Secukinumab Loss of Efficacy Is Perfectly Counteracted by the Introduction of Combination Therapy (Rescue Therapy): Data from a Multicenter Real-Life Study in a Cohort of Italian Psoriatic Patients That Avoided Secukinumab Switching

Since psoriasis (PsO) is a chronic inflammatory disease, patients may experience a drug failure also with very effective drugs (i.e., secukinumab) and, consequently, dermatologists have two therapeutic options: switching or perform a combination therapy (rescue therapy) to save the drug that had decreased its efficacy. At the moment no studies focused on combination/rescue therapy of secukinumab, so we performed a 52-weeks multicenter retrospective observational study that involved 40 subjects with plaque psoriasis that experienced a secondary failure and were treated with combination therapy (ciclosporin (n = 11), MTX (n = 15), NB-UVB (n = 7) and apremilast (n = 7)). After 16 weeks of rescue/combination therapy, PASI and a DLQI varied respectively from 8 [7.0–9.0] and 13 [12.0–15.0], to 3 [2.8–4.0] and 3 [2.0–3.3]), suggesting a significant improvement of daily functionality and quality of life. Results were maintained at 52 weeks. No side effects were experienced during the study. Secukinumab remains a safety and effective drug for PsO patients also in the IL-23 and JAK inhibitors era. The rescue therapy is a valid therapeutic option in case of secukinumab secondary failure.

Selecting the Appropriate First-Line Strategy Based on Hyperdense Vessel Sign in Acute Ischemic Stroke Increases First Pass Recanalization: A Tertiary Center Experience

Background: The data pertaining to selecting an optimal first-line strategy (stent retriever [SR] vs. contact aspiration [CA]) based on noncontrast computed tomography (NCCT) in cases of acute ischemic stroke consequent to large vessel occlusion (LVO) is lacking. Aims: This article studies the influence of hyperdense vessel sign (HVS) in selecting optimal first-line strategy, with intention of increasing first-pass recanalization (FPR). Methods: Upfront approach at our center is SR technique with rescue therapy (CA) adoption consequent to three failed SR attempts to achieve successful recanalization. Data of patients with acute LVO who underwent mechanical thrombectomy from June 2017 to May 2020 was retrospectively analyzed. Patients were classified into HVS (+) and HVS (–) cohort. Rate of successful recanalization (first pass, early, and final) and efficacy of rescue therapy was assessed between the two cohorts. Results: Of 52 patients included, 28 and 24 were assigned to the HVS (+) and HVS (–) cohort, respectively. FPR was observed in 50% of HVS (+) and 20.9% of HVS (–) (p = 0.029). Early recanalization was documented in 64.2% of HVS (+) and 37.5% of HVS (–) (p = 0.054). Rescue therapy need was higher in patients not demonstrating HVS (p = 0.062). Successful recanalization was achieved with rescue therapy in 50% of HVS (–) group. Conclusion: A higher FPR is achievable following individualized first-pass strategy (based on NCCT appearance of clot), instead of a generalized SR first-pass approach. This CT imaging-based strategy is a step closer to achieving primary angiographic goal of FPR.

Plasmapheresis with Convalescent Plasma as a Rescue Therapy for COVID-19 Patients: A Case Series

: On December 29, 2019, an epidemic of an infectious disease caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was declared in Wuhan, China. The first case of COVID-19 in Iran (Qom Province) was reported in February 2020, and within a short period, the number of infected cases increased rapidly around the country. Evidence suggests that the levels of pro-inflammatory cytokines are high in critically ill patients, and there is a correlation between the high level of cytokines and the pathogenesis of COVID-19; consequently, COVID-19 may have complications, such as acute respiratory distress syndrome (ARDS) and even death. These inflammatory factors can lead to a cytokine storm, while counteracting this storm seems to be an effective therapeutic approach. In this case series, we reported two critically ill patients with COVID-19, undergoing plasmapheresis with convalescent plasma, corticosteroid therapy, and interferon administration.

Cytokine Hemoadsorption as Rescue Therapy for Critically Ill Patients With SARS-CoV-2 Pneumonia With Severe Respiratory Failure and Hypercytokinemia

Introduction: A dysregulated inflammatory response, known as “cytokine storm”, plays an important role in the pathophysiology of coronavirus 2019 disease (COVID-19). Identifying patients with a dysregulated inflammatory response and at high risk for severe respiratory failure, organ dysfunction, and death is clinically relevant, as they could benefit from the specific therapies, such as cytokine removal by hemoadsorption. This study aimed to evaluate cytokine hemoadsorption as rescue therapy in critically ill patients with SARS-CoV-2 pneumonia, severe respiratory failure refractory to prone positioning, and hypercytokinemia.Methods: In this single center, observational and retrospective study, critically ill patients with SARS-CoV-2 pneumonia, severe acute respiratory failure, and hypercytokinemia were analyzed. All the patients underwent cytokine hemoadsorption using CytoSorb® (Cytosorbents Europe, Berlin, Germany). The indication for treatment was acute respiratory failure, inadequate clinical response to the prone position, and hypercytokinemia.Results: Among a total of 343 patients who were admitted to the intensive care unit (ICU) due to SARS-CoV-2 infection between March 3, 2020 and June 22, 2020, six patients received rescue therapy with cytokine hemoadsorption. All the patients needed invasive mechanical ventilation and prone positioning. A significant difference was found in the pre- and post-treatment D-dimer (17,868 mcg/ml [4,196–45,287] vs. 4,488 mcg/ml [3,166–17,076], p = 0.046), C-reactive protein (12.9 mg/dl [10.6] vs. 3.5 mg/dl [2.8], p = 0.028), ferritin (1,539 mcg/L [764–27,414] vs. 1,197 ng/ml [524–3,857], p = 0.04) and interleukin-6 (17,367 pg/ml [4,539–22,532] vs. 2,403 pg/ml [917–3,724], p = 0.043) levels. No significant differences in the pre- and post-treatment interleukin-10 levels (22.3 pg/ml [19.2–191] vs. 5.6 pg/ml [5.2–36.6], p = 0.068) were observed. Improvements in oxygenation (prehemoadsorption PaO2/FIO2 ratio 103 [18.4] vs. posthemoadsorption PaO2/FIO2 ratio 222 [20.9], p = 0.029) and in the organ dysfunction (prehemoadsorption SOFA score 9 [4.75] vs. posthemoadsorption SOFA score 7.7 [5.4], p = 0.046) were observed. ICU and in-hospital mortality was 33.7%.Conclusions: In this case series, critically ill patients with COVID-19 with severe acute respiratory failure refractory to prone positioning and hypercytokinemia who received adjuvant treatment with cytokine hemoadsorption showed a significant reduction in IL-6 plasma levels and other inflammatory biomarkers. Improvements in oxygenation and SOFA score were also observed.

Heterogeneity of the Relative Benefits of TICI 2c/3 over TICI 2b50/2b67

Purpose Incomplete reperfusion after mechanical thrombectomy (MT) is associated with a poor outcome. Rescue therapy would potentially benefit some patients with an expanded treatment in cerebral ischemia score (eTICI) 2b50/2b67 reperfusion but also harbors increased risks. The relative benefits of eTICI 2c/3 over eTICI 2b50/67 in clinically important subpopulations were analyzed. Methods Retrospective analysis of our institutional database for all patients with occlusion of the intracranial internal carotid artery (ICA) or the M1/M2 segment undergoing MT and final reperfusion of ≥eTICI 2b50 (903 patients). The heterogeneity in subgroups of different time metrics, age, National Institutes of Health Stroke Scale (NIHSS), number of retrieval attempts, Alberta Stroke Programme Early CT Score (ASPECTS) and site of occlusion using interaction terms (pi) was analyzed. Results The presence of eTICI 2c/3 was associated with better outcomes in most subgroups. Time metrics showed no interaction of eTICI 2c/3 over eTICI 2b50/2b67 and clinical outcomes (onset to reperfusion pi = 0.77, puncture to reperfusion pi = 0.65, onset to puncture pi = 0.63). An eTICI 2c/3 had less consistent association with mRS ≤2 in older patients (>82 years, pi = 0.038) and patients with either lower NIHSS (≤9) or very high NIHSS (>19, pi = 0.01). Regarding occlusion sites, the beneficial effect of eTICI 2c/3 was absent for occlusions in the M2 segments (aOR 0.73, 95% confidence interval [CI] 0.33–1.59, pi = 0.018). Conclusion Beneficial effect of eTICI 2c/3 over eTICI 2b50/2b67 only decreased in older patients, M2-occlusions and patients with either low or very high NIHSS. Improving eTICI 2b50/2b67 to eTICI 2c/3 in those subgroups may be more often futile.

Clinical Use of Extracorporeal Membrane Oxygenation for Rescue Therapy in Covid-19 Era

The article's abstract is not available.

The impact of Sofosbuvir/Velpatasvir/Voxilaprevir treatment on serum hyperglycemia in HCV infections: A Systematic Review

Review question / Objective: To assess the possible cause of events, the incidence of grade 3 hyperglycemia after treating Sofosbuvir/Velpatasvir/Voxilaprevir in HCV infections. Condition being studied: Sofosbuvir, velpatasvir, and voxilaprevir (SOF/VEL/VOX) is an effective, safe rescue therapy regimen for patients have previously been treated failure. Initiating Direct-Acting Antiviral (DAA) treatment for HCV infection with diabetes have experienced hypoglycemia, it could improve insulin resistance due to clean HCV. However, some studies shown that SOF/VEL/VOX has Grade 3 hyperglycemia adverse events. This finding contradicts that other DAAs studies. Information sources: Conducting a comprehensive literature search on the pubmed, Cochrane, clinicalkey, Embase, and MEDLINE electronic databases.

COVID-19 vaccination in patients with immune thrombocytopenia

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by low platelet count and increased bleeding risk. COVID-19 vaccination has been described as risk factor for de novo ITP, but the effects of COVID-19 vaccination in patients with ITP are unknown. Our aims were to investigate the effects of COVID-19 vaccination in ITP patients on platelet count, bleeding complications and ITP exacerbation (any of: ≥50% decline in platelet count; or nadir platelet count <30x109/L with >20% decrease from baseline; or use of rescue therapy). Platelet counts of ITP patients and healthy controls were collected immediately before, 1 and 4 weeks after first and second vaccination. Linear mixed-effects modelling was applied to analyze platelet counts over time. We included 218 ITP patients (50.9% female, mean age 55 years and median platelet count of 106x109/L) and 200 healthy controls (60.0% female, mean age 58 years and median platelet count of 256x109/L). Platelet counts decreased by 6.3% after vaccination. We observed no difference in decrease between the groups. Thirty ITP patients (13.8%, 95%CI 9.5%-19.1%) had an exacerbation and 5 (2.2%, 95%CI 0.7%-5.3%) suffered from a bleeding event. Risk factors for ITP exacerbation were platelet count <50x109/L (OR 5.3, 95%CI 2.1-13.7), ITP treatment at time of vaccination (OR 3.4, 95%CI 1.5-8.0) and age (OR 0.96 per year, 95%CI 0.94-0.99). Our study highlights safety of COVID-19 vaccination in ITP patients and importance of close monitoring platelet counts in a subgroup of ITP patients. ITP patients with exacerbation responded well on therapy.