Unveiling a Biomarker Signature of Meningioma: the Need for a Panel of Genomic, Epigenetic, Proteomic, and RNA Biomarkers to Advance Diagnosis and Prognosis

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation in grades classified from I to III. Meningiomas tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment. A deeper comprehension of the molecular pathways and cellular microenvironment factors implicated in meningioma survival and pathology is needed. This review summarizes the known genetic and epigenetic aberrations involved in meningioma, with a focus on Neurofibromatosis type 2 (NF2) and non-NF2 mutations. Novel potential biomarkers for meningioma diagnosis and prognosis are also discussed, including epigenetic-, RNA-, and protein-based markers. Finally, the landscape of available meningioma-specific animal models is overviewed. Use of these animal models can enable planning of adjuvant treatment, potentially assisting in preoperative and postoperative decision-making. Discovery of novel biomarkers will allow more precise meningioma grading, including meningioma identification, subtype determination, and prediction of metastasis, recurrence, and response to therapy. Moreover, these biomarkers may be exploited in the development of personalized targeted therapies that can distinguish between the 15 diverse meningioma subtypes.This research is funded by a grant from Morehouse School of Medicine to Firas Kobeissy and a grant from Qatar University to Abdullah A. Shaito

Novel therapeutic strategies for spinal osteosarcomas

At the dawn of the third millennium, cancer has become the bane of twenty-first century man, and remains a predominant public health burden, affecting welfare and life expectancy globally. Spinal osteogenic sarcoma, a primary spinal malignant tumor, is a rare and challenging neoplastic disease to treat. After the conventional therapeutic modalities of chemotherapy, radiation and surgery have been exhausted, there is currently no available alternative therapy in managing cases of spinal osteosarcoma. The defining signatures of tumor survival are characterised by cancer cell ability to stonewall immunogenic attrition and apoptosis by various means. Some of these biomarkers, namely immune-checkpoints, have recently been exploited as druggable targets in osteosarcoma and many other different cancers. These promising strides made by the use of reinvigorated immunotherapeutic approaches may lead to significant reduction in spinal osteosarcoma disease burden and corresponding reciprocity in increase of survival rates. In this review, we provide the background to spinal osteosarcoma, and proceed to elaborate on contribution of the complex ecology within tumor microenvironment giving arise to cancerous immune escape, which is currently receiving considerable attention. We follow this section on the tumor microenvironment by a brief history of cancer immunity. Also, we draw on the current knowledge of treatment gained from incidences of osteosarcoma at other locations of the skeleton (long bones of the extremities in close proximity to the metaphyseal growth plates) to make a case for application of immunity-based tools, such as immune-checkpoint inhibitors and vaccines, and draw attention to adverse upshots of immune-checkpoint blockers as well. Finally, we describe the novel biotechnique of CRISPR/Cas9 that will assist in treatment approaches for personalized medication.This work is funded by a grant (MPP 320133) from the American University of Beirut to Dr. Ali H. Eid

Minimally Invasive Transforaminal Versus Direct Lateral Lumbar Interbody Fusion: Effect on Return to Work, Narcotic Use, and Quality of life

BACKGROUND: Direct lateral (DLIF) and transforaminal (TLIF) lumbar interbody fusions have been shown to produce satisfactory clinical outcomes with significant reduction in pain and functional disability. Despite their increasing use in complex spinal deformity surgeries, there is a paucity of data comparing outcome measures, which this study addresses. METHODS: This is a retrospective, comparative study of patients who underwent minimally invasive, 1-level TLIF or DLIF between 2013 and 2015. Only patients 18 years and older were included. Preoperative and demographic variables were collected, and clinical outcome measures were compared between cohorts. RESULTS: In total, 46 patients were included (DLIF: 17 patients; TLIF: 29 patients). Preoperatively, there was no difference in visual analog scale pain score or Oswestry Disability Index. Overall, there was a significant improvement in the postoperative visual analog scale score and Oswestry Disability Index in the separate cohorts, without significant difference when compared. The duration of postoperative narcotic use was similar in both cohorts (DLIF: 4.8 ± 4.7 months vs. TLIF: 5.2 ± 5.1 months, P = 0.82). Significantly more patients in DLIF cohort were cleared for work after surgery. Patients who underwent MIS TLIF had a significantly longer time to return to work (7.1 ± 4.8 months) compared with patients undergoing DLIF (2.3 ± 1.3, P = 0.006). There was a greater incidence of reoperation in the TLIF cohort. CONCLUSIONS: Both MIS TLIF and DLIF provide long-term improvement in pain andfunctional outcomes, with an overall reduction in postoperative narcotic requirement. However, there was a significantly longer time to return to work and a greater incidence of reoperation in the TLIF cohort compared with the patients who underwent DLIF

Unveiling a Biomarker Signature of Meningioma: The Need for a Panel of Genomic, Epigenetic, Proteomic, and RNA Biomarkers to Advance Diagnosis and Prognosis

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation into advanced grades classified by World Health Organization (WHO) into Grades 1 to 3. Meningiomas’ tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment. A deeper comprehension of the molecular pathways and cellular microenvironment factors implicated in meningioma survival and pathology is needed. This review summarizes the known genetic and epigenetic aberrations involved in meningiomas, with a focus on neurofibromatosis type 2 (NF2) and non-NF2 mutations. Novel potential biomarkers for meningioma diagnosis and prognosis are also discussed, including epigenetic-, RNA-, metabolomics-, and protein-based markers. Finally, the landscape of available meningioma-specific animal models is overviewed. Use of these animal models can enable planning of adjuvant treatment, potentially assisting in pre-operative and post-operative decision making. Discovery of novel biomarkers will allow, in combination with WHO grading, more precise meningioma grading, including meningioma identification, subtype determination, and prediction of metastasis, recurrence, and response to therapy. Moreover, these biomarkers may be exploited in the development of personalized targeted therapies that can distinguish between the 15 diverse meningioma subtypes

The impact of COVID-19 on health care–associated infections in intensive care units in low- and middle-income countries: International Nosocomial Infection Control Consortium (INICC) findings

•Due to the COVID pandemic, health care–associated infection rates increased in resource-limited countries.•Due to the COVID pandemic, rates of central line–associated bloodstream infections increased.•Due to the COVID pandemic, rates of central ventilator–associated events increased.•Due to the COVID pandemic, mortality rates increased in intensive care units of resource-limited countries in 2020.•Due to the COVID pandemic, average length of stay increased in resource-limited countries in 2020. This study examines the impact of the COVID-19 pandemic on health care–associated infection (HAI) incidence in low- and middle-income countries (LMICs). Patients from 7 LMICs were followed up during hospital intensive care unit (ICU) stays from January 2019 to May 2020. HAI rates were calculated using the International Nosocomial Infection Control Consortium (INICC) Surveillance Online System applying the Centers for Disease Control and Prevention's National Healthcare Safety Network (CDC-NHSN) criteria. Pre–COVID-19 rates for 2019 were compared with COVID-19 era rates for 2020 for central line–associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated events (VAEs), mortality, and length of stay (LOS). A total of 7,775 patients were followed up for 49,506 bed days. The 2019 to 2020 rate comparisons were 2.54 and 4.73 CLABSIs per 1,000 central line days (risk ratio [RR] = 1.85, p = .0006), 9.71 and 12.58 VAEs per 1,000 mechanical ventilator days (RR = 1.29, p = .10), and 1.64 and 1.43 CAUTIs per 1,000 urinary catheter days (RR = 1.14; p = .69). Mortality rates were 15.2% and 23.2% for 2019 and 2020 (RR = 1.42; p < .0001), respectively. Mean LOS for 2019 and 2020 were 6.02 and 7.54 days (RR = 1.21, p < .0001), respectively. This study documents an increase in HAI rates in 7 LMICs during the first 5 months of the COVID-19 pandemic and highlights the need to reprioritize and return to conventional infection prevention practices