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2.
Quant Imaging Med Surg ; 13(12): 8157-8172, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38106243

RESUMEN

Background: Amide proton transfer (APT) imaging has been gradually applied to cervical cancer, yet the relationships between APT and multiple model diffusion-weighted imaging (DWI) have yet to be investigated. This study attempted to evaluate the added value of 3-dimensional (3D) APT imaging to multiple model DWI for assessing prognostic factors of cervical cancer. Methods: This prospective diagnostic study was conducted in The First Affiliated Hospital of Zhengzhou University. A total of 88 consecutive patients with cervical cancer underwent APT imaging and DWI with 11 b-values (0-2,000 s/mm2). The apparent diffusion coefficient (ADC), pure molecular diffusion (D), perfusion fraction (f), pseudo-diffusion (D*), mean kurtosis (MK), and mean diffusivity (MD) were calculated based on mono-exponential, bi-exponential, and kurtosis models. The mean, minimum, and maximum values of APT signal intensity (APT SI) and DWI-derived metrics were compared based on tumor stages, subtypes, grades, and lymphovascular space invasion status by Student's t-test or Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the parameters. Results: APT SImax, APT SImin, MKmean, and MKmax showed significant differences between adenocarcinoma (AC) and squamous cell carcinoma (SCC) (all P<0.05). APT SImean, APT SImax, and MKmax were higher and ADCmin, Dmean, Dmin, and MDmin were lower in the high-grade tumor than in low-grade tumor (all P<0.05). For distinguishing lymphovascular space invasion, only MKmean showed significant difference (P=0.010). APT SImax [odds ratio (OR) =2.347, P=0.029], APT SImin (OR =0.352; P=0.024), and MKmean (OR =6.523; P=0.001) were the independent predictors for tumor subtype, and APT SImax (OR =2.885; P=0.044), MDmin (OR =0.155, P=0.012) were the independent predictors for histological grade of cervical cancer. When APT SImin and APT SImax was combined with MKmean and MKmax, the diagnostic performance was significantly improved for differentiating AC and AC [area under the curve (AUC): 0.908, sensitivity: 87.5%; specificity: 83.3%; P<0.001]. The combination of APT SImean, APT SImax, ADCmin, MKmax, and MDmin demonstrated the highest diagnostic performance for predicting tumor grade (AUC: 0.903, sensitivity: 78.6%; specificity: 88.9%; P<0.001). Conclusions: Addition of APT to DWI may improve the ability to noninvasively predict poor prognostic factors of cervical cancer.

3.
Cancers (Basel) ; 15(15)2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37568819

RESUMEN

Patients with pre-existing autoimmune disorders and cancer considering immune checkpoint inhibitors (ICIs) need to receive balanced information about the benefits and risk of developing immune-related adverse events (irAEs) and flare-ups of their autoimmune disease. To assess the learning needs of patients with cancer and pre-existing autoimmune disease regarding ICI treatment, we interviewed 29 patients with autoimmune disease and cancer from a comprehensive cancer center, of whom 20 had received ICI and 9 were candidates to receive ICI at a US Cancer Center. In-depth semi-structured interviews were conducted from August 2021 and January 2022. Interviewee's opinions and preferences about content and information delivery methods were collected. We recorded and transcribed interviews and analyzed them using thematic analysis. Half of the participants were female, and their median (SD) age was 62.9 (±10.9) years. The identified health information needs included the following: (1) information on irAEs and autoimmune disease flare-ups; (2) benefits of ICI; (3) ICI mechanism in the context of autoimmune disease; (4) management of flare-ups; (5) reasons for stopping or modifying cancer or autoimmune disease treatment; (6) likelihood of autoimmune disease progression or organ damage; and (7) lifestyle changes that could help avoid irAEs. Patients who had received ICI and those who had not yet received treatment reported similar needs, although patients who had received ICI had more questions about cancer treatment modifications. Patients also expressed the need to better understand when to contact their provider and how to share information with multiple providers. Most patients wanted to receive information in visual formats for review at home and at their own pace. Patients expressed interest in having educational tools to facilitate shared decision-making with their physicians, and they identified several areas of health information concerning therapy with ICI. They also highlighted the importance of communication among their various providers.

4.
J Immunother Cancer ; 11(6)2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37328287

RESUMEN

BACKGROUND: Management of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the safety and effectiveness of anti-interleukin-6 receptor (anti-IL-6R) as therapy for irAEs. METHODS: We performed a retrospective multicenter study evaluating patients diagnosed with de novo irAEs or flare of pre-existing autoimmune disease following ICI and were treated with anti-IL-6R. Our objectives were to assess the improvement of irAEs as well as the overall tumor response rate (ORR) before and after anti-IL-6R treatment. RESULTS: We identified a total of 92 patients who received therapeutic anti-IL-6R antibodies (tocilizumab or sarilumab). Median age was 61 years, 63% were men, 69% received anti-programmed cell death protein-1 (PD-1) antibodies alone, and 26% patients were treated with the combination of anti-cytotoxic T lymphocyte antigen-4 and anti-PD-1 antibodies. Cancer types were primarily melanoma (46%), genitourinary cancer (35%), and lung cancer (8%). Indications for using anti-IL-6R antibodies included inflammatory arthritis (73%), hepatitis/cholangitis (7%), myositis/myocarditis/myasthenia gravis (5%), polymyalgia rheumatica (4%), and one patient each with autoimmune scleroderma, nephritis, colitis, pneumonitis and central nervous system vasculitis. Notably, 88% of patients had received corticosteroids, and 36% received other disease-modifying antirheumatic drugs (DMARDs) as first-line therapies, but without adequate improvement. After initiation of anti-IL-6R (as first-line or post-corticosteroids and DMARDs), 73% of patients showed resolution or change to ≤grade 1 of irAEs after a median of 2.0 months from initiation of anti-IL-6R therapy. Six patients (7%) stopped anti-IL-6R due to adverse events. Of 70 evaluable patients by RECIST (Response Evaluation Criteria in Solid Tumors) V.1.1 criteria; the ORR was 66% prior versus 66% after anti-IL-6R (95% CI, 54% to 77%), with 8% higher complete response rate. Of 34 evaluable patients with melanoma, the ORR was 56% prior and increased to 68% after anti-IL-6R (p=0.04). CONCLUSION: Targeting IL-6R could be an effective approach to treat several irAE types without hindering antitumor immunity. This study supports ongoing clinical trials evaluating the safety and efficacy of tocilizumab (anti-IL-6R antibody) in combination with ICIs (NCT04940299, NCT03999749).


Asunto(s)
Antirreumáticos , Neoplasias Pulmonares , Melanoma , Receptores de Interleucina-6 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corticoesteroides/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Estudios Retrospectivos , Receptores de Interleucina-6/antagonistas & inhibidores
5.
Br J Radiol ; 96(1148): 20220952, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37183908

RESUMEN

OBJECTIVE: To evaluate the clinical feasibility of T1 mapping and multimodel diffusion-weighted imaging (DWI) for assessing the histological type, grade, and lymphovascular space invasion (LVSI) of cervical cancer. METHODS: Eighty patients with cervical cancer and 43 patients with a normal cervix underwent T1 mapping and DWI with 11 b-values (0-2000 s/mm2). Monoexponential, biexponential, and kurtosis models were fitted to calculate the apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion (D*), perfusion fraction (f), mean diffusivity (MD), and mean kurtosis (MK). Native T1 and DWI-derived parameters (ADCmean, ADCmin, Dmean, Dmin, D*, f, MDmean, MDmin, MKmean, and MKmax) were compared based on histological type, grade, and LVSI status. RESULTS: Native T1 and DWI-derived parameters differed significantly between cervical cancer and normal cervix (all p < 0.05), except D* (p = 0.637). Native T1 and MKmean varied significantly between squamous cell carcinoma (SCC) and adenocarcinoma (both p < 0.05). ADCmin, Dmin, and MDmin were significantly lower while MKmax was significantly higher in the high-grade SCC group than in the low-grade SCC group (all p < 0.05). LVSI-positive SCC had a significantly higher MKmean than LVSI-negative SCC (p < 0.05). CONCLUSION: Both T1 mapping and multimodel DWI can effectively differentiate cervical cancer from a normal cervix and cervical adenocarcinoma from SCC. Furthermore, multimodel DWI may provide quantitative metrics for non-invasively predicting histological grade and LVSI status in SCC patients. ADVANCES IN KNOWLEDGE: Combined use of T1 mapping and multimodel DWI may provide more comprehensive information for non-invasive pre-operative evaluation of cervical cancer.


Asunto(s)
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Imagen de Difusión por Resonancia Magnética/métodos , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología
7.
Nat Commun ; 13(1): 1970, 2022 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-35413951

RESUMEN

Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Management of arthritis-irAE is challenging because immunomodulatory therapy for arthritis should not impede antitumor immunity. Understanding of the mechanisms of arthritis-irAE is critical to overcome this challenge, but the pathophysiology remains unknown. Here, we comprehensively analyze peripheral blood and/or synovial fluid samples from 20 patients with arthritis-irAE, and unmask a prominent Th1-CD8+ T cell axis in both blood and inflamed joints. CX3CR1hi CD8+ T cells in blood and CXCR3hi CD8+ T cells in synovial fluid, the most clonally expanded T cells, significantly share TCR repertoires. The migration of blood CX3CR1hi CD8+ T cells into joints is possibly mediated by CXCL9/10/11/16 expressed by myeloid cells. Furthermore, arthritis after combined CTLA-4 and PD-1 inhibitor therapy preferentially has enhanced Th17 and transient Th1/Th17 cell signatures. Our data provide insights into the mechanisms, predictive biomarkers, and therapeutic targets for arthritis-irAE.


Asunto(s)
Artritis , Neoplasias , Artritis/inducido químicamente , Artritis/tratamiento farmacológico , Linfocitos T CD8-positivos , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/efectos adversos , Neoplasias/tratamiento farmacológico , Neoplasias/etiología
8.
J Allergy Clin Immunol ; 149(5): 1525-1560, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35176351

RESUMEN

Secondary hypogammaglobulinemia (SHG) is characterized by reduced immunoglobulin levels due to acquired causes of decreased antibody production or increased antibody loss. Clarification regarding whether the hypogammaglobulinemia is secondary or primary is important because this has implications for evaluation and management. Prior receipt of immunosuppressive medications and/or presence of conditions associated with SHG development, including protein loss syndromes, are histories that raise suspicion for SHG. In patients with these histories, a thorough investigation of potential etiologies of SHG reviewed in this report is needed to devise an effective treatment plan focused on removal of iatrogenic causes (eg, discontinuation of an offending drug) or treatment of the underlying condition (eg, management of nephrotic syndrome). When iatrogenic causes cannot be removed or underlying conditions cannot be reversed, therapeutic options are not clearly delineated but include heightened monitoring for clinical infections, supportive antimicrobials, and in some cases, immunoglobulin replacement therapy. This report serves to summarize the existing literature regarding immunosuppressive medications and populations (autoimmune, neurologic, hematologic/oncologic, pulmonary, posttransplant, protein-losing) associated with SHG and highlights key areas for future investigation.


Asunto(s)
Agammaglobulinemia , Inmunodeficiencia Variable Común , Síndromes de Inmunodeficiencia , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/etiología , Agammaglobulinemia/terapia , Inmunodeficiencia Variable Común/complicaciones , Humanos , Enfermedad Iatrogénica , Inmunidad , Inmunoglobulinas , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/diagnóstico , Síndromes de Inmunodeficiencia/terapia
9.
Joint Bone Spine ; 89(2): 105308, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34774793

RESUMEN

OBJECTIVE: Aromatase inhibitors (AIs) are widely used in the adjuvant therapy setting in patients with estrogen receptor-positive breast cancer. Rheumatic side effects of AIs have been reported, including bone loss, arthralgias, myalgias, and tenosynovitis. There is emerging evidence that AIs are linked to new-onset autoimmune diseases. Here, we describe three novel cases of inflammatory myopathies that occurred during AI therapy. METHODS: In total, three patients with inflammatory myopathy in the setting of AI therapy were treated in the Section of Rheumatology, MD Anderson Cancer Center. All the patients were retrospectively chart reviewed. We obtained verbal consent from the patients for use of their cases for teaching and publication purposes and only de-identified data have been used. RESULTS: None of our patients from these three cases had a history of autoimmune disease and all had undergone recent cancer screenings, indicating no re-occurrence of breast cancer and no evidence of new cancer. The completion or discontinuation of AI therapy was associated with the resolution of the myopathies in all three cases. CONCLUSIONS: This case series suggests a link between AIs and the new onset of inflammatory myopathy. If a patient develops an inflammatory myopathy while on an AI, the AI therapy should be considered the possible trigger. If the myopathy cannot be controlled with immunosuppression, then discontinuation of the AI should be considered.


Asunto(s)
Neoplasias de la Mama , Miositis , Inhibidores de la Aromatasa/efectos adversos , Artralgia/inducido químicamente , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Miositis/inducido químicamente , Miositis/diagnóstico , Miositis/tratamiento farmacológico , Estudios Retrospectivos
10.
JBMR Plus ; 5(8): e10518, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34368608

RESUMEN

Bone disease is common in patients with multiple myeloma (MM), which manifests as bone pain and skeletal-related events (SREs) such as pathological fractures and spinal cord compression. Myeloma bone disease (MBD) can adversely affect the quality of life of patients and have negative effects on morbidity and mortality. The pathogenesis of MBD is complex, and several factors are involved in the dysregulation of bone metabolism and uncoupling of bone remodeling, which result in net bone loss and devastating SREs. Broadly speaking, elevated osteoclast activity, suppressed osteoblast activity, and an aberrant marrow microenvironment play a role in MBD. Interaction of MM cells with the main bone cell osteocytes also promote further bone destruction. This review focuses on the role of bone-modifying agents in the prevention and treatment of MBD. The mainstay of MBD prevention are antiresorptive agents, bisphosphonates and denosumab. However, these agents do not play a direct role in bone formation and repair of existing MBD. Newer agents with anabolic effects such as anti-sclerostin antibodies, parathyroid hormone, anti-Dickkopf-1 antibodies, and others have shown potential in repair of MBD lesions. With the development of several new agents, the treatment landscape of MBD is likely to evolve in the coming years. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

11.
Eur J Radiol ; 139: 109684, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33836336

RESUMEN

PURPOSE: The study aimed to analyze the feasibility of a radial turbo-spin-echo (TSE) T2 mapping to differentiate the histological grades and lymphovascular space invasion (LVSI) of cervical squamous cell carcinoma (CSCC) in comparison with diffusion-weighted imaging (DWI). METHODS: A total of 58 patients with CSCC and 40 healthy volunteers underwent T2 mapping and DWI before therapy. The T2 and apparent diffusion coefficient (ADC) values were calculated using different tumor characteristics. The differences, efficacies and correlations between parameters were determined. RESULTS: The T2 and ADC values were significantly different between CSCC and normal cervical stroma (both p < 0.05). Poorly differentiated (G3) tumor showed lower T2 and ADC values than well differentiated (G1) and moderately differentiated (G2) tumor (all p < 0.05). The T2 values were significantly lower in LVSI-positive CSCC than LVSI-negative CSCC (p < 0.05). No significant difference was found in ADC values for LVSI status (p = 0.561). The area under the ROC (AUC) for T2 and ADC values to distinguish G1/G2 and G3 tumor were 0.741 and 0.763, respectively. The AUC for T2 and ADC values to distinguish LVSI-positive and LVSI-negative CSCC were 0.877 and 0.537, respectively. The T2 and ADC values were negatively correlated with the tumor grades (r = -0.402 and r = -0.339, respectively). CONCLUSIONS: Radial TSE T2 mapping is feasible for CSCC. Similar to ADC values, quantitative T2 values could serve as a noninvasive biomarker to predict histological grades preoperatively. Moreover, T2 values could determine the presence of LVSI better than ADC values.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias del Cuello Uterino , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/cirugía , Imagen de Difusión por Resonancia Magnética , Estudios de Factibilidad , Femenino , Humanos , Estudios Retrospectivos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/cirugía
12.
J Bone Miner Res ; 36(5): 861-871, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33484602

RESUMEN

Women with estrogen receptor-positive breast cancer who receive an aromatase inhibitor (AI) are at risk for fractures. We aim to determine if dual-energy X-ray absorptiometry (DXA) scans made at the time of AI initiation are associated with decreased fractures. We retrospectively identified 25,158 women with local or regional breast cancer diagnosed between 2005 and 2013 who received AI therapy between 2007 and 2013 from the Medicare-linked Surveillance, Epidemiology, and End Results Program and Texas Cancer Registry databases. We defined baseline DXA screening using claims made between 1 year before and 6 months after each patient's first AI claim to examine determinants of baseline screening using a multivariable GENMOD model. We included a propensity score adjustment in Cox proportional hazard models to assess the association between time-varying DXA screening and the risk of fractures. Additionally, we compared the use of antiresorptive therapy drugs between the two groups. Of the study cohort, 14,738 (58.6%) received DXA screening. The screening rates increased annually from 52.1% in 2007 to 61.7% in 2013. Higher screening rates were observed in patients with younger age, married status, non-Hispanic white race, localized disease, fewer comorbidities, more than one type of aromatase inhibitor drug claim, no state buy-in (surrogate for low socioeconomic status), higher education level, and prior osteoporosis diagnosis. Baseline DXA screening was associated with decreased risk of subsequent fractures (hazard ratio = 0.91; 95% confidence interval, 0.86-0.97, p < .001) after multivariable and propensity score adjustment. Bone-modifying drugs were prescribed to 4440 (30.1%) patients with screening compared with 1766 (16.9%) without (p < .001). Of the 4440 patients who received treatment, 95% received bisphosphonates. Our study demonstrated baseline DXA screening was associated with a decreased risk of fractures and a higher likelihood of receiving antiresorptive therapies. Improvement of the baseline DXA screening is still needed in practice. © 2021 American Society for Bone and Mineral Research (ASBMR).


Asunto(s)
Neoplasias de la Mama , Fracturas Óseas , Absorciometría de Fotón , Anciano , Inhibidores de la Aromatasa/uso terapéutico , Densidad Ósea , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Femenino , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/epidemiología , Humanos , Medicare , Estudios Retrospectivos , Estados Unidos/epidemiología
13.
Dermatol Online J ; 26(8)2020 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-32941716

RESUMEN

We present a rare case of dermatomyositis associated with nivolumab therapy for melanoma. Nivolumab is an immune checkpoint inhibitor that blocks the programmed death-1 (PD1) receptor and has a number of associated immunotherapy related adverse events. Although most are T-cell mediated, some are antibody mediated mimics of classical autoimmune diseases. We review the characteristics of other cases of anti-PD1 associated dermatomyositis and the recent literature to better understand how to classify and treat this challenging immunotherapy related adverse event.


Asunto(s)
Dermatomiositis/inducido químicamente , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Nivolumab/efectos adversos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adulto , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Dermatomiositis/patología , Humanos , Masculino , Melanoma/tratamiento farmacológico , Nivolumab/uso terapéutico
14.
J Oncol Pharm Pract ; 26(4): 982-985, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31433727

RESUMEN

INTRODUCTION: Cyclophosphamide is a nitrogen mustard alkylator employed in the treatment of many malignancies and autoimmune disorders. Despite reports of cyclophosphamide hypersensitivity ranging from rash to anaphylaxis, no cases of desensitization have been reported in the oncologic setting. CASE REPORT: We report a cyclophosphamide desensitization protocol used for two patients who experienced severe hypersensitivity to bendamustine, a structurally related drug with potential cross immunogenicity. MANAGEMENT AND OUTCOME: An interdisciplinary approach including immunologist, oncologist, and clinical pharmacists resulted in the development of a multi-step desensitization protocol for cyclophosphamide. The desensitization protocol described enabled the safe administration of cyclophosphamide for the two patients with limited treatment alternatives. DISCUSSION: To the authors' knowledge, this is the first report of cyclophosphamide desensitization in the oncologic setting. Two patients with advanced hematologic malignancies were able to receive cyclophosphamide with minimal adverse effects, despite experiencing previous severe hypersensitivity to another nitrogen mustard analogue.


Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Clorhidrato de Bendamustina/efectos adversos , Ciclofosfamida/uso terapéutico , Desensibilización Inmunológica/métodos , Hipersensibilidad a las Drogas/diagnóstico , Índice de Severidad de la Enfermedad , Anciano , Antineoplásicos Alquilantes/efectos adversos , Hipersensibilidad a las Drogas/tratamiento farmacológico , Femenino , Humanos , Persona de Mediana Edad
15.
Sci Rep ; 9(1): 17256, 2019 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-31754222

RESUMEN

Cancer is a major cause of death worldwide, and an early diagnosis is required for a favorable prognosis. Histological examination is the gold standard for cancer identification; however, large amount of inter-observer variability exists in histological diagnosis. Numerous studies have shown cancer genesis is accompanied by an accumulation of harmful mutations, potentiating the identification of cancer based on genomic information. We have proposed a method, GDL (genome deep learning), to study the relationship between genomic variations and traits based on deep neural networks. We analyzed 6,083 samples' WES (Whole Exon Sequencing) mutations files from 12 cancer types obtained from the TCGA (The Cancer Genome Atlas) and 1,991 healthy samples' WES data from the 1000 Genomes project. We constructed 12 specific models to distinguish between certain type of cancer and healthy tissues, a total-specific model that can identify healthy and cancer tissues, and a mixture model to distinguish between all 12 types of cancer based on GDL. We demonstrate that the accuracy of specific, mixture and total specific model are 97.47%, 70.08% and 94.70% for cancer identification. We developed an efficient method for the identification of cancer based on genomic information that offers a new direction for disease diagnosis.


Asunto(s)
Genómica/métodos , Neoplasias/clasificación , Neoplasias/genética , Bases de Datos Genéticas , Aprendizaje Profundo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Mutación/genética , Redes Neurales de la Computación
16.
J Immunother Cancer ; 7(1): 2, 2019 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-30612580

RESUMEN

RATIONALE & OBJECTIVE: The approved therapeutic indication for immune checkpoint inhibitors (CPIs) are rapidly expanding including treatment in the adjuvant setting, the immune related toxicities associated with CPI can limit the efficacy of these agents. The literature on the nephrotoxicity of CPI is limited. Here, we present cases of biopsy proven acute tubulointerstitial nephritis (ATIN) and glomerulonephritis (GN) induced by CPIs and discuss potential mechanisms of these adverse effects. STUDY DESIGN, SETTING, & PARTICIPANTS: We retrospectively reviewed all cancer patients from 2008 to 2018 who were treated with a CPI and subsequently underwent a kidney biopsy at The University of Texas MD Anderson Cancer Center. RESULTS: We identified 16 cases diagnosed with advanced solid or hematologic malignancy; 12 patients were male, and the median age was 64 (range 38 to 77 years). The median time to developing acute kidney injury (AKI) from starting CPIs was 14 weeks (range 6-56 weeks). The average time from AKI diagnosis to obtaining renal biopsy was 16 days (range from 1 to 46 days). Fifteen cases occurred post anti-PD-1based therapy. ATIN was the most common pathologic finding on biopsy (14 of 16) and presented in almost all cases as either the major microscopic finding or as a mild form of interstitial inflammation in association with other glomerular pathologies (pauci-immune glomerulonephritis, membranous glomerulonephritis, C3 glomerulonephritis, immunoglobulin A (IgA) nephropathy, or amyloid A (AA) amyloidosis). CPIs were discontinued in 15 out of 16 cases. Steroids and further immunosuppression were used in most cases as indicated for treatment of ATIN and glomerulonephritis (14 of 16), with the majority achieving complete to partial renal recovery. CONCLUSIONS: Our data demonstrate that CPI related AKI occurs relatively late after CPI therapy. Our biopsy data demonstrate that ATIN is the most common pathological finding; however it can frequently co-occur with other glomerular pathologies, which may require immune suppressive therapy beyond corticosteroids. In the lack of predictive blood or urine biomarker, we recommend obtaining kidney biopsy for CPI related AKI.


Asunto(s)
Antineoplásicos Inmunológicos/efectos adversos , Inmunomodulación/efectos de los fármacos , Terapia Molecular Dirigida/efectos adversos , Neoplasias/complicaciones , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/etiología , Adulto , Anciano , Antineoplásicos Inmunológicos/uso terapéutico , Biomarcadores de Tumor/antagonistas & inhibidores , Biopsia , Femenino , Glomerulonefritis/diagnóstico , Glomerulonefritis/etiología , Glomerulonefritis/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Nefritis Intersticial/metabolismo , Nefritis Intersticial/terapia , Pronóstico
17.
Lancet Haematol ; 5(10): e474-e478, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30290904

RESUMEN

BACKGROUND: Patients previously infected with hepatitis B virus (HBV; indicated by positivity for anti-HBc) can experience HBV reactivation during cancer chemotherapy. Intravenous immunoglobulin infusion, which is frequently used in supportive care, might facilitate passive transfer of anti-HBc. We aimed to estimate the probability of passive transfer of anti-HBc after intravenous immunoglobulin infusion in patients with cancer. METHODS: We reviewed institutional databases to identify adult patients who received outpatient chemotherapy between Jan 1, 2004, and Dec 31, 2011, at the University of Texas MD Anderson Cancer Center, Houston, TX, USA. Eligible patients had received intravenous immunoglobulin therapy, had tested negative for both anti-HBc and HBsAg before infusion, and had been tested for anti-HBc after infusion. The primary endpoint was the proportion of patients who became positive for anti-HBc after intravenous immunoglobulin infusion. FINDINGS: 950 of 18 874 patients who underwent chemotherapy within the study time frame received intravenous immunoglobulin, of whom 870 had been tested for anti-HBc before infusion. 199 patients who were negative for anti-HBc before receiving intravenous immunoglobulin were retested after infusion, of whom 29 (15% [95% CI 10-20]) became positive for anti-HBc. The probability of anti-HBc conversion at 1 week after intravenous immunoglobulin infusion was 34% (95% CI 22-48) and at 12 weeks was 4% (2-7). INTERPRETATION: Conversion of patients from anti-HBc negativity to anti-HBc positivity was common after intravenous immunoglobulin administration. However, the probability of a positive test decreased with time since infusion. Positive anti-HBc tests done shortly after intravenous immunoglobulin infusion should be interpreted with caution because they might indicate passive transfer instead of true infection. FUNDING: None.


Asunto(s)
Antígenos del Núcleo de la Hepatitis B/inmunología , Inmunización Pasiva , Inmunoglobulinas Intravenosas/inmunología , Neoplasias/inmunología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/virología , Estudios Retrospectivos , Adulto Joven
18.
Medicine (Baltimore) ; 97(17): e0474, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29703003

RESUMEN

BACKGROUND: The endometrial carcinoma (EC) is the most frequently occurring female genital cancer. The authors performed this network meta-analysis to compare operative time and the incidence of bowel injury and wound infection of 3 operative approaches (laparoscopy, laparotomy, and laparoscopic-assisted vaginal hysterectomy [LAVH]) in the treatment of EC. METHODS: The Cochrane Library, PubMed, and Embase databases were searched. Randomized controlled trials (RCTs) for EC from the day of databases establishment to February 2017 were included. Direct and indirect evidences were combined to calculate the combined weighted mean difference (WMD) or odd ratio values and the surface under the cumulative ranking curve (SUCRA) value of 3 operative approaches in the treatment of EC. RESULTS: A total of 9 qualified RCTs were included into the study. The results showed that laparotomy had a shorter-operative time than LAVH (WMD = -40.36, 95% confidence interval = -75.03 to -2.57). However, there was no significant difference in the incidence of bowel injury and wound infection among 3 operative approaches. Besides, the SUCRA values indicated that laparotomy had the shortest operative time but the incidence of bowel injury and wound infection was relatively higher. CONCLUSION: The results from this study indicate that laparotomy had highest incidence of bowel injury and wound infection but shortest operative time among 3 operative approaches in the treatment of EC.


Asunto(s)
Neoplasias Endometriales/cirugía , Histerectomía/métodos , Histeroscopía/métodos , Femenino , Humanos , Histerectomía Vaginal/métodos , Intestinos/lesiones , Tempo Operativo , Complicaciones Posoperatorias , Ensayos Clínicos Controlados Aleatorios como Asunto , Infección de la Herida Quirúrgica/epidemiología
19.
Arch Osteoporos ; 13(1): 38, 2018 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-29619576

RESUMEN

We aimed to study the utility of the FRAX tool in predicting fractures in patient's receiving a hematopoietic stem cell transplantation (HSCT). Our results indicate that the FRAX tool has modest fracture predictive ability in patients greater than 50 years of age at the time of HSCT. PURPOSE: Identifying patients at high risk of osteoporotic fractures following HSCT is challenging. We aimed to evaluate the utility of the FRAX tool at the time of HSCT in predicting fractures following transplant. METHODS: We conducted a retrospective chart review of adults (> 18 years) who underwent HSCT at MD Anderson Cancer Center from January 1, 2001, to December 31, 2010, and were followed until December 31, 2013, to identify osteoporotic fractures. Multivariate Cox regression models were built using FRAX score thresholds of low risk < 10%, medium risk 10 to 20%, and high risk > 20% probability of osteoporotic fracture. RESULTS: We identified 5170 patients who had undergone HSCT, 10% of whom developed an osteoporotic fracture during a median follow-up of 3.2 years. In patients > 65 years of age, those with medium risk (hazard ratio (HR) 2.38, 95% confidence interval (CI) 1.27-4.47) and high risk (HR 3.41, 95% CI 1.73-6.75) had a greater probability of developing an osteoporotic fracture compared to those at low risk. Similar trends were seen in patients 50 to 65 years of age. CONCLUSIONS: In patients greater than 50 years, the FRAX tool has modest predictive ability and could be used to aid in preventive treatment decision-making at the time of transplant.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Fracturas Osteoporóticas/etiología , Adulto , Factores de Edad , Anciano , Densidad Ósea/fisiología , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Fracturas Osteoporóticas/fisiopatología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores de Riesgo , Adulto Joven
20.
Dermatol Online J ; 24(1)2018 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-29469761

RESUMEN

Schnitzler syndrome is a rare disease characterized by chronic urticaria and a monoclonal gammopathy, most commonly IgM with light chains of the kappa type. There are currently no known risk factorsassociated with development of the disease. We report a case of Schnitzler syndrome in a 48-year-old man with a family history of monoclonal gammopathies. The patient's disease has been well controlled with anakinra therapy. Our case may contribute to a better understanding of the etiology of Schnitzler syndrome as his history could suggest a hereditarypredisposition for the disease. Further studies are necessary to determine whether a genetic component of Schnitzler syndrome exists, as first-degree relatives of patients with monoclonal gammopathies may be at risk for the development of the disease.


Asunto(s)
Predisposición Genética a la Enfermedad , Inmunoglobulina M/análisis , Síndrome de Schnitzler/genética , Piel/patología , Antirreumáticos/uso terapéutico , Biopsia , Humanos , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Masculino , Persona de Mediana Edad , Paraproteinemias/genética , Síndrome de Schnitzler/tratamiento farmacológico , Síndrome de Schnitzler/inmunología , Síndrome de Schnitzler/patología , Piel/inmunología
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