Surgical Management of Thoracolumbar Adjacent Segment Disease: Techniques and Outcomes in 107 Patients Undergoing Surgical Intervention.

BACKGROUND: Adjacent segment disease (ASD) is a known sequela of thoracolumbar instrumented fusions. Various surgical options are available to address ASD in patients with intractable symptoms who have failed conservative measures. However, the optimal treatment strategy for symptomatic ASD has not been established. We examined several clinical outcomes utilizing different surgical interventions for symptomatic ASD. METHODS: A retrospective review was performed for a consecutive series of patients undergoing revision surgery for thoracolumbar ASD between October 2011 and February 2022. Patients were treated with endoscopic decompression (N = 17), microdiscectomy (N = 9), lateral lumbar interbody fusion (LLIF; N = 26), or open laminectomy and fusion (LF; N = 55). The primary outcomes compared between groups were re-operation rates and numeric pain scores for leg and back at 2 weeks, 10 weeks, 6 months, and 12 months postoperation. Secondary outcomes included time to re-operation, estimated blood loss, and length of stay. RESULTS: Of the 257 patients who underwent revision surgery for symptomatic ASD, 107 patients met inclusion criteria with a minimum of 1-year follow-up. The mean age of all patients was 67.90 ± 10.51 years. There was no statistically significant difference between groups in age, gender, preoperative American Society of Anesthesiologists scoring, number of previously fused levels, or preoperative numeric leg and back pain scores. The re-operation rates were significantly lower in LF (12.7%) and LLIF cohorts (19.2%) compared with microdiscectomy (33%) and endoscopic decompression (52.9%; P = 0.005). Only LF and LLIF cohorts experienced significantly decreased pain scores at all 4 follow-up visits (2 weeks, 10 weeks, 6 months, and 12 months; P < 0.001 and P < 0.05, respectively) relative to preoperative scores. CONCLUSION: Symptomatic ASD often requires treatment with revision surgery. Fusion surgeries (either stand-alone lateral interbody or posterolateral with instrumentation) were most effective and durable with respect to alleviating pain and avoiding additional revisions within the first 12 months following revision surgery. CLINICAL RELEVANCE: This study emphasizes the importance of risk-stratifying patients to identify the least invasive approach that treats their symptoms and reduces the risk of future surgeries.

Antiretroviral Drug Repositioning for Glioblastoma.

Outcomes for glioblastoma (GBM) remain poor despite standard-of-care treatments including surgical resection, radiation, and chemotherapy. Intratumoral heterogeneity contributes to treatment resistance and poor prognosis, thus demanding novel therapeutic approaches. Drug repositioning studies on antiretroviral therapy (ART) have shown promising potent antineoplastic effects in multiple cancers; however, its efficacy in GBM remains unclear. To better understand the pleiotropic anticancer effects of ART on GBM, we conducted a comprehensive drug repurposing analysis of ART in GBM to highlight its utility in translational neuro-oncology. To uncover the anticancer role of ART in GBM, we conducted a comprehensive bioinformatic and in vitro screen of antiretrovirals against glioblastoma. Using the DepMap repository and reversal of gene expression score, we conducted an unbiased screen of 16 antiretrovirals in 40 glioma cell lines to identify promising candidates for GBM drug repositioning. We utilized patient-derived neurospheres and glioma cell lines to assess neurosphere viability, proliferation, and stemness. Our in silico screen revealed that several ART drugs including reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs) demonstrated marked anti-glioma activity with the capability of reversing the GBM disease signature. RTIs effectively decreased cell viability, GBM stem cell markers, and proliferation. Our study provides mechanistic and functional insight into the utility of ART repurposing for malignant gliomas, which supports the current literature. Given their safety profile, preclinical efficacy, and neuropenetrance, ARTs may be a promising adjuvant treatment for GBM.

Minimally invasive resection of intracranial lesions using tubular retractors: A single surgeon series.

OBJECTIVE: Tubular retractors are increasingly used due to their low complication rates, providing easier access to lesions while minimizing trauma from brain retraction. Our study presents the most extensive series of cases performed by a single surgeon aiming to assess the effectiveness and safety of a transcortical-transtubular approach for removing intracranial lesions. METHODS: We performed a retrospective review of patients who underwent resection of an intracranial lesion with the use of tubular retractors. Electronic medical records were reviewed for patient demographics, preoperative clinical deficits, diagnosis, preoperative and postoperative magnetic resonance imaging (MRI) scans, lesion characteristics including location, volume, extent of resection (EOR), postoperative complications, and postoperative deficits. RESULTS: 112 transtubular resections for intracranial lesions were performed. Patients presented with a diverse number of pathologies including metastasis (31.3 %), GBM (21.4 %), and colloid cysts (19.6 %) The mean pre-op lesion volume was 14.45 cm3. A gross total resection was achieved in 81 (71.7 %) cases. Seventeen (15.2 %) patients experienced early complications which included confusion, short-term memory difficulties, seizures, meningitis and motor and visual deficits. Four (3.6 %) patients had permanent complications, including one with aphasia and difficulty finding words, another with memory loss, a third with left-sided weakness, and one patient who developed new-onset long-term seizures. Mean post-operative hospitalization length was 3.8 days. CONCLUSION: Tubular retractors provide a minimally invasive approach for the extraction of intracranial lesions. They serve as an efficient tool in neurosurgery, facilitating the safe resection of deep-seated lesions with minimal complications.

Intrathecal chemotherapy for leptomeningeal disease in high-grade gliomas: a systematic review.

BACKGROUND: Leptomeningeal disease (LMD) secondary to high grade glioma (HGG), such as glioblastoma (GBM), are characterized by the spread of tumor cells to the leptomeninges which further complicates treatment approaches. Intrathecal (IT) chemotherapy has surfaced as a potential strategy to bypass the blood-brain barrier and address the challenges posed by disseminated disease. Here, we present a review of the safety and efficacy of IT chemotherapy in the treatment of LMD secondary to HGG. METHODS: A systematic review following PRISMA guidelines was conducted searching PubMed and Embase from January 1995 to September 2022 using specified terms related to IT chemotherapy for LMD. Included articles involved patients diagnosed with LMD from HGG, treated with intrathecal chemotherapy, and provided survival data. Data, including demographics, tumor characteristics, treatment, and survival information, were collected and independently extracted. RESULTS: A total of 68 patients across 10 clinical studies were diagnosed with LMD from HGG and included in the review. Among these patients, the average age at diagnosis was 44.2 years. GBM was the most common tumor type (n = 58, 85.3%). A majority of the patients presented with recurrent disease (n = 29, 60.4%). The review encompassed various IT chemotherapy regimens, including mafosfamide, thio-TEPA, 5-fluoro-2'-deoxyuridine (FdUrd), methotrexate (MTX), and cytarabine; however, dosages and frequencies were inconsistently reported. The mean progression-free survival (PFS) and overall survival (OS) for this cohort were 7.5 months and 11.7 months, respectively. Common side effects of IT chemotherapy included headaches, nausea, and vomiting, with more severe complications such as myelotoxicity, disseminated intravascular coagulopathy, meningitis, and gastrointestinal toxicity reported in some cases. CONCLUSION: LMD continues to be an uncommon complication associated with HGG with a poor prognosis. This article provides an overview of the presently available literature on IT chemotherapy for LMD secondary to HGG, and their respective treatment protocols with overall survival attributes. Additional research is warranted to ascertain how to maximize the potential efficacy of IT chemotherapy as a treatment option.

A review on graphene-based nanocomposites for electrochemical and fluorescent biosensors.

Biosensors with high sensitivity, selectivity and a low limit of detection, reaching nano/picomolar concentrations of biomolecules, are important to the medical sciences and healthcare industry for evaluating physiological and metabolic parameters. Over the last decade, different nanomaterials have been exploited to design highly efficient biosensors for the detection of analyte biomolecules. The discovery of graphene has spectacularly accelerated research on fabricating low-cost electrode materials because of its unique physical properties, including high specific surface area, high carrier mobility, high electrical conductivity, flexibility, and optical transparency. Graphene and its oxygenated derivatives, including graphene oxide (GO) and reduced graphene oxide (rGO), are becoming an important class of nanomaterials in the field of biosensors. The presence of oxygenated functional groups makes GO nanosheets strongly hydrophilic, facilitating chemical functionalization. Graphene, GO and rGO nanosheets can be easily combined with various types of inorganic nanoparticles, including metals, metal oxides, semiconducting nanoparticles, quantum dots, organic polymers and biomolecules, to create a diverse range of graphene-based nanocomposites with enhanced sensitivity for biosensor applications. This review summarizes the advances in two-dimensional (2D) and three-dimensional (3D) graphene-based nanocomposites as emerging electrochemical and fluorescent biosensing platforms for the detection of a wide range of biomolecules with enhanced sensitivity, selectivity and a low limit of detection. The biofunctionalization and nanocomposite formation processes of graphene-based materials and their unique properties, surface functionalization, enzyme immobilization strategies, covalent immobilization, physical adsorption, biointeractions and direct electron transfer (DET) processes are discussed in connection with the design and fabrication of biosensors. The enzymatic and nonenzymatic reactions on graphene-based nanocomposite surfaces for glucose- and cholesterol-related electrochemical biosensors are analyzed. This review covers a very broad range of graphene-based electrochemical and fluorescent biosensors for the detection of glucose, cholesterol, hydrogen peroxide (H2O2), nucleic acids (DNA/RNA), genes, enzymes, cofactors nicotinamide adenine dinucleotide (NADH) and adenosine triphosphate (ATP), dopamine (DA), ascorbic acid (AA), uric acid (UA), cancer biomarkers, pathogenic microorganisms, food toxins, toxic heavy metal ions, mycotoxins, and pesticides. The sensitivity and selectivity of graphene-based electrochemical and fluorescent biosensors are also examined with respect to interfering analytes present in biological systems. Finally, the future outlook for the development of graphene based biosensing technology is outlined.

Flexible Graphene-Based Wearable Gas and Chemical Sensors.

Wearable electronics is expected to be one of the most active research areas in the next decade; therefore, nanomaterials possessing high carrier mobility, optical transparency, mechanical robustness and flexibility, lightweight, and environmental stability will be in immense demand. Graphene is one of the nanomaterials that fulfill all these requirements, along with other inherently unique properties and convenience to fabricate into different morphological nanostructures, from atomically thin single layers to nanoribbons. Graphene-based materials have also been investigated in sensor technologies, from chemical sensing to detection of cancer biomarkers. The progress of graphene-based flexible gas and chemical sensors in terms of material preparation, sensor fabrication, and their performance are reviewed here. The article provides a brief introduction to graphene-based materials and their potential applications in flexible and stretchable wearable electronic devices. The role of graphene in fabricating flexible gas sensors for the detection of various hazardous gases, including nitrogen dioxide (NO2), ammonia (NH3), hydrogen (H2), hydrogen sulfide (H2S), carbon dioxide (CO2), sulfur dioxide (SO2), and humidity in wearable technology, is discussed. In addition, applications of graphene-based materials are also summarized in detecting toxic heavy metal ions (Cd, Hg, Pb, Cr, Fe, Ni, Co, Cu, Ag), and volatile organic compounds (VOCs) including nitrobenzene, toluene, acetone, formaldehyde, amines, phenols, bisphenol A (BPA), explosives, chemical warfare agents, and environmental pollutants. The sensitivity, selectivity and strategies for excluding interferents are also discussed for graphene-based gas and chemical sensors. The challenges for developing future generation of flexible and stretchable sensors for wearable technology that would be usable for the Internet of Things (IoT) are also highlighted.