tbuckley/cabot-search huggingface dataset:
The clinical spectrum of pulmonary aspergillosis
Authors: C. Kosmidis, D. W. Denning
Journal: Thorax (2014)

The clinical presentation of <i>Aspergillus</i> lung disease is determined by the interaction between fungus and host. Invasive aspergillosis develops in severely immunocompromised patients, including those with neutropenia, and increasingly in the non-neutropenic host, including lung transplant recipients, the critically ill patients and patients on steroids. A high index of suspicion is required in patients without the classical risk factors as early presentation is usually silent and non-specific, pyrexia uncommon and timely treatment is crucial for survival. Invasive aspergillosis has also been diagnosed in normal hosts after massive exposure to fungal spores. Chronic pulmonary aspergillosis affects patients without obvious immune compromise, but with an underlying lung condition such as COPD or sarcoidosis, prior or concurrent TB or non-tuberculous mycobacterial disease. <i>Aspergillus</i> bronchitis may be responsible for persistent respiratory symptoms in patients with <i>Aspergillus</i> detected repeatedly in sputum without evidence of parenchymal <i>Aspergillus</i> disease, especially in patients with bronchiectasis and cystic fibrosis. Allergic bronchopulmonary aspergillosis affects patients with asthma and cystic fibrosis, and is important to recognise as permanent lung or airways damage may accrue if untreated. Changes in the classification of <i>Aspergillus</i> allergic lung disease have been proposed recently. Cases of extrinsic allergic alveolitis and chronic pulmonary aspergillosis have been observed after <i>Aspergillus</i> exposure. Asymptomatic colonisation of the respiratory tract needs close monitoring as it can lead to clinical disease especially with ongoing immunosuppression. The various syndromes should be viewed as a semicontinuous spectrum of disease and one form may evolve into another depending on the degree of ongoing immunosuppression.
Modern management of splenic trauma
Authors: D. R. Hildebrand, A. Ben-sassi, N. P. Ross, R. Macvicar, F. A. Frizelle, A. J. M. Watson
Journal: BMJ (2014)

#### Summary points

Trauma is a major cause of morbidity and mortality; in the developed world, road traffic accidents are one of the leading causes. Up to 45% of patients with blunt abdominal trauma will have a splenic injury,1 which may require urgent operative management, angioembolisation, or non-operative management in the form of active observation.

The management of splenic injuries has evolved over the past three decades with the realisation of the importance of the spleen in immunological defence against encapsulated organisms and a better understanding of the role of non-operative management of splenic injuries. Such management has been aided by better diagnostic and monitoring facilities and by advances in interventional radiology. This article aims to review the best available evidence for the management of patients with blunt splenic trauma.

#### Sources and selection criteria

We did a literature review by searching the Medline database to locate English language articles, using the terms “blunt splenic injury,” “spleen,” “trauma,” “investigation,” “computed tomography,” “splenic angioembolisation,” and “non-operative management” and then by carrying out a hand search of reference lists of …
Aortic Pulse Wave Velocity Improves Cardiovascular Event Prediction
Authors: Yoav Ben-Shlomo, Melissa Spears, Chris Boustred, Margaret May, Simon G. Anderson, Emelia J. Benjamin, Pierre Boutouyrie, James Cameron, Chen-Huan Chen, J. Kennedy Cruickshank, Shih-Jen Hwang, Edward G. Lakatta, Stephane Laurent, João Maldonado, Gary F. Mitchell, Samer S. Najjar, Anne B. Newman, Mitsuru Ohishi, Bruno Pannier, Telmo Pereira, Ramachandran S. Vasan, Tomoki Shokawa, Kim Sutton-Tyrell, Francis Verbeke, Kang-Ling Wang, David J. Webb, Tine Willum Hansen, Sophia Zoungas, Carmel M. McEniery, John R. Cockcroft, Ian B. Wilkinson
Journal: Journal of the American College of Cardiology (2013)
Assessment of the sensitivity and specificity of Xpert MTB/RIF assay as an early sputum biomarker of response to tuberculosis treatment
Authors: Sven O Friedrich, Andrea Rachow, Elmar Saathoff, Kasha Singh, Chacha D Mangu, Rodney Dawson, Patrick PJ Phillips, Amour Venter, Anna Bateson, Catharina C Boehme, Norbert Heinrich, Robert D Hunt, Martin J Boeree, Alimuddin Zumla, Timothy D McHugh, Stephen H Gillespie, Andreas H Diacon, Michael Hoelscher
Journal: The Lancet Respiratory Medicine (2013)

BackgroundAn accurate biomarker is urgently needed to monitor the response to treatment in patients with pulmonary tuberculosis. The Xpert MTB/RIF assay is a commercially available real-time PCR that can be used to detect Mycobacterium-tuberculosis-specific DNA sequences in sputum samples. We therefore evaluated this assay with serial sputum samples obtained over 26 weeks from patients undergoing treatment for tuberculosis.MethodsWe analysed sputum samples from 221 patients with smear-positive tuberculosis enrolled at two sites (Cape Town, South Africa, and Mbeya, Tanzania) of a multicentre randomised clinical trial REMoxTB of antituberculosis treatment on a weekly basis (weeks 0 to 8), then at weeks 12, 17, 22, and 26 after treatment initiation. The Xpert MTB/RIF results over time were compared with the results of standard smear microscopy and culture methods.FindingsWe obtained and analysed 2741 sputum samples from 221 patients. The reduction in positivity rates with Xpert MTB/RIF were slower than those with the standard methods. At week 8, positive results were obtained for 62 (29%) of 212 sputum samples with smear microscopy, 46 (26%) of 175 with solid culture (Löwenstein-Jensen medium), 77 (42%) of 183 with liquid culture (Bactec MGIT960 system), and 174 (84%) of 207 with Xpert MTB/RIF; at 26 weeks, positive results were obtained for ten (5%) of 199, four (3%) of 157, seven (4%) of 169, and 22 (27%) of 83 sputum samples, respectively. The reduction in detection of quantitative M tuberculosis DNA with Xpert MTB/RIF correlated with smear grades (ρ=–0·74; p<0·0001), solid culture grades (ρ=–0·73; p<0·0001), and time to liquid culture positivity (ρ=0·73; p<0·0001). Compared with the combined binary smear and culture results as a reference standard, the Xpert MTB/RIF assay had high sensitivity (97·0%, 95% CI 95·8–97·9), but poor specificity (48·6%, 45·0–52·2).InterpretationThe poor specificity precludes the use of the Xpert MTB/RIF assay as a biomarker for monitoring tuberculosis treatment, and should not replace standard smear microscopy and culture.FundingGlobal Alliance for TB Drug Development, Bill & Melinda Gates Foundation, UK Medical Research Council, German Ministry of Science and Technology.
Population and individual benefits of colorectal cancer screening
Authors: C. Campbell
Journal: Gut (2010)

The randomised controlled trial (RCT) of colorectal cancer screening carried out in Nottingham between 1981 and 1991 was one of a small number of pivotal studies which demonstrated the effectiveness of the Haemoccult faecal occult blood (FOB) test in reducing colorectal cancer mortality. Meta-analysis of the results of these trials provided an evidence base to support the introduction of population-based colorectal cancer screening programmes both in the UK and internationally,1 and a recent updated systematic review of follow-up data from each of the earlier studies has confirmed the reduction in colorectal cancer-related mortality.2

However, no reduction in all-cause mortality has been demonstrated in any of the trials and it has been posited that the impact of screening may be confined to ‘mortality substitution’ where those who would have died from colorectal cancer indeed did die from another cause, but without any benefit in terms of overall life years gained.3

This has led to a call for further analyses relating to the specific reasons for the deaths contributing to all-cause mortality, as well as of the mean life years gained in screened versus control populations. The study by Whynes and colleagues ( see page 1088 ) providing updated outcomes relating to the cause and timing of death of >78 000 subjects in the Nottingham …
Vasa Vasorum of the Pulmonary Artery of the Rabbit
Authors: Sidney S. Sobin, Wallace G. Frasher, Herta M. Tremer
Journal: Circulation Research (1962)

In the rabbit, the arterial and venous vasa vasorum of the pulmonary artery from its origin to the entrance of the right and left pulmonary arteries into the lung were studied and described through the use of a specially prepared silicone rubber injection mass. The physical-chemical characteristics of this material allowed detailed filling of the vascular bed under physiological conditions. Special features of the rich arterial and venous vasa vasorum of the pulmonary artery include: (1) spiral palisading of small vessels and (2)arterial and venous vasal confluences that result from the junction of branches from multiple supply and drainage sites. Both of these may be special adaptations for the normal rapid stretch of the pulmonary artery.
The liver X receptor pathway is highly upregulated in rheumatoid arthritis synovial macrophages and potentiates TLR-driven cytokine release
Authors: Darren Lee Asquith, Lucy E Ballantine, Jagtar Singh Nijjar, Manhal Khuder Makdasy, Sabina Patel, Pamela B Wright, James H Reilly, Shauna Kerr, Mariola Kurowska-Stolarska, J Alastair Gracie, Iain B McInnes
Journal: Annals of the Rheumatic Diseases (2013)

Objectives Macrophages are central to the inflammatory processes driving rheumatoid arthritis (RA) synovitis. The molecular pathways that are induced in synovial macrophages and thereby promote RA disease pathology remain poorly understood. Methods We used microarray to characterise the transcriptome of synovial fluid (SF) macrophages compared with matched peripheral blood monocytes from patients with RA (n=8). Results Using in silico pathway mapping, we found that pathways downstream of the cholesterol activated liver X receptors (LXRs) and those associated with Toll-like receptor (TLR) signalling were upregulated in SF macrophages. Macrophage differentiation and tumour necrosis factor α promoted the expression of LXRα. Furthermore, in functional studies we demonstrated that activation of LXRs significantly augmented TLR-driven cytokine and chemokine secretion. Conclusions The LXR pathway is the most upregulated pathway in RA synovial macrophages and activation of LXRs by ligands present within SF augments TLR-driven cytokine secretion. Since the natural agonists of LXRs arise from cholesterol metabolism, this provides a novel mechanism that can promote RA synovitis.
Hemodialysis-Related Lymphomononuclear Release of Interleukin-12 in Patients with End-Stage Renal Disease
Authors: BRUNO MEMOLI, LUIGI MARZANO, VINCENZO BISESTI, MICHELE ANDREUCCI, BRUNA GUIDA
Journal: Journal of the American Society of Nephrology (1999)

Interleukin-12 (IL-12) is a cytokine produced by peripheral blood mononuclear cells (PBMC) that causes interferon-gamma (IFN-gamma) production and enhancement of cell-mediated cytotoxicity. To clarify the role of hemodialysis biocompatibility on IL-12 production and uremic immunodeficiency, we have studied the IL-12 and IFN-gamma release by PBMC harvested from 12 patients dialyzed with cuprophan membrane (CU), eight patients dialyzed with polymethylmethacrylate membrane (PMMA), and eight nondialyzed uremic patients (UR). Ten healthy subjects constituted the control group (CON). PBMC were cultured for 48 h with and without nonspecific mitogen stimulation. In unstimulated conditions, CU showed an IL-12 PBMC production higher than CON, UR, and PMMA (46.67 +/- 30.13 versus 2.56 +/- 1.38, 6.16 +/- 7.09, and 4.62 +/- 4.76 pg/ml, respectively; P < 0.01). IL-12 production was correlated with C3a concentration measured at the outlet of hemodialyzer after 15 min of dialysis (r = 0.69, P < 0.01). IL-12 release in CU remained unchanged under mitogen stimulation (44.34 +/- 23.86 pg/ml) and was lower than in CON, UR, and PMMA (66.0 +/- 12.41, 68.37 +/- 25.78, and 67.75 +/- 22.61 pg/ml, respectively; P < 0.05). IFN-gamma production was similar, in unstimulated conditions, in all groups. Under stimulation, IFN-gamma release was lower in CU (13.42 +/- 12.04 IU/ml) than in CON, UR, and PMMA (51.84 +/- 30.74, 32.16 +/- 13.86, and 32.16 +/- 13.86 IU/ml, respectively; P < 0.01). These results demonstrate that hemodialysis with CU induces monocyte activation with an enhanced release of IL-12. On the contrary, stimulated PBMC production of both IL-12 and IFN-gamma is lower in these patients than in CON, UR, and PMMA. The altered release of these cytokines could play a role in cell-mediated immunodeficiency of the uremic patients dialyzed with CU.
Overwhelming pneumococcal bacteraemia in systemic lupus erythematosus.
Authors: D Petros, S West
Journal: Annals of the Rheumatic Diseases (1989)

An 18 year old woman presented with fulminant pneumococcal bacteraemia and subsequently died with multisystem organ failure. A search for diseases predisposing to overwhelming encapsulated bacterial infections was negative except for previously undiagnosed systemic lupus erythematosus (SLE). This case emphasises the severity of immune system dysfunction in some patients with SLE, regardless of immunosuppressive treatment. The possible relation between Fc receptor dysfunction and pneumococcal bacteraemia in SLE is discussed.
Independent Modulation of Engagement and Connectivity of the Facial Network During Affect Processing by<i>CACNA1C</i>and<i>ANK3</i>Risk Genes for Bipolar Disorder
Authors: Danai Dima, Jigar Jogia, David Collier, Evangelos Vassos, Katherine E. Burdick, Sophia Frangou
Journal: JAMA Psychiatry (2013)

Genome-wide association studies (GWASs) indicate that single-nucleotide polymorphisms in the CACNA1C and ANK3 genes increase the risk for bipolar disorder (BD). The genes influence neuronal firing by modulating calcium and sodium channel functions, respectively. Both genes modulate γ-aminobutyric acid-transmitting interneuron function and can thus affect brain regional activation and interregional connectivity.To determine whether the genetic risk for BD associated with 2 GWAS-supported risk single-nucleotide polymorphisms at CACNA1C rs1006737 and ANK3 rs10994336 is mediated through changes in regional activation and interregional connectivity of the facial affect-processing network.Cross-sectional functional magnetic resonance imaging study at a research institute of 41 euthymic patients with BD and 46 healthy participants, all of British white descent.Blood oxygen level-dependent signal and effective connectivity measures during the facial affect-processing task.In healthy carriers, both genetic risk variants were independently associated with increased regional engagement throughout the facial affect-processing network and increased effective connectivity between the visual and ventral prefrontal cortical regions. In contrast, BD carriers of either genetic risk variant exhibited pronounced reduction in ventral prefrontal cortical activation and visual-prefrontal effective connectivity.Our data demonstrate that the effect of CACNA1C rs1006737 and ANK3 rs10994336 (or genetic variants in linkage disequilibrium) on the brain converges on the neural circuitry involved in affect processing and provides a mechanism linking BD to genome-wide genetic risk variants.
Early antibiotic treatment for<i>Pseudomonas aeruginosa</i>eradication in patients with cystic fibrosis: a randomised multicentre study comparing two different protocols
Authors: Giovanni Taccetti, Elisa Bianchini, Lisa Cariani, Roberto Buzzetti, Diana Costantini, Francesca Trevisan, Lucia Zavataro, Silvia Campana
Journal: Thorax (2012)

<h3>Background</h3> <i>Pseudomonas aeruginosa</i> chronic pulmonary infection is an unfavourable event in cystic fibrosis. Bacterial clearance is possible with an early antibiotic treatment upon pathogen isolation. Currently, no best practice exists for early treatment. The efficacy of two different regimens against initial <i>P aeruginosa</i> infection was assessed. <h3>Methods</h3> In a randomised, open-label, parallel-group study involving 13 centres, the superiority of inhaled tobramycin/oral ciprofloxacin compared with inhaled colistin/oral ciprofloxacin (reference treatment) over 28 days was evaluated. Patients were eligible if they were older than 1 year with first or new <i>P aeruginosa</i> isolation. Treatments were assigned equally by centralised balanced randomisation, stratified by age and forced expiratory volume in 1 s values. The participants and those giving the intervention were not masked to arm assignments. The primary endpoint was <i>P aeruginosa</i> eradication, defined as three successive negative cultures in 6 months. Analysis was by intention to treat. This trial was registered with EudraCT, number 2008-006502-42. <h3>Results</h3> 105 patients were assigned to inhaled colistin/oral ciprofloxacin (arm A) and 118 to inhaled tobramycin/oral ciprofloxacin (arm B). All patients were analysed. <i>P aeruginosa</i> was eradicated in 66 (62.8%) patients in arm A and in 77 (65.2%) in arm B (OR 0.90, 95% CI 0.52 to 1.55, p=0.81). Following treatment, an increase in <i>Stenotrophomonas maltophilia</i> was noted (OR 3.97, 95% CI 2.27 to 6.94, p=0.001) with no differences between the two arms (OR 0.89, 95% CI 0.44 to 1.78, p=0.88). <h3>Conclusions</h3> No superiority of treatment under study was demonstrated in comparison to the reference treatment. Early eradication treatment was associated with an increase in <i>S maltophilia</i>.
How Do Integrated Health Care Systems Address Racial and Ethnic Disparities in Colon Cancer?
Authors: Kim F. Rhoads, Manali I. Patel, Yifei Ma, Laura A. Schmidt
Journal: Journal of Clinical Oncology (2015)

Purpose Colorectal cancer (CRC) disparities have persisted over the last two decades. CRC is a complex disease requiring multidisciplinary care from specialists who may be geographically separated. Few studies have assessed the association between integrated health care system (IHS) CRC care quality, survival, and disparities. The purpose of this study was to determine if exposure to an IHS positively affects quality of care, risk of mortality, and disparities. Patients and Methods This retrospective secondary-data analysis study, using the California Cancer Registry linked to state discharge abstracts of patients treated for colon cancer (2001 to 2006), compared the rates of National Comprehensive Cancer Network (NCCN) guideline–based care, the hazard of mortality, and racial/ethnic disparities in an IHS versus other settings. Results More than 30,000 patient records were evaluated. The IHS had overall higher rates of adherence to NCCN guidelines. Propensity score–matched Cox models showed an independent and protective association between care in the IHS and survival (hazard ratio [HR], 0.87; 95% CI, 0.85 to 0.90). This advantage persisted across stage groups. Black race was associated with increased hazard of mortality in all other settings (HR, 1.15; 95% CI, 1.04 to 1.27); however, there was no disparity within the IHS for any minority group (P &gt; .11 for all groups) when compared with white race. Conclusion The IHS delivered higher rates of evidence-based care and was associated with lower 5-year mortality. Racial/ethnic disparities in survival were absent in the IHS. Integrated systems may serve as the cornerstone for developing accountable care organizations poised to improve cancer outcomes and eliminate disparities under health care reform.
Biocompatibility Evaluation of Ionic‐ and Photo‐Crosslinked Methacrylated Gellan Gum Hydrogels: In Vitro and In Vivo Study
Authors: Joana Silva‐Correia, Barbara Zavan, Vincenzo Vindigni, Tiago H. Silva, Joaquim M. Oliveira, Giovanni Abatangelo, Rui L. Reis
Journal: Advanced Healthcare Materials (2012)

Abstract In this study, the stability and biocompatibility of methacrylated gellan gum hydrogels, obtained either by ionic‐ (iGG‐MA) or photo‐crosslinking (phGG‐MA), were evaluated in vitro and in vivo. Size exclusion chromatography analysis of the methacrylated gellan gum (GG‐MA) powder revealed that molecular weight is lower as compared to the non‐modified material, i.e., low acyl gellan gum. The water uptake and swelling of iGG‐MA and phGG‐MA hydrogels were investigated in phosphate‐buffered saline solution (pH 7.4). The biocompatibility of the hydrogels was firstly evaluated by producing cell‐laden hydrogels. The in vitro cells encapsulation study showed that lung fibroblast cells (L929 cells) and human intervertebral disc (hIVD) cells are viable when cultured within both hydrogels, up to 21 days of culturing. The iGG‐MA and phGG‐MA hydrogels were also subcutaneously implanted in Lewis rats for 10 and 18 days. Tissue response to the hydrogels implantation was determined by histological analysis (haematoxylin‐eosin staining). A thin fibrous capsule was observed around the implanted hydrogels. No necrosis, calcification, and acute inflammatory reaction were observed. The results presented in this study demonstrate that iGG‐MA and phGG‐MA hydrogels are stable in vitro and in vivo, support L929 and hIVD cells’ encapsulation and viability, and were found to be well‐tolerated and non‐toxic in vivo.
Unusual Lymphoma Manifestations
Authors: Robin B. Gear, Sue Heffelfinger, Herbert C. Flessa
Journal: Journal of Clinical Oncology (2004)

In 1996 we reported a 73-year-old man with natural killer cell (NK) leukemia complicated by severe dermal erythema secondary to vascular epidermal growth factor (VEGF) secretion by the leukemic cells [1]. He presented with fever, itching, splenomegaly, and profound dermal erythema, especially of his trunk and lower extremities (Figs 1A, 1B). Generalized adenopathy was not present. A computed tomography scan of the abdomen showed splenomegally without adenopathy. A skin biopsy showed an increased number of moderately dilated and irregular vascular channels in the superficial dermis (Fig 2). The white count was 11,300/ L with 13% neutrophils and 82% lymphocytes. The predominant cells in the peripheral blood and in the bone marrow were large granular lymphocytes (CD16, CD7, CD2 and CD3, CD4, and CD8 ; Fig 3). With treatment, splenomegaly disappeared. Slowly, over a period of months, the dermal erythema disappeared. The treatment consisted of lowdose oral cytoxan and low-dose oral prednisone. We tested the hypothesis that the dermal erythema was a manifestation of VEGF production by examining this patient’s peripheral leukocytes and leukocytes of six other patients for the production of VEGF by reverse transcriptase polymerase chain reaction. The cells from our NK leukemia patients expressed all forms of VEGF. VEGF was not identified in our control patients, including a patient with chronic lymphocytic leukemia, chronic myelocytic leukemia, and four normal volunteers. After treatment the VEGF completely disappeared, and the profound erythema slowly resolved. The patient continues in complete remission 6 years later, on therapy (low dose cytoxan and low dose prednisone). There are no NK cells in the peripheral blood. The spleen is not palpable, and his skin is perfectly normal. The morphology, cytochemistry, and surface markers of NK lymphocytes have been presented in considerable detail [2]. In addition, several publications during the last decade have outlined and discussed neoplastic diseases of NK cells [3-5]. To our knowledge, there has been no previous description of a patient with NK leukemia whose cells secreted VEGF, causing a dermal erythema that disappeared following resolution of the leukemia. Robin B. Gear, Sue Heffelfinger, and Herbert C. Flessa University of Cincinnati College of Medicine; Department of Internal Medicine, Division of Hematology-Oncology, Cincinnati, OH