In Reply: Three-Vessel Anastomosis for Direct Bihemispheric Cerebral Revascularization.
Oper Neurosurg (Hagerstown). 2020 09 15;19(4):E458-E460
Authors: Sekhar LN, Zeeshan Q, Natarajan SK
PMID: 32629481 [PubMed - indexed for MEDLINE]
Rapid Improvement in Gemcitabine-associated Thrombotic Microangiopathy After a Single Dose of Eculizumab: Case Report and Review of the Literature.
Anticancer Res. 2020 Jul;40(7):3995-4000
Authors: Burns ST, Damon L, Akagi N, Laszik Z, Ko AH
Abstract
We present here the case of a 39-year-old man with metastatic pancreatic carcinoma receiving chemotherapy with the combination of gemcitabine and nab-paclitaxel as part of a clinical trial. Despite an impressive response to therapy, he ultimately developed profound anasarca, renal insufficiency, progressive cytopenias, and malignant hypertension 6 months into his treatment course. The diagnosis of gemcitabine-associated thrombotic microangiopathy (G-TMA) was made based on renal biopsy, and receipt of the anti-C5 monoclonal antibody eculizumab proved successful at reversing his deteriorating clinical course and improving his laboratory parameters. This case illustrates the importance of recognizing this rare but serious complication, and highlights one potential therapeutic option that can be used in the appropriate clinical context.
PMID: 32620643 [PubMed - indexed for MEDLINE]
Multimodal single-cell analysis reveals distinct radioresistant stem-like and progenitor cell populations in murine glioma.
Glia. 2020 Jul 04;:
Authors: Alexander J, LaPlant QC, Pattwell SS, Szulzewsky F, Cimino PJ, Caruso FP, Pugliese P, Chen Z, Chardon F, Hill AJ, Spurrell C, Ahrendsen D, Pietras A, Starita LM, Hambardzumyan D, Iavarone A, Shendure J, Holland EC
Abstract
Radiation therapy is part of the standard of care for gliomas and kills a subset of tumor cells, while also altering the tumor microenvironment. Tumor cells with stem-like properties preferentially survive radiation and give rise to glioma recurrence. Various techniques for enriching and quantifying cells with stem-like properties have been used, including the fluorescence activated cell sorting (FACS)-based side population (SP) assay, which is a functional assay that enriches for stem-like tumor cells. In these analyses, mouse models of glioma have been used to understand the biology of this disease and therapeutic responses, including the radiation response. We present combined SP analysis and single-cell RNA sequencing of genetically-engineered mouse models of glioma to show a time course of cellular response to radiation. We identify and characterize two distinct tumor cell populations that are inherently radioresistant and also distinct effects of radiation on immune cell populations within the tumor microenvironment.
PMID: 32621641 [PubMed - as supplied by publisher]
Head and Brain Postmortem Computed Tomography-Autopsy Correlation in Hospital Deaths.
Am J Forensic Med Pathol. 2020 Sep;41(3):163-175
Authors: Serinelli S, Richardson TE, Destian S, Mirchia K, Williams M, Medina-Perez M, Gitto L
Abstract
The use of postmortem computed tomography (PMCT) to support autopsy pathology has increased in recent decades. To some extent, PMCT has also been contemplated as a potential alternative to conventional postmortem examination. The purpose of this study was to investigate the ability of PMCT to detect specific pathologic findings in the head and brain in natural hospital deaths.We examined postmortem CT images and autopsy data from 31 subjects who died at SUNY (State University of New York) Upstate University Hospital between 2013 and 2018. Each subject underwent a noncontrast PMCT and a traditional autopsy. A neuroradiologist analyzed PMCT images for head and brain abnormalities. The autopsies were performed by pathologists who were aware of the radiology results.In our series, PMCT was able to detect the majority of the significant space-occupying lesions, although it was not always reliable in ascertaining their nature. Postmortem computed tomography revealed findings usually challenging to detect at autopsy. Unfortunately, there were also situations in which PMCT was misleading, showing changes that were difficult to interpret, or that could be related to postmortem events. Therefore, we conclude PMCT should be used as an adjunct rather than a substitute to autopsy.
PMID: 32618580 [PubMed - indexed for MEDLINE]
"It's Not the Shunt": An Algorithm for the Assessment of Other Medically Actionable Causes of Vomiting in Children With Craniofacial Malformations.
Cleft Palate Craniofac J. 2019 07;56(6):814-816
Authors: Maxey D, Lee A, Wenger T
Abstract
BACKGROUND: After shunt malfunction has been ruled out in children with craniofacial malformations with vomiting, it can be challenging to effectively communicate with front-line providers about their unique medically actionable causes of vomiting as compared to children whose shunts were placed for other reasons (eg, prematurity/intraventricular hemorrhage).
SOLUTION: An algorithm to facilitate communication "What we did that is new": We developed an algorithm to facilitate communication regarding emergent evaluation of vomiting in this population.
PMID: 30587011 [PubMed - indexed for MEDLINE]
The Synaptic Scaling Literature: A Systematic Review of Methodologies and Quality of Reporting.
Front Cell Neurosci. 2020;14:164
Authors: Moulin TC, Rayêe D, Williams MJ, Schiöth HB
Abstract
The maintenance of the excitability of neurons and circuits is a fundamental process for healthy brain functions. One of the main homeostatic mechanisms responsible for such regulation is synaptic scaling. While this type of plasticity is well-characterized through a robust body of literature, there are no systematic evaluations of the methodological and reporting features from these studies. Our review yielded 168 articles directly investigating synaptic scaling mechanisms, which display relatively high impact, with a median impact factor of 7.76 for the publishing journals. Our methodological analysis identified that 86% of the articles made use of inhibitory interventions to induce synaptic scaling, while only 41% of those studies contain excitatory manipulations. To verify the effects of synaptic scaling, the most assessed outcome was miniature excitatory postsynaptic current (mEPSC) recordings, performed in 71% of the articles. We could also observe that the field is mostly focused on mechanistic studies of the synaptic scaling pathways (70%), rather than the interaction with other types of plasticity, such as Hebbian processes (4%). We found that more than half of the articles failed to describe simple features, such as regulatory compliance statements, ethics committee approval, or statements of conflict of interests. In light of these results, we discuss the strengths and pitfalls existing in synaptic scaling literature.
PMID: 32612512 [PubMed]
Predicting the Trajectory of Any COVID19 Epidemic From the Best Straight Line.
medRxiv. 2020 Jun 28;:
Authors: Levitt M, Scaiewicz A, Zonta F
Abstract
A pipeline involving data acquisition, curation, carefully chosen graphs and mathematical models, allows analysis of COVID-19 outbreaks at 3,546 locations world-wide (all countries plus smaller administrative divisions with data available). Comparison of locations with over 50 deaths shows all outbreaks have a common feature: H(t) defined as loge(X(t)/X(t 1)) decreases linearly on a log scale, where X(t) is the total number of Cases or Deaths on day, t (we use ln for loge). The downward slopes vary by about a factor of three with time constants (1/slope) of between 1 and 3 weeks; this suggests it may be possible to predict when an outbreak will end. Is it possible to go beyond this and perform early prediction of the outcome in terms of the eventual plateau number of total confirmed cases or deaths? We test this hypothesis by showing that the trajectory of cases or deaths in any outbreak can be converted into a straight line. Specifically , is a straight line for the correct plateau value N, which is determined by a new method, Best-Line Fitting (BLF). BLF involves a straight-line facilitation extrapolation needed for prediction; it is blindingly fast and amenable to optimization. We find that in some locations that entire trajectory can be predicted early, whereas others take longer to follow this simple functional form. Fortunately, BLF distinguishes predictions that are likely to be correct in that they show a stable plateau of total cases or death (N value). We apply BLF to locations that seem close to a stable predicted N value and then forecast the outcome at some locations that are still growing wildly. Our accompanying web-site will be updated frequently and provide all graphs and data described here.
PMID: 32607515 [PubMed]
An American Physiological Society cross-journal Call for Papers on "Deconstructing Organs: Single-Cell Analyses, Decellularized Organs, Organoids, and Organ-on-a-Chip Models".
Am J Physiol Lung Cell Mol Physiol. 2020 08 01;319(2):L266-L272
Authors: Adams JC, Bell PD, Bodine SC, Brooks HL, Bunnett N, Joe B, Keehan KH, Kleyman TR, Marette A, Morty RE, Ramírez JM, Thomsen MB, Yates BJ, Zucker IH
PMID: 32609556 [PubMed - indexed for MEDLINE]
Spasm, stenosis and shelves: balloon-assisted tracking techniques in endovascular interventions.
J Cerebrovasc Endovasc Neurosurg. 2020 Mar;22(1):26-30
Authors: Walker M, Kim LJ, Levitt MR, Ghodke B
Abstract
The technique of balloon-assisted tracking (BAT) has been demonstrated in transradial cardio-angiographic procedures. Using three commonly encountered clinical scenarios, we outline the technical details of BAT for managing peripheral and cerebral interventions with challenging vascular access. We describe methods used to overcome vasospasm, stenosis and vascular shelves during interventions for acute ischemic stroke, but these issues are not unique to neuroendovascular cases and the techniques can be applied across all endovascular interventions. We present three acute stroke interventions where anatomic challenges were overcome with the use of endovascular BAT. This article describes a novel application for BAT techniques in endovascular interventions to assist with access in peripheral, cervical and intracranial vessels. These methods can also be used to improve access during diagnostic cerebral angiography. BAT is a useful adjunct when navigating catheters through vasospasm, tortuous anatomy, vascular step-offs or intraluminal plaques.
PMID: 32596141 [PubMed]
The feasibility and safety of early ileostomy reversal: a systematic review and meta-analysis.
ANZ J Surg. 2020 Jun 28;:
Authors: Ng ZQ, Levitt M, Platell C
Abstract
BACKGROUND: Recent evidence supports the safety of early reversal of a temporary stoma, within 14 days of construction. The aim of this systematic review and meta-analysis was to evaluate the post-operative morbidity and overall feasibility of early stoma reversal.
METHODS: Medline and Cochrane databases were searched for studies up to June 2019 that investigated the outcomes of early stoma reversal (EC, defined as closure ≤14 days from the index operation) versus late stoma reversal (LC, ≥8 weeks from the index operation). Meta-analysis was performed on the respective rates of post-operative morbidity, anastomotic leak, wound infection, bleeding, sepsis, small bowel obstruction and ileus.
RESULTS: Nine studies were included (667 patients analysed). Meta-analysis showed no significant difference in the post-operative morbidity rate, anastomotic leak rate, rates of small bowel obstruction, bleeding and ileus between EC and LC. However, the wound infection rate was significantly higher after EC than LC; relative difference 0.10 (95% confidence interval 0.00-0.19, P = 0.047). The stoma-related complication rate was significantly higher after LC than EC; relative difference -0.28 (95% confidence interval -0.45 to -0.11, P = 0.001).
CONCLUSION: The concept of early stoma reversal is appealing, and this meta-analysis confirms the safety of early stoma closure with an associated reduction in stoma-related complications despite higher wound infection rates. However, the results need to be interpreted with caution due to the heterogeneity of the studies included, especially in respect of the definition of complications that were used. Further well-designed prospective studies are required prior to confident adoption of early stoma closure into clinical practice.
PMID: 32597018 [PubMed - as supplied by publisher]
The Future of Skull Base Surgery: A View Through Tinted Glasses.
World Neurosurg. 2020 10;142:29-42
Authors: Sekhar LN, Juric-Sekhar G, Qazi Z, Patel A, McGrath LB, Pridgeon J, Kalavakonda N, Hannaford B
Abstract
In the present report, we have broadly outlined the potential advances in the field of skull base surgery, which might occur within the next 20 years based on the many areas of current research in biology and technology. Many of these advances will also be broadly applicable to other areas of neurosurgery. We have grounded our predictions for future developments in an exploration of what patients and surgeons most desire as outcomes for care. We next examined the recent developments in the field and outlined several promising areas of future improvement in skull base surgery, per se, as well as identifying the new hospital support systems needed to accommodate these changes. These include, but are not limited to, advances in imaging, Raman spectroscopy and microscopy, 3-dimensional printing and rapid prototyping, master-slave and semiautonomous robots, artificial intelligence applications in all areas of medicine, telemedicine, and green technologies in hospitals. In addition, we have reviewed the therapeutic approaches using nanotechnology, genetic engineering, antitumor antibodies, and stem cell technologies to repair damage caused by traumatic injuries, tumors, and iatrogenic injuries to the brain and cranial nerves. Additionally, we have discussed the training requirements for future skull base surgeons and stressed the need for adaptability and change. However, the essential requirements for skull base surgeons will remain unchanged, including knowledge, attention to detail, technical skill, innovation, judgment, and compassion. We believe that active involvement in these rapidly evolving technologies will enable us to shape some of the future of our discipline to address the needs of both patients and our profession.
PMID: 32599213 [PubMed - indexed for MEDLINE]
Age-of-onset information helps identify 76 genetic variants associated with allergic disease.
PLoS Genet. 2020 06;16(6):e1008725
Authors: Ferreira MAR, Vonk JM, Baurecht H, Marenholz I, Tian C, Hoffman JD, Helmer Q, Tillander A, Ullemar V, Lu Y, Grosche S, Rüschendorf F, Granell R, Brumpton BM, Fritsche LG, Bhatta L, Gabrielsen ME, Nielsen JB, Zhou W, Hveem K, Langhammer A, Holmen OL, Løset M, Abecasis GR, Willer CJ, Emami NC, Cavazos TB, Witte JS, Szwajda A, 23andMe Research Team, collaborators of the SHARE study, Hinds DA, Hübner N, Weidinger S, Magnusson PK, Jorgenson E, Karlsson R, Paternoster L, Boomsma DI, Almqvist C, Lee YA, Koppelman GH
Abstract
Risk factors that contribute to inter-individual differences in the age-of-onset of allergic diseases are poorly understood. The aim of this study was to identify genetic risk variants associated with the age at which symptoms of allergic disease first develop, considering information from asthma, hay fever and eczema. Self-reported age-of-onset information was available for 117,130 genotyped individuals of European ancestry from the UK Biobank study. For each individual, we identified the earliest age at which asthma, hay fever and/or eczema was first diagnosed and performed a genome-wide association study (GWAS) of this combined age-of-onset phenotype. We identified 50 variants with a significant independent association (P<3x10-8) with age-of-onset. Forty-five variants had comparable effects on the onset of the three individual diseases and 38 were also associated with allergic disease case-control status in an independent study (n = 222,484). We observed a strong negative genetic correlation between age-of-onset and case-control status of allergic disease (rg = -0.63, P = 4.5x10-61), indicating that cases with early disease onset have a greater burden of allergy risk alleles than those with late disease onset. Subsequently, a multivariate GWAS of age-of-onset and case-control status identified a further 26 associations that were missed by the univariate analyses of age-of-onset or case-control status only. Collectively, of the 76 variants identified, 18 represent novel associations for allergic disease. We identified 81 likely target genes of the 76 associated variants based on information from expression quantitative trait loci (eQTL) and non-synonymous variants, of which we highlight ADAM15, FOSL2, TRIM8, BMPR2, CD200R1, PRKCQ, NOD2, SMAD4, ABCA7 and UBE2L3. Our results support the notion that early and late onset allergic disease have partly distinct genetic architectures, potentially explaining known differences in pathophysiology between individuals.
PMID: 32603359 [PubMed - indexed for MEDLINE]
A Phase 2 Study of Allogeneic GM-CSF Transfected Pancreatic Tumor Vaccine (GVAX) with Ipilimumab as Maintenance Treatment for Metastatic Pancreatic Cancer.
Clin Cancer Res. 2020 Jun 26;:
Authors: Wu AA, Bever KM, Ho WJ, Fertig EJ, Niu N, Zheng L, Parkinson RM, Durham JN, Onners BL, Ferguson A, Wilt C, Ko AH, Wang-Gillam A, Laheru DA, Anders RA, Thompson ED, Sugar EA, Jaffee EM, Le DT
Abstract
PURPOSE: This phase 2 study tested granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells (GVAX) and ipilimumab in metastatic pancreatic ductal adenocarcinoma (PDA) in the maintenance setting.
METHODS: Patients with PDA who were treated with front-line chemotherapy consisting of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) in the metastatic setting and had ongoing response or stable disease after 8-12 doses were eligible. Patients were randomized 1:1 to treatment with GVAX and ipilimumab given every 3 weeks for 4 doses then every 8 weeks (Arm A) or to FOLFIRINOX continuation (Arm B). The primary objective was to compare overall survival (OS) between the two arms.
RESULTS: Eighty-two patients were included in the final analysis (Arm A: 40; Arm B: 42). The study was stopped for futility after interim analysis. Median overall survival (OS) was 9.38 months (95% CI: 5.0, 12.2) for Arm A and 14.7 months (95% CI: 11.6, 20.0) for Arm B (HR 1.75, p=0.019). Using immune related-response criteria, 2 partial responses (5.7%) were observed in Arm A and 4 (13.8%) in Arm B. GVAX + ipilimumab promoted T cell differentiation into effector memory phenotypes both in the periphery and in the tumor microenvironment and increased M1 macrophages in the tumor.
CONCLUSIONS: GVAX and ipilimumab maintenance therapy did not improve OS over continuation of chemotherapy and resulted in a numerically inferior survival in metastatic PDA. However, clinical responses and biological effects on immune cells were observed. Further study of novel combinations in the maintenance treatment of metastatic PDA is feasible.
PMID: 32591464 [PubMed - as supplied by publisher]
Mathematical modeling of PDGF-driven glioma reveals the dynamics of immune cells infiltrating into tumors.
Neoplasia. 2020 Jun 22;22(9):323-332
Authors: Niu B, Zeng X, Phan TA, Szulzewsky F, Holte S, Holland EC, Tian JP
Abstract
BACKGROUND: Tumor-infiltrated immune cells compose a significant component of many cancers. They have been observed to have contradictory impacts on tumors. Although the primary reasons for these observations remain elusive, it is important to understand how immune cells infiltrating into tumors is regulated. Recently our group conducted a series of experimental studies, which showed that muIDH1 gliomas have a significant global reduction of immune cells and suggested that the longer survival time of mice with CIMP gliomas may be due to the IDH mutation and its effect on reducing of the tumor-infiltrated immune cells. However, to comprehend how IDH1 mutants regulate infiltration of immune cells into gliomas and how they affect the aggressiveness of gliomas, it is necessary to integrate our experimental data into a dynamical system to acquire a much deeper understanding of subtle regulation of immune cell infiltration.
METHODS: The method is integration of mathematical modeling and experiments. According to mass conservation laws and assumption that immune cells migrate into the tumor site along a chemotactic gradient field, a mathematical model is formulated. Parameters are estimated from our experiments. Numerical methods are developed to solve the problem. Numerical predictions are compared with experimental results.
RESULTS: Our analysis shows that the net rate of increase of immune cells infiltrated into the tumor is approximately proportional to the 4/5 power of the chemoattractant production rate, and it is an increasing function of time while the percentage of immune cells infiltrated into the tumor is a decreasing function of time. Our model predicts that wtIDH1 mice will survive longer if the immune cells are blocked by reducing chemotactic coefficient. For more aggressive gliomas, our model shows that there is little difference in their survivals between wtIDH1 and muIDH1 tumors, and the percentage of immune cells infiltrated into the tumor is much lower. These predictions are verified by our experimental results. In addition, wtIDH1 and muIDH1 can be quantitatively distinguished by their chemoattractant production rates, and the chemotactic coefficient determines possibilities of immune cells migration along chemoattractant gradient fields.
CONCLUSIONS: The chemoattractant gradient field produced by tumor cells may facilitate immune cells migration to the tumor cite. The chemoattractant production rate may be utilized to classify wtIDH1 and muIDH1 tumors. The dynamics of immune cells infiltrating into tumors is largely determined by tumor cell chemoattractant production rate and chemotactic coefficient.
PMID: 32585427 [PubMed - as supplied by publisher]
Insights on cross-species transmission of SARS-CoV-2 from structural modeling.
bioRxiv. 2020 Jun 05;:
Authors: Rodrigues JP, Barrera-Vilarmau S, Teixeira JM, Seckel E, Kastritis P, Levitt M
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 6 million people in more than 180 countries worldwide. Like other coronaviruses, SARS-CoV-2 is thought to have been transmitted to humans from wild animals. Given the scale and widespread geographical distribution of the current pandemic, the question emerges whether human-to-animal transmission is possible and if so, which animal species are most at risk. Here, we investigated the structural properties of several ACE2 orthologs bound to the SARS-CoV-2 spike protein. We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important considerations when designing these computational studies and analyzing their results.
PMID: 32577636 [PubMed]
Anti-NMDAR-Positive Small-Cell Lung Cancer Paraneoplastic Limbic Encephalitis: A Case Report and Literature Review.
Case Rep Neurol Med. 2020;2020:5269352
Authors: Sohal R, Adams SH, Phogat V, Harish A, Lopez CYD, Williams MPA, Khurana KK, Abuzuaiter B, Jagroop N, Narapureddy B
Abstract
Introduction: Paraneoplastic limbic encephalitis (PLE) is a rare disease that presents as rapid onset dementia characterized by short-term memory loss (STM), anxiety, and behavioral changes. Anti-NMDAR antibodies are unfrequently reported in PLE associated with small-cell lung cancer (SCLC). Given that PLE can precede the diagnosis of cancer, it is very important that once infectious, metabolic, nutritional, or structural disorders associated with short-term memory loss are ruled out that vigorous effort must be made to rule out underlying malignancy.
Case: We report a rare case of PLE as the presenting symptom of SCLC. A 72-year-old male with history of COPD was brought to the ED by his wife after he was found to have short-term memory loss, including forgetfulness of his wedding anniversary the day before, and anxiety. Neurological exam showed impaired short-term recall on MOCA. CT head showed no evidence of infarct. Lumbar puncture was performed which showed lymphocytic pleocytosis, a nonspecific inflammatory change. CSF panel was negative for HSV, Neisseria, Hemophilus, E. coli, and HIV. Initial EEG was unremarkable, though a repeat EEG showed mild slowing of the posterior dominant rhythm consistent with mild encephalopathy. MRI showed equivocal increased FLAIR on T2-weighted images in the bilateral temporal lobes, left greater than right. CTA thorax showed bulky mediastinal and right hilar LAD. FNA of the R4 lymph node revealed SCLC. The NM bone scan showed no osteoblastic lesions. While the serum autoantibody panel was positive for anti-NMDAR, the CSF autoantibody panel returned entirely negative. Chemotherapy with etoposide and cisplatin was started on Day 4 of admission. The patient's neurological symptoms showed improvement following chemotherapy.
Conclusion: This case highlights the importance of recognizing short-term memory loss as a feature of PLE.
PMID: 32566334 [PubMed]
Commentary: Stereotactic Radiosurgery for Intracranial Noncavernous Sinus Benign Meningioma: International Stereotactic Radiosurgery Society Systematic Review, Meta-Analysis and Practice Guideline.
Neurosurgery. 2020 10 15;87(5):E537-E538
Authors: Song AJ, Shi W, Ellenbogen RG, Venur VA, Lo SS
PMID: 32570276 [PubMed - indexed for MEDLINE]
Moyamoya disease and moyamoya syndrome in Ireland: patient demographics, mode of presentation and outcomes of EC-IC bypass surgery.
Ir J Med Sci. 2020 Jun 19;:
Authors: Doherty RJ, Caird J, Crimmins D, Kelly P, Murphy S, McGuigan C, Tubridy N, King MD, Lynch B, Webb D, O'Neill D, McCabe DJH, Boers P, O'Regan M, Moroney J, Williams DJ, Cronin S, Javadpour M
Abstract
BACKGROUND: There are no previously published reports regarding the epidemiology and characteristics of moyamoya disease or syndrome in Ireland.
AIMS: To examine patient demographics, mode of presentation and the outcomes of extracranial-intracranial bypass surgery in the treatment of moyamoya disease and syndrome in Ireland.
METHODS: All patients with moyamoya disease and syndrome referred to the National Neurosurgical Centre during January 2012-January 2019 were identified through a prospective database. Demographics, clinical presentation, radiological findings, surgical procedures, postoperative complications and any strokes during follow-up were recorded.
RESULTS: Twenty-one patients were identified. Sixteen underwent surgery. Median age at diagnosis was 19 years. Fifteen were female. Mode of presentation was ischaemic stroke in nine, haemodynamic TIAs in eight, haemorrhage in three and incidental in one. Sixteen patients had Moyamoya disease, whereas five patients had moyamoya syndrome. Surgery was performed on 19 hemispheres in 16 patients. The surgical procedures consisted of ten direct (STA-MCA) bypasses, five indirect bypasses and four multiple burr holes. Postoperative complications included ischaemic stroke in one patient and subdural haematoma in one patient. The median follow-up period in the surgical group was 52 months; there was one new stroke during this period. Two patients required further revascularisation following recurrent TIAs. One patient died during follow-up secondary to tumour progression associated with neurofibromatosis type 1.
CONCLUSIONS: Moyamoya is rare but occurs in Caucasians in Ireland. It most commonly presents with ischaemic symptoms. Surgical intervention in the form of direct and indirect bypass is an effective treatment in the majority of cases.
PMID: 32562218 [PubMed - as supplied by publisher]
Impact of Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features on Revised Bethesda System Malignancy Rates at a Single Institution.
J Surg Res. 2020 11;255:152-157
Authors: Linhares SM, Whitfield BW, Lee AF, Gordillo D, Picado O, Jeraq M, Farrá JC, Lew JI
Abstract
BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) standardizes thyroid cytopathology reporting in six tier diagnostic categories. In recent years, noninvasive encapsulated follicular variant of papillary thyroid carcinoma was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This study examines the impact of NIFTP on the BSRTC risk of malignancy (ROM).
METHODS: This was a retrospective review of prospectively collected data from 565 patients who underwent fine needle aspiration and thyroidectomy at a single institution. ROM for each Bethesda category was analyzed and calculated with NIFTP classified as a malignant and nonmalignant lesion. Absolute and relative differences between ROM were compared.
RESULTS: Of 565 patients, 19 were Bethesda I, 159 were Bethesda II, 178 were Bethesda III, 46 were Bethesda IV, 42 were Bethesda V, and 121 were Bethesda VI. ROM differences with NIFTP classified as malignant versus nonmalignant for each class were as follows: Bethesda I, no change; Bethesda II, 18%-14%; Bethesda III, 55%-48%; Bethesda IV, 50%-35%; Bethesda V, 93%-91%; and Bethesda VI, 99%-98%. Absolute ROM differences for each category were as follows: Bethesda I, 0%; Bethesda II, 4%; Bethesda III, 7%; Bethesda IV, 15%; Bethesda V, 2%; and Bethesda VI, 1%.
CONCLUSIONS: A decreasing trend in absolute and relative ROM was seen in Bethesda II, III, and IV categories; however, exclusion of NIFTP as a malignant lesion did not significantly alter the ROM of BSRTC categories. Surgeons should assess their respective institution's experiences with NIFTP and the BSRTC.
PMID: 32563006 [PubMed - indexed for MEDLINE]
Multicellular 3D Neurovascular Unit Model for Assessing Hypoxia and Neuroinflammation Induced Blood-Brain Barrier Dysfunction.
Sci Rep. 2020 06 17;10(1):9766
Authors: Nzou G, Wicks RT, VanOstrand NR, Mekky GA, Seale SA, El-Taibany A, Wicks EE, Nechtman CM, Marrotte EJ, Makani VS, Murphy SV, Seeds MC, Jackson JD, Atala AJ
Abstract
The blood-brain barrier (BBB) is a dynamic component of the brain-vascular interface that maintains brain homeostasis and regulates solute permeability into brain tissue. The expression of tight junction proteins between adjacent endothelial cells and the presence of efflux proteins prevents entry of foreign substances into the brain parenchyma. BBB dysfunction, however, is evident in many neurological disorders including ischemic stroke, trauma, and chronic neurodegenerative diseases. Currently, major contributors to BBB dysfunction are not well understood. Here, we employed a multicellular 3D neurovascular unit organoid containing human brain microvascular endothelial cells, pericytes, astrocytes, microglia, oligodendrocytes and neurons to model the effects of hypoxia and neuroinflammation on BBB function. Organoids were cultured in hypoxic chamber with 0.1% O2 for 24 hours. Organoids cultured under this hypoxic condition showed increased permeability, pro-inflammatory cytokine production, and increased oxidative stress. The anti-inflammatory agents, secoisolariciresinol diglucoside and 2-arachidonoyl glycerol, demonstrated protection by reducing inflammatory cytokine levels in the organoids under hypoxic conditions. Through the assessment of a free radical scavenger and an anti-inflammatory endocannabinoid, we hereby report the utility of the model in drug development for drug candidates that may reduce the effects of ROS and inflammation under disease conditions. This 3D organoid model recapitulates characteristics of BBB dysfunction under hypoxic physiological conditions and when exposed to exogenous neuroinflammatory mediators and hence may have potential in disease modeling and therapeutic development.
PMID: 32555384 [PubMed - indexed for MEDLINE]
