RESUMEN
AIMS: Despite known short-term mortality risk of immune checkpoint inhibitor (ICI) pneumonitis, its impact on 1-year mortality, long-term pulmonary function, symptom persistence, and radiological resolution remains unclear. METHODS: We retrospectively analyzed 71 nonsmall cell lung cancer (NSCLC) patients treated with anti-PD(L)1 monoclonal antibodies between 2018-2021, who developed pneumonitis. Clinical and demographic covariates were collected from electronic medical record. Cox regression assessed associations with mortality, while logistic regression evaluated associations with persistent symptoms, hypoxemia, and radiological resolution. RESULTS: Steroid-refractory pneumonitis (hazard ratio [HR] = 15.1, 95% confidence interval [95% CI]:3.9-57.8, P < .0001) was associated with higher 1-year mortality compared to steroid-responsive cases. However, steroid-resistant (odds ratio [OR] = 1.4, 95% CI: 0.4-5.1, P = .58) and steroid-dependent (OR = 0.4, 95% CI: 0.1-1.2, P = .08) pneumonitis were not. Nonadenocarcinoma histology (OR = 6.7, 95% CI: 1.6-46.6, P = .01), grade 3+ pneumonitis (OR = 4.6, 95% CI: 1.3-22.7, P = .03), and partial radiological resolution (OR = 6.3, 95% CI: 1.8-23.8, P = .004) were linked to increased pulmonary symptoms after pneumonitis resolution. Grade 3+ pneumonitis (OR = 8.1, 95% CI: 2.3-31.5, P = .001) and partial radiological resolution (OR = 5.45, 95% CI: 1.29-37.7, P = .03) associated with residual hypoxemia. Nonadenocarcinoma histology (OR = 3.6, 95% CI: 1.01-17.6, P = .06) and pretreatment ILAs (OR = 4.8, 95% CI: 1.14-33.09, P = .05) were associated with partial radiological resolution. CONCLUSIONS: Steroid refractory pneumonitis increases 1-year mortality in NSCLC patients. Pretreatment ILAs may signal predisposition to fibrosis-related outcomes, seen as partial resolution, which in turn is associated with postresolution symptoms and residual hypoxemia. These findings offer insights for identifying patients at risk of adverse outcomes post-pneumonitis resolution.
RESUMEN
Small cell bladder cancer (SCBC) is a rare and aggressive disease, often treated with platinum/etoposide-based chemotherapy. Key molecular drivers include the inactivation of onco-suppressor genes (TP53, RB1) and amplifications in proto-oncogenes (MYC). We report a patient with SCBC who achieved an objective and prolonged response to lurbinectedin, which has been approved for metastatic small cell lung cancer, after developing disease progression on cisplatin/etoposide and nivolumab/ipilimumab. A genomic analysis of a metastatic biopsy prior to lurbinectedin initiation revealed a TP53 mutation and amplification of the cell cycle regulators E2F3 and MYCL. A repeat biopsy following the development of lurbinectedin resistance showed a new actionable ERBB2 alteration without significant change in the tumor mutation burden (six mutations/Mb). The present report suggests that lurbinectedin may be active and should be further explored in SCBC harboring TP53 mutations and amplifications in E2F3 and MYC family complexes.
Asunto(s)
Carbolinas , Compuestos Heterocíclicos de 4 o más Anillos , Mutación , Proteína p53 Supresora de Tumor , Neoplasias de la Vejiga Urinaria , Humanos , Carbolinas/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Proteína p53 Supresora de Tumor/genética , Masculino , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/genética , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Antineoplásicos/uso terapéutico , Persona de Mediana EdadRESUMEN
VEXAS syndrome is a recently described entity characterized by systemic inflammatory and hematologic manifestations. The disease was first characterized by Beck et al. in 2020 in a study characterizing 25 patients with undiagnosed adult-onset inflammatory syndromes. While the literature regarding VEXAS syndrome has grown exponentially since 2020, there is still much to be understood. This lack of information leads to challenges in both the diagnosis and treatment of patients with VEXAS syndrome. Patients will often have a variety of clinical symptoms that can lead to missed or delayed diagnoses. Additionally, awareness of VEXAS syndrome is still developing among clinicians. In this comprehensive review, we summarize the current literature regarding VEXAS syndrome, and explore clinical updates of this emerging disease state. Our aim of this review is to increase awareness regarding this new disease state and identify research areas to better understand future treatment approaches for patients with VEXAS syndrome.
RESUMEN
Silicon vacancy centers (SiVs) in diamond have emerged as a promising platform for quantum sciences due to their excellent photostability, minimal spectral diffusion, and substantial zero-phonon line emission. However, enhancing their slow nanosecond excited-state lifetime by coupling to optical cavities remains an outstanding challenge, as current demonstrations are limited to â¼10-fold. Here, we couple negatively charged SiVs to sub-diffraction-limited plasmonic cavities and achieve an instrument-limited ≤8 ps lifetime, corresponding to a 135-fold spontaneous emission rate enhancement and a 19-fold photoluminescence enhancement. Nanoparticles are printed on ultrathin diamond membranes on gold films which create arrays of plasmonic nanogap cavities with ultrasmall volumes. SiVs implanted at 5 and 10 nm depths are examined to elucidate surface effects on their lifetime and brightness. The interplay between cavity, implantation depth, and ultrathin diamond membranes provides insights into generating ultrafast, bright SiV emission for next-generation diamond devices.
RESUMEN
Non-clear cell renal cell carcinoma (nccRCC) makes up nearly one quarter of all RCC subtypes, commonly impacts younger patients, and is often metastatic at presentation. Compared to clear-cell RCC (ccRCC), nccRCC typically has a worse prognosis in the metastatic setting, with overall survival durations that are ~10 months shorter. The nccRCC consists of a wide range of different histological subtypes, the majority of which are composed of papillary, chromophobe, renal medullary carcinoma, translocation RCC, collecting duct carcinoma and unclassified RCC. Most clinical trials have either excluded or only included small numbers of patients with nccRCC; owing to the lack of prospective studies focusing on this population, data on response rates and survival outcomes are lacking. NccRCC treatment is a nascent field with various therapeutic modalities and combinations under investigation, often based on data extrapolated from therapeutic studies in ccRCC. We herein review the use and outcomes of cytotoxic chemotherapy, various combination modalities of tyrosine kinase inhibitors and immune checkpoint inhibitors, and targeted agents. We discuss active ongoing clinical trials for patients with nccRCC and future directions in the treatment of this rare disease. Historically, treatment for nccRCC has been adopted from the standard of care for patients with ccRCC, although these treatments are less effective in the nccRCC population. As we begin to understand the underlying biology of these tumors, clinical trials have been able to slowly accrue and include more patients with various subtypes of nccRCC. There remains much room for improvement in this area of need, but there is hope on the horizon.
Asunto(s)
Antineoplásicos , Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/patología , Pronóstico , Antineoplásicos/uso terapéutico , BiologíaRESUMEN
OBJECTIVE: To compare rates of reduction loss, nonunion, and infection in intra-articular distal tibia fractures (IADTF) treated with limited open reduction internal fixation and intramedullary nailing (IMN) as compared to open reduction internal fixation with plate and screws (plate fixation [PF]). DESIGN: Retrospective review. SETTING: Level-I academic trauma center. PATIENT SELECTION CRITERIA: Patients age ≥ 18 with OTA/AO 43C1 and C2 IADTF treated with IMN or PF between 2013-2021. OUTCOME MEASURES AND COMPARISONS: Loss of reduction, surgical site infection (SSI), nonunion, and patient-reported outcomes (PROs) were compared for IMN versus PF treatments. RESULTS: One hundred ten patients met the inclusion criteria (IMN 33 and PF 77). There was no loss of reduction found. Seventeen nonunions (15% overall; IMN 4/33 and PF 13/77) and 13 SSIs (12% overall; IMN 2/33 and PF11/77) were identified. Despite several risk factors being identified for nonunion and SSI in bivariate analysis, only open fracture remained significant as a risk factor for both nonunion (odds ratio 0.09 for closed fracture, 95% confidence interval, 0.02-0.56, P = 0.009) and SSI (odds ratio 0.07 for closed fracture, 95% confidence interval, 0.06-0.26, P = 0.012) in the multivariate model. Propensity scoring based on presurgical variables was significantly different between patients who received IMN versus PF ( P = 0.03); however, logistic regression incorporating the propensity score revealed no significant association with nonunion and SSI. Adjusting for the propensity score, there remained no association comparing IMN versus PF with nonunion and SSI ( P = 0.54 and P = 0.17, respectively). There was also no difference in PROs between IMN and PF (physical function: P = 0.25 and pain interference: P = 0.21). CONCLUSIONS: Overall nonunion and SSI prevalence was 15% and 12%, respectively, in operatively treated OTA/AO 43C1 and C2 IADTF. An open fracture was a significant risk factor for nonunion and SSI. Metaphyseal fixation through IMN or PF did not affect loss of reduction, nonunion, SSI, or PROs. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Asunto(s)
Fracturas de Tobillo , Fijación Intramedular de Fracturas , Fracturas Cerradas , Fracturas Abiertas , Fracturas de la Tibia , Humanos , Fijación Intramedular de Fracturas/efectos adversos , Tibia/cirugía , Fracturas Abiertas/etiología , Puntaje de Propensión , Fracturas de la Tibia/cirugía , Fracturas de la Tibia/etiología , Estudios Retrospectivos , Análisis Multivariante , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Fracturas de Tobillo/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Few studies have examined the use of immunoassay urine drug testing of cancer patients in palliative care clinics. OBJECTIVES: We examined the frequency of immunoassay urine drug test (UDT) abnormalities and the factors associated with aberrancy at a safety-net hospital palliative medicine clinic. METHODS: A retrospective review of the electronic medical records of consecutive eligible patients seen at the outpatient palliative medicine clinic in a resource-limited safety-net hospital system was conducted between 1 September 2015 and 31 December 2020. We collected longitudinal data on patient demographics, UDT findings, and potential predictors of aberrant results. RESULTS: Of the 913 patients in the study, 500 (55%) underwent UDT testing, with 455 (50%) having the testing within the first three visits. Among those tested within the first three visits, 125 (27%) had aberrant UDT results; 44 (35%) of these 125 patients were positive for cocaine. In a multivariable regression model analysis of predictors for aberrant UDT within the first three visits, non-Hispanic White race (odds ratio (OR) = 2.13; 95% confidence interval (CI): 1.03-4.38; p = 0.04), history of illicit drug use (OR = 3.57; CI: 1.78-7.13; p < 0.001), and history of marijuana use (OR = 7.05; CI: 3.85-12.91; p < 0.001) were independent predictors of an aberrant UDT finding. CONCLUSION: Despite limitations of immunoassay UDT, it was able to detect aberrant drug-taking behaviors in a significant number of patients seen at a safety-net hospital palliative care clinic, including cocaine use. These findings support universal UDT monitoring and utility of immunoassay-based UDT in resource-limited settings.
RESUMEN
BACKGROUND: Neoadjuvant chemotherapy (neoCTX) has been recommended as the optimal strategy in surgically resectable neuroendocrine carcinoma (NEC) of the urinary tract (NEC-URO). OBJECTIVE: To determine the systemic therapy regimen and timing, which are most active against NEC-URO. DESIGN, SETTING, AND PARTICIPANTS: We used our institutional historical clinical and pathological database to study 203 patients (cT2, 74%; cT3/4a, 22%; and cTx, 4%) with surgically resectable NEC-URO between November 1985 and May 2020. A total of 141 patients received neoCTX and 62 underwent initial radical surgery, 24 of whom received adjuvant CTX (adjCTX). INTERVENTION: Neoadjuvant CTX with etoposide/cisplatin (EP), an alternating doublet of ifosfamide/doxorubicin (IA) and EP, dose-dense methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), gemcitabine/cisplatin (GC), or others. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS), downstaging rate, and pathological complete response using a multivariable model adjusting for tumor- and patient-related factors. RESULTS AND LIMITATIONS: Downstaging rate was significantly improved with neoCTX versus initial surgery (49.6% vs 14.5%, pâ¯<â¯0.0001), stage cT2N0 versus cT3/4N0 (44% vs 25%, pâ¯=â¯0.01), or presence of carcinoma in situ (47% vs 28%, pâ¯=â¯0.01). Downstaging was greatest with IA/EP (65%) versus EP (39%), MVAC/GC (27%), or others (36%, pâ¯=â¯0.04). After adjusting for age and Eastern Cooperative Oncology Group performance status, IA/EP was still associated with improved downstaging (odds ratioâ¯=â¯3.7 [1.3-10.2], pâ¯=â¯0.01). At a median follow-up of 59.7 mo, 5-yr OS rates for neoCTX followed by surgery, surgery alone, and surgery followed by adjCTX were 57%, 22%, and 30%, respectively. An NEC regimen (IA/EP or EP) versus a urothelial regimen (MVAC/GC or others) was associated with improved survival (145.4 vs 42.5 mo, hazard ratioâ¯=â¯0.49, 95% confidence interval: 0.25-0.94). CONCLUSIONS: Neoadjuvant CTX remains the standard-of-care treatment for NEC-URO with an advantage for NEC regimens over traditional urothelial regimens. IA/EP improves pathological downstaging at the time of surgery compared with EP, but is reserved for younger and higher function patients. PATIENT SUMMARY: In this report, we looked at the outcomes from invasive neuroendocrine carcinoma of the urinary tract in a large US population. We found that the outcomes varied with treatment strategy. We conclude that the best outcomes are seen in patients treated with chemotherapy prior to surgery and regimens tailored to histology and tolerance.
Asunto(s)
Carcinoma Neuroendocrino , Neoplasias de la Vejiga Urinaria , Sistema Urinario , Humanos , Neoplasias de la Vejiga Urinaria/patología , Cisplatino/uso terapéutico , Gemcitabina , Desoxicitidina/uso terapéutico , Sistema Urinario/patología , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/cirugíaRESUMEN
An abundance of metallic metasurfaces have been realized with miniscule, intricate features capable of tailored scattering, reflection, and absorption; however, high losses through heat limit their use in optoelectronics. Here, codesign of a detector and a polarization-sensing metasurface overcomes this challenge by utilizing the heat generation for integrated pyroelectric detection of the incoming light polarization. Using a nanogap metasurface with asymmetric metallic elements, polarization-sensitive photodetection exhibits high extinction ratios up to 19 for orthogonally polarized light and allows extraction of Stokes parameters with <12% deviation from theoretical values. This polarization-sensitive photodetector is ultrathin, consisting of active layers of only 290 nm, and exhibits fast response times of â¼2 ns. The structure is fully integrated, requiring no external cameras, detectors, or power sources, and points toward the creation of layered, multifunctional devices that utilize exotic metasurface properties for novel and compact sensing and imaging.
RESUMEN
PURPOSE: Treatment outcomes in patients with relapsed/refractory (R/R) myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) remains dismal. On the basis of both extensive preclinical data and emerging clinical data, treatment with bromodomain and extra-terminal domain inhibitors (BETi) is a potential approach for patients with high-risk myeloid malignancies. PATIENTS AND METHODS: We conducted a phase I trial to study the safety and efficacy of PLX51107 (BETi) and azacitidine combination therapy in patients with R/R AML and high-risk (HR) MDS and studied mechanisms of resistance to the combination therapy. RESULTS: Thirty-seven patients with HR R/R MDS (n = 4) and R/R AML (n = 33) were treated. Sixteen patients (43%) had MECOM gene rearrangement and 7 other patients had TP53 mutation. Median prior number of therapies was three (range 1-9); 97% had received prior hypomethylating agent and 84% prior venetoclax. Overall response rate was 8/37 (22%): complete remission with incomplete platelet recovery (n = 1); morphologic leukemia-free state (n = 2); hematologic improvement (n = 5). The most common nonhematologic toxicities were febrile neutropenia and pneumonia in 12 (32%) patients each; 6 patients (17%) had severe hyperbilirubinemia. RNA-sequencing analysis of mononuclear cells harvested on treatment (day 3) versus pretreatment showed significant changes in mRNA expressions in responders: downregulation of MYC, BCL2, IL7R, and CDK6 and upregulation of HEXIM1, CD93, DCXR, and CDKN1A. Immunoblot analyses confirmed reduction in protein levels of c-Myc, CDK6, BCL2, and BCL-xL, and induction of BRD4 and HEXIM1 protein levels in responders. CONCLUSIONS: In a heavily pretreated patient cohort with R/R MDS and AML, PLX51107+ azacitidine was well-tolerated and resulted in modest clinical benefit.
Asunto(s)
Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Azacitidina , Proteínas Nucleares , Factores de Transcripción , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Recurrencia , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Proteínas Proto-Oncogénicas c-bcl-2 , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Proteínas de Unión al ARN , Proteínas de Ciclo CelularRESUMEN
Patient prescriber agreements, also known as opioid contracts or opioid treatment agreements, have been recommended as a strategy for mitigating non-medical opioid use (NMOU). The purpose of our study was to characterize the proportion of patients with PPAs, the rate of non-adherence, and clinical predictors for PPA completion and non-adherence. This retrospective study covered consecutive cancer patients seen at a palliative care clinic at a safety net hospital between 1 September 2015 and 31 December 2019. We included patients 18 years or older with cancer diagnoses who received opioids. We collected patient characteristics at consultation and information regarding PPA. The primary purpose was to determine the frequency and predictors of patients with a PPA and non-adherence to PPAs. Descriptive statistics and multivariable logistic regression models were used for the analysis. The survey covered 905 patients having a mean age of 55 (range 18-93), of whom 474 (52%) were female, 423 (47%) were Hispanic, 603 (67%) were single, and 814 (90%) had advanced cancer. Of patients surveyed, 484 (54%) had a PPA, and 50 (10%) of these did not adhere to their PPA. In multivariable analysis, PPAs were associated with younger age (odds ratio [OR] 1.44; p = 0.02) and alcohol use (OR 1.72; p = 0.01). Non-adherence was associated with males (OR 3.66; p = 0.007), being single (OR 12.23; p = 0.003), tobacco (OR 3.34; p = 0.03) and alcohol use (OR 0.29; p = 0.02), contact with persons involved in criminal activity (OR 9.87; p < 0.001), use for non-malignant pain (OR 7.45; p = 0.006), and higher pain score (OR 1.2; p = 0.01). In summary, we found that PPA non-adherence occurred in a substantial minority of patients and was more likely in patients with known NMOU risk factors. These findings underscore the potential role of universal PPAs and systematic screening of NMOU risk factors to streamline care.
RESUMEN
The androgen receptor (AR) is one of the oldest therapeutic targets in oncology and continues to dominate the treatment landscape for advanced prostate cancer, where nearly all treatment regimens include some form of AR modulation. In this regard, AR remains the central driver of prostate cancer cell biology. Emerging preclinical and clinical data implicate key roles for AR in additional cancer types, thereby expanding the importance of this drug target beyond prostate cancer. In this mini-review, new roles for AR in other cancer types are discussed as well as their potential for treatment with AR-targeted agents. Our understanding of these additional functions for AR in oncology expand this receptor's potential as a therapeutic target and will help guide the development of new treatment approaches.
Asunto(s)
Antineoplásicos , Neoplasias de la Próstata Resistentes a la Castración , Neoplasias de la Próstata , Humanos , Masculino , Antagonistas de Receptores Androgénicos/farmacología , Antagonistas de Receptores Androgénicos/uso terapéutico , Antineoplásicos/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Transducción de SeñalRESUMEN
INTRODUCTION: Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially. METHODS: We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy. Clinical, imaging, and microbiological data were evaluated by multidisciplinary adjudication teams. The primary outcome of interest was grade ≥2 (CTCAEv5) pneumonitis. Clinicopathologic variables, tobacco use, cancer therapies, and preexisting lung disease were assessed for univariate effects using Cox proportional hazards models. We created multivariate Cox proportional hazards models to assess risk factors for pneumonitis and mortality. Pneumonitis, pneumonia, and progression were modeled as time-dependent variables in mortality models. RESULTS: We evaluated 419 patients between 2013 and 2021. The cumulative incidence of pneumonitis was 9.5% (40/419). In a multivariate model, pneumonitis increased the risk for mortality (HR 1.6, 95% CI, 1.0-2.5), after adjustment for disease progression (HR 1.6, 95% CI, 1.4-1.8) and baseline shortness of breath (HR 1.5, 95% CI, 1.2-2.0). Incomplete resolution was more common with more severe pneumonitis. Interstitial lung disease was associated with higher risk for pneumonitis (HR 5.4, 95% CI, 1.1-26.6), particularly in never smokers (HR 26.9, 95% CI, 2.8-259.0). CONCLUSION: Pneumonitis occurred at a high rate and significantly increased mortality. Interstitial lung disease, particularly in never smokers, increased the risk for pneumonitis.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Neumonía , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Incidencia , Neoplasias Pulmonares/tratamiento farmacológico , Neumonía/epidemiología , Factores de Riesgo , Enfermedades Pulmonares Intersticiales/complicaciones , Estudios RetrospectivosRESUMEN
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with historically poor outcomes and no worldwide consensus treatment approach. Unique among most hematologic malignancies for its frequent cutaneous involvement, BPDCN can also invade other extramedullary compartments, including the central nervous system. Generally affecting older adults, many patients are unfit to receive intensive chemotherapy, and although hematopoietic stem cell transplantation is preferred for younger, fit individuals, not all are eligible. One recent therapeutic breakthrough is that all BPDCNs express CD123 (IL3Rα) and that this accessible surface marker can be pharmacologically targeted. The first-in-class agent for BPDCN, tagraxofusp, which targets CD123, was approved in December 2018 in the United States for patients with BPDCN aged ≥2 years. Despite favorable response rates in the frontline setting, many patients still relapse in the setting of monotherapy, and outcomes in patients with relapsed/refractory BPDCN remain dismal. Therefore, novel approaches targeting both CD123 and other targets are actively being investigated. To begin to formally address the state of the field, we formed a new collaborative initiative, the North American BPDCN Consortium (NABC). This group of experts, which includes a multidisciplinary panel of hematologists/oncologists, hematopoietic stem cell transplant physicians, pathologists, dermatologists, and pediatric oncologists, was tasked with defining the current standard of care in the field and identifying the most important research questions and future directions in BPDCN. The position findings of the NABC's inaugural meetings are presented herein.
Asunto(s)
Neoplasias Hematológicas , Trastornos Mieloproliferativos , Neoplasias Cutáneas , Niño , Humanos , Anciano , Nivel de Atención , Subunidad alfa del Receptor de Interleucina-3 , Células Dendríticas/patología , Recurrencia Local de Neoplasia/patología , Trastornos Mieloproliferativos/patología , Neoplasias Hematológicas/patología , Neoplasias Cutáneas/patología , Enfermedad Aguda , América del NorteRESUMEN
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy that is categorized by the production and accumulation of CD5+ monoclonal B cell lymphocytes, commonly in the spleen, bone marrow, and peripheral blood; these are morphologically mature lymphocytes with abnormal immune function. Ascites, although common in solid organ malignancies such as ovarian, breast, and gastrointestinal, is a rare clinical manifestation in hematological malignancies. The case presented herein describes an elderly male patient with CLL who presented with transudative ascites 7 years after the completion of chemotherapy. Microscopic analysis and flow cytometry of the patient's ascitic fluid were consistent with CLL, and he was treated with six cycles of obinutuzumab immunotherapy with the addition of acalabrutinib, resulting in near resolution of malignant ascites. A few cases have reported CLL manifesting as transudative or exudative ascites in elderly patients. A few previous cases have reported the development of ascites between 12 and 21 months after the initial treatment of CLL with chemotherapy. A unique feature of our patient is the presentation with malignant ascites nearly 7 years after the initial CLL treatment with chemotherapy. The intent of this case report is to bring awareness of ascites as a possible initial presenting symptom of CLL in patients with isolated abdominal distention with or without common clinical features of leukemia (i.e., splenomegaly, lymphadenopathy, and B-symptoms) and the therapeutic management thereafter. Malignant ascites may be associated with relapse or the transformation of leukemia; thus, prompt diagnosis and treatment should not be delayed.
Asunto(s)
Leucemia Linfocítica Crónica de Células B , Humanos , Masculino , Anciano , Leucemia Linfocítica Crónica de Células B/complicaciones , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Ascitis/etiología , Ascitis/complicacionesRESUMEN
Coxa profunda presents a unique challenge in surgical treatment approach given global acetabular overcoverage. Arthroscopic treatment can be fraught with difficulty obtaining hip distraction for safe arthroscopic instrumentation, and limited arthroscopic access may prevent sufficient osseous resection of the excess acetabular rim. Although hip arthroscopy use has increased markedly over the past decades for all types of hip pathology, coxa profunda may represent one unique indication for surgical hip dislocation. This technique describes open surgical hip dislocation, rim resection, femoral osteoplasty, and labral reconstruction using anterior tibialis allograft for coxa profunda with combined-type femoroacetabular impingement syndrome and labral ossification.
RESUMEN
PURPOSE: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hematologic malignancy associated with overexpression of CD123. Allogeneic chimeric antigen receptor T cells (CAR-T) directed against CD123 in BPDCN have been studied in clinical trials. We performed post-mortem analysis of a patient treated with anti-CD123 CAR-T to elucidate cause of death, development of cytokine release syndrome (CRS), and tissue distribution of UCART123 cells. METHODS: A post-mortem multidisciplinary clinicopathologic analysis was performed with digital droplet polymerase chain reaction of isolated blood and tissue ribonucleic acid (RNA) to evaluate tissue distribution of infused CAR-T. Multiparameter flow cytometry for detection of CAR-T was used for whole blood samples. Cytokine levels in plasma were measured using multiplex bead assay. Gene expression profiling on isolated RNA was performed using semi-custom Nanostring immune gene panel and RNA-sequence method. RNA in situ hybridization was performed using CAR-specific probe. RESULTS: The patient developed severe clinical CRS refractory to corticosteroids, tocilizumab, and lymphodepletion. Despite significant reduction in BPDCN lesions, the patient passed away on day 9 of CAR-T. Autopsy results show that following lymphodepletion and UCART123 administration, the patient remained severely lymphopenic with few UCART123 cells detected, predominantly localized to spleen. CONCLUSIONS: No definitive cause of death was determined, but we hypothesized that the patient may have succumbed to CAR-T-mediated cardiopulmonary toxicity. UCART123 cells displayed low overall distribution, with predominance in immune organs and tissues. Mechanism of CRS development is still poorly understood in patients receiving CAR-T therapy. Future directions in the field developing CD123-targeted agents in BPDCN are discussed.
Asunto(s)
Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Trastornos Mieloproliferativos , Receptores Quiméricos de Antígenos , Neoplasias Cutáneas , Enfermedad Aguda , Citocinas/metabolismo , Células Dendríticas/patología , Neoplasias Hematológicas/patología , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Subunidad alfa del Receptor de Interleucina-3 , Trastornos Mieloproliferativos/patología , ARN/metabolismo , ARN/uso terapéutico , Receptores Quiméricos de Antígenos/metabolismo , Receptores Quiméricos de Antígenos/uso terapéutico , Neoplasias Cutáneas/metabolismoRESUMEN
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from precursor dendritic cells. BPDCN cells characteristically express several markers on their cell surfaces including CD123, CD4, and CD56. Because of its rarity and challenging clinical presentation, there was no standard of care in managing BPDCN for decades and its prognosis overall was poor. However, as understanding of this rare neoplasm has increased, so have treatment options. The conventional cytotoxic chemotherapy regimens once used in the treatment of BPDCN were modest in their impact on disease relapse until paired with hematopoietic stem cell transplant. Although recent data suggest that there still remains a role for chemotherapeutic agents, targeted modalities have expanded the overall BPDCN treatment landscape. The CD123-targeted agent, tagraxofusp, was the first Food and Drug Administration-approved monotherapy in the treatment of BPDCN. Since its inception, several CD123-targeted and other cell-surface agents have been investigated, with many agents still in the preclinical stages. Although relapsed/refractory disease and central nervous system disease both remain formidable areas of research, there are several promising therapeutic approaches that could have a significant impact on the trajectory of treatment. This review will provide detailed insight on the novel drugs currently in use and those being explored in the management of BPDCN.