BackgroundOral immunotherapy (OIT) has been recognized as a promising treatment for severe and long-lasting cow's milk (CM) allergy. Once maintenance has been achieved, patients should maintain daily intake of CM to ensure desensitization. Clinical experience concerning long-term follow-up is scarce.ObjectiveThe authors aimed to assess long-term efficacy and safety of a maintenance phase of OIT in real life.MethodsProspective study of all children and adolescents, who underwent CM-OIT and were subsequently followed at our allergy center on maintenance dose (200 mL daily) for at least 36 months after reaching the maintenance phase (from 2009 to 2016).ResultsForty-two patients were enrolled: 60% male, 36% with history of anaphylaxis and 57% with asthma. The median time of follow-up was 69 months (range, 39–105 months) and the median age at the last clinical evaluation was 13 years (range, 6–23 years). Regarding adherence to the protocol: 92% are on free diet (at least 200 mL of CM daily; 7-g protein); 14% had transient interruptions and 7% definitely withdrawn with loss of tolerance. During maintenance, 45% developed mild to severe allergic reactions, and 7% had more than 3 episodes. A positive correlation between the occurrence of allergic reactions and history of anaphylaxis (p < 0.001) was found. The coexistence of asthma was risk factor for the occurrence of allergic reactions during maintenance.ConclusionThis real-life study supports long-term efficacy and safety of CM-OIT. Despite daily intake, 41% had symptoms at some moment during the complete follow-up period; a total of 33 symptomatic days in patients with mean follow-up time of 67.5 months. Clinical tolerance depends on daily intake. The protective effect reached can be lost after CM withdrawal. History of anaphylaxis was a risk factor for the occurrence of allergic reactions during the maintenance phase.
Sepsis leads to a systemic immune response, and despite the progress of modern medicine, it is still responsible for a high mortality rate. The immune response to sepsis is dependent on the innate and adaptive immune systems. The first line is the innate system, which requires complex and multiple pathways in order to eliminate the invading threats. The adaptive responses start after the innate response. The cell-mediated arm of CD4+ and CD8+ T and B cells is the main responsible for this response. A coordinated cytokine response is essential for the host immune response. A dysregulated response can lead to a hyperinflammatory condition (cytokine storm). This hyperinflammation leads to neutrophils activation and may also lead to organ dysfunction. An imbalance of this response can increase the anti-inflammatory response, leading to compensatory anti-inflammatory response syndrome (CARS), persistent inflammation-immunsupression, catabolism syndrome (PICS), and, above all, an immune paralysis stat. This immune paralysis leads to opportunistic infections, Candida species being one of the emerging microorganisms involved. The host immune response is different for bacterial or Candida sepsis. Immune responses for bacterial and Candida sepsis are described in this paper.
Th17 cells, a CD4+ T-cell subset, produce interleukin (IL)-17, a pro-inflammatory cytokine that has been shown to be involved in several forms of infectious and noninfectious uveitis. Here, we explore the roles of this IL in uveitic disorders as well as in experimental autoimmune uveitis, the possible pathogenic implications of several cytokines associated with IL-17 and analyze the current outcomes and goals for drugs aiming for the IL-17 pathway.
Aims Atrial electrical remodelling (AER) is a transitional period associated with the progression and long-term maintenance of atrial fibrillation (AF). We aimed to study the progression of AER in individual patients with implantable devices and AF episodes. Methods and results Observational multicentre study (51 centres) including 4618 patients with implantable cardioverter-defibrillator +/−resynchronization therapy (ICD/CRT-D) and 352 patients (2 centres) with pacemakers (median follow-up: 3.4 years). Atrial activation rate (AAR) was quantified as the frequency of the dominant peak in the signal spectrum of AF episodes with atrial bipolar electrograms. Patients with complete progression of AER, from paroxysmal AF episodes to electrically remodelled persistent AF, were used to depict patient-specific AER slopes. A total of 34 712 AF tracings from 830 patients (87 with pacemakers) were suitable for the study. Complete progression of AER was documented in 216 patients (16 with pacemakers). Patients with persistent AF after completion of AER showed ∼30% faster AAR than patients with paroxysmal AF. The slope of AAR changes during AF progression revealed patient-specific patterns that correlated with the time-to-completion of AER (R2 = 0.85). Pacemaker patients were older than patients with ICD/CRT-Ds (78.3 vs. 67.2 year olds, respectively, P < 0.001) and had a shorter median time-to-completion of AER (24.9 vs. 93.5 days, respectively, P = 0.016). Remote transmissions in patients with ICD/CRT-D devices enabled the estimation of the time-to-completion of AER using the predicted slope of AAR changes from initiation to completion of electrical remodelling (R2 = 0.45). Conclusion The AF progression shows patient-specific patterns of AER, which can be estimated using available remote-monitoring technology.
Introduction SARS-CoV-2 infection is associated with multiple cardiac manifestations. Left atrial strain (LA-S) by speckle tracking echocardiography (STE) is a novel transthoracic echocardiography (TTE) measure of LA myocardial deformation and diastolic dysfunction, which could lead to early recognition of cardiac injury in severe COVID-19 patients with possible implications on clinical management, organ dysfunction, and mortality. Cardiac injury may occur by direct viral cytopathic effects or virus-driven immune activation, resulting in heart infiltration by inflammatory cells, despite limited and conflicting data are available on myocardial histology. Purpose We aimed to explore LA-S and immune profiles in COVID-19 patients admitted to the intensive care unit (ICU) to identify distinctive features in patients with cardiac injury. Methods We enrolled 30 patients > 18 years with positive SARS-CoV-2 RT-PCR, admitted to ICU. Acute myocardial infarction and pulmonary embolism were exclusion criteria. On days D1, D3, and D7 after ICU admission, patients performed TTE, hemogram, cardiac (pro-BNP; troponin) and inflammatory biomarkers (ESR; ferritin; IL1β; IL6; CRP; d-dimer; fibrinogen; PCT; adrenomedullin, ADM), and immunophenotyping by flow cytometry. Results Patient’s mean age was 60.7 y, with 63% males. Hypertension was the most common risk factor (73%; with 50% of patients under ACEi or ARA), followed by obesity (40%, mean BMI = 31 kg/m2). Cardiac dysfunction was detected by STE in 73% of patients: 40% left ventricle (LV) systolic dysfunction, 60% LV diastolic dysfunction, 37% right ventricle systolic dysfunction. Mortality, hospitalization days, remdesivir use, organ dysfunction, cardiac and serum biomarkers were not different between patients with (DYS) and without cardiac dysfunction (nDYS), except for ADM (increased in nDYS group at D7). From the 77 TTE, there was a striking difference between diastolic dysfunction evaluation by classic criteria compared to STE (28.6% vs. 57.1%, p = 0.0006). Lower reservoir (Ɛ) and contraction (ƐCT) LA-S correlated with IL-6 (Ɛ, p = 0.009, r = − 0.47; ƐCT, p = 0.0002, r = − 0.63) and central memory CD4 T-cells (ƐCT, p = 0.049, r = − 0.24). Along all timepoints, DYS patients showed persistent low lymphocyte counts that recovered at D7 in nDYS patients. DYS patients had lower platelets at D3 and showed a slower recovery in platelet counts and CRP levels; the latter significantly decreased at D7 in nDYS patients (p = 0.009). Overall, patients recovered with an increasing P/F ratio, though to a lesser extent in DYS patients. Discussion Our study shows that LA-S may be a more sensitive marker for diastolic dysfunction in severe COVID-19, which could identify patients at risk for a protracted inflammatory state. A differential immune trait in DYS patients at ICU admission, with persistent lymphopenia, enriched CM T-cells, and higher IL-6 may suggest distinct inflammatory states or migration patterns in patients that develop cardiac injury.
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