Outcome of tonsillotomy in children with obstructive sleep-disordered breathing.

OBJECTIVE/BACKGROUND: Most children treated for obstructive sleep disordered breathing (oSDB) are not systematically assessed by polysomnography (PSG) nor by structuredsymptom quantification before surgical treatment. The main objective of this study wasto investigate the effect of adeno-tonsillotomy (ATO) on symptom burden and PSGparameters. METHODS: Children aged 2-10 years with oSDB were selected for ATO based uponclinical findings according to current standards of care in Denmark. Each childunderwent standardized assessment before and 3 months after surgery, including aPSG, tonsil size assessment, and the Pediatric Sleep Questionnaire -Sleep RelatedBreathing Disorder (PSQ) to quantify symptom burden. Obstructive sleep apnea (OSA)was defined as an obstructive apnea-hypopnea index (oAHI) ≥2/h. Successfultreatment was defined as post-surgery oAHI ≤5/h, and complete cure as oAHI ≤2/h. RESULTS: Fifty-two children were included. Mean age was 5.0 years (SD ± 1.76). Thirteen children were identified with baseline oAHI <2/h. Significant improvement inOSA severity was observed in children with moderate-to-severe OSA, in whom oAHI decreased from 15.7/h to 2.6/h (p < 0.001). Treatment success was obtained in 85% and cure was obtained in 42% of children. PSQ-score significantly improved from 0.52 (CI 0.47-0.56) to 0.26 (CI 0.21-0.32) (p < 0.001). Baseline OSA severity was notcorrelated to baseline symptom burden nor to symptom relief after ATO. There were noserious adverse events. CONCLUSIONS: Adeno-tonsillotomy significantly reduced symptom burden in otherwise healthy children with oSDB symptoms. Significant improvement in oAHI was observedonly in children with moderate-to-severe OSA. We recommend combining clinicalevaluation with PSQ and oAHI.

Quantum Gas-Enabled Direct Mapping of Active Current Density in Percolating Networks of Nanowires.

Electrically percolating nanowire networks are among the most promising candidates for next-generation transparent electrodes. Scientific interest in these materials stems from their intrinsic current distribution heterogeneity, leading to phenomena like percolating pathway rerouting and localized self-heating, which can cause irreversible damage. Without an experimental technique to resolve the current distribution and an underpinning nonlinear percolation model, one relies on empirical rules and safety factors to engineer materials. We introduce Bose-Einstein condensate microscopy to address the longstanding problem of imaging active current flow in 2D materials. We report on performance improvement of this technique whereby observation of dynamic redistribution of current pathways becomes feasible. We show how this, combined with existing thermal imaging methods, eliminates the need for assumptions between electrical and thermal properties. This will enable testing and modeling individual junction behavior and hot-spot formation. Investigating both reversible and irreversible mechanisms will contribute to improved performance and reliability of devices.

Single-cell multi-omic analysis of the vestibular schwannoma ecosystem uncovers a nerve injury-like state.

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq (n = 6) and exome sequencing (n = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, and scATAC-seq identifies transcription factors associated with nerve repair SCs from Injury-like tumors. Ligand-receptor analysis and in vitro experiments suggest that Injury-like VS-SCs recruit myeloid cells via CSF1 signaling. Our study indicates that Injury-like SCs may cause tumor growth via myeloid cell recruitment and identifies molecular pathways that may be therapeutically targeted.

Promising New Diagnostic and Treatment Modalities for Allergic Rhinitis: What's Coming Next?

Novel diagnostic tests may help diagnose patients with local allergic rhinitis (AR) when systemic testing is negative or inconclusive. Surgical approaches including septoplasty, inferior turbinate reduction, nasal swell body reduction, and posterior nasal nerve ablation may improve symptoms in patients whose symptoms are refractory to medical therapy, though high-quality evidence is lacking in the AR population. Intralymphatic and epicutaneous immunotherapy have the potential to improve adherence to allergen immunotherapy, though comparisons with current gold standard treatments are lacking and studies reporting long-term outcomes are needed. Immunomodulatory agents in combination with subcutaneous immunotherapy (SCIT) may improve tolerance of SCIT but reports to date do not demonstrate a clear benefit in symptom alleviation. Future work in these areas may support these options as beneficial for testing and treatment of AR.

Postoperative Angiotensin Receptor Blocker Use is Associated With Decreased Rates of Manipulation Under Anesthesia, Arthroscopic Lysis of Adhesions, and Prosthesis-Related Complications in Patients Undergoing Total Knee Arthroplasty.

BACKGROUND: The cellular mechanisms underlying excess scar tissue formation in arthrofibrosis following total knee arthroplasty (TKA) are well-described. Angiotensin receptor blockers (ARB), particularly losartan, is a commonly prescribed antihypertensive with demonstrated antifibrotic properties. This retrospective study aimed to assess the rates of 1- and 2-year postoperative complications in patients who filled prescriptions for ARBs during the 90 days after TKA. METHODS: Patients undergoing primary TKA were selected from a large national insurance database, and the impact of ARB use after TKA on complications was assessed. Of the 1,299,106 patients who underwent TKA, 82,065 had filled at least a 90-day prescription of losartan, valsartan, or olmesartan immediately following their TKA. The rates of manipulation under anesthesia (MUA), arthroscopic lysis of adhesions (LOA), aseptic loosening, periprosthetic fracture, and revision at 1 and 2 years following TKA were analyzed using multivariable logistic regressions to control for various comorbidities. RESULTS: ARB use was associated with decreased rates of MUA (odds ratio [OR] = 0.94, 95% confidence interval (CI), 0.90 to 0.99), arthroscopy/LOA (OR = 0.86, 95% CI, 0.77 to 0.95), aseptic loosening (OR = 0.71, 95% CI, 0.61 to 0.83), periprosthetic fracture (OR = 0.58, 95% CI, 0.46 to 0.71), and revision (OR = 0.79, 95% CI, 0.74 to 0.85) 2 years after TKA. CONCLUSIONS: ARB use throughout the 90 days after TKA is associated with a decreased risk of MUA, arthroscopy/LOA, aseptic loosening, periprosthetic fracture, and revision, demonstrating the potential protective abilities of ARBs. Prospective studies evaluating the use of ARBs in patients at risk for postoperative stiffness would be beneficial to further elucidate this association.

Shoulder Adhesive Capsulitis Prior to Total Knee Arthroplasty is Associated With Increased Rates of Postoperative Stiffness Requiring Manipulation Under Anesthesia and Arthroscopic Lysis of Adhesions.

BACKGROUND: Arthrofibrosis following total knee arthroplasty (TKA) and adhesive capsulitis (AC) of the shoulder develop via a similar pathologic process. The purpose of this study was to examine the relationship between these two conditions. METHODS: This was a retrospective cohort study using a large nationwide claims database. Patients who had a history of shoulder AC prior to TKA were compared to TKA patients who did not have AC history comparing rates of postoperative stiffness, manipulation under anesthesia (MUA), arthroscopic lysis of adhesions (LOAs), and revision arthroplasty at postoperative timepoints (3 months, 6 months, 1 year, and 2 years). RESULTS: Within 3 months, 6 months, 1 year, and 2 years of their TKAs, patients who had a history of AC prior to TKA were significantly more likely to experience stiffness (OR [odds ratio] = 1.29, 1.28, 1.32, and 1.36, respectively) and LOAs (OR = 6.78, 3.65, 2.99, and 2.81, respectively). They also showed increased risk of MUA within 6 months, 1 year, and 2 years (OR = 1.15, 1.15, and 1.16, respectively) of their TKAs. Patients having a preoperative diagnosis of AC did not have an increased risk of undergoing revision surgery 1 year or 2 years after their TKAs (P > .05). CONCLUSIONS: Patients diagnosed with AC prior to TKA experience higher rates of postoperative stiffness, resulting in additional interventions such as MUA and LOAs. These findings identify a particularly high-risk patient population that may benefit from additional interventions prior to and following TKA. LEVEL OF EVIDENCE: This is a level III prognostic study.

Gathering validity evidence for a 3D-printed simulator for training of myringotomy and ventilation tube insertion.

Objectives: This study aimed to gather validity evidence according to Messick's framework for a novel 3D-printed simulator for myringotomy with ventilation tube insertion for use in technical skills training of otorhinolaryngology (ORL) residents. Methods: The study included 15 junior ORL residents (trainees) and 13 experienced teaching otolaryngologists (experts). Experts and trainees first received an identically structured introduction to the procedure, simulator, and simulation setup. Five procedures performed by each participant were video-recorded and ordered randomly for blinded rating by two independent raters. The rating tools used were a global rating scale (GBRS) and a task-specific checklist. Validity evidence was collected according to Messick's framework. Differences in time consumption and performance scores were analyzed. Finally, a pass/fail standard was established using the contrasting groups' method. Results: Trainees used significantly more time per procedure (109 s, 95% CI: 99-120) than experts (82 s, 95% CI: 71-93; p < .001). Adjusted for repetition and rater leniency, experts achieved an average GBRS score of 18.8 (95% CI: 18.3-19.2) out of 20 points, whereas trainees achieved an average of 17.1 points (95% CI: 16.6-17.5; p < .001). In contrast to the task-specific checklist, the GBRS score discriminated between repetition number and participant experience. The pass/fail standard for the GBRS was established at 18.4 points. Conclusion: We established educational validity evidence for a novel 3D-printed model for simulation-based training of ventilation tube insertion and established a reliable pass/fail standard. Level of Evidence: 1b.

Ear tubes in children with otitis media reduce parental sick leave from work and socioeconomic costs.

INTRODUCTION: This study aimed to investigate changes in parental sick leave after tympanostomy tube (TT) insertion in children with otitis media (OM) and to estimate the overall cost reduction in case of decreased caregiver sick leave from work during a 12-month period after TT insertion. METHODS: A total of 4,708 children less-than 12 years from the database of the Danish ENT Specialists Organisation were included. Questionnaires were sent two days prior to TT insertion and subsequently 1, 3, 6, 9, 12, 15, 18, 21 and 24 months after TT insertion. The questions included symptom duration, patient satisfaction and symptom relief. Furthermore, parental sick leave occurrence was registered before and after TT insertion. The overall cost reduction estimate was based on comparison of the direct and indirect costs of two treatment regimes. Treatment A was non-surgical and antibiotics only. Treatment B comprised TT insertion and antibiotics as needed. RESULTS: The main results were that the risk of parental sick leave decreased significantly (p less-than 0.005) one month after TT insertion compared with baseline; odds ratio = 0.21 (95% confidence interval: 0.19-0.24). The decrease remained stable during the entire follow-up period. The estimate of the total cost reduction between Treatment A (non-TT insertion) and Treatment B (TT insertion) was 3,118.34 DKK/child/year. CONCLUSION: TT insertion is associated with a significant decrease in parental sick leave and may possibly contribute to substantial socioeconomic savings. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Hallmarks of transcriptional intratumour heterogeneity across a thousand tumours.

Each tumour contains diverse cellular states that underlie intratumour heterogeneity (ITH), a central challenge of cancer therapeutics1. Dozens of recent studies have begun to describe ITH by single-cell RNA sequencing, but each study typically profiled only a small number of tumours and provided a narrow view of transcriptional ITH2. Here we curate, annotate and integrate the data from 77 different studies to reveal the patterns of transcriptional ITH across 1,163 tumour samples covering 24 tumour types. Among the malignant cells, we identify 41 consensus meta-programs, each consisting of dozens of genes that are coordinately upregulated in subpopulations of cells within many tumours. The meta-programs cover diverse cellular processes including both generic (for example, cell cycle and stress) and lineage-specific patterns that we map into 11 hallmarks of transcriptional ITH. Most meta-programs of carcinoma cells are similar to those identified in non-malignant epithelial cells, suggesting that a large fraction of malignant ITH programs are variable even before oncogenesis, reflecting the biology of their cell of origin. We further extended the meta-program analysis to six common non-malignant cell types and utilize these to map cell-cell interactions within the tumour microenvironment. In summary, we have assembled a comprehensive pan-cancer single-cell RNA-sequencing dataset, which is available through the Curated Cancer Cell Atlas website, and leveraged this dataset to carry out a systematic characterization of transcriptional ITH.

A scoping review of institutional policies and recommendations for trans inpatient mental health care.

WHAT IS KNOWN ON THE SUBJECT?: International guidelines for trans-and-gender-non-conforming (TGNC) exists in outpatient settings. Compared to cisgender and heterosexual people, TGNC individuals are at a higher risk of mental health difficulties and have higher rates of inpatient mental health treatment. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: An international scoping review identifying the lack of guidelines existing for TGNC individuals in inpatient mental health settings. Compared to psychiatrists and psychologists, mental health nursing has the most contact with patients admitted for inpatient psychiatric treatment. The study identifies unaddressed needs in gender affirming policies and outlines preliminary policy recommendations to assist mental health staff in improving TGNC patient quality of care within the United States. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Reforming existing guidelines or creating new guidelines based on the identified themes and gaps to improve the well-being and treatment outcomes of TGNC individuals in inpatient psychiatric settings within the United States. ABSTRACT: INTRODUCTION: Access to culturally sensitive care is critical for addressing known mental health disparities among trans-and gender-non-conforming (TGNC) individuals. Although there has been a proliferation of TGNC healthcare guidelines from accrediting bodies, policies have failed to address the needs of TGNC patients in inpatient psychiatric settings. AIM: To identify unaddressed needs in policies and policy recommendations for the care of TGNC patients to inform recommendations for change. METHOD: A scoping review protocol was developed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 850 articles were reduced to seven relevant articles with six themes identified via thematic analysis. RESULTS: Six themes were identified: lack of consistency in preferred and pronoun use, lack of communication among providers, lack of training in TGNC healthcare, personal bias, lack of formal policies, and housing segregation by sex rather than gender. DISCUSSION: The creation of new guidelines or bolstering of existing guidelines to specifically address identified themes and gaps may improve the well-being and treatment outcomes of TGNC individuals in inpatient psychiatric settings. IMPLICATIONS FOR PRACTICE: To provide a foundation for future studies to integrate these identified gaps and inform the future development of comprehensive formal policies that generalize TGNC care in inpatient settings.

Cellular states are coupled to genomic and viral heterogeneity in HPV-related oropharyngeal carcinoma.

Head and neck squamous cell carcinoma (HNSCC) includes a subset of cancers driven by human papillomavirus (HPV). Here we use single-cell RNA-seq to profile both HPV-positive and HPV-negative oropharyngeal tumors, uncovering a high level of cellular diversity within and between tumors. First, we detect diverse chromosomal aberrations within individual tumors, suggesting genomic instability and enabling the identification of malignant cells even at pathologically negative margins. Second, we uncover diversity with respect to HNSCC subtypes and other cellular states such as the cell cycle, senescence and epithelial-mesenchymal transitions. Third, we find heterogeneity in viral gene expression within HPV-positive tumors. HPV expression is lost or repressed in a subset of cells, which are associated with a decrease in HPV-associated cell cycle phenotypes, decreased response to treatment, increased invasion and poor prognosis. These findings suggest that HPV expression diversity must be considered during diagnosis and treatment of HPV-positive tumors, with important prognostic ramifications.

Evidence-Based Medicine for Mandible Fracture Repair: Current Controversies and Future Opportunities.

Mandibular fractures are among the most common facial fractures resulting from trauma. The nature of the injury, involved facial structures, presence of associated injuries, the dental status of the patient, comorbid conditions, and psychosocial context all must be considered by the surgeon when planning the optimal treatment for these patients. While consensus exists for many aspects of the management of mandibular trauma, some elements remain controversial. Three such topics-antibiotic therapy, treatment of subcondylar fractures, and management of the third molar-remain particularly controversial, with significant heterogeneity in practice patterns and without widely accepted evidence-based guidelines to standardize care. The goals of this work are to (1) review the historical perspective underlying these controversies, (2) summarize recent evidence shaping the current debate, and (3) highlight opportunities for continued efforts to identify best practices.

ManyFold: an efficient and flexible library for training and validating protein folding models.

SUMMARY: ManyFold is a flexible library for protein structure prediction with deep learning that (i) supports models that use both multiple sequence alignments (MSAs) and protein language model (pLM) embedding as inputs, (ii) allows inference of existing models (AlphaFold and OpenFold), (iii) is fully trainable, allowing for both fine-tuning and the training of new models from scratch and (iv) is written in Jax to support efficient batched operation in distributed settings. A proof-of-concept pLM-based model, pLMFold, is trained from scratch to obtain reasonable results with reduced computational overheads in comparison to AlphaFold. AVAILABILITY AND IMPLEMENTATION: The source code for ManyFold, the validation dataset and a small sample of training data are available at https://github.com/instadeepai/manyfold. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Increased Risk of Hospital Readmissions and Implant-Related Complications in Patients Who Had a Recent History of Fragility Fracture: A Matched Cohort Analysis.

BACKGROUND: With the increasing utilization of total knee arthroplasty (TKA) in a continually aging US population, the number of patients who have low bone mineral density who undergo TKA may concomitantly increase. This study aimed to assess the rates of short-term complications following TKA in patients who did and did not have a recent history of a prior fragility fracture. METHODS: A matched retrospective cohort study analyzing 48,796 patients was performed using a national database to determine the impact of a preceding fragility fracture on rates of short-term complications following TKA. The rates of complications at 1 and 2 years post-TKA were analyzed using multivariate logistic regressions. RESULTS: Prior fragility fracture was associated with increased rates of 1-year hospital readmissions (hazard ratio = 1.30, 95% CI, 1.22-1.38), periprosthetic fractures (odds ratio [OR] = 2.72, 95% CI, 1.89-3.99), non-infection-related revisions (OR = 1.32, 95% CI, 1.09-1.60), secondary fragility fractures (OR = 4.62, 95% CI, 4.19-5.12), prosthesis dislocations (OR = 1.76, 95% CI, 1.22-2.56), prosthesis instabilities (OR = 1.64, 95% CI, 1.25-2.15), and periprosthetic infections (OR = 1.49, 95% CI, 1.29-1.71), with similar trends in implant-related complications also seen at the 2-year mark. Patients who filled a prescription for osteoporosis pharmacotherapy had clinically similar rates of these complications compared to those who did not. CONCLUSION: Sustaining a fragility fracture prior to TKA is associated with an increased risk of hospital readmission and significant implant-related postoperative complications, potentially increasing the morbidity and mortality of TKA in these patients.

Plasma IL13Rα2 as a novel liquid biopsy biomarker for glioblastoma.

PURPOSE: Glioblastoma (GBM) is the most common and deadliest brain tumor with unrelenting and rapid disease progression. The standard of care for GBM is surgical excision followed by radiation with concurrent and adjuvant temozolomide-centered chemotherapy (TMZ). Treatment failure and resistance is the rule and despite advances in imaging technology, early detection of treatment failure or impending resistance remains a challenge. There is a dire, unmet, need in clinical practice for minimally-invasive diagnostic tools to enable timely understanding of disease progression and treatment response. Here, we aim to address this clinical need by leveraging a unique characteristic of GBM: the overexpression of the α2 variant of the IL-13 receptor in over 75% of GBM tumors. METHODS: In this study we examined patients with primary GBM from Penn State and Cleveland Clinic compared to healthy controls. RESULTS: IL13Rα2 was detectable in plasma of GBM patients using ELISA but detection could be optimized by PEG precipitation to enrich for extracellular vesicles (EVs). Patients with GBM had elevated levels of plasma IL13Rα2, which correlated to levels of this receptor in the tumor tissue. Elevated plasma levels of IL13Rα2 predicted longer overall survival (OS) (19.8 vs. 13.2 months). Similarly, detection of IL13Rα2 + cells in tumor tissue also predicted longer OS (22.1 vs. 12.2 months). CONCLUSION: These findings strongly suggest that expression of the IL13Rα2 receptor confer survival advantage in GBM patients, which can be determined through a minimally-invasive liquid biopsy. Detection of plasma IL13Rα2 can also be used to select GBM patients for targeted tumor therapy.

All-Carbon Nanotube Solar Cell Devices Mimic Photosynthesis.

Both solar cells and photosynthetic systems employ a two-step process of light absorption and energy conversion. In photosynthesis, they are performed by distinct proteins. However, conventional solar cells use the same semiconductor for optical absorption and electron-hole separation, leading to inefficiencies. Here, we show that an all-semiconducting single-walled carbon nanotube (s-SWCNTs) device provides an artificial system that models photosynthesis in a tandem geometry. We use distinct chirality s-SWCNTs to separate the site and direction of light absorption from those of power generation. Using different bandgap s-SWCNTs, we implement an energy funnel in dual-gated p-n diodes. The device captures photons from multiple regions of the solar spectrum and funnels photogenerated excitons to the smallest bandgap s-SWCNT layer, where they become free carriers. We demonstrate an increase in the photoresponse by adding more s-SWCNT layers of different bandgaps without a corresponding deleterious increase in the dark leakage current.

The Case of Disappearing Tibia in Rheumatoid Knee Tenosynovitis.

Introduction: Knee pain and osteoarthritis are frequent patient complaints, with a rapidly increasing prevalence. By comparison, the prevalence of rheumatoid arthritis (RA) is significantly lower at around 1%. Inflammatory arthropathies, like RA, are difficult to differentiate from infection, crystal arthropathies, or malignancy. In addition, radiography and roentgenograms are often inconclusive or non-specific, making it much more difficult to evaluate, diagnose, and manage this condition. The current case is unique due to its location in the knee joint, rather than more common presentations in the upper extremities, and use of MRI imaging for diagnosis of RA with tenosynovitis. Case Report: In a Caucasian 70-year-old female with sudden debilitating knee pain and a large atraumatic defect over tibial plateau, MRI showed a large fluid collection within the left gracilis muscle. Gram stain and culture of the aspirate remained negative. The only significant history involved a possible diagnosis of RA. Conclusion: While rheumatoid tenosynovitis is common in the upper extremities, lower extremity features have not been well reported before. We diagnosed the patient with progressive RA and rheumatoid tenosynovitis. This unique presentation and rare usage of MRI imaging may be contributing to an underreporting of this diagnosis in the lower extremities.

Epithelial-Mesenchymal Plasticity in Tumor Immune Evasion.

Epithelial-mesenchymal transition (EMT) is a fundamental process that occurs during embryogenesis and tissue repair. However, EMT can be hijacked by malignant cells, where it may promote immune evasion and metastasis. Classically considered a dichotomous transition, EMT in cancer has recently been considered a plastic process whereby malignant cells display and interconvert among hybrid epithelial/mesenchymal (E/M) states. Epithelial-mesenchymal plasticity (EMP) and associated hybrid E/M states are divergent from classical EMT, with unique immunomodulatory effects. Here, we review recent insights into the EMP-immune cross-talk, highlighting possible mechanisms of immune evasion conferred by hybrid E/M states and roles of immune cells in EMP.