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Intramural hematoma of the aorta: predictors of progression to dissection and rupture.

BACKGROUND: Aortic intramural hematoma (IMH) is a variant of overt aortic dissection. The predictors of progression of IMH to dissection and rupture are still unknown, and strategies for management are not established. METHODS AND RESULTS: A multicenter study was conducted comprising 66 patients with IMH and hospital admission <or=48 hours after onset of initial symptoms. Among these, progression to aortic dissection or rupture occurred in 30 (45%) and death occurred in 13 (20%) patients within 30 days. Late progression was noted in 14 (21%) and death in 11 (17%) patients, yielding a 1-, 2-, and 5-year survival of 76%, 73%, and 43%, respectively. In a set of 9 variables, multivariate analysis identified IMH location in the ascending aorta (type A; P=0.02) and moderately ectatic aortic diameters (49+/-13 mm with progression versus 57+/-16 mm without progression; P=0.03) as independent predictors of early progression. In type A IMH, early mortality was 8% with swift surgery versus 55% without surgery (P=0.004). The risk of late progression of IMH was independently associated with age at index diagnosis (P=0.01) and absence of beta-blocker therapy during follow-up (P=0.03). Kaplan-Meier analysis confirmed improved 1-year survival of IMH with beta-blocker therapy (95% versus 67% without beta-blockers; P=0.004). CONCLUSIONS: Regardless of aortic diameter, IMH of the ascending aorta (type A) is at high risk for early progression, and, thus, undelayed surgical repair should be performed. Moreover, oral beta-blocker therapy may improve long-term prognosis of IMH independent of anatomical location.

Adult↗

Statins but not angiotensin-converting enzyme inhibitors delay progression of aortic stenosis.

BACKGROUND: Recently, statins and angiotensin-converting enzyme inhibitors (ACEIs) have been shown to slow aortic valve calcium accumulation. Although several studies also suggest that statins may reduce the hemodynamic progression of aortic stenosis (AS), no data are available for ACEIs or the combination of both. METHODS AND RESULTS: A total of 211 consecutive patients (aged 70+/-10 years, 104 females) with native AS, defined by a peak velocity >2.5 m/s (valve area 0.84+/-0.23 cm(2), mean gradient 42+/-19 mm Hg), with normal left ventricular function and no other significant valvular lesion who were examined between 2000 and 2002 and who had 2 echocardiograms separated by at least 6 months were included. Of these, 102 patients were treated with ACEIs, 50 patients received statins, and 32 patients received both. Hemodynamic progression of AS was assessed and related to medical treatment. Annualized increase in peak aortic jet velocity for the entire study group was 0.32+/-0.44 m x s(-1) x y(-1). Progression was significantly lower in patients treated with statins (0.10+/-0.41 m x s(-1) x y(-1)) than in those who were not (0.39+/-0.42 m x s(-1) x y(-1); P<0.0001). This effect was observed both in mild-to-moderate and severe AS. ACEI use, however, did not significantly affect hemodynamic progression (P=0.29). Furthermore, ACEIs had no additional effect on AS progression when given in combination with statins (0.11+/-0.42 versus 0.08+/-0.43 m x s(-1) x y(-1) for combination versus statin only; P=0.81). Cholesterol levels did not correlate with hemodynamic progression either in the group receiving statins or in the group that did not. CONCLUSIONS: ACEIs do not appear to slow AS progression. However, statins significantly reduce the hemodynamic progression of both mild-to-moderate and severe AS, an effect that may not be related to cholesterol lowering.

Aged↗

Markers of inflammation and rapid coronary artery disease progression in patients with stable angina pectoris.

BACKGROUND: Both endothelial cell activation and macrophage activation play a significant role in atherogenesis and atheromatous plaque vulnerability and may determine rapid coronary artery disease (CAD) progression. We sought to assess the association between serum inflammatory markers and rapid CAD progression in patients with chronic stable angina pectoris. METHODS AND RESULTS: We studied 124 chronic stable angina pectoris patients (84 men; mean age, 61+/-10 years) who were on a waiting list for coronary angioplasty for a mean time of 4.8+/-2.4 months. CAD progression was defined as > or =10% diameter reduction of a pre-existing stenosis > or =50%, > or =30% diameter reduction of a stenosis <50%, development of a new stenosis > or =30% in a previously normal segment, or progression of any stenosis to total occlusion. CAD progression occurred in 35 patients (28%). After adjustment with binary logistic regression, neopterin (P<0.001), high-sensitivity C-reactive protein (P=0.017), matrix metalloproteinase-9 (P=0.002), soluble intercellular adhesion molecule 1 (P<0.001), and previous history of unstable angina (P=0.01) were independent predictors of rapid CAD progression. The association between rapid disease progression and inflammatory markers remained significant even when presence of complex lesions was introduced into the multivariate model. CONCLUSIONS: Rapid CAD progression in patients with stable angina pectoris is associated with increased C-reactive protein levels and raised concentrations of biochemical markers of endothelial and macrophage activation.

Aged↗

Rapid angiographic progression of coronary artery disease in patients with elevated lipoprotein(a)

BACKGROUND: The mechanisms underlying rapid angiographic progression of coronary artery disease are still unknown. Intravascular thrombosis with or without plaque rupture may be involved. METHODS AND RESULTS: In a prospective study in 79 patients with coronary artery disease and at least one coronary diameter stenosis > or = 50%, possible risk factors for rapid progression were investigated. Quantitative coronary angiography was performed twice at a mean time interval of 66 +/- 25 days. Rapid progression of coronary disease defined as (1) an increase > 10% in stenosis severity in at least one stenosis > or = 50%, (2) occurrence of a new stenosis > or = 50%, or (3) occlusion of a formerly patent vessel was found in 21 patients (27%). Between patients with rapid progression and those without, there were no significant differences in sex distribution, age, smoking history, frequency of hypertension or diabetes mellitus, and serum LDL cholesterol, HDL cholesterol, and apolipoprotein B concentrations. In contrast, serum lipoprotein(a) [Lp(a)] concentrations > or = 25 mg/dL were found in 14 of 21 patients (67%) with rapid progression of coronary artery disease but in only 19 of 58 (33%) in the group without progression (P = .007). The respective median Lp(a) concentrations were 66 mg/dL (range, 2 to 139) and 13 mg/dL (range, 2 to 211; P = .01). CONCLUSIONS: Lp(a) appears to be a risk factor for the rapid angiographic progression of coronary artery disease. The pathophysiological link between Lp(a) and rapid progression may be an interference with thrombolysis through the partial structural homology of Lp(a) with plasminogen.

Blood Pressure↗

C-reactive protein predicts progression of atherosclerosis measured at various sites in the arterial tree: the Rotterdam Study.

UNLABELLED: Background and Purpose- C-reactive protein (CRP) predicts myocardial infarction and stroke. Its role as a predictor of the progression of subclinical atherosclerosis is not yet known. We investigated whether CRP predicts progression of atherosclerosis measured at various sites in the arterial tree. METHODS: CRP levels were measured in a random sample of 773 subjects >/=55 years of age who were participating in the Rotterdam Study. Subclinical atherosclerosis was assessed at various sites at 2 points in time, with a mean duration between measurements of 6.5 years. RESULTS: After adjustment for age, sex, and smoking habits, odds ratios (ORs) associated with CRP levels in the highest compared with the lowest quartile were increased for progression of carotid (OR, 1.9; 95% CI, 1.1 to 3.3), aortic (OR, 1.7; 95% CI, 1.0 to 3.0), iliac (OR, 2.0; 95% CI, 1.2 to 3.3), and lower extremity (OR, 1.9; 95% CI, 1.0 to 3.7) atherosclerosis. The OR for generalized progression of atherosclerosis as indicated by a composite progression score was 4.5 (95% CI, 2.3 to 8.5). Except for aortic atherosclerosis, these estimates hardly changed after additional adjustment for multiple cardiovascular risk factors. In addition, ORs for progression of atherosclerosis associated with high CRP levels were as high as those associated with the traditional cardiovascular risk factors high cholesterol, hypertension, and smoking. Geometric mean levels of CRP increased with the total number of sites showing progression of atherosclerosis (P=0.002 for trend). CONCLUSIONS: CRP predicts progression of atherosclerosis measured at various sites in the arterial tree.

Age Distribution↗

Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors.

BACKGROUND: Recent studies demonstrated an influence of atherosclerotic risk factors on the progression of aortic valve stenosis. The extent of aortic valve calcification (AVC) was also found to be a strong predictor of stenosis progression. We investigated the influence of the LDL cholesterol level (LDL), other standard cardiovascular risk factors, and the extent of coronary calcification (CC) on the progression of AVC quantified by electron beam tomography (EBT). METHODS AND RESULTS: In 104 patients (64.7+/-8 years, 89 male) with an EBT scan positive for AVC, CC and AVC were quantified using a volumetric score. EBT was repeated at a mean interval of 15 months (10 to 36 months), and the progression of AVC and CC was determined. Patients were divided into 2 groups according to LDL: group 1, LDL</=3.36 mmol/L (130 mg/dL), 57 patients; group 2, LDL>3.36 mmol/L (130 mg/dL), 47 patients. Mean values for CC were 546+/-932 mm(3) in scan 1 and 665+/-1085 mm(3) in scan 2 for AVC 324+/-796 mm(3) and 404+/-1076 mm(3), respectively. The mean progression of CC was 27+/-37% (group 1, 16+/-22%; group 2, 39+/-46%, P</=0.001) and of AVC was 25+/-38% (group 1, 9+/-22%; group 2, 43+/-44%, P</=0.001). CONCLUSIONS: Quantification of AVC by EBT permits new insights into the progression of aortic valve sclerosis. We observed a strong influence of LDL cholesterol level on the progression of AVC and CC, suggesting that lipid-lowering therapy may decrease the progression of aortic valve calcification.

Aged↗

Accommodation and related risk factors associated with myopia progression and their interaction with treatment in COMET children.

PURPOSE: To examine baseline measurements of accommodative lag, phoria, reading distance, amount of near work, and level of myopia as risk factors for progression of myopia and their interaction with treatment over 3 years, in children enrolled in the Correction of Myopia Evaluation Trial (COMET). METHODS: COMET enrolled 469 ethnically diverse children (ages, 6-11 years) with myopia between -1.25 and -4.50 D. They were randomly assigned to either progressive addition lenses (PALs) with a +2.00 addition (n = 235) or single vision lenses (SVLs; n = 234), the conventional spectacle treatment, and were observed for 3 years. The primary outcome measure was progression of myopia by autorefraction after cycloplegia with 2 drops of 1% tropicamide. Other measurements included accommodative response (by an open field of view autorefractor), phoria (by cover test), reading distance, and hours of near work. Independent and interaction analyses were based on the mean of the two eyes. Results were adjusted for important covariates with multiple linear regression. RESULTS: Children with larger accommodative lags (>0.43 D for a 33 cm target) wearing SVLs had the most progression at 3 years. PALs were effective in slowing progression in these children, with statistically significant 3-year treatment effects (mean +/- SE) for those with larger lags in combination with near esophoria (PAL - SVL progression = -1.08 D - [-1.72 D] = 0.64 +/- 0.21 D), shorter reading distances (0.44 +/- 0.20 D), or lower baseline myopia (0.48 +/- 0.15 D). The 3-year treatment effect for larger lags in combination with more hours of near work was 0.42 +/- 0.26 D, which did not reach statistical significance. Statistically significant treatment effects were observed in these four groups at 1 year and became larger from 1 to 3 years. CONCLUSIONS: The results support the COMET rationale (i.e., a role for retinal defocus in myopia progression). In clinical practice in the United States children with large lags of accommodation and near esophoria often are prescribed PALs or bifocals to improve visual performance. Results of this study suggest that such children, if myopic, may have an additional benefit of slowed progression of myopia.

Accommodation, Ocular↗

Monitoring glaucomatous visual field progression: the effect of a novel spatial filter.

PURPOSE: To assess the impact of a novel visual field spatial filtering technique on the detection of glaucomatous progression. METHODS: One hundred ninety-eight ocular hypertensive (OHT) and 21 control subjects were examined prospectively (1994-2001) with regular full-threshold Humphrey visual field (VF) testing. VF progression was assessed by point-wise linear regression (PLR) of sensitivity/time in Progressor for Windows software modified to include a novel spatial filter. Standard progression criteria (slope > -1 dB/year, P < 0.01) were applied to both "raw" (unfiltered) and "filtered" VF series. Three-omitting confirmatory VF criteria were also applied to unfiltered VF series. Specificity was estimated as the proportion of progressing control subjects and as the proportion of significantly improving subjects (both OHT and control) at the end of the study period. RESULTS: Applying standard PLR, specificity was estimated at 91.8% to 97.5% using unfiltered standard PLR, compared with 93.5% to 98.4% using filtered standard PLR and 95.4% to 99.3% using unfiltered three-omitting PLR. The rate of identified VF progression in the OHT cohort was 32.3% with unfiltered standard PLR, 28.7% with filtered standard PLR, and 18.6% with unfiltered three-omitting PLR. There was no significant difference in time to detected progression between filtered and unfiltered standard PLR. CONCLUSIONS: The use of confirmatory tests resulted in improved specificity using unfiltered data; however, application of the spatial filter resulted in similar specificity but with a higher rate of detected progression. This filter may therefore be useful in the monitoring of glaucomatous progression as it may reduce the dependence on confirmatory testing, although it has yet to be applied to longitudinal SITA data.

Adult↗

Prediction of short-term progression or regression of atherosclerotic coronary artery disease by lipoprotein (a): a quantitative coronary angiographic study.

This study assessed whether progression of coronary artery atherosclerotic lesions could be predicted in the short term using various lipid profiles. In 37 patients (61.9 +/- 9.5 years) undergoing coronary angioplasty and with 6-month follow-up angiography, quantitative coronary angiography of a new or changed lesion was performed in the follow-up examination, except for intervention vessels. The progression-regression score of the assessed lesion was calculated as the baseline minus the follow-up minimal lumen diameter. The serum lipoprotein (a) level was higher in the progression group (progression-regression score > 0.15 mm), than in the regression group (< or = -0.15 mm; p < 0.01) and the no change group (within +/- 0.15 mm; p < 0.05). Remnant-like lipoprotein particle-cholesterol and apolipoprotein-B levels were also higher in the progression group. However, multiple regression analysis of the progression showed that the progression-regression score was independently correlated with lipoprotein (a) alone (R = 0.50, p < 0.05). This shows that lipoprotein (a) is an independent predictor of coronary atherosclerotic lesion progression over the short term.

Coronary Angiography↗

Lymphocytosis decline is not responsible for tumor progression in cancer patients chronically treated with interleukin-2.

AIMS AND BACKGROUND: The antitumor activity of IL-2 is mediated by an increase in lymphocyte number. Moreover, our previous studies have shown that therapy for 1 week/month with low-dose subcutaneous IL-2 is sufficient to maintain high levels of lymphocytes in cancer patient who have had tumor regression or stable disease (SD) in response to IL-2 immunotherapeutic cycles. This study was performed to establish whether tumor progression in cancer patients chronically treated with IL-2 may be associated with lymphocyte number decline. METHODS: The study included 53 metastatic renal cell cancer patients, who were treated with 2 induction cycles of IL-2 subcutaneous immunotherapy (6 million IU/day for 5 days/week for 6 weeks, corresponding to one cycle). Tumor regression occurred in 15/53 patients, 20 patients had a SD, and the remaining 18 cases progressed. Non progressed patients (n = 35) underwent a maintenance therapy consisting of one week of therapy every month. After a median follow-up of 18 months, 26/35 patients with response or SD had progressed. The immune investigation consisted of lymphocyte, T lymphocyte, NK cell number determination and sCD25 level detection. RESULTS: The mean number of lymphocytes, T lymphocytes and NK cells observed on IL-2 maintenance therapy was significantly higher than that seen before beginning the immunotherapy. Moreover, mean number of lymphocytes and mean levels of sCD25 observed at the time of tumor progression were respectively lower and higher than those seen on maintenance therapy in the same patients, without, however, significant differences. CONCLUSION: Despite the importance of lymphocytes in mediating the antitumor activity of IL-2, this study shows that tumor progression in cancer patients chronically treated with low-dose IL-2 after response or SD during IL-2 induction cycles is not associated with a significant decline in lymphocyte, T lymphocyte or NK cell numbers. Further studies, carried out to analyze the functional status of immune cells at the time of tumor progression, will be necessary to define the role of immunity in cancer patients progressing under IL-2 chronic therapy.

Carcinoma, Renal Cell↗

Predicting cancer progression in patients with stage T1 bladder carcinoma.

PURPOSE: A significant number of patients with stage T1 bladder carcinoma are at risk for cancer progression. We sought to identify factors associated with cancer progression in a series of patients with stage T1 bladder carcinoma treated with a contemporary therapeutic approach. PATIENTS AND METHODS: The study population consisted of 83 consecutive patients in whom stage T1 bladder carcinoma was diagnosed at the Mayo Clinic between 1987 and 1992. All patients underwent transurethral resection of the bladder (TURB) and had histologic confirmation of the diagnosis. The mean age was 71 years (range, 47 to 94 years). The male-to-female ratio was 3.9:1. The mean length of follow-up was 5.2 years (range, 1 day to 10.4 years). The depth of lamina propria invasion in the TURB specimens was measured with an ocular micrometer. Cancer progression was defined as the development of muscle-invasive or more advanced stage carcinoma, distant metastasis, or death from bladder cancer. RESULTS: The overall 5- and 7-year progression-free survival rates were 82% and 80%, respectively. The depth of invasion in the TURB specimens was associated with cancer progression (hazards ratio, 1.6 for doubling of depth of invasion; 95% confidence interval, 1.03 to 2.4; P =.037). The 5-year progression-free survival rate for patients with depth of invasion of >/= 1.5 mm was 67%, compared with 93% for those with depth of invasion of less than 1.5 mm (P =.009). No other variable, including age, sex, tobacco use, alcohol use, the presence of carcinoma-in-situ, histologic grade, lymphocytic infiltration, or muscularis mucosae invasion, was associated with cancer progression. CONCLUSION: The depth of invasion in the TURB specimens, measured with a micrometer, is predictive of cancer progression in patients with stage T1 bladder carcinoma.

Aged↗

Vascular risk factors, incidence of MCI, and rates of progression to dementia.

OBJECTIVE: To estimate prevalence, incidence, and rate of progression of mild cognitive impairment (MCI) to dementia and correlated vascular risk factors with incident MCI and its progression to dementia. METHODS: The authors evaluated 2,963 individuals from the population-based sample of 5,632 subjects 65 to 84 years old, at the first (1992 to 1993) and second survey (1995 to 1996) of the Italian Longitudinal Study on Aging (ILSA), with a 3.5-year follow-up. Dementia, Alzheimer disease (AD), vascular dementia (VaD), other types of dementia, and MCI were classified using current clinical criteria. RESULTS: Among the 2,963 participants, 139 MCI patients were diagnosed at the first ILSA survey. During the 3.5-year follow-up, 113 new events of MCI were diagnosed with an estimated incidence rate of 21.5 per 1,000 person-years. We found a progression rate to dementia (all causes) of 3.8/100 person-years. Specific progression rates for AD, VaD, and other types of dementia were 2.3, 1.3, and 0.3/100 person-years. Furthermore, age was a risk factor for incident MCI (RR: 5.93, 95% CI: 3.17 to 11.10), while education was protective (RR: 0.06, 95% CI: 0.03 to 0.10), and serum total cholesterol evidenced a borderline nonsignificant trend for a protective effect. There was a nonsignificant trend for stroke as a risk factor of progression of MCI to dementia. CONCLUSIONS: In this population, among those who progressed to dementia, 60% progressed to AD and 33% to VaD. Vascular risk factors influence incident mild cognitive impairment and the rate of progression to dementia.

Aged↗

Comparison of apraxia in corticobasal degeneration and progressive supranuclear palsy.

OBJECTIVE: To describe ideomotor apraxia in patients with corticobasal degeneration and those with progressive supranuclear palsy, two parkinsonian disorders that are often misdiagnosed due to the overlap in their clinical features, and to determine whether systematic apraxia testing is useful for differential diagnosis. METHODS: Fourteen patients fulfilling National Institute of Neurological Disorders and Stroke-Society for Progressive Supranuclear Palsy clinical criteria for progressive supranuclear palsy, 13 patients fulfilling modified Lang criteria for corticobasal degeneration, and 12 normal healthy control subjects were given the Test of Oral and Limb Apraxia, which was scored according to the Florida Apraxia Battery for occurrence of various types of apraxic errors. RESULTS: Both patients with progressive supranuclear palsy and corticobasal degeneration committed a greater number of apraxic errors than normal healthy control subjects on both transitive and intransitive tasks (p < 0.001 in both cases), but apraxia was much more severe in patients with corticobasal degeneration than progressive supranuclear palsy (p < 0.001). The index of apraxia severity, in combination with the assessment of the two key features of progressive supranuclear palsy (falls and vertical gaze palsy), correctly classified all patients. CONCLUSIONS: Patients with corticobasal degeneration show more severe ideomotor apraxia than patients with progressive supranuclear palsy, and systematic assessment of ideomotor apraxia facilitates the differential diagnosis between patients with progressive supranuclear palsy and those with corticobasal degeneration.

Aged↗

Progression of asbestosis predicts lung cancer.

STUDY OBJECTIVES: To explore whether the progression of asbestosis correlates with the risk of lung cancer among patients with asbestosis. DESIGN: A group of 85 asbestosis patients (78 men and 7 women) were radiographically followed up between 1979 and 1987. Two or three posteroanterior radiographs taken from each patient in 1978 to 1979, 1983 to 1984, and 1986 to 1987 were classified according to the International Labour Office 1980 classification and were used to divide the patients into progressors and nonprogressors. Follow-up for cancer was done automatically through the files of the Finnish Cancer Registry from the time of determination of the progression status to December 31, 1994. Predictors of lung cancer risk were studied with a logistic regression model, and the standardized incidence ratio (SIR) was calculated for lung cancer. RESULTS: Of the 24 male patients with progressive small opacity profusion, 11 (46%) developed lung cancer, as opposed to 5 (9%) of the 54 male patients without progression. The SIR for lung cancer was 37 (95% confidence interval, 18 to 66) for the progressors and 4.3 (1.4 to 9.9) for the nonprogressors. In both groups, all the lung cancer cases occurred among smokers or ex-smokers. None of the seven female patients showed progressive small opacity profusion. One of them developed lung cancer. In the logistic regression model including all 85 asbestosis patients, radiographic progression of small opacity profusion (p=0.0009) and current smoking (0.0021) were significant predictors of lung cancer morbidity. CONCLUSIONS: Asbestosis patients with radiographic progression of small opacity profusion over a few years are at a higher risk of lung cancer than those with a less aggressive course of the disease. The progression of pulmonary fibrosis may be an independent risk factor that, in addition to smoking history and the intensity of asbestos exposure, could be used to estimate lung cancer risk.

Adult↗

Apolipoprotein A-IV predicts progression of chronic kidney disease: the mild to moderate kidney disease study.

It has not been established firmly whether dyslipidemia contributes independently to the progression of kidney disease. Lipid and lipoprotein parameters, including levels of total, HDL, and LDL cholesterol; triglycerides; lipoprotein(a); apolipoprotein A-IV; and the apolipoprotein E and A-IV polymorphisms, were assessed in 177 patients who had mostly mild to moderate renal insufficiency and were followed prospectively for up to 7 yr. Progression of kidney disease was defined as doubling of baseline serum creatinine and/or terminal renal failure necessitating renal replacement therapy. In univariate analysis, patients who reached a progression end point (n = 65) were significantly older and had higher serum creatinine and proteinuria as well as lower GFR and hemoglobin levels. In addition, baseline apolipoprotein A-IV and triglyceride concentrations were higher and HDL cholesterol levels were lower. Multivariate Cox regression analysis revealed that baseline GFR (hazard ratio 0.714; 95% confidence interval [CI] 0.627 to 0.814 for an increment of 10 ml/min per 1.73 m(2); P < 0.0001) and serum apolipoprotein A-IV concentrations (hazard ratio 1.062; 95% CI 1.018 to 1.108 for an increment of 1 mg/dl; P = 0.006) were significant predictors of disease progression. Patients with apolipoprotein A-IV levels above the median had a significantly faster progression (P < 0.0001), and their mean follow-up time to a progression end point was 53.7 mo (95% CI 47.6 to 59.8) as compared with 70.0 mo (95% CI 64.6 to 75.4) in patients with apolipoprotein A-IV levels below the median. For the apolipoprotein E polymorphism, only the genotype epsilon2/epsilon4 was associated with an increased risk for progression. In summary, this prospective study in patients with nondiabetic primary kidney disease demonstrated that apolipoprotein A-IV concentration is a novel independent predictor of progression.

Adult↗

Progression of chronic renal disease in the dog.

Progressive loss of nephron function may be caused by persistence of factors that initiated renal disease. However, newer studies suggest that nephron damage is self-perpetuating once renal mass is reduced to some critical level. Original theories on mechanisms of self-perpetuated nephron injury focused on intraglomerular hypertension and glomerular hypertrophy, but several other factors have now been incriminated, including tubulointerstitial responses, proteinuria, and oxidative stress. Studies of dogs with surgically reduced renal mass (remnant kidney model of chronic renal disease) have allowed investigation of the self-progression theory in this species. Use of this model eliminates pre-existing renal disease as a confounding factor. Data from these studies indicate that self-perpetuated renal injury is initiated when mild azotemia is induced (plasma creatinine concentration = 2 to 4 mg/dL). Thus, with naturally occurring renal disease(s), it is likely that self-perpetuated nephron damage is occurring before or at the time when most cases of chronic renal disease are diagnosed. In dogs with remnant kidneys, loss of renal function often occurs at a linear rate over time, but non-linear patterns are common as well. The reciprocal of plasma creatinine concentration, which has been used to monitor rate of progression, is only a fair marker of renal function when compared to GFR. Thus, clinical results from creatinine measurements on cases of naturally occurring disease should not be interpreted too stringently. In remnant kidney dogs, the magnitude of proteinuria (UPC ratio) was not predictive of the rate in decline of GFR, casting doubt on importance of proteinuria in causing progression of renal disease. However, progressive increases in UPC may be a marker of an accelerated rate of renal injury. Self-perpetuation of renal injury in dogs could be the sole mechanism by which naturally occurring renal diseases progress. When more information is available on the rate of progression of naturally occurring diseases, it may become apparent whether factors initially inciting renal damage have an additive effect on rate of progression.

Animals↗

Osteopenia: a new prognostic factor of curve progression in adolescent idiopathic scoliosis.

BACKGROUND: Studies have shown that 27% to 38% of girls with adolescent idiopathic scoliosis have systemic osteopenia. The aim of this study was to investigate whether osteopenia could serve as one of the important prognostic factors in predicting curve progression. METHODS: A prospective study was performed in 324 adolescent girls with adolescent idiopathic scoliosis who had a mean age of thirteen and a half years. Bone mineral density of the spine and both hips was measured at the time of the clinical diagnosis of scoliosis. All patients were followed longitudinally until skeletal maturity or until the curve had progressed > or =6 degrees . The univariate chi-square test and stepwise logistic regression were used to predict the prevalence of curve progression, and a receiver operating characteristic curve was plotted. RESULTS: The overall prevalence of curve progression was 50%. The prevalence of osteopenia at the spine and hips was 27.5% and 23.1%, respectively. A larger initial Cobb angle (odds ratio = 4.6), a lower Risser grade (odds ratio = 4.7), premenarchal status (odds ratio = 2.5), osteopenia in the femoral neck of the hip on the side of the concavity (odds ratio = 2.3), and a younger age at the time of diagnosis (odds ratio = 2.1) were identified as risk factors in predicting curve progression. A predictive model was established, and the area under the receiver operating characteristic curve of the model was 0.80 (p < 0.01). CONCLUSION: Osteopenia may be an important risk factor in curve progression. The measurement of bone mineral density at the time of diagnosis may serve as an additional objective measurement in predicting curve progression in adolescent idiopathic scoliosis. The bone mineral density-inclusive predictive model may be used in treatment planning for patients with adolescent idiopathic scoliosis who are at high risk of curve progression.

Adolescent↗

Impact of simultaneous pancreas and kidney transplantation on progression of coronary atherosclerosis in patients with end-stage renal failure due to type 1 diabetes.

OBJECTIVE: Mortality in type 1 diabetic patients with end-stage renal failure is high and dominated by coronary atherosclerotic events. With regard to prognosis, simultaneous transplantation of pancreas and kidney (SPK) may be superior to kidney transplantation alone (KTA) in type 1 diabetic patients, because normalization of blood glucose levels may reduce progression of coronary atherosclerosis and because it is well known that progression of coronary atherosclerosis is one of the major factors that determines clinical prognosis. However, no data are available on progression of coronary atherosclerosis after SPK. RESEARCH DESIGN AND METHODS: We performed an observational angiographic study comparing progression of coronary atherosclerosis, analyzed with quantitative coronary angiography, in patients with (n = 26) and those without (n = 6) a functioning pancreas graft after SPK, to test the hypothesis that normalization of blood glucose levels by SPK may indeed reduce progression of coronary atherosclerosis in type 1 diabetic patients and thereby improve prognosis. RESULTS: Mean follow-up was 3.9 years. Average glucose control was significantly worse for the patients without a pancreas graft than for patients with a functioning pancreas graft: 11.3 (SD 3.5) vs. 5.9 mmol/l (SD 1.1) (P = 0.03). Mean segment diameter loss (progression of diffuse coronary atherosclerosis) was 0.024 mm/year (SD 0.067) in patients with a functioning pancreas graft, compared with 0.044 mm/year (SD 0.038) in patients in whom the pancreas graft was lost. Minimum obstruction diameter loss (progression of focal coronary atherosclerosis) was 0.037 mm/year (SD 0.086) in patients with a functioning pancreas graft compared with 0.061 mm/year (SD 0.038) in patients in whom the pancreas graft was lost. Regression of atherosclerosis occurred in 38% of patients with a functioning pancreas graft compared with 0% of patients of whom the pancreas graft was lost (P = 0.035). CONCLUSIONS: Our study provides, for the first time, evidence that in patients who have undergone SPK, progression of coronary atherosclerosis in patients with a functioning pancreas graft is reduced compared with patients with pancreas graft failure. Our observation is an important part of the explanation for the observed improved mortality rates reported in type 1 diabetic patients with end-stage renal failure after SPK compared with KTA. In light of these findings described above, SPK must to be carefully considered for all diabetic transplant candidates.

Adult↗