Framework for prioritizing head and neck surgery during the COVID‐19 pandemic

The COVID‐19 pandemic has placed an extraordinary demand on the United States health care system. Many institutions have canceled elective and non‐urgent procedures to conserve resources and limit exposure. While operational definitions of elective and urgent categories exist, there is a degree of surgeon judgment in designation. In the present commentary, we provide a framework for prioritizing head and neck surgery during the pandemic. Unique considerations for the head and neck patient are examined including risk to the oncology patient, outcomes following delay in head and neck cancer therapy, and risk of transmission during otolaryngologic surgery. Our case prioritization criteria consist of four categories: urgent—proceed with surgery, less urgent—consider postpone > 30 days, less urgent—consider postpone 30 to 90 days, and case‐by‐case basis. Finally, we discuss our preoperative clinical pathway for transmission mitigation including defining low‐risk and high‐risk surgery for transmission and role of preoperative COVID‐19 testing.     

Cognitive impairment in rapid‐onset dystonia‐parkinsonism

Rapid‐onset dystonia‐parkinsonism (RDP) is caused by mutations in the ATP1A3 gene. This observational study sought to determine if cognitive performance is decreased in patients with RDP compared with mutation‐negative controls. We studied 22 familial RDP patients, 3 non‐motor‐manifesting mutation‐positive family members, 29 mutation‐negative family member controls in 9 families, and 4 unrelated RDP patients, totaling 58 individuals. We administered a movement disorder assessment, including the Burke‐Fahn‐Marsden Dystonia Rating Scale (BFMDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS) and a cognitive battery of memory and learning, psychomotor speed, attention, and executive function. The cognitive battery was designed to evaluate a wide range of functions; recognition memory instruments were selected to be relatively pure measures of delayed memory, devoid of significant motor or vocal production limitations. Comparisons of standardized cognitive scores were assessed both with and without controlling for psychomotor speed and similarly for severity of depressive symptoms. A majority of RDP patients had onset of motor symptoms by age 25 and had initial symptom presentation in the upper body (face, mouth, or arm). Among patients, the BFMDRS (mean ± SD, 52.1 ± 29.5) and UPDRS motor subscore (29.8 ± 12.7) confirmed dystonia‐parkinsonism. The affected RDP patients performed more poorly, on average, than mutation‐negative controls for all memory and learning, psychomotor speed, attention, and executive function scores (all P ≤ 0.01). These differences persisted after controlling for psychomotor speed and severity of depressive symptoms. Impaired cognitive function may be a manifestation of ATP1A3 mutation and RDP. © 2014 International Parkinson and Movement Disorder Society     

Metacognitive mastery moderates the relationship of alexithymia with cluster C personality disorder traits in adults with substance use disorders

Cluster C personality disorder traits have been observed in substance use disorders and linked with poorer outcome. One potential factor which may cause these disturbances in personality function is alexithymia, or the inability to name and express emotion. There may be other proximate factors which moderate the impact of alexithymia on the expression of cluster C traits, such as metacognitive mastery, which is the ability to use knowledge about mental states of self and others to cope with distress and solve social problems. To examine the possibility that mastery mediated the effects of alexithymia on cluster C traits, we assessed each of these constructs using the Metacognitive Assessment Scale Abbreviated, Toronto Alexithymia Scale and SCID II among 58 adults in an early phase of recovery from substance misuse disorders in a residential setting. Results of a multiple regression revealed that, after controlling for symptom severity and severity of substance misuse history, metacognitive mastery moderated the effect of alexithymia on number of cluster C traits. A median split and subsequent ANCOVA revealed that participants with higher levels of alexithymia and poorer metacognitive mastery had more cluster C traits than the other groups. These findings may have clinical implications, suggesting that patients with substance use disorders may benefit from treatment which addresses metacognitive mastery.     

Structural Analysis and Whole Genome Mapping of a New Type of Plant Virus Subviral RNA: Umbravirus-Like Associated RNAs

We report the biological and structural characterization of umbravirus-like associated RNAs (ulaRNAs), a new category of coat-protein dependent subviral RNA replicons that infect plants. These RNAs encode an RNA-dependent RNA polymerase (RdRp) following a −1 ribosomal frameshift event, are 2.7–4.6 kb in length, and are related to umbraviruses, unlike similar RNA replicons that are related to tombusviruses. Three classes of ulaRNAs are proposed, with citrus yellow vein associated virus (CYVaV) placed in Class 2. With the exception of CYVaV, Class 2 and Class 3 ulaRNAs encode an additional open reading frame (ORF) with movement protein-like motifs made possible by additional sequences just past the RdRp termination codon. The full-length secondary structure of CYVaV was determined using Selective 2’ Hydroxyl Acylation analyzed by Primer Extension (SHAPE) structure probing and phylogenic comparisons, which was used as a template for determining the putative structures of the other Class 2 ulaRNAs, revealing a number of distinctive structural features. The ribosome recoding sites of nearly all ulaRNAs, which differ significantly from those of umbraviruses, may exist in two conformations and are highly efficient. The 3′ regions of Class 2 and Class 3 ulaRNAs have structural elements similar to those of nearly all umbraviruses, and all Class 2 ulaRNAs have a unique, conserved 3′ cap-independent translation enhancer. CYVaV replicates independently in protoplasts, demonstrating that the reported sequence is full-length. Additionally, CYVaV contains a sequence in its 3′ UTR that confers protection to nonsense mediated decay (NMD), thus likely obviating the need for umbravirus ORF3, a known suppressor of NMD. This initial characterization lays down a road map for future investigations into these novel virus-like RNAs.     

Outcomes of junctional ectopic tachycardia ablation in adult population—a multicenter experience

Purpose

Idiopathic junctional ectopic tachycardia (JET) is typically refractory to antiarrhythmic agents. Catheter ablation for JET is feasible but is associated with high risk of unintended atrioventricular (AV) block. There is limited data on the appropriate procedural technique and clinical outcomes with catheter ablation for idiopathic JET in adults.

Methods

This is a multicenter, retrospective study of all adult patients (age?≥?18 years) who underwent catheter ablation for idiopathic JET. Patient, procedural characteristics, and long-term outcomes were evaluated.

Results

Fifteen patients [radiofrequency ablation (RF)?=?14 and cryoablation?=?1) were treated with catheter ablation. The median age was 58 years with 67% males. All patients underwent mapping of the right atrium and the aortic cusps prior to energy delivery. The location of earliest activation in relation to the atrioventricular (AV) node was postero-superior in 73% (11/15), posterior in 13% (2/15), and superior in 13% (2/15) respectively. Acute success was 100%. Arrhythmia recurrence occurred in 53% (8/15) all of whom underwent a repeat ablation. High-grade AV block requiring permanent pacemaker occurred in 20% (3/15). At 12-month follow-up in the redo-ablation group, 37.5% (3/8) had recurrence of the arrhythmia two of which underwent a third ablation procedure.

Conclusion

Catheter ablation of idiopathic JET in adults is associated with a high rate of recurrence requiring multiple procedures and high risk of AV block requiring a permanent pacemaker. Mapping and ablation of the non-coronary cusp can be considered as the arrhythmia was controlled in 3 patients with no inadvertent AV block.

     

In vivo supramolecular templating enhances the activity of multivalent ligands: a potential therapeutic against the Escherichia coli O157 AB5 toxins

We demonstrate that interactions between multimeric receptors and multivalent ligands are dramatically enhanced by recruiting a complementary templating receptor such as an endogenous multimeric protein but only when individual ligands are attached to a polymer as preorganized, covalent, heterobifunctional pairs. This effect cannot be replicated by a multivalent ligand if the same recognition elements are independently arrayed on the scaffold. Application of this principle offers an approach to create high-avidity inhibitors for multimeric receptors. Judicious selection of the ligand that engages the templating protein allows appropriate effector function to be incorporated in the polymeric construct, thereby providing an opportunity for therapeutic applications. The power of this approach is exemplified by the design of exceptionally potent Escherichia coli Shiga toxin antagonists that protect transgenic mice that constitutively express a human pentraxin, serum amyloid P component.     

Notch-1 activation and dendritic atrophy in prion disease

In addition to neuronal vacuolation and astrocytic hypertrophy, dendritic atrophy is a prominent feature of prion disease. Because increased Notch-1 expression and cleavage releasing its intracellular domain (NICD) inhibit both dendrite growth and maturation, we measured their levels in brains from mice inoculated with Rocky Mountain Laboratory (RML) prions. The level of NICD was elevated in the neocortex, whereas the level of beta-catenin, which stimulates dendritic growth, was unchanged. During the incubation period, levels of the disease-causing prion protein isoform, PrPSc, and NICD increased concomitantly in the neocortex. Additionally, increased levels of Notch-1 mRNA and translocation of NICD to the nucleus correlated well with regressive dendritic changes. In scrapie-infected neuroblastoma (ScN2a) cells, the level of NICD was elevated compared with uninfected control (N2a) cells. Long neurofilament protein-containing processes extended from the surface of N2a cells, whereas ScN2a cells had substantially shorter processes. Transfection of ScN2a cells with a Notch-1 small interfering RNA decreased Notch-1 mRNA levels, diminished NICD concentrations, and rescued the long process phenotype. These results suggest that PrPSc in neurons and in ScN2a cells activates Notch-1 cleavage, resulting in atrophy of dendrites in the CNS and shrinkage of processes on the surface of cultured cells. Whether diminishing Notch-1 activation in vivo can prevent or even reverse neurodegeneration in prion disease remains to be established.     

Side-to-side nerve bridges reduce muscle atrophy after peripheral nerve injury in a rodent model

Background

Peripheral nerve injury can result in muscle atrophy and long-term disability. We hypothesize that creating a side-to-side bridge to link an injured nerve with a healthy nerve will reduce muscle atrophy and improve muscle function.

Methods

Sprague-Dawley rats were divided into four groups (n = 7 per group). Group 1: transection only—a 10-mm gap was created in the proximal tibial nerve; group 2: transected plus repaired—the transected tibial nerve was repaired; group 3: transected plus repaired plus nerve bridge—transected nerve repaired with a distal nerve bridge between the tibial and peroneal nerves via epineurial windows; and group 4: transected plus nerve bridge—transected tibial nerve left unrepaired and distal bridge added. Gait was assessed every 2 wk. At 90 d the following measures were determined: gastrocnemius mass, muscle and nerve nuclear density, and axonal infiltration into the nerve bridge.

Results

Groups 3 and 4 had greater improvements in walking track recovery than groups 1 and 2. Group 3's gastrocnemius muscles exhibited the least amount of atrophy. Groups 1, 2, and 4 exhibited greater histologic appearance of muscle breakdown compared with group 3 and control muscle. Finally, most bridges in groups 3 and 4 had neuronal sprouting via the epineurial windows.

Conclusions

Our study demonstrated reduced muscle atrophy with a side-to-side nerve bridge in the setting of peripheral nerve injury. These results support the application of novel side-to-side bridges in combination with traditional end-to-end neurorrhaphy to preserve muscle viability after peripheral nerve injuries.