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Gains in pitch from gender affirming voice training (GVT) alone in trans women have historically been shown to decline after 1 year. Currently no standard exists for length and type of GVT that yields meaningful behavioral change and patient satisfaction with voice outcomes in trans women. This study aims to determine whether GVT alone leads to sustained pitch elevation and patient satisfaction in trans women.Retrospective review from 2016 to 2020 of trans women patients who underwent GVT alone for voice change. Charts were reviewed for acoustic analysis of pitch including sustained vowel fundamental frequency, speaking fundamental frequency, and quality of life data from the Trans Woman Voice Questionnaire at pre-therapy, immediate post-therapy, and extended post-therapy time intervals.A total of 157 patients presented to our Voice Center, of which 34 participated in the full course of GVT. Patients underwent an average of six sessions of GVT (range 5-7) over an average of 13.14 weeks (range 6-16). Average time between completing GVT and presenting for extended follow-up was 11.37 months (range 6-31). Compared to initial presentation prior to therapy, at extended follow-up after completing GVT average change in F0/a/, SF0, and TWVQ were 64.6 Hz, 31.3 Hz, and 32.45. No significant change was noted between immediate post-therapy and extended post-therapy acoustic measures. TWVQ demonstrated continued improvement between immediate post-therapy and extended post-therapy.In self-selected patients who present for extended follow-up, GVT alone can result in sustained pitch elevation and voice-related quality life in trans women.4 Laryngoscope, 2023.

Aptamers face challenges for use outside the ideal conditions in which they are developed. These difficulties are most palpable in vivo due to nuclease activities, rapid clearance, and off-target binding. Herein, we demonstrate that a polyphosphodiester-backboned molecular brush can suppress enzymatic digestion, reduce non-specific cell uptake, enable long blood circulation, and rescue the bioactivity of a conjugated aptamer in vivo. The backbone along with the aptamer is assembled via solid-phase synthesis, followed by installation of poly(ethylene glycol) (PEG) side chains using a two-step process with near-quantitative efficiency. The synthesis allows for precise control over polymer size and architecture. Consisting entirely of building blocks that are generally recognized as safe for therapeutics, this novel molecular brush is expected to provide a highly translatable route for aptamer-based therapeutics.

OBJECTIVES/HYPOTHESIS An artificial intelligence (AI) tool was developed using audio clips of cis-male and cis-female voices based on spectral analysis to assess %probability of a voice being perceived as female (%Prob♀). This program was validated with 92% accuracy in cisgender speakers. The aim of the study was to assess the relationship of fo on %Prob♀ by a validated AI tool in a cohort of trans females who underwent intervention to feminize their voice with behavioral modification and/or surgery. STUDY DESIGN Cohort study. METHODS Fundamental frequency (fo ) from prolonged vowel sounds (fo /a/) and fo from spontaneous speech (fo -sp) were measured using the Kay Pentax Computerized Speech Lab (Montvale, NJ) in trans females postintervention. The same voice samples were analyzed by the AI tool for %Prob♀. Chi-square analysis and regression models were performed accepting >50% Prob♀ as female voice. RESULTS Forty-two patients were available for analysis after intervention. fo -sp post-treatment was positively correlated with %Prob♀ (R = 0.645 [P 50% for the speech samples and fo -sp >160 Hz (P 160 Hz. Of these, the AI program only perceived nine patients as female (>50 %Prob♀). CONCLUSION Patients with fo -sp >160 Hz after feminization treatments are not necessarily perceived as having a high probability of being female by a validated AI tool. AI may represent a useful outcome measurement tool for patients undergoing gender affirming voice care. LEVEL OF EVIDENCE 3 Laryngoscope, 131:2567-2571, 2021.

In April 2020, in light of COVID-19-related blood shortages, the US Food and Drug Administration (FDA) reduced the deferral period for men who have sex with men (MSM) from its previous duration of 1 year to 3 months. Although originally born out of necessity, the decades-old restrictions on MSM donors have been mitigated by significant advancements in HIV screening, treatment, and public education. The severity of the ongoing COVID-19 pandemic—and the urgent need for safe blood products to respond to such crises—demands an immediate reconsideration of the 3-month deferral policy for MSM. We review historical HIV testing and transmission evidence, discuss the ethical ramifications of the current deferral period, and examine the issue of noncompliance with donor deferral rules. We also propose an eligibility screening format that involves an individual risk-based screening protocol and, unlike current FDA guidelines, does not effectively exclude donors on the basis of gender identity or sexual orientation. Our policy proposal would allow historically marginalized community members to participate with dignity in the blood donation process without compromising blood donation and transfusion safety outcomes.

To date, 1-year evaluation of pitch elevation in patients undergoing modified Wendler glottoplasty (WG) in combination with VT has not been assessed.To determine whether 1-year pitch elevation is sustained in patients who undergo modified WG in combination with VT for voice feminization.A retrospective review of patients who underwent WG in combination with voice therapy (VT) was performed from 2016 to 2020. Charts were reviewed for sustained vowel fundamental frequency (F0/a/), speaking fundamental frequency (SF0), and Trans Woman Voice Questionnaire (TWVQ) at preoperative, initial postoperative (3-6 months after surgery), and 12-month postoperative visits.Change in average F0/a/, SF0 and TWVQ was 50.25 Hz, 32.96 Hz, and 32.6 at 12-months postoperatively compared to preoperative values. Initial and 12-month postoperative SF0 were significantly higher than preoperative SF0 (Mann-Whitney U test p = 0.0042, p = 0.0010). There was no difference in initial postoperative and 12-month postoperative SF0 (p = 0.50). TWVQ at 12 months was significantly lower than preoperative TWVQ (ANOVA p 0.001, Tukey honestly significant difference HSD p 0.05).Pitch elevation remains sustained at one year in patients undergoing modified WG in combination with VT. Modified Wendler glottoplasty combined with VT results in relatively long-term improvements in voice-related quality of life and is possibly a beneficial addition in the long-term management of patients who desire voice feminization.4 Laryngoscope, 2022.

An understanding of the ethical underpinnings of human subjects research that involves some risk to participants without anticipated direct clinical benefit-such as the kidney biopsy procedure as part of the Kidney Precision Medicine Project (KPMP)-requires a critical examination of the risks as well as the diverse set of countervailing potential benefits to participants. This kind of deliberation has been foundational to the development and conduct of the KPMP. Herein, we use illustrative features of this research paradigm to develop a more comprehensive conceptualization of the types of benefits that may be important to research participants, including respecting pluralistic values, supporting the opportunity to act altruistically, and enhancing benefits to a participant's community. This approach may serve as a model to help researchers, ethicists, and regulators to identify opportunities to better respect and support participants in future research that entails some risk to these participants as well as to improve the quality of research for people with kidney disease.

We show the therapeutic potential of myeloid-directed immunomodulatory treatment for medulloblastoma. Patients with medulloblastoma, the most common malignant pediatric brain tumor, need new treatments, as standard therapy produces disabling neurotoxicities and fails 20% of patients. About 30% of medulloblastomas show hyperactivation of the SHH (Sonic Hedgehog) signaling pathway, and these tumors have large myeloid populations in the tumor microenvironment (TME). We analyzed whether activating toll-like receptors on these myeloid cells would slow tumor growth. Our prior single-cell RNA sequencing studies in both patient samples and mouse models showed that 10% of the cells in SHH medulloblastoma are myeloid cells and that these cells uniquely express TLR7 and TLR8. We treated mice genetically engineered to develop SHH medulloblastomas with the TLR7/8 agonist resiquimod, administered systemically either as free drug or in polyoxazoline nanoparticles (POx-resiquimod), and compared POx-resiquimod+radiotherapy to radiotherapy alone. We found that POx-resiquimod extended the survival time of mice with medulloblastoma, while free drug failed to show benefit. PK studies showed that POx-resiquimod increased tumor drug exposure, consistent with increased efficacy. Mechanistically, POx-resiquimod increases tumor myeloid populations and decreased the fraction of myeloid cells that expressed IGF1. POx-resiquimod plus radiation therapy, moreover, was superior to either POx-resiquimod alone, or radiotherapy alone. Together our data show that the TLR7/8 agonist resiquimod, delivered in nanoparticle formulation, produces a significant anti-tumor effect in SHH medulloblastoma, and increased the efficacy of radiotherapy. As radiotherapy is the mainstay of current medulloblastoma treatment, we propose that TLR7/8-agonist therapy such as resiquimod may be added to current regimens to reduce the radiation dose needed for efficacy, and to increase the fraction of successfully treated patients.

BACKGROUND Monitoring for dissemination in medulloblastoma involves spinal MRIs (sMRIs) and lumbar punctures (LPs). The frequency and duration of these studies vary depending on risk of dissemination; general practice varies between and within institutions. Our goal is to review the current practice in post-treatment monitoring via examination of published data, clinical trial standards, and expert practice. METHODS We reviewed the available literature and accessible clinical trial protocols. Using PRISMA guidelines, we conducted searches of Ovid MEDLINE, Embase, and PubMed to identify studies which detailed relapse rates and patterns, and recommended practice for patients with medulloblastoma aged 3-21 years. Eligible studies from 1990 to present were included. RESULTS Thirteen multi-institutional clinical trials from North America and Europe were analyzed for frequency of post-therapy surveillance with LPs/sMRIs. Several studies (n=8) recommend LPs/sMRIs every 3-6 months in standard risk and every 3 months in high risk disease for two years when initially completing therapy, and then often diverge in frequency after 2 years. Some studies (n=5) did not include post-treatment recommendations. Cumulative data on relapse from available clinical trial reports and single institution studies (n=673 relapses) demonstrated local failure rate of 18.4%, distant failure of 49.1%, and combined distant and local failure of 32.5%. Spine-only relapses were reported to occur in approximately 13-20%, with one small study reporting spine-only relapse rate of 37.5%. DISCUSSION Patterns of recurrence in medulloblastoma have shifted over time as therapeutic approaches have evolved, including more spinal-only recurrences. Standardized guidance regarding surveillance could have significant impact on clinical detection and streamline management to minimize unnecessary examinations. Early detection of recurrent disease could optimize treatment options for providers and families, whether focusing on curative approaches or quality of life.

Purpose To investigate the influence of abutment material properties on the fracture resistance and failure mode of lithium disilicate (IPS e.max) CAD/CAM (computer-aided design/manufacturing) crowns on traditionally and minimally prepared simulated tooth substrates. Materials and methods Thirty lithium disilicate (IPS e.max) CAD/CAM crowns were divided into three groups (n = 10): TD: traditional thickness crowns cemented on Paradigm MZ100 abutments; MD: minimal thickness crowns cemented on Paradigm MZ100 abutments; ME: minimal thickness crowns cemented on e.max abutments. The 3Shape system was used to scan, design and mill all abutments and crowns with a die space set to 40 µm. Traditional thickness crowns were designed based on manufacturer guidelines with 1.5 mm occlusal thickness and 1.0 mm margins. Minimal thickness crowns were designed with 0.7 mm occlusal thickness and 0.5 mm margins. MZ100 composite and e.max abutments were selected to simulate dentin and enamel substrates, respectively, based on their elastic-modulus. Variolink Esthetic was used to cement all samples following manufacturer's instructions. A universal testing machine was used to load all specimens to fracture with a 3 mm radius stainless steel hemispherical tip at a crosshead speed 0.5 mm/minute along the longitudinal axis of the abutment with a 1 mm thermoplastic film placed between the loading tip and crown surface. Data was analyzed using ANOVA and Bonferroni post hoc assessment. Fractographic analysis was performed with scanning electron microscopy (SEM). Results The mean fracture load (standard deviation) was 1499 (241) N for TD; 1228 (287) N for MD; and 1377 (96) N for ME. Statistically significant difference between groups did not exist (p = 0.157, F = 1.995). In groups TD and MD with low e-modulus abutments, the dispersion of a probability distribution (coefficient of variation: CV) was statistically higher than that of group ME with high e-modulus abutments. SEM illustrated larger micro-fracture dimensions in Group MD than Group ME. Conclusion Minimal thickness e.max crowns did not demonstrate statistical difference in fracture resistance from traditional thickness crowns. Fracture mechanisms of minimal thickness e.max crowns may be affected by the e-modulus of the substrate. Minimal thickness e.max crowns may be a viable restorative option when supported by high e-modulus materials.

Background Treatment options to assist patients to produce a more perceptually feminine voice include voice therapy (VT) and surgeries to elevate pitch such as the Wendler glottoplasty (WG). The Trans Woman Voice Questionnaire (TWVQ) is a validated quality of life measure for trans women's self-reported perceptions of their voice and is frequently administered before and after such interventions. The 30 statements broadly pertain to how feminine a patient feels their voice is, how effortful it is to produce their voice, and how their voice impacts them psychosocially, making it a useful and specific outcome measure when treating trans females for voice concerns. Objective To compare quality of life outcomes between VT and VT with adjunct WG (VT+WG) based on changes in ratings of individual statements on the TWVQ. Materials and Methods A retrospective case series of 31 trans female patients treated was completed. A total of 17 patients underwent VT and 14 underwent VT with adjunctive WG. Ratings for each of the 30 TWVQ statements were compared before and after treatment for each group. Wilcoxon rank-sum tests were used to compare rating changes before and after treatment. Spearman rank-order correlation tests were used to assess the association between total TWVQ score and “current voice” rating. Results WG was associated with statistically significantly improved ratings for every statement on the TWVQ except one. In contrast, VT was associated with statistically significant improvements in 16 of the 30 statements, which largely pertained to patient emotions surrounding their voice rather than physical aspects such as pitch and dysphonia. Furthermore, while both WG+VT and VT improved the “current voice” rating significantly, WG improved the score by nearly 1 unit more. Lastly, we found a positive association between the total TWVQ score and current voice rating, indicating that lower scores were associated with more self-perceived feminine-sounding voices (P Conclusions Both VT and VT+WG result in improvements in the TWVQ. The specific statements on the TWVQ offer insight into specific quality of life treatment outcomes, with VT associated with improvements in mostly psychosocial aspects of voice production and VT+WG with both psychosocial and physical aspects.

Chronic kidney disease (CKD) and acute kidney injury (AKI) are common, heterogeneous, and morbid diseases. Mechanistic characterization of CKD and AKI in patients may facilitate a precision medicine approach to prevention, diagnosis, and treatment. The Kidney Precision Medicine Project aims to ethically and safely obtain kidney biopsies from participants with CKD or AKI, create a reference kidney atlas, and characterize disease subgroups to stratify patients based on molecular features of disease, clinical characteristics, and associated outcomes. An additional aim is to identify critical cells, pathways, and targets for novel therapies and preventive strategies. This project is a multicenter prospective cohort study of adults with CKD or AKI who undergo a protocol kidney biopsy for research purposes. This investigation focuses on kidney diseases that are most prevalent and therefore substantially burden the public health, including CKD attributed to diabetes or hypertension and AKI attributed to ischemic and toxic injuries. Reference kidney tissues (for example, living kidney donor biopsies) will also be evaluated. Traditional and digital pathology will be combined with transcriptomic, proteomic, and metabolomics analysis of the kidney tissue as well as deep clinical phenotyping for supervised and unsupervised subgroup analysis and systems biology analysis. Participants will be followed prospectively for ten years to ascertain clinical outcomes. Cell types, locations, and functions will be characterized in health and disease in an open, searchable, online kidney tissue atlas. All data from the Kidney Precision Medicine Project will be made readily available for broad use by scientists, clinicians, and patients.

OBJECTIVE Burnout is defined as work-related emotional exhaustion, depersonalization, and decreased sense of accomplishment. Virtual reality (VR) has emerged as an effective treatment modality for various conditions related to anxiety, however, few studies have assessed its role for stress management in residents. We hypothesize that VR-based mindfulness meditation can reduce resident burnout in real-world settings. STUDY DESIGN Prospective randomized crossover trial. METHODS Resident participants completed the validated Maslach Burnout Inventory (MBI). One group used a VR-based meditation app; the second group received no intervention. After a 2-month rotation, all subjects completed an MBI and crossed over to the other arm. Wilcoxon rank-sum tests were used to compare MBI scores before and after intervention, and to compare results by gender and postgraduate year. Mann-Whitney U tests were used to assess qualitative differences between participants. RESULTS Eighteen residents completed the study. Five participants were female and 13 were male. Weekly use of VR-guided meditation and paced breathing was associated with a significant decrease in emotional exhaustion (P = .009), and on subgroup analysis, male gender specifically was associated with a decrease in emotional exhaustion (P = .027). In the post-intervention survey, 42.9% subjects reported that VR encouraged them to employ paced breathing techniques, 71.4% reported that they would use the technology if regularly available, and 21.4% reported they would use paced breathing in the future. CONCLUSION VR-based therapy may serve as a successful tool in stress management and reduce the rate of burnout among otolaryngology residents. LEVEL OF EVIDENCE NA Laryngoscope, 131:1972-1976, 2021.

Cancer immunotherapy, the utilization of the patients’ own immune system to treat cancer, has emerged as a powerful new strategy in cancer treatment. Recent clinical data has demonstrated immunotherapy to be effective in a wide range of cancers, including lung, bladder, renal cell, colorectal, gastro-esophageal, and head and neck cancers5-11. However, clinical reports of immune-based treatments for medulloblastomas are scarce and preliminary. Therefore, there is a need in developing strategies to improve medulloblastoma immunotherapy. Our recent studies have confirmed that SHH medulloblastomas are enriched in Tumor Associated Macrophages (TAMs) and unlike other tumors, TAMs are associated with positive outcomes and play a positive role by impairing tumor growth. Overall, analysis of TME in medulloblastomas reveals TAMs as a potential therapeutic target. Resiquimod is a synthetic small molecule agonist of Toll-like receptors 7 and 8 (TLR7/8) that modulates innate immune cells. We have loaded resiquimod into ultra-high-capacity polyoxazoline (POx) block copolymers forming small, homogeneous nanoparticles (POx-resiquimod). Our recent study shows that loading into POx nanoparticles improves drug delivery to tumors and treatment with 3 injections of POx-res as the single-agent treatment results in a profound anti-tumor effect G-Smo mice while treatment with free drug shows no therapeutic benefit. Our data also shows that that the tumors of G-Smo mice are enriched with the mixed populations of anti-inflammatory and pro-inflammatory macrophages and the treatment with POx-resiquimod have enhanced infiltration of macrophages into the tumors, enhanced the repolarization of macrophages to M1 subtype and decreased tumor cells viability. These studies show for the first time that targeting the medulloblastoma TME with POx-resiquimod can produce a significant anti-tumor effect. Furthermore, combination of POx-resiquimod with radiation resulted in long term survivals, showing potential therapeutic combination. The expression of TLR7/8 on TAMs in patient-derived medulloblastoma samples suggests that resiquimod may produce similar anti-medulloblastoma effects in humans.

OBJECTIVES The ideal timing and technique of tracheostomy vary among patients and may impact outcomes. We aim to examine the association between tracheostomy timing, placement technique, and patient demographics on survival. STUDY DESIGN Retrospective cohort study. METHODS A retrospective review was performed for all patients who underwent tracheostomy in 2016 and 2017 at one urban academic tertiary-care hospital. Kaplan-Meier curves were created based on combinations of tracheostomy timing and technique (early percutaneous, early non-percutaneous, late percutaneous, and late non-percutaneous). Cox proportional hazard models were used to determine multivariable effects of timing, technique, and other demographic factors. Primary outcome measures were tracheostomy-related mortality and overall survival. Secondary outcomes were in-hospital, 30-day, and 90-day mortality. RESULTS Our study included 523 patients. There were six tracheostomy-related deaths, with hemorrhage and tracheoesophageal fistula being the most common causes. Tracheostomy timing and technique combinations were not associated with differences in all-cause mortality or survival following discharge. Cox proportional hazard models showed that Charlson Comorbidity Index (CCI) and unknown partner status were associated with a decrease in survival (P

OBJECTIVES/HYPOTHESIS Little data exists regarding the relationship between socioeconomic and demographic factors and tracheostomy outcomes. The goal of this study was to determine associations between socioeconomic status (SES), demographic factors, and insurance status with hospital length of stay (LOS), intensive care unit (ICU) LOS, and mortality following tracheostomy. STUDY DESIGN Retrospective cohort study. METHODS A retrospective analysis of all patients who underwent tracheostomy at an urban tertiary-care academic hospital from 2016 to 2017 was performed. Patients were aggregated into low-, middle-, and high-income brackets. Other variables included age, sex, race, ethnicity, body mass index, and Charlson Comorbidity Index (CCI). Outcomes included hospital and ICU LOS, in-hospital mortality, and 30-day mortality following tracheostomy. Outcomes were compared using Kruskal-Wallis tests for continuous variables and χ2 or Fisher exact tests for categorical variables. The α level was set to .05. RESULTS In total, 523 patients were included in the study. Patients from high-income areas were more likely to be male (P

Resiquimod is a synthetic small molecule agonist of Toll-like receptors 7 and 8 (TLR-7/8) that modulates innate immune cells. We found TLR-7/8 are expressed in medulloblastoma exclusively by tumor-associated myeloid cells (TAMs). We tested whether systemically administered resiquimod modulated TAMs in a genetic Sonic hedgehog (SHH) medulloblastoma model, and whether this modulation would be therapeutically beneficial. We generated mice with medulloblastoma by crossing hGFAP-Cre and SmoM2 mouse lines. The resulting hGFAP-Cre/SmoM2 (G-Smo) mice developed medulloblastoma with 100% frequency and showed a median survival of 14.5 days (n=12). Treatment with 3 doses of resiquimod at postnatal days 10, 12 and 14 reduced tumor size and increased median survival to 37 days (n=10) (p=0.003508). Cellular studies showed that resiquimod altered TAM phenotype, rapidly inducing expression of the inflammatory marker VCAM1, and more slowly increasing TAM populations. Responses to the 3-dose regimen were ultimately limited by recurrence and all mice eventually died of tumor progression. Continued resiquimod therapy with every other day dosing was less effective than the 3-dose regimen, suggesting that TAM responses to resiquimod are dynamic and change with prolonged exposure. Our data show that innate immunity, mediated by TAMs and stimulated by TLR-7/8 agonist therapy, can produce a significant anti-tumor effect in medulloblastoma. The common expression of TLR-7/8 on TAMs in patient-derived medulloblastoma samples and in the mouse model suggests that resiquimod may produce similar anti-medulloblastoma effects in humans. Further studies are needed to define the mechanism of the anti-tumor effect in detail, to determine the optimal dose regimen, and to determine if resiquimod can combine effectively with additional adjuvant therapies to produce curative effects.

BACKGROUND New, non-cytotoxic treatments may improve outcomes for medulloblastoma, the most common malignant pediatric brain tumor. Sonic hedgehog (SHH) subgroup medulloblastoma, which includes subtypes with poor prognosis, can be modeled in immunocompetent, transgenic mice. These models are ideal for preclinical testing of immunotherapies. Here, we show that immune stimulation using resiquimod, a small molecule agonist of Toll-like receptor 7 and 8 (TLR 7/8), alters myeloid populations in medulloblastoma and significantly reduces tumor growth. METHOD We generated mice with medulloblastoma by interbreeding the hGFAP-Cre and SmoM2 mouse lines. The resultant hGFAP-Cre/SmoM2 (G-Smo) mice develop SHH medulloblastoma with 100% frequency. We analyzed myeloid populations and demonstrated TLR7/8 expression patterns in G-Smo tumors. We then compared survival of untreated G-Smo mice versus G-Smo mice treated with three doses of resiquimod at postnatal days 10, 12, and 14. We also assessed pharmacodynamic effects at progressive intervals after a single dose. RESULTS Approximately 10% of cells in G-Smo medulloblastomas were myeloid cells, and these cells were the only cells that expressed TLR7/8. Resiquimod slowed tumor growth and increased the survival of mice with medulloblastoma. Untreated median survival was 14.5 days (n=12), compared to resiquimod-treated median survival of 37 days (n=10; p=0.0003). All treated mice eventually demonstrated tumor progression. Immunohistochemistry for IBA1, a pan-macrophage marker, demonstrated significant increase in myeloid cells within the tumor by 24 hours after treatment (p=0.0178), however the IGF1+ fraction of myeloid cells decreased (p=0.0275). CONCLUSION Resiquimod prolongs survival in mice with SHH-driven medulloblastoma, demonstrating the potential for therapies that target myeloid cells to produce significant anti-tumor effects. Myeloid-derived IGF-1 has been shown to support tumor progression and resiquimod may act by disrupting this paracrine signaling.

The purpose of this study is to define value in bundled total joint arthroplasty (TJA) from the differing perspectives of the patient, payer/employer, and hospital/provider.Demographic, psychosocial, clinical, financial, and patient-reported outcomes (PROs) data from 2017 to 2018 elective TJA cases at a multihospital academic health system were queried. Value was defined as improvement in PROs (preoperatively to 1 year postoperatively) for patients, improvement in PROs per $1000 of bundle cost for payers, and the normalized sum of improvement in PROs and hospital bundle margin for providers. Bivariate analysis was used to compare high value vs low value (50th percentile vs50th percentile). Multivariate analysis was performed to identify predictors.A total of 280 patients had PRO data, of which 71 had Medicare claims data. Diabetes (odds ratio [OR], 0.45; P = .02) predicted low value for patients; female gender (OR, 0.25), hypertension (OR, 0.17), pulmonary disease (OR, 0.12), and skilled nursing facility discharge (OR, 0.17) for payers (P ≤ .03 for all); and pulmonary disease (OR, 0.16) and skilled nursing facility discharge (OR, 0.19) for providers (P ≤ .04 for all).This is the first article to define value in TJA under a bundle payment model from multiple perspectives, providing a foundation for future studies analyzing value-based TJA.

Multiple sclerosis (MS) is a neuroinflammatory disorder resulting from infiltration of T cells into the central nervous system (CNS) and demyelination of neurons. Since T follicular helper (TFH) cells are associated with MS relapse, their selective inhibition could be an ideal therapeutic. TFH cells require transcription factor BCL6 and active mTORC1/2 for development. When mTORC is active, cap-binding protein eukaryotic translation initiation factor 4E (eIF4E) initiates translation of selective mRNAs. However, the requirement of eIF4E for translation of mRNAs necessary for TFH cell development has not been investigated. Disruption of eIF4E binding to the 5′ mRNA cap with drug 4EGI-1 inhibits TFH and germinal center (GC) B cell development while having no effect on differentiation and effector function of TH1, TH2, TH17, or Tregs. Silencing of eIF4E in only CD4 T cells is sufficient to inhibit their formation of TFH cells. We used polysome profiling to determine which mRNAs are selectively translated by eIF4E and identified salient programs regulated by transcription (BCL6, NFAT) and costimulation (CD28, SLAM). eIF4E is required for translation of BCL6 in human lymph node TFH and GC B cells. Administration of 4EGI-1 during experimental autoimmune encephalitis (EAE) results in significantly decreased infiltration of CD4 T cells in the CNS, demyelination, and clinical score. Further, 4EGI-1 treatment following initiation of symptoms results in rapid improvement of symptoms and partial remission earlier than vehicle-treated animals. Thus, eIF4E is required for differentiation of TFH cells and pathogenesis of autoimmune encephalitis, and 4EGI-1 represents a potential therapeutic.

BACKGROUND Heart failure (HF) is a condition that affects approximately 6.2 million people in the United States and has a 5-year mortality rate of approximately 42%. With the prevalence expected to exceed 8 million cases by 2030, projections estimate that total annual HF costs will increase to nearly US $70 billion. Recently, the advent of remote monitoring technology has significantly broadened the scope of the physician’s reach in chronic disease management. OBJECTIVE The goal of our program, named the Heart Health Program, was to examine the feasibility of using digital health monitoring in real-world home settings, ascertain patient adoption, and evaluate impact on 30-day readmission rate. METHODS A digital medicine software platform developed at Mount Sinai Health System, called RxUniverse, was used to prescribe a digital care pathway including the HealthPROMISE digital therapeutic and iHealth mobile apps to patients’ personal smartphones. Vital sign data, including blood pressure (BP) and weight, were collected through an ambulatory remote monitoring system that comprised a mobile app and complementary consumer-grade Bluetooth-connected smart devices (BP cuff and digital scale) that send data to the provider care teams. Care teams were alerted via a Web-based dashboard of abnormal patient BP and weight change readings, and further action was taken at the clinicians’ discretion. We used statistical analyses to determine risk factors associated with 30-day all-cause readmission. RESULTS Overall, the Heart Health Program included 58 patients admitted to the Mount Sinai Hospital for HF. The 30-day hospital readmission rate was 10% (6/58), compared with the national readmission rates of approximately 25% and the Mount Sinai Hospital’s average of approximately 23%. Single marital status (P=.06) and history of percutaneous coronary intervention (P=.08) were associated with readmission. Readmitted patients were also less likely to have been previously prescribed angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (P=.02). Notably, readmitted patients utilized the BP and weight monitors less than nonreadmitted patients, and patients aged younger than 70 years used the monitors more frequently on average than those aged over 70 years, though these trends did not reach statistical significance. The percentage of the 58 patients using the monitors at least once dropped from 83% (42/58) in the first week after discharge to 46% (23/58) in the fourth week. CONCLUSIONS Given the increasing burden of HF, there is a need for an effective and sustainable remote monitoring system for HF patients following hospital discharge. We identified clinical and social factors as well as remote monitoring usage trends that identify targetable patient populations that could benefit most from integration of daily remote monitoring. In addition, we demonstrated that interventions driven by real-time vital sign data may greatly aid in reducing hospital readmissions and costs while improving patient outcomes.

Background Heart failure (HF) is a condition that affects approximately 6.2 million people in the United States and has a 5-year mortality rate of approximately 42%. With the prevalence expected to exceed 8 million cases by 2030, projections estimate that total annual HF costs will increase to nearly US $70 billion. Recently, the advent of remote monitoring technology has significantly broadened the scope of the physician’s reach in chronic disease management. Objective The goal of our program, named the Heart Health Program, was to examine the feasibility of using digital health monitoring in real-world home settings, ascertain patient adoption, and evaluate impact on 30-day readmission rate. Methods A digital medicine software platform developed at Mount Sinai Health System, called RxUniverse, was used to prescribe a digital care pathway including the HealthPROMISE digital therapeutic and iHealth mobile apps to patients’ personal smartphones. Vital sign data, including blood pressure (BP) and weight, were collected through an ambulatory remote monitoring system that comprised a mobile app and complementary consumer-grade Bluetooth-connected smart devices (BP cuff and digital scale) that send data to the provider care teams. Care teams were alerted via a Web-based dashboard of abnormal patient BP and weight change readings, and further action was taken at the clinicians’ discretion. We used statistical analyses to determine risk factors associated with 30-day all-cause readmission. Results Overall, the Heart Health Program included 58 patients admitted to the Mount Sinai Hospital for HF. The 30-day hospital readmission rate was 10% (6/58), compared with the national readmission rates of approximately 25% and the Mount Sinai Hospital’s average of approximately 23%. Single marital status (P=.06) and history of percutaneous coronary intervention (P=.08) were associated with readmission. Readmitted patients were also less likely to have been previously prescribed angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (P=.02). Notably, readmitted patients utilized the BP and weight monitors less than nonreadmitted patients, and patients aged younger than 70 years used the monitors more frequently on average than those aged over 70 years, though these trends did not reach statistical significance. The percentage of the 58 patients using the monitors at least once dropped from 83% (42/58) in the first week after discharge to 46% (23/58) in the fourth week. Conclusions Given the increasing burden of HF, there is a need for an effective and sustainable remote monitoring system for HF patients following hospital discharge. We identified clinical and social factors as well as remote monitoring usage trends that identify targetable patient populations that could benefit most from integration of daily remote monitoring. In addition, we demonstrated that interventions driven by real-time vital sign data may greatly aid in reducing hospital readmissions and costs while improving patient outcomes.

Summary Objectives Radiation treatment for laryngeal cancer has been shown to cause tissue changes to the vocal folds, which can result in degradation of voice. Our objective in this study was to investigate changes in perceptual, acoustic, and patient-reported outcomes over an extended period of follow-up after radiation. Design Retrospective review. Methods All patients treated with radiation for early-stage laryngeal carcinoma (in situ, T1, or T2) by a single surgeon from 2011–2018 were reviewed. Demographics and treatment information were recorded. Only patients with at least two dates of follow-up with acoustic data (cepstral spectral index of dysphonia [CSID]) and patient-reported surveys (voice handicap index-10 [VHI-10]) were included. Voice samples were rated by two senior speech-language pathologists on the grade, roughness, breathiness, asthenia, and strain scale. Results Of 115 patients with early-stage laryngeal cancer, 31 patients met inclusion criteria. The average follow-up from time of treatment was 9.6 years (range 3.0–20.3 years), and the average time in between the first and last voice recordings was 2.6 years (range 0.3–5.5 years). The lesions represented were carcinoma in situ (n = 4), T1 (n = 22), and T2 (n = 5). The VHI-10 scores worsened slightly (mean increase +0.27, median +1) from first to last measurements as did the CSID score (median increase +7.0, median +7.4), though neither reached statistical significance when correlated with time since radiation (P = 0.269 and P = 0.0850). Perceptual analysis as rated by two speech-language pathologists raters showed excellent inter-rater reliability (Cronbach's alpha = 0.84), with no significant change over time (mean +0.39, median, with P = 0.347). Grade, roughness, breathiness, asthenia, and strain, VHI-10, and CSID were all correlated (all pairwise comparisons P Conclusion Perceptual, acoustic, and patient-reported outcomes years after radiation for early-stage laryngeal cancer do not show voice degradation over time in this preliminary analysis. Further research with a larger cohort may elucidate voice changes in this population.

BACKGROUND Issues with patient recruitment and enrollment are the primary barriers for missed clinical trial timelines; 8 out of 10 clinical trials are delayed or unable to be completed because of lack of timely patient recruitment. Current patient recruitment efforts are inefficient and time-consuming, since they are typically dependent on manually screening patients during face-to-face visits to the clinic or hospital. With the rapid development of digital communication platforms within health care and the broad consumer adoption of smartphones, there are increasing opportunities to overcome some of these barriers. These platforms have particularly great potential for research and clinical care of chronic conditions, such as inflammatory bowel disease (IBD), an often debilitating disease which currently affects over three million adults in the United States. OBJECTIVE To integrate and utilize a digital medicine platform to improve patient recruitment and enrollment processes in clinical trials. METHODS Patients enrolled in the Mount Sinai Crohn’s and Colitis Registry (MSCCR) were remotely approached about enrolling in a mindfulness study for IBD patients. A text-based clinical rules engine was used to inform registry patients about the trial and to allow patients to indicate interest in participating via text message. Eligible IBD patients were bulk “prescribed” a notification through RxHealth’s digital medicine platform, RxUniverse. Characteristics of the enrolled population, characteristics of patients who responded, and timeliness of responses were analyzed. RESULTS Of the 1364 patients in the MSCCR with available phone numbers, 270 patients affirmatively replied they wanted to participate in to the study. Patients who opted into receiving more information about the study were more likely to have inadequate control of their IBD (25.64% vs 18.97%; P CONCLUSIONS Digital medicine software platforms can facilitate large-scale, lower-effort recruitment of eligible patients for clinical trials. Future research should be done to explore their expanded use for recruitment, patient education, and study data collection. Additional technologies such as patient-powered networks, social media, e-recruiting bots, and other remote engagement platforms can aid clinical trials by saving time and reducing costs of patient recruitment.

BACKGROUND Congestive heart failure (CHF) is a disease that affects about 6.5 million people in the United States with a mortality rate of around 30%. With the incidence rate projected to rise by 46% to exceed 8 million cases by 2030, projections estimate that total CHF costs will increase about to nearly $70 billion. Recently, the advent of remote monitoring technology has significantly broadened the scope of the physician’s reach in chronic disease management. Using remotely monitored health data, providers may be able to better manage and predict their patients’ outcomes, leading to reduced incidence and hospital admission costs. OBJECTIVE This project aimed to demonstrate the feasibility of a digital medicine engagement platform for CHF patients, including identifying factors associated with increased risk of readmission and assessing usage patterns of remote monitoring devices. METHODS The project included 60 patients admitted to Mount Sinai Hospital for CHF. A digital medicine platform by Rx.Health, called RxUniverse, was used to prescribe HealthPROMISE and iHealth mobile apps. Patients updated and recorded their CHF-related symptoms and quality of life measures daily on HealthPROMISE. Vital sign data, including blood pressure and weight, were collected through an ambulatory remote monitoring system that integrated the iHealth app and complementary consumer grade Bluetooth-connected smart devices (blood pressure cuff and digital scale). Physicians were notified of abnormal patient blood pressure and weight change readings and further action was left to the physician’s discretion. We used statistical analyses to determine risk factors associated with 30-day all-cause readmission. RESULTS Overall, there were six 30-day hospital readmissions (10%), compared to the national readmission rates of around 25%. Single marital status (P CONCLUSIONS Given the increasing burden of CHF, there is a need for an effective and sustainable remote monitoring system for CHF patients following hospital discharge. We identified clinical and social factors as well as remote monitor usage trends that identify targetable patient populations that could benefit most from integration of daily remote monitoring. In addition, we demonstrated that interventions driven by real-time vitals data may greatly aid in reducing hospital readmissions and costs while improving patient outcomes. Future studies should seek to implement remote monitoring and confirm usage trends as well as risk factors in a large-scale population.