tbuckley/cabot-search huggingface dataset:
PF622 CARFILZOMIB‐LENALIDOMIDE‐DEXAMETHASONE IN THE MANAGEMENT OF LENALIDOMIDE‐REFRACTORY MULTIPLE MYELOMA
Authors: C. Cerchione, G. Martinelli, D. Nappi, A.E. Pareto, M. Di Perna, K. Ferrara, A. Ferrari, G. Simonetti, F. Pane, L. Catalano
Journal: HemaSphere (2019)

Background: Carfilzomib is an epoxyketone proteasome inhibitor of second generation, proved to be effective and safe in relapsed and refractory Multiple Myeloma (rrMM), in combination with dexamethasone or lenalidomide and dexamethasone. Aims: In this retrospective observational trial, it has been evaluated efficacy and safety of carfilzomib, in combination with lenalidomide‐dexamethasone (KRD) as salvage regimen in patients with rrMM, refractory to lenalidomide, whose prognosis is particularly severe. Methods: 41 patients (23 M/18 F), with rrMM, median age at diagnosis 63.7 years (r. 43–82), median age at start of treatment 67 years (r. 48–84) previously treated with several lines of treatments (median 3, r. 2–11), underwent to KRD regimen (ASPIRE trial schedule) for a median treatment cycles of 8 (r 2–18). ISS was equally distributed, and all patients had previously been treated with bortezomib and IMIDs, and were refractory to this agents. 61% (19/31) of them had undergone at least to a single ASCT. Results: According to IMWG criteria, after a median follow‐up of 9 months (r. 2–18), ORR was 68,2% (28/41: 9 CR, 12 VGPR, 7 PR) with 5 progressive diseases (PD) and 8 patients in stable disease (SD): this can be considered as an impressive result in this subset of rrMM patients, refractory to lenalidomide. In particular, for 11 patients, KRD was, after having achieved at least a PR, a bridge to second/third autologous SCT. Median time to response was 1.3 months (r.1–4), median OS from diagnosis was 62 months (r. 9–170), median OS from start of Carfilzomib was 11 months (r. 2–18). Carfilzomib was well tolerated, with grade 2 anemia in 39% (16/41) of patients, successfully managed by ESAs, without necessity of blood transfusions; 29% (12/41) grade 3–4 neutropenia (pegfilgrastim in primary prophylaxis was given, no ospedalization was required, no septic shocks were observed); 34% (14/41) grade 2, 21% (9/41) grade 3 and 12% (5/41) grade 4 thrombocytopenia, without hemorrhagic events and transfusion‐dependency. Moreover, it was observed pneumonia in 39% (16/41) of patients, treated by common antibiotic drugs and always solved. A cardiac monitoring was performed for all patients: hypertension (grade 2–3) in 34% (14/41) of patients; fatigue in 39% (16/31) of patients. Summary/Conclusion: Carfilzomib‐Lenalidomide‐Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, also lenalidomide, and it could be considered as a bridge to a second autologous or allogenic SCT.
The Unreasonable Effectiveness of Convolutional Neural Networks in Population Genetic Inference
Authors: Lex Flagel, Yaniv Brandvain, Daniel R Schrider
Journal: Molecular Biology and Evolution (2018)

Population-scale genomic data sets have given researchers incredible amounts of information from which to infer evolutionary histories. Concomitant with this flood of data, theoretical and methodological advances have sought to extract information from genomic sequences to infer demographic events such as population size changes and gene flow among closely related populations/species, construct recombination maps, and uncover loci underlying recent adaptation. To date, most methods make use of only one or a few summaries of the input sequences and therefore ignore potentially useful information encoded in the data. The most sophisticated of these approaches involve likelihood calculations, which require theoretical advances for each new problem, and often focus on a single aspect of the data (e.g., only allele frequency information) in the interest of mathematical and computational tractability. Directly interrogating the entirety of the input sequence data in a likelihood-free manner would thus offer a fruitful alternative. Here, we accomplish this by representing DNA sequence alignments as images and using a class of deep learning methods called convolutional neural networks (CNNs) to make population genetic inferences from these images. We apply CNNs to a number of evolutionary questions and find that they frequently match or exceed the accuracy of current methods. Importantly, we show that CNNs perform accurate evolutionary model selection and parameter estimation, even on problems that have not received detailed theoretical treatments. Thus, when applied to population genetic alignments, CNNs are capable of outperforming expert-derived statistical methods and offer a new path forward in cases where no likelihood approach exists.
PF778 ANALYSIS OF CENTRAL NERVOUS SYSTEM COMPLICATIONS AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: C. Insua Vilas, R.M. Rodríguez Núñez, P.M. García Cereijo, Ó. Domínguez Muñiz, C. Albo López, M.D. L.Á. Fernández Fernández
Journal: HemaSphere (2019)

Background: In the context of significant advances in the treatment of hematological diseases using the method of autologous hematopoietic stem cell transplantation (auto-HSCT), the number of patients requiring early vaccination against pneumococcal infection increases worldwide. Current guidelines indicate the early initiation of pneumococcal vaccination starting from 3 months after HSCT. Still, the topical issue is the determination of the earliest optimal dates for the start of vaccination after transplantation, taking into account the dynamics of immunological recovery. Aims: The aim of this study was to determine the optimal timeline for the onset of vaccination with conjugated pneumococcal vaccine in patients with multiple myeloma after auto-HSCT. Methods: The immune response to the conjugated pneumococcal vaccine is based on the T-dependent (CD4+) activation of B-cells, what was taken into account when estimating the timing of immune reconstitution after auto-HSCT in candidates for vaccination. An immunological study using flow cytometry was performed in 37 adult patients with multiple myeloma prior to the auto-HSCT procedure, as well as on days +30, +60, +90, +180 after transplantation. Results: After auto-HSCT, the level of naive B-cells returns to its original value by the 60th day from transplantation (Kruskal-Wallis test 41.97; P < 0.001), shown on Fig. 1. At the same time, the level of CD4 + cells did not fall below 200 cells/μl starting from day +30, what indicates the effectiveness of early vaccination with T-dependent vaccines in this category of patients with immunosuppression. Dendritic cells (DC1 and DC2) are restored in parallel by the 30th day from auto-HSCT (Kruskal-Wallis test 25.78; P <0.001 for DC-1 cells and Kruskal-Wallis test 11,17; P <0.025, respectively), what confirms the basis for the early vaccination with conjugated pneumococcal vaccines in this category of patients.Summary/Conclusion: The obtained data allows planning the introduction of the first dose of the conjugated pneumococcal vaccine 60 days after autologous HSCT, with the perspective of introducing an individualized vaccination calendar based on immunological parameters. It is also necessary to further implement immunization programs for immunocompromised patients, especially in hematology and cancer setting with the participation of a multidisciplinary team of specialists.
Carbon monoxide poisoning
Authors: James Ashcroft, Emma Fraser, Sanjay Krishnamoorthy, Sue Westwood-Ruttledge
Journal: BMJ (2019)

### What you need to know

A 23 year old man with no medical history presents to the emergency department with a three day history of headache, transient visual disturbance, dizziness, and hypertension. On clinical examination the patient is flushed and drowsy with redness in the sclera, with no further visual or systemic symptoms. A venous blood gas on air shows a carboxyhaemoglobin level (COHb) grossly elevated at 26.0 (0-3), which leads to the diagnosis of carbon monoxide poisoning. 

Carbon monoxide (CO) is a poisonous gas produced through burning fuel. Sources of CO in the home include boilers and central heating systems, cookers and barbecues, and fireplaces and chimneys (figure).1 Owners of such appliances are required to have them serviced by registered technicians as per recommended individual guidance (usually once per year).1 If outlets from these appliances (such as flues and chimneys) become blocked or if they are operated as normal in a closed environment with no ventilation, dangerous levels of CO can build up in living spaces.1 When inhaled in high quantities, CO enters the bloodstream and binds to haemoglobin molecules with a much greater affinity (230 times higher) than oxygen, creating carboxyhaemoglobin.2 The binding of CO results in reduced delivery of oxygen to tissues, which leads to tissue ischaemia.2



Figure 
Common domestic sources of CO



Presentation of CO poisoning is not frequent enough for the condition to prioritised in medical training, diagnostic decision making, initial patient testing, and publicity and public …
Abstract 20795: Assessing Atherosclerotic Cardiovascular Disease Risk in Population With Aortic Atherosclerosis
Authors: Rabia Razi, Michael B Jorgensen, David Yi, Daniel Zisook, Somjot S Brar
Journal: Circulation (2016)

Background: Recent literature has shown that the pooled cohort equation (described in the 2013 ACC/AHA Guidelines on the Treatment of Blood Cholesterol) may overestimate atherosclerotic cardiovascu...
Sixty seconds on . . . prostate cancer screening
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Screening is often a controversial topic within medicine, and a new £5m (€5.6m; $6.3m) trial offering magnetic resonance imaging (MRI) scans to test asymptomatic men for prostate cancer will have raised eyebrows this week after being hyped in the national press. The trial, starting in August, is funded by the Medical Research Council and Cancer Research UK. It will invite 1000 men aged between 55 and 75 years to …
SP0093 MANAGING MORE THAN RMDS
Authors: Kristien Van der Elst
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Increasing emphasis has been placed on the concept of multi-morbidity or the coexistence of two or more chronic diseases in adult patients with rheumatic conditions. A few years ago a EULAR initiative raised some points to consider for management of comorbidities, such as cardiovascular diseases and depression, in chronic inflammatory rheumatic diseases in daily practice (1). Nevertheless, improved management of comorbidities, including prevention, remains a commonly identified unmet need in rheumatology (2). Multi-morbidity can be quite challenging to manage, while the perspective of the individuals having to cope with multiple chronic diseases could differ from that of health professionals taking care of them. Awareness and regular assessment are key, as well as a collaboration between health professionals and well-informed patients. This lecture aims to provide practical information about how to manage more than the rheumatic disease as such, focussing as well on topics of specific interest to young people. <h3>References:</h3> [1] Baillet, et al. Points to consider for reporting, screening for and preventing selected comorbidities in chronic inflammatory rheumatic diseases in daily practice: a EULAR initiative. Ann Rheum Dis. 2016 [2] Winthrop, et al. Unmet need in rheumatology: reports from the Targeted Therapies meeting 2018. Ann Rheum Dis. 2019 <h3>Disclosure of Interests:</h3> None declared
PB2336 PRIMARY AND SECOND GRAFT FAILURES IN ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION: PRE-TRANSPLANT RECIPIENT / DONOR CYTOMEGALOVIRUS SEROSTATUS CAN HAVE AN EFFECT ON GRAFT FAILURE
Authors: M. Pamukcuoglu, M. S. Pepeler, N. A. Baysal, B. Ulkuden, S. Z. Aki, G. T. Sucak
Journal: HemaSphere (2019)

Background: Graft failure is a complication of hematopoietic stem cell transplantation (HSCT) which is mostly effected achievement of HSCT. The incidence of graft failure is variable 4% to 20 % according to donor types. Determination of factors that affecting on graft failure will help to physicians for improving achievement of HSCT and prevention from graft failure. In this retrospective review, we analyzed some parameters that can have an effect on primary and secondary graft failure and we also reviewed treatment options that had been used in primary and secondary graft failure. Aims: Determination of factors that have been affected on graft failure and treatment options in graft failure. Methods: We retrospectively examined 345 recipient/donor's clinicopathologic characteristics which may have an effect on graft failure after allogenic HSCT. Results: Fifteen (4,3%) of 345 recipient had graft failure. Eight (53,3%) of 15 recipient had primary graft failure, 7 (46.7%) of 15 recipient had secondary graft failure. We found significant relationship between graft failure with conditioning, recipient/ donor (R/D) HLA status, R/D ABO status, R/D Cytomegaliovirus (CMV) status at pre transplant evaluation. (p<0,05). Treatment options and response in graft failure are as following : 7 of 15 recipient received DLI treatment;. 4 of 7 recipient responded to DLI treatment. Three of 15 recipient received CD 34+ cells from the same donor; 2 of 3 recipient responded to CD 34+ cells treatment. Seven of 15 recipient underwent a second allogeneic HSCT ; 6 of 7 recipient responded to second transplant. Summary/Conclusion: Significant relationship between R/D CMV serostatus at pre-transplant evaluation with graft failure is different finding from the previous studies. However; Second HSCT still seems as a best treatment option in this retrospective review.
PB2220 SURVIVAL OUTCOME OF HIGH‐RISK PATIENTS WITH MYELOFIBROSIS TREATED WITH ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FOLLOWING REDUCED‐INTENSITY CONDITIONING REGIMENS
Authors: J. Lee, J.‐H. Yoon, S. Y. Yoon, C. Kim, S.‐S. Park, H.‐J. Kim, J. W. Lee, S. Lee, K.‐S. Eom
Journal: HemaSphere (2019)

Background: Allogeneic hematopoietic cell transplantation (allo‐HCT) is the only curative treatment for myelofibrosis (MF), but substantial risk of transplantation‐related mortality (TRM) is a considerable obstacle especially in elderly patients or in patients with severe comorbidity. In the era of Janus kinase (JAK) inhibitors, transplantation may be delayed in good responders but cytopenia is a major complication, and we confront refractory patients who should be treated with allo‐HCT immediately. Aims: Here, we are going to show our experiences on high‐risk MF patients who were treated with reduced‐intensity conditioning (RIC) allo‐HCT. Methods: Here, we are going to show our experiences on high‐risk MF patients who were treated with reduced‐intensity conditioning (RIC) allo‐HCT. Results: All showed successful engraftment. Including 2 patients who were conditioned with nonmyeloablative regimen, total 6 (15.8%) showed delayed graft failure at a median 8 months post‐HCT (range, 3.8‐13.8). Two recovered after stem cell booster from the same donor, other 2 received donor lymphocyte infusion but showed progression, and 1 died after 2 nd allo‐HCT. Among the 33 patients with post‐HCT bone marrow (BM) exam results, 29 (87.8%) showed significant improvement of BM fibrosis (range, 14‐661 days). After median follow‐up duration of 24.6 months (range, 6.1‐124.8), 2‐year OS was 64.6% (64.3% in triple‐negative subgroup), 2‐year nonrelapse mortality was 27.4%, and 2‐year graft‐and‐relapse‐free survival (GRFS) was 28.4%, which suggested there were fatal high‐grade GVHD in this cohort. Acute GVHD was observed in 18 patients (5 grade II, 7 grade III, 4 grade IV) and a cumulative incidence of grade III‐IV acute GVHD was 30.6%. Chronic GVHD was observed in 13 (4 mild, 2 moderate, 7 severe), and a cumulative incidence of severe chronic GVHD was 27.5%. Among them, severe hepatic GVHD was observed in 9 patients (5 acute, 4 chronic). Among 11 dead patients, 7 died due to fatal hepatic GVHD, 1 died of lung GVHD, and 3 died due to septic pneumonia. Multivariate analysis revealed 2‐year OS was significantly poorer in patients who suffered from hepatic GVHD (HR = 9.8, 95%CI 1.0‐94.7, p = 0.022) and the significant cause of fatal hepatic GVHD was unrelated or mismatched donor HCT. Summary/Conclusion: RIC allo‐HCT can be a valid choice providing graft‐versus‐myelofibrosis effect for advanced and triple‐negative MF patients, but fatal hepatic GVHD was frequently observed especially in unrelated or mismatched donor transplants which should be overcome in the future.
The Development of Clinical Guidelines and Guidance Statements by the Clinical Guidelines Committee of the American College of Physicians: Update of Methods
Authors: Amir Qaseem, Devan Kansagara, Jennifer S. Lin, Reem A. Mustafa, Timothy J. Wilt
Journal: Annals of Internal Medicine (2019)

The American College of Physicians (ACP) was one of the first organizations in the United States to develop evidence-based clinical guidelines and has been developing guidelines since 1981. ACP's Clinical Guidelines Committee (CGC), in collaboration with staff from the Clinical Policy department, develops clinical guidelines and guidance statements and continues to refine and enhance its methodology. This article presents an update of the CGC's 2010 paper outlining policies, methods, and presentation format of ACP's clinical guidelines and guidance statements. Updated methods include more stringent policies about disclosure of interests and conflict management; inclusion of public perspective; full adoption of GRADE (Grading of Recommendations Assessment, Development and Evaluation) methods; more standardized reporting formats that consider value of care, patient comorbid conditions, patient values and preferences, and costs; and further clarification of guidance statement methods.
PB1831 PRELIMINARY RESULTS OF THE COMBINED TREATMENT PRIMARY NON‐HODGKIN ORBITAL LYMPHOMAS
Authors: A. Jazyltayeva, A. Jazyltayeva, S. Gabbasova, R. Karakulov, N. Kemelbekov, G. Sagyndikov, B. Nassipov, A. Akanov, A. Taktybayeva
Journal: HemaSphere (2019)

Background: Non‐Hodgkin Lymphomas (NHL) effected organ of vision compose 8–12 % of all primary extranodal NHL, and may be the first and only sign of the disease. Aims: To estimate a therapy of patients with extranodal orbital lesion in our cancer center. Methods: Since 2014 to 2018 in our center treated 17 patients with extranodal damage to the orbit of the eyes. The age of patients ranged from 23 to 92 years, the average age of patients was 57 years. The number of men were 8 people, women ‐ 9. Unilateral orbital damage was registered in 15 patients, bilaterally in 2 patients. In 12 cases process localized in the anterior part of the orbit, in 5 ‐ in the middle and deep parts of the orbit with the spread in the maxillary sinus. Clinical sings of NHL characterized with exophthalmos in varying degrees of severity, difficult reposition, displacement of the eyeball and restriction of its mobility, swelling of the eyelid. By all the observations: to 12 patients performed biopsy of the tumor, 4 patients underwent therapeutic and diagnostic orbitotomy by Killian, to 1 patient ‐ eye orbit exentation. Histological variants: MALT‐ lymphomas – 4 patients, Diffuse B‐cell Lymphoma – 8, Mantle Cell Lymphoma – 2 and Follicular Lymphoma ‐ 2 patients. Results: All patients underwent 6 courses of chemotherapy according to the R‐EPOCH protocol. Complete answer registered in 16 cases, partial answer in 1 of cases, and this patient received a course of radiation therapy on the affected area. Observation median was 3 years (15 month‐5 years). Summary/Conclusion: Therefore, treating orbital NHL requires complex multidisciplinary approach, allowing determining the correct diagnosis and prescribing adequate treatment. Standart first line therapy achieved good results of relapse‐free survival. Chemotherapy showed the same results as the combined treatment (chemotherapy and orbitotomy).
The Autism-Associated Gene Scn2a Contributes to Dendritic Excitability and Synaptic Function in the Prefrontal Cortex
Authors: Perry W.E. Spratt, Roy Ben-Shalom, Caroline M. Keeshen, Kenneth J. Burke, Rebecca L. Clarkson, Stephan J. Sanders, Kevin J. Bender
Journal: Neuron (2019)
Reducing Firearm Injuries and Deaths in the United States
Authors: Renee Butkus, Robert Doherty, Sue S. Bornstein
Journal: Annals of Internal Medicine (2019)

Letters18 June 2019Reducing Firearm Injuries and Deaths in the United StatesRenee Butkus, BA, Robert Doherty, BA, and Sue S. Bornstein, MDRenee Butkus, BAAmerican College of Physicians, Washington, DC (R.B., R.D.)Search for more papers by this author, Robert Doherty, BAAmerican College of Physicians, Washington, DC (R.B., R.D.)Search for more papers by this author, and Sue S. Bornstein, MDTexas Medical Home Initiative, Dallas, Texas (S.S.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0162 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We discussed the personalized, or smart gun, technology mentioned by Dr. Franke in the rationale for Position 8, a position that was reaffirmed from the 2014 position paper on reducing firearm injuries and deaths in the United States (1). We determined that further research on the development of personalized guns was needed but do support any efforts to improve and modify firearms to make them as safe as possible. The 2014 position paper (1) discussed this technology further.Dr. Webster advocates gun registration; we have not taken a position on this issue but will consider doing so in ...Reference1. Butkus R, Doherty R, Daniel H; Health and Public Policy Committee of the American College of Physicians. Reducing firearm-related injuries and deaths in the United States: executive summary of a policy position paper from the American College of Physicians. Ann Intern Med. 2014;160:858-60. [PMID: 24722815]. doi:10.7326/M14-0216 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: American College of Physicians, Washington, DC (R.B., R.D.)Texas Medical Home Initiative, Dallas, Texas (S.S.B.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-1530. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoReducing Firearm Injuries and Deaths in the United States: A Position Paper From the American College of Physicians Renee Butkus , Robert Doherty , Sue S. Bornstein , and Reducing Firearm Injuries and Deaths in the United States James Webster Reducing Firearm Injuries and Deaths in the United States Ethan B. Ludmir , M. Ali Elahi , and B. Ashleigh Guadagnolo Reducing Firearm Injuries and Deaths in the United States Paul Franke Metrics Cited byGun Violence as an Infectious Disease 18 June 2019Volume 170, Issue 12Page: 911-912KeywordsDisclosureFirearm injuriesForecastingTaxes ePublished: 18 June 2019 Issue Published: 18 June 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...