Identity and nature of neural stem cells in the adult human subventricular zone.

The existence of neural stem cells (NSCs) in adult human brain neurogenic regions remains unresolved. To address this, we created a cell atlas of the adult human subventricular zone (SVZ) derived from fresh neurosurgical samples using single-cell transcriptomics. We discovered 2 adult radial glia (RG)-like populations, aRG1 and aRG2. aRG1 shared features with fetal early RG (eRG) and aRG2 were transcriptomically similar to fetal outer RG (oRG). We also captured early neuronal and oligodendrocytic NSC states. We found that the biological programs driven by their transcriptomes support their roles as early lineage NSCs. Finally, we show that these NSCs have the potential to transition between states and along lineage trajectories. These data reveal that multipotent NSCs reside in the adult human SVZ.

A Multicenter Validity Study of Four Smartphone Hearing Test Apps in Optimized and Home Environments.

OBJECTIVE: Pure tone audiometry (PTA) is the gold standard for hearing assessment. However, it requires access to specialized equipment. Smartphone audiometry applications (apps) have been developed to perform automated threshold audiometry and could allow patients to perform self-administered screening or monitoring. This study aimed to assess the validity and feasibility of patients using apps to self-assess hearing thresholds at home, with comparison to PTA. METHODS: A multi-center, prospective randomized study was conducted amongst patients undergoing PTA in clinics. Participants were randomly allocated to one of four publicly-available apps designed to measure pure tone thresholds. Participants used an app once in optimal sound-treated conditions and a further three times at home. Ear-specific frequency-specific thresholds and pure tone average were compared using Pearson correlation coefficient. The percentage of app hearing tests with results within ±10 dB of PTA was calculated. Patient acceptability was assessed via an online survey. RESULTS: One hundred thirty-nine participants submitted data. The results of two at-home automated smartphone apps correlated strongly/very strongly with PTA average and their frequency-specific median was within ±10 dB accuracy. Smartphone audiometry performed in sound-treated and home conditions were very strongly correlated. The apps were rated as easy/very easy to use by 90% of participants and 90% would be happy/very happy to use an app to monitor their hearing. CONCLUSION: Judicious use of self-performed smartphone audiometry was both valid and feasible for two of four apps. It could provide frequency-specific threshold estimates at home, potentially allowing assessments of patients remotely or monitoring of fluctuating hearing loss. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:2864-2870, 2024.

Analysis of google trends and search results for ophthalmic symptoms of monkeypox.

PURPOSE: In July 2022, the World Health Organization (WHO) declared monkeypox virus's global spread a "public health emergency of international concern." About a quarter of monkeypox cases feature ophthalmic symptoms. We assessed trends in worldwide search interest in monkeypox ophthalmic involvement and inclusion in online search engine queries. METHODS: The following keywords were searched on Google Trends from April 1, 2022, to August 12, 2022: monkeypox + eye, pink eye, eye infection, eyelid, vision, blurry vision, vision loss, blindness, eye symptoms, eye problems, eye pain, eye redness, conjunctivitis, conjunctiva, cornea, keratitis, corneal ulcer, and blepharitis. We analyzed trends, correlated search interest with case count data, and compared popularity of search terms via nonparametric Mann-Whitney-U analysis. Inclusion of ophthalmic symptoms in Google search results for "monkeypox symptoms" was assessed. RESULTS: "Monkeypox eye" had the highest average search interest worldwide and in the United States. Search interest peaked between mid-May and late July 2022. When compared to interest in "monkeypox rash," the most searched monkeypox symptom, the average interest in "monkeypox eye" was lower (p < 0.01). Of the first 50 results from the Google search of "monkeypox symptoms," 10/50 (20%) mentioned ophthalmic symptoms. 6/50 (12%) mentioned the eye as a route of virus transmission. CONCLUSION: Search interest in monkeypox ophthalmic symptoms corresponds with geographic and temporal trends, i.e., timing and location of the first reported non-endemic cases and WHO announcement. Although ophthalmic symptoms are not as widely searched currently, inclusion in public health messaging is key for diagnosis, appropriate management, and reduction of further transmission.

Exploring patient experiences and concerns in the online Cochlear implant community: A cross-sectional study and validation of automated topic modelling.

OBJECTIVE: There is a paucity of research examining patient experiences of cochlear implants. We sought to use natural language processing methods to explore patient experiences and concerns in the online cochlear implant (CI) community. MATERIALS AND METHODS: Cross-sectional study of posts on the online Reddit r/CochlearImplants forum from 1 March 2015 to 11 November 2021. Natural language processing using the BERTopic automated topic modelling technique was employed to cluster posts into semantically similar topics. Topic categorisation was manually validated by two independent reviewers and Cohen's kappa calculated to determine inter-rater reliability between machine vs human and human vs human categorisation. RESULTS: We retrieved 987 posts from 588 unique Reddit users on the r/CochlearImplants forum. Posts were initially categorised by BERTopic into 16 different Topics, which were increased to 23 Topics following manual inspection. The most popular topics related to CI connectivity (n = 112), adults considering getting a CI (n = 107), surgery-related posts (n = 89) and day-to-day living with a CI (n = 85). Cohen's kappa among all posts was 0.62 (machine vs. human) and 0.72 (human vs. human), and among categorised posts was 0.85 (machine vs. human) and 0.84 (human vs. human). CONCLUSIONS: This cross-sectional study of social media discussions among the online cochlear implant community identified common attitudes, experiences and concerns of patients living with, or seeking, a cochlear implant. Our validation of natural language processing methods to categorise topics shows that automated analysis of similar Otolaryngology-related content is a viable and accurate alternative to manual qualitative approaches.

From Fitting the Average to Fitting the Individual: A Cautionary Tale for Mathematical Modelers.

An outstanding challenge in the clinical care of cancer is moving from a one-size-fits-all approach that relies on population-level statistics towards personalized therapeutic design. Mathematical modeling is a powerful tool in treatment personalization, as it allows for the incorporation of patient-specific data so that treatment can be tailor-designed to the individual. Herein, we work with a mathematical model of murine cancer immunotherapy that has been previously-validated against the average of an experimental dataset. We ask the question: what happens if we try to use this same model to perform personalized fits, and therefore make individualized treatment recommendations? Typically, this would be done by choosing a single fitting methodology, and a single cost function, identifying the individualized best-fit parameters, and extrapolating from there to make personalized treatment recommendations. Our analyses show the potentially problematic nature of this approach, as predicted personalized treatment response proved to be sensitive to the fitting methodology utilized. We also demonstrate how a small amount of the right additional experimental measurements could go a long way to improve consistency in personalized fits. Finally, we show how quantifying the robustness of the average response could also help improve confidence in personalized treatment recommendations.

Echocardiographic and Other Preprocedural Predictors of Heart Failure After TIPS Placement in Patients With Cirrhosis: A Single-Center 15-Year Analysis.

BACKGROUND. Heart failure (HF) is an uncommon complication after TIPS placement; its development represents a poor prognostic factor. OBJECTIVE. The purpose of our study was to evaluate the frequency, risk factors, and association with survival of HF developing within 90 days after TIPS placement in patients with cirrhosis. METHODS. This retrospective single-center study included patients with cirrhosis who underwent nonemergent covered-stent TIPS placement from June 2003 to December 2018 and who underwent echocardiography within 2 months before TIPS placement and had at least 90 days of post-TIPS follow-up. Development of HF within 90 days after TIPS was recorded. Frequency of TIPS reduction for post-TIPS HF was determined. Univariable logistic regression analysis and ROC curve analysis were performed to assess potential risk factors for post-TIPS HF. Association of post-TIPS HF and 1-year survival was assessed by the log rank test. RESULTS. The study sample included 107 patients (71 men and 36 women; median age, 58 years). Post-TIPS HF developed in 11 of 107 (10%) patients; median time to development of HF was 16 days (range, 2-62 days). Of these 11 patients, three (27%) required TIPS reduction to achieve resolution of HF symptoms after unsuccessful diuretic therapy. Pre-TIPS right atrium size (odds ratio [OR], 3.26 [95% CI, 1.22-10.16]; p = .03], left ventricle (LV) end-systolic dimension (OR, 5.43 [95% CI, 1.44-24.50], p = .02), LV end-diastolic dimension (OR, 4.12 [95% CI, 1.51-13.47]; p = .009), and estimated peak pulmonary artery systolic pressure (PASP) (OR, 1.27 [95% CI, 1.12-1.50]; p = .001) were associated with post-TIPS HF. AUC of right atrium size, LV end-systolic dimension, LV end-diastolic dimension, and estimated peak PASP for development of post-TIPS HF were 0.71, 0.74, 0.72, and 0.83, respectively. At a cutoff of 31 mm Hg, PASP achieved sensitivity of 70% and specificity of 86% for post-TIPS HF. Patients with post-TIPS HF and those without post-TIPS HF had 1-year survival of 46% versus 73% (p = .06). CONCLUSION. Multiple pre-TIPS echocardiographic variables predict the development of post-TIPS HF in patients with cirrhosis. CLINICAL IMPACT. Preprocedural echocardiography may guide risk stratification in patients with cirrhosis being considered for TIPS placement.

Lumen-apposing covered self-expanding metallic stent for symptomatic pancreatic fluid collections: assessment of outcomes and complications with CT and MRI.

PURPOSE: To assess technical and clinical outcomes following lumen-apposing covered self-expanding metallic stent (LAMS) placement for symptomatic pancreatic fluid collections (PFC) with CT and MRI. METHODS: In this retrospective study, patients with PFC who underwent LAMS placement between March 2015 and June 2018 were included. Primary outcomes included technical success, defined as successful stent placement with resolution of PFC, and clinical success, defined as lack of fluid recurrence after stent removal. Secondary outcomes included time duration from stent placement to removal, complications, and re-intervention need. RESULTS: 28 consecutive patients (20 men, mean age: 53 years ± 17; range 21-75) who underwent endoscopic drainage of symptomatic walled-off necrosis (WON, 21/28, 75%), pseudocyst (PC, 5/28, 18%) or acute necrotic collection (ANC, 2/28, 7%) were included. LAMS were placed successfully in 27/28 (96%) patients. On follow-up imaging after at least one month (n = 24), the volume of the PFC decreased by 99.9% from 425 cm3 [IQR 214 - 636] to 0.6 cm3 [IQR 0-43.9]. After stent removal, 26/27 (96%) patients remained collection free. The median time duration from stent placement to removal was 42 days [IQR 34-71]. Complications (10/28; 36%) included stent occlusion (n = 1), stent migration (n = 3), intraprocedural bleeding (n = 2), postprocedural bleeding (n = 2), and pseudoaneurysm formation (n = 2). Re-intervention was required in 7/27 (26%). CONCLUSION: Following LAMS placement in patients with symptomatic PFC, high technical and clinical success rates of 96% and 96%, respectively, are achieved. Awareness of common complications seen on cross-sectional imaging might help radiologists and gastroenterologist in the patients' management.

Clonal hematopoiesis and inflammation: Partners in leukemogenesis and comorbidity.

Clonal hematopoiesis (CH) of indeterminate potential (CHIP), defined as the presence of a somatic mutation in the peripheral blood at a variant allele frequency (VAF) ≥2%, affects at least 10% of individuals older than 65, but low-VAF clones can be detected in 95% of individuals older than 50. CHIP associates with a wide range of comorbidities from atherosclerosis to pulmonary disease. A growing body of evidence, primarily from studies involving Tet2-knockout and stem cell transplant models of CH, suggest that dysregulated inflammation contributes to clonal expansion and associated comorbidities. Mutant leukocytes from animal models contribute to an inflammatory milieu that may confer a selective advantage to the clone, thus perpetuating a cycle of inflammation and expansion. Although it is unclear whether inflammation or expansion sets this cycle in motion, some evidence suggests that inflammation from infections or pre-existing comorbidities initiates this cycle. The pro-inflammatory phenotypes of macrophages from mutant clones and their contributions to disease are well characterized in murine models, but have not yet been confirmed in humans. Furthermore, the roles of other cell types that can carry mutations of CHIP are not fully understood. We propose a rationale for further investigation of neutrophils, other granulocytes and T, B, and NK cells as they may play a role in CHIP-associated comorbidities. As the understanding of CH has advanced, potential interventions, especially those targeting aberrant inflammation, have been proposed. We are hopeful that as studies continue to unravel the complex links between CHIP, inflammation, and leukocyte dysfunction, CHIP-related comorbidities may be more effectively managed.

Electronic IR Group Peer Review and Learning Performed during Daily Clinical Rounds.

PURPOSE: To describe the implementation and efficacy of electronic capture of interventional radiology (IR) group peer review performed during morning rounds in an academic institution. MATERIALS AND METHODS: Peer-review submissions 24 months before (July 2012 through June 2014) and 24 months after (July 2014 through June 2016) implementation of an electronic group IR peer review were evaluated. Electronic IR peer review assessed clinical decision-making, patient care, and technique appropriateness by using the following responses: agree, acceptable alternative, or inappropriate. Complications, near-misses, and learning opportunities were also noted, and explanations were provided in the comments. An IR attending physician documented the consensus discussion via an online form or mobile app. RESULTS: After implementation of electronic capture of IR group peer reviews, 9.5% of all IR procedures (773 of 8,152) were reviewed, compared with 0.9% (63 of 7,152) before the implementation (P < .0001). On average, 3.4 ± 0.5 IR attending physicians participated in each review, and 17.3 ± 9.7 IR cases were reviewed per month by each attending physician. Peers fully agreed with the chosen technique in 729 of 773 cases (94.3%) and noted an acceptable alternative technique in 40 of 773 (5.2%). In 4 cases (0.5%), the chosen technique was rated as inappropriate. Peers fully agreed with chosen clinical decision-making and patient care in 765 of 773 cases (99%), with 8 cases (1%) deemed as acceptable alternatives. Learning opportunities were documented in 9.6% of cases (74 of 773). CONCLUSIONS: Electronic IR-specific group peer review captures the clinical decision-making process, patient outcomes, technical appropriateness, and short-term complications and may provide practice-improvement solutions.

Integrative Transcriptomic Analysis Reveals a Multiphasic Epithelial-Mesenchymal Spectrum in Cancer and Non-tumorigenic Cells.

Epithelial-mesenchymal transition (EMT), the conversion between rigid epithelial cells and motile mesenchymal cells, is a reversible cellular process involved in tumorigenesis, metastasis, and chemoresistance. Numerous studies have found that several types of tumor cells show a high degree of cell-to-cell heterogeneity in terms of their gene expression signatures and cellular phenotypes related to EMT. Recently, the prevalence and importance of partial or intermediate EMT states have been reported. It is unclear, however, whether there is a general pattern of cancer cell distribution in terms of the overall expression of epithelial-related genes and mesenchymal-related genes, and how this distribution is related to EMT process in normal cells. In this study, we performed integrative transcriptomic analysis that combines cancer cell transcriptomes, time course data of EMT in non-tumorigenic epithelial cells, and epithelial cells with perturbations of key EMT factors. Our statistical analysis shows that cancer cells are widely distributed in the EMT spectrum, and the majority of these cells can be described by an EMT path that connects the epithelial and the mesenchymal states via a hybrid expression region in which both epithelial genes and mesenchymal genes are highly expressed overall. We found that key patterns of this EMT path are observed in EMT progression in non-tumorigenic cells and that transcription factor ZEB1 plays a key role in defining this EMT path via diverse gene regulatory circuits connecting to epithelial genes. We performed Gene Set Variation Analysis to show that the cancer cells at hybrid EMT states also possess hybrid cellular phenotypes with both high migratory and high proliferative potentials. Our results reveal critical patterns of cancer cells in the EMT spectrum and their relationship to the EMT process in normal cells, and provide insights into the mechanistic basis of cancer cell heterogeneity and plasticity.

Structured Reporting of IR Procedures: Effect on Report Compliance, Accuracy, and Satisfaction.

PURPOSE: To compare effect of free-text versus structured reporting of IR procedures on report quality and report coding and value. MATERIALS AND METHODS: In this retrospective study, 432 common consecutive free-text IR reports created during 4 months (from September 2013 to December 2013) before implementation of structured reporting (February 2014) and 415 structured IR reports created after implementation (from September 2014 to December 2014) were reviewed to assess ease of use and compliance with reporting requirements for regulatory requirements and coding. IR staff and trainees and referring physicians to IR were surveyed on procedure report attributes, such as detail, quality, and clarity. RESULTS: Structured reporting increased compliance with reporting fluoroscopy time, radiation dose, and contrast administration compared with free-text reports (402/432 [93.1%] vs 251/415 [60.5%], P < .001; 402/432 [93.1%] vs 242/415 [58.3%], P < .001; and 395/432 [91.4%] vs 257/415 [61.9%], P < .001). Structured reporting decreased addendum requests for insufficient documentation from 43% (121/435 [28%] to 50/415 [12%], P = .01). Most IR physicians found structured reports to require less time to complete (21/26 [81%]), to be easier to complete (23/26 [89%]), and to have a similar or higher level of detail (19/26 [73%]) compared with free-text reports. Referring physicians were more satisfied with structured reports compared with free-text reports (6.9/10 vs 5.6/10, P = .03). CONCLUSIONS: Structured IR reporting compared with free-text reporting improves compliance with radiation dose and contrast reporting, reporting and coding efficiency, and satisfaction among IR and referring physicians.

Does Implant Design Influence the Accuracy of Patient Specific Instrumentation in Total Knee Arthroplasty?

PSI software adjusts preoperative planning to accommodate differences in implant design. Such adjustments may influence the accuracy of intraoperative jig placement, bone resection, or component placement. Our purpose was to determine whether implant design influences PSI accuracy. 96 and 123 PSI TKA were performed by a single surgeon using two different implant systems and identical PSI software. Femoral coronal alignment outliers were greater for Implant 1 (23.9% Implant 1 vs. 13.4% Implant 2; P=0.050). Tibial coronal alignment outliers were greater for Implant 2 (10.9% Implant 1 vs. 22.7% Implant 2; P=0.025). There was no difference in overall mechanical axes. Differences in implant design can influence bone resection and component alignment. PSI software rationale must align with surgeons' intraoperative goals.

Clinical, functional, and radiographic outcomes following total knee arthroplasty with patient-specific instrumentation, computer-assisted surgery, and manual instrumentation: a short-term follow-up study.

PURPOSE: The purpose of this study was to evaluate clinical, functional, and radiographic outcomes following total knee arthroplasty (TKA) performed with patient-specific instrumentation (PSI), computer-assisted surgery (CAS), and manual instruments at short-term follow-up. METHODS: 122 TKAs were performed by a single surgeon: 42 with PSI, 38 with CAS, and 40 with manual instrumentation. Preoperative, 1-month, and 6-month clinical and functional outcomes were measured using the Knee Society scoring system (knee score, function score, range of motion, and pain score). Improvements in clinical and functional outcomes from the preoperative to postoperative period were analyzed. Preoperative and postoperative radiographs were measured to evaluate limb and component alignment. RESULTS: Preoperative, 1-month postoperative, and 6-month postoperative knee scores, function scores, range of motion, and pain scores were highest in the PSI group compared to CAS and manual instrumentation. At 6-month follow-up, PSI TKA was associated with a statistically significant improvement in functional score when compared to manual TKA. Otherwise, there were no statistically significant differences in improvements among PSI, CAS, and manual TKA groups. CONCLUSION: The higher preoperative scores in the PSI group limits the ability to draw definitive conclusions from the raw postoperative scores, but analyzing the changes in scores revealed that PSI was associated with a statistically significant improvement in Knee Society Functional score at 6-month post-TKA as compared to CAS or manual TKA. This may be attributable to improvements in component rotation and positioning, improved component size accuracy, or other factors that are not discernible on plain radiograph.

Computer-assisted versus manual TKA: no difference in clinical or functional outcomes at 5-year follow-up.

The purpose of this study was to determine whether differences in clinical, functional, or radiographic outcomes existed at 5-year follow-up between patients who underwent computer-assisted or manual total knee arthroplasty (TKA). Seventy-eight consecutive TKAs were performed by a single surgeon who had extensive experience performing computer-assisted and manual TKA. The manual group (n=40) and computer-assisted group (n=38) were similar with regard to age, sex, diagnosis, body mass index, surgical technique, implants, perioperative management, Knee Society scores, and anteroposterior mechanical axis. Sixty-three (manual group, n=34; computer-assisted group, n=29) patients were available for final follow-up. At 5-year follow-up, no statistically significant differences were found in Knee Society knee score (P=.289), function score (P=.272), range of motion (P=.284), pain score (P=.432), or UCLA activity score (P=.109) between the 2 groups. Postoperative radiographs showed a significant difference in the mechanical axis (P=.004) between the 2 groups; however, both groups achieved a neutral mechanical axis of ±3° (computer-assisted group mean, 2.0°; manual group mean, -0.24°).When TKA was performed by an experienced surgeon, no significant difference was identified at 5-year follow-up between patients who underwent computer-assisted vs manual TKA.

Component sizing in total knee arthroplasty: patient-specific guides vs. computer-assisted navigation.

INTRODUCTION: Patient-specific guides (PSG) and computer-assisted navigation (CAN) are technologies that have been developed to improve the accuracy and reproducibility of total knee arthroplasty (TKA). The purpose of this study is to compare the methodology by which a PSG system and an intraoperative navigation system (CAN) perform an anatomical registration and correctly predict femoral component size in TKA. METHODS: One hundred and eleven PSG TKA were performed, 30 of which were concurrently evaluated with CAN. PSG-predicted and CAN-predicted femoral component size were compared with the actual component selection. The process by which PSG and CAN determines component sizing was evaluated. RESULTS: The PSG system was both more accurate and more precise than the CAN navigation system in predicting femoral component size in TKA. CONCLUSION: In this study, the surgeon's final component selection was more likely to be in accordance with the PSG rather than the CAN sizing algorithm. This study suggests that intraoperative surface registration may not be as accurate as preoperative three-dimensional magnetic resonance imaging reconstructions for establishing optimal femoral component sizing.

Synthesis of carbon-11-labeled tariquidar derivatives as new PET agents for imaging of breast cancer resistance protein (ABCG2).

Carbon-11-labeled tariquidar derivatives were first designed and synthesized as new PET agents for imaging of breast cancer resistance protein. The target tracers were prepared by O-[(11)C]methylation of their corresponding acid precursors using [(11)C]CH3OTf under basic conditions and isolated by a simplified solid-phase extraction (SPE) method in 50-60% radiochemical yields based on [(11)C]CO(2) and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 15-20 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 111-185 GBq/micromol.