High Prevalence of Long COVID in Common Variable Immunodeficiency: An Italian Multicentric Study.

The long-term effects of SARS-CoV-2 infection represent a relevant global health problem. Long COVID (LC) is defined as a complex of signs and symptoms developed during or after SARS-CoV-2 infection and lasting > 12 weeks. In common variable immunodeficiency (CVID) patients, we previously reported higher risk of hospitalization and death during SARS-CoV-2 infection, as well as prolonged swab positivity and frequent reinfections. The aim of the present study was to assess the risk of LC in an Italian cohort of CVID patients. We used a translated version of the survey proposed by Centers for Disease Control and Prevention (CDC) to collect data on LC. In the enrolled cohort of 175 CVID patients, we found a high prevalence of LC (65.7%). The most frequent LC symptoms were fatigue (75.7%), arthralgia/myalgia (48.7%), and dyspnea (41.7%). The majority of patients (60%) experienced prolonged symptoms, for at least 6 months after infection. In a multivariate analysis, the presence of complicated phenotype (OR 2.44, 95% CI 1.88-5.03; p = 0.015), obesity (OR 11.17, 95% CI 1.37-90.95; p = 0.024), and female sex (OR 2.06, 95% CI 1.09-3.89; p = 0.024) significantly correlated with the development of LC. In conclusion, in this multicenter observational cohort study, we demonstrated that CVID patients present an increased prevalence of LC when compared to the general population. Improved awareness on the risk of LC in CVID patients could optimize management of this new and alarming complication of SARS-CoV-2 infection.

Healthy overweight and obesity in the young: Prevalence and risk of major adverse cardiovascular events.

AIMS: To investigate the prevalence of metabolically healthy overweight/obesity and to study its longitudinal association with major adverse cardiovascular and renal events (MARCE). METHODS AND RESULTS: The study was conducted in 1210 young-to-middle-age subjects grouped according to their BMI and metabolic status. The risk of MARCE was evaluated during 17.4 years of follow-up. Forty-eight-percent of the participants had normal weight, 41.9% had overweight, and 9.3% had obesity. Metabolically healthy status was found in 31.1% of subjects with normal weight and in 20.0% of those with overweight/obesity. During the follow-up, there were 108 MARCE. In multivariate Cox analysis adjusted for confounders and risk factors, no association was found between MARCE and overweight/obesity (p = 0.49). In contrast, metabolic status considered as a two-class variable (0 versus at least one metabolic abnormality) was a significant predictor of MARCE (HR, 2.11; 95%CI, 1.21-3.70, p = 0.009). Exclusion of atrial fibrillation from MARCE (N = 87) provided similar results (HR, 2.11; 95%CI, 1.07-4.16, p = 0.030). Inclusion of average 24 h BP in the regression model attenuated the strength of the associations. Compared to the group with healthy metabolic status, the metabolically unhealthy overweight/obesity participants had an increased risk of MARCE with an adjusted HR of 2.33 (95%CI, 1.05-5.19, p = 0.038). Among the metabolically healthy individuals, the CV risk did not differ according to BMI group (p = 0.53). CONCLUSION: The present data show that the risk of MARCE is not increased in young metabolically healthy overweight/obesity suggesting that the clinical approach to people with high BMI should focus on parameters of metabolic health rather than on BMI.

NETosis in Acute Thrombotic Disorders.

The release of extracellular traps by neutrophils (NETs) represents a novel active mechanism of cell death that has been recently implicated in the pathogenesis of thrombotic disorders. The aim of this study was to investigate the generation of NETs in different groups of patients with acute thrombotic events (ATEs) and to establish whether NETs markers can predict the risk of new cardiovascular events. We performed a case-control study of patients with ATE, including acute coronary syndrome (n = 60), cerebrovascular accident (n = 50), and venous thromboembolism (n = 55). Control subjects (n = 70) were identified among patients admitted for acute chest pain and in which a diagnosis of ATE was excluded. Serum levels of NET markers and neutrophil activation, such as myeloperoxidase (MPO)-DNA complexes, neutrophil gelatinase-associated lipocalin, polymorphonuclear neutrophil elastase, lactoferrin, and MPO, were measured in each patient. We found that circulating levels of MPO-DNA complexes were significantly increased in patients with ATE (p < 0.001) compared with controls and that this association remained significant even after fully adjustment for traditional risk factors (p = 0.001). A receiver operating characteristics analysis of circulating MPO-DNA complexes in discriminating between controls and patients with ATE showed a significant area under the curve of 0.76 (95% confidence interval: 0.69-0.82). After a median follow-up of 40.7 (± 13.8) months, 24 out of the 165 patients with ATE presented a new cardiovascular event and 18 patients died. None of the markers under investigation influenced survival or the incidence of new cardiovascular events. In conclusion, we found that increase of markers of NETosis can be observed in acute thrombotic conditions, occurring both on the arterial and venous site. Nevertheless, the level of neutrophil markers measured during the ATE is not predictive of future risk of mortality and cardiovascular events.

Hyperuricemia increases the risk of cardiovascular mortality associated with very high HdL-cholesterol level.

BACKGROUND AND AIMS: Whether the association between very high HDL-cholesterol levels and cardiovascular mortality (CVM) is modulated by some facilitating factors is unclear. Aim of the study was to investigate whether the risk of CVM associated with very high HDL-cholesterol is increased in subjects with hyperuricemia. METHODS AND RESULTS: Multivariable Cox analyses were made in 18,072 participants from the multicentre URRAH study stratified by sex and HDL-cholesterol category. During a median follow-up of 11.4 years there were 1307 cases of CVM. In multivariable Cox models a J-shaped association was found in the whole population, with the highest risk being present in the high HDL-cholesterol group [>80 mg/dL, adjusted hazard ratio (HR), 1.28; 95%CI, 1.02-1.61; p = 0.031)]. However, a sex-specific analysis revealed that this association was present only in women (HR, 1.34; 95%CI, 1.02-1.77; p = 0.034) but not in men. The risk of CVM related to high HDL-cholesterol was much greater in the women with high uric acid (>0.30 mmol/L, HR 1.61; 95%CI, 1.08-2.39) than in those with low uric acid (HR, 1.17; 95%CI, 0.80-1.72, p for interaction = 0.016). In women older than 70 years with hyperuricemia the risk related to high HDL-cholesterol was 1.83 (95%CI, 1.19-2.80, p < 0.005). Inclusion of BMI in the models weakened the strength of the associations. CONCLUSION: Our data indicate that very high HDL-cholesterol levels in women are associated with CVM in a J-shaped fashion. The risk of CVM is increased by concomitant hyperuricemia suggesting that a proinflammatory/oxidative state can enhance the detrimental cardiovascular effects associated with high HDL-cholesterol.

Exaggerated blood pressure response to standing in young-to-middle-age subjects: prevalence and factors involved.

PURPOSE: To investigate the prevalence of orthostatic hypertension and the association of the blood pressure (BP) level, supine BP decline, and white-coat effect with the orthostatic pressor response. METHODS: We studied 1275 young-to-middle-age individuals with stage-1 hypertension. Orthostatic response was assessed three times over a 3 month period. The white-coat effect was assessed at baseline and after 3 months, and was calculated as the difference between office and average 24 h BP. In 660 participants, urinary epinephrine and norepinephrine were also measured. RESULTS: An orthostatic systolic BP increase ≥ 20 mmHg was observed in 0.6-1.2% of the subjects during the three visits. Using the 20 mmHg cut-off, the prevalence of orthostatic hypertension was 0.6%. An orthostatic BP increase of ≥ 5 mmHg was found in 14.4% of participants. At baseline, the orthostatic response to standing showed an independent negative association with the supine BP level (p < 0.001), the supine BP change from the first to third measurement (p < 0.001), and the white-coat effect (p < 0.001). Similar results were obtained in the 1080 participants assessed at the third visit. Urinary epinephrine showed higher values in the top BP response decile (systolic BP increase ≥ 6 mmHg, p = 0.002 versus rest of the group). CONCLUSION: An orthostatic systolic BP reaction ≥ 20 mmHg is rare in young adults. However, even lower BP increases may be clinically relevant. The BP level, the supine BP decline over repeated measurement, and the white-coat effect can influence the estimate of the BP response to standing and should be considered in clinical and pathogenetic studies.

Cytokines in Spondyloarthritis and Inflammatory Bowel Diseases: From Pathogenesis to Therapeutic Implications.

Spondyloarthritis and inflammatory bowel diseases are chronic immune disorders of the joints and the gut that often coexist in the same patient, increasing the burden of each disorder, worsening patients' quality of life, and influencing therapeutic strategies. Genetic predisposition, environmental triggers, microbiome features, immune cell trafficking, and soluble factors such as cytokines contribute to the pathogenesis of both articular and intestinal inflammation. Most of the molecular targeted biological therapies developed over the last two decades were based on evidence that specific cytokines may be involved in these immune diseases. Despite pro-inflammatory cytokine pathways sharing the pathogenesis of both articular and gut diseases (i.e., tumor necrosis factor and interleukin-23), several other cytokines (i.e., interleukin-17) may be differently involved in the tissue damage process, depending on the specific disease and the organ involved in inflammation, making difficult the identification of a therapeutic plan that is efficacious for both inflammatory manifestations. In this narrative review, we comprehensively summarize the current knowledge on cytokine involvement in spondyloarthritis and inflammatory bowel diseases, underlining similarities and differences among their pathogenetic pathways; finally, we provide an overview of current and potential future treatment strategies to simultaneously target both articular and gut immune disorders.

The Role of Neutrophils in Lower Limb Peripheral Artery Disease: State of the Art and Future Perspectives.

In recent years, increasing attention has been paid to the role of neutrophils in cardiovascular (CV) disease (CVD) with evidence supporting their role in the initiation, progression, and rupture of atherosclerotic plaque. Although these cells have long been considered as terminally differentiated cells with a relatively limited spectrum of action, recent research has revealed intriguing novel cellular functions, including neutrophil extracellular trap (NET) generation and inflammasome activation, which have been linked to several human diseases, including CVD. While most research to date has focused on the role of neutrophils in coronary artery and cerebrovascular diseases, much less information is available on lower limb peripheral artery disease (PAD). PAD is a widespread condition associated with great morbidity and mortality, though physician and patient awareness of the disease remains low. To date, several studies have produced some evidence on the role of certain biomarkers of neutrophil activation in this clinical setting. However, the etiopathogenetic role of neutrophils, and in particular of some of the newly discovered mechanisms, has yet to be fully elucidated. In the future, complementary assessment of neutrophil activity should improve CV risk stratification and provide personalized treatments to patients with PAD. This review aims to summarize the basic principles and recent advances in the understanding of neutrophil biology, current knowledge about the role of neutrophils in atherosclerosis, as well as available evidence on their role of PAD.

Serum uric acid levels threshold for mortality in diabetic individuals: The URic acid Right for heArt Health (URRAH) project.

BACKGROUND AND AIM: The URRAH (URic acid Right for heArt Health) Study has identified cut-off values of serum uric acid (SUA) predictive of total mortality at 4.7 mg/dl, and cardiovascular (CV) mortality at 5.6 mg/dl. Our aim was to validate these SUA thresholds in people with diabetes. METHODS AND RESULTS: The URRAH subpopulation of people with diabetes was studied. All-cause and CV deaths were evaluated at the end of follow-up. A total of 2570 diabetic subjects were studied. During a median follow-up of 107 months, 744 deaths occurred. In the multivariate Cox regression analyses adjusted for several confounders, subjects with SUA ≥5.6 mg/dl had higher risk of total (HR: 1.23, 95%CI: 1.04-1.47) and CV mortality (HR:1.31, 95%CI:1.03-1.66), than those with SUA <5.6 mg/dl. Increased all-cause mortality risk was shown in participants with SUA ≥4.7 mg/dl vs SUA below 4.7 mg/dl, but not statistically significant after adjustment for all confounders. CONCLUSIONS: SUA thresholds previously proposed by the URRAH study group are predictive of total and CV mortality also in people with diabetes. The threshold of 5.6 mg/dl can predict both total and CV mortality, and so is candidate to be a clinical cut-off for the definition of hyperuricemia in patients with diabetes.

Subclinical atherosclerosis evolution during 5 years of anti-TNF-alpha treatment in psoriatic arthritis patients.

OBJECTIVES: Our aim was to evaluate subclinical atherosclerosis progression during 5 years of anti-tumour necrosis factor (TNF)-α treatment in psoriatic arthritis (PsA) patients. METHODS: Thirty-two consecutive PsA patients starting TNF-α inhibitors were enrolled and evaluated at baseline (T0), 2 years (FU1) and 5 years (FU2) of treatment. Arterial structural properties were evaluated by B-mode ultrasound of mean carotid intima-media thickness (mean-IMT) and maximum IMT (M-MAX) in each segment (common, bulb, internal), bilaterally. Endothelial function was assessed by post-occlusion flow-mediated dilation (FMD) of the brachial artery using high-sensitivity ultrasonography. Treatment response was studied through DAS28 (disease activity score) and inflammatory biomarkers (C-reactive protein, TNF-α, osteoprotegerin). Metrologic and metabolic data were collected. RESULTS: At T1, a significant decrease of DAS28 (4.2±0.7 vs. 2.3±0.8, p<0.001) and CRP (11.25±9.16 vs. 2.91±1.72, p<0.01) was observed. Efficacy was preserved at FU2 (DAS28 2.4±0.9, CRP 2.73±2.51; p=ns vs. FU1). Systolic blood pressure and BMI remained stable throughout the follow-up, while diastolic blood pressure decreased significantly from FU1 to FU2 (80±10 vs. 74±7 mmHg, p=0.001). From T0 to FU1 there was an increase of IMT-mean and M-MAX (0.7±0.1 vs. 0.9±0.4 and 0.9±0.2 vs. 1.1±0.4, p<0.01). At FU2, IMT-mean and M-max did not change significantly (0.9±0.3 and 1.1±0.3, p=ns vs. FU1). No significant variation in FMD values was observed during the study period. CONCLUSIONS: A slight progression of subclinical atherosclerosis in PsA was observed in the first 2 years of anti-TNF-α treatment. This process seemed to decelerate in follow-up extension to 5 years.

Developing an instrument for an early prediction model of long-term functional outcomes in people with acquired injuries of the central nervous system: protocol and methodological aspects.

Severe acquired brain injury (ABI) is a major cause of long-term disability and is the main determinant of health and societal costs. Early identification of favourable long-term recovery would allow personalized rehabilitative programs and better health care resources allocation. In light of the higher survival rate from intensive care units (ICU) in recent years, there is a growing need for early prognostication markers of functional recovery; to date, these data have been mainly collected at rehabilitation unit admission and not during the acute phase. We present the protocol and methodology to develop prediction models in people with severe acquired brain injury (GCS at admission to ICU < 8) for the functional and cognitive outcome at 12 months from the event. Predictors will be collected during the acute stage. Participants will be recruited within the first 72 h from the event in the ICUs of two teaching hospitals (Padova and Treviso). Participants will be followed up at discharge from ICU, admission and discharge from Neurorehabilitation and after 12 months from the event. Clinical and functional scales, electroencephalography, evoked potentials, magnetic resonance imaging and serological markers will be entered into a digital registry. Survival will be estimated using the Cox proportional hazard model. A multivariate prediction model will be developed for each of the functional and cognitive outcomes at 12 months from the event.

Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis.

Calcific aortic valve stenosis (CAVS), the most common heart valve disease, is characterized by the slow progressive fibro-calcific remodeling of the valve leaflets, leading to progressive obstruction to the blood flow. CAVS is an increasing health care burden and the development of an effective medical treatment is a major medical need. To date, no effective pharmacological therapies have proven to halt or delay its progression to the severe symptomatic stage and aortic valve replacement represents the only available option to improve clinical outcomes and to increase survival. In the present report, the current knowledge and latest advances in the medical management of patients with CAVS are summarized, placing emphasis on lipid-lowering agents, vasoactive drugs, and anti-calcific treatments. In addition, novel potential therapeutic targets recently identified and currently under investigation are reported.

Intima-media thickness remodelling in hypertensive subjects with long-term well-controlled blood pressure levels.

Aim of this study was to evaluate in a long follow-up the carotid artery remodelling in a cohort of young hypertensive subjects having good blood pressure (BP) control. We studied 20 grade I hypertensives (HT) by assessing the B-mode ultrasound of mean carotid intima-media thickness (mean-IMT) and maximum IMT (M-MAX) in each carotid artery segment (common, bulb, internal), bilaterally. We compared their ultrasound measurements with those recorded 5 and 10 years earlier. While the first 5-year follow-up was observational, in the second 5-year follow-up, lifestyle modifications and/or pharmacological therapy were started to obtain well-controlled BP levels. Office BP was measured at the time of the ultrasound studies and every 6 months during the follow-up. BP levels were: 10 years 144/91 mmHg, 5 years 143/90 mmHg and 129 ± 79 mmHg at the time of the study. In the first 5-year observational follow-up, both mean-IMT and M-MAX increased (Δ 0.116 and Δ 0.165 mm, respectively, p < 0.0005). In the 5-year intervention follow-up, characterized by well-controlled BP, mean-IMT slightly but significantly increased (Δ 0.084 mm, p = 0.004), whereas M-MAX remained stable (Δ 0.026 mm). In our HT, well-controlled BP levels were able to prevent pro-atherogenic remodelling (expressed by M-MAX). Conversely, good BP control slightly decreased but did not stop the progression in mean-IMT, which is likely to reflect some hypertrophy of the arterial media layer.

Association between the metabolic syndrome, its individual components, and unprovoked venous thromboembolism: results of a patient-level meta-analysis.

OBJECTIVE: The metabolic syndrome (MetS) may contribute to the pathogenesis of venous thromboembolism (VTE), but this association requires additional investigation. APPROACH AND RESULTS: We performed a patient-level meta-analysis of case-control and cohort studies that evaluated the role of MetS and risk of unprovoked VTE. For case-control studies, odds ratios and 95% confidence intervals were calculated using logistic regression analysis to estimate the influence of individual variables on the risk of VTE; χ(2) tests for trend were used to investigate the effect of increasing number of components of MetS on the risk of VTE and to explore the influence of abdominal obesity on this relationship. For cohort studies, hazard ratios and 95% confidence interval were calculated using multivariable Cox regression analysis. Six case-control studies were included (908 cases with unprovoked VTE and 1794 controls): in multivariate analysis, MetS was independently associated with VTE (odds ratio, 1.91; 95% confidence interval, 1.57-2.33), and both MetS and abdominal obesity were better predictors of unprovoked VTE than obesity defined by the body mass index. Two prospective cohort studies were included (26,531 subjects and 289 unprovoked VTE events): age, obesity, and abdominal obesity, but not MetS were associated with VTE. CONCLUSIONS: Case-control but not prospective cohort studies support an association between MetS and VTE. Abdominal adiposity is a strong risk factor for VTE.

Psychometric and EEG changes after carotid endarterectomy.

The influence of carotid stenosis and its surgical treatment on brain function is still poorly defined. We therefore performed a study to assess psychometric and quantified EEG findings after carotid endarterectomy (CEA). Sixty-nine non-demented patients (aged 72 ± 7 years) with severe carotid stenosis (≥ 70%) eligible for CEA were studied. Forty patients (group A) had unilateral stenosis, and 29 patients (group B) had bilateral stenosis. Before and 5 months after CEA all the patients were evaluated by the Trail Making Test A, the Symbol Digit Test, and spectral EEG analysis. At baseline, compared to group A, group B patients performed slowly the Trail Making Test A (Z: 1.45 ± 1.4 vs. 0.76 ± 1.3; p < 0.05), but not the Symbol Digit Test (Z: 0.83 ± 1.38 vs. 0.64 ± 1.26; p = 0.59). Altogether, the patients with at least one abnormal psychometric test were 29% (group A: 26%; group B: 33%, p = 0.56). The EEG did not differ significantly between patients of group A compared to group B. After CEA, psychometric tests improved (mean Z score from 0.73 ± 1.12 to 0.45 ± 1.15, p < 0.05). The improvement was similar in group A and B. The EEG mean dominant frequency improved only in group B patients and it was related to the improvement in psychometric tests (r = 0.43, p = 0.05). Low psychometric performance was detectable in about 1/ 3 of non-demented patients with severe carotid stenosis. CEA improved mental performance and, in patients with severe bilateral stenosis, accelerated the EEG frequency.

No peptide left behind: the "out of range" recovery in IPG-IEF fractionation.

IEF is often used in multidimensional shotgun proteomics and the narrow range of 3.5-4.5 is the recommended pH interval for the fractionation of tryptic peptides. Usually, even if IEF is performed in IPG strip with a narrow range pH, the entire sample must be loaded onto the strip, including the "out of IPG range" peptides. We describe a simple protocol to recover at least a part of these missing peptides and show that this recovery significantly influences the overall fractionation result, increasing the number of the identified proteins and the protein coverage.

Where AIRE we now? Where AIRE we going?

PURPOSE OF REVIEW: The purpose of the review is to describe the most recent advancement in understanding of the pivotal role of autoimmune regulator ( AIRE ) gene expression in central and peripheral tolerance, and the implications of its impairment in the genetic and pathogenesis of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) manifestations with insight into possible treatment options. RECENT FINDINGS: AIRE gene expression has an important role of central and peripheral tolerance. Different AIRE gene mutations cause APECED, whereas polymorphisms and some variants may be implicated in development of other more frequently autoimmune diseases. Impaired negative T cell selection, reduction of T regulatory function, altered germinal center response, activated B cells and production of autoantibodies explain the development of autoimmunity in APECED. Recent data suggest that an excessive interferon-γ response may be the primer driver of the associated organ damage. Therefore, Janus kinase (JAK)-inhibitors may be promising therapies for treatment of broad spectrum of manifestations. SUMMARY: AIRE has a pivotal role in immune tolerance. Disruption of this delicate equilibrium results in complex immune perturbation, ranging from severe autoimmunity, like APECED, to more common organ-specific disorders. Therefore, a deeper understanding of the correlation between AIRE function and clinical phenotype is warranted given the potential translational implication in clinical practice.

Reproducibility of daytime hypertension, night-time hypertension, and nocturnal blood pressure dipping patterns in young to middle age patients with stage 1 hypertension.

OBJECTIVE: To investigate the reproducibility of ambulatory BP sub-periods and nocturnal dipping phenotypes assessed twice 3 months apart in young-to-middle-age untreated individuals screened for stage 1 hypertension. DESIGN AND METHODS: We investigated 1096, 18-to-45-year old participants from the HARVEST. Their office BP was 145.8 ±â€Š10.4/93.7 ±â€Š5.7 mmHg. Office BP and 24 h BP were measured at baseline and after 3 months. Office, 24-h, daytime and night-time hypertensions, and nocturnal dipping patterns were defined according to the 2023 ESH guidelines. Between-recording agreement was evaluated with kappa statistics. RESULTS: Reproducibility evaluated with weighted kappa was moderate for both 24 h hypertension ( K  = 0.48) and daytime hypertension ( K  = 0.50) and was only fair for night-time hypertension ( K  = 0.36). Between-measurement agreement was even worse for isolated night-time hypertension ( K  = 0.24), and was poor for office hypertension ( K  = 0.14). The better reproducibility of daytime than night-time period was confirmed by the analysis of BP as continuous variable (all between-period differences, P  < 0.001). Nondipping was present in 31.8%, and showed a fair agreement ( K  = 0.28,). Poorer agreement was shown by extreme dipping ( K  = 0.18) and reverse dipping ( K  = 0.07). CONCLUSIONS: These data show that within the ambulatory sub-periods, daytime hypertension has a better reproducibility than night-time hypertension. This suggests that the better association with adverse outcomes shown by sleep BP compared to wake BP in observational studies is not due to a better reproducibility of the former. The between-measurement agreement is even worse for isolated nocturnal hypertension and dipping patterns, especially for extreme and reverse dipping. Thus, these BP phenotypes should be confirmed with repeat ambulatory BP monitoring.

COVID-19 Clinical Features and Outcome in Italian Patients Treated with Biological Drugs Targeting Type 2 Inflammation.

This is a multicentric investigation involving two Italian centers that examined the clinical course of COVID-19 in patients receiving biological therapy targeting type 2 inflammation and those not receiving biologicals. Since the beginning of the COVID-19 pandemic, the management of respiratory and allergic disorders and the potential impact of biological therapy in the most severe forms has been a point of uncertainty. Our multicentric investigation aimed to compare the clinical course of COVID-19 and the impact of vaccination in an Italian cohort of patients with atopic disorders caused by a type 2 inflammation, such as eosinophilic asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). A questionnaire was given to patients coming to our outpatient clinic for the first evaluation or follow-up visit, asking for the clinical characteristics of the infection, the ongoing therapy during the infection, any relevant change, and the patient's vaccination status. We enrolled 132 atopic patients from two Italian centers; 62 patients were on biological therapy at the time of infection (omalizumab 31%, mepolizumab 26%, benralizumab 19%, and dupilumab 24%). The median age was 56 (IQR 22.8) for patients on biologicals and 48 (IQR 26.5) for those not on biologicals (p = 0.028). The two groups were comparable in terms of sex, body mass index (BMI), smoking history, and systemic oral corticosteroid use (OCS). There were no significant differences in non-biological therapy and comorbidity between the two groups. The patients not on biological therapy had a prevalence of 87% for asthma, 52% for CRSwNP, 10% for CSU, and 6% for AD. The patients on biologicals had a prevalence of 93% for asthma, 17% for CRSwNP, and 10% for CSU. In our work, we observed that mAbs targeting type 2 inflammation in patients with COVID-19 appeared to be safe, with no worsening of symptoms, prolongation of infection, or increase in hospitalizations. Between the two groups, there were no significant differences in the duration of swab positivity (p = 0.45) and duration of symptoms (p = 0.38). During COVID-19, patients on biologicals experienced a significant increase in common cold-like symptoms (p = 0.038), dyspnea (p = 0.016), and more, but not significant, asthma exacerbations, with no significant differences between the different biologicals. Regarding the vaccination status, we observed that there was an increased number of hospitalizations among unvaccinated patients in both groups, although the difference did not reach statistical significance. No patients on biologicals reported safety issues or adverse effects associated with the use of biological treatments during COVID-19. Our investigation showed that mAbs against type 2 inflammation given during Coronavirus Disease 2019 are safe and do not impact the clinical course or main outcomes. Therefore, we found no signals suggesting that anti-Th2 biological therapy should be discontinued during SARS-CoV-2 infection. Controlled studies and analysis, including data from registries and real-life studies, are required to draw firm conclusions regarding the safety or possible advantages that anti-type 2 mAbs could offer in particular clinical contexts, such as infections.

Instability of Healthy Overweight and Obesity Phenotypes over the Long Term in Young Participants in the HARVEST Study: Influence of Sex.

BACKGROUND: Whether healthy metabolic status is stable or only temporary is still controversial. The aim of the present study was to determine the frequency of the transition from metabolically healthy to metabolically unhealthy status, or vice versa, over the long term. METHODS: We examined 970 individuals of 18 to 45 years of age. The participants' mean age was 33.1 ± 8.6 years and mean BP was 145.5 ± 10.6/93.5 ± 5.7 mmHg. Participants were classified into four groups according to whether they had normal weight or overweight/obesity (OwOb) and were metabolically healthy or unhealthy. After 7.5 years, 24.3% of men and 41.9% of women in the metabolically healthy normal-weight group remained metabolically healthy (p < 0.0001). Among the metabolically healthy OwOb participants, 31.9% remained metabolically healthy, with a similar frequency in men and women. However, more OwOb women (19.1%) than men (5.7%) achieved normal weight (p < 0.0001). Among the metabolically unhealthy OwOb subjects, 81.8% of men and 69.3% of women remained metabolically unhealthy, 7.4% of men and 12.0% of women transitioned to OwOb healthy status, and 10.7% of men and 18.7% of women achieved normal weight (men versus women, p < 0.0001). Predictors of transition to unhealthy status were high BP, high BMI, and smoking. Male sex was a borderline predictor of progression to unhealthy status in OwOb participants (p = 0.073). CONCLUSION: These data show that metabolically healthy status is a highly unstable condition in both normal-weight and OwOb individuals. The impairment of metabolic status was more frequent in men than in women. Lifestyle counseling produced beneficial effects in almost one-third of metabolically unhealthy OwOb women and in less than one-fifth of men.

Sarcoidosis versus Granulomatous and Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency: A Comparative Review.

Sarcoidosis and Granulomatous and Lymphocytic Interstitial Lung Diseases (GLILD) are two rare entities primarily characterised by the development of Interstitial Lung Disease (ILD) in the context of systemic immune dysregulation. These two conditions partially share the immunological background and pathologic findings, with granuloma as the main common feature. In this narrative review, we performed a careful comparison between sarcoidosis and GLILD, with an overview of their main similarities and differences, starting from a clinical perspective and ending with a deeper look at the immunopathogenesis and possible target therapies. Sarcoidosis occurs in immunocompetent individuals, whereas GLILD occurs in patients affected by common variable immunodeficiency (CVID). Moreover, peculiar extrapulmonary manifestations and radiological and histological features may help distinguish the two diseases. Despite that, common pathogenetic pathways have been suggested and both these disorders can cause progressive impairment of lung function and variable systemic granulomatous and non-granulomatous complications, leading to significant morbidity, reduced quality of life, and survival. Due to the rarity of these conditions and the extreme clinical variability, there are still many open questions concerning their pathogenesis, natural history, and optimal management. However, if studied in parallel, these two entities might benefit from each other, leading to a better understanding of their pathogenesis and to more tailored treatment approaches.