tbuckley/cabot-search huggingface dataset:
OS06.5A Fluorescence image-guided resection of intracranial meningioma: an experimental in vivo study on nude mice
Authors: S Linsler, S Senger, S Müller, A Müller, J Oertel
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The use of photodynamic agents in malignant cranial tumor surgery is quite common. For example five-aminolevulinic acid (5-ALA)-induced porphyrins in malignant gliomas are potent photosensitizers. Until today there is no comparable selective fluorescent substance available for meningiomas. Nevertheless, there is a demand for intraoperative fluorescent identification of e.g. invasive skull base meningiomas to increase radicality. This study was established to investigate fluorescent image-guided resection with somatostatin receptor labelled fluorescence dye for intracranial meningioma in the nude mice. MATERIAL AND METHODS Primary meningioma cell culture samples were stereotactically implanted subdural into 20 nude mice. 90 days after inoculation of the cells, a cranial MRI with contrast agent revealed tumor growth. After detection of tumor mass in MRI, FAM-TOC5,6-Carboxyfluoresceine-Tyr3-Octreotide was injected intravenously and tumor mass was hereafter resected under visualization via fluorescence microscope and endoscope. After attempted total resection, animal were sacrificed brain slices were obtained and histologically analysed to verify the resection extent. RESULTS In 18 mice tumor growth was detected in MRI after 90 days of inoculation. The tumor mass could be clearly identified with fluorescence microscope and endoscope after injecting FAM-TOC5,6-Carboxyfluoresceine-Tyr3-Octreotide. The tumor margins could be better visualized. After fluorescence-guided resection no remaining tumor could be identified in histological analysis. CONCLUSION This study describes for the first time the use of FAM-TOC5,6-Carboxyfluoresceine-Tyr3-Octreotide and demonstrates its value of fluorescent identification of meningioma cells in vivo. Furthermore, the authors established a new experimental animal model for fluorescence meningioma surgery.
P14.88 Management of primary CNS lymphomas. Experience of 32 cases
Authors: A S Simonyan, L T Lepsveridze, Z K Simavonyan, A A Davtyan, A D Mikhaylova, V M Tyurnikov, A O Gushcha
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Lymphomas (primary and secondary) are rare tumors of the central nervous system. They can involve both the supratentorial areas and the posterior cranial fossa. Modern management of patients with suspected CNS lymphoma should include a stereotactic or navigation-guided biopsy and subsequently carrying out chemotherapy and, in rare cases, radiosurgery. MATERIAL AND METHODS We analyzed our experience of the diagnosis and treatment of PCNSL. Our work included 32 patients with PCNSL. The study did not include patients with suspected CNS lymphoma, according to MRI data, in whom the diagnosis was not confirmed after biopsy. RESULTS Thirty patients underwent biopsy (20 - navigation guided, 1 - open, 9 - “burr hole”) with preliminary intraoperative histological verification. Gross total resection was performed in 2 cases since, according to preoperative MRI data, it was assumed that the patient had glial tumors. Postoperative histological examination confirmed the diagnosis of CNS lymphoma in all cases. Subsequently, after detailed histological and immunohistochemical studies, 30 patients underwent intra-arterial chemotherapy or high-dose chemotherapy according to NCCN protocols. Palliative treatment was recommended in 2 cases due to acute deterioration of patients. In our work, we would like to present a diagnostic algorithm and treatment regimens used in the management of our patients. CONCLUSION In the treatment of CNS lymphomas, careful histological verification is required, which is possible if several key points are performed - discontinuation of dexamethasone at least 24 hours before the biopsy, MRI for intraoperative neuronavigation after discontinuation of dexamethasone, intraoperative preliminary histological verification. In our opinion, complete removal of the tumor is possible if there are no risks of developing a persistent neurological deficit. Various methods of opening the blood-brain barrier are currently used, which can significantly reduce the effective dosage of drugs and, accordingly, the side effects. Further research is needed to determine the dependence of the prognosis of the disease on the type of surgery (biopsy or resection).
KS02.4.A Olaparib in Recurrent IDH-mutant High-Grade Glioma (OLAGLI)
Authors: F Ducray, M Sanson, O Chinot, M Fontanilles, R Rivoirard, L Thomas-Maisonneuve, S Cartalat, E Tabouret, A Bonneville-Levard, A Darlix, R Ameli, D Meyronet, F Gueyffier, L Remontet, D Maucort-Boulch, C Dehais, J Honnorat
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND There is a need to develop new treatments in IDH-mutant high-grade gliomas recurring after radiotherapy and chemotherapy. Based on preclinical studies showing that IDH-mutant tumors could be vulnerable to PARP inhibition we launched a phase II study to test the efficacy of olaparib (Lynparza) monotherapy in this population. METHODS Adults with recurrent high-grade IDH-mutant gliomas after radiotherapy and at least one line of alkylating chemotherapy (PCV or TMZ), KPS &amp;gt; 60, normal organ function were enrolled. The primary endpoint was 6 months PFS according to RANO criteria. Patients were treated with olaparib 300 mg twice daily. We used a single-stage Fleming design with p0 = 30%, p1 = 50%, a type I unilateral error rate of 5% and a power of 80%. RESULTS 35 patients with recurrent IDH-mutant gliomas (IDH1R132H-mutant n = 32, other IDH mutation n = 3, 1p/19 codeleted n = 16, 1p/19q non-codeleted n = 14) were enrolled (malignantly transformed low-grade gliomas n = 21, anaplastic gliomas n = 8, glioblastomas n = 6). Median time since diagnosis was 7.4 years (1–22 years), median time since radiotherapy was 2.8 years (0.6–18 years), median number of previous chemotherapy lines was 2 (1–5). With a median follow-up of 11 months, 30 patients had stopped treatment due to tumor progression and 2 patients were still on treatment 16 to 18 months after treatment start. At 6 months, 11/35 patients were progression-free (31 %). According to RANO criteria, based on local investigator analysis, 2 patients (5%) had a partial response and 14 patients a stable disease (37%) with a median duration of response of 9 months (4–18+). Median PFS and OS were 2.3 and 15.9 months and were similar in 1p/19q codeleted and non-codeleted patients. A grade 3 olaparib-related adverse event was observed in 5 patients (14%, lymphopenia n = 3, fatigue n = 2, diarrhea n = 1) and a grade 2 in 15 patients (43%), most frequently consisting in fatigue (23%), gastrointestinal disorders (20%) and lymphopenia (20%). No patient definitively stopped olaparib due to side effects. CONCLUSIONS In this heavily pre-treated population of recurrent IDH-mutant gliomas, olaparib monotherapy was well tolerated and resulted in some activity supporting its evaluation in association with alkylating chemotherapy in recurrent IDH-mutant gliomas in future studies.
Autophagy in Alzheimer’s disease pathogenesis: Therapeutic potential and future perspectives
Authors: Zhigang Zhang, Xifei Yang, You-Qiang Song, Jie Tu
Journal: Ageing Research Reviews (2021)

Alzheimer's disease (AD) is a complex neurodegenerative disease in the elderly and the most common cause of human dementia. AD is characterized by accumulation of abnormal protein aggregates including amyloid plaques (composed of beta-amyloid (Aβ) peptides) and neurofibrillary tangles (formed by hyper-phosphorylated tau protein). Synaptic plasticity, neuroinflammation, calcium signaling etc. also show dysfunction in AD patients. Autophagy is an evolutionarily conserved lysosome-dependent cellular event in eukaryotes. It is closely linked to modulation of protein metabolism, through which damaged organelles and mis-folded proteins are degraded and then recycled to maintain protein homeostasis. Accumulating evidence has shown that impaired autophagy also contributes to AD pathogenesis. In the present review, we highlight the role of autophagy, including bulk and selective autophagy, in regulating metabolic circuits in AD pathogenesis. We also discuss the potential and future perspectives of autophagy-inducing strategies in AD therapeutics.
Rituximab versus Tocilizumab in anti-TNF inadequate responder patients with Rheumatoid Arthritis (R4RA): a stratified, biopsy-driven, multi-centre, randomised, open label, controlled clinical trial – 16 week outcomes
Authors: Frances Humby, Patrick Durez, Maya Buch, Myles J Lewis, Hasan Rizvi, Felice Rivellese, Alessandra Nerviani, Giovanni Giorli, Arti Mahto, Carlomaurizio Montecucco, Bernard R Lauwerys, Nora Ng, Pauline Ho, Michele Bombardieri, Vasco C Romão, P Verschueren, Stephen Kelly, Pier Paolo Sainaghi, Nagui Gendi, Bhaskar Dasgupta, Alberto Cauli, Piero Reynolds, Juan D Cañete, R Moots, Taylor Peter, Christopher J Edwards, John Isaacs, Peter Sasieni, Ernest Choy, Costantino Pitzalis
Journal: The Lancet (2020)
Cardiac autonomic function and sleep patterns after training sessions and matches in female soccer players
Authors: Júlio Alejandro Henriques Costa
Journal: British Journal of Sports Medicine (2021)

I investigated the impact of training sessions and official matches performed at different locations, times of the day and phases of the season (in-season and international tournaments) on nocturnal cardiac autonomic activity and sleep patterns in female soccer players using non-invasive and time-efficient equipment.

In some countries, most of the young adult female players usually start training sessions at very late hours, close to bedtime sleep, due to their daily life commitments. In this scenario, during my Ph.D., I published four observational studies on sleep and nocturnal heart rate variability (HRV) of elite and semiprofessional female soccer players aiming to better assist coaches and clinical experts to identify sleep and HRV disturbances.

First, I investigated the sensitivity of nocturnal HRV to evaluate the effects of late-night soccer training sessions on nocturnal cardiac autonomic activity of semiprofessional female players (n=11) throughout a 1-week competitive in-season microcycle.1

I then conducted two additional longitudinal studies.2 3 The main purpose of study 2 was to analyse for three consecutive weeks whether exercise training conducted at night disturbs sleep and affects nocturnal cardiac autonomic activity in female soccer players (n=18).2 Study 3 aimed …
Improving oral oncolytic education in a safety-net outpatient hematology-oncology practice.
Authors: Ana I. Velazquez Manana, Piera Wong, Katherine Pang, Pelin Cinar, Niharika Dixit
Journal: Journal of Clinical Oncology (2021)

266 Background: Oral oncolytics (OO) offer convenient administration and reduce the burden of cancer treatment, while creating particular challenges regarding safety monitoring and adherence. A baseline review of oral oncolytic education (OOE) at our safety-net institution identified that none of the patients who started OO therapy from September to December 2019 had complete documentation of OOE and a care plan. This results in potential increased risk of toxicity, non-adherence to therapy, and poor adherence to follow-up schedule for lab monitoring, dose adjustment, and toxicity assessment. Therefore, we sought to increase the percentage of completed components of an OOE and care plan that are documented in the EHR prior to new oral oncolytic initiation to 60% over a 6-month period. Methods: A multidisciplinary Quality Training Program team consisting of 2 physicians, an oncology pharmacist, and an oncology RN specialist was created. With stakeholder engagement, we identified barriers to quality OOE and documentation, including: unfamiliarity of staff with ASCO-ONS standards, adoption of a new EMR, lack of standardized structure and documentation for OOE, and limited number of staff. PDSA cycle 1 defined RN role as staff in charge of oral oncolytic prior-auth, coordination, and education process, reinforced communication of providers with RNs, and defined the components of oral oncolytic education and care plan that meets QOPI &amp; ASCO-ONS standards. PDSA cycle 2 implemented a new simplified workflow which included (1) EHR worksheet to document oral oncolytic education, (2) in-person RN teaching, (3) printed education materials, pill box, and thermometer, and (4) 1-week follow up calls. Results: Our baseline data revealed that only 55% of patients had any documentation of OOE. Content of documented OOE varied significantly with only a mean of 37% ASCO-ONS safety standards being documented. During PDSA cycle 1 documentation improved to a mean 54% standards, and with PDSA cycle 2 82% standards of an OOE documented. Overall documentation of OOE, increased to 83% by PDSA cycle 2. Symptom check 1-week follow-up calls increased from 22% at baseline to 78% after PDSA cycle 2. Conclusions: Over a 6-month period, we improved OOE and documentation by meeting our goal of increasing the number of documented components from 40% to 82%. Review of processes with stakeholders is imperative to practice improvement. Implementation of an EHR tool is an easy way to improve quality standardized OOE and has the potential to increase OO adherence and decrease toxicity.
Delayed circadian rhythms and substance abuse: dopamine transmission’s time has come
Authors: Brant P. Hasler, Colleen A. McClung
Journal: Journal of Clinical Investigation (2021)

Disrupted sleep and circadian rhythms are linked with substance abuse risk. Human studies that investigate relationships between sleep, circadian rhythm, and substance use reward generally rely on indirect means to infer dopaminergic function, such as functional magnetic resonance imaging. In this issue of the JCI, Zhang and colleagues used positron emission tomography (PET) to image striatal dopamine D1 (D1R) and D2/3 receptor (D/3R) availability in healthy adults. The authors assessed rest-activity rhythms, then conducted PET scans using radioligand antagonists selective for D1 receptors or D2/D3 receptors to measure D1R and D2/3R availability. They also measured the subjective drug effects of oral methylphenidate. Higher D1R availability in caudate and a greater methylphenidate reward sensitivity were associated with delayed rest-activity rhythms. Unexpectedly, lower overall activity was associated with higher D2/3R availability in the nucleus accumbens, which coincided with greater methylphenidate reward score. These findings may inform personalized prevention and/or treatment interventions.
Navigating the Complex Ecosystem of Race, Ethnicity, Structural Racism, Socioeconomic Factors, Medical Care Delivery, and End-of-Life Care—Casting Away the Compass to Make a Map
Authors: Adjoa Boateng, Rebecca A. Aslakson
Journal: JAMA Network Open (2021)

Stephanie Deeb, BS; Fumiko L. Chino, MD; Lisa C. Diamond, MD, MPH; Anna Tao, BS; Abraham Aragones, MD; Armin Shahrokni, MD; Divya Yerramilli, MD, MBE; Erin F. Gillespie, MD; C. Jillian Tsai, MD, PhD
Gender-based differences in community-wide screening for pulmonary tuberculosis in Karachi, Pakistan: an observational study of 311 732 individuals undergoing screening
Authors: Shifa Salman Habib, Syed Mohammad Asad Zaidi, Wafa Zehra Jamal, Kiran Sohail Azeemi, Salman Khan, Saira Khowaja, Abdul Khalique Domki, Aamir Khan, Faiz Ahmad Khan
Journal: Thorax (2021)

We describe gender-based differences in a community-wide TB screening programme in Karachi, Pakistan, in which 311 732 individuals were screened in mobile camps using symptom questionnaires and van-mounted digital chest X-ray, between 1 January 2018 and 31 December 2019. Only 22.4% (69 869) of camp attendees were women. Female attendees were less likely to have sputum collected and tested (31.5% (95% CI 30.4% to 32.7%) vs 38.5% (95% CI 37.6% to 39.1%)) or to initiate TB treatment (75.9% (95% CI 68.1% to 82.6%) vs 82.8% (95% CI 78.9% to 86.2%)), when indicated. Among the participants, the age-standardised prevalence of active TB was higher among women (prevalence ratio 1.4, 95% CI 1.1 to 1.7). These findings underscore the importance of integrating gender into the design and monitoring of TB screening programmes to ensure that women and men benefit equally from this important intervention.
Machine Learning-Derived Echocardiographic Phenotypes Predict Heart Failure Incidence in Asymptomatic Individuals
Authors: Masatake Kobayashi, Olivier Huttin, Martin Magnusson, João Pedro Ferreira, Erwan Bozec, Anne-Cecile Huby, Gregoire Preud’homme, Kevin Duarte, Zohra Lamiral, Kevin Dalleau, Emmanuel Bresso, Malika Smaïl-Tabbone, Marie-Dominique Devignes, Peter M. Nilsson, Margret Leosdottir, Jean-Marc Boivin, Faiez Zannad, Patrick Rossignol, Nicolas Girerd
Journal: JACC. Cardiovascular imaging (2021)

This study sought to identify homogenous echocardiographic phenotypes in community-based cohorts and assess their association with outcomes.Asymptomatic cardiac dysfunction leads to a high risk of long-term cardiovascular morbidity and mortality; however, better echocardiographic classification of asymptomatic individuals remains a challenge.Echocardiographic phenotypes were identified using K-means clustering in the first generation of the STANISLAS (Yearly non-invasive follow-up of Health status of Lorraine insured inhabitants) cohort (N = 827; mean age: 60 ± 5 years; men: 48%), and their associations with vascular function and circulating biomarkers were also assessed. These phenotypes were externally validated in the Malmö Preventive Project cohort (N = 1,394; mean age: 67 ± 6 years; men: 70%), and their associations with the composite of cardiovascular mortality (CVM) or heart failure hospitalization (HFH) were assessed as well.Three echocardiographic phenotypes were identified as "mostly normal (MN)" (n = 334), "diastolic changes (D)" (n = 323), and "diastolic changes with structural remodeling (D/S)" (n = 170). The D and D/S phenotypes had similar ages, body mass indices, cardiovascular risk factors, vascular impairments, and diastolic function changes. The D phenotype consisted mainly of women and featured increased levels of inflammatory biomarkers, whereas the D/S phenotype, consisted predominantly of men, displayed the highest values of left ventricular mass, volume, and remodeling biomarkers. The phenotypes were predicted based on a simple algorithm including e', left ventricular mass and volume (e'VM algorithm). In the Malmö cohort, subgroups derived from e'VM algorithm were significantly associated with a higher risk of CVM and HFH (adjusted HR in the D phenotype = 1.87; 95% CI: 1.04 to 3.37; adjusted HR in the D/S phenotype = 3.02; 95% CI: 1.71 to 5.34).Among asymptomatic, middle-aged individuals, echocardiographic data-driven classification based on the simple e'VM algorithm identified profiles with different long-term HF risk. (4th Visit at 17 Years of Cohort STANISLAS-Stanislas Ancillary Study ESCIF [STANISLASV4]; NCT01391442).
Impact of the covid-19 pandemic in the MR availability for iron overloaded patients
Authors: A. Meloni, L. Pistoia, R. Righi, M. Missere, S. Renne, A. Vallone, A. Riva, P. Fina, D. Maddaloni, A. Ermini, V. Spadola, A. Pepe
Journal: HemaSphere (2021)

Background: The T2∗ magnetic resonance imaging (MRI) technique for the noninvasive quantification of iron overload has significantly improved the survival of patients with hemoglobinopathies by tailoring the chelation therapy. In Italy, the E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) Network, a collaborative project among MRI and hematological centers, has assured high-quality quantification of iron in vital organs such as heart, liver, and pancreas. The COVID-19 pandemic has disrupted healthcare services around the world, also leading to postpone or delete deferable diagnostic evaluations. Aims: We evaluated the impact of the COVID-19 pandemic on MRI services for iron overload quantification in Italy. Methods: The activity of the MRI centers of the E-MIOT Network in the year 2020 was compared to the activity in the same months of 2019. A specific survey was filled out by the MRI operators to evaluate if the availability of MRI slots for patients with hemoglobinothies was reduced and the reasons. Results: In comparison with the year 2019, in 2020 there was a significant reduction in the number of T2∗ MRIs performed (350 vs 656;P<0.0001). The comparison month by month between the two years highlighted a marked decline (86.9%) in the four-month period March-June 2020, a reduction in the gap between the two years in the three-month period July-September, and a new decline (41.4%) in the three-month period October-December (Figure 1A). No patient with hemoglobinopathy could undergo an MRI scan during the Italian lockdown (9 March-10 May 2020). Figure 1B shows the percentage of decline (year 2020 vs 2019) in the number of T2∗MRI scans for each MRI center. If no decline or an increase were present, the vertical axis was set at 0. All centers experienced a significant drop in the number of the T2∗ MRIs in the fourmonth period March-June (from 75 to 100%). In the three-month period July-September only the centers of Pisa and Taranto dropped the number of T2∗ MRIs due to the rescheduling of the other MRI appointments deleted during the lockdown. In the three-month period October- December a reduction of the T2∗ MRI scans was experienced by all centers, except for Campobasso. In the centers of Ferrara and Lamezia Terme the reduction was the consequence of the general reduction in the number of the total MRIs scheduled per day for the sanitation procedures. In the other centers, the availability for T2∗ MRI scans was unchanged in comparison to 2019, but the patients refused the MRI follow up for fear of getting sick of COVID. Summary/Conclusion: The COVID-19 pandemic is having a strong negative impact on the quantification of iron overload by MRI, which may seriously worsen the prognosis of patients with hemoglobinopathies. Strategies to ensure proved lifesaving MRI exam and to reassure patients about the health safety of the hospitals are recommended.
OS10.3.A Predicting delirium after craniotomy in neuro-oncology
Authors: P R Kappen, H J Kappen, C Dirven, M Klimek, R Osse, A Vincent
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Post-operative delirium (POD) is a frequent and severe complication after neurosurgical operations. Good prediction of POD after craniotomy in neuro-oncologic patients is important to install prophylactic measures, increase recognition and apply early treatment. Hence, we compared logistic regression with machine learning to build an accurate predictive model in a large dataset. MATERIAL AND METHODS POD was defined in case of a Delirium Observation Scale (DOS) ≥ 3 or start of antipsychotic treatment for delirium within 10 days after surgery. Adult patients undergoing a craniotomy for a neuro-oncologic disease in the Erasmus Medical Centre in Rotterdam were retrospectively included. The cohort was split into a training (75%), after three-fold cross validation, and test set (25%). Logistic regression and Lasso Elastic-Net Regularized Generalized Linear Models (GLMNet) were trained based on 19 pre- and intra-operative features and risk factors were identified based on the superior model. RESULTS We included 1025 neuro-oncologic craniotomies between June 2017 and September 2020. Overall incidence of POD was 18.6% (95%CI 17.4–19.8). Compared to logistic regression, Lasso GLMNet performed superior (AUC 0.73 vs. 0.76) based on the optimal tuning parameters (α=1, λ=0.014). Several non-modifiable risk factors such as age (OR1.01), prior delirium (OR1.04), memory problems (OR1.12), surgery duration (OR1.01) and modifiable risk factors, such as low potassium (OR0.97) levels and opioid administration (OR1.03), were identified. CONCLUSION POD is a frequent complication after craniotomy in neuro-oncologic patients. Lasso GLMNet was useful in predicting POD in this cohort. Validation in a prospective cohort of this model should be applied to further evaluate its value in diminishing POD.