JAMA otolaryngology-- head & neck surgery最新文献

Importance: Genome-wide association studies have identified germline variants associated with the development of papillary thyroid carcinoma (PTC) that can be used to construct a polygenic score (PGS). It is important to determine whether patients with higher germline genetic risk, as summarized using PGS, present with more aggressive disease and/or develop worse clinical outcomes.

Objective: To assess whether germline risk defined by PGS is associated with clinicopathologic features and survival outcomes for patients with PTC.

Design, setting, and participants: This retrospective cohort study included patients with newly diagnosed PTC who presented to The University of Texas MD Anderson Cancer Center for treatment between 1999 and 2014, with a median follow-up of 12 years. Data were analyzed from December 2023 to April 2024.

Exposure: Germline risk, as defined by PGS.

Main outcomes and measures: Genomic DNA was extracted from buffy coat cells isolated from peripheral blood samples, and genotyping for germline polymorphisms was performed. Germline risk for PTC was estimated with a previously validated PGS calculated from 10 single-nucleotide variations identified through genome-wide association studies. Stage; PTC-specific survival, defined as the time from PTC diagnosis to death caused by PTC; and overall survival, defined as the time from PTC diagnosis to death by any cause, were analyzed.

Results: A total of 366 patients were included in the study (261 women [71.3%]; mean [SD] age at diagnosis, 44.3 [13.8] years). There was a statistically significant association between higher PGS and multifocality (β [SE], 0.40 [0.23]; P = .045) and cervical lymph node involvement (N stage) (β [SE], 0.62 [0.35]; P = .009) at diagnosis. PGS was associated with PTC-specific survival (hazard ratio, 2.66; 95% CI, 1.03-6.85; P = .04), but this association was not independent of age and overall stage. There was not a statistically significant association between PGS and overall survival.

Conclusions and relevance: Findings of this cohort study suggest that patients with a higher germline risk of PTC, as estimated by PGS, present with more aggressive clinicopathologic features. These results contribute to the current understanding of inherited risk in PTC and how germline variants could potentially contribute to disease presentation and clinical outcomes.

Importance: Retrograde cricopharyngeus dysfunction (R-CPD) is an emerging disorder associated with disabling symptoms. The origin of R-CPD remains unknown.

Objective: To investigate the development of symptoms, diagnosis approach, and therapeutic outcomes of R-CPD in patients treated with in-office botulinum toxin injection (BTI) into the cricopharyngeus.

Design, setting, and participants: This was a case series including patients with R-CPD who were consecutively and prospectively recruited from April 2022 to May 2024 in an academic hospital. Semistructured interviews were conducted to collect and analyze data on each patient's clinical history, potential causes or factors associated with R-CPD development, diagnostic approaches, and symptom presentation.

Intervention: Clinic-based (in-office) BTI into the cricopharyngeus.

Outcomes and measures: Associations with laryngopharyngeal reflux disease, patients' Reflux Symptom Score-12 (RSS-12), and BTI effectiveness, revisions, and complications were evaluated.

Results: The case series comprised 106 patients with R-CPD treated with BTI (52 females [49.1%] and 54 males [51.9%]). Their mean (SD) age at symptom onset was 13.6 (7.7) years, and at diagnosis, 30.4 (6.4) years. Sixty-eight patients (64.2%) had potential congenital R-CPD, according to the parents' testimonies. A family history was reported in 18 of 62 cases (29.0%). In 105 cases (99.1%), patients made the diagnosis themselves despite medical consultations (n = 162), empirical treatments (n = 113), and additional examinations (n = 92). The cumulative success rate of BTI was 90.6% (96 of 106 patients). In 26 cases (24.5%), additional injections were administered to address the symptoms. Family history of R-CPD was a negative predictor of single-BTI success. Dysphagia was the primary adverse effect occurring after 89 of 126 BTIs (70.6%) and lasted a mean (SD) of 16.3 (12.0) days. In 10 cases, operating-room BTI was administered after primary in-office BTI.

Conclusions and relevance: R-CPD is an emerging and poorly known disorder associated with high rates of ineffective consultations, additional examinations, and self-diagnosis by patients. In-office BTI was associated with a high rate of partial or total symptom relief and long-term effectiveness.

Importance: Airway stenosis is a rare but debilitating disorder that significantly degrades the quality of life in affected patients. Treatments are primarily surgical, and disease management lacks established medical therapies. The North American Airway Collaborative held its third symposium at The Johns Hopkins Hospital in Baltimore, Maryland, on April 15, 2024, focused on strategies to advance the care of these patients. The proceedings summarize the discussion of trial design in airway stenosis and the resulting North American Airway Collaborative consensus regarding clinical end points for rigorous study of novel therapies.

Observations: The lectures and panels centered on the translation of a growing body of preclinical data into therapeutic targets. Additionally, detailed discussion explored design of clinical trials to evaluate safety and efficacy of novel therapeutics. The need for a consensus regarding clinically meaningful end points in airway stenosis was identified to facilitate the comparison of outcomes across institutions and future multi-institutional trials.

Conclusions and relevance: The group achieved consensus regarding change in peak expiratory flow as the primary clinical end point in airway stenosis. Additional clinical measures, such as disease recurrence (identified as time to recurrent intervention), anatomical characterization of subglottic scar via axial computed tomography imaging, and patient-reported outcome measures (Clinical COPD Questionnaire [CCQ], Voice Handicap Index-10 [VHI-10], Eating Assessment Tool-10 [EAT-10], and 12-Item Short-Form Health Survey, version 2 [SF-12]) were identified as essential secondary outcomes.