Allergic fungal rhinosinusitis linked to other hyper-IgE syndromes through defective TH17 responses.

BACKGROUND: In a gene expression analysis comparing sinus mucosa samples from allergic fungal rhinosinusitis (AFRS) patients with samples from non-AFRS chronic rhinosinusitis with nasal polyp (CRSwNP) patients, the antimicrobial peptide (AMP) histatin 1 (HTN1) was found to be the most differentially downregulated gene in AFRS. OBJECTIVE: We sought to identify the molecular etiology of the downregulated expression of HTN1. METHODS: We used RT-PCR to compare the expression of AMPs and a fungistasis assay to evaluate the antifungal activity of sinus secretions. Using flow cytometry, we characterized the presence of TH17/TH22 cells and signal transducer and activator of transcription (STAT) signaling from AFRS patients, non-AFRS CRSwNP patients, and healthy controls. RESULTS: We confirmed decreased expression of AMPs in AFRS sinus mucosa with concordant decrease in antifungal activity in sinus secretions. IL-22 and IL-22-producing T cells were deficient within sinus mucosa of AFRS patients. In vitro studies demonstrated a defect in IL-6/STAT3 signaling critical for TH17/TH22 differentiation. Epithelial cells from AFRS patients could express AMPs when stimulated with exogenous IL-22/IL-17 and circulating TH17 cell abundance was normal. CONCLUSIONS: Similar to other hyper-IgE syndromes, but distinct from CRSwNP, AFRS patients express a defect in STAT3 activation limited to IL-6-dependent STAT3 phosphorylation that is critical for TH17/TH22 differentiation. This defect leads to a local deficiency of IL-17/IL-22 cytokines and deficient AMP expression within diseased sinus mucosa of AFRS patients. Our findings support evaluation of therapeutic approaches that enhance airway AMP production in AFRS.

Antiplatelet and anticoagulation therapy and the risk of pituitary apoplexy in pituitary adenoma patients.

PURPOSE: Pituitary apoplexy can be a life threatening and vision compromising event. Antiplatelet and anticoagulation use has been reported as a contributing factor in pituitary apoplexy (PA). Utilizing one of the largest cohorts in the literature, this study aims to determine the risk of PA in patients on antiplatelet/anticoagulation (AP/AC) therapy. METHODS: A single center, retrospective study was conducted on 342 pituitary adenoma patients, of which 77 patients presented with PA (23%). Several potential risk factors for PA were assessed, including: patient demographics, tumor characteristics, pre-operative hormone replacement, neurologic deficits, coagulation studies, platelet count, and AP/AC therapy. RESULTS: Comparing patients with and without apoplexy, there was no significant difference in the proportion of patients taking aspirin (45 no apoplexy vs. 10 apoplexy; p = 0.5), clopidogrel (10 no apoplexy vs. 4 apoplexy; p = 0.5), and anticoagulation (7 no apoplexy vs. 3 apoplexy; p = 0.7). However, male sex (p-value < 0.001) was a predictor for apoplexy while pre-operative hormone treatment was a protective factor from apoplexy (p-value < 0.001). A non-clinical difference in INR was also noted as a predictor for apoplexy (no apoplexy: 1.01 ± 0.09, apoplexy: 1.07 ± 0.15; p < 0.001). CONCLUSIONS: Although pituitary tumors have a high risk for spontaneous hemorrhage, the use of aspirin is not a risk for hemorrhage. Our study did not find an increased risk of apoplexy with clopidogrel or anticoagulation, but further investigation is needed with a larger cohort. Confirming other reports, male sex is associated with an increased risk for PA.

Management of Acute Pain From Non-Low Back, Musculoskeletal Injuries : A Systematic Review and Network Meta-analysis of Randomized Trials.

BACKGROUND: Patients and clinicians can choose from several treatment options to address acute pain from non-low back, musculoskeletal injuries. PURPOSE: To assess the comparative effectiveness of outpatient treatments for acute pain from non-low back, musculoskeletal injuries by performing a network meta-analysis of randomized clinical trials (RCTs). DATA SOURCES: MEDLINE, EMBASE, CINAHL, PEDro (Physiotherapy Evidence Database), and Cochrane Central Register of Controlled Trials to 2 January 2020. STUDY SELECTION: Pairs of reviewers independently identified interventional RCTs that enrolled patients presenting with pain of up to 4 weeks' duration from non-low back, musculoskeletal injuries. DATA EXTRACTION: Pairs of reviewers independently extracted data. Certainty of evidence was evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. DATA SYNTHESIS: The 207 eligible studies included 32 959 participants and evaluated 45 therapies. Ninety-nine trials (48%) enrolled populations with diverse musculoskeletal injuries, 59 (29%) included patients with sprains, 13 (6%) with whiplash, and 11 (5%) with muscle strains; the remaining trials included various injuries ranging from nonsurgical fractures to contusions. Topical nonsteroidal anti-inflammatory agents (NSAIDs) proved to have the greatest net benefit, followed by oral NSAIDs and acetaminophen with or without diclofenac. Effects of these agents on pain were modest (around 1 cm on a 10-cm visual analogue scale, approximating the minimal important difference). Regarding opioids, compared with placebo, acetaminophen plus an opioid improved intermediate pain (1 to 7 days) but not immediate pain (≤2 hours), tramadol was ineffective, and opioids increased the risk for gastrointestinal and neurologic harms (all moderate-certainty evidence). LIMITATIONS: Only English-language studies were included. The number of head-to-head comparisons was limited. CONCLUSION: Topical NSAIDs, followed by oral NSAIDs and acetaminophen with or without diclofenac, showed the most convincing and attractive benefit-harm ratio for patients with acute pain from non-low back, musculoskeletal injuries. No opioid achieved benefit greater than that of NSAIDs, and opioids caused the most harms. PRIMARY FUNDING SOURCE: National Safety Council. (PROSPERO: CRD42018094412).

Safety of laser-generated shockwave treatment for bacterial biofilms in a cutaneous rodent model.

Bacterial biofilms are often found in chronically infected wounds. Biofilms protect bacteria from antibiotics and impair wound healing. Surgical debridement is often needed to remove the biofilm from an infected wound. Laser-generated shockwave (LGS) treatment is a novel tissue-sparing treatment for biofilm disruption. Previous studies have demonstrated that LGS is effective in disrupting biofilms in vitro. In this study, we aim to determine the safety threshold of the LGS technology in an in vivo rodent model. To understand the in vivo effects of LGS on healthy cutaneous tissue, the de-haired dorsal skin of Sprague-Dawley rats were treated with LGS at three different peak pressures (118, 296, 227 MPa). These pressures were generated using a 1064 nm Nd/YAG laser (pulse duration 5 ns and laser fluence of 777.9 mJ) with laser spot size diameters of 2.2, 3.0, and 4.2 mm, respectively. Following treatment, the animals were observed for 72 h, and a small subset was euthanized at 1-h, 24-h, and 72-h post-treatment and assessed for tissue injury or inflammation under histology. Each treatment group consisted of 9 rats (n = 3/time point for 1-h, 24-h, 72-h post-treatment). An additional 4 control (untreated) rats were included in the analysis, for a total of 31 animals. Gross injuries occurred in 21 (77%) animals and consisted of minor erythema, with prevalence positively correlated with peak pressure (p < 0.05). Of injuries under gross observation, 94% resolved within 24 h. Under histological analysis, the injuries and tissue inflammation were found to be localized to the epidermis and superficial dermis. LGS appears to be well tolerated by cutaneous tissue for the laser energy settings shown to be effective against bacterial biofilm in vitro. All injuries incurred, at even the highest peak pressures, were clinically mild and resolved within 1 day. This lends further support to the overall safety of LGS and serves to translate LGS towards in vivo efficacy studies.

The role of CT and endoscopy in the evaluation of patients referred for intranasal Cryoablation.

BACKGROUND: Cryoablation (CA) of the posterior nasal nerves has garnered increasing interest as an office-based procedure for chronic rhinitis (CR). Standardized preoperative evaluation, specifically the role of computed tomography (CT) and nasal endoscopy, has yet to be defined. We report a series of patients who underwent CT and endoscopy as part of CR work-up in patients referred for CA. OBJECTIVE: Highlight the importance of both nasal endoscopy and CT scan in the evaluation of CR given significant overlap of symptoms and common occurrence of related sinonasal conditions. METHODS: Retrospective analysis of all patients referred to a single tertiary rhinology practice for CA was performed. RESULTS: Fifteen patients were sent for CA by medical allergists. Five patients were deemed CA candidates, and 1 patient received only medical CR treatment. Four patients had evidence of incomplete prior sinus surgery and/or continued chronic rhinosinusitis on endoscopic exam. These 4 patients received a combination of medical and surgical management with either complete resolution or improvement in CR symptoms. In 3 patients, CT confirmed chronic rhinosinusitis that was not apparent on endoscopy, and received a combination of medical and surgical management with symptom improvement. In the last two patients, final diagnoses were nasal valve collapse and recurrent acute rhinosinusitis. CONCLUSIONS: Referrals for CA are becoming more common and the optimal preoperative work up remains unclear. In this limited retrospective review, 67% of patients had diagnoses other than CR and thus were not deemed candidates for CA. Both CT and endoscopy are complementary to a detailed history and physical examination and can aid in CA candidate selection.

N95 respirator reuse, decontamination methods, and microbial burden: A randomized controlled trial.

PURPOSE: To evaluate the effectiveness and ease of N95 respirator decontamination methods in a clinic setting and to identify the extent of microbial colonization on respirators associated with reuse. METHODS: In a prospective fashion, N95 respirators (n = 15) were randomized to a decontamination process (time, dry heat, or ultraviolet C light [UVC]) in outpatient clinics. Each respirator was re-used up to 5 separate clinic sessions. Swabs on each respirator for SARS-CoV-2, bacteria, and fungi were obtained before clinic, after clinic and post-treatment. Mask integrity was checked after each treatment (n = 68). Statistical analyses were performed to determine factors for positive samples. RESULTS: All three decontamination processes reduced bacteria counts similarly. On multivariate mixed model analysis, there were an additional 8.1 colonies of bacteria (95% CI 5.7 to 10.5; p < 0.01) on the inside compared to the outside surface of the respirators. Treatment resulted in a decrease of bacterial load by 8.6 colonies (95% CI -11.6 to -5.5; p < 0.01). Although no decontamination treatment affected the respirator filtration efficiency, heat treatments were associated with the breakdown of thermoplastic elastomer straps. Contamination with fungal and SARS-CoV-2 viral particles were minimal to non-existent. CONCLUSIONS: Time, heat and UVC all reduced bacterial load on reused N95 respirators. Fungal contamination was minimal. Heat could permanently damage some elastic straps making the respirators nonfunctional. Given its effectiveness against microbes, lack of damage to re-treated respirators and logistical ease, UVC represents an optimal decontamination method for individual N95 respirators when reuse is necessary.

Holliday junction recognition protein interacts with and specifies the centromeric assembly of CENP-T.

The centromere is an evolutionarily conserved eukaryotic protein machinery essential for precision segregation of the parental genome into two daughter cells during mitosis. Centromere protein A (CENP-A) organizes the functional centromere via a constitutive centromere-associated network composing the CENP-T complex. However, how CENP-T assembles onto the centromere remains elusive. Here we show that CENP-T binds directly to Holliday junction recognition protein (HJURP), an evolutionarily conserved chaperone involved in loading CENP-A. The binding interface of HJURP was mapped to the C terminus of CENP-T. Depletion of HJURP by CRISPR-elicited knockout minimized recruitment of CENP-T to the centromere, indicating the importance of HJURP in CEPN-T loading. Our immunofluorescence analyses indicate that HJURP recruits CENP-T to the centromere in S/G2 phase during the cell division cycle. Significantly, the HJURP binding-deficient mutant CENP-T6L failed to locate to the centromere. Importantly, CENP-T insufficiency resulted in chromosome misalignment, in particular chromosomes 15 and 18. Taken together, these data define a novel molecular mechanism underlying the assembly of CENP-T onto the centromere by a temporally regulated HJURP-CENP-T interaction.

Contributions of Innate Lymphoid Cells in Chronic Rhinosinusitis.

PURPOSE OF REVIEW: To review innate lymphoid cells (ILCs) and their role in chronic rhinosinusitis (CRS). RECENT FINDINGS: The immune system consists of the innate and adaptive response. Until the recognition of ILCs, chronic inflammatory diseases were characterized by cytokines linked only to T helper cells. However, these immune responses are now described more broadly to include contributions from both the innate and adaptive immunity. In CRS, focus had been on ILC2s in CRS with nasal polyps. These studies also highlight the importance of epithelial cell-derived cytokines in coordinating these responses. In addition to indirect crosstalk via cytokines, ILCs and T helper cells can utilize the OX40/OX40 ligand and major histocompatibility complex class II pathways to directly interact and coordinate responses. In addition to T helper cells, ILCs contribute to the inflammatory response associated with CRS. The understanding of these cells along with pathways that activate and perpetuate these cells leads to new potential therapeutic targets for CRS treatment.

In-depth analysis of antibacterial mechanisms of laser generated shockwave treatment.

Background and Objectives Laser generated shockwave (LGS) is a novel modality for minimally invasive disruption of bacterial biofilms. The objectives of this study are to determine the mechanisms behind LGS treatment and non-biofilm effects on bacterial disruption, including (1) comparing bacterial load with and without LGS in its planktonic form and (2) estimating bacterial cell permeability following LGS. Study Design/Materials and Methods For the first study, planktonic S. epidermidis were treated with gentamicin (0, 8, 16, 32, 64 µg/ml) with and without LGS (1064 nm Nd:YAG laser, 110.14 mJ/mm2 , pulse duration 9 ns, spot size 3 mm, n = 8/group), and absorbances at 600 nm compared. For the second study, four samples of planktonic S. epidermidis were treated with LGS (same settings). Propidium iodide (PI) uptake via flow cytometry as a measure of cell permeability was measured at 0, 10, and 20 minutes following LGS. RESULTS: In comparing corresponding gentamicin concentrations within both LGS-treated samples and controls at 0 hours, there were no differences in absorbance (P = 0.923 and P = 0.814, respectively). Flow cytometry found modest PI uptake (10.4 ± 2.5%) immediately following LGS treatment, with time-dependent increase and persistence of the signal at 20 minutes (R2 = 0.449, P = 0.048). CONCLUSION: Taken together, LGS does not appear to have direct bacteriocidal properties, but rather by allowing for biofilm disruption and bacterial cell membrane permeabilization, both of which likely increase topical antibiotic delivery to pathogenic organisms. Insight into the mechanisms of LGS will allow for improved clinical applications and facilitate safe and effective translation of this technology. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

Nonpharmacological Relaxation Technology for Office-Based Rhinologic Procedures.

BACKGROUND: Office-based rhinologic procedures are increasingly performed to control costs and enhance patient convenience. Adequate management of pain and anxiety is essential for the technical performance of these procedures, in addition to ensuring patient comfort. Pharmacologic agents are often used to manage anxiety and pain. Nonpharmacological adjuncts may be useful for achieving these effects without oral opioids and benzodiazepines. METHODS: Charts of patients who underwent office-based rhinologic procedures with the NuCalm system (Solace Lifesciences, Inc., Wilmonton, DE, USA) in combination with local anesthesia were reviewed. NuCalm is a proprietary system that combines cranial electrotherapy stimulation, neuroacoustic software, light-blocking lenses, and topical γ--aminobutyric acid. Patients rated their pain and anxiety before, during, and after the procedure. RESULTS: Twenty-five patients underwent office procedures using the NuCalm system. Preoperative anxiety (2.00) was significantly higher than postoperative anxiety (1.25) according to patient reporting on a 5-point scale (p = 0.005). Preoperative pain (1.83) was not significantly different from intraoperative (2.54) and postoperative pain (2.04, p = 0.054). CONCLUSIONS: A variety of office-based rhinologic procedures are technically feasible and can be performed with adequate patient comfort without the use of oral drugs. Adjuncts to pharmacologic agents may enhance pain control and anxiety management and improve patient tolerance of these procedures.

Laser-generated shockwaves enhance antibacterial activity against biofilms in vitro.

BACKGROUND AND OBJECTIVES: Bacterial biofilm formation within chronic wound beds, which provides an effective barrier against antibiotics, is a known cause of recalcitrant infections and a significant healthcare burden, often requiring repeated surgical debridements. Laser-generated shockwaves (LGS) is a novel, minimally invasive, and nonthermal modality for biofilm mechanical debridement which utilizes compressive stress waves, generated by photonic absorption in thin titanium films to mechanically disrupt the biofilm. Prior studies have demonstrated LGS monotherapy to be selectively efficacious for biofilm disruption and safe for host tissues. In this study, we sought to determine if LGS can enhance the antimicrobial activity and biofilm disruption capability of topical antibiotic therapy. STUDY DESIGN/MATERIALS AND METHODS: Staphylococcus epidermidis biofilms grown in vitro on glass were treated with topical gentamicin (31, 62, and 124 µg/ml) with and without LGS (n = 3-11/treatment group). Mechanical shockwaves were generated with a 1,064 nm Nd:YAG laser (laser fluence 110.14 mJ/mm2 , pulse duration 5 ns, spot size 3 mm). Following a 24-hour incubation period, bacterial viability was assessed by determining the number of colony-forming units (CFU) via the Miles and Misra method. Residual biofilm bioburden was analyzed using the crystal violet biofilm assay. RESULTS: With gentamicin monotherapy, CFU density (CFU/mm2 ) at 31, 62, and 124 µg/ml were (282 ± 84) × 104 , (185 ± 34) × 104 , and (113 ± 9) × 104 , respectively. With LGS and gentamicin therapy, CFU density decreased to (170 ± 44) × 104 , (89 ± 24) × 104 , and (43 ± 3) × 104 , respectively (P = 0.1704, 0.0302, and 0.0004 when compared with gentamicin alone). Biofilm burden as measured by the assay in the gentamicin 31, 62, and 124 µg/ml groups was reduced by 80%, 95%, and 98% when LGS was added (P = 0.0102, >0.0001, and 0.0001 for all groups when compared with gentamicin alone). Furthermore, samples treated with LGS saw an increase in susceptibility to gentamicin, in terms of reduced biofilm bioburden and CFU densities. CONCLUSION: LGS enhances the efficacy of topical antibiotics in an in vitro model. This has significant implications for clinical applications in the management of chronic soft tissue infections and recalcitrant chronic rhinosinusitis. Lasers Surg. Med. 49:539-547, 2017. © 2017 Wiley Periodicals, Inc.

Sinocutaneous Fistula Formation After Forehead Recontouring Surgery for Transgender Patients.

Forehead recontouring is a common part of facial feminization surgery. The procedure, which alters the shape and structure of the frontal bone, is regarded as safe and well tolerated by patients. The occurrence of delayed complications, however, is much less understood. The authors describe a patient involving the development of a sinocutaneous fistula as a delayed complication of forehead recontouring surgery. The clinical presentation and management of this patient are discussed. As facial feminization surgery expands as a cosmetic option for patients who desire more feminine facial features, practitioners should recognize the potential risk of sinonasal complications associated with forehead recontouring surgery.

Cell Polarity Kinase MST4 Cooperates with cAMP-dependent Kinase to Orchestrate Histamine-stimulated Acid Secretion in Gastric Parietal Cells.

The digestive function of the stomach depends on acidification of the gastric lumen. Acid secretion into the lumen is triggered by activation of the PKA cascade, which ultimately results in the insertion of gastric H,K-ATPases into the apical plasma membranes of parietal cells. A coupling protein is ezrin, whose phosphorylation at Ser-66 by PKA is required for parietal cell activation. However, little is known regarding the molecular mechanism(s) by which this signaling pathway operates in gastric acid secretion. Here we show that PKA cooperates with MST4 to orchestrate histamine-elicited acid secretion by phosphorylating ezrin at Ser-66 and Thr-567. Histamine stimulation activates PKA, which phosphorylates MST4 at Thr-178 and then promotes MST4 kinase activity. Interestingly, activated MST4 then phosphorylates ezrin prephosphorylated by PKA. Importantly, MST4 is important for acid secretion in parietal cells because either suppression of MST4 or overexpression of non-phosphorylatable MST4 prevents the apical membrane reorganization and proton pump translocation elicited by histamine stimulation. In addition, overexpressing MST4 phosphorylation-deficient ezrin results in an inhibition of gastric acid secretion. Taken together, these results define a novel molecular mechanism linking the PKA-MST4-ezrin signaling cascade to polarized epithelial secretion in gastric parietal cells.

Benefit of Preoperative Oral Steroids during Sinus Surgery when Utilizing Concentrated Topical Epinephrine.

BACKGROUND/AIMS: Oral steroids have been advocated in the preoperative setting as a means of reducing intraoperative blood loss and surgical time during sinus surgery. The purpose of this study was to analyze the impact of preoperative oral steroid administration on intraoperative bleeding and surgical duration when coupled with concentrated topical epinephrine. METHODS: The medical records of 302 patients who underwent bilateral 'full house' sinus surgery were reviewed. Concentrated topical epinephrine and inhalational anesthesia was used in all patients. Surgical duration and estimated blood loss were compared between the preoperative steroid-exposed and steroid-naive groups. χ2 and Student's t tests were used for statistical analysis. RESULTS: One hundred and forty-two patients were exposed to steroid, while the remaining 160 were steroid naive. No significant differences were found with respect to surgical time between the steroid-exposed (96.91 ± 25.97 min) and steroid-naive patients (91.24 ± 32.29 min, p = 0.100). The steroid-exposed group demonstrated a marginally increased blood loss (66.03 ± 55.81 ml) as compared to steroid-naive patients (55.00 ± 38.71 ml, p = 0.048). CONCLUSION: When coupled with intraoperative concentrated topical epinephrine use, preoperative oral steroid administration provides no clinically significant benefit with respect to reduced intraoperative bleeding or surgical duration.

Spatial control of proton pump H,K-ATPase docking at the apical membrane by phosphorylation-coupled ezrin-syntaxin 3 interaction.

The digestive function of the stomach depends on acidification of the gastric lumen. Acid secretion into the lumen is triggered by activation of a cAMP-dependent protein kinase (PKA) cascade, which ultimately results in the insertion of gastric H,K-ATPases into the apical plasma membranes of parietal cells. A coupling protein is ezrin whose phosphorylation at Ser-66 by PKA is required for parietal cell activation. However, little is known regarding the molecular mechanism(s) by which ezrin operates in gastric acid secretion. Here we show that phosphorylation of Ser-66 induces a conformational change of ezrin that enables its association with syntaxin 3 (Stx3) and provides a spatial cue for H,K-ATPase trafficking. This conformation-dependent association is specific for Stx3, and the binding interface is mapped to the N-terminal region. Biochemical analyses show that inhibition of ezrin phosphorylation at Ser-66 prevents ezrin-Stx3 association and insertion of H,K-ATPase into the apical plasma membrane of parietal cells. Using atomic force microscopic analyses, our study revealed that phosphorylation of Ser-66 induces unfolding of ezrin molecule to allow Stx3 binding to its N terminus. Given the essential role of Stx3 in polarized secretion, our study presents the first evidence in which phosphorylation-induced conformational rearrangement of the ezrin molecule provides a spatial cue for polarized membrane trafficking in epithelial cells.

Cone-beam computed tomographic comparison of surgically assisted rapid palatal expansion and multipiece Le Fort I osteotomy.

PURPOSE: To examine and compare the skeletal and dental effects of surgically assisted rapid palatal expansion (SARPE) and multipiece Le Fort osteotomy using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: This was a prospective cohort study. Patients underwent SARPE or multipiece Le Fort I osteotomy to address maxillary transverse deficiency. CBCT scans were taken preoperatively, immediately postoperatively or after retention, and at least 6 months postoperatively. Four landmark measurements and ratios of dental-to-skeletal change were used to follow skeletal and dental widths in the posterior and anterior maxillary regions. Wilcoxon signed-rank test and Wilcoxon 2-sample rank-sum test were used to compare the landmark measurements and the ratio of dental-to-skeletal change for the 2 surgeries. A P value less than .05 was statistically significant. RESULTS: Thirteen patients (mean, 28.3 yr old; 7 women) were enrolled: 9 were treated by multipiece Le Fort I osteotomy and 4 were treated by SARPE. The ratios of dental-to-skeletal expansion in the posterior maxilla for the Le Fort procedure and SARPE were 0.70 ± 0.41 and 25.20 ± 15.8, respectively, and the dental-to-skeletal relapses were 1.17 ± 0.80 and -3.63 ± 3.70, respectively. The ratios of dental-to-skeletal expansion in the anterior maxilla for the Le Fort procedure and SARPE were 0.58 ± 0.38 and 31.80 ± 59.4, respectively, and the dental-to-skeletal relapses were 2.25 ± 3.41 and 4.86 ± 8.10, respectively. CONCLUSION: There was greater correlation between dental and skeletal changes in the multipiece Le Fort procedure, indicating bodily separation of the segments, whereas the SARPE showed noteworthy dental and skeletal tipping. Dental relapse was greater than skeletal relapse for these 2 procedures.

C-Jun N-terminal kinase (JNK) isoforms play differing roles in otitis media.

BACKGROUND: Innate immunity and tissue proliferation play important roles in otitis media (OM), the most common disease of childhood. CJUN terminal kinase (JNK) is potentially involved in both processes. RESULTS: Genes involved in both innate immune and growth factor activation of JNK are upregulated during OM, while expression of both positive and negative JNK regulatory genes is altered. When compared to wildtypes (WTs), C57BL/6 mice deficient in JNK1 exhibit enhanced mucosal thickening, with delayed recovery, enhanced neutrophil recruitment early in OM, and delayed bacterial clearance. In contrast, JNK2-/- mice exhibit delayed mucosal hyperplasia that eventually exceeds that of WTs and is slow to recover, delayed recruitment of neutrophils, and failure of bacterial clearance. CONCLUSIONS: The results suggest that JNK1 and JNK2 play primarily opposing roles in mucosal hyperplasia and neutrophil recruitment early in OM. However, both isoforms are required for the normal resolution of middle ear infection.

Semi-Automated Virtual Endoscopy of the Frontal Recess.

INTRODUCTION: Virtual endoscopy (VE) is the computer-based reprocessing of diagnostic imaging to simulate endoscopy of an anatomic region of interest. VE of the Frontal Sinus Outflow Tract (FSOT) may assist surgical planning and education. METHOD: VE was performed on 16 normal sinus computed tomography (CT) scans for a total of 32 sides using the "path-to-target" tool on the TruDi surgical navigation system (ver. 2.3; Acclarent, Irving, CA, USA). To aid orientation during VE, planning points were placed on the middle turbinate, ethmoidal bulla, and skull base. The VE representation of anatomy and FSOT accuracy was manually confirmed by reviewing the corresponding orthogonal CT images and comparing them to the computed pathway. RESULTS: Of the 32 sides, the software successfully calculated the FSOT in 22 sides (69%). Of those 22 sides, the calculated FSOT, depicted in the VE sequences accurately represented the FSOT. Among sides with an accurately calculated FSOT, the VE sequences depicted a "fly-through" from a starting point in the middle meatus around various frontal recess cells to the end point in the frontal sinus. CONCLUSION: This pilot study demonstrates that software-generated VE of the FSOT is indeed feasible but requires confirmation by the surgeon for accuracy. Instances in which the software did not achieve its objective may drive further refinements of the protocol. VE of the FSOT should be explored as a tool for preoperative planning and surgical education.

Temperature-controlled radiofrequency treatment of the nasal valve in nasal airway obstruction patients with septal deviation.

KEY POINTS: Nasal valve treatment with TCRF results in NAO symptom improvement in the presence of septal deviation. Severe septal deviation does not impact the beneficial effect of TCRF nasal valve treatment. Symptoms improve with TCRF nasal valve treatment even if septal deviations involve the nasal valve.

Two-year outcomes of temperature-controlled radiofrequency device treatment of the nasal valve for patients with nasal airway obstruction.

Background: The objective of this study was to evaluate long-term symptom improvements in patients with nasal airway obstruction (NAO) secondary to nasal valve collapse (NVC) following minimally invasive temperature-controlled radiofrequency (TCRF) treatment. Methods: A prospective, single-arm, multicenter study in patients >18 years with NAO due to NVC. Inclusion criteria were response to nasal valve dilation (e.g., modified Cottle maneuver) and baseline Nasal Obstruction Symptom Evaluation (NOSE) Scale score ≥60. Patients were treated in the nasal valve region with a TCRF device and followed through 2 years. A responder was ≥20% reduction NOSE Scale score or ≥1 reduction in severity class. Results: A total of 122 patients were treated and 91 reached 2 years. The mean baseline NOSE Scale score was 80.3 (95% CI, 78.1-82.6). The adjusted mean change in score at 2 years was -45.8 (95% CI, -53.5 to -38.1), p < 0.001; a 57.0% improvement. The 2-year responder rate was 90.1% (95% CI, 82.3%-94.7%). Significant and sustained symptom improvement was achieved in subpopulations based on sex, age, body mass index, baseline NAO severity, nasal surgery history, NVC mechanism, septal deviation, and other anatomic contributors of NAO. No serious adverse events with a relationship to the study device and/or procedure were reported. Conclusions: Minimally invasive TCRF device treatment of the internal nasal valve for NAO is well tolerated and leads to significant and sustained improvement in NAO symptom severity through 2 years, including in patients with both static and dynamic NVC, septal deviation, turbinate enlargement, or prior nasal surgery. Level of Evidence: 2b.