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Development and validation of an echocardiographic model for predicting progression of discrete subaortic stenosis in children.

The clinical course of discrete subaortic stenosis (DSS) varies considerably between patients. This study was performed to identify echocardiographic characteristics of DSS that distinguish progressive from nonprogressive disease. The study included 100 patients from 2 institutions and was performed in 2 stages. In phase I, a prediction model was developed based on multivariate analysis of morphometric and Doppler variables obtained from the initial echocardiogram in 52 children with DSS from Texas Children's Hospital. In phase II, the performance characteristics of the prediction model were tested in 48 patients with DSS followed at Children's Hospital in Boston. Patients were divided into 3 outcome groups: nonprogressive, progressive, and intermediate progression. In phase I, multivariate analysis identified 3 independent predictors of progressive disease: indexed aortic valve to subaortic membrane distance, anterior mitral leaflet involvement, and initial Doppler gradient. The logistic regression equation--Probability = [1 + e-(-322+0.334X1+4.06X2-0.708X3)](-1), where X = initial gradient in mm Hg; X2 = absence (0) or presence (1) of mitral leaflet involvement; and X3 = indexed distance between aortic valve and subaortic membrane in mm/body surface area0.5 were used to predict progression. When the prediction model was applied to phase II study patients, none of the patients with nonprogressive DSS had a prediction value > 0.29 and none of the patients with progressive DSS had a prediction value < 0.58. Thus, a prediction value > 0.55 yielded a 100% sensitivity and 100% specificity for distinguishing progressive from nonprogressive DSS. Patients with intermediate progression were indistinguishable from progressive DSS but were clearly separable from nonprogressing patients. We conclude that progressive subaortic obstruction in children with DSS can be predicted from morphologic, morphometric, and Doppler echocardiographic analysis of left ventricular outflow.

Aortic Valve Stenosis↗

Factors associated with long-term progression or stability in primary open-angle glaucoma.

PURPOSE: To evaluate long-term risk factors for progression or stability in patients with primary open-angle glaucoma. METHOD: We retrospectively included consecutively reviewed patients who had primary open-angle glaucoma for at least 5 years in this multicenter trial. Historical and clinical factors in these patients were evaluated for their association with stability or progression of the glaucoma. RESULTS: We included 218 patients in this study; of these, 34 progressed over an average length of follow-up of 45.5 +/- 30.0 months, and 184 were stable over an average of 72.8 +/- 18.3 months. The mean intraocular pressure over the follow-up period for the progressed group was 19.5 +/- 3.8 mm Hg and for the stable group 17. 2 +/- 3.1 mm Hg (P =.001). The average standard deviation of individual intraocular pressures was greater in the progressed group (5.1 mm Hg) than the stable group (3.9 mm Hg, P =.012). Baseline characteristics indicating a greater potential to progress were a larger cup-to-disk ratio (P <.001), a greater number of medications (P =.02), older age (P.007), and worse visual acuity (P =.003). However, no difference was observed in pressure levels that prevented progression in these subpopulations compared with the total sample size. CONCLUSIONS: This study suggests that lowering the intraocular pressure is important in the treatment of primary open-angle glaucoma to help prevent long-term progression. Lowering the pressure, however, is not uniformly effective in preventing progression. Additionally, risk factors for progression do not further help identify pressure levels that prevent worsening of glaucoma.

Aged↗

Calpain released from dying hepatocytes mediates progression of acute liver injury induced by model hepatotoxicants.

Liver injury is known to progress even after the hepatotoxicant is long gone and the mechanisms of progressive injury are not understood. We tested the hypothesis that hydrolytic enzymes such as calpain, released from dying hepatocytes, destroy the surrounding cells causing progression of injury. Calpain inhibitor, N-CBZ-VAL-PHE-methyl ester (CBZ), administered 1 h after a toxic but nonlethal dose of CCl(4) (2 ml/kg, ip) to male Sprague Dawley rats substantially mitigated the progression of liver injury (6 to 48 h) and also led to 75% protection against CCl(4)-induced lethality following a lethal dose (LD75) of CCl(4) (3 ml/kg). Calpain leakage in plasma and in the perinecrotic areas increased until 48 h and decreased from 72 h onward paralleling progression and regression of liver injury, respectively, after CCl(4) treatment. Mitigation of progressive injury was accompanied by substantially low calpain in perinecrotic areas and in plasma after CBZ treatment. Normal hepatocytes incubated with the plasma collected from CCl(4)-treated rats (collected at 12 h when most of the CCl(4) is eliminated) resulted in extensive cell death prevented by CBZ. Cell-impermeable calpain inhibitor E64 also protected against progression of CCl(4)-induced liver injury, thereby confirming the role of released calpain in progression of liver injury. Following CCl(4) treatment, calpain-specific breakdown of alpha-fodrin increased, while it was negligible in rats receiving CBZ after CCl(4). Hepatocyte cell death in incubations containing calpain was completely prevented by CBZ. Eighty percent of Swiss Webster mice receiving a lethal dose (LD80) of acetaminophen (600 mg/kg, ip) survived if CBZ was administered 1 h after acetaminophen, suggesting that calpain-mediated progression of liver injury is neither species nor chemical specific. These findings suggest the role of calpain in progression of liver injury.

Acetaminophen↗

Chronic progressive hematomyelia: case reports and review of the literature.

BACKGROUND: Hematomyelia usually has an acute onset and rapid progression, which results in a poor prognosis. However, there have been a few cases in which the clinical symptoms have progressed chronically, with a good prognosis. These two different clinical courses should be analyzed separately. The differential diagnosis of spinal tumor and other chronic progressive diseases due to the similarity of the clinical courses is also important. CASE DESCRIPTION: Two cases of hematomyelia with slowly progressive symptoms are reported. Unlike the acute onset and rapid progression or recurrent episodic deterioration usually seen in hematomyelia, the symptoms of chronic hematomyelia progressed over months and resulted in a better clinical prognosis than the acute course. The cases of "chronic progressive hematomyelia" from the literature are briefly summarized. CONCLUSIONS: Chronic progressive hematomyelia should be considered as a different clinical entity from the acute version because of its slowly progressive clinical course and good outcome. Magnetic resonance imaging is the procedure of choice to exclude spinal tumors or other slowly progressive intraspinal diseases.

Chronic Disease↗

Seminal vesicle involvement after radical prostatectomy: predicting risk factors for progression.

OBJECTIVES: To evaluate and study the factors for progression after radical prostatectomy with seminal vesicle invasion in a cohort of European and American patients. METHODS: The data of 137 patients with isolated seminal vesicle invasion who underwent radical retropubic prostatectomy between 1988 and 2001 were analyzed. The Gleason score of the specimen, presence of capsular invasion, and surgical margin status were noted. Follow-up data were obtained through routine serum prostate-specific antigen (PSA) assays and digital rectal examinations. A defining criterion for progression was a postoperative serum PSA level greater than 0.2 ng/mL or any postoperative radiotherapy or hormonal treatment. Kaplan-Meier analysis was used to determine the actuarial biochemical recurrence-free likelihood, and the log-rank test was used to compare these results. Differences were considered statistically significant when the P value was less than 0.05. RESULTS: After a mean follow-up of 4.9 years (range 0.9 to 13.4), 70 patients (51.9%) had progression. The biochemical 5-year progression-free survival rate was 33.8%. In univariate and multivariate analyses, only preoperative PSA level (P = 0.001) and Gleason score of the specimen (P = 0.01) were independent predictors of progression. Neither capsular invasion nor positive surgical margins predicted progression. When an analysis was performed according to the major Gleason grade of the radical prostatectomy specimen, Gleason grade 5 was associated with a worse prognosis compared with Gleason grade 3 and 4 (P = 0.01). The mean time to progression was 20.5, 17.1, and 10.1 months for Gleason grade 3, 4, and 5, respectively. CONCLUSIONS: Seminal vesicle invasion after radical prostatectomy has historically been associated with a poor prognosis. However, in the present study, seminal vesicle invasion was associated with a 34% rate of freedom from progression at 5 years after surgery alone. Preoperative PSA and Gleason score of the radical prostatectomy specimen were independent factors for progression in the present study, which described the largest patient group to date. The Gleason grade of the radical prostatectomy specimen distinguished among different times to progression.

Aged↗

Darkness and near work: myopia and its progression in third-year law students.

PURPOSE: To evaluate myopia prevalence, myopia progression, and various potential myopia risk factors in third-year law students. DESIGN: Cross-sectional study and survey. PARTICIPANTS: One hundred seventy-nine third-year law students at the University of Pennsylvania. METHODS: We administered a questionnaire to assess the prevalence of myopia, myopia progression, and risk factors, including near work, family history, and daily light/dark exposure. We conducted a screening eye examination to ascertain myopia status. Myopia was defined as the mean spherical equivalent of the two eyes of </=-0.5 diopters; myopia progression was defined by the self-reported need for a stronger eyeglass prescription during law school. MAIN OUTCOME MEASURES: (1) prevalence of myopia, (2) progression of myopia. RESULTS: Seventy-nine percent of the class participated (n = 179, two were excluded for amblyopia leaving 177 students). Fifty-eight percent were male, 75% were Caucasian, and the mean age was 27 years. Seventy-nine percent reported parental myopia. The mean amount of near work was 7.4 hours/day; mean sleep was 7.9 hours/day; mean darkness was 5.3 hours/day. Sixty-six percent of the students were myopic. Of 96 participants myopic before law school, myopia increased in 83 (86%) during law school. Among 75 students not myopic at the beginning of law school, 14 (19%) became myopic. The onset of myopia could not be determined for 6 patients. There were trends for higher myopia prevalence among those with a parental myopia history (P = 0.14) and for increased myopia progression among those reporting more daily near work (P = 0.18). Students with </=5.6 hours of daily darkness were more likely to report myopia progression than those with >5.6 hours of darkness per day (95% vs. 80%, P = 0.07). To account for possible confounding effects of risk factors with myopia progression, logistic regression with categorization of the continuous exposure variables (hours of near work, sleep, and darkness) above or below median values weakened the near work association (odds ratio 1.8, 95% confidence interval 0.5-6.7, P = 0.35) but continued to identify darkness association with daily hours of darkness (odds ratio 4.8, 95% confidence interval 1.0 >/= 23.3, P < 0.05). Among the 77 students with myopia onset before college, those with </=5.6 hours of daily darkness were more likely to progress than those with more hours of daily darkness (97% vs. 76%, P = 0.01). CONCLUSIONS: This study confirms high rates of myopia prevalence and myopia progression among law students. The strongest association, especially in those with myopia onset before college, was a relation of myopia progression during law school with less daily exposure to darkness, a potential risk factor previously identified in childhood myopia. The role of exposure to darkness in refractive development warrants additional study.

Adult↗

Effect of ketoconazole plus low-dose prednisone on progression of chronic renal failure.

Patients with any of four different types of chronic renal failure (CRF) (glomerular disease, interstitial nephritis, diabetic nephropathy, or polycystic disease) were observed using sequential determinations of glomerular filtration rate (GFR). Those whose GFR showed progression were either given ketoconazole 200 to 600 mg/d (to suppress cortisol production) plus prednisone 2.5 mg/d (to prevent anterior pituitary escape) and observed with the use of more GFRs, or were observed while four additional GFRs were determined before starting these drugs; some patients were subsequently withdrawn from these drugs and were observed using more GFRs. The effect of these drugs on rate of progression was estimated by a linear spline technique, using observations before, during, and (when available) after treatment. In 20 patients, sufficient data were obtained to estimate the magnitude of this effect. In seven patients with chronic glomerular disease, progressing at -0.62 +/- 0.12 mL/min/mo, progression slowed by 66% +/- 12% (P < 0.01). In five patients with interstitial nephritis of various etiologies, progressing at -1.19 +/- 0.34 mL/min/mo, progression slowed by 55% +/- 27% (P < 0.05). In five diabetic patients progressing at -1.22 +/- 0.14 mL/min/mo, progression slowed by an average of 77% +/- 14% (P < 0.01). In contrast, in four patients with polycystic kidney disease, progression accelerated by 99% +/- 63%. Mean urinary steroid excretion decreased significantly; plasma corticotropin did not increase. Neither proteinuria nor serum lipid levels changed. Urinary nitrate excretion decreased significantly, but serum nitrate did not change. Blood pressure decreased slightly (4.3 mm Hg). Three patients developed transiently elevated serum transaminase levels; two others withdrew because of side effects. We conclude that in chronic glomerular disease, diabetic nephropathy, and interstitial nephritis, this combination of drugs is as safe as ketoconazole in the absence of renal disease and shows promise of slowing progression. In polycystic kidney disease, it is apparently ineffective or harmful.

Adrenocorticotropic Hormone↗

The urologist view of BPH progression: results of an international survey.

OBJECTIVES: To assess the opinion amongst the international urological community on whether benign prostatic hyperplasia (BPH) is a progressive disease. METHODS: A 15-item questionnaire was distributed to the mailing list of the publication European Urology Today as well as being accessed through the website of the European Association of Urology (EAU). The survey included questions on: whether BPH was a progressive disorder; what evidence there was to support this, including clinical parameters that could be identified; risk factors for progression; and prevention of progression. RESULTS: A total of 472 completed questionnaires from 47 countries were evaluated. Overall, the urologists surveyed agreed that BPH was a progressive disease, and that some patients were more prone to this than others. Increased post-void residual urine, reduced flow rate, increased urinary symptoms and urodynamic evidence of obstruction were considered to be the most significant risk factors for progression. Half of the urologists surveyed considered that current medical therapies could prevent progression of BPH, while a significant proportion thought that surgery was an effective preventative measure. CONCLUSIONS: BPH, although a benign disease, has a considerable impact on the patient's quality of life. Its progressive nature and the identification of risk factors for progression warrant further investigation. In the future, there is likely to be a shift in the paradigm from treatment of BPH complications to include the prevention of BPH progression.

Adult↗

Quantitative analysis of cathepsin L mRNA and protein expression during oral cancer progression.

Although an important risk factor for oral cancer is the presence of epithelial dysplasia, most of these lesions will not progress to malignancy. Presently, for the individual patient with dysplasia, there are few reliable markers that may indicate the likelihood of progression to oral cancer. Cathepsin L is a lysosomal protease that degrades extracellular matrix material. Because cathepsin L is frequently overexpressed in oral squamous cell carcinoma (SCC) we hypothesized that it is also overexpressed in oral premalignancy and that premalignant lesions that progressed to oral cancer expressed higher levels of cathepsin L than those premalignant lesions that did not. In this retrospective pilot study we examined changes in cathepsin L expression at the mRNA level using quantitative TaqMan RT-PCR and at the protein level by immunohistochemistry in 33 routinely processed oral dysplastic lesions and 14 SCCs obtained from 33 patients. Sixteen of the dysplastic lesions progressed to oral SCC and 17 did not after several years of follow-up. Cathepsin L mRNA was overexpressed in 16/33 (48%) dysplastic lesions and in 9/14 (64%) oral SCC. Cathepsin L protein was also overexpressed in a large proportion of dysplasias and cancers. Overexpression was independent of dysplasia grade and identified in both those patients who progressed to oral SCC and in those who did not. Levels of cathepsin L mRNA and protein did not differ significantly in the progressing versus non-progressing dysplasias (P=0.27). However, cathepsin L mRNA and protein were significantly lower in the non-progressing dysplasias when compared to the oral cancers (P=0.03) but not in the progressing dysplasias suggesting a trend for dysplasias with overexpressed cathepsin L to be more likely to progress to oral cancer.

Adult↗

Prediction of progressive liver fibrosis in hepatitis C infection by serum and tissue levels of transforming growth factor-beta.

Although many patients with chronic viral hepatitis C infection suffer from progressive liver disease, the rate of fibrosis progression is highly variable and some patients do not show any measurable progression. However, our ability to predict which patients progress is very limited. Since transforming growth factor-beta (TGF-beta) is a key mediator of liver fibrogenesis, we assessed the predictive role of TGF-beta for fibrogenesis in chronic hepatitis C. We studied 39 patients with chronic hepatitis C in whom two liver biopsies were taken at least 12 months apart, and who did not receive therapy during this period. TGF-beta was measured by bioassay and by ELISA in serum samples taken at the time of the first biopsies, and TGF-beta was determined semiquantitatively by immunostaining of liver biopsy sections. Fibrosis was scored blinded in the biopsy samples by two pathologists independently. There was a close correlation between TGF-beta serum levels and the rate of fibrosis progression. Patients with no progression of fibrosis had significantly lower (59 ng/mL +/- 22) TGF-beta serum levels than patients with progressive disease (115 ng/mL +/- 20), and a TGF-beta level below 75 ng/mL was predictive for stable disease. Immunohistology for TGF-beta in biopsy samples was also predictive for progressive liver disease with fibrosis progression found in those patients displaying staining of hepatocytes and sinusoidal cells. No such correlation was found with other markers such as procollagen III peptide, viral load or transaminase levels. These results further support the role of TGF-beta in liver fibrogenesis, and offer an opportunity to predict clinical disease progression, which may help in selecting patients who are in need of therapeutic interventions.

Alanine Transaminase↗

Cigarette smoking and increased urine albumin excretion are interrelated predictors of nephropathy progression in type 2 diabetes.

BACKGROUND: Increased urine albumin excretion (UAE) predicts nephropathy progression in type 2 diabetes, whereas improved blood pressure (BP) control and angiotensin-converting enzyme (ACE) inhibition ameliorate both albuminuria and nephropathy progression. Cigarette smoking (CS) predicts nephropathy progression in patients with type 2 diabetes despite improved BP control and ACE inhibition. We tested the hypothesis that CS and increased UAE are interrelated predictors of nephropathy progression in patients with type 2 diabetes undergoing improved BP control and ACE inhibition. METHODS: We prospectively followed plasma creatinine (P(cr)) levels and UAE as albumin-creatinine (alb-cr) ratio for 63.9 +/- 0.6 months in 84 patients with type 2 diabetes undergoing BP control with regimens including ACE inhibitors. RESULTS: Despite ACE inhibition and mean BP reduction from 113.7 +/- 1.8 to 92.3 +/- 0.6 mm Hg (P < 0.001), P(cr) increased (1.03 +/- 0.02 to 1.25 +/- 0.04 mg/dL [91.1 +/- 1.8 to 110.5 +/- 3.5 micromol/L]; P < 0.001) during follow-up. Regression analysis showed that entry alb-cr ratio, but not CS, predicted nephropathy progression when considering both factors together, but CS predicted progression only when excluding alb-cr ratio. Nephropathy progression was minimal for lower levels of alb-cr ratio at entry, but increased progressively for levels greater than 300. Alb-cr ratio increment during follow-up directly correlated with nephropathy progression (r2 = 0.307; P < 0.001) and was greater in smokers than nonsmokers (1,878 +/- 346 versus 553 +/- 214; P < 0.001). CONCLUSION: Data show that CS and increased UAE are interrelated predictors of nephropathy progression in patients with type 2 diabetes, and CS increases UAE in these patients despite improved BP control and ACE inhibition.

Adult↗

Patterns of gene expression in peripheral blood mononuclear cells of rhesus macaques infected with SIVmac251 and exhibiting differential rates of disease progression.

Using the Affymetrix HuGeneFL GeneChip, the global expression patterns of genes in the peripheral blood mononuclear cells (PBMCs) of rhesus macaques, infected with SIVmac251 and exhibiting rapid, typical, or slow rates of disease progression, were examined. Assessments of the change in gene expression (fold change), the temporal coordination of gene expression (self-organizing map analysis), and the similarities and significant differences in gene expression across the groups were performed on samples taken before infection and 3 and 7 weeks postinfection. An upregulation of the p27 interferon-inducible gene and of genes associated with cellular activation and immune response was observed in all three groups. Rapidly progressing animals exhibited a modest number of genes with a change in expression of 3-fold or greater, typically progressing animals exhibited the greatest number, and slowly progressing animals exhibited the fewest. Self-organizing map cluster analysis indicated that rapidly progressing animals exhibited the least coordinated gene expression over the three study time points, typically progressing animals exhibited a moderate degree, and animals with slow progression exhibited the most coordinated gene expression. Mann-Whitney U analysis indicated that differences in gene expression were most pronounced between the rapidly and slowly progressing groups and least pronounced between the rapidly and typically progressing animals. These observations elucidate distinct features of gene expression in animals with different rates of disease progression.

Animals↗

Probabilistic diffusion tractography: a potential tool to assess the rate of disease progression in amyotrophic lateral sclerosis.

The goal of probabilistic tractography is to obtain a connectivity index along a white matter pathway that reflects fibre organization and is sensitive to pathological abnormalities contributing to disability. Here, we present the development of voxel-based connectivity measures along the tractography-derived corticospinal tract (CST). We investigated whether these connectivity measures are different in patients with amyotrophic lateral sclerosis (ALS) and correlate with the rate of disease progression. We also investigated whether fractional anisotropy (FA), which reflects directional coherence of fibre tracts, is reduced in the CST of ALS patients and relates to disease progression rate. Thirteen patients with probable or definite ALS and 19 healthy subjects were studied. The probabilistic tractography algorithm segmented the bilateral CST, along which FA and connectivity values were obtained. To take into account the asymmetric distribution of connectivity values, two summary statistic measures that focused on voxels with higher connectivity values were selected and then used in the analysis, together with the mean connectivity and the mean FA. To complete the analysis, the same summary measures for FA were included. Differences in all these indices between patients with moderate or rapid disease progression rate and controls were investigated using linear regression, adjusted for age and white matter fraction. The association between FA or connectivity in the CST and the disease progression rate was assessed using linear regression. Patients with a rapid disease progression rate had significantly lower summary connectivity measures than controls in the left CST, but there was only a borderline statistical difference in mean connectivity. Patients with rapid progression had a significantly lower mean FA, and any other FA measure, in both CSTs than controls. When only patients were considered, strong associations between the rate of disease progression and all the connectivity measures in the left CST were found (P-values between P < 0.001 and P = 0.002, partial correlation coefficients between -0.90 and -0.82). However, there was no evidence of an association between disease progression rate and any of the FA measures in the bilateral CST. Our findings suggest that FA and connectivity provide complementary information, since FA is sensitive to the detection of all the group differences, whereas the summary connectivity measures correlate with disease progression rate. The development of such connectivity measures raises their potential as markers of disease progression in ALS, and provides guidance for their use in other neurological diseases.

Adult↗

Prediction of progression following radical prostatectomy. A multivariate analysis of 721 men with long-term follow-up.

We studied 721 men with clinically confined disease who underwent radical prostatectomy. No patient received preoperative or postoperative radiotherapy or hormone therapy until progression occurred. For those men without progression, the mean follow-up was 6.5 years with a median of 6 years (range 1 to 12 years). Because patients with lymph node metastases or seminal vesicle invasion had such a high risk of progression, enhanced prognostication was not needed in men with these findings. Thus we focused this analysis on the 617 men without lymph node metastases or seminal vesicle invasion. In the multivariate analysis, Gleason score (P < 0.0001), surgical margins (P = 0.004), and capsular penetration (P = 0.007) were all independent predictors of progression. Tumors with a Gleason score of 2 through 4 were almost invariably cured, with a 10-year progression-free risk of 96%. At the opposite end of the spectrum, the 10-year actuarial progression-free risk for men with a Gleason score of 8 through 9 was 35%. Men with Gleason score 2 through 4 or 8 through 9 tumors could not be stratified into different risks of progression based on the presence or extent of capsular penetration or margin status. For the men with Gleason score 5 through 7 tumors (88.2% of cases), predicting their risk of progression was enhanced by knowledge of their tumor's capsular penetration and margin status. Tumors with a Gleason score of 5 through 6 and 7 were each stratified into three groups with different risks of progression. Using the actuarial curves within this study, physicians will be able to more accurately determine a patient's risk of progression following radical prostatectomy based on a combination of the radical prostatectomy Gleason score, extent of capsular penetration, and status of surgical margins of resection.

Disease Progression↗

HIV disease progression in a patient cohort treated via a clinical research network in a resource limited setting.

OBJECTIVE: To examine HIV disease progression in a cohort of adult patients treated with antiretroviral therapy (ART) via a clinical research network in Thailand. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A cohort of 417 patients enrolled in a series of randomized ART trials, between 1996 and December 2002. MAIN OUTCOME MEASURES: Progression to combined endpoint of AIDS defining illness or death according to baseline characteristics, ART used, immunological and virological responses to initial 6 months of ART. RESULTS: During 1677 person years of follow-up, 29 of 417 patients progressed; tuberculosis was the most common event defining progression (14 of 29 events). The rates of progression to combined endpoint or death alone were 1.7 [95% confidence interval (CI), 1.1-2.4] and 0.7 (95% CI, 0.3-1.3) per 10 person years respectively. Compared to patients with baseline CD4 cell counts > or =350 x 10/l, the adjusted hazard ratio (HR) for progression was 3.67 (95% CI, 1.31-10.27) for patients with <200 x 10 cells/l. Responses to 6 months of therapy were the strongest predictors of disease progression; compared to patients with undetectable viral load at 6 months, HR for progression was 4.95 (95% CI, 2.14-11.46) for viral load >4 log10. Compared to patients with a 6-month CD4 cell count > or =350 x 10/l, HR for progression was 5.22 (95% CI, 1.90-14.37) for patients with <200 x 10 cells/l. CONCLUSIONS: HIV-infected patients in Thailand who had access to ART, appropriate care, CD4 cell and viral load monitoring facilities via a clinical research network had progression rates comparable to those in developed countries. In this setting, ART initiation could generally be delayed until the CD4 cell count approaches 200 x 10/l.

AIDS-Related Opportunistic Infections↗

Predictive value of pelvic incidence in progression of spondylolisthesis.

STUDY DESIGN: Retrospective analysis of pelvic incidence and other radiographic parameters as a predictor of progression of isthmic spondylolisthesis. OBJECTIVES: To evaluate the predictive value of various radiographic parameters, including pelvic incidence, in determining the risk for progression of lumbosacral isthmic spondylolisthesis. SUMMARY OF BACKGROUND DATA Although pelvic incidence has recently been shown to be positively correlated to the severity of spondylolisthesis, it has not been confirmed as a predictor of spondylolisthetic progression. MATERIALS AND METHODS: Thirty-six patients who have undergone primary posterior lumbosacral fusion for isthmic spondylolisthesis at our institution from 1977 to 2001 were retrospectively analyzed. There were 24 females and 12 males with a mean age of 21.3 +/- 2.0 years (range, 12 to 53 y). Twenty-two patients had high-grade (Meyerding class III, IV, V) and 14 patients had low-grade (Meyerding class I, II) spondylolisthesis, respectively. Factors evaluated included age, gender, neurologic deficits, reason for surgery, and documented evidence of progression. Slip percentage, high-grade or low-grade slip, slip angle, sacral inclination, sacral rounding, trapezoidal L5 vertebra, and pelvic incidence were measured from immediate preoperative standing lateral radiographs. These factors were statistically analyzed for risk of progression. Continuous variables were analyzed using one-way analysis of variance. Nominal variables were analyzed using chi2 test. RESULTS: Pelvic incidence (P = 0.66) was not predictive of spondylolisthetic progression. Of the other radiographic measurements, slip percentage (P < 0.001), slip angle (P = 0.016), and high-grade spondylolisthesis (P < 0.0001) were highly predictive of progression. Interestingly, sacral inclination (P = 0.33) was not predictive of progression. CONCLUSIONS: Pelvic incidence cannot adequately predict the probability of spondylolisthetic progression. Analysis of the other clinical and radiographic parameters revealed that slip percentage and high-grade spondylolisthesis remain the most positive predictors of progression.

Adolescent↗

How does the ossification area of the posterior longitudinal ligament progress after cervical laminoplasty?

STUDY DESIGN: Retrospective case series. OBJECTIVE: To investigate the progression pattern of ossification of the posterior longitudinal ligament (OPLL) after cervical laminoplasty. SUMMARY OF BACKGROUND DATA: OPLL is a progressive disease, and an increased area of ossification affects the surgical results after laminoplasty. However, it is uncertain how the ossification area progresses with time after surgery. METHODS: Fifty-five patients who were available for serial radiographs of more than 5 years were included. The extent of ossification in the longitudinal axis was assessed using computer software. The associations between the progression of OPLL and the clinical and radiologic data were analyzed. RESULTS: Forty-one patients had OPLL progression. The patients were divided into three groups according to the pattern of progression. Group 1 consisted of patients 40 to 49 years of age with continuous or mixed type, showing slow progression at the beginning, then fast. Group 2 consisted of patients older than 50 years with continuous or mixed type, showing rapid progression at the beginning and then slow. The patients in Group 3 had segmental type with no or slight progression. CONCLUSIONS: We speculated that the progression of OPLL decreases as the patient ages. These findings will be important for the management of patients with OPLL after surgery.

Adult↗

Disease progression and survival in patients with prostate carcinoma and positive lymph nodes after radical retropubic prostatectomy.

OBJECTIVE: To determine disease progression and survival in patients with lymph node-positive prostate carcinoma after ascending radical retropubic prostatectomy (RP) and pelvic lymphadenectomy with different forms of postoperative adjuvant treatment. PATIENTS AND METHODS: We analysed 82 patients with lymph node metastases at the time of surgery and who had a RP between 1993 and 2002. Data from clinical records and follow-up questionnaires were used. Overall survival, time to clinical disease progression and time to biochemical progression were used as endpoints to assess the outcome. Clinical progression was defined as documented local recurrence or distant metastases, and biochemical as an increase in prostate-specific antigen (PSA) of > or = 0.4 ng/mL. Variables analysed included PSA level, Gleason score before and after RP, clinical and pathological stage, number of positive lymph nodes and hormone therapy after RP. The statistical assessment included univariate regression analysis, and to analyse the distribution of clinical findings in different groups, Mantel-Haenszel statistics were used to test for differences in the numbers of patients. Survival and progression-free interval were assessed by Kaplan-Meier estimates and differences between groups calculated by log-rank statistics and Cox regression models. RESULTS: The median (range) follow-up was 55 (10-125) months. Adjuvant hormonal treatment was used in 77 patients, five of whom had immediate adjuvant radiotherapy, and nine delayed radiotherapy because of local progression or symptomatic bone metastases; five had no additional treatment. The rates for 5- and 10-year overall survival, clinical progression-free survival and biochemical progression-free survival were 84% and 79%, 83% and 77%, and 70% and 60%, respectively. Ten patients died (12%), eight (10%) of them from the cancer; bone metastases were detected in nine (11%). Local recurrences developed in three (4%) patients, 10 (12%) had a PSA increase of > or = 0.4 ng/mL alone and 58 (71%) had no signs of progression, but two died from other causes. CONCLUSIONS: Most patients with prostate cancer who had RP and pelvic lymphadenectomy followed by adjuvant hormone therapy, and who had lymph node metastases at the time of surgery, had excellent overall and progression-free survival in the long term.

Adult↗