Clinical Benefit
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Stroke ◽  
2021 ◽  
Rachel Beekman ◽  
Jie-Lena Sun ◽  
Brooke Alhanti ◽  
Lee H. Schwamm ◽  
Eric E. Smith ◽  

Background and Purpose: Patients with prestroke mobility impairment (PSMI) were excluded from endovascular clinical trials. There are limited data regarding safety and outcomes of endovascular thrombectomy in this population. We used a large, national data set (Get With The Guidelines–Stroke) to evaluate the safety and outcomes of endovascular thrombectomy in patients with PSMI. Methods: We included patients who underwent endovascular thrombectomy in the Get With The Guidelines–Stroke registry between 2015 and 2019. PSMI was defined as the inability to ambulate independently. Generalized estimating equations for logistic regression models were used to evaluate the association between PSMI and outcomes. Results: Of 56 762 patients treated with endovascular thrombectomy, 2919 (5.14%) had PSMI. PSMI was not associated with symptomatic intracranial hemorrhage (6.0% versus 5.4%; P =0.979). In-hospital death or discharge to hospice occurred in 32.3% of patients with PSMI versus 17.5% without PSMI (adjusted odds ratio, 1.45 [1.32–1.58]). Conclusions: While procedural adverse outcomes were no higher in patients with PSMI, further study is necessary to determine clinical benefit in this population.

2021 ◽  
Vol 22 (18) ◽  
pp. 9769
Rebekah de Nys ◽  
Raman Kumar ◽  
Jozef Gecz

Steroids yield great influence on neurological development through nuclear hormone receptor (NHR)-mediated gene regulation. We recently reported that cell adhesion molecule protocadherin 19 (encoded by the PCDH19 gene) is involved in the coregulation of steroid receptor activity on gene expression. PCDH19 variants cause early-onset developmental epileptic encephalopathy clustering epilepsy (CE), with altered steroidogenesis and NHR-related gene expression being identified in these individuals. The implication of hormonal pathways in CE pathogenesis has led to the investigation of various steroid-based antiepileptic drugs in the treatment of this disorder, with mixed results so far. Therefore, there are many unmet challenges in assessing the antiseizure targets and efficiency of steroid-based therapeutics for CE. We review and assess the evidence for and against the implication of neurosteroids in the pathogenesis of CE and in view of their possible clinical benefit.

2021 ◽  
Stacey M Stein ◽  
Jeremy Snider ◽  
Siraj M Ali ◽  
Rebecca A Miksad ◽  
Brian M Alexander ◽  

Aim: To assess concordance between HER2 status measured by traditional methods and ERBB2 amplification measured by next-generation sequencing and its association with first-line trastuzumab clinical benefit in patients with advanced esophagogastric cancer. Methods: Retrospective analysis of HER2/ ERBB2 concordance using a deidentified USA-based clinicogenomic database. Clinical outcomes were assessed for patients with HER2+ advanced esophagogastric cancer who received first-line trastuzumab. Results: Overall HER2/ ERBB2 concordance was 87.5%. Among patients who received first-line trastuzumab, concordant HER2/ ERBB2 was associated with longer time to treatment discontinuation (adjusted hazard ratio [aHR]: 0.63; 95% CI: 0.43–0.90) and overall survival (aHR: 0.51; 95% CI: 0.33–0.79). ERBB2 copy number ≥25 (median) was associated with longer time to treatment discontinuation (aHR: 0.56; 95% CI: 0.35–0.88) and overall survival (aHR: 0.52; 95% CI: 0.30–0.91). Conclusion: HER2/ ERBB2 concordance and higher ERBB2 copy number predicted clinical benefit from trastuzumab.

Children ◽  
2021 ◽  
Vol 8 (9) ◽  
pp. 767
Giulia Sapuppo ◽  
Martina Tavarelli ◽  
Emanuela Cannata ◽  
Milena La Spina ◽  
Marco Russo ◽  

Background: Patients treated for paediatric/adolescent (P/A) neoplasia have a high incidence of both benign and malignant thyroid diseases. Given the high incidence of sequelae, literature data show a clinical benefit of morpho-functional thyroid screening in paediatric/adolescent cancer survivors and a careful lifetime follow-up. Patients and methods: The incidence of thyroid alterations was evaluated in a consecutive series of 343 patients treated with chemotherapy (CHE) and radiotherapy (RTE) or only with CHE for P/A tumours between 1976 and 2018 (mean age at time of primary paediatric malignancy 7.8 ± 4.7 years). All patients underwent thyroidal morpho-functional evaluation between 2000 and 2019. Results: 178 patients (51.9%) were treated only with CHE and 165 (48.1%) with CHE+RTE. A functional and/or structural thyroid disease was diagnosed in 147 (42.5%; 24.2% in CHE and 62.4% in CHE+RTE group; p = 0.0001). Of note, 71 (20.7%) patients with no evidence of disease at first evaluation developed a thyroid alteration during the follow-up. Primitive hypothyroidism was diagnosed in 54 patients (15.7%; 11.2% in CHE vs. 20.6% in CHE+RTE group; p = 0.01) and hyperthyroidism in 4. Sixty-three patients developed thyroid nodules (18.4%; 4.0% in CHE and 14.1% in CHE+RTE group; p < 0.001); thyroid cancer was diagnosed in 30 patients (8.7%; 4.5% in CHE and 12.4% in CHE + RTE group; p = 0.007). Conclusions: In patients treated with CHE+RTE, the prevalence of hypothyroidism and nodular pathology, both malignant and benign, were significantly greater than in patients treated with CHE. However, also in the CHE group, the frequency of thyroid disease is not negligible and the pathogenetic mechanisms remain to be clarified. Our data suggest the clinical benefit of morpho-functional thyroid screening in P/A cancer survivors.

2021 ◽  
Vol 10 (17) ◽  
pp. 3932
Pierluigi Toniutto ◽  
Elisa Fumolo ◽  
Ezio Fornasiere ◽  
Davide Bitetto

The Milan criteria (MC) were developed more than 20 years ago and are still considered the benchmark for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). However, the strict application of MC might exclude some patients who may receive a clinical benefit of LT. Several expanded criteria have been proposed. Some of these consider pretransplant morphological and biological variables of the tumor, others consider post-LT variables such as the histology of the tumor, and others combine pre- and post-LT variables. More recently, the HCC response to locoregional treatments before transplantation emerged as a surrogate marker of the biological aggressiveness of the tumor to be used as a better selection criterion for LT in patients beyond the MC at presentation. This essential review aims to present the current data on the pretransplant selection criteria for LT in patients with HCC exceeding the MC at presentation based on morphological and histological characteristics of the tumor and to critically discuss those that have been validated in clinical practice. Moreover, the role of HCC biological markers and the tumor response to downstaging procedures as new tools for selecting patients with a tumor burden outside of the MC for LT is evaluated.

Philippe Noriel Q. Pascua ◽  
Jeremy C. Jones ◽  
Bindumadhav M. Marathe ◽  
Patrick Seiler ◽  
William V. Caufield ◽  

Clinical efficacy of the influenza antiviral baloxavir marboxil (baloxavir) is compromised by treatment-emergent variants harboring a polymerase acidic protein I38T substitution. However, the fitness of I38T-containing influenza B viruses (IBVs) remains inadequately defined. After confirming the pharmacokinetics of the compound in ferrets, animals were injected subcutaneously with 8 mg/kg of baloxavir acid (BXA) 24 h post-inoculation with recombinant BXA-sensitive (BXA- Sen , I38) or BXA-resistant (BXA- Res , I38T) B/Brisbane/60/2008 (Victoria lineage) virus. BXA treatment of donor ferrets reduced virus replication and delayed transmission of the BXA- Sen but not the BXA- Res IBV. The I38 genotype remained dominant in the BXA- Sen animals, even under BXA treatment. In competitive-mixture experiments, no transmission to aerosol-contacts was seen from BXA-treated donors coinfected with the BXA- Sen and BXA- Res B/Brisbane/60/2008 viruses. However, in parallel mixed-infections with the B/Phuket/3073/2013 (Yamagata lineage) virus background, BXA treatment failed to block airborne transmission of the BXA- Res virus and the I38T genotype generally predominated. Therefore, relative fitness of BXA- Res IBVs is complex and dependent on the virus backbone and within-host virus competition. BXA treatment of single-virus infected ferrets hampers aerosol transmission of the BXA- Sen virus and does not readily generate BXA- Res variants, while mixed-infections may result in propagation of BXA- Res IBVs of the Yamagata lineage. Our findings confirm the antiviral potency of baloxavir against IBVs while supporting optimization of the dosing regimen to maximize clinical benefit.

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