Traumatic Brain Injury in Patients With Frontal Sinus Fractures.

Traumatic brain injury (TBI) is an insult to the brain from an external mechanical force that may lead to short or long-term impairment. Traumatic brain injury has been reported in up to 83% of craniofacial fractures involving the frontal sinus. However, the risk factors for TBI at presentation and persistent neurological sequelae in patients with frontal sinus fractures remain largely unstudied. The authors aim to evaluate the prevalence and risk factors associated with TBI on presentation and neurological sequelae in these patients. The authors retrospectively reviewed patients who presented with traumatic frontal sinus fractures in 2019. The authors' primary outcome was the prevalence of concomitant TBI on presentation, which authors defined as any patient with neurological symptoms/signs on presentation and/or patients with a Glasgow Coma Scale <15 with no acute drug or alcohol intoxication or history of dementia or other neurocognitive disorder. The authors' secondary outcome was the incidence of neurological sequelae after 1 month of injury. Bivariate analysis and multivariate logistic regression were performed. A total of 56 patients with frontal sinus fractures were included. Their median (interquartile range) age was 47 (31-59) years, and the median (interquartile range) follow-up was 7.3 (1.3-76.5) weeks. The majority were males [n = 48 (85.7%)] and non-Hispanic whites [n = 35 (62.5%)]. Fall was the most common mechanism of injury [n = 15 (26.8%)]. Of the 56 patients, 46 (82.1%) had concomitant TBI on presentation. All patients who had combined anterior and posterior table frontal sinus fractures [n = 37 (66.1%)] had TBI on presentation. These patients had 13 times the odds of concomitant TBI on presentation [adjusted odds ratio (95% CI): 12.7 (2.3-69.0)] as compared with patients with isolated anterior or posterior table fractures. Of 34 patients who were followed up more than 1 month after injury, 24 patients (70.6%) had persistent neurological sequelae, most commonly headache [n = 16 (28.6%)]. Patients who had concomitant orbital roof fractures had 32 times the odds of neurological sequelae after 1 month of injury [adjusted odds ratio (95% CI): 32 (2.4->100)]. Emergency physicians and referring providers should maintain a high degree of suspicion of TBI in patients with frontal sinus fractures. Head computed tomography at presentation and close neurological follow-up are recommended for patients with frontal sinus fracture with combined anterior and posterior table fractures, as well as those with concomitant orbital roof fractures.

How should we treat painful sensitivity in the hand? An international e-Delphi study.

BACKGROUND: Evidence synthesis suggests allodynia resulting from neuropathic pain has few interventions with clear effectiveness. As research continues to build this needed evidence base, expert consensus recommendations can address the conflicting approaches within current hand therapy practice. PURPOSE: This study aimed to develop consensus recommendations for the clinical management of allodynia from an international panel of hand therapists. STUDY DESIGN: This was an international e-Delphi survey study. METHODS: We recruited international hand rehabilitation experts to participate in an e-Delphi survey. Consensus was defined as 75% or more of participants agreeing with a recommendation, and at least 3 rounds of consensus building were anticipated. Experts were identified from 21 countries, and clinical vignettes describing a spectrum of patients with painful sensitivity in the hand were provided to elicit treatment recommendations. Initial recommendations were summarized, and consensus sought for clinical practice recommendations. RESULTS: Sixty-eight participants were invited, with 44 more added through peer nominations. Fifty-four participants from 19 countries completed the initial survey and were invited to participate in all subsequent rounds. Over 900 treatment suggestions were provided from the initial vignettes across domains, including sensory, physical, and functional interventions, education, and cortical representation techniques: 46 ultimately reached consensus. However, important discrepancies in justification (eg, why allodynia should be covered) and implementation of techniques (eg, desensitization, sensory reeducation) were identified as the consensus exercise progressed. CONCLUSIONS: Experts recommend individually tailored programs to treat allodynia using a variety of physical/movement, sensory-based, and "top-down" approaches; this is highly aligned with contemporary theories, such as the Neuromatrix Model of Pain. However, consensus was not reached on the justification and implementation of some of these approaches, reflecting the lack of a taxonomy and supporting evidence for tactile stimulation approaches in the current literature. Trials directly comparing the effectiveness of these approaches are needed.

How should we define and assess painful sensitivity in the hand? An international e-Delphi study.

BACKGROUND: Painful sensitivity in the hand is commonly seen with neuropathic pain, interfering with daily activities including rehabilitation. However, there are currently several terms used to describe the problem and a lack of guidance on what assessments should be used. PURPOSE: To gather expert opinion a) identifying current and common terminology used in hand therapy, b) developing a consensus definition of hypersensitivity, and c) developing consensus guidance on how to best assess allodynia. STUDY DESIGN: International e-Delphi survey study. METHODS: We conducted an e-Delphi consensus study drawing on international experts in hand rehabilitation. We planned up to four rounds of consensus-seeking, defining consensus as 75% or more of participants agreeing with a definition or recommendation. Experts were identified from 21 countries, with the nomination of other experts encouraged for 'snowball sampling'. The first round included clinical vignettes describing 'painful sensitivity of the hand' and asked participants to describe how they would assess each case. Definitions for hypersensitivity, tactile hyperesthesia, and allodynia were also requested. RESULTS: We invited 68 participants: 44 more were added through nominations. Sixty-three agreed to participate and were sent the round one survey; 54 participants from 19 countries completed this survey and were invited to participate in all subsequent rounds. No two definitions of hypersensitivity were the same, while 87% of the definitions for allodynia and 78% for tactile hyperesthesia were concordant with a published taxonomy. Over 700 assessment items were proposed in round one: ultimately 38 items representing eight distinct constructs reached a consensus for assessing allodynia. CONCLUSIONS: Therapists definitions were consistent with an existing taxonomy for allodynia. Although hypersensitivity conceptualizations varied regarding the qualities of stimulus and response, a working definition was reached. Recommended assessments were relatively consistent internationally, holistic, and reflected a potential link between allodynia and central sensitization.

Management of Frontal Sinus Fractures at a Level 1 Trauma Center: Retrospective Study and Review of the Literature.

Study Design: Case series. Objective: This retrospective review of frontal sinus fractures aims to describe our current experience managing these fractures at an urban level I trauma center. Methods: An institutional database of 2081 patients who presented with maxillofacial fractures on computed tomography face/sinus in 2019 was queried for all patients with traumatic frontal sinus fractures. Demographics, trauma-related history, management approach, and follow-up data were collected and analyzed. Results: Sixty-three (7.3%) patients had at least one fracture involving the frontal sinus. The most common etiologies were assaults, falls, and motor vehicle accidents. Surgical repair was performed in 26.8% of patients with frontal sinus fractures, and the other 73.2% were observed. Fractures that were displaced, comminuted, obstructive of the frontal sinus outflow tract, or associated with a dural tear or cerebrospinal fluid leak were more likely to be operative. Conclusions: The majority of frontal sinus fractures in this study were treated with observation. Despite advances in transnasal endoscopic approaches, many surgeons still rely on open approaches to repair frontal sinus fractures.

An Algorithm for the Use of Free Tissue Graft Reconstruction in the Endoscopic Endonasal Approach for Pituitary Tumors.

OBJECTIVE: To identify factors associated with successful use of free tissue grafting versus vascularized reconstruction after resection of pituitary tumors. METHODS: A retrospective chart review of 2 tertiary academic medical centers over 3.5 years was conducted. Variables assessed included age, sex, body mass index, pathology, extent of surgical exposure, cavernous sinus or suprasellar extension, intraoperative cerebrospinal fluid (CSF) leak, grade of leak, previous radiation, and previous surgery. Reconstructive techniques were divided into no reconstruction, free tissue grafts, and vascularized flaps. RESULTS: A total of 485 patients were included. Free grafts were used in 299/485 cases (61.6%) and were more commonly used with smaller approaches (P < 0.001). Larger exposure size and CSF leak grades 2 and 3 were associated with vascularized flap use (P < 0.001 and P = 0.012, respectively). Using multivariate regression, type of reconstruction could be predicted by increasing extent of approach, intraoperative CSF leak grade, and suprasellar extension (odds ratio [OR], 2.014, P < 0.001, 95% confidence interval [CI], 1.335-3.039; OR, 1.636, P = 0.025, 95% CI, 1.064-2.517; OR, 1.975, P < 0.001, 95% CI, 1.554-2.510, respectively). Postoperative CSF leak occurred in 9 of 173 patients (5.2%) with intraoperative leak and was not associated with any factors on analysis. CONCLUSIONS: We propose an algorithm whereby grade 1 CSF leaks in sellar and parasellar resections can be successfully reconstructed with a free graft. Vascularized flaps may be reserved for grade 2 or 3 intraoperative CSF leaks, extended approaches, or tumors with suprasellar extension.

Measurement properties of the MacHANd performance assessment: a pilot study.

BACKGROUND: There is a need for a standardized, performance-based hand function assessment with strong psychometric properties to evaluate persons following a traumatic hand injury. PURPOSE: To conduct a preliminary investigation of the reliability and validity of the MacHANd performance assessment (MPA), a new standardized hand function test. METHODS: Forty-one people receiving treatment for hand injuries were evaluated using the MPA, Patient-rated Wrist and Hand Evaluation, and Jebsen-Taylor Hand Function Test. RESULTS: The MPA demonstrated adequate inter-rater reliability and excellent test-retest reliability, and it confirmed three validation hypotheses. IMPLICATIONS: This pilot study suggests that the MPA has good psychometric properties when used with individuals following a hand injury; however more research is needed.

The association of active and passive tobacco smoke exposure with chronic rhinosinusitis symptom severity: A cross-sectional study.

BACKGROUND: Chronic rhinosinusitis (CRS) causes a great deal of morbidity. There are a multitude of causal factors, though their precise contribution to symptom severity has yet to be defined.  We hypothesized that exposure to both primary and secondhand tobacco smoke would correlate with more severe symptoms of CRS. METHODS: This is a prospective cross-sectional study performed at an academic tertiary care medical center from 2010 to 2013. A total of 85 consecutive patients with chronic sinusitis were screened; 70 with medically refractory CRS requiring functional Endoscopic sinus surgery (FESS) were enrolled. Recent tobacco exposure was assessed using serum cotinine levels. Sinonasal mucosa was biopsied to assess ciliary architecture. Demographics, medical history, tobacco and environmental exposures, and computed tomography (CT) imaging were also collected. Two quality of life (QOL) surveys were administered: one disease specific, Sinonasal Outcomes Test-20 (SNOT-20), and one general, Short Form-12 (SF-12). Results were correlated with the aforementioned exposures. RESULTS: The 70 patients had an average age of 46 years, and 42% were male.  Variables that correlated with worse SNOT-20 scores included serum cotinine (r = 0.43, p = 0.002), number of cigarettes smoked daily (r = 0.27, p = 0.03), and number of secondhand cigarettes exposed to per day (r = 0.29, p = 0.04). There were no significant correlations between SNOT-20 scores and Lund-MacKay or axonemal ultrastructural abnormalities (AUA)-ciliary scores. The two five-variable models best predicted disease-specific QOL. CONCLUSIONS: Increased amounts of serum cotinine and primary and secondhand smoke exposure were associated with worse sinonasal QOL. This study establishes an objective relationship between smoke exposure and patient-perceived severity of CRS, emphasizing the importance of tobacco cessation counseling as part of management.

Prion variants and species barriers among Saccharomyces Ure2 proteins.

As hamster scrapie cannot infect mice, due to sequence differences in their PrP proteins, we find "species barriers" to transmission of the [URE3] prion in Saccharomyces cerevisiae among Ure2 proteins of S. cerevisiae, paradoxus, bayanus, cariocanus, and mikatae on the basis of differences among their Ure2p prion domain sequences. The rapid variation of the N-terminal Ure2p prion domains results in protection against the detrimental effects of infection by a prion, just as the PrP residue 129 Met/Val polymorphism may have arisen to protect humans from the effects of cannibalism. Just as spread of bovine spongiform encephalopathy prion variant is less impaired by species barriers than is sheep scrapie, we find that some [URE3] prion variants are infectious to another yeast species while other variants (with the identical amino acid sequence) are not. The species barrier is thus prion variant dependent as in mammals. [URE3] prion variant characteristics are maintained even on passage through the Ure2p of another species. Ure2p of Saccharomyces castelli has an N-terminal Q/N-rich "prion domain" but does not form prions (in S. cerevisiae) and is not infected with [URE3] from Ure2p of other Saccharomyces. This implies that conservation of its prion domain is not for the purpose of forming prions. Indeed the Ure2p prion domain has been shown to be important, though not essential, for the nitrogen catabolism regulatory role of the protein.

Endoscopic Nasopharyngectomy Combined with a Nerve-sparing Transpterygoid Approach.

OBJECTIVES/HYPOTHESIS: Surgical management of nasopharyngeal tumors has evolved in the endoscopic era. Lateral exposure remains difficult especially near the petrous internal carotid artery and bony Eustachian tube (ET). Our study examines the need to sacrifice the vidian and greater palatine nerves in order to successfully perform en bloc endoscopic nasopharyngectomy. METHODS: Four cadaveric specimens (eight sides) were dissected bilaterally using a binarial, extended, endoscopic endonasal approach (EEA). Nasopharyngectomy was completed including an extended transptyergoid approach for resection of the cartilaginous ET at its junction with the bony ET. Dissection was attempted without sacrifice of the vidian or palatine nerves. RESULTS: Successful en bloc nasopharyngectomy combined with a nerve-sparing transpterygoid approach was achieved in all specimens with successful preservation of the palatine and vidian nerves. The approach provided exposure of foramen lacerum, the petrous carotid, foramen spinosum, and foramen ovale as well as all segments of the cartilaginous Eustachian tube, Meckel's cave and the parapharyngeal carotid. There was no inadvertent exposure or injury of the internal carotid artery. CONCLUSION: Endoscopic nasopharyngectomy combined with a nerve-sparing transpterygoid approach allows for en bloc resection of the cartilaginous Eustachian tube and nasopharyngeal contents with broad skull base exposure and preservation of the internal carotid artery, vidian and palatine nerves. LEVEL OF EVIDENCE: VI Laryngoscope, 130:2343-2348, 2020.

ZSCAN4 facilitates chromatin remodeling and promotes the cancer stem cell phenotype.

Cancer stem cells (CSCs) are cells within tumors that maintain the ability to self-renew, drive tumor growth, and contribute to therapeutic resistance and cancer recurrence. In this study, we investigate the role of Zinc finger and SCAN domain containing 4 (ZSCAN4) in human head and neck squamous cell carcinoma (HNSCC). The murine Zscan4 is involved in telomere maintenance and genomic stability of mouse embryonic stem cells. Our data indicate that the human ZSCAN4 is enriched for, marks and is co-expressed with CSC markers in HNSCC. We show that transient ZSCAN4 induction for just 2 days increases CSC frequency both in vitro and in vivo and leads to upregulation of pluripotency and CSC factors. Importantly, we define for the first time the role of ZSCAN4 in altering the epigenetic profile and regulating the chromatin state. Our data show that ZSCAN4 leads to a functional histone 3 hyperacetylation at the promoters of OCT3/4 and NANOG, leading to an upregulation of CSC factors. Consistently, ZSCAN4 depletion leads to downregulation of CSC markers, decreased ability to form tumorspheres and severely affects tumor growth. Our study suggests that ZSCAN4 plays an important role in the maintenance of the CSC phenotype, indicating it is a potential therapeutic target in HNSCC.

Intrabronchial Catheter Resuscitation for Respiratory and Cardiorespiratory Arrest.

INTRODUCTION: We sought to determine whether intrabronchial oxygenation would provide adequate gas exchange during both anesthesia induced apneic and cardiopulmonary arrest and cardiac massage (CPR). METHODS: Ten pigs underwent general anesthesia with mechanical ventilation. Blood gases were measured in each animal at 4 min intervals for up to 28 min. An intrabronchial catheter (4 L/min O2) was inserted through an endotracheal tube after respirator cessation. Group A animals (6) were resuscitated with the catheter but without CPR. Group B animals (4) were rendered apneic and cardioplegic and resuscitated by CPR for 28 min using the intrabronchial device. RESULTS: All group A animals were resuscitated and survived after 24 min of apnea. Mean pO2 decreased from 378 mmHg (95% confidence interval [CI], 288-468) to 292 mmHg (95% CI, 246-339), P = 0.009; pCO2 increased from 52 mmHg (95% CI, 43-61) to 137 mmHg (95% CI, 116-158), P < 0.0001; and pH decreased from 7.32 (7.29-7.36) to 6.98 (6.92-7.03), P < 0.0001. In a control animal bronchial catheter oxygen flow ceased at baseline and pO2 decreased from 268 to 30 mmHg by 20 min. In group B animals mean pO2 decreased from 426 mmHg (95% CI, 273-579) to 130 mmHg (95% CI, 92-168) after 28 min, P < 0.0001; pCO2 increased from 49 mmHg (95% CI, 41-58) to 73 mmHg (95% CI, 61-86), P = 0.03; and pH decreased from 7.34 (7.33-7.35) to 7.07 (6.98-7.16), P < 0.0001. In the control receiving intratracheal oxygen pO2 decreased from 324 to 88 mmHg after 16 minu of CPR. CONCLUSIONS: Intrabronchial oxygenation provides sustained hyperoxemia during complete apnea and cardiac arrest with CPR.

Evaluation of Intranasal Flap Perfusion by Intraoperative Indocyanine Green Fluorescence Angiography.

BACKGROUND: Vascularized intranasal flaps are the primary reconstructive option for endoscopic skull base defects. Flap vascularity may be compromised by injury to the pedicle or prior endonasal surgery. There is currently no validated technique for intraoperative evaluation of intranasal flap viability. OBJECTIVE: To evaluate the efficacy of indocyanine green (ICG) near-infrared angiography in predicting the viability of pedicled intranasal flaps during endoscopic skull base surgery through a pilot study. METHODS: ICG near-infrared fluorescence endoscopy was performed during endoscopic endonasal surgery for skull base tumors. Intraoperative and postoperative data were collected regarding enhancement of the flap body and pedicle. Fluorescence was rated qualitatively. Postoperatively, flap perfusion was evaluated via MRI-contrast enhancement in addition to clinical outcomes (cerebrospinal fluid leak and endoscopic flap appearance). RESULTS: Thirty-eight patients underwent ICG fluorescence angiography. Both the body and pedicle enhanced in 20 patients (53%), while the pedicle only enhanced for 12 patients (32%), the body only for 3 (8%), and neither for 3 (8%). When both the pedicle and body enhanced with ICG, the rate of postoperative MRI contrast enhancement was 100% and the rate of flap necrosis was 0%. The sensitivity and specificity of flap pedicle ICG enhancement for predicting postoperative flap MRI enhancement were 97% and 67%, respectively. Two of 3 patients without enhancement developed flap necrosis. CONCLUSION: ICG fluorescence angiography of intraoperative flap perfusion is feasible and correlates well with outcomes of postoperative MRI flap enhancement and flap necrosis. Additional study is needed to further refine the imaging technique and optimally characterize the clinical utility.

DNA polymorphisms in the pepA and PPE18 genes among clinical strains of Mycobacterium tuberculosis: implications for vaccine efficacy.

Tuberculosis continues to be a leading cause of death worldwide. Development of an effective vaccine against Mycobacterium tuberculosis is necessary to reduce the global burden of this disease. Mtb72F, consisting of the protein products of the pepA and PPE18 genes, is the first subunit tuberculosis vaccine to undergo phase I clinical trials. To obtain insight into the ability of Mtb72F to induce an immune response capable of recognizing different strains of M. tuberculosis, we investigated the genomic diversity of the pepA and PPE18 genes among 225 clinical strains of M. tuberculosis from two different geographical locations, Arkansas and Turkey, representing a broad range of genotypes of M. tuberculosis. A combination of single nucleotide polymorphisms (SNPs) and insertion/deletions resulting in amino acid changes in the PPE18 protein occurred in 47 (20.9%) of the 225 study strains, whereas SNPs resulted in amino acid changes in the PepA protein in 14 (6.2%) of the 225 study strains. Of the 122 Arkansas study strains and the 103 Turkey study strains, 32 (26.2%) and 15 (14.6%), respectively, had at least one genetic change leading to an alteration of the amino acid sequence of the PPE18 protein, and many of the changes occurred in regions previously reported to be potential T-cell epitopes. Thus, immunity induced by Mtb72F may not recognize a proportion of M. tuberculosis clinical strains.

A dominant negative mutant beta 2-microglobulin blocks the extracellular folding of a major histocompatibility complex class I heavy chain.

The major histocompatibility complex class I (MHC1) molecule plays a crucial role in cytotoxic lymphocyte function. beta 2-Microglobulin (beta 2m) has been demonstrated to be both a structural component of the MHC1 complex and a chaperone-like molecule for MHC1 folding. beta 2m binding to an isolated alpha 3 domain of MHC1 heavy chain at micromolar concentrations has been shown to accurately model the biochemistry and thermodynamics of beta 2m-driven MHC1 folding. These results suggested a model in which the chaperone-like role of beta 2m is dependent on initial binding to the alpha 3 domain interface of MHC1 with beta 2m. Such a model predicts that a mutant beta 2m molecule with an intact MHC1 alpha 3 domain interaction but a defective MHC1 alpha 1 alpha 2 domain interaction would block beta2m-driven folding of MHC1. In this study we generated such a beta 2m mutant and demonstrated that it blocks MHC1 folding by normal beta 2m at the expected micromolar concentrations. Our data support an initial interaction of beta 2m with the MHC1 alpha 3 domain in MHC1 folding. In addition, the dominant negative mutant beta 2m can block T-cell functional responses to antigenic peptide and MHC1.