Citations

Abstract Objectives We aimed to explore current practice and interregional differences in the treatment of idiopathic inflammatory myopathies (IIMs). We triangulated these observations considering countries' gross national income (GNI), disease subtypes, and symptoms using patient-reported information. Methods A cross-sectional ancillary analysis of the ‘COVID-19 vaccination in auto-immune disease’ (COVAD) e-survey containing demographic characteristics, IIM subtypes (DM, PM, IBM, anti-synthetase syndrome [ASSD], immune-mediated necrotizing myopathy [IMNM], overlap myopathies [OM]), current symptoms (surrogate for organ involvement) and treatments (corticosteroids [CS], immunomodulators [IM], i.e. antimalarials, immunosuppressants [IS], IVIG, biologic treatments and targeted-synthetic small molecules). Treatments were presented descriptively according to continents, GNI, IIM and organ involvement, and associated factors were analysed using multivariable binary logistic regressions. Results Of 18 851 respondents from 94 countries, 1418 with IIM were analysed (age 61 years, 62.5% females). DM (32.4%), IBM (24.5%) and OM (15.8%) were the most common subtypes. Treatment categories included IS (49.4%), CS (38.5%), IM (13.8%) and IVIG (9.4%). Notably, treatments varied across regions, GNI categories (IS mostly used in higher-middle income, IM in lower-middle income, IVIG and biologics largely limited to high-income countries), IIM subtypes (IS and CS associated with ASSD, IM with OM and DM, IVIG with IMNM, and biologic treatments with OM and ASSD) and disease manifestations (IS and CS with dyspnoea). Most inter-regional treatment disparities persisted after multivariable analysis. Conclusion We identified marked regional treatment disparities in a global cohort of IIM. These observations highlight the need for international consensus-driven management guidelines considering patient-centred care and available resources.

Sleep quality and its association with cognition has been widely studied in some neurodegenerative diseases, but less is known about this association in spinal muscular atrophy (SMA). In adult SMA ( n = 21) patients and age-matched controls ( n = 23), we assessed subjectively measured sleep quality and daytime somnolence. Cognition was assessed with a multi-domain neuropsychological battery. Further, we investigated the association between clinical functional scores and sleep questionnaire scores. Among SMA patients, better motor and limb function was associated with better subjective sleep quality ( p’s< 0.05). Clinicians should consider sleep quality in patient care and future studies are needed to better understand these relationships.

Meniscal lesions in skeletally immature patients can lead to joint degradation and knee instability. Meniscal allograft transplant (MAT) surgery is a solution to maintain knee stability. There is a lack of consensus on MAT surgery outcomes in pediatric patients. A systematic review was conducted according to the PRISMA guidelines. PubMed, Scopus and EMBASE databases were searched from 1965 to June 2022. Studies were evaluated using the Newcastle–Ottawa Scale (NOS). Three studies were selected, and 58 patients were included (mean age 15.9 years) in total. The lateral meniscus was involved in 82.8% of all MAT surgeries. Post-meniscectomy syndrome and discoid meniscus were the main indications for MAT surgery. All studies reported improved subjective clinical scores and levels of sport after the surgery. The complication rate was 27.5%. Partial meniscectomy, meniscus knot removal, chondral defect treatment and lysis of adhesions were the most frequent procedures performed during reoperation. MAT surgery can improve clinical outcomes in pediatric patients with strictly selected indications. MAT surgery is safe when there are no limb asymmetries or malalignments, but it remains a challenging procedure with a high complication rate. Long-term follow-up is needed for definitive statements on the use of MAT in skeletally immature patients.

Abstract Functional testing with stress echocardiography is based on the detection of regional wall motion abnormality with two-dimensional echocardiography and is embedded in clinical guidelines. Yet, it under-uses the unique versatility of the technique, ideally suited to describe the different functional abnormalities underlying the same wall motion response during stress. Five parameters converge conceptually and methodologically in the state-of-the-art ABCDE protocol, assessing multiple vulnerabilities of the ischemic patient. The five steps of the ABCDE protocol are (1) step A: regional wall motion; (2) step B: B-lines by lung ultrasound assessing extravascular lung water; (3) step C: left ventricular contractile reserve by volumetric two-dimensional echocardiography; (4) step D: coronary flow velocity reserve in mid-distal left anterior descending coronary with pulsed-wave Doppler; and (5) step E: assessment of heart rate reserve with a one-lead electrocardiogram. ABCDE stress echo offers insight into five functional reserves: epicardial flow (A); diastolic (B), contractile (C), coronary microcirculatory (D), and chronotropic reserve (E). The new format is more comprehensive and allows better functional characterization, risk stratification, and personalized tailoring of therapy. ABCDE protocol is an ‘ecumenic’ and ‘omnivorous’ functional test, suitable for all stresses and all patients also beyond coronary artery disease. It fits the need for sustainability of the current era in healthcare, since it requires universally available technology, and is low-cost, radiation-free, and nearly carbon-neutral.

Abstract Objectives Disease flares in the post–coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs). Methods The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with &gt;7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression models. Results Of 15 165 total respondents, 1278 IIMs (age 63 years, 70.3% female, 80.8% Caucasians) and 3453 AIRDs were included. Flares of IIM were seen in 9.6%, 12.7%, 8.7% and 19.6% patients by definitions (a) to (d), respectively, with a median time to flare of 71.5 (10.7–235) days, similar to AIRDs. Patients with active IIMs pre-vaccination (OR 1.2; 95% CI 1.03, 1.6, P = 0.025) were prone to flares, while those receiving rituximab (OR 0.3; 95% CI 0.1, 0.7, P = 0.010) and AZA (OR 0.3, 95% CI 0.1, 0.8, P = 0.016) were at lower risk. Female gender and comorbidities predisposed to flares requiring changes in IS. Asthma (OR 1.62; 95% CI 1.05, 2.50, P = 0.028) and higher pain visual analogue score (OR 1.19; 95% CI 1.11, 1.27, P &lt; 0.001) were associated with disparity between self-reported and IS-denoted flares. Conclusion A diagnosis of IIMs confers an equal risk of flares in the post–COVID-19 vaccination period to AIRDs, with active disease, female gender and comorbidities conferring a higher risk. Disparity between patient- and physician-reported outcomes represents a future avenue for exploration.

BACKGROUND: Acute respiratory failure (ARF) remains the most frequent reason for ICU admission in patients who are immunocompromised. This study reports etiologies and outcomes of ARF in subjects with solid tumors. METHODS: This study was a post hoc analysis of the EFRAIM study, a prospective multinational cohort study that included 1611 subjects who were immunocompromised and with ARF admitted to the ICU. Subjects with solid tumors admitted to the ICU with ARF were included in the analysis. RESULTS: Among the subjects from the EFRAIM cohort, 529 subjects with solid tumors (32.8%) were included in the analysis. At ICU admission, the median (interquartile range) Sequential Organ Failure Assessment score was 5 (3–9). The types of solid tumor were mostly lung cancer ( n = 111, 21%), breast cancer ( n = 52, 9.8%), and digestive cancer ( n = 47, 8.9%). A majority, 379 subjects (71.6%) were full code at ICU admission. The ARF was caused by bacterial or viral infection ( n = 220, 41.6%), extrapulmonary sepsis ( n = 62, 11.7%), or related to cancer or treatment toxicity ( n = 83, 15.7%), or fungal infection ( n = 23, 4.3%). For 63 subjects (11.9%), the ARF etiology remained unknown after an extensive diagnostic workup. The hospital mortality rate was 45.7% ( n = 232/508). Hospital mortality was independently associated with chronic cardiac failure (odds ratio 1.78, 95% CI 1.09–2.92; P = .02), lung cancer (odds ratio 2.50, 95% CI 1.51–4.19; P < .001), day 1 Sequential Organ Failure Assessment score (odds ratio 1.97, 95% CI 1.32-2.96; P < .001). ARF etiologies other than infectious, related to cancer, or treatment toxicity were associated with better outcomes (odds ratio 0.32, 95% CI 0.16–0.61; P < .001). CONCLUSIONS: Infectious diseases remained the most frequent cause of ARF in subjects with solid tumors admitted to the ICU. Hospital mortality was related to severity at ICU admission, previous comorbidities, and ARF etiologies related to non-malignant causes or pulmonary embolism. Lung tumor was also independently associated with higher mortality.

Abstract Background: Arginine deprivation with ADI-PEG20 (pegargiminase) alone or combined with chemotherapy displayed antitumor activity in early phase clinical trials of argininosuccinate synthase 1 (ASS1)-deficient cancers, including pleural mesothelioma (PM). The non-epithelioid subtype of mesothelioma is particularly aggressive and arginine-auxotrophic due to frequent ASS1 loss. ATOMIC-meso is a pivotal phase 2-3 trial comparing standard of care (SOC) chemotherapy plus pegargiminase or placebo for patients (pts) with non-epithelioid PM. Methods: In this double-blind, placebo-controlled, phase 2-3 trial, we randomly assigned ECOG PS 0-1 pts with chemonaïve non-epithelioid PM in an intention-to-treat 1:1 ratio to receive q3 week SOC chemotherapy with pemetrexed (500mg/m2 i.v.) and cisplatin (75mg/m2 i.v.) with q1 week pegargiminase (36 mg/m2 i.m.) or placebo i.m. up to 6 cycles. Carboplatin (AUC5) was permitted in the phase 3 portion instead of cisplatin. Maintenance therapy with pegargiminase or placebo was continued until progression, toxicity or 24 months. The primary end point was median OS (mOS) and secondary end points included median PFS (mPFS), safety, pharmacodynamics and immunogenicity. ORR was assessed by blinded independent central review (BICR) for the phase 2 portion only using modified RECIST or RECIST v1.1. Results: 249 pts with non-epithelioid PM (median age 71, range 28-86; male 82.7%; 48.2% biphasic and 51.8% sarcomatoid) from 5 countries were randomized between Aug 2017 and Aug 2021: 125 pts were assigned to the pegargiminase-chemotherapy group and 124 pts to the placebo-chemotherapy group. The experimental arm showed a superior mOS respect to SOC: 9.3 months (95% confidence interval [CI], 7.9-11.8) vs. 7.7 months (95% CI, 6.1-9.5) (hazard ratio [HR], 0.71; 95% CI, 0.55-0.93; p=0.023). Also, the mPFS was higher in the experimental vs. control arm: 6.2 months (95% CI, 5.8-7.4) vs. 5.6 months (95% CI, 4.14-5.91) ([HR], 0.65; 95% CI, 0.46-0.90; p=0.019). The ORR by BICR was 13.8% in the pegargiminase-chemotherapy group vs. 13.5% in the placebo-chemotherapy group (p=0.95) with more stable disease in the former (71.3% vs. 62.9%). Plasma arginine declined with a reciprocal increase in citrulline. Anti-ADI-PEG20 antibodies were detected in 97.4% of patients by week 25 on pegargiminase. Grade ≥ 3 treatment-related adverse events to pegargiminase occurred in 28.8% and to placebo in 16.9%; grade ≥ 3 drug hypersensitivity and skin reactions occurred in 3.2% and 1.6% in the experimental arm, respectively, and none on placebo. Post-study drug treatment was comparable in both arms (45.6% post-pegargiminase vs. 46.8% post-placebo). Conclusions: In this first randomized trial of an arginine-depleting chemotherapy in cancer, the pegargiminase-pemetrexed-platinum triplet prolonged survival and had a favorable safety profile in pts with non-epithelioid PM (ClinicalTrials.gov Identifier NCT02709512) Citation Format: Peter W. Szlosarek, Ben Creelan, Thomas Sarkodie, Luke Nolan, Paul Taylor, Olga Olevsky, Federica Grosso, Diego Cortinovis, Meenali Chitnis, Amy Roy, David Gilligan, Hedy Kindler, Dionysis Papadatos-Pastos, Giovanni L. Ceresoli, Aaron Mansfield, Anne Tsao, Ken O’Byrne, Anna K. Nowak, Jeremy Steele, Michael Sheaff, Amanda Johnston, John Bomalaski, Marjorie Zauderer, Dean A. Fennell. Phase 2-3 trial of pegargiminase plus chemotherapy versus placebo plus chemotherapy in patients with non-epithelioid pleural mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT007.

Objective: To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS). Background: Liver resections for HCC on MS are associated with high perioperative morbidity and mortality. No data on the minimally invasive approach in this setting exist. Material and Methods: A multicenter study involving 24 institutions was conducted. Propensity scores were calculated, and inverse probability weighting was used to weight comparisons. Short-term and long-term outcomes were investigated. Results: A total of 996 patients were included: 580 in OLR and 416 in MILR. After weighing, groups were well matched. Blood loss was similar between groups (OLR 275.9±3.1 vs MILR 226±4.0, P=0.146). There were no significant differences in 90-day morbidity (38.9% vs 31.9% OLRs and MILRs, P=0.08) and mortality (2.4% vs 2.2% OLRs and MILRs, P=0.84). MILRs were associated with lower rates of major complications (9.3% vs 15.3%, P=0.015), posthepatectomy liver failure (0.6% vs 4.3%, P=0.008), and bile leaks (2.2% vs 6.4%, P=0.003); ascites was significantly lower at postoperative day 1 (2.7% vs 8.1%, P=0.002) and day 3 (3.1% vs 11.4%, P<0.001); hospital stay was significantly shorter (5.8±1.9 vs 7.5±1.7, P<0.001). There was no significant difference in overall survival and disease-free survival. Conclusions: MILR for HCC on MS is associated with equivalent perioperative and oncological outcomes to OLRs. Fewer major complications, posthepatectomy liver failures, ascites, and bile leaks can be obtained, with a shorter hospital stay. The combination of lower short-term severe morbidity and equivalent oncologic outcomes favor MILR for MS when feasible.

Abstract Objective Flares of autoimmune rheumatic diseases (AIRDs) following COVID-19 vaccination are a particular concern in vaccine-hesitant individuals. Therefore, we investigated the incidence, predictors and patterns of flares following vaccination in individuals living with AIRDs, using global COVID-19 Vaccination in Autoimmune Diseases (COVAD) surveys. Methods The COVAD surveys were used to extract data on flare demographics, comorbidities, COVID-19 history, and vaccination details for patients with AIRDs. Flares following vaccination were identified as patient-reported (a), increased immunosuppression (b), clinical exacerbations (c) and worsening of PROMIS scores (d). We studied flare characteristics and used regression models to differentiate flares among various AIRDs. Results Of 15 165 total responses, the incidence of flares in 3453 patients with AIRDs was 11.3%, 14.8%, 9.5% and 26.7% by definitions a–d, respectively. There was moderate agreement between patient-reported and immunosuppression-defined flares (K = 0.403, P = 0.022). Arthritis (61.6%) and fatigue (58.8%) were the most commonly reported symptoms. Self-reported flares were associated with higher comorbidities (P = 0.013), mental health disorders (MHDs) (P &lt; 0.001) and autoimmune disease multimorbidity (AIDm) (P &lt; 0.001). In regression analysis, the presence of AIDm [odds ratio (OR) = 1.4; 95% CI: 1.1, 1.7; P = 0.003), or a MHD (OR = 1.7; 95% CI: 1.1, 2.6; P = 0.007), or being a Moderna vaccine recipient (OR = 1.5; 95% CI: 1.09, 2.2; P = 0.014) were predictors of flares. Use of MMF (OR = 0.5; 95% CI: 0.3, 0.8; P = 0.009) and glucocorticoids (OR = 0.6; 95% CI: 0.5, 0.8; P = 0.003) were protective. A higher frequency of patients with AIRDs reported overall active disease post-vaccination compared with before vaccination (OR = 1.3; 95% CI: 1.1, 1.5; P &lt; 0.001). Conclusion Flares occur in nearly 1 in 10 individuals with AIRDs after COVID vaccination; people with comorbidities (especially AIDm), MHDs and those receiving the Moderna vaccine are particularly vulnerable. Future avenues include exploring flare profiles and optimizing vaccine strategies for this group.