tbuckley/cabot-search huggingface dataset:
Cell therapy with adipose tissue-derived stem/stromal cells for elastase-induced pulmonary emphysema in rats
Authors: Naoki Furuya, Mitsuko Takenaga, Teruomi Miyazawa
Journal: European Respiratory Journal (2012)

Background: Studies demonstrating lung repair by stem cells or growth factors have been reported in animal emphysema. We focused on adipose tissue-derived stromal/stem cells (ASC) for regenerative medicine, since it has a high potential to secrete multiple angiogenic factors and differentiate various kinds of cells.  Aim: To demonstrate the therapeutic impact of ASC transplantation and to elucidate mechanisms of the effects in rat emphysema models.  Methods: ASC were isolated from rat subcutaneous adipose tissue. Emphysema was induced by intratracheal instillation of porcine pancreatic elastase (PPE). One week after PPE, cell transplantation was performed intravenously. One and 2 weeks after transplantation, we assessed pulmonary function and histopathological changes and measurement of chemokine levels in lung tissue.  Results: ASC transplantation restored pulmonary function to near normal levels and enlargement of the alveolar airspaces was also inhibited. Immunohistochemical analysis revealed some transplanted ASC were localized at damaged alveolar spaces. Vascular endothelial growth factor (VEGF) was significantly reduced by PPE. After ASC transplantation, VEGF level was not reduced. Hepatocyte growth factor (HGF) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) levels were significantly higher than PPE.  Conclusion: Transplantation of ASC for emphysema rats improved pulmonary function and inhibit enlargement of the airspaces. Secretion of HGF, VEGF, and CINC-1 by surviving ASC after transplantation may have contributed to lung repair. Cell theropy with ASC may be new therapeutic strategy to improve pulmonary function and inhibit alveolar destruction.
Religious Service Attendance and Deaths Related to Drugs, Alcohol, and Suicide Among US Health Care Professionals
Authors: Ying Chen, Howard K. Koh, Ichiro Kawachi, Michael Botticelli, Tyler J. VanderWeele
Journal: JAMA Psychiatry (2020)

The increase in deaths related to drugs, alcohol, and suicide (referred to as deaths from despair) has been identified as a public health crisis. The antecedents associated with these deaths have, however, seldom been investigated empirically.To prospectively examine the association between religious service attendance and deaths from despair.This population-based cohort study used data extracted from self-reported questionnaires and medical records of 66 492 female registered nurses who participated in the Nurses' Health Study II (NHSII) from 2001 through 2017 and 43 141 male health care professionals (eg, dentist, pharmacist, optometrist, osteopath, podiatrist, and veterinarian) who participated in the Health Professionals Follow-up Study (HPFS) from 1988 through 2014. Data on causes of death were obtained from death certificates and medical records. Data analysis was conducted from September 2, 2018, to July 14, 2019.Religious service attendance was self-reported at study baseline in response to the question, "How often do you go to religious meetings or services?"Deaths from despair, defined specifically as deaths from suicide, unintentional poisoning by alcohol or drug overdose, and chronic liver diseases and cirrhosis. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) of deaths from despair by religious service attendance at study baseline, with adjustment for baseline sociodemographic characteristics, lifestyle factors, psychological distress, medical history, and other aspects of social integration.Among the 66 492 female participants in NHSII (mean [SD] age, 46.33 [4.66] years), 75 incident deaths from despair were identified (during 1 039 465 person-years of follow-up). Among the 43 141 male participants in HPFS (mean [SD] age, 55.12 [9.53] years), there were 306 incident deaths from despair (during 973 736 person-years of follow-up). In the fully adjusted models, compared with those who never attended religious services, participants who attended services at least once per week had a 68% lower hazard (HR, 0.32; 95% CI, 0.16-0.62) of death from despair in NHSII and a 33% lower hazard (HR, 0.67; 95% CI, 0.48-0.94) of death from despair in HPFS.The findings suggest that religious service attendance is associated with a lower risk of death from despair among health care professionals. These results may be important in understanding trends in deaths from despair in the general population.
Does the addition of biologic agents to chemotherapy in patients with unresectable colorectal cancer metastases result in a higher proportion of patients undergoing resection? A systematic review and meta-analysis.
Authors: Jessica Bogach, Oren Hannun Levine, Leyo Ruo, Pablo Emilio Serrano Aybar
Journal: Journal of Clinical Oncology (2017)

690 Background: The likelihood of converting unresectable metastatic colorectal cancer (CRC) to operable disease with systemic therapy is unknown. The purpose of this study was to determine the proportion of patients with unresectable CRC metastases that become resectable on combination systemic therapy, and whether biologic agents (antiantiogenics, anti-EGFR and multitargeted agents) improve the rate of resection (primary outcome). Methods: We searched Medline, Embase, CENTRAL and PubMed for randomized controlled trials comparing chemotherapy and biologics (intervention) vs. combination chemotherapy alone (control) in patients with unresectable CRC metastases. Study selection, data abstraction, risk of bias and quality of the evidence assessment were carried out in duplicate. Secondary outcomes included overall survival (OS) and progression free survival (PFS). Risk of bias was assessed using the Cochrane tool. Statistical heterogeneity was calculated using chi-squared and I 2 . Clinical heterogeneity was explored via subgroup analyses. The quality of the evidence was assessed using GRADE. Protocol was published in PROSPERO. Results: Of 7954 abstracts retrieved, 12 studies were analyzed and 8 reported the primary outcome, with 2604 intervention and 2661 control patients. The proportion of patients resected was higher in the intervention group, Relative Risk 1.36, 95% confidence interval (CI) 1.08-1.69, p = 0.008. The absolute risk of undergoing resection was 48 per 1000 (control); compared to 65 per 1000 (intervention). There was no difference in OS, Hazard Ratio (HR) 0.91, 95% CI 0.82-1.01. PFS was better in the intervention group (HR 0.83, 95% CI 0.74-0.92). Overall the risk of bias for the included studies was low. Statistical test for heterogeneity was low (I 2 was 0%, p = 0.72). There was significant clinical heterogeneity, which was not explained with subgroup analyses. The quality of the evidence (GRADE) was moderate. Conclusions: The addition of biologic agents to systemic chemotherapy in patients with unresectable CRC metastasis improves resectability and PFS but not OS.
Abstract 5591: Clinical significance of EML4-ALK fusion gene and association with EGFR and KRAS gene mutations in 208 Chinese patients with non-small cell lung cancer.
Authors: Jun Chen, Hongyu Liu, Ying Li, Yongwen Li, Tong Yang, Sen Wei, Jing Wang, Qinghua Zhou
Journal: Cancer Research (2013)

Abstract EML4-ALK fusion gene has been recently identified in a small subset of non-small cell lung cancer (NSCLC) patients who respond positively to ALK inhibitors. The characteristics of EML4-ALK fusion gene in Chinese patients with NSCLC are poorly understood. Here, we report on the prevalence of EML4-ALK, EGFR status and KRAS mutations in 208 Chinese patients with NSCLC. EGFR mutations were found in 24.5% (51/208) of patients. In concordance with previous reports, these mutations were identified at high frequencies in females (47.5% vs 15.0% in males; P &amp;gt; 0.05); never-smokers (42.3% vs 13.9% in smokers; P &amp;lt; 0.05), and adenocarcinoma patients (44.2% vs 8.0% in non-adenocarcinoma patients; P &amp;lt; 0.05). There were only 2.88% (6/208) patients with KRAS mutations in our study group. We identified 7 patients who harbored the EML4-ALK fusion gene (3.37%, 7/208), including 4 cases with variant 3 (57.1%), 2 with variant 1, and 1 with variant 2. All positive cases corresponded to female patients (11.5%, 7/61). Six of the positive cases were non-smokers (7.69%, 6/78). The incidence of EML4-ALK translocation in female, non-smoking adenocarcinoma patients was as high as 15.2% (5/33). No EGFR/KRAS mutations were detected among the EML4-ALK positive patients. Pathological analysis showed no difference between solid signet-ring cell pattern (4/7) and mucinous cribriform pattern (3/7) in ALK-positive patients. Immunostaining showed intratumor heterogeneity of ALK rearrangement in primary carcinomas and 50% (3/6) of metastatic tumors with ALK-negative staining. Meta-analysis demonstrated that EML4-ALK translocation occurred in 4.84% (125/2580) of unselected patients with NSCLC, and was also predominant in non-smoking patients with adenocarcinoma. Taken together, EML4-ALK translocations were infrequent in the entire NSCLC patient population, but were frequent in the NSCLC subgroup of female, non-smoker, adenocarcinoma patients. There was intratumor heterogeneity of ALK rearrangement in primary carcinomas and at metastatic sites. Citation Format: Jun Chen, Hongyu Liu, Ying Li, Yongwen Li, Tong Yang, Sen Wei, Jing Wang, Qinghua Zhou. Clinical significance of EML4-ALK fusion gene and association with EGFR and KRAS gene mutations in 208 Chinese patients with non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5591. doi:10.1158/1538-7445.AM2013-5591
Case 26-1995
Authors: H.M. Dick, A.E. Rosenberg
Journal: New England Journal of Medicine (1995)

Presentation of CaseA 29-year-old woman was admitted to the hospital because of a pathologic fracture of the right femur.The patient had been well until 31 days earlier, when she crawled under a machine at work to connect a belt and began to have pain in the anterior portion of the right thigh, which became progressively worse. Five days later x-ray films of the thigh, obtained elsewhere, were normal. The pain persisted, and the patient began to walk on crutches.One day before admission an orthopedic consultant made a diagnosis of a “sprain.” On the next morning the patient . . .
Chromosomal alterations in oligodendroglial tumors over multiple surgeries: Is progression associated with change in 1p/19q status?
Authors: B. Campbell, D. Horsman, J. Maguire, S. Young, D. Curman, R. Ma, B. Thiessen
Journal: Journal of Clinical Oncology (2007)

10577 Background: There is morphologic and genotypic heterogeneity of oligodendroglial neoplasms. Tumors with loss of heterozygosity (LOH) of 1p and/or 19q are associated with increased chemo-sensitivity and survival. Despite treatment, rates of recurrence and malignant transformation are high. The pathogenesis of treatment-resistance is unknown. We aim to determine if tumour progression is associated with a proliferation of clonagens with retention of heterozygosity (ROH) of 1p, or if progressing tumours remain 1p/19q LOH. Methods: Between 1/1/2001 and 7/31/2006, 24 patients with oligodendroglial neoplasms, and possessing serial biopsies taken at diagnosis and at progression, were identified. Using PCR amplification of multiple microsatellite markers, a total of 53 tumour specimens were available for LOH analysis of 1p and 19q; 40 were also tested for 9p and 10q. Results: At diagnosis, the median age was 34 (24–66) years and 14 were male. Using the WHO criteria, 19 tumors were Grade II oligodendrogliomas or oligoastrocytomas, and 5 were high grade. The most common genomic status was 19q LOH (88%); 54% had 1p LOH. Of the 13 primary biopsies with 1p LOH, 11 had 19q LOH, 1 had 19q ROH, and 1 was 19q non-informative. A further 2 primaries were mixed 1p LOH/ROH, and 9 were 1p ROH. At progression, 10 of 11 patients with 1p/19q LOH had persistent co-deletion. The patient with 1p LOH and 19q ROH at diagnosis, had 1p/19q LOH at progression. Of the mixed 1p primaries, 1 was 1p ROH, and the other remained mixed LOH/ROH at progression. 8 of 9 primaries with 1p ROH remained 1p ROH. There was also little heterogeneity of 9p and 10q between primary and progressive tumours. Using Kaplain-Meier analysis, mean overall survival (OS) for the group was 102 (95% CI: 77–127) months. Mean progression-free survival was 52 (95% CI: 33–72) months. OS was not statistically significant between patients with 1p LOH and 1p ROH primary tumours. Conclusions: 91% of repeat biopsies of oligodendroglial tumors, demonstrated persistent 1p/19q LOH. Therefore, progression of 1p/19q LOH primary tumours is not due to a proliferating sub-group of chemo-resistant, 1p ROH clonagens. We propose that additional mutations contribute to this aggressive phenotype. No significant financial relationships to disclose.
INDEPENDENT PREDICTORS OF MACE AT DIFFERENT TIME POINTS AFTER THE TREATMENT OF NON-SELECTED PATIENTS WITH DRUG-ELUTING STENTS: AN ANALYSIS OF THE DESIRE REGISTRY
Authors: Jose de Ribamar Costa, Amanda Sousa, Adriana Moreira, Ricardo Costa, Dimytri Siqueira, Manuel Cano, Galo Maldonado, Cantídio Campos Neto, Lucas Damiani, Ricardo Pavanello, J. Eduardo Sousa
Journal: Journal of the American College of Cardiology (2016)
Long Survival and Prolonged Remission after Surgery and Chemotherapy in a Metastatic Mismatch Repair Deficient Pancreatic Neuroendocrine Carcinoma with MLH1/PMS2 Immunodeficiency and Minimal Microsatellite Shift
Authors: Alessandro Vanoli, Vittorio Perfetti, Daniela Furlan, Giuseppe Neri, Alessandra Viglio, Fausto Sessa, Michele Martino, Antonio Di Sabatino, Enrico Solcia, Stefano La Rosa
Journal: Endocrine Pathology (2020)
Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome
Authors: Puja Mehta, Randy Q Cron, James Hartwell, Jessica J Manson, Rachel S Tattersall
Journal: The Lancet Rheumatology (2020)

The term cytokine storm syndromes describes conditions characterised by a life-threatening, fulminant hypercytokinaemia with high mortality. Cytokine storm syndromes can be genetic or a secondary complication of autoimmune or autoinflammatory disorders, infections, and haematological malignancies. These syndromes represent a key area of interface between rheumatology and general medicine. Rheumatologists often lead in management, in view of their experience using intensive immunosuppressive regimens and managing cytokine storm syndromes in the context of rheumatic disorders or infection (known as secondary haemophagocytic lymphohistiocytosis or macrophage activation syndrome [sHLH/MAS]). Interleukin (IL)-1 is pivotal in hyperinflammation. Anakinra, a recombinant humanised IL-1 receptor antagonist, is licenced at a dose of 100 mg once daily by subcutaneous injection for rheumatoid arthritis, systemic juvenile idiopathic arthritis, adult-onset Still's disease, and cryopyrin-associated periodic syndromes. In cytokine storm syndromes, the subcutaneous route is often problematic, as absorption can be unreliable in patients with critical illness, and multiple injections are needed to achieve the high doses required. As a result, intravenous anakinra is used in clinical practice for sHLH/MAS, despite this being an off-licence indication and route of administration. Among 46 patients admitted to our three international, tertiary centres for sHLH/MAS and treated with anakinra over 12 months, the intravenous route of delivery was used in 18 (39%) patients. In this Viewpoint, we describe current challenges in the management of cytokine storm syndromes and review the pharmacokinetic and safety profile of intravenous anakinra. There is accumulating evidence to support the rationale for, and safety of, intravenous anakinra as a first-line treatment in patients with sHLH/MAS. Intravenous anakinra has important clinical relevance when high doses of drug are required or if patients have subcutaneous oedema, severe thrombocytopenia, or neurological involvement. Cross-speciality management and collaboration, with the generation of international, multi-centre registries and biobanks, are needed to better understand the aetiopathogenesis and improve the poor prognosis of cytokine storm syndromes.
Type I IFN immunoprofiling in COVID-19 patients
Authors: Sophie Trouillet-Assant, Sebastien Viel, Alexandre Gaymard, Sylvie Pons, Jean-Christophe Richard, Magali Perret, Marine Villard, Karen Brengel-Pesce, Bruno Lina, Mehdi Mezidi, Laurent Bitker, Alexandre Belot, William Mouton, Guy Oriol, Christelle Compagnon, Laurence Generenaz, Valérie Cheynet, Florence Ader, Agathe Becker, Nicholas Benech, Pierre Chauvelot, Christian Chidiac, Anne Conrad, Tristan Ferry, Patrick Miailhes, Thomas Perpoint, Marielle Perry, Cécile Pouderoux, Sandrine Roux, Claire Triffault-Fillit, Florent Valour, Yonis Hodane, Louis Chauvelot, Paul Chabert, Judith Provoost, Guillaume David, Laure Folliet, Pierre Lecam, Geneviève Billaud, Maude Bouscambert, Vanessa Escuret, Emilie Frobert, Antonin Bal, Grégory Destras, Laurence Josset, Florence Morfin, Clément Munier, Martine Valette, Fabienne Venet, Lorna Garnier, Rémi Pescarmona, Christine Lombard, Thierry Walzer
Journal: Journal of Allergy and Clinical Immunology (2020)
The Changing Face of Adrenoleukodystrophy
Authors: Jia Zhu, Florian Eichler, Alessandra Biffi, Christine N Duncan, David A Williams, Joseph A Majzoub
Journal: Endocrine Reviews (2020)

Adrenoleukodystrophy (ALD) is a rare X-linked disorder of peroxisomal oxidation due to mutations in ABCD1. It is a progressive condition with a variable clinical spectrum that includes primary adrenal insufficiency, myelopathy, and cerebral ALD. Adrenal insufficiency affects over 80% of ALD patients. Cerebral ALD affects one-third of boys under the age of 12 and progresses to total disability and death without treatment. Hematopoietic stem cell transplantation (HSCT) remains the only disease-modifying therapy if completed in the early stages of cerebral ALD, but it does not affect the course of adrenal insufficiency. It has significant associated morbidity and mortality. A recent gene therapy clinical trial for ALD reported short-term MRI and neurological outcomes comparable to historical patients treated with HSCT without the associated adverse side effects. In addition, over a dozen states have started newborn screening (NBS) for ALD, with the number of states expecting to double in 2020. Genetic testing of NBS-positive neonates has identified novel variants of unknown significance, providing further opportunity for genetic characterization but also uncertainty in the monitoring and therapy of subclinical and/or mild adrenal insufficiency or cerebral involvement. As more individuals with ALD are identified at birth, it remains uncertain if availability of matched donors, transplant (and, potentially, gene therapy) centers, and specialists may affect the timely treatment of these individuals. As these promising gene therapy trials and NBS transform the clinical management and outcomes of ALD, there will be an increasing need for the endocrine management of presymptomatic and subclinical adrenal insufficiency. (Endocrine Reviews 41: 1 - 17, 2020).
Multiple Sclerosis and Amyotrophic Lateral Sclerosis
Authors: Leonard T. Kurland, Donald W. Mulder, Knut B. Westlund
Journal: New England Journal of Medicine (1955)

Amyotrophic Lateral SclerosisClinical and Pathological CharacteristicsAmyotrophic lateral sclerosis is used here synonymously with the term "progressive motor-system disease." With its clinical components, progressive muscular atrophy and progressive bulbar palsy, it is a disease in which slowly progressive degeneration of anterior-horn cells in the spinal cord and of motor nuclei in the brain stem is the most prominent feature. Betz cells in the motor cortex may also degenerate, with secondary degeneration of the corticospinal and corticobulbar tracts.27 Muscular atrophy, which is secondary to lesions of the motor cells of the spinal cord, is nearly always pronounced at the time . . .
Risk stratification in pulmonary arterial hypertension using Bayesian analysis
Authors: Manreet K. Kanwar, Mardi Gomberg-Maitland, Marius Hoeper, Christine Pausch, David Pittrow, Geoff Strange, James J. Anderson, Carol Zhao, Jacqueline V. Scott, Marek J. Druzdzel, Jidapa Kraisangka, Lisa Lohmueller, James Antaki, Raymond L. Benza
Journal: European Respiratory Journal (2020)

Background Current risk stratification tools in pulmonary arterial hypertension (PAH) are limited in their discriminatory abilities, partly due to the assumption that prognostic clinical variables have an independent and linear relationship to clinical outcomes. We sought to demonstrate the utility of Bayesian network-based machine learning in enhancing the predictive ability of an existing state-of-the-art risk stratification tool, REVEAL 2.0. Methods We derived a tree-augmented naïve Bayes model (titled PHORA) to predict 1-year survival in PAH patients included in the REVEAL registry, using the same variables and cut-points found in REVEAL 2.0. PHORA models were validated internally (within the REVEAL registry) and externally (in the COMPERA and PHSANZ registries). Patients were classified as low-, intermediate- and high-risk (&lt;5%, 5–20% and &gt;10% 12-month mortality, respectively) based on the 2015 European Society of Cardiology/European Respiratory Society guidelines. Results PHORA had an area under the curve (AUC) of 0.80 for predicting 1-year survival, which was an improvement over REVEAL 2.0 (AUC 0.76). When validated in the COMPERA and PHSANZ registries, PHORA demonstrated an AUC of 0.74 and 0.80, respectively. 1-year survival rates predicted by PHORA were greater for patients with lower risk scores and poorer for those with higher risk scores (p&lt;0.001), with excellent separation between low-, intermediate- and high-risk groups in all three registries. Conclusion Our Bayesian network-derived risk prediction model, PHORA, demonstrated an improvement in discrimination over existing models. This is reflective of the ability of Bayesian network-based models to account for the interrelationships between clinical variables on outcome, and tolerance to missing data elements when calculating predictions.
The complexity of T cell–mediated penicillin hypersensitivity reactions
Authors: Shawn J. R. Goh, Johanna E. E. Tuomisto, Anthony W. Purcell, Nicole A. Mifsud, Patricia T. Illing
Journal: Allergy (2020)

Abstract Penicillin refers to a group of beta‐lactam antibiotics that are the first‐line treatment for a range of infections. However, they also possess the ability to form novel antigens, or neoantigens, through haptenation of proteins and can stimulate a range of immune‐mediated adverse reactions—collectively known as drug hypersensitivity reactions (DHRs). IgE‐mediated reactions towards these neoantigens are well studied; however, IgE‐independent reactions are less well understood. These reactions usually manifest in a delayed manner as different forms of cutaneous eruptions or liver injury consistent with priming of an immune response. Ex vivo studies have confirmed the infiltration of T cells into the site of inflammation, and the subsets of T cells involved appear dependent on the nature of the reaction. Here, we review the evidence that has led to our current understanding of these immune‐mediated reactions, discussing the nature of the lesional T cells, the characterization of drug‐responsive T cells isolated from patient blood, and the potential mechanisms by which penicillins enter the antigen processing and presentation pathway to stimulate these deleterious responses. Thus, we highlight the need for a more comprehensive understanding of the underlying genetic and molecular basis of penicillin‐induced DHRs.