tbuckley/cabot-search huggingface dataset:
Evaluation of Prevention Interventions for Taxane-Induced Dermatologic Adverse Events
Authors: Dustin H. Marks, Azam Qureshi, Adam Friedman
Journal: JAMA Dermatology (2018)

<h3>Importance</h3> Chemotherapy-induced alopecia as well as nail and cutaneous changes occur in up to 89% of patients receiving taxane-based chemotherapy and are associated with cosmetic concerns, psychosocial distress, and overall morbidity. <h3>Objective</h3> To review the efficacy and safety of interventions to prevent taxane-induced dermatologic adverse events. <h3>Evidence Review</h3> PubMed and Scopus databases were systematically reviewed for studies published in the English language from January 1, 1980, to August 13, 2018. Specific search terms included but were not limited to<i>taxane</i>,<i>docetaxel</i>,<i>paclitaxel</i>,<i>prevent</i>,<i>nail</i>,<i>skin</i>,<i>hair</i>,<i>alopecia</i>, and<i>onycholysis</i>. Primary clinical studies that detailed preventive interventions for taxane-induced dermatologic adverse events and that classified results according to a taxane-specific chemotherapy regimen were reviewed and graded according to a 5-point scale, modified from the Oxford Centre for Evidence-based Medicine. <h3>Findings</h3> The 34 original reports that met the inclusion criteria consisted of 6 randomized clinical trials, 4 nonrandomized clinical trials, 18 cohort studies, 3 case-control studies, 1 cross-sectional study, and 2 case reports and involved a total of 5647 unique participants. A total of 22 studies addressed preventive interventions for alopecia associated with taxane use, whereas 12 studies focused on taxane-induced skin and nail changes. Specifically, 20 (95%) of 21 studies supported the use of either a cold cap or a scalp cooling system to reduce alopecia but reported substantial differences in efficacy depending on the chemotherapy regimen. Scalp cooling was generally considered safe by all pertinent studies despite a single report of scalp skin metastasis. Similarly, use of frozen gloves and frozen socks in the prevention of nail and cutaneous hand and foot toxic effects was considered safe in 7 (88%) of 8 studies, although discomfort was common and frostbite was noted in 1 patient. Overall, use of frozen gloves was endorsed by 4 (67%) of 6 studies to prevent nail toxic effects and by 3 (60%) of 5 studies to prevent cutaneous hand changes. <h3>Conclusions and Relevance</h3> Scalp hypothermia with cold caps or scalp cooling systems has demonstrated efficacy as a monotherapy in preventing taxane-induced alopecia, and use of frozen gloves and socks has been associated with reduced nail and skin changes. Future studies should establish the routine usage protocols, standard outcome measures, and long-term efficacy and safety for these interventions.
Dampening of CD8+ T Cell Response by B Cell Depletion Therapy in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors: Antoine Néel, Marie Bucchia, Mélanie Néel, Gaelle Tilly, Aurélie Caristan, Michele Yap, Marie Rimbert, Sarah Bruneau, Marion Cadoux, Christian Agard, Maryvonne Hourmant, Pascal Godmer, Sophie Brouard, Céline Bressollette, Mohamed Hamidou, Regis Josien, Fadi Fakhouri, Nicolas Degauque
Journal: Arthritis & Rheumatology (2018)

Objective To compare the effects of rituximab ( RTX ) and conventional immunosuppressants ( CIs ) on CD 4+ T cells, Treg cells, and CD 8+ T cells in antineutrophil cytoplasmic antibody–associated vasculitis ( AAV ). Methods A thorough immunophenotype analysis of CD 4+, Treg, and CD 8+ cells from 51 patients with AAV was performed. The production of cytokines and chemokines by CD 8+ T cells stimulated in vitro was assessed using a multiplex immunoassay. The impact of AAV B cells on CD 8+ T cell response was assessed using autologous and heterologous cocultures. Results CD 4+ and Treg cell subsets were comparable among RTX ‐treated and CI ‐treated patients. In contrast, within the CD 8+ T cell compartment, RTX , but not CIS , reduced CD 45 RA + CCR 7– ( TEMRA ) cell frequency (from a median of 39% before RTX treatment to 10% after RTX treatment [ P &lt; 0.01]) and efficiently dampened cytokine/chemokine production (e.g., the median macrophage inflammatory protein 1α level was 815 pg/ml in patients treated with RTX versus 985 pg/ml in patients treated with CIs versus 970 pg/ml in those with active untreated AAV [ P &lt; 0.01]). CD 8+ T cell subsets cocultured with autologous B cells produced more proinflammatory cytokines in AAV patients than in controls (e.g., for tumor necrosis factor–producing effector memory CD8+ T cells: 14% in AAV patients versus 9.2% in controls [ P &lt; 0.05]). In vitro disruption of AAV B cell– CD 8+ T cell cross‐talk reduced CD 8+ T cell cytokine production, mirroring the reduced CD 8+ response observed ex vivo after RTX treatment. Conclusion The disruption of a pathogenic B cell/ CD 8+ T cell axis may contribute to the efficacy of RTX in AAV . Further studies are needed to determine the value of CD 8+ T cell immunomonitoring in B cell–targeted therapies.
Tipping the Scales: The Migration–Selection Balance Leans toward Selection in Snake Venoms
Authors: Mark J Margres, Austin Patton, Kenneth P Wray, Alyssa T B Hassinger, Micaiah J Ward, Emily Moriarty Lemmon, Alan R Lemmon, Darin R Rokyta
Journal: Molecular Biology and Evolution (2018)

The migration–selection interaction is the strongest determinant of whether a beneficial allele increases in frequency within a population. Results of empirical studies examining the role of gene flow in an adaptive context, however, have largely been equivocal, with examples of opposing outcomes being repeatedly documented (e.g., local adaptation with high levels of gene flow vs. gene swamping). We compared neutral genomic and venom expression divergence for three sympatric pit vipers with differing ecologies to determine if and how migration–selection disequilibria result in local adaptation. We specifically tested whether neutral differentiation predicted phenotypic differentiation within an isolation-by-distance framework. The decoupling of neutral and phenotypic differentiation would indicate selection led to adaptive divergence irrespective of migration, whereas a significant relationship between neutral and venom expression differentiation would provide evidence in favor of the constraining force of gene flow. Neutral differentiation and geographic distance predicted phenotypic differentiation only in the generalist species, indicating that selection was the predominant mechanism in the migration–selection balance underlying adaptive venom evolution in both specialists. Dispersal is thought to be a stronger influence on genetic differentiation than specialization, but our results suggest the opposite. Greater specialization may lead to greater diversification rates, and extreme spatial and temporal variation in selective pressures can favor generalist phenotypes evolving under strong stabilizing selection. Our results are consistent with these expectations, suggesting that the equivocal findings of studies examining the role of gene flow in an adaptive context may be explained by ecological specialization theory.
Abstract 16688: Trans-Satellite Wireless 12 Lead ECG Transmission From the Ambulance to the Primary PCI Facility as Part of Nationwide Primary PCI Program for ST-Elevation Myocardial Infarction
Authors: Abdurrazzak Gehani, Jassim Al Suwaidi, Omer Tamimi, Salah Arafa, Awad Al Qahtani, Abdulrahman Arabi, Ihsan Rafie, Abdulrahman Nabti, Salem ABujalala, Magdi Yacoub
Journal: Circulation (2014)

Introduction: Time is recognized as a crucial factor in the success of Primary PCI (PPCI). We have installed a “Nationwide” Trans-Satellite Wireless ECG Transfer (W-ECG) which enables swift identification of STEMI and direct transfer to the PPCI facility in Heart Hospital (HH). It also initiates PPCI staff to be ready even before patient arrives, and eliminates delays in Emergency rooms. Methods: Of 510 patients who had PPCI for STEMI, 282 (55%) were transferred directly to the Heart Hospital (HH). These were compared with 228 patients (45%) who went to other hospitals first (OH) before transfer to the HH. Age was similar 50.2 vs 50 years and there was no Ethnic difference (73% Asians and 26% Arabs) in both groups. We compared the two with regard to achieving the optimal Door to Balloon Time (DBT) of 90min for PPCI facility (HH), versus 120min for the OH group, as per guidelines. Results: The DBT was 53±23min for HH group vs 104±55min in OH group (p&lt;0.001). However, while 88% achieved &lt;90min in HH group, only 70% achieved &lt;120min in OH group, p&lt;0.001. Furthermore, Out of Hospital Delay ( OHD i.e delay from symptoms until arrival to hospital) was also different. Patients who had W-ECG arrived faster to HH and thus had shorter OHD (198±183min) than those using own transport to HH (287±276min). Although OHD was longer in HH group (216±212) than OH group (201±172min), the combined OHD+DBT= (Total delay from symptoms to Balloon) was still shorter in HH (W-ECG) group (269min) than similar group going to OH (305min), thus saving 36 vital minutes. Although initial TIMI-0 flow was similar (HH 46% vs OH 44%), TIMI-III flow was achieved more often in HH (97%) than in OH group (92%). Peak Troponin (ng/ml) was also higher in OH group (71251) vs (6576) in HH, p&lt;0.05. While Ejection fraction was similar (HH 45% vs OH 43%), in-hospital mortality was higher in OH group (3.5%) vs (2.5%) in HH, p=0.05. Length of stay was also longer in OH (4.3±4.7) compared to 3.4±3.1 in HH group, p=0.005. Conclusion: Trans-satellite wireless ECG from the ambulance to Primary PCI facility results in significantly shorter DBT, total symptoms to balloon time, and length of stay, as well lower peak Troponin and a trend towards lower in-hospital mortality. Continued study and wider use will further confirm the impact of this technology.
Reducing Firearm Injuries and Deaths in the United States: A Position Paper From the American College of Physicians
Authors: Renee Butkus, Robert Doherty, Sue S. Bornstein
Journal: Annals of Internal Medicine (2018)

For more than 20 years, the American College of Physicians (ACP) has advocated for the need to address firearm-related injuries and deaths in the United States. Yet, firearm violence continues to be a public health crisis that requires the nation's immediate attention. The policy recommendations in this paper build on, strengthen, and expand current ACP policies approved by the Board of Regents in April 2014, based on analysis of approaches that the evidence suggests will be effective in reducing deaths and injuries from firearm-related violence.
Fludarabine with a higher versus lower dose of myeloablative timed-sequential busulfan in older patients and patients with comorbidities: an open-label, non-stratified, randomised phase 2 trial
Authors: Uday R Popat, Rohtesh S Mehta, Roland Bassett, Julianne Chen, Benigno C Valdez, Jitesh Kawedia, Sairah Ahmed, Amin M Alousi, Paolo Anderlini, Geath Al-Atrash, Qaiser Bashir, Stefan O Ciurea, Chitra M Hosing, Jin S Im, Roy Jones, Partow Kebriaei, Issa Khouri, David Marin, Yago Nieto, Amanda Olson, Betul Oran, Simrit Parmar, Katayoun Rezvani, Muzaffar H Qazilbash, Nina Shah, Samer A Srour, Elizabeth J Shpall, Richard E Champlin, Borje S Andersson
Journal: The Lancet Haematology (2018)
A Biomimetic Gold Nanocages-Based Nanoplatform for Efficient Tumor Ablation and Reduced Inflammation
Authors: Qingbo Xu, Jiangshan Wan, Nana Bie, Xianlin Song, Xiaoquan Yang, Tuying Yong, Yanbing Zhao, Xiangliang Yang, Lu Gan
Journal: Theranostics (2018)

Gold nanocages (AuNCs), with high photothermal conversion efficiency and unique hollow interiors, have become a promising nanoplatform for synergistic phototheraml therapy (PTT)-chemotherapy. However, the insufficient tumor targeting, in vivo premature drug leakage and low drug loading efficiency responsible for the spatial-temporal un-synchronization of PTT-chemotherapy, as well as inflammatory response might compromise the anticancer treatment of AuNCs-based drug delivery systems. Methods: Cancer cell membrane (CCM)-coated AuNCs were developed to load anticancer drug doxorubicin (DOX@CAuNCs) by transmembrane ammonium sulfate gradient method. In vitro and in vivo analysis, including characterization, macrophage phagocytosis and tumor targeting capacity, near-infrared (NIR) laser-induced drug release, antitumor efficacy and inflammation response were systematically performed. Results: DOX@CAuNCs showed a high DOX loading capacity and on-demand NIR laser-triggered DOX release compared with CAuNCs passively loading DOX by electrostatic adsorption, a commonly used method to load drug to AuNCs. Meanwhile, in view of the properties of CCM coated on AuNCs, DOX@CAuNCs exhibited decreased macrophage phagocytosis, prolonged blood circulation and enhanced internalization by cancer cells, generating preferable tumor targeting ability. With these integrated advantages, DOX@CAuNCs demonstrated highly efficient and precise spatial-temporal synchronization of PTT-chemotherapy, achieving complete tumor ablation with no obvious side effects. Besides, coating with CCM significantly alleviated AuNCs-induced inflammatory response. Conclusion: This biomimetic AuNCs-based platform might be a prospective drug delivery system for precision PTT and chemotherapy, acquiring desired cancer treatment efficacy and low inflammatory response.
The ECHELON-2 Trial: Results of a Randomized, Double-Blind, Active-Controlled Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Versus CHOP in the Frontline Treatment of Patients with CD30+ Peripheral T-Cell Lymphomas
Authors: Steven M. Horwitz, Owen A. O'Connor, Barbara Pro, Tim M. Illidge, Michelle A. Fanale, Ranjana H Advani, Nancy L. Bartlett, Jacob Haaber Christensen, Franck Morschhauser, Eva Domingo-Domenech, Giuseppe Rossi, Won Seog Kim, Tatyana A. Feldman, Anne Lennard, David Belada, Árpád Illés, Kensei Tobinai, Kunihiro Tsukasaki, Su-Peng Yeh, Andrei R. Shustov, Andreas Hüttmann, Kerry J Savage, Sam Yuen, Pier Luigi Zinzani, Zhaowei Hua, Meredith Little, Shangbang Rao, Joseph Woolery, Thomas Manley, Lorenz Trümper
Journal: Blood (2018)
CXCL12 blockade preferentially regenerates lost podocytes in cortical nephrons by targeting an intrinsic podocyte-progenitor feedback mechanism
Authors: Simone Romoli, Maria Lucia Angelotti, Giulia Antonelli, Santhosh Kumar VR, Shrikant R. Mulay, Jyaysi Desai, Lidia Anguiano Gomez, Dana Thomasova, Dirk Eulberg, Sven Klussmann, Maria Elena Melica, Carolina Conte, Duccio Lombardi, Laura Lasagni, Hans-Joachim Anders, Paola Romagnani
Journal: Kidney International (2018)

Insufficient podocyte regeneration after injury is a central pathomechanism of glomerulosclerosis and chronic kidney disease. Podocytes constitutively secrete the chemokine CXCL12, which is known to regulate homing and activation of stem cells; hence we hypothesized a similar effect of CXCL12 on podocyte progenitors. CXCL12 blockade increased podocyte numbers and attenuated proteinuria in mice with Adriamycin-induced nephropathy. Similar studies in lineage-tracing mice revealed enhanced de novo podocyte formation from parietal epithelial cells in the setting of CXCL12 blockade. Super-resolution microscopy documented full integration of these progenitor-derived podocytes into the glomerular filtration barrier, interdigitating with tertiary foot processes of neighboring podocytes. Quantitative 3D analysis revealed that conventional 2D analysis underestimated the numbers of progenitor-derived podocytes. The 3D analysis also demonstrated differences between juxtamedullary and cortical nephrons in both progenitor endowment and Adriamycin-induced podocyte loss, with more robust podocyte regeneration in cortical nephrons with CXCL12 blockade. Finally, we found that delayed CXCL12 inhibition still had protective effects. In vitro studies found that CXCL12 inhibition uncoupled Notch signaling in podocyte progenitors. These data suggest that CXCL12-driven podocyte-progenitor feedback maintains progenitor quiescence during homeostasis, but also limits their intrinsic capacity to regenerate lost podocytes, especially in cortical nephrons. CXCL12 inhibition could be an innovative therapeutic strategy in glomerular disorders.
IFNγ-activated dermal lymphatic vessels inhibit cytotoxic T cells in melanoma and inflamed skin
Authors: Ryan S. Lane, Julia Femel, Alec P. Breazeale, Christopher P. Loo, Guillaume Thibault, Andy Kaempf, Motomi Mori, Takahiro Tsujikawa, Young Hwan Chang, Amanda W. Lund
Journal: The Journal of Experimental Medicine (2018)

Mechanisms of immune suppression in peripheral tissues counteract protective immunity to prevent immunopathology and are coopted by tumors for immune evasion. While lymphatic vessels facilitate T cell priming, they also exert immune suppressive effects in lymph nodes at steady-state. Therefore, we hypothesized that peripheral lymphatic vessels acquire suppressive mechanisms to limit local effector CD8+ T cell accumulation in murine skin. We demonstrate that nonhematopoietic PD-L1 is largely expressed by lymphatic and blood endothelial cells and limits CD8+ T cell accumulation in tumor microenvironments. IFNγ produced by tissue-infiltrating, antigen-specific CD8+ T cells, which are in close proximity to tumor-associated lymphatic vessels, is sufficient to induce lymphatic vessel PD-L1 expression. Disruption of IFNγ-dependent crosstalk through lymphatic-specific loss of IFNγR boosts T cell accumulation in infected and malignant skin leading to increased viral pathology and tumor control, respectively. Consequently, we identify IFNγR as an immunological switch in lymphatic vessels that balances protective immunity and immunopathology leading to adaptive immune resistance in melanoma.
HLA-Cw6 等位基因和苏金单抗的疗效
Authors: A. Costanzo, L. Bianchi, M.L. Flori, G. Malara, L. Stingeni, M. Bartezaghi, L. Carraro, G. Castellino
Journal: British Journal of Dermatology (2018)

这项来自意大利的研究调查了中度至重度银屑病成人对苏金单抗 (一种称为人单克隆抗体的治疗形式) 的治疗反应, 尤其是, 在存在称为 HLA‐Cw6 特定基因的人中的效果是更好还是更差。存在这种基因个体发生银屑病的风险增高 10 倍, 他们的银屑病更可能在生命早期开始, 并且更严重。另一种人单克隆抗体优特克单抗已被证实在有HLA‐Cw6 基因的患者中疗效比无此基因患者中更迅速且更有效。在此研究中接受研究的特定类型银屑病患者有着长期存在的大块、红色、高起、平伏银屑病区域, 上有银色鳞屑 (慢性斑块型银屑病)。这项研究证实了一些已知的事实: 如, 苏金单抗是一种起效迅速的极为有效治疗。另外, 如同预期, 存在 HLA‐Cw6 基因的患者组平均较无此基因患者年轻, 他们的银屑病开始年龄更早。就HLA‐Cw6 基因本身而言, 在最初入选此研究的 434 名患者中, 有 431 名接受了此基因的检测。32 名患者脱落。在其余患者中, 227 名有HLA‐Cw6 基因患者在 24 周苏金单抗治疗后的状况并不优于 172 名无此基因的患者。换而言之, 苏金单抗在两个组中似乎一样有效, 似乎没有理由在开始治疗前检测这一基因。 Linked Article:Costanzo et al. Br J Dermatol 2018; 179:1072–1080
Immune Monitoring of Vaccine Quality and Persistence of Specific T Cell Responses in Five AML Patients Receiving Extended Dendritic Cell Vaccination Under Compassionate Use
Authors: Iris Bigalke, Judith Eckl, Guri Solum, Kirsti Hønnåshagen, Lisbeth Skoge, Yngvar Fløisand, Dag Josefsen, Stein Sæbøe-Larssen, Christiane Geiger, Dolores Schendel, Gunnar Kvalheim
Journal: Blood (2018)
The further paradoxes of asthma management: time for a new approach across the spectrum of asthma severity
Authors: Richard Beasley, Grace Bird, James Harper, Mark Weatherall
Journal: European Respiratory Journal (2018)

<b>A paradigm shift in asthma management that addresses the paradoxes of SABA reliever therapy is required; consideration needs to be given to replacement of SABA reliever with ICS/fast-onset β-agonist reliever therapy across the range of asthma severity</b>http://ow.ly/ccff30lNLPv
Myopic maculopathy: Current status and proposal for a new classification and grading system (ATN)
Authors: Jorge Ruiz-Medrano, Javier A. Montero, Ignacio Flores-Moreno, Luis Arias, Alfredo García-Layana, José M. Ruiz-Moreno
Journal: Progress in Retinal and Eye Research (2018)

Myopia is a highly frequent ocular disorder worldwide and pathologic myopia is the 4th most common cause of irreversible blindness in developed countries. Pathologic myopia is especially common in East Asian countries. Ocular alterations associated with pathologic myopia, especially those involving the macular area—defined as myopic maculopathy—are the leading causes of vision loss in patients with pathologic myopia. High myopia is defined as the presence of a highly negative refractive error (>−6 to −8 diopters) in the context of eye elongation (26–26.5 mm). Although the terms high myopia and pathologic myopia are often used interchangeably, they do not refer to the same eye disease. The two key factors driving the development of pathologic myopia are: 1) elongation of the axial length and 2) posterior staphyloma. The presence of posterior staphyloma, which is the most common finding in patients with pathologic myopia, is the key differentiating factor between high and pathologic myopia. The occurrence of staphyloma will, in most cases, eventually lead to other conditions such as atrophic, traction, or neovascular maculopathy. Posterior staphyloma is for instance, responsible for the differences between a myopic macular hole (MH)—with and without retinal detachment—and idiopathic MH. Posterior staphyloma typically induces retinal layer splitting, leading to foveoschisis in myopic MH, an important differentiating factor between myopic and emmetropic MH. Myopic maculopathy is a highly complex disease and current classification systems do not fully account for the numerous changes that occur in the macula of these patients. Therefore, a more comprehensive classification system is needed, for several important reasons. First, to more precisely define the disease stage to improve follow-up by enabling clinicians to more accurately monitor changes over time, which is essential given the progressive nature of this condition. Second, unification of the currently-available classification systems would establish standardized classification criteria that could be used to compare the findings from international multicentric studies. Finally, a more comprehensive classification system could help to improve our understanding of the genetic origins of this disease, which is clearly relevant given the interchangeable—but erroneous—use of the terms high and pathologic myopia in genetic research.
Multiple Intravascular Papillary Endothelial Hyperplasia of Bone Mimicking Malignancy on 99mTc-MDP Bone Scan and 18F-FDG PET/CT
Authors: Kun Tang, Wenwen Sun, Jie Lin, Ling Wang
Journal: Clinical Nuclear Medicine (2018)

Multiple intravascular papillary endothelial hyperplasia involved with bone is rare. In this study, we present the case of a 53-year-old woman having occasional chest pains located in the middle of the sternum and the left chest wall. Multiple intravascular papillary endothelial hyperplasia lesions with high metabolism distributed in the sternum, left ribs, 12th thoracic vertebra, and left ilium on bone scintigraphy as well as PET/CT, which were easily misdiagnosed as bone malignant tumors. Increased awareness of this benign lesion and its high metabolic findings will improve preoperative diagnosis and avoid misinterpretation that may lead to an unnecessary invasive treatment.
Complete Remission After Single Radioiodine Therapy in Malignant Struma Ovarii With Bone and Lymph Node Metastases
Authors: Philipp Seifert, Falk Gühne, Sarah Theurer, Martin Freesmeyer
Journal: Clinical Nuclear Medicine (2018)

A 67-year-old woman presented with malignant struma ovarii after radical bilateral salpingo-oophorectomy. The surgery revealed a 4.4 cm papillary thyroid carcinoma (follicular variant) within a right-sided ovarian teratoma. I sodium iodide positron emission tomography / computed tomography and cervical ultrasound showed 2 slightly hyperfunctional thyroid nodules and several metastases, including bone metastases with intense iodine uptake. Thyroidectomy was necessary in preparation for radioiodine therapy and proofed the thyroid nodules to be benign. Complete remission was achieved by single radioiodine therapy (30 months of follow-up).