RESUMO
BACKGROUND: Anal squamous cell carcinoma patients often present with significant symptoms, including pain, bleeding, and obstructive symptoms. This requires palliation-directed therapy as a first-line treatment to alleviate symptoms. The proportion of patients receiving first-line palliative treatments is unknown. We aimed to study the factors associated with the use of first-line palliative treatments in stage II-IV anal squamous cell carcinoma patients. METHODS: We used the National Cancer Database to identify adult patients diagnosed with stage II-IV anal squamous cell carcinoma between 2004 and 2016. We performed univariable and multivariable logistic regression analysis to determine the clinical and sociodemographic variables associated with the utilization of palliative treatment in the first-line setting, including palliative radiotherapy, chemotherapy, surgery, and pain management. RESULTS: Among 16,944 patients diagnosed with stage II-IV anal squamous cell carcinoma, only a small proportion of 492 (2.9%) required first-line palliative treatments to control symptoms. The majority of these patients received palliative radiotherapy (32%), followed by palliative surgery (25%), palliative chemotherapy (19%), combination therapies (14%), and pain management (10%). On multivariable analysis, higher stage disease, lower income, Medicare and Medicaid insurance, and life expectancy <6 months were associated with higher odds of use of first-line palliative therapy. CONCLUSIONS: First-line use of palliative treatments to control symptoms is needed in a small proportion of anal squamous cell cancer patients. It was utilized in all stages, but it was most frequently observed in patients with stage IV disease and patients with <6 months life expectancy. First-line palliative therapy was also more frequent in lower-income patients and patients with Medicare and Medicaid insurance which highlights the disparities in anal cancer management.
Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Adulto , Humanos , Idoso , Estados Unidos , Cuidados Paliativos , Estadiamento de Neoplasias , Medicare , Carcinoma de Células Escamosas/patologia , Neoplasias do Ânus/patologia , Estudos RetrospectivosRESUMO
Ocular manifestations of thrombotic thrombocytopenic purpura (TTP) are uncommon, and bilateral retinal detachment is a rare presentation of TTP. We report a rare case of bilateral retinal detachment from underlying TTP in a patient presenting with vision loss. A 56-year-old man presented with a 4-day history of bilateral vision loss. Bilateral serous retinal detachment was confirmed using dilated ophthalmoscope examination. Laboratory results were significant for severe thrombocytopenia, peripheral smear revealed numerous schistocytes and ADAMTS13 activity of less than 1%. The patient was treated with plasma exchange (PLEX), prednisone, rituximab and caplacizumab. This case report highlights that prompt treatment of TTP with PLEX, prednisone, rituximab and caplacizumab could result in significant vision recovery.
Assuntos
Miopia , Púrpura Trombocitopênica Trombótica , Descolamento Retiniano , Proteína ADAMTS13 , Humanos , Masculino , Pessoa de Meia-Idade , Troca Plasmática , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Rituximab/uso terapêuticoRESUMO
Inherited predisposition to myeloid malignancies is more common than previously appreciated. We analyzed the whole-exome sequencing data of paired leukemia and skin biopsy samples from 391 adult patients from the Beat AML 1.0 consortium. Using the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines for variant interpretation, we curated 1547 unique variants from 228 genes. The pathogenic/likely pathogenic (P/LP) germline variants were identified in 53 acute myeloid leukemia (AML) patients (13.6%) in 34 genes, including 6.39% (25/391) of patients harboring P/LP variants in genes considered clinically actionable (tier 1). 41.5% of the 53 patients with P/LP variants were in genes associated with the DNA damage response. The most frequently mutated genes were CHEK2 (8 patients) and DDX41 (7 patients). Pathogenic germline variants were also found in new candidate genes (DNAH5, DNAH9, DNMT3A, and SUZ12). No strong correlation was found between the germline mutational rate and age of AML onset. Among 49 patients who have a reported history of at least one family member affected with hematological malignancies, 6 patients harbored known P/LP germline variants and the remaining patients had at least one variant of uncertain significance, suggesting a need for further functional validation studies. Using CHEK2 as an example, we show that three-dimensional protein modeling can be one of the effective methodologies to prioritize variants of unknown significance for functional studies. Further, we evaluated an in silico approach that applies ACMG curation in an automated manner using the tool for assessment and (TAPES) prioritization in exome studies, which can minimize manual curation time for variants. Overall, our findings suggest a need to comprehensively understand the predisposition potential of many germline variants in order to enable closer monitoring for disease management and treatment interventions for affected patients and families.
Assuntos
Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Leucemia Mieloide Aguda/genética , Proteínas de Neoplasias/genética , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Encapsulating chondrocytes in synthetic and degradable hydrogels for cartilage tissue engineering enables tuning of scaffold degradation, but provides no biological cues. Culture medium that recapitulates the physiological osmolarity of the interstitial fluid in cartilage can enhance matrix synthesis in the short term, but long-term benefits remain to be determined. This study investigates the long-term effect of culture medium osmolarity on tissue synthesis using chondrocytes isolated from three skeletally mature bovine donors encapsulated in degradable poly(ethylene glycol) hydrogels. The cell-laden hydrogels were cultured up to 4 weeks in standard chondrocyte-specific medium (330 mOsm) or medium adjusted by sucrose or salts (NaCl and KCl) to reach a physiological osmolarity (400 mOsm). Neocartilaginous matrix synthesis and matrix catabolism were evaluated by quantitative and immunofluorescence methods. Hydrogel degradation kinetics of acellular constructs were not affected by medium osmolarity or osmolyte. Matrix composition was predominantly aggrecan and collagen type II for all conditions. One day after encapsulation, total collagen accumulated in the constructs was increased by 80-90% in 400 mOsm medium, regardless of osmolyte. However, this effect did not persist, and at 4 weeks, total collagen synthesized and released to the medium was more than three times higher in 330 mOsm medium. Medium osmolarity had minimal effects on sulfated glycosaminoglycan content and did not affect catabolic activity. These findings suggest that culture medium at physiological osmolarities may not be beneficial for long-term chondrocyte culture in degradable hydrogels, but that initially culturing chondrocytes at a higher osmolarity may enhance early tissue deposition.