tbuckley/cabot-search huggingface dataset:
Eliminating Unnecessary Opioid Exposure After Common Children’s Surgeries
Authors: Calista M. Harbaugh, Gracia Vargas, Courtney Shepard Streur, G. Ying Li, Aaron L. Thatcher, Jennifer F. Waljee, Samir K. Gadepalli
Journal: JAMA Surgery (2019)

Eliminating Unnecessary Opioid Exposure After Common Children's SurgeriesFrom 1999 to 2016, opioid-related overdoses rose by 250% among children and adolescents. 1Acute pain after surgery or injury is the most frequent indication for pediatric opioid prescribing. 2However, prescribing is variable, and little is known regarding patient-reported opioid consumption and pain after pediatric operations to guide opioid prescribing. 3,4 Methods | As part of a multispecialty quality improvement project to reduce opioid prescribing, this study was deemed exempt by the University of Michigan institutional review board.Children younger than 18 years undergoing umbilical or epigastric herniorrhaphy; laparoscopic appendectomy; inguinal herniorrhaphy and/or hydrocelectomy; adenoidectomy; circumcision; percutaneous pinning for elbow fracture (supracondylar, epicondylar, or condylar); or scrotal-incision orchiopexy at a tertiary care facility were screened for eligibility (April 2018 to November 2018).Exclusion criteria were enrollment in another study, admission greater than 7 days, and any previous or concurrent operations during the study period.Caregivers received pain journals to record postoperative analgesic use.Caregivers were contacted at 7 to 21 days postoperatively by telephone, email, or follow-up appointment regarding pain control and analgesic use.Verbal consent was obtained prior to survey administration.Outpatient opioid prescriptions and emergency department (ED) visits within 30 days of discharge were collected from the electronic medical record.Number of doses was calculated as total quantity divided by minimum dose.
Anetoderma Associated With a Succinate Dehydrogenase Gene Mutation
Authors: Adam K. Brys, Larissa G. Rodriguez-Homs, Samantha Wennerberg, Russell P. Hall, Matilda W. Nicholas
Journal: JAMA Dermatology (2019)

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EMPD 中的 CYFRA 21‐1 和 CEA 联合分析
Authors: Y. Nakamura, K. Tanese, I. Hirai, M. Amagai, Y. Kawakami, T. Funakoshi
Journal: British Journal of Dermatology (2019)

乳房外 Paget 病 (EMPD) 是一种影响生殖器和腋窝部位的罕见皮肤病。EMPD 主要发生在大于 60 岁的高加索裔女性和亚洲男性,发生率不到 0.6 例/10 万人。基本治疗包括手术切除(去除),但是可在大约 10% 患者中见到转移(意味着肿瘤播散)。如果癌症播散,尽早发现和开始治疗的确很重要,因为此病到晚期可能难以治疗。生物标志物,或标志物,是一种存在于血液中的分子,生物标志物的不同水平会相应影响身体对于某种治疗的反应,或者疾病的进展过程。癌胚抗原 (CEA) 和细胞角蛋白 19 片段 21-1 (CYFRA 21-1)都是某些其他癌症的生物标志物,已经有人指出,它们还可能是监测 EMPD 中肿瘤进展的标志物;但是,尚未在 EMPD 患者中检测这些标志物的准确性或之间的相关性。这项来自日本的研究旨在明确不同疾病进展状态 EMPD 患血液中 CEA 和 CYFRA21-1 的水平的用途和关系。该研究共入选了 30 例 EMPD 病例。在所有早期患者中,CEA 和 CYFRA 都在正常水平内。在晚期患者中,分别有 79% 和 63% 患者的 CEA 和 CYFRA 水平升高。在 95% 的晚期患者中发现 CEA 或 CYFRA 增高,提示一定数量患者只有一种标志物的水平增高。此外,在所有患者中,这两种标志物都与治疗反应明显相关。这项研究显示,对 CEA 和 CYFRA 同时进行检查可能有助于发现晚期 EMPD 患者,它们对于监测治疗反应是有帮助的。
Precision detection of liver metastasis by collagen-targeted protein MRI contrast agent
Authors: Mani Salarian, Hua Yang, Ravi Chakra Turaga, Shanshan Tan, Jingjuan Qiao, Shenghui Xue, Zongxiang Gui, Guangda Peng, Hongwei Han, Pardeep Mittal, Hans E. Grossniklaus, Jenny J. Yang
Journal: Biomaterials (2019)
Correspondence on ‘Standardisation of myositis-specific antibodies: where are we today?’
Authors: Maria Infantino, Mariangela Manfredi, Nicola Bizzaro
Journal: Annals of the Rheumatic Diseases (2019)

We have read with great interest the recent article from Espinosa-Ortega et al 1 and the commenting letter by Mahler et al 2 on the reliability of line immunoassay (LIA) versus immunoprecipitation (IP) in the detection of myositis-specific autoantibodies (MSAs) for the diagnosis of idiopathic inflammatory myopathies (IIM). Even if the search for MSA by dot immunoassay (DIA) or LIA has been used for over a decade and represents a ‘non-criteria’ test to assist clinicians in IIM diagnosis, MSAs have been included in classification criteria only for a couple of years.3 However, initial studies on the clinical utility of the DIA/LIA methods in diagnosing IIM were conducted on a restricted panel of MSA and mainly on selected IIM patients.4 …
OS8.6 Sensitivity of human meningioma cells to the cyclin-dependent kinase inhibitor, TG02
Authors: E Le Rhun, C von Achenbach, F Sahm, S S Wang, M C Neidert, E Rushing, T Lawhon, H Schneider, A von Deimling, M Weller
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Standards of care for meningioma include surgical resection, which may be curative, and radiotherapy as required. Pharmacotherapy plays only a minor role in this disease; however, novel systemic approaches are urgently needed for patients who are no longer candidates for local therapy. MATERIAL AND METHODS We generated primary cultures from surgically removed meningiomas to explore the activity of a novel cyclin-dependent kinase inhibitor, TG02, in meningioma cell cultures. Tumor and cell cultures were characterized by mutation profiling and DNA methylation profiling. DNA methylation data were used to allot each sample to one out of six previously established meningioma methylation classes: benign (ben)-1, 2, 3, intermediate (int)-A, B, and malignant (mal). The activity of TG02 was assessed by standard cell culture assays. RESULTS Cell cultures were derived from nine meningiomas. Four tumors assigned to the methylation class ben-2 showed the same class in the cell culture whereas cell cultures from five non-ben-2 tumors showed a different class, a more malignant class in four of five patients. Cell cultures were uniformly sensitive to the growth inhibitory effects of TG02 in the nanomolar range. Assignment of the cell cultures to a more malignant methylation classifier appeared to be more closely associated with TG02 sensitivity than assignment to a higher WHO grade of the primary tumors. CONCLUSION Primary cell cultures from meningioma facilitate the investigation of the anti-meningioma activity of novel agents. TG02, an orally available cyclin-dependent kinase inhibitor, warrants further exploration in this disease.
Abstract P29: The Efficacy of Emergency Coronary Reperfusion Therapy for Comatose Survivors After Out-of-hospital Cardiac Arrest is Equivalent to Cardiogenic Shock Complicating ST-elevation Myocardial Infarction
Authors: Eizo Tachibana, Ken Nagao, Kimio Kikushima, Tadateru Takayama, Naoki Satoh, Kyoushi Yamada, Morimasa Takayama
Journal: Circulation (2009)

BACKGROUNDS: AHA guidelines for ST-elevation myocardial infarction (STEMI) have recommended early coronary revascularization for patients with cardiogenic shock complicating STEMI ( Circulation 2004 ; 110 : 586 – 636 ). ILCOR has suggested that STEMI patients with post-cardiac arrest should undergo emergency coronary angiography, with subsequent reperfusion therapy ( Circulation 2008 ; 118 : 2452 –2483 ). We investigated whether early coronary reperfusion therapy had survival benefits for STEMI patients with post-cardiac arrest. METHODS: We did a multicenter observation study of STEMI patients. Of those patients, comatose survivor or cardiogenic shock were enrolled in this study. The primary endpoint was survival to hospital discharge. RESULTS: A total of 3,633 STEMI patients were admitted to the CCU in the Tokyo CCU network. Of those, 249 were enrolled in this study (88 in comatose survivors after out-of-hospital cardiac arrest and 161 in cardiogenic shock). Emergency coronary reperfusion therapy was performed 80 % in the cardiac arrest(CA) group, and 78% in the shock group (p=0.67). In the overall survival rate, no significant difference was seen between the CA-group and the Shock-group (66 % vs. 60%; p=0.32). However, the survival rates were significant higher in each group of patients treated with reperfusion therapy than no-reperfusion therapy (the CA-group: 77% vs. 25%, P&lt;0.01, the Shock-group: 69% vs. 29%, P&lt;0.01). And no significant difference was seen between the CA-group and the Shock-group in the survival rate of the patients who underwent reperfusion therapy (the CA-group: 77% vs. 69%, P=0.3). CONCLUSIONS: Emergency coronary reperfusion therapy improved the survival in STEMI patients with not only cardiogenic shock but also out-of-hospital cardiac arrest, and the two groups had similar survival rate at about 70%. This research has received full or partial funding support from the American Heart Association, National Center.
Haploidentical Donors in Addition to Transplantation in Chronic Phase Associate with Improved Gvhd-Free Relapse-Free Survival (GRFS) for Patients with Advanced CML
Authors: Piyanuch Kongtim, Kehinde U. A. Adekola, Denái R. Milton, Reshma Ramlal, Antonio M. Jimenez, Julianne Chen, Gabriela Rondon, Sairah Ahmed, Betul Oran, Uday R. Popat, Jorge Cortes, Richard E. Champlin, Stefan O. Ciurea
Journal: Blood (2016)
Anticitrullinated protein antibodies facilitate migration of synovial tissue-derived fibroblasts
Authors: Meng Sun, Bence Rethi, Akilan Krishnamurthy, Vijay Joshua, Alexandra Circiumaru, Aase Haj Hensvold, Elena Ossipova, Caroline Grönwall, Yanying Liu, Marianne Engstrom, Sergiu Bogdan Catrina, Johanna Steen, Vivianne Malmstrom, Lars Klareskog, Camilla Svensson, Caroline Ospelt, Heidi Wähämaa, Anca Irinel Catrina
Journal: Annals of the Rheumatic Diseases (2019)

Rheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide antibodies (ACPAs) might contribute to bone loss and arthralgia before the onset of joint inflammation. We aimed to dissect additional mechanisms by which ACPAs might contribute to development of joint pathology.Fibroblast-like synoviocytes (FLS) were isolated from the synovial membrane of patients with RA. The FLS cultures were stimulated with polyclonal ACPAs (anti-CCP-2 antibodies) purified from the peripheral blood of patients with RA or with monoclonal ACPAs derived from single synovial fluid B cells. We analysed how ACPAs modulate FLS by measuring cell adhesion and mobility as well as cytokine production. Expression of protein arginine deiminase (PAD) enzymes and protein citrullination were analysed by immunofluorescence, and signal transduction was studied using immunoblotting.Challenge of FLS by starvation-induced stress or by exposure to the chemokine interleukin-8 was essential to sensitise the cells to ACPAs. These challenges led to an increased PAD expression and protein citrullination and an ACPA-mediated induction of FLS migration through a mechanism involving phosphoinositide 3-kinase activation. Inhibition of the PAD enzymes or competition with soluble citrullinated proteins or peptides completely abolished the ACPA-induced FLS migration. Different monoclonal ACPAs triggered distinct cellular effects in either fibroblasts or osteoclasts, suggesting unique roles for individual ACPA clones in disease pathogenesis.We propose that transient synovial insults in the presence of a certain pre-existing ACPA repertoire might result in an ACPA-mediated increase of FLS migration.
P14.14 Scalp invasion of diffuse large b-cell lymphoma without systemic involvement
Authors: A E Hasturk, E E Eyupoglu, G Gel, C Gokce
Journal: Neuro-Oncology (2019)

Abstract Diffuse large B-cell lymphoma of the scalp with extra and intracranial extension without systemic invasion in a non-immune compromised patient is extremely rare. It should be considered in the differential diagnosis of scalp masses and meningeal lesions. Early diagnosis and surgical treatment is associated with a good outcome. 74 years old male patient with no known history of malignancy came to our clinic for left frontal swelling. He had no systemic cancer involvement. Contrast-enhanced cranial MRI showed a mass lesion invading left frontal skin, subcutaneous tissue, temporal muscle, bone and the underlying dural layer (Figure 1). Surgical excision was decided and after planning with the plastic surgery consultation, the patient was taken into surgery. Skin was lifted with a left frontal flap and the invasion was observed. Skin flap was placed down and the tumoral tissue was totally excised with a margin of normal bone tissue. The pathology assessment of the frozen specimen was found concordant with lymphoma. No injury or invasion of the dura was seen macroscopically. After dural closure, metacrilate cranioplasty was performed in order to replace the removed bone flap. Afterwards patient was handed over to the plastic surgeon. To ensure tumor resection with a safe margin, a transposition scalp flap was designed in the parieto-occipital region. The flap was raised in the supraperiosteal plane with preservation of the pericranium and it was transferred to the defect site. In addition, the flap donor area was reconstructed with a split-thickness skin graft taken from the right thigh region. Then, a wound dressing was applied to the surgical area and opened on postoperative 4th day. No complications such as necrosis, hematoma, infection or wound dehiscence occurred postoperatively. Both the graft and the flap completely healed (Figure 2). The patient showed no new neurological deficits or wound problems postoperatively and did not experience any problems both in plastic surgical and neurosurgical follow-up period (Figure 3). The final pathology result reported as diffuse large B cell lymphoma with invasion of the skin, subcutaneous tissue, temporal muscle and bone. Afterwards, medical treatment was planned with consultation to the hematology and radiotherapy clinics. Primary Non-Hodgkin’s lymphoma (NHL) extending extra cranially and intra cranially without any systemic or skeletal findings is extremely rare. These lesions usually get misdiagnosed as they mimic other conditions such as meningiomas. Both radiological and histopathological diagnoses are very important. Radical surgical resection and reconstruction must be contemplated in treatment and also chemotherapy and radiotherapy alternatives should be considered. Malignant NHL should be taken into account for differential diagnosis in the mass lesions of the scalp.
Limbic Hyperactivity in Response to Emotionally Neutral Stimuli in Schizophrenia: A Neuroimaging Meta-Analysis of the Hypervigilant Mind
Authors: Jules R. Dugré, Nathalie Bitar, Alexandre Dumais, Stéphane Potvin
Journal: American Journal of Psychiatry (2019)

It has long been assumed that paranoid ideation may stem from an aberrant limbic response to threatening stimuli. However, results from functional neuroimaging studies using negative emotional stimuli have failed to confirm this assumption. One of the potential reasons for the lack of effect is that study participants with psychosis may display aberrant brain responses to neutral material rather than to threatening stimuli. The authors conducted a functional neuroimaging meta-analysis to test this hypothesis.A literature search was performed with PubMed, Google Scholar, and Embase to identify functional neuroimaging studies examining brain responses to neutral material in patients with psychosis. A total of 23 studies involving schizophrenia patients were retrieved. Using t-maps of peak coordinates to calculate effect sizes, a random-effects model meta-analysis was performed with the anisotropic effect-size version of Seed-based d Mapping software.In schizophrenia patients relative to healthy control subjects, increased activations were observed in the left and right amygdala and parahippocampus and the left putamen, hippocampus, and insula in response to neutral stimuli.Given that several limbic regions were found to be more activated in schizophrenia patients than in control subjects, the results of this meta-analysis strongly suggest that these patients confer aberrant emotional significance to nonthreatening stimuli. In theory, this abnormal brain reactivity may fuel delusional thoughts. Studies are needed in individuals at risk of psychosis to determine whether aberrant limbic reactivity to neutral stimuli is an early neurofunctional marker of psychosis vulnerability.
P10.05 NKG2DL expression and dormancy in cerebral metastases: impact of chemotherapeutic treatment
Authors: C Flueh, R Hufnagel, M Synowitz, J Held-Feindt
Journal: Neuro-Oncology (2019)

Abstract Background: Cerebral metastases are common intracranial lesions and have enormous prognostic impact. In many cases, brain metastases seem to be insensitive to chemotherapeutic treatment and are often source of recurrence. To date, the reasons for this are not entirely known. Dormant tumor cells are a population of non-apoptotic, low proliferating cells, which have the ability to be reactivated and can be the source of recurrence. Another mechanism of tumor cell survival are immunological escape mechanisms, involving the Natural Killer Group 2, member D (nkg2d) receptor-ligand system. In a previous study we were able to show that human brain metastases of pulmonary and breast cancer harbor a significant amount of dormant tumor cells, which often coexpress NKG2D ligands. We now wanted to investigate, whether chemotherapeutic treatment has an effect on expression of dormancy markers and nkg2d ligands. Materials and Methods: The murine breast cancer cell line E0771 and the murine pulmonary cancer cell line LLC were treated with ascending doses of cisplatin and cyclophosphamid, two chemotherapeutics which are also used in humans, for 2 to 10 days in comparison to negative controls. We performed a cytotoxicity assay. Expression of the dormancy-associated markers pdgf, fgf2, hif1alpha, epha5, h2bk and igfbp5 and the nkg2d ligands mult1, h60a, h60b, h60c and raet1b were analyzed by qrtPCR and immunocytochemistry (IHC). Results: Cytotoxicity assay revealed, that cells from both lines died significantly after treatment with Cisplatin in comparison to control conditions. Whereas cyclophosphamide had no effect on dormancy marker and nkg2dl expression, treatment with cisplatin led to a significant upregulation of many nkg2dl and dormancy marker expression in LLC and E0771 in a dose and time dependent manner. Results were confirmed via IHC.Conclusions: Although chemotherapy with cisplatin leads to death of many cells in culture, the surviving cells show a high expression of dormancy markers and of certain nkg2d ligands. Not only acquisition of dormancy but also nkg2d ligand expression might play an important role in chemoresistance of brain metastases. Markers from both groups could therefore be effective therapeutic targets.
Reanalysis of Data Comparing Prophylactic Cranial Irradiation vs Observation in Patients With Locally Advanced Non–Small Cell Lung Cancer—In Reply
Authors: Alexander Sun, Chen Hu
Journal: JAMA Oncology (2019)

In Reply We greatly appreciate Yin and Zhang’s comments and the opportunity to further elaborate on the interpretation of our findings,1 and more generally, to describe a fitted Cox model for competing risk data and standard survival data if the proportional hazard (PH) assumption is in doubt.
P11.44 Conception of a promising future therapy: Drug loaded-microbubbles against glioblastoma
Authors: E Schulz, V Mawamba, V Sturm, R Ernestus, U Schatzschneider, M Löhr, C Hagemann
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Major obstacles for an effective chemotherapy of glioblastomas (GBM) are the blood-brain-barrier (BBB) and serious systemic side effects of the cytotoxic drugs. A new promising strategy could be the delivery of microbubbles, encapsulating the chemotherapeutics, across the BBB to the tumor site. This will shield the drug from detrimental systemic effects. Low intensity focused ultrasound (LIFU) is able to open the BBB and triggers targeted release of the drugs within the tumor. First data on the synthesis of microbubbles, specifically designed new drugs and the targeted rupture of microbubbles by LIFU are presented. MATERIAL AND METHODS Thin-film hydration of lipids was utilized to prepare microbubbles, which were tested for toxicity on the GBM cell lines GaMG, U87, U138 and U343. In addition these cells were treated with 6 platinum(II) and palladium(II) complexes conjugated to lipophilic side chains of different length (C1, C8, C10) for 72h. To evaluate cell viability and calculate EC50 values MTT assays and a real-time proliferation assay using the impedance-based xCELLigence DP-System were executed. RESULTS Microbubbles ≤ 2µm in diameter were synthesized and could be disintegrated by applying LIFU. Neither the intact bubbles nor the lipids alone had any toxic effects on the GBM cells. In contrast, all six drugs were highly effective with EC50 values far below those of Temozolomide (67µM) and in the range of the reference drug cisplatin (3µM). Especially the palladium(II) compound with the C1-chain displayed a very low EC50 value (&lt;10µM), while the longer chains and the platinum(II) compounds were less effective (EC50 10–40µM). An early and concentration-dependent onset of the cytotoxic effect of drugs with C1 and C8 side chains was revealed in the real time proliferation assay. CONCLUSION All components for a new microbubble-based therapeutic strategy are in place. Microbubbles were synthesized without having toxic effects in cell culture. New highly potent palladium(II) and platinum(II) compounds with low EC50 values were developed. The next step will be their encapsulation into the microbubbles via their lipophilic side chains to develop an effective drug-delivery system for the treatment of GBM in combination with LIFU. This will allow increasing the local concentration of chemotherapeutic agents at the tumor site, irrespectively of their molecular size and BBB penetration capacity.