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Biomedical subjects

Andrew Schmidt

Publications and source records attributed to Andrew Schmidt.

5 recordsLinked to original sources

A Phase I and Biodistribution Study of Ifabotuzumab, a Humanized Agonistic EphA3-Targeted Antibody, in Patients with Recurrent Glioblastoma.

PURPOSE: To conduct a phase I and biodistribution study of the EphA3 antibody ifabotuzumab and zirconium-89-labeled ifabotuzumab (89Zr-ifabotuzumab) in patients with glioblastoma (GBM). PATIENTS AND METHODS: This multisite study was conducted in adults with recurrent GBM whose tumors were measurable according to Response Assessment in Neuro-Oncology (RANO) criteria and whose Eastern Cooperative Oncology Group performance status was 0 to 1. Patients underwent a biodistribution study with PET scans with 89Zr-ifabotuzumab, followed by three infusions of ifabotuzumab at either 3.5 or 5.25 mg/kg before undergoing a second study with 89Zr-ifabotuzumab PET scans. Resected patient diagnostic tumor samples were collected for multiplex immunofluorescence and spatial transcriptomics analyses. RESULTS: Twelve patients were recruited, of which six were treated with 3.5 mg/kg and six with 5.25 mg/kg of ifabotuzumab. 89Zr-ifabotuzumab and associated PET scanning were well tolerated, as was ifabotuzumab. There were no objective responses, but one patient had prolonged stable disease. In addition, two patients showed changes in peritumor edema that were suggestive of modulation of tumor vasculature. 89Zr-ifabotuzumab scans showed highly specific tumor uptake in all patients concordant with disease sites on MRI and PET imaging, without evidence of nonspecific binding. Spatial transcriptomics and immunofluorescence analyses of the patient's archival tissue specimens showed that EphA3 was expressed in the tumor microenvironment in all patients and tumor cells with different transcriptional states. CONCLUSIONS: Targeting EphA3 with ifabotuzumab in patients with GBM is safe and attractive, showing chronologic stable expression across both tumor compartments (particularly in cells with a mesenchymal phenotype) and nontumor compartments (particularly the vascular compartment) with evidence of target modulation.

Humans↗

Intramedullary nailing following external fixation in femoral and tibial shaft fractures.

BACKGROUND: Intramedullary nailing is the standard of care for the definitive management of lower extremity long bone fractures. Occasionally, temporary external fixation is used in fractures with severe open wounds or vascular injury before definitive intramedullary nailing. Secondary intramedullary nailing following external fixation is somewhat controversial, especially with respect to the duration of external fixation that is allowable before the risk of infection following later nailing becomes too great. Several recent studies have provided further insight into this issue. OBJECTIVE: The primary objective is to evaluate infection and nonunion rates in patients treated with temporary external fixation and secondary intramedullary nailing for lower extremity long bone fractures. The secondary objective is to evaluate whether the duration of external fixation and the interval time (defined as the time from external fixator removal to intramedullary nailing) influence the risk of infection after intramedullary nailing.

External Fixators↗

Pharmacological treatment of social anxiety disorder: a meta-analysis.

Placebo-controlled trials have evaluated the efficacy of several medications in the treatment of social anxiety disorder but information regarding their relative efficacy is lacking. We compared the efficacy of medications systematically studied for the treatment of social anxiety disorder using meta-analytic techniques. The methodology included a database search of articles published between January 1980 and June 2001 and manual searches of bibliographies in published manuscripts. Trials were included if they reported outcome data on the Liebowitz Social Anxiety Scale (LSAS) or a categorical measure of responder status. Data were extracted independently by two authors. The Q statistic was used to assess homogeneity across trials. All analyses were conducted using intent-to-treat data. There was substantial heterogeneity across trials. The medications with largest effect sizes were phenelzine [effect size, 1.02; 95% Confidence Interval (CI), 0.52-1.52], clonazepam (effect size, 0.97; 95% CI, 0.49-1.45), gabapentin (effect size, 0.78; 95% CI, 0.29-1.27), brofaromine (effect size, 0.66; 95% CI, 0.38-0.94), and the selective serotonin reuptake inhibitors (SSRIs; effect size, 0.65; 95% CI, 0.50-0.81). There were no statistically significant differences between medications or medication groups. However, formal methods of interim monitoring adapted for meta-analyses suggested strongest evidence of efficacy for SSRIs and brofaromine. Several medications are efficacious for the treatment of social anxiety disorder. The stability of the SSRI effect size estimate in conjunction with other evidence for safety and tolerability and their ability to treat comorbid conditions supports the use of SSRIs as the first-line treatment. Direct comparisons of SSRIs vs. other promising medications deserve consideration.

Acetates↗

Comparative phenomenology of ataques de nervios, panic attacks, and panic disorder.

This article examines a clinical sample of 66 Dominican and Puerto Rican subjects who reported ataques de nervios and also psychiatric disorder, and disentangles the phenomenological experiences of ataque de nervios, panic attacks, and panic disorder. In-depth cultural interviews assessed the symptomatic phenomenology of ataque episodes from the local perspective as well as in terms of key panic features, such as recurrence, rapid peaking of symptoms, and lack of provocation. Independent diagnostic assessments of panic attacks and disorder were also used to establish the phenomenological overlap between ataque and panic. Our findings indicate that 36 percent of ataques de nervios fulfill criteria for panic attacks and between 17 percent and 33 percent for panic disorder, depending on the overlap method used. The main features distinguishing ataques that fulfill panic criteria from ataques that do not include whether the episodes were provoked by an upsetting event in the person's life and the rapidity of crescendo of the actual attack. A key finding is that ataques often share individual phenomenological features with panic episodes, but that these features usually do not "run together" during the ataque experience. This confirms previous findings that ataque is a more inclusive construct than panic disorder. The importance of these findings for the clinical diagnosis and treatment of persons with ataques is discussed.

Adolescent↗