Identification of the Minimal Disease Activity Domains Achieved Based on Different Treatments in Psoriatic Arthritis

Introductionthe aim of this work is to characterize which minimal disease activity (MDA) domains are mainly achieved, based on different treatments, in psoriatic arthritis (PsA) patients. Moreover, the association between MDA achievement and the different treatment groups was assessed.MethodsWe conducted a cross-sectional analysis of two longitudinal PsA groups. Inclusion criteria were: age & GE; 18 years, PsA diagnosis, stable treatment for at least 6 months. patients were grouped depending on the therapy: group 1: non-steroidal anti-inflammatory drugs (NSAIDs)/cyclooxygenase 2 inhibitors (COX2i)/steroids, group 2: conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), group 3: tumor necrosisfFactor & alpha; inhibitors (TNFi), group 4: interleukin inhibitors (IL)12-23i or IL-23i, group 5: IL-17i, group 6: phosphodiesterase 4 inhibitors (PD4i). For each group, the achieved domains based on therapy were assessed. Multivariate logistic regression analysis was performed to assess the association between the treatment groups and the MDA achievement.resultsA total of 220 patients were enrolled, and MDA was achieved in 45.8% of them. In all treatment groups, the first MDA domains achieved were: body surface area & LE; 3, swollen joint count & LE; 1 and Leeds Enthesitis Index & LE; 1, while MDA domains less frequently achieved were Patient Global Assessment (PtgA) & LE; 2 cm and pain on visual analogue scale & LE; 1.5 cm. The logistic regression analysis showed higher odds ratios for the achievement of the MDA in those patients in groups 3 and 4.ConclusionsIn each treatment group, MDA domains less frequently achieved were PtGA and pain, suggesting that "patient-driven domains" are still an unmet need.Due to the study design and the low number of patients in some groups, it is not possible to clearly define which MDA domain was achieved or not based on treatment; however, it seems that some differences could be present. If larger and prospective studies confirm our preliminary results, we could move toward a personalized/domain treatment approach in PsA.ConclusionsIn each treatment group, MDA domains less frequently achieved were PtGA and pain, suggesting that "patient-driven domains" are still an unmet need.due to the study design and the low number of patients in some groups, it is not possible to clearly define which MDA domain was achieved or not based on treatment; however, it seems that some differences could be present. If larger and prospective studies confirm our preliminary results, we could move toward a personalized/domain treatment approach in PsA

Targeting interleukin-1β protects from aortic aneurysms induced by disrupted transforming growth factor β signaling

Aortic aneurysms are life-threatening conditions with effective treatments mainly limited to emergency surgery or trans-arterial endovascular stent grafts, thus calling for the identification of specific molecular targets. Genetic studies have highlighted controversial roles of transforming growth factor β (TGF-β) signaling in aneurysm development. Here, we report on aneurysms developing in adult mice after smooth muscle cell (SMC)-specific inactivation of Smad4, an intracellular transducer of TGF-β. The results revealed that Smad4 inhibition activated interleukin-1β (IL-1β) in SMCs. This danger signal later recruited innate immunity in the adventitia through chemokine (C-C motif) ligand 2 (CCL2) and modified the mechanical properties of the aortic wall, thus favoring vessel dilation. SMC-specific Smad4 deletion in Il1r1- or Ccr2-null mice resulted in milder aortic pathology. A chronic treatment with anti-IL-1β antibody effectively hampered aneurysm development. These findings identify a mechanistic target for controlling the progression of aneurysms with compromised TGF-β signaling, such as those driven by SMAD4 mutations

[18F]ZCDD083: a PFKFB3-targeted PET tracer for atherosclerotic plaque imaging

Copyright © 2020 American Chemical Society. Funding We thank the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie ITNEuropean Joint Doctorate MOGLYNET (grant agreement No. 675527).Peer reviewedPostprin

Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine. A post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial

Background: The PRESTO study of non-invasive vagus nerve stimulation (nVNS; gammaCore®) featured key primary and secondary end points recommended by the International Headache Society to provide Class I evidence that for patients with an episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. Here, we examined additional data from PRESTO to provide further insights into the practical utility of nVNS by evaluating its ability to consistently deliver clinically meaningful improvements in pain intensity while reducing the need for rescue medication. Methods: Patients recorded pain intensity for treated migraine attacks on a 4-point scale. Data were examined to compare nVNS and sham with regard to the percentage of patients who benefited by at least 1 point in pain intensity. We also assessed the percentage of attacks that required rescue medication and pain-free rates stratified by pain intensity at treatment initiation. Results: A significantly higher percentage of patients who used acute nVNS treatment (n = 120) vs sham (n = 123) reported a ≥ 1-point decrease in pain intensity at 30 min (nVNS, 32.2%; sham, 18.5%; P = 0.020), 60 min (nVNS, 38.8%; sham, 24.0%; P = 0.017), and 120 min (nVNS, 46.8%; sham, 26.2%; P = 0.002) after the first attack. Similar significant results were seen when assessing the benefit in all attacks. The proportion of patients who did not require rescue medication was significantly higher with nVNS than with sham for the first attack (nVNS, 59.3%; sham, 41.9%; P = 0.013) and all attacks (nVNS, 52.3%; sham, 37.3%; P = 0.008). When initial pain intensity was mild, the percentage of patients with no pain after treatment was significantly higher with nVNS than with sham at 60 min (all attacks: nVNS, 37.0%; sham, 21.2%; P = 0.025) and 120 min (first attack: nVNS, 50.0%; sham, 25.0%; P = 0.018; all attacks: nVNS, 46.7%; sham, 30.1%; P = 0.037). Conclusions: This post hoc analysis demonstrated that acute nVNS treatment quickly and consistently reduced pain intensity while decreasing rescue medication use. These clinical benefits provide guidance in the optimal use of nVNS in everyday practice, which can potentially reduce use of acute pharmacologic medications and their associated adverse events. Trial registration: ClinicalTrials.gov identifier: NCT02686034

Botulinum toxin type-A in the prophylactic treatment of medication-overuse headache: a multicenter, double-blind, randomized, placebo-controlled, parallel group study

Medication-overuse headache (MOH) represents a severely disabling condition, with a low response to prophylactic treatments. Recently, consistent evidences have emerged in favor of botulinum toxin type-A (onabotulinum toxin A) as prophylactic treatment in chronic migraine. In a 12-week double-blind, parallel group, placebo-controlled study, we tested the efficacy and safety of onabotulinum toxin A as prophylactic treatment for MOH. A total of 68 patients were randomized (1:1) to onabotulinum toxin A (n = 33) or placebo (n = 35) treatment and received 16 intramuscular injections. The primary efficacy end point was mean change from baseline in the frequency of headache days for the 28-day period ending with week 12. No significant differences between onabotulinum toxin A and placebo treatment were detected in the primary (headache days) end point (12.0 vs. 15.9; p = 0.81). A significant reduction was recorded in the secondary end point, mean acute pain drug consumption at 12 weeks in onabotulinum toxin A-treated patients when compared with those with placebo (12.1 vs. 18.0; p = 0.03). When we considered the subgroup of patients with pericranial muscle tenderness, we recorded a significant improvement in those treated with onabotulinum toxin A compared to placebo treated in both primary (headache days) and secondary end points (acute pain drug consumption, days with drug consumption), as well as in pain intensity and disability measures (HIT-6 and MIDAS) at 12 weeks. Onabotulinum toxin A was safe and well tolerated, with few treatment-related adverse events. Few subjects discontinued due to adverse events. Our data identified the presence of pericranial muscle tenderness as predictor of response to onabotulinum toxin A in patients with complicated form of migraine such as MOH, the presence of pericranial muscle tenderness and support it as prophylactic treatment in these patients

Effects of Germline VHL Deficiency on Growth, Metabolism, and Mitochondria.

Mutations in VHL, which encodes von Hippel-Lindau tumor suppressor (VHL), are associated with divergent diseases. We describe a patient with marked erythrocytosis and prominent mitochondrial alterations associated with a severe germline VHL deficiency due to homozygosity for a novel synonymous mutation (c.222C→A, p.V74V). The condition is characterized by early systemic onset and differs from Chuvash polycythemia (c.598C→T) in that it is associated with a strongly reduced growth rate, persistent hypoglycemia, and limited exercise capacity. We report changes in gene expression that reprogram carbohydrate and lipid metabolism, impair muscle mitochondrial respiratory function, and uncouple oxygen consumption from ATP production. Moreover, we identified unusual intermitochondrial connecting ducts. Our findings add unexpected information on the importance of the VHL-hypoxia-inducible factor (HIF) axis to human phenotypes. (Funded by Associazione Italiana Ricerca sul Cancro and others.)

Patient-reported impact of spondyloarthritis on work disability and working life: The ATLANTIS survey

44noopenopenRamonda, Roberta; Marchesoni, Antonio; Carletto, Antonio; Bianchi, Gerolamo; Cutolo, Maurizio; Ferraccioli, Gianfranco; Fusaro, Enrico; De Vita, Salvatore; Galeazzi, Mauro; Gerli, Roberto; Matucci-Cerinic, Marco; Minisola, Giovanni; Montecucco, Carlomaurizio; Pellerito, Raffaele; Salaffi, Fausto; Paolazzi, Giuseppe; Sarzi-Puttini, Piercarlo; Scarpa, Raffaele; Bagnato, Gianfilippo; Triolo, Giovanni; Valesini, Guido; Punzi, Leonardo; Olivieri, Ignazio; Ortolan, Augusta; Lorenzin, Mariagrazia; Frallonardo, Paola; Giollo, Alessandro; Locaputo, Antonella; Paolino, Sabrina; Simone, Davide; Quartuccio, Luca; Bartoloni, Elena; Luca, Rossella De; Bartoli, Francesca; Sensi, Felice; Caporali, Roberto; Carlo, Marco Di; Roberto, Bortolotti; Atzeni, Fabiola; Costa, Luisa; Ciccia, Francesco; Perrotta, Fabio; Gilio, Michele; ATLANTIS study groupRamonda, Roberta; Marchesoni, Antonio; Carletto, Antonio; Bianchi, Gerolamo; Cutolo, Maurizio; Ferraccioli, Gianfranco; Fusaro, Enrico; De Vita, Salvatore; Galeazzi, Mauro; Gerli, Roberto; Matucci-Cerinic, Marco; Minisola, Giovanni; Montecucco, Carlomaurizio; Pellerito, Raffaele; Salaffi, Fausto; Paolazzi, Giuseppe; Sarzi-Puttini, Piercarlo; Scarpa, Raffaele; Bagnato, Gianfilippo; Triolo, Giovanni; Valesini, Guido; Punzi, Leonardo; Olivieri, Ignazio; Ortolan, Augusta; Lorenzin, Mariagrazia; Frallonardo, Paola; Giollo, Alessandro; Locaputo, Antonella; Paolino, Sabrina; Simone, Davide; Quartuccio, Luca; Bartoloni, Elena; Luca, Rossella De; Bartoli, Francesca; Sensi, Felice; Caporali, Roberto; Carlo, Marco Di; Roberto, Bortolotti; Atzeni, Fabiola; Costa, Luisa; Ciccia, Francesco; Perrotta, Fabio; Gilio, Michele; ATLANTIS study, Grou

Appendectomy during the COVID-19 pandemic in Italy: a multicenter ambispective cohort study by the Italian Society of Endoscopic Surgery and new technologies (the CRAC study)

Major surgical societies advised using non-operative management of appendicitis and suggested against laparoscopy during the COVID-19 pandemic. The hypothesis is that a significant reduction in the number of emergent appendectomies was observed during the pandemic, restricted to complex cases. The study aimed to analyse emergent surgical appendectomies during pandemic on a national basis and compare it to the same period of the previous year. This is a multicentre, retrospective, observational study investigating the outcomes of patients undergoing emergent appendectomy in March-April 2019 vs March-April 2020. The primary outcome was the number of appendectomies performed, classified according to the American Association for the Surgery of Trauma (AAST) score. Secondary outcomes were the type of surgical technique employed (laparoscopic vs open) and the complication rates. One thousand five hundred forty one patients with acute appendicitis underwent surgery during the two study periods. 1337 (86.8%) patients met the inclusion criteria: 546 (40.8%) patients underwent surgery for acute appendicitis in 2020 and 791 (59.2%) in 2019. According to AAST, patients with complicated appendicitis operated in 2019 were 30.3% vs 39.9% in 2020 (p = 0.001). We observed an increase in the number of post-operative complications in 2020 (15.9%) compared to 2019 (9.6%) (p < 0.001). The following determinants increased the likelihood of complication occurrence: undergoing surgery during 2020 (+ 67%), the increase of a unit in the AAST score (+ 26%), surgery performed > 24 h after admission (+ 58%), open surgery (+ 112%) and conversion to open surgery (+ 166%). In Italian hospitals, in March and April 2020, the number of appendectomies has drastically dropped. During the first pandemic wave, patients undergoing surgery were more frequently affected by more severe appendicitis than the previous year's timeframe and experienced a higher number of complications. Trial registration number and date: Research Registry ID 5789, May 7th, 202