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INTRODUCTION: It is common for cancer patients to seek a second opinion for a variety of reasons. Understanding what drives patients to choose to receive treatment with their second opinion provider may uncover opportunities to improve the second opinion process. Therefore, we sought to identify the patient, disease, and treatment characteristics that were associated with second opinion retention rates in patients seeking a second surgical opinion for breast, colon, and pancreatic cancer. METHODS: We conducted a retrospective cohort study to evaluate patients who sought a second opinion within a large academic health-care system for breast, colon, and pancreatic cancer. Electronic medical records were reviewed for second opinions. Patient demographics and characteristics were collected and compared between the retained group and the nonretained groups. RESULTS: A total of 237 patients obtained second opinions for breast, colorectal, and pancreatic cancer. Patients that were offered a different treatment plan at their second opinion were more likely to be retained for systemic therapy (P = 0.009) for pancreatic cancer and any treatment for colon cancer (P = 0.003). Seeing a radiation oncologist (P = 0.007) or a plastic surgeon (P = 0.02) during the multidisciplinary consultation increased retention rates for breast cancer. CONCLUSIONS: Surgeons can better identify patients that are more likely to be retained after a second opinion by the individual patient characteristics and treatment factors. Understanding the factors that lead to retention for these three cancer types may help physicians provide the best possible resources for most patients presenting for second opinion evaluations.
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PURPOSE: In this study, we aimed to determine the incidence of receptor conversions after neoadjuvant chemotherapy (NAC) for breast cancer and assess the rate at which receptor conversion leads to changes in adjuvant therapy regimens. METHODS: We performed a retrospective review of female breast cancer patients treated with NAC at an academic breast center between January 2017 and October 2021. Patients with residual disease on surgical pathology and complete receptor status information for both pre-NAC and post-NAC specimens were included. Incidence of receptor conversions, defined as a change in at least one hormone receptor (HR) or HER2 status compared to preoperative specimens, was tabulated, and adjuvant therapy modalities were reviewed. Factors associated with receptor conversion were analyzed using chi-square tests and a binary logistic regression. RESULTS: Of the 240 patients with residual disease after NAC, 126 (52.5%) had receptor testing repeated. After NAC, 37 specimens (29%) had a receptor conversion. Receptor conversion resulted in the addition or removal of an adjuvant therapy in 8 patients (6%), indicating a number needed to screen of 16. Prior history of cancer, receipt of initial biopsy at an outside site, HR-positive tumors, and a pathologic stage of II or lower were factors associated with receptor conversions. CONCLUSION: HR and HER2 expression profiles frequently change after NAC and drive adjustments in adjuvant therapy regimens. Repeat testing of HR and HER2 expression should be considered in patients who receive NAC, especially in patients with early stage, HR-positive tumors whose initial biopsies were performed externally.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Pronóstico , Terapia Neoadyuvante/métodos , Receptor ErbB-2/metabolismo , Mama/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia AdyuvanteRESUMEN
BACKGROUND: Completion axillary lymph node dissection (cALND) was standard treatment for breast cancer with positive sentinel lymph nodes (SLNs) until 2011, when data from the Z11 and AMAROS trials challenged its survival benefit in early stage breast cancer. We assessed the contribution of patient, tumor, and facility factors on cALND use in patients undergoing mastectomy and SLN biopsy. PATIENTS AND METHODS: Using the National Cancer Database, patients diagnosed from 2012 to 2017 who underwent upfront mastectomy and SLN biopsy with at least one positive SLN were included. A multivariable mixed effects logistic regression model was used to determine the effect of patient, tumor, and facility variables on cALND use. Reference effect measures (REM) were used to compare the contribution of general contextual effects (GCE) to variation in cALND use. RESULTS: From 2012 to 2017, the overall use of cALND decreased from 81.3% to 68.0%. Overall, younger patients, larger tumors, higher grade tumors, and tumors with lymphovascular invasion were more likely to undergo cALND. Facility variables, including higher surgical volume and facility location in the Midwest, were associated with increased use of cALND. However, REM results showed that the contribution of GCE to the variation in cALND use exceeded that of the measured patient, tumor, facility, and time variables. CONCLUSIONS: There was a decrease in cALND use during the study period. However, cALND was frequently performed in women after mastectomy found to have a positive SLN. There is high variability in cALND use, mainly driven by interfacility practice variation rather than specific high-risk patient and/or tumor characteristics.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/patología , Mastectomía , Biopsia del Ganglio Linfático Centinela , Metástasis Linfática/patología , Escisión del Ganglio Linfático/métodos , Axila/patología , Ganglios Linfáticos/patologíaRESUMEN
INTRODUCTION: In this embedded substudy of a longitudinal, randomized controlled trial, we sought to evaluate the effects of patient engagement and results feedback on longitudinal patient-reported outcome (PRO) survey completion rates. METHODS: Newly diagnosed stage 0-III breast cancer patients seen at an academic breast center between June 2019 and December 2021 were invited to participate in a longitudinal PRO study. Participants were emailed the BREAST-Q survey, a validated PRO scale, preoperatively and at regular intervals during their postoperative course. Patients were randomized into the intervention group, who received survey results upon completion, or the control group, who received no feedback. The primary endpoint was postoperative survey completion rate. An intention to treat analysis was performed and a quasi-Poisson regression was used to compare rates of longitudinal survey completion between the two groups. RESULTS: Of the 253 patients offered the preoperative survey, 115 were in the intervention group and 138 were in the control group. Postoperative survey completion rate was 54% for the intervention group and 47% for the control group. There was no significant difference in longitudinal postoperative survey completion rate between the two groups (rate ratio 1.10; 95% confidence interval [CI] 0.93-1.31). CONCLUSIONS: In this prospective randomized controlled study, patients did not complete surveys at a higher rate when their survey results were shared with them, suggesting that viewing these results without appropriate clinical context does not generate significant enhancement in patient engagement. Effective interventions to improve survey response rate must be identified to better evaluate PROs.
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Medición de Resultados Informados por el Paciente , Proyectos de Investigación , Humanos , Estudios ProspectivosRESUMEN
BACKGROUND: Completion lymph node dissection (CLND) was the standard treatment for patients with melanoma with positive sentinel lymph nodes (SLN) until 2017 when data from the DeCOG-SLT and MLST-2 randomized trials challenged the survival benefit of this procedure. We assessed the contribution of patient, tumor and facility factors on the use of CLND in patients with surgically resected Stage III melanoma. METHODS: Using the National Cancer Database, patients who underwent surgical excision and were found to have a positive SLN from 2012 to 2017 were included. A multivariable mixed-effects logistic regression model with a random intercept for the facility was used to determine the effect of patient, tumor, and facility variables on the risk of CLND. Reference effect measures (REMs) were used to compare the contribution of contextual effects (unknown facility variables) versus measured variables on the variation in CLND use. RESULTS: From 2012 to 2017, the overall use of CLND decreased from 59.9% to 26.5% (p < 0.0001). Overall, older patients and patients with government-based insurance were less likely to undergo CLND. Tumor factors associated with a decreased rate of CLND included primary tumor location on the lower limb, decreasing depth, and mitotic rate <1. However, the contribution of contextual effects to the variation in CLND use exceeded that of the measured facility, tumor, time, and patient variables. CONCLUSIONS: There was a decrease in CLND use during the study period. However, there is still high variability in CLND use, mainly driven by unmeasured contextual effects.
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Melanoma , Ganglio Linfático Centinela , Neoplasias Cutáneas , Humanos , Biopsia del Ganglio Linfático Centinela/métodos , Tipificación de Secuencias Multilocus , Melanoma/patología , Neoplasias Cutáneas/patología , Escisión del Ganglio Linfático/métodos , Ganglio Linfático Centinela/cirugía , Ganglio Linfático Centinela/patologíaRESUMEN
BACKGROUND: The main objective of this research was to analyze the characteristics of electrical activity in the brain during REM (Rapid Eye Movements) sleep, by using an experimental model a pathology that affects the frontal lobes, such as brain tumors. In addition to determining the impact of variables such as the frontal area (dorsolateral, medial and orbital), laterality and size of the lesion; as well as the demographic and clinical characteristics of the patients evaluated. METHODS: By using polysomnographic recordings, 10 patients were evaluated. We obtained power spectra through a homemade program. For quantitative EEG (Electroencephalogram) (qEEG) analysis, the Fast Fourier Transform (FFT) algorithm was used to obtain the spectral power of each participant, channel, and frequency band. RESULTS: Sleep architecture and spectral power was found to be modified in patients compared to normative values. Other sociodemographic and clinical characteristics of the patients were also influenced, such as age range and antiepileptic drugs. CONCLUSIONS: Brain tumors in the frontal lobe can modify the rhythmogenesis of REM sleep, possibly due to changes of brain plasticity as an effect of the pathology. In addition to this, through this study we were able to show the association between neuroanatomical and functional changes, on the characteristics of brain electrical activity in patients with frontal brain tumor. Finally, this qEEG analysis technique allows, on the one hand, to deepen the knowledge and relationship between psychophysiological processes and, on the other hand, to be able to guide therapeutic decisions.
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Neoplasias Encefálicas , Sueño REM , Humanos , Sueño REM/fisiología , Electroencefalografía/métodos , Sueño/fisiología , EncéfaloRESUMEN
OBJECTIVE: To assess the contribution of unknown institutional factors (contextual effects) in the de-implementation of cALND in women with breast cancer. SUMMARY OF BACKGROUND DATA: Women included in the National Cancer Database with invasive breast carcinoma from 2012 to 2016 that underwent upfront lumpectomy and were found to have a positive sentinel node. METHODS: A multivariable mixed effects logistic regression model with a random intercept for site was used to determine the effect of patient, tumor, and institutional variables on the risk of cALND. Reference effect measureswere used to describe and compare the contribution of contextual effects to the variation in cALND use to that of measured variables. RESULTS: By 2016, cALND was still performed in at least 50% of the patients in a quarter of the institutions. Black race, younger women and those with larger or hormone negative tumors were more likely to undergo cALND. However, the width of the 90% reference effect measures range for the contextual effects exceeded that of the measured site, tumor, time, and patient demographics, suggesting institutional contextual effects were the major drivers of cALND de-implementation. For instance, a woman at an institution with low-risk of performing cALND would have 74% reduced odds of havinga cALND than if she was treated at a median-risk institution, while a patient at a high-risk institution had 3.91 times the odds. CONCLUSION: Compared to known patient, tumor, and institutional factors, contextual effects had a higher contribution to the variation in cALND use.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Biopsia del Ganglio Linfático Centinela , Axila , Metástasis Linfática/patología , Escisión del Ganglio Linfático , Ganglios Linfáticos/patologíaRESUMEN
INTRODUCTION: For patients with stage III melanoma with occult lymph node metastasis, the use of adjuvant therapy is increasing, and completion lymph node dissection (CLND) is decreasing. We sought to evaluate the use of modern adjuvant therapy and outcomes for patients with stage III melanoma who did not undergo CLND. METHODS: Patients with a positive SLNB from 2015 to 2020 who did not undergo CLND were evaluated retrospectively. Nodal recurrence, recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and melanoma-specific survival were evaluated. RESULTS: Among 90 patients, 56 (62%) received adjuvant therapy and 34 (38%) underwent observation alone. Patients who received adjuvant therapy were younger (mean age: 53 vs. 65, p < 0.001) and had higher overall stage (Stage IIIb/c 75% vs. 54%, p = 0.041). Disease recurred in 12 of 34 patients (35%) in the observation group and 11 of 56 patients (20%) in the adjuvant therapy group. The most common first site of recurrence was distant recurrence alone (5/34 patients) in the observation group and nodal recurrence alone (8/90 patients) in the adjuvant therapy group. Despite more adverse nodal features in the adjuvant therapy group, 24-month nodal recurrence rate and RFS were not significantly different between the adjuvant and observation cohorts (nodal recurrence rate: 26% vs. 20%, p = 0.68; RFS: 75% vs. 61%, p = 0.39). Among patients with stage IIIb/c disease, adjuvant therapy was associated with a significantly improved 24-month DMFS (86% vs. 59%, p = 0.04). CONCLUSIONS: In this early report, modern adjuvant therapy in patients who forego CLND is associated with longer DMFS among patients with stage IIIb/c disease.
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Melanoma , Ganglio Linfático Centinela , Neoplasias Cutáneas , Humanos , Escisión del Ganglio Linfático , Melanoma/cirugía , Persona de Mediana Edad , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/cirugíaRESUMEN
INTRODUCTION: Patient-reported outcome measures (PROMs/PROM) are standardized, validated instruments used to measure the patient's perception of their own health status including their symptoms, functional wellbeing, and mental health. Although PROMs were initially developed as research tools, their use in clinical practice for shared decision-making and to assess the impact of disease and treatment on quality of life of individual patients has been increasing. There is a paucity of research exploring providers' perspectives on the clinical integration of PROMs. We sought to use a qualitative methodology to understand surgeons' perceptions of integrating PROMs into their clinical practices. METHODS: Semistructured interviews were performed from November 2019 until August 2020. All interviews were recorded and transcribed verbatim. Thematic saturation was achieved after interviewing nine surgeons representing eight surgical specialties. Qualitative interview data were thematically analyzed using an inductive approach facilitated by Atlas.ti qualitative software. RESULTS: Forty seven unique codes were identified that fit into 21 themes that revealed five novel insights. Key insights included: (1) PROM data can modify surgical practice on an individual and institutional level, (2) Surgeon's view PROM clinical integration as a potential method of advancing patient-centered care, (3) There are various institutional processes that must be in place, including strong leadership and an integrative platform, to enable successful clinical PROM integration, (4) Surgeons appreciate challenges of integrating PROMs into surgical practice including risks of incorrect use or interpretation, and (5) A PROM platform must be adaptable to the diversity within surgery and to unique physician workflows. CONCLUSIONS: Surgeons perceived value from integrating PROMs into routine care to better inform patients during preoperative discussions and to help identify at-risk patients in the postoperative period. However, they also identified numerous barriers to the implementation of an integrated system for the routine use of PROMs in clinical practice and expressed concern about using PROMs to compare operative outcomes between surgeons. Based on this work, institutions that want to incorporate PROMs into surgical practice need a leadership team capable of supporting the change management necessary for effective integration and use a PROM platform that gives individual surgeons and surgical teams the ability to customize platforms for their unique practices.
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Calidad de Vida , Cirujanos , Humanos , Medición de Resultados Informados por el Paciente , Atención Dirigida al Paciente , Toma de Decisiones ConjuntaRESUMEN
With ongoing global change, shifts in the ranges of non-native species and resulting novel communities can modify biotic interactions and ecosystem processes. We hypothesized that traits and not biogeographic origin of novel plant communities will determine community structure of organisms that depend on plants for habitat or as a food resource. We tested the functional redundancy of novel tree communities by verifying if six pairs of congeneric European and North American tree species bearing similar leaf litter traits resulted in similar ecological filters influencing the assembly of springtail (Collembola) communities at two sites. Litter biogeographic origin (native versus non-native) did not influence springtail community structure, but litter genus, which generally reflected trait differences, did. Our empirical evidence suggests that a functional trait approach may be indeed as relevant as, and complementary to, studying biogeographic origin to understand the ecological consequences of non-native tree species in soils of novel forest ecosystems.
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Artrópodos/fisiología , Biodiversidad , Rasgos de la Historia de Vida , Hojas de la Planta/química , Animales , Bosques , Minnesota , Quebec , Árboles/químicaRESUMEN
BACKGROUND AND PURPOSE: There are few effective therapies to achieve functional recovery from motor-related disabilities affecting the upper limb after stroke. This feasibility study tested whether a powered exoskeleton driven by a brain-computer interface (BCI), using neural activity from the unaffected cortical hemisphere, could affect motor recovery in chronic hemiparetic stroke survivors. This novel system was designed and configured for a home-based setting to test the feasibility of BCI-driven neurorehabilitation in outpatient environments. METHODS: Ten chronic hemiparetic stroke survivors with moderate-to-severe upper-limb motor impairment (mean Action Research Arm Test=13.4) used a powered exoskeleton that opened and closed the affected hand using spectral power from electroencephalographic signals from the unaffected hemisphere associated with imagined hand movements of the paretic limb. Patients used the system at home for 12 weeks. Motor function was evaluated before, during, and after the treatment. RESULTS: Across patients, our BCI-driven approach resulted in a statistically significant average increase of 6.2 points in the Action Research Arm Test. This behavioral improvement significantly correlated with improvements in BCI control. Secondary outcomes of grasp strength, Motricity Index, and the Canadian Occupational Performance Measure also significantly improved. CONCLUSIONS: The findings demonstrate the therapeutic potential of a BCI-driven neurorehabilitation approach using the unaffected hemisphere in this uncontrolled sample of chronic stroke survivors. They also demonstrate that BCI-driven neurorehabilitation can be effectively delivered in the home environment, thus increasing the probability of future clinical translation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02552368.
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Brazo/fisiopatología , Interfaces Cerebro-Computador , Evaluación de Resultado en la Atención de Salud , Prótesis e Implantes , Recuperación de la Función/fisiología , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/terapia , Adulto , Anciano , Enfermedad Crónica , Electroencefalografía , Estudios de Factibilidad , Humanos , Masculino , Persona de Mediana Edad , Rehabilitación de Accidente Cerebrovascular/instrumentación , SobrevivientesRESUMEN
Mutations in Notch signaling pathway members cause developmental phenotypes that affect the liver, skeleton, heart, eye, face, kidney, and vasculature. Notch associated disorders include the autosomal dominant, multi-system, Alagille syndrome caused by mutations in both a ligand (Jagged1 (JAG1)) and receptor (NOTCH2) and autosomal recessive spondylocostal dysostosis, caused by mutations in a ligand (Delta-like-3 (DLL3)), as well as several other members of the Notch signaling pathway. Mutations in NOTCH2 have also recently been connected to Hajdu-Cheney syndrome, a dominant disorder causing focal bone destruction, osteoporosis, craniofacial morphology and renal cysts. Mutations in the NOTCH1 receptor are associated with several types of cardiac disease and mutations in NOTCH3 cause the dominant adult onset disorder CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a vascular disorder with onset in the 4th or 5th decades. Studies of these human disorders and their inheritance patterns and types of mutations reveal insights into the mechanisms of Notch signaling.
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Receptores Notch/fisiología , Transducción de Señal , Anomalías Múltiples/genética , Anomalías Múltiples/metabolismo , Síndrome de Alagille/genética , Síndrome de Alagille/metabolismo , Animales , Proteínas de Unión al Calcio/genética , Síndrome de Hajdu-Cheney/genética , Síndrome de Hajdu-Cheney/metabolismo , Cardiopatías Congénitas/genética , Cardiopatías Congénitas/metabolismo , Cardiopatías/genética , Cardiopatías/metabolismo , Hernia Diafragmática/genética , Hernia Diafragmática/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Proteína Jagged-1 , Proteínas de la Membrana/genética , Mutación , Receptores Notch/genética , Receptores Notch/metabolismo , Proteínas Serrate-JaggedRESUMEN
We present the literature review of ring chromosome 7 and clinical, cytogenetic and fine molecular mapping of the first postnatal report of a male child with a non-supernumerary ring chromosome 7, r(7). The patient had dysmorphic features, developmental delay, dermatologic lesions with variable pigmentation, hypogenitalism, lumbar dextroscoliosis, cerebellar and ophthalmological abnormalities, and melanocytic congenital nevi. Cytogenetic analysis of peripheral blood and the nevus sample showed the presence of three different cell lines r(7), monosomy 7, and duplicated r(7) (idic r(7)), while findings on fibroblasts from both light and dark skin showed only mosaicism with r(7) and monosomy 7 cell lines in various proportions. FISH assay of the ring chromosome showed subtelomeric loss in both chromosome arms in all tissues studied. Analysis by genome-wide single-nucleotide polymorphism array showed a 0.8 Mb deletion in 7p22.3 (involving eight genes) and a 7.5 Mb deletion in 7q36 (involving 29 genes including some involved in genital and central nervous system development). The combination of results from our karyotypic and array analyses enabled us to establish an accurate genotype-phenotype relationship.
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Trastornos de los Cromosomas/diagnóstico , Trastornos de los Cromosomas/genética , Análisis Citogenético , Mosaicismo , Fenotipo , Bandeo Cromosómico , Cromosomas Humanos Par 7/genética , Hibridación Genómica Comparativa , Estudios de Asociación Genética , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , Cromosomas en AnilloRESUMEN
BACKGROUND: Axillary management for node-positive breast cancer continues to evolve. Data further supporting targeted axillary dissection after neoadjuvant chemotherapy was published in 2016 and may have induced changes in practice. METHODS: Patients included in the National Cancer Database from 2014 to 2017 with clinical T1 to T4 and node-positive disease who underwent neoadjuvant chemotherapy before surgical axillary management were evaluated. Patients were divided into the following 3 groups: selective axillary dissection, minimal axillary dissection, and maximal axillary dissection, according to surgical axillary management and pathological node status. RESULTS: Patients who underwent selective axillary dissection were younger (52.4 years ± 12.4, P < .0001) compared to maximal axillary dissection (55.1 ± 12.7) and minimal axillary dissection (54.6 ± 12.7). Patients with higher clinical stage more frequently underwent maximal axillary dissection, and those with lower tumor grade more frequently underwent minimal axillary dissection (P < .0001). Community cancer programs were more likely to perform maximal axillary dissection compared to all other types of programs and had the slowest rate of adoption of selective axillary dissection. Integrated Network Cancer Programs had the lowest proportion of maximal axillary dissection performed and the highest proportion of selective axillary dissection. Uninsured patients were more likely to receive maximal axillary dissection, and those with private insurance were more likely to undergo selective axillary dissection (P < .0001). Selective axillary dissection rates increased from 29.8% of procedures in 2016 to 41.5% in 2017, and MaxAD rates decreased from 62.4% in 2016 to 47.9% in 2017. CONCLUSION: Utilization of selective axillary dissection has increased since 2016; however, discrepancies in surgical axillary management after neoadjuvant chemotherapy still exist.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Terapia Neoadyuvante , Escisión del Ganglio Linfático/métodos , Axila/patología , Bases de Datos Factuales , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela , Estadificación de NeoplasiasRESUMEN
INTRODUCTION: As part of the 21st Century Cures Act (April 2021), electronic health information (EHI) must be immediately released to patients. In this study, we sought to evaluate clinician and patient perceptions regarding this immediate release. METHODS: After surveying 33 clinicians and 30 patients, semi-structured interviews were conducted with a subset of the initial sample, comprising 8 clinicians and 12 patients. Open-ended questions explored clinicians' and patients' perceptions of immediate release of EHI and how they adjusted to this change. RESULTS: Ten themes were identified: Interpreting Results, Strategies for Patient Interaction, Patient Experiences, Communication Strategies, Provider Limitations, Provider Experiences, Health Information Interfaces, Barriers to Patient Understanding, Types of Results, and Changes due to Immediate Release. Interviews demonstrated differences in perceived patient distress and comprehension, emphasizing the impersonal nature of electronic release and necessity for therapeutic clinician-patient communication. CONCLUSIONS: Clinicians and patients have unique insights on the role of immediate release. Understanding these perspectives will help improve communication and develop patient-centered tools (glossaries, summary pages, additional resources) to aid patient understanding of complex medical information.
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Comunicación , Pacientes , Humanos , Investigación CualitativaRESUMEN
BACKGROUND: Alagille syndrome (ALGS) is a dominant, multisystem disorder caused by mutations in the Jagged1 (JAG1) ligand in 94% of patients, and in the NOTCH2 receptor in <1%. There are only two NOTCH2 families reported to date. This study hypothesised that additional NOTCH2 mutations would be present in patients with clinical features of ALGS without a JAG1 mutation. METHODS: The study screened a cohort of JAG1-negative individuals with clinical features suggestive or diagnostic of ALGS for NOTCH2 mutations. RESULTS: Eight individuals with novel NOTCH2 mutations (six missense, one splicing, and one non-sense mutation) were identified. Three of these patients met classic criteria for ALGS and five patients only had a subset of features. The mutations were distributed across the extracellular (N=5) and intracellular domains (N=3) of the protein. Functional analysis of four missense, one nonsense, and one splicing mutation demonstrated decreased Notch signalling of these proteins. Subjects with NOTCH2 mutations demonstrated highly variable expressivity of the affected systems, as with JAG1 individuals. Liver involvement was universal in NOTCH2 probands and they had a similar prevalence of ophthalmologic and renal anomalies to JAG1 patients. There was a trend towards less cardiac involvement in the NOTCH2 group (60% vs 100% in JAG1). NOTCH2 (+) probands exhibited a significantly decreased penetrance of vertebral abnormalities (10%) and facial features (20%) when compared to the JAG1 (+) cohort. CONCLUSIONS: This work confirms the importance of NOTCH2 as a second disease gene in ALGS and expands the repertoire of the NOTCH2 related disease phenotype.
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Síndrome de Alagille/genética , Mutación , Receptor Notch2/genética , Animales , Línea Celular , Análisis Mutacional de ADN , Facies , Expresión Génica , Estudios de Asociación Genética , Células HEK293 , Humanos , Ratones , Fenotipo , Receptor Notch2/metabolismo , Transducción de SeñalRESUMEN
INTRODUCTION: Resident physicians are uniquely at high financial risk given their long training programs, lack of financial education, and documented poor financial literacy. Budgeting for retirement savings is an important metric for financial literacy. METHODS: Semi-structured interviews were conducted with residents from two distinct surgery programs to assess their current financial status and their knowledge of and attitudes toward retirement savings strategies. Qualitative analysis was performed and the themes identified were examined in the context of previously reported quantitative survey data. RESULTS: As previously reported, 105 residents at Site 1 completed a comprehensive financial survey 56% of respondents reported having no retirement savings. On additional analysis, only 26% residents surveyed reported optimal savings habits defined as contributing $5000/year to a retirement account starting their first year of training. 23 residents from both sites and representing all post-graduate-year (PGY) levels then participated in the focused, semi-structured interviews. Site 2 residents were less likely to be female (P = .02) and carried a significantly larger debt burden (p < .01) but were otherwise comparable to residents from Site 1. On qualitative analysis three consistent themes emerged: (1) Resident understanding of strategies for retirement savings is poor; (2) Lack of knowledge is the primary barrier; (3) Surgical residents desire financial education. CONCLUSIONS: Surgery residents have a large debt burden, minimal retirement savings and an overall lack of understanding of savings strategies. Well-designed, early, and accessible educational interventions may improve the "financial vital signs" of surgical trainees and establish habits for long-term financial success.
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Internado y Residencia , Alfabetización , Humanos , Femenino , Masculino , Renta , Escolaridad , Encuestas y CuestionariosRESUMEN
Introduction: Receiving a new breast cancer diagnosis can cause anxiety and distress, which can lead to psychologic morbidity, decreased treatment adherence, and worse clinical outcomes. Understanding sources of distress is crucial in providing comprehensive care. This study aims to evaluate the relationship between delays in breast cancer diagnosis and patient-reported distress. Secondary outcomes include assessing patient characteristics associated with delay. Methods: Newly diagnosed breast cancer patients who completed a distress screening tool at their initial evaluation at an academic institution between 2014 and 2019 were retrospectively evaluated. The tool captured distress levels in the emotional, social, health, and practical domains with scores of "high distress" defined by current clinical practice guidelines. Delay from mammogram to biopsy, whether diagnostic or screening mammogram, was defined as >30 days. Result: 745 newly diagnosed breast cancer patients met inclusion criteria. Median time from abnormal mammogram to core biopsy was 12 days, and 11% of patients experienced a delay in diagnosis. The non-delayed group had higher emotional (p = 0.04) and health (p = 0.03) distress than the delayed group. No statistically significant differences in social distress were found between groups. Additionally, patients with higher practical distress had longer time interval between mammogram and surgical intervention compared to those with lower practical distress. Older age, diagnoses of invasive lobular carcinoma or ductal carcinoma in situ, and clinical anatomic stages 0-I were associated with diagnostic delay. Conclusion: Patients with higher emotional or health-related distress were more likely to have timely diagnoses of breast cancer, suggesting that patients with higher distress may seek healthcare interventions more promptly. Improved understanding of sources of distress will permit early intervention regarding the devastating impact of breast cancer diagnosis.
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Alagille syndrome (ALGS) is an autosomal dominant condition, primarily caused by mutations in JAGGED1. ALGS is defined by cholestatic liver disease, cardiac disease and involvement of the face, skeleton, and eyes with variable expression of these features. Renal involvement has been reported though not formally described. The objective of this study was to systematically characterize the renal involvement in ALGS. We performed a retrospective review of 466 JAGGED1 mutation-positive ALGS patients. Charts were reviewed for serum biochemistries, renal ultrasounds or other imaging, urinalysis, and clinical reports from pediatric nephrologists. The clinical data were reviewed by two pediatric hepatologists and a pediatric nephrologist. Of 466 charts reviewed we found 187 yielded evaluable renal information. Of these, 73/187 were shown to have renal involvement, representing 39% of the study cohort. Renal dysplasia was the most common anomaly seen. Genotype analysis of the JAGGED1 mutations in the patients with and without renal involvement did not reveal an association with mutation type. From the study we concluded that renal involvement has a prevalence of 39% in ALGS in our evaluable patients. Renal dysplasia is the most common renal anomaly. This finding correlates with the known role of the Notch pathway in glomerular development. Since renal disease of the type seen in ALGS can impair growth and impact liver transplantation, there is a clear need for a prospective study of renal involvement in ALGS and the development of guidelines for evaluation and management. These data also suggest that renal involvement be considered the sixth defining criterion for ALGS.