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PURPOSE: The purpose of this study was to identify barriers and facilitators influencing implementation of the diagnosis and intervention clinical practice guidelines (CPGs) related to the management of patients with breast cancer-related lymphedema (BCRL). METHODS: A descriptive, cross-sectional web-based survey was conducted. Participants included physical therapists and assistants who were members of the APTA's Academy of Oncologic Physical Therapy and Lymphology Association of North America. Desriptive statisitcs were computed for all demographic and barriers and facilitators data. Individual exploratory factor analyses (EFA) were performed on survey items for both CPGs to identify themes of barriers and facilitators to implementation. RESULTS: A total of 180 respondents completed the survey. 34.9% of respondents read the diagnosis CPG and 22.4% read the intervention CPG. A total of 77.8% reported that they did not have issues in changing their clinical routines and 69.5% did not have resistance working according to CPGs. The EFA resulted in 3 themes for each CPG, accounting for 46% of the variance for the diagnostic CPG and 54% of the variance for the intervention CPG. The 3 themes, clinician characteristics, patient demographics, therapist practice setting and beliefs/values, were weighted differently for each EFA. CONCLUSION: Most respondents did not read either CPG, however, report a willingness to make changes to clinical practice and utilization of CPGs. For those who have attempted to implement the CPGs, this study was the first to identify the barriers and facilitators impacting the implementation of the CPGs related to the management of BCRL. IMPLICATIONS FOR CANCER SURVIVORS: The results will inform the development of targeted implementation strategies to improve access to and adherence to recommendations from the CPGs ultimately improving the efficiency and efficacy of care delivery to patients.
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The early innate immune response to coccidioidomycosis has proven to be pivotal in directing the adaptive immune response and disease outcome in mice and humans but is unexplored in dogs. The objectives of this study were to evaluate the innate immune profile of dogs with coccidioidomycosis and determine if differences exist based on the extent of infection (i.e., pulmonary or disseminated). A total of 28 dogs with coccidioidomycosis (pulmonary, n = 16; disseminated, n = 12) and 10 seronegative healthy controls were enrolled. Immunologic testing was performed immediately, without ex vivo incubation (i.e., constitutive), and after coccidioidal antigen stimulation of whole blood cultures. Whole blood cultures were incubated with a phosphate-buffered solution (PBS) (negative control) or a coccidioidal antigen (rCTS1 (105-310); 10 µg/mL) for 24 h. A validated canine-specific multiplex bead-based assay was used to measure 12 cytokines in plasma and cell culture supernatant. Serum C-reactive protein (CRP) was measured with an ELISA assay. Leukocyte expression of toll-like receptors (TLRs)2 and TLR4 was measured using flow cytometry. Dogs with coccidioidomycosis had higher constitutive plasma keratinocyte chemotactic (KC)-like concentrations (p = 0.02) and serum CRP concentrations compared to controls (p < 0.001). Moreover, dogs with pulmonary coccidioidomycosis had higher serum CRP concentrations than those with dissemination (p = 0.001). Peripheral blood leukocytes from dogs with coccidioidomycosis produced higher concentrations of tumor necrosis factor (TNF)-α (p = 0.0003), interleukin (IL)-6 (p = 0.04), interferon (IFN)-γ (p = 0.03), monocyte chemoattractant protein (MCP)-1 (p = 0.02), IL-10 (p = 0.02), and lower IL-8 (p = 0.003) in supernatants following coccidioidal antigen stimulation when compared to those from control dogs. There was no detectable difference between dogs with pulmonary and disseminated disease. No differences in constitutive or stimulated leukocyte TLR2 and TLR4 expression were found. These results provide information about the constitutive and coccidioidal antigen-specific stimulated immune profile in dogs with naturally acquired coccidioidomycosis.
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Clinical Practice Guidelines (CPGs) aim to improve patient outcomes through implementation of proven interventions and decrease variation in practices. The relevance of this article is to describe the current state practice of physical therapists who diagnose and treat patients with Breast Cancer Related Lymphedema (BCRL). It also provides a description of physical therapist-reported adherence to the BCRL CPG recommendations which establishes the need for implementation interventions to improve adherence. PURPOSE: The purpose of this study is to describe practice patterns of physical therapists (PT) and physical therapist assistants (PTA) who treat patients with breast cancer-related lymphedema and determine if they are adherent to best evidence recommendations for lymphedema diagnosis and intervention. METHODS: An electronic survey to collect practice pattern data of PTs and PTAs who treat patients with BCRL was distributed. A descriptive and quantitative statistical analysis was performed. RESULTS: Twenty-six percent of respondents read the American Physical Therapy Association sponsored lymphedema diagnosis clinical practice guideline (CPG) and 20% read the lymphedema intervention CPG. Lymphoscintigraphy was the only diagnosis or intervention tool with a significant difference in use between therapists who read versus did not read the CPGs. Adherence to "should do" recommendations was variable: bioimpedance (18.2%), volume calculation (49.3%), ultrasound (0%), patient reported outcome tools (64.9%), compression garments (43.9%), exercise (87.2%), and compression bandaging (56.8%). CONCLUSIONS: There is variability in adherence to recommendations for both the lymphedema diagnosis and intervention CPGs. Interventions to improve implementation and adherence to CPG recommendations are warranted.
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Linfedema Relacionado a Câncer de Mama , Neoplasias da Mama , Linfedema , Assistentes de Fisioterapeutas , Fisioterapeutas , Humanos , Feminino , Linfedema Relacionado a Câncer de Mama/terapia , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Linfedema/terapiaRESUMO
PURPOSE: To report outcomes of glaucoma drainage device (GDD) surgery based on primary or secondary glaucoma diagnosis and lens status. DESIGN: Single-center, retrospective, consecutive cohort study. METHODS: University of Florida patients aged 18 to 93 years who underwent nonvalved GDD surgery between 1996 and 2015 with a minimum of 1-year follow-up were examined. Of the 186 eyes of 186 patients enrolled, 108 had a primary glaucoma and 78 a secondary glaucoma diagnosis. Excluding 13 aphakic patients, 57 eyes were phakic and 116 pseudophakic. Mean intraocular pressure (IOP), mean number of medications, visual acuity (VA), surgical complications, and failure (IOP ≥18âmm Hg, IOP <6âmm Hg, reoperation for glaucoma, or loss of light perception) were the main outcome measures. RESULTS: No significant difference was noted in mean IOP and mean medication use (12.8â±â4.5 and 13.0â±â6.6 mm Hg on 2.0â±â1.2 and 1.5â±â1.1 medication classes, respectively), mean VA (1.08â±â0.98 and 0.94â±â0.89, respectively), failure, or numbers of complications and reoperations (Pâ>â0.05) between eyes with primary and secondary glaucomas at up to 5âyears postoperatively. Comparison of phakic and pseudophakic eyes showed a statistically significant higher success rate for the pseudophakic patient group at the ≥18âmm Hg upper limit and <6 mm Hg lower limit (Pâ=â0.01), and significantly fewer eyes required reoperation to lower IOP (6.9% vs 23%). CONCLUSIONS: GDD surgery appears equally effective for secondary glaucomas as for primary glaucomas, and has a better outcome for pseudophakic eyes than phakic eyes.
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Implantes para Drenagem de Glaucoma , Glaucoma , Estudos de Coortes , Seguimentos , Glaucoma/cirurgia , Humanos , Pressão Intraocular , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PRECIS: A comparison of 186 glaucoma patients with mixed diagnoses who underwent nonvalved glaucoma drainage device (GDD) implant surgery showed similar long-term intraocular pressure (IOP), medication, and visual acuity (VA) outcomes between those with prior failed trabeculectomy surgery versus those without. PURPOSE: The purpose of this study was to evaluate whether prior failed trabeculectomy adversely affects the outcome of glaucoma tube surgery. PATIENTS AND METHODS: A total of 186 eyes of 186 patients who underwent a nonvalved GDD implant surgery by a single surgeon between 1996 and 2015 at a University practice were included. Patients were of mixed diagnoses and over 18 years old. Before the GDD surgery, 65 had a previous failed glaucoma filtering surgery and 121 had no prior glaucoma surgery. Demographic information, preoperative and postoperative IOP, medication, VA, and complications were collected from chart review. RESULTS: No significant difference was noted in mean IOP and mean medication use (13.0 and 12.6 mm Hg on 2.0 and 1.7 medication classes at 5 y postoperatively, respectively), mean VA and change in VA from baseline, or numbers of complications (P>0.05), between eyes that had a prior failed filtration surgery and those that had not. Kaplan-Meier plots for failure over 5 years using a lower limit of <5 mm Hg and an upper limit of ≥18, ≥15, or ≥12 mm Hg did not show a significant difference between groups. Subanalyses were performed to examine only primary glaucoma eyes and results were similar. Further group subanalyses comparing those with baseline IOP ≥25 or <25 mm Hg, age 65 and above or below 65 years and those specifically with Baerveldt 350 mm2 implants also did not show significant differences. CONCLUSION: Prior failed filtration surgery does not appear to affect the outcome of future GDD surgery.
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Implantes para Drenagem de Glaucoma , Glaucoma , Trabeculectomia , Adolescente , Idoso , Seguimentos , Glaucoma/cirurgia , Humanos , Pressão Intraocular , Implantação de Prótese , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Bevacizumab and ranibizumab, which are anti-vascular endothelial growth factor (VEGF) medications, are used frequently in the treatment for retinopathy of prematurity (ROP) in infants. Aflibercept, or VEGF Trap, has been used anecdotally, but translation and clinical studies are lacking. OBJECTIVE: This study investigates the efficacy of aflibercept at reducing areas of non-perfused retina and studies its effect on normal angiogenesis in the oxygen-induced retinopathy mouse model of ROP. METHODS: C57BL/6 J mice were assigned to room air control (n = 21 eyes) or hyperoxia with 75% oxygen (n = 84 eyes). The hyperoxic mice were assigned to 1 of 3 groups: 0 ng (n = 14 eyes), 100 ng (n = 35 eyes), or 1,000 ng (n = 35 eyes) of intravitreal aflibercept administered on postnatal day 14. Eyes were enucleated at PN17 and PN25 postinjection. Retinas were stained with anti-collagen IV antibody and photographed with microscopy. Areas of perfused and non-perfused retina were quantified using ImageJ software. Statistical comparisons were made using ANOVA with Tukey post hoc comparisons. RESULTS: At PN17, there was no significant difference in the area of non-perfused retina between the hyperoxic control and the 100 and 1,000 ng aflibercept groups. At PN25, the 100 ng (p < 0.05) and 1,000 ng (p = 0.008) treatment groups displayed less non-perfusion compared to hyperoxic controls. At the 1,000 ng dose, there was increased non-perfusion compared to the 100 ng dose (p = 0.02). There was reduced non-perfusion by PN25 compared to PN17 for the 100 ng group (p < 0.05), with no difference in the 1,000 ng group. CONCLUSIONS: The study shows that the area of non-perfused retina decreases effectively with aflibercept at PN25 with 100 ng dosage. With the 1,000 ng dosage, there is an inhibition of the physiologic angiogenesis with a higher area of non-perfused retina.
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Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Retina/fisiopatologia , Retinopatia da Prematuridade/tratamento farmacológico , Acuidade Visual , Inibidores da Angiogênese/administração & dosagem , Animais , Modelos Animais de Doenças , Injeções Intravítreas , Camundongos , Camundongos Endogâmicos C57BL , Oxigênio/toxicidade , Retina/efeitos dos fármacos , Retinopatia da Prematuridade/induzido quimicamente , Retinopatia da Prematuridade/fisiopatologia , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
BACKGROUND: Studies on total knee arthroplasty (TKA) with computer-assisted orthopedic surgery (CAOS) are limited by sample size or overlooked longitudinal performance of the system. This study aimed to assess resection accuracy across the entire TKA application history of a modern CAOS system considering multiple factors. METHODS: A retrospective analysis was performed based on a database that archives technical logs of all TKAs performed using a CAOS system. Coronal resection errors and percentage of outliers (<2° alignment error) in the proximal tibia and distal femur were assessed. Multilevel modeling was used to understand whether and where the resection error variability was located in the grouping categories, which included geographic region, individual established surgeon, preoperative alignment, adoption phase (learning/proficient), and version of the CAOS software application. RESULTS: A total of 10,144 cases were reviewed. The accuracy (mean) and precision (standard deviation) of the coronal alignment for both the tibia and femur were at the sub-degree level. High percentages of acceptable resections were observed across the pooled and each grouping category. The accountability for the amounts of total variability in tibial and femoral resection errors was negligible for all grouping categories, demonstrated by ICC values less than the common variations in observational studies. CONCLUSIONS: The study applied advanced analyses to assess alignment outcome in TKA bony resection alignment across the history of a specific CAOS system. The results demonstrated high resection alignment accuracy insensitive to geographic region, CAOS software application, adoption phase, preoperative alignment, and inter-surgeon differences.
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Artroplastia do Joelho , Mau Alinhamento Ósseo/prevenção & controle , Osteoartrite do Joelho/cirurgia , Cirurgia Assistida por Computador , Idoso , Feminino , Fêmur/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/etiologia , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Tíbia/cirurgiaRESUMO
PURPOSE: The aim of this study is to evaluate whether trabeculectomy with antimetabolites or glaucoma drainage device (GDD) surgery is more likely to achieve an intraocular pressure (IOP) ≤10 mm Hg. DESIGN: Retrospective, nonrandomized, cohort study of pseudophakic, primary glaucoma patients. METHODS: 53 pseudophakic patients underwent trabeculectomy and 65 received GDD at the University of Florida by one surgeon between 1993 and 2015. The main outcome measures were mean IOP and percentage of patients obtaining an IOP ≤10 mm Hg for up to 5 years postoperatively. A subgroup undergoing a first time glaucoma surgery was also analyzed because there were more redo glaucoma procedures in the GDD group. RESULTS: Over 5 years, the mean annual IOP for the trabeculectomy eyes was between 6.9 and 7.8 mm Hg on an average of 0.2 medications, and that for GDD eyes was between 11.4 and 12.1 mm Hg on a mean of 1.6 to 1.9 medications (Pâ<â0.002). A significantly higher percentage of trabeculectomy eyes than GDD eyes achieved a pressure of ≤10 mm Hg, for years 1 to 4 (Pâ<â0.05). Visual acuity (VA) change was not statistically different between the groups, both for mean logMAR acuity and percentage of patients that lost ≥2 Snellen lines. Complication rates were similar between the groups. Postoperative VA change was similar for eyes achieving low IOP ≤5 mm Hg and those eyes with an IOP ≥10 mm Hg. CONCLUSIONS: Trabeculectomy provided significantly lower IOP for 5 years postoperatively in pseudophakic primary glaucoma patients, and was more likely to achieve an IOP ≤10 mm Hg.
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Glaucoma/cirurgia , Pressão Intraocular/fisiologia , Pseudofacia/cirurgia , Trabeculectomia/métodos , Idoso , Feminino , Glaucoma/fisiopatologia , Implantes para Drenagem de Glaucoma , Humanos , Masculino , Pessoa de Meia-Idade , Pseudofacia/fisiopatologia , Estudos Retrospectivos , Acuidade VisualRESUMO
BACKGROUND: High rates of radiographic glenoid loosening following anatomic total shoulder arthroplasty (TSA) are documented at midterm follow-up. Small studies remain conflicted on the impact of lucent lines on clinical outcomes. This study assesses the impact of radiolucent lines on function and patient-reported outcomes (PROs) following TSA. METHODS: We retrospectively evaluated 492 primary TSAs performed between February 2005 and April 2016. Radiographs were evaluated for glenoid loosening according to the Lazarus grade at a mean of 5.3 years (range, 2-12 years). Clinical outcome measures included range of motion and American Shoulder and Elbow Surgeons, Constant, University of California-Los Angeles, Simple Shoulder Test, and Shoulder Pain and Disability Index scores. Outcomes were compared between patients with and patients without glenoid lucent lines and in relation to lucency grade. RESULTS: At most recent follow-up, 308 glenoids (63%) showed no radiolucent lines (group 0) and 184 demonstrated peri-glenoid lucencies (group 1). The groups were similar regarding age, sex, body mass index, comorbidities, and prior surgery. At follow-up, group 1 demonstrated significantly lower improvements in forward elevation (P = .02) and all PROs (P ≤ .005). Subgroup analysis by radiolucency grade showed that forward elevation diminished with increasing radiolucent score and exceeded the minimal clinically important difference (MCID) above grade 2 lucencies. A similar decline in PROs was observed with increasing lucency grade. These differences did not exceed the MCID below grade 5 lucencies. DISCUSSION: Peri-implant glenoid lucencies following TSA are associated with lower forward elevation and PROs. Lucencies above grade 2 are associated with clinically important losses in overhead motion. However, differences below the MCID are maintained for PROs below grade 5 glenoid lucencies.
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Artroplastia do Ombro , Cavidade Glenoide/diagnóstico por imagem , Amplitude de Movimento Articular , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/fisiopatologia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Diferença Mínima Clinicamente Importante , Medidas de Resultados Relatados pelo Paciente , Falha de Prótese/efeitos adversos , Radiografia , Estudos Retrospectivos , Articulação do Ombro/cirurgia , Dor de Ombro/etiologia , Prótese de Ombro/efeitos adversosRESUMO
BACKGROUND: Preoperative factors that most influence postoperative outcomes of both anatomic total shoulder arthroplasty (aTSA) and reverse total shoulder arthroplasty (rTSA) are unknown. The purpose of this study was to identify the preoperative parameters that significantly influence postoperative outcomes of aTSA and rTSA. METHODS: The outcomes of 1089 aTSA patients and 1332 rTSA patients (mean follow-up period, 49 months) from an international registry with a single platform system were analyzed. A multiple linear regression model with backward stepwise selection identified the preoperative parameters that were significant predictors of postoperative clinical outcome metric scores and motion measures for both rTSA and aTSA. RESULTS: For both aTSA and rTSA patients, numerous preoperative parameters that influence postoperative outcomes were identified. Greater postoperative range of motion (ROM) was significantly influenced by greater preoperative ROM. For aTSA, greater postoperative American Shoulder and Elbow Surgeons (ASES) scores were significantly influenced by greater preoperative ASES scores, no history of shoulder surgery, and the presence of greater preoperative active external rotation. For rTSA, greater postoperative ASES scores were significantly influenced by greater preoperative ASES scores, no history of shoulder surgery, no history of tobacco use, less preoperative passive external rotation, and greater preoperative active external rotation. CONCLUSIONS: This study quantified the preoperative predictors of postoperative clinical outcome metric scores and ROM for both aTSA and rTSA. Numerous significant associations were identified, including demographic and comorbidity risk factors. These associations may be helpful for surgeons to consider when counseling patients regarding aTSA versus rTSA and to establish more accurate expectations prior to surgery.
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BACKGROUND: An improved understanding of how gender differences and the natural aging process are associated with differences in clinical improvement in outcome metric scores and ROM measurements after reverse total shoulder arthroplasty (rTSA) may help physicians establish more accurate patient expectations for reducing postoperative pain and improving function. QUESTIONS/PURPOSES: (1) Is gender associated with differences in rTSA outcome scores like the Simple Shoulder Test (SST), the UCLA Shoulder score, the American Shoulder and Elbow Surgeons (ASES) Shoulder score, the Constant Shoulder score, and the Shoulder Pain and Disability Index (SPADI) and ROM? (2) Is age associated with differences in rTSA outcome scores and ROM? (3) What factors are associated with the combined interaction effect between age and gender? (4) At what time point during recovery does most clinical improvement occur, and when is full improvement reached? METHODS: We quantified and analyzed the outcomes of 660 patients (424 women and 236 men; average age, 72 ± 8 years; range, 43-95 years) with cuff tear arthropathy or osteoarthritis and rotator cuff tear who were treated with rTSA by 13 shoulder surgeons from a longitudinally maintained international database using a linear mixed effects statistical model to evaluate the relationship between clinical improvements and gender and patient age. We used five outcome scoring metrics and four ROM assessments to evaluate clinical outcome differences. RESULTS: When controlling for age, men had better SST scores (mean difference [MD] = 1.41 points [95% confidence interval {CI}, 1.07-1.75], p < 0.001), UCLA scores (MD = 1.76 [95% CI, 1.05-2.47], p < 0.001), Constant scores (MD = 6.70 [95% CI, 4.80-8.59], p < 0.001), ASES scores (MD = 7.58 [95% CI, 5.27-9.89], p < 0.001), SPADI scores (MD = -12.78 [95% CI, -16.28 to -9.28], p < 0.001), abduction (MD = 5.79° [95% CI, 2.74-8.84], p < 0.001), forward flexion (MD = 7.68° [95% CI, 4.15-11.20], p < 0.001), and passive external rotation (MD = 2.81° [95% CI, 0.81-4.8], p = 0.006). When controlling for gender, each 1-year increase in age was associated with an improved ASES score by 0.19 points (95% CI, 0.04-0.34, p = 0.011) and an improved SPADI score by -0.29 points (95% CI, -0.46 to 0.07, p = 0.020). However, each 1-year increase in age was associated with a mean decrease in active abduction by 0.26° (95% CI, -0.46 to 0.07, p = 0.007) and a mean decrease of forward flexion by 0.39° (95% CI, -0.61 to 0.16, p = 0.001). A combined interaction effect between age and gender was found only with active external rotation: in men, younger age was associated with less active external rotation and older age was associated with more active external rotation (ß0 [intercept] = 11.029, ß1 [slope for age variable] = 0.281, p = 0.009). Conversely, women achieved no difference in active external rotation after rTSA, regardless of age at the time of surgery (ß0 [intercept] = 34.135, ß1 [slope for age variable] = -0.069, p = 0.009). Finally, 80% of patients achieved full clinical improvement as defined by a plateau in their outcome metric score and 70% of patients achieved full clinical improvement as defined by a plateau in their ROM measurements by 12 months followup regardless of gender or patient age at the time of surgery with most improvement occurring in the first 6 months after rTSA. CONCLUSIONS: Gender and patient age at the time of surgery were associated with some differences in rTSA outcomes. Men had better outcome scores than did women, and older patients had better outcome scores but smaller improvements in function than did younger patients. These results demonstrate rTSA outcomes differ for men and women and for different patient ages at the time of surgery, knowledge of these differences, and also the timing of improvement plateaus in outcome metric scores and ROM measurements can both improve the effectiveness of patient counseling and better establish accurate patient expectations after rTSA. LEVEL OF EVIDENCE: Level III, therapeutic study.
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Fatores Etários , Artroplastia do Ombro/estatística & dados numéricos , Dor Pós-Operatória/epidemiologia , Fatores Sexuais , Dor de Ombro/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/fisiopatologia , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Sistema de Registros , Estudos Retrospectivos , Articulação do Ombro/fisiopatologia , Articulação do Ombro/cirurgia , Dor de Ombro/etiologia , Dor de Ombro/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: To illustrate the 10-year risks of urinary adverse events (UAEs) among men diagnosed with prostate cancer and treated with different types of therapy, accounting for the competing risk of death. METHODS: Prostate cancer is the second most common malignancy among adult males in the United States. Few studies have reported the long-term post-treatment risk of UAEs and those that have, have not appropriately accounted for competing deaths. This paper conducts an inverse probability of treatment (IPT) weighted competing risks analysis to estimate the effects of different prostate cancer treatments on the risk of UAE, using a matched-cohort of prostate cancer/non-cancer control patients from the Surveillance, Epidemiology and End Results (SEER) Medicare database. RESULTS: Study dataset included men age 66 years or older that are 83% white and had a median follow-up time of 4.14 years. Patients that underwent combination radical prostatectomy and external beam radiotherapy experienced the highest risk of UAE (IPT-weighted competing risks: HR 3.65 with 95% CI (3.28, 4.07); 10-yr. cumulative incidence = 36.5%). CONCLUSIONS: Findings suggest that IPT-weighted competing risks analysis provides an accurate estimator of the cumulative incidence of UAE taking into account the competing deaths as well as measured confounding bias.
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Prostatectomia/efeitos adversos , Neoplasias da Próstata/terapia , Radioterapia/efeitos adversos , Doenças Urológicas/etiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Medicare/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Pontuação de Propensão , Modelos de Riscos Proporcionais , Fatores de Risco , Programa de SEER/estatística & dados numéricos , Estados Unidos/epidemiologia , Estreitamento Uretral/diagnóstico , Estreitamento Uretral/epidemiologia , Estreitamento Uretral/etiologia , Obstrução do Colo da Bexiga Urinária/diagnóstico , Obstrução do Colo da Bexiga Urinária/epidemiologia , Obstrução do Colo da Bexiga Urinária/etiologia , Doenças Urológicas/diagnóstico , Doenças Urológicas/epidemiologiaRESUMO
AIMS: Oncogenic gene fusions involving the anaplastic lymphoma kinase (ALK) tyrosine kinase have been identified in several haematopoietic and sporadically also in solid tumour types. Preliminary results from clinical trials suggest that patients with ALK fusion positive cancers might optimally benefit from the tyrosine kinase inhibitor crizotinib, but a comprehensive analysis of solid tumour types for ALK fusion and fusion associated expression is lacking. METHODS: In order to identify human solid cancers carrying ALK alterations, we performed real-time PCR screening of 1000 tumour samples representing 29 different tumour entities. ALK-positive samples were then transferred into a tissue microarray format and subjected to ALK break-apart fluorescence in situ hybridisation (FISH) analysis and ALK immunohistochemistry (IHC) analysis. RESULTS: ALK expression was detected by real-time PCR in 260 of 896 (29%) interpretable tumour samples. FISH analysis was successful in 189 of 260 arrayed cancers but did not detect ALK rearrangement. There was also no ALK expression detectable by IHC. CONCLUSIONS: Different levels of ALK expression can be found in various cancer types using sensitive methods like real-time PCR. However, such low-level expression is independent from oncogenic ALK fusions and cannot be detected with less-sensitive methods like IHC. ALK fusion is a rare event in human solid cancers.
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Biomarcadores Tumorais/análise , Neoplasias/enzimologia , Receptores Proteína Tirosina Quinases/análise , Quinase do Linfoma Anaplásico , Biomarcadores Tumorais/genética , Fusão Gênica , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias/classificação , Neoplasias/genética , Neoplasias/patologia , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Receptores Proteína Tirosina Quinases/genética , Análise Serial de TecidosRESUMO
Tumor protein D52 (TPD52) is located at chromosome 8q21, a region that is frequently gained or amplified in multiple human cancer types. TPD52 has been suggested as a potential target for new anticancer therapies. In order to analyze TPD52 expression in the most prevalent human cancer types, we employed quantitative PCR to measure TPD52 mRNA levels in formalin-fixed tissue samples from more than 900 cancer tissues obtained from 29 different human cancer types. TPD52 was expressed at varying levels in all tested normal tissues, including skin, lymph node, lung, oral mucosa, breast, endometrium, ovary, vulva, myometrium, liver, pancreas, stomach, kidney, prostate, testis, urinary bladder, thyroid gland, brain, muscle and fat tissue. TPD52 was upregulated in 18/29 (62%) tested cancer types. Strongest expression was found in non-seminoma (56-fold overexpression compared to corresponding normal tissue), seminoma (42-fold), ductal (28-fold) and lobular breast cancer (14-fold). In these tumor types, TPD52 upregulation was found in the vast majority (>80%) of tested samples. Downregulation was found in 11 (38%) tumor types, most strongly in papillary renal cell cancer (-8-fold), leiomyosarcoma (-6-fold), clear cell renal cell cancer (-5-fold), liposarcoma (-5-fold) and lung cancer (-4-fold). These results demonstrate that TPD52 is frequently and strongly upregulated in many human cancer types, which may represent candidate tumor types for potential anti-TPD52 therapies.