Prediction of acute myeloid leukaemia risk in healthy individuals

The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure(1). The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion(2,3). However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)(4-8). Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention

Comparative Treatment Outcomes for Patients With Idiopathic Subglottic Stenosis.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadImportance: Surgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research. Objective: To prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a rare airway disease. Design, setting, and participants: In this international, prospective, 3-year multicenter cohort study, 810 patients with untreated, newly diagnosed, or previously treated iSGS were enrolled after undergoing a surgical procedure (endoscopic dilation [ED], endoscopic resection with adjuvant medical therapy [ERMT], or cricotracheal resection [CTR]). Patients were recruited from clinician practices in the North American Airway Collaborative and an online iSGS community on Facebook. Main outcomes and measures: The primary end point was days from initial surgical procedure to recurrent surgical procedure. Secondary end points included quality of life using the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), Voice Handicap Index-10 (VHI-10), Eating Assessment Test-10 (EAT-10), the 12-Item Short-Form Version 2 (SF-12v2), and postoperative complications. Results: Of 810 patients in this cohort, 798 (98.5%) were female and 787 (97.2%) were white, with a median age of 50 years (interquartile range, 43-58 years). Index surgical procedures were ED (n = 603; 74.4%), ERMT (n = 121; 14.9%), and CTR (n = 86; 10.6%). Overall, 185 patients (22.8%) had a recurrent surgical procedure during the 3-year study, but recurrence differed by modality (CTR, 1 patient [1.2%]; ERMT, 15 [12.4%]; and ED, 169 [28.0%]). Weighted, propensity score-matched, Cox proportional hazards regression models showed ED was inferior to ERMT (hazard ratio [HR], 3.16; 95% CI, 1.8-5.5). Among successfully treated patients without recurrence, those treated with CTR had the best CCQ (0.75 points) and SF-12v2 (54 points) scores and worst VHI-10 score (13 points) 360 days after enrollment as well as the greatest perioperative risk. Conclusions and relevance: In this cohort study of 810 patients with iSGS, endoscopic dilation, the most popular surgical approach for iSGS, was associated with a higher recurrence rate compared with other procedures. Cricotracheal resection offered the most durable results but showed the greatest perioperative risk and the worst long-term voice outcomes. Endoscopic resection with medical therapy was associated with better disease control compared with ED and had minimal association with vocal function. These results may be used to inform individual patient treatment decision-making.Patient-Centered Outcomes Research Institute - PCOR

Developing a Tracheal Rendezvous Procedure for Complete High Subglottic Stenosis.

Complete subglottic stenosis is often managed with surgical resection. However, involvement of the high subglottis can limit candidacy for open resection, and there are few treatment options for these patients. We refined an endoscopic approach that evolved into a tracheal rendezvous technique with T-tube placement as an alternative to open surgical resection. Here, we present our series, technique, and outcomes. A retrospective review was performed to identify patients who underwent endoscopic management of complete high subglottic stenosis at the University of California San Diego. The surgical technique was initially a two-step staged procedure and was subsequently revised to a single-stage procedure with stenosis ablation, dilation, and insertion of a T-tube, which was completed in one day. Patients were seen at regular follow-up intervals for reassessment. Five patients were identified with complete stenosis not amenable to surgical resection. The average age of the cohort was 44.8 years. The etiology of stenosis in all patients was related to prolonged intubation and tracheostomy, and the average length of stenosis was 19.6 mm. Stenosis resection was accomplished via laser ablation and balloon dilation, and the average T-tube length was 50.3 mm. All patients were discharged on postoperative day one. Two patients developed airway crusting within the T-tube and required emergency department visits. Decannulation was attempted in three patients, although failed in two. Tracheal rendezvous is a safe and effective procedure for patients with grade IV subglottic stenosis. This provides a feasible endoscopic alternative to patients who are not candidates for open surgical resection, ye are motivated to have phonatory capacity

An update on current treatment strategies for laryngopharyngeal reflux symptoms.

Laryngopharyngeal reflux (LPR) is a syndrome caused by reflux of gastric contents into the pharynx or larynx, which leads to symptoms of throat clearing, hoarseness, pain, globus sensation, cough, excess mucus production in the throat, and dysphonia. LPR is a challenging condition, as there is currently no gold standard for diagnosis or treatment, and thus this presents a burden to the healthcare system. Strategies for treatment of LPR are numerous. Medical therapies include proton pump inhibitors, which are first line, H2 receptor antagonists, alginates, and baclofen. Other noninvasive treatment options include lifestyle therapy and the external upper esophageal sphincter compression device. Endoscopic and surgical options include antireflux surgery, magnetic sphincter augmentation, and transoral incisionless fundoplication. Functional laryngeal disorders and laryngeal hypersensitivity can present as LPR symptoms with or without gastroesophageal reflux disease. Though there are minimal studies in this area, neuromodulators and behavioral interventions are potential treatment options. Given the complexity of these patients and numerous available treatment options, we propose a treatment algorithm to help clinicians diagnose and triage patients into an appropriate therapy

Patient‐worn endoscopy mask to protect against viral transmission

ObjectivesTo design and evaluate patient-worn personal protective equipment (PPE) that allows providers to perform endoscopy while protecting against droplet and airborne disease transmission.Study designSingle subject study.MethodsMask efficacy was evaluated using a cough simulator that sprays dye visible under ultra-violet light. User-testing was performed on an airway trainer mannequin where each subject performed the endoscopy with and without the mask in random orders. Their time to completion and number of attempts before successful completion were recorded, and each subject was asked to fill out a NASA Task Load Index (TLX) form with respect to their experience.ResultsThe mask has a filtration efficiency of 97.31% and eliminated any expelled particles with the cough simulator. Without the mask, a simulated cough is visualized as it progresses away from the cough origin. Subjects who performed trans-nasal endoscopy spent 27.8 ± 8.0 s to visualize the vocal cords for the no mask condition and 28.7 ± 13.6 s for the mask condition (mean ± SD, p > .05). There was no statistically significant difference found in the mental demand, physical demand, temporal demand, performance, effort, and frustration of endoscopy under the no mask and mask conditions (all p > .05).ConclusionThe designed PPE provides an effective barrier for viral droplet and airborne transmission while allowing the ability to perform endoscopy with ease.Level of evidence3 Laryngoscope, 2021

Preclinical experience with a novel single-port platform for transoral surgery.

BackgroundWe investigated a novel minimally invasive surgical platform for use in the oropharynx, hypopharynx, and larynx for single-port transoral surgery used in concert with standard transoral laryngeal and pharyngeal instrumentation.MethodsThe preclinical investigational device by Fortimedix Surgical B.V. (Netherlands) features two channels for manually controlled flexible articulating surgical instruments. A third central channel accepts both rigid and flexible endoscopes. The system is coupled to a standard laryngoscope for transoral access. In three cadaver models, we evaluated the surgical capabilities using wristed grasping instruments, microlaryngeal scissors, monopolar cautery, and a laser fiber sheath. Procedures were performed within the oropharynx, supraglottis, glottis, subglottis, and hypopharynx.ResultsWithin the oropharynx, we found adequate strength, range of motion, and dexterity to perform lateral oropharyngectomy and tongue base resection. Within the larynx, visualization was achieved with a variety of instruments including a flexible, 0° and 30° rigid endoscope. The glottis, supraglottis, pyriform sinuses, post-cricoid space, and esophageal inlet were readily accessible. Visualization and manipulation of grasping, laser, and monopolar cautery instruments were also possible within the subglottis. Instrument reach and accuracy facilitated completion of a delicate micro-flap on the true vocal fold. Other procedures included vocal fold resection, cricopharyngeal myotomy, and resection of subglottic mucosa.ConclusionsFrom this initial proof of concept experience with this novel platform, we found a wide range of procedures within the oropharynx, larynx, and hypopharynx to be feasible. Further work is needed to evaluate its applicability to the clinical setting. The ability of this platform to be used with conventional instrumentation may provide an opportunity for complex transoral surgery to be performed in a facile manner at greatly reduced cost