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BACKGROUND: Establishing care preferences and selecting a prepared medical decision-maker (MDM) are basic components of advance care planning (ACP) and integral to treatment planning. Systematic ACP in the cancer setting is uncommon. We evaluated a systematic social work (SW)-driven process for patient selection of a prepared MDM. METHODS: We used a pre/post design, centered on SW counseling incorporated into standard-of-care practice. New patients with gynecologic malignancies were eligible if they had an available family caregiver or an established Medical Power of Attorney (MPOA). Questionnaires were completed at baseline and 3 months to ascertain MPOA document (MPOAD) completion status (primary objective) and evaluate factors associated with MPOAD completion (secondary objectives). RESULTS: Three hundred and sixty patient/caregiver dyads consented to participate. One hundred and sixteen (32%) had MPOADs at baseline. Twenty (8%) of the remaining 244 dyads completed MPOADs by 3 months. Two hundred and thirty-six patients completed the values and goals survey at both baseline and follow-up: at follow-up, care preferences were stable in 127 patients (54%), changed toward more aggressive care in 60 (25%), and toward the focus on the quality of life in 49 (21%). Correlation between the patient's values and goals and their caregiver's/MPOA's perception was very weak at baseline, improving to moderate at follow-up. Patients with MPOADs by study completion had statistically significant higher ACP Engagement scores than those without. CONCLUSION: A systematic SW-driven intervention did not engage new patients with gynecologic cancers to select and prepare MDMs. Change in care preferences was common, with caregivers' knowledge of patients' treatment preferences moderate at best.
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Planificación Anticipada de Atención , Neoplasias de los Genitales Femeninos , Humanos , Femenino , Participación del Paciente , Calidad de Vida , Directivas Anticipadas , Neoplasias de los Genitales Femeninos/terapiaRESUMEN
Enhanced osteoclast-mediated bone resorption and diminished formation may promote bone loss. Pleckstrin homology (PH) domain and leucine-rich repeat protein phosphatase 1 (Phlpp1) regulates protein kinase C (PKC) and other proteins in the control of bone mass. Germline Phlpp1 deficiency reduces bone volume, but the mechanisms remain unknown. Here, we found that conditional Phlpp1 deletion in murine osteoclasts increases their numbers, but also enhances bone mass. Despite elevating osteoclasts, Phlpp1 deficiency did not increase serum markers of bone resorption, but elevated serum markers of bone formation. These results suggest that Phlpp1 suppresses osteoclast formation and production of paracrine factors controlling osteoblast activity. Phlpp1 deficiency elevated osteoclast numbers and size in ex vivo osteoclastogenesis assays, accompanied by enhanced expression of proto-oncogene C-Fms (C-Fms) and hyper-responsiveness to macrophage colony-stimulating factor (M-CSF) in bone marrow macrophages. Although Phlpp1 deficiency increased TRAP+ cell numbers, it suppressed actin-ring formation and bone resorption in these assays. We observed that Phlpp1 deficiency increases activity of PKCζ, a PKC isoform controlling cell polarity, and that addition of a PKCζ pseudosubstrate restores osteoclastogenesis and bone resorption of Phlpp1-deficient osteoclasts. Moreover, Phlpp1 deficiency increased expression of the bone-coupling factor collagen triple helix repeat-containing 1 (Cthrc1). Conditioned growth medium derived from Phlpp1-deficient osteoclasts enhanced mineralization of ex vivo osteoblast cultures, an effect that was abrogated by Cthrc1 knockdown. In summary, Phlpp1 critically regulates osteoclast numbers, and Phlpp1 deficiency enhances bone mass despite higher osteoclast numbers because it apparently disrupts PKCζ activity, cell polarity, and bone resorption and increases secretion of bone-forming Cthrc1.
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Osteogénesis , Fosfoproteínas Fosfatasas/metabolismo , Animales , Densidad Ósea , Resorción Ósea/metabolismo , Resorción Ósea/patología , Huesos/diagnóstico por imagen , Huesos/fisiología , Diferenciación Celular/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Factor Estimulante de Colonias de Macrófagos/farmacología , Masculino , Ratones , Ratones Noqueados , Osteoclastos/citología , Osteoclastos/metabolismo , Osteogénesis/efectos de los fármacos , Fosfoproteínas Fosfatasas/antagonistas & inhibidores , Fosfoproteínas Fosfatasas/genética , Proteína Quinasa C/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismoRESUMEN
Importance: Increased cancer risk in first-degree relatives of probands with pancreatic ductal adenocarcinoma (PDAC probands) who carry pathogenic or likely pathogenic germline variants (PGVs) in cancer syndrome-associated genes encourages cascade genetic testing. To date, unbiased risk estimates for the development of cancers on a gene-specific basis have not been assessed. Objective: To quantify the risk of development of PDAC and extra-PDAC among first-degree relatives of PDAC probands who carry a PGV in 1 of 9 cancer syndrome-associated genes-ATM, BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6, PMS2, and CDKN2A. Design, Setting, and Participants: This case series focused on first-degree relatives of PDAC probands carrying PGVs in specific cancer syndrome-associated genes. The cohort comprised clinic-ascertained patients enrolled in the Mayo Clinic Biospecimen Resource for Pancreas Research registry with germline genetic testing. In total, 234 PDAC probands carrying PGVs were drawn from the prospective research registry of 4562 participants who had undergone genetic testing of cancer syndrome-associated genes. Demographic and cancer-related family histories were obtained by questionnaire. The data were collected from October 1, 2000, to December 31, 2021. Main Outcomes and Measures: For the PDAC probands, the genetic test results of the presence of PGVs in 9 cancer syndrome-associated genes were obtained by clinical testing. Cancers (ovary, breast, uterus or endometrial, colon, malignant melanoma, and pancreas) among first-degree relatives were reported by the probands. Standardized incidence ratios (SIRs) were used to estimate cancer risks among first-degree relatives of PDAC probands carrying a PGV. Results: In total, 1670 first-degree relatives (mean [SD] age, 58.1 [17.8] years; 853 male [51.1%]) of 234 PDAC probands (mean [SD] age, 62.5 [10.1] years; 124 male [53.0%]; 219 [94.4%] White; 225 [98.7%] non-Hispanic or non-Latino]) were included in the study. There was a significantly increased risk of ovarian cancer in female first-degree relatives of probands who had variants in BRCA1 (SIR, 9.49; 95% CI, 3.06-22.14) and BRCA2 (SIR, 3.72; 95% CI, 1.36-8.11). Breast cancer risks were higher with BRCA2 variants (SIR, 2.62; 95% CI, 1.89-3.54). The risks of uterine or endometrial cancer (SIR, 6.53; 95% CI, 2.81-12.86) and colon cancer (SIR, 5.83; 95% CI, 3.70-8.75) were increased in first-degree relatives of probands who carried Lynch syndrome mismatch repair variants. Risk of PDAC was also increased for variants in ATM (SIR, 4.53; 95% CI, 2.69-7.16), BRCA2 (SIR, 3.45; 95% CI, 1.72-6.17), CDKN2A (SIR, 7.38; 95% CI, 3.18-14.54), and PALB2 (SIR, 5.39; 95% CI, 1.45-13.79). Melanoma risk was elevated for first-degree relatives of probands with CDKN2A variants (SIR, 7.47; 95% CI, 3.97-12.77). Conclusions and Relevance: In this case series, the presence of PGVs in 9 cancer syndrome-associated genes in PDAC probands was found to be associated with increased risk of 6 types of cancers in first-degree relatives. These gene-specific PDAC and extra-PDAC cancer risks may provide justification for clinicians to counsel first-degree relatives about the relevance and importance of genetic cascade testing, with the goal of higher uptake of testing.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Predisposición Genética a la Enfermedad , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/genética , Mutación de Línea Germinal , Carcinoma Ductal Pancreático/epidemiología , Carcinoma Ductal Pancreático/genética , Células Germinativas , Neoplasias PancreáticasRESUMEN
Oral mucositis is a painful inflammatory response that can lead to infection, cachexia, and therapy termination. This immune-related adverse event (IRAE) has been well documented within the newly developing field of immunotherapy. This case series presents three patients, aged 73 to 81 years, who were undergoing treatment with programmed death-1 (PD-1) immunotherapy for cancer; each patient developed grade III mucositis, one after the fourth cycle and two after the seventh. All three patients had no prior history of oral pathology, yet each patient reported ulcerated and inflamed oral mucosa that was swollen and painful. These lesions involved various locations within the oral cavity and caused irritation to the point of dysphagia and odynophagia. Conservative treatments such as oral anesthetic and mouthwashes with antimicrobial properties had minimal effects. Each patient thereafter was started on systemic glucocorticoids in addition to the local treatments. The initiation of a systemic treatment resulted in a resolution of the oral lesions allowing each patient the option to return to their prior immunotherapy. Mucositis is uncommon and has no standardized treatment. This case series emphasizes the debilitative result of immunotherapy-induced mucositis and illustrates the need for systemic glucocorticoids. While conservative treatments such as oral mouthwashes can be effective in treating the symptoms of mucositis, the initiation of high-dose steroids with a prolonged taper has been shown to treat the condition at its source. Early recognition of mucositis with prompt initiation of steroids has proven to be the effective mainstay treatment to relieve mucositis while limiting pauses in cancer treatment.
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Complex regional pain syndrome (CRPS) is a debilitating disorder that causes significant pain and can decrease the quality of life of affected individuals. This is the first report of CRPS in an adolescent oncology patient, whose symptoms successfully resolved with 3 weeks of intensive, multimodal, and multidisciplinary therapies. She experienced a complete return to pre-CRPS functional status within 10 weeks. The successful outcome of this case highlights the importance of early recognition of CRPS in the adolescent population and the need for a multimodal intensive treatment regimen to prevent the development of chronic pain and loss of limb function.
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Síndromes de Dolor Regional Complejo , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Humanos , Calidad de Vida , Terapia Combinada , Síndromes de Dolor Regional Complejo/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMEN
BACKGROUND: ABO blood group is associated with pancreatic cancer risk. Whether ABO blood group alone or when combined with inherited mutation status of index pancreatic cancer cases (probands) can enhance pancreatic cancer risk estimation in first-degree relatives (FDR) is unclear. We examined FDRs' risk for pancreatic cancer based on probands' ABO blood group and probands' cancer susceptibility gene mutation status. METHODS: Data on 23,739 FDRs, identified through 3,268 pancreatic cancer probands, were analyzed. Probands' ABO blood groups were determined serologically or genetically, and 20 cancer susceptibility genes were used to classify probands as "mutation-positive" or "mutation-negative." SIRs and 95% confidence intervals (CI) were calculated, comparing observed pancreatic cancer cases in the FDRs with the number expected in SEER-21 (reference population). RESULTS: Overall, FDRs had 2-fold risk of pancreatic cancer (SIR = 2.00; 95% CI = 1.79-2.22). Pancreatic cancer risk was higher in FDRs of mutation-positive (SIR = 3.80; 95% CI = 2.81-5.02) than mutation-negative (SIR = 1.79; 95% CI = 1.57-2.04) probands (P < 0.001). The magnitude of risk did not differ by ABO blood group alone (SIRblood-group-O = 1.57; 95% CI = 1.20-2.03, SIRnon-O = 1.83; 95% CI = 1.53-2.17; P = 0.33). Among FDRs of probands with non-O blood group, pancreatic cancer risk was higher in FDRs of mutation-positive (SIR = 3.98; 95% CI = 2.62-5.80) than mutation-negative (SIR = 1.66; 95% CI = 1.35-2.03) probands (P < 0.001), but risk magnitudes were statistically similar when probands had blood group O (SIRmutation-positive = 2.65; 95% CI = 1.09-5.47, SIRmutation-negative = 1.48; 95% CI = 1.06-5.47; P = 0.16). CONCLUSIONS: There is a range of pancreatic cancer risk to FDRs according to probands' germline mutation status and ABO blood group, ranging from 1.48 for FDRs of probands with blood group O and mutation-negative to 3.98 for FDRs of probands with non-O blood group and mutation-positive. IMPACT: Combined ABO blood group and germline mutation status of probands can inform pancreatic cancer risk estimation in FDRs.
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Sistema del Grupo Sanguíneo ABO/sangre , Predisposición Genética a la Enfermedad , Neoplasias Pancreáticas/sangre , Anciano , Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/genética , Sistema de Registros , Factores de RiesgoRESUMEN
PURPOSE: With little to no infrastructure or standardized methodology in place to actively engage patients in advance care planning (ACP), The University of Texas MD Anderson Cancer Center set out to identify needed resources, develop an intervention to improve ACP, and evaluate the intervention's effects. METHODS: With the support of executive leadership, a multidisciplinary workgroup enlisted the support of ACP champions, performed a root-cause analysis, developed a detailed ACP process flow by provider role, developed patient and family education resources, and developed faculty and staff training materials. The workgroup also implemented two Plan-Do-Study-Act intervention cycles, which identified difficulty using the ACP note function in our electronic health record (EHR) as a barrier to ACP adoption. By educating patients, families, and providers and improving the EHR's functionality, the workgroup aimed to increase the percentage of ambulatory patients with a diagnosis of advanced or metastatic cancer who had a documented ACP conversation with a provider by their third office visit. Our goal was to improve this percentage from 20% at baseline to 50% after the intervention. Data were obtained from our institution's EHRs. RESULTS: The percentage of patients who had documented ACP conversations increased from 20% at baseline to 34% at the end of fiscal year 2017 and 54% at the end of fiscal year 2018. CONCLUSION: Owing to the dedicated efforts of many individuals across the institution, the postintervention goal was surpassed. Additional efforts to facilitate ACP conversations are ongoing.
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Planificación Anticipada de Atención , Registros Electrónicos de Salud , Neoplasias/epidemiología , Actitud del Personal de Salud , Comunicación , Femenino , Humanos , Masculino , Neoplasias/psicología , Neoplasias/terapia , Participación del Paciente/psicologíaRESUMEN
OBJECTIVES: We developed a conceptual model to define key concepts associated with patients' experiences with the signs, symptoms, and impacts of non-metastatic castration-resistant prostate cancer (M0-CRPC). METHODS: A targeted review of peer-reviewed literature, and other publicly available information, identified and categorized symptoms and impacts related to early-stage prostate cancer. Semi-structured interviews with five clinical experts helped determine the most relevant and important concepts for patients with M0-CRPC. Qualitative interviews with 17 patients with M0-CRPC identified the most frequently experienced symptoms and impacts, and their degree of interference with patients' lives. The findings from these three lines of evidence were summarized in a conceptual model. RESULTS: Literature searches identified mainly urinary, intestinal, and sexual symptoms. Experts noted the symptoms most frequently mentioned by patients include erectile dysfunction, loss of sexual desire or interest, incontinence/leaking, urgency, and hot flashes. Patient interviews confirmed the high frequency of erectile dysfunction, loss of libido, urinary urgency, and incontinence. The most frequently mentioned impacts expressed by patients were the need to monitor/plan for urinary frequency, interference with/restriction of daily activities, and frustration or anxiety over diagnosis, symptoms, or treatment. Symptoms and impacts most frequently experienced by patients were typically not those with the greatest effects on their lives; rather, those with the greatest consequences were related to treatment. CONCLUSIONS: The leading concerns associated with M0-CRPC were related to voiding and sexual dysfunction. The most relevant symptoms and impacts expressed by patients may be a consequence of therapy rather than of the disease.
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Libido , Neoplasias de la Próstata Resistentes a la Castración/psicología , Calidad de Vida/psicología , Disfunciones Sexuales Fisiológicas/psicología , Trastornos Urinarios/psicología , Antagonistas de Andrógenos/efectos adversos , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Medición de Resultados Informados por el Paciente , Neoplasias de la Próstata Resistentes a la Castración/complicaciones , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Investigación Cualitativa , Disfunciones Sexuales Fisiológicas/etiología , Trastornos Urinarios/etiologíaRESUMEN
PURPOSE: his study evaluated several factors that were thought to contribute to African American women's disproportionate incidence and sequelae of diabetes. METHODS: African American women (1055) living in San Diego County completed surveys about diabetes-related beliefs, screening behaviors, knowledge, and attitudes. Participants' ages ranged from 20 to 94 years, and 33.7% of the women reported completing college. RESULTS: Most of the women (59%) perceived diabetes to be a serious health threat to African American women. Thirty-two percent of the total sample and 37% of the high-risk group reported having been screened for diabetes within the past year. Nearly 37% reported never having been screened for diabetes, and 31% of those at above-average risk of developing diabetes could not recall ever having been screened. Women had a limited knowledge of the symptoms of diabetes, ways to decrease the risk factors and the sequelae of diabetes. Higher-risk women showed greater diabetes knowledge. CONCLUSIONS: Most participants reported that diabetes was a significant threat to their health but lacked sufficient knowledge to protect themselves from the disease. A focused, aggressive education campaign could yield better health outcomes.
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Población Negra , Cosméticos , Diabetes Mellitus/prevención & control , Diabetes Mellitus/psicología , Educación en Salud , Promoción de la Salud , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Factores de Riesgo , Estados UnidosRESUMEN
Comprehensive perioperative information technology (IT) systems can help health care organizations and their ORs reduce costs, increase revenues, improve processes, and enhance caregiver and patient satisfaction. This article examines what perioperative IT systems have done for two health care organizations and details implementation, the benefits these hospitals derived, next steps, and lessons learned.
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Sistemas de Información en Quirófanos , Quirófanos/organización & administración , Citas y Horarios , Humanos , Administración de Materiales de Hospital , New Jersey , Quirófanos/economía , Oregon , Estudios de Casos OrganizacionalesRESUMEN
The microcirculation of choroidal and ciliary body melanomas is remodeled into architecturally distinctive patterns. The presence of two histologic microvascular patterns, networks and parallel vessels with cross-linking, is strongly associated with metastasis. This study was designed to test the hypothesis that networks and parallel vessels with cross-linking patterns are not distributed evenly throughout the tumor. From a set of 234 eyes removed for ciliary body or choroidal melanoma, 152 tumors contained at least one focus of either vascular networks or parallel vessels with cross-linking. Histological cross-sections were digitized and foci of tumor containing these patterns were pseudocolorized so that their location within the periphery or central tumor zone could be mapped. Ciliary body and choroidal melanomas vary widely in size and shape and it is not appropriate to describe the periphery of a tumor as a fixed value because in a small tumor, the periphery thus defined would occupy a larger percent area than in a larger tumor. In this study, the peripheral and central zones of each tumor were described by a function that was constant from tumor to tumor, allowing the width of the peripheral and central zones to vary proportionally with tumor size. Observed counts of vascular patterns per zone were compared statistically with expected counts based upon the percent area occupied by the peripheral and central zones. Discrete foci of networks and parallel with cross-linking vessels are over-represented in the tumor periphery (p < 0.0001).