Post-traumatic osteoarthritis: the worst associated injuries and differences in patients' profile when compared with primary osteoarthritis.

BACKGROUND: The estimated prevalence of post-traumatic osteoarthritis (PTOA) is 10-12% and in this study 12.4%. Different knee and hip injuries have been identified as risk factors for PTOA, but there is no consensus regarding the most painful and disabling injuries. Identifying these injuries might help in the prevention of PTOA. Additionally, patients with PTOA have a higher risk for complications after arthroplasty than patients with primary OA, perhaps due to differences in the profile and comorbidity that might help to explain the difference. This work aims 1) to identify the most common past injuries associated with the most painful and disabling PTOA cases in non-athlete patients and 2) to compare the comorbidities and characteristics between PTOA and primary OA. METHODS: Retrospective hospital-based cohort study with 1290 participants with joint complaints or who received arthroplasty. Medical records included demographic information, diagnosis, medication, smoking, alcohol history and comorbidities. Data from January 2012 orthopaedic consults till December 2019 was reviewed and had the type and date of injury, pain score by the numerical rating scale and walking disability. Odds Ratio (OR) and 95% confidence intervals are presented. RESULTS: There were 641 cases with primary OA (65% females) and 104 with PTOA (61% males). Patients with PTOA were 7.5 years younger (P < 0.001), reported more alcohol consumption (P = 0.01) and had higher odds of osteoporotic fractures (OP) and psychosis than patients with primary OA (OR = 2.0, CI = 1.06-3.78 and OR = 2.90, CI = -0.91-9.18, respectively). Knee fractures were most common in males and hip fractures in females (31% and 37.5%, respectively, P < 0.005). The PTOA-associated injuries with the highest pain and disability scores were meniscal injuries and hip fractures. Besides, in the group with primary OA, there were more diabetes, hypertension and hypothyroidism cases than in PTOA. However, after adjustment, differences were only significant for diabetes (ORadj = 1.78, CI = 1.0-3.2). CONCLUSIONS: Past meniscal injuries and hip fractures were the most relevant PTOA-associated injuries regarding pain and walking disability. This, together with differences in their profile when compared with primary OA, might help to decide the orthopaedic management of these injuries to prevent complications such as PTOA and recurrence, with appropriate preoperative planning, surgery choice and comorbidity treatment.

Lung Cancer Mortality and the Availability of Chest Computerized Tomography: A Longitudinal Nationwide Study.

Lung-cancer screening with chest computerized tomography (CT) is not easy to introduce in low-medium resource countries due to cost issues. We investigated whether the increasing availability of chest CT exams in Brazil, in spite of no lung-cancer screening protocol, was associated with lung-cancer death rate along 10-year follow-up. We performed regressions to estimate the rate ratio between chest CT exams and lung-cancer deaths per 105 inhabitants. We stratified data per municipality. Regressions were adjusted for physicians and hospital beds per 105 inhabitants and per capita gross domestic product. Increasing availability of chest CT exams predicted decreasing lung-cancer death rate.

Role of GAD peptides p217 and p290 in the repair of INS receptor in salivary tissues of type 1 diabetic mice.

Glutamate decarboxylase or glutamic acid decarboxylase (GAD) is a protein associated with autoimmune diseases, including type-1 diabetes. This disease is primarily associated with the occurrence of a specific isoform: GAD65. Conversely, some specific peptides of this protein may block autoimmunity in diabetes. In this respect, understanding the relationship between GAD and the development of diabetes is important, and it is necessary to understand the role of each GAD peptide to design effective autoimmune diabetes treatments. The purpose of the present study was to analyze the effects of treatment with GAD-derived peptides p217 and p290 on INS receptors in the salivary epithelium of nonobese diabetic (NOD) animals. Three groups of 7 mice each were studied: I, BALB/c mice (control); II, NOD mice; and III, NOD mice treated with peptides p290 and p217. Groups I and II only received buffered saline solution. Glucose levels were measured daily during the 21 days of the experiment. After the study, the animals were euthanized and the parotid and submandibular glands were removed for the analysis of INS-R by fluorescence microscopy. Therapy with two peptides together was associated with reduced glucose levels in NOD mice and intense INS-R expression in both salivary organs. Our approach of combining GAD p217 and p290 peptides contributed to hormonal balance and promoted the repair of INS-R.

Profile of Metalloproteinases and Their Association with Inflammatory Markers in Pleural Effusions.

BACKGROUND: Matrix metalloproteinases (MMPs) are responsible for the breakdown of the extracellular matrix and play an important role in the inflammatory processes of pleural exudates. The imbalance between MMPs and their inhibitors (TIMPs) is present in various pathological processes. OBJECTIVE: To evaluate the profile of MMPs and TIMPs in pleural effusions of different etiologies correlated with inflammatory markers. METHODS: The patients with pleural effusion due to tuberculosis (TB), cancer (CA) or transudate were prospectively evaluated. Pleural fluid was submitted to cytological, biochemical, cytokines, MMP, and TIMP analysis. Statistical analysis was performed using ANOVA and Spearman's correlation, and p < 0.05 was considered significant. RESULTS: One hundred and fourteen patients were enrolled, 80 exudates (41 TB and 39 CA) and 34 transudates. The levels of MMP-8 and MMP-9 were higher in exudates compared to transudates. The level of MMP-8 was significantly higher in TB than in CA. TIMP-1 levels were higher in exudates. IL-6, VEGF, and TGF-ß1 showed differences between exudates and transudates. However, IL-6 level was higher in TB than in CA. We found a significant correlation between MMPs and TIMPs with inflammation markers. MMP-1 was correlated with LDH levels. MMP-8 was correlated with LDH, total cell count, neutrophils, and ADA as well as MMP-1 levels. MMP-9 was correlated with IL-6, TGF-ß1, and VEGF. TIMP-1 was correlated with MMP-9 and IL-6. CONCLUSIONS: MMPs and TIMPs are expressed in pleural fluid of different etiologies and correlate with inflammatory mediators. MMPs may be useful in determining the cause of fluid, but more studies are needed to determine the spectrum of diseases associated with the various isoforms of MMPS and TIMPs.

A modified experimental model of malignant pleural disease induced by lung Lewis carcinoma (LLC) cells.

BACKGROUND: Malignant pleural effusion resulting mainly from pleural metastases of lung adenocarcinoma has clinical relevance, being a sign of poor prognosis and low life expectancy. Experimental models can mimic the human condition, contributing to advances in current understanding of the mechanisms patients' pleural fluid accumulation and possible therapeutic strategies. The objective of this study is to evaluate the role of different concentrations of Lewis lung carcinoma cells (LLC cells) at the time of induction of experimental MPE and the main effects on survival of animals. METHODS: C57BL/6 mice received intrapleural injection of 0.1, 0.5 or 1.5 × 10(5) LLC cells and survival curve, biochemical and pathological analyses of pleural fluid and tissue were analyzed. RESULTS: Evaluation of weight loss, mobility and survival showed that animals that received 0.5 × 10(5) cells maintained more stable condition up to day 14 and a gain of 6 days survival over mice that received the highest concentration. CONCLUSION: This study may allow a better understanding the mechanisms involved in the development of malignant pleural effusion and it may be promising in evaluating therapy to avoid recurrence, as the best time to indicate pleurodesis or target therapies.

Inflammatory Cytokines Contribute to Asbestos-Induced Injury of Mesothelial Cells.

BACKGROUND: Several diseases have been related to asbestos exposure, including the pleural tumor mesothelioma. The mechanism of pleural injury by asbestos fibers is not yet fully understood. The inflammatory response with release of mediators leading to a dysregulation of apoptosis may play a pivotal role in the pathophysiology of asbestos-induced pleural disease. OBJECTIVE: To determine whether pro-inflammatory cytokines produced by asbestos-exposed pleural mesothelial cells modify the injury induced by the asbestos. METHODS: Mouse pleural mesothelial cells (PMC) were exposed to crocidolite or chrysotile asbestos fibers (3.0 µg/cm(2)) for 4, 24, or 48 h and assessed for viability, necrosis and apoptosis, and the production of cytokines IL-1ß, IL-6 and macrophage inflammatory protein-2 (MIP-2). Cells exposed to fibers were also treated with antibodies anti-IL-1ß, anti-IL-6, anti- IL-1ß+anti-IL-6 or anti-MIP-2 or their irrelevant isotypes, and assessed for apoptosis and necrosis. Non-exposed cells and cells treated with wollastonite, an inert particle, were used as controls. RESULTS: Mesothelial cells exposed to either crocidolite or chrysotile underwent both apoptosis and necrosis and released cytokines IL-1ß, IL-6 and MIP-2. In the crocidolite group, apoptosis and the levels of all cytokines were higher than in the chrysotile group, at comparable concentrations. Neutralization of IL-1ß andIL-6, but not MIP-2, inhibited apoptosis and necrosis, especially in the cells exposed to crocidolite fibers. CONCLUSIONS: Both crocidolite and chrysotile asbestos fibers induced apoptosis and produced an acute inflammatory response characterized by elevated levels of IL-1ß, IL-6 and MIP-2 in cultured mouse PMC. IL-1ß and IL-6, but not MIP-2, were shown to contribute to asbestos-induced injury, especially in the crocidolite group.

Monoclonal antibodies anti-TGFß1 and anti-VEGF inhibit the experimental pleurodesis induced by silver nitrate.

BACKGROUND: The mechanisms underlying pleural inflammation and pleurodesis are poorly understood. We hypothesized that the cytokines transforming growth factor ß (TGFß1) and vascular endothelial growth factor (VEGF) play a major role in pleurodesis after intrapleural silver nitrate (SN) injection. METHOD: Forty rabbits received intrapleurally 0.5% SN alone or 0.5% SN + anti-TGFß1, anti-IL-8, or anti-VEGF. After 28 days, the animals were euthanized and macroscopic pleural adhesions, microscopic pleural fibrosis, and collagen deposition were analyzed for characterization of the degree of pleurodesis (scores 0-4). RESULTS: Scores of pleural adhesions, pleural fibrosis, total collagen, and thin collagen fibers deposition after 28 days were significantly lower for 0.5% SN + anti-TGFß1 and 0.5% SN + anti-VEGF. Significant correlations were found between macroscopic adhesion and microscopic pleural fibrosis with total collagen and thin collagen fibers. CONCLUSIONS: We conclude that both TGFß1 and VEGF, but not IL-8, mediate the pleural inflammatory response and pleurodesis induced by SN.

Role of central obesity on pain onset and its association with cardiovascular disease: a retrospective study of a hospital cohort of patients with osteoarthritis.

OBJECTIVES: To determine the role of central obesity (CO) in the onset and severity of joint pain and in predicting cardiovascular disease (CVD) in subjects affected with osteoarthritis (OA). DESIGN: Retrospective analysis on the onset of OA joint pain and CO. Waist circumference (WC), Waist-to-height ratio andwaist-to-hip ratio (WHR) were measured at the interview and defined according to the WHO criteria. Cross-sectional analyses on the association of comorbidities, including CVD, pain severity (number of joints and pain score) and CO. SETTINGS AND PARTICIPANTS: Medical records and interviews of a hospital cohort study of 609 patients with OA. Analyses included analysis of variance, mean differences (MDs), SE and logistic regression. Areas under the receiver operating characteristic curve (AUROC) compared the predictive value of the sex-specific CVD models. OUTCOME MEASURES: Onset of OA joint pain (years) and severity according to body mass index (BMI) and WC categories. Predictive value of WC for CVD by sex. Education level, disability, smoking and alcohol use were used to adjust the analysis. RESULTS: Subjects with OA and CO by WHR started 2 years earlier with pain symptoms and had more joints affected than those without CO (MD=1.96 years, SE=0.95, p=0.04 and MD=0.32, SE=0.15 and p=0.04, respectively). Age and hypertension were associated with CVD in both genders, and NSAIDs use only in males. In addition, respiratory disease, hypercholesterolaemia, stairs difficulty, a wider WC and obesity were significant risk factors in females, improving 12.7% in the prediction of CVD cases, compared with only age and BMI (AUROCC=0.793 and 0.666, respectively, p=0.03 for the difference between AUROCs). CONCLUSION: CO is associated with the onset of joint pain, and all pain analysed variables. CO has a role in CVD in women affected with OA and might help predict CVD cases.

Experimental Evaluation of Chitosan Membrane and Collagen Sponge (TachoSil®) as Sealants in Cardiovascular Surgery.

INTRODUCTION: The objectives of this study are to experimentally evaluate the haemostatic effects of two organic substances, a membrane of chitosan and a collagen sponge coated with thrombin and human fibrinogen (TachoSil®), in sealing 7-0 needle stitches holes on the femoral arteries of rats as well as to evaluate local histological reactions. METHODS: Twenty-four rats were included, and four holes were made in each common femoral artery. In the control group, haemostasis was achieved only by compression with gauze sponge; and in the two other groups, haemostasis was achieved with application of one of these two substances. RESULTS: Membrane of chitosan and TachoSil® showed a power to reduce the time to achieve haemostasis compared with the control group (P=0.001), and the haemostatic effects of these two substances were comparable. There was lower blood loss in the groups where these two substances were used when compared with the control group, but no difference was found comparing the two substances. CONCLUSION: The use of these sealants did not promote more adhesion or local histological reactions when compared to the control group. Since chitosan is easy to find in nature, has a positive effect to promote haemostasis, and did not bring considerable local reactions, it might be used as a sealant in cardiovascular surgery.

Nonoperative vs Operative Management of Uncomplicated Acute Appendicitis: A Systematic Review and Meta-analysis.

Importance: Appendectomy remains the standard of care for uncomplicated acute appendicitis despite several randomized clinical trials pointing to the safety and efficacy of nonoperative management of this disease. A meta-analysis of randomized clinical trials may contribute to the body of evidence and help surgeons select which patients may benefit from surgical and nonsurgical treatment. Objective: To assess the efficacy and safety of nonoperative management vs appendectomy for acute uncomplicated appendicitis. Data Sources: A systematic review was conducted using indexed sources (Embase and PubMed) to search for published randomized clinical trials in English comparing nonoperative management with appendectomy in adult patients presenting with uncomplicated acute appendicitis. To increase sensitivity, no limits were set for outcomes reported, sex, or year of publication. All nonrandomized or quasi-randomized trials were excluded, and validated primers were used. Study Selection: Among 1504 studies imported for screening, 805 were duplicates, and 595 were excluded for irrelevancy. A further 96 were excluded after full-text review, mainly owing to wrong study design or inclusion of pediatric populations. Eight studies met the inclusion criteria and were selected for the meta-analysis. Data Extraction and Synthesis: Meta-extraction was conducted with independent extraction by multiple reviewers using the Covidence platform for systematic reviews and in accordance with PRISMA guidelines. Data were pooled by a random-effects model. Main Outcomes and Measures: Treatment success and major adverse effects at 30 days' follow-up. Results: The main outcome (treatment success proportion at 30 days of follow-up) was not significantly different in the operative and nonoperative management cohorts (risk ratio [RR], 0.85; 95% CI, 0.66-1.11). Likewise, the percentage of major adverse effects was similar in both cohorts (RR, 0.72; 95% CI, 0.29-1.79). However, in the nonoperative management group, length of stay was significantly longer (RR, 1.48; 95% CI, 1.26-1.70), and a median cumulative incidence of 18% of recurrent appendicitis was observed. Conclusions and Relevance: These results point to the general safety and efficacy of nonoperative management of uncomplicated acute appendicitis. However, this strategy may be associated with an increase in duration of hospital stay and a higher rate of recurrent appendicitis. This meta-analysis may help inform decision-making in nonoperative management of uncomplicated acute appendicitis.

Seroepidemiological investigation of COVID-19: A cross-sectional study in Jundiai, São Paulo, Brazil.

The dramatic increase in the number of COVID-19 cases has been a threat to global health and a challenge for health systems. Estimating the prevalence of infection in the population is essential to provide support for action planning. Within this scenario, the aim of the present study was to analyze the seroprevalence and associated factors of COVID-19 Jundiaí, São Paulo, Brazil. This cross-sectional study was conducted from June 1st to June 19th, 2020. The participants were patients with respiratory symptoms who sought Primary Care Units (UBS) (n = 1,181) and subjects recruited from randomly selected households by probability sampling (n = 3,065), as screening strategy. All participants, in both phases, were submitted to SARS-CoV-2 rapid antigen tests (IgG and IgM) and responded to a questionnaire including sociodemographic characteristics based on Behavioural Insights for COVID-19. Total seroprevalence (positive/negative) was the outcome and the independent variables were sociodemographic variables, health behavior and signs/symptoms. The chi-squared test was used for association analysis (p<0.05) and variables with p<0.20 were entered into the logistic regression model (p<0.05). A total of 1,181 subjects from the UBS and 3,065 from the selected households participated in the study. The seroprevalence was 30.8% in the UBS and 3.1% in the households. The adjusted logistic regression identified that lower educational level (OR 2.68; 95%CI 1.59-4.54), household member testing positive (OR 1.67; 95%CI 1.16-2.39), presence of anosmia (OR 3.68, 95%CI 2.56-5.28) and seeking UBS (OR 3.76; 95%CI 2.08-6.82) was risk factors to test positive for SARS-CoV-2. Estimating the seroprevalence in the population was important to know the disease extension that was higher than the notified cases. These results showed socioeconomic aspects associated with COVID-19 even adjusted by symptoms. Populational epidemiologic studies that investigate the associated factors of COVID-19 are relevant to plan strategies to control the pandemic.

Hospital admission rate in children and adolescents with mild persistent asthma.

INTRODUCTION: The health and financial burden of mild-persistent asthma has been poorly investigated. OBJECTIVE: Our aim was to compare the rate of hospital admissions that have occurred during the preceding year between children and adolescents with current mild-persistent (MP) and moderate-severe (MS) asthma. METHODS: We screened children and adolescents with asthma at eight outpatient clinics. The inclusion criteria were asthma diagnosis, age from 6 to 18 years and follow-up with a physician during the preceding 6 months. Subjects answered standardized questionnaires and underwent spirometry. RESULTS: We enrolled 220 MP and 102 MS asthmatic subjects. The proportion of subjects with HA during the preceding year was similar between MP and MS asthma groups (7% vs. 7%; p = .89). Symptoms score and the financial values spent by the family in the care of asthma were lower in MP asthma as compared with MS asthma group (asthma control questionnaire score 0.7 [0.3-1.0) vs. 2.0 [1.1-2.5]; p < .01) (asthma expenses in USD 13 [2-43] vs. 28 [10-83]; p < .01). The frequency of subjects using inhaled corticosteroids maintenance therapy was lower in the MP asthma group as compared with the MS asthma group (54% vs. 100%; p < .01). CONCLUSION: We conclude that the frequency of hospital admissions that have occurred during the preceding year was similar between subjects with current MP and MS asthma. Symptoms score and the financial values spent by the family in the care of asthma were lower in the MP asthma group.

[Perioperative central venous oxygen saturation and its correlation with mortality during cardiac surgery: an observational prospective study]. / Correlação entre saturação venosa central de oxigênio perioperatória e mortalidade em cirurgia cardíaca: estudo prospectivo observacional.

BACKGROUND: Cardiac surgery can produce persistent deficit in the ratio of Oxygen Delivery (DO2) to Oxygen Consumption (VO2). Central venous oxygen Saturation (ScvO2) is an accessible and indirect measure of DO2/VO2 ratio. OBJECTIVE: To monitor perioperative ScvO2 and assess its correlation with mortality during cardiac surgery. METHODS: This prospective observational study evaluated 273 patients undergoing cardiac surgery. Blood gas samples were collected to measure ScvO2 at three time points: T0 (after anesthetic induction), T1 (end of surgery), and T2 (24hours after surgery). The patients were divided into two groups (survivors and nonsurvivors). The following outcomes were analyzed: intrahospital mortality, length of Intensive Care Unit (ICU) and hospital stay (LOS), and variation in ScvO2. RESULTS: Of the 273 patients, 251 (92%) survived and 22 (8%) did not. There was a significant perioperative reduction of ScvO2 in both survivors (T0=78%± 8.1%, T1=75.4%±7.5%, and T2=68.5%±9%; p<0.001) and nonsurvivors (T0=74.4%±8.7%, T1=75.4%±7.7%, and T2=66.7%±13.1%; p <0.001). At T0, the percentage of patients with ScvO2 <70% was greater in the nonsurvivor group (31.8% vs. 13.1%; p=0.046) and the multiple logistic regression showed that ScvO2 is an independent risk factor associated with death, OR=2.94 (95% CI 1.10-7.89) (p=0.032). The length of ICU and LOS were 3.6±3.1 and 7.4±6.0 days respectively and was not significantly associated with ScvO2. CONCLUSIONS: Early intraoperative ScvO2 <70% indicated a higher risk of death. A perioperative reduction of ScvO2 was observed in patients undergoing cardiac surgery, with high intraoperative and lower postoperative levels.

Evaluating the FEV1/FVC ratio in the lower range of normality as a marker of worse clinical outcomes in asthmatic subjects without airway obstruction.

BACKGROUND: We should continually improve tools for evaluating asthma. The aim of this study was to evaluate whether the FEV1/FVC ratio in the lower range of normality is associated with worse outcomes in asthmatics without airway obstruction. METHODS: We screened asthmatics at eight clinics. Subjects answered the Asthma Control Questionnaire and underwent spirometry. We assigned individuals without airway obstruction in three groups according to the post bronchodilator FEV1/FVC ratio: lower range of normality, intermediary range of normality and upper range of normality. Asthma outcomes were hospital admission due to asthma during the preceding year, non-controlled asthma symptoms and moderate-high inhaled maintenance therapy need. RESULTS: In subjects from six to 18 years old, the rate of hospital admission was higher in the group with FEV1/FVC ratio in the lower range of normality as compared with the other two groups but the frequency of non-controlled symptoms of asthma and moderate-high dose of inhaled maintenance therapy need was similar. From 19 to 59 years old, the rate of moderate-high inhaled maintenance therapy need was higher in the group with FEV1/FVC ratio in the lower range of normality as compared with the other two groups, but the frequency of hospital admissions and non-controlled symptoms of asthma was similar. Above 59 years old, there was no difference in clinical asthma outcomes between lung function groups. CONCLUSIONS: FEV1/FVC ratio in the lower range of normality is a marker of worse clinical outcomes in asthmatics without airway obstruction.

Evaluation of cellular alterations and inflammatory profile of mesothelial cells and/or neoplastic cells exposed to talc used for pleurodesis.

Introdution: To determine the role of Pleural Mesothelial Cells (PMC) and/or Neoplasic Cells (NC) in the initiation and regulation of acute inflammatory response after exposure to talc for evaluating inflammatory mediators and cellular alterations. MATERIALS AND METHODS: PMC cultures, human lung (A549) and breast (MCF7) adenocarcinoma cells were divided in 5 groups: 100% PMC, 100% NC, 25% PMC + 75% NC, 50% of each type and 75% PMC + 25% NC. All groups were exposed to talc and measured IL-6, IL-1ß, IL-10, TNF-α, TNFRI, pH, LDH, apoptosis and necrosis. STATISTICAL ANALYSIS: One-way Anova. RESULTS: High IL-6, IL-1ß and TNFRI levels were found in PMC and NC exposed to talc. IL-6 was higher at the points of more confluence of PMC. The highest levels of IL-1ß and TNFRI were found in mixed cultures. In pure cultures TNFRI was higher in A549 followed by PMC and MCF7. LDH was higher in A549 than PMC. The lowest pH was found in 100% NC. All cell line exposed to talc reduced viability and increased necrosis. Apoptotic cells exposed to talc were higher in pure cultures of NC than in PMC. Mixed cultures of PMC and A549 showed lower levels of apoptosis in cultures with more NC. CONCLUSIONS: PMC after talc exposure participates in the inflammatory process contributing to production of molecular mediators, necessary for effective pleurodesis. Talc acted in NC causing higher rates of apoptosis, contributing in a modest way to tumoral decrease. Different types of tumor cells may respond differently to exposure to talc.

Low doses of silver nitrate induce pleurodesis with a limited systemic response.

BACKGROUND AND OBJECTIVE: Both talc and 0.5% silver nitrate have been shown to induce effective pleurodesis. However, acute adverse systemic inflammatory effects have been described with both agents. The aim of this study was to assess in rabbits the systemic effects associated with a new technique of pleurodesis using repeated low doses of 0.1% silver nitrate. METHODS: Rabbits were injected intrapleurally through a chest tube with 0.1% silver nitrate at 0, 24 and 48 h. Other groups received a single injection of 0.5% silver nitrate or 400 mg/kg of talc. Blood samples were collected at 24, 48 and 72 h, and at 7 days, and cytological and biochemical measurements were performed. After 28 days, the presence of macroscopic pleural adhesions and microscopic pleural fibrosis in the pleural cavity were evaluated. RESULTS: Both talc and 0.5% silver nitrate caused significant increases in blood neutrophils, serum LDH, IL-8, transforming growth factor-beta and CRP in comparison with control at almost all time points, whereas sequential doses of 0.1% silver nitrate only increased LDH and CRP in the first 24 h and transforming growth factor-beta at all time points. All groups showed efficient pleurodesis, with no differences in pleural adhesions or fibrosis. CONCLUSIONS: Sequential doses of 0.1% silver nitrate produced efficient pleurodesis in rabbits, with a low systemic inflammatory response in comparison with 400 mg/kg of talc or 0.5% silver nitrate.

Monoclonal anti-vascular endothelial growth factor antibody reduces fluid volume in an experimental model of inflammatory pleural effusion.

BACKGROUND AND OBJECTIVE: Vascular endothelial growth factor (VEGF) is known to increase vascular permeability and promote angiogenesis. It is expressed in most types of pleural effusions. However, the exact role of VEGF in the development of pleural effusions has yet to be determined. The anti-VEGF mAb, bevacizumab, has been used in the treatment of cancer to reduce local angiogenesis and tumour progression. This study describes the acute effects of VEGF blockade on the expression of inflammatory cytokines and pleural fluid accumulation. METHODS: One hundred and twelve New Zealand rabbits received intrapleural injections of either talc or silver nitrate. In each group, half the animals received an intravenous injection of bevacizumab, 30 min before the intrapleural agent was administered. Five animals from each subgroup were sacrificed 1, 2, 3, 4 or 7 days after the procedure. Twelve rabbits were used to evaluate vascular permeability using Evans's blue dye. Pleural fluid volume and cytokines were quantified. RESULTS: Animals pretreated with anti-VEGF antibody showed significant reductions in pleural fluid volumes after talc or silver nitrate injection. IL-8 levels, vascular permeability and macroscopic pleural adhesion scores were also reduced in the groups that received bevacizumab. CONCLUSIONS: This study showed that bevacizumab interferes in the acute phase of pleural inflammation induced by silver nitrate or talc, reinforcing the role of VEGF as a key mediator in the production of pleural effusions. The results also suggest that bevacizumab should probably be avoided in patients requiring pleurodesis.

Gender differences in the effect of diabetes mellitus and its treatment on osteoarthritic pain.

Objective: (1) To investigate differences in pain severity and its distribution between patients with and without diabetes mellitus (DM) in a population with advanced osteoarthritis (OA). (2) To explore the role of medication used for diabetes in these associations. Research design and methods: This is a hospital-based cohort study of patients with advanced OA requiring total joint arthroplasty. Interviews and electronic records included: age, gender, occupation, DM (including medication and duration), analgesics used, anthropometry, joints affected by pain and disease duration. Joint pain was scored by the patients using numerical rating scale. Pain severity score was calculated by adding the number of joints affected by pain and the maximum pain score. All analyses were adjusted and/or stratified by gender, age and body mass index. Results: In total, 489 patients with painful OA were included. From those, 139 patients had DM (30% males and 28% females, p=0.03). Pain severity, principally the number of joints affected by pain, and analgesic consumption, was higher in males with diabetes compared with males without diabetes (p=0.012 and OR=3.03; 95% CI 1.24 to 7.36, p=0.015, respectively). These associations were not significant in females (p=0.41 and p=0.66). Pain was more severe in males using insulin versus those who did not (p=0.025). Male subjects with diabetes had higher odds of hand pain or knee and hand pain compared with males without diabetes (OR=3.7, 95% CI 1.15 to 12; p=0.028 and OR=5.54; 95% CI 1.43 to 21.5, p=0.013, respectively). Conclusions: Males with diabetes, especially those who require insulin, have more severe joint pain and consume more analgesics than males without diabetes or those who have DM and use other DM medication.

Pattern of Intraoperative Parathyroid Hormone and Calcium in the Treatment of Tertiary Hyperparathyroidism.

OBJECTIVE: Tertiary hyperparathyroidism, an autonomous hyperproduction of parathyroid hormone (PTH), has a challenge in its treatment. This study asked whether the intraoperative PTH and calcium drop can confirm the resection of all parathyroid tissues. STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary referral medical center. SUBJECTS AND METHODS: The study assessed patients with tertiary hyperparathyroidism who were treated at the Hospital of the State University of Campinas from 2007 to 2015. All patients underwent total parathyroidectomy with autotransplantation of parathyroid fragments. PTH and calcium were collected during the preoperative period; at 10, 20, and 240 minutes after resection of the glands; and at 1 year after the procedure. Data were analyzed by analysis of variance and logistic regression analysis with statistical values of P < .05. RESULTS: Thirty-five patients were assessed: 17 women (48.57%) and 18 men (51.43%). The percentage of PTH drop was statistically significant at all times, unlike the calcium analysis, but only PTH collected at 20 minutes was able to confirm the removal of all parathyroid tissues (P = .029). Based on the receiver operating characteristic curve, the 71.2% drop obtained high sensitivity and specificity (P = .028). CONCLUSIONS: Treatment success can be predicted by analyzing the decrease of intraoperative PTH and not by calcium. The 71.2% PTH drop at 20 minutes after parathyroidectomy had high sensitivity and specificity to predict surgical cure.

Is a low level of education a limiting factor for asthma control in a population with access to pulmonologists and to treatment?

OBJECTIVE: To determine whether a low level of education is a risk factor for uncontrolled asthma in a population of patients who have access to pulmonologists and to treatment. METHODS: This was a cross-sectional study involving outpatients > 10 years of age diagnosed with asthma who were followed by a pulmonologist for at least 3 months in the city of Jundiai, located in the state of São Paulo, Brazil. The patients completed a questionnaire specifically designed for this study, the 6-item Asthma Control Questionnaire (to assess the control of asthma symptoms), and a questionnaire designed to assess treatment adherence. Patients underwent spirometry, and patient inhaler technique was assessed. RESULTS: 358 patients were enrolled in the study. Level of education was not considered a risk factor for uncontrolled asthma symptoms (OR = 0.99; 95% CI: 0.94-1.05), spirometry findings consistent with obstructive lung disease (OR = 1.00; 95% CI: 0.99-1.01), uncontrolled asthma (OR = 1.03; 95% CI: 0.95-1.10), or the need for moderate/high doses of inhaled medication (OR = 0.99; 95% CI: 0.94-1.06). The number of years of schooling was similar between the patients in whom treatment adherence was good and those in whom it was poor (p = 0.08), as well as between those who demonstrated proper inhaler technique and those who did not (p = 0.41). CONCLUSIONS: Among asthma patients with access to pulmonologists and to treatment, a low level of education does not appear to be a limiting factor for adequate asthma control.