Langerhans cell histiocytosis of the sella in a pediatric patient: case report with review of the literature.

PURPOSE: Langerhans cell histiocytosis (LCH) is a rare condition arising from the monoclonal expansion of myeloid precursor cells, which results in granulomatous lesions that characteristically express CD1a/CD207. We report a case of LCH in a 3-year-old male involving the sphenoid bone with extension into the sellar/suprasellar region. CASE REPORT: A 3-year-old male presented with progressively worsening headaches and associated night sweats, neck stiffness, and fatigue over the previous 4 weeks. Magnetic resonance imaging (MRI) revealed a 2.4-cm lytic lesion within the basisphenoid, exerting mass effect upon the pituitary gland. A biopsy was performed to determine the etiology of the lesion. Postoperatively, the patient developed an intralesional hematoma with visual complications requiring emergent surgical resection via endoscopic endonasal approach. Final pathology confirmed LCH. The patient had improvement in his vision long term. CONCLUSIONS: LCH extending into the sella is a rare but important diagnosis to consider in pediatric patients presenting with lesions in this region. We presented a case of a pediatric patient presenting with LCH of the sphenoid bone extending into the sella, with subsequent apoplexy and vision loss. Review of the literature showed varying treatment options for these patients, including purely surgical and non-surgical treatments. Early intervention may be necessary to avoid potentially devastating neurologic sequelae.

Traumatic atlantoaxial rotatory fixation in adults: a systematic review of published cases.

Atlantoaxial rotatory fixation (AARF) in adults is a rare and clinically challenging condition characterized by a spectrum of etiological factors, predominantly attributed to traumatic and inflammatory pathologies within the craniovertebral region. Trauma is the most frequently identified cause within the adult population, with the first case report published in 1907. This study aims to conduct a systematic review that addresses the clinical presentations and management strategies relating to traumatic atlantoaxial rotatory fixation in adults. A comprehensive search of the PubMed database was executed, adhering to the PRISMA guidelines. The inclusion criteria encompassed case reports and series documenting AARF cases in individuals aged 18 and above, spanning database inception to July 2022. Studies not published in the English language were excluded. A total of 61 articles reporting cases of AARF in the adult population were included in the study. The mean age of affected individuals was 36.1 years (± 15.6), with a distribution of 46% females and 54% males. Predominant mechanisms of injury included motor vehicle accidents and falls, constituting 38% and 22% of cases, respectively. Among the classification systems employed, Fielding and Hawkins type I accounted for the majority at 63%, followed by type II at 10%, and type III at 4%. Conservative management was used for treatment in 65% of acute (65%) cases and 29% of chronic cases. Traumatic AARF is a rare phenomenon in the adult population, is more common in younger adults, and does not often present with neurologic deficits. Patients diagnosed acutely are more likely to be successfully treated with conservative management, while patients diagnosed chronically are less likely to be reduced with conservatively and often require surgical treatment. Surgery should be considered for patients with irreducible dislocations, ligamentous injuries, unstable associated fractures, and persistent pain resistant to conservative management.

Traumatic Brain Injury: A Comprehensive Review of Biomechanics and Molecular Pathophysiology.

Traumatic brain injury (TBI) is a critical public health concern with profound consequences for affected individuals. This comprehensive literature review delves into TBI intricacies, encompassing primary injury biomechanics and the molecular pathophysiology of the secondary injury cascade. Primary TBI involves a complex interplay of forces, including impact loading, blast overpressure, and impulsive loading, leading to diverse injury patterns. These forces can be categorized into inertial (e.g., rotational acceleration causing focal and diffuse injuries) and contact forces (primarily causing focal injuries like skull fractures). Understanding their interactions is crucial for effective injury management. The secondary injury cascade in TBI comprises multifaceted molecular and cellular responses, including altered ion concentrations, dysfunctional neurotransmitter networks, oxidative stress, and cellular energy disturbances. These disruptions impair synaptic function, neurotransmission, and neuroplasticity, resulting in cognitive and behavioral deficits. Moreover, neuroinflammatory responses play a pivotal role in exacerbating damage. As we endeavor to bridge the knowledge gap between biomechanics and molecular pathophysiology, further research is imperative to unravel the nuanced interplay between mechanical forces and their consequences at the molecular and cellular levels, ultimately guiding the development of targeted therapeutic strategies to mitigate the debilitating effects of TBI. In this study, we aim to provide a concise review of the bridge between biomechanical processes causing primary injury and the ensuing molecular pathophysiology of secondary injury, while detailing the subsequent clinical course for this patient population. This knowledge is crucial for advancing our understanding of TBI and developing effective interventions to improve outcomes for those affected.

Rosai-Dorfman disease of the cauda equina: illustrative case.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare, nonmalignant histiocytosis. It typically occurs in lymph nodes, skin, and soft tissues, but numerous reports of central nervous system involvement exist in the literature. The peripheral nervous system has rarely been involved. In this study, the authors present a case of RDD isolated to the cauda equina. The presentation, management, surgical technique, and adjunctive treatment strategy are described. OBSERVATIONS: A 31-year-old female presented with 6 months of progressive left lower-extremity numbness involving the lateral aspect of the foot and weakness of the left toes. Magnetic resonance imaging of the lumbar spine demonstrated a homogeneously enhancing intradural lesion involving the cauda equina at the L2-3 levels. Histopathology after resection revealed a histiocytic infiltrate, positive for CD68 and S100, and emperipolesis consistent with RDD. No adjuvant therapy was administered, and the patient had full remission at the 1-year follow-up. Only five other cases of intradural RDD lesions of the cauda equina have been reported in the literature. LESSONS: RDD of the cauda equina is an especially rare and challenging diagnosis that can mimic other dura-based lesions, such as meningiomas. A definitive diagnosis of RDD relies on pathognomonic histopathological and immunohistochemical findings.

A Drug-Eluting Injectable NanoGel for Localized Delivery of Anticancer Drugs to Solid Tumors.

Systemically administered chemotherapy reduces the efficiency of the anticancer agent at the target tumor tissue and results in distributed drug to non-target organs, inducing negative side effects commonly associated with chemotherapy and necessitating repeated administration. Injectable hydrogels present themselves as a potential platform for non-invasive local delivery vehicles that can serve as a slow-releasing drug depot that fills tumor vasculature, tissue, or resection cavities. Herein, we have systematically formulated and tested an injectable shear-thinning hydrogel (STH) with a highly manipulable release profile for delivering doxorubicin, a common chemotherapeutic. By detailed characterization of the STH physical properties and degradation and release dynamics, we selected top candidates for testing in cancer models of increasing biomimicry. Two-dimensional cell culture, tumor-on-a-chip, and small animal models were used to demonstrate the high anticancer potential and reduced systemic toxicity of the STH that exhibits long-term (up to 80 days) doxorubicin release profiles for treatment of breast cancer and glioblastoma. The drug-loaded STH injected into tumor tissue was shown to increase overall survival in breast tumor- and glioblastoma-bearing animal models by 50% for 22 days and 25% for 52 days, respectively, showing high potential for localized, less frequent treatment of oncologic disease with reduced dosage requirements.

Middle Fossa Approach for Resection of a Petrous Bone Hemangioma Compressing the Geniculate Ganglion.

Facial nerve hemangiomas are a rare entity of skull base lesions that arise within the temporal bone and affect the seventh cranial nerve.1 They are vascular malformations arising from the vascular plexuses surrounding the nerve. Although slow growing and overall benign in nature, they can cause significant facial nerve dysfunction even at small sizes.2 Facial nerve hemangiomas can arise within different segments of the facial nerve within the temporal bone, but most commonly arise near the geniculate ganglion.3 We describe the case of a 34-year-old female who presented with progressive right facial palsy (House-Brackmann 4) and a calcified lesion arising from the petrous temporal bone. Resection of the lesion was performed with a posterior to anterior middle fossa approach, with identification of the greater superficial petrosal nerve and geniculate ganglion, sectioning of the middle meningeal artery, and identification of V2 and V3 segments of the trigeminal nerve (Video 1). The bony mass was peeled off the petrous temporal bone and the geniculate ganglion without sacrifice of the facial nerve. Postoperative imaging showed gross total resection, and the patient's facial palsy improved to House-Brackmann 1. A comprehensive literature review on surgical approaches and outcomes for the resection of hemangiomas involving the geniculate ganglion or the facial nerve is also provided.2,4-18 The case presentation, surgical anatomy, operative nuances with technical considerations, and postoperative course with imaging are reviewed. The patient and family provided informed consent for the procedure and publication of patient images.

A Survey of Transcription Factors in Cell Fate Control.

Transcription factors (TFs) play a cardinal role in the development and maintenance of human physiology by acting as mediators of gene expression and cell state control. Recent advancements have broadened our knowledge on the potency of TFs in governing cell physiology and have deepened our understanding of the mechanisms through which they exert this control. The ability of TFs to program cell fates has gathered significant interest in recent decades, and high-throughput technologies now allow for the systematic discovery of forward programming factors to convert pluripotent stem cells into numerous differentiated cell types. The next generation of these technologies has the potential to improve our understanding and control of cell fates and states and provide advanced therapeutic modalities to address many medical conditions.

Gliomas Infiltrating the Corpus Callosum: A Systematic Review of the Literature.

Background: Gliomas infiltrating the corpus callosum (G-I-CC) majorly impact patient quality-of-life, but maximally safe tumor resection is challenging. We systematically reviewed the literature on G-I-CC. Methods: PubMed, EMBASE, Scopus, Web of Science, and Cochrane were searched following the PRISMA guidelines to include studies of patients with G-I-CC. Clinicopathological features, treatments, and outcomes were analyzed. Results: We included 52 studies comprising 683 patients. Most patients experienced headache (33%), cognitive decline (18.7%), and seizures (17.7%). Tumors mostly infiltrated the corpus callosum genu (44.2%) with bilateral extension (85.4%) into frontal (68.3%) or parietal (8.9%) lobes. Most G-I-CC were glioblastomas (84.5%) with IDH-wildtype (84.9%) and unmethylated MGMT promoter (53.5%). Resection (76.7%) was preferred over biopsy (23.3%), mostly gross-total (33.8%) and subtotal (32.5%). The tumor-infiltrated corpus callosum was resected in 57.8% of cases. Radiation was delivered in 65.8% of patients and temozolomide in 68.3%. Median follow-up was 12 months (range, 0.1−116). In total, 142 patients (31.8%) experienced post-surgical complications, including transient supplementary motor area syndrome (5.1%) and persistent motor deficits (4.3%) or abulia (2.5%). Post-treatment symptom improvement was reported in 42.9% of patients. No differences in rates of complications (p = 0.231) and symptom improvement (p = 0.375) were found in cases with resected versus preserved corpus callosum. Recurrences occurred in 40.9% of cases, with median progression-free survival of 9 months (0.1−72). Median overall survival was 10.7 months (range, 0.1−116), significantly longer in low-grade tumors (p = 0.013) and after resection (p < 0.001), especially gross-total (p = 0.041) in patients with high-grade tumors. Conclusions: G-I-CC show clinicopathological patterns comparable to other more frequent gliomas. Maximally safe resection significantly improves survival with low rates of persistent complications.

Aneurysm presence at the anterior communicating artery bifurcation is associated with caliber tapering of the A1 segment.

OBJECTIVE: Vessel tapering results in blood flow acceleration at downstream bifurcations (firehose nozzle effect), induces hemodynamics predisposing to aneurysm initiation, and has been associated with middle cerebral artery (MCA) aneurysm presence and rupture status. The authors sought to determine if vessel caliber tapering is a generalizable predisposing factor by evaluating upstream A1 segment profiles in association with aneurysm presence in the anterior communicating artery (ACoA) complex, the most prevalent cerebral aneurysm location associated with a high rupture risk. METHODS: Three-dimensional rotational angiographic studies were analyzed for 68 patients with ACoA aneurysms, 37 nonaneurysmal contralaterals, and 53 healthy bilateral controls (211 samples total). A1 segments were determined to be dominant, codominant, or nondominant based on flow and size. Equidistant cross-sectional orthogonal cuts were generated along the A1 centerline, and cross-sectional area (CSA) was evaluated proximally and distally, using intensity-invariant edge detection filtering. The relative tapering of the A1 segment was evaluated as the tapering ratio (distal/proximal CSA). Computational fluid dynamics was simulated on ACoA parametric models with and without tapering. RESULTS: Aneurysms occurred predominantly on dominant (79%) and codominant (17%) A1 segments. A1 segments leading to unruptured ACoA aneurysms had significantly greater tapering compared to nonaneurysmal contralaterals (0.69 ± 0.13 vs 0.80 ± 0.17, p = 0.001) and healthy controls (0.69 ± 0.13 vs 0.83 ± 0.16, p < 0.001), regardless of dominance labeling. There was no statistically significant difference in tapering values between contralateral A1 and healthy A1 controls (0.80 ± 0.17 vs 0.83 ± 0.16, p = 0.56). Hemodynamically, A1 segment tapering induces high focal pressure, high wall shear stress, and high velocity at the ACoA bifurcation. CONCLUSIONS: Aneurysmal, but not contralateral or healthy control, A1 segments demonstrated significant progressive vascular tapering, which is associated with aneurysmogenic hemodynamic conditions at the ACoA complex. Demonstration of the upstream tapering effect in the communicating ACoA segment is consistent with its prior detection in the noncommunicating MCA bifurcation, which together form more than 50% of intracranial aneurysms. The mechanistic characterization of this upstream vascular tapering phenomenon is warranted to understand its clinical relevance and devise potential therapeutic strategies.

Cell therapy strategies for COVID-19: Current approaches and potential applications.

Coronavirus disease 2019 (COVID-19) continues to burden society worldwide. Despite most patients having a mild course, severe presentations have limited treatment options. COVID-19 manifestations extend beyond the lungs and may affect the cardiovascular, nervous, and other organ systems. Current treatments are nonspecific and do not address potential long-term consequences such as pulmonary fibrosis, demyelination, and ischemic organ damage. Cell therapies offer great potential in treating severe COVID-19 presentations due to their customizability and regenerative function. This review summarizes COVID-19 pathogenesis, respective areas where cell therapies have potential, and the ongoing 89 cell therapy trials in COVID-19 as of 1 January 2021.

Increased focal internal carotid artery angulation in patients with posterior communicating artery aneurysms.

BACKGROUND: Aneurysms at the posterior communicating artery (PCOM) origin represent the most common location on the internal carotid artery (ICA), and are associated with greater recurrence following endovascular treatment. We evaluate the association between ICA angulation in three-dimensional (3D) space and PCOM aneurysmal development, using high-resolution 3D rotational angiography (3DRA) studies. METHODS: 3DRA datasets were evaluated in 70 patients with PCOM aneurysms, 31 non-aneurysmal contralateral, and 86 healthy controls (187 total). The local angle formed by upstream and downstream ICA segments at the PCOM origin, αICA@PCOM, was measured using 3DRA multiplanar reconstruction. Computational fluid dynamics (CFD) analysis was performed on parametric and patient-based models. RESULTS: αICA@PCOM was significantly larger in aneurysm-bearing ICA segments (68.14±11.91°) compared with non-aneurysmal contralateral (57.17±10.76°, p<0.001) and healthy controls (48.13±13.68°, p<0.001). A discriminant threshold αICA@PCOM value of 61° (87% specificity, 80% sensitivity) was established (area under the curve (AUC)=0.88). Ruptured PCOM aneurysms had a significantly larger αICA@PCOM compared to unruptured (72.65±15.16° vs 66.35±9.94°, p=0.04). In parametric and patient-based CFD analysis, a large αICA@PCOM induces high focal pressure at the PCOM origin, relatively low wall shear stress (WSS), and high proximal WSS spatial gradients (WSSG). CONCLUSION: ICA angulation at PCOM origin is significantly higher in vessels harboring PCOM aneurysms compared with contralateral and healthy ICAs. This sharper bend in the ICA leads to high focal pressure at the aneurysm neck, low focal WSS and high proximal WSSG. These findings underline the importance of morphological ICA variations and the likelihood of PCOM aneurysm, an association which can inform clinical decisions and may serve in predictive analytics.

Customizable Composite Fibers for Engineering Skeletal Muscle Models.

Engineering tissue-like scaffolds that can mimic the microstructure, architecture, topology, and mechanical properties of native tissues while offering an excellent environment for cellular growth has remained an unmet need. To address these challenges, multicompartment composite fibers are fabricated. These fibers can be assembled through textile processes to tailor tissue-level mechanical and electrical properties independent of cellular level components. Textile technologies also allow control of the distribution of different cell types and the microstructure of fabricated constructs and the direction of cellular growth within the 3D microenvironment. Here, we engineered composite fibers from biocompatible cores and biologically relevant hydrogel sheaths. The fibers are mechanically robust to being assembled using textile processes and could support adhesion, proliferation, and maturation of cell populations important for the engineering of skeletal muscles. We also demonstrated that the changes in the coating of the multicompartment fibers could potentially enhance myogenesis in vitro.

Fluoroscopy-free ultrasonography-guided percutaneous nephrolithotomy in pediatric patients: a single-center experience.

OBJECTIVES: To present the safety and efficacy of fluoroscopy-free ultrasound-guided PCNL for the treatment of renal calculi in pediatric patients of all ages. METHODS: 30 children with mean age of 5 years (6 months-12 years) underwent totally ultrasound-guided PCNL from March 2013 to August 2016. The pyelocalyceal system was punctured in prone position using only ultrasonography guidance, and the tract was dilated using a single shot dilation technique. No fluoroscopy was used during any of the stages of renal access. The procedure was performed using adult-sized instruments. RESULTS: The mean stone size was 27.1 ± 8.7 mm. Mean access time was 4.3 ± 2 min. Mean nephroscopic time was 34.6 ± 15.2 min. Mean hospital stay of patients was 3 days (range 2-5). 21 patients were stone-free after the procedure (70% success rate). Only four patients out of 30 experienced postoperative complications. CONCLUSIONS: The results of this study showed that fluoroscopic-free ultrasound-guided PCNL in pediatric patients of all ages is safe, highly efficient, and minimizes potential radiation exposure risks associated with the procedure.

Corrigendum: Engineering and optimising deaminase fusions for genome editing.

This corrects the article DOI: 10.1038/ncomms13330.

Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9.

Xenotransplantation is a promising strategy to alleviate the shortage of organs for human transplantation. In addition to the concerns about pig-to-human immunological compatibility, the risk of cross-species transmission of porcine endogenous retroviruses (PERVs) has impeded the clinical application of this approach. We previously demonstrated the feasibility of inactivating PERV activity in an immortalized pig cell line. We now confirm that PERVs infect human cells, and we observe the horizontal transfer of PERVs among human cells. Using CRISPR-Cas9, we inactivated all of the PERVs in a porcine primary cell line and generated PERV-inactivated pigs via somatic cell nuclear transfer. Our study highlights the value of PERV inactivation to prevent cross-species viral transmission and demonstrates the successful production of PERV-inactivated animals to address the safety concern in clinical xenotransplantation.

Engineering and optimising deaminase fusions for genome editing.

Precise editing is essential for biomedical research and gene therapy. Yet, homology-directed genome modification is limited by the requirements for genomic lesions, homology donors and the endogenous DNA repair machinery. Here we engineered programmable cytidine deaminases and test if we could introduce site-specific cytidine to thymidine transitions in the absence of targeted genomic lesions. Our programmable deaminases effectively convert specific cytidines to thymidines with 13% efficiency in Escherichia coli and 2.5% in human cells. However, off-target deaminations were detected more than 150 bp away from the target site. Moreover, whole genome sequencing revealed that edited bacterial cells did not harbour chromosomal abnormalities but demonstrated elevated global cytidine deamination at deaminase intrinsic binding sites. Therefore programmable deaminases represent a promising genome editing tool in prokaryotes and eukaryotes. Future engineering is required to overcome the processivity and the intrinsic DNA binding affinity of deaminases for safer therapeutic applications.

Flexible pH-Sensing Hydrogel Fibers for Epidermal Applications.

Epidermal pH is an indication of the skin's physiological condition. For example, pH of wound can be correlated to angiogenesis, protease activity, bacterial infection, etc. Chronic nonhealing wounds are known to have an elevated alkaline environment, while healing process occurs more readily in an acidic environment. Thus, dermal patches capable of continuous pH measurement can be used as point-of-care systems for monitoring skin disorder and the wound healing process. Here, pH-responsive hydrogel fibers are presented that can be used for long-term monitoring of epidermal wound condition. pH-responsive dyes are loaded into mesoporous microparticles and incorporated into hydrogel fibers using a microfluidic spinning system. The fabricated pH-responsive microfibers are flexible and can create conformal contact with skin. The response of pH-sensitive fibers with different compositions and thicknesses are characterized. The suggested technique is scalable and can be used to fabricate hydrogel-based wound dressings with clinically relevant dimensions. Images of the pH-sensing fibers during real-time pH measurement can be captured with a smart phone camera for convenient readout on-site. Through image processing, a quantitative pH map of the hydrogel fibers and the underlying tissue can be extracted. The developed skin dressing can act as a point-of-care device for monitoring the wound healing process.

Genome-wide inactivation of porcine endogenous retroviruses (PERVs).

The shortage of organs for transplantation is a major barrier to the treatment of organ failure. Although porcine organs are considered promising, their use has been checked by concerns about the transmission of porcine endogenous retroviruses (PERVs) to humans. Here we describe the eradication of all PERVs in a porcine kidney epithelial cell line (PK15). We first determined the PK15 PERV copy number to be 62. Using CRISPR-Cas9, we disrupted all copies of the PERV pol gene and demonstrated a >1000-fold reduction in PERV transmission to human cells, using our engineered cells. Our study shows that CRISPR-Cas9 multiplexability can be as high as 62 and demonstrates the possibility that PERVs can be inactivated for clinical application of porcine-to-human xenotransplantation.

Ankylosing spondylitis: A state of the art factual backbone.

Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects 1% of the general population. As one of the most severe types of spondyloarthropathy, AS affects the spinal vertebrae and sacroiliac joints, causing debilitating pain and loss of mobility. The goal of this review is to provide an overview of AS, from the pathophysiological changes that occur as the disease progresses, to genetic factors that are involved with its onset. Considering the high prevalence in the population, and the debilitating life changes that occur as a result of the disease, a strong emphasis is placed on the diagnostic imaging methods that are used to detect this condition, as well as several treatment methods that could improve the health of individuals diagnosed with AS.

PRIMARY HYPERPARATHYROIDISM: COMPARING BETWEEN SOLID AND CYSTIC ADENOMAS AND THE EFFICACY OF ULTRASOUND AND SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY IN THEIR DIAGNOSIS.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is a disorder that results from abnormal functioning of the parathyroid glands. The purpose of this study was to compare cystic and solid adenomas by analyzing different variables associated with PHPT and parathyroid adenomas (age, calcium, phosphorus, and parathyroid hormone [PTH] levels, adenoma volume) while comparing the efficacy of ultrasound and single-photon emission computed tomography in differentiating between both types of adenoma. METHODS: From 152 patients diagnosed with PHPT between January 2013 and 2014, only 109 patients who had positive ultrasonographic findings for single parathyroid adenoma were included in the study. RESULTS: A total of 26 patients had cystic adenomas and 83 patients had solid adenomas. Sestamibi (MIBI) was negative in 50% of the cystic adenoma group and 27.7% of the solid adenoma group, with an overall technetium-MIBI efficacy of 67%. Age, phosphorus level, and adenoma volume were significantly higher in patients with cystic adenomas (P = .001, P = .02, and P = .02, respectively), whereas calcium and PTH levels were significantly higher in patients with solid adenomas (P = .02, P = .038, respectively). MIBI had a significant correlation with PTH levels (P = .031) and adenoma volume (P = .05) only in patients with solid adenomas. No significant correlation was found between sex and type of parathyroid adenoma. CONCLUSION: The current study is the first to compare age, PTH levels, and adenoma volume between cystic and solid adenoma patients, providing more information for the poorly understood pathology of cystic adenomas. Our findings showed that age and calcium and PTH levels are significantly higher in patients with solid adenomas, whereas adenoma volume and phosphorus levels are significantly higher in patients with cystic adenomas.