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.

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.

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.

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.

High levels of soluble tumor necrosis factor superfamily receptors in patients with hepatitis C virus infection and lymphoproliferative disorders.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with a variety of extrahepatic disorders that may relate to direct or indirect effects of virus infection. Increased levels of soluble forms of tumor necrosis factor (TNF) receptors I and II, found in lymphoproliferative and infectious diseases, can interfere with TNF induced apoptotic cell death. The aim of the present study was to evaluate soluble TNF family receptors levels in lymphoproliferative disorders associated with HCV infection. METHODS: One hundred and forty-nine subjects were studied, including 120 anti-HCV positive patients (60 without lymphoproliferative manifestations, 47 with type II cryoglobulinemia and 13 with low-grade B-cell non-Hodgkin's lymphoma (B-NHL)) and 29 anti-HCV negative subjects (19 with low-grade B-NHLs and ten normal controls). RESULTS: Soluble forms of TNF receptor I, TNF receptor II and Fas were significantly higher in HCV positive patients compared with normal controls. The highest levels were found in patients affected by type II cryoglobulinemia or HCV positive lymphoplasmacytoid lymphomas (LP-NHLs), while HCV positive patients without type II cryoglobulinemia or with other B-NHLs had lower values (P < 0.01). CONCLUSIONS: Among HCV infected individuals, very high levels of soluble TNF receptors are significantly associated with type II cryoglobulinemia and LP-NHLs, suggesting that they may be involved in these proliferative disorders.

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.

B7 costimulatory molecules from malignant cells in patients with b-cell chronic lymphoproliferative disorders trigger t-cell proliferation.

BACKGROUND: B7 family molecules are involved in T-B-cell communications after interaction with their ligands CD28 and CD152. They play a key role in costimulatory mechanisms and during antigen presentation by efficient antigen presenting cells. B7 molecules are usually absent or expressed at low intensity on B lymphocytes from healthy subjects. In this study, the authors addressed the questions of whether B7 molecules are expressed and modulated in vitro on malignant B lymphocytes from patients with chronic lymphoproliferative diseases of B-cell type and whether they are able to trigger allogenic T-cell reactions. METHODS: Malignant B cells from the peripheral blood of 32 patients with B-cell chronic lymphocytic leukemia, mantle cell lymphoma, hairy cell leukemia, and its variant form were investigated for the expression of B7 molecules on the cell surface and for the ability to trigger allogenic T lymphocytes in different experimental conditions. RESULTS: Flow cytometry analysis demonstrated that freshly isolated malignant B cells express B7 molecules and that their expression may be up-regulated by the in vitro triggering of the CD40 molecule. Furthermore, freshly isolated malignant B cells induce allogenic T-cell proliferation. The in vitro triggering of malignant B lymphocytes by CD40, alone and in combination with interleukin-4, elicits a strong allogenic T-cell proliferation. This T-cell proliferation is related mainly to the presence of B7 molecules on malignant and normal B lymphocytes. CONCLUSIONS: These findings indicate that malignant B cells are efficient antigen presenting cells. It might be suggested that vaccination with pulsed malignant B cells themselves or dendritic cells with in vitro preactivated tumor B cells may represent an alternative therapeutic approach in these patients to generate an antilymphoma T-cell response in vivo.

Multiple radiculopathy of the lower limbs in a cancer patient with meningeal carcinomatosis.

Meningeal carcinomatosis occurs in 1%-5% of patients with breast cancer. Early diagnosis and aggressive treatment of neurologic involvement are important factors of prognosis. We report a case of a 52-year-old woman who was affected by bilateral breast carcinoma treated with surgery and chemotherapy. Six years after she had become asymptomatic, X-rays showed lumbar spine metastases which were treated with radiotherapy. After 1 year she began to suffer from lower limb paresthesias, unsteadiness and unstable gait. Clinical examination showed lower limb sensory ataxia with lack of knee and ankle reflexes, and hypopallesthesia from the iliac spine to the foot. Spinal magnetic resonance imaging (MRI) with contrast agent revealed no medullar compression. Electromyography disclosed bilateral involvement of L4-L5-S1 roots and corresponding paraspinal muscles. Sensory and motor conductions were normal. Cerebrospinal fluid (CSF) examination showed the presence of neoplastic cells, confirming the diagnosis of meningeal carcinomatosis. Our patient underwent 9 cycles of intrathecal methotrexate therapy (25 mg/cycle) with improvement of ataxia and relief of paresthesias. One year later, CSF examination is still negative. We point out the importance of electrodiagnostic studies and CSF examination in the early documentation of root involvement in cancer patients, when computed tomography, MRI and myelography are normal. Early diagnosis may lead to effective therapy which prolongs survival.

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.

New pathogenetic insights into the sarcoid granuloma.

Although the most important enigma of sarcoidosis, ie, its etiology, remains an unsolved problem, the past few years have seen remarkable advances in understanding general immunologic and molecular aspects of the mechanisms leading to granuloma formation in sarcoidosis. It is now clear that during the sarcoid inflammatory process several cytokines are secreted at sites of disease activity; in addition, high affinity receptors for cytokines participating in the granuloma development have been recently identified. This article provides a detailed description of recent data that have clarified cellular interactions governing the dynamics of granuloma formation in sarcoidosis. Together, these new results provide important insights that can refocus efforts at developing immunotherapeutic methods of inhibiting cytokine production at sites of granuloma formation.

Regulation of alveolar macrophage-T cell interactions during Th1-type sarcoid inflammatory process.

The accessory function of antigen-presenting cells depends on the presence of a number of costimulatory molecules, including members of the B7 family (CD80 and CD86) and the CD5 coligand CD72. The aim of this study was to evaluate the regulation of T cell-antigen-presenting cell costimulatory pathways in the lung of patients with a typical Th1-type reaction, i.e., sarcoidosis. Although normal alveolar macrophages (AMs) did not bear or bore low levels of costimulatory molecules, AMs from sarcoid patients with CD4 T-cell alveolitis upmodulated CD80, CD86, and CD72 and expressed high levels of interleukin (IL)-15; lymphocytes accounting for T-cell alveolitis expressed Th1-type cytokines [interferon (IFN)-gamma and/or IL-2] and bore high levels of CD5 and CD28 but not of CD152 molecules. In vitro stimulation of AMs with Th1-related cytokines (IL-15 and IFN-gamma) upregulated the expression of CD80 and CD86 molecules. However, stimulation with IL-15 induced the expression of Th1-type cytokines (IFN-gamma) and CD28 on sarcoid T cells, suggesting a role for this macrophage-derived cytokine in the activation of the sarcoid T-cell pool. The hypothesis that CD80 and CD86 molecules regulate the sarcoid T-cell response was confirmed by the evidence that AMs induced a strong proliferation of T cells that was inhibited by pretreatment with CD80 and CD86 monoclonal antibodies. To account for these data, it is proposed that locally released cytokines provide AMs with accessory properties that contribute to the development of sarcoid T-cell alveolitis.

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.

Human myeloma cells express the CD38 ligand CD31.

Multiple myeloma (MM) plasma cells (PC) are CD38+. A ligand for CD38 is the adhesion molecule CD31. By flow cytometry and immunocytochemistry we have investigated whether malignant PC co-express CD38 and CD31. All 68 patients studied were CD38+. 14/14 monoclonal gammopathies of undetermined significance (MGUS) and 39/39 plasmacytic MM patients co-expressed CD38 and CD31 at high density. Only 1/11 plasmablastic MM and 1/4 plasma cell leukaemias (PCL) expressed CD31. These data indicated that PC malignancies co-expressed high levels of both CD38 and its ligand CD31, with the exception of plasmablastic MM and PCL.