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Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454-489.
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Neoplasias Encefálicas , Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Encefálicas/terapia , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/terapia , Terapia Combinada , Humanos , Neoplasias Renales/patología , Neoplasias Renales/terapiaRESUMEN
The latent reservoir for HIV-1 in resting memory CD4+ T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4+ T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription. These cells allowed completion of steps in the HIV-1 life cycle through integration but suppressed HIV-1 gene transcription, thus allowing the establishment of latency. CD4+ T cells in this stage were substantially more permissive for HIV-1 latent infection than other CD4+ T cells. Establishment of latent HIV-1 infection in CD4+ T could be inhibited by viral-specific CD8+ T cells, a result with implications for elimination of latent HIV-1 infection by T cell-based vaccines.
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Linfocitos T CD4-Positivos/inmunología , Reprogramación Celular/inmunología , VIH-1/inmunología , Memoria Inmunológica/inmunología , Transcripción Genética , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/virología , Células Cultivadas , Reprogramación Celular/genética , Citocinas/genética , Citocinas/inmunología , Femenino , Citometría de Flujo , Perfilación de la Expresión Génica/métodos , VIH-1/fisiología , Interacciones Huésped-Patógeno/inmunología , Humanos , Memoria Inmunológica/genética , Activación de Linfocitos/genética , Activación de Linfocitos/inmunología , Masculino , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/metabolismo , Latencia del Virus/inmunología , Replicación Viral/inmunologíaRESUMEN
The gastropod mollusk Aplysia is an important model for cellular and molecular neurobiological studies, particularly for investigations of molecular mechanisms of learning and memory. We developed an optimized assembly pipeline to generate an improved Aplysia nervous system transcriptome. This improved transcriptome enabled us to explore the evolution of cognitive capacity at the molecular level. Were there evolutionary expansions of neuronal genes between this relatively simple gastropod Aplysia (20,000 neurons) and Octopus (500 million neurons), the invertebrate with the most elaborate neuronal circuitry and greatest behavioral complexity? Are the tremendous advances in cognitive power in vertebrates explained by expansion of the synaptic proteome that resulted from multiple rounds of whole genome duplication in this clade? Overall, the complement of genes linked to neuronal function is similar between Octopus and Aplysia. As expected, a number of synaptic scaffold proteins have more isoforms in humans than in Aplysia or Octopus. However, several scaffold families present in mollusks and other protostomes are absent in vertebrates, including the Fifes, Lev10s, SOLs, and a NETO family. Thus, whereas vertebrates have more scaffold isoforms from select families, invertebrates have additional scaffold protein families not found in vertebrates. This analysis provides insights into the evolution of the synaptic proteome. Both synaptic proteins and synaptic plasticity evolved gradually, yet the last deuterostome-protostome common ancestor already possessed an elaborate suite of genes associated with synaptic function, and critical for synaptic plasticity.
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Aplysia , Evolución Biológica , Cognición , Sinapsis , Animales , Aplysia/genética , Aplysia/metabolismo , Plasticidad Neuronal/genética , Neuronas/metabolismo , Isoformas de Proteínas/genética , Proteoma , Sinapsis/metabolismo , TranscriptomaRESUMEN
INTRODUCTION: The incidence of esophagogastric junction adenocarcinoma (EGJAC) has been rising. Intestinal metaplasia of the esophagogastric junction (EGJIM) is a common finding in gastroesophageal reflux (irregular Z-line) and may represent an early step in the development of EGJAC in the West. Worldwide, EGJIM may represent progression along the Correa cascade triggered by Helicobacter pylori . We sought to evaluate the cost-effectiveness of endoscopic surveillance of EGJIM. METHODS: We developed a decision analytic model to compare endoscopic surveillance strategies for 50-year-old patients after diagnosis of non-dysplastic EGJIM: (i) no surveillance (standard of care), (ii) endoscopy every 3 years, (iii) endoscopy every 5 years, or (iv) 1-time endoscopy at 3 years. We modeled 4 progression scenarios to reflect uncertainty: A (0.01% annual cancer incidence), B (0.05%), C (0.12%), and D (0.22%). RESULTS: Cost-effectiveness of endoscopic surveillance depended on the progression rate of EGJIM to cancer. At the lowest progression rate (scenario A, 0.01%), no surveillance strategies were cost-effective. In moderate progression scenarios, 1-time surveillance at 3 years was cost-effective, at $30,989 and $16,526 per quality-adjusted life year for scenarios B (0.05%) and C (0.12%), respectively. For scenario D (0.22%), surveillance every 5 years was cost-effective at $77,695 per quality-adjusted life year. DISCUSSION: Endoscopic surveillance is costly and can cause harm; however, low-intensity longitudinal surveillance (every 5 years) is cost-effective in populations with higher EGJAC incidence. No surveillance or 1-time endoscopic surveillance of patients with EGJIM was cost-effective in low-incidence populations. Future studies to better understand the natural history of EGJIM, identify risk factors of progression, and inform appropriate surveillance strategies are required.
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Adenocarcinoma , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Progresión de la Enfermedad , Neoplasias Esofágicas , Unión Esofagogástrica , Metaplasia , Humanos , Unión Esofagogástrica/patología , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/epidemiología , Persona de Mediana Edad , Metaplasia/patología , Adenocarcinoma/patología , Adenocarcinoma/epidemiología , Lesiones Precancerosas/patología , Masculino , Femenino , Años de Vida Ajustados por Calidad de Vida , Neoplasias Gástricas/patología , Neoplasias Gástricas/epidemiología , Incidencia , Infecciones por Helicobacter/complicaciones , Esófago de Barrett/patologíaRESUMEN
Objectives. To identify nationwide census tractâlevel areas where improving colorectal cancer (CRC) screening uptake via targeted local preventive intervention may benefit Hispanic or Latino/a (H/L) groups defined by region or country of origin. Methods. Using 2021 Centers for Disease Control and Prevention PLACES and American Community Survey data, we applied geographically weighted regression and Getis-Ord Gi* hot spot procedures to identify CRC screening priority zones for H/L groups in the United States. Priority zones can be conceptualized as census tracts with strong inverse associations between percentage of a particular H/L group in the population and CRC screening rate, after adjusting for socioeconomic deprivation and lack of insurance. Results. We identified 6519, 3477, 3522, 1069, and 1424 census tract CRC screening priority zones for H/L communities of Mexican, Puerto Rican, Central/South American, Dominican, and Cuban heritage, respectively. Priority zones for H/L groups had strong spatial heterogeneity, and overlap of geographic patterns among H/L groups varied by region. Conclusions. Our findings and interactive web map may serve as a translational tool for public health authorities, policymakers, clinicians, and other stakeholders to target investment and interventions to increase guideline-concordant CRC screening uptake benefitting specific H/L communities in the United States. (Am J Public Health. 2024;114(S6):S515-S524. https://doi.org/10.2105/AJPH.2024.307733) [Formula: see text].
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Neoplasias Colorrectales , Detección Precoz del Cáncer , Hispánicos o Latinos , Humanos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/prevención & control , Neoplasias Colorrectales/etnología , Hispánicos o Latinos/estadística & datos numéricos , Estados Unidos , Detección Precoz del Cáncer/estadística & datos numéricos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Factores Socioeconómicos , Tamizaje Masivo/estadística & datos numéricosRESUMEN
BACKGROUND AND AIMS: Studies show variability in gastroenterologists' management of gastric intestinal metaplasia (GIM) in the United States. In 2020, the American Gastroenterological Association published GIM guidelines, recommending physician-patient shared decision-making on GIM surveillance based on risk factors. We compared gastroenterologists' communication trends of a GIM finding and surveillance recommendations before and after 2020 and evaluated patient and provider factors associated with a surveillance recommendation. METHODS: A sample of patients diagnosed with GIM on biopsies from upper endoscopies performed in 2018 (cohort A) and 2021 (cohort B) were included. Logistic regression analysis assessed the association between patient/provider characteristics and surveillance recommendations in the overall cohort and over time. MATERIALS: In all, 347 patients were included: 175 in cohort A and 172 in B. Median age was 65.7 (56.0, 73.4), and 54.5% were females. Communication to patients about GIM findings and surveillance recommendations increased from 24.6% <2020 to 50% >2020 (P<0.001) and 20% <2020 to 41.3% >2020 (P<0.001), respectively. Overall, endoscopy >2020, family history of gastric cancer, autoimmune gastritis, female providers, and gastroenterologists with 10 to 20 years of experience were associated with a surveillance recommendation. The effect of family history of gastric cancer and the effect of the patient's female sex on surveillance was significantly different between both cohorts [Odds ratio (OR): 0.13, 95% (Confidence interval) CI: 0.02, 0.97 and OR 3.39, 95% CI: 1.12, 10.2, respectively). CONCLUSIONS: Despite a 2-fold increase in surveillance recommendations after 2020, there was no meaningful effect of any of the patients' factors on a recommendation for surveillance over time, which raises the question as to whether surveillance is being offered to both average and high-risk patients without thorough risk stratification.
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BACKGROUND: Gastric intestinal metaplasia (GIM) is a precancerous condition. Limited data exist on real-world clinical practice relative to guidelines. AIM: The aim of this study was to evaluate adherence to GIM risk stratification and identify factors associated with follow-up endoscopy. MATERIALS AND METHODS: We conducted manual chart review of patients with histologically confirmed GIM at an urban, tertiary medical center were identified retrospectively and details of their demographics, Helicobacter pylori, biopsy protocol, endoscopic/histologic findings, and postendoscopy follow-up were recorded. Multivariable logistic regression was used to identify factors independently associated with follow-up endoscopy. RESULTS: Among 253 patients, 59% were female, 37% non-Hispanic White (NHW), 26% Hispanic, 16% non-Hispanic Black (NHB). The median age at index endoscopy was 63.4 years (IQR: 55.9 to 70.0), with median follow-up of 65.1 months (IQR: 44.0 to 72.3). H. pylori was detected in 21.6% patients at index EGD. GIM extent and subtype data were frequently missing (22.9% and 32.8%, respectively). Based on available data, 26% had corpus-extended GIM and 28% had incomplete/mixed-type GIM. Compared with NHW, Hispanic patients had higher odds of follow-up EGD (OR=2.48, 95% CI: 1.23-5.01), while NHB patients had 59% lower odds of follow-up EGD (OR=0.41, 95% CI: 0.18-0.96). Corpus-extended GIM versus limited GIM (OR=2.27, 95% CI: 1.13-4.59) was associated with follow-up EGD, but GIM subtype and family history of gastric cancer were not. CONCLUSIONS: We observed suboptimal risk stratification among patients with GIM and notable race and ethnic disparities with respect to endoscopic surveillance. Targeted interventions are needed to improve practice patterns and mitigate observed disparities.
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INTRODUCTION: Accurate in vivo prostate volume (PV) estimation is important for obtaining prostate-specific antigen density (PSAD) and further predicting clinically significant prostate cancer (csPCa). We aimed to evaluate the accuracy of multiparametric magnetic resonance imaging (mpMRI)-estimated PV compared to both volume and weight of radical prostatectomy (RP). METHODS: We identified 310 PCa patients who underwent RP following combined targeted and systematic biopsy in our institution from September 2019 to February 2021. The MRI PV was determined using a semiautomated segmentation algorithm. RP PV was calculated using the prolate ellipsoid formula (length × width × height × π/6). Formula (prostate weight = [actual weight-3.8 g]/1.05 g/mL) was applied, and the resulting volume was used in further analysis. RESULTS: The median PV from MRI, RP, and RP weight were 39 mL, 38 mL, and 44 mL, respectively. Spearman's rank correlation coefficients (ρ) were 0.841 (MRI PV vs. RP weight), 0.758 (RP PV vs. RP weight), and 0.707 (MRI PV vs. RP PV) (all p < 0.001). Decreased correlation between the MRI PV and RP PV was observed in the larger (more than 55 mL) prostate. The PSAD derived from MRI PV showed most efficient to detect csPCa in RP specimen (57.9% vs. 57.6% vs. 45.4%). CONCLUSION: MRI PV is correlated better with RP weight than calculated RP PV, especially in larger prostate. The high csPCa detection rate in final pathology suggested that PSAD derived from MRI PV can be confidently used in clinical practice.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/patología , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Prostatectomía , Biopsia Guiada por Imagen/métodosRESUMEN
Ozone is the third most important anthropogenic greenhouse gas after carbon dioxide and methane but has a larger uncertainty in its radiative forcing, in part because of uncertainty in the source characteristics of ozone precursors, nitrogen oxides, and volatile organic carbon that directly affect ozone formation chemistry. Tropospheric ozone also negatively affects human and ecosystem health. Biomass burning (BB) and urban emissions are significant but uncertain sources of ozone precursors. Here, we report global-scale, in situ airborne measurements of ozone and precursor source tracers from the NASA Atmospheric Tomography mission. Measurements from the remote troposphere showed that tropospheric ozone is regularly enhanced above background in polluted air masses in all regions of the globe. Ozone enhancements in air with high BB and urban emission tracers (2.1 to 23.8 ppbv [parts per billion by volume]) were generally similar to those in BB-influenced air (2.2 to 21.0 ppbv) but larger than those in urban-influenced air (-7.7 to 6.9 ppbv). Ozone attributed to BB was 2 to 10 times higher than that from urban sources in the Southern Hemisphere and the tropical Atlantic and roughly equal to that from urban sources in the Northern Hemisphere and the tropical Pacific. Three independent global chemical transport models systematically underpredict the observed influence of BB on tropospheric ozone. Potential reasons include uncertainties in modeled BB injection heights and emission inventories, export efficiency of BB emissions to the free troposphere, and chemical mechanisms of ozone production in smoke. Accurately accounting for intermittent but large and widespread BB emissions is required to understand the global tropospheric ozone burden.
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Contaminantes Atmosféricos , Contaminación del Aire , Biomasa , Ozono , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/química , Atmósfera , Ecosistema , Incendios , Ozono/análisis , Ozono/químicaRESUMEN
Ticks are major arthropod vectors of disease, transmitting tick-borne pathogens during blood meal episodes. Rickettsia spp. and Borrelia spp. are two tick-borne pathogens of zoonotic concern previously identified in DNA isolates from the tick genera Amblyomma and Bothriocroton associated with reptilian hosts in Australia. Some reports suggest that these reptile ticks bite and attach to humans via accidental parasitism and transmit disease, with the tick Bothriocroton hydrosauri known to transmit Rickettsia honei or Flinders Island Spotted Fever Rickettsia to humans. This descriptive study aims to identify the ticks collected from wild reptiles submitted to veterinary clinics and captured by snake rescuers from New South Wales (NSW), Australia, and detect the presence of tick-borne bacterial DNA using quantitative polymerase chain reaction (qPCR) to detect Rickettsia spp. and Bartonella spp. and conventional nested-PCR to detect Borrelia spp. Morphological identification revealed ticks removed from one eastern blue-tongued lizard (Tiliqua scincoides scincoides) from North-Eastern NSW (Lismore), one eastern blue-tongued lizard from the Greater Sydney area (Canley Heights), one diamond python (Morelia spilota spilota) from the Greater Sydney area (Woronora Heights) and one red-bellied black snake (Pseudechis porphyriacus) from the Greater Sydney Area (Cronulla) in New South Wales were Amblyomma moreliae. No ticks were positive for Bartonella spp. and Borrelia spp. DNA using real-time PCR targeting ssrA gene and nested PCR targeting Borrelia-specific 16S rRNA gene, respectively. Real-time PCR targeting gltA, ompA, ompB and 17kDa gene of Rickettsia spp. revealed 14 out of 16 ticks were positive. The undescribed Rickettsia sp. DNA was identical to that previously recovered from reptile ticks in Australia and closely related to Rickettsia tamurae and Rickettsia monacensis, both of which are aetiologic pathogens of the Spotted Fever Group Rickettsiosis (SFGR). These results accentuate the ongoing need for increased study efforts to understand zoonotic potential of bacteria from reptile ticks and the tick-reptile-human relationship.
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Bartonella , Borrelia , Ixodidae , Lagartos , Rickettsia , Garrapatas , Humanos , Animales , Amblyomma , Nueva Gales del Sur , ADN Bacteriano/genética , ARN Ribosómico 16S/genética , Australia , Rickettsia/genéticaRESUMEN
An increased risk of new-onset diabetes mellitus has been recently reported for statin therapy, and experimental studies have shown reduced glucose-stimulated insulin secretion (GSIS) and mitochondrial dysfunction in beta cells with effects differing among agents. Organic anion transporting polypeptide (OATP) 2B1 contributes to hepatic uptake of rosuvastatin, atorvastatin and pravastatin, three known substrates. Since OATP2B1 is present in beta cells of the human pancreas, we investigated if OATP2B1 facilitates the local accumulation of statins in a rat beta cell model INS-1 832/13 (INS-1) thereby amplifying statin-induced toxicity. OATP2B1 overexpression in INS-1 cells via adenoviral transduction showed 2.5-, 1.8- and 1.4-fold higher cellular retention of rosuvastatin, atorvastatin and pravastatin, respectively, relative to LacZ control, while absolute intracellular concentration was about twice as high for the lipophilic atorvastatin compared to the more hydrophilic rosuvastatin and pravastatin. After 24 h statin treatment at high concentrations, OATP2B1 enhanced statin toxicity involving activation of intrinsic apoptosis (caspase 3/7 activation) and mitochondrial dysfunction (NADH dehydrogenase activity) following rosuvastatin and atorvastatin, which was partly reversed by isoprenoids. OATP2B1 had no effect on statin-induced reduction in GSIS, mitochondrial electron transport chain complex expression or caspase 9 activation. We confirmed a dose-dependent reduction in insulin secretion by rosuvastatin and atorvastatin in native INS-1 with a modest change in cellular ATP. Collectively, our results indicate a role of OATP2B1, which is abundant in human beta cells, in statin accumulation and statin-induced toxicity but not insulin secretion of rosuvastatin and atorvastatin in INS-1 cells.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Enfermedades Mitocondriales , Humanos , Ratas , Animales , Inhibidores de Hidroximetilglutaril-CoA Reductasas/toxicidad , Inhibidores de Hidroximetilglutaril-CoA Reductasas/metabolismo , Atorvastatina/toxicidad , Rosuvastatina Cálcica/toxicidad , Pravastatina , Enfermedades Mitocondriales/inducido químicamenteRESUMEN
Surgical resection represents the standard of care for people with newly diagnosed diffuse gliomas, and the neuropathological and molecular profile of the resected tissue guides clinical management and forms the basis for research. The Response Assessment in Neuro-Oncology (RANO) consortium is an international, multidisciplinary effort that aims to standardise research practice in neuro-oncology. These recommendations represent a multidisciplinary consensus from the four RANO groups: RANO resect, RANO recurrent glioblastoma, RANO radiotherapy, and RANO/PET for a standardised workflow to achieve a representative tumour evaluation in a disease characterised by intratumoural heterogeneity, including recommendations on which tumour regions should be surgically sampled, how to define those regions on the basis of preoperative imaging, and the optimal sample volume. Practical recommendations for tissue sampling are given for people with low-grade and high-grade gliomas, as well as for people with newly diagnosed and recurrent disease. Sampling of liquid biopsies is also addressed. A standardised workflow for subsequent handling of the resected tissue is proposed to avoid information loss due to decreasing tissue quality or insufficient clinical information. The recommendations offer a framework for prospective biobanking studies.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Estudios Prospectivos , Bancos de Muestras Biológicas , Recurrencia Local de Neoplasia/cirugía , Glioma/diagnóstico por imagen , Glioma/cirugíaRESUMEN
BACKGROUND: High-grade gliomas have a poor prognosis and do not respond well to treatment. Effective cancer immune responses depend on functional immune cells, which are typically absent from the brain. This study aimed to evaluate the safety and activity of two adenoviral vectors expressing HSV1-TK (Ad-hCMV-TK) and Flt3L (Ad-hCMV-Flt3L) in patients with high-grade glioma. METHODS: In this dose-finding, first-in-human trial, treatment-naive adults aged 18-75 years with newly identified high-grade glioma that was evaluated per immunotherapy response assessment in neuro-oncology criteria, and a Karnofsky Performance Status score of 70 or more, underwent maximal safe resection followed by injections of adenoviral vectors expressing HSV1-TK and Flt3L into the tumour bed. The study was conducted at the University of Michigan Medical School, Michigan Medicine (Ann Arbor, MI, USA). The study included six escalating doses of viral particles with starting doses of 1×1010 Ad-hCMV-TK viral particles and 1×109 Ad-hCMV-Flt3L viral particles (cohort A), and then 1×1011 Ad-hCMV-TK viral particles and 1×109 Ad-hCMV-Flt3L viral particles (cohort B), 1×1010 Ad-hCMV-TK viral particles and 1×1010 Ad-hCMV-Flt3L viral particles (cohort C), 1×1011 Ad-hCMV-TK viral particles and 1×1010 Ad-hCMV-Flt3L viral particles (cohort D), 1×1010 Ad-hCMV-TK viral particles and 1×1011 Ad-hCMV-Flt3L viral particles (cohort E), and 1×1011 Ad-hCMV-TK viral particles and 1×1011 Ad-hCMV-Flt3L viral particles (cohort F) following a 3+3 design. Two 1 mL tuberculin syringes were used to deliver freehand a mix of Ad-hCMV-TK and Ad-hCMV-Flt3L vectors into the walls of the resection cavity with a total injection of 2 mL distributed as 0·1 mL per site across 20 locations. Subsequently, patients received two 14-day courses of valacyclovir (2 g orally, three times per day) at 1-3 days and 10-12 weeks after vector administration and standad upfront chemoradiotherapy. The primary endpoint was the maximum tolerated dose of Ad-hCMV-Flt3L and Ad-hCMV-TK. Overall survival was a secondary endpoint. Recruitment is complete and the trial is finished. The trial is registered with ClinicalTrials.gov, NCT01811992. FINDINGS: Between April 8, 2014, and March 13, 2019, 21 patients were assessed for eligibility and 18 patients with high-grade glioma were enrolled and included in the analysis (three patients in each of the six dose cohorts); eight patients were female and ten were male. Neuropathological examination identified 14 (78%) patients with glioblastoma, three (17%) with gliosarcoma, and one (6%) with anaplastic ependymoma. The treatment was well-tolerated, and no dose-limiting toxicity was observed. The maximum tolerated dose was not reached. The most common serious grade 3-4 adverse events across all treatment groups were wound infection (four events in two patients) and thromboembolic events (five events in four patients). One death due to an adverse event (respiratory failure) occurred but was not related to study treatment. No treatment-related deaths occurred during the study. Median overall survival was 21·3 months (95% CI 11·1-26·1). INTERPRETATION: The combination of two adenoviral vectors demonstrated safety and feasibility in patients with high-grade glioma and warrants further investigation in a phase 1b/2 clinical trial. FUNDING: Funded in part by Phase One Foundation, Los Angeles, CA, The Board of Governors at Cedars-Sinai Medical Center, Los Angeles, CA, and The Rogel Cancer Center at The University of Michigan.
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Antineoplásicos , Glioblastoma , Glioma , Adulto , Femenino , Humanos , Masculino , Quimioradioterapia , Terapia Genética , Glioblastoma/genética , Glioblastoma/terapia , Glioma/genética , Glioma/terapia , Adolescente , Persona de Mediana Edad , AncianoRESUMEN
Brain metastases are an increasing global public health concern, even as survival rates improve for patients with metastatic disease. Both metastases and the sequelae of their treatment are key determinants of the inter-related priorities of patient survival, function, and quality of life, mandating a multidimensional approach to clinical care and research. At a virtual National Cancer Institute Workshop in September, 2022, key stakeholders convened to define research priorities to address the crucial areas of unmet need for patients with brain metastases to achieve meaningful advances in patient outcomes. This Policy Review outlines existing knowledge gaps, collaborative opportunities, and specific recommendations regarding consensus priorities and future directions in brain metastases research. Achieving major advances in research will require enhanced coordination between the ongoing efforts of individual organisations and consortia. Importantly, the continual and active engagement of patients and patient advocates will be necessary to ensure that the directionality of all efforts reflects what is most meaningful in the context of patient care.
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Investigación Biomédica , Neoplasias Encefálicas , Estados Unidos , Humanos , Calidad de Vida , National Cancer Institute (U.S.) , Consenso , Neoplasias Encefálicas/terapiaRESUMEN
Among Asian Americans, cancer is the leading cause of death and colorectal cancer (CRC) is the second most common cancer.1 The uptake of CRC screening influences incidence and mortality trends; however, the most recent American Cancer Society CRC statistics reveals ongoing disparities in screening based on race and ethnicity, with people of Asian descent demonstrating the lowest CRC screening rates despite being the fastest growing racial or ethnic group in the United States.2,3.
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Asiático , Neoplasias Colorrectales , Humanos , Estados Unidos/epidemiología , Incidencia , Etnicidad , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Detección Precoz del CáncerRESUMEN
BACKGROUND & AIMS: Gastric cancer (GC) remains a leading cause of cancer and cancer-related mortality. Recent reports suggest noncardia GC is increasing in certain U.S. POPULATIONS: However, whether these trends are driven by gastric adenocarcinoma (GA) or other histologies, including neuroendocrine tumors (NETs), lymphoma, or gastrointestinal stromal tumors (GISTs), is unclear. METHODS: We analyzed the Surveillance, Epidemiology and End Results-18 cancer registry (2000-2018) to determine age-standardized incidence rates (ASIR) and annual percentage change (APC) trends for histologically-confirmed GCs, stratified by anatomic location (noncardia vs cardia), age group (20-49 vs 50+ years), sex, race, and ethnicity. Joinpoint regression modeling estimated the statistical significance of trend comparisons. RESULTS: Of 74,520 individuals with noncardia GC, most (66.2%) were GA, with the next largest categories being non-mucosa-associated lymphoid tissue (non-MALT) lymphomas (6.9%), GIST (6.7%), NET (6.4%), and MALT lymphoma (5.6%). Noncardia GA ASIR was significantly higher than other histologies and demonstrated the greatest differences by race and ethnicity. APCs for GA and MALT, both Helicobacter pylori-associated cancers, declined significantly over time, which was driven primarily by trends among individuals ≥50 years-old. NET and GIST APCs significantly increased irrespective of age group, with the highest APCs observed among non-Hispanic white individuals. Cardia GC was rarer than noncardia GC and comprised primarily by GA (87.9%). Cardia GC incidence fell during the study period, which was primarily driven by decline in cardia GA. CONCLUSIONS: GA was the most common histology. On the basis of our findings, the rise in noncardia GC among certain U.S. populations appears predominantly driven by NET and GIST, not GA. Further studies are needed to clarify underlying etiologies for these findings.
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Adenocarcinoma , Tumores del Estroma Gastrointestinal , Neoplasias Gástricas , Humanos , Persona de Mediana Edad , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/patología , Incidencia , Tumores del Estroma Gastrointestinal/patología , Cardias/patología , Adenocarcinoma/epidemiología , Adenocarcinoma/patologíaRESUMEN
Gastrointestinal neuroendocrine tumors are increasingly common. Practitioners should examine these lesions carefully found on routine endoscopy. Obtaining accurate neuroendocrine tumors stage and grade is critical to patient assessment and management, and assistance from advanced endoscopists may be needed.
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Gastroenterólogos , Neoplasias Intestinales , Tumores Neuroendocrinos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/terapiaRESUMEN
PURPOSE: Our goal was to compare outcomes of early vs delayed transurethral surgery for benign prostatic hyperplasia after an episode of acute urinary retention compared to men without preoperative acute retention. MATERIALS AND METHODS: We conducted a retrospective cohort analysis using data from the New York Statewide Planning and Research Cooperative System from 2002-2016. We identified men ≥40 years old who underwent primary ambulatory transurethral resection or photoselective vaporization of the prostate, assessing surgical failure as time to reoperation or recatheterization. We categorized presurgical acute urinary retention by number of episodes: none (reference), 1, or ≥2 precatheterizations, and time from first retention episode to surgery: none (reference), 0-6 months, and >6 months. We used Fine-Gray competing-risk models to predict surgical failure at 10 years, with presurgical acute retention as the primary predictor, adjusted for age, race, insurance, Charlson Comorbidity Index score, preoperative urinary infection, and procedure type, with death as the competing risk. RESULTS: Among 17,474 patients undergoing transurethral surgery, 10% had preoperative acute retention with a median time to surgery of 2.4 months (IQR: 1-18). Among men with preoperative retention, 37% had ≥6 months of delay to surgery. The 10-year cumulative treatment failure rate was 17.2% among catheter naïve men vs 34.0% with ≥2 precatheterizations and 32.9% with ≥6 months delay to surgery. Delays from catheterization to surgery were associated with higher rates of treatment failure (<6 months SHR 1.49, P < .001; ≥6 months SHR 2.11, P < .001) vs catheter naïve men. CONCLUSIONS: Preoperative acute urinary retention and delay to surgery once catheterized are associated with poorer long-term postoperative outcomes after surgery for benign prostatic hyperplasia.
Asunto(s)
Hiperplasia Prostática , Resección Transuretral de la Próstata , Retención Urinaria , Masculino , Humanos , Adulto , Retención Urinaria/cirugía , Retención Urinaria/complicaciones , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/cirugía , Resección Transuretral de la Próstata/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Current success in transplant oncology for select liver tumors, such as hepatocellular carcinoma, has ignited international interest in liver transplantation (LT) as a therapeutic option for nonresectable colorectal liver metastases (CRLM). In the United States, the CRLM LT experience is limited to reports from a handful of centers. This study was designed to summarize donor, recipient, and transplant center characteristics and posttransplant outcomes for the indication of CRLM. METHODS: Adult, primary LT patients listed between December 2017 and March 2022 were identified by using United Network Organ Sharing database. LT for CRLM was identified from variables: "DIAG_OSTXT"; "DGN_OSTXT_TCR"; "DGN2_OSTXT_TCR"; and "MALIG_TY_OSTXT." RESULTS: During this study period, 64 patients were listed, and 46 received LT for CRLM in 15 centers. Of 46 patients who underwent LT for CRLM, 26 patients (56.5%) received LTs using living donor LT (LDLT), and 20 patients received LT using deceased donor (DDLT) (43.5%). The median laboratory MELD-Na score at the time of listing was statistically similar between the LDLT and DDLT groups (8 vs. 9, P = 0.14). This persisted at the time of LT (8 vs. 12, P = 0.06). The 1-, 2-, and 3-year, disease-free, survival rates were 75.1, 53.7, and 53.7%. Overall survival rates were 89.0, 60.4, and 60.4%, respectively. CONCLUSIONS: This first comprehensive U.S. analysis of LT for CRLM suggests a burgeoning interest in high-volume U.S. transplant centers. Strategies to optimize patient selection are limited by the scarce oncologic history provided in UNOS data, warranting a separate registry to study LT in CRLM.
Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Trasplante de Hígado , Adulto , Humanos , Estados Unidos , Estudios Retrospectivos , Neoplasias Hepáticas/cirugía , Donadores Vivos , Neoplasias Colorrectales/cirugía , Receptores de Antígenos de Linfocitos T , Resultado del TratamientoRESUMEN
Community mobilization (CM) is a vital yet under-explored avenue for increasing HIV testing in generalized HIV epidemic settings. Using multi-stage cluster sampling, a population-based sample of 3535 Zambian adults (mean age: 28 years, 50% women) were recruited from 14 districts to complete a household survey. Exploratory factor analysis (EFA) was used to re-validate a 23-item, 5-factor CM scale. Multivariable logistic and Poisson regression were then used to identify associations of CM with HIV testing behaviors and their psychosocial antecedents. A 21-item, 3-factor ("Leadership", "Collective Action Capacity", and "Social Cohesion") CM solution emerged from EFA (Cronbach's α 0.88). Among men and in rural settings, higher CM was significantly (p < 0.05) associated with elevated odds of HIV testing and more past-year HIV testing discussion sources, controlling for socio-demographics and sexual behaviors. Results underscore the importance of prioritizing CM to cultivate more favorable environments for HIV testing uptake, especially for men and rural residents.