RESUMEN
Unstable gamma globin variants can cause transient neonatal hemolytic anemia. We have identified a novel variant in a newborn who presented with jaundice and anemia requiring phototherapy and red blood cell transfusion. The patient was found to be heterozygous for the mutation HGB2:c.290T>C, p.Leu97Pro, which we have termed hemoglobin (Hb) Wareham. This substitution is expected to generate an unstable hemoglobin with increased oxygen affinity based on the homologous mutation previously described in the beta globin gene, which is termed as Hb Debrousse. The patient fully recovered by 9 months of age as expected with the transition from fetal to adult hemoglobin.
Asunto(s)
Anemia Hemolítica , Hemoglobinas Anormales , gamma-Globinas , Humanos , Recién Nacido , Anemia Hemolítica/genética , Globinas beta/genética , gamma-Globinas/genética , Hemoglobinas Anormales/genética , Heterocigoto , Mutación , LactanteRESUMEN
BACKGROUND: Holistic approaches are sought to improve lifestyle behaviors and health of cancer survivors long term. OBJECTIVE: Our aim was to explore whether a home-based vegetable gardening intervention is feasible and whether it improves diet and other health-related outcomes among older cancer survivors. DESIGN: We conducted a feasibility trial in which cancer survivors were randomized to receive a year-long gardening intervention immediately or to a wait-list control arm. Home visits at baseline and 1 year assessed physical performance, anthropometric indices, behavioral and psychosocial outcomes, and biomarkers. PARTICIPANTS/SETTING: Participants included 46 older (aged 60+ years) survivors of locoregionally staged cancers across Alabama from 2014 to 2016. Forty-two completed 1-year follow-up. INTERVENTION: Cooperative extension master gardeners delivered guidance to establish three seasonal vegetable gardens at survivors' homes. Plants, seeds, and gardening supplies were provided. OUTCOMES: Primary outcomes were feasibility targets of 80% accrual and retention, and an absence of serious adverse events; other outcomes were secondary and explored potential benefits. STATISTICAL ANALYSES: Baseline to follow-up changes were assessed within and between arms using paired t, McNemar's, and χ2 tests. RESULTS: This trial proved to be safe and demonstrated 91.3% retention; 70% of intervention participants rated their experience as "excellent," and 85% would "do it again." Data suggest significantly increased reassurance of worth (+0.49 vs -0.45) and attenuated increases in waist circumference (+2.30 cm vs +7.96 cm) in the gardening vs control arms (P=0.02). Vegetable and fruit consumption increased by approximately 1 serving/day within the gardening arm from baseline to follow-up (mean [standard error]=1.34 [1.2] to 2.25 [1.9] servings/day; P=0.02)] compared to controls (1.22 [1.1] to 1.12 [0.7]; P=0.77; between-arm P=0.06). CONCLUSIONS: The home vegetable gardening intervention among older cancer survivors was feasible and suggested improvements in vegetable and fruit consumption and reassurance of worth; data also suggest attenuated increases in waist circumference. Continued study of vegetable gardening interventions is warranted to improve health, health behaviors, and well-being of older cancer survivors.
Asunto(s)
Supervivientes de Cáncer/psicología , Dieta/métodos , Frutas , Jardinería/métodos , Verduras , Adiposidad , Alabama , Dieta/psicología , Ingestión de Alimentos/fisiología , Ingestión de Alimentos/psicología , Estudios de Factibilidad , Femenino , Conductas Relacionadas con la Salud , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Satisfacción del Paciente , Proyectos Piloto , Calidad de Vida , Deseabilidad Social , Circunferencia de la CinturaRESUMEN
BACKGROUND: Neoadjuvant chemotherapy (NCT) downstages advanced primary tumors, with magnetic resonance imaging (MRI) being the most sensitive imaging predictor of response. However, the impact of MRI evaluation on surgical treatment decisions in the neoadjuvant setting has not been well described. We report surgical patterns of care across 8 National Cancer Institute comprehensive cancer centers in women receiving both NCT and MRI to evaluate the impact of MRI findings on surgical planning. METHODS: Seven hundred seventy women from 8 institutions received NCT with MRI obtained both before and after systemic treatment. Univariate and multivariate analyses of imaging, patient-, and tumor-related covariates associated with choice of breast surgery were conducted. RESULTS: MRI and surgical data were available on 759 of 770 patients. A total of 345 of 759 (45 %) patients received breast-conserving surgery and 414 of 759 (55 %) received mastectomy. Mastectomy occurred more commonly in patients with incomplete MRI response versus complete (58 vs. 43 %) (p = 0.0003). On multivariate analysis, positive estrogen receptor status (p = 0.02), incomplete MRI response (p = 0.0003), higher baseline T classification (p < 0.0001), younger age (p < 0.0006), and institution (p = 0.003) were independent predictors of mastectomy. A statistically significant trend toward increasing use of mastectomy with increasing T stage at presentation (p < 0.0001) was observed in patients with incomplete response by MRI only. Among women with complete response on MRI, 43 % underwent mastectomy. CONCLUSIONS: Within a multi-institutional cohort of women undergoing neoadjuvant treatment for breast cancer, MRI findings were not clearly associated with extent of surgery. This study shows that receptor status, T stage at diagnosis, young age, and treating institution are more significant determinants of surgical treatment choice than MRI response data.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Imagen por Resonancia Magnética , Mastectomía , Terapia Neoadyuvante , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/patología , Carcinoma Lobular/cirugía , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: We related changes in American Urological Association symptom index scores with bother measures and global ratings of change in men with lower urinary tract symptoms who were enrolled in a saw palmetto trial. MATERIALS AND METHODS: To be eligible for study men were 45 years old or older, and had a peak uroflow of 4 ml per second or greater and an American Urological Association symptom index score of 8 to 24. Participants self-administered the American Urological Association symptom index, International Prostate Symptom Score quality of life item, Benign Prostatic Hyperplasia Impact Index and 2 global change questions at baseline, and at 24, 48 and 72 weeks. RESULTS: In 357 participants global ratings of a little better were associated with a mean decrease in American Urological Association symptom index scores from 2.8 to 4.1 points across 3 time points. The analogous range for mean decreases in Benign Prostatic Hyperplasia Impact Index scores was 1.0 to 1.7 points and for the International Prostate Symptom Score quality of life item it was 0.5 to 0.8 points. At 72 weeks for the first global change question each change measure discriminated between participants who rated themselves at least a little better vs unchanged or worse 70% to 72% of the time. A multivariate model increased discrimination to 77%. For the second global change question each change measure correctly discriminated ratings of at least a little better vs unchanged or worse 69% to 74% of the time and a multivariate model increased discrimination to 79%. CONCLUSIONS: Changes in American Urological Association symptom index scores could discriminate between participants rating themselves at least a little better vs unchanged or worse. Our findings support the practice of powering studies to detect group mean differences in American Urological Association symptom index scores of at least 3 points.
Asunto(s)
Síntomas del Sistema Urinario Inferior/diagnóstico , Fitoterapia/métodos , Preparaciones de Plantas/uso terapéutico , Hiperplasia Prostática/diagnóstico , Micción/fisiología , Humanos , Síntomas del Sistema Urinario Inferior/etiología , Masculino , Persona de Mediana Edad , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Resultado del Tratamiento , Micción/efectos de los fármacosRESUMEN
PURPOSE: Saw palmetto extracts are used to treat lower urinary tract symptoms in men despite level I evidence that saw palmetto is ineffective in reducing these lower urinary tract symptoms. We determined whether higher doses of saw palmetto as studied in the CAMUS (Complementary and Alternative Medicine for Urologic Symptoms) trial affect serum prostate specific antigen levels. MATERIALS AND METHODS: The CAMUS trial was a randomized, placebo controlled, double-blind, multicenter, North American trial conducted between June 5, 2008 and October 10, 2012, in which 369 men older than 45 years with an AUA symptom score of 8 to 24 were randomly assigned to placebo or dose escalation of saw palmetto, which consisted of 320 mg for the first 24 weeks, 640 mg for the next 24 weeks and 960 mg for the last 24 weeks of this 72-week trial. Serum prostate specific antigen levels were obtained at baseline and at weeks 24, 48 and 72, and were compared between treatment groups using the pooled t test and Fisher's exact test. RESULTS: Serum prostate specific antigen was similar at baseline for the placebo (mean ± SD 1.93 ± 1.59 ng/ml) and saw palmetto groups (2.20 ± 1.95, p = 0.16). Changes in prostate specific antigen during the study were similar, with a mean change in the placebo group of 0.16 ± 1.08 ng/ml and 0.23 ± 0.83 ng/ml in the saw palmetto group (p = 0.50). In addition, no differential effect on serum prostate specific antigen was observed between treatment arms when the groups were stratified by baseline prostate specific antigen. CONCLUSIONS: Saw palmetto extract does not affect serum prostate specific antigen more than placebo, even at relatively high doses.
Asunto(s)
Antagonistas de Andrógenos/administración & dosificación , Extractos Vegetales/administración & dosificación , Antígeno Prostático Específico/sangre , Hiperplasia Prostática/sangre , Hiperplasia Prostática/tratamiento farmacológico , Antagonistas de Andrógenos/uso terapéutico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Humanos , Masculino , Persona de Mediana Edad , Extractos Vegetales/uso terapéutico , SerenoaRESUMEN
CONTEXT: Saw palmetto fruit extracts are widely used for treating lower urinary tract symptoms attributed to benign prostatic hyperplasia (BPH); however, recent clinical trials have questioned their efficacy, at least at standard doses (320 mg/d). OBJECTIVE: To determine the effect of saw palmetto extract (Serenoa repens, from saw palmetto berries) at up to 3 times the standard dose on lower urinary tract symptoms attributed to BPH. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, multicenter, placebo-controlled randomized trial at 11 North American clinical sites conducted between June 5, 2008, and October 10, 2010, of 369 men aged 45 years or older, with a peak urinary flow rate of at least 4 mL/s, an American Urological Association Symptom Index (AUASI) score of between 8 and 24 at 2 screening visits, and no exclusions. INTERVENTIONS: One, 2, and then 3 doses (320 mg/d) of saw palmetto extract or placebo, with dose increases at 24 and 48 weeks. MAIN OUTCOME MEASURES: Difference in AUASI score between baseline and 72 weeks. Secondary outcomes included measures of urinary bother, nocturia, peak uroflow, postvoid residual volume, prostate-specific antigen level, participants' global assessments, and indices of sexual function, continence, sleep quality, and prostatitis symptoms. RESULTS: Between baseline and 72 weeks, mean AUASI scores decreased from 14.42 to 12.22 points (-2.20 points; 95% CI, -3.04 to -1.36) [corrected]with saw palmetto extract and from 14.69 to 11.70 points (-2.99 points; 95% CI, -3.81 to -2.17) with placebo. The group mean difference in AUASI score change from baseline to 72 weeks between the saw palmetto extract and placebo groups was 0.79 points favoring placebo (upper bound of the 1-sided 95% CI most favorable to saw palmetto extract was 1.77 points, 1-sided P = .91). Saw palmetto extract was no more effective than placebo for any secondary outcome. No clearly attributable adverse effects were identified. CONCLUSION: Increasing doses of a saw palmetto fruit extract did not reduce lower urinary tract symptoms more than placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00603304.
Asunto(s)
Antagonistas de Andrógenos/administración & dosificación , Extractos Vegetales/administración & dosificación , Hiperplasia Prostática/complicaciones , Trastornos Urinarios/tratamiento farmacológico , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Humanos , Masculino , Persona de Mediana Edad , Serenoa , Resultado del Tratamiento , Trastornos Urinarios/etiologíaRESUMEN
BACKGROUND: The use of relaxation and guided imagery to reduce stress and improve immune function has great potential benefits for patients with breast cancer. METHODS: This pilot study used a pretest-posttest experimental design with 28 breast cancer patients, aged 25 to 75 years, with the diagnosis of stage 0, 1, or 2 breast cancer. The experimental group received a relaxation and guided imagery intervention and the control group received standard care. The effects of the intervention on immune function were measured by natural killer (NK) cell cytotoxicity and IL-2-activated NK cell activity prior to surgery and 4 weeks postsurgery. NK cell activity was measured using a 15-hr incubation chromium release assay. Cytotoxicity of NK cells was measured against chromium-labeled K-562 target cells. IL-2 was used to enhance reactivity of NK cells against tumor cells. After incubation for 15 hr, cytotoxicity was measured through the release of radioactive chromium. RESULTS: Significant differences between groups were found at 4 weeks postsurgery. T-tests showed increased NK cell cytotoxicity for the intervention group at 100:1, 50:1, and 25:1 effector cell: target cell ratios (E:T) (p < .01 to p < .05) and increased activation for IL-2 at 100:1, 50:1, 25:1, and 12.5:1 (E:T) (p < .01 to p < .05) for the intervention group as compared to the control group. DISCUSSION: These findings suggest that a relaxation intervention such as guided imagery could have an effect on NK cell cytotoxicity and NK cell cytotoxicity after activation with IL-2 in patients undergoing surgery for breast cancer.
Asunto(s)
Neoplasias de la Mama/inmunología , Imágenes en Psicoterapia , Adulto , Anciano , Neoplasias de la Mama/psicología , Neoplasias de la Mama/terapia , Femenino , Humanos , Interleucina-2/inmunología , Células Asesinas Naturales/inmunología , Persona de Mediana EdadRESUMEN
PURPOSE: To determine the biochemical outcomes of patients with intermediate-risk prostate cancer treated at the H. Lee Moffitt Cancer Center with an I-125 permanent seed implant without supplemental pelvic radiotherapy. METHODS AND MATERIALS: Under an institutional review board approved protocol, the charts of 88 patients with intermediate-risk prostate cancer and a minimum follow-up of 36 months treated with brachytherapy without supplemental pelvic radiotherapy were reviewed. Median follow-up for the whole cohort was 57 months (range 37-121). Biochemical failure was defined using the American Society for Therapeutic Radiology and Oncology definition. RESULTS: The 5-year biochemical failure-free survival for the cohort was 83%. Patients with perineural invasion had a worse biochemical outcome, which was statistically significant (perineural invasion vs. no perineural invasion, 5-year biochemical failure-free survival 64% vs. 89%, P = 0.004). None of the following factors were found significant in this subset of patients: Gleason scores 6 versus 7, primary Gleason grades 3 versus 4, percentage of core positive <20% versus >20%, number of cores positive <2 versus 2 versus >2, hormonal therapy versus no hormonal therapy, T1 versus T2, prostate-specific antigen <10 versus >10, or > or =2 intermediate risk factors versus 1 intermediate risk factor. CONCLUSIONS: Our data suggest that patients with intermediate-risk prostate cancer may be treated effectively with brachytherapy without supplemental pelvic radiotherapy. However, because of the limited nature of our study, we cannot exclude that patients with intermediate-risk prostate cancer may benefit from supplemental external beam radiotherapy.
Asunto(s)
Braquiterapia/métodos , Neoplasias de la Próstata/radioterapia , Humanos , Radioisótopos de Yodo/uso terapéutico , Masculino , Estadificación de Neoplasias , Pronóstico , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The evaluation of sentinel lymph nodes (SLNs) for the presence of malignant epithelial cells is essential to the staging of breast cancer patients. Recently, increased attention has focused on the possibility that epithelial cells may reach SLNs by benign mechanical means, rather than by metastasis. The purpose of this study was to test the hypothesis that pre-SLN biopsy breast massage, which we currently use to facilitate the localization of SLNs, might represent a mode of benign mechanical transport. We studied 56 patients with invasive and/or in situ ductal carcinoma and axillary SLNs with only epithelial cells and/or cell clusters (< or =0.2 mm in diameter and not associated with features of established metastases) detected predominantly in subcapsular sinuses of SLNs on hematoxylin and eosin- and/or anti-cytokeratin-stained sections. No patient had an SLN involved by either micro- or macro-metastatic carcinoma. Epithelial cells and cell clusters, < or =0.2 mm in size and without features of established metastases, occurred more frequently in the SLNs of patients who underwent pre-SLN biopsy breast massage (P < 0.001, chi2 test). The latter finding supports the hypothesis that pre-SLN biopsy breast massage is a mode of benign mechanical transport of epithelial cells to SLNs.
Asunto(s)
Neoplasias de la Mama/cirugía , Células Epiteliales/citología , Ganglios Linfáticos/citología , Masaje , Biopsia del Ganglio Linfático Centinela , Neoplasias de la Mama/patología , Carcinoma Ductal/patología , Carcinoma Ductal/cirugía , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/cirugía , Células Epiteliales/patología , Humanos , Ganglios Linfáticos/cirugía , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela/métodosRESUMEN
AIMS: To evaluate the effectiveness of supplementing a group of early stage prostate cancer patients, with 60 mg of soy isoflavones in producing a change in hormonal and proliferative risk parameters that are implicated in prostate cancer promotion. METHODS: Seventy six eligible prostate cancer patients with a Gleason score of 6 or below, between ages 50 and 80 were admitted and supplemented with soy isoflavones or placebo for a 12 week period and changes in PSA and steroid hormones were analyzed at baseline and post intervention. RESULTS: Fifty-nine patients completed the 12-week intervention. Serum free testosterone was reduced or showed no change in 61% of subjects in the isoflavone group compared to 33% in the placebo group. Serum total PSA decreased or was unchanged in 69% of the subjects in the isoflavone treated group compared to 55% in the placebo group. However, we did not see an increase in SHBG levels. Nineteen percent of subjects receiving soy isoflavones reduced total PSA by two points or more during the intervention period. CONCLUSIONS: These data suggest that supplementing early stage prostate cancer patients with soy isoflavones, even in a study of short duration, altered surrogate markers of proliferation such as serum PSA and free testosterone in a larger number of subjects in the isoflavone supplemented group than the group receiving placebo. The study establishes the need to explore further the effects of prolonged and consistent soy consumption, which could potentially delay onset of histologic disease in this patient population.
Asunto(s)
Biomarcadores de Tumor/análisis , Isoflavonas/farmacología , Neoplasias de la Próstata/prevención & control , Administración Oral , Anciano , Anciano de 80 o más Años , Suplementos Dietéticos , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Placebos , Antígeno Prostático Específico/análisis , Factores de Riesgo , Glycine max/química , Testosterona/sangreRESUMEN
BACKGROUND: The purpose of this study was to prospectively observe the relative contribution of each viable mechanism such as hyperphagia, physical activity, body composition, steroid hormonal and thyroid function, fatigue scores on changes in body weight in breast cancer patients, receiving adjuvant chemotherapy. METHODS: This was a prospective observational research design where 198 consecutive breast cancer patients receiving adjuvant chemotherapy were monitored from start to end and 6 months post-therapy on changes in anthropometics, fatigue, nutritional intake, physical activity, thyroid and steroid hormones. RESULTS: We observed a weight gain over >5 lb in 22.2% of this patient population with a significant and progressive gain of 6.7 lb (P < 0.0001) at 6 months. Ninety four percent of all patients reported fatigue and 56% of patients reported lowered physical activity. A significant reduction in serum free and total estradiol (P < 0.0001) was observed indicative of reduction in ovarian function with 86% amenorrehic at the end of treatment. A significant reduction in mean serum triiodothyronine uptake levels (P < 0.05), in addition to a significant increase in TBG (P < 0.0001) from baseline to end of chemotherapy, was observed. In addition 20-25% of this patient group was already diagnosed with clinical hypothyroidism at diagnosis and treated. Changes in fatigue frequency and serum sex-hormone-binding globulin (SHBG) were variables significantly predictive of weight gain (P < 0.0001). CONCLUSIONS: Cytotoxic agents may influence thyroid function in breast cancer patients contributing to and progressively worsening symptoms such as weight gain, amenorrhea, fatigue and lowered physical activity in this population. The present study indicates the value of screening breast cancer patients for thyroid function at diagnosis or pre-treatment.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Hipotiroidismo/inducido químicamente , Adulto , Anciano , Amenorrea , Neoplasias de la Mama/patología , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Estradiol/sangre , Fatiga , Femenino , Fluorouracilo/administración & dosificación , Humanos , Hipotiroidismo/sangre , Metotrexato/administración & dosificación , Persona de Mediana Edad , Estudios Prospectivos , Fases del Sueño , Tiroxina/sangre , Aumento de PesoRESUMEN
BACKGROUND: To the authors' knowledge, few data currently are available regarding the tolerance to chemotherapy in older cancer patients. This prospective pilot study evaluated the changes in functional, mental, nutritional, and comorbid status, as well as the quality of life (QOL), in geriatric oncology patients receiving chemotherapy. METHODS: Sixty patients age > or = 70 years who were undergoing cancer chemotherapy were recruited in a university-based comprehensive cancer center. Changes in physical function were measured by the Eastern Cooperative Oncology Group performance status (ECOG PS) and Instrumental Activities of Daily Living (IADLs), mental health changes were measured by the Mini-Mental State Examination and the Geriatric Depression Scale (GDS), comorbidity was measured by Charlson's index and the Cumulative Illness Rating Scale-Geriatric, nutrition was measured by the Mini-Nutritional Assessment, and QOL was measured by the Functional Assessment of Cancer Therapy-General (FACT-G). Changes were assessed at baseline and at the end of treatment (EOT). Grade 4 hematologic and Grade 3-4 nonhematologic toxicities were recorded. RESULTS: Thirty-seven patients (63%) completed both assessments. Older cancer patients demonstrated a significant decline in measurements of physical function after receiving chemotherapy, as indicated by changes in scores on the IADL (P = 0.04) and on the physical (P = 0.01) and functional (P = 0.03) subscales of the FACT-G. They also displayed worse scores on the GDS administered postchemotherapy (P < 0.01). Patients who experienced severe chemotoxicity had more significant declines in ECOG PS (P = 0.03), IADL (P = 0.03), and GDS (P = 0.04), and more gain in the social well-being subscale (P = 0.02) of the FACT-G, than those who did not experience severe chemotoxicity. However, changes in most scores were small in magnitude clinically. No significant change was found between baseline and EOT in nutrition, comorbidity, and other aspects of the FACT-G. CONCLUSIONS: Older cancer patients undergoing chemotherapy may experience toxicity but generally can tolerate it with limited impact on independence, comorbidity, and QOL levels. It is important to recognize and monitor these changes during geriatric oncology treatment.