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PREGCARE is a new strategy for families who had a child with a pathogenic de novo mutation, that efficiently identifies couples at higher recurrence risk due to parental mosaicism, while reassuring many others that their recurrence risk is negligible.

eIF5A is critical for protein synthesis but has not yet been associated with congenital human disease. Here, the authors show that EIF5A variants cause a Mendelian disorder via reduced eIF5A-ribosome interactions and this phenotype is partially corrected by spermidine supplementation in yeast and zebrafish.

Objectives This study aimed to explore the experiences of parents caring for children with intellectual and developmental disabilities (IDD) during the UK national lockdown in spring 2020, resulting from the COVID-19 pandemic.Design Participants were identified using opportunity sampling from the IMAGINE-ID national (UK) cohort and completed an online survey followed by a semistructured interview. Interviews were analysed using thematic analysis.Setting Interviews were conducted over the telephone in July 2020 as the first UK lockdown was ending.Participants 23 mothers of children with intellectual and developmental disabilities aged 5–15 years were recruited.Results Themes reported by parents included: managing pre-existing challenges during a time of extreme change, having mixed emotions about the benefits and difficulties that arose during the lockdown and the need for appropriate, individualised support.Conclusions Our findings confirm observations previously found in UK parents of children with IDD and provide new insights on the use of technology during the pandemic for schooling and healthcare, as well as the need for regular check-ins.

Background: Large contiguous gene deletions at the distal end of the short arm of chromosome 9 result in the complex multi-organ condition chromosome 9p deletion syndrome. A range of clinical features can result from these deletions with the most common being facial dysmorphisms and neurological impairment. Congenital hyperinsulinism is a rarely reported feature of the syndrome with the genetic mechanism for the dysregulated insulin secretion being unknown. Methods: We studied the clinical and genetic characteristics of 12 individuals with chromosome 9p deletions who had a history of neonatal hypoglycaemia. Using off-target reads generated from targeted next-generation sequencing of the genes known to cause hyperinsulinaemic hypoglycaemia (n=9), or microarray analysis (n=3), we mapped the minimal shared deleted region on chromosome 9 in this cohort. Targeted sequencing was performed in three patients to search for a recessive mutation unmasked by the deletion. Results: In 10/12 patients with hypoglycaemia, hyperinsulinism was confirmed biochemically. A range of extra-pancreatic features were also reported in these patients consistent with the diagnosis of the Chromosome 9p deletion syndrome. The minimal deleted region was mapped to 7.2 Mb, encompassing 38 protein-coding genes. In silico analysis of these genes highlighted SMARCA2 and RFX3 as potential candidates for the hypoglycaemia. Targeted sequencing performed on three of the patients did not identify a second disease-causing variant within the minimal deleted region. Conclusions: This study identifies 9p deletions as an important cause of hyperinsulinaemic hypoglycaemia and increases the number of cases reported with 9p deletions and hypoglycaemia to 15 making this a more common feature of the syndrome than previously appreciated. Whilst the precise genetic mechanism of the dysregulated insulin secretion could not be determined in these patients, mapping the deletion breakpoints highlighted potential candidate genes for hypoglycaemia within the deleted region.

Companion animal relocation programs are an important method to address geographic and resource disparities in pet overpopulation through transport from areas with high homeless pet populations to areas with high adopter demand. Despite mitigation by following best practices, a potential risk of animal relocation is increased disease incidence related to infectious disease spread and the effects of stress during transport. Surgical sterilization may compound disease risk due to the impact of surgical stress on disease susceptibility and the potential for disease exposure from other patients. Our study aimed to provide information about disease and surgical complication incidence as relates to the timing of surgical sterilization in relocated dogs. A population of 431 dogs relocated to a shelter in Washington State was monitored for disease while at the destination shelter and immediately post-adoption. No increased disease incidence was identified for dogs altered within two weeks of transport at the destination shelter compared with those altered within two weeks prior to transport at the source shelter. Because of disparities addressed by relocation programs, surgical sterilization of relocated companion animals is typically best performed at the destination shelter. Our study indicates that disease incidence is not increased by spay-neuter at the destination shelter.

We report molecular genetic analysis of 42 affected individuals referred with a diagnosis of aniridia who previously screened as negative for intragenic PAX6 mutations. Of these 42, the diagnoses were 31 individuals with aniridia and 11 individuals referred with a diagnosis of Gillespie syndrome (iris hypoplasia, ataxia and mild to moderate developmental delay). Array-based comparative genomic hybridization identified six whole gene deletions: four encompassing PAX6 and two encompassing FOXC1. Six deletions with plausible cis-regulatory effects were identified: five that were 3' (telomeric) to PAX6 and one within a gene desert 5' (telomeric) to PITX2. Sequence analysis of the FOXC1 and PITX2 coding regions identified two plausibly pathogenic de novo FOXC1 missense mutations (p.Pro79Thr and p.Leu101Pro). No intragenic mutations were detected in PITX2. FISH mapping in an individual with Gillespie-like syndrome with an apparently balanced X;11 reciprocal translocation revealed disruption of a gene at each breakpoint: ARHGAP6 on the X chromosome and PHF21A on chromosome 11. In the other individuals with Gillespie syndrome no mutations were identified in either of these genes, or in HCCS which lies close to the Xp breakpoint. Disruption of PHF21A has previously been implicated in the causation of intellectual disability (but not aniridia). Plausibly causative mutations were identified in 15 out of 42 individuals (12/32 aniridia; 3/11 Gillespie syndrome). Fourteen of these mutations presented in the known aniridia genes; PAX6, FOXC1 and PITX2. The large number of individuals in the cohort with no mutation identified suggests greater locus heterogeneity may exist in both isolated and syndromic aniridia than was previously appreciated.

Neurosurgery is a field with complex ethical issues. In this article, we aim to provide an overview of key and emerging ethical issues in neurosurgery with a focus on issues relevant to practicing neurosurgeons. These issues include those of informed consent, capacity, clinical trials, emerging neurotechnology, innovation, equity and justice, and emerging bioethics areas including community engagement and organizational ethics. We argue that bioethics can help neurosurgeons think about and address these issues, and, in turn, the field of bioethics can benefit from engagement by neurosurgeons. Several ideas for increasing engagement in bioethics are proposed., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Federal regulations require a history and physical (H&P) update performed 30 days or less before a planned procedure. We evaluated the use and burdens of H&P update visits by determining impact on operative management, suitability for telehealth, and visit time and travel burden., Study Design: We identified H&P update visits performed in our health system during 2019 for 8 surgical specialties. As available, up to 50 visits per specialty were randomly selected. Primary outcomes were interval changes in history, examination, or operative plan between the initial and updated H&P notes, and visit suitability for telehealth, as determined by 2 independent physician reviewers. Clinic time was captured, and round-trip driving time and distance between patients' home and clinic ZIP codes were estimated., Results: We identified 8,683 visits and 362 were randomly selected for review. Documented changes were most commonly identified in histories (60.8%), but rarely in physical examinations (11.9%) and operative plans (11.6%). Of 362 visits, 359 (99.2%) visits were considered suitable for telehealth. Median clinic time was 52 minutes (interquartile range 33.8 to 78), driving time was 55.6 minutes (interquartile range 35.5 to 85.5), and driving distance was 20.2 miles (interquartile range 8.5 to 38.4). At the health system level, patients spent an estimated aggregate 7,000 hours (including 4,046 hours of waiting room and travel time) and drove 142,273 miles to attend in-person H&P update visits in 2019., Conclusions: Given their minimal impact on operative management, regulatory requirements for in-person H&P updates should be reconsidered. Flexibility in update timing and modality might help defray the substantial burdens these visits impose on patients., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Return-to-work (RTW) is an important outcome for employed patients considering surgery for cervical spondylotic myelopathy (CSM). We conducted a post hoc analysis of patients as-treated in the Cervical Spondylotic Myelopathy Surgical Trial, a prospective, randomized trial comparing surgical approaches for CSM to evaluate factors associated with RTW., Methods: In the trial, patients were randomized (2:3) to either anterior surgery (anterior cervical decompression/fusion [ACDF]) or posterior surgery (laminoplasty [LP], or posterior cervical decompression/fusion [PCDF], at surgeon's discretion). Work status was recorded at 1, 3, 6, and 12 months postoperatively. For patients working full-time or part-time on enrollment, time to RTW was compared across as-treated surgical groups using discrete-time survival analysis. Multivariate logistic regression was used to assess predictors of RTW. Clinical outcomes were compared using a linear mixed-effects model., Results: A total of 68 (42%) of 163 patients were working preoperatively and were analyzed. In total, 27 patients underwent ACDF, 29 underwent PCDF, and 12 underwent LP. 45 (66%) of 68 patients returned to work by 12 months. Median time to RTW differed by surgical approach (LP = 1 month, ACDF = 3 months, PCDF = 6 months; P = .02). Patients with longer length-of-stay were less likely to be working at 1 month (odds ratio 0.51; 95% CI, 0.29-0.91; P = .022) and 3 months (odds ratio 0.39; 95% CI, 0.16-0.96; P = .04). At 3 months, PCDF was associated with lower Short-Form 36 physical component summary scores than ACDF (estimated mean difference [EMD]: 6.42; 95% CI, 1.4-11.4; P = .007) and LP (EMD: 7.98; 95% CI, 2.7-13.3; P = .003), and higher Neck Disability Index scores than ACDF (EMD: 12.48; 95% CI, 2.3-22.7; P = .01) and LP (EMD: 15.22; 95% CI, 2.3-28.1; P = .014), indicating worse perceived physical functioning and greater disability, respectively., Conclusion: Most employed patients returned to work within 1 year. LP patients resumed employment earliest, while PCDF patients returned to work latest, with greater disability at follow-up, suggesting that choice of surgical intervention may influence occupational outcomes., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: In Mexico, anemia prevalence among women of reproductive age (WRA) decreased from 16.4% in 2006 to 11.6% in 2012, only to increase to 18.3% in 2016. The factors associated with this fluctuation are uncertain., Objective: We conducted a systematic in-depth assessment of the quantitative and qualitative determinants of anemia among WRA in Mexico between 2006 and 2018., Methods: Using multivariate stepwise linear regression, we analyzed Mexico's Encuesta Nacional de Salud y Nutrición (ENSANUT) surveys from 2006, 2012, and 2018 to identify determinants of WRA anemia. We also conducted a review of anemia-relevant programs and policies, including financing documents, and conducted in-depth interviews and focus group discussions with key stakeholders in Mexico., Results: Among non-pregnant women (NPW) 15-49 years, mean hemoglobin (Hb) increased from 13.8 g/dL in 2006 to 14.0 g/dL in 2012, decreasing to 13.2 g/dL in 2018 (p<0.001). Inequities by geographical region and household wealth persisted throughout this period, with household wealth, urban residence and gravidity emerging as significant predictors of Hb among NPW. Qualitative analyses generally supported these findings. The most discussed program was Progresa-Oportunidades-Prospera (POP), where most resources for health were invested and most participants acknowledged that its cancellation in 2019 would lead to worsening in health and nutrition among the poor. Financing analyses showed a drop of funding for nutrition-related programs between 2014 and 2018. Cultural norms around gender roles were still prevalent, along with increasing rates of teenage pregnancy., Conclusions: Anemia prevention efforts need to refocus on poverty alleviation, continuity of adequate coverage and financing of nutrition programs, especially with safety nets, and increase in uptake of family planning, especially among adolescent girls., Competing Interests: Declaration of Competing Interest ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Zulfiqar Bhutta reports financial support and article publishing charges were provided by Bill and Melinda Gates Foundation. Zulfiqar Bhutta reports financial support was provided by Gates Ventures. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The authors designed a low-profile device for reliable ventricular access and prospectively studied its safety, efficacy, and accuracy at a large academic center., Methods: A novel device for ventricular entry, the Device for Intraventricular Entry (DIVE) guide, was designed and created by the first and senior authors. Fifty patients undergoing external ventricular drainage (EVD) or shunt placement were prospectively enrolled for DIVE-assisted catheter placement at a single academic center. The primary outcome was the catheter tip location on postprocedural CT. Secondary outcomes included number of catheter passes, clinically significant hemorrhages, and procedure-related infections., Results: Fifty patients were enrolled. Indications included subarachnoid hemorrhage, intraventricular hemorrhage, traumatic brain injury, hydrocephalus, pseudotumor, and postsurgical wound drainage. In total, 76% (38/50) of patients underwent right-sided placement and 24% (12/50) underwent left-sided placement. All 100% (50/50) of patients had successful cannulation with an average of 1.06 passes. Postprocedural head CT confirmed ipsilateral frontal horn or third ventricle placement (Kakarla grade 1) in 92% (46/50) of patients and placement in the contralateral lateral ventricle in 8% (4/50) (Kakarla grade 2). There were no clinically significant track hemorrhages or procedural infections., Conclusions: This single-center prospective study investigated the safety and efficacy of DIVE-assisted ventricular access. In total, 100% of procedures had successful ventricular cannulation, with 92% achieving Kakarla grade 1, with an average of 1.06 passes without any clinical complications.

Background: There remains a number of factors thought to be associated with survival in spinal metastatic disease, but evidence of these associations is lacking. In this study, we examined factors associated with survival among patients undergoing surgery for spinal metastatic disease., Methods: We retrospectively examined 104 patients who underwent surgery for spinal metastatic disease at an academic medical center. Of those patients, 33 received local preoperative radiation (PR) and 71 had no PR (NPR). Disease-related variables and surrogate markers of preoperative health were identified, including age, pathology, timing of radiation and chemotherapy, mechanical instability by spine instability neoplastic score, American Society of Anesthesiologists (ASA) classification, Karnofsky performance status (KPS), and body mass index (BMI). We performed survival analyses using a combination of univariate and multivariate Cox proportional hazards models to assess significant predictors of time to death., Results: Local PR (Hazard Ratio [HR] = 1.84, P = 0.034), mechanical instability (HR = 1.11, P = 0.024), and melanoma (HR = 3.60, P = 0.010) were significant predictors of survival on multivariate analysis when controlling for confounders. PR vs NPR cohorts exhibited no statistically significant differences in preoperative age ( P = 0.22), KPS ( P = 0.29), BMI ( P = 0.28), or ASA classification ( P = 0.12). NPR patients had more reoperations for postoperative wound complications (11.3% vs 0%, P < 0.001)., Conclusions: In this small sample, PR and mechanical instability were significant predictors of postoperative survival, independent of age, BMI, ASA classification, and KPS and in spite of fewer wound complications in the PR group. It is possible that PR was a surrogate of more advanced disease or poor response to systemic therapy, independently portending a worse prognosis. Future studies in larger, more diverse populations are crucial for understanding the relationship between PR and postoperative outcomes to determine the optimal timing for surgical intervention., Clinical Relevance: These findings are clinically relevent as they provide insight into factors associated with survival in metastatic spinal disease., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Objective: To determine the in-hospital cost implications of an endoscopic expanded endonasal approach (EEEA) for meningioma resection relative to the open transcranial approach., Methods: All anterior skull base meningioma surgeries performed over a period from January 1 st , 2015 to October 31th, 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate analysis was performed using R software. All cost data were converted into August 2021-equivalent dollar amounts using the United States Bureau of Labor Statistics consumer price index., Results: Thirty-five patients met study criteria, including 27 patients undergoing an open transcranial approach and 8 undergoing an EEEA. Average length of stay for patients undergoing an open approach was 9.3 days compared to 5.6 within the EEEA group ( P  = .126). The average total in-hospital cost of patient undergoing an EEEA was $35417.1 compared to $46406.9 among patients undergoing an open transcranial approach ( P  = .168). On univariate analysis, the cost of an open transcranial approach relative to the EEEA was $10989.8 ( P  = .411)., Conclusions: The open transcranial approach remained the dominant surgical approach to anterior skull base meningiomas over our study time period. However, despite limited patient numbers the EEEA was associated with decreased total in-hospital costs.

Background: We implemented a streamlined care pathway for patients undergoing endoscopic transsphenoidal (TSA) pituitary surgery. Select patients are recovered in the postanesthesia care unit and transferred to a step-down unit for intermediate neurologic care (INCU), with clinicians trained to manage cerebrospinal fluid leak, diabetes insipidus (DI), and other complications., Methods: We evaluated all TSA surgeries performed at 1 academic medical center from 7 th January, 2017 to 30 th March, 2020, collecting patient factors, tumor characteristics, cost variables, and outcomes. The INCU pathway was implemented on 7 th January 2018. Pathway patients were compared with nonpathway patients across the study period. Outcomes were assessed using multivariate regression, adjusting for patient and surgical characteristics, including intraoperative cerebrospinal fluid leak, postoperative DI, and tumor dimensions., Results: One hundred eighty-seven patients were identified. Seventy-nine were on the INCU pathway. Mean age was 53.5 years. Most patients were male (66%), privately insured (62%), and white (66%). Mean total cost of admission was $27,276. Mean length of stay (LOS) was 3.97 days. Use of the INCU pathway was associated with total cost reduction of $6376.33 (P < 0.001, 95% confidence interval [CI]: $3698.21-$9054.45) and LOS reduction by 1.27 days (P = 0.008, 95% CI: 0.33-2.20). In-hospital costs were reduced across all domains, including $1964.87 in variable direct labor costs (P < 0.001, 95% CI: $1142.08-$2787.64) and $1206.52 in variable direct supply costs (P < 0.001, 95% CI: $762.54-$1650.51). Pathway patients were discharged earlier despite a higher rate of postoperative DI (25% vs. 11%, P = 0.011), with fewer readmissions (0% vs. 6%, P = 0.021)., Conclusions: A streamlined care pathway following TSA surgery can reduce in-hospital costs and LOS without compromising patient outcomes., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Avoiding intracranial hypertension after traumatic brain injury (TBI) is a foundation of neurocritical care, to minimize secondary brain injury related to elevated intracranial pressure (ICP). However, this approach at best is reactive to episodes of intracranial hypertension, allowing for periods of elevated ICP before therapies can be initiated. Accurate prediction of ICP crises before they occur would permit clinicians to implement preventive strategies, minimize total time with ICP above threshold, and potentially avoid secondary injury. The objective of this study was to develop an algorithm capable of predicting the onset of ICP crises with sufficient lead time to enable application of preventative therapies., Methods: Thirty-six patients admitted to a level I trauma center with severe TBI (Glasgow Coma Scale score < 8) between April 2015 and January 2019 who underwent continuous intraparenchymal ICP monitor placement were retrospectively identified. Continuous ICP data were extracted from each monitoring period (range 4-96 hours of monitoring). An ICP crisis was treated as a binary outcome, defined as ICP > 22 mm Hg for at least 75% of the data within a 5-minute interval. ICP data preceding each ICP crisis were grouped into four total data sets of 1- and 2-hour epochs, each with 10- to 20-minute lead-time intervals before an ICP crisis. Crisis and noncrisis events were identified from continuous time-series data and randomly split into 70% for training and 30% for testing, from a subset of 30 patients. Machine learning algorithms were trained to predict ICP crises, including light gradient boosting, extreme gradient boosting, and random forest. Accuracy and area under the receiver operating characteristic curve (AUC) were measured to compare performance. The most predictive algorithm was optimized using feature selection and hyperparameter tuning to avoid overfitting, and then tested on a validation subset of 5 patients. Precision, recall, F1 score, and accuracy were measured., Results: The random forest model demonstrated the highest accuracy (range 0.82-0.88) and AUC (range 0.86-0.88) across all four data sets. Further validation testing revealed high precision (0.76), relatively low recall (0.46), and overall strong predictive performance (F1 score 0.57, accuracy 0.86) for ICP crises. Decision curve analysis showed that the model provided net benefit at probability thresholds above 0.1 and below 0.9., Conclusions: The presented model can provide accurate and timely forecasts of ICP crises in patients with severe TBI 10-20 minutes prior to their occurrence. If validated and implemented in clinical workflows, this algorithm can enable earlier intervention for ICP crises, more effective treatment of intracranial hypertension, and potentially improved outcomes following severe TBI.

Objective: To determine the in-hospital cost implications of an expanded endoscopic endonasal approach (EEEA) for craniopharyngioma resection relative to the traditional open transcranial approach., Methods: All craniopharyngioma surgeries performed at a single institution over a period from January 1st 2001 to October 31th 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate regression analysis was performed using R software., Results: Thirty-six patients met study criteria, including 22 undergoing an open approach and 14 undergoing an EEEA. There was a significantly longer average length of stay among patients undergoing open resection (21.5 vs. 10.6 days, p = 0.024). The average total in-hospital cost of a patient undergoing an EEEA was $58979.3 compared to $89142.3 for an open approach (p = 0.127). On univariate regression analysis, the total in-hospital cost for a patient undergoing an open approach relative to an EEEA was $30163.0 (p = 0.127). The open approach was exclusively performed from study onset until April 2010 (16 patients). From April 2010 to August 2013, 6 open approaches and 5 EEEA were performed. The EEEA has been exclusively performed from August 2013 until the conclusion of our study period (9 patients)., Conclusions: There has been a shift toward surgical resection of craniopharyngioma via an EEEA approach for amenable tumors. Our study demonstrates that the EEEA has become the preferred surgical approach at our institution, and shows that the EEEA is associated with shorter postoperative length of stay and lower total in-hospital cost. Laryngoscope, 133:83-87, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Postoperative C5-6 palsies can occur in 5%-10% of cases after cervical spine surgery. In this video, the authors demonstrate operative techniques for nerve transfer to restore function for postoperative C5-6 palsy. The patient underwent C3-6 laminectomy and posterior fusion for cervical spondylotic myelopathy and developed weakness postoperatively in the C5-6 distribution bilaterally. He experienced spontaneous recovery to near full strength in the most affected muscle groups by 12 months except the left biceps (2/5), with at least antigravity shoulder abduction. He underwent left ulnar to musculocutaneous nerve fascicular transfer to improve elbow flexion and supination in the setting of good hand function. The video can be found here: https://stream.cadmore.media/r10.3171/2022.10.FOCVID22100., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication.The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication., (© 2023, The Authors.)

Acellularized nerve allografts (ANAs) have been developed as substitutes for nerve autograft to promote nerve regeneration after surgical repair. In this video, the authors demonstrate operative techniques for using ANAs to repair potentially functional nerve fascicles during tumor resection. A 67-year-old female with schwannomatosis requested resection of a painful enlarging mass of the left ulnar nerve proximal to the elbow. During surgery, neuromonitoring suggested that fascicles entering the tumor could be functional. Therefore, nerve allograft was used to repair the transected fascicles. The patient recovered with full strength and sensation in the ulnar distribution, with resolution of her preoperative symptoms. The video can be found here: https://stream.cadmore.media/r10.3171/2022.10.FOCVID22101., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication.The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication., (© 2023, The Authors.)

One core measure of healthcare quality set forth by the Institute of Medicine is whether care decisions match patient goals. High-quality "serious illness communication" about patient goals and prognosis is required to support patient-centered decision-making, however current methods are not sensitive enough to measure the quality of this communication or determine whether care delivered matches patient priorities. Natural language processing (NLP) offers an efficient method for identification and evaluation of documented serious illness communication, which could serve as the basis for future quality metrics in oncology and other forms of serious illness. In this study, we trained NLP algorithms to identify and characterize serious illness communication with oncology patients., (©2022 AMIA - All rights reserved.)

Purpose: It is well documented that the interaction between many social factors can affect clinical outcomes. However, the independent effects of economics on outcomes following surgery are not well understood. The goal of this study is to investigate the role socioeconomic status has on postoperative outcomes in a cerebellopontine angle (CPA) tumor resection population., Materials and Methods: Over 6 years (07 June 2013 to 24 April 2019), 277 consecutive CPA tumor cases were reviewed at a single, multihospital academic medical center. Patient characteristics obtained included median household income, Charlson Comorbidity Index (CCI), race, BMI, tobacco use, amongst 23 others. Outcomes studied included readmission, ED evaluation, unplanned return to surgery (during and after index admission), return to surgery after index admission, and mortality within 90 days, in addition to reoperation and mortality throughout the entire follow-up period. Univariate analysis was conducted amongst the entire population with significance set at a p value <0.05. The population was divided into quartiles based on median household income and univariate analysis conducted between the lowest (Q1) and highest (Q4) socioeconomic quartiles, with significance set at a p value <0.05. Stepwise regression was conducted to determine the correlations amongst study variables and identify confounding factors., Results: Regression analysis of 273 patients did not find household income to be associated with any of the long-term outcomes assessed. Similarly, a Q1 vs Q4 comparison did not yield significantly different odds of outcomes assessed., Conclusion: Although not statistically significant, the odds ratios suggest socioeconomic status may have a clinically significant effect on postsurgical outcomes. Further studies in larger, matched populations are necessary to validate these findings.

Background: Early, high-quality advance care planning discussions are essential for supporting goal-concordant care among glioblastoma (GBM) patients. Objective: Using mixed methods, we sought to characterize current serious illness (SI) communication practices at our institution. Methods: The electronic medical records of 240 deceased GBM patients cared for at the Abramson Cancer Center in Philadelphia, PA between 2017 and 2019 were systematically reviewed for documented SI conversations about four domains: prognosis, goals, end-of-life planning, and code status. Patient outcomes and SI conversation characteristics were analyzed using descriptive statistics. Standardized interviews about GBM care were held with five clinicians. Interview transcripts were analyzed using grounded-theory coding to identify emergent themes. Results: Nearly all patients (96%) had at least one documented SI conversation (median: 4, interquartile range [IQR] 2-7), mostly outpatient with medical oncology physicians. Median timing of first SI conversation was 360 days before death. SI conversations were not significantly associated with patient outcomes, including inpatient death and hospice enrollment. Seven themes emerged from clinician interviews: balancing hope and reality, anticipatory guidance, neglect of the "big picture," need for earlier conversations, care coordination, the role of clinical expertise, and communication training. Conclusion: SI conversations were documented early and often in our sample, but their quality was difficult to assess. Contrary to our quantitative findings, interviewees reported that SI conversations were late, infrequent, inadequate, and fragmented across specialties, failing to explore critical issues such as prognosis and functional decline.

Background: Brain metastases are the most common central nervous system (CNS) tumors, occurring in 300,000 people per year in the US. While there are immediate local benefits to surgical resection for dominant lesions, including reduction of tumor burden and edema, the survival benefits of surgical resection, over radiosurgery, remains unclear., Methods: The University of Pennsylvania Health System database was retrospectively reviewed for patients presenting with multiple brain metastases from 1/1/16-8/31/18 with one dominant lesion > 2 cm in diameter, who underwent initial treatment with either resection of the dominant lesion or Gamma Knife radiosurgery (GKS). Inclusion criteria were age > 18, > 1 brain metastasis, and presence of a dominant lesion (>2 cm). We analyzed factors associated with mortality., Results: 129 patients were identified (surgery=84, GKS=45). The median number of intracranial metastases was 3 (IQR: 2-5). The median diameter of the largest lesion was 31 mm (IQR: 25-38) in the surgery group vs 21 mm (IQR: 20-24) in the GKS group (p < 0.001). Mortality did not differ between surgery and GKS patients (69.1% vs 77.8%, p = 0.292). In a multivariate survival analysis, there was no difference in mortality between the surgery and GKS cohorts (aHR: 1.35, 95% CI: 0.74-2.45 p = 0.32). Pre-operative KPS (aHR: 0.97, 95% CI: 0.95-0.99, p = 0.004), CNS radiotherapy (aHR: 0.33, 95% CI: 0.19-0.56 p < 0.001), chemotherapy (aHR: 0.27, 95% CI: 0.15-0.47, p < 0.001), and immunotherapy (aHR: 0.41, 95% CI: 0.25-0.68, p = 0.001) were associated with decreased mortality., Conclusion: In our institution, patients with multiple brain metastases and one symptomatic dominant lesion demonstrated similar survival after GKS when compared with up-front surgical resection of the dominant lesion., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cancer cell lines, which are cell cultures derived from tumor samples, represent one of the least expensive and most studied preclinical models for drug development. Accurately predicting drug responses for a given cell line based on molecular features may help to optimize drug-development pipelines and explain mechanisms behind treatment responses. In this study, we focus on DNA methylation profiles as one type of molecular feature that is known to drive tumorigenesis and modulate treatment responses. Using genome-wide, DNA methylation profiles from 987 cell lines in the Genomics of Drug Sensitivity in Cancer database, we used machine-learning algorithms to evaluate the potential to predict cytotoxic responses for eight anti-cancer drugs. We compared the performance of five classification algorithms and four regression algorithms representing diverse methodologies, including tree-, probability-, kernel-, ensemble-, and distance-based approaches. We artificially subsampled the data to varying degrees, aiming to understand whether training based on relatively extreme outcomes would yield improved performance. When using classification or regression algorithms to predict discrete or continuous responses, respectively, we consistently observed excellent predictive performance when the training and test sets consisted of cell-line data. Classification algorithms performed best when we trained the models using cell lines with relatively extreme drug-response values, attaining area-under-the-receiver-operating-characteristic-curve values as high as 0.97. The regression algorithms performed best when we trained the models using the full range of drug-response values, although this depended on the performance metrics we used. Finally, we used patient data from The Cancer Genome Atlas to evaluate the feasibility of classifying clinical responses for human tumors based on models derived from cell lines. Generally, the algorithms were unable to identify patterns that predicted patient responses reliably; however, predictions by the Random Forests algorithm were significantly correlated with Temozolomide responses for low-grade gliomas., Competing Interests: The authors have declared that no competing interests exist.

Objective: To characterize the patient and clinical factors that determine variability in hospital costs following endoscopic transphenoidal pituitary surgery., Methods: All endoscopic transphenoidal pituitary surgeries performed from January 1, 2015, to October 24, 2017, with complete data were evaluated in this retrospective single-institution study. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables during each hospital stay. Multivariate linear regression was performed using Stata software., Results: The analysis included 190 patients and average length of stay was 4.71 days. Average total in-hospital cost was $28,624 (95% confidence interval $25,094-$32,155) with average total direct cost of $19,444 ($17,136-$21,752) and total indirect cost of $9181 ($7592-$10,409). On multivariate regression, post-operative cerebrospinal fluid (CSF) leak was associated with a significant increase in all cost variables, including a total cost increase of $40,981 ($15,474-$66,489, P = .002). Current smoking status was associated with an increased total cost of $20,189 ($6,638-$33,740, P = .004). Self-reported Caucasian ethnicity was associated with a significant decrease in total cost of $6646 (-$12,760 to -$532, P = .033). Post-operative DI was associated with increased costs across all variables that were not statistically significant., Conclusions: Post-operative CSF leak, current smoking status, and non-Caucasian ethnicity were associated with significantly increased costs. Understanding of cost drivers of endoscopic transphenoidal pituitary surgery is critical for future cost control and value creation initiatives., Level of Evidence: 3 Laryngoscope, 131:760-764, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Objectives  The objective of this study is to elucidate the impact of income on short-term outcomes in a cerebellopontine angle (CPA) tumor resection population. Design  This is a retrospective regression analysis. Setting  This study was done at a single, multihospital, urban academic medical center. Participants  Over 6 years (from June 7, 2013, to April 24, 2019), 277 consecutive CPA tumor cases were reviewed. Main Outcome Measures  Outcomes studied included readmission, emergency department evaluation, unplanned return to surgery, return to surgery after index admission, and mortality. Univariate analysis was conducted among the entire population with significance set at a p -value <0.05. The population was divided into quartiles based on median household income and univariate analysis conducted between the lowest (quartile 1 [Q1]) and highest (quartile 4 [Q4]) socioeconomic quartiles, with significance set at a p -value <0.05. Stepwise regression was conducted to determine the correlations among study variables and to identify confounding factors. Results  Regression analysis of 273 patients demonstrated decreased rates of unplanned reoperation ( p  = 0.015) and reoperation after index admission ( p  = 0.035) at 30 days with higher standardized income. Logistic regression between the lowest (Q1) and highest (Q4) socioeconomic quartiles demonstrated decreased unplanned reoperation ( p  = 0.045) and decreasing but not significant reoperation after index admission ( p  = 0.15) for Q4 patients. No significant difference was observed for other metrics of morbidity and mortality. Conclusion  Higher socioeconomic status is associated with decreased risk of unplanned reoperation following CPA tumor resection., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Human brain organoids emerged in 2013 as a technology that, unlike prior in Vitro neural models, recapitulates brain development with a high degree of spatial and temporal fidelity. As the platform matured with more accurate reproduction of cerebral architecture, brain organoids became increasingly valuable for studying both normal cortical neurogenesis and a variety of congenital human brain disorders. While the majority of research utilizing human brain organoids has been in the realm of basic science, clinical applications are forthcoming. These present and future translational efforts have the potential to make a considerable impact on the field of neurosurgery. For example, glioma organoids are already being used to study tumor biology and drug responses, and adaptation for the investigation of other neurosurgery-relevant diseases is underway. Moreover, organoids are being explored as a structured neural substrate for repairing brain circuitry. Thus, we believe it is important for our field to be aware and have an accurate understanding of this emerging technology. In this review, we describe the key characteristics of human brain organoids, review their relevant translational applications, and discuss the ethical implications of their use through a neurosurgical lens., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Despite the substantial growth of telemedicine and the evidence of its advantages, the use of telemedicine in neurosurgery has been limited. Barriers have included medicolegal issues surrounding provider reimbursement, interstate licensure, and malpractice liability as well as technological challenges. Recently, the coronavirus disease 2019 (COVID-19) pandemic has limited typical evaluation of patients with neurologic issues and resulted in a surge in demand for virtual medical visits. Meanwhile, federal and state governments took action to facilitate the rapid implementation of telehealth programs, placing a temporary lift on medicolegal barriers that had previously limited its expansion. This created a unique opportunity for widespread telehealth use to meet the surge in demand for remote medical care. After initial hurdles and challenges, our experience with telemedicine in neurosurgery at Penn Medicine has been overall positive from both the provider and the patients' perspective. One of the unique challenges we face is guiding patients to appropriately set up devices in a way that enables an effective neuroexamination. However, we argue that an accurate and comprehensive neurologic examination can be conducted through a telemedicine platform, despite minor weaknesses inherent to absence of physical presence. In addition, certain neurosurgical visits such as postoperative checks, vascular pathology, and brain tumors inherently lend themselves to easier evaluation through telehealth visits. In the era of COVID-19 and beyond, telemedicine remains a promising and effective approach to continue neurologic patient care., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Neurosurgeons care for critically ill patients near the end of life, yet little is known about how well their training prepares them for this role. We surveyed a random sample of neurosurgery residents to describe the quantity and quality of teaching activities related to serious illness communication and palliative care, and resident attitudes and perceived preparedness to care for seriously ill patients., Methods: A previously validated survey instrument was adapted to reflect required communication and palliative care competencies in the 2015 the Accreditation Council for Graduate Medical Education (ACGME) Milestones for Neurological Surgery. The survey was reviewed for content validity by independent faculty neurosurgeons, piloted with graduating neurosurgical residents, and distributed online in August 2016 to neurosurgery residents in the United States using the American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Joint Section on Neurotrauma and Critical Care email listserv. Multiple choice and Likert scale responses were analyzed using descriptive statistics., Results: Sixty-two responses were recorded between August 2016 and October 2016. Most respondents reported no explicit teaching on: explaining risks and benefits of intubation and ventilation (69%), formulating prognoses in neurocritical care (60%), or leading family meetings (69%). Compared to performing craniotomies, respondents had less frequent practice leading discussions about withdrawing life-sustaining treatment (61% vs. 90%, p < 0.01, "weekly or more frequently"), and were less often observed (18% vs. 87%, p < 0.01) and given feedback on their performance (11% vs. 58%, p < 0.01). Nearly all respondents (95%) felt "prepared to discuss withdrawing life-sustaining treatments," however half (48%) reported they "would benefit from more communication training during residency." Most (87%) reported moral distress, agreeing that they "participated in operations and worried whether surgery aligned with patient goals.", Conclusions: Residents in our sample reported limited formal training, and relatively less observation and feedback, on required ACGME competencies in palliative care and communication. Most reported preparedness in this domain, but many were receptive to more training. Better quality and more consistent palliative care education in neurosurgery residency could improve competency and help ensure that neurosurgical care aligns with patient goals., (Copyright © 2019 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Importance: Earlier clinician-patient conversations about patients' values, goals, and preferences in serious illness (ie, serious illness conversations) are associated with better outcomes but occur inconsistently in cancer care., Objective: To evaluate the efficacy of a communication quality-improvement intervention in improving the occurrence, timing, quality, and accessibility of documented serious illness conversations between oncology clinicians and patients with advanced cancer., Design, Setting, Participants: This cluster randomized clinical trial in outpatient oncology was conducted at the Dana-Farber Cancer Institute and included physicians, advanced-practice clinicians, and patients with cancer who were at high risk of death., Main Outcomes and Measures: The primary outcomes (goal-concordant care and peacefulness at the end of life) are published elsewhere. Secondary outcomes are reported herein, including (1) documentation of at least 1 serious illness conversation before death, (2) timing of the initial conversation before death, (3) quality of conversations, and (4) their accessibility in the electronic medical record (EMR)., Results: We enrolled 91 clinicians (48 intervention, 43 control) and 278 patients (134 intervention, 144 control). Of enrolled patients, 58% died during the study (n=161); mean age was 62.3 years (95% CI, 58.9-65.6 years); 55% were women (n=88). These patients were cared for by 76 of the 91 enrolled clinicians (37 intervention, 39 control); years in practice, 11.5 (95% CI, 9.2-13.8); 57% female (n=43). Medical record review after patients' death demonstrated that a significantly higher proportion of intervention patients had a documented discussion compared with controls (96% vs 79%, P = .005) and intervention conversations occurred a median of 2.4 months earlier (median, 143 days vs 71 days, P < .001). Conversation documentation for intervention patients was significantly more comprehensive and patient centered, with a greater focus on values or goals (89% vs 44%, P < .001), prognosis or illness understanding (91% vs 48%, P < .001), and life-sustaining treatment preferences (63% vs 32%, P = .004). Documentation about end-of-life care planning did not differ between arms (80% intervention vs 68% control, P = .08). Significantly more intervention patients had documentation that was accessible in the EMR (61% vs 11%, P < .001)., Conclusions and Relevance: This communication quality-improvement intervention resulted in more, earlier, better, and more accessible serious illness conversations documented in the EMR. To our knowledge, this is the first such study to demonstrate improvement in all 4 of these outcomes., Trial Registration: ClinicalTrials.gov identifier: NCT01786811.

Background: Early, high-quality serious illness (SI) conversations are critical for patients with glioblastoma (GBM) but are often mistimed or mishandled., Objective: To describe the prevalence, timing, and quality of documented SI conversations and evaluate their focus on patient goals/priorities., Design/participants: Thirty-three patients with GBM enrolled in the control group of a randomized controlled trial of a communication intervention and were followed for 2 years or until death. At baseline, all patients answered a validated question about preferences for life-extending versus comfort-focused care and completed a Life Priorities Survey about their goals/priorities. In this secondary analysis, retrospective chart review was performed for 18 patients with GBM who died. Documented SI conversations were systematically identified and evaluated using a codebook reflecting 4 domains: prognosis, goals/priorities, end-of-life planning, and life-sustaining treatments. Patient goals/priorities were compared to documentation., Measurements/results: At baseline, 16 of 24 patients preferred life-extending care. In the Life Priorities Survey, goals/priorities most frequently ranked among the top 3 were "Live as long as possible," "Be mentally aware," "Provide support for family," "Be independent," and "Be at peace." Fifteen of 18 patients had at least 1 documented SI conversation (range: 1-4). Median timing of the first documented SI conversation was 84 days before death (range: 29-231; interquartile range: 46-119). Fifteen patients had documentation about end-of-life planning, with "hospice" and "palliative care" most frequently documented. Five of 18 patients had documentation about their goals., Conclusion: Patients with GBM had multiple goals/priorities with potential treatment implications, but documentation showed SI conversations occurred relatively late and infrequently reflected patient goals/priorities.

Objective: Despite caring for patients near the end-of-life (EOL), surgeons and anesthesiologists report low confidence in their ability to facilitate EOL conversations. This discrepancy exists despite competency requirements and professional medical society recommendations. The objective of this systematic review is to identify articles describing EOL communication training available to surgeons and anesthesiologists, and to assess their methodological rigor to inform future curricular design and evaluation., Methods: This PRISMA-concordant systematic review identified English-language articles from PubMed, EMBASE, and manual review. Eligible articles included viewpoint pieces, and observational, qualitative, or case studies that featured an educational intervention for surgeons or anesthesiologists on EOL communication skills. Data on the study objective, setting, design, participants, intervention, and results were extracted and analyzed. The Newcastle-Ottawa Scale was used to assess methodological quality., Results: Database and manual search returned 2710 articles. A total of 2268 studies were screened by title and abstract, 46 reviewed in full-text, and 16 included in the final analysis. Fifteen studies were conducted exclusively in academic hospitals. Two studies included attending surgeons as participants; all others featured residents, fellows, or a mix thereof. Fifteen studies used simulated role-playing to teach and assess EOL communication skills. Measured outcomes included knowledge, attitudes, confidence, self-rated or observer-rated communication skills, and curriculum feedback; significance of results varied widely. Most studies lacked adequate methodological quality and appropriate control groups to be confident about the significance and applicability of their results., Conclusions: There are few quality studies evaluating EOL communication training for surgeons and anesthesiologists. These programs frequently use role-playing to teach and assess EOL communication skills. More studies are needed to evaluate the effect of these interventions on patient outcomes. However, evaluating the effectiveness of these initiatives poses methodological challenges., (Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The 2016 Mexican Report Card on Physical Activity for Children and Youth aims to assess how Mexico is doing in terms of providing physical activity (PA) opportunities for Mexican children and youth. The purpose of this article is to summarize results from the Mexican 2016 Report Card., Methods: A literature search was conducted in Spanish and English languages using major databases, and complemented with a review of government/nongovernment documents, websites, and national health surveys. Information on the 9 indicators outlined in the Global Matrix of Report Card Grades was extracted. A team of Mexican experts met to discuss and assign a grade on each indicator based on the best available evidence and established benchmarks., Results: Daily behaviors grades were Overall PA (C), Organized Sport Participation (D), Active Play (D-), Active Transportation (C), and Sedentary Behavior (D). For Settings and Sources of Influence, grades were Family and Peers (INC), School (D-), and Community and Environment (D). Strategies and Investments grades were Government Strategies (C) and Non-Government (F)., Conclusions: PA and sedentary behaviors among Mexican children and youth remain below the recommended levels. Government and communities are far from providing appropriate and sufficient physical activity opportunities for children and youth.

Background The identification of high-risk stage II colon cancers is key to the selection of patients who require adjuvant treatment after surgery. Microarray-based multigene-expression signatures derived from stem cells and progenitor cells hold promise, but they are difficult to use in clinical practice. Methods We used a new bioinformatics approach to search for biomarkers of colon epithelial differentiation across gene-expression arrays and then ranked candidate genes according to the availability of clinical-grade diagnostic assays. With the use of subgroup analysis involving independent and retrospective cohorts of patients with stage II or stage III colon cancer, the top candidate gene was tested for its association with disease-free survival and a benefit from adjuvant chemotherapy. Results The transcription factor CDX2 ranked first in our screening test. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. In the discovery data set, which included 466 patients, the rate of 5-year disease-free survival was lower among the 32 patients (6.9%) with CDX2-negative colon cancers than among the 434 (93.1%) with CDX2-positive colon cancers (hazard ratio for disease recurrence, 3.44; 95% confidence interval [CI], 1.60 to 7.38; P=0.002). In the validation data set, which included 314 patients, the rate of 5-year disease-free survival was lower among the 38 patients (12.1%) with CDX2 protein-negative colon cancers than among the 276 (87.9%) with CDX2 protein-positive colon cancers (hazard ratio, 2.42; 95% CI, 1.36 to 4.29; P=0.003). In both these groups, these findings were independent of the patient's age, sex, and tumor stage and grade. Among patients with stage II cancer, the difference in 5-year disease-free survival was significant both in the discovery data set (49% among 15 patients with CDX2-negative tumors vs. 87% among 191 patients with CDX2-positive tumors, P=0.003) and in the validation data set (51% among 15 patients with CDX2-negative tumors vs. 80% among 106 patients with CDX2-positive tumors, P=0.004). In a pooled database of all patient cohorts, the rate of 5-year disease-free survival was higher among 23 patients with stage II CDX2-negative tumors who were treated with adjuvant chemotherapy than among 25 who were not treated with adjuvant chemotherapy (91% vs. 56%, P=0.006). Conclusions Lack of CDX2 expression identified a subgroup of patients with high-risk stage II colon cancer who appeared to benefit from adjuvant chemotherapy. (Funded by the National Comprehensive Cancer Network, the National Institutes of Health, and others.).

Background: Chiari I malformation (CM-I) is defined by cerebellar tonsillar herniation through the foramen magnum. Patients typically present with chronic complaints, including headache, dizziness, and numbness, although there are few reports in the literature of pediatric patients presenting acutely with neurological deficit caused by CM-I. We report a child who presented acutely with hemiparesis and magnetic resonance imaging findings consistent with CM-I and spinal cord edema., Case Description: A 3-year old boy with normal development presented with difficulty walking and increased drooling. His mother stated he was running into objects and had balance issues for several days. Neurological examination showed ataxia with falling to the right after a few steps and weakness of the right arm and leg. His medical history was remarkable only for mild asthma, although he had recently been treated for an upper respiratory viral infection. Computed tomography of the head demonstrated no brainstem mass. Magnetic resonance imaging of the head and cervical spine showed tonsillar ectopia approximately 2 cm below the craniocervical junction with increased T2 signal in the spinal cord from C1 to C3 consistent with syringomyelia and cord edema. The patient underwent suboccipital craniectomy with removal of the posterior arch of C1 and dural patch graft. His postoperative course was unremarkable, with complete resolution of his symptoms at his 1-month follow-up visit., Conclusions: This case highlights an unusual presentation of CM-I with neurological deficit related to spinal cord edema, possibly precipitated by the "water-hammer" effect of this patient's coughing fits. Providers should be aware of the acute presentations of CM-I., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Purpose: Intestinal mucositis is a common side-effect of irinotecan-based cancer chemotherapy regimens. This mucositis is associated with cytokine activation and NO synthesis. Production of IL-18 is up-regulated in patients suffering from inflammatory bowel disease. Therefore, we have investigated the role of IL-18 in the pathogenesis of irinotecan-induced intestinal mucositis., Experimental Approach: Wild type (WT), IL-18 or caspase-1 knockout mice were treated with either saline or irinotecan (60 mg·kg⁻¹ per 4 days, i.p.) or the IL-18 binding protein (IL-18bp, 10 mg·kg⁻¹) before irinotecan. On day 5, diarrhoea was monitored and proximal intestinal strips were obtained for histopathology, in vitro gut contractility, myeloperoxidase (MPO) and inducible NOS (iNOS) activity, and detection of IL-18 expression., Key Results: Irinotecan induced severe diarrhoea accompanied by intestinal injury (villi shortening and increased crypt depth). Additionally, irinotecan treatment increased MPO and iNOS activity, iNOS immunostaining and IL-18 expression in WT mice compared with saline treatment. The IL-18 production was associated with macrophages. In vitro, intestinal smooth muscle strips were hyperresponsive to ACh after irinotecan treatment. Increases in MPO and iNOS activity, intestinal contractility and diarrhoea were prevented in caspase-1 knockout and IL-18 knockout mice, and in IL-18bp-treated WT mice. Furthermore, the Survival of irinotecan-treated mice was increased and iNOS immunoexpression and IL-18 production prevented in IL-18 knockout mice., Conclusions and Implications: Targeting IL-18 function may be a promising therapeutic approach to decreasing the severity of intestinal mucositis during irinotecan treatment regimens., (© 2014 The British Pharmacological Society.)

We report 7 uterine cavity calcification cases and systematically review the literature on cases presenting this finding. In our series of cases, the mean age of patients was 31.6 ± 5.4 years, with an infertility period ranging from 2 to 8 years. None of our patients had a history of intrauterine contraceptive device use, and 3 had undergone operative termination of pregnancy. Diagnostic and therapeutic hysteroscopy with complete removal of the calcifications was performed in all patients with fertility restoration in 5 of them. Our review included 35 articles published from 1989 to 2013 reporting endometrial calcification cases, with a total of 85 cases. Analyzed variables included patient age, abortion antecedents, clinical presentation, diagnostic method, treatment, and outcome. The mean age of the analyzed cases was 34.3 years, ranging from 19 to 62 years. Abortion antecedents were present in most patients (76.5%). The most frequently used diagnostic methods were ultrasound (88.5% of articles) and hysteroscopy (85.7%). Regarding the clinical presentation, infertility was the most common feature (72.9% of cases) followed by menstrual abnormalities (30.3%). Hysteroscopic removal, whether alone or combined with other techniques, was the most used method for the removal of osseous tissue (70.6% of cases) followed by curettage (27.1%). After removal of the bony fragments, 55.6% of the infertile patients achieved a pregnancy. A total of 14 cases reported relief of symptoms other than infertility. All of the data concerning outcome were stratified according to the treatment modality used. We conclude that endometrial calcifications in the uterine cavity are a relevant cause of secondary infertility, which can generally be properly diagnosed and treated through hysteroscopy, with successful restoration of fertility in most cases., (Copyright © 2014 AAGL. Published by Elsevier Inc. All rights reserved.)

This study was undertaken to investigate the expression of p53, Ki-67, and CD31 proteins in endometrial polyps of postmenopausal women treated with tamoxifen (TAM). Postmenopausal women with endometrial polyps treated with TAM (n = 20), postmenopausal women with endometrial polyps without hormone use (n = 20), postmenopausal women with atrophic endometrium (n = 20), and postmenopausal women with endometrial adenocarcinoma (n = 20) were prospectively investigated. Tissue samples were immunohistochemically evaluated by monoclonal antibodies for p53, Ki-67, and CD31. The data were analyzed using the Student t test, analysis of variance, and χ2 to evaluate significant differences between the groups. The level of significance was set at P < 0.05. There was no difference in the expression of p53 between the groups (P = 0.067). The expression of Ki-67 was higher in the polyp samples from TAM-treated women compared with those from the women using no hormone (P = 0.0047) and those from the women with atrophic endometrium (P = 0.008). Samples from the women with endometrial cancer was associated with higher Ki-67 expression compared with the polyp samples from TAM-treated women (P = 0.004). The expression of CD31 was higher in the polyp samples of TAM-treated women compared with that of the samples from the women with atrophic endometrium (P < 0.001) and similar to the polyp samples from the women using no hormone (P = 0.319) and to the samples from the women with endometrial cancer (P = 0.418). The use of TAM in postmenopausal women might be associated with increased cellular proliferation in endometrial polyps without interfering angiogenesis or inactivation of tumor suppressor proteins.