Efficacy of interleukin 17 inhibitor therapy in overweight and obese psoriasis patients (preliminary data)

In recent years, comorbidity in psoriasis has been actively studied, one of the most significant of which is obesity. Obesity is a risk factor for dermatosis in susceptible individuals, which can affect the effectiveness of therapy for the disease, including genetically engineered biological drugs.The aim of the study. To study the effectiveness of therapy with an interleukin‑17 inhibitor (iskekizumab) and the dynamics of lipid parameters in patients with psoriasis and overweight and obesity.Material and methods. A retrospective study of 25 patients diagnosed with psoriasis vulgaris was carried out. Inclusion criteria were PASI more than 12 points, BSA more than 10% and sPGA more than 3 points, age over 18 years. Anthropomeric parameters and lipid profile data were studied. All patients received iksekizumab treatment according to the standard regimen. Evaluation of the effectiveness of therapy was carried out according to the dynamics of PASI indicators, as well as the frequency of patients achieving the response PASI 75, PASI 90 and PASI 100.Results. Obesity and overweight were diagnosed in 13 patients who made up the main observation group. The comparison group included 12 nonobese patients. Patients in the observation groups did not differ in sex and severity of psoriasis. In patients of the main group, hypertriglyceridemia was significantly more often diagnosed (55.6%; 95% CI: 33.7–75.4; in its absence in the comparison group; p = 0.0200), as well as other comorbidity – hypertension and metabolic syndrome (p = 0.0016 and p = 0.0052, respectively). On the background of therapy, skin rashes were resolved in patients of both observation groups. By the seventh week of therapy, there was a significant decrease in PASI, sPGA and BSA, by the 36th week, the rash was completely resolved in all patients (p < 0.001). There were no significant differences between the groups in the dynamics of clinical indicators of the severity of the disease. Body mass index did not change statistically significantly over the observation period in patients of both groups (p = 0.6690). Changes in lipid profile for all parameters were statistically insignificant. There were no significant differences in the frequency of achieving PASI of 75, 90 and 100% between the groups.

Biomarker profiles in obesity patients and their relation to cardiac dysfunction

Aim: Current knowledge on the role of obesity in causing cardiac dysfunction is insufficient. Several biomarkers reflecting biological processes that may play a role in the occurrence of cardiac dysfunction in obesity patients are available. Purpose: To compare cardiovascular biomarker profiles between obesity patients and nonobese controls, and between obesity patients with and without cardiac dysfunction, in order to better understand the underlying pathophysiology of cardiac dysfunction in obesity patients. Materials & methods: Blood samples were obtained from 100 obesity patients (BMI ≥35 kg/m2) without known cardiovascular disease, and from 50 age- and gender-matched nonobese controls (BMI ≤30 kg/m2). The third cardiovascular panel of the Olink Multiplex platform was used for the measurement of 92 biomarkers. Results: The majority (53%) of biomarkers were elevated in obesity patients compared with nonobese controls. Only 5% of the biomarkers were elevated in obesity patients with cardiac dysfunction compared with those without. Biomarkers discriminating cardiac dysfunction from no cardiac dysfunction in obesity patients differed from those discriminating obese from nonobese patients. An elastic net model for the prediction of cardiac dysfunction in obesity patients had a high area under the receiver operating curve of 0.87 (95% CI: 0.79–0.94; p < 0.001). The sensitivity of this model was 84% and the specificity was 79%. Conclusion: A multiplex immunoassay was used for the first time in obesity patients without known cardiovascular disease. These patients have cardiovascular biomarker profiles that are clearly different from nonobese controls. Comparison of obesity patients with and without cardiac dysfunction suggested an important role for inflammation, atherosclerosis and insulin resistance in the underlying pathophysiology of cardiac dysfunction in obesity patients.

Understanding the Link Between Obesity and Severe COVID-19 Outcomes: Causal Mediation by Systemic Inflammatory Response

Background Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood. Objective To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes. Methods This hospital-based, observational study included 3828 SARS-CoV-2-infected patients who were hospitalized February to May 2020 at Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/New York Presbyterian Hospital (CUIMC/NYP). We use mediation analysis to evaluate whether peak inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], D-dimer, ferritin, white blood cell count and interleukin-6) are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care. Results In the MGH cohort (n = 1202), obesity was associated with greater likelihood of ventilation or death (OR = 1.73; 95% CI = [1.25, 2.41]; P = 0.001) and higher peak CRP (P &lt; 0.001) compared with nonobese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (P &lt; 0.001). Evidence of mediation was more pronounced in patients &lt; 65 years (proportion mediated = 0.52 [P &lt; 0.001] vs 0.44 [P = 0.180]). Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (n = 2626). Conclusion Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients &lt; 65 years, captured by CRP and ESR. Contextualized in clinical trial findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients.

Similar Piperacillin/Tazobactam Target Attainment in Obese versus Nonobese Patients despite Differences in Interstitial Tissue Fluid Pharmacokinetics

Precision dosing of piperacillin/tazobactam in obese patients is compromised by sparse information on target-site exposure. We aimed to evaluate the appropriateness of current and alternative piperacillin/tazobactam dosages in obese and nonobese patients. Based on a prospective, controlled clinical trial in 30 surgery patients (15 obese/15 nonobese; 0.5-h infusion of 4 g/0.5 g piperacillin/tazobactam), piperacillin pharmacokinetics were characterized in plasma and at target-site (interstitial fluid of subcutaneous adipose tissue) via population analysis. Thereafter, multiple 3–4-times daily piperacillin/tazobactam short-term/prolonged (recommended by EUCAST) and continuous infusions were evaluated by simulation. Adequacy of therapy was assessed by probability of pharmacokinetic/pharmacodynamic target-attainment (PTA ≥ 90%) based on time unbound piperacillin concentrations exceed the minimum inhibitory concentration (MIC) during 24 h (%fT>MIC). Lower piperacillin target-site maximum concentrations in obese versus nonobese patients were explained by the impact of lean (approximately two thirds) and fat body mass (approximately one third) on volume of distribution. Simulated steady-state concentrations were 1.43-times, 95%CI = (1.27; 1.61), higher in plasma versus target-site, supporting targets of %fT>2×MIC instead of %fT>4×MIC during continuous infusion to avoid target-site concentrations constantly below MIC. In all obesity and renally impairment/hyperfiltration stages, at MIC = 16 mg/L, adequate PTA required prolonged (thrice-daily 4 g/0.5 g over 3.0 h at %fT>MIC = 50) or continuous infusions (24 g/3 g over 24 h following loading dose at %fT>MIC = 98) of piperacillin/tazobactam.

Obesity is associated with severe disease and mortality in patients with coronavirus disease 2019 (COVID-19): a meta-analysis

Background The coronavirus disease 2019 (COVID-19) pandemic has led to global research to predict those who are at greatest risk of developing severe disease and mortality. The aim of this meta-analysis was to determine the associations between obesity and the severity of and mortality due to COVID-19. Methods We searched the PubMed, EMBASE, Cochrane Library and Web of Science databases for studies evaluating the associations of obesity with COVID-19. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Meta-regression analyses were conducted to estimate regression coefficients. Results Forty-six studies involving 625,153 patients were included. Compared with nonobese patients, obese patients had a significantly increased risk of infection. (OR 2.73, 95% CI 1.53–4.87; I2 = 96.8%), hospitalization (OR 1.72, 95% CI 1.55–1.92; I2 = 47.4%), clinically severe disease (OR 3.81, 95% CI 1.97–7.35; I2 = 57.4%), mechanical ventilation (OR 1.66, 95% CI 1.42–1.94; I2 = 41.3%), intensive care unit (ICU) admission (OR 2.25, 95% CI 1.55–3.27; I2 = 71.5%), and mortality (OR 1.61, 95% CI 1.29–2.01; I2 = 83.1%). Conclusion Patients with obesity may have a greater risk of infection, hospitalization, clinically severe disease, mechanical ventilation, ICU admission, and mortality due to COVID-19. Therefore, it is important to increase awareness of these associations with obesity in COVID-19 patients.

Does minimally invasive spine surgery improve outcomes in the obese population? A retrospective review of 1442 degenerative lumbar spine surgeries

OBJECTIVE The effect of obesity on outcomes in minimally invasive surgery (MIS) approaches to posterior lumbar surgery is not well characterized. The authors aimed to determine if there was a difference in operative variables and complication rates in obese patients who underwent MIS versus open approaches in posterior spinal surgery, as well as between obese and nonobese patients undergoing MIS approaches. METHODS A retrospective review of all consecutive patients who underwent posterior lumbar surgery from 2013 to 2016 at a single institution was performed. The primary outcome measure was postoperative complications. Secondary outcome measures included estimated blood loss (EBL), operative time, the need for revision, and hospital length of stay (LOS); readmission and disposition were also reviewed. Obese patients who underwent MIS were compared with those who underwent an open approach. Additionally, obese patients who underwent an MIS approach were compared with nonobese patients. Bivariate and multivariate analyses were carried out between the groups. RESULTS In total, 423 obese patients (57.0% decompression and 43.0% fusion) underwent posterior lumbar MIS. When compared with 229 obese patients (56.8% decompression and 43.2% fusion) who underwent an open approach, patients in both the obese and nonobese groups who underwent MIS experienced significantly decreased EBL, LOS, operative time, and surgical site infections (SSIs). Of the nonobese patients, 538 (58.4% decompression and 41.6% fusion) underwent MIS procedures. When compared with nonobese patients, obese patients who underwent MIS procedures had significantly increased LOS, EBL, operative time, revision rates, complications, and readmissions in the decompression group. In the fusion group, only LOS and disposition were significantly different. CONCLUSIONS Obese patients have poorer outcomes after posterior lumbar MIS when compared with nonobese patients. The use of an MIS technique can be of benefit, as it decreased EBL, operative time, LOS, and SSIs for posterior decompression with or without instrumented fusion in obese patients.

Obesity as a Risk Factor for Failure to Wean from ECMO: A Systematic Review and Meta-Analysis

Purpose. Obesity has been associated with an increased risk of respiratory complications and other systemic illnesses. Respiratory dynamics in an obese patient, combined with modified lung physiology of ARDS, present a significant challenge in managing obese patients with ARDS. Many physicians think of obesity as a relative contraindication to ECMO. We performed a meta-analysis to see the effect of obesity on weaning from ECMO and survival to hospital discharge. Methods. We searched online databases for studies on ECMO and obesity. The search yielded 49 citations in total; after extensive review, six studies were assessed and qualified to be included in the final analysis. Patients were stratified into BMI >30 kg/m2 (obese) and BMI < 30 kg/m2 (nonobese). Results. In meta-analysis, there was a total sample population of 1285 patients, with 466 in the obese group and 819 in the nonobese group. There was no significant difference in weaning from ECMO when compared between obese and nonobese patients, with a risk ratio of 1.03 and 95% confidence interval (CI) of 0.94–1.13 (heterogeneity: chi2 = 7.44, df = 4 ( p = 0.11 ), I2 = 46%). There was no significant difference in survival rates between obese and nonobese patients who were treated with ECMO during hospitalization, with a risk ratio of 1.04 and 95% CI of 0.86–1.25 (heterogeneity: Tau2 0.03, chi2 = 14.61, df = 5 ( p = 0.01 ), I2 = 66%). Conclusion. Our findings show no significant difference in survival and weaning from ECMO in obese vs. nonobese patients. ECMO therapy should not be withheld from obese patients, as obesity is not a contraindication to ECMO.