Pediatric Traumatic Injuries Due to Agrarian Hay-Hole Falls.

Hay-holes are a design feature in many traditionally built barns that serve as a portal through which stored hay is passed to the lower level where animals are fed. Unfortunately, children sometimes fall through the hay-hole to the concrete or packed earth below. Available data on the frequency and types of hay-hole injuries is limited. The purpose of this study was to better characterize the resultant injuries and identify prognostic factors that predict outcomes from them. We performed a retrospective review of 53 children admitted to the Penn State Hershey Children's Hospital at the Penn State Hershey Medical Center with injuries due to a fall through a hay-hole over 15 years. Compared to urban trauma, hay-hole falls more frequently involve younger children and craniofacial injuries. Although they may result in significant injuries, they are rarely fatal. Greater fall height is associated with longer length of stay (LOS) but not with a greater frequency of intubation, intracranial hemorrhage, or skull fracture. A re-examination of barn design may help to reduce the frequency of this injury type.

Tumor-Derived Biomarkers in Liquid Biopsy of Glioblastoma.

There is a pressing clinical need for minimally invasive liquid biopsies to supplement imaging in the treatment of glioblastoma. Diagnostic imaging is often difficult to interpret and the medical community is divided on distinguishing among complete response, partial response, stable disease, and progressive disease. A minimally invasive liquid biopsy would supplement imaging and clinical findings and has the capacity to be helpful in several ways: 1) diagnosis, 2) selection of patients for specific treatments, 3) tracking of treatment response, and 4) prognostic value. The liquid biome is the combination of biological fluids including blood, urine, and cerebrospinal fluid that contain small amounts of tumor cells, DNA/RNA coding material, peptides, and metabolites. Within the liquid biome, 2 broad categories of biomarkers can exist: tumor-derived, which can be directly traced to the tumor, and tumor-associated, which can be traced back to the response of the body to disease. Although tumor-associated biomarkers are promising liquid biopsy candidates, recent advances in biomarker enrichment and detection have allowed concentration on a new class of biomarker: tumor-derived biomarkers. This review focuses on making the distinction between the 2 biomarker categories and highlights promising new direction.

Minimally Invasive Ventriculo-Cholecystic Shunt Placement Utilizing Combined Ultrasound and Fluoroscopic Guidance.

For the management of hydrocephalus with ventricular cerebrospinal fluid (CSF) shunting, multiple therapeutic options are available. Among these routes, the most commonly used are ventriculo-peritoneal, ventriculo-atrial, and ventriculo-pleural, while ventriculo-cholecystic is a less common option. Although ventriculo-peritoneal is accepted as the first option, ventriculo-cholecystic shunting may be performed in patients who are poor candidates for other routes of shunt placement. Open cholecystic shunt placement may be contraindicated in patients who have undergone previous surgeries or other comorbidities. Here, we present the case of a 25-year-old female with a complex medical history who presented with a posterior fossa intraparenchymal hemorrhage and subsequent hydrocephalus. She was unable to undergo a ventriculo-peritoneal, atrial, or pleural shunt placement, and thus, a cholecystic shunt placement was chosen. Due to a history of previous surgeries and comorbidities as well as a large volume of idiopathic and recurrent ascites, open placement was contraindicated in this patient. To the best of our knowledge, we present the first successful adult case of a minimally invasive ventriculo-cholecystic shunt placement under ultrasound and fluoroscopic guidance.

Plasma IL13Rα2 as a novel liquid biopsy biomarker for glioblastoma.

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

Bioinspired Super-Strong Aqueous Synthetic Tissue Adhesives.

Existing tissue adhesives and sealants are far from satisfactory when applied on wet and dynamic tissues. Herein, we report a strategy for designing biodegradable super-strong aqueous glue (B-Seal) for surgical uses inspired by an English ivy adhesion strategy and a cement particle packing theory. B-Seal is a fast-gelling, super-strong, and elastic adhesive sealant composed of injectable water-borne biodegradable polyurethane (WPU) nanodispersions with mismatched particle sizes and counterions in its A-B formulation. B-Seal showed 24-fold greater burst pressure than DuraSeal®, 138-fold greater T-pull adhesive strength than fibrin glue, and 16-fold greater lap shear strength than fibrin glue. In vivo evaluation on a rat cerebrospinal fluid (CSF) rhinorrhea model and a porcine craniotomy model validated the safety and efficacy of B-Seal for effective CSF leak prevention and dura repair. The plant-inspired adhesion strategy combined with particle packing theory represents a new direction of designing the next-generation wet tissue adhesives for surgeries.

Myxopapillary Ependymoma with Anaplastic Features: A Case Series and Review of the Literature.

BACKGROUND: Myxopapillary ependymomas (MPEs) with anaplastic features are rarely reported, with only 21 cases identified to date, and long-term recurrence is rarely presented. A case series is presented to expand understanding of this disease by describing 3 unique cases, including 2 that arose from MPE after a prolonged clinical course. METHODS: A literature review was performed, and 3 cases of MPE with anaplastic features from our institution were included. RESULTS: Patient 1 was a 13-year-old boy who presented with an avidly enhancing intradural lumbar mass. On gross total resection, the tumor was found to be a solid mass with areas of myxopapillary architecture and MIB-1 (Ki-67) index of 12%. Patient 2 was a woman who initially presented at age 22 with a lumbosacral tumor that was treated with surgery and radiation. A recurrent tumor was resected at age 24. At age 50, the patient presented with a large heterogeneous exophytic mass in the sacrum extending into the presacral space and Ki-67 index of 8%. This was treated with complete resection. Patient 3 was a man who initially presented at age 35 with a lower thoracic, upper lumbar mass at L2 extending into the sacrum. Following resection and radiation, a metastatic focus followed an indolent course until causing pain at the age of 48. Ki-67 index was 16%. CONCLUSIONS: The presented cases of MPE with anaplastic features make a total of 24 cases on record in the medical literature and demonstrate 2 examples of late recurrence.

The Potential of Glioblastoma Patient Symptoms to Diagnose and Predict Survival.

Glioblastoma is a devastating malignancy with a dismal survival rate and median survival time of 14 months. Currently, the biomarkers for glioblastoma are mostly molecular and include EGFRvIII, ATRX, PTEN, IDH1, MGMT, and others. These prognostic tumor biomarkers are obtained through a surgical biopsy and thus are not easily attainable. Clinicians would benefit from a robust, non-invasive, and readily available indicator for early diagnosis and accurate prognostication for glioblastoma patients. In this study, we assessed whether specific patient symptoms could provide an early diagnosis of glioblastoma. Further, we also assessed if any patient symptomatology could provide clinicians with the ability to prognosticate patient survival more accurately. We retrospectively reviewed the clinical data for 218 patients. We determined whether symptoms including headache, weakness, seizure, memory loss/confusion, visual changes, speech changes, and loss of consciousness led to a patient being diagnosed earlier and if any of these symptoms predicted diminished patient survival. Our study determined that weakness and memory loss/confusion were the symptoms that predicted diminished survival, and weakness alone was the symptom that predicted an earlier diagnosis. This study further elucidates the complexities of glioblastoma and provides clinicians with more data for their patients when discussing prognostication after diagnosis of glioblastoma.

Spontaneous Hip Dislocation Complicating the Management of Malignant Peripheral Nerve Sheath Tumor Arising Within a Plexiform Neurofibroma.

Neurofibromatosis type 1 (NF1) is one of the most common inherited neurological disorders. It can cause plexiform neurofibromas, leading to diffuse enlargement of a nerve or nerves within the body. There are benign in general, however, can cause significant symptoms due to their size, including bony erosion, pain, and joint instability. Unfortunately, they also have the capacity to become malignant by internal transformation into a malignant peripheral nerve sheath tumor (MPNST). The case presented here is a 27-year-old male with NF1 that was followed for years with a pelvic girdle plexiform neurofibroma whose course was complicated by transformation to MPNST and a spontaneous hip dislocation. He underwent excision, Girdlestone procedure, chemotherapy, and radiation. Unfortunately, he subsequently developed lung metastases and is part of a clinical trial with an MDM2 inhibitor and pembrolizumab.

Aneurysmal and arteriovenous malformation hemorrhage during pregnancy: An update on the epidemiology, risk factors and prognosis.

INTRODUCTION: Intracranial hemorrhage (ICH) is a devastating condition with a high rate of morbidity and mortality. Aneurysm or arteriovenous malformation (AVM) rupture are two common etiologies leading to ICH. Here we provide an update on ICH during pregnancy with a focus on those caused by aneurysm or AVM rupture. METHODS: Here we systematically review 25 studies reported in the literature to provide an update on ICH during pregnancy focusing on aneurysm or AVM rupture. We also reviewed the prognosis of ICH during puerperium. RESULTS: Discrepancies exist between studies supporting or refuting the hypothesis of a higher rate of ICH during pregnancy, obscuring the overall rate of aneurysm and AVM rupture in pregnant ICH patients. However, risk factors such as maternal age and hypertension have shown to increase the frequency of ICH in pregnant patients. We also show increased morbidity and mortality in patients suffering from preeclampsia/eclampsia. DISCUSSION: ICH is rare, but the various studies demonstrating its increased frequency, morbidity, and mortality during pregnancy should raise our awareness of this condition. The management and treatment decisions for a pregnant ICH patient should follow the same principles as nonpregnant patients, but with the knowledge that not all medications are appropriate for use in the pregnant patient. Although there seems to be a higher frequency of AVM rupture, further research must be conducted in order to fully determine the effects of pregnancy on aneurysm and AVM ruptures.

Congenital Spinal Cysts: An Update and Review of the Literature.

Congenital spinal cysts are rare and encompass a wide variety of diseases including arachnoid, enterogenous, teratomatous, neurenteric, foregut, bronchogenic, epithelial, ependymal, dermoid, and epidermoid cysts. Here, we elucidate the epidemiology, pathology, pathogenesis, and diagnostic findings of the most common congenital spinal cysts, followed by a discussion of their presentation and treatment options. Differentiating the cause of each lesion is crucial for targeted clinical and surgical management for the patient. Our review describes how arachnoid cysts can be observed, fenestrated, percutaneously drained, or shunted; however, the primary goal for neurenteric, dermoid, and epidermoid cysts is removal. Further, we discuss how patient presentation is dependent on the rate of growth and location of compression on the spinal cord and nerve roots. However, although many of these lesions are discovered incidentally on imaging, the spectrum of possible symptoms include pain, weakness, ataxia, bladder incontinence, and progressive or acute neurologic deficits. We present and review the histology and imaging of a variety of cysts and discuss how although the goal of treatment is resection, the risks of surgery must be considered against the benefits of complete resection in each case.

A Unique Case of a High-Grade Neuroepithelial Tumor With EML4-ALK Fusion in a Five-Month-Old.

We present a unique and challenging case of a high-grade neuroepithelial tumor with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion in a five-month-old child. This tumor was difficult to classify, with glial and ependymal features, reinforcing the impact of a molecular-based diagnosis in correct classification and management. The patient had two tumor resections and underwent chemotherapy following the Head Start trial treatment regimen. The patient remains well, with no residual disease on MRI 15 months after initial resection. Further studies are needed to determine the frequency of EML4-ALK fusions in these types of tumors and to optimize therapeutic protocols for children and adults, alike, suffering from this disease.

Post-Laminectomy Kyphosis in Achondroplasia Patients: To Concurrently Fuse or Not.

The purpose of this review is to look at the incidence of post-laminectomy kyphosis in achondroplasia patients and to determine whether skeletal maturity and the number and location of laminectomies predict kyphosis in this patient population. Our review of the literature included all articles from MEDLINE/PubMed and Ovid from inception to 2019. After removing duplicates and checking for relevancy, the final number of articles yielded was eight. The results of this review summarize the incidence of post-laminectomy kyphosis in achondroplasia patients. In conclusion, we suggest fusion be considered in conjunction with multilevel laminectomies due to a high incidence of kyphosis with a need for stabilization in the pediatric achondroplastic patient population.

Clostridium difficile Infection of a Total Hip Arthroplasty: Case Report and Review of the Literature.

CASE: We describe the case of an 85-year-old woman who presented with worsening right hip pain after a conversion hip replacement. Subsequent imaging demonstrated a gas-containing collection in the lateral thigh. She was taken to the operating room for irrigation and debridement, where intraoperative cultures returned positive for Clostridium difficile. Surgical management was followed by a prolonged course of antibiotics. CONCLUSIONS: Clostridium difficile as the etiology of infection in a conversion arthroplasty is exceedingly rare. Orthopaedic surgeons and infectious disease specialists should consider C. diff as a potential cause of infection in conversion hip arthroplasty because management options will need to be tailored.

Suprasellar central nervous system ganglioneuroblastoma: a case in a 9-year-old child and review of the literature.

PURPOSE: Intracranial ganglioneuroblastomas are incredibly rare neuroectodermal tumors with only 8 described cases total, 5 of those having imaging findings METHODS: Here we present a 9-year-old female patient with 4 months progressive headaches, personality changes, and vomiting. We also present a review of the current literature of intracranial ganglioneuroblastomas. RESULTS: Imaging demonstrated a partially calcified suprasellar mass measuring 4.6 × 6.3 × 5 cm composed of both solid and cystic components, diagnosed to be a ganglioneuroblastoma, with mass effect on the lateral and 3rd ventricles, with a midline shift of right to left of 6-7 mm. She was treated with subtotal surgical resection, an intensive chemotherapeutic regimen, and radiation and has no residual disease on imaging 1 year and 4 months status post-surgery. CONCLUSION: To our knowledge, this is the first case of a ganglioneuroblastoma to mimic a craniopharyngioma based upon imaging findings and suprasellar location. As these cases are extremely rare, an optimal therapeutic regimen has not been defined. However, a combination of surgical resection, chemotherapy, and radiation therapy can be effective, as shown here with successful treatment and no evidence of residual disease.

Dual BRAF/MEK therapy in BRAF V600E-mutated primary brain tumors: a case series showing dramatic clinical and radiographic responses and a reduction in cutaneous toxicity.

OBJECTIVE: BRAF V600E is a common oncogenic driver in a variety of primary brain tumors. Dual inhibitor therapy using dabrafenib (a selective oral inhibitor of several mutated forms of BRAF kinase) and trametinib (a reversible inhibitor of MEK1 and MEK2) has been used successfully for treatment of metastatic melanoma, anaplastic thyroid cancer, and other tumor types, but has been reported in only a few patients with primary brain tumors and none with pleomorphic xanthoastrocytoma. Here, the authors report on the substantial clinical response and reduction in cutaneous toxicity in a case series of BRAF V600E primary brain cancers treated with dual BRAF/MEK inhibitor therapy. METHODS: The authors treated 4 BRAF V600E patients, each with a different type of primary brain tumor (pilocytic astrocytoma, papillary craniopharyngioma, ganglioglioma, and pleomorphic xanthoastrocytoma) with the combination of dabrafenib and trametinib. RESULTS: The patients with pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and papillary craniopharyngioma experienced near-complete radiographic and complete clinical responses after 8 weeks of therapy. A substantial partial response (by RANO [Response Assessment in Neuro-Oncology] criteria) was observed in the patient with ganglioglioma. The patient with craniopharyngioma developed dramatic, diffuse verrucal keratosis within 2 weeks of starting dabrafenib. This completely resolved within 2 weeks of adding trametinib. CONCLUSIONS: Dual BRAF/MEK inhibitor therapy represents an exciting treatment option for patients with BRAF V600E primary brain tumors. In addition to greater efficacy than single-agent dabrafenib, this combination has the potential to mitigate cutaneous toxicity, one of the most common and concerning BRAF inhibitor-related adverse events.

The Relative Location of the Major Femoral Nerve Motor Branches in the Thigh.

In peripheral nerve surgery, repair of the femoral nerve (FN) requires identification of normal nerve elements both proximal and distal to the level of the injury. We identified FN branches to the sartorius (SRT) and quadriceps muscles in 16 embalmed specimens and calculated the length of each branch to its point of entry into its respective muscle. The SRT and rectus femoris (RF) muscles were mobilized but not transected to mimic the surgical approach. Ratios of the length of each motor branch as a unit of the total length of the thigh, defined as the FN at the inguinal ligament to the superior margin of the patella were also calculated. The proximal branch to RF spanned a ratio of .19 ± .11 (mean ± standard deviation) from the FN at the inguinal ligament to its endpoint. The ratio of the distal branch to the RF was .29 ± .08. The ratio of the proximal SRT branch was .20 ± .05. The distal branch to SRT was located at a ratio of .43 ± .11. The proximal branch to vastus lateralis (VL) was .26 ± .08. The distal branch to VL was .39 ± .07. The ratio of the motor branch to vastus intermedius (VI) was .30 ± .05. Lastly, the branch to vastus medialis (VM) was .55 ± .06. The motor branch to SRT frequently emerged as a bifurcation of itself and saphenous nerve within the adductor canal. Knowledge of the relative location of the motor branches of the FN in the thigh can be helpful to surgeons during the nerve exploration and repair.

STEMI: rare initial presentation of a mediastinal mass supplied by the RCA.

In the setting of severe septic shock, a 70-year-old woman had an ST segment myocardial infarction with ST elevations in the inferolateral leads. On cardiac catheterisation, no obstructive pathology was noted. Chest imaging revealed a large mediastinal mass measuring 8.5×6.5×7.5 cm in the visceral compartment of the mediastinum, with contrast enhancement from the right coronary artery (RCA). A biopsy was preformed and cytology was consistent with a well-differentiated neuroendocrine neoplasm. On review of the cardiac catherisation, it was noted that the mass was deriving blood supply from the RCA. Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a rare but well-documented phenomenon. In this case, MINOCA was caused by coronary steal syndrome in the setting of profound hypotension. Immediate management is with haemodynamic support; there is no role for coronary intervention.

Exosomes and their implications in central nervous system tumor biology.

Exosomes are 20-100 nm cellular derived vesicles that upon discovery, were thought to be a form of cellular recycling of intracellular contents. More recently, these vesicles are under investigation for their purported significant roles in intercellular communication in both healthy and diseased states. Herein, we focus on the secretion of exosomes associated with glioblastoma, as most exosome studies on brain tumors have been performed in this tumor type. However, we included exosomes secreted from other forms of brain tumors for comparison as available. Exosomes contain intracellular content that can be transferred to other cells in the tumor or to cells of the immune system and endothelial cells. These recipient cells may subsequently take on oncogenic properties, including therapeutic resistance, cancer progression, and angiogenesis. Genetic components (DNA, RNA and miRNA) of the cell of origin may be included in the secreted exosomes. The presence of genetic material in the exosomes could serve as a biomarker for mutations in tumors, potentially leading to novel treatment strategies. In the last decade, exosomes have been identified as having a major impact on multiple aspects of medicine and tumor biology, and appear to be primed for a critical position in cancer diagnosis, prognosis, and treatment.

Exosomes impact survival to radiation exposure in cell line models of nervous system cancer.

Radiation is utilized in the therapy of more than 50% of cancer patients. Unfortunately, many malignancies become resistant to radiation over time. We investigated the hypothesis that one method of a cancer cell's ability to survive radiation occurs through cellular communication via exosomes. Exosomes are cell-derived vesicles containing DNA, RNA, and protein. Three properties were analyzed: 1) exosome function, 2) exosome profile and 3) exosome uptake/blockade. To analyze exosome function, we show radiation-derived exosomes increased proliferation and enabled recipient cancer cells to survive radiation in vitro. Furthermore, radiation-derived exosomes increased tumor burden and decreased survival in an in vivo model. To address the mechanism underlying the alterations by exosomes in recipient cells, we obtained a profile of radiation-derived exosomes that showed expression changes favoring a resistant/proliferative profile. Radiation-derived exosomes contain elevated oncogenic miR-889, oncogenic mRNAs, and proteins of the proteasome pathway, Notch, Jak-STAT, and cell cycle pathways. Radiation-derived exosomes contain decreased levels of tumor-suppressive miR-516, miR-365, and multiple tumor-suppressive mRNAs. Ingenuity pathway analysis revealed the most represented networks included cell cycle, growth/survival. Upregulation of DNM2 correlated with increased exosome uptake. To analyze the property of exosome blockade, heparin and simvastatin were used to inhibit uptake of exosomes in recipient cells resulting in inhibited induction of proliferation and cellular survival. Because these agents have shown some success as cancer therapies, our data suggest their mechanism of action could be limiting exosome communication between cells. The results of our study identify a novel exosome-based mechanism that may underlie a cancer cell's ability to survive radiation.