tbuckley/cabot-search huggingface dataset:
Clinical Characteristics of Connective Tissue Nevi in Tuberous Sclerosis Complex With Special Emphasis on Shagreen Patches
Authors: Michelle A. Bongiorno, Neera Nathan, Oyetewa Oyerinde, Ji-an Wang, Chyi-Chia Richard Lee, G. Thomas Brown, Joel Moss, Thomas N. Darling
Journal: JAMA Dermatology (2017)

Patients with tuberous sclerosis complex (TSC) frequently develop collagenous connective tissue nevi. The prototypical lesion is a large shagreen patch located on the lower back, but some patients only manifest small collagenomas or have lesions elsewhere on the body. The ability to recognize these variable presentations can be important for the diagnosis of TSC.To describe the clinical characteristics of connective tissue nevi on the trunk and extremities of patients with tuberous sclerosis complex.A retrospective analysis of patient medical records and skin photography was performed; 104 adult patients with TSC were enrolled in an observational cohort study that was enriched for those with pulmonary lymphangioleiomyomatosis, and was therefore composed mostly of women (99 women, 5 men). All patients included were examined at the National Institutes of Health (NIH) in Bethesda, Maryland, from 1998 to 2013. Connective tissue nevi were categorized per anatomic location and size. Lesions less than 1 cm in diameter were termed collagenomas. Shagreen patches were characterized as small (1 to <4 cm), medium (4 to <8 cm), and large (≥8 cm).Frequency, anatomic location, size, and histological appearance of connective tissue nevi in patients with TSC.Overall, 58 of 104 patients (median [range] age, 42 [19-70] years) with TSC (56%) had at least 1 connective tissue nevus on the trunk or thighs; of these, 28 of 58 patients (48%) had a solitary lesion, and 30 of 58 patients (52%) had 2 or more lesions. Overall, 120 lesions from 55 patients were classified by size; 46 lesions (38%) were collagenomas; 39 lesions (32%) were small shagreen patches; 21 lesions (18%), medium shagreen patches; and 14 lesions (12%), large shagreen patches. The distribution of lesions was 9% (n = 11), upper back; 29% (n = 35), middle back; 51% (n = 61), lower back; and 11% (n = 13), other locations. All 26 shagreen patches that were analyzed histopathologically had coarse collagen fibers and 24 of 26 stained with Miller elastic stain had decreased elastic fibers. On immunoblot analysis, fibroblasts grown from shagreen patches expressed higher levels of phosphorylated ribosomal protein S6 than paired fibroblasts from normal-appearing skin.Tuberous sclerosis complex-related connective tissue nevi are not limited to the lower back, and occasionally present on the central or upper back, buttocks, or thighs. Elastic fibers are typically decreased. Recognition of these variable presentations can be important for TSC diagnosis.
Evaluation of the osseointegration of dental implants coated with calcium carbonate: an animal study
Authors: Yi Liu, Yi Zhou, Tao Jiang, You-De Liang, Zhen Zhang, Yi-Ning Wang
Journal: International Journal of Oral Science (2017)

In an attempt to overcome the limitations of titanium in dental and orthopaedic clinical applications, a new method has been developed to prepare calcium carbonate coatings on sandblasted and acid-etched (SA) titanium implants. The purpose of this study was to investigate the effect of calcium carbonate-SA (CC-SA) implants on osseointegration in vivo. The surfaces of SA and CC-SA implants were characterised for surface morphology and surface chemistry. Subsequently, these two kinds of implants were implanted in the femoral condyles of rabbits. The implants were retrieved and prepared for histological and histomorphometric evaluation 1, 2, 4, 8 and 12 weeks after implantation. Significantly higher values of bone-to-implant contact of the entire implant except the gap area (BIC_ALL) and the bone-to-implant contact of the gap area (BIC_GAP) were found in animals with the CC-SA implants than in those with the SA implants at 4 weeks. Higher values of total gap bone were found in those with the CC-SA implants than in those with the SA implants at 1, 2 and 4 weeks. In conclusion, the current findings demonstrate that the calcium carbonate coating can improve and accelerate the early ingrowth of bone and osseointegration at the early healing phase. This may reduce clinical healing times and thus improve implant success rates. Coating titanium implants with calcium carbonate (CC) may improve their integration with the surrounding bone tissue. Yining Wang of China's Wuhan University and colleagues tested a new method to prepare CC coatings for titanium implants. CC is resorbable, that is, it is absorbed by the body after a period of time. Current implants coated with non-resorbable materials show decreasing success rates several years after implantation. CC-coated and control implants were embedded in the legs of rabbits and extracted one, two, four, eight and 12 weeks after surgery. The CC-coated implants integrated earlier with the surrounding bone tissue than the controls. The method needs improvement due to incomplete coating of the titanium surface but the team believes CC-coating of titanium implants could reduce healing times and lead to higher implant success rates.
Human Alternative Macrophages Populate Calcified Areas of Atherosclerotic Lesions and Display Impaired RANKL-Induced Osteoclastic Bone Resorption Activity
Authors: Giulia Chinetti-Gbaguidi, Mehdi Daoudi, Mickael Rosa, Manjula Vinod, Loïc Louvet, Corinne Copin, Mélanie Fanchon, Jonathan Vanhoutte, Bruno Derudas, Loic Belloy, Stephan Haulon, Christophe Zawadzki, Sophie Susen, Ziad A. Massy, Jérôme Eeckhoute, Bart Staels
Journal: Circulation Research (2017)

Vascular calcification is a process similar to bone formation leading to an inappropriate deposition of calcium phosphate minerals in advanced atherosclerotic plaques. Monocyte-derived macrophages, located in atherosclerotic lesions and presenting heterogeneous phenotypes, from classical proinflammatory M1 to alternative anti-inflammatory M2 macrophages, could potentially display osteoclast-like functions.To characterize the phenotype of macrophages located in areas surrounding the calcium deposits in human atherosclerotic plaques.Macrophages near calcium deposits display an alternative phenotype being both CD68 and mannose receptor-positive, expressing carbonic anhydrase type II, but relatively low levels of cathepsin K. In vitro interleukin-4-polarization of human primary monocytes into macrophages results in lower expression and activity of cathepsin K compared with resting unpolarized macrophages. Moreover, interleukin-4 polarization lowers expression levels of the osteoclast transcriptional activator nuclear factor of activated T cells type c-1, associated with increased gene promoter levels of the transcriptional repression mark H3K27me3 (histone 3 lysine 27 trimethylation). Despite higher expression of the receptor activator of nuclear factor κB receptor, receptor activator of nuclear factor κB ligand/macrophage colony-stimulating factor induction of nuclear factor of activated T cells type c-1 and cathepsin K expression is defective in these macrophages because of reduced Erk/c-fos-mediated downstream signaling resulting in impaired bone resorption capacity.These results indicate that macrophages surrounding calcium deposits in human atherosclerotic plaques are phenotypically defective being unable to resorb calcification.
Decrease in an anti-ageing factor, growth differentiation factor 11, in chronic obstructive pulmonary disease
Authors: Katsuhiro Onodera, Hisatoshi Sugiura, Mitsuhiro Yamada, Akira Koarai, Naoya Fujino, Satoru Yanagisawa, Rie Tanaka, Tadahisa Numakura, Shinsaku Togo, Kei Sato, Yorihiko Kyogoku, Yuichiro Hashimoto, Tatsuma Okazaki, Tsutomu Tamada, Seiichi Kobayashi, Masaru Yanai, Motohiko Miura, Yasushi Hoshikawa, Yoshinori Okada, Satoshi Suzuki, Masakazu Ichinose
Journal: Thorax (2017)

<h3>Rationale</h3> Cellular senescence is observed in the lungs of patients with COPD and may contribute to the disease pathogenesis. Growth differentiation factor 11 (GDF11) belongs to the transforming growth factor β superfamily and was recently reported to be a circulating protein that may have rejuvenating effects in mice. We aimed to investigate the amounts of GDF11 in the plasma and the lungs of patients with COPD and elucidate the possible roles of GDF11 in cellular senescence. <h3>Methods</h3> The plasma levels of GDF11 were investigated in two separate cohorts by western blotting. The localisation and expression of GDF11 in the lungs were investigated by immunohistochemistry and quantitative reverse transcription PCR, respectively. The effects of GDF11 on both cigarette smoke extract (CSE)-induced cellular senescence in vitro and on elastase-induced cellular senescence in vivo were investigated. <h3>Results</h3> The levels of plasma GDF11 in the COPD group were decreased compared with the control groups in the two independent cohorts. The levels of plasma GDF11 were significantly positively correlated with pulmonary function data. The mRNA expression of GDF11 in mesenchymal cells from the COPD group was decreased. Chronic exposure to CSE decreased the production of GDF11. Treatment with GDF11 significantly inhibited CSE-induced cellular senescence and upregulation of inflammatory mediators, partly through Smad2/3 signalling in vitro. Daily GDF11 treatment attenuated cellular senescence and airspace enlargement in an elastase-induced mouse model of emphysema. <h3>Conclusions</h3> The decrease in GDF11 may be involved in the cellular senescence observed in COPD.
Abstract 79: Autophagy Is Necessary in Reversal of Left Ventricular Hypertrophy
Authors: Jota Oyabu, Osamu Yamaguchi, Kinya Otsu
Journal: Circulation Research (2012)

Myocardial hypertrophy occurs in response to a variety of stresses as a compensatory mechanism to maintain cardiac output and normalize wall stress. Left ventricular hypertrophy (LVH) in the long term is an independent risk factor for a range of adverse consequences, such as cardiac dysfunction and cardiac mortality. Therefore, prevention or regression of LVH can be a major therapeutic target. Although reversal of LVH occurs after control of etiological factors, the molecular mechanisms remain to be clarified. We have previously reported that inhibition of autophagy, an evolutionarily conserved process for the bulk degradation of cytoplasmic components, induces cardiomyocyte hypertrophy. In the present study, we investigated the role of autophagy in the course of reversal of LVH. Wild-type mice showed left ventricular hypertrophy by continuous injection of angiotensin II (A-II) for 14 days using osmotic mini-pump, and LVH was reversed 7 days after removal of pump. Autophagy was induced after removal of pump, as evidenced by an increase in LC3-II protein levels. Next, we crossed floxed Atg5 mice with transgenic mice expressing Cre recombinase in cardiac specific manner to generate cardiac-specific autophagy-deficient mice (CKO). We subjected CKO and control mice (CTL) to continuous injection of A-II for 14 days. CKO and CTL showed LVH similarly (LV weight/body weight, CKO 4.60±0.16 versus CTL 4.44±0.08, p=n.s., LV mass index, CKO 69.0±5.5 versus CTL 72.1±2.2, p=n.s.) without showing contractile dysfunction 14 days after injection of A-II. Cross-sectional area of cardiomyocytes was similar in CKO and CTL (CKO 281.0±1.0 μm 2 versus CTL 274.0±1.5 μm 2 , p=n.s.). 7days after removal of pump, CKO showed significantly less reversal of LVH compared with CTL (LV weight/body weight, CKO 4.30±0.13 versus CTL 3.65±0.09, p&lt;0.05, LV mass index, CKO 67.8±3.8 versus CTL 56.2±2.6, p&lt;0.05). Cross-sectional area of cardiomyocytes also showed less reversal of LVH in CKO (CKO 270.6.0±7.0 μm 2 versus CTL 220.9±11.4 μm 2 , p&lt;0.05), indicating that reversal of LVH didn’t occur sufficiently in autophagy-deficient heart. Autophagy was suppressed during reversal of LVH in CKO. These results suggest that autophagy is necessary in reversal of LVH.
Generic Drugs—Changes in Cost and Challenges in Practice
Authors: Joslyn S. Kirby, Jeffrey J. Miller
Journal: JAMA Dermatology (2017)

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P09.34 Limitations of visualized fluorescence in malignant gliomas: an objective quantification of protoporphyrin levels and correlation with histopathology: Implications on fluorescence-guided resections
Authors: A. Moiyadi, E. Sridhar
Journal: Neuro-Oncology (2017)

Introduction: Fluorescence guided resection (FGR) using 5-aminolevulinic acid has become standard of care in surgery for potentially resectable malignant gliomas. Its benefit in improving gross-total resection rates hinges on the high positive predictive value of strong fluorescence (as visualized under the microscope) in detecting coalescent tumor. However it is possible to miss tumor remnants even with fluorescence techniques. We correlate the spatial distribution of visualized fluorescence (subjective) with protoporphyrin [PPIX] estimation (objective) and histopathological features. METHODS: 9 patients with suspected malignant glioma were operated using FGR on a prospective, IRB approved project. During surgery, variably fluorescing areas (strong - SF, weak-WF, none-N) were collected in each patient. For each collected specimen, PPIX was objectively quantified as per a previously published protocol (Johansson et al). A neuropathologist analyzed each sample again for routine histopathology and classified them into coalescent (C) or infiltrating (I) tumor depending on tumor cell density and proliferative index (Mib LI). Results: Total of 28 samples were collected (12 SF, 2 WF, 14 N). Mean PPIX levels in all fluorescing samples (SF + WF) was 2.3 µg/gm (range- 0.8 to 5.8; SD 1.58) versus 0.15 µg/gm (range- 0 to 0.35; SD 0.1) in non-fluorescing samples. There was a mild overlap between one SF sample and both the WF samples at the lower limit of the range; but no overlap of values with non-fluorescing samples which were distinctly well below the lower limit of the fluorescing tumor sample range. On histology, there were 19 C and 9 I samples. On correlating visualized fluorescence with histology, SF had a 100% PPV for coalescent tumor. Interestingly WF or N predicted non-coalescent tumor (NPV) in only 56% cases. There were 7 samples (6N+1WF) showing coalescent tumor. Excluding the WF sample (PPIX 1.65 µg/gm), the PPIX levels in the remaining N samples were all below 0.3 µg/gm. In 4 patients, there were paired samples showing coalescent tumor but diametrically opposite fluorescent qualities (i.e. strong versus none; confirmed with objective PPIX estimates) within the same tumor. Conclusions: Visualized SF strongly predicts presence of coalescent tumor which needs to be removed. WF on the other hand is very variable and unreliable. Further, by improving sensitivity of fluorescence detection methods as is being attempted by many groups, it may be unlikely that all the coalescent tumor would be visualized (as we show that some coalescent tumor biopsies show negligible PPIX levels). Moreover this study also confirms the presence of heterogeneity of fluorescence even within histologically similar areas within tumors.
P10.01 Epilepsy following low grade glioma surgery
Authors: E. Agushi, R. Mohanraj
Journal: Neuro-Oncology (2017)

Aims: Our aim was to review the role of prophylactic AEDs and the effect of surgical technique (awake craniotomy versus resection under general anaesthetic) on seizure outcomes in patients undergoing surgery for low grade glioma (LGG) Methods: In our retrospective study we included all patients aged >18 years with a confirmed diagnosis of WHO grade II glioma within a 3-year period. Seizure incidence was recorded in the early post-operative period (up to 10 days post operatively) and in the longer term (3 to 12 months). To investigate the effect of AED treatment, patients were categorised into 3 groups: patients pre-established on AEDs (minimum 2 weeks prior to surgery), those started on prophylactic AEDs prior to the surgery (within 24 hours prior to surgery) and those who were not prescribed AEDs during follow up. Results: A total of 135 patients met the inclusion criteria. In the early post-operative period, out of the 24 patients suffered seizures, only 1 patient who had total tumour resection (4.1%), 5 patients (20.8%) of those who had near-total resection, 11 patients (45.8%) of who underwent subtotal/partial and 7(29.1%) of those who had biopsy (p=0.03). During long term follow up, 40(29.6%) patients had seizures, 3 (7.5%) of those who had total resection, 8 (20%) of near-total resection, 18 (45%) of subtotal/partial and 11 (27.5%) of biopsies (p=0.005). 34 (25.2%) underwent awake craniotomy, and 101 (74.8%) underwent resection under GA. 26 of them (33.3%) were in pre-established group, 6 (28.6%) in the prophylactic group and 8(22.3%) in the no AED group (p=0.41). Awake craniotomy was associated with greater extent of resection(total and near total resection) compared to the GA (67.6% v/s 45.4%; OR = 2.5, p=0.028) 78 patients (57.8%) were pre-established on AEDs, 21 (15.6%) received prophylactic AED, and 36 patients (26.7%) no AEDs during follow up. 24 (17.8%) experienced seizures in the early postoperative period (defined as 10 days post-surgery). 4 patients on prophylactic AED group (19.1%); 14 patients on pre-established AED (17.9 %); and 6 (16.7%) in the no AED groups, no statistical significant difference was found between the three groups (p=0.97).; Prophylactic AED treatment did not reduce seizures in the early post-operative period (OR 1.10, p=0.87). Conclusions: Gross resection was associated with lower seizure incidence in the immediate post-operative period, and during long term follow-up. There was no significant difference in seizure incidence between patients treated with prophylactic AEDs and those who were not.
Clinical effect of pancreaticojejunostomy with a long-internal stent during pancreaticoduodenectomy in patients with a main pancreatic duct of small diameter
Authors: Tomohisa Yamamoto, Sohei Satoi, Hiroaki Yanagimoto, Satoshi Hirooka, So Yamaki, Hironori Ryota, Masaya Kotsuka, Yoichi Matsui, Masanori Kon
Journal: International Journal of Surgery (2017)
P08.46 Synergistic Therapeutic Efficacy via Immunomodulatory Platelet Rich Fibrin Patch (PRF-P) in Combination with Oncolytic Adenovirus for the Treatment of Glioma
Authors: W. K. Panek, Julius W. Kim, Katarzyna C. Pituch, Joshua R. Kane, Deepak Kanojia, Alex Cordero, Jason Miska, Aida Rashidi, Jacob S. Young, Maciej S. Lesniak
Journal: Neuro-Oncology (2017)

Introduction: Oncolytic virotherapy is an interesting approach for the treatment of cancer, including glioblastoma. Recent studies in this area suggest a synergistic approach to combine oncolytic virotherapy with immunomodulatory approaches. In this study, we have examined the role of platelet-rich fibrin patch (PRF-P) to enhance anti-tumoral immune response in immune-competent murine model C57/BL when used in conjunction with tumor specific oncolytic Ad5RGD-CMV-E1Δ24. This PRF-P is derived from blood, enriched with lymphocytes, platelets, macrophages (M1), and pro-inflammatory cytokines. Application of PRF-P has been shown to enhance immune cell migration and proliferation. HYPOTHESIS: We hypothesize that PRF-P provides local immunomodulation by supplying pro-inflammatory chemokines, as well as recruiting and enhancing proliferation of cytotoxic T cells, which may lead to an enhanced anti-tumoral immune response when combined with oncolytic virotherapy. METHODS: Blood from donor mice bearing GL261-OVA, a murine glioma cell line expressing ovalbumin (OVA), as a model antigen was collected into non-anticoagulant tubes and processed according to platelet-rich fibrin protocol. Five days after tumor implantation, a stereotactic intra-tumor injection of Ad5RGD-CMVΔ24 viral vector was performed. 48 hours post viral vector administration, a craniotomy was performed and the autologous PRF-P was applied over the tumor. For immunological flow and immunohistochemical analyses, mice were sacrificed five days post treatment. Results: We first performed a survival analysis in immuno-competent murine model. Mice injected with oncolytic virus alone had a significantly prolonged survival compared to PBS treated group (P<0.001). In addition, when used in combination with immunomodulatory PRF-P, this prolonged survival benefit was extended (P<0.001). Also, immunohistochemical analysis showed a decreased implanted tumor size in both virus alone and combinatory ­treatment groups. Most interestingly, we observed an increased number of tumor specific CD8+ cells and antigen cross-presenting and lymph node tropic dendritic cells (CD11b-/CD11C+/ CD103+) from therapeutic treatment groups. CONCLUSION: Our observation collectively represents a novel anti-glioma oncotherapy and immunomodulatory approach and provides a platform for the evaluation and translation of this promising anti-glioma strategy. We will further discuss additional immunomodulatory application: oncolytic virus expressing checkpoint inhibitor PD-1 along with the PRF-P treatment.
P10.22 Preoperative embolization of intracranial hemangiopericytoma with n-butylcyanoacrylate
Authors: M. Oinuma, M. Sato
Journal: Neuro-Oncology (2017)

OBJECTIVE: Intracranial hemangiopericytomas are highly vascular tumors. Preoperative endovascular embolization of hyperbascular tumors is performed to mitigate anticipated intraoperative blood loss. The usage of a wide array of embolic agents, particularly polyvinyl alcohol and gelatin microspheres which is particle, has been described for a variety of tumors. We describe a case of hemangiopericytoma embolized with n-butylcyanoacrylate (NBCA) which is liquid agents. Materials and Methods: A 32-year-old man presented with a grand mal seizure. The patient has a history of resection and irradiation of hemangiopericytoma deriving from the left temporal skull base at 25 years old. A magnetic resonance imaging scan revealed a very large tumor that crosses both sides of the tentorium on the left. Preoperatively, digital subtraction angiography was performed to reveal the tumour’s angioarchitecture, revealing blood supply to the tumor from middle meningeal artery, occipital artery, posterior meningeal branch of the vertebral artery and branch of internal carotid artery. Superselective catheterization of totally 5 feeding vessels (2 OA and 3 MMA) was performed with a microcatheter. We then proceeded to inject 15% NBCA into the vascular bed of the tumor. Preoperative embolization with NBCA allowed significant devascularization of the majority of the tumor. Embolization proceeded uneventfully and there were no complications. Results: There was no significant bleeding during the surgery, where complete resection of the tumor. Postoperative course was uneventful and there has been no recurrence. The results of pathology confirmed hemangiopericytoma. Conclusions: In our case NBCA embolization of highly vascularized hemangiopericytoma was shown to be a safe and efficient tool prior to surgery. The perioperative blood loss could be substantially diminished.