Citations

Objectives: An unexpectedly low word recognition (WR) score may be taken as evidence of increased risk for retrocochlear tumor. We sought to develop evidence for or against using a standardized WR (sWR) score in detecting retrocochlear tumors. The sWR is a z score expressing the difference between an observed WR score and a Speech Intelligibility Index–based predicted WR score. We retrospectively compared the sensitivity and specificity of pure-tone asymmetry-based logistic regression models that incorporated either the sWR or the raw WR scores in detecting tumor cases. Two pure-tone asymmetry calculations were used: the 4-frequency pure-tone asymmetry (AAO) calculation of the American Academy of Otolaryngology–Head and Neck Surgery and a 6-frequency pure-tone asymmetry (6-FPTA) calculation previously optimized to detect retrocochlear tumors. We hypothesized that a regression model incorporating the 6-FPTA calculation and the sWR would more accurately detect retrocochlear tumors. Design: Retrospective data from all patients seen in the audiology clinic at Mayo Clinic in Florida in 2016 were reviewed. Cases with retrocochlear tumors were compared with a reference group with noise- or age-related hearing loss or idiopathic sensorineural hearing loss. Two pure-tone–based logistic regression models were created (6-FPTA and AAO). Into these base models, WR variables (WR, sWR, WR asymmetry [WRΔ], and sWR asymmetry [sWRΔ]) were added. Tumor detection performance for each regression model was compared twice: first, using all qualifying cases (61 tumor cases; 2332 reference group cases), and second, using a data set filtered to exclude hearing asymmetries greater than would be expected from noise-related or age-related hearing loss (25 tumor cases; 2208 reference group cases). The area under the curve and the DeLong test for significant receiver operating curve differences were used as outcome measures. Results: The 6-FPTA model significantly outperformed the AAO model—with or without the addition of WR or WRΔ variables. Including sWR into the AAO base regression model significantly improved disease detection performance. Including sWR into the 6-FPTA model significantly improved disease detection performance when large hearing asymmetries were excluded. In the data set that included large pure-tone asymmetries, area under the curve values for the 6-FPTA + sWR and AAO + sWR models were not significantly better than the base 6-FPTA model. Conclusions: The results favor the superiority of the sWR computational method in identifying reduced WR scores in retrocochlear cases. The utility would be greatest where undetected tumor cases are embedded in a population heavily representing age- or noise-related hearing loss. The results also demonstrate the superiority of the 6-FPTA model in identifying tumor cases. The 2 computational methods may be combined (ie, the 6-FPTA + sWR model) into an automated tool for detecting retrocochlear disease in audiology and community otolaryngology clinics. The 4-frequency AAO-based regression model was the weakest detection method considered. Including raw WR scores into the model did not improve performance, whereas including sWR into the model did improve tumor detection performance. This further supports the contribution of the sWR computational method for recognizing low WR scores in retrocochlear disease cases.

ImportanceHead and neck cancer–associated lymphedema (HNCaL) affects up to 90% of survivors of head and neck cancer and is a substantial contributor to disability following head and neck cancer treatment. Despite the prevalence and morbidity associated with HNCaL, rehabilitation interventions are not well studied.ObjectiveTo identify and appraise the current evidence for rehabilitation interventions in HNCaL.Evidence ReviewFive electronic databases were searched systematically from inception to January 3, 2023, for studies on HNCaL rehabilitation interventions. Study screening, data extraction, quality rating, and risk of bias assessment were performed by 2 independent reviewers.FindingsOf 1642 citations identified, 23 studies (1.4%; n = 2147 patients) were eligible for inclusion. Six studies (26.1%) were randomized clinical trials (RCTs) and 17 (73.9%) were observational studies. Five of the 6 RCTs were published during 2020 to 2022. Most studies had fewer than 50 participants (5 of 6 RCTs; 13 of 17 observational studies). Studies were categorized by intervention type, including standard lymphedema therapy (11 studies [47.8%]) and adjunct therapy (12 studies [52.2%]). Lymphedema therapy interventions included standard complete decongestive therapy (CDT) (2 RCTs, 5 observational studies), modified CDT (3 observational studies), therapy setting (1 RCT, 2 observational studies), adherence (2 observational studies), early manual lymphatic drainage (1 RCT), and inclusion of focused exercise (1 RCT). Adjunct therapy interventions included advanced pneumatic compression devices (APCDs) (1 RCT, 5 observational studies), kinesio taping (1 RCT), photobiomodulation (1 observational study), acupuncture/moxibustion (1 observational study), and sodium selenite (1 RCT, 2 observational studies). Serious adverse events were either not found (9 [39.1%]) or not reported (14 [60.9%]). Low-quality evidence suggested the benefit of standard lymphedema therapy, particularly in the outpatient setting and with at least partial adherence. High-quality evidence was found for adjunct therapy with kinesio taping. Low-quality evidence also suggested that APCDs may be beneficial.Conclusions and RelevanceThe results of this systematic review suggest that rehabilitation interventions for HNCaL, including standard lymphedema therapy with kinesio taping and APCDs, appear to be safe and beneficial. However, more prospective, controlled, and adequately powered studies are needed to clarify the ideal type, timing, duration, and intensity of lymphedema therapy components before treatment guidelines can be established.

Importance Lensectomy with primary intraocular lens (IOL) implantation is often used in the management of nontraumatic pediatric cataract, but long-term data evaluating the association of age and IOL location with the incidence of complications are limited. Objective To describe the incidence of complications and additional eye surgeries through 5 years following pediatric lensectomy with primary IOL implantation and association with age at surgery and IOL location. Design, Setting, and Participants This prospective cohort study used Pediatric Eye Disease Investigator Group cataract registry data from 61 institution- and community-based practices over 3 years (June 2012 to July 2015). Participants were children younger than 13 years without baseline glaucoma who had primary IOL implantation (345 bilateral and 264 unilateral) for nontraumatic cataract. Data analysis was performed between September 2021 and January 2023. Exposures Lensectomy with primary IOL implantation. Main Outcome and Measures Five-year cumulative incidence of complications by age at surgery (<2 years, 2 to <4 years, 4 to <7 years, and 7 to <13 years) and by IOL location (sulcus vs capsular bag) were estimated using Cox proportional hazards models. Results The cohort included 609 eyes from 491 children (mean [SD] age, 5.6 [3.3] years; 261 [53%] male and 230 [47%] female). Following cataract extraction with primary IOL implantation, a frequent complication was surgery for visual axis opacification (VAO) (cumulative incidence, 32%; 95% CI, 27%-36%). Cumulative incidence was lower with anterior vitrectomy at the time of IOL placement (12%; 95% CI, 8%-16%) vs without (58%; 95% CI, 50%-65%), and the risk of undergoing surgery for VAO was associated with not performing anterior vitrectomy (hazard ratio [HR], 6.19; 95% CI, 3.70-10.34; P < .001). After adjusting for anterior vitrectomy at lens surgery, there were no differences in incidence of surgery for VAO by age at surgery (<2 years, HR, 1.35 [95% CI, 0.63-2.87], 2 to <4 years, HR, 0.86 [95% CI, 0.44-1.68], 4 to <7 years, HR, 1.06 [95% CI, 0.72-1.56]; P = .74) or by capsular bag vs sulcus IOL fixation (HR, 1.22; 95% CI, 0.36-4.17; P = .75). Cumulative incidence of glaucoma plus glaucoma suspect by 5 years was 7% (95% CI, 4%-9%), which did not differ by age after controlling for IOL location and laterality. Conclusions and Relevance In this cohort study, a frequent complication following pediatric lensectomy with primary IOL was surgery for VAO, which was associated with primary anterior vitrectomy not being performed but was not associated with age at surgery or IOL location. The risk of glaucoma development across all ages at surgery suggests a need for long-term monitoring.

Abstract Objective Prospective data on determinants of muscle strength impairment and quality of life in patients with various subtypes and severity of endogenous hypercortisolism are lacking. Design Single-center cross-sectional study, 2019 to 2022. Methods Patients with Cushing syndrome (CS) and mild autonomous cortisol secretion (MACS) were assessed with clinical and biochemical severity scores, muscle function (nondominant hand grip strength and sit-to-stand test), and quality of life (Short Form-36 [SF36] and CushingQoL). Referent subjects were recruited from the local population undergoing abdominal imaging for reasons other than suspected adrenal disorder. Results Of 164 patients, 81 (49%) had MACS, 14 (9%) had adrenal CS, 60 (37%) had pituitary CS, and 9 (5%) had ectopic CS. Median age was 53 years (interquartile range: 42-63 years), and 126 (77%) were women. The SF36 mental component score was similarly low in patients with MACS vs CS, but physical component score was lower in CS when compared to MACS (mean of 34.0 vs 40.5, P = .001). Compared to MACS, patients with CS had lower scores on the standardized CushingQoL (mean of 47.1 vs 34.2, P < .001). Compared to referent subjects, patients with MACS demonstrated reduced muscle strength, similar to patients with CS (mean sit to stand Z-score of −0.47 vs −0.54, P = .822). Clinical severity (r = −0.22, P = .004) but not biochemical severity was associated with sit-to-stand test performance. Conclusions Both patients with overt CS and MACS demonstrate reduced muscle strength and low quality of life. The clinical severity score utilized is associated with both physical and psychosocial components of CushingQoL and with the physical component of SF36.

Background: There is a paucity of research on the management of partial-thickness tears of the distal bicep tendon, and even less is known about the long-term outcomes of this condition. Purpose: To identify patients with partial-thickness distal bicep tendon tears and determine (1) patient characteristics and treatment strategies, (2) long-term outcomes, and (3) any identifiable risk factors for progression to surgery or complete tear. Study Design: Case-control study; Level of evidence, 3. Methods: A fellowship-trained musculoskeletal radiologist identified patients diagnosed with a partial-thickness distal bicep tendon tear on magnetic resonance imaging between 1996 and 2016. Medical records were reviewed to confirm the diagnosis and record study details. Multivariate logistic regression models were created using baseline characteristics, injury details, and physical examination findings to predict operative intervention. Results: In total, 111 patients met inclusion criteria (54 treated operatively, 57 treated nonoperatively), with 53% of tears in the nondominant arm and a mean follow-up time after surgery of 9.7 ± 6.5 years. Only 5% of patients progressed to full-thickness tears during the study period, at a mean of 35 months after the initial diagnosis. Patients who were nonoperatively treated were less likely to miss time from work (12% vs 61%; P < .001) and missed fewer days (30 vs 97 days; P < .016) than those treated surgically. Multivariate regression analyses demonstrated increased risk of progression to surgery with older age at initial consult (unit odds ratio [OR], 1.1), tenderness to palpation (OR, 7.5), and supination weakness (OR, 24.8). Supination weakness at initial consult was a statistically significant predictor for surgical intervention (OR, 24.8; P = .001). Conclusion: Clinical outcomes were favorable for patients regardless of treatment strategy. Approximately 50% of patients were treated surgically; patients with supination weakness were 24 times more likely to undergo surgery than those without. Progression to full-thickness tear was a relatively uncommon reason for surgical intervention, with only 5% of patients progressing to full-thickness tears during the study period and the majority occurring within 3 months of initial diagnosis.

Abstract The geroscience hypothesis posits that by targeting key hallmarks of aging we may simultaneously prevent or delay several age-related diseases and thereby increase healthspan, or life span spent free of significant disease and disability. Studies are underway to examine several possible pharmacological interventions for this purpose. As part of a National Institute on Aging workshop on the development of function-promoting therapies, scientific content experts provided literature reviews and state-of-the-field assessments for the studies of senolytics, nicotinamide adenine dinucleotide (NAD+) boosters, and metformin. Cellular senescence increases with age, and preclinical studies demonstrate that the use of senolytic drugs improves healthspan in rodents. Human studies using senolytics are in progress. NAD+ and its phosphorylated form, NADP+, play vital roles in metabolism and cellular signaling. Increasing NAD+ by supplementation with precursors including nicotinamide riboside and nicotinamide mononucleotide appears to extend healthspan in model organisms, but human studies are limited and results are mixed. Metformin is a biguanide widely used for glucose lowering, which is believed to have pleiotropic effects targeting several hallmarks of aging. Preclinical studies suggest it improves life span and healthspan, and observational studies suggest benefits for the prevention of several age-related diseases. Clinical trials are underway to examine metformin for healthspan and frailty prevention. Preclinical and emerging clinical studies suggest there is potential to improve healthspan through the use of pharmacologic agents reviewed. However, much further research is needed to demonstrate benefits and general safety for wider use, the appropriate target populations, and longer-term outcomes.

Introduction: Peripheral microvascular endothelial dysfunction (PMED) is a marker and precursor of atherosclerosis and is associated with an increased risk of cardiovascular events. The present study aims to identify the best cut-off value of PMED, assessed by the reactive hyperemia index, in predicting major adverse cardiovascular events (MACE). Additionally, we investigate whether integrating PMED to CHA2DS2-Vasc score improves the predicting accuracy of cardiovascular disease. Methods: this is a retrospective study of patients who underwent reactive hyperemia peripheral arterial tonometry (PAT). The optimal cut-off value of reactive hyperemia index associated with MACE was calculated using the area under the receiver-operating curve and the maximum Youden index. Traditional cardiovascular risk factors such as age, sex, congestive heart failure, hypertension, diabetes, stroke, vascular disease were determined to calculate the CHA2DS2-VASc score. MACE was defined as myocardial infarction, heart failure hospitalization, and cerebrovascular events. Results: 1,690 patients were enrolled (average age 51.1±13.9, 64.1% female). The optimal cut-off value of the reactive hyperemia index was 2.0 in the overall population and females and 2.17 in males. The risk of MACE during 10 (Interquartile range: 4,16) years of follow-up was 15.3%. Multivariable logistic regression revealed that PMED as an independent predictor of MACE (PMED: OR, 3.6, 95% CI, 2.6-4.9, p<0.001) (Table1). Furthermore, integrating PMED to CHA2DS2-VASc significantly improved the predictive accuracy (area under the curve, 0.747 vs. 0.708, p<0.001). Conclusion: PMED is a strong predictor of cardiovascular events. Non-invasive assessment of peripheral endothelial function may be useful in early detection and improving the stratification of high-risk patients for cardiovascular events.

Introduction: Recent studies have indicated high rates of future major adverse cardiovascular events in patients with Takotsubo cardiomyopathy (TTC). This study sought to evaluate the prognostic value of our institutional artificial intelligence-augmented electrocardiography (AI-ECG) algorithms in patients with TTC. Methods: This study enrolled consecutive patients in the prospective and observational Mayo Clinic Takotsubo syndrome registry. TTC was diagnosed according to the Mayo Clinic diagnostic. Our clinic’s previously developed and validated AI-ECG algorithms were used for detection of ECG-Age, probability of low ejection fraction, and probability of atrial fibrillation.Multivariable models were constructed to evaluate the association of AI-ECG and other clinical characteristics with major adverse cardiac events (MACE), defined as cardiac death, recurrence of TTC, nonfatal myocardial infarction, hospitalization for congestive heart failure, and stroke. Results: In the final analysis, 305 patients were studied over a median follow-up of 4.8 years. Patients with MACE were more likely to be older, have history of hypertension and chronic heart failure (CHF), worse renal function as well as having high-risk AI-ECG findings compared to those without. In the multivariate Cox proportional hazard analysis, the presence of 3 or 4 high-risk findings detected by AI-ECG, remained a significant predictor of MACE in the patients with TTC after adjusted by conventional risk factors (hazard ratio (HR) 2.17, 95% CI [1.33, 3.53], P=0.002; HR 2.44, 95% CI [1.38, 4.29], P=0.002, respectively). Conclusions: The combined use of developed AI-ECG algorithms derived from a single 12-lead ECG might identify ECG correlates of underlying non-transient myocardial dysfunction and detect subtle underlying patterns associated with worse outcomes in patients with TTC. This approach might be beneficial for stratifying high-risk patients with TTC.

Introduction: In the randomized VALOR-HCM study of symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM), mavacamten reduced the need for septal reduction therapy at 16 weeks. The current sub-study sought to assess the impact of mavacamten on systolic anterior motion (SAM) of the mitral valve and associated mitral regurgitation (MR). Methods: Patients on maximally-tolerated medical therapy referred for septal reduction therapy were randomized 1:1 to mavacamten or placebo. Echocardiographic assessment was performed by an independent, blinded core laboratory. SAM was assessed as none, mild (anterior leaflet >/= 1 cm from the septum), moderate (anterior leaflets <1cm from the septum), and severe (anterior leaflet in contact with septum). MR was assessed according to ASE guidelines. Results: Among 112 enrolled patients, 23.2% (n=27) had at least moderate (2+) MR. Most (92.9%, n=104) had at least moderate resting SAM, of whom 55.4% (n = 62) had severe SAM. At 16 weeks, 53.7% of patients treated with mavacamten had at least one level improvement in resting SAM compared to 21.6% of patients treated with placebo ( p = 0.001), and 35.2% had at least a two level improvement in SAM compared with 11.8% of placebo patients ( p = 0.007)(Figure 1A). Similarly, patients treated with mavacamten had an improvement of -36.0 + 28.8 mmHg in resting left ventricular outflow tract gradient at week 16 compared to -1.5 + 26.5 mmHg with placebo (<0.001). At week 16, 48.1% of patients treated with mavacamten had at least a one grade improvement in MR, and 23.1% had at least a two grade improvement compared to 12.2% and 6.1% of patients treated with placebo ( p <0.001 and 0.025, respectively)(Figure 1B). Conclusions: In highly symptomatic patients with oHCM, treatment with mavacamten reduced resting SAM with an improvement in associated MR.