Citations

Aim Preclinical evidence suggests that oxidized macrophage migration inhibitory factor (oxMIF) may be involved in carcinogenesis. This phase 1 study (NCT01765790) assessed the safety, tolerability, pharmacokinetics and antitumour activity of imalumab, an oxMIF inhibitor, in patients with advanced cancer using ‘3 + 3’ dose escalation. Methods In Schedule 1, patients with solid tumours received doses from 1 to 50 mg/kg IV every 2 weeks. In Schedule 2, patients with metastatic colorectal adenocarcinoma, non‐small‐cell lung, or ovarian cancer received weekly doses of 10 or 25 mg/kg IV (1 cycle = 28 days). Treatment continued until disease progression, unacceptable toxicity, dose‐limiting toxicity, or withdrawal of consent. Results Fifty of 68 enrolled patients received imalumab. The most common treatment‐related adverse events (TRAEs) included fatigue (10%) and vomiting (6%); four grade 3 serious TRAEs (two patients) occurred. The dose‐limiting toxicity was allergic alveolitis (one patient, 50 mg/kg every 2 weeks). The maximum tolerated and biologically active doses were 37.5 mg/kg every 2 weeks and 10 mg/kg weekly, respectively. Of 39 assessed patients, 13 had stable disease (≥4 months in 8 patients). Conclusions Imalumab had a maximum tolerated dose of 37.5 mg/kg every 2 weeks in patients with advanced solid tumours, with a biologically active dose of 10 mg/kg weekly. Further investigation will help define the role of oxMIF as a cancer treatment target.

Background Seasonal influenza is a respiratory illness caused by the influenza virus. During the 2017–2018 flu season, the Centers for Disease Control and Prevention noted approximately 959,000 hospitalizations and 79,400 deaths from influenza. We sought to evaluate the educational quality of informational videos pertaining to seasonal influenza on the popular social media forum, YouTube. Methods Using the keywords “seasonal influenza,” all videos from 28 January to 5 February 2017 were included and analyzed for characteristics, source, and content. The source was further classified as healthcare provider, alternative-medicine provider, the patient and/or their parents, company, media, or professional society. Videos about other categories of influenza (e.g. swine or Spanish) or in foreign languages were excluded. A total of 10 blinded reviewers scored each video independently. Results Overall, 300 videos were analyzed, with a median of 341.50 views, 1.00 likes, 0 dislikes, and 0 comments. Based on the average scores of videos by source, there was statistically significant difference in the average score among videos by video source ( p < 0.01). Healthcare provider videos had the highest mean scores whereas alternative medicine provider videos had the lowest. Conclusions Although the aforementioned video sources scored higher than others, these videos did not fulfill our criteria as far as educating patients thoroughly. Our data also suggest alternative medicine and patient source videos were misleading for patients. Clinical implications: Although videos by healthcare providers were a better source of information, videos on seasonal influenza were shown to be poor sources of valid healthcare information. This study reiterates the need for higher-quality educational videos on seasonal influenza by the medical community.

Abstract SPECC1L mutations have been identified in patients with rare atypical orofacial clefts and with syndromic cleft lip and/or palate (CL/P). These mutations cluster in the second coiled-coil and calponin homology domains of SPECC1L and severely affect the ability of SPECC1L to associate with microtubules. We previously showed that gene-trap knockout of Specc1l in mouse results in early embryonic lethality. We now present a truncation mutant mouse allele, Specc1lΔC510, that results in perinatal lethality. Specc1lΔC510/ΔC510 homozygotes showed abnormal palate rugae but did not show cleft palate. However, when crossed with a gene-trap allele, Specc1lcGT/ΔC510 compound heterozygotes showed a palate elevation delay with incompletely penetrant cleft palate. Specc1lcGT/ΔC510 embryos exhibit transient oral epithelial adhesions at E13.5, which may delay shelf elevation. Consistent with oral adhesions, we show periderm layer abnormalities, including ectopic apical expression of adherens junction markers, similar to Irf6 hypomorphic mutants and Arhgap29 heterozygotes. Indeed, SPECC1L expression is drastically reduced in Irf6 mutant palatal shelves. Finally, we wanted to determine if SPECC1L deficiency also contributed to non-syndromic (ns) CL/P. We sequenced 62 Caucasian, 89 Filipino, 90 Ethiopian, 90 Nigerian and 95 Japanese patients with nsCL/P and identified three rare coding variants (p.Ala86Thr, p.Met91Iso and p.Arg546Gln) in six individuals. These variants reside outside of SPECC1L coiled-coil domains and result in milder functional defects than variants associated with syndromic clefting. Together, our data indicate that palate elevation is sensitive to deficiency of SPECC1L dosage and function and that SPECC1L cytoskeletal protein functions downstream of IRF6 in palatogenesis.

Migraine is the most common acute and recurrent headache syndrome in children. This condition has unique clinical characteristics in the pediatric population, that can evolve with age, and significantly impact a child's quality of life, affecting their education, socialization, and family life. The purpose of this review is to describe the varied clinical features of migraine seen in children, and discuss potential treatment options for pediatric migraine, including chronic migraine. In many patients a multifaceted approach involving lifestyle changes, treatment of comorbid conditions, and pharmacological treatments are needed for optimal headache control.What this paper adds Migraine presents as various phenotypes in children, sometimes evolving as the child ages. An expanded range of treatment options exists for the challenging chronic migraine patient.

ObjectiveThis study was performed to outline and analyze the overall Medicare landscape with respect to otolaryngologists and beneficiaries, services, and reimbursements.MethodsThis is a retrospective analysis of publicly available Medicare utilization and payment data for all otolaryngologists in facility and nonfacility practice settings who provided services to Medicare beneficiaries between January 1, 2012, and December 31, 2016.ResultsIn 2016, a total of $701,195,375 was distributed to 8572 otolaryngology physician providers for 815 unique Healthcare Common Procedure Coding System codes for 13,942,536 procedure claims. Of specialty care, otolaryngology ranks 20th among 54 subspecialties for total Medicare payments. The average number of services coded per provider was 1627. The average otolaryngologist was paid $81,800.67. Thirty‐two percent of otolaryngologists did not receive reimbursement for services from Medicare in 2016.DiscussionIn 2016, the most significant contributors to Medicare payments to otolaryngologists were large‐scale, low‐cost events that are relatively short procedures done in clinic. Utilization of nasal endoscopy was up trending from 2012 to 2016. Some of the Current Procedural Terminology codes with the greatest discrepancies between submitted charge and Medicare payment among nonfacility otolaryngology providers are more involved than simple office procedures.Implications for PracticeIt is increasingly valuable for physicians to know factors that affect reimbursement for procedures and operations in different settings and to be aware of the trends in variation in their specialty. Otolaryngologists should communicate with policy makers in efforts toward sustainable reimbursement models.

Chronically implantable neurostimulation devices are becoming a clinically viable option for treating patients with neurological disease and psychiatric disorders. Neurostimulation offers the ability to probe and manipulate distributed networks of interacting brain areas in dysfunctional circuits. Here, we use tools from network control theory to examine the dynamic reconfiguration of functionally interacting neuronal ensembles during targeted neurostimulation of cortical and subcortical brain structures. By integrating multimodal intracranial recordings and diffusion-weighted imaging from patients with drug-resistant epilepsy, we test hypothesized structural and functional rules that predict altered patterns of synchronized local field potentials. We demonstrate the ability to predictably reconfigure functional interactions depending on stimulation strength and location. Stimulation of areas with structurally weak connections largely modulates the functional hubness of downstream areas and concurrently propels the brain towards more difficult-to-reach dynamical states. By using focal perturbations to bridge large-scale structure, function, and markers of behavior, our findings suggest that stimulation may be tuned to influence different scales of network interactions driving cognition.

AbstractPHACE(S) syndrome is a condition characterized by posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities, sternal cleft, and supraumbilical raphe. We present four children with PHACE(S) syndrome who have absence of or severe malformation of the roots of their permanent first molars (PFMs). Root abnormalities in the children's molars were bilateral and not restricted to the segments affected by cutaneous hemangioma. The reason for root abnormalities is unknown, but given the rarity of these findings in healthy children, it is likely an additional dental manifestation of PHACE syndrome. The absence of functional roots in the PFMs can result in significant consequences. Therefore, we recommend a panoramic dental radiograph during transitional dentition for children with PHACE syndrome to screen for dental root abnormalities.

OBJECTIVEThe authors sought to investigate the incidence and predictors of venous thromboembolic events (VTEs) after craniotomy for tumor resection, which are not well established, and the efficacy of and risks associated with VTE chemoprophylaxis, which remains controversial.METHODSThe authors investigated the incidence of VTEs in a consecutive series of patients presenting to the authors’ institution for resection of an intracranial lesion between 2012 and 2017. Information on patient and tumor characteristics was collected and independent predictors of VTEs were determined using stepwise multivariate logistic regression analysis. Review of the literature was performed by searching MEDLINE using the keywords “venous thromboembolism,” “deep venous thrombosis,” “pulmonary embolism,” “craniotomy,” and “brain neoplasms.”RESULTSThere were 1622 patients included for analysis. A small majority of patients were female (52.6%) and the mean age of the cohort was 52.9 years (SD 15.8 years). A majority of intracranial lesions were intraaxial (59.3%). The incidence of VTEs was 3.0% and the rates of deep venous thromboses and pulmonary emboli were 2.3% and 0.9%, respectively. On multivariate analysis, increasing patient age (unit OR 1.02, 95% CI 1.00–1.05; p = 0.018), history of VTE (OR 7.26, 95% CI 3.24–16.27; p < 0.001), presence of motor deficit (OR 2.64, 95% CI 1.43–4.88; p = 0.002), postoperative intracranial hemorrhage (OR 4.35, 95% CI 1.51–12.55; p < 0.001), and prolonged intubation or reintubation (OR 3.27, 95% CI 1.28–8.32; p < 0.001) were independently associated with increased odds of a VTE. There were 192 patients who received VTE chemoprophylaxis (11.8%); the mean postoperative day of chemoprophylaxis initiation was 4.6 (SD 3.8). The incidence of VTEs was higher in patients receiving chemoprophylaxis than in patients not receiving chemoprophylaxis (8.3% vs 2.2%; p < 0.001). There were 30 instances of clinically significant postoperative hemorrhage (1.9%), with only 1 hemorrhage occurring after initiation of VTE chemoprophylaxis (0.1%).CONCLUSIONSThe study results show the incidence and predictors of VTEs after craniotomy for tumor resection in this patient population. The incidence of VTE within this cohort appears low and comparable to that observed in other institutional series, despite the lack of routine prophylactic anticoagulation in the postoperative setting.