Higher rates of COVID-19 but less severe infections reported for patients on Dupilumab: a Big Data analysis of the World Health Organization VigiBase.

OBJECTIVE: Dupilumab (Dupixent®) is a monoclonal antibody that inhibits IL-4 and IL-13 signaling used for the treatment of allergic diseases. Whilst biologic therapy is traditionally regarded as immunosuppressive and capable to increase the infectious risk, Dupilumab does not display these characteristics and may be even protective in certain cases. We investigated the link between Dupilumab therapy and SARS-CoV-2 infection. MATERIALS AND METHODS: We carried out a comprehensive data mining and disproportionality analysis of the WHO global pharmacovigilance database. One asymptomatic COVID-19 case, 106 cases of symptomatic COVID-19, and 2 cases of severe COVID-19 pneumonia were found. RESULTS: Dupilumab treated patients were at higher risk of COVID-19 (with an IC0.25 of 3.05), even though infections were less severe (IC0.25 of -1.71). The risk of developing COVID-19 was significant both among males and females (with an IC0.25 of 0.24 and 0.58, respectively). The risk of developing COVID-19 was significant in the age-group of 45-64 years (with an IC0.25 of 0.17). CONCLUSIONS: Dupilumab use seems to reduce COVID-19 related severity. Further studies are needed to better understand the immunological mechanisms and clinical implications of these findings. Remarkably, the heterogenous nature of the reports and the database structure did not allow to establish a cause-effect link, but only an epidemiologically decreased risk in the patients subset treated with dupilumab.

Safety profile of Dupilumab during pregnancy: a data mining and disproportionality analysis of over 37,000 reports from the WHO individual case safety reporting database (VigiBase™).

Atopic dermatitis, known also as atopic eczema, represents a commonly diagnosed, chronic or recurrent/relapsing inflammatory disorder. From a clinical point of view, it is characterized by acute flare-ups of intense itching, eczematous pruritic lesions involving dry skin. Dupilumab is the only biologic agent approved to treat moderate to severe course of atopic dermatitis, which can be particularly severe during pregnancy causing distress and impacting on maternal and fetal health. However, there is a dearth of data concerning the safety profile of Dupilumab during gestation. Therefore, we took advantage of a large global pharmacovigilance database. From inception up to March 9, 2021, 94,065 adverse drug reactions (ADRs) from 37,848 unique reports were retrieved. Of these, 36 reports related to pregnancy, puerperium and perinatal ADR could be extracted from the pharmacovigilance database. More than half of reports (n = 21; 58.3%) were spontaneous abortion, followed by other events, including exposure to the drug during the pregnancy (n = 8; 22.2%). Two cases of abortion were reported. No studied pregnancy, puerperium and perinatal ADR was found to be associated with the use of Dupilumab. The only OR significantly greater than 1 was the OR associated with the risk of developing heterotopic pregnancy (21.66 [95% CrI 2.95-159.02]) even if the IC was highly imprecise (1.45 [95% CrI from -2.34 to 3.09]), probably because of the single case of heterotopic pregnancy reported. In conclusion, Dupilumab use appears safe during gestation. Further studies are needed, especially to better understand the mechanisms underlying the pharmacological actions and ADR of Dupilumab.

Antioxidant Enzyme Activity and Cognition in Obese Individuals with or without Metabolic Risk Factors.

Background: The metabolic syndrome may be associated with cognitive impairment and increased oxidative stress. Aim: To document the association between metabolic syndrome, cognitive impairment and oxidative stress activity in metabolically healthy obese and in metabolically unhealthy obese individuals. Methods: 60 obese individuals aged (49±10 years, 52% male) were enrolled. Obesity was defined as BMI>30. Metabolic syndrome was defined according to ATP III guidelines. Obese individuals were divided into 2 groups: Group 1, metabolically healthy obese (≤2 components of metabolic syndrome), and Group 2, metabolically unhealthy obese (>2 components of metabolic syndrome). Cognitive dysfunction was determined by Montreal cognitive assessment score. Liver Fibro scan (Elastography), Inflammation (CRP), pro oxidants (MDA), antioxidant activity (SOD, PON, GSH, GPx) and insulin resistance (HOMA-IR) were measured. Results: Of the 30 metabolically unhealthy obese individuals, 13% developed dementia, 51% had mild cognitive impairment, and 36% had a normal cognitive score. In the metabolically healthy obese group, 3% developed dementia, 7% had mild cognitive impairment, and 90% had a normal cognitive score. There was a significant difference in liver stiffness (7±3 vs. 5.2±2.7 kpa, p<0.001), liver fat measurement (337±51 vs. 280±20 db/m, p<0.001), MDA (4.7±0.9 vs. 5.47±1.12 mM, P<0.003), Glutathione GSH (27.2±2.4 vs. 28.4±2.3, P<0.03), CRP (9±6 vs. 7±6 P<0.001) and insulin resistance (2.5±1 vs. 6±5.5 p<0.02) between the 2 groups. Correlations were significant between GPx activity and liver stiffness (r=0.37), GPx activity and abdominal girth (r=-0.22) and glucose concentration and SOD activity (r=0.4). Multivariate analysis showed that HOMA-IR, MDA and GSH were the most powerful predictors of metabolically unhealthy obesity. Conclusion: There is a significant mild cognitive impairment and increased oxidative stress activity in the metabolically unhealthy obese. Whether treatment with anti-oxidants improves cognitive dysfunction remains to be determined.

Significance of MPV, RDW with the Presence and Severity of Metabolic Syndrome.

PURPOSE: Metabolic syndrome (MS) is a multiplex risk factor that arises from insulin resistance accompanying abnormal adipose deposition and function. It is a risk factor for coronary heart disease, as well as for diabetes, fatty liver, and several cancers. Recent studies showed that there was a correlation between inflammatory mediators and MS. The aim of this study was to investigate the relationship between the MS and new inflammatory markers as mean platelet volume (MPV) and red blood cell distribution width (RDW), they are simple and reliable indicators of inflammation. METHOD: 200 patients who met the MS criteria and other 100 age- and sex-matched control subjects were included in this randomized controlled trial. Patients were classified into 2 groups each 100 subjects based on the number of MS criteria: group 1 (patients with 3 MS criteria), group 2 (patients with 5 MS criteria). MPV and RDW were calculated from complete blood count. RESULTS: Patients with MS had significantly higher MPV and RDW correspondingly compared to those without MS. (MPV: 8.4±0.61 v 8.80±0.60, 9.56±0.48, respectively, p<0.001) (RDW:12.38±0.77, 13.15±062, 13.90±0.55). Moreover, patients meeting 5 MS criteria had higher MPV and RDW than those meeting 3 criteria (p<0.001) and 0.000, respectively) CONCLUSION: The present study indicated, for the first time, a significant correlation between the 2 criteria of MS and inflammation based on these new markers that should be simple and reliable indicator of inflammation.

Length of stay and outcome of hospitalized chronic obstructive pulmonary disease patients, differences between General Medical Ward and Intensive Care Unit: a cohort study / Duración de la estancia y resultado de los lacientes hospitalizados por la enfermedad pulmonar obstructiva crónica, diferencias entre la Sala Médica General y la Unidad de Cuidados Intensivos:: un estudio de cohortes

BACKGROUND: Exacerbations of Chronic Obstructive Pulmonary Disease (ECOPD) are a major problem worldwide and usually a leading cause for hospitalizations and in some cases, indication for invasive mechanical ventilation (IMV). OBJECTIVE: The aim of this study was to determine the length of stay in hospital and outcome of ECOPD patients. We compared the length of hospital stay in the medical ward, intensive care unit (ICU) departments and discharges during a period of six months. METHODS: This was an observational, longitudinal prospective study of 242 COPD patients that were admitted with COPD exacerbation. In each patient, acute physiology and chronic health evaluation (APACHE) II score and serial arterial blood gases (ABG) were measured upon and during admission. RESULTS: Eighty per cent (194) of242 COPD patients were admitted to the medical department and most of them were discharged within five days. Forty-eight needed IMV and stayed in hospital more than ten days; overall mortality rate was about 5%. CONCLUSION: Most of the hospitalized patients with COPD exacerbation (60%) were discharged within five days, 20% needed IMV and stayed in hospital more than ten days.

ANTECEDENTES: Las exacerbaciones de la enfermedad pulmonar obstructiva crónica (EPOC) representan un problema grave en todo el mundo, constituyen generalmente una de las causas principales de las hospitalizaciones, y son en algunos casos la indicación de que se requiere ventilación mecánica invasiva (VMI). OBJETIVO: El objetivo de este estudio fue determinar la duración de la estancia en el hospital y el resultado de los pacientes de EPOC. Comparamos la duración de la estancia hospitalaria en la sala médica, las unidades de cuidados intensivos (UCI), y las altas producidas en un período de seis meses. MÉTODOS: Se trata de un estudio prospectivo, observacional, y longitudinal de 242 pacientes con EPOC que fueron ingresados con exacerbación de la EPOC. A cada paciente se le hicieron mediciones mediante la puntuación de la escala de Evaluación de la fisiología aguda y salud crónica (APACHE II) y la gasometría arterial seriada, tanto al momento de ingresar como durante el ingreso. RESULTADOS: El ochenta por ciento (194) de los pacientes 242 pacientes con EPOC, fueron ingresados en el departamento médico, y la mayoría de ellos fueron dados de alta en cinco días. Cuarenta y ocho necesitaron VMI, y permanecieron en el hospital más de diez días. La tasa de mortalidad general fue alrededor del 5%. CONCLUSIÓN: La mayoría de los pacientes hospitalizados con exacerbación de la EPOC (60%) fueron dados de alta dentro de cinco días. El 20% necesitó VMI, y se permaneció en el hospital más de diez días.

Calcium channel blocker effect on insulin resistance and inflammatory markers in essential hypertension patients.

AIM: Insulin resistance, inflammation and oxidative stress (OS), are among the mechanisms that have been implicated in pathogenesis of essential hypertension (EH). Peripheral polymorphonuclear leukocytes (PMNLs) are primed in EH patients, releasing uncontrolled superoxide anion contributing to OS in these patients. PMNL priming correlates with insulin resistance and with PMNL intracellular calcium ([Ca2+]i). Recent studies have attributed to the anti-hypertensive drug lercanidipine, a third generation calcium-channel blocker, and additional anti-ischemic and anti-oxidative characteristics. Aim of the study was to evaluate the possible non-traditional effect of two months of lercanidipine treatment on insulin resistance and on PMNL-related inflammation in EH patients. METHODS: Non-smoking EH patients with untreated mild to moderate high blood pressure (BP) were included. Low-graded inflammation was reflected by WBC and PMNL counts and by PMNL apoptosis. Systemic inflammation was measured by plasma fibrinogen, CRP and albumin levels. Fasting serum insulin levels served as a marker of insulin resistance. RESULTS: Two months of lercanidipine treatment showed significant decrease in BP, in WBC and PMNL counts, in PMNL apoptosis, in CRP and serum insulin levels and significant increase in serum albumin levels. Rates of superoxide release from PMNLs, WBC and PMNL counts and insulin levels positively correlated with mean arterial blood pressure values. CONCLUSION: We imply that use of this CCB lercanidipine can be favored in EH patients due to its combined anti-PMNL priming and anti-inflammatory effects, in addition to its anti-hypertensive characteristics.

Length of Stay and Outcome of Hospitalized Chronic Obstructive Pulmonary Disease Patients, Differences between General Medical Ward and Intensive Care Unit: A Cohort Study.

BACKGROUND: Exacerbations of Chronic Obstructive Pulmonary Disease (ECOPD) are a major problem worldwide and usually a leading cause for hospitalizations and in some cases, indication for invasive mechanical ventilation (IMV). OBJECTIVE: The aim of this study was to determine the length of stay in hospital and outcome of ECOPD patients. We compared the length of hospital stay in the medical ward, intensive care unit (ICU) departments and discharges during a period of six months. METHODS: This was an observational, longitudinal prospective study of 242 COPD patients that were admitted with COPD exacerbation. In each patient, acute physiology and chronic health evaluation (APACHE) II score and serial arterial blood gases (ABG) were measured upon and during admission. RESULTS: Eighty per cent (194) of 242 COPD patients were admitted to the medical department and most of them were discharged within five days. Forty-eight needed IMV and stayed in hospital more than ten days; overall mortality rate was about 5%. CONCLUSION: Most of the hospitalized patients with COPD exacerbation (60%) were discharged within five days, 20% needed IMV and stayed in hospital more than ten days.

Effects of statins on oxidative stress and primed polymorphonuclear leukocytes in hyperlipidemic patients.

Inflammation and oxidative stress are among the factors that have been implicated in the pathogenesis of hyperlipidemia. In metabolic syndrome and hyperlipidemic patients, peripheral polymorphonuclear leukocytes (PMNL) are primed and they release uncontrolled superoxide that contributes to oxidative stress and inflammation. Recent studies have demonstrated that the anti-hyperlipidemic drug, Atrovastatin effects improvement in endothelial function, exhibits anti-oxidative characteristics and reduces lipid markers of oxidation. To evaluate possible nontraditional effects of treatment with Atrovastatin on PMNL priming, oxidative stress and inflammation in hyperlipidemia, 50 non-smoking hyperlipidemic patients were treated for 6 months with Atrovastatin and compared to age and gender-matched healthy controls. PMNL priming was assessed by the rate of superoxide release from separated, phorbol ester-stimulated PMNL and by PMNL-CD11b levels. Inflammation was reflected by blood inflammatory markers including albumin, transferrin, C-reactive protein (CRP) and fibrinogen levels, white blood cells (WBC), PMNL counts and PMNL apoptosis. Atrovastatin treatment showed a reduction in PMNL priming, PMNL apoptosis, fibrinogen and CRP levels concomitant with decreased lipid levels. Atrovastatin may be preferred for hyperlipidemic patients owing to its combined anti-PMNL priming and anti-inflammatory effects in addition to its anti-atherogenic effects.