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Introduction: Olfactory dysfunction (OD) is common among people with cystic fibrosis (PwCF). The Questionnaire of Olfactory Disorders (QOD) is a validated instrument that evaluates olfactory‐specific quality‐of‐life. The QOD minimal clinically important difference (MCID) and factors associated with olfactory improvement after elexacaftor/tezacaftor/ivacaftor have not been determined for PwCF. Methods: Prospective observational data were pooled from three studies that enrolled adult PwCF with chronic rhinosinusitis (CRS). QOD scores and disease characteristics were assessed. To evaluate internal consistency and calculate the QOD MCID, Cronbach's alpha and four distribution‐based methods were employed. For participants who enrolled prior to elexacaftor/tezacaftor/ivacaftor, QOD scores were obtained at baseline and after elexacaftor/tezacaftor/ivacaftor initiation. Multivariable regression was used to identify factors associated with QOD improvement. Results: Of 129 PwCF included, 65 had QOD scores before and 3–6 months after starting elexacaftor/tezacaftor/ivacaftor. Mean baseline QOD score was 6.5 ± 7.9. Mean Cronbach's alpha was ≥0.85. The MCID estimates were as follows: Cohen's effect size = 1.6, standard error of measurement = 2.5, ½ baseline standard deviation = 4.0, and minimal detectable change = 6.9. Mean MCID was 3.7. Of those with pre/post elexacaftor/tezacaftor/ivacaftor QOD scores, the mean change in QOD was −1.3 ± 5.4. After elexacaftor/tezacaftor/ivacaftor, QOD improvement surpassed the MCID in 22% of participants (14/65). Worse baseline QOD scores and nasal polyps were associated with improved QOD scores after elexacaftor/tezacaftor/ivacaftor (both p < 0.04). Conclusion: The QOD MCID in PwCF was estimated to be 3.7. Elexacaftor/tezacaftor/ivacaftor led to qualitative but not clinically meaningful improvements in QOD score for most PwCF; PwCF with worse baseline QOD scores and nasal polyps improved in a clinically significant manner. [ABSTRACT FROM AUTHOR]

This research note discusses the role of individual sinus inflammation in chronic rhinosinusitis (CRS) and olfaction after highly effective modulator therapy. The study found that individual sinus opacification (ISO) can be measured using a convolutional neural network approach. ISO decreased over a two-year period after initiating modulator therapy. However, ISO did not correlate with quality of life or olfaction in adults with cystic fibrosis. The study highlights the importance of understanding disease in specific sinuses for targeted treatments. Another article discusses the relationship between sinus opacification (SO) and patient outcomes in individuals with cystic fibrosis (CF) who have undergone highly effective modulator therapy. The study found that greater sphenoid SO was correlated with worse rhinologic and extranasal rhinologic scores after 24 months of therapy. However, the clinical significance of this correlation is unknown. The study also found that there was no consistent correlation between SO and other outcome measures such as health utility value and smell identification test scores. The findings suggest that further research is needed to understand the impact of individual sinus inflammation on chronic rhinosinusitis and olfaction in individuals with CF. [Extracted from the article]

Key Points Patients with giant adenomas are more likely to have tumor extension into the paranasal sinuses. Compared to macroadenomas, giant adenomas are not associated with worse preoperative SNOT‐22 scores. [ABSTRACT FROM AUTHOR]

After a nasoseptal flap (NSF) is performed for skull base reconstruction, patients often have significant crusting along the exposed anterior cartilaginous septum and delayed remucosalization. Placing a free mucosal graft (FMG) on the NSF donor site cartilage can help improve postoperative sinonasal symptoms. In this video, we demonstrate the use of a septal stapler to secure a septal FMG to the NSF donor site following endoscopic endonasal resection of a pituitary adenoma.By Jessa E. Miller; Jakob L. Fischer and Marilene B. WangReported by Author; Author; Author [Extracted from the article]

This article, titled "Endoscopic Skull Base Surgery among Pediatric Patients: A 14-Year Review," explores the use and outcomes of endoscopic skull base surgery in pediatric patients. The study analyzed data from a tertiary care center from 2009 to 2023 and compared pediatric patients (under 18 years old) to adult patients. The most common indication for surgery in both groups was a pituitary adenoma. The study found that the rate of intraoperative cerebrospinal fluid (CSF) leaks was high in both pediatric and adult patients, but postoperative CSF leaks were rare. The length of hospital stay after surgery was similar for both groups. [Extracted from the article]

Cystic fibrosis (CF) is an autosomal recessive disorder that results in deranged ion transport and affects multiple organ systems, including the upper and lower respiratory tracts. People with CF (PwCF) often develop chronic rhinosinusitis (CRS) with or without nasal polyposis. CRS can significantly decrease quality of life for PwCF and can lead to more frequent pulmonary exacerbations. The management of CRS in PwCF is different from that in individuals without CF. Novel therapies have emerged in the last several years that have drastically altered the progression of both pulmonary and sinonasal disease in people with CF. It is critical for providers who manage CF-related CRS to understand the unique characteristics and challenges that coincide with this disease process. This review article aims to provide readers with an overview of the pathophysiology of CF and to summarize best practice strategies for the management of CF-related CRS. [ABSTRACT FROM AUTHOR]

Treating AECRS based on culture results can improve antibiotic stewardship; however, this can also put patients at risk for worsening symptoms due to treatment delays. Keywords: bacteriology; chronic rhinosinusitis; medical therapy of chronic rhinosinusitis; sinusitis EN bacteriology chronic rhinosinusitis medical therapy of chronic rhinosinusitis sinusitis 950 953 4 04/25/23 20230501 NES 230501 INTRODUCTION The 2021 International Consensus Statement on Allergy and Rhinology defines acute exacerbation of chronic rhinosinusitis (AECRS) as a sudden worsening of CRS symptoms with a return to baseline, often after treatment with corticosteroids and/or antibiotics.[1] Bacterial infections are thought to have a significant role in the development of AECRS.[[1]] Studies have cited I Staphylococcus aureus i , I Pseudomonas aeruginosa i , I Streptococcus pneumoniae i , I Haemophilus influenzae i , and anaerobic species as common pathogens in AECRS.[[3], [5]] Patients seen in clinic for AECRS can either be started on empiric antibiotics, or treatment can be delayed for culture-directed therapy (CDT). Empiric antibiotics and CDT are both reasonable treatment strategies for AECRS, and the approach taken can be chosen based on clinical judgment, severity of symptoms, and patient preference. [Extracted from the article]

Introduction. Osteochondromas are relatively common benign bone tumors often located at the metaphyseal ends of long bones; however, they are rare in the head and neck region. The objective of this study is to present a case of an osteochondroma arising from the thyroid cartilage causing insidious dysphonia and to present a literature review. Methods. The medical record of a patient treated for osteochondroma of the thyroid cartilage was reviewed. A literature search on osteochondromas was conducted using PubMed and Google Scholar. The epidemiology, presentation, diagnosis, treatment, and outcomes of osteochondromas were reviewed. Results. A 50-year-old female presented with nine months of dysphonia and aphonic voice breaks. Laryngovideostroboscopy revealed a left false vocal fold fullness, glottal gap, and vibratory phase asymmetry. A CT neck demonstrated a well-circumscribed 5 × 8 × 9 mm mass arising from the left thyroid cartilage lamina with a thin calcified rim and a heterogeneous decreased attenuation center. The tumor was excised surgically. Histopathologic analysis demonstrated hyaline cartilage overlying lamellar bone with fatty bone marrow, consistent with osteochondroma. English language literature review revealed no cases of osteochondroma of the thyroid cartilage. The presenting features of osteochondroma may depend on the size and location of the lesion. It is critical to differentiate between benign and malignant bone tumors, and physicians must rely on their clinical examination, radiographic findings, and histopathologic analysis to make the correct diagnosis. Conclusions. Osteochondromas of the laryngeal framework are extremely rare, and to our knowledge, there have been no reports in the literature of this tumor arising from the thyroid cartilage. Dysphonia may be the presenting symptom in a patient with a thyroid cartilage mass causing restricted mobility of the true vocal folds. [ABSTRACT FROM AUTHOR]

• HEMT improves multiple measures of sinusitis through 2 years of therapy in adults. • Sinus CT scans analyzed via machine learning methods and sinus symptoms improved. • Health utility increased and productivity loss decreased with 24 months of HEMT. • HEMT initiated in adulthood did not fully resolve chronic rhinosinusitis in adults. [ABSTRACT FROM AUTHOR]

This article discusses the use of different techniques for skull base reconstruction in endoscopic pituitary surgery and their association with cerebrospinal fluid (CSF) leaks. The Hadad-Bassagasteguy nasoseptal flap (NSF) has been effective in reducing CSF leaks, but there is limited data on the appearance of different reconstruction techniques on MRI and their relationship to CSF leak rates. The study reviewed patient data and imaging to compare the vascularization patterns of free mucosal grafts (FMG) and NSF, and found that patients with NSF reconstruction had higher rates of intraoperative CSF leaks. However, there was no association between patterns of flap enhancement on MRI and CSF leaks. FMGs showed a predictable change in enhancement pattern over 3 months, while NSFs without flap enhancement at 1 week still demonstrated neovascularization without increased risk of complications. [Extracted from the article]

Background: After initial surgical treatment of differentiated thyroid cancer (DTC) residual lymph node metastases are often found at the time of radioactive iodine (131I) therapy. Recurrence of DTC is due to persistent disease not removed at initial surgery which also did not respond to 131I treatment. This study aimed at determining locations of, and reasons for, residual nodal metastases detected by 131I scans with single-photon emission computed tomography (SPECT/CT) obtained prior to radioiodine therapy following surgical treatment of DTC. Methods: This is a retrospective study of 352 patients with intermediate and high-risk DTC treated with 131I therapy at the University of Michigan from 2007 to 2014. All patients underwent total thyroidectomy with or without lymph node dissection followed by radioiodine therapy. Pre-ablation diagnostic 131I scans with SPECT/CT were used postoperatively to localize nodal metastases, which were then compared with the cervical lymph node basins dissected at the time of surgery to determine the reason for residual nodal metastases: incomplete nodal dissection versus preoperative unrecognized nodal metastases. Results: Of the 352 patients in the study, 146 (41.5%) had residual nodal metastases detected on 131I scans with SPECT/CT following initial surgery but prior to 131I therapy. Among the 146 patients with residual disease, there were a total of 218 distinct nodal metastases. Relative to the primary tumor, 71.6% (n = 156) of metastases were ipsilateral, 22.0% (n = 48) were contralateral, and 6.4% (n = 14) were non-sided in the central neck (level VI/VII). Cervical lymph node levels VI, III, and II had the greatest frequencies of residual metastases (33.9%, 22.9%, 18.8%, respectively). Residual metastases occurred because of incomplete nodal dissection (49.3%), lack of preoperative identification (37.7%), or a combination of both (13%). Conclusion: Residual nodal metastasis following initial surgical treatment for regionally advanced differentiated thyroid cancer is rather common on highly sensitive 131I scans with SPECT/CT and is due to both unrecognized nodal involvement preoperatively and incomplete removal of metastatic lymph nodes during compartment-orientated nodal dissection. The surgical management of high-risk DTC should include preoperative imaging to evaluate for nodal metastases in the central and lateral neck and compartment-orientated nodal dissection of involved compartments. Attention should be given to complete dissection in levels VI, III, and II, particularly when dissecting compartments ipsilateral to the primary tumor. [ABSTRACT FROM AUTHOR]

Internal maxillary artery (IMA) pseudoaneurysms are rare, and typically occur following trauma or orthognathic surgery. Pseudoaneurysms are life-threatening conditions, and expeditious workup and treatment is critical. Endoscopic treatment of an IMA pseudoaneurysm is a feasible option and should be considered when IR embolization is not available. The objective of this study is to review the literature on IMA pseudoaneurysms and present the first reported case of an IMA pseudoaneurysm successfully treated endoscopically. [ABSTRACT FROM AUTHOR]

Keywords: computed tomography; cystic fibrosis; modulator; quality of life; sinusitis EN computed tomography cystic fibrosis modulator quality of life sinusitis 1435 1438 4 11/15/22 20221101 NES 221101 INTRODUCTION The highly effective cystic fibrosis transmembrane conductance regulator modulator therapy (HEMT) with elexacaftor/tezacaftor/ivacaftor (ETI) improves pulmonary disease and chronic rhinosinusitis (CRS) in people with cystic fibrosis (PwCF).1,2 Adequately managing the sinonasal manifestations of CF is critical for maximizing quality of life (QOL) and optimizing pulmonary status.3 CRS severity can be quantified by patient-reported, radiographic, and endoscopic methods, with patient-reported and objective measures thought to represent different constructs of disease. Computed tomography, cystic fibrosis, quality of life, sinusitis, modulator Objective and patient-based measures of chronic rhinosinusitis in people with cystic fibrosis treated with highly effective modulator therapy. [Extracted from the article]

Microaggressions are one form of gender bias contributing to gender disparities and mistreatment, but their prevalence during virtual residency interviews has not been explored. To explore applicants' recall of experiencing gender microaggressions during virtual residency interviews and whether these experiences affected programs' rank position on applicants' rank lists. Fourth-year medical students at a single institution who participated in the 2021 Match were surveyed after submitting their rank lists. Students were surveyed categorically on (1) their recall of the frequency they experienced 17 gender microaggressions during interviews, and (2) how these affected reported ranking of programs on their rank lists. Sixty-one percent (103 of 170) of eligible students responded to the survey. Seventy-two percent (36 of 50) of women experienced at least one microaggression compared to 30% (9 of 30) of men. The largest difference was in the experience of environmental microaggressions, which are demeaning cues communicated individually or institutionally, delivered visually, or that refer to climate (P<.001). Women experienced more microaggressions than men in nonsurgical (P=.003) and surgical specialties excluding obstetrics and gynecology (P=.009). When microaggressions were experienced at 1 to 2 programs, 36% of applicants (26 of 73) reported significantly lowering program ranking, compared to 5% (1 of 19) when microaggressions occurred at more than 5 programs (P=.038). Women applicants experience more microaggressions than men do during nonsurgical and male-dominated surgical specialty residency interviews. Respondents who recalled experiencing microaggressions at fewer programs were more likely to report significantly lowering the rank of those programs compared to those who experienced them at more programs. [ABSTRACT FROM AUTHOR]

• CT and PET imaging features are associated with oropharynx cancer treatment efficacy. • Extra nodal extension strongly predicts early failure in low-risk patients. • Pre-treatment imaging should guide cancer therapy de-escalation regimens. To assess associations between imaging biomarkers from standard of care pre-treatment CT and FDG-PET scans and locoregional (LR) and distant metastatic (DM) recurrences in patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) treated with definitive chemoradiotherapy (CRT). An institutional database from a single NCI-designated cancer center identified 266 patients with p16+ OPSCC treated with definitive CRT in our department from 2005 to 2016 with evaluable pre-treatment FDG-PET scans. Quantitative SUV metrics and qualitative imaging metrics were determined from FDG-PET and CT scans, while clinical characteristics were abstracted from the medical record. Associations between clinical/imaging features and time to LR (TTLRF) or DM (TTDMF) failure and overall survival (OS) were assessed using univariable Cox regression and penalized stepwise regression for multivariable analyses (MVA). There were 27 LR and 32 DM recurrences as incident failures. Imaging biomarkers were significantly associated with TTLRF, TTDMF and OS. FDG-PET metrics outperformed CT and clinical metrics for TTLRF, with metabolic tumor volume being the only significant feature selected on MVA: C-index = 0.68 (p = 0.01). Radiographic extranodal extension (rENE), positive retropharyngeal nodes (RPN+), and clinical stage were significant on MVA for TTDMF: C-index = 0.84 (p < 0.001). rENE, group stage, and RPN+ were significant on MVA for OS: C-index = 0.77 (p < 0.001). In the largest study to date of uniformly treated patients with CRT to evaluate both pretreatment CT and FDG-PET, radiographic biomarkers were significantly associated with TTLRF, TTDMF and OS among patients with p16+ OPSCC treated with CRT. CT metrics performed best to predict TTDMF, while FDG-PET metrics showed improved prediction for LRRFS. These metrics may help identify candidates for treatment intensification or de-escalation of therapy. Pre-treatment imaging features from standard-of-care PET/CT imaging show promise for predicting long-term outcomes following HPV-associated oropharynx cancer (HPV-OPC) therapy. This study comprehensively characterizes qualitative and quantitative pre-treatment imaging metrics associated with time to pattern-specific failure in a cohort of 266 patients treated uniformly with definitive chemoradiation. Multivariate analysis (MVA) for time to locoregional failure (TTLRF), time to distant metastatic failure (TTDMF), and overall survival (OS) was performed. FDG-PET metrics outperformed CT and clinical metrics for TTLRF. CT radiographic extranodal extension, positive retropharyngeal nodes, and stage strongly predicted TTDMF (combined C-index = 0.84, log rank p < 0.001). Number of smoking pack-years complemented clinical and imaging features only in patients without radiographic extranodal extension or positive retropharyngeal nodes. Time to pattern-specific failure is important for guiding treatment de-escalation strategies, which intend to reduce treatment-related toxicity in patients with relatively long expected survival times. This study suggests that PET/CT features should play a crucial role in future de-escalation trials and management of HPV-OPC patients. [ABSTRACT FROM AUTHOR]

In the last few decades, the increased survival of premature infants and critically ill children have led to the increased frequency and complexity of pediatric airway procedures. Minimizing readmission rates following these procedures is important to maximize health outcomes and cost effectiveness. This study examines the incidence, reasons, and risk factors for hospital readmissions following pediatric airway surgeries in a large, nationally representative sample. Pediatric airway surgeries performed across 22 states in 2014 were identified using data from the Nationwide Readmissions Database (NRD). Airway surgeries were identified and categorized using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes into the following categories: tracheostomy, repair of larynx, repair of trachea, laryngeal excision, tracheal excision, bronchoscopy, laryngoscopy, laryngotracheal diagnostic procedures, other operations on larynx, and other operations on trachea. Univariate and multivariate analyses were used to identify factors significantly correlated with readmissions. 10,289 pediatric airway procedures over 7120 visits were identified. 954 readmissions were identified for an overall readmission rate of 13.4%. 613 of these readmissions were related to the initial procedure, yielding a relevant readmission rate of 8.6%. On univariate analysis, factors that varied significantly with readmission rates included number of diagnoses on record (OR 1.06), number of chronic conditions (OR 1.18), number of procedures (OR 1.07), public insurance status (OR 1.39), bottom quartile median household income in patient zip code (OR 1.29), teaching hospital status (OR 1.60), and chronic perinatal respiratory disease (OR 1.45). On multivariate analysis, significant predictors included number of diagnoses (OR 1.02), number of chronic conditions (OR 1.13), and bottom quartile median household income in patient zip code (OR 1.20). The most common categories for readmission were respiratory distress (36%), infection (24%), and pneumonia (14%). The top overall individual reasons for readmission were stenosis of larynx (7.3%) and pneumonia (5.9%). Pediatric airway surgeries have relatively high rates of readmission. Strategies to reduce readmissions should involve addressing health disparities and employing a multidisciplinary approach to improve care for medically complex patients. [ABSTRACT FROM AUTHOR]

Type VI secretion systems (T6SS) function to deliver lethal payloads into target cells. Many studies have shown that protection against a single, lethal T6SS effector protein requires a cognate antidote immunity protein, both of which are often encoded together in a two-gene operon. The T6SS and an effector-immunity pair is sufficient for both killing and immunity. HereIn this paper we describe a T6SS effector operon that differs from conventional effector-immunity pairs in that eight genes are necessary for lethal effector function, yet can be countered by a single immunity protein. In this study, we investigated the role that the PefE T6SS immunity protein plays in recognition between two strains harboring nearly identical effector operons. Interestingly, despite containing seven of eight identical effector proteins, the less conserved immunity proteins only provided protection against their native effectors, suggesting that specificity and recognition could be dependent on variation within an immunity protein and one effector gene product. The variable effector gene product, PefD, is encoded upstream from pefE, and displays toxic activity that can be countered by PefE independent of T6SS-activity. Interestingly, while the entire pef operon was necessary to exert toxic activity via the T6SS in P. mirabilis, production of PefD and PefE alone was unable to exert this effector activity. Chimeric PefE proteins constructed from two P. mirabilis strains were used to localize immunity function to three amino acids. A promiscuous immunity protein was created using site-directed mutagenesis to change these residues from one variant to another. These findings support the notion that subtle differences between conserved effectors are sufficient for T6SS-mediated kin discrimination and that PefD requires additional factors to function as a T6SS-dependent effector. [ABSTRACT FROM AUTHOR]

The Type VI Secretion System (T6SS) functions in bacteria as a contractile nanomachine that punctures and delivers lethal effectors to a target cell. Virtually nothing is known about the lifestyle or physiology that dictates when bacteria normally produce their T6SS, which prevents a clear understanding of how bacteria benefit from its action in their natural habitat. Proteus mirabilis undergoes a characteristic developmental process to coordinate a multicellular swarming behavior and will discriminate itself from another Proteus isolate during swarming, resulting in a visible boundary termed a Dienes line. Using transposon mutagenesis, we discovered that this recognition phenomenon requires the lethal action of the T6SS. All mutants identified in the genetic screen had insertions within a single 33.5-kb region that encodes a T6SS and cognate Hcp-VrgG-linked effectors. The identified T6SS and primary effector operons were characterized by killing assays, by construction of additional mutants, by complementation, and by examining the activity of the type VI secretion system in real-time using live-cell microscopy on opposing swarms. We show that lethal T6SS-dependent activity occurs when a dominant strain infiltrates deeply beyond the boundary of the two swarms. Using this multicellular model, we found that social recognition in bacteria, underlying killing, and immunity to killing all require cell-cell contact, can be assigned to specific genes, and are dependent on the T6SS. The ability to survive a lethal T6SS attack equates to “recognition”. In contrast to the current model of T6SS being an offensive or defensive weapon our findings support a preemptive mechanism by which an entire population indiscriminately uses the T6SS for contact-dependent delivery of effectors during its cooperative mode of growth. [ABSTRACT FROM AUTHOR]