tbuckley/cabot-search huggingface dataset:
Genomic characteristics and prognostic significance of co‐mutated<i><scp>ASXL1</scp>/<scp>SRSF2</scp></i>acute myeloid leukemia
Authors: Daniel R. Richardson, David M. Swoboda, Dominic T. Moore, Steven M. Johnson, Onyee Chan, Jonathan Galeotti, Sonia Esparza, Mohammad O. Hussaini, Hendrick Van Deventer, Matthew C. Foster, Catherine C. Coombs, Nathan D. Montgomery, David A. Sallman, Joshua F. Zeidner
Journal: American Journal of Hematology (2021)

Abstract The ASXL1 and SRSF2 mutations in AML are frequently found in patients with preexisting myeloid malignancies and are individually associated with poor outcomes. In this multi‐institutional retrospective analysis, we assessed the genetic features and clinical outcomes of 43 patients with ASXL1 mut SRSF2 mut AML and compared outcomes to patients with either ASXL1 (n = 57) or SRSF2 (n = 70) mutations. Twenty‐six (60%) had secondary‐AML (s‐AML). Variant allele fractions suggested that SRSF2 mutations preceded ASXL1 mutational events. Median overall survival (OS) was 7.0 months (95% CI:3.8,15.3) and was significantly longer in patients with de novo vs s‐AML (15.3 vs 6.4 months, respectively; P = .04 on adjusted analysis). Compared to ASXL1 mut SRSF2 wt and ASXL1 wt SRSF2 mut , co‐mutated patients had a 1.4 and 1.6 times increase in the probability of death, respectively ( P = .049), with a trend towards inferior OS (median OS = 7.0 vs 11.5 vs 10.9 months, respectively; P = .10). Multivariable analysis suggests this difference in OS is attributable to the high proportion of s‐AML patients in the co‐mutated cohort (60% vs 32% and 23%, respectively). Although this study is limited by the retrospective data collection and the relatively small sample size, these data suggest that ASXL1 mut SRSF2 mut AML is a distinct subgroup of AML frequently associated with s‐AML and differs from ASXL1 mut SRSF2 wt / ASXL1 wt SRSF2 mut with respect to etiology and leukemogenesis.
Effectiveness of Systematic Echocardiographic Screening for Rheumatic Heart Disease in Nepalese Schoolchildren
Authors: Prahlad Karki, Surendra Uranw, Santosh Bastola, Rajan Mahato, Nikesh Raj Shrestha, Kunjang Sherpa, Sahadeb Dhungana, Ayodele Odutayo, Keshar Gurung, Naveen Pandey, Krishna Agrawal, Prashant Shah, Martina Rothenbühler, Peter Jüni, Thomas Pilgrim
Journal: JAMA Cardiology (2021)

Echocardiographic screening allows for early detection of subclinical stages of rheumatic heart disease among children in endemic regions.To investigate the effectiveness of systematic echocardiographic screening in combination with secondary antibiotic prophylaxis on the prevalence of rheumatic heart disease.This cluster randomized clinical trial included students 9 to 16 years of age attending public and private schools in urban and rural areas of the Sunsari district in Nepal that had been randomly selected on November 17, 2012. Echocardiographic follow-up was performed between January 7, 2016, and January 3, 2019.In the experimental group, children underwent systematic echocardiographic screening followed by secondary antibiotic prophylaxis in case they had echocardiographic evidence of latent rheumatic heart disease. In the control group, children underwent no echocardiographic screening.Prevalence of the composite of definite or borderline rheumatic heart disease according to the World Heart Federation criteria in experimental and control schools as assessed 4 years after intervention.A total of 35 schools were randomized to the experimental group (n = 19) or the control group (n = 16). After a median of 4.3 years (interquartile range [IQR], 4.0-4.5 years), 17 of 19 schools in the experimental group (2648 children; median age at follow-up, 12.1 years; IQR, 10.3-12.5 years; 1308 [49.4%] male) and 15 of 16 schools in the control group (1325 children; median age at follow-up, 10.6 years; IQR, 10.0-12.5 years; 682 [51.5%] male) underwent echocardiographic follow-up. The prevalence of definite or borderline rheumatic heart disease was 10.8 per 1000 children (95% CI, 4.7-24.7) in the control group and 3.8 per 1000 children (95% CI, 1.5-9.8) in the experimental group (odds ratio, 0.34; 95% CI, 0.11-1.07; P = .06). The prevalence in the experimental group at baseline had been 12.9 per 1000 children (95% CI, 9.2-18.1). In the experimental group, the odds ratio of definite or borderline rheumatic heart disease at follow-up vs baseline was 0.29 (95% CI, 0.13-0.65; P = .008).School-based echocardiographic screening in combination with secondary antibiotic prophylaxis in children with evidence of latent rheumatic heart disease may be an effective strategy to reduce the prevalence of definite or borderline rheumatic heart disease in endemic regions.ClinicalTrials.gov Identifier: NCT01550068.
Comparison of house dust mite sensitization profiles in allergic adults from Canada, Europe, South Africa and USA
Authors: Varun Muddaluru, Rudolf Valenta, Susanne Vrtala, Thomas Schlederer, James Hindley, Pascal Hickey, Mark Larché, Elena Tonti
Journal: Allergy (2021)

Sensitization to house dust mite (HDM) is a leading cause of allergic rhinitis and asthma. Despite more than 30 HDM-derived allergens having been identified to date, specific therapeutic approaches do not yet take into account the local sensitization profiles of patients. This study aimed to identify patterns of HDM sensitization in HDM-allergic adults living in distinct geographic areas, to inform the development of targeted diagnostic and therapeutic tools.Serum samples from 685 HDM-allergic subjects from Canada, Europe, South Africa, and the USA were tested for levels of IgE specific for 17 micro-arrayed HDM allergens by ImmunoCAP Immuno Solid-phase Allergen Chip (ISAC) technology.The results confirmed significant geographical variability in sensitization patterns and levels of IgE. In all areas, the major sensitizers were the group 1 and group 2 allergens and Der p 23. Der p 23 was a frequent sensitizer: 64% of the subjects had IgE specific for Der p 23, and 2.3% were monosensitized to it. In South Africa, Der p 23 was the dominant HDM allergen (86% prevalence) and Der p 7 achieved major allergen status (56%). IgE sensitization to HDM was influenced by asthmatic status, levels of allergen exposure, age, race-ethnicity and smoking status, but not by BMI.Sensitization profiles to HDM allergens differ considerably among distinct geographic areas, with Der p 7 and Der p 23 being major sensitizers in South Africa. Such heterogeneity should be taken into account in the diagnosis and treatment of HDM-allergic patients.
EULAR recommendations for the reporting of ultrasound studies in rheumatic and musculoskeletal diseases (RMDs)
Authors: Félicie Costantino, Loreto Carmona, Maarten Boers, Marina Backhaus, Peter V Balint, George A Bruyn, Robin Christensen, Philip G Conaghan, Ricardo J O Ferreira, Juan Luis Garrido-Castro, Francis Guillemin, Hilde Berner Hammer, Désirée van der Heijde, Annamaria Iagnocco, Marion C Kortekaas, Robert BM Landewé, Peter Mandl, Esperanza Naredo, Wolfgang A Schmidt, Lene Terslev, Caroline B Terwee, Ralf Thiele, Maria-Antonietta D'Agostino
Journal: Annals of the Rheumatic Diseases (2021)

To produce European League Against Rheumatism (EULAR) recommendations for the reporting of ultrasound studies in rheumatic and musculoskeletal diseases (RMDs).Based on the literature reviews and expert opinion (through Delphi surveys), a taskforce of 23 members (12 experts in ultrasound in RMDs, 9 in methodology and biostatistics together with a patient research partner and a health professional in rheumatology) developed a checklist of items to be reported in every RMD study using ultrasound. This checklist was further refined by involving a panel of 79 external experts (musculoskeletal imaging experts, methodologists, journal editors), who evaluated its comprehensibility, feasibility and comprehensiveness. Agreement on each proposed item was assessed with an 11-point Likert scale, grading from 0 (total disagreement) to 10 (full agreement).Two face-to-face meetings, as well as two Delphi rounds of voting, resulted in a final checklist of 23 items, including a glossary of terminology. Twenty-one of these were considered 'mandatory' items to be reported in every study (such as blinding, development of scoring systems, definition of target pathologies) and 2 'optional' to be reported only if applicable, such as possible confounding factors (ie, ambient conditions) or experience of the sonographers.An EULAR taskforce developed a checklist to ensure transparent and comprehensive reporting of aspects concerning research and procedures that need to be presented in studies using ultrasound in RMDs. This checklist, if widely adopted by authors and editors, will greatly improve the interpretability of study development and results, including the assessment of validity, generalisability and applicability.
THU0106 The expression of ip-10 and mig chemokines in rheumatoid synovial tissue
Authors: J Niederlova, J Vencovsky, O Krystufkova, D Veigl, S Ruzickova
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Rheumatoid arthritis (RA) is characterised by chronic synovial inflammation, which results in progressive polyarticular destruction. Immunohistological characterisation of infiltrating cells may help to elucidate the role of specific chemokines and their receptors in pathological processes. In this regard we previously described high expression of chemokine receptor CXCR-3 in synovial tissue. Now we have investigated expression of chemotactic factors IP-10 and Mig, which are ligands for CXCR-3. <h3>Methods</h3> Synovial tissue samples were obtained from 5 RA patients who have undergone total joint replacement or synovectomy. Native cryostat tissue sections were examined for CD3, CD4, CD8, CD19, CD14, CD31, CD68, CXCR-3, IP-10 and Mig with mouse anti-human monoclonal antibodies. Two-step visualisation with DAKO EnVision was applied. This visualisation system is based on enzyme-conjugated dextrane polymer, which carriers secondary antibody molecules. Negative controls were performed by using izotype-matched irrelevant antibodies. <h3>Results</h3> A strong positive reaction for CXCR-3 was detected on lymphocytes and macrophage-like synoviocytes; weak and irregular staining was seen in endothelial cells. IP-10 and Mig were expressed in all tissue samples. The positivity was found mainly in the lymphoid infiltrating cells and the staining also co-localised with CD68 positive synoviocytes. In addition, a stronger expression of IP-10 than of Mig was seen, particularly in tissues with a strong vascularity. Endothelial cells were strongly positive for IP-10 and weakly also for Mig. In general, IP-10 and Mig staining was observed in sporadic aggregates surrounding blood vessels. <h3>Conclusion</h3> High expression of IP-10 and Mig on a majority of the infiltrating cells suggests a role for interferon-g in RA inflammation, as IP-10 and Mig are induced by this cytokine. They may play a role in the attraction of CD4 positive T cells into the synovial environment. Furthermore, a frequent expression of CXCR3 on synovial resident cells propounds a possible role for IP-10 and Mig in their activation, perhaps even in the autocrine fashion. This work was supported by a grant NI/6459 from IGA MZ CR.
Significant lipid and neutrophil accumulation and active inflammasome in high BMI tumor regions of human pancreatic ductal adenocarcinoma.
Authors: Ahmed Khattab, Sunita Patruni, Yesica Garciafigueroa, Brett Phillips, Carl Engman, Nazia Khatoon, Karthik Shankar, Ali Rizvi, Stacey Miller, Nick Giannoukakis, Dulabh K. Monga
Journal: Journal of Clinical Oncology (2021)

438 Background: Obesity is an established risk factor for cancer and cancer-related mortality. Adipocytes may act as a “damage” signal resulting in the accumulation of innate immune cells, fueling an inflammatory micro-environment. Among the innate immune cells, tumor-associated neutrophils (TANs) are confirmed to accumulate inside the tumor. As obesity is a significant risk factor for a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), we hypothesize that obesity-driven adipose fuels the progression of PDAC in a TAN and inflammasome-facilitated manner. This may happen through several mechanisms, including genomic instability of aggressive PDAC clonal populations. Methods: Tissue from resected tumors of PDAC patients (n = 44) with a body-mass index (BMI) &gt; 27 (obese [n = 21]) and BMI &lt; 22 (normal [n = 23]) were incubated with anti-human CD66b antibodies and detected using standard immunofluorescent microscopy techniques. Images were acquired in a Zeiss Axioplan microscope workstation and analyzed by ZEN and Metamorph software. Results: We identified the presence of adipocytes in all tissue sections and CD66b+ neutrophils in all tissue sections of normal BMI patients and in 81% of high BMI patients. There is a significantly greater density of adipocytes in the tumor environment when compared to adjacent normal areas, suggesting that these cells are acting as a damage signal. Our novel data also shows that high BMI results in a significantly higher neutrophil count in tumor specific tissue when compared to patients with a low BMI. These data suggest an association between BMI and inflammasome accumulation in the tumor environment. Conclusions: Our data uniquely shows that CD66b+ neutrophils tend to accumulate inside PDAC in high BMI patients and this is associated with intra-tumoral active inflammasomes. The higher concentrations of these inflammasomes in higher BMI patients may be of mechanistic relevance in understanding how inflammation induces progression of PDAC. A larger cohort of tissues from PDAC obtained from low and high BMI individuals will be needed to test our hypothesis and to begin to decipher the role of obesity on inflammation and PDAC progression.
AB0171 Impact of degenerative radiological abnormalities and vertebral fractures on the evaluation of spinal bone density in women with osteoporosis
Authors: L Paiva, S Filardi, AM Pinto-Neto, A Samara, JF Marques-Neto
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Osteophytes and lumbar spine fractures can hinder bone density interpretation. <h3>Objectives</h3> The objective of this study was to establish the relationship between densitometric measurements and degenerative radiological findings of the lumbar spine, in women with osteoporosis. <h3>Methods</h3> The study consisted of ninety-six postmenopausal women presenting osteoporosis in their lumbar spine bone density, DEXA, LUNAR-DPX. Fractures, osteophytes and aortic calcifications were evaluated by simple x-rays of thoracic and lumbar spine. <h3>Results</h3> The X-rays confirmed lumbar fractures in 24.7%, osteophytes in 33.3% and calcifications of the aorta in 30.2%. The mean BMD was 0.783 g/cm<sup>2</sup> and the mean T-score was ?3.47 DP. Neither fractures, nor aortic calcifications had significant influence on BMD (p = 0,36 e p = 0,09 respectively) despite the fractured vertebrae having greater BMD (p &lt; 0,02). Patients with lumbar spine osteophytes showed greater BMD (p = 0,04). Only osteophytosis was associated to lumbar spine BMD (p = 0,008). <h3>Conclusion</h3> Osteophytes and lumbar spine fractures can hinder bone density interpretation. Based on these findings, the interpretation of densitometric results should be carried out together with that of a simple lumbar spine X-ray. <h3>References</h3> Heaney RP, Recker RR, Saville PD. Menopasal changes in bone remodeling. J Lab Clin Med. 1978;92:953–63 Kleerekoperm KS. <i>Metabolic bone diseases sec IV primer on the metabolic diseases and disorders of mineral metabolism</i>. 4th edn. Philadephia: Lippincott Williams &amp; Wilkins, 1999
Time-ordered comorbidity correlations identify patients at risk of mis- and overdiagnosis
Authors: Isabella Friis Jørgensen, Søren Brunak
Journal: npj Digital Medicine (2021)

Abstract Diagnostic errors are common and can lead to harmful treatments. We present a data-driven, generic approach for identifying patients at risk of being mis- or overdiagnosed, here exemplified by chronic obstructive pulmonary disease (COPD). It has been estimated that 5–60% of all COPD cases are misdiagnosed. High-throughput methods are therefore needed in this domain. We have used a national patient registry, which contains hospital diagnoses for 6.9 million patients across the entire Danish population for 21 years and identified statistically significant disease trajectories for COPD patients. Using 284,154 patients diagnosed with COPD, we identified frequent disease trajectories comprising time-ordered comorbidities. Interestingly, as many as 42,459 patients did not present with these time-ordered, common comorbidities. Comparison of the individual disease history for each non-follower to the COPD trajectories, demonstrated that 9597 patients were unusual. Survival analysis showed that this group died significantly earlier than COPD patients following a trajectory. Out of the 9597 patients, we identified one subgroup comprising 2185 patients at risk of misdiagnosed COPD without the typical events of COPD patients. In all, 10% of these patients were diagnosed with lung cancer, and it seems likely that they are underdiagnosed for lung cancer as their laboratory test values and survival pattern are similar to such patients. Furthermore, only 4% had a lung function test to confirm the COPD diagnosis. Another subgroup with 2368 patients were found to be at risk of “classically” overdiagnosed COPD that survive &gt;5.5 years after the COPD diagnosis, but without the typical complications of COPD.
How can I boost team morale?
Authors: Abi Rimmer
Journal: BMJ (2021)

How can I boost team morale?The wellbeing of our teams is more important than ever.Abi Rimmer asks experts how we can boost our colleagues' morale Abi Rimmer Promote small acts of kindnessHeidi Edmundson, emergency medicine consultant, says, "It's important to remember that looking after morale is not the same as making people happy.So, focus on creating an environment where everyone feels comfortable expressing their feelings freely and without judgment.Model this and be open about how you're feeling too.
Incidence, mortality and hospital resource utilization in patients with gastrointestinal cancer and malnutrition: A nationwide analysis.
Authors: Vatsala Katiyar, Ishaan Vohra, Prasanth Lingamaneni, Binav Baral, Rohit Kumar
Journal: Journal of Clinical Oncology (2021)

466 Background: Malignancies are associated with a high prevalence of cachexia, protein energy malnutrition (PEM) and failure to thrive. We analyzed the National inpatient Sample database (NIS) to understand the temporal trends and differences between gastrointestinal cancers (GIC) patients with and without malnutrition. Methods: All adults admitted with GIC including esophageal, gastric, pancreatic, hepatic, gall bladder, small and large intestine and anal cancers from 2012-2016 were identified from the NIS using the ICD 9 and ICD 10 codes. We analyzed the temporal trends of mortality and resource utilization. Multivariable logistic regression was used to evaluate the risk factors for malnutrition in patients with GIC. Results: There were 2,645,285 GIC inpatient admissions between 2012-2016, out of which 6.1% patients died. 11.1% (±0.22) patients had PEM and three most common GIC associated with PEM were Esophageal (19.7±0.24%), gastric (16.5±0.22%) and small intestine (15.2±0.41%). On multivariate analysis, PEM was more common in male gender (OR: 1.07, 95% CI:1.05-1.08, P&lt;0.01), African- American race (OR:1.14, 95% CI: 1.10-1.17, P&lt;0.01) and Charlson comorbidity index &gt;=2(OR:1.5, 95% 1.42-1.51, P&lt;0.01). Malnourished patients were often terminally ill (48.8% vs 39.8%), in intensive care unit (7.89% vs 3.75%), were more likely to be seen by palliative care team (17.6 % vs 9.8%) and were more likely to die (9.6% vs 5.70%, OR-1.76; p &lt;0.01). The incidence, mortality, and total charge of PEM in patients with GIC significantly increased from 2012 to 2016 as shown in the table below. Conclusions: Malnourished patients with GIC tend to have more advanced disease and have an increased mortality as compared to patients with adequate nutritional status. Optimization of their nutritional status can greatly improve outcomes and curb healthcare costs. [Table: see text]
Overall survival based on MSI and BRAF mutation status for stage II/III colorectal cancer.
Authors: Sophiya Karki, Rashna Madan, Sarah Schmitt, Ziyan Y. Pessetto, Andrew K. Godwin, Weijing Sun, Anup Kasi
Journal: Journal of Clinical Oncology (2021)

132 Background: Colorectal cancer (CRC) is the second leading cause of cancer-associated deaths in the United States. Some of the poor prognostic factors for metastatic CRC (mCRC) include BRAF V600E mutation and microsatellite instability (MSI) that result from mutation or loss of mismatch-repair genes. While the prognostic value of MSI-high CRC for early-stage patients treated with resection and adjuvant chemotherapy is favorable, the prognostic value of BRAF mutation is still unclear. Furthermore, the impact of BRAF mutation with concurrent microsatellite instability on overall survival has not been well investigated. Methods: Here, we collected BRAF mutation status and MSI status of stage II/III CRC patients (n=106) treated at the University of Kansas Cancer Center between September 2009 and July 2020 and compared overall survival between 4 subtypes:MSI-H/BRAF mutant (n=16), MSS/BRAF mutant (n=4), MSI-H/BRAF WT (n=17) and MSS/BRAF WT (n=69), further stratifying patients by age at diagnosis and tumor location. Molecular data were obtained from molecular oncology laboratory as PCR or IHC-based or acquired from outside records. Subgroup analyses were done for stage II and stage III cancers. Results: Table shows the patient characteristics. From our preliminary analysis, MSI-H CRC was found to be primarily a right-sided tumor (MSI-H/BRAF mutant: 94% and MSI-H/BRAF WT 76%). On the contrary, MSS CRC had a more heterogenous localization, spanning left colon, right colon and rectum. In our patient cohort, median survival was not reached for stage II patients whereas for stage III patients, BRAF mutation was associated with poor median survival irrespective of MSI status (MSS/BRAF mutant: 27 months and MSI-H/BRAF mutant 29 months). Median overall survival was found to be 87 months, not reached, 27 months and 29 months for MSS/BRAF WT, MSI-H/BRAF WT, MSS/BRAF mutant and MSI-H/BRAF mutant, respectively. Although associated with poor survival, MSI-H/BRAF mutant displayed later age at diagnosis (mean age 73) compared to MSS/BRAF mutant (mean age 60, p-value&lt;0.029). Conclusions: Our finding suggests that BRAF mutation has poor prognosis even at earlier stages of the disease and that MSS/BRAF mutation, in particular, has the worst prognostic features. These findings highlight the need for BRAF-targeted therapy for CRC at any stage. Due to small sample size, however, our results warrant validation in a larger cohort. [Table: see text]