Characterizing Adverse Events of Biologic Treatment of T2 Disease: A Disproportionality Analysis of the FDA Adverse Event Reporting System.

INTRODUCTION: Over the last 3 years, the FDA has approved dupilumab, omalizumab, and mepolizumab for the treatment of CRSwNP; however, adverse events of these biologics have not been described in post-marketing surveillance trials. By utilizing the FDA Adverse Event Reporting System (FAERS), this study describes and compares biologic-associated adverse events in T2 disease. METHODS: This case-non-case study assessed disproportionate reporting rates using reporting odds ratios (RORs). RORs and p values for biologic-associated AEs were categorized and compared among dupilumab, omalizumab, and mepolizumab. This analysis included AEs associated with all treatment indications. Relative AE rates and outcomes were calculated. RESULTS: There were a total of 112,560, 24,428, and 18,741 unique AE reports associated with dupilumab, omalizumab, and mepolizumab, respectively. Omalizumab had the strongest association with anaphylaxis (ROR = 20.80, 95% confidence interval [CI]: 18.58, 23.29). Dupilumab had large relative proportions and positive signals in the ophthalmologic category (7.76%, ROR = 6.20, 95% CI: 6.06, 6.35), such as with blurry vision (ROR = 3.80, CI: 3.52, 4.12) and visual impairment (ROR = 1.98, CI: 1.80, 2.19). Dupilumab was the only biologic associated with injection-site reactions (7.98%, ROR = 8.17, 95% CI: 7.98, 8.37). DISCUSSION/CONCLUSION: This is the first large-scale comparative analysis of the AE profiles of dupilumab, omalizumab, and mepolizumab. Our data suggest possible relations between dupilumab and ophthalmologic and injection-site AEs. Omalizumab was the only biologic with a positive anaphylaxis signal. This FAERS investigation suggests important AE differences among these biologics.

Unusual Vascular Distribution in the Third Segment of the Axillary Artery.

The third segment of the axillary artery (TSAA) is the main vascular supply to the muscles of the upper limb. Numerous studies have reported atypical branching patterns of the TSAA, which can complicate operative interventions involving structures supplied by this segment of the artery. Our current study evaluated a previously undescribed branching pattern in the TSAA, in which the subscapular artery gave rise to an unusual posterior humeral circumflex artery, and a second subscapular artery. In addition, a third variant was found in the origin of the thoracodorsal artery: two collateral horizontal arteries supplying the deep medial surface of the latissimus dorsi muscle. Vascular anatomical variants may affect the classical upper limb interventions requiring modification of the traditional surgical approaches. This case report aims to evaluate these variants from a clinical perspective regarding the management of upper limb trauma, axillary, breast, and muscle flap surgery.

Comparing the Efficacy of Radiation Free Machine-Vision Image-Guided Surgery With Traditional 2-Dimensional Fluoroscopy: A Randomized, Single-Center Study.

Background: Three-dimensional (3D) computer-assisted navigation (CAN) has emerged as a potential alternative to 2-dimensional (2D) fluoroscopy in the surgical placement of spinal instrumentation. Recently, 3D-CAN systems have improved significantly in their ability to provide real-time anatomical referencing while shortening the registration and set-up time. A novel system in navigation, Machine-Vision Image-Guided Surgery (MvIGS; 7D Surgical, Toronto, Canada) was cleared by the US Food and Drug Administration, but its potential benefits in reducing intra-operative radiation exposure to patients and enhancing surgical accuracy of pedicle screw placement are not fully known. Purpose: We sought to conduct a prospective, randomized, clinical study comparing the 3D-MvIGS spinal navigation system and 2D-fluoroscopy for pedicle screw insertion up to 3 levels (T10-S1) and for various measures of surgical efficacy. Methods: Sixty-two eligible patients were randomized to receive spine surgery using either the 3D-MvIGS group or the conventional 2D-fluoroscopy for pedicle screw fixation for the treatment of spinal stenosis and degenerative spondylolisthesis. Intra-operative parameters and procedure-related unintended protocol violations were recorded. Results: Operative time and estimated blood loss were not significantly different between groups. Radiation time and exposure to patients were significantly reduced in the 3D-MvIGS group. There was no difference between groups in pedicle screw placement accuracy (2D-fluoroscopy group, 96.6%; 3D-MvIGS group, 94.2%). There were no major complications or cases that required revision surgery. Conclusion: The 3D-MvIGS navigation system performed comparably with 2D-fluoroscopy in terms of pedicle screw placement accuracy and operative time. The 3D-MvIGS showed a significant reduction in radiation exposure to patients. In more complex cases or larger cohorts, the true value of greater anatomical visualization can be elucidated.

Behavioral analysis of HPV+ oropharyngeal cancer: Do you know your patients?

OBJECTIVE: Evaluate the epidemiologic makeup of a population of HPV+ OPSCC patients treated at one institution over approximately a decade. STUDY DESIGN: Prospective survey study of HPV+ OPSCC treated between 2007 and 2016. SETTING: Mount Sinai Health System SUBJECTS AND METHODS: Patients aged 18+ who underwent treatment for HPV+ OPSCC. 223 patients were asked to complete a health survey including substance use and sexual history in order to specifically characterize the social behaviors of patients with HPV + OPSCC. RESULTS: Eighty-two patients responded, 70 male (85.4%) and 12 female (14.6%). While half of patients were nonsmokers, 18.3% had a smoking history of <15 pack years, and 32.9% had a 15+ pack-year smoking history. Nearly 25% reported significant drinking history (3+ drinks/day). Males had an average of 18 lifetime sexual partners, and females had 7 partners. Eight patients reported >100 sexual partners. CONCLUSIONS: HPV+ OPSCC was more prevalent in white males with a high number of lifetime sexual partners, as expected. Careful evaluation revealed other findings of significance that are not generally associated with this population. Half of our patients had significant historical tobacco and alcohol consumption. One quarter of patients had a history of another malignancy. These findings highlight the importance of taking a comprehensive history when determining appropriate treatment or designing future de-escalation trials in HPV+ OPSCC.

Cortactin Is a Regulator of Activity-Dependent Synaptic Plasticity Controlled by Wingless.

Major signaling molecules initially characterized as key early developmental regulators are also essential for the plasticity of the nervous system. Previously, the Wingless (Wg)/Wnt pathway was shown to underlie the structural and electrophysiological changes during activity-dependent synaptic plasticity at the Drosophila neuromuscular junction. A challenge remains to understand how this signal mediates the cellular changes underlying this plasticity. Here, we focus on the actin regulator Cortactin, a major organizer of protrusion, membrane mobility, and invasiveness, and define its new role in synaptic plasticity. We show that Cortactin is present presynaptically and postsynaptically at the Drosophila NMJ and that it is a presynaptic regulator of rapid activity-dependent modifications in synaptic structure. Furthermore, animals lacking presynaptic Cortactin show a decrease in spontaneous release frequency, and presynaptic Cortactin is necessary for the rapid potentiation of spontaneous release frequency that takes place during activity-dependent plasticity. Most interestingly, Cortactin levels increase at stimulated synaptic terminals and this increase requires neuronal activity, de novo transcription and depends on Wg/Wnt expression. Because it is not simply the presence of Cortactin in the presynaptic terminal but its increase that is necessary for the full range of activity-dependent plasticity, we conclude that it probably plays a direct and important role in the regulation of this process.SIGNIFICANCE STATEMENT In the nervous system, changes in activity that lead to modifications in synaptic structure and function are referred to as synaptic plasticity and are thought to be the basis of learning and memory. The secreted Wingless/Wnt molecule is a potent regulator of synaptic plasticity in both vertebrates and invertebrates. Understanding the molecular mechanisms that underlie these plastic changes is a major gap in our knowledge. Here, we identify a presynaptic effector molecule of the Wingless/Wnt signal, Cortactin. We show that this molecule is a potent regulator of modifications in synaptic structure and is necessary for the electrophysiological changes taking place during synaptic plasticity.

The Effect of Obesity on the Improvement in Health State Outcomes following Minimally Invasive Transforaminal Interbody Fusion.

Study Design Observational study. Objective Studies have shown a correlation between obesity and lumbar spine pathology, but also that obese patients have higher rates of complication following lumbar spine surgery. It is unknown if obese patients have clinical gains following lumbar spine surgery comparable to the gain of normal-weight patients. This study investigated the correlation of obesity and the delta change in outcomes in a single surgeon's cohort of normal-weight and obese patients undergoing minimally invasive (MIS) transforaminal lumbar interbody fusion (TLIF). Methods A retrospective review was performed of a single surgeon's patients at an academic medical center who underwent MIS TLIF between July 2011 and December 2013. Statistical analyses included independent sample t test for continuous variables, Fisher exact test for categorical data, and repeated measures two-way analysis of variance to assess the interaction between obesity status and the change in Short-Form Health Survey 12 (SF-12) results. Results Thirty-eight patients from a single institution were reviewed, and 19 had a body mass index greater than 30. The nonobese and obese postoperative SF-12 mental composite scores (MCS; 52.70 ± 2.50 versus 52.16 ± 1.91; p = 0.87) and physical composite scores (PCS; 45.56 ± 2.72 versus 41.03 ± 2.65; p = 0.24) did not show any significant differences. There was no significant interaction between obesity and change in SF-12 MCS (F [1, 36] = 0.96, p = 0.33) or SF-12 PCS (F [1, 36] = 0.74, p = 0.40) between the pre- and postoperative scores. There was a significant effect of obesity on SF-12 PCS scores (F [1, 36] = 7.15, p = 0.01). Conclusions Patients undergoing MIS TLIF sustain meaningful and significant gains in SF-12 MCS and PCS that is not impacted by their obesity status.

Adar is essential for optimal presynaptic function.

RNA editing is a powerful way to recode genetic information. Because it potentially affects RNA targets that are predominantly present in neurons, it is widely hypothesized to affect neuronal structure and physiology. Across phyla, loss of the enzyme responsible for RNA editing, Adar, leads to behavioral changes, impaired locomotion, neurodegeneration and death. However, the consequences of a loss of Adar activity on neuronal structure and function have not been studied in detail. In particular, the role of RNA editing on synaptic development and physiology has not been investigated. Here we test the physiological and morphological consequences of the lack of Adar activity on the Drosophila neuromuscular junction (NMJ). Our detailed examination of synaptic transmission showed that loss of Adar increases quantal size, reduces the number of quanta of neurotransmitter released and perturbs the calcium dependence of synaptic release. In addition, we find that staining for several synaptic vesicle proteins is abnormally intense at Adar deficient synapses. Consistent with this finding, Adar mutants showed a major alteration in synaptic ultrastructure. Finally, we present evidence of compensatory changes in muscle membrane properties in response to the changes in presynaptic activity within the Adar mutant NMJs.