Protocadherin-1 is essential for cell entry by New World hantaviruses.

The zoonotic transmission of hantaviruses from their rodent hosts to humans in North and South America is associated with a severe and frequently fatal respiratory disease, hantavirus pulmonary syndrome (HPS)1,2. No specific antiviral treatments for HPS are available, and no molecular determinants of in vivo susceptibility to hantavirus infection and HPS are known. Here we identify the human asthma-associated gene protocadherin-1 (PCDH1)3-6 as an essential determinant of entry and infection in pulmonary endothelial cells by two hantaviruses that cause HPS, Andes virus (ANDV) and Sin Nombre virus (SNV). In vitro, we show that the surface glycoproteins of ANDV and SNV directly recognize the outermost extracellular repeat domain of PCDH1-a member of the cadherin superfamily7,8-to exploit PCDH1 for entry. In vivo, genetic ablation of PCDH1 renders Syrian golden hamsters highly resistant to a usually lethal ANDV challenge. Targeting PCDH1 could provide strategies to reduce infection and disease caused by New World hantaviruses.

Validation of smartphone app-based digital patient reported outcomes in full-endoscopic spine surgery.

PURPOSE: Patient reported outcome measures (PROMs) are important tools to assess patient function, pain, disability, and quality of life. We aim to study the efficiency and validity of digital PROMs collection using a smartphone app compared to traditional paper PROMs. METHODS: Patients undergoing evaluation for full-endoscopic spine surgery were recruited from the outpatient clinic at Harborview Medical Center. Visual analogue scale (VAS), Oswestry disability index (ODI), and EQ5-5D PROMs were administered on paper and through a smartphone app called SpineHealthie. Compliance rates were collected, and PROM results were assessed for correlation between paper and digital methods. RESULTS: 123 patients were enrolled. 57.7% of patients completed paper PROMs, 82.9% completed digital PROMs, and 48.8% completed both. Of the patients that completed both, Spearman's correlation was greatest for VAS leg, ODI, and EQ5 index scores. Correlation was weaker for VAS back pain, neck pain, and upper extremity pain. Patients tended to report lower disability and higher quality of life on the digital PROM compared to the paper PROM. CONCLUSION: The SpineHealthie app effectively and accurately collects PROMs digitally, showing strong concordance with traditional paper PROMs. We conclude that digital PROMs constitute a promising strategy for monitoring patients after spine surgery over time.

Innate Control of Tissue-Reparative Human Regulatory T Cells.

Regulatory T cell (Treg) therapy is a potential curative approach for a variety of immune-mediated conditions, including autoimmunity and transplantation, in which there is pathological tissue damage. In mice, IL-33R (ST2)-expressing Tregs mediate tissue repair by producing the growth factor amphiregulin, but whether similar tissue-reparative Tregs exist in humans remains unclear. We show that human Tregs in blood and multiple tissue types produced amphiregulin, but this was neither a unique feature of Tregs nor selectively upregulated in tissues. Human Tregs in blood, tonsil, synovial fluid, colon, and lung tissues did not express ST2, so ST2+ Tregs were engineered via lentiviral-mediated overexpression, and their therapeutic potential for cell therapy was examined. Engineered ST2+ Tregs exhibited TCR-independent, IL-33-stimulated amphiregulin expression and a heightened ability to induce M2-like macrophages. The finding that amphiregulin-producing Tregs have a noneffector phenotype and are progressively lost upon TCR-induced proliferation and differentiation suggests that the tissue repair capacity of human Tregs may be an innate function that operates independently from their classical suppressive function.

Functional genomic characterization of a synthetic anti-HER3 antibody reveals a role for ubiquitination by RNF41 in the anti-proliferative response.

Dysregulation of the ErbB family of receptor tyrosine kinases is involved in the progression of many cancers. Antibodies targeting the dimerization domains of family members EGFR and HER2 are approved cancer therapeutics, but efficacy is restricted to a subset of tumors and resistance often develops in response to treatment. A third family member, HER3, heterodimerizes with both EGFR and HER2 and has also been implicated in cancer. Consequently, there is strong interest in developing antibodies that target HER3, but to date, no therapeutics have been approved. To aid the development of anti-HER3 antibodies as cancer therapeutics, we combined antibody engineering and functional genomics screens to identify putative mechanisms of resistance or synthetic lethality with antibody-mediated anti-proliferative effects. We developed a synthetic antibody called IgG 95, which binds to HER3 and promotes ubiquitination, internalization, and receptor down-regulation. Using an shRNA library targeting enzymes in the ubiquitin proteasome system, we screened for genes that effect response to IgG 95 and uncovered the E3 ubiquitin ligase RNF41 as a driver of IgG 95 anti-proliferative activity. RNF41 has been shown previously to regulate HER3 levels under normal conditions and we now show that it is also responsible for down-regulation of HER3 upon treatment with IgG 95. Moreover, our findings suggest that down-regulation of RNF41 itself may be a mechanism for acquired resistance to treatment with IgG 95 and perhaps other anti-HER3 antibodies. Our work deepens our understanding of HER3 signaling by uncovering the mechanistic basis for the anti-proliferative effects of potential anti-HER3 antibody therapeutics.

Stereotactic radiosurgery for central nervous system hemangioblastoma: systematic review and meta-analysis.

Hemangioblastomas are rare, benign, vascular tumors of the central nervous system (CNS), often associated with von-hippel lindau (VHL) disease. Current therapeutic options include microsurgical resection or stereotactic radiosurgery (SRS). With no randomized controlled studies and minimal data beyond single-institution reviews, the optimal management approach for patients with CNS hemangioblastomas is unclear. We completed a Pubmed/SCOPUS literature search from January 1990 to January 2017 for eligible studies on SRS for CNS hemangioblastomas. Relevant articles were identified and reviewed in accordance to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. 26 studies met eligibility criteria for qualitative synthesis, representing 596 subjects and 1535 tumors. The Gamma Knife was the most published SRS method for CNS hemangioblastomas. After critical study appraisal for intra-study bias, 14 studies were used for quantitative meta-analysis of 5-year progression free survival (PFS). The pooled 5-year PFS across all eligible studies was 88.4%. No difference was observed between spine versus intracranial studies. Individual patient data (IPD) was extracted from 14 studies, representing 322 tumors. Univariate analysis of IPD revealed that VHL patients were younger, and had smaller tumors compared to those with sporadic disease. Adverse events were associated with increasing marginal dose, independent of tumor volume. VHL status, sex, radiosurgical method, tumor location, and tumor volume were not found to be significantly associated with tumor progression. Multiple studies show excellent tumor control at 5-year follow up, however, the long-term efficacy of SRS for CNS hemangioblastomas still needs to be investigated, and the studies exploring the role of SRS for early treatment of asymptomatic lesions is wanting.

The Kil peptide of bacteriophage λ blocks Escherichia coli cytokinesis via ZipA-dependent inhibition of FtsZ assembly.

Assembly of the essential, tubulin-like FtsZ protein into a ring-shaped structure at the nascent division site determines the timing and position of cytokinesis in most bacteria and serves as a scaffold for recruitment of the cell division machinery. Here we report that expression of bacteriophage λ kil, either from a resident phage or from a plasmid, induces filamentation of Escherichia coli cells by rapid inhibition of FtsZ ring formation. Mutant alleles of ftsZ resistant to the Kil protein map to the FtsZ polymer subunit interface, stabilize FtsZ ring assembly, and confer increased resistance to endogenous FtsZ inhibitors, consistent with Kil inhibiting FtsZ assembly. Cells with the normally essential cell division gene zipA deleted (in a modified background) display normal FtsZ rings after kil expression, suggesting that ZipA is required for Kil-mediated inhibition of FtsZ rings in vivo. In support of this model, point mutations in the C-terminal FtsZ-interaction domain of ZipA abrogate Kil activity without discernibly altering FtsZ-ZipA interactions. An affinity-tagged-Kil derivative interacts with both FtsZ and ZipA, and inhibits sedimentation of FtsZ filament bundles in vitro. Together, these data inspire a model in which Kil interacts with FtsZ and ZipA in the cell to prevent FtsZ assembly into a coherent, division-competent ring structure. Phage growth assays show that kil+ phage lyse ∼30% later than kil mutant phage, suggesting that Kil delays lysis, perhaps via its interaction with FtsZ and ZipA.

Image-guided stereotactic radiosurgery for treatment of spinal hemangioblastoma.

OBJECTIVE Stereotactic radiosurgery (SRS) has been an attractive treatment option for hemangioblastomas, especially for lesions that are surgically inaccessible and in patients with von Hippel-Lindau (VHL) disease and multiple lesions. Although there has been a multitude of studies examining the utility of SRS in intracranial hemangioblastomas, SRS has only recently been used for spinal hemangioblastomas due to technical limitations. The purpose of this study is to provide a long-term evaluation of the effectiveness of image-guided radiosurgery in halting tumor progression and providing symptomatic relief for spinal hemangioblastomas. METHODS Between 2001 and 2011, 46 spinal hemangioblastomas in 28 patients were treated using the CyberKnife image-guided radiosurgery system at the authors' institution. Fourteen of these patients also had VHL disease. The median age at treatment was 43.5 years (range 19-85 years). The mean prescription radiation dose to the tumor periphery was 21.6 Gy (range 15-35 Gy). The median tumor volume was 0.264 cm3 (range 0.025-70.9 cm3). Tumor response was evaluated on serial, contrast-enhanced CT and MR images. Clinical response was evaluated by clinical and imaging evaluation. RESULTS The mean follow-up for the cohort was 54.3 months. Radiographic follow-up was available for 19 patients with 34 tumors; 32 (94.1%) tumors were radiographically stable or displayed signs of regression. Actuarial control rates at 1, 3, and 5 years were 96.1%, 92.3%, and 92.3%, respectively. Clinical evaluation on follow-up was available for 13 patients with 16 tumors; 13 (81.2%) tumors in 10 patients had symptomatic improvement. No patient developed any complications related to radiosurgery. CONCLUSIONS Image-guided SRS is safe and effective for the primary treatment of spinal hemangioblastomas and is an attractive alternative to resection, especially for those with VHL disease.

Impact of consensus statements and reimbursement on vena cava filter utilization.

OBJECTIVE: Pulmonary embolism is the third most common cause of death in hospitalized patients. Vena cava filters (VCFs) are indicated in patients with venous thromboembolism with a contraindication to anticoagulation. Prophylactic indications are still controversial. However, the utilization of VCFs during the past 15 years may have been affected by societal recommendations and reimbursement rates. The aim of this study was to evaluate the impact of societal guidelines and reimbursement on national trends in VCF placement from 1998 to 2012. METHODS: The National Inpatient Sample was used to identify patients who underwent VCF placement between 1998 and 2012. VCF placement yearly rates were evaluated. Societal guidelines and consensus statements were identified using a PubMed search. Reimbursement rates for VCF were determined on the basis of published Medicare reports. Statistical analysis was completed using descriptive statistics, Fisher exact test, and trend analysis using the Mann-Kendall test and considered significant for P < .05. RESULTS: The use of VCFs increased 350% between January 1998 and January 2008. Consensus statements in favor of VCFs published by the Eastern Association for the Surgery of Trauma (July 2002) and the Society of Interventional Radiology (March 2006) were temporally associated with a significant 138% and 122% increase in the use of VCFs, respectively (P = .014 and P = .023, respectively). The American College of Chest Physicians guidelines (February 2008 and 2012) discouraging the use of VCFs were preceded by an initial stabilization in the use of VCFs between 2008 and 2012, followed by a 16% decrease in use starting in March 2012 (P = .38). Changes in Medicare reimbursement were not followed by a change in VCF implantation rates. CONCLUSIONS: There is a temporal association between the societal guidelines' recommendations regarding VCF placement and the actual rates of insertion. More uniform consensus statements from multiple societies along with the use of level I evidence may be required to lead to a definitive change in practice.

Predictors of poor outcome after carotid intervention.

BACKGROUND: A variety of patient factors are known to adversely impact outcomes after carotid endarterectomy (CEA) or carotid artery stenting (CAS). However, their specific impact on complications and mortality and how they differ between CEA and CAS is unknown. The purpose of this study is to identify patient and hospital factors that adversely impact outcomes. METHODS: Patients who underwent CEA or CAS between 1998 and 2012 (N = 1,756,445) were identified using the Agency for Healthcare Research and Quality National Inpatient Sample and State Ambulatory Services Databases. A multivariate analysis was completed to evaluate the impact of demographics, patient factors, type of symptoms (transient ischemic attack or cerebrovascular accident), volume of cases (3 per year vs 1-2 interventions), and interventions upon outcomes, perioperative complications (stroke, myocardial infarction, and bleeding), duration of stay, inpatient mortality, and cost. Significant factors were then used as part of a multivariate regression analysis to determine odds ratios. A subgroup analysis using propensity matching evaluating 1:1 risk-matched asymptomatic and symptomatic patients was completed. Patient cohorts were matched on the basis of Charlson scores. RESULTS: Over the study period a total of 1,583,614 asymptomatic CEA, 7317 asymptomatic CAS, 162,362 symptomatic CEA, and 3149 symptomatic CAS patients were included. Symptomatic disease portends a worse outlook after either CEA or CAS. Costs of the procedure increased with complications with stroke adding the most significant cost burden. For risk-matched asymptomatic and symptomatic patients, female gender (P < .001) and performing one or two cases per year (P < .05) were associated with higher cerebrovascular accident risk. In asymptomatic and symptomatic patients, predictors of myocardial infarction included congestive heart failure (P < .001) and peripheral artery disease (P < .05) and predictors of bleeding included peripheral artery disease (P < .05) and chronic obstructive pulmonary disease (P < .01) for symptomatic patients only. For both asymptomatic and symptomatic patients, predictors of mortality included female gender (P < .001) and performing one or two cases per year (P < .01). Female gender was one of the strongest overall predictors of adverse outcome after CAS (odds ratio, 21.39 for death; P < .001). Low volume (<3 cases per year per practitioner) is a predictor of adverse outcome after CAS only. CONCLUSIONS: Higher rates of postoperative stroke and inpatient mortality for women undergoing CAS is an unexpected finding, and may indicate that this population is vulnerable to complications after endovascular management. Low volume is a predictor of complications and subsequent mortality primarily for CAS. Patients who undergo CEA continue to have superior outcomes compared with matched cohorts who undergo CAS.

The Impact of Physician Specialization on Clinical and Hospital Outcomes in Patients Undergoing EVAR and TEVAR.

BACKGROUND: Endovascular aneurysm repair (EVAR) and Thoracic endovascular aortic repair (TEVAR) are commonly performed by interventional radiologists, cardiologists, general surgeons, cardiothoracic surgeons, and vascular surgeons, with each specialty having differences in residency structure, operative experience, and subspecialty training. The aim of this study is to evaluate the impact of surgeon specialty on outcomes following EVAR and TEVAR. METHODS: Patients who underwent EVAR and TEVAR were identified from the 2007 to 2009 Nationwide Inpatient Sample (NIS). Physician identifiers in the NIS were used to determine surgical specialty and operative experience. Multivariate analysis adjusted for mortality risk was used to compare differences in demographics, complications, outcomes, and hospital covariates. RESULTS: A total of 5147 EVARs were identified within the NIS, of which 88.3% were completed by vascular surgeons. There were no significant differences in demographics between the specialties. Cardiothoracic surgeons were more likely to have a postoperative stroke (3.1% vs. 0.2%, odds ratio [OR] 14.6, 95% confidence interval [CI] 1.8-117.8, P < 0.05) and cardiac complications (9.4% vs. 2.0%, OR 5.0, 95% CI 1.5-16.6, P < 0.01) compared with other specialties. Costs were lowest for vascular surgeons ($32,094), and highest for cardiothoracic surgeons ($41,663, P < 0.05). Only vascular surgeons completed more than 10 EVARs per year. A total of 2531 TEVAR cases were completed during the study period, of which 73.8% were completed by vascular surgeons, 15.8% by cardiothoracic surgeons, 8.0% by interventional radiologists, and the remainder by interventional cardiologists and general surgeons. Interventional radiologists had significantly more elective cases (77.8%, P < 0.001) than cardiothoracic surgeons (47.2%) or vascular surgeons (53.8%), but had a significantly higher rate of stroke (7.6% vs. 1.1%, P < 0.001) and cardiac events (7.2% vs. 3.6%, P < 0.001). Length of stay (LOS, 10.7 days) and median costs ($52,156) were similar across specialties. Vascular surgeons have a low stroke rate (1.1%, P < 0.05 vs. interventional radiologists) and lower rate of cardiac events (3.6% vs. 6.1%, P < 0.01) despite caring for patients with higher diagnosis-related group mortality scores (3.6 vs. 3.4, P < 0.05). CONCLUSIONS: Vascular surgeons appear to have a comparative advantage over other specialties for EVAR because not only are their complication and mortality rates comparable but overall LOS and hospital charges are lower. Furthermore, primarily only vascular surgeons are performing the high volume of annual EVARs necessary to ensure optimal patient outcomes. For TEVAR, vascular surgeons have the lowest overall morbidity compared with the other specialties, and lower mortality compared with cardiothoracic surgeons. These findings may impact patient referral patterns and hospital privileges for providers.

Sports-related brain injuries: connecting pathology to diagnosis.

Brain injuries are becoming increasingly common in athletes and represent an important diagnostic challenge. Early detection and management of brain injuries in sports are of utmost importance in preventing chronic neurological and psychiatric decline. These types of injuries incurred during sports are referred to as mild traumatic brain injuries, which represent a heterogeneous spectrum of disease. The most dramatic manifestation of chronic mild traumatic brain injuries is termed chronic traumatic encephalopathy, which is associated with profound neuropsychiatric deficits. Because chronic traumatic encephalopathy can only be diagnosed by postmortem examination, new diagnostic methodologies are needed for early detection and amelioration of disease burden. This review examines the pathology driving changes in athletes participating in high-impact sports and how this understanding can lead to innovations in neuroimaging and biomarker discovery.

Therapeutic strategies to improve drug delivery across the blood-brain barrier.

Resection of brain tumors is followed by chemotherapy and radiation to ablate remaining malignant cell populations. Targeting these populations stands to reduce tumor recurrence and offer the promise of more complete therapy. Thus, improving access to the tumor, while leaving normal brain tissue unscathed, is a critical pursuit. A central challenge in this endeavor lies in the limited delivery of therapeutics to the tumor itself. The blood-brain barrier (BBB) is responsible for much of this difficulty but also provides an essential separation from systemic circulation. Due to the BBB's physical and chemical constraints, many current therapies, from cytotoxic drugs to antibody-based proteins, cannot gain access to the tumor. This review describes the characteristics of the BBB and associated changes wrought by the presence of a tumor. Current strategies for enhancing the delivery of therapies across the BBB to the tumor will be discussed, with a distinction made between strategies that seek to disrupt the BBB and those that aim to circumvent it.

Incidence and Risk Model of Post-Traumatic Hydrocephalus in Patients with Traumatic Brain Injury.

OBJECTIVE: Post-traumatic hydrocephalus (PTH) is a complication following traumatic brain injury (TBI). Early diagnosis and treatment are essential to improving outcomes. We report the incidence and risk factors of PTH in a large TBI population while considering death as a competing risk. METHODS: We conducted a retrospective cohort study on consecutive TBI patients with radiographic intracranial abnormalities admitted to our academic medical center from 2009 to 2015. We assessed patient demographics, perioperative data, and in-hospital data as risk factors for PTH using survival analysis with death as a competing risk. RESULTS: Among 7,473 patients, the overall incidence of PTH requiring shunt surgery was 0.94%. The adjusted cumulative incidence was 0.99%. The all-cause cumulative hazard for death was 32.6%, which was considered a competing risk during analysis. Craniectomy (HR 11.53, P < 0.001, 95% CI 5.57-223.85), venous sinus injury (HR 4.13, P = 0.01, 95% CI 1.53-11.16), and age ≤5 (P < 0.001) were significant risk factors for PTH. Glasgow Coma Score (GCS) > 13 was protective against shunt placement (HR 0.50, P = 0.04, 95% CI 0.26-0.97). Shunt surgery occurred after hospital discharge in 60% of patients. CONCLUSIONS: We describe the incidence and risk factors for PTH in a large traumatic brain injury (TBI) population. Most cases of PTH were diagnosed after hospital discharge, suggesting that close follow-up and multidisciplinary diagnostic vigilance for PTH are needed to prevent morbidity and disability.

Telemedicine screening for cytomegalovirus retinitis using digital fundus photography.

BACKGROUND: Screening for cytomegalovirus retinitis (CMVR) is important in patients with acquired immune deficiency syndrome and low CD4(+) counts. However, many human immunodeficiency virus (HIV) patients lack access to specialist ophthalmological care. Telemedicine screening is a cost-effective method for screening these patients. We aimed to report the use of composite nine-field digital fundus photography (DFP) images for CMVR screening. We report its sensitivity and specificity in detecting CMVR and the level of agreement with gold-standard binocular indirect ophthalmoscopy. MATERIALS AND METHODS: An audit was performed on our national CMVR screening program that screened all HIV patients referred to the Ophthalmology Department at Tan Tock Seng Hospital, Singapore. All patients underwent retinal screening with DFP. Images were categorized as CMVR-positive, CMVR-negative, suspicious, or unreadable by blinded retinal specialists. Patients subsequently underwent dilated gold-standard indirect ophthalmoscopy by a different retinal specialist. Diagnoses were categorized as CMVR-positive, CMVR-negative, or unreadable. Sensitivity and specificity of retinal findings on DFP and kappa values for level of agreement between the two screening methods were calculated. RESULTS: Three hundred seventy screenings on 188 patients were performed. Twenty-three eyes diagnosed with CMVR on indirect ophthalmoscopy were also identified on DFP (100% sensitivity). A 99.9% specificity was achieved. The fundus photograph of one eye without CMVR was read as CMVR-positive because of an artifact, accounting for a false-positive. Kappa values ranged from 0.739 to 0.987. CONCLUSIONS: DFP is a sensitive and specific method of screening HIV patients for CMVR and has a high level of agreement with indirect ophthalmoscopy.

Incidence and Risk Model of Venous Thromboembolism in Patients with Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Venous thromboembolism (VTE) is a significant source of morbidity and mortality in hospitalized patients. We describe our experience with VTE prophylaxis and treatment in patients with aneurysmal subarachnoid hemorrhage (aSAH), risk factors for VTE, and a hazard model describing the daily risk of VTE. METHODS: A retrospective cohort study was performed on patients with aSAH admitted from 2014 to 2018. Patients were screened for VTE based on clinical suspicion. Demographics, perioperative data, and in-hospital data were assessed as risk factors for VTE using survival analysis with death as a competing risk. RESULTS: Among 485 patients, the overall incidence of VTE, deep vein thrombosis, and pulmonary embolism were 5.6%, 4.3%, and 2.3%, respectively. Increasing length of stay in the intensive care unit (hazard ratio [HR], 1.79; P < 0.0001; 95% confidence interval [CI], 1.49-2.16) and ventilation immediately after aneurysm treatment was associated with VTE (HR, 8.87; P < 0.01; 95% CI, 1.86-42.38). Hunt and Hess grade was negatively associated with VTE (HR, 0.61; P = 0.045; 95% CI, 0.37-1.00) due to its increased association with the competing risk of death (HR, 2.57; P < 0.0001; 95% CI, 1.89-3.49). The adjusted 4-year cumulative incidence for VTE is 11.1% and at mean day of hospital discharge is 5.4%. Treatment of VTEs with anticoagulation and/or inferior vena cava filter placement was not associated with immediate complications. CONCLUSIONS: We describe the largest single-institution cohort of VTEs in aSAH patients. Our hazard model quantifies the cumulative incidence of VTEs during the course of hospitalization. We suggest a standardized protocol for screening, prophylaxis, and treatment of VTEs in this patient population.

Remote patient monitoring following full endoscopic spine surgery: feasibility and patient satisfaction.

OBJECTIVE: The utilization of telemedicine in healthcare has increased dramatically during the recent COVID-19 pandemic. This study aimed to investigate the feasibility to perform remote patient monitoring after full endoscopic spine surgery via a smartphone application that also allows communication with patients. METHODS: A smartphone application (SPINEhealthie) was designed at the University of Washington and used to collect patient-reported outcome measures (PROMs) and to provide chat communication between patients and their care team. A total of 71 patients were included in the study and prospectively followed for 3 months postoperatively. Patient demographic characteristics, compliance with surveys, and frequency of chat utilization were recorded. The ease of use, the participants' experiences with the app interface design, and the usefulness of the app were assessed by using the mHealth App Usability Questionnaire (MAUQ). RESULTS: Of all eligible patients, 71/78 (91.0%) agreed to participate. Of these, 60 (85%) patients provided at least 1 postoperative PROM. There was good coverage of the immediate postoperative period with 45 (63.4%) patients providing ≥ 5 PROMs within the 1st week after surgery. The authors observed a 33.2% increase in patient compliance in postoperative PROMs and a 45.7% increase in chat function utilization between the first and last of the three enrollment periods of the study, during which continuous updates were made to improve the app's functionality. Sixty-two (87.3%) patients responded to the user satisfaction survey after using the app for at least 40 days. The MAUQ results revealed excellent rates of satisfaction for ease of use (78.6% of the maximum score), app interface design (71.4%), and usefulness (71.4%), resulting in a total mean MAUQ score of 110 (74.8%). Communication with the doctor (38 votes) was found to be the top feature of the app. Additionally, physical therapy instructions (33 votes) and imaging review (29 votes) were the top two features that patients would like to see in future app versions. Lastly, the authors have presented a case example of a 68-year-old man who used the app for postoperative monitoring and communication after undergoing a two-level lumbar endoscopic unilateral laminotomy for bilateral decompression. CONCLUSIONS: Postoperative remote patient monitoring and communication after full endoscopic surgery is feasible using the SPINEhealthie app. Importantly, patients were willing to share their medical information using a mobile device, and they were eager to use it postoperatively as a supplementary tool.

Perioperative complications and secondary retethering after pediatric tethered cord release surgery.

OBJECTIVE: Tethered cord syndrome refers to a constellation of symptoms characterized by neurological, musculoskeletal, and urinary symptoms, caused by traction on the spinal cord, which can be secondary to various etiologies. Surgical management of simple tethered cord etiologies (e.g., fatty filum) typically consists of a single-level lumbar laminectomy, intradural exploration, and coagulation and sectioning of the filum. More complex etiologies such as lipomyelomeningoceles or scar formation after myelomeningocele repair involve complex dissection and dural reconstruction. The purpose of this study was to evaluate operative complications and long-term outcomes of secondary retethering related to pediatric tethered cord release (TCR) at a tertiary children's hospital. METHODS: Medical records of children who underwent surgery for TCR from July 2014 to March 2023 were retrospectively reviewed. Data collected included demographics, perioperative characteristics, surgical technique, and follow-up duration. Primary outcomes were 60-day postoperative complications and secondary retethering requiring repeat TCR surgery. Univariate and multivariate analyses were performed to identify risk factors associated with complications and secondary retethering. RESULTS: A total of 363 TCR surgeries (146 simple, 217 complex) in 340 patients were identified. The mean follow-up was 442.8 ± 662.2 days for simple TCRs and 733.9 ± 750.3 days for complex TCRs. The adjusted 60-day complication-free survival rate was 96.3% (95% CI 91.3%-98.4%) for simple TCRs and 88.7% (95% CI 82.3%-91.4%) for complex TCRs. Lower weight, shorter surgical times, and intensive care unit admission were associated with complications for simple TCRs. Soft-tissue drains increased complications for complex TCRs. The secondary retethering rates were 1.4% for simple TCRs and 11.9% for complex TCRs. The 1-, 3-, and 5-year progression-free survival rates in complex cases were 94.7% (95% CI 89.1%-97.4%), 77.7% (95% CI 67.3%-85.3%), and 62.6% (95% CI 46.5%-75.1%), respectively. Multivariate analysis revealed that prior detethering (OR 8.15, 95% CI 2.33-28.50; p = 0.001) and use of the operative laser (OR 10.43, 95% CI 1.36-80.26; p = 0.024) were independently associated with secondary retethering in complex cases. CONCLUSIONS: This is the largest series to date examining postoperative complications and long-term secondary retethering in TCR surgery. Simple TCR surgeries demonstrated safety, rare complications, and low secondary retethering rates. Complex TCR surgeries presented higher risks of complications and secondary retethering. Modifiable risk factors such as operative laser use influenced secondary retethering in complex cases.

Cyclin D1 is a direct target of JAG1-mediated Notch signaling in breast cancer.

The Notch ligand, JAG1 is associated with breast cancer recurrence. Herein, we report on a genomics approach to elucidate mechanisms downstream of JAG1 that promote breast cancer growth. In a survey of 46 breast cancer cell lines, we found that triple negative (TN; basal and mesenchymal ER-, PR-, and Her2-negative) lines express JAG1 at significantly higher levels than do HER2(+) or luminal (ER(+)) Her2(-) cell lines. In contrast to the luminal lines tested (T47D and MCF7), TN breast cancer cell lines (HCC1143 and MDA MB231) display high-level JAG1 expression and growth inhibition with RNA interference-induced JAG1 down-regulation. We used microarray profiling of TN tumor cells transfected with JAG1 siRNA to identify JAG1-regulated genes (P or=1.5). Among JAG1-regulated genes identified, cyclin D1 was found to be a direct target of NOTCH1 and NOTCH3. We show that JAG1 down-regulation reduces direct binding of Notch to the cyclin D1 promoter, reduced cyclin D1 expression and inhibition of cell cycle progression through the cyclin D1-dependant G1/S checkpoint. Furthermore, we show that cyclin D1 and JAG1 expression correlate in TN breast cancer expression datasets. These data suggest a model whereby JAG1 promotes cyclin D1-mediated proliferation of TN breast cancers.

Economic Impact of COVID-19 on a High-Volume Academic Neurosurgical Practice.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a novel disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that rapidly spread around the globe. The dramatic increase in the number of cases and deaths have placed tremendous strain on health care systems worldwide. As health care workers and society adjust to focus treatment and prevention of COVID-19, other facets of the health care enterprise are affected, particularly surgical volume and revenue. The purpose of this study was to describe the financial impact of COVID-19 on an academic neurosurgery department. METHODS: A retrospective review of weekly average daily work relative value units (wRVUs) were compared before and after COVID-19 in the fiscal year 2020. A comparative time period of the same months in the year prior was also included for review. We also review strategies for triaging neurosurgical disease as needing emergent, urgent, or routine operative treatment. RESULTS: Daily average wRVU after COVID-19 dropped significantly with losses in all weeks examined. Of the 7 weeks in the current post-COVID period, the weekly daily average wRVU was 173 (range, 128-363). The mean decline was 51.4% compared with the pre-COVID era. Both inpatient and outpatient revenue was affected. CONCLUSIONS: COVID-19 had a profound detrimental effect on surgical productivity and revenue generation.

Tiger Nut (Cyperus esculentus) as a Functional Ingredient in Gluten-Free Extruded Snacks.

Tiger nut (TN) is a nutritious source of gluten-free flour, used generally in healthy beverages, but its incorporation in gluten-free extruded snacks has not been explored. TN flour was blended at different concentrations (up to 70%) with rice flour and soluble fiber, for the development of gluten-free snacks on a twin-screw extruder. The effect of TN inclusion in the formulations was evaluated on relevant physiochemical characteristics of the snacks. Viscoamylograph of the raw formulations showed that TN addition increased (p < 0.01) onset temperature and delayed peak viscosity. In the extruded flours, TN contributed to limit the starch degradation during extrusion. Diameter, expansion ratio, true density, and total pore volume of the extrudates were reduced (pf < 0.01) by the increased TN content in the formulations, while bulk density rose. The surfaces of the extruded snacks were modified by the increasing inclusion of TN in substitution of rice in the formulations. Extrudates containing 10% TN showed the best overall texture profile. Moreover, TN addition enhanced the ash and protein content of the snacks and increased their total antioxidant activity. This study demonstrated that incorporation of 10% TN flour into rice-based formulation was suitable for making gluten-free snacks with acceptable physical properties.