tbuckley/cabot-search huggingface dataset:
Long-term outcome of high-dose chemotherapy and autologous stem cell transplantation in relapsed/refractory Hodgkin’s disease: A cohort of 199 pts from Royal Marsden Hospital
Authors: B. Sirohi, D. Cunningham, A. R. Norman, J. Oates, A. Wotherspoon, G. Chong, T. Arkenau, A. Horwich
Journal: Journal of Clinical Oncology (2006)

7622 Background: The purpose was to assess prognostic factors and outcome of pts with relapsed/refractory Hodgkin disease (HD) who have received high-dose chemotherapy and autologous stem cell transplant (ASCT). Methods: The retrospective study was approved by Research Ethics Committee. Primary end-point was overall (OS) and progression free survival (PFS). OS was defined as death from any cause measured from date of transplant and PFS defined as disease progression or death from any cause. Data on 199 pts who received ASCT between 1985–6/05 was reviewed. Results: Median time from 1 st treatment(tx) to ASCT was 2.5 y (0.5–27.3). Demography at ASCT:61% Stage IV, median age 31y(18–69); median prior tx regimens 3 (1–7); median Hasenclever index 3 (0–6); 150 pts had responding disease (53 CR, 97 PR), 49 pts had stable/untested relapse/refractory disease. 62% pts received MBE as conditioning tx and bone marrow was source of stem cells in 57%. Post-ASCT, 61% (122/199) pts attained CR with an overall response (CR+PR) of 85%. 12 pts had non-relapse mortality;10 died before 1990 of interstitial pneumonitis (with higher dose BCNU). Of 122 pts attaining CR, 27 relapsed;3 after attaining CR for &gt;5y and 1 after attaining CR for&gt;10-y. 5-y risk of relapse in patients attaining CR was 21%. Median OS/PFS from ASCT was 9y/2.6y. 105 pts are alive at median follow-up of 10.3y. 5-y OS/PFS was 52/45% and 10-y OS/PFS was 49.5/41% for whole group. 10-y OS/PFS for pts in CR vs PR vs rest at ASCT was 72/66% vs 55/44% vs 11/5%. 20(10%) pts developed 2nd cancer (7 secondary AML/MDS). Probability of developing 2 nd cancer at 10y is 6.9% (95%CI 3.6–13%) and 19.8% (95%CI 12–32%) at 20-y. Conclusions: These data provide the longest followup reported for patients receiving ASCT for relapsed/refractory HD. In addition to previously described prognostic factors, our data shows that Hasenclever index &lt;3 influences outcome favorably and attaining CR at ASCT leads to a significantly better outcome. [Table: see text] No significant financial relationships to disclose.
Needle Biopsy of the Liver
Authors: Norman Zamcheck, Oscar Klausenstock
Journal: New England Journal of Medicine (1953)

Complications of Liver BiopsyMost needle biopsies are free of complications. Klatskin194 reported that more than 80 per cent of 352 needle biopsies were without mishap (Table 1). Terry,195 reviewing 7532 biopsies noted 24 "significant" complications, an incidence of only 0.23 per cent.Pain, the most frequent complication of liver biopsy, variously reported in 5 to 50 per cent of patients,5 is usually short lasting and may be controlled readily by routine analgesics.196 Perhaps, the best indication of this is the willingness of almost all patients to permit repeat biopsy. Multiple biopsies have been performed on many patients, as many . . .
A reference genome for pea provides insight into legume genome evolution
Authors: Jonathan Kreplak, Mohammed-Amin Madoui, Petr Cápal, Petr Novák, Karine Labadie, Grégoire Aubert, Philipp E. Bayer, Krishna K. Gali, Robert A. Syme, Dorrie Main, Anthony Klein, Aurélie Bérard, Iva Vrbová, Cyril Fournier, Leo d’Agata, Caroline Belser, Wahiba Berrabah, Helena Toegelová, Zbyněk Milec, Jan Vrána, HueyTyng Lee, Ayité Kougbeadjo, Morgane Térézol, Cécile Huneau, Chala J. Turo, Nacer Mohellibi, Pavel Neumann, Matthieu Falque, Karine Gallardo, Rebecca McGee, Bunyamin Tar’an, Abdelhafid Bendahmane, Jean-Marc Aury, Jacqueline Batley, Marie-Christine Le Paslier, Noel Ellis, Thomas D. Warkentin, Clarice J. Coyne, Jérome Salse, David Edwards, Judith Lichtenzveig, Jiří Macas, Jaroslav Doležel, Patrick Wincker, Judith Burstin
Journal: Nature Genetics (2019)

We report the first annotated chromosome-level reference genome assembly for pea, Gregor Mendel's original genetic model. Phylogenetics and paleogenomics show genomic rearrangements across legumes and suggest a major role for repetitive elements in pea genome evolution. Compared to other sequenced Leguminosae genomes, the pea genome shows intense gene dynamics, most likely associated with genome size expansion when the Fabeae diverged from its sister tribes. During Pisum evolution, translocation and transposition differentially occurred across lineages. This reference sequence will accelerate our understanding of the molecular basis of agronomically important traits and support crop improvement. The first annotated chromosome-level reference genome assembly for pea, Gregor Mendel's original genetic model, provides insights into legume genome evolution and the molecular basis of agricultural traits for pea improvement.
P14.99 Clinical and biologic features predictive of survival after relapse of childhood medulloblastoma
Authors: S Huybrechts, A Chivet, A Tauziede-Espariat, C Rossoni, E Indersie, P Varlet, S Puget, R Abbas, O Ayrault, L Guerrini-Rousseau, J Grill, D Valteau-Couanet, C Dufour
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Salvage therapy for recurrent medulloblastoma (MB) is not standardized. Factors associated with survival after recurrence have not been reported. MATERIAL AND METHODS Medical records were reviewed for 155 consecutive patients with newly diagnosed MB between 2007 and 2017, treated at Gustave Roussy and Hospital Necker. The following variables were collected for all patients: age at diagnosis, stage, histology (central review according to WHO 2016 classification), molecular subgrouping (DNA methylation), first-line treatment modalities, time to relapse, pattern of recurrence and current status. RESULTS A disease recurrence was observed in 47 patients (30%) at a median time of 15 months (range, 1–88 months). The 1-year survival after recurrence was 44% (CI 95%,29.6 to 58.8). The pattern of recurrence was local in 9 patients, metastatic in 21 and combined local and metastatic in 17 patients. The time to first recurrence, less or more than 12 months from diagnosis, was a predictor of post-recurrence overall survival (p &lt; 0.0001) after adjustment for age, treatment, MYC amplification and molecular subgroups. Twenty-seven patients (57%) experiencing recurrent or progressive disease more than 12 months after diagnosis, had an estimated 1-year survival after recurrence of 100% (CI 95%, 100.0 to 100.0) vs 30% (CI 95%, 12.2 to 50.1) with an earlier recurrence. Early relapse was more frequent in children younger than 5 years of age at diagnosis (75% vs 37%, p =0.009), anaplastic/large cell MB (30% vs 3.7%, p=0.046) and Group 3 tumours (76.5% vs 20.8%, p=0.003). Other factors influencing post-relapse survival were metastatic disease and treatment modalities at diagnosis. Multivariable analyses will be presented. CONCLUSION The overall prognosis after relapse remains poor. Time to relapse is a significant prognostic factor for postrelapse survival and may help in the design of clinical trials evaluating new agents.
Patient choice in the NHS: health professionals are not obliged to meet every patient wish
Authors: Robert Dingwall
Journal: BMJ (2019)

Kar expresses a dilemma that is well recognised, but often ducked, by medical sociologists: is genuine patient choice possible?1 In 1951 Talcott Parsons said that the “sick role” (a theory of the rights and responsibilities of those who are ill) attempted to resolve an inherent tension between the desires of those who were unwell …
Hughes' Practice of Medicine
Journal: JAMA (1935)

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P14.49 Primary central nervous system lymphoma presenting as dementia: do not forget IL10 in CSF analysis
Authors: A Blain, A Brinet, M Berthel, A Camoyret, C Gaultier, L Droy-Dupré, H Oesterlé, R Hurstel, A Debliquis, M Costopoulos, M Le Garff-Tavernier, F Sellal, G Ahle
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that aﬀects the central nervous system without systemic involvement. Clinical presentation depends on its localization: Focal deficits usually lead to prompt neuroradiologic evaluation, whereas cognitive or behavioral changes can lead to diagnostic delay. Rapidly progressive dementia (RPD), defined as a 1- to 2-year course from symptom onset to cognitive and functional debilitation, is a clinical presentation of PCNSL and thus a potentially curable cause of dementia, leading to death if it remains untreated. Nevertheless, its diagnosis is frequently delayed as other origins (CJD, autoimmune, paraneoplastic, infectious, and neurodegenerative disorders) are more frequently considered. We aimed to describe diagnostic features and treatment modalities in a series of patients presenting with RPD diagnosed as PCNSL. METHODS Patients with RPD and final diagnosis of PCNSL were retrospectively identified from 2012 to 2019 from the database of our academic teaching hospital. Clinical presentation, neuroimaging, and cerebro-spinal fluid (CSF) analysis were assessed from their medical records. Interleukin (IL) 10 and 6 concentrations were measured by flow cytometry using the cytometric bead array (CBA) technique (BD Biosciences) with a detection limit set at 2.5 pg/ml. RESULTS 50 patients with diagnosis of PCNSL were identified, 7 (3 women, 4 men) presented with RPD.Median age was 69 years (range 59–84). Time from symptom onset to diagnostic confirmation of PCNSL ranged from 1–12 months (median 3). All patients presented with cognitive impairment (disorientation, memory disorders), accompanied by psycho-behavioral disorders in 6 of them. MRI disclosed enhancing lesions in all patients. Lumbar puncture was performed in 5 patients. All of them presented pleiocytosis, and lymphomatous meningitis was detected in 4/5 of them by cytology or flow cytometry (FCM). Elevated interleukin 10 (IL-10) was found in all patients with available CSF sample, 4 of them had an IL-10/IL-6 ratio &gt;1. DISCUSSION AND CONCLUSION Patients presenting with rapidly progressive dementia should be evaluated for treatable forms of dementia. PCSNL has to be considered as soon as possible as diagnostic delay impacts its outcome. Imaging studies, usually contrast-enhanced MRI, is recommended, although nonspecific findings are not uncommon, especially in case of non-enhancing lesions. CSF sampling can help to prove diagnosis of PCNSL by cytology (generally associated with FCM), but it requires an experienced cytologist and immediate sample analysis.IL10 and IL10/6 ratio can be used as a more easily available marker to support suspicion of PNSCL, leading to further specific workup. ACKNOWLEDGMENTS NENO &amp; LOC Network
Role of gemcitabine-based combination therapy in the management of advanced pancreatic cancer: A systematic review and meta-analysis of randomized trials.
Authors: Domenico Ciliberto, Cirino Botta, Pierpaolo Correale, Roberto Mazzanti, Giovanni Mantovani, Pierfrancesco Tassone, Pierosandro Tagliaferri
Journal: Journal of Clinical Oncology (2012)

e14577 Background: Pancreatic cancer is the 4th leading cause of cancer-related death worldwide. Single-agent chemotherapy with gemcitabine represents a cornerstone for advanced disease treatment. To date, almost all trials, designed to evaluate the benefit of the addition of a second agent to gemcitabine, failed to demonstrate an improvement in overall survival (OS). We performed a systematic review and a meta-analysis of randomized clinical trials to assess the efficacy and safety of gemcitabine-based combination regimens versus gemcitabine alone in the management of pancreatic cancer. Methods: Clinical trials were selected by searching Medline database and abstracts from major cancer meetings. We considered the Jan 1997 - Jan 2012 time frame. Primary end-point was OS, secondary end-points were response rate (RR), disease control rate (DCR) and safety. Hazard ratios (HRs) of OS, odds-ratios (ORs) of RR, DCR and risk ratios of grade 3-4 toxicity rates, were extracted as presented in retrieved studies and used for statistical analysis. Meta-analytic estimates were derived using random-effects model. Results: Thirty-three trials for a total of 10371 patients were selected and included in the final analysis. The analysis showed for combination chemotherapy a benefit in terms of OS (HR: 0.92; 95%CI: 0.88-0.96; p &lt; 0.001). OR of both RR and DCR demonstrated a significant advantage for combination therapy (OR for RR: 0.63, 95%CI: 0.50-0.80, p=0.006; OR for DCR: 0.78; 95%CI: 0.64-0.94; p=0.002). Toxicities were more frequent in the combination treatment group and a significant value in term of risk ratio was reached for diarrhea (0.53, 95%CI: 0.36-0.79), nausea (0.74, 95%CI: 0.56-0.96), neutropenia (0.74, 95%CI: 0.62-0.89) and thrombocytopenia (0.59, 95%CI: 0.44-0.79). Conclusions: Combinationchemotherapy compared to gemcitabine alone significantly improves OS. However, this advantage seems to be marginal and at the cost of increased toxicity, suggesting the use of gemcitabine-based combination regimens only in selected patients. New approaches based on preclinical findings, in the era of targeted therapy, are eagerly awaited on this specific topic.
Effects of a structured intervention program to improve physical activity (PA) of adolescents and young adult cancer survivors (AYAs): Final results of the randomized Motivate AYA–MAYA trial.
Authors: Jannike Lisa Salchow, Wiebke Jensen, Barbara Koch, Julia von Grundherr, Simon Elmers, Gabriele Escherich, Rüdiger Reer, Carsten Bokemeyer, Julia Mann, Alexander Stein
Journal: Journal of Clinical Oncology (2019)

11518 Background: Major cardiovascular (CV) events are the most common late toxicities among AYAs. Although regular PA of vigorous intensity (≥ 9 metabolic equivalent [MET]-hours/week) lowers the risk for CV events and mortality, no larger randomized controlled trials on interventions are available. Our aim was to assess whether a 12-week structured intervention increases the vigorous PA of AYAs. Methods: AYAs aged 15 to 39 years, after curative intent cancer treatment with at least one CV risk factor, were randomized to usual-care control group (CG) and to intervention group (IG). The CG received standard recommendations, and the IG participated at a semi-structured interview and phone consulting focusing on PA and behavioral change. At baseline, post-intervention (12 wks), and at follow-up (52 wks), participants completed the International Physical Activity Questionnaire (IPAQ) and quality of life assessment (EORTC QLQ-C30). Primary endpoint was the rate of AYAs with ≥ 9 MET-hours/week of vigorous activity (IPAQ) at 12 weeks. This single center trial was registered (DRKS00009453). Results: Among 115 screened AYA 89 eligible patients were randomized; 69 (77.5%) completed the intervention and the endpoint assessment; 36 (52.2%) were in the IG and 33 (47.8%) in the CG. Median age was 24.3 years (range, 18 to 39). CV risk factors were use of anthracyclines (94.2%), chest radiation (47.8%), or both (44.9%). At baseline 49.2% of all AYAs reported to perform vigorous PA with at least 9 MET-hours/week, although reporting was individually biased. Post-intervention this rate significantly increased in the IG from 45.7% to 69.7% (p = 0.007), whereas in the CG only a modest non-significant increase was noted (53.3% to 65.6%, p = 0.134). Notably, upon long-term follow up (52 wks) AYAs did not keep their increased vigorous PA, whereas improved moderate PA was achieved (MET score in IG p = 0,044). Also, both groups reduced significantly the time they spent sitting from 6.5 (SD, 2.9) to 5.4 (SD, 2.7) hours/day (p = 0.001). Conclusions: Intensified PA counseling improves short term vigorous PA and long term moderate PA of AYAs and, should thus be part of survivorship programs. Further studies with AYAs will be required to establish reliable PA screening methods and to confirm the results in larger cohorts. Clinical trial information: DRKS00009453.
Estimating health-related costs of ten US climate-sensitive events in 2012: a retrospective study
Authors: Vijay S Limaye, Wendy Max, Juanita Constible, Kim Knowlton
Journal: The Lancet Planetary Health (2019)

BackgroundClimate change threatens human health, but there is a lack of evidence on the economic toll of these risks. Health-related cost estimates for climate-sensitive impacts illuminate an understudied impact of climate change and highlight how this threat is affecting sectors beyond property and infrastructure. Furthermore, cost estimates can guide health interventions and help public health professionals assess whether climate change adaptation measures are achieving their intended benefits.MethodsWe estimate mortality and morbidity costs associated with ten climate-sensitive case studies spanning eleven US states in 2012 (when the country experienced some of its warmest weather to date); the case studies include wildfires, extreme heat, West Nile Virus and Lyme disease, extreme precipitation and flooding, harmful algal blooms, allergenic pollen, ozone air pollution, and a major hurricane. We estimate the mortality and morbidity associated with each event using data reported in peer-reviewed epidemiology studies, state and federal data, and environmental public health tracking network data collected by state public health agencies. We augment this information with imputed incidence data from national healthcare utilisation statistics.FindingsApplying value of a statistical life and cost-of-illness approaches to publicly-available data from the Agency for Healthcare Research and Quality, we estimate total health-related costs associated with these case studies (from 917 deaths, 20 568 hospitalisations and 17 857 emergency department visits) of about $10·0 billion in 2018 dollars, with a sensitivity range of $2·7 billion to $24·6 billion.InterpretationBy better characterising these health damages in economic terms, this work helps characterise the burden that climate change already places on human health. In doing so, we provide a quantitative framework for broader estimation of climate-sensitive health-related costs. Expanded quantification of the budgetary pressures posed by climate change can help decision makers engage with the scale of the challenge and prioritise efficient adaptation strategies to protect public health.FundingNone.
Long-Term Outcomes of Treatment with Biological Agents in Eyes with Refractory, Active, Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis
Authors: Ahmed Al-Janabi, Amgad El Nokrashy, Lazha Sharief, Vivekka Nagendran, Sue Lightman, Oren Tomkins-Netzer
Journal: Ophthalmology (2019)
Amazon deforestation drives malaria transmission, and malaria burden reduces forest clearing: a retrospective study
Authors: Andrew J MacDonald, Erin A Mordecai
Journal: The Lancet Planetary Health (2019)

BackgroundDeforestation and other forms of land use change are among the most pressing anthropogenic environmental impacts. In Brazil, a recent resurgence of malaria paralleled rapid deforestation and settlement in the Amazon basin, yet empirical evidence of a deforestation-driven increase in malaria remains surprisingly equivocal. We hypothesise that an underlying cause of this ambiguity is that deforestation and malaria influence each other in bidirectional causal relationships, where deforestation increases malaria through ecological mechanisms and malaria simultaneously reduces deforestation through socioeconomic mechanisms.MethodsWe tested our hypotheses with a large and robust geospatial dataset encompassing 807 municipalities across 13 years and show that deforestation has a strong positive effect on human malaria incidence, controlling for variation over space and time and across gradients of land use intensification.FindingsOur results suggest that a 10% increase in deforestation leads to a 3·7% increase in Plasmodium falciparum malaria cases (about 1730 additional cases in 2008). The effect is larger in the interior and absent on the fringe of the Amazon where little forest remains. However, this strong effect is only detectable after controlling for a feedback of malaria burden on forest loss, whereby increased malaria burden significantly reduces forest clearing, possibly mediated by human behaviour or economic development. We estimated that for a 1% increase in P falciparum malaria, we would expect a 1·5% decrease in forest area cleared (about 235 fewer km2 lost in 2008).InterpretationThis bidirectional socioecological feedback between deforestation and malaria, which attenuates as land use intensifies, shows the intimate ties between environmental change and human health.FundingUS National Science Foundation Postdoctoral Research Fellowship in Biology (#1611767).