EXAMINATION OF LIQUOR AMNII AS A METHOD OF PREDICTING SEVERITY OF HAEMOLYTIC DISEASE OF NEWBORN.
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Amniotic Fluid↗
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Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis.
BACKGROUND: Platelet activating factor (PAF) is believed to amplify the activity of key mediators of the systemic inflammatory response syndrome (SIRS) in acute pancreatitis, resulting in multiorgan dysfunction syndrome. We tested the hypothesis that a potent PAF antagonist, lexipafant, could dampen SIRS and reduce organ failure in severe acute pancreatitis. METHODS: We conducted a randomised, double blind, placebo controlled, multicentre trial of lexipafant (100 mg/24 hours intravenously for seven days commenced within 72 hours of the onset of symptoms) involving 290 patients with an APACHE II score >6. Power calculations assumed that complications would be reduced from 40% to 24%. Secondary end points studied included severity of organ failure, markers of the inflammatory response, and mortality rate. FINDINGS: Overall, 80/138 (58%) patients in the placebo group and 85/148 (57%) in the lexipafant group developed one or more organ failures. The primary hypothesis was invalidated by the unexpected finding that 44% of patients had organ failure on entry into the study; only 39 (14%) developed new organ failure. Organ failure scores were reduced in the lexipafant group only on day 3: median change -1 (range -4 to +8) versus 0 (-4 to +10) in the placebo group (p=0.04). Systemic sepsis affected fewer patients in the lexipafant group (13/138 v 4/148; p=0.023). Local complications occurred in 41/138 (30%) patients in the placebo group and in 30/148 (20%) in the lexipafant group (20%; p=0.065); pseudocysts developed in 19 (14%) and eight (5%) patients, respectively (p=0.025). Deaths attributable to acute pancreatitis were not significantly different. Interleukin 8, a marker of neutrophil activation, and E-selectin, a marker of endothelial damage, decreased more rapidly in the lexipafant group (both p<0.05); however, absolute values were not different between the two groups. INTERPRETATION: The high incidence of organ failure within 72 hours of the onset of symptoms undermined the primary hypothesis, and power calculations for future studies in severe acute pancreatitis will need to allow for this. Lexipafant had no effect on new organ failure during treatment. This adequately powered study has shown that antagonism of PAF activity on its own is not sufficient to ameliorate SIRS in severe acute pancreatitis
Acute Disease↗
Failure of ST segment elevation to predict severity of acute myocardial infarction.
Praecordial ST segment elevation was measured at 35 electrode positions in each of 40 patients admitted to a coronary care unit after acute transmural anterior myocardial infarction. Serial praecordial electrocardiographic maps were recorded to determine (a) the time course as well as reproducibility of measurements of ST segment alterations, and (b) the degree of correlation between the magnitude of ST segment elevation and the severity of infarction, as assessed clinically or by sequential estimations of serum creatine kinase activity. Large variations in ST segment elevation were found in different patients with a comparable degree of myocardial damage, and at intervals of as little as four hours in the same patient. These variations were greater than could be explained by technical factors, and were not related to apparent changes in the patients' clinical status. The patterns of release of myocardial creatine kinase showed that the time course of ST segment elevation was longer than the period of myocardial necrosis. No correlation was found between the myocardial infarct size as determined by enzyme release and the highest levels of ST segment elevation recorded. The findings suggest that ST segment elevation as measured by praecordial electrocardiographic mapping does not constitute a reliable index of the size or severity of myocardial infarcts in man.
Adult↗
Mixed lymphocyte reactions do not predict severity of graft versus host disease (GVHD) in HLA-DR compatible, sibling bone marrow transplants.
Mixed lymphocyte reactions (MLRs) were measured in 25 HLA-A, B and DR compatible sibling bone marrow transplants. Only four of 25 MLRs were positive and in these the low reactivity was of doubtful clinical importance. There was no correlation between MLR and the subsequent development or severity of graft versus host disease (GVHD). A survey of bone marrow transplant units in the United Kingdom showed that most centres perform HLA-DR typing as well as an assessment of the MLR. Factors other than histocompatibility are important in the pathogenesis of GVHD and the data from this study suggest that conventional MLRs can be omitted in HLA-A, B and DR compatible sibling bone marrow transplants.
Adult↗
Markers of microvascular instability predict severity and survival in idiopathic pulmonary fibrosis.
INTRODUCTION: Most research on idiopathic pulmonary fibrosis (IPF) has focused on the interplay among fibroblasts, the immune system and epithelial cells. There is growing evidence that microvascular dysfunction also plays a role in disease progression, but large human translational studies are lacking. In this research, we aim to identify a proteomic signature of microvascular instability and assess the impact of current therapeutics on the microvasculature. METHODS: Olink proteomic data from patients with IPF were obtained from the Pulmonary Fibrosis Foundation Patient Registry (PFF-PR) (n=914) and an independent validation cohort (n=366). Among the PFF-PR, 640 patients also have whole-blood RNA sequencing data available. A subset of 79 microvascular-associated proteins was curated, and their associations with disease severity and transplant-free survival were examined. An adaptive least absolute shrinkage and selection operator was used to generate a novel microvascular risk score. RESULTS: Higher plasma levels of five microvascular-associated proteins (SDC1, MMP10, THBS2, HGF and SERPINA5) were associated with lung function and survival in both cohorts. Whole-blood RNA sequencing of patients with microvascular risk revealed enrichment of immune-mediated processes. Patients with higher microvascular risk who were subsequently put on nintedanib in the following year had significantly better 3-year transplant-free survival compared with patients who did not receive antifibrotic intervention (HR 0.56, 95% CI 0.35 to 0.89, p=0.0142). DISCUSSION: Integrative multi-omics analyses suggest that perturbations to microvascular remodelling contribute to disease severity and progression in IPF. This analysis offers a framework for a precision medicine approach for IPF.
Idiopathic pulmonary fibrosis↗
Dose-volumetric parameters for predicting severe radiation pneumonitis after three-dimensional conformal radiation therapy for lung cancer.
PURPOSE: To retrospectively evaluate dose-volumetric parameters for association with risk of severe (grade >/=3) radiation pneumonitis (RP) in patients after three-dimensional (3D) conformal radiation therapy for lung cancer. MATERIALS AND METHODS: The study was approved by the institutional review board, which did not require informed consent. Data from 76 patients (66 men, 10 women; median age, 60 years; range, 35-79 years) with histologically proved lung cancer treated curatively with 3D conformal radiation therapy between August 2001 and October 2002 were retrospectively analyzed. Twenty patients underwent surgery before radiation therapy; 57 patients received chemotherapy. Median total radiation dose of 60 Gy (range, 54-66 Gy) was delivered in 30 (range, 27-33) fractions over 6 weeks. RP was scored by using Radiation Therapy Oncology Group criteria. Clinical parameters were analyzed. Dose-volumetric parameters analyzed were percentage of lung volume that received a dose of 20 Gy or more (V20), 30 Gy or more (V30), 40 Gy or more (V40), or 50 Gy or more (V50); mean lung dose (MLD); normal tissue complication probability (NTCP); and total dose. Fisher exact test was performed to compare clinical parameters between patients who developed severe RP and those who did not. Univariate and multivariate logistic regression analyses were performed to evaluate data for association between dose-volumetric parameters and severe RP. Pearson chi(2) test was used to assess data for correlations among dose-volumetric parameters. P < or = .05 was considered to indicate statistically significant difference. RESULTS: Of 76 patients, 30 (39%) did not develop RP; 23 (30%) developed RP of grade 1; 11 (14%), grade 2; 11 (14%), grade 3; and 1 (1%), grade 4. None had grade 5 RP. Age (< 60 vs > or =60), sex, Karnofsky performance status (< 70 vs > or =70), forced expiratory volume in 1 second, presence of weight loss, preexisting lung disease, history of thoracic surgery, and history of chemotherapy did not significantly differ between patients who developed severe RP and those who did not. In univariate analyses, MLD, V20, V30, V40, V50, and NTCP were associated with severe RP (P < .05). In multivariate analysis, MLD was the only variable associated with severe RP. CONCLUSION: MLD is a useful indicator of risk for development of severe RP after 3D conformal radiation therapy in patients with lung cancer.
Adult↗
Stiffness of systemic arteries in patients with myocardial infarction. A noninvasive method to predict severity of coronary atherosclerosis.
The static elastic properties of arterial tree (abdominal aorta and common carotid artery) were studied in 19 normal subjects and in 49 patients with myocardial infarction with an ultrasonic phase-locked echo-tracking system that allows continuous transcutaneous measurement of the arterial diameter. The stiffness index beta, which represented the mechanical properties in the arterial wall, was calculated from the relation between systemic blood pressure and the diameter of the artery. Patients with myocardial infarction underwent coronary angiography in their convalescent period to determine involved vessels. In 11 patients, coronary artery was patent; 15 patients had one-vessel disease, 12 had two-vessel disease, and the remaining 11 patients had three-vessel disease. In normal subjects, increasing age was associated with an increase in arterial stiffness. An average value of the stiffness index of the abdominal aorta was 8.58 +/- 3.02 (mean +/- SD) and that of common carotid artery was 9.17 +/- 2.22. In patients with three-vessel disease, these values were significantly higher (22.37 +/- 4.29 in abdominal aorta and 13.17 +/- 4.56 in common carotid artery) than those in normal subjects. Stiffness index of patients with two- or one-vessel disease was also increased but lower than those in patients with three-vessel disease (p less than 0.05). Forty-four of 49 patients with infarction had an arterial stiffness index of abdominal aorta higher than the 95% confidence limits of the normal data (p less than 0.05). Twenty-eight patients were outside the nomogram of common carotid artery (p less than 0.05). The mechanical properties of these elastic arteries provided sufficiently reliable information on changes caused by atherosclerosis.
Adult↗
The role of SN-38 exposure, UGT1A1*28 polymorphism, and baseline bilirubin level in predicting severe irinotecan toxicity.
Irinotecan, an anticancer drug, is associated with severe and potentially fatal diarrhea and neutropenia. The objective of this analysis was to evaluate the role of SN-38 exposure, the active metabolite of irinotecan, UGT1A1 genotypes, and baseline bilirubin on the maximum decrease (nadir) in absolute neutrophil counts following irinotecan. This analysis extended the work of a previous study that examined the effect of UGT1A1 genotypes on the incidence of severe neutropenia in 86 advanced cancer patients following irinotecan treatment. Regression analysis showed that the absolute neutrophil count nadir depended on SN-38 exposure (AUC) and UGT1A1*28 homozygous 7/7 genotype. An increased SN-38 AUC and the 7/7 genotype were significantly associated with a lower absolute neutrophil count nadir (R2 = .49). An alternate model suggested that higher baseline bilirubin and the 7/7 genotype were also significantly associated with a lower absolute neutrophil count nadir, although with a lower coefficient of determination (R2 = .31). Based on these findings and other reports, the irinotecan label was modified to indicate the role of UGT1A1*28 polymorphism in the metabolism of irinotecan and the associated increased risk of severe neutropenia. The label modifications also included recommendations for lower starting doses of irinotecan in patients homozygous for the UGT1A1*28 (7/7) polymorphism.
Antineoplastic Agents, Phytogenic↗
Does technical failure of revascularization during coronary artery bypass grafting predict severity of poststernotomy mediastinitis?
BACKGROUND AND AIMS: To assess the impact of unsuccessful revascularization in relation to poststernotomy mediastinitis (PSM), which affects long-term outcome after coronary artery bypass grafting (CABG). MATERIAL AND METHODS: An active approach for the follow-up of PSM involved a step by step treatment protocol of conventional surgery and plastic reconstructive surgery. 47 patients treated for PSM after CABG were identified and further evaluated. Complete revascularization was considered unsuccessful when technical hazards were reported during CABG. When PSM subsided after thorough debridement and sternal refixation without plastic reconstructive surgery, such as omentoplasty or muscle transposition, PSM was categorized as mild PSM. If treatment required plastic reconstructive surgery, PSM was categorized as severe PSM. Preoperative coronary artery angiographic status and success of revascularization were compared to postoperative outcome in relation to mild and severe PSM. RESULTS: 36 patients suffered from mild PSM and 11 patients from severe PSM. Preoperative clinical status did not differ among patients. Two patients (4.3 %) died during hospitalization. The need for plastic reconstructive surgery was significant (p < 0.05) among patients with unsuccessful revascularization. 35 out of 41 patients (85 %) without problems of graft anastomosis during CABG (successful revascularization) were associated with mild PSM, whereas only 6 out of 41 patients (15 %) with successful revascularization during CABG required plastic reconstructive surgery (p < 0.05). Technical failure of graft anastomosis (3 cases) or poor outflow of internal thoracic artery (2 cases) were statistically associated with severe PSM. CONCLUSION: Technical failures of revascularization during CABG may delay recovery from PSM.
Aged↗
American Society of Anesthesiology classification may predict severe post-tonsillectomy haemorrhage in children.
OBJECTIVE: The purpose of this study was to identify pre- or intraoperative markers for post-tonsillectomy haemorrhage (PTH) that may help to define in-/outpatient tonsillectomy. DESIGN: A retrospective case-control study of tonsillectomized patients. SETTING: A tertiary referral university hospital. METHODS: Twenty-three children with PTH were compared with 69 tonsillectomized age- and sex-matched children without bleeding. The cohort consisted of 559 individuals under 18 years old who were scheduled for tonsillectomy or adenotonsillectomy between 1996 and 2000. MAIN OUTCOME MEASURES: Physical and analytical variables were investigated, including blood pressure, haemoglobin and haematocrit levels, coagulation profile, American Society of Anesthesiology (ASA) physical status classification, indications for surgery, obstructive sleep apnea and snoring, surgical experience, addition of adenoidectomy, method of tonsillectomy, type of anaesthesia, method of haemostasis, and total surgical time. Statistical significance was calculated by the Mann-Whitney U test and Fisher's exact test. RESULTS: The incidence of PTH was 4.11%, and all but one case were primary bleedings. Nineteen cases occurred within the first 8 hours. A possible risk marker identified was ASA class 2 (odds ratio = 5.69, p = .04). Other investigated factors were not significant. CONCLUSIONS: The ASA classification may be a predictor for PTH and could be used to select outpatients before tonsillectomy.
Adenoidectomy↗
Serum ACE predicts severe hypoglycemia in children and adolescents with type 1 diabetes.
OBJECTIVE: To investigate whether risk of severe hypoglycemia is related to serum (S) ACE level during intensive treatment in type 1 diabetic children. RESEARCH DESIGN AND METHODS: A cohort of 86 intensively treated type 1 diabetic patients was studied during 1999-2000. In 1999, the age range was 7-19 years (median 12.8), diabetes duration was 1.2-14.7 years (5.3), insulin dose was 0.4-1.7 units x kg(-1) x 24 h(-1) (1.0), and the HbA(1c) year mean was 4.7-10.2% (6.8). HbA(1c), insulin doses, and events of severe hypoglycemia (needing assistance from another person) were prospectively registered at regular visits, scheduled quarterly. S-ACE was determined once. RESULTS: Severe hypoglycemia was correlated to S-ACE (r = 0.22, 95% CI 0.01-0.41, P = 0.0093). The square root of severe hypoglycemia was correlated to S-ACE (r = 0.27, 95% CI 0.06-0.45, P = 0.0093). Patients with S-ACE at the median level or above (n = 44) reported a mean of 3.0 yearly events of severe hypoglycemia compared with 0.5 events in patients with S-ACE lower than the median (n = 42) (P = 0.0079). Of the patients with an S-ACE at the median level or above, 27 (61%) reported severe hypoglycemia, compared with 17 (40%) patients with an S-ACE lower than the median (P = 0.0527). Insulin dose, HbA(1c), age, onset age, duration, C-peptide, and sex did not differ between these two groups. S-ACE was negatively correlated with age (r = -0.27, 95% CI -0.46 to 0.07, P = 0.0265) but not with HbA(1c), duration, or blood pressure. CONCLUSIONS: The elevated rate of severe hypoglycemia among patients with higher S-ACE suggests, among other factors, that a genetic determinant for severe hypoglycemia exists. Further evaluation is needed before the clinical usefulness of this test can be elucidated.
Adolescent↗
Randomized controlled trial of the effect of early enteral nutrition on markers of the inflammatory response in predicted severe acute pancreatitis.
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Acute Disease↗
[Fall in aortic diastolic pressure immediately after aortic valve destruction can predict severity of regurgitation through the valve and chronic morphological changes in the left ventricle].
Aortic regurgitation (AR) has been studied experimentally, however these reports did not investigate compensatory mechanisms in AR in relation with the severity of regurgitation. If the severity of AR can be changed voluntarily, we can evaluate the pathophysiological response to AR in wide range. The purposes of this study were 1) to see if the extent of fall in aortic diastolic pressure immediately after the production of AR (delta AoDP) was a reliable predictor of the severity of AR and 2) to evaluate the process of adaptation through acute and chronic stage in moderate AR in the rabbit model. AR was produced by perforating the aortic valves in Japanese white rabbits. First, aortic pressure, volume, weight and wall thickness of the left ventricle were measured. Correlations between delta AoDP and body weight-corrected volume (LVV/BW) and weight (LVW/BW) were studied in 18 rabbits soon after, 19 one week after, 23 four weeks after and 10 eight weeks after the production of AR. delta AoDP was closely correlated with LVV/BW after 1 week (1 week: R = 0.667, p less than 0.01, 4 weeks: R = 0.733, p less than 0.01, 8 weeks: R = 0.757, p less than 0.05) and with LVW/BW after 4 weeks (4 weeks: R = 0.484, p less than 0.05, 8 weeks: R = 0.651, p less than 0.05). The slope of these regression equations increased with time (delta AoDP and LVV/BW: 1 week: 0.0138, 4 weeks: 0.0361, 8 weeks: 0.0577 ml/kg.mmHg; delta AoDP and LVW/BW; 4 weeks: 0.0142 8 weeks: 0.0310 g/kg.mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Predicting severity of erythroblastosis.
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Adult↗
Spectrophotometric examination of amniotic fluid as a means of predicting severity of intrauterine erythroblastosis.
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Adult↗
The physical nature of a large bowel perforation predicts severity of the subsequent inflammatory response.
The aim of the study was to determine how the physical nature of a large bowel perforation influences the host inflammatory response. Two rat models were used: a 4 mm cecal perforation (CP) and a cecal ligation with 23 gauge needle puncture (CLP). CP gave a more fulminant course and this was reflected in higher levels of bacteria, endotoxin, tumor necrosis factor, interleukin-1 (IL-1), and IL-6, which were all strongly compartmentalized in the peritoneal cavity. Despite a sustained enhancement of cytokines in peritoneal fluid, only a temporary burst of tumor necrosis factor, and no release of IL-1, were seen in serum, whereas IL-6 was continuously released. Depletion of leukocytes was more pronounced in CP than CLP. In summary, a large bowel perforation like CP triggers an overwhelming host reaction with leukocytopenia, cytokine release, dehydration, hypoperfusion, and death. The smaller fecal inoculum in CLP gives a more subacute inflammatory response.
Animals↗
CNA study predicts severe nursing shortage.
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Canada↗
Clinical usefulness of polymorphonuclear elastase in predicting the severity of acute pancreatitis: results of a multicentre study.
The usefulness and clinical applicability of quantitative plasma polymorphonuclear elastase determinations in the diagnosis of the severity of acute pancreatitis was analysed in a multicentre study and was compared with the usual prognostic systems of Ranson and Osborne et al. The study comprised 182 patients, 154 with a mild episode of acute pancreatitis and 28 with a severe episode, defined by the development of major complications or a fatal outcome. In the severe cases neutrophilic elastase reached significantly higher values than in mild cases (P less than 0.001) by the time the patient was admitted (2-12 h after the onset of the disease), reflecting considerable leucocyte activation. The sensitivity and specificity of this test are therefore greater than 90 per cent, with a positive severity predictive value of almost 80 per cent at the time of admission and 97 per cent after 24 h, and a negative predictive value of approximately 98 per cent. In addition to requiring 48 h for evaluation, the usual prognostic systems show a sensitivity of 77-85 per cent, a specificity of 70-77 per cent, a positive predictive value of 40-48 per cent, and a negative predictive value of 92-95 per cent, clearly lower than those obtained with leucocyte elastase. Polymorphonuclear elastase is therefore a very early and reliable marker in the diagnosis of the severity of acute pancreatitis, in addition to being easily adaptable to the routine of any hospital laboratory.
Acute Disease↗