Faculty Bibliography

Moderate-to-severe fatigue occurs in up to 94% of oncology patients undergoing active treatment. Current interventions for fatigue are not efficacious. A major impediment to the development of effective treatments is a lack of understanding of the fundamental mechanisms underlying fatigue. In the current study, differences in phenotypic characteristics and gene expression profiles were evaluated in a sample of breast cancer patients undergoing chemotherapy (CTX) who reported low (n = 19) and high (n = 25) levels of evening fatigue. Compared to the low group, patients in the high evening fatigue group reported lower functional status scores, higher comorbidity scores, and fewer prior cancer treatments. One gene was identified as upregulated and 11 as downregulated in the high evening fatigue group. Gene set analysis found 24 downregulated and 94 simultaneously up- and downregulated pathways between the two fatigue groups. Transcript origin analysis found that differential expression (DE) originated primarily from monocytes and dendritic cell types. Query of public data sources found 18 gene expression experiments with similar DE profiles. Our analyses revealed that inflammation, neurotransmitter regulation, and energy metabolism are likely mechanisms associated with evening fatigue severity; that CTX may contribute to fatigue seen in oncology patients; and that the patterns of gene expression may be shared with other models of fatigue (e.g., physical exercise and pathogen-induced sickness behavior). These results suggest that the mechanisms that underlie fatigue in oncology patients are multifactorial.

OBJECTIVES: To develop consensus recommendations for peri-operative tracheotomy care in pediatric patients. METHODS: Expert opinion by the members of the International Pediatric Otolaryngology Group (IPOG). The mission of the IPOG is to develop expertise-based consensus recommendations for the management of pediatric otolaryngologic disorders with the goal of improving patient care. The consensus recommendations herein represent the first publication by the group. RESULTS: Consensus recommendations including pre-operative, intra-operative, and post-operative considerations, as well as sedation and nutrition management are described. These recommendations are based on the collective opinion of the IPOG members and are targeted to (i) otolaryngologists who perform tracheotomies on pediatric patients, (ii) intensivists who are involved in the shared-care of these patients, and (iii) allied health professionals. CONCLUSION: Pediatric peri-operative tracheotomy care consensus recommendations are aimed at improving patient-centered care in this patient population.

BACKGROUND: Commonly occurring in the head and neck, paragangliomas are typically benign, highly vascular neoplasms embryologically originating from the extra-adrenal paraganglia of the neural crest. Frequently, these tumors are associated with the vagus or tympanic plexus nerve or the carotid artery, or jugular bulb. Their clinical presentation can vary across a wide spectrum of signs and symptoms. METHODS: We reviewed and compared standard treatment approaches for paragangliomas of the head and neck. RESULTS: In general, surgery is the first-line choice of therapy for carotid body tumors, whereas radiotherapy is the first-line option for jugular and vagal paragangliomas. CONCLUSIONS: Because of the complexity of clinical scenarios and treatment options for paragangliomas, a multidisciplinary algorithmic approach should be used for treating paragangliomas. The approach should emphasize single-modality treatment that yields excellent rates of tumor control, low rates of severe, iatrogenic morbidity, and the preservation of long-term function in this patient population.

BACKGROUND: Tenecteplase, a modified plasminogen activator with higher fibrin specificity and longer half-life, may have advantages over alteplase in acute ischemic stroke thrombolysis. AIMS: We undertook an individual patient data meta-analysis of randomized controlled trials that compared alteplase with tenecteplase in acute stroke. METHODS: Eligible studies were identified by a MEDLINE search, and individual patient data were acquired. We compared clinical outcomes including modified Rankin Scale at three months, early neurological improvement at 24 h, intracerebral hemorrhage, symptomatic intracerebral hemorrhage, and mortality at three months between all dose tiers of tenecteplase and alteplase. RESULTS: Three relevant studies (Haley et al., Parsons et al., and ATTEST) included 291 patients and investigated three doses of tenecteplase (0.1, 0.25, 0.4 mg/kg). There were no differences between any dose of tenecteplase and alteplase for either efficacy or safety end points. Tenecteplase 0.25 mg/kg had the greatest odds to achieve early neurological improvement (OR [95%CI] 3.3 [1.5, 7.2], p = 0.093), excellent functional outcome (modified Rankin Scale 0-1) at three months (OR [95%CI] 1.9 [0.8, 4.4], p = 0.28), with reduced odds of intracerebral hemorrhage (OR [95%CI] 0.6 [0.2, 1.8], P = 0.43) compared with alteplase. Only 19 patients were treated with tenecteplase 0.4 mg/kg, which showed increased odds of symptomatic intracerebral hemorrhage compared with alteplase (OR [95% CI] 6.2 [0.7, 56.3]). CONCLUSIONS: While no significant differences between tenecteplase and alteplase were found, point estimates suggest potentially greater efficacy of 0.25 and 0.1 mg/kg doses with no difference in symptomatic intracerebral hemorrhage, and potentially higher symptomatic intracerebral hemorrhage risk with the 0.4 mg/kg dose. Further investigation of 0.25 mg/kg tenecteplase is warranted.

INTRODUCTION: Although rare, complications in cochlear implantation may result from surgical or technical mishaps, reaction to the foreign body, infection, or mechanical device failure. Delayed cerebrospinal fluid (CSF) leak is a rarely reported condition that may present with asymptomatic swelling over the receiver-stimulator (RS). In our practice, meticulous drilling of a bony well is important in preventing device migration and maintaining a low device profile but there is the potential for immediate or delayed complication from this technique. OBJECTIVE: We report two cases of the diagnosis and management of delayed extradural CSF collection of the RS bony well and describe its successful management. PATIENTS: Two pediatric cochlear implant patients, 10 and 17 months of age with devices from different manufacturers. INTERVENTION(S): Operative exploration and repair without device removal. MAIN OUTCOME AND RESULTS: Although the initial postoperative course was uncomplicated with both patients receiving benefit from their device, both presented at varying intervals month(s) later with swelling over the RS. There were no signs of infection but the swelling prevented use of the device. Extradural CSF collection was suspected, confirmed operatively, and repaired with complete resolution without the need for reimplantation. CONCLUSION: Delayed CSF leak may present as an asymptomatic swelling over the RS after cochlear implantation. Sterile fluid aspiration may confirm the diagnosis and management can proceed conservatively or with operative exploration and repair. Future device designs with lower profiles may facilitate device fixation while allowing for a more shallow well, further reducing the risk of this rare complication.

A craniotomy over the superior cerebellar convexity for approaches to this region typically involves a small infratentorial craniotomy and then drilling down of the bone to expose some portion of the transverse/sigmoid sinuses. The authors describe the anatomy of the region and the method for a two-part paramedian occipital and suboccipital craniotomy (supra and infratentorial) that may have time-saving, safety, and cosmetic advantages. For this technique, a supratentorial craniotomy is used to expose the transverse sinus from above, and subsequently, dissection across the sinus over the cerebellar convexity can be done under direct vision. The two bone pieces are joined on the inner table side while plates for fixation above the superior nuchal line can be counter-sunk to avoid post-operative pain from the prominence of screws. There is no need for cranioplasty materials since there is no burring down of bone for adequate exposure of the transverse sinus. The technique has been used by two senior surgeons over the years convincing them of the speed, safety, and utility of the technique. Here, the authors present a single example of the technique.