Surgical Management of Craniovertebral Junction Schwannomas: A Systematic Review

Background: Craniovertebral junction (CVJ) schwannomas are rare, with surgery and stereotactic radiosurgery (SRS) being effective yet challenging options. We systematically reviewed the literature on CVJ schwannomas. Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA statement to include studies reporting CVJ schwannomas. Clinical features, management, and outcomes were analyzed. Results: We collected 353 patients from 101 included articles. Presenting symptoms were mostly neck pain (30.3%) and headache (26.3%), with most cranial neuropathies involving the XII (31.2%) and X (24.4%) nerves. Most tumors originated from C2 (30.9%) and XII (29.4%) nerves, being extracranial (45.1%) and intradural-extradural (44.2%). Erosion of C1–C2 vertebrae (37.1%), the hypoglossal canal (28.3%), and/or jugular foramen (20.1%) were noted. All tumors were operated, preferably with the retrosigmoid approach (36.5%), with the far-lateral approach (29.7%) or with the posterior approach and cervical laminectomy (26.9%), far-lateral approaches (14.2%), or suboccipital craniotomy with concurrent cervical laminectomy (14.2%). Complete tumor resection was obtained most frequently (61.5%). Adjuvant post-surgery stereotactic radiosurgery was delivered in 5.9% patients. Median follow-up was 27 months (range, 12–252). Symptom improvement was noted in 88.1% of cases, and cranial neuropathies showed improvement in 10.2%. Post-surgical complications occurred in 83 patients (23.5%), mostly dysphagia (7.4%), new cranial neuropathies (6.2%), and cerebrospinal fluid leak (5.9%). A total of 16 patients (4.5%) had tumor recurrence and 7 died (2%), with median overall survival of 2.7 months (range, 0.1–252). Conclusions: Microsurgical resection is safe and effective for CVJ schwannomas. Data on SRS efficacy and indications are still lacking, and its role deserves further evaluation.     

Skeletal myoblast based delivery of angiogenic growth factors: a comparison between angiopoietin-1 and VEGF gene delivery for therapeutic angiogenesis in the heart

Introduction Extensive cell death and an associated myocardial dys- function are the common features of chronic heart disease. Given the inadequate ability of the human heart to regenerate, a more recent approach to counter the remodel- ing process is to compensate for the loss of functioning cardiomyocyte number through stem cell transplantation with angiomyogenic potential.1,2 The novel approach of heart cell therapy is to repopulate the scar tissue with myogenic cells that may be functional…     

The turmoil around the drug-eluting stents

Of 141 hospital survivors after intracardiac repair of tetralogy of Fallot, eight died suddenly 6–23 years later. Compared with the other 133 patients, these eight were older at operation, with higher post-repair systolic right ventricular pressure and more often complete atrioventricular block; ventricular arrhythmia was diagnosed before death in three cases. In follow-up totalling 2255 patient years, the linearized rate of sudden death was 0.35%/year. The instantaneous risk of sudden death showed continuous increase with the length of follow-up. Of 80 survivors electrocardiographically evaluated 13–26 (median 20) years postoperatively, none had complete block, but 79 had complete right bundle branch block, including seven with left anterior hemiblock. Ventricular extrasystoles were recorded in 1% at rest, in 34% during exercise and in 83% during 24-hour ambulatory monitoring, with Lown Grade ≥II in 27%. Old age and possibly presence of fibrosis and/or fibroelastosis in right ventricular outflow tract muscle correlated independently with high Lown Grade. A patient with Lown grade III died suddenly 2 years after our follow-up. Old age at repair thus was associated with increased risk of late sudden death and with frequent ventricular arrhythmia in long-term survivors.     

Development of ultrasound-assisted dispersive liquid–liquid microextraction–large volume injection–gas chromatography–tandem mass spectrometry method for determination of pyrethroid metabolites in brain of cypermethrin-treated rats

3-Phenoxybenzoic acid (3-PBA) and 4-hydroxy-3-phenoxybenzoic acid (OH-PBA) are the two common metabolites for most pyrethroid insecticides. A rapid, sensitive, and eco-friendly method has been developed based on ultrasound-assisted dispersive liquid–liquid microextraction (DLLME) coupled to large volume injection–gas chromatography–tandem mass spectrometry for the simultaneous determination of pyrethroid metabolites in rat brain treated with cypermethrin (CYP). Brain samples were homogenized in methanol (disperser solvent) followed by derivatization with methyl chloroformate (MCF) and extraction using DLLME. Factors that influence the extraction and derivatization efficiency such as type and volume of extraction and disperser solvent, sonication time, pH, ionic strength, and volumes of MCF and pyridine were optimized. Under optimized conditions, the limits of detection were 1 and 4 ng/g for 3-PBA and OH-PBA, respectively. Mean recoveries of pyrethroid metabolites in rat brain were in the range of 83–95 %. The developed method was successfully applied for determination of 3-PBA and OH-PBA in brain samples of CYP-treated rats. The developed method can be adopted for rapid and sensitive analysis of pyrethroid metabolites in toxicological and forensic laboratories.     

Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance,and is associated with worse prognosis in triple-negative breast cancer

Background Glutamine (Gln) is an abundant nutrient used by cancer cells. Breast cancers cells and particularly triple-receptor negative breast cancer (TNBC) are reported to be dependent on Gln to produce the energy required for survival and proliferation. Despite intense research on the role of the intracellular Gln pathway, few reports have focussed on Gln transporters in breast cancer and TNBC.Methods The role and localisation of the Gln transporter SLC38A2/SNAT2 in response to Gln deprivation or pharmacological stresses was examined in a panel of breast cancer cell lines. Subsequently, the effect of SLC38A2 knockdown in Gln-sensitive cell lines was analysed. The prognostic value of SLC38A2 in a cohort of breast cancer was determined by immunohistochemistry.Results SLC38A2 was identified as a strongly expressed amino acid transporter in six breast cancer cell lines. We confirmed an autophagic route of degradation for SLC38A2. SLC38A2 knockdown decreased Gln consumption, inhibited cell growth, induced autophagy and led to ROS production in a subgroup of Gln-sensitive cell lines. High expression of SLC38A2 protein was associated with poor breast cancer specific survival in a large cohort of patients (p = 0.004), particularly in TNBC (p = 0.02).Conclusions These results position SLC38A2 as a selective target for inhibiting growth of Gln-dependent breast cancer cell lines.Subject terms: Breast cancer, Cancer metabolism     

Kidney progression project (KiPP): Protocol for a longitudinal cohort study of progression in chronic kidney disease of unknown etiology in Sri Lanka

Over the last two decades, a global epidemic of chronic kidney disease of unknown etiology (CKDu) has emerged in rural, arid, agricultural, lowland areas. Endemic regions have reported 15 to 20% prevalence among residents aged 30–60 years. CKDu is a progressive and irreversible disease resulting in renal failure and death in the absence of dialysis or a kidney transplant. While much of the research has focused on identifying etiology, this project seeks to ascertain factors associated with the rapidity of kidney disease progression in one of Sri Lanka’s CKDu endemic areas. A sample of 296 male and female residents aged 21 to 65 with moderate CKD, as measured by their serum creatinine level, and a clinical diagnosis of CKDu are followed using quarterly serum testing to track the rate of progression. A baseline survey administered to the entire sample addresses potential risk factors, supplemented by a short survey focusing on changes through time. Concurrently water, soil and air are tested at the local and household levels. The study is the first to foster a multi-disciplinary approach that focuses on disease progression, identifying behavioural and exposure risk factors for rapid kidney function decline, in this progressively fatal disease.