The historic term ‘histiocytosis’ meaning ‘tissue cell’ is used as a unifying concept for disease... more The historic term ‘histiocytosis’ meaning ‘tissue cell’ is used as a unifying concept for diseases characterized by pathogenic myeloid cells that share histological features with macrophages or dendritic cells. These cells may arise from the embryonic yolk sac, fetal liver or postnatal bone marrow. Prior classification schemes align disease designation with terminal phenotype: for example, Langerhans cell histiocytosis (LCH) shares CD207 + antigen with physiological epidermal Langerhans cells. LCH, Erdheim–Chester disease (ECD), juvenile xanthogranuloma (JXG) and Rosai–Dorfman disease (RDD) are all characterized by pathological ERK activation driven by activating somatic mutations in MAPK pathway genes. The title of this Primer (Histiocytic disorders) was chosen to differentiate the above diseases from Langerhans cell sarcoma and malignant histiocytosis, which are hyperproliferative lesions typical of cancer. By comparison LCH, ECD, RDD and JXG share some features of malignant cells including activating MAPK pathway mutations, but are not hyperproliferative. ‘Inflammatory myeloproliferative neoplasm’ may be a more precise nomenclature. By contrast, haemophagocytic lymphohistiocytosis is associated with macrophage activation and extreme inflammation, and represents a syndrome of immune dysregulation. These diseases affect children and adults in varying proportions depending on which of the entities is involved. Histiocytic disorders are characterized by proliferation of cells with macrophage or dendritic cell phenotype and intense inflammation. Clinical signs and symptoms depend on the specific disease and the tissues and organs affected.
Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents. The etiology... more Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents. The etiology of OS is largely unknown but may be informed by comparisons of incidence and trends between geographic regions. Using the Cancer Incidence in Five Continents (CI5) data from 1988 to 2012, we present OS age‐standardized incidence rates (ASRs; cases/million) and average annual percent change (AAPC) and 95% confidence interval (CI) by geographic region among the age groups 0‐9, 10‐19, 20‐29, 30‐59, 60‐79, 0‐79. Among the 10‐19 age group, we also used the most recent data (2008‐2012) to present the ASRs for each country. We observed little variation in OS incidence between geographic regions in 2008‐2012 across all age groups. Overall, the ASR for 0‐79 ranged from 2 cases per million in Southern Asia to 4.2 in Sub‐Saharan Africa. A bimodal distribution in incidence was observed with peaks in the 10‐19 and 60‐79 age groups across all regions over time. Overall, OS incidence was relatively stable across 1988‐2012 with the only statistically significant increases in the 0‐79 age group observed in Eastern Asia (AAPC: 1.8; 95% CI: 0.6, 1.9) and Sub‐Saharan Africa (AAPC: 3.1; 95% CI: 0.5, 5.8). The small variation in incidence between regions and the stability in incidence over time suggests that OS carcinogenesis is not influenced by environmental or time‐varying exposures.
Background Heterogeneity in COVID-19 morbidity and mortality is often associated with a country&#... more Background Heterogeneity in COVID-19 morbidity and mortality is often associated with a country's health-services structure and social inequality. This study aimed to characterize social inequalities in COVID-19 mortality in São Paulo, the most populous city in Brazil and Latin America. Methods We conducted a population-based study, including COVID-19 deaths among São Paulo residents from March to September 2020. Age-standardized mortality rates and unadjusted rate ratios (RRs) [with corresponding 95% confidence intervals (CIs)] were estimated by race, sex, age group, district of residence, household crowding, educational attainment, income level and percentage of households in subnormal areas in each district. Time trends in mortality were assessed using the Joinpoint model. Results Males presented an 84% increase in COVID-19 mortality compared with females (RR = 1.84, 95% CI 1.79–1.90). Higher mortality rates were observed for Blacks (RR = 1.77, 95% CI 1.67–1.88) and mixed (RR...
Background: Modern therapeutic advances in high-risk neuroblastoma have improved overall survival... more Background: Modern therapeutic advances in high-risk neuroblastoma have improved overall survival (OS), but it is unclear whether these survival gains have been equitable. This study sought to examine the relationship between socioeconomic status (SES) and OS in children with high-risk neuroblastoma, and to investigate whether SES-associated disparities have changed over time. Procedure: In this population-based cohort study, children <18 years diagnosed with high-risk neuroblastoma (diagnosis at age ≥12 months with metastatic disease) from 1991-2015 were identified through the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. Associations of county-level SES variables and OS were tested with univariate Cox proportional hazards regression. For a sub-cohort diagnosed after 2007, insurance status was examined as an individual-level SES variable. Multivariable regression analyses with treatment era and interaction terms were performed when SES variabl...
OBJETIVO: Investigar os fatores associados ao óbito domiciliar entre idosos que morreram por cânc... more OBJETIVO: Investigar os fatores associados ao óbito domiciliar entre idosos que morreram por câncer em uma cidade de grande porte. MÉTODOS: Estudo descritivo, incluindo todos os óbitos por câncer (CID C00-C97) ocorridos entre 2006 e 2012, entre residentes do município de São Paulo com 60 anos de idade ou mais. A fonte de dados foi o Sistema de Informações de Mortalidade e a proporção de óbitos foi estimada segundo local, sexo, faixa etária, raça/cor, escolaridade, estado civil, tipo de câncer, disponibilidade de leitos hospitalares e ano do óbito. O teste qui-quadrado foi utilizado para investigar as associações entre o local do óbito e as variáveis sociodemográficas e clínicas. A regressão logística foi empregada para identificar fatores associados à morte domiciliar. Foram estimadas as razões de chance brutas e ajustadas e os intervalos de confiança de 95%. RESULTADOS: A maioria dos óbitos ocorreu em hospitais (88,2%). Houve associação significativa entre o local de óbito e as seg...
Handovers are associated with medical errors, and our primary objective is to identify missed dia... more Handovers are associated with medical errors, and our primary objective is to identify missed diagnosis and goals immediately after a shift handover. Our secondary objective is to assess clinicians' diagnostic accuracy in anticipating clinical events during the night shift. Single-center prospective observational cohort study. Thirty-bed tertiary ICU in Sao Paulo, Brazil. Three-hundred fifty-two patient encounters over 44 day-to-night handovers. None. We used a multimethods approach to measure transmission of information among staff physicians on diagnoses and goals for the night shift. We surveyed clinicians immediately after a handover and identified clinical events through chart abstractions and interviews with clinicians the next morning. Nighttime clinicians correctly identified 454 of 857 diagnoses (53%; 95% CI 50-56) and 123 of 304 goals (40%; 95% CI, 35-46). Daytime clinicians were more sensitive (65% vs 46%; p < 0.01) but less specific (82% vs 91%; p < 0.01) than ...
IMPORTANCE Most children with retinoblastoma in the United States are diagnosed as having a large... more IMPORTANCE Most children with retinoblastoma in the United States are diagnosed as having a large intraocular tumor burden that requires intensive ocular-salvage treatment or enucleation. OBJECTIVE To investigate the effect of socioeconomic status, race, and ethnicity on the extent of disease and the outcomes of retinoblastoma.
The evaluation of a cancer patient can be affected by many factors. Cancer patients often have ot... more The evaluation of a cancer patient can be affected by many factors. Cancer patients often have other diseases or medical conditions in addition to their cancer. These conditions are referred to as comorbidities. They can influence the treatment option, the rate of complications, the outcome, and can confound the survival analysis. It was the aim of this study to measure comorbidities in patients with laryngeal squamous cell carcinoma. Ninety adult patients treated for newly diagnosed laryngeal squamous cell carcinoma were studied. We measured comorbid illness applying the following validated scales: the Cumulative Illness Rating Scale (CIRS), the Kaplan-Feinstein Classification (KFC), the Charlson index, the Index of Coexistent Disease (ICED), the Adult Comorbidity Evaluation-27 (ACE-27), the Alcohol-Tobacco-Related Comorbidities Index (ATC), and the Washington University Head and Neck Comorbidity Index (WUHNCI). Survival analysis was performed using the Kaplan-Meier method (with the log-rank test value being used to compare groups). The Cox proportional hazards model was chosen to identify independent prognostic factors. The mean age was 62.3 years. The majority of patients (36.7%) had early tumors. Forty patients were treated by surgery only, while the remaining 49 patients also received postoperative radiation therapy. Only 5 patients (5.6%) were lost to follow-up. Median follow-up time was 42.5 months. The 4-year overall survival was 63%. There was a statistically significant difference between survival rates according to clinical stage (CS I 87.3%, CS II 48.9%, CS III 74.7%, CS IV 23.9%; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Patients treated by surgery only presented a better survival rate (79.6%) than those receiving postoperative radiation therapy (48.9%; p = 0.001). A statistically significant difference in survival rates was also noted when patients were analyzed according to the type of surgical procedure. In a univariate analysis, comorbidity had impact on prognosis, no matter which scale was utilized: CIRS (p = 0.008), ACE-27 (p = 0.010), ATC (p = 0.004), WUHNCI (p = 0.003), Charlson index (p = 0.020), KFC (p = 0.001), and ICED (p = 0.010). However, in the multivariate analysis, only CIRS and TNM staging were identified as independent prognostic factors. The comorbidity is an independent prognostic factor in patients with surgically treated laryngeal cancer. In the univariate analysis, all indexes were able to stratify patients. However, in the multiple analysis, only the CIRS was predictive of death. Comorbidities are an important factor in the analysis of overall survival.
Understanding the physiological function of the cellular prion (PrP c) depends on the investigati... more Understanding the physiological function of the cellular prion (PrP c) depends on the investigation of PrP c-interacting proteins. Stressinducible protein 1 (STI1) is a specific PrP c ligand that promotes neuroprotection of retinal neurons through cAMP-dependent protein kinase A (PKA). Here, we examined the signaling pathways and functional consequences of the PrP c interaction with STI1 in hippocampal neurons. Both PrP c and STI1 are abundantly expressed and highly colocalized in the hippocampus in situ, indicating that they can interact in vivo. Recombinant STI1 (His 6-STI1) added to hippocampal cultures interacts with PrP c at the neuronal surface and elicits neuritogenesis in wild-type neurons but not in PrP c-null cells. This effect was abolished by antibodies against either PrP c or STI1 and was dependent on the STI1 domain that binds PrP c. Binding of these proteins induced the phosphorylation/activation of the mitogenactivated protein kinase, which was essential for STI1-promoted neuritogenesis. His 6-STI1, but not its counterpart lacking the PrP c binding site, prevented cell death via PKA activation. These results demonstrate that two parallel effects of the PrP c-STI1 interaction, neuritogenesis and neuroprotection, are mediated by distinct signaling pathways.
To describe the clinical characteristics and estimate the survival of children and adolescents wi... more To describe the clinical characteristics and estimate the survival of children and adolescents with germ cell tumors treated with cisplatin-based combination chemotherapy according to three different protocols in Brazil. From 1983 to 1997, 106 patients were treated at the Hospital do Cancer, Sao Paulo for a diagnosis of germ cell tumor. We performed a retrospective review of the clinical and histopathological data to identify prognostic factors and evaluate their outcome. Patients were treated with only surgery (n = 32), surgery and radiotherapy (n = 1) and chemotherapy (n = 73). From 1983 to 1986 (period I), there were 30 patients and 21 received chemotherapy according to the modified VAB-6 protocol. Twenty-two of 35 patients registered between 1987 and 1991 (period II) were treated with EPO/VAC combination chemotherapy. From 1991 to 1997 (period III), there were 41 patients and 31 received chemotherapy according to the Brazilian TCG-91 protocol. Important prognostic factors included stage (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), metastatic status (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and surgical procedure at diagnosis (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). An incremental improvement in outcomes was noted across the periods of treatment (P = 0.070). Five-year OS was respectively 42.9 +/- 10.8%, 53.9 +/- 11.4% and 80.6 +/- 7.1% for periods I, II, and III for the patients who received chemotherapy. An improvement in the survival of children with germ cell tumors was achieved in the most recent trial (TCG-91) with a risk adapted approach incorporating only cisplatin and etoposide. These results indicate that in selected patients complex three-agent regimens may not be necessary to achieve long term survival.
Hodgkin and Reed-Sternberg (H-RS) cells of classical Hodgkin lymphoma (cHL) present an impaired e... more Hodgkin and Reed-Sternberg (H-RS) cells of classical Hodgkin lymphoma (cHL) present an impaired expression of immunoglobulin genes, but escape apoptotic death. We investigated whether nitric oxide synthases (NOS) are expressed by H-RS cells, studied their association with EBV status and the expression of apoptotic proteins, and investigated their relationship to the clinical outcome of 171 patients. NOS1 and NOS2 were expressed in a large number of cases, whereas NOS3 expression was not detected. Positive associations were found between NOS1 and p53, bax and NOS2, bcl-2 and NOS2, bax and p53, and between bax and fasL. Inverse correlations were established between EBV and NOS2 and between EBV and bcl-2. A shorter overall survival (OS) was associated with strong expression of NOS2. In conclusion, NOS are expressed by H-RS cells of cHL.
Purpose In 1988, we formed a consortium of Brazilian institutions to develop uniform standards fo... more Purpose In 1988, we formed a consortium of Brazilian institutions to develop uniform standards for the diagnostic assessment and multidisciplinary treatment of children and adolescents with germ cell tumors. We also implemented the first childhood Brazilian germ cell tumor protocol, GCT-91, evaluating two-agent chemotherapy with cisplatin and etoposide (PE). We now report on the clinical characteristics and survival of children and adolescents with germ cell tumors treated on this protocol. Patients and Methods From May 1991 to April 2000, 115 patients (106 assessable patients) were enrolled onto the Brazilian protocol with a diagnosis of germ cell tumor. Results Patients were treated with surgery only (n = 35) and chemotherapy (n = 71). Important prognostic factors included stage (P = .025), surgical procedure at diagnosis according to resectability (P < .032), and abnormal lactate dehydrogenase value at diagnosis (P < .001). Conclusion The improvement in survival by the intr...
The physiological functions of the cellular prion protein, PrPC, as a cell surface pleiotropic re... more The physiological functions of the cellular prion protein, PrPC, as a cell surface pleiotropic receptor are under debate. We report that PrPC interacts with vitronectin but not with fibronectin or collagen. The binding sites mediating this PrPC-vitronectin interaction were mapped to residues 105-119 of PrPC and the residues 307-320 of vitronectin. The two proteins were co-localized in embryonic dorsal root ganglia from wild-type mice. Vitronectin addition to cultured dorsal root ganglia induced axonal growth, which could be mimicked by vitronectin peptide 307-320 and abrogated by anti-PrPC antibodies. Full-length vitronectin, but not the vitronectin peptide 307-320, induced axonal growth of dorsal root neurons from two strains of PrPC-null mice. Functional assays demonstrated that relative to wild-type cells, PrPC-null dorsal root neurons were more responsive to the Arg-Gly-Asp peptide (an integrin-binding site), and exhibited greater αvβ3 activity. Our findings indicate that PrPC p...
To investigate the association of childhood ALL and SES, we collected data on 507 children aged 0... more To investigate the association of childhood ALL and SES, we collected data on 507 children aged 0-14 years diagnosed with ALL between 1997 and 2002 from the population-based Cancer Registry of São Paulo, Brazil, covering 96 districts. Each child was assigned to an SES category based on the district of residence at diagnosis. Four SES categories were created from high to low, based on the Social Exclusion Index (SEI) that includes the following indicators: poverty, employment, inequality, education and violence. Using Census data, cases were also classified into quintiles according to the percentage of households with more than 7 persons. Age-specific and age-standardized incidence rates were calculated using the 1960 world standard population. Age-adjusted incidence rate was 3.68/100,000 for males and 2.87/100,000 for females. Children living in areas with lowest SES presented a significant lower risk of ALL compared with those living in the wealthiest districts (Rate Ratio [RR] 5 0.34; 95% Confidence Interval [CI] 5 0.28-0.44). Lower incidence rates of childhood ALL were also found in areas with high percentages of households with more than 7 persons (!5.7%) compared with areas where there were 2.2% (RR 5 0.32, 95% CI 0.25-0.43). There was a strong correlation between SEI and crowding (rho 5 20.95, p < 0.001). Population-based attributes for SES and household size may be useful surrogate markers of early exposure to childhood infections, which has been found to decrease the risk of ALL.
The historic term ‘histiocytosis’ meaning ‘tissue cell’ is used as a unifying concept for disease... more The historic term ‘histiocytosis’ meaning ‘tissue cell’ is used as a unifying concept for diseases characterized by pathogenic myeloid cells that share histological features with macrophages or dendritic cells. These cells may arise from the embryonic yolk sac, fetal liver or postnatal bone marrow. Prior classification schemes align disease designation with terminal phenotype: for example, Langerhans cell histiocytosis (LCH) shares CD207 + antigen with physiological epidermal Langerhans cells. LCH, Erdheim–Chester disease (ECD), juvenile xanthogranuloma (JXG) and Rosai–Dorfman disease (RDD) are all characterized by pathological ERK activation driven by activating somatic mutations in MAPK pathway genes. The title of this Primer (Histiocytic disorders) was chosen to differentiate the above diseases from Langerhans cell sarcoma and malignant histiocytosis, which are hyperproliferative lesions typical of cancer. By comparison LCH, ECD, RDD and JXG share some features of malignant cells including activating MAPK pathway mutations, but are not hyperproliferative. ‘Inflammatory myeloproliferative neoplasm’ may be a more precise nomenclature. By contrast, haemophagocytic lymphohistiocytosis is associated with macrophage activation and extreme inflammation, and represents a syndrome of immune dysregulation. These diseases affect children and adults in varying proportions depending on which of the entities is involved. Histiocytic disorders are characterized by proliferation of cells with macrophage or dendritic cell phenotype and intense inflammation. Clinical signs and symptoms depend on the specific disease and the tissues and organs affected.
Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents. The etiology... more Osteosarcoma (OS) is the most common primary bone tumor in children and adolescents. The etiology of OS is largely unknown but may be informed by comparisons of incidence and trends between geographic regions. Using the Cancer Incidence in Five Continents (CI5) data from 1988 to 2012, we present OS age‐standardized incidence rates (ASRs; cases/million) and average annual percent change (AAPC) and 95% confidence interval (CI) by geographic region among the age groups 0‐9, 10‐19, 20‐29, 30‐59, 60‐79, 0‐79. Among the 10‐19 age group, we also used the most recent data (2008‐2012) to present the ASRs for each country. We observed little variation in OS incidence between geographic regions in 2008‐2012 across all age groups. Overall, the ASR for 0‐79 ranged from 2 cases per million in Southern Asia to 4.2 in Sub‐Saharan Africa. A bimodal distribution in incidence was observed with peaks in the 10‐19 and 60‐79 age groups across all regions over time. Overall, OS incidence was relatively stable across 1988‐2012 with the only statistically significant increases in the 0‐79 age group observed in Eastern Asia (AAPC: 1.8; 95% CI: 0.6, 1.9) and Sub‐Saharan Africa (AAPC: 3.1; 95% CI: 0.5, 5.8). The small variation in incidence between regions and the stability in incidence over time suggests that OS carcinogenesis is not influenced by environmental or time‐varying exposures.
Background Heterogeneity in COVID-19 morbidity and mortality is often associated with a country&#... more Background Heterogeneity in COVID-19 morbidity and mortality is often associated with a country's health-services structure and social inequality. This study aimed to characterize social inequalities in COVID-19 mortality in São Paulo, the most populous city in Brazil and Latin America. Methods We conducted a population-based study, including COVID-19 deaths among São Paulo residents from March to September 2020. Age-standardized mortality rates and unadjusted rate ratios (RRs) [with corresponding 95% confidence intervals (CIs)] were estimated by race, sex, age group, district of residence, household crowding, educational attainment, income level and percentage of households in subnormal areas in each district. Time trends in mortality were assessed using the Joinpoint model. Results Males presented an 84% increase in COVID-19 mortality compared with females (RR = 1.84, 95% CI 1.79–1.90). Higher mortality rates were observed for Blacks (RR = 1.77, 95% CI 1.67–1.88) and mixed (RR...
Background: Modern therapeutic advances in high-risk neuroblastoma have improved overall survival... more Background: Modern therapeutic advances in high-risk neuroblastoma have improved overall survival (OS), but it is unclear whether these survival gains have been equitable. This study sought to examine the relationship between socioeconomic status (SES) and OS in children with high-risk neuroblastoma, and to investigate whether SES-associated disparities have changed over time. Procedure: In this population-based cohort study, children <18 years diagnosed with high-risk neuroblastoma (diagnosis at age ≥12 months with metastatic disease) from 1991-2015 were identified through the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. Associations of county-level SES variables and OS were tested with univariate Cox proportional hazards regression. For a sub-cohort diagnosed after 2007, insurance status was examined as an individual-level SES variable. Multivariable regression analyses with treatment era and interaction terms were performed when SES variabl...
OBJETIVO: Investigar os fatores associados ao óbito domiciliar entre idosos que morreram por cânc... more OBJETIVO: Investigar os fatores associados ao óbito domiciliar entre idosos que morreram por câncer em uma cidade de grande porte. MÉTODOS: Estudo descritivo, incluindo todos os óbitos por câncer (CID C00-C97) ocorridos entre 2006 e 2012, entre residentes do município de São Paulo com 60 anos de idade ou mais. A fonte de dados foi o Sistema de Informações de Mortalidade e a proporção de óbitos foi estimada segundo local, sexo, faixa etária, raça/cor, escolaridade, estado civil, tipo de câncer, disponibilidade de leitos hospitalares e ano do óbito. O teste qui-quadrado foi utilizado para investigar as associações entre o local do óbito e as variáveis sociodemográficas e clínicas. A regressão logística foi empregada para identificar fatores associados à morte domiciliar. Foram estimadas as razões de chance brutas e ajustadas e os intervalos de confiança de 95%. RESULTADOS: A maioria dos óbitos ocorreu em hospitais (88,2%). Houve associação significativa entre o local de óbito e as seg...
Handovers are associated with medical errors, and our primary objective is to identify missed dia... more Handovers are associated with medical errors, and our primary objective is to identify missed diagnosis and goals immediately after a shift handover. Our secondary objective is to assess clinicians' diagnostic accuracy in anticipating clinical events during the night shift. Single-center prospective observational cohort study. Thirty-bed tertiary ICU in Sao Paulo, Brazil. Three-hundred fifty-two patient encounters over 44 day-to-night handovers. None. We used a multimethods approach to measure transmission of information among staff physicians on diagnoses and goals for the night shift. We surveyed clinicians immediately after a handover and identified clinical events through chart abstractions and interviews with clinicians the next morning. Nighttime clinicians correctly identified 454 of 857 diagnoses (53%; 95% CI 50-56) and 123 of 304 goals (40%; 95% CI, 35-46). Daytime clinicians were more sensitive (65% vs 46%; p < 0.01) but less specific (82% vs 91%; p < 0.01) than ...
IMPORTANCE Most children with retinoblastoma in the United States are diagnosed as having a large... more IMPORTANCE Most children with retinoblastoma in the United States are diagnosed as having a large intraocular tumor burden that requires intensive ocular-salvage treatment or enucleation. OBJECTIVE To investigate the effect of socioeconomic status, race, and ethnicity on the extent of disease and the outcomes of retinoblastoma.
The evaluation of a cancer patient can be affected by many factors. Cancer patients often have ot... more The evaluation of a cancer patient can be affected by many factors. Cancer patients often have other diseases or medical conditions in addition to their cancer. These conditions are referred to as comorbidities. They can influence the treatment option, the rate of complications, the outcome, and can confound the survival analysis. It was the aim of this study to measure comorbidities in patients with laryngeal squamous cell carcinoma. Ninety adult patients treated for newly diagnosed laryngeal squamous cell carcinoma were studied. We measured comorbid illness applying the following validated scales: the Cumulative Illness Rating Scale (CIRS), the Kaplan-Feinstein Classification (KFC), the Charlson index, the Index of Coexistent Disease (ICED), the Adult Comorbidity Evaluation-27 (ACE-27), the Alcohol-Tobacco-Related Comorbidities Index (ATC), and the Washington University Head and Neck Comorbidity Index (WUHNCI). Survival analysis was performed using the Kaplan-Meier method (with the log-rank test value being used to compare groups). The Cox proportional hazards model was chosen to identify independent prognostic factors. The mean age was 62.3 years. The majority of patients (36.7%) had early tumors. Forty patients were treated by surgery only, while the remaining 49 patients also received postoperative radiation therapy. Only 5 patients (5.6%) were lost to follow-up. Median follow-up time was 42.5 months. The 4-year overall survival was 63%. There was a statistically significant difference between survival rates according to clinical stage (CS I 87.3%, CS II 48.9%, CS III 74.7%, CS IV 23.9%; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Patients treated by surgery only presented a better survival rate (79.6%) than those receiving postoperative radiation therapy (48.9%; p = 0.001). A statistically significant difference in survival rates was also noted when patients were analyzed according to the type of surgical procedure. In a univariate analysis, comorbidity had impact on prognosis, no matter which scale was utilized: CIRS (p = 0.008), ACE-27 (p = 0.010), ATC (p = 0.004), WUHNCI (p = 0.003), Charlson index (p = 0.020), KFC (p = 0.001), and ICED (p = 0.010). However, in the multivariate analysis, only CIRS and TNM staging were identified as independent prognostic factors. The comorbidity is an independent prognostic factor in patients with surgically treated laryngeal cancer. In the univariate analysis, all indexes were able to stratify patients. However, in the multiple analysis, only the CIRS was predictive of death. Comorbidities are an important factor in the analysis of overall survival.
Understanding the physiological function of the cellular prion (PrP c) depends on the investigati... more Understanding the physiological function of the cellular prion (PrP c) depends on the investigation of PrP c-interacting proteins. Stressinducible protein 1 (STI1) is a specific PrP c ligand that promotes neuroprotection of retinal neurons through cAMP-dependent protein kinase A (PKA). Here, we examined the signaling pathways and functional consequences of the PrP c interaction with STI1 in hippocampal neurons. Both PrP c and STI1 are abundantly expressed and highly colocalized in the hippocampus in situ, indicating that they can interact in vivo. Recombinant STI1 (His 6-STI1) added to hippocampal cultures interacts with PrP c at the neuronal surface and elicits neuritogenesis in wild-type neurons but not in PrP c-null cells. This effect was abolished by antibodies against either PrP c or STI1 and was dependent on the STI1 domain that binds PrP c. Binding of these proteins induced the phosphorylation/activation of the mitogenactivated protein kinase, which was essential for STI1-promoted neuritogenesis. His 6-STI1, but not its counterpart lacking the PrP c binding site, prevented cell death via PKA activation. These results demonstrate that two parallel effects of the PrP c-STI1 interaction, neuritogenesis and neuroprotection, are mediated by distinct signaling pathways.
To describe the clinical characteristics and estimate the survival of children and adolescents wi... more To describe the clinical characteristics and estimate the survival of children and adolescents with germ cell tumors treated with cisplatin-based combination chemotherapy according to three different protocols in Brazil. From 1983 to 1997, 106 patients were treated at the Hospital do Cancer, Sao Paulo for a diagnosis of germ cell tumor. We performed a retrospective review of the clinical and histopathological data to identify prognostic factors and evaluate their outcome. Patients were treated with only surgery (n = 32), surgery and radiotherapy (n = 1) and chemotherapy (n = 73). From 1983 to 1986 (period I), there were 30 patients and 21 received chemotherapy according to the modified VAB-6 protocol. Twenty-two of 35 patients registered between 1987 and 1991 (period II) were treated with EPO/VAC combination chemotherapy. From 1991 to 1997 (period III), there were 41 patients and 31 received chemotherapy according to the Brazilian TCG-91 protocol. Important prognostic factors included stage (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), metastatic status (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and surgical procedure at diagnosis (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). An incremental improvement in outcomes was noted across the periods of treatment (P = 0.070). Five-year OS was respectively 42.9 +/- 10.8%, 53.9 +/- 11.4% and 80.6 +/- 7.1% for periods I, II, and III for the patients who received chemotherapy. An improvement in the survival of children with germ cell tumors was achieved in the most recent trial (TCG-91) with a risk adapted approach incorporating only cisplatin and etoposide. These results indicate that in selected patients complex three-agent regimens may not be necessary to achieve long term survival.
Hodgkin and Reed-Sternberg (H-RS) cells of classical Hodgkin lymphoma (cHL) present an impaired e... more Hodgkin and Reed-Sternberg (H-RS) cells of classical Hodgkin lymphoma (cHL) present an impaired expression of immunoglobulin genes, but escape apoptotic death. We investigated whether nitric oxide synthases (NOS) are expressed by H-RS cells, studied their association with EBV status and the expression of apoptotic proteins, and investigated their relationship to the clinical outcome of 171 patients. NOS1 and NOS2 were expressed in a large number of cases, whereas NOS3 expression was not detected. Positive associations were found between NOS1 and p53, bax and NOS2, bcl-2 and NOS2, bax and p53, and between bax and fasL. Inverse correlations were established between EBV and NOS2 and between EBV and bcl-2. A shorter overall survival (OS) was associated with strong expression of NOS2. In conclusion, NOS are expressed by H-RS cells of cHL.
Purpose In 1988, we formed a consortium of Brazilian institutions to develop uniform standards fo... more Purpose In 1988, we formed a consortium of Brazilian institutions to develop uniform standards for the diagnostic assessment and multidisciplinary treatment of children and adolescents with germ cell tumors. We also implemented the first childhood Brazilian germ cell tumor protocol, GCT-91, evaluating two-agent chemotherapy with cisplatin and etoposide (PE). We now report on the clinical characteristics and survival of children and adolescents with germ cell tumors treated on this protocol. Patients and Methods From May 1991 to April 2000, 115 patients (106 assessable patients) were enrolled onto the Brazilian protocol with a diagnosis of germ cell tumor. Results Patients were treated with surgery only (n = 35) and chemotherapy (n = 71). Important prognostic factors included stage (P = .025), surgical procedure at diagnosis according to resectability (P < .032), and abnormal lactate dehydrogenase value at diagnosis (P < .001). Conclusion The improvement in survival by the intr...
The physiological functions of the cellular prion protein, PrPC, as a cell surface pleiotropic re... more The physiological functions of the cellular prion protein, PrPC, as a cell surface pleiotropic receptor are under debate. We report that PrPC interacts with vitronectin but not with fibronectin or collagen. The binding sites mediating this PrPC-vitronectin interaction were mapped to residues 105-119 of PrPC and the residues 307-320 of vitronectin. The two proteins were co-localized in embryonic dorsal root ganglia from wild-type mice. Vitronectin addition to cultured dorsal root ganglia induced axonal growth, which could be mimicked by vitronectin peptide 307-320 and abrogated by anti-PrPC antibodies. Full-length vitronectin, but not the vitronectin peptide 307-320, induced axonal growth of dorsal root neurons from two strains of PrPC-null mice. Functional assays demonstrated that relative to wild-type cells, PrPC-null dorsal root neurons were more responsive to the Arg-Gly-Asp peptide (an integrin-binding site), and exhibited greater αvβ3 activity. Our findings indicate that PrPC p...
To investigate the association of childhood ALL and SES, we collected data on 507 children aged 0... more To investigate the association of childhood ALL and SES, we collected data on 507 children aged 0-14 years diagnosed with ALL between 1997 and 2002 from the population-based Cancer Registry of São Paulo, Brazil, covering 96 districts. Each child was assigned to an SES category based on the district of residence at diagnosis. Four SES categories were created from high to low, based on the Social Exclusion Index (SEI) that includes the following indicators: poverty, employment, inequality, education and violence. Using Census data, cases were also classified into quintiles according to the percentage of households with more than 7 persons. Age-specific and age-standardized incidence rates were calculated using the 1960 world standard population. Age-adjusted incidence rate was 3.68/100,000 for males and 2.87/100,000 for females. Children living in areas with lowest SES presented a significant lower risk of ALL compared with those living in the wealthiest districts (Rate Ratio [RR] 5 0.34; 95% Confidence Interval [CI] 5 0.28-0.44). Lower incidence rates of childhood ALL were also found in areas with high percentages of households with more than 7 persons (!5.7%) compared with areas where there were 2.2% (RR 5 0.32, 95% CI 0.25-0.43). There was a strong correlation between SEI and crowding (rho 5 20.95, p < 0.001). Population-based attributes for SES and household size may be useful surrogate markers of early exposure to childhood infections, which has been found to decrease the risk of ALL.
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Papers by Karina Ribeiro