Orally administered 5-aminolevulinic acid for isolation and characterization of circulating tumor-derived extracellular vesicles in glioblastoma patients

Background: In glioblastoma (GB), tissue is required for accurate diagnosis and subtyping. Tissue can be obtained through resection or (stereotactic) biopsy, but these invasive procedures provide risks for patients. Extracellular vesicles (EVs) are small, cell-derived vesicles that contain miRNAs, proteins, and lipids, and possible candidates for liquid biopsies. GB-derived EVs can be found in the blood of patients, but it is difficult to distinguish them from circulating non-tumor EVs. 5-aminolevulinic acid (5-ALA) is orally administered to GB patients to facilitate tumor visualization and maximal resection, as it is metabolized to fluorescent protoporphyrin IX (PpIX) that accumulates in glioma cell

Adult Sacrococcygeal Teratoma: The third leg

Introduction: Sacrococcygeal Teratoma (SCT) is a rare benign neoplasm comprised of mixed elements derived from two or more germ cell layers. They are extremely rare in adults. They attract attention because of their gross appearance and bizarre histology. Presentation of case: A 25 year old male presented to Surgical OPD, Government General Hospital, Guntur Medical College, Guntur with a large mass comprising a partially developed 3rd leg and rudimentary external genitalia in the lower back. He complained of cosmetic blemish, difficulty in sitting, sleeping and walking. Discussion: He was diagnosed mature Sacrococcygeal Teratoma Altman Type II based on history, clinical examination, ultrasound, MRI. Histopathology confirmed the diagnosis. He had complete surgical excision with primary wound closure and a good postoperative recovery. A 3-year follow-up using clinical, biochemical and radiological assessment revealed no evidence of recurrence. Conclusion: Mature SCT, though very rare in adults, are usually benign. Complete surgical excision remains the mainstay of treatment

Single-Cell RNA Sequencing of Cerebrospinal Fluid as an Advanced Form of Liquid Biopsy for Neurological Disorders

Diagnosis and longitudinal monitoring of neurological diseases are limited by the poor specificity and limited resolution of currently available techniques. Analysis of circulating cells in cerebrospinal fluid (CSF) has emerged as a promising strategy for the diagnosis, molecular characterization, and monitoring of neurological disease. In comparison to bulk sequencing analysis, single-cell sequencing studies can provide novel insights into rare cell populations and uncover heterogeneity in gene expression at a single-cell resolution, which has several implications for understanding disease pathology and treatment. Parallel development of standardized biofluid collection protocols, pre-processing strategies, reliable single-cell isolation strategies, downstream genomic analysis, and robust computational analysis is paramount for comprehensive single-cell sequencing analysis. Here we perform a comprehensive review of studies focusing on single-cell sequencing of cells in the CSF of patients with oncological or non-oncological diseases of the central nervous system

Clinical and genetic characterization of patients with Pierre Robin sequence and spinal disease: review of the literature and novel terminal 10q deletion.

IntroductionThe Pierre-Robin sequence (PRS) is a pattern of congenital facial abnormalities comprising micrognathia, glossoptosis, and airway obstruction. Associated spinal pathologies have rarely been reported with PRS.MethodsWe explore the molecular genetic basis of this association through a systematic review of spinal disease in patients with PRS. We also present an illustrative case of a PRS patient with tethered cord in the setting of chromosome 10q terminal deletion.ResultsOur systematic literature review of spinal disease in patients with PRS revealed several patterns in the underlying genetic syndromes causing these conditions to co-occur. These principles are illustrated in the case of a 6-month-old female with PRS and a 14.34-Mb terminal deletion of chromosome 10q, who was found to have a sacral dimple during a routine outpatient checkup. Magnetic resonance imaging of the spine revealed a lumbar syrinx associated with tethered spinal cord. Surgical de-tethering was undertaken, with subsequent improvement in motor function and decrease in the size of the syrinx. The deletion of chromosome 10q in our patient had not previously been described in association with tethered cord or PRS.ConclusionSpinal pathologies are understudied contributors to disease burden in patients with PRS. The range of predisposing syndromes and mutations in patients with both PRS and spinal disorders remains poorly characterized but may be more defined than previously conceived. Clinical screening is most critical during neonatal and adolescent developmental periods with continued neurological assessment. This study emphasizes the need for early genetic testing and counseling in this patient population, in parallel with research efforts to develop molecular classifications to guide clinical management

Clinical and genetic characterization of patients with Pierre Robin sequence and spinal disease: review of the literature and novel terminal 10q deletion.

IntroductionThe Pierre-Robin sequence (PRS) is a pattern of congenital facial abnormalities comprising micrognathia, glossoptosis, and airway obstruction. Associated spinal pathologies have rarely been reported with PRS.MethodsWe explore the molecular genetic basis of this association through a systematic review of spinal disease in patients with PRS. We also present an illustrative case of a PRS patient with tethered cord in the setting of chromosome 10q terminal deletion.ResultsOur systematic literature review of spinal disease in patients with PRS revealed several patterns in the underlying genetic syndromes causing these conditions to co-occur. These principles are illustrated in the case of a 6-month-old female with PRS and a 14.34-Mb terminal deletion of chromosome 10q, who was found to have a sacral dimple during a routine outpatient checkup. Magnetic resonance imaging of the spine revealed a lumbar syrinx associated with tethered spinal cord. Surgical de-tethering was undertaken, with subsequent improvement in motor function and decrease in the size of the syrinx. The deletion of chromosome 10q in our patient had not previously been described in association with tethered cord or PRS.ConclusionSpinal pathologies are understudied contributors to disease burden in patients with PRS. The range of predisposing syndromes and mutations in patients with both PRS and spinal disorders remains poorly characterized but may be more defined than previously conceived. Clinical screening is most critical during neonatal and adolescent developmental periods with continued neurological assessment. This study emphasizes the need for early genetic testing and counseling in this patient population, in parallel with research efforts to develop molecular classifications to guide clinical management

The role of extracellular vesicles in acquisition of resistance to therapy in glioblastomas

Glioblastoma (GBM) is the most aggressive primary brain tumor with a median survival of 15 months despite standard care therapy consisting of maximal surgical debulking, followed by radiation therapy with concurrent and adjuvant temozolomide treatment. The natural history of GBM is characterized by inevitable recurrence with patients dying from increasingly resistant tumor regrowth after therapy. Several mechanisms including inter- and intratumoral heterogeneity, the evolution of therapy-resistant clonal subpopulations, reacquisition of stemness in glioblastoma stem cells, multiple drug efflux mechanisms, the tumor-promoting microenvironment, metabolic adaptations, and enhanced repair of drug-induced DNA damage have been implicated in therapy failure. Extracellular vesicles (EVs) have emerged as crucial mediators in the maintenance and establishment of GBM. Multiple seminal studies have uncovered the multi-dynamic role of EVs in the acquisition of drug resistance. Mechanisms include EV-mediated cargo transfer and EVs functioning as drug efflux channels and decoys for antibody-based therapies. In this review, we discuss the various mechanisms of therapy resistance in GBM, highlighting the emerging role of EV-orchestrated drug resistance. Understanding the landscape of GBM resistance is critical in devising novel therapeutic approaches to fight this deadly disease

Direct stick embolization of a rectal venous malformation via transanal minimally invasive surgery

Rectal venous malformations (VMs) are rare clinical entities with variable patterns of presentation. Treatment requires unique, targeted strategies based on the symptoms, associated complications, and location, depth, and extent of the lesion. We present a rare case of a large, isolated rectal VM treated by direct stick embolization (DSE) using transanal minimally invasive surgery (TAMIS). A 49-year-old man had presented with a rectal mass incidentally detected on computed tomography urography. Magnetic resonance imaging and endoscopy revealed an isolated rectal VM. Elevated D-dimer levels concerning for localized intravascular coagulopathy warranted the use of prophylactic rivaroxaban. To avoid invasive surgery, DSE using TAMIS was performed successfully without complications. His postoperative recovery was uneventful, aside from a self-limiting and expected course of postembolization syndrome. To the best of our knowledge, this is the first reported case of TAMIS-assisted DSE of a colorectal VM. TAMIS shows promise for more widespread use in the minimally invasive, interventional management of colorectal vascular anomalies

Navigating the Landscape of Tumor Extracellular Vesicle Heterogeneity

The last decade has seen a rapid expansion of interest in extracellular vesicles (EVs) released by cells and proposed to mediate intercellular communication in physiological and pathological conditions. Considering that the genetic content of EVs reflects that of their respective parent cell, many researchers have proposed EVs as a source of biomarkers in various diseases. So far, the question of heterogeneity in given EV samples is rarely addressed at the experimental level. Because of their relatively small size, EVs are difficult to reliably isolate and detect within a given sample. Consequently, standardized protocols that have been optimized for accurate characterization of EVs are lacking despite recent advancements in the field. Continuous improvements in pre-analytical parameters permit more efficient assessment of EVs, however, methods to more objectively distinguish EVs from background, and to interpret multiple single-EV parameters are lacking. Here, we review EV heterogeneity according to their origin, mode of release, membrane composition, organelle and biochemical content, and other factors. In doing so, we also provide an overview of currently available and potentially applicable methods for single EV analysis. Finally, we examine the latest findings from experiments that have analyzed the issue at the single EV level and discuss potential implications