The economic burden of overweight and obesity in Brazil: perspectives for the Brazilian Unified Health System.

OBJECTIVES: Parallel to rising obesity prevalence in Brazil, there is expected to be increased direct health care costs related to non-communicable diseases (NCDs). In this study, we estimated the economic burden of NCDs attributable to overweight and obesity in the Brazilian Unified Health System (SUS). METHODS: We used self-reported body mass index of 85,715 adults from the 2019 Brazilian National Health Survey. Annual costs (1 US$ = 2.281 Reais) with inpatient and outpatient procedures were obtained from the Hospital and Ambulatory Information Systems of the Brazilian SUS. Relative risks for cardiovascular disease, chronic respiratory disease, neoplasm, digestive disease, musculoskeletal disorders, diabetes and kidney diseases, sense organ diseases, and neurological disorders were retrieved from the Global Burden of Disease study. RESULTS: Annually, US$ 654 million (95% uncertainty interval: US$ 418.4 to US$ 893.2) direct health care costs related to NCDs were attributable to overweight and obesity. Attributable costs were higher in women than men. Cardiovascular diseases had the highest attributable costs (US$ 289 million), followed by chronic respiratory diseases (US$ 110 million), neoplasms (US$ 96 million), digestive diseases (US$ 60 million), musculoskeletal disorders (US$ 44 million), diabetes and kidney disease (US$ 31 million), sense organ diseases (US$ 22 million) and neurological disorders (US$ 11 million). CONCLUSIONS: Overweight and obesity account for US$ 654 million direct costs of NCDs annually. Effective policies to promote healthy body weight may have economic benefits.

Quality of life on hemodialysis and inflammation: a descriptive analysis.

Chronic kidney disease (CKD) is highly prevalent worldwide. Patients with CKD on hemodialysis are more likely to present behavioral changes and worse quality of life as a result of their routine and complications. They also have higher levels of cytokines. The aim of this study is to assess the relationship between the inflammatory profile and quality of life measured by KDOQL-SF36 in hemodialysis outpatients. Patients older than 21 years of age and on routine hemodialysis for at least 6 months with treatment on a regular weekly basis were included and their anthropometric parameters and serum inflammatory markers were evaluated. Thirty patients consented to participate. Homocysteine (Hcy) levels were correlated with worse glomerular filtration rate (GFR; P=0.003) and creatinine (P=0.002). IL-6 was not correlated with worse nutritional status taking into account body mass index (BMI; kg/m2; P=0.83). On the other hand, TNF-alpha was positively correlated with albumin (P=0.008), nutritional status by BMI (P=0.04), and nutritional status by arm circumference area (P=0.04). IL-6 was correlated with activity limitation (P=0.02) and Hcy with work status (P=0.04). Hcy was correlated with nutritional status and inflammatory markers. In this population, the majority of the sections in KDOQL-SF36 were not correlated with cytokines levels.

The chemokine receptor CXCR3 is expressed on malignant B cells and mediates chemotaxis.

B- and T-cell recirculation is crucial for the function of the immune system, with the control of cell migration being mainly mediated by several chemokines and their receptors. In this study, we investigated the expression and function of CXCR3 on normal and malignant B cells from 65 patients with chronic lymphoproliferative disorders (CLDs). Although CXCR3 is lacking on CD5(+) and CD5(-) B cells from healthy subjects, it is expressed on leukemic B lymphocytes from all (31/31) patients with chronic lymphocytic leukemia (CLL). The presence of CXCR3 was heterogeneous in other B-cell disorders, being expressed in 2 of 7 patients with mantle cell lymphoma (MCL), 4 of 12 patients with hairy cell leukemia (HCL), and 11 of 15 patients with other subtypes of non-Hodgkin's lymphomas (NHLs). Chemotaxis assay shows that normal B cells from healthy subjects do not migrate in response to IFN-inducible protein 10 (IP-10) and IFN-gamma-induced monokine (Mig). In contrast, a definite migration in response to IP-10 and Mig has been observed in all malignant B cells from patients with CLL, but not in patients with HCL or MCL (1/7 cases tested). Neoplastic B cells from other NHLs showed a heterogenous pattern. The migration elicited by IP-10 and Mig was inhibited by blocking CXCR3. No effect of IP-10 and Mig chemokines was observed on the cytosolic calcium concentration in malignant B cells. The data reported here demonstrate that CXCR3 is expressed on malignant B cells from CLDs, particularly in patients with CLL, and represents a fully functional receptor involved in chemotaxis of malignant B lymphocytes.

Expression and functional role of the p75 interleukin 2 receptor chain on leukemic hairy cells.

Hairy cell leukemia is a chronic lymphoproliferative disorder characterized by the expansion of neoplastic B-cells expressing the p55 chain of the interleukin 2 receptor (IL-2R) system that is recognized by anti-CD25 monoclonal antibodies (mAb) and binds interleukin 2 (IL-2) with low affinity. In the present study we investigated leukemic hairy cells (HC) for the presence of the p75 IL-2R chain which binds IL-2 with intermediate affinity and plays a crucial role in transducing the message to the cell. For this purpose, we tested highly enriched leukemic HC from six hairy cell leukemia patients for the presence of IL-2R transcripts and for the expression of the p55 and p75 IL-2R chains on their surface membrane by flow cytometry and immunoprecipitation analyses. The functional role of IL-2 in the regulation of HC proliferation was also investigated. Our results indicate that freshly isolated HC express detectable messages for both the p75 IL-2R and the p55 IL-2R. Flow cytometry analysis demonstrated detectable levels of p75 IL-2R on the HC from all patients tested. A mixture of two specific mAb was able to immunoprecipitate detectable amounts of p75 IL-2R from leukemic HC. When leukemic HC were cultured in the presence of several concentrations of IL-2 a low proliferative response was observed. Moreover, the IL-2-driven proliferation of HC was markedly inhibited by anti-p75 IL-2R mAb and to a lesser extent by anti-p55 IL-2R mAb. These findings provide direct evidence of the expression of different IL-2 receptors on leukemic HC and suggest that these molecules might play a role in leukemic cell growth.

B lymphocytes from patients with chronic lymphoproliferative disorders are equipped with different costimulatory molecules.

Several costimulatory molecules play a key role in the differentiation of B lymphocytes and in T-B-cell interactions. In this study, we addressed the question of whether different receptors and counter-receptors may be expressed on malignant B lymphocytes from chronic B-cell malignancies. Using flow cytometry and reverse transcription PCR analyses, the expression of molecules belonging to the tumor necrosis factor receptor (TNFR) and tumor necrosis factor ligand (TNFL) families, as well as the expression of CD80 and CD86 molecules, was analyzed in normal B cells and in different chronic lymphoproliferative disorders of B-cell type, including B-cell chronic lymphocytic leukemia (CLL), mantle cell lymphoma, hairy cell leukemia (HCL), and HCL variant. Different patterns of expression of TNFR and TNFL superfamily molecules were demonstrated among B-cell malignancies. In particular, CD40 was commonly observed on all B cells (both tumor and normal), whereas its ligand (CD40L), which is usually undetectable on resting normal B lymphocytes, was expressed in CLL and HCL but not in other chronic lymphoproliferative disorders. CD27 was not shown in normal B cells, although it was present in all malignancies and with particularly high density in mantle cell lymphoma. CD70 was widely distributed on tumor B lymphocytes, but not on the CD5+ normal counterpart. CD30 was strongly expressed in HCL variant and weakly in B-cell CLL, whereas its ligand showed a wide pattern of expression, including all neoplastic and normal B cells. TNFR II (CD120b) and CD80 were distributed on neoplastic B cells from all groups, usually at an intermediate to high degree of intensity, whereas the CD86 molecule was present at lower intensity than CD80. Finally, reverse transcription PCR analysis confirmed the presence of CD40L, CD30, and CD30L mRNAs in those B cells expressing the corresponding membrane-bound proteins at low density. Our data indicate that TNFR and TNFL molecules are of use clinically both in differentiating B-cell malignancies from the normal counterpart (i.e., CD27, CD70, CD40L, CD30, and CD80) and in defining different chronic B-cell disorders (i.e., CD40L, CD27, and CD30). Interestingly, the observation that several receptors and their ligands (i.e., CD40/CD40L, CD30/CD30L, and CD27/CD70) can be expressed on the same cell suggests that these molecules play a role in initiating and maintaining the neoplastic process by mediating B-T and B-B interactions.

Leukemic cells in hairy cell leukemia and B cell chronic lymphocytic leukemia release soluble TNF receptors.

The two tumor necrosis factor receptors (TNF-Rs) exist in their soluble form in different biological fluids. In this study we investigated the concentrations of soluble tumor necrosis factor receptors (sTNF-Rs) in the culture supernatants of leukemic cells and in the serum obtained from 33 patients: 12 with hairy cell leukemia (HCL) and 21 with B cell chronic lymphocytic leukemia (B-CLL). In seven patients with HCL, sTNF-Rs were also evaluated following in vivo treatment with interferon-alpha (IFN-alpha). Purified leukemic cells from patients with HCL and B-CLL spontaneously released sTNF-R75 but not sTNF-R55. The levels of sTNF-R75 were higher in supernatants obtained from cultured hairy cells than from cultures of B-CLL cells. The shedding of sTNF-R75 was further increased both in HCL and B-CLL subjects by some B cell-related stimuli, including BCGF, PMA, SAC and was partially inhibited by IFN-alpha in patients with HCL. Sera from HCL patients presented increased levels of both sTNF-Rs with respect to normal controls. Treatment of HCL patients with IFN-alpha resulted in a decrease in serum levels of sTNF-Rs, particularly sTNF-R75. These findings suggest that leukemic cells account for the increased serum levels of sTNF-R75 observed in patients with HCL and B-CLL, but not for sTNF-R55.

IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients.

Community-acquired pneumonia (CAP) is amongst the leading causes of death worldwide. As inflammatory markers, cytokines can predict outcomes, if interpreted together with clinical data and scoring systems such as CURB-65, CRB, and Acute Physiology and Chronic Health Evaluation II (APACHE II). The aim of this study was to determine the impact of inflammatory biomarkers on the early mortality of hospitalized CAP patients. Twenty-seven CAP patients needing hospitalization were enrolled for the study and samples of interleukin-1 (IL-1) and interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and homocystein were collected at the time of admission (day 1) as well as on the seventh day of the treatment. There was a significant reduction in the levels of IL-6 between the first and the second collections. Median IL-6 values decreased from 24 pg/mL (day 1) to 8 pg/mL (day 7) (P=0.016). The median levels of TNF-α were higher in patients: i) with acute kidney injury (AKI) (P=0.045), ii) requiring mechanical ventilation (P=0.040), iii) with short hospital stays (P=0.009), iv) admitted to the intensive care unit (ICU) (P=0.040), v) who died early (P=0.003), and vi) with worse CRB scores (P=0.013). In summary, IL-6 and TNF-α levels were associated with early mortality of CAP patients. Longer admission levels demonstrated greater likelihood of early death and overall mortality, necessity of mechanical ventilation, and AKI.

Serum levels of tumour necrosis factor-alpha in patients with B-cell chronic lymphocytic leukaemia.

Serum levels of tumour necrosis factor-alpha (TNF-alpha) have been evaluated in the peripheral blood of 91 patients with B-cell chronic lymphocytic leukaemia (B-CLL), and have been correlated with the clinical stage (according to Rai's staging system) and relevant haematological and immunological data. Increased values were detected, compared to 36 normal age-matched controls (36 pg/ml +/- 5 versus 0.11 pg/ml +/- 0.08; P < 0.05). An increase of TNF-alpha serum levels was observed in all stages including stage 0, with a progressive increase in relation to the stage of the disease. A significant relationship between serum TNF-alpha levels and the number of circulating monocytes (P < 0.002) and an inverse correlation with the level of the haemoglobin (P < 0.001) was established, as defined by the Pearson's correlation test. In contrast, no correlation was observed between TNF-alpha serum levels and the other parameters taken into account, including the white blood cell and platelet counts, the absolute number of peripheral blood (PB) lymphocytes, CD5+ B lymphocytes, CD57+ lymphocytes, serum levels of lactic dehydrogenase, total serum immunoglobulins and the serum levels of IgG, IgA and IgM. These data suggest that, in addition to the B-CLL neoplastic cells, the PB monocytes may be involved in the release of TNF-alpha.

Radiotherapy for non-small cell lung cancer in patients aged 75 and over: safety, effectiveness and possible impact on survival.

For patients with advanced, inoperable non-small cell lung cancer (NSCLC), increasing age seems to be the primary reason of receiving no treatment. The elderly aged 75 years and over are more likely to be given only supportive care (irrespective of symptoms) or no therapy at all. We evaluated the outcome of 48 patients, aged 75 years and over, treated with radiation therapy for advanced (stage IIIA-B), inoperable, symptomatic NSCLC. A median dose of 50 Gy was delivered to the primary site and mediastinum with standard fractionation. Based on WHO criteria, of 47 assessable patients, 21 had partial remission, 17 stable disease, and nine had progressive disease. Most symptoms were successfully palliated. Toxicity was negligible and mainly consisted of WHO grade I-II esophagitis. Despite the overall median survival being short (5 months), dose-related survival was much better in patients given at least 50 Gy than in those treated with lower doses: 52% versus 35% at 6 months, and 28% versus 4% at 13 months. These results confirm that radiation therapy may be safely delivered to very aged patients with advanced NSCLC at not merely palliative doses, both to achieve better local control and to give likely survival benefits. Adequate pretreatment evaluation should be always performed to exclude any comorbidity unfit to chest radiation and to individualize treatment to the single patient requirements. Because a large amount of literature data now concurs with the feasibility and safety of high-dose radiotherapy in the elderly, specifically designed, age-oriented trials are needed to settle definitively the issue of survival advantage from curative radiotherapy in these patients.

Gastrointestinal autonomic nerve tumor: case report and review of the literature.

Gastrointestinal autonomic nerve (GAN) tumor is an uncommon specialized form of gastrointestinal stromal tumor (GIST). We report the case of a 46-year-old man affected by this tumor. The neoplasm arose from the sigmoid colon. The patient underwent surgery but eight months later an omental relapse occurred. A second laparotomy was successfully performed and the patient is free of disease at 21 months of follow-up. To our knowledge this is the first case of a large bowel GAN tumor described in the literature.

Epirubicin, cisplatin and continuous infusion 5-fluorouracil (ECF) in locally advanced or metastatic gastric cancer: a single institution experience.

AIMS AND BACKGROUND: The role of chemotherapy in locally advanced or metastatic gastric cancer has been controversial, but chemotherapy has recently been shown to relieve tumor-related symptoms, improve quality of life and prolong survival when compared with best supportive care. Furthermore, palliative chemotherapy is also cost-effective. "Second-generation" combination chemotherapy regimens were developed in the 1980s with high activity in advanced or metastatic gastric cancer (EAP, FAMTX, PELF, ECF). In randomized studies, EAP demonstrated no difference in activity but a significantly higher overall toxicity and toxic death rate than FAMTX, and the ECF (epirubicin, cisplatin, 5-fluorouracil) regimen gave a survival and response advantage, tolerable toxicity, better quality of life and was more cost-effective than FAMTX. METHODS: Sixty patients with locally advanced or metastatic gastric cancer were treated with the ECF regimen (21 weeks of 5-fluorouracil given by continuous infusion through a central line at 200 mg/m2 for 24-hr combined with cisplatin at 60 mg/M2 iv and epirubicin at 50 mg/M2 iv beginning on day 1 and repeated every 3 weeks for 8 courses). There were 42 males and 18 females, with a median age of 64 years (range, 40-74). The median performance status was 1. The histologic type was adenocarcinoma in 44 patients and undifferentiated carcinoma in 16 (27%). Three patients had locally advanced disease (5%) and 57 had metastatic disease (95%). Seven patients (12%) had received prior chemotherapy for advanced disease. RESULTS: All patients were assessable for toxicity and 55 for response (5 had insufficient treatment). Toxicity was mild or moderate, and there was no toxic death. Incidence of WHO toxicity > or = 2 was nausea and vomiting in 3%, mucositis in 3%, leukopenia in 7%, anemia in 3%, and thrombocytopenia in 2%. Port-a-Cath toxicity was thrombosis in 4, dislocation in 2 and infection in 3 patients. Seven complete responses and 13 partial responses (overall response rate, 36%) were achieved, with a response rate of 39% in untreated and 17% in pretreated patients. Nine patients (16%) had stable disease and 26 (47%) progressive disease. Most patients felt symptomatically improved on ECF. CONCLUSIONS: Our study confirms that the ECF regimen has a favorable pattern of toxicity and is feasible on an outpatient basis. However, it did not confirm the high response rate reported in other phase II trials.

[Juvenile rheumatoid arthritis appearing after hepatitis. Causal or casual relationship]. / Artrite reumatoide giovanile insorta dopo l'epatite. Rapporto casuale o causale?

High fever, spleen and lymph node enlargement, and joint pains that assumed the character of rheumatoid arthritis in the ensuing months were noted after a viral hepatitis episode in a 21-year-old woman. Serious anaemia and myocarditis also appeared when the picture was at its worst. A lymphoma was suspected, and the spleen and some abdominal lymph nodes were removed. These displayed signs of intense follicular reaction unaccompanied by atypia. The possibility that juvenile rheumatoid arthritis may be triggered by hepatitis is examined.

[Prognostic factors in breast carcinoma with negative axillary lymph nodes]. / Fattori prognostici nel carcinoma mammario con linfonodi ascellari negativi.

Conventionally, tumor size, axillary lymph nodes status, histologic type and grading, proliferative activity, steroid receptors have been used to predict the natural history of breast cancer. In node-negative patients with breast cancer it is most important to identify biological markers that can predict the risk of systemic relapse. These features have been used to allow selection of the best treatment. In this paper we describe the prognostic significance of new tumoral markers in breast cancer patients without axillary involvement. We analyze the prognostic role and the correlation with response to treatment of these parameters: ploidy, oncogenes, p53, epidermal growth factor receptor and cathepsin D.

Quality of life on hemodialysis and inflammation: a descriptive analysis

Chronic kidney disease (CKD) is highly prevalent worldwide. Patients with CKD on hemodialysis are more likely to present behavioral changes and worse quality of life as a result of their routine and complications. They also have higher levels of cytokines. The aim of this study is to assess the relationship between the inflammatory profile and quality of life measured by KDOQL-SF36 in hemodialysis outpatients. Patients older than 21 years of age and on routine hemodialysis for at least 6 months with treatment on a regular weekly basis were included and their anthropometric parameters and serum inflammatory markers were evaluated. Thirty patients consented to participate. Homocysteine (Hcy) levels were correlated with worse glomerular filtration rate (GFR; P=0.003) and creatinine (P=0.002). IL-6 was not correlated with worse nutritional status taking into account body mass index (BMI; kg/m2; P=0.83). On the other hand, TNF-alpha was positively correlated with albumin (P=0.008), nutritional status by BMI (P=0.04), and nutritional status by arm circumference area (P=0.04). IL-6 was correlated with activity limitation (P=0.02) and Hcy with work status (P=0.04). Hcy was correlated with nutritional status and inflammatory markers. In this population, the majority of the sections in KDOQL-SF36 were not correlated with cytokines levels.

IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients

Community-acquired pneumonia (CAP) is amongst the leading causes of death worldwide. As inflammatory markers, cytokines can predict outcomes, if interpreted together with clinical data and scoring systems such as CURB-65, CRB, and Acute Physiology and Chronic Health Evaluation II (APACHE II). The aim of this study was to determine the impact of inflammatory biomarkers on the early mortality of hospitalized CAP patients. Twenty-seven CAP patients needing hospitalization were enrolled for the study and samples of interleukin-1 (IL-1) and interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and homocystein were collected at the time of admission (day 1) as well as on the seventh day of the treatment. There was a significant reduction in the levels of IL-6 between the first and the second collections. Median IL-6 values decreased from 24 pg/mL (day 1) to 8 pg/mL (day 7) (P=0.016). The median levels of TNF-α were higher in patients: i) with acute kidney injury (AKI) (P=0.045), ii) requiring mechanical ventilation (P=0.040), iii) with short hospital stays (P=0.009), iv) admitted to the intensive care unit (ICU) (P=0.040), v) who died early (P=0.003), and vi) with worse CRB scores (P=0.013). In summary, IL-6 and TNF-α levels were associated with early mortality of CAP patients. Longer admission levels demonstrated greater likelihood of early death and overall mortality, necessity of mechanical ventilation, and AKI.