tbuckley/cabot-search huggingface dataset:
Multicenter phase ii study of a combination of cyclosporine a, methotrexate and mycophenolate mofetil for GVHD prophylaxis: results of the Chinese Bone Marrow Transplant Cooperative Group (CBMTCG)
Authors: Yong-rong Lai, Yu-hong Chen, Deng-ming Hu, Ming Jiang, Qi-fa Liu, Lin Liu, Jian Hou, Paul Schwarzenberger, Qiao-chuan Li, Zhong-ming Zhang, Kai-yan Liu, Xiao-jun Huang
Journal: Journal of Hematology & Oncology (2014)

Improvement of current GVHD prophylactic therapies remains an important goal in the allo-HSCT. We have described a novel prophylaxis regimen in a single institution trial. The Chinese Bone Marrow Transplant Cooperative Group (CBMTCG) initiated a phase II multicenter study. The study was designed as a prospective, single arm phase II open-label, multicenter clinical trial. The primary endpoint was improvement of aGVHD by 25% over historical control (40%) in Chinese patients. 508 patients were enrolled. All of the patients received cyclosporine A (CsA), methotrexate (MTX) and mycophenolate mofetil (MMF) (0.5-1.0 g daily for 30 days) as GVHD prophylaxis regimen. The primary endpoint was met with cumulative incidences of grades 2 to 4 and grades 3 to 4 aGVHD of 23.2% and 10.3%, respectively. Incidence for cGVHD was 67.4%. The non-relapse mortality (NRM) rate was 18.4% at 2 years. The probabilities of leukemia free survival (LFS) for non-advanced stage and advanced stage patients at 2 years were 69.7% and 44.8% respectively (p = 0.000). Recipient age ≥ 40 years, advanced stage and Busulfan-Fludarabine(BuFlu) conditioning regimen were identified as major risk factors for aGVHD. Recipient age ≥ 40 years, BuFlu conditioning regimens, female donor/male recipient and prior aGVHD were associated with cGVHD. Despite lower RM (relapse mortality), patients with grade 2–4 aGVHD had higher NRM and worse OS and LFS compared to patients with grade 0–1 aGVHD. In contrast, patients with cGVHD had better OS and LFS and lower RM compared to patients without cGVHD. The novel GVHD regimen decreased the risk for aGVHD by 42% without improving the risk for cGVHD compared to historical controls. Development of aGVHD was associated with worse OS and LFS as well as higher NRM. In contrast, cGVHD was associated with improved OS and LFS likely attributed to a GVL effect.
Wilms tumour as a possible early manifestation of hereditary leiomyomatosis and renal cell cancer?
Authors: S. Badeloe, K.Y. van Spaendonck-Zwarts, M.A.M. van Steensel, A.M.W. van Marion, A.J. van Essen, M.F. Jonkman, P.M. Steijlen, P. Poblete-Gutiérrez, M. van Geel, J. Frank
Journal: British Journal of Dermatology (2009)

Conflicts of interest: none declared. Hereditary leiomyomatosis and renal cell cancer (HLRCC) (OMIM 605839) is a autosomal dominantly inherited tumour predisposition syndrome, characterized by cutaneous and uterine leiomyoma and renal cell cancer (RCC).1 It is caused by heterozygous mutations in the fumarate hydratase (FH) gene that codes for the enzyme fumarate hydratase (FH) and catalyses the conversion of fumarate to malate in the Krebs cycle.1, 2 The exact mechanism by which improper FH function leads to tumour formation is still unclear. However, recent studies suggest a pseudohypoxic drive as a possible link between FH dysfunction, the von Hippel‐Lindau–hypoxia‐inducible factor (HIF) pathway, and cancer development.3 To date, only four different types of RCC have been observed in HLRCC: papillary type 2 RCC; collecting duct carcinoma; and RCC with oncocytic and with clear cell foci.4 A 31‐year‐old white woman (individual III‐2 in Fig. 1a) had developed progressive cutaneous (Fig. 1b) and uterine leiomyoma since the age of 25 years. Her family history revealed cutaneous leiomyoma in her father and sister and uterine leiomyoma in her paternal aunt and grandmother (Fig. 1a). Interestingly, she had been diagnosed at the age of 2 years with a single Wilms tumour (WT) that revealed two solitary metastases in the left and right lung and was successfully treated with surgery and chemotherapy, consisting of dactinomycin and vincristine.
In Humans, Chronic Atrial Fibrillation Decreases the Transient Outward Current and Ultrarapid Component of the Delayed Rectifier Current Differentially on Each Atria and Increases the Slow Component of the Delayed Rectifier Current in Both
Authors: Ricardo Caballero, Marta González de la Fuente, Ricardo Gómez, Adriana Barana, Irene Amorós, Pablo Dolz-Gaitón, Lourdes Osuna, Jesús Almendral, Felipe Atienza, Francisco Fernández-Avilés, Ana Pita, Jorge Rodríguez-Roda, Ángel Pinto, Juan Tamargo, Eva Delpón
Journal: Journal of the American College of Cardiology (2010)
Sudden Death After Myocardial Infarction
Authors: A. Selcuk Adabag
Journal: JAMA (2008)

Sudden cardiac death after myocardial infarction (MI) has not been assessed recently in the community. Risk stratification for sudden cardiac death after MI commonly relies on baseline characteristics and little is known about the relationship between recurrent ischemia or heart failure and sudden cardiac death.To evaluate the risk of sudden cardiac death after MI and the impact of recurrent ischemia and heart failure on sudden cardiac death.Population-based surveillance study of 2997 residents (mean [SD] age, 67 [14] years; 59% were men) experiencing an MI in Olmsted County, Minnesota, between 1979 and 2005, and followed up through February 29, 2008.Sudden cardiac death defined as out-of-hospital death due to coronary disease; and observed survival free of sudden cardiac death compared with that expected in Olmsted County, Minnesota.During a median follow-up of 4.7 years (25th-75th percentile, 1.6-7.1 years), 1160 deaths occurred, 282 from sudden cardiac death (24%). The 30-day cumulative incidence of sudden cardiac death was 1.2% (95% confidence interval [CI], 0.8%-1.6%). Thereafter, the rate of sudden cardiac death was constant at 1.2% per year yielding a 5-year cumulative incidence of 6.9% (95% CI, 5.9%-7.9%). The 30-day incidence of sudden cardiac death was 4-fold higher than expected (standardized mortality ratio, 4.2; 95% CI, 2.9-5.8). The risk of sudden cardiac death has declined significantly over time (hazard ratio [HR], 0.62 [95% CI, 0.44-0.88] for MIs that occurred between 1997 and 2005 compared with between 1979 and 1987; P = .03). The recurrent events of ischemia (n = 842), heart failure (n = 365), or both (n = 873) occurred in 2080 patients. After adjustment for baseline characteristics, recurrent ischemia was not associated with sudden cardiac death (HR, 1.26 [95% CI, 0.96-1.65]; P = .09), while heart failure markedly increased the risk of sudden cardiac death (HR, 4.20 [95% CI, 3.10-5.69]; P < .001).The risk of sudden cardiac death following MI in community practice has declined significantly over the past 30 years. Sudden cardiac death is independently associated with heart failure but not with recurrent ischemia.
Combining information from prognostic scoring tools for CAP: an American view on how to get the best of all worlds
Authors: M. S. Niederman, C. Feldman, G. A. Richards
Journal: European Respiratory Journal (2005)

Many studies of the epidemiology of patients with community-acquired pneumonia (CAP) have demonstrated the importance of assessing severity of illness and stratifying patients on the basis of their risk of mortality 1–3. Optimal management of this illness requires prompt recognition of seriously ill patients to avoid mistakes such as the failure to use a hospital or intensive care unit (ICU) for patients who could benefit from care and observation in such settings. The major impact on the cost of CAP care is determined by whether or not a patient is admitted to the hospital. In the USA,  90% of the total cost of care for this disease 4.

Prognostic scoring systems for CAP have been developed to address these issues. The two prominent tools for this purpose are the Pneumonia Severity Index (PSI), developed in the USA, and the British Thoracic Society rule, which has recently been modified to the CURB-65 rule (referring to its assessment of: Confusion, elevated blood Urea nitrogen, elevated Respiratory rate, low systolic or diastolic Blood pressure, and age >65 yrs) 1, 3. Although each of the two approaches has been proposed as a tool to guide the site of care decision, neither is ideal by itself, and both can be regarded only as providing decision support information that must be supplemented by clinical assessment and judgment. In fact, the two scoring approaches should be viewed as being complementary, as each has different strengths and weaknesses. The PSI seems to have been developed, and best validated, as a way to identify low mortality risk patients, but the scoring system can occasionally underestimate severity of illness, especially in young patients without comorbid illness 2 …
Transmission of Hepatitis C Virus to Several Organ and Tissue Recipients from an Antibody-Negative Donor
Authors: Barna D. Tugwell, Priti R. Patel, Ian T. Williams, Katrina Hedberg, Feng Chai, Omana V. Nainan, Ann R. Thomas, Judith E. Woll, Beth P. Bell, Paul R. Cieslak
Journal: Annals of Internal Medicine (2005)

Although hepatitis C virus (HCV) transmission through tissue transplantation has been rarely reported, a donor with undetected viremia may infect several recipients. A patient developed acute hepatitis C shortly after tissue transplantation. Ninety-one tissues or organs had been recovered from the donor.To determine whether the donor was the source of infection and the extent of transmission to other organ and tissue recipients.Descriptive epidemiologic study; serum testing for HCV infection.Recipients were located in 16 states and 2 other countries.Donor and graft recipients.Hepatitis C virus infection was defined as the presence of anti-HCV or HCV RNA. The authors determined the genetic relatedness of viral isolates from the donor and recipients by genotype comparison and quasi-species analysis.The donor was anti-HCV-negative but was HCV RNA-positive (genotype 1a). Forty persons received transplants during 22 months. Five persons were HCV-infected before transplantation or had a genotype other than 1a, and 5 persons had no post-transplantation serum specimens available. Of the remaining 30 recipients, HCV infection occurred in 8 recipients: 3 of 3 organ recipients, 1 of 2 saphenous vein recipients, 1 of 3 tendon recipients, and 3 of 3 tendon with bone recipients. These 8 recipients had viral isolates genetically related to those of the donor. No cases occurred in recipients of skin (n = 2), cornea (n = 1), or irradiated bone (n = 16).Post-transplantation serum specimens were unavailable for 5 recipients.An anti-HCV-negative donor was the source of HCV infection for 8 recipients of organs or tissues. Although HCV transmission from anti-HCV-negative donors is probably uncommon, changes in donor screening to include routine testing for HCV RNA merit further consideration to improve the safety of transplantation.
U-serrated immunodeposition pattern differentiates type VII collagen targeting bullous diseases from other subepidermal bullous autoimmune diseases
Authors: R.M. Vodegel, M.f. Jonkman, H.H. Pas, M.C.J.M. De Jong
Journal: British Journal of Dermatology (2004)

Journal Article U‐serrated immunodeposition pattern differentiates type VII collagen targeting bullous diseases from other subepidermal bullous autoimmune diseases Get access R.M. Vodegel, R.M. Vodegel Center for Blistering Diseases, Department of Dermatology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar M.f. Jonkman, M.f. Jonkman Center for Blistering Diseases, Department of Dermatology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar H.H. Pas, H.H. Pas Center for Blistering Diseases, Department of Dermatology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar M.C.J.M. De Jong M.C.J.M. De Jong Center for Blistering Diseases, Department of Dermatology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, the Netherlands M.C.J.M. de Jong. E‐mail: m.c.j.m.de.jong@derm.azg.nl Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 151, Issue 1, 1 July 2004, Pages 112–118, https://doi.org/10.1111/j.1365-2133.2004.06006.x Published: 01 July 2004 Article history Accepted: 23 December 2003 Published: 01 July 2004
Neutrophil-activating protein 1/interleukin 8 stimulates the binding activity of the leukocyte adhesion receptor CD11b/CD18 on human neutrophils.
Authors: P A Detmers, S K Lo, E Olsen-Egbert, A Walz, M Baggiolini, Z A Cohn
Journal: The Journal of Experimental Medicine (1990)

The cytokine NAP-1/IL-8 is produced by a variety of different cells in response to inflammatory stimuli and elicits several biological responses from PMN. Experiments presented here demonstrate that PMN exposed to NAP-1/IL-8 expressed increased amounts of CD11b/CD18, as well as CD11c/CD18 and CR1, on their cell surface, while expression of Fc gamma RIII and HLA-A,B,C remained essentially unchanged. Increased CD11b/CD18 and CD11c/CD18 appears to correspond with the release of specific granules by NAP-1/IL-8. NAP-1/IL-8 was also a potent stimulator of several of the binding activities of CD11b/CD18. Ligation of EC3bi by CD11b/CD18 was rapidly enhanced by NAP-1/IL-8, but phagocytosis of the ligated particles was not induced by the agonist. In addition, enhanced binding of EC3bi was observed in the absence of an increase in receptor expression as shown with PMN cytoplasts. NAP-1/IL-8 promoted additional adhesive interactions between CD11b/CD18 and the biosynthetic precursor of LPS, lipid IVa, fibrinogen, and endothelial cells, suggesting that NAP-1/IL-8 may promote leukocyte adhesion in vivo that could lead to recruitment of PMN to sites of tissue inflammation.
Pseudomonas aeruginosa, cyanide accumulation and lung function in CF and non-CF bronchiectasis patients
Authors: B. Ryall, J. C. Davies, R. Wilson, A. Shoemark, H. D. Williams
Journal: European Respiratory Journal (2008)

In patients with cystic fibrosis (CF) and non-CF bronchiectasis, Pseudomonas aeruginosa is the most important respiratory pathogen. It is able to synthesise hydrogen cyanide, a potent inhibitor of cellular respiration. The present study investigated whether cyanide is present in the sputum of CF and non-CF bronchiectasis patients infected with P. aeruginosa , and whether the detection of cyanide affected lung function. Cyanide was measured in sputum using a cyanide ion selective electrode. Cyanide was detected in sputum from 15 out of 25 CF and non-CF bronchiectasis patients with current P. aeruginosa infection; however, it was not detected in any of the 10 patients without this organism. Maximum levels were 130 µM (mean± se 72±6.6 µM). Concurrent lung function data were available on all 21 P. aeruginosa -infected CF patients; the group with measurable sputum cyanide (n = 11) was not different from those without (n = 10) on the basis of age or sex. However, those with detectable cyanide had significantly poorer lung function than those without (forced expiratory volume in one second (% predicted) 26.8±3.8 versus 46.0±6.7%; forced vital capacity (% pred) 44.4±4.9 versus 60.1±7.7%). Cyanide is detectable in sputum from cystic fibrosis and non-cystic fibrosis bronchiectasis patients infected with Pseudomonas aeruginosa , and is also associated with impaired lung function.
Seronegative chronic polyarthritis: clinical and serological correlates.
Authors: J L Rasker, P Davis, P A Bacon
Journal: Annals of the Rheumatic Diseases (1980)

Twenty-seven patients with chronic, active, seronegative polyarthritis were assessed clinically and serologically by accepted criteria for evidence of connective tissue diseases. The patients were divided into 2 groups, 13 positive for fluorescent antinuclear antibody (FANA) and 14 that were negative. All but 1 patient fulfilled the clinical criteria for the diagnosis of definite rheumatoid arthritis. Four patients (2 in each group) fulfilled the preliminary criteria for the classification of systemic lupus erythematosus. Antiperinuclear factor was positive in 5 of the FANA-negative patients, consistent with a diagnosis of rheumatoid arthritis. By contrast, this factor was absent in all the FANA-positive patients. Positive DNA binding was found in 7 of the FANA-positive patients, in high titre in 4, consistent with a diagnosis of 9minimal lupus9 with predominantly 9unisystem9 disease. DNA binding was positive in low titre in 2 of the FANA-negative patients. Antibodies to extractable nuclear antigens (ENA) were found in 4 patients with a positive FANA and in only 1 FANA-negative patient. The current clinical criteria showed poor discriminatory value in classifying cases of seronegative polyarthritis, which may represent mild cases of other connective tissue disease presenting with synovitis in the absence of extra-articular disease manifestations.
STUDIES ON CYANOSIS
Authors: Christen Lundsgaard
Journal: The Journal of Experimental Medicine (1919)

1. The primary cause of cyanosis is an increase in the reduced hemoglobin, or oxygen unsaturation, of the blood in the peripheral capillaries. 2. When the mean capillary oxygen unsaturation, which is calculated as the mean between venous and arterial unsaturation, and is normally about 2 to 3 volumes per cent, is increased to about 6 to 7 volumes per cent, cyanosis appears. For this reason 6 to 7 volumes per cent may be called the threshold value of mean capillary oxygen unsaturation for the incidence of cyanosis. 3. The increased mean capillary oxygen unsaturation is produced in two ways (secondary causes of cyanosis), either by an abnormally great reduction during passage through the capillaries (Text-fig. I, Diagram II) or by a state of partial reduction in the arterial blood entering the capillaries (Text-fig. I, Diagram III). The first condition (abnormally great reduction) occurs during exercise, or when the blood flow is retarded, as in decompensated heart condition. The second condition (partial arterial unsaturation) occurs in certain lung and heart diseases, and when the alveolar oxygen tension is greatly decreased, as at high altitudes. 4. If the blood is completely saturated with oxygen in the lungs, the oxygen unsaturation of the venous blood may increase to 13 to 14 volumes per cent before cyanosis appears. 5. If cyanosis appears at a venous oxygen unsaturation less than 13 to 14 volumes per cent, some arterial oxygen unsaturation may be assumed, and the more the lower the venous oxygen unsaturation is. 6. Even if neither râles nor dullness can be detected in the lungs, conditions may exist which prevent complete oxidation of the arterial hemoglobin. This is especially frequent in patients with mitral lesions. 7. Cyanosis cannot be produced in patients whose hemoglobin percentage is below 35 per cent on the Haldane scale (oxygen capacity of 6.5 volumes per cent).
Intensive Insulin Therapy in Postoperative Intensive Care Unit Patients
Authors: Moritoki Egi, Rinaldo Bellomo, Edward Stachowski, Craig J. French, Graeme Hart, Peter Stow, Weiqui Li, Samantha Bates
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Intensive insulin therapy (IIT) may reduce mortality in mechanically ventilated postoperative patients.To assess the risks and benefits of IIT in different institutions.Retrospective, blinded-to-outcome selection of patient cohorts from four hospitals.Selection of a cohort of patients with clinical features similar to those reported in a recent study of IIT and of all mechanically ventilated postoperative patients from each hospital. Retrieval of information on glucose control. Assessment of risks and benefits and final outcomes.We selected 783 consecutive patients with similar clinical and demographic features to the IIT trial control group and four general cohorts for a total of 4,150 consecutive mechanically ventilated postoperative patients. In these patients, glucose levels were measured 212,663 times for a mean value of 8.22 +/- 2.7 mmol/L (148 +/- 49 mg/dl). Intensive care unit (ICU) mortality varied from 2.2 to 13.6%. The incidence of hypoglycemia (defined as < 2.2 mmol/L) varied from 1.4 to 2.7%. Assuming a beneficial effect of IIT as reported, the number needed to treat to save one life varied from 38 in one ICU to 125 in another, whereas the rate of hypoglycemia (number needed to harm) varied from 7 to 13.The number needed to treat to prevent an ICU death and the associated risk of hypoglycemia (number needed to harm) with IIT vary widely according to baseline mortality, case mix, and case selection. Rational decision analysis in individual ICUs should take these factors into account.
Key Concepts and Limitations of Statistical Methods for Evaluating Biomarkers of Kidney Disease
Authors: Chirag R. Parikh, Heather Thiessen-Philbrook
Journal: Journal of the American Society of Nephrology (2014)

Interest in developing and using novel markers of kidney injury is increasing. To maintain scientific rigour in these endeavors, a comprehensive understanding of statistical methodology is required to rigorously assess the incremental value of novel biomarkers in existing clinical risk prediction models. Such knowledge is especially relevant, because no single statistical method is sufficient to evaluate a novel biomarker. In this review, we highlight the strengths and limitations of various traditional and novel statistical methods used in the literature for biomarker studies and use biomarkers of AKI as examples to show limitations of some popular statistical methods.
Prevention of postischemic ventricular fibrillation late after right or left stellate ganglionectomy in dogs.
Authors: P E Puddu, R Jouve, F Langlet, J C Guillen, M Lanti, A Reale
Journal: Circulation (1988)

To gain insight into the differences in antiarrhythmic potential of right vs left stellate ganglionectomy, 72 dogs were randomized to either unilateral stellectomy or second intercostal space thoracotomy and left circumflex coronary arteriovenous pedicle occlusion was performed, without vagotomy, a mean of 8 weeks later under anesthesia. The type and timing of ventricular ectopic beats, including both nonsustained and sustained ventricular tachycardia and ventricular fibrillation, were investigated. Several covariates, including postischemic electrocardiographic changes, were considered. Both right and left stellate ganglionectomy reduced the incidence of early (0 to 10 min) (p = .004 and p = .001, respectively) and total (0 to 60 min) (p = .009 and p = .008, respectively) ischemia-induced ventricular fibrillation, and improved outcome (p = .0013 and p = .0012, respectively). Early sustained ventricular tachycardia was similarly reduced (p = .02) in both stellectomized groups. By contrast, neither the type nor the time distribution of the other forms of ventricular arrhythmias differed significantly among the randomized groups. The multivariate Cox's regression model showed that ST segment elevation at 3 min postocclusion, unilateral stellate ganglionectomy (either right or left), sex, and weight were significant independent predictors of the incidence of ventricular fibrillation during the occlusion period. Lower ST segment elevation and reduced incidence of sustained ventricular tachycardia in the early postischemic period might explain improved outcome in stellectomized dogs by Cox analysis. The side of intervention (either stellectomy or sham operation) did not influence survival; however, left-sided interventions were more effective than right-sided ones. These results confirm the previously reported antifibrillatory effect of left and indicate like effects of right stellate ganglionectomy in a randomized experimental study.