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Macro-scale changes in longitudinal bone growth resulting from mechanical loading were shown in Part 1 of this review to depend on load magnitude, anatomical location, and species. While no significant effect on longitudinal growth was observed by varying frequency and amplitude of cyclic loading, such variations, in addition to loading duration and species, were shown to affect the morphology, viability, and gene and protein expression within the growth plate. Intermittent compression regimens were shown to preserve or increase growth plate height while stimulating increased chondrocyte presence in the hypertrophic zone relative to persistent and static loading regimens. Gene and protein expressions related to matrix synthesis and degradation, as well as regulation of chondrocyte apoptosis were shown to exhibit magnitude-, frequency-, and duration-dependent responses to loading regimen. Chondrocyte viability was shown to be largely preserved within physiological bounds of magnitude, frequency, amplitude, and duration. Persistent static loading was shown to be associated with overall growth plate height in tension only, reducing it in compression, while affecting growth plate zone heights differently across species and encouraging mineralization relative to intermittent cyclic loading. Lateral loading of the growth plate, as well as microfluidic approaches are relatively understudied, and age, anatomical location, and species effects within these approaches are undefined. Understanding the micro-scale effects of varied loading regimes can assist in the development of growth modulation methods and device designs optimized for growth plate viability preservation or mineralization stimulation based on patient age and anatomical location.

The density and distribution of the tumor immune microenvironment associated with brain metastases (BM) from gynecologic malignancies are unknown and have not been previously reported. We sought to describe the clinical features of a cohort of patients with BM from gynecologic malignancies and to characterize the tumor immune microenvironment from available archival surgical specimens.We performed a retrospective review of electronic medical records from 2002 to 2018 for patients with BM from gynecologic malignancies. Data on patient characteristics, treatment regimens, and clinical outcomes were procured. CD4, CD8, CD45RO, CD68, CD163, and FOXP3 immunohistochemistry were evaluated from available archival surgical specimens from primary disease site and neurosurgical resection.A cohort of 44 patients with BM from gynecologic malignancies was identified, 21 (47.7%) endometrial primaries and 23 (52.3%) ovarian primaries. Tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) were evaluated in 13 primary cases and 15 BM cases. For the 13 primary cases, CD4An active tumor immune microenvironment is present with similar distribution in the primary disease site and BM from patients with gynecologic malignancies.

The genetic alterations that define primary central nervous system lymphoma (PCNSL) are incompletely elucidated, and the genomic evolution from diagnosis to relapse is poorly understood. We performed whole-exome sequencing (WES) on 36 PCNSL patients and targeted MYD88 sequencing on a validation cohort of 27 PCNSL patients. We also performed WES and phylogenetic analysis of 3 matched newly diagnosed and relapsed tumor specimens and 1 synchronous intracranial and extracranial relapse. Immunohistochemistry (IHC) for programmed death-1 ligand (PD-L1) was performed on 43 patient specimens. Combined WES and targeted sequencing identified MYD88 mutation in 67% (42 of 63) of patients, CDKN2A biallelic loss in 44% (16 of 36), and CD79b mutation in 61% (22 of 36). Copy-number analysis demonstrated frequent regions of copy loss (ie, CDKN2A), with few areas of amplification. CD79b mutations were associated with improved progression-free and overall survival. We did not identify amplification at the PD-1/PD-L1 loci. IHC for PD-L1 revealed membranous expression in 30% (13 of 43) of specimens. Phylogenetic analysis of paired primary and relapsed specimens identified MYD88 mutation and CDKN2A loss as early clonal events. PCNSL is characterized by frequent mutations within the B-cell receptor and NF-κB pathways. The lack of PD-L1 amplifications, along with membranous PD-L1 expression in 30% of our cohort, suggests that PD-1/PD-L1 inhibitors may be useful in a subset of PCNSL. WES of PCNSL provides insight into the genomic landscape and evolution of this rare lymphoma subtype and potentially informs more rational treatment decisions.

Asylum seekers report exposure to human rights violations associated with a range of psychological and medical sequelae. Clinical evaluators can provide forensic evaluations that document evidence associated with their reports of persecution. The aim of this study was to characterize the forms of abuse experienced by asylum seekers, the psychological consequences of abuse, and the frequency with which clinician-evaluators found evidence that corroborated asylum seekers' reports.We completed a retrospective chart review of 121 asylum seekers who received pro bono medical-legal evaluations through a human rights program and analyzed data using the constant comparative method.Eighty-eight percent of the clients reported experiencing multiple human rights abuses. Ninety-one percent of the clients who received psychological evaluations presented with symptoms associated with depression, anxiety, or trauma and stressor-related disorders. Clinician-evaluators found physical or psychological evidence consistent with the clients' reports in 97% of cases. Forms, perpetrators, and psychological consequences of abuse varied significantly by gender and geographic region.Asylum seekers report diverse forms of persecution in their countries of origin that differ by gender and geographic region. Clinician-evaluators overwhelmingly found physical and psychological evidence consistent with the asylum seekers' accounts of persecution.

Objective Posterior fossa meningiomas are surgically challenging tumors that are associated with high morbidity and mortality. We sought to investigate the anatomical distribution of clinically actionable mutations in posterior fossa meningioma to facilitate identifying patients amenable for systemic targeted therapy trials. Methods Targeted sequencing of clinically targetable AKT1, SMO, and PIK3CA mutations was performed in 61 posterior fossa meningioma using Illumina NextSeq 500 to a target depth of >500 × . Samples were further interrogated for 53 cancer-relevant RNA fusions by the Archer FusionPlex panel to detect gene rearrangements. Results AKT1 (E17K) mutations were detected in five cases (8.2%), four in the foramen magnum and one in the cerebellopontine angle. In contrast, none of the posterior fossa tumors harbored an SMO (L412F) or a PIK3CA (E545K) mutation. Notably, the majority of foramen magnum meningiomas (4/7, 57%) harbored an AKT1 mutation. In addition, common clinically targetable gene fusions were not detected in any of the cases. Conclusion A large subset of foramen magnum meningiomas harbor AKT1 E17K mutations and are therefore potentially amenable to targeted medical therapy. Genotyping of foramen magnum meningiomas may enable more therapeutic alternatives and guide their treatment decision process.

Glioblastomas are malignant neoplasms composed of diverse cell populations. This intratumoral diversity has an underlying architecture, with a hierarchical relationship through clonal evolution from a common ancestor. Therapies are limited by emergence of resistant subclones from this phylogenetic reservoir. To characterize this clonal ancestral origin of recurrent tumors, we determined phylogenetic relationships using whole exome sequencing of pre-treatment IDH1/2 wild-type glioblastoma specimens, matched to post-treatment autopsy samples (n = 9) and metastatic extracranial post-treatment autopsy samples (n = 3). We identified “truncal” genetic events common to the evolutionary ancestry of the initial specimen and later recurrences, thereby inferring the identity of the precursor cell population. Mutations were identified in a subset of cases in known glioblastoma genes such as NF1(n = 3), TP53(n = 4) and EGFR(n = 5). However, by phylogenetic analysis, there were no protein-coding mutations as recurrent truncal events across the majority of cases. In contrast, whole copy-loss of chromosome 10 (12 of 12 cases), copy-loss of chromosome 9p21 (11 of 12 cases) and copy-gain in chromosome 7 (10 of 12 cases) were identified as shared events in the majority of cases. Strikingly, mutations in the TERT promoter were also identified as shared events in all evaluated pairs (9 of 9). Thus, we define four truncal non-coding genomic alterations that represent early genomic events in gliomagenesis, that identify the persistent cellular reservoir from which glioblastoma recurrences emerge. Therapies to target these key early genomic events are needed. These findings offer an evolutionary explanation for why precision therapies that target protein-coding mutations lack efficacy in GBM., Brain cancer: Non-coding genomic changes fuel glioblastoma growth Non-coding and structural alterations may be early drivers of brain cancer development. A team led by Priscilla Brastianos and Tracy Batchelor from Massachusetts General Hospital, Boston, USA, analyzed the genetic landscape of glioblastoma by comparing pre-treatment and autopsy tumor specimens from 12 patients who died of the aggressive brain cancer. They identified a common set of four genetic events that occurred early in the evolution of nearly every patient’s cancer: three losses or gains of chromosome regions or entire chromosomes, and mutations in the gene-activating promoter of TERT, which encodes an enzyme implicated in the cancer’s growth. The findings help explain why therapies that target protein-coding mutations don’t work in brain cancer when they do in other tumor types. They also point to new drug targets.

OBJECTIVEMeningiomas located in the skull base are surgically challenging. Recent genomic research has identified oncogenic SMO and AKT1 mutations in a small subset of meningiomas.METHODSThe authors performed targeted sequencing in a large cohort of patients with anterior skull base meningiomas (n = 62) to better define the frequency of SMO and AKT1 mutations in these tumors.RESULTSThe authors found SMO mutations in 7 of 62 (11%) and AKT1 mutations in 12 of 62 (19%) of their cohort. Of the 7 meningiomas with SMO mutations, 6 (86%) occurred in the olfactory groove. Meningiomas with an SMO mutation presented with significantly larger tumor volume (70.6 ± 36.3 cm3) compared with AKT1-mutated (18.2 ± 26.8 cm3) and wild-type (22.7 ± 23.9 cm3) meningiomas, respectively.CONCLUSIONSCombined, these data demonstrate clinically actionable mutations in 30% of anterior skull base meningiomas and suggest an association between SMO mutation status and tumor volume. Genotyping of SMO and AKT1 is likely to be high yield in anterior skull base meningiomas with available surgical tissue.

Introduction: Every year, thousands of women flee gender-based violence in Honduras, El Salvador, and Guatemala (sometimes collectively referred to as the Northern Triangle) in an attempt to seek asylum in the United States. Once in the United States, their legal teams may refer them for a psychological evaluation as part of their application for asylum. Licensed clinicians conduct in-depth interviews in order to document the psychological impact of the reported human rights violations. Method: Using archival de-identified data from a human rights program, this study gathered the experiences of gender-based violence reported by 70 asylum-seeking women from Honduras, El Salvador, and Guatemala who participated in pro bono psychological evaluation. Descriptive data were analyzed using a modified consensual qualitative research (CQR-M) method.Results: These asylum seekers reported exposure to systemic violence, including severe intimate partner violence, as well as physical and sexual assaults, and threats of death by organized criminal groups in their communities. Additionally, over a third of women reported experiences of violence during their migration. The majority of asylum seekers endorsed symptoms associated with anxiety (80%) and depression (91%), as well as trauma-and stressor-related symptoms (80%). Discussion: The results of this study elucidate the manyforms of gender-based violence experienced by women in this region, the physical and psychological sequelae of this persecution, and the systemic forces that prevent them from remaining in their countries of origin. The research results also highlight the potential impact of trauma on the women’s ability to testify effectively during asylum legal hearings, elucidate factors that may contribute to their resilience in light of the human rights violations they survived, and suggest implications for clinical practice.

Although lung adenocarcinomas frequently metastasize to the brain, treatment options for lung adenocarcinoma brain metastases are limited. We discovered novel candidate drivers of progression by using case-control analyses to compare whole-exome sequencing data from a cohort of 73 lung adenocarcinoma brain metastases to a control cohort of 503 primary lung adenocarcinomas. We identified 3 genomic regions with significantly more frequent amplifications in brain metastases compared to the control cohort: MYC (12% vs 6%), YAP1 (7% vs 0.8%) and MMP13 (10% vs 0.6%). We also identified CDKN2A/B as a region deleted at a significantly greater frequency in brain metastases compared to primary lung adenocarcinomas (27% vs 13%, respectively). We confirmed frequent amplifications of MYC and YAP1/MMP13 in an independent validation cohort of 105 lung adenocarcinoma brain metastasis samples using fluorescence in situ hybridization. We further validated that MYC, YAP1 and MMP13 can drive brain metastases in a patient-derived xenograft mouse model. We found a higher incidence of metastases to the brain in mice receiving intracardiac injections of tumor cells expressing the candidate drivers compared to tumor cells expressing LacZ as a control. These results indicate that somatic alterations can drive lung adenocarcinomas to metastasize to the brain. The candidate brain metastasis drivers that we identified may serve as therapeutic targets in patients with lung adenocarcinomas who develop this devastating complication.

The development of guidelines for opioid prescribing, including those from the Society of Hospital Medicine and the Centers for Disease Control and Prevention, has been associated with changes in prescription patterns. However, many providers remain unaware of best practices surrounding appropriate opioid prescribing.The research team implemented a multimodal quality improvement intervention, led by first-year medical students, designed to increase clinician adherence to current prescribing guidelines for patients discharged on opioids. This intervention included an awareness campaign, educational sessions for providers, and weekly performance feedback.A total of 4,993 discharges were identified in the baseline period and 4,811 discharges in the intervention period. During the baseline period, 12.3% of all patients discharged were discharged with opioid prescriptions vs. 11.4% during the intervention period (p = 0.165). Of these, approximately 60% were new opioid prescriptions during both periods (p = 0.991). The study's efforts were associated with a decrease in the percentage of patients discharged with opioid prescriptions longer than seven days (45.2% preintervention to 39.5% postintervention, p0.042); an increase in the percentage of patients with follow-up appointments within seven days of discharge (38.6% to 65.9%, p = 0.001); and an increase in documentation of prescription history obtained from the state Prescription Monitoring Program registry (32.5% to 39.7%, p = 0.042).This intervention provided a successful framework to engage learners in improving opioid prescribing practices. The results are promising, but the experiences highlight the significant effort and resources needed to change prescriber practices, potentially limiting sustainability.

Resumen Introducción: Los condilomas o verrugas genitales (VG) son la infección de transmisión sexual (ITS) más diagnosticada en los centros de ITS en Chile, pero no existen estadísticas poblacionales. Objetivos: Describir la prevalencia de VG en pacientes de 18-60 años que acuden a consulta ambulatoria de dermatología, ginecología y urología; características demográficas de los pacientes y prácticas de diagnóstico y tratamiento. Material y Métodos: A una muestra de especialistas chilenos estratificados por región, población y sexo de pacientes se les proporcionó un diario de registro y aplicó un cuestionario. Resultados: Prevalencia VG grupo total: 2,4%; en grupo etario 18-34 años: 3,7%; en grupo etario 35-60 años: 1,29% (p = 0,0000). La edad media de los pacientes con VG fue 29,4 años en mujeres y 32,7 años en hombres (p = 0,019); la distribución por edad fue diferente según sexo y sistema de salud. La inspección visual fue el método diagnóstico más frecuente y la crema de imiquimod el tratamiento más común. Hubo diferencias en el uso de herramientas diagnósticas y terapéuticas según sexo del paciente, especialidad del médico y sistema de salud. Conclusiones: Existe una alta prevalencia de VG, que debería ser tomada en cuenta para planificar las intervenciones de salud pública para abordar este problema.

Resumen Introducción: Los condilomas o verrugas genitales (VG) son la infección de transmisión sexual (ITS) más diagnosticada en los centros de ITS en Chile, pero no existen estadísticas poblacionales. Objetivos: Describir la prevalencia de VG en pacientes de 18-60 años que acuden a consulta ambulatoria de dermatología, ginecología y urología; características demográficas de los pacientes y prácticas de diagnóstico y tratamiento. Material y Métodos: A una muestra de especialistas chilenos estratificados por región, población y sexo de pacientes se les proporcionó un diario de registro y aplicó un cuestionario. Resultados: Prevalencia VG grupo total: 2,4%; en grupo etario 18-34 años: 3,7%; en grupo etario 35-60 años: 1,29% (p = 0,0000). La edad media de los pacientes con VG fue 29,4 años en mujeres y 32,7 años en hombres (p = 0,019); la distribución por edad fue diferente según sexo y sistema de salud. La inspección visual fue el método diagnóstico más frecuente y la crema de imiquimod el tratamiento más común. Hubo diferencias en el uso de herramientas diagnósticas y terapéuticas según sexo del paciente, especialidad del médico y sistema de salud. Conclusiones: Existe una alta prevalencia de VG, que debería ser tomada en cuenta para planificar las intervenciones de salud pública para abordar este problema. Introduction: Condylomas or genital warts (GW) are the most frequently diagnosed sexually transmitted infection (STI) in STI centers in Chile, but there are no population statistics available. Objectives: To describe the prevalence of GW in patients from 18-60 years of age who attend outpatient dermatology, gynecology and urology practice; the demographic characteristics of the patients and the diagnostic and treatment tools. Methods: A sample of Chilean specialists stratified by region, population and gender of patients was provided with a logbook and answered a questionnaire. Results: The GW prevalence was 2.44% for the whole group; 3.76% for the 18-34 age group and 1.29% for the 35-60 years group (p = 0.0000). The average age of patients with GW was 29.4 years in women and 32.7 years in men (p = 0.019). The distribution by age was different according to gender and health system. Visual inspection was the most frequent diagnostic method used and imiquimod cream the most common treatment, however, there were differences in the use of diagnostic and therapeutic tools according to the patient's gender, specialty of the doctor and health system. Conclusions: The high prevalence of GW confirmed the need and importance of public health interventions to address this problem.

Background Biliary tract cancers (BTCs) are highly fatal malignancies that make up less than 1% of all cancers. BTC is often diagnosed at an unresectable stage; surgical resection remains the only definitive treatment. Brain metastases (BMs) from BTC are extremely rare, and few studies on patients with BMs from BTC exist. The aim of this study was to identify clinical characteristics associated with poor prognosis for patients with BMs from BTC. Materials and Methods We performed a retrospective review of electronic medical records for patients with BMs from BTC managed at Mount Sinai Hospital from 2000 to 2017. Data on patient characteristics, magnetic resonance imaging findings, treatment regimens, and clinical outcomes were analyzed. Results We identified 1,910 patients with BTC. Nine patients developed BMs, with an incidence of 0.47%. Of these nine patients, six had intrahepatic cholangiocarcinoma, two had extrahepatic cholangiocarcinoma, and one had gallbladder cancer. Six (66.7%) patients had one BM, one (11.1%) patient had two BMs, and two (22.2%) patients had three or more BMs. Four (44.4%) patients underwent BM resection, and seven (77.8%) received BM radiation. Median overall survival from time of BM diagnosis was 3.8 months (95% confidence interval 0.1–16.9). Conclusion Development of BMs from BTC is rare; however, prognosis is less than 4 months. BM diagnosis can occur within 2 years of primary diagnosis. As targeted therapeutics emerge, future studies ought to focus on identifying genomic BM markers associated with BTC subtypes. Implications for Practice In the largest retrospective study of biliary tract cancer brain metastases, the clinical presentation and outcomes are reported of nine patients with an extremely rare clinical entity. The genomic literature and potential therapeutic targets for these patients with limited treatment options is comprehensively and exhaustively discussed.

Background In 2016, around 65 000 women fled gender-based violence in the Northern Triangle (NTCA) countries of El Salvador, Honduras, and Guatemala, and attempted to seek asylum in the USA. Some women participate in medical evaluations by clinicians to document the effect of these human rights violations as part of the asylum process. The aim of this study is to elucidate the forms of persecution experienced by women in this region, and the physical and psychological sequelae of this violence. Methods We undertook a retrospective, qualitative study of asylum-seeking adult women fleeing gender-based violence from the NTCA who were seen by evaluators in the Mount Sinai Human Rights Program from February, 2014, to August, 2018. We included any case in which the client self-identified as female, came from an NTCA country, and received a psychological evaluation. This study was approved by the Mount Sinai Institutional Review Board. We used a modified consensual qualitative research (CQR-M) approach to identify themes found across the archived and de-identified affidavits written as part of the medical evaluation. Findings We included data from 70 women; mean age was 29·4 years (SD 6·5; range 18–55 years]. 24 women identified as Salvadoran, 15 as Guatemalan, and 31 as Honduran. All women reported violence perpetrated by their communities, families, intimate partners, and/or powerful gangs, and faced justice systems in their countries that they felt would not protect them. They had been subject to: verbal (50 women [71%]), physical (57 [81%]), and sexual (59 [84%]) assaults; death threats (58 [83%]); control (40 [57%]); extortion (24 [34%]); and harm, or threats of harm, to their children (50 [43%] and 22 [31%], respectively). Evaluators identified psychological symptoms associated with anxiety (56 women [80%]), depression (64 [91%]), and post-traumatic stress disorder (56 [80%]), as well as suicidality (33 [47%]). Women also reported physical injury including bruising, head injury and loss of consciousness, and gynaecological harm including miscarriage and forced sterilisation. Many women had been displaced within their own countries before fleeing and stated that they travelled with their children, experienced hazardous conditions and violence during their journey, and were detained on arrival in the USA. Finally, the women reported resilience associated with their religious beliefs, family, temperament, and ability to make meaning from their experiences. Interpretation This study highlights the systemic nature of gender-based violence in the NTCA. The results also describe the perils that women from the NTCA encountered during their migration and demonstrate the continued structural violence that awaits them if they are denied asylum and returned to their countries of origin. Funding None.

Blockade of secreted and transmembrane protein translocation into the endoplasmic reticulum represents a potentially multifactorial approach to inhibiting tumor growth. We have shown that small molecule inhibitors of the Sec61 translocon can inhibit expression of autocrine growth factors, receptor oncogenes, and immune checkpoints. We nominated KZR-261 for clinical development and describe here bioinformatic analysis of in vitro cancer cell line screens and primary tumor samples that prioritizes potentially sensitive tumor types for clinical evaluation. Anti-tumor activity of KZR-834, a structurally related analog of KZR-261, was assessed in two cell line cytotoxicity screens totaling over 400 cell lines. Broad anti-cancer activity across tumor types was observed in both screens, with median IC50 of 0.39 µM and 0.15 µM. We next demonstrated that KZR-261 has equivalent activity to KZR-834 by testing it on a subset of 48 cell lines (R2=0.91). For cell lines with RNA-Seq gene expression profiles available in CCLE (N=232), we correlated sensitivity to KZR-834 with each gene's expression. This analysis revealed a modest correlation between expression and cell line sensitivity for many genes. However, even the gene with the strongest correlation between expression and sensitivity provided only a partial explanation for KZR-834 sensitivity (CCND2, Spearman ρ = 0.31, P-val = 10−4). Levels of Sec61 were not associated with cell line sensitivity (SEC61A1, ρ = -0.05, P-val = 0.57). We therefore surveyed the gene-level results for enrichment of over 7,000 modules by performing fGSEA analysis. Enriched modules were hierarchically clustered revealing 6 primary clusters associated with sensitivity. The 6 clusters highlighted processes such as transcription, translation, metabolism, golgi vesicle transport, as well as genes encoding proteins that are secreted or plasma membrane localized. While fGSEA did not identify basal levels of ER stress as a process correlated with sensitivity, cell lines treated with KZR-834 have consistently shown activation of ER stress pathways at the mRNA and protein level, which led to its inclusion in subsequent analyses. Modules representing these 7 processes were then utilized to search tumor and normal tissue gene expression data from TCGA, TARGET and GTEx. Tumor types such as ALL, DLBCL, uveal and cutaneous melanoma, and mesothelioma were more enriched for expression of these modules than other tumor types and the vast majority of normal tissues. Our novel small molecule inhibitors of Sec61 dependent protein translocation exhibit broad anti-tumor activity in vitro. Large cell line screens and bioinformatic analyses identifying tumor intrinsic sensitivities led to a prioritized list of potentially sensitive tumor types that has guided tumor type selection for our initial Phase 1 clinical trial of KZR-261 in solid tumors. Citation Format: Eric Lowe, R. Andrea Fan, Henry W.B. Johnson, Christopher J. Kirk, Dustin McMinn, Yu Qian, Brian Tuch. Prioritizing tumor types for clinical study of novel Sec61 inhibitors by searching for expression profiles of sensitive cell lines in tumor sample databases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2226.

Although lung adenocarcinomas frequently metastasize to the brain, treatment options for lung adenocarcinoma brain metastases (BM-LUAD) are limited. We discovered novel candidate drivers of progression by using case-control analyses to compare whole-exome sequencing data from a cohort of 73 BM-LUAD to a control cohort of 503 primary lung adenocarcinomas. We identified MYC, YAP1 and MMP13 as genomic regions with significantly more frequent amplifications in BM-LUAD compared to control cohort. We validated that MYC, YAP1 and MMP13 can drive brain metastases in a patient-derived xenograft mouse model, where incidence of brain metastases was higher in mice injected with tumor cells expressing the candidate drivers compared to tumor cells expressing LacZ. These results indicate that somatic alterations can drive lung adenocarcinomas to metastasize to the brain. These candidate drivers may serve as therapeutic targets in patients with brain metastatic lung adenocarcinomas. Citation Format: Naema Nayyar, David J. Shih, Ivanna Bihun, Ibiayi Dagogo-Jack, Corey M. Gill, Elisa Aquilanti, Mia Bertalan, Alexander Kaplan, Megan R. D'Andrea, Ugonma Chukwueke, Christopher Alvarez-Breckenridge, Matthew Lastrapes, Ben Kuter, Matthew R. Strickland, Juan Carlos Martinez-Gutierrez, Deepika Nagabhushan, Magali De Sauvage, Michael D. White, Brandyn A. Castro, Kaitlin Hoang, Sun Ha Paek, Sun Hye Park, Maria Martinez-Lage, Anna S. Berghoff, Parker Merrill, Elizabeth R. Gerstner, Tracy T. Batchelor, Matthew P. Frosch, Ryan P. Frazier, Darrell R. Borger, A John Iafrate, Sandro Santagata, Matthias Preusser, Daniel P. Cahill, Scott L. Carter, Priscilla K. Brastianos. Identifying genomic drivers of lung adenocarcinoma brain metastases [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4729.

3582 Background: Secreted and transmembrane proteins play key roles in malignant transformation and growth, including in autocrine growth factor expression, receptor oncogene signaling, and immune system evasion. Biogenesis of these proteins involves translocation of the nascent polypeptides into the endoplasmic reticulum (ER) through the Sec61 channel, providing an untapped therapeutic target for a broad spectrum of malignancies. Here we describe preclinical activity of KZR-261 and related inhibitors of Sec61-dependent protein secretion. Methods: Sec61 inhibition with KZR-261 and related analog KZR-834 were evaluated using cell lines overexpressing proteins of interest tagged with luciferase. In vitro anti-tumor activity was assessed against a panel of 346 cell lines across 25 tumor types. Quantitative proteomic profiling by mass spec and gene expression profiling by RNAseq were conducted following treatment in multiple solid and heme tumor cell lines. Anti-tumor efficacy was evaluated in athymic nude mice implanted with the cancer cell lines H82 (SCLC), HT29 (CRC), BxPC3 (Pancreatic), 22RV1 (Prostate), H929 (Myeloma) and RL (NHL). Activity was also evaluated in a MC38 syngeneic colon tumor model. Results: KZR-261 and KZR-834 exhibited nanomolar potency against many therapeutic targets, including immune checkpoints, VEGF-A, VEGFR and EGFR. Broad in vitro anti-cancer activity was observed with KZR-834, which potently decreased cell viability across both solid and heme tumor types including CRC, Pancreatic, HNSCC, HCC, Lymphoma and Myeloma. Global proteomic analysis observed more than 1.5 fold downregulation of < 10% of detected Sec61 client proteins following treatment, while gene expression profiling revealed upregulation of ER stress response genes in sensitive versus resistant cell lines. Analysis of the TCGA database also found these genes upregulated in a number of different tumor types. In vivo, weekly IV administration was well tolerated and induced a dose dependent anti-tumor response at doses below the MTD in solid and heme xenograft models. In the syngeneic MC38 model, administration of KZR-834 in combination with anti-PD1 antibody resulted in greater anti-tumor activity than either single agent. Conclusions: Novel Sec61 inhibitors potently block expression of secreted and membrane proteins, translating into anti-tumor activity against many tumor types in vitro and in vivo, suggesting broad therapeutic potential. Clinical trials are being planned with KZR-261 to understand safety and early efficacy of this novel compound and therapeutic target.

"Reforzar la conducta blanco induce un aumento en la frecuencia de otras conductas en la misma dimensión. Hemos estudiado este fenómeno usado una cámara con siete palancas alineadas en el panel frontal. Reforzar las presiones a una sola palanca induce presiones en las otras palancas, pero con una frecuencia que disminuye al aumentar la distancia de la palanca operativa. En esta investigación se observó la resurgencia de las presiones en las siete palancas. Durante la primera fase se reforzaron las presiones a la palanca central con un programa de intervalo al azar de 15 s. Durante la segunda fase se suspendió el reforzamiento a la palanca central y con el mismo programa se reforzó el tirar de una cadena suspendida en el techo de la cámara. En la tercera fase se eliminó el reforzamiento por completo. En ausencia de reforzamiento las presiones a la palanca central resurgieron en conjunción con las presiones a las otras palancas. También la distribución de las presiones a todas las palancas fue similar a la que se obtuvo durante la primera fase. Se concluyó que la resurgencia consiste en patrones complejos que incluyen conducta condicionada e inducida."

RESUMEN La enfermedad inflamatoria pélvica (EIP) es un síndrome clínico que incluye todas aquellas alteraciones inflamatorias e infecciosas que comprenden los órganos de la pelvis menor. La infección es habitualmente polimicrobiana y está asociada a mujeres jóvenes con vida sexual activa, nulíparas y usuarias de dispositivo intrauterino (DIU Los abscesos tubo-ováricos son una complicación aguda o crónica, asociada a dicho proceso.). CASO CLÍNICO Presentamos el caso de una mujer de 47 años con dolor abdominal intenso, usuaria de DIU. La primera sospecha diagnóstica fue de EIP con presencia de absceso tuboovárico anexial. Sin embargo la exploración física no orientó en este sentido, por lo que se solicitó TAC abdominopélvico, en el que se informó de la posibilidad de linfangioma quístico mesentérico. Por ello, se contactó con el servicio de Cirugía General que procedió a su resección satisfactoria y sin incidencias. El estudio anatomopatológico confirmo la sospecha radiológica. CONCLUSIÓN Una adecuada exploración física es fundamental en el diagnóstico de la EIP y el absceso tuboovárico. El linfangioma quístico mesentérico puede formar parte del diagnóstico diferencial de las masas anexiales en este contexto. ABSTRACT Pelvic inflammatory disease (PID) is a clinical syndrome involving all those inflammatory and infectious alterations affecting the minor pelvis organs. Any infection is often multibacterial and more frequent in sexually active nulliparous young women and intrauterine device (IUD) users. Tuboovarian abscesses can be an acute or chronic complication associated to that process. Our patient was a 47 year old IUD user consulting about intense abdominal pain. The initial clinical suspicion pointed at a case of PID associated to a tubo-ovarian anexial abscess. However, a physical examination did not support this suspicion and an abdominopelvian CAT scan was therefore requested, reporting a possible mesenteric cystic lymphangioma. The General Surgery service was reached for treatment, successfully excising the growth without further incident. Histological analysis confirmed the radiological diagnosis. An adequate physical examination is instrumental while diagnosing PID and tuboovarian abscesses. A mesenteric cystic lymphangioma should be included in a differential diagnosis of anexial growths in such a context

Objective Posterior fossa meningiomas are surgically challenging tumors that are associated with high morbidity and mortality. We sought to investigate the anatomical distribution of clinically actionable mutations in posterior fossa meningioma to facilitate identifying patients amenable for systemic targeted therapy trials. Methods Targeted sequencing of clinically targetable AKT1 , SMO , and PIK3CA mutations was performed in 61 posterior fossa meningioma using Illumina NextSeq 500 to a target depth of >500 × . Samples were further interrogated for 53 cancer-relevant RNA fusions by the Archer FusionPlex panel to detect gene rearrangements. Results AKT 1 ( E17K ) mutations were detected in five cases (8.2%), four in the foramen magnum and one in the cerebellopontine angle. In contrast, none of the posterior fossa tumors harbored an SMO ( L412F ) or a PIK3CA ( E545K ) mutation. Notably, the majority of foramen magnum meningiomas (4/7, 57%) harbored an AKT1 mutation. In addition, common clinically targetable gene fusions were not detected in any of the cases. Conclusion A large subset of foramen magnum meningiomas harbor AKT1 E17K mutations and are therefore potentially amenable to targeted medical therapy. Genotyping of foramen magnum meningiomas may enable more therapeutic alternatives and guide their treatment decision process.

Resumen Introducción: Una de las formas de presentación de la enfermedad pilonidal sacrococcígea (EPSC) es el absceso, para el que existen distintas alternativas de tratamiento. Objetivo: Presentar nuestra experiencia con la técnica de Bascom para el tratamiento de la EPSC abscedada. Material y Método: Serie prospectiva, consecutiva y no aleatoria. Incluye todos los pacientes mayores de 15 años que presentan un absceso o supuración masiva al momento de la cirugía. Resultados: La serie corresponde a 10 pacientes, 7 de género masculino. No se encuentran los factores de riesgo reconocidos por la literatura como riesgo de EPSC. Ocho pacientes mejoran completamente en un período máximo de 18 días y 2 presentan supuración persistente, por lo que se considera fracaso del tratamiento. Estos son sometidos a una segunda cirugía con otra técnica, con curación de la enfermedad. Conclusión: La técnica de Bascom es sencilla, segura y ofrece una curación de un 80% en un período corto de cicatrización. Introduction: One of the form of presentation of the sacral coccygeal pilonidal disease is the abscess, for this cases there are various treatment alternatives. Objective: We present our experience with Bascom technique for the treatment of pilonidal abscess. Material and Method: Prospective, consecutive, non-randomized series. It includes all patients older than 15 years who have an abscess or mass discharge at the time of surgery. Results: The series consists of 10 patients, 7 males. They are not risk factors recognized in the literature as risk of pilonidal disease. Eight patients completely better within a maximum period of 18 days and two with persistent discharge by what is considered treatment failure. They were subjected to a second surgery treatment with another technique with good results. Conclusion: Bascom's technique is simple, safe and offers a 80% cure in a short period of healing.

Objetivo: Determinar la prevalencia del Síndrome del Túnel Carpiano (STC) y sus factores asociados en odontólogos de la ciudad de Bucaramanga y su área metropolitana.Materiales y métodos: Se realizó un estudio observacional analítico de corte transversal. El universo se constituyó por 250 y la muestra por 156 seleccionados mediante muestreo aleatorio simple. Se analizó la relación de presencia de STC con cada variable, mediante test de chi2 y test exacto de Fischer. El análisis multivariado mediante un modelo de regresión binomial, considerado como variable de salida la presencia de STC y como variable explicatoria las relacionadas con factores de riesgo.Resultados: La prevalencia de STC en odontólogos de Bucaramanga fue de 15.8%. El 40% de los endodoncistas registraron STC; se observó que el 33% de los odontólogos que registraban compromiso sistémico presentaban la condición de interés y que el 25% de las personas que usaban instrumental manual durante tiempos menores de 240 min/día registraban STC. Hubo una asociación seis veces mayor de tener STC en personas con compromiso sistémico y 0.13 de no tenerlo en personas que trabajan instrumental manual tiempos superiores a 240 min/día.Conclusión: Se estableció que el compromiso sistémico fue un factor determinante en la aparición de STC y el uso de instrumental rotario por tiempos prolongados, fue un factor relacionado con el ejercicio profesional, asociado con el fenómeno.[Rodríguez A, Morales K, Maldonado LP, Jiménez GE, Quiroz LF, Concha SC, Rueda SJ. Prevalencia del sindrome de túnel carpiano y sus factores asociados en odontólogos de la ciudad de Bucaramanga y su área metropolitana. Ustasalud Odontología 2005; 4: 73 - 80] Objective: To determine the prevalence of Carpal Tunnel Syndrome (CTS) and its associated factors in dentists of Bucaramanga and its metropolitan area.Materials and methods: An analytical cross section observational study was made. The universe were 250 dentists and the sample 156 dentists that were chosen by a simple random sampling. The relationship between the presence of CTS with each variable was analyzed by means of test of chi2 and Fisher´s exact test. The multivaried analysis included binomial regression model that considered as an exit variable the presence of CTS and like explicatory variables those related risk factors.Results: The prevalence of CTS in dentists who work in Bucaramanga was 15.8%. After analyzing the results according to each specialty, 40% of the endodontists had CTS, 30% of the dentists who had systemic compromise had CTS and 25% of the dentists who used manual instruments during time periods less than 240 min/day had CTS. There was an association six times greater of having CTS in people with systemic compromise and 0.13 of not having CTS in persons who work with manual instruments during time periods greater than 240 min/day.Conclusion: It was established that systemic compromise is determining factor in the appearance of CTS, the use of rotatory instruments for long time periods was a factor related to the professional exercise, associated to the phenomena.

Objective: To determine the prevalence of Carpal Tunnel Syndrome (CTS) and its associated factors in dentists of Bucaramanga and its metropolitan area.Materials and methods: An analytical cross section observational study was made. The universe were 250 dentists and the sample 156 dentists that were chosen by a simple random sampling. The relationship between the presence of CTS with each variable was analyzed by means of test of chi2 and Fisher´s exact test. The multivaried analysis included binomial regression model that considered as an exit variable the presence of CTS and like explicatory variables those related risk factors.Results: The prevalence of CTS in dentists who work in Bucaramanga was 15.8%. After analyzing the results according to each specialty, 40% of the endodontists had CTS, 30% of the dentists who had systemic compromise had CTS and 25% of the dentists who used manual instruments during time periods less than 240 min/day had CTS. There was an association six times greater of having CTS in people with systemic compromise and 0.13 of not having CTS in persons who work with manual instruments during time periods greater than 240 min/day.Conclusion: It was established that systemic compromise is determining factor in the appearance of CTS, the use of rotatory instruments for long time periods was a factor related to the professional exercise, associated to the phenomena. Objetivo: Determinar la prevalencia del Síndrome del Túnel Carpiano (STC) y sus factores asociados en odontólogos de la ciudad de Bucaramanga y su área metropolitana.Materiales y métodos: Se realizó un estudio observacional analítico de corte transversal. El universo se constituyó por 250 y la muestra por 156 seleccionados mediante muestreo aleatorio simple. Se analizó la relación de presencia de STC con cada variable, mediante test de chi2 y test exacto de Fischer. El análisis multivariado mediante un modelo de regresión binomial, considerado como variable de salida la presencia de STC y como variable explicatoria las relacionadas con factores de riesgo.Resultados: La prevalencia de STC en odontólogos de Bucaramanga fue de 15.8%. El 40% de los endodoncistas registraron STC; se observó que el 33% de los odontólogos que registraban compromiso sistémico presentaban la condición de interés y que el 25% de las personas que usaban instrumental manual durante tiempos menores de 240 min/día registraban STC. Hubo una asociación seis veces mayor de tener STC en personas con compromiso sistémico y 0.13 de no tenerlo en personas que trabajan instrumental manual tiempos superiores a 240 min/día.Conclusión: Se estableció que el compromiso sistémico fue un factor determinante en la aparición de STC y el uso de instrumental rotario por tiempos prolongados, fue un factor relacionado con el ejercicio profesional, asociado con el fenómeno.[Rodríguez A, Morales K, Maldonado LP, Jiménez GE, Quiroz LF, Concha SC, Rueda SJ. Prevalencia del sindrome de túnel carpiano y sus factores asociados en odontólogos de la ciudad de Bucaramanga y su área metropolitana. Ustasalud Odontología 2005; 4: 73 - 80]

EnglishIn the view of the redundant and contradictory provision of Italian Criminal Code about medical malpractice (art. 590 sexies), the comparison with the Anglo-American experiences (where the issue of the legal value of the guidelines and the relationship with the good clinical practices has long been addressed in regulations and case law) seems to highlight the interaction existent between guidelines and good practices; the compliance with the guidelines, i.e. the medical treatment consistent with the guidelines, seems to involve a relative presumption of diligence, except when proved that the guidelines are inappropriate to the specifics of the case; few lights and many shadows can be found, instead, in the sentence "Mariotti" of the Italian Supreme Court, Joint Session. Analysis of the sources of the guidelines and the competent bodies (in this regard) follows; the role of public agencies appears to be characterized by greater impartiality and independence in an health system financed mainly on private bases, such as the United States, while in public health systems, such as English and Italian, the risk is that the production of guidelines “centralised” by the public body (not usual in the United States "polycentric” experiences) can lead to guidelines mainly aimed to contain the medical costs, rather than to promote the quality of care. In order to deal with any conflict of interest (interests of public finance or professional categories) that may affect the guidelines, it seems important to focus on the one hand the objectives, on the other the methodologies of the development of guidelines, "participatory" and “evidence-based"; and to verify before the courts the adequacy of the guidelines to the specifics of the case, according to the classical dynamics of the interaction between "specific" and “generic” fault, i.e. the interaction between guidelines and good practices, having a subsidiary role. italianoA fronte della ridondante e contraddittoria previsione dell’art. 590 sexies c.p. in materia di colpa medica, il confronto con le esperienze angloamericane, ove il tema del valore giuridico delle linee guida e della relazione con le buone pratiche clinico-assistenziali e stato da tempo affrontato a livello normativo e giurisprudenziale, sembra evidenziare il rapporto di integrazione sussistente tra linee guida e buone pratiche; il rispetto delle linee guida, da intendere quale condotta conforme alle linee guida, pare costituire una presunzione relativa di perizia, salvo prova contraria rappresentata dall’inadeguatezza delle linee guida stesse alle specificita del caso concreto; poche luci e molte ombre sembrano invece rinvenirsi nella sentenza “Mariotti” delle Sez. Un. Segue un’analisi delle fonti delle linee guida e degli organi competenti a tal riguardo; il ruolo delle agenzie pubbliche appare caratterizzato da maggiore terzieta ed indipendenza in un sistema sanitario di matrice prevalentemente privata, come quello statunitense, mentre in sistemi finanziati su basi pubbliche, come quelli inglese ed italiano, occorre contrastare il rischio che l’“accentramento” della produzione delle linee guida in capo ad un ente statale (non praticato nelle esperienze statunitensi “policentriche”) conduca a linee guida aventi quale principale obiettivo il contenimento della spesa medica pubblica, anziche la qualita delle cure. Per far fronte agli eventuali conflitti d’interessi (interessi della finanza pubblica o delle categorie professionali) che possono condizionare le linee guida, appare importante focalizzare da un lato gli obiettivi, dall’altro le metodologie di sviluppo delle linee guida, “partecipative” e fondate su “evidenze scientifiche”; e verificare in sede giudiziale l’adeguatezza delle linee guida alle specificita del caso concreto, secondo la classica dinamica dell’interazione tra colpa “specifica” e colpa “generica”, ovvero dell’interazione tra linee guida e buone pratiche, dal ruolo sussidiario.

"La investigación anterior sobre la acumulación de comida en ratas ha usado diferentes situaciones de ensayo discreto. El descubrimiento que la variable activa en la acumulación es la magnitud de reforzamiento demorado hizo evidente la relación entre la acumulación y los estudios clásicos y los modernos sobre demora de reforzamiento. Dado que los estudios modernos sobre demora han usado operantes libres, este trabajo intentó replicar la típica función creciente entre la respuesta de procuración de comida y la duración de la demora empleando una operante libre. Se expuso directamente a tres ratas a un programa tándem modificado intervalo fijo (IF) 30 s tiempo fijo (TF) de 0, 2, 4, 8, 16 o 32 s. El tándem se adaptó para que el número de presiones a la palanca durante el IF entregara el mismo número de bolitas al finalizar el TF. Se encontró que la tasa global de respuesta durante las sesiones (y el número de bolitas) aumentó monotónicamente al alargar la demora de reforzamiento. Estos datos muestran que la acumulación de comida no está limitada a situaciones de ensayo discreto. Además, que el fenómeno de acumulación contradice la presunta universalidad de la disminución en la respuesta en gradientes de demora de reforzamiento."

Immunohistochemistry (IHC) is used to detect antibody-specific antigens in tissues; the results depend on the ability of the primary antibodies to bind to their antigens. Therefore, results depend on the quality of preservation of the specimen. Many investigators have overcome the deleterious effects of over-fixation on the binding of primary antibodies to specimen antigens using IHC, but if the specimen is under-fixed or fixation is delayed, false negative results could be obtained despite certified laboratory practices. Microtubule-associated protein 2 (MAP2) is an abundant microtubule-associate protein that participates in the outgrowth of neuronal processes and synaptic plasticity; it is localized primarily in cell bodies and dendrites of neurons. MAP2 immunolabeling has been reported to be absent in areas of the entorhinal cortex and hippocampus of Alzheimer's disease brains that were co-localized with the dense-core type of amyloid plaques. It was hypothesized that the lack of MAP2 immunolabeling in these structures was due to the degradation of the MAP2 antigen by the neuronal proteases that were released as the neurons lysed leading to the formation of these plaques. Because MAP2 is sensitive to proteolysis, we hypothesized that changes in MAP2 immunolabeling may be correlated with the degree of fixation of central nervous system (CNS) tissues. We detected normal MAP2 immunolabeling in fixed rat brain tissues, but MAP2 immunolabeling was decreased or lost in unfixed and delayed-fixed rat brain tissues. By contrast, two ubiquitous CNS-specific markers, myelin basic protein and glial fibrillary acidic protein, were unaffected by the degree of fixation in the same tissues. Our observations suggest that preservation of various CNS-specific antigens differs with the degree of fixation and that the lack of MAP2 immunolabeling in the rat brain may indicate inadequate tissue fixation. We recommend applying MAP2 IHC for all CNS tissues as a pre-screen to assess the quality of the tissue preservation and to avoid potentially false negative IHC results.

Introducción: Los "Criterios Médicos de Elegibilidad para el Uso de Anticonceptivos" de la Organización Mundial de la Salud (OMS) son una guía para la correcta elección y uso de los métodos anticonceptivos en variadas condiciones de salud. En este documento revisaremos las principales modificaciones en su quinta y última edición publicada en inglés el año 2015. Desarrollo: Las modificaciones de la quinta edición son fundamentalmente la adición de nuevos métodos y la modificación de la categoría de recomendación para algunas condiciones de salud. Se agregan el acetato de medroxiprogesterona de depósito vía subcutánea, el anillo vaginal de progesterona, el implante anticonceptivo subcutáneo sinoimplant(II)® y el método anticonceptivo de emergencia acetato de ulipristal. Se modifican las recomendaciones para las mujeres en lactancia, permitiendo el uso de algunos métodos de progestágeno solo desde el posparto inmediato, salvo el acetato de medroxiprogesterona de depósito por entregar una dosis elevada del esteroide y el dispositivo intrauterino (DIU) con levonorgestrel, el cual sigue las normas de los DIU con cobre. También hay modificación en las recomendaciones en cuanto al uso de anticonceptivos combinados en el puerperio, con más restricciones para mujeres sin lactancia. Por último, sobre el uso de terapia antiretroviral, cambian algunas categorías y se amplía el listado de fármacos detallados. Conclusión: Es necesario que los profesionales de salud conozcan estas modificaciones para poder entregar una atención de calidad a las usuarias de anticoncepción. Introduction: The "Medical Eligibility Criteria for Contraceptive Use" published by the World Health Organization (WHO) is a guide for the correct choice and use of the contraceptive methods in many different health conditions. In this document we will review the main changes made in the fifth and last edition of this guide published in English in 2015. Development: The modifications of this last edition are the addition of new contraceptive methods and the modification of the category of the recommendation for some health conditions. It adds the medroxiprogesterone acetate subcutaneous injection, the progesterone vaginal ring, the subcutaneous contraceptive implant sinoimplant(II)® and ulipristal acetate as emergency contraception. There are modifications of the recommendations for breastfeeding women, allowing the use of some progestin only methods since the immediate postpartum, with the exception of medroxiprogesterone acetate because it delivers a high dose of the steroid and the levonorgestrel intrauterine device that follows the same recommendations as the copper intrauterine device. There are also modifications in the recommendations for the use of combined contraceptives in the first 42 days postpartum, with more restrictions for non-breastfeeding women. Finally, on the use of antiretroviral therapy drugs, there were changes of some categories and a detailed categorization for each drug. Conclusion: It is necessary for health care providers to know these changes in order to deliver a quality care to contraception users.

Glioneuronal tumors constitute a histologically diverse group of primary central nervous system neoplasms that are typically slow-growing and managed conservatively. Genetic alterations associated with glioneuronal tumors include BRAF mutations and oncogenic fusions. To further characterize this group of tumors, we collected a cohort of 26 glioneuronal tumors and performed in-depth genomic analysis. We identified mutations in BRAF (34%) and oncogenic fusions (30%), consistent with previously published reports. In addition, we discovered novel oncogenic fusions involving members of the NTRK gene family in a subset of our cohort. One-patient with BCAN exon 13 fused to NTRK1 exon 11 initially underwent a subtotal resection for a 4th ventricular glioneuronal tumor but ultimately required additional therapy due to progressive, symptomatic disease. Given the patient’s targetable fusion, the patient was enrolled on a clinical trial with entrectinib, a pan-Trk, ROS1, and ALK (anaplastic lymphoma kinase) inhibitor. The patient was treated for 11 months and during this time volumetric analysis of the lesion demonstrated a maximum reduction of 60% in the contrast-enhancing tumor compared to his pre-treatment magnetic resonance imaging study. The radiologic response was associated with resolution of his clinical symptoms and was maintained for 11 months on treatment. This report of a BCAN-NTRK1 fusion in glioneuronal tumors highlights its clinical importance as a novel, targetable alteration.

Background The postpartum period is a high risk period for unintended pregnancies which can be associated with negative outcomes for mother and infant. Effective contraception is important during this time and thus the AAP advises pediatricians to ask mothers about family planning by the two-month visit. Previous work has shown family planning screening can be implemented in a pediatric resident clinic, with residents providing referrals to needed services. Objective To assess resident knowledge, attitudes and confidence around discussing family planning with mothers of their young patients. Methods Anonymous surveys were administered to pediatric residents in an inner city pediatric residency program. Group comparisons were made using Fisher's exact test and chi-square test. Results 39 residents completed the survey for a response rate of 65%. 39% of respondents were in their 1st year of residency, 36% were in the 2nd year, and 25% were in their 3rd year or higher. More than half (55%) of respondents felt knowledgeable or very knowledgeable about guidelines around providing contraceptive care for adolescents. These residents were more likely to be farther along in residency (p=0.04) and to correctly identify first line contraception for adolescents (p=0.006). Respondents who felt knowledgeable about providing contraceptive care for adolescents were more likely to feel confident speaking with mothers about their contraceptive needs (p Conclusions While most residents surveyed were not aware of guidelines recommending screening mothers of young children for family planning needs, they felt pediatricians have a role in such discussions. These data highlight resident willingness to screen mothers of infants for family planning needs and the opportunity to build on their current knowledge and practices.