Photo-induced Stevens-Johnson syndrome Moghaddam, Sara, MD; Connolly, Deirdre, BA
Journal of the American Academy of Dermatology,
09/2014, Volume:
71, Issue:
3
Journal Article
Background Orthotopic liver transplantation is the definitive treatment modality for patients with end-stage liver disease. Pre–orthotopic liver transplantation renal dysfunction has a significant ...negative influence on outcomes post–orthotopic liver transplantation. Intraoperative renal replacement therapy is an adjunctive therapy to address the metabolic challenges during orthotopic liver transplantation in patients with a high acuity of illness. The impact of intraoperative renal replacement therapy on post–orthotopic liver transplantation outcomes, however, is unclear. Methods From October of 2012 to April of 2016, 96 adult patients underwent orthotopic liver transplantation for end-stage liver disease. Three groups were identified: (1) Group I: patients with pre–orthotopic liver transplantation renal dysfunction who underwent intraoperative renal replacement therapy, (2) Group II: patients with pre–orthotopic liver transplantation renal dysfunction who did not receive intraoperative renal replacement therapy, and (3) Group III: patients with orthotopic liver transplantation without evidence of pretransplant renal dysfunction. Results At 17.7 months follow-up, there was no difference in survival among the study groups. Physiologic model for end-stage liver disease at the time of orthotopic liver transplantation was significantly higher in both groups with renal dysfunction (I = 43, II = 39) than in Group III (18). Post–orthotopic liver transplantation, 12-month patient survival in Group II was 100%. While the model for end-stage liver disease score at orthotopic liver transplantation was significantly different between Group I and Group III, the 12-month, post–orthotopic liver transplantation patient survival was comparable at 78% vs 88%, respectively. Conclusion Intraoperative renal replacement therapy is a safe adjunctive therapy during liver transplantation of critically ill patients with renal dysfunction. Identifying patients who require intraoperative renal replacement therapy would improve intraoperative and post–liver transplant survival and may facilitate recovery of native kidney function after transplant.
Summary
Background According to a recent hypothesis, the profound loss of body protein that occurs in critically ill patients is triggered and maintained by cell shrinkage secondary to cellular ...dehydration. We tested this hypothesis by studying sequential changes in intracellular water, total body protein, total body potassium, and intracellular potassium in patients receiving intensive care for blunt trauma or sepsis.
Methods Nine patients with multiple blunt trauma and 11 with severe sepsis were studied in an intensive care unit for 21 days. Intracellular water was measured in two ways—by subtraction of extracellular water (bromide dilution) from total body water (tritium dilution), and by bioimpedance spectroscopy. Total body protein was measured by whole-body neutron activation analysis and total body potassium by whole-body counting.
Findings Over the study period intracellular water decreased by 15-20%, total body protein by 15%, and total body potassium by about 20%. Intracellular potassium concentration did not change, and was similar to that in healthy adult volunteers. In the trauma patients, sequential measurements of the ratio of potassium to protein in lost tissue indicated that cells were losing water in quantities greater than would be expected from protein losses.
Interpretation The loss of protein and potassium from body stores in major trauma or sepsis is accompanied by progressive cellular dehydration. This insight opens up new therapeutic options for limiting the loss of body protein in critically ill patients.
Rates of propagule supply can be important determinants of spatial and temporal patterns in community structure. In the northeast Pacific Ocean, large-scale differences in the structure of intertidal ...invertebrate communities have been attributed to a latitudinal gradient in recruitment in this region. To determine whether such a gradient exists, recruitment of intertidal barnacles and mussels was monitored at 17 sites across this region in 1996 and 1997. A latitudinal gradient in recruitment was detected in this study. This gradient was approximately a stepcline: annual recruitment, on average, was 1-2 orders of magnitude higher in central and northern Oregon than in central and northern California. In contrast to the regional differences, large-scale gradients in recruitment within California were small; correlations of recruitment with latitude were weak, and in all but one case, statistically insignificant. Nonetheless, trends in the data suggest that recruitment within central and northern California was highest between San Francisco and Monterey Bay, where larvae may be retained more nearshore than to the north or south. If so, apparently conflicting claims about latitudinal gradients in recruitment within California can be reconciled. The large-scale transition in recruitment rates supports the hypothesis that a marked shift in the intensity of upwelling near Cape Blanco in southern Oregon is a major cause of a coincident transition in community structure. Stronger upwelling (and thus offshore flow) to the south has been hypothesized to transport larvae further offshore and thereby reduce larval supply to nearshore benthic communities. This study confirms that the predicted differences in recruitment exist, and that these differences are large. Preliminary calculations indicate that regional differences in offshore flow are likely to make a larger contribution to the recruitment transitions than several other plausible causes. In addition, recruitment transitions are larger, more abrupt, and more consistent across species than corresponding shifts in percentage cover, which favor competitive dominants. This supports model predictions that competition for space is more intense where recruitment is high. However, the absence of strong, large-scale recruitment gradients within California suggests that mesoscale processes are relatively more important than latitudinal trends in upwelling as determinants of community structure patterns at smaller scales.
Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from the European Medicines Agency, Health Canada, and ...the United States (US) Food and Drug Administration established a collaboration to evaluate the absolute risk of arterial (ATE) and venous thromboembolism (VTE) in the 90 days after diagnosis of COVID-19 in the ambulatory (eg, outpatient, emergency department, nursing facility) setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability.
We conducted cohort studies of patients initially diagnosed with COVID-19 in the ambulatory setting from the seven specified countries. Patients were followed for 90 days after COVID-19 diagnosis. The primary outcomes were ATE and VTE over 90 days from diagnosis date. We measured country-level estimates of 90-day absolute risk (with 95% confidence intervals) of ATE and VTE.
The seven cohorts included 1,061,565 patients initially diagnosed with COVID-19 in the ambulatory setting before COVID-19 vaccines were available (through November 2020). The 90-day absolute risk of ATE during this period ranged from 0.11% (0.09-0.13%) in Canada to 1.01% (0.97-1.05%) in the US, and the 90-day absolute risk of VTE ranged from 0.23% (0.21-0.26%) in Canada to 0.84% (0.80-0.89%) in England. The seven cohorts included 3,544,062 patients with COVID-19 during vaccine availability (beginning December 2020). The 90-day absolute risk of ATE during this period ranged from 0.06% (0.06-0.07%) in England to 1.04% (1.01-1.06%) in the US, and the 90-day absolute risk of VTE ranged from 0.25% (0.24-0.26%) in England to 1.02% (0.99-1.04%) in the US.
There was heterogeneity by country in 90-day absolute risk of ATE and VTE after ambulatory COVID-19 diagnosis both before and during COVID-19 vaccine availability.
TAM (Tyro3, Axl, MerTK) receptor tyrosine kinases mediate apoptotic cell uptake by phagocytes through the bridging molecules Protein S or growth arrest specific 6 (Gas6), and are critical for lung ...immune homeostasis.4 We and others have shown that Axl is specifically expressed on mouse airway macrophages, is constitutively bound to its ligand Gas6, and is critical for efficient efferocytosis.5,6 Axl-deficient mice develop exaggerated lung inflammation upon influenza infection associated with accumulation of apoptotic cells in the airways,5 indicating a critical role for Axl in apoptotic cell clearance from the inflamed lung. ...we report for the first time that (1) the apoptotic cell recognition receptor Axl is exclusively expressed by human airway/alveolar macrophages, (2) Axl expression depends on the presence of type I/III IFNs, (3) increased shedding of sAxl occurs in sputum from patients with moderate-to-severe asthma, and (4) Axl mRNA expression in airway macrophages isolated from sputum is reduced in patients with moderate-to-severe asthma. Methods Study population and sample collection Paired peripheral blood and sputum samples (spontaneous or induced by using hypertonic saline) were collected from 15 healthy individuals and 46 patients with moderate-to-severe asthma fulfilling the British Thoracic Society criteria (disease steps 3-5).E1 Clinical characteristics of patients are presented in Table E1. Feature Moderate-to-severe asthma (n = 46) Healthy control (n = 15) Sex: male/female 19/27 4/11 Age (y) 55 (45-63) 37.2 (30-46) Smoking history Never 21 11 Ex 18 4 Current 7 0 Asthma severity BTS step 3 8 BTS step 4 12 BTS step 5 26 FEV1 (L) 2.14 (1.63-2.73) NA FEV1 % predicted 77 (64-94) NA FVC (L) 3.10 (2.63-3.69) NA FVC % predicted 93 (83-109) NA FEV1/FVC ratio 0.7 (0.59-0.79) NA 1 R. Fernandez-Boyanapalli, E. Goleva, C. Kolakowski, E. Min, B. Day, D.Y. Leung, Obesity impairs apoptotic cell clearance in asthma, J Allergy Clin Immunol, Vol. 131, 2013, 1041-1047, 1047.e1-3 2 M.L. Huynh, K.C. Malcolm, C. Kotaru, J.A. Tilstra, J.Y. Westcott, V.A. Fadok, Defective apoptotic cell phagocytosis attenuates prostaglandin E2 and 15-hydroxyeicosatetraenoic acid in severe asthma alveolar macrophages, Am J Respir Crit Care Med, Vol. 172, 2005, 972-979 3 J.L. Simpson, P.G. Gibson, I.A. Yang, J. Upham, A. James, P.N. Reynolds, Impaired macrophage phagocytosis in non-eosinophilic asthma, Clin Exp Allergy, Vol. 43, 2013, 29-35 4 A.M. Grabiec, T. Hussell, The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation, Semin Immunopathol, Vol. 38, 2016, 409-423 5 T. Fujimori, A.M. Grabiec, M. Kaur, T.J. Bell, N. Fujino, P.C. Cook, The Axl receptor tyrosine kinase is a discriminator of macrophage function in the inflamed lung, Mucosal Immunol, Vol. 8, 2015, 1021-1030 6 E.T. Schmid, I.K. Pang, E.A. Carrera Silva, L. Bosurgi, J.J. Miner, M.S. Diamond, AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity, Elife, Vol. 5, 2016, e12414 7 C.P. Ko, Y.L. Yu, P.C. Hsiao, S.F. Yang, C.B. Yeh, Plasma levels of soluble Axl correlate with severity of community-acquired pneumonia, Mol Med Rep, Vol. 9, 2014, 1400-1404 8 M. Contoli, S.D. Message, V. Laza-Stanca, M.R. Edwards, P.A. Wark, N.W. Bartlett, Role of deficient type III interferon-lambda production in asthma exacerbations, Nat Med, Vol. 12, 2006, 1023-1026 9 R. Djukanovic, T. Harrison, S.L. Johnston, F. Gabbay, P. Wark, N.C. Thomson, The effect of inhaled IFN-beta on worsening of asthma symptoms caused by viral infections: a randomized trial, Am J Respir Crit Care Med, Vol. 190, 2014, 145-154
OBJECTIVE To compare the risk of cardiovascular-related hospitalization, statin adherence, and direct (medical and drug) and indirect (disability and medically related absenteeism) costs in US ...employees in whom atorvastatin or simvastatin was newly prescribed. PATIENTS AND METHODS Active employees aged 18 to 64 years with a new atorvastatin or simvastatin prescription were identified from a deidentified claims database for 23 privately insured US companies from January 1, 1999, through December 31, 2006. Employees given atorvastatin were matched to those given simvastatin according to propensity scores based on patient characteristics, index statin dose, preindex cardiovascular events, and wage. Outcomes were compared between matched cohorts during the 2-year postindex period, including the risk of cardiovascular-related hospitalization, adherence to the index statin, use of other lipid-lowering drugs, direct medical costs for third-party payers, and indirect costs to employers. Indirect costs were computed as follows: Disability Payments + Daily Wage × Days of Medically Related Absenteeism. Atorvastatin and simvastatin drug costs were imputed using recent pricing to account for the availability of lower-cost generic simvastatin after the study period. RESULTS Among 13,584 matched pairs, treatment with atorvastatin vs simvastatin was associated with a reduced risk of cardiovascular-related hospitalization, higher adherence, and less use of other lipid-lowering drugs. The increase in statin costs associated with atorvastatin vs simvastatin therapy was almost completely offset by reductions in medical service and indirect costs. CONCLUSION In this study, treatment with atorvastatin compared with simvastatin was associated with a reduced risk of cardiovascular events, reduced indirect costs, and a minimal difference in total costs to employers.
Abstract
Background
Myocardial infarction (MI) and hypertension lead to myocardial injury, which induces negative remodelling and cardiac fibrosis. Cardiac fibrosis, which involves inflammatory cell ...infiltration and myofibroblast activation, causes worldwide mortality and morbidity. In response to MI or hypertension induced by prolonged angiotensin II (AngII) exposure, activated myofibroblasts produce extracellular matrix proteins. However, if unchecked, excessive collagen deposition occurs leading to myocardial stiffening, heart failure and arrhythmias.
Purpose
The underlying mechanisms leading to pathological collagen deposition are not fully elucidated. There is debate regarding the involvement of the Wnt signalling pathway and its product Wnt Inducible Signalling pathway protein-1 (WISP-1) in cardiac fibrosis. Therefore, this project aimed to investigate the interaction of AngII and the Wnt/β-catenin signalling pathway in cardiac fibrosis.
Methods
The effect of AngII (100nM) on collagen levels in human cardiac fibroblasts was investigated in vitro (data expressed as fold change from control ± SEM). In vivo experiments (n=6–8) determined the involvement of the Wnt/b-catenin pathway, specifically WISP-1, in response to AngII infusion (500ng/kg/min) for 4 weeks (Apolipoprotein E−/−/WISP-1+/+ vs. ApolipoproteinE−/−/WISP-1−/− mice on a high-fat diet, data expressed as mean positive pixel % ± SEM).
Results
AngII significantly increased collagen type 1 protein levels produced by human cardiac fibroblasts (2.94±0.75 vs 1±0, p<0.05). Inhibition of Wnt/b-catenin signalling with 25nM iCRT14 significantly suppressed AngII-induced collagen levels (0.46±0.07 vs. 1±0, p<0.05). As expected, AngII infusion significantly induced hypertension in all mice. Immunohistochemistry demonstrated type 1 collagen was markedly higher in AngII mice than control mice (1.07±0.27 vs. 0.29±0.06, p<0.05). However, in the absence of WISP-1, AngII did not enhance collagen type 1 levels. Further immunohistochemical analysis of murine hearts demonstrated that AngII infusion caused significant alterations in the Wnt/β-catenin signalling markers AXIN-2 (35±3.9 vs. 10.7±2.6 p<0.05) and PPAR-d (92±1.4 vs. 17.3±4.3 p<0.05). This effect was reduced by WISP-1 deletion. Furthermore, AngII-infusion disrupted N-cadherin junctions (0.55±0.08 vs. 0.29±0.02 p<0.05) suggesting modulation of cell-to-cell contacts and enhanced β-catenin signalling.
Conclusion
This study indicates that AngII enhances cardiac fibrosis via modulation of the Wnt signalling pathway, in part via WISP-1. Further delineation of this interaction may lead to the use of Wnt/β-catenin or WISP-1 inhibitors to suppress myocardial injury induced cardiac fibrosis in post-MI or hypertensive patients.
Acknowledgement/Funding
Elizabeth Blackwell Institute, British Heart Foundation
Multiple key cardiology trials with the potential to change practice or advance understanding have been presented over the past 12 months at international meetings, including the American College of ...Cardiology (ACC, Chicago, USA, March 2012), European Association for Percutaneous Cardiovascular Interventions (EuroPCR, Paris, France, May 2012), European Society of Cardiology (ESC, Munich, Germany, August 2012), Transcatheter Cardiovascular Therapeutics (TCT, Miami, USA, October 2012), and the American Heart Association (AHA, Los Angeles, USA, November 2012). In this paper, the authors describe and place in clinical context new acute coronary syndrome data, including use of oral antiplatelets and anticoagulants (prasugrel, rivaroxaban, vorapaxar), personalized antiplatelet therapy guided by platelet aggregometry, glucose-insulin-potassium infusion, and changing trends in myocardial infarction. New trial data are also described for interventional cardiology (revascularization in multivessel disease, fractional flow reserveguided intervention, radial access, bioabsorbable polymer stents, drug-eluting balloons, intraaortic balloon pump use, transcatheter aortic valve implantation), in heart failure (copeptin, angiotensin receptor neprilysin inhibition, aldosterone blockade in diastolic heart failure, biventricular pacing), atrial fibrillation (surgical ablation, antithrombotic strategy after stenting), implantable defibrillator use, and in prevention (renal denervation in hypertension, dalcetrapib, lomitapide, proprotein convertase subtilisin/kexin type 9 in dyslipidemia, insulin glargine/fish oils, and bariatric surgery in diabetes).
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