Citations

Objective To introduce and discuss implementation strategy for the Complete Cochlear Implant Care (CCIC) model, a highly-coordinated cochlear implant (CI) care delivery model requiring a single on-site visit for preoperative workup, surgery, and postoperative programming. Study Design Prospective, nonrandomized, two-arm clinical trial. Setting Tertiary referral CI center. Patients Adults who meet audiologic criteria for cochlear implantation. Interventions Cochlear implantation, coordinated care delivery, including remote programming. Main outcome measures Care delivery model feasibility and process implementation. Results Patients determined to be likely CI candidates based on routine audiometry are eligible for enrollment. The CCIC model uses telemedicine and electronic educational materials to prepare patients for same-day on-site consultation with CI surgery, same or next-day activation, and postoperative remote programming for 12 months. Implementation challenges include overcoming inertia related to the implementation of a new clinical workflow, whereas scalability of the CCIC model is limited by current hardware requirements for remote programming technology. A dedicated CCIC process coordinator is critical for overcoming obstacles in implementation and process improvement through feedback and iterative changes. Team and patient-facing materials are included and should be tailored to fit each unique CI program looking to implement CCIC. Conclusion The CCIC model has the potential to dramatically streamline hearing healthcare delivery. Implementation requires an adaptive approach, as obstacles may vary according to institutional infrastructure and policies.

NOTCH1 belongs to the NOTCH family of proteins that regulate cell fate and inflammatory responses. Somatic and germline NOTCH1 variants have been implicated in cancer, Adams‐Oliver syndrome, and cardiovascular defects. We describe 7 unrelated patients grouped by the presence of leukoencephalopathy with calcifications and heterozygous de novo gain‐of‐function variants in NOTCH1. Immunologic profiling showed upregulated CSF IP‐10, a cytokine secreted downstream of NOTCH1 signaling. Autopsy revealed extensive leukoencephalopathy and microangiopathy with vascular calcifications. This evidence implicates that heterozygous gain‐of‐function variants in NOTCH1 lead to a chronic central nervous system (CNS) inflammatory response resulting in a calcifying microangiopathy with leukoencephalopathy. ANN NEUROL 2022;92:895–901

AbstractBackgroundHigh titers of cold agglutinins jeopardize the quality of an apheresis product meant for autologous or allogeneic transplant. Management of transplant patients with cold agglutinin disease (CAD) is often experience‐based and under reported, yet decisions must be made quickly to optimize product management and patient outcomes. There remains a lack of data quantifying cell recovery and viability when using various warming methodologies.Study Design and MethodsTo expand the published experimental data on this subject, our human cellular therapy lab compared cellular recoveries and viabilities after manipulation of cryopreserved apheresis products through various warming methodologies: (1) extended warming in a water bath, (2) warming via blood warmer and infusion pump, and (3) warming in a water bath followed by infusion pump as a control to assess potential shear stress effects.ResultsThe presented studies demonstrate that all methods of product warming produce the same rates of recovery of total and viable cells across vital cell types prior to patient administration. Statistically, use of an extended water bath protocol provided a marginal benefit in recovery of total nucleated cells, though this effect is diminished when products are held for an extended period to simulate a delay in administration.DiscussionThese results can inform decisions to improve patient care and minimize product manipulation and loss. Centers are encouraged to use this information to guide proactive measures to establish a standard operating procedure to manage CAD cases.

Background: 5-aminolevulinic acid (5-ALA; GleolanTM, NX Development Corps., Lexington, USA) is approved for fluorescence-guided resections of suspected malignant gliomas. Experience has demonstrated that meningiomas also show fluorescence, which may be a useful surgical adjunct. We present an innovative design for a multi-center, prospective study to determine the clinical safety and potential benefit of fluorescence-guided resection of meningiomas with utmost bias reduction. Methods: All patients with suspected meningioma (all grades) receive GleolanTM 20 mg/kg 2–4 h prior to surgery supported by fluorescence excitation from a blue light source (Blue400, Zeiss Meditech, Oberkochen, Germany; FL400, Leica Microsystems, Heerbrugg, Switzerland). Surgeons are asked whether a residual tumor can be observed to fluoresce under blue light (BL) after the tumor is no longer recognizable using conventional illumination at the end of surgery. In addition, when faced with tissues of uncertain tissue type (so-called “indeterminate” tissue), this study records how often surgeons make a correct decision based on fluorescence and how this influences surgical strategy. The primary endpoint is the percentage of patients in whom one of these two benefits are observed. Other endpoints include the diagnostic accuracy of fluorescence compared to white light (WL) versus correlative histology. For bias reduction, pertinent data are derived from surgical videos reviewed by independent reviewers blinded to surgeons’ assessments of tissue type and fluorescence status. Data will be included from approximately 100 study participants completing the study at approximately 15 centers in the United States, Germany, and Austria. Results: As of May 2022, 88 patients have completed the study. No adverse safety signal has been detected. Conclusions: Preliminary data confirm the feasibility of our study design. Accrual is targeted for completion in the third quarter of 2022.

Objective: To present key data from a private marketing report that characterizes US hearing aid (HA) utilization, HA candidate and user population sizes, and HA pricing. Patients: HA candidates and users in the United States. Interventions: Hearing amplification. Main Outcome Measures: HA utilization, HA candidate and user population sizes, HA market size and value, and HA pricing. Results: In 2015, an estimated 8.5 million HA users accounted for a total of 15.4 million individual HA devices in the United States. Approximately 81% of HA users owned bilateral devices. In 2015, approximately 87% of devices were purchased as replacements by current HA users, while the remaining 13% of devices were purchased by new HA users. HA utilization rates among the candidate population approximated 21% in 2015, which was stable over the 3-year study period. In 2015, there was a net increase of 696,060 individuals who met HA candidacy criteria but did not undergo treatment with HAs, adding to the backlog of 31.0 million untreated HA candidates who existed before that year. The HA market was valued at $6.0 billion in 2015, with an average retail selling price of $1798 per device ($3596 per pair). In the same year, the average manufacturer selling price was $495 per device ($990 per pair), or nearly 1 quarter of the retail price. Conclusions: HAs are substantially under-utilized in the United States with an annually growing backlog of untreated HA candidates.

Abstract Background Multisystem inflammatory syndrome in children (MIS-C), linked to antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with considerable morbidity. Prevention of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) by vaccination might also decrease MIS-C likelihood. Methods In a multicenter, case-control, public health investigation of children ages 5–18 years hospitalized from 1 July 2021 to 7 April 2022, we compared the odds of being fully vaccinated (2 doses of BNT162b2 vaccine ≥28 days before hospital admission) between MIS-C case-patients and hospital-based controls who tested negative for SARS-CoV-2. These associations were examined by age group, timing of vaccination, and periods of Delta and Omicron variant predominance using multivariable logistic regression. Results We compared 304 MIS-C case-patients (280 [92%] unvaccinated) with 502 controls (346 [69%] unvaccinated). MIS-C was associated with decreased likelihood of vaccination (adjusted OR [aOR]: .16; 95% CI: .10–.26), including among children ages 5–11 years (aOR: .22; 95% CI: .10–.52), ages 12–18 years (aOR: .10; 95% CI: .05–.19), and during the Delta (aOR: .06; 95% CI: .02–.15) and Omicron (aOR: .22; 95% CI: .11–.42) variant-predominant periods. This association persisted beyond 120 days after the second dose (aOR: .08; 95% CI: .03–.22) in 12–18-year-olds. Among all MIS-C case-patients, 187 (62%) required intensive care unit admission and 280 (92%) vaccine-eligible case-patients were unvaccinated. Conclusions Vaccination with 2 doses of BNT162b2 is associated with reduced likelihood of MIS-C in children ages 5–18 years. Most vaccine-eligible hospitalized patients with MIS-C were unvaccinated.

This case involves a patient with severe COVID-19 pneumonia and massive pulmonary embolism requiring mechanical ventilation. His clinical course was complicated by delirium likely triggered by his critical illness and failed initial extubation, isolation from family, and escalating fear and desperation. In hopeful preparation for subsequent successful extubation, a unique approach was taken to decrease the risk of panic, delirium, and decompensation leading to reintubation. As a means of orienting him to his treatment pathway and to provide encouragement for continued recovery, an impromptu patient-directed checklist was constructed. The recovery checklist, written in simplified language, outlined the stages of severe illness that the patient had overcome after his emergent intubation. The list also outlined the tasks he needed to complete prior to hospital discharge. Unexpectedly, the checklist received a great deal of engagement from both the patient and medical team and played an important role in this patient’s successful recovery and rehabilitation.

Objective: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons. Background: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC. Methods: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014–2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter <3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers. Results: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤5.2%; comprehensive complication index at 1 year of ≤33.7; grade ≥3 complication rates ≤66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n=106) (62% vs 32%, P<0.001). Conclusion: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC.

Abstract The INSPIRE trial was a Phase 3, open‐label, multicenter trial (LTI‐301) that enrolled patients with pulmonary arterial hypertension (PAH) ≥ 18 years of age who transitioned to Yutrepia from nebulized treprostinil (Transition) or added Yutrepia to prostacyclin naïve patients on ≤2 nonprostacyclin oral therapies. The objectives of the trial were to evaluate the safety and tolerability of Yutrepia (dry‐powder formulation of treprostinil) in patients with PAH. The primary safety measures were the incidence of adverse events (AEs) and serious AEs. Exploratory efficacy measures were also assessed during the trial. Transition patients initiated Yutrepia at a dose comparable to their nebulized treprostinil dose while prostacyclin naïve patients received 26.5‐mcg QID; up‐titration in 26.5‐mcg increments was permitted for both groups. A total of 121 patients were enrolled, of which 29 patients discontinued from the trial, with the most common reason being AEs. Eighty percent of the Transition group and 96% of the prostacyclin naïve group titrated to a dose ≥79.5 mcg QID at Day 360, respectively, with one patient achieving a dose of 212‐mcg QID. The most common AEs were cough, headache, upper respiratory tract infection, dyspnea, dizziness, throat irritation, diarrhea, chest discomfort, fatigue, and nasopharyngitis. Most of these events were considered treatment‐related though mild to moderate in severity and expected for prostacyclin therapy administered by inhalation. In an evaluation of exploratory efficacy measures, patients remained stable or improved over the 1 year of treatment. Yutrepia was found to be a convenient, safe, and well‐tolerated inhaled prostacyclin treatment option for PAH patients.