available data from a minimum of three studies. Pooled estimates of the effect of exercise on histological endpoints were calculated using random-effects models. RESULTS: We identified three controlled clinical trials that assessed the independent effect of exercise on histological outcomes in patients with biopsy-proven NAFLD. The studies consisted of 72 total participants, including 40 subjects in the exercise intervention and 32 individuals in the comparison group. Meta-analysis showed that exercise did not significantly improve Brunt grade, NAFLD activity score, and fibrosis in NAFLD. DISCUSSION: Exercise alone may not lead to significant histopathological improvement in NAFLD. Future well-powered randomized controlled trials are needed to better characterize the impact of exercise on histological outcomes and clinical endpoints.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Exercício Físico , Biópsia
4.
Cancer Inform ; 22: 11769351231177269, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37313373

RESUMO

Introduction: One of the most pressing goals for cancer immunotherapy at this time is the identification of actionable antigens. Methods: This study relies on the following considerations and approaches to identify potential breast cancer antigens: (i) the significant role of the adaptive immune receptor, complementarity determining region-3 (CDR3) in antigen binding, and the existence cancer testis antigens (CTAs); (ii) chemical attractiveness; and (iii) informing the relevance of the integration of items (i) and (ii) with patient outcome and tumor gene expression data. Results: We have assessed CTAs for associations with survival, based on their chemical complementarity with tumor resident T-cell receptor (TCR), CDR3s. Also, we have established gene expression correlations with the high TCR CDR3-CTA chemical complementarities, for Granzyme B, and other immune biomarkers. Conclusions: Overall, for several independent TCR CDR3 breast cancer datasets, the CTA, ARMC3, stood out as a completely novel, candidate antigen based on multiple algorithms with highly consistent approaches. This conclusion was facilitated by use of the recently constructed Adaptive Match web tool.

5.
J Gastrointest Cancer ; 54(4): 1300-1307, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37103748

RESUMO

INTRODUCTION: There remains a lack of knowledge regarding the effects of the intratumor microbiome on the tumor immune milieu. We aimed to investigate whether intratumoral bacterial RNA sequence abundance in gastric and esophageal cancers is associated with T-cell infiltrate features. METHODS: We assessed cases representing the stomach adenocarcinoma (STAD) and esophageal cancer (ESCA) databases of The Cancer Genome Atlas. RNA-seq data estimating intratumoral bacterial abundance was obtained from publicly available sources. TCR recombination reads were mined from exome files. Survival models were generated using the lifelines python package. RESULTS: Increasing levels of the Klebsiella genus were associated with a better OS probability (hazard ratio, 0.5), via a Cox proportional hazards model. The higher Klebsiella abundance was associated with a significantly increased overall (p = 0.0001) and disease-specific survival (p = 0.0289) probability for the STAD dataset. Cases representing the upper 50th percentile of Klebsiella abundance also represented a significantly increased recovery of TRG and TRD recombination reads (p = 0.00192). Analogous results were found for the Aquincola genus in ESCA. CONCLUSIONS: This is the first report of associations between low biomass bacterial samples from primary tumor samples with patient survival and with an increased gamma-delta T cell infiltrate. Results indicate that the gamma-delta T cells potentially play a role in the dynamics of the bacterial infiltration of primary tumors of the alimentary tract.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Probabilidade , Neoplasias Esofágicas/genética , Recombinação Genética
6.
BMJ Open Gastroenterol ; 10(1)2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36822658

RESUMO

OBJECTIVE: Although appendiceal cancer remains a rare gastrointestinal malignancy compared with colorectal cancer, incidence rates of appendiceal cancer have increased in the last two decades. Appendiceal and cecal adenocarcinomas have distinct genomic profiles, but chemotherapy protocols for these malignancies are the same and survival outcomes between them have not been compared extensively. To this end, we conducted a comparative survival analysis of appendiceal and cecal adenocarcinomas. DESIGN: Using the Surveillance, Epidemiology and End Results (SEER) database, we identified individuals ≥30 years of age with appendiceal or cecal adenocarcinoma from 1975 to 2016. Demographic, clinical and county-level socioeconomic data were extracted using SEER*Stat software. Survival was compared by Mantel-Haenszel log-rank test, and survival curves were generated using the Kaplan-Meier method. Relative HRs for death in the 5-year period following diagnosis were calculated using multivariable Cox regression analysis, adjusted for all other covariates. The significance level was set at p<0.05 for two-tailed tests. Data were analysed using SAS V.9.4 and R software. RESULTS: We identified 6491 patients with appendiceal adenocarcinoma and 99 387 patients with cecal adenocarcinoma. Multivariable Cox regression analysis demonstrated significantly higher cancer-specific and overall survival in appendiceal adenocarcinoma compared with cecal adenocarcinoma. Male sex, older age, earlier year of diagnosis, black race, single marital status, non-Hispanic ethnicity, and non-mucinous histology were associated with increased mortality rates. In addition, counties with lower percentage of individuals below the poverty line and higher colorectal cancer screening rates had better survival. CONCLUSION: This is the first study to show greater survival in appendiceal adenocarcinoma compared with cecal adenocarcinoma. We also highlighted novel associations of county-level socioeconomic factors with increased mortality in appendiceal adenocarcinoma. Future efforts to develop targeted molecular therapies and reduce socioeconomic barriers to diagnosis and treatment are warranted to improve survival.


Assuntos
Adenocarcinoma , Neoplasias do Apêndice , Neoplasias do Colo , Neoplasias Colorretais , Humanos , Masculino , Neoplasias do Apêndice/epidemiologia , Neoplasias do Apêndice/patologia , Estadiamento de Neoplasias , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Prognóstico , Neoplasias Colorretais/patologia , Neoplasias do Colo/patologia
7.
Mol Biotechnol ; 65(9): 1476-1484, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36653589

RESUMO

Bacteremia poses great risk for morbidity and mortality for immunocompromised cancer patients. Although the presence of bacteria within solid tumors is gaining greater attention, few studies have analyzed species of bacteria in the blood and their effect on cancer clinical outcomes. Using the Kraken 2 taxonomic profiling tool, we classified bacteria present in blood and primary tumors of cervical cancer and melanoma cases. The Cancer Genome Atlas (TCGA) melanoma blood exome files with Pseudomonas species were found to represent a worse disease-free survival (DFS) probability, while a worse overall survival (OS) result was evidenced for both the TCGA and Moffitt Cancer Center melanoma datasets. Cervical cancer cases with reads representing the Bradyrhizobium genus and Bradyrhizobium sp. BTAi1 found in blood and tumor exome files were found to have lower DFS. Additionally, reduced DFS and OS were observed for cervical cancer cases positive for Bacteroides species including Bacteroides fragilis. This study provides novel evidence and a novel approach for indicating that bacteria in blood is associated with cancer recurrence. These findings may guide the development of more efficient prognostic and screening tools related to bacterial blood infections of melanoma and cervical cancer patients.


Assuntos
Melanoma , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/genética , Exoma , Melanoma/genética , Intervalo Livre de Doença , Bactérias/genética
8.
Int J Immunogenet ; 50(2): 41-47, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36585798

RESUMO

Understanding racial disparities in cancer outcomes continues to be a challenge, with likely many factors at play, including socioeconomic factors and genetic polymorphisms impacting basic cellular and molecular functions. Additionally, it is possible that specific combinations of environment and genetics have specific impacts. T-cell receptor (TCR) gene segment usage, HLA allele combinations have been associated with autoimmune and infectious disease courses, and more recently, TCR gene segment usage, HLA allele combinations have been associated with distinct survival outcomes in cancer as well. We examined several such, previously reported cancer-related TCR gene segment usage, HLA allele combinations for evidence of racial disparities, with regard to the prevalence of the combination in different racial groups. Results indicated that TCR gene segment usage, potentially reflecting environmental factors related to previous pathogen exposure, in combination with certain HLA alleles or independently, may represent a novel explanation for racial disparities in cancer outcomes. Overall, at this point, a genetic connection to racial disparities in cancer outcomes is detectable but remains modest, suggesting that other factors, such as socioeconomic factors, remain as important considerations.


Assuntos
Genes Codificadores dos Receptores de Linfócitos T , Neoplasias , Humanos , Alelos , Taxa de Sobrevida
9.
Mol Immunol ; 150: 58-66, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35987136

RESUMO

Cancer testis antigens have been of interest as possible targets for cancer immunotherapies. To better understand the opportunities for the use of such immunotherapy targets, we used a chemical complementarity scoring algorithm and an original web tool to establish aspects of electrostatic complementarity of the CTAs, MAGEA3 and MAGEA6, with melanoma specimen resident, T-cell receptor (TCR) complementarity determining region 3 (CDR3) amino acid sequences. Greater electrostatic complementarity between T-cell receptor CDR3 and tumor CTAs MAGEA3/6 was associated with a greater probability of overall survival, for both the cancer genome atlas and Moffitt Cancer Center samples; and was associated with high levels of T-cell cytotoxicity-related gene expression. Most importantly, this approach allowed for the highly efficient screening of specific segments of the MAGEA3/6 antigens which indicated that certain MAGE segments would have either more or less risk of auto-reactivity. In sum, the chemical complementarity algorithm, and its efficient application via the web tool, adaptivematch.com, offers a convenient opportunity to identify likely parameters important for immunotherapy considerations and melanoma patient risk stratifications.


Assuntos
Melanoma , Receptores de Antígenos de Linfócitos T/imunologia , Vacinas , Antígenos de Neoplasias , Regiões Determinantes de Complementaridade/genética , Humanos , Imunoterapia , Masculino , Proteínas de Neoplasias/metabolismo , Linfócitos T
10.
Mol Immunol ; 135: 247-253, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33933816

RESUMO

Physicochemical assessments of a vast accumulation of adaptive immune receptor (IR) recombinations have led to correlations of those properties with sub-divisions of various diseases. In the cancer setting, such assessments, particularly for the complementarity determining region-3 (CDR3) immune receptor domain, have been used to establish chemical complementarity matches to mutant amino acids (AA). These matches, in some cases, over very large numbers of tumor samples, have correlated with survival and gene expression distinctions. For example, in melanoma, electrostatic charge based, T-cell receptor CDR3-DNAH9 mutant AA complementarity represents better survival over multiple datasets that represent tumor tissue, T-cell receptor CDR3s. In this report, the complementarity approach has been expanded to include a more comprehensive representation of the interaction of T-cell receptor CDR3s and mutant AAs by incorporating the impact of the wild-type AAs surrounding the mutant AA. This "sliding window" approach was benchmarked against two large datasets of empirically determined CDR3-epitope pairs; showed more significant patient subdivisions; revealed a novel, TRG CDR3-mutant PIK3CA linkage in breast cancer; and was particularly suited to use with big data collections using only modest and widely-available processors. Thus, the algorithm should support more rapid and convenient indications (or prescreens) of CDR3-mutant peptide interactions for more focused studies and more efficient development of patient immunology-related prognostic tools and therapies.


Assuntos
Neoplasias da Mama/patologia , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Regiões Determinantes de Complementaridade/imunologia , Domínios Proteicos/fisiologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Algoritmos , Ensaios de Triagem em Larga Escala , Humanos
11.
Transl Oncol ; 14(6): 101069, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33780706

RESUMO

Uterine cancer has been associated with a T-cell immune response that leads to increased survival. Therefore, we used several bioinformatics approaches to explore specific interactions between T-cell receptor (TCR) and tumor mutant peptide sequences. Using endometrioid uterine cancer exome files from the The Cancer Genome Atlas database, we obtained tumor resident V-J recombinations for the T-Cell Receptor alpha gene (TRA). The charged-based, chemical complementarity for each patient's LRP2 or TTN mutant amino acids (AAs) and the recovered, TRA complementarity determining region-3 (CDR3) sequences was calculated, allowing a division of patients into complementary and noncomplementary groups. Complementary groups with TTN mutants had increased disease-free survival and increased expression of complement genes. Furthermore, the survival distinction based on CDR3-mutant peptide complementarity was independent of programmatically assessed HLA class II binding and was not observable based on the CDR3 AA chemical features alone. The above approach provides a potential, highly efficient method for identifying TCR targets in uterine cancer and may aid in the development of novel prognostic tools.

12.
J Mol Neurosci ; 71(11): 2393-2404, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33666857

RESUMO

We mined a set of neuroblastoma (NBL) exomes for immune receptor recombinations representing all seven, human adaptive immune receptor genes, using a very high standard for identifications of V- and J-gene segments in sequencing reads. Results indicated an unusually large number of TRD recombination reads in the NBL samples, possibly related to the younger age of the patients. In general, recovery of immune receptor (IR) recombination reads representing any of the immune receptors, from either blood or tumor samples, was associated with a lower overall survival rate, consistent with an emerging literature indicating that systemic immunology parameters can be informative for cancer evaluations. Despite the overall negative association of IR recombination frequencies and outcomes, survival rate distinctions could still be established as associated with certain chemical features of IR complementarity determining region-3 (CDR3) amino acid sequences, thereby likely revealing a distinction between the negative impacts of a general adaptive immune response versus the positive aspects of specific CDR3 chemical interaction potentials. These data underscore the relevance of gamma-delta T cells in the development of cancer in younger patients. And for the first time, these data allow a distinction within an NBL cohort with active disease, between two contrasting systemic immune states: (i) general and likely harmful adaptive immunity development versus (ii) a likely positive, adaptive immune response with particular antigenic specificities.


Assuntos
Neoplasias Encefálicas/imunologia , Linfócitos Intraepiteliais/imunologia , Neuroblastoma/imunologia , Imunidade Adaptativa , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Humanos , Neuroblastoma/genética , Neuroblastoma/patologia , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia , Análise de Sobrevida
13.
Leuk Lymphoma ; 62(7): 1711-1720, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33622167

RESUMO

Multiple myeloma (MM) immunogenomics studies related to T-cell characterizations and involving large patient sets have been lacking, particularly in comparison to solid tumor types. Thus, we evaluated (i) HLA alleles, and (ii) T-Cell Receptor (TCR) V- and J-gene segment, HLA allele combinations, based on TCR recombinations in blood samples, for their potential associations with overall survival distinctions among an MM cohort. Two HLA alleles, and seven TCR V- or J-gene segment, HLA allele combinations were found to be associated with distinct overall survival rates. For examples, HLA-C*08:02, and the TRAV19, HLA-C*07:01 combination, were found to be associated with negative outcomes. In addition, anti-cytomegalovirus immune receptor sequences, from blood samples, were found to be associated with a positive outcome (p = 0.012, n = 278). These data, and other related immunogenomics data, indicate a potential opportunity to use personal immunogenetics parameters as guides to prognosis and therapies.


Assuntos
Mieloma Múltiplo , Alelos , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Taxa de Sobrevida , Linfócitos T
14.
Eur Urol Focus ; 7(2): 373-380, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-31901438

RESUMO

BACKGROUND: Accumulating evidence suggests that alternative RNA splicing has an important role in cancer development and progression by driving the expression of a diverse array of RNA and protein isoforms from a handful of genes. However, our understanding of the clinical significance of cancer-specific RNA splicing in renal cell carcinoma (RCC) is limited. OBJECTIVE: To characterize and validate a novel oncogene RNA splicing event discovered in patients with RCC and to correlate expression with clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: Using DNA and RNA sequencing, we identified a novel epidermal growth factor receptor (EGFR) splicing alteration (EGFR_pr20CTF) in RCC tumor tissue. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We confirmed the frequency and specificity of the EGFR_pr20CTF variant by analyzing cohorts of patients from our institution (n = 699) and The Cancer Genome Atlas (TCGA; n = 832). Furthermore, we analyzed its expression in tumor tissue and a human kidney cancer cell line using reverse transcriptase-polymerase chain reaction. Variant expression was also correlated with survival and response to systemic therapy. RESULTS AND LIMITATIONS: EGFR_pr20CTF expression was identified in 71.7% (n = 71/99) of patients with RCC in our institutional cohort and in 56.7% (n = 279/492) of patients in the TCGA cohort. EGFR_pr20CTF was found to be specific to clear cell renal cell carcinoma (ccRCC), occurring in <0.2% of non-RCC tumors (n = 2/1091). High levels of EGFR_pr20CTF correlated with lower survival at 48 mo following immunotherapy (p = 0.036). The average survival in patients with high EGFR_pr20CTF expression was <16 mo. CONCLUSIONS: The EGFR_pr20CTF RNA splice variant occurs frequently, is specific to patients with advanced ccRCC, and is associated with a poor response to immunotherapy. PATIENT SUMMARY: Cancer-specific RNA alternative splicing may portend a poor prognosis in patients with advanced clear cell renal cell carcinoma. Further investigation will help clarify whether EGFR_pr20CTF can be used as a biomarker for this patient population.


Assuntos
Carcinoma de Células Renais/genética , Receptores ErbB/genética , Neoplasias Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/terapia , Expressão Gênica , Humanos , Imunoterapia , Neoplasias Renais/metabolismo , Neoplasias Renais/terapia , Prognóstico , RNA , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Breast Cancer Res Treat ; 185(3): 591-600, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33180235

RESUMO

PURPOSE: Immunogenomics and earlier, pioneering studies, particularly by Whiteside and colleagues, have indicated a positive role for B-cells in breast cancer, as well as a positive role for gamma-delta T-cells. However, these studies have been completely limited to assessing breast cancer tumor tissue. METHODS AND RESULTS: Our analyses here has shown that blood-borne T-cell receptor gamma (TRG) chain sequences were associated with greater overall survival, of particular note due to the comparative longevity of primary breast cancer patients, whereby assessments of disease-free, but rarely overall survival parameters are possible. Additional immunogenomics approaches narrowed the overall survival correlations to specific, TRG complementarity determining region-3, amino acid (AA) sequence chemical features, independently of many common, confounding variables in the breast cancer setting, such as estrogen or progesterone receptor status. CONCLUSIONS: These results are discussed in the context of patient age and with regard to potential antigenic targets, based on the chemistry of the TRG CDR3 AA sequences associated with the higher survival rates.


Assuntos
Neoplasias da Mama , Sequência de Aminoácidos , Neoplasias da Mama/genética , Regiões Determinantes de Complementaridade , Feminino , Humanos , Receptores de Antígenos de Linfócitos T gama-delta , Linfócitos T
16.
Eur J Orthop Surg Traumatol ; 31(2): 235-243, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32797351

RESUMO

BACKGROUND: Subtrochanteric femur fractures associate with a relatively high complication rate and are traditionally treated operatively with a period of limited weight bearing. Transitioning from extramedullary to intramedullary implants, there are increasing biomechanical and clinical data to support early weight bearing. This multicenter retrospective study examines the effect of postoperative weight bearing as tolerated (WBAT) for subtrochanteric femur fractures. We hypothesize that WBAT will result in a decreased length of stay (LOS) without increasing the incidence of re-operation. METHODS: This study assesses total LOS and postoperative LOS after intramedullary fixation for subtrochanteric fractures between postoperative weight bearing protocols across 6 level I trauma centers (n = 441). Analysis techniques consisted of multivariable linear regression and nonparametric comparative tests. Additional subanalyses were performed, targeting mechanism of injury (MOI), Winquist-Hansen fracture comminution, 20-year age strata, and injury severity score (ISS). RESULTS: Total LOS was shorter in WBAT protocol within the overall sample (7.4 vs 9.7 days; p < 0.01). Rates of re-operation were similar between the two groups (10.6% vs 10.5%; p = 0.99). Stratified analysis identified patients between ages 41-80, WH comminution 2-3, high MOI, and ISS between 6-15 and 21-25 to demonstrate a significant reduction in LOS as a response to WBAT. CONCLUSION: An immediate postoperative weight bearing as tolerated protocol in patients with subtrochanteric fractures reduced length of hospital stay with no significant difference in reoperation and complication rates. If no contraindication exists, immediate weight bearing as tolerated should be considered for patients with subtrochanteric femur fractures treated with statically locked intramedullary nails. LEVEL OF EVIDENCE: Therapeutic Level III.


Assuntos
Fixação Intramedular de Fraturas , Fraturas do Quadril , Adulto , Idoso , Idoso de 80 Anos ou mais , Pinos Ortopédicos , Fixação Intramedular de Fraturas/efeitos adversos , Fraturas do Quadril/cirurgia , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Estudos Retrospectivos , Suporte de Carga
17.
Hum Immunol ; 81(12): 692-696, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32950267

RESUMO

Common or dominant, T-cell receptor (TCR), V and J usage, in combination with particular human leukocyte antigen (HLA) alleles, has been associated with differing outcomes in viral infections, autoimmunity, and more recently, in cancer. Cervical cancer in particular represents the most dramatic series of distinctions of outcomes associated with differing combinations of dominant V or J usage and HLA alleles, possibly because of the strong association of cervical cancer with human papilloma virus (HPV), in turn leading to a likely molecular consistency in the mechanism of HPV antigen presentation. Thus, we considered assessing TRB V and J usage, HLA allele combinations, for their associations with survival rates and related data, in the cancer genome atlas head and neck cancer dataset. We obtained the TRB VDJ recombination reads from both the blood and tumor exome files and determined the V and J identities. We then established case ID (patient) subsets of V or J usage, HLA alleles, and determined, for example, that the TRBJ2-7, HLA-B*40:01 combination was associated with a better disease free survival rate than were either the TRBJ1-3, HLA-DPB1*03:01 or the TRBJ2-1, HLA-DPB1*02:01 combinations. Furthermore, these analyses led to the conclusion that TRBJ1-5 usage, and the HLA-C*08:02 and HLA-DRB1*03:01 alleles, had independent associations with distinct overall survival rates. In sum, the results suggest that dominant V or J usage, HLA allele combinations, and in certain cases, dominant V or J usage independently of HLA, could be useful in prognosis and in guiding immunotherapies.


Assuntos
Alelos , Genes Codificadores da Cadeia beta de Receptores de Linfócitos T , Antígenos HLA/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe I/genética , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Recombinação V(D)J , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Exoma , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Taxa de Sobrevida
18.
Cancer Treat Res Commun ; 24: 100196, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32769037

RESUMO

Immunogenomics studies of colon cancer have lagged behind other cancer types, such as melanoma and lung cancer, potentially limiting immunotherapy approaches to colon cancer, also less common than in the cases of melanoma and lung cancer. Here we applied an extensively benchmarked algorithm for retrieving immune receptor recombination sequencing reads from colon cancer exomes available via the cancer genome atlas. Assessment of the complementarity determining region-3 chemical features represented by the reads revealed associations of distinct chemical features with better or worse survival rates, for both T-cell and B-cell receptor, recombination reads. A follow up assessment of immune gene expression correlations with the recovery of the recombination reads revealed a consistent association of high level expression of BTN gene family members and better survival rates. Overall, these approaches provide several striking consistencies connecting immunogenomics features with colon cancer survival rates, potentially providing a basis for guiding immuno-therapy applications.


Assuntos
Adenocarcinoma/mortalidade , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Colorretais/mortalidade , Regulação Neoplásica da Expressão Gênica/imunologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Assistência ao Convalescente , Biomarcadores Tumorais/química , Butirofilinas/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Regiões Determinantes de Complementaridade/química , Regiões Determinantes de Complementaridade/genética , Biologia Computacional , Intervalo Livre de Doença , Exoma/genética , Humanos , Estimativa de Kaplan-Meier , RNA-Seq , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/imunologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Recombinação Genética , Taxa de Sobrevida
19.
J Surg Orthop Adv ; 29(2): 117-120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584227

RESUMO

Arthrofibrosis of the knee continues to challenge Orthopaedic surgeons. With a wide etiology, lack of knee motion can be debilitating. Its surgical management has several complications. The purpose of this study is to describe a modification of previously described techniques to aid in the management of knee arthrofibrosis. Arthroscopic vastus elevation in conjunction with adjuvant hemostatic agents allows for a controlled quadriceps elevation in the setting of arthrofibrosis. In addition to a thorough intra-articular lysis of adhesions, this appears to improve motion, while minimizing postoperative complications. Minimized postoperative complications include extensor lag, skin necrosis, and bleeding complications. (Journal of Surgical Orthopaedic Advances 29(2):117-120, 2020).


Assuntos
Artroscopia , Artropatias , Fibrose , Humanos , Artropatias/patologia , Joelho , Articulação do Joelho/cirurgia , Complicações Pós-Operatórias , Amplitude de Movimento Articular
20.
Viral Immunol ; 33(5): 404-412, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32315578

RESUMO

Human papilloma virus has a clearly demonstrated role in cervical and head and neck cancers, but viral etiology for other solid tumors is less well understood. To expand this area of research, we obtained and analyzed the immune receptor recombinations available from both blood and tumor samples, through mining of exome files produced from those sources, for 32 cancer types represented by the cancer genome atlas (TCGA). Among TCGA data sets, the recovery frequency for antiviral complementarity determining region-3 sequences (CDR3s), for T cell receptor-alpha and T cell receptor-beta, ranged from 0% to 21% of the patients, for the different cancer types, with breast, lung, pancreatic, and thymus cancers representing the highest of that range, particularly for tumor tissue resident T cells. In several cases, recovery of the antiviral CDR3s associated with distinct survival rates, and in all of these cases, the recovery of an antiviral CDR3 associated with a worse survival rate.


Assuntos
Regiões Determinantes de Complementaridade/genética , Neoplasias/mortalidade , Neoplasias/virologia , Receptores de Antígenos de Linfócitos T/genética , Exoma/genética , Genoma , Humanos , Neoplasias/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Taxa de Sobrevida , Recombinação V(D)J , Vírus/patogenicidade
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