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OBJECTIVES: Primary mucinous ovarian carcinoma represents 3% of ovarian cancers and is typically diagnosed early, yielding favorable outcomes. This study aims to identify risk factors, focussing on the impact of age and ethnicity on survival from primary mucinous ovarian cancer. METHODS: A retrospective observational study of patients treated at Sandwell and West Birmingham Hospitals NHS Trust and University Hospital Coventry and Warwickshire. Patients included were women aged ≥16 years, with primary mucinous ovarian cancer confirmed by specialist gynecological histopathologist and tumor immunohistochemistry, including cytokeratin-7, cytokeratin-20, and CDX2. Statistical analyses were performed using R integrated development environment, with survival assessed by Cox proportional hazards models and Kaplan-Meier plots. RESULTS: A total of 163 patients were analyzed; median age at diagnosis was 58 years (range 16-92), 145 (89%) were International Federation of Gynecology and Obstetrics stage I and 43 (26%) patients had infiltrative invasion. Women aged ≤45 years were more likely to have infiltrative invasion (RR=1.38, 95% CI 0.78 to 2.46), with increased risk of death associated with infiltrative invasion (HR=2.29, 95% CI 1.37 to 5.83). Compared with White counterparts, South Asian women were more likely to undergo fertility-sparing surgery (RR=3.52, 95% CI 1.48 to 8.32), and have infiltrative invasion (RR=1.25, 95% CI 0.60 to 2.58). South Asian women undergoing fertility-sparing surgery had worse prognosis than those undergoing traditional staging surgery (HR=2.20, 95% CI 0.39 to 13.14). In FIGO stage I disease, 59% South Asian and 37% White women received adjuvant chemotherapy (p=0.06). South Asian women exhibited a worse overall prognosis than White women (HR=2.07, 95% CI 0.86 to 4.36), particularly pronounced in those aged ≤45 years (HR=8.75, 95% CI 1.22 to 76.38). CONCLUSION: This study identified young age as a risk factor for diagnosis of infiltrative invasion. Fertility-sparing surgery in South Asian women is a risk factor for poorer prognosis. South Asian women exhibit poorer overall survival than their White counterparts.
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Uterine sarcomas are rare; most are either smooth muscle or endometrial stromal in origin. Recent molecular advances have identified several, genetically defined entities with specific morphologic, clinicopathological associations, and therapeutic options. We report 3 cases of uterine neurotrophic tyrosine receptor kinase (NTRK)-rearranged spindle cell neoplasms," currently classified as "emerging entities" in the WHO Classification of Female Genital Tract Tumors, 2020, Fifth Edition. The affected patients were 32, 34, and 42 years of age. Two patients presented with vaginal bleeding; the third presented with a cervical mass found incidentally during laparoscopy for an ectopic gestation. All 3 tumors were polypoid masses that distorted the cervix. Microscopically, they comprised cellular, fascicular, and storiform, plump spindle cells, with occasional rounded cells, and frequent mitoses (4-48/10 high power fields) in a myxoid stroma. All 3 cases showed entrapment of benign cervical glands. Inflammatory cell infiltrates, including plasma cells, were noted in all 3 tumors. One case had tumor cell necrosis, osteoid-like material, and osteoclast-like giant cells and showed lymphovascular invasion. Immunohistochemically, our cases showed patchy S100 (2/3) and CD34 (3/3) positivity. CD10 was positive in 2/3 cases. 3/3 cases showed pan-tropomyosin receptor kinase positivity (cytoplasmic). The NTRK-translocations demonstrated were: NTRK1::TMP3, NTRK1::TPR, and NTRK3::SPECC1L. Two of the patients had extensive disease and underwent chemotherapy. Larotrectinib was approved for one patient who demonstrated a striking reduction in tumor volume upon initiation of this treatment.
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BACKGROUND: People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against breakthrough SARS-CoV-2 infections in patients with cancer at a population level. METHODS: In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021. Adults (aged ≥18 years) with cancer in the UKCCEP registry were identified via Public Health England's Rapid Cancer Registration Dataset between Jan 1, 2018, and April 30, 2021, and comprised the cancer cohort. We constructed a control population cohort from adults with PCR tests in the UKCCEP registry who were not contained within the Rapid Cancer Registration Dataset. The coprimary endpoints were overall vaccine effectiveness against breakthrough infections after the second dose (positive PCR COVID-19 test) and vaccine effectiveness against breakthrough infections at 3-6 months after the second dose in the cancer cohort and control population. FINDINGS: The cancer cohort comprised 377 194 individuals, of whom 42 882 had breakthrough SARS-CoV-2 infections. The control population consisted of 28 010 955 individuals, of whom 5 748 708 had SARS-CoV-2 breakthrough infections. Overall vaccine effectiveness was 69·8% (95% CI 69·8-69·9) in the control population and 65·5% (65·1-65·9) in the cancer cohort. Vaccine effectiveness at 3-6 months was lower in the cancer cohort (47·0%, 46·3-47·6) than in the control population (61·4%, 61·4-61·5). INTERPRETATION: COVID-19 vaccination is effective for individuals with cancer, conferring varying levels of protection against breakthrough infections. However, vaccine effectiveness is lower in patients with cancer than in the general population. COVID-19 vaccination for patients with cancer should be used in conjunction with non-pharmacological strategies and community-based antiviral treatment programmes to reduce the risk that COVID-19 poses to patients with cancer. FUNDING: University of Oxford, University of Southampton, University of Birmingham, Department of Health and Social Care, and Blood Cancer UK.
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COVID-19 , Neoplasias , Vacinas Virais , Adolescente , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos de Casos e Controles , Humanos , Neoplasias/epidemiologia , SARS-CoV-2 , Eficácia de VacinasRESUMO
INTRODUCTION: Narrative approaches to assessment provide meaningful and valid representations of trainee performance. Yet, narratives are frequently perceived as vague, nonspecific and low quality. To date, there is little research examining factors associated with narrative evaluation quality, particularly in undergraduate medical education. The purpose of this study was to examine associations of faculty- and student-level characteristics with the quality of faculty member's narrative evaluations of clerkship students. METHODS: The authors reviewed faculty narrative evaluations of 50 students' clinical performance in their inpatient medicine and neurology clerkships, resulting in 165 and 87 unique evaluations in the respective clerkships. The authors evaluated narrative quality using the Narrative Evaluation Quality Instrument (NEQI). The authors used linear mixed effects modelling to predict total NEQI score. Explanatory covariates included the following: time to evaluation completion, number of weeks spent with student, faculty total weeks on service per year, total faculty years in clinical education, student gender, faculty gender, and an interaction term between student and faculty gender. RESULTS: Significantly higher narrative evaluation quality was associated with a shorter time to evaluation completion, with NEQI scores decreasing by approximately 0.3 points every 10 days following students' rotations (p = .004). Additionally, women faculty had statistically higher quality narrative evaluations with NEQI scores 1.92 points greater than men faculty (p = .012). All other covariates were not significant. CONCLUSIONS: The quality of faculty members' narrative evaluations of medical students was associated with time to evaluation completion and faculty gender but not faculty experience in clinical education, faculty weeks on service, or the amount of time spent with students. Findings advance understanding on ways to improve the quality of narrative evaluations which are imperative given assessment models that will increase the volume and reliance on narratives.
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Estágio Clínico , Educação de Graduação em Medicina , Estudantes de Medicina , Masculino , Feminino , Humanos , Faculdades de Medicina , Competência Clínica , Docentes de MedicinaRESUMO
BACKGROUND: Cancer cachexia causes significant morbidity and mortality in advanced lung cancer patients. Clinical benefit of ß-hydroxy-ß-methylbutyrate, arginine, and glutamine (HMB/Arg/Gln) was assessed in newly diagnosed patients. METHODS: NOURISH, a prospective, two-arm, open-label, multi-centre, randomised controlled phase II trial compared cachexia in patients who received HMB/Arg/Gln with those who did not. All patients received structured nutritional, exercise and symptom control via a Macmillan Durham Cachexia Pack. Conducted in five UK centres, patients aged > 18 years, with newly diagnosed advanced small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), who were able to take oral nutrition, with a performance status of 0-to-2 and a life expectancy > 4 months were eligible for trial entry. Patients suitable for treatment with curative intent were ineligible. The trial was designed as a signal-seeking pilot study with target recruitment of 96 patients. One-to-one randomisation was stratified by diagnosis (SCLC or NSCLC), stage of disease (locally advanced or metastatic) and performance status. The primary outcome measure was treatment success defined as a patient being alive without significant loss of lean body mass (not > 5%) by 12 weeks. Secondary outcome measures included quality of life. RESULTS: Between February-2012 and February-2013, 38 patients were recruited, 19 to each arm. Baseline characteristics were balanced. The trial was halted due to slow accrual and partial adherence. Trial data demonstrated no evidence of treatment benefit. No serious adverse events were reported during the trial. CONCLUSIONS: Further evaluation of HMB/Arg/Gln in this setting could not be recommended on the basis of this trial. CLINICAL TRIAL REGISTRATION: ISRCTN registry: 39911673; 14-Apr-2011 https://doi.org/10.1186/ISRCTN39911673 .
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Arginina/uso terapêutico , Caquexia/tratamento farmacológico , Glutamina/uso terapêutico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Arginina/farmacologia , Feminino , Glutamina/farmacologia , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
Outcomes of secondary cytoreduction surgery (SCS) were evaluated for morbidity, progression free survival (PFS) and overall survival (OS) and factors influencing results were explored. Retrospective analysis of all cases of SCS for epithelial ovarian cancer (EOC) was performed from October 2010 to December 2017. 62 patients were prospectively identified as candidates for SCS and 57 underwent SCS. 20(35%) patients required bowel resection/s, 24(42%) had nodal resections and 11(19%) had extensive upper abdominal surgery. 51(89%) achieved complete cytoreduction. After a median follow-up of 30 months (range 9-95 months), median PFS was 32 months (CI 17-76 months) and median OS has not reached. Seventeen patients have died and 32 have progressed. Three patients had Clavien-Dindo grade-3 and two had grade-4 morbidity. Patients who had multi-site recurrence had shorter median PFS (p = 0.04) and patients who required bowel resections had lower median OS (p = 0.009) compared to rest of the cohort.IMPACT STATEMENTWhat is already known on this subject? Retrospective studies have confirmed survival advantage for recurrence in epithelial ovarian cancer and recommend SCS for carefully selected patients. This finding is being evaluated in randomised control trials currently.What do the results of this study add? This study presents excellent results for survival outcomes after SCS and highlights importance of careful selection of patients with a goal to achieve complete cytoreduction. In addition, for the first time in literature, this study also explores various factors that may influence results and finds that there are no differences in survival outcomes whether these patients had early stage or advanced stage disease earlier. Patients who have multisite recurrence tend to have shorter PFS but no difference were noted for overall survival. Patients who have recurrence in bowels necessitating resection/s have a shorter median OS compared to rest of cohorts, however, still achieving a good survival time.What are the implications of these findings for clinical practice and/or further research? These findings will raise awareness for the clinicians and patients while discussing surgical outcomes and would set an achievable standard to improve cancer services. The pattern of recurrence and associated outcomes also point towards difference in biological nature of recurrent disease and could provide an opportunity for scientists to study the biological makeup of these recurrent tumours.
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Carcinoma Epitelial do Ovário/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Ovário/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Ovário/cirurgia , Intervalo Livre de Progressão , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
PURPOSE: Survival difference between socioeconomic groups with ovarian cancer has persisted in the United Kingdom despite efforts to reduce disparities in care. Our aim was to delineate critical episodes in the patient journey, where deprivation has most impact on survival. METHODS: A retrospective review of 834 patients with advanced ovarian cancer (AOC) between 16/8/07-16/2/17 at a large cancer centre serving one of the most deprived areas of the UK. Using the Index of Multiple Deprivation (IMD), patients were categorised into five groups. RESULTS: Surgery was more common in less deprived patients (p < 0.00001). Across IMD groups, there were no differences in complete (R0) cytoreduction rate (r = 0.18, p > 0.05), age, or comorbidity. The R0/total cohort rate increased with increasing IMD group (p < 0.0001). Patients refusing any intervention belonged exclusively to the three most deprived groups; 5/7 patients who refused surgery belonged to the most deprived IMD group. Overall survival in the total patient group was less in IMD group 1-2 compared to 9-10 (p = 0.002). On multivariate analysis, IMD group was not an independent predictor of survival (p > 0.05). CONCLUSIONS: Socioeconomic differences in survival manifest in patients not receiving surgical treatment for AOC and are not purely explained by comorbidity, age, stage, or histological factors.
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Neoplasias Ovarianas , Fatores Socioeconômicos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Estudos Retrospectivos , Análise de SobrevidaRESUMO
PURPOSE: Bias exists in the internal medicine (IM) clinical learning environment; however, it is unclear how often bias is identified by clerkship directors (CDs), how bias is addressed, and whether best practices exist for identifying or mitigating bias. This study investigated how IM CDs receive and respond to bias reports in the clinical learning environment. METHOD: In May 2021, the Clerkship Directors in Internal Medicine (CDIM) created an 18-question survey assessing the frequency of bias reports, macroaggressions and microaggressions, and report outcomes. Of the 152 U.S. medical schools that met study accreditation criteria, the final survey population included 137 CDs (90%) whose medical schools held valid CDIM membership. RESULTS: Of the 137 surveys sent, 100 were returned (survey response rate, 73%). Respondents reported a median of 3 bias events (interquartile range, 1-4; range, 0-50) on the IM clerkship in the past year. Among 76 respondents who reported 1 or more event, microaggressions represented 43 of the 75 total events (57%). No mechanism emerged as the most commonly used method for reporting bias. Race/ethnicity (48 of 75 [64%]) and gender (41 of 75 [55%]) were cited most as the basis for bias reports, whereas the most common sources of bias were student interactions with attending physicians (51 of 73 [70%]) and residents (40 of 73 [55%]). Of the 75 respondents, 53 (71%) described the frequency of bias event reports as having increased or remained unchanged during the past year. Only 48 CDs (49%) responded that they were "always" aware of the outcome of bias reports. CONCLUSIONS: Bias reports remain heterogeneous, are likely underreported, and lack best practice responses. There is a need to systematically capture bias events to work toward a just culture that fosters accountability and to identify bias events through more robust reporting.
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Estágio Clínico , Diretores Médicos , Humanos , Estados Unidos , Estágio Clínico/métodos , Inquéritos e Questionários , Aprendizagem , Medicina Interna/educaçãoRESUMO
Importance: Accurate identification of patient groups with the lowest level of protection following COVID-19 vaccination is important to better target resources and interventions for the most vulnerable populations. It is not known whether SARS-CoV-2 antibody testing has clinical utility for high-risk groups, such as people with cancer. Objective: To evaluate whether spike protein antibody vaccine response (COV-S) following COVID-19 vaccination is associated with the risk of SARS-CoV-2 breakthrough infection or hospitalization among patients with cancer. Design, Setting, and Participants: This was a population-based cross-sectional study of patients with cancer from the UK as part of the National COVID Cancer Antibody Survey. Adults with a known or reported cancer diagnosis who had completed their primary SARS-CoV-2 vaccination schedule were included. This analysis ran from September 1, 2021, to March 4, 2022, a period covering the expansion of the UK's third-dose vaccination booster program. Interventions: Anti-SARS-CoV-2 COV-S antibody test (Elecsys; Roche). Main Outcomes and Measures: Odds of SARS-CoV-2 breakthrough infection and COVID-19 hospitalization. Results: The evaluation comprised 4249 antibody test results from 3555 patients with cancer and 294â¯230 test results from 225â¯272 individuals in the noncancer population. The overall cohort of 228â¯827 individuals (patients with cancer and the noncancer population) comprised 298â¯479 antibody tests. The median age of the cohort was in the age band of 40 and 49 years and included 182â¯741 test results (61.22%) from women and 115â¯737 (38.78%) from men. There were 279â¯721 tests (93.72%) taken by individuals identifying as White or White British. Patients with cancer were more likely to have undetectable anti-S antibody responses than the general population (199 of 4249 test results [4.68%] vs 376 of 294â¯230 [0.13%]; P < .001). Patients with leukemia or lymphoma had the lowest antibody titers. In the cancer cohort, following multivariable correction, patients who had an undetectable antibody response were at much greater risk for SARS-CoV-2 breakthrough infection (odds ratio [OR], 3.05; 95% CI, 1.96-4.72; P < .001) and SARS-CoV-2-related hospitalization (OR, 6.48; 95% CI, 3.31-12.67; P < .001) than individuals who had a positive antibody response. Conclusions and Relevance: The findings of this cross-sectional study suggest that COV-S antibody testing allows the identification of patients with cancer who have the lowest level of antibody-derived protection from COVID-19. This study supports larger evaluations of SARS-CoV-2 antibody testing. Prevention of SARS-CoV-2 transmission to patients with cancer should be prioritized to minimize impact on cancer treatments and maximize quality of life for individuals with cancer during the ongoing pandemic.
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COVID-19 , Neoplasias , Vacinas , Feminino , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Vacinas contra COVID-19 , Glicoproteína da Espícula de Coronavírus , Estudos Transversais , Formação de Anticorpos , Qualidade de Vida , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Neoplasias/epidemiologia , Anticorpos Antivirais , Atenção à SaúdeRESUMO
Patients with cancer are at increased risk of hospitalisation and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the SARS-CoV-2 phenotype evolution in patients with cancer since 2020 has not previously been described. We therefore evaluated SARS-CoV-2 on a UK populationscale from 01/11/2020-31/08/2022, assessing case-outcome rates of hospital assessment(s), intensive care admission and mortality. We observed that the SARS-CoV-2 disease phenotype has become less severe in patients with cancer and the non-cancer population. Case-hospitalisation rates for patients with cancer dropped from 30.58% in early 2021 to 7.45% in 2022 while case-mortality rates decreased from 20.53% to 3.25%. However, the risk of hospitalisation and mortality remains 2.10x and 2.54x higher in patients with cancer, respectively. Overall, the SARS-CoV-2 disease phenotype is less severe in 2022 compared to 2020 but patients with cancer remain at higher risk than the non-cancer population. Patients with cancer must therefore be empowered to live more normal lives, to see loved ones and families, while also being safeguarded with expanded measures to reduce the risk of transmission.
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COVID-19 , Neoplasias , Humanos , Masculino , Feminino , Estudos de Casos e Controles , Resultado do Tratamento , Neoplasias/complicações , Neoplasias/epidemiologia , COVID-19/complicações , COVID-19/epidemiologia , Inglaterra/epidemiologia , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou maisRESUMO
PURPOSE: People living with cancer and haematological malignancies are at an increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2. Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated. METHODS: This study is a population-scale real-world evaluation of the United Kingdom's third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England's national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess the third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population. RESULTS: The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5%, respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Patients with lymphoma had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at an increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01, respectively. p < 0.001 for both). CONCLUSIONS: Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous and lower than the general population. Many patients with cancer will remain at the increased risk of coronavirus infections even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit the disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic.
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COVID-19 , Neoplasias , COVID-19/epidemiologia , COVID-19/prevenção & controle , Hospitalização , Humanos , Pandemias , Vacinação , Eficácia de VacinasRESUMO
Lung and bladder cancers are mostly incurable because of the early development of drug resistance and metastatic dissemination. Hence, improved therapies that tackle these two processes are urgently needed to improve clinical outcome. We have identified RSK4 as a promoter of drug resistance and metastasis in lung and bladder cancer cells. Silencing this kinase, through either RNA interference or CRISPR, sensitized tumor cells to chemotherapy and hindered metastasis in vitro and in vivo in a tail vein injection model. Drug screening revealed several floxacin antibiotics as potent RSK4 activation inhibitors, and trovafloxacin reproduced all effects of RSK4 silencing in vitro and in/ex vivo using lung cancer xenograft and genetically engineered mouse models and bladder tumor explants. Through x-ray structure determination and Markov transient and Deuterium exchange analyses, we identified the allosteric binding site and revealed how this compound blocks RSK4 kinase activation through binding to an allosteric site and mimicking a kinase autoinhibitory mechanism involving the RSK4's hydrophobic motif. Last, we show that patients undergoing chemotherapy and adhering to prophylactic levofloxacin in the large placebo-controlled randomized phase 3 SIGNIFICANT trial had significantly increased (P = 0.048) long-term overall survival times. Hence, we suggest that RSK4 inhibition may represent an effective therapeutic strategy for treating lung and bladder cancer.
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Neoplasias Pulmonares , Neoplasias da Bexiga Urinária , Animais , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Humanos , Pulmão/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Camundongos , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genéticaRESUMO
PURPOSE OF REVIEW: Febrile neutropenia causes significant morbidity and mortality in patients receiving antineoplastic chemotherapy. Antibiotic prophylaxis reduces the incidence of fever during chemotherapy, but its routine use remains controversial for patients at low risk of neutropenic infection. This article reviews recent research to clarify the issue. RECENT FINDINGS: Randomized controlled trials and meta-analyses demonstrate that antibiotic prophylaxis reduces the incidence of febrile neutropenia and infection-related mortality both in patients receiving high-dose chemotherapy and in those receiving moderately myelosuppressive chemotherapy for solid tumours. The evidence that antibiotic prophylaxis results in adverse patient outcomes, through colonization or infection with resistant microorganisms is limited and unconvincing. Retrospective reanalysis of trial data indicates that for patients on moderately myelosuppressive out-patient chemotherapy, the greatest risk of infection and the greatest prophylactic benefit is on the first cycle. SUMMARY: Current guidelines recommend that antibiotic prophylaxis is considered in all patients at high and intermediate risk of febrile neutropenia. Clinical evidence now also supports antibiotic prophylaxis for low-risk patients. The impact of antibiotic prophylaxis during cyclical out-patient chemotherapy on microbial resistance should be determined. The hypothesis that, for low-risk patients, prophylaxis should be targeted to first chemotherapy cycles to retain efficacy but limit antibiotic exposure should be tested.
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Antibacterianos/uso terapêutico , Neutropenia/prevenção & controle , Antibioticoprofilaxia , Antineoplásicos/efeitos adversos , Febre/etiologia , Humanos , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Resultado do TratamentoRESUMO
Hospitalist educators face a number of challenges in teaching clinical reasoning to residents and medical students. Helping to develop trainees' clinical acumen is an essential and highly nuanced process, yet complex patients, documentation requirements, and productivity goals compete with teaching time. Workplace-based assessment is particularly important for residents with the institution of the developmental milestones for meeting Accreditation Council for Graduate Medical Education competencies. Two frameworks for facilitating the clinical reasoning discussion-the One-Minute Preceptor preceptor and SNAPPS-have been well studied in the outpatient setting with positive results. Both models show promise for use in the inpatient teaching environment with little modification. This narrative review compares and contrasts these 2 teaching frameworks and discusses their application to the inpatient teaching environment. These models can provide opportunities for hospitalist educators to better assess trainees, integrate regular feedback, and encourage self-directed learning. These teaching frameworks can also allow hospitalists to provide more focused education to trainees without taking additional valuable time.
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Estágio Clínico/métodos , Internato e Residência/métodos , Modelos Educacionais , Preceptoria/métodos , Estudantes de Medicina , Ensino/métodos , Estágio Clínico/normas , Competência Clínica/normas , Médicos Hospitalares/normas , Humanos , Internato e Residência/normasRESUMO
AIM: Temsirolimus has shown efficacy as first-line treatment of patients with metastatic renal cell carcinoma and poor prognostic features. The efficacy of temsirolimus in other clinical settings, such as second-line therapy, is unclear. The aim of this study was to investigate the outcomes of an unselected group of patients with renal cancer treated with temsirolimus in a compassionate use program. PATIENTS AND METHODS: This retrospective analysis included all patients receiving temsirolimus at a tertiary referral center between November 2007 and October 2008. Information was obtained through review of patient notes, electronic records, and pharmacy records. Baseline characteristics, prognostic features, and previous treatments were recorded for all patients. Outcome measures were response rate, progression-free survival (PFS), overall survival (OS), and toxicities. RESULTS: Thirty-eight patients were included in the analysis, with median age of 62 years, among whom 37% were untreated and 63% had received one or more previous treatments. Thirty-four percent of the patients had three or more poor prognostic factors. Four patients (11%) achieved a partial response (PR); in all four of these patients, the PR was confirmed by two subsequent computed tomography (CT) scans, and in one patient, the PR lasted for more than 18 months. A total of 34% achieved stable disease, and 50% had disease progression. Median OS was 7.6 months (95% confidence interval [CI] 4.8-10.5), and median PFS was 3.2 months (95% CI 1.0-5.5). Patients with two or fewer poor prognostic factors had a survival of 10.12 months compared with 5.03 months of those with three or more. Median survival was 14.9 months for untreated patients and 6.4 months for previously treated patients. CONCLUSION: Our results indicate some efficacy of temsirolimus in untreated patients with renal tumors and poor-intermediate prognosis, although the limitations of small sample size and retrospective nature must be taken into account. The role of temsirolimus in previously treated patients remains controversial given the recently published results of the INTORSECT trial and the discrepancies between the few published series.
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Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Ensaios de Uso Compassivo , Neoplasias Renais/tratamento farmacológico , Sirolimo/análogos & derivados , Centros de Atenção Terciária , Administração Intravenosa , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/diagnóstico , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/secundário , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Sirolimo/uso terapêutico , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE OF REVIEW: Febrile neutropenia causes significant morbidity and mortality in patients receiving cytotoxic chemotherapy. Antibiotic and granulocyte colony stimulating factor prophylaxis reduce the incidence of febrile neutropenia but uncertainty remains regarding their role in clinical practice. We review recent literature to clarify the issue. RECENT FINDINGS: Recent research confirms that prophylactic antibiotics decrease febrile neutropenia and infection-related mortality in acute leukaemia patients and those receiving high dose chemotherapy. Fluoroquinolone prophylaxis also decreases the incidence of febrile neutropenia and all-cause mortality in the first cycle of moderately myelosuppressive chemotherapy for solid tumours. There is no convincing evidence that colonization of individuals with resistant organisms due to antibiotic prophylaxis increases febrile neutropenia or mortality. Granulocyte colony stimulating factor prophylaxis reduces infection-related mortality in patients with greater than 20% risk of febrile neutropenia. SUMMARY: Antibiotic prophylaxis should be offered to patients receiving chemotherapy for acute leukaemia and high dose chemotherapy for solid tumours. It should also be offered to those receiving moderately myelosuppressive chemotherapy for solid tumours and lymphomas during the first cycle of chemotherapy. Prophylactic granulocyte colony stimulating factor is indicated for patients at greater than 20% risk of febrile neutropenia. Further research is indicated to determine whether combining granulocyte colony stimulating factor and antibiotic prophylaxis causes a further reduction in infection-related mortality.