Acompanhamento de pacientes submetidos à cirurgia bariátrica : aspectos laboratoriais nos períodos pré e pós-operatório

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmácia, Florianópolis, 2017A obesidade é uma doença crônica e endócrino-metabólica caracterizada pelo acúmulo excessivo de triacilgliceróis no tecido adiposo, capaz de ser revertida ou amenizada através de intervenção cirúrgica. Epidemiologicamente têm sido descritas associações entre o excesso de peso, resistência à insulina e processo inflamatório crônico. Além disso, nas últimas décadas o sistema complemento foi associado a doenças metabólicas e cardiovasculares e intimamente relacionado com a obesidade e resistência à insulina. Sendo assim, a melhora do estado metabólico e a remissão da inflamação em pacientes obesos submetidos à cirurgia bariátrica foram avaliadas, bem como a associação dos fatores 3 e 4 (C3 e C4) do sistema complemento com a sensibilidade à insulina e a perda de peso após a cirurgia bariátrica. Para isso, a presença de comorbidades e as concentrações séricas de leptina, adiponectina, resistina e grelina foram avaliados em pacientes obesos mórbidos antes, 1, 3 e 6 meses após a cirurgia bariátrica. Também foram medidas as concentrações de IL-1ß, IL-6, TNF-a, proteína amiloide sérica A (SAA), proteína quimiotática de monócitos 1 (MCP-1), C3, C4, glicose, insulina, colesterol total, triacilglicerol, LDL- colesterol, HDL-colesterol e foi realizado o cálculo do modelo de avaliação da homeostase da resistência à insulina (HOMA-IR) durante o seguimento da cirurgia, bem como em comparação com um grupo de indivíduos não-obesos. Como resultado, observou-se uma redução significativa de peso acompanhada de melhora do perfil lipídico, da sensibilidade à insulina e das comorbidades. Ainda, houve diminuição de leptina e aumento de adiponectina no período pós-cirúrgico. IL-1ß, IL-6, TNF-a, MCP-1 e SAA não mostraram diferença no acompanhamento da cirurgia, porém SAA correlacionou-se com o IMC e apresentou-se muito mais alto no grupo de pacientes obesos. Além disso, C3 e C4 foram significativamente maiores em indivíduos obesos quando comparados aos indivíduos não-obesos e C3 e C4 foram positivamente correlacionados com HOMA-IR e as concentrações de C3 foram significativamente diminuídas após a cirurgia. Com base nesses resultados, a cirurgia bariátrica mostrou melhorar o estado metabólico melhorando as comorbidades associadas à obesidade e os biomarcadores de adiposidade leptina e adiponectina, mas não os demais hormônios e citocinas inflamatórias e C3 e C4 foram fortemente associados à sensibilidade à insulina.Abstract: Obesity is a chronic and endocrine-metabolic disease characterized by triacylglycerol accumulation in the adipose tissue, which can be reversed or improved through surgical intervention. Epidemiologically, associations between overweight, insulin resistance and chronic inflammatory process have been described. Furthermore, in the last decades the complement system was associated with metabolic and cardiovascular diseases and related to obesity and insulin resistance. Thus, metabolic status improvement and inflammation remission in obese patients undergoing bariatric surgery were evaluated, as well as the association of complement system factors 3 and 4 (C3 and C4) with insulin sensitivity and weight loss after bariatric surgery. For this, comorbidities and leptin, adiponectin, resistin and ghrelin serum concentrations were evaluated in morbidly obese patients before, 1, 3 and 6 months after bariatric surgery. IL-1ß, IL-6, TNF-a, serum amyloid A protein (SAA), monocyte chemotactic protein 1 (MCP-1), C3, C4, glucose, insulin, total cholesterol, triacylglycerol, LDL-cholesterol, HDL-cholesterol concentrations and the calculation of the homeostasis model of insulin resistance (HOMA-IR) were performed during the surgery follow-up, as well in a group of non-obese individuals. As a result, significant weight loss followed by improvement in lipid profile, insulin sensitivity and comorbidities were observed. Still, there was a decrease in leptin and an increase in adiponectin in the postoperative period. IL-1ß, IL-6, TNF-a, MCP-1 and SAA showed no difference after surgery, but SAA correlated with BMI and was much higher in obese patients. In addition, both C3 and C4 were significantly higher in obese individuals when compared to lean individuals and positively correlated with HOMA-IR. C3 concentrations were significantly decreased after surgery. Based on these results, bariatric surgery has been shown to improve metabolic status by improving obesity-associated comorbidities and adiposity biomarkers leptin and adiponectin but not the other hormones and inflammatory cytokines and C3 and C4 were strongly associated with insulin sensitivity

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

VO₂ kinetics expressed as MRT is correlated with VO₂max when measured using a PRBS protocol

[Extract] Oxygen uptake (VO₂) kinetics, measured using a pseudo-random binary sequence (PRBS) exercise test, has been proposed as a convenient low intensity method of determining cardiovascular fitness in sports people unwilling or unable to perform maximal exercise (Edwards et al., 1999). Although frequency domain analysis of PRBS exercise has shown that VO₂ kinetics are related to maximal oxygen uptake (VO₂max) (Eβfeld 1987), the application of the PRBS technique to assess cardiovascular (CV) fitness has been limited perhaps because of the difficulty of interpreting the frequency responses. Calculation of the mean response time (MRT) provides an alternative to frequency domain analysis (Hughson et al., 1991) and has the advantage of providing a single test measure of VO₂ kinetics, however this technique has not been widely used. The purpese of this study was to utilise MRT to examine the relationship between VO₂ kinetics and VO₂max

Time domain analysis of oxygen uptake kinetics in elite runners by pseudo random binary sequence (PRBS) exercise

Oxygen uptake kinetics assessed in the frequency domain are known to be differentially faster in elite endurance runners than in elite sprinters. Breath-by-breath data from PRBS testing have routinely been analysed by application of Fourier methods, however, it is possible to analyse the data in the time domain in the form of a Total Lag Time (TLT). In this study, correlational techniques were applied to yield an output response to a work rate input. An autocorrelation function was performed on the input work rate (WR) and a cross correlation function was performed on input (WR) and output (vO₂). The cross correlation function was analysed by fitting a linear summation of the ramp form of a two-component exponential function to a triangular pulse. Twelve elite male sprinters and 12 elite male endurance runners completed 3 identical PRBS cycles of 300 s with 20 s work rate changes between 25 and 85 W on an electrically braked cycle ergometer at a pedal cadence of 1 Hz. Oxygen uptake was measured on a breath-by-breath basis using a respiratory mass spectrometer. Statistical analysis using the analysis of variance revealed significantly faster oxygen uptake kinetics (TLT) in the elite endurance runners compared with the elite sprinters (33.3 s 3.39SD and 39.91 s 7.14SD respectively) (p < 0.01). The results of this study show that time domain analysis represents a possible alternative to frequency analysis in the study of oxygen uptake kinetics described by PRBS exercise

The test-retest reliability of gas exchange kinetics in humans using a pseudo random binary sequence exercise test

The purpose of this study was to compare the test-retest reliability of oxygen uptake (VO2) kinetics with carbon dioxide output (VCO2) kinetics using a pseudo random binary sequence (PRBS) exercise test. A reliable test of gas exchange kinetics would have the potential of being applied as a sports fitness test. Ten healthy male subjects agreed to participate in the study and all subjects completed two identical PRBS exercise tests (test 1 and test 2), separated by a 30 min period of inactivity. Three consecutive 300 s PRBS cycles were completed in each test with 20 s exercise intensity changes between 25 and 85 W using an electrically braked cycle ergometer. Fourier analysis was computed for frequencies 3.3, 6.7 and 10 mHz. Statistical analysis by two-way ANOVA with repeated measures did not reveal significant differences between test 1 and test 2 for either VO2 kinetics or VCO2 kinetics. Static gain of VO2 for test 1 [9.11 (SD 0.59) ml.min-1.W-1] and test 2 [9.23 (SD 0.64) ml.min-1.W-1] did not differ significantly between tests. The 95% limits of agreement for VCO2 kinetics displayed increased variability in comparison to VO2 kinetics at each frequency of amplitude ratio and phase shift. Systematic bias ranged between 0% and 4%, except at frequency 10 mHz of VCO2 kinetics phase shift which showed a 10% bias for slower VO2 kinetics in test 2. It is possible that the increased variability of VCO2 kinetics compared to VO2 kinetics might be attributable to a lower signal to noise ratio in VCO2 kinetics, variations in ventilation or the storage mechanisms of CO2. The lower variability of VO2 kinetics compared with VCO2 kinetics suggests that the PRBS test of VO2 kinetics has the greater potential for further development as an indicator of aerobic fitness