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PubMed1989

The dynamics of progression of coronary atherosclerosis studied in 168 medically treated patients who underwent coronary arteriography three times.

To study the dynamics of progression of coronary atherosclerosis we analyzed findings in 168 patients who underwent coronary arteriography three times without undergoing coronary surgery or percutaneous transluminal coronary angioplasty. Of 66 patients who had progression in interval 1 (from first to second coronary arteriogram), 32 also had progression in interval 2 (from second to third coronary arteriogram); of 102 patients who had no progression in interval 1, 37 had progression in interval 2. In only 9 of the 32 patients who had progression during both intervals was the same lesion involved, and in six of these patients other lesions were also involved. Progression correlated with the duration of the interval between catheterizations, an increase in symptoms, and the occurrence of myocardial infarction. Analysis of variance showed no significant differences in mean values for age, blood pressure, total serum cholesterol, and serum triglycerides in the four main progression groups. Progression of coronary atherosclerosis is a highly unpredictable process. It follows a nonlinear course, and information derived from sequential coronary arteriograms is of little value in predicting future progression.

Angiography↗

PubMed1984

Progression of atherosclerosis in coronary arteries and bypass grafts: ten years later.

Progression of atherosclerosis in aortocoronary saphenous vein grafts is frequent and is the predominant cause of late graft closure after CABG. Only approximately 60% of grafts remain patent between 10 and 12 years after surgery. Of patent grafts, 45% show angiographic evidence of atherosclerosis between 10 and 12 years after surgery and 70% of the atherosclerotic lesions reduce the graft lumen diameter by 50% or more. Atherosclerosis of saphenous vein grafts does not appear to be related to age, sex or cigarette smoking, but is associated with abnormalities of cholesterol lipoprotein fractions. Progression of atherosclerosis in the native coronary arteries is also very significant after CABG. Progression of CAD between 10 and 12 years after surgery occurs in approximately 50% of nongrafted arteries. Between 10 and 12 years after surgery, the rate of progression of disease in nongrafted arteries is not different from that of grafted arteries with patent grafts; however, progression is more frequent in grafted arteries with occluded grafts. The rate of progression is not related to age, sex, risk factors or extent of disease at baseline coronary arteriography. Progression of preexisting stenoses is more frequent than appearance of new stenosis. Progression is related to the severity of the preexisting stenosis only in nongrafted arteries. Finally, progression is related to alterations of left ventricular function during follow-up. Because of these progressive late changes, CABG should probably remain limited to patients with incapacitating anginal symptoms or to those with severe lesions for whom surgery might enhance long-term survival, such as patients with severe left main CAD and 3-vessel CAD.

Adult↗

PubMed1984

Is progression of coronary artery disease occurring at bouts or as a continuous process? Serial cineangiographic studies in 44 patients.

In order to assess if coronary artery disease progression occurs as a slow, continuous process or at bouts, the coronary angiograms of 44 patients catheterized three times were reviewed. A previously developed logistic model, taking into account time interval between the angiograms, age, occurrence of unstable angina, and extent score of coronary artery disease, was used to compute a probability of progression from the second to the third angiogram. Two groups of patients were considered: those with (n = 15) and those without (n = 29) progression from the first to the second angiogram (PROGRESSION 1-2). A simulation provided in each group the distribution of the expected number of patients with progression from the second to the third catheterization. In the group without PROGRESSION 1-2, the observed number of progressions from the second to the third angiogram was in agreement with the expected one. However, in the group with PROGRESSION 1-2, the progression from the second to the third angiogram was more frequent than expected (p = 0.068). These results suggest that, in many patients, coronary artery disease progression is continuous over several years.

Cineangiography↗

PubMed1996

Signal-averaged electrocardiography and echocardiography in the evaluation of myocardial involvement in progressive systemic sclerosis.

To assess the myocardial involvement in progressive systemic sclerosis we evaluated the presence of late potentials by signal-averaged electrocardiography (signal-averaged ECG) and the left ventricular function by M-mode, two dimensional and Doppler echocardiography. Fifteen outpatients, 7 with diffuse progressive systemic sclerosis and 8 with CREST syndrome variant, without clinical or electrocardiographic evidence of cardiac disease were studied and compared with 18 normal subjects. Late potentials occurred in 5 out of 15 progressive systemic sclerosis patients (33%) with a significant difference versus controls (P < 0.05) and were present only in the patients with diffuse progressive systemic sclerosis (P < or = 0.001 vs. controls). All progressive systemic sclerosis patients showed a normal left ventricular systolic function. Abnormal left ventricular filling was found in 9 progressive systemic sclerosis patients (5 with diffuse progressive systemic sclerosis and 4 with CREST). A more severe impairment of the mean values of diastolic function indexes was found in diffuse progressive systemic sclerosis than in CREST. In all diffuse progressive systemic sclerosis patients at least one method showed altered results, whereas half the CREST patients showed no pathological findings with both techniques. These results confirm a lower myocardial involvement in the CREST syndrome than in diffuse progressive systemic sclerosis and consequently this is probably related to a better prognosis.

Adult↗

PubMed1990

Progression of native coronary artery disease at 10 years: insights from a randomized study of medical versus surgical therapy for angina.

Repeat coronary angiography was performed in 42 patients 10 years after randomization to medical (n = 21) or surgical (n = 21) therapy for chronic angina. The native coronary arteries were classified into 15 angiographic segments and 3 arterial trunks for analysis of progression of coronary artery disease. The incidence rate of disease progression in coronary segments was 24% and 28% in medically and surgically treated patients, respectively (p = NS). Grafted segments showed a 38% rate of disease progression, which was higher than the 18% rate of for nongrafted segments (p less than 0.001) and the overall rate of 24% for medically treated patients (p less than 0.01). Similarly, 29 (94%) of 31 grafted arteries exhibited disease progression compared with 19 (59%) of 32 nongrafted arteries (p less than 0.01) and 42 (67%) of 63 arteries in medically treated patients (p less than 0.01). In grafted vessels, disease progression occurred more often in arteries proximal (84%) to the anastomosis than in arteries distal (16%) to graft insertion (p less than 0.001). Progression occurred in 46% of proximal segments compared with 23% of distal segments (p less than 0.02). Progression was seen in 23 (55%) of 43 segments with an occluded graft compared with 30 (31%) of 96 segments with a patent graft (p less than 0.02). Ten years after randomization, medically and surgically treated patients showed a comparable rate of disease progression in coronary segments. However, surgical therapy appeared to significantly accelerate atherosclerotic progression in the grafted vessels, especially in the proximal portions. Occluded grafts also correlated with an adverse effect on disease progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

PubMed1996

Differential progression of complex culprit stenoses in patients with stable and unstable angina pectoris.

OBJECTIVES: This study sought to compare the evolution of complex culprit stenoses in patients with stable and those with unstable angina pectoris. BACKGROUND: Complex coronary stenoses are associated with adverse clinical and angiographic outcomes. However, it is not known whether the evolution of complex stenoses differs in unstable angina versus stable angina pectoris. METHODS: We prospectively assessed stenosis progression in 95 patients with unstable angina whose angina stabilized with medical therapy (Group 1) and 200 patients presenting with stable angina (Group 2). After diagnostic angiography, all patients were placed on a waiting list for coronary angioplasty and restudied at 8 +/- 4 (mean +/- SD) months later. In each patient the presumed culprit stenosis was identified and classified as complex (irregular borders, overhanging edges or thrombus) or smooth (absence of complex features). Stenosis progression, as assessed by computerized angiography, was defined as > or = 20% diameter reduction or new total occlusion. RESULTS: At the first angiogram, 364 stenoses > or = 50% and 383 stenoses < 50% were identified. At restudy, 36 (15%) of 236 stenoses progressed in 29 Group 1 patients and 36 (7%) of 502 stenoses in 31 Group 2 patients (p = 0.001). Forty-five (88%) of 51 stenoses > or = 50% and 6 (29%) of 21 stenoses < 50% that progressed developed to total coronary occlusion (p = 0.001). More culprit stenoses progressed in Group 1 than in Group 2 (p = 0.006), whereas progression of nonculprit stenoses was not significantly different in both groups. Culprit complex stenoses progressed more frequently in Group 1 than in Group 2 (p = 0.01). During follow-up, 3 patients died (myocardial infarction), and 51 had a nonfatal coronary event. Culprit stenoses progressed in 15 (54%) of the 28 patients with a nonfatal coronary event in Group 1 and in 9 (39%) of 23 patients in Group 2 (p = NS). Complex morphology (p < 0.001) and unstable angina at initial presentation (p < 0.01) were predictive factors for progression of culprit stenoses. CONCLUSIONS: A larger proportion of culprit complex stenoses progress in unstable angina than stable angina, and this is frequently associated with recurrence of coronary events.

Adult↗

PubMed1992

Progression of nonproliferative diabetic retinopathy and visual outcome after extracapsular cataract extraction and intraocular lens implantation.

Twenty-one patients with symmetric nonproliferative retinopathy who underwent extracapsular cataract extraction and intraocular lens implantation were followed up postoperatively for an average (+/- standard deviation) of 18 +/- 7 months to determine the incidence of progression of diabetic retinopathy, the final visual acuity, and factors predictive of progression of retinopathy and final visual acuity. Progression of retinopathy, defined as the development of clinically significant macular edema, an increase in intraretinal hemorrhages or hard exudate, or the development of proliferative diabetic retinopathy, was assessed in both eyes of 19 patients; in two remaining patients, dense preoperative cataract in the fellow eye precluded comparison of retinopathy progression in the operated-on eye to progression in the fellow eye. Overall, retinopathy progressed in 14 of 19 operated-on eyes (74%). Cataract extraction was highly associated with asymmetric progression of nonproliferative retinopathy; it progressed only in the operated-on eye in seven of 19 patients (37%), but in no patients did progression occur in the fellow eye alone (P = .0078). Women had a significantly increased risk of progression of retinopathy in the operated-on eye compared to men (P = .005). Visual acuity improved in 19 of 21 operated-on eyes (86%); however, only 11 eyes (52%) achieved a visual acuity of 20/50 or better and only six eyes (14%) achieved a visual acuity of 20/25 or better. In only five eyes was the final visual acuity in the operated-on eye more than two lines better than the final visual acuity in the fellow eye.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed2000

HCV-related fibrosis progression following liver transplantation: increase in recent years.

BACKGROUND/AIMS: The natural history and predictors of HCV-related disease severity post-transplantation are uncertain. The aims of this study were to define the natural history of post-transplantation HCV infection by assessing the rate of fibrosis progression, to determine if the post-transplantation natural history differs from that observed pre-transplantation, and to identify predictors of post-transplantation disease progression. METHODS: Post-transplantation biopsies (mean: 3+/-1.6/patient) from 284 patients were scored according to histologic stage, using the method of Desmet et al. Change in fibrosis score (fibrosis progression/year) post-transplantation was used as the primary outcome. Predictors analyzed included viral factors (genotype and viral load at transplantation), patient demographics, year of transplantation, country of transplantation, pre-transplantation fibrosis progression, immunosuppression and laboratory data. RESULTS: There was a linear association between change in fibrosis score and time from transplantation, with a median rate of fibrosis progression per year of 0.3 (0.004-2.19/year). Using parametric time-to-event analysis, the expected median duration to cirrhosis was 10 years. The rate of post-transplantation fibrosis progression was significantly higher than pre-transplantation (0.2/year (0.09-0.8) p<0.0001), and higher in Spanish than US centers (0.48 (0.01-2.19) vs 0.28 (0.004-2.08); p=0.09) despite similar progression rates prior to transplantation. Variables independently associated with post-transplantation progression included year of transplantation (p=0.0001), race (p=0.02), number of methyl-prednisolone boluses (p=0.03), and HCV RNA levels at transplantation (p=0.01). CONCLUSIONS: HCV-related disease progression is accelerated in immunocompromised compared to immunocompetent patients, with a progressive increase in patients who have recently undergone liver transplantation. Changes in patient management post-transplantation over time and between transplant centers may account for the increase in fibrosis progression observed in recent years.

Adult↗

PubMed1990

Progressive transformation of germinal centers with and without association to Hodgkin's disease.

Progressively transformed germinal centers occurred in about 3.5% of cases of chronic nonspecific lymphadenitis. They are larger than germinal centers and are composed of follicular mantle lymphocytes, small clusters of proliferating mainly medium-sized B- and T-cells, as well as an extensive network of follicular dendritic cells. Sixty-six patients with lymph node enlargement containing progressively transformed germinal centers and staging and sequential biopsies of 213 patients with Hodgkin's disease (mixed and nodular sclerosis type) were investigated with special reference to the relationship of this lesion to Hodgkin's disease. In most cases, progressively transformed germinal centers developed without any obvious signs of illness and seemed to have no association with Hodgkin's disease. The patients could be differentiated into two groups. The larger group, Group 1 (n = 55 of 66) consisted of patients showing progressively transformed germinal centers without association to Hodgkin's disease. The smaller group, Group 2 (n = 11 of 66) showed progressively transformed germinal centers obviously with association to nodular paragranuloma (Hodgkin's disease lymphocytic predominance type). Progressively transformed germinal centers preceding (n = 3), simultaneously (n = 4), and after development of nodular paragranuloma (n = 4) were found. With regard to subtypes of Hodgkin's disease other than paragranuloma, progressively transformed germinal centers also could be found in sequential biopsies of Hodgkin's disease of mixed and nodular sclerosis type. In one case, progressively transformed germinal centers preceded, in another case they occurred simultaneously in mixed type of Hodgkin's disease, and in two cases of nodular sclerosis type progressively transformed germinal centers developed after the onset of Hodgkin's disease. These findings suggest that progressively transformed germinal centers may be a result of different processes that may be occasionally related not only to nodular paragranuloma, but also in rare cases to nodular sclerosis and mixed type of Hodgkin's disease.

Adolescent↗

PubMed1996

Convex spinal epiphysiodesis in the management of progressive infantile idiopathic scoliosis.

STUDY DESIGN: Retrospective review of patient records with current clinical and radiographic assessment. OBJECTIVE: To evaluate the long-term result of anterior and posterior convex spinal growth arrest, with or without instrumentation, in managing infantile idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: There were 12 male and 10 female patients studied, with a mean follow-up period of 10 years, 9 months. The mean Cobb angle before surgery was 65 degrees. All had a rib vertebral angle difference more than 20 degrees. The mean age at surgery was 6 years. Nine patients had epiphysiodesis alone; nine patients also underwent Harrington instrumentation simultaneously, and four underwent Harrington instrumentation 2-4 years later. METHOD: Clinical evaluation and sequential measurements of Cobb angle were done. RESULTS: The epiphysiodesis-only group had a mean preoperative Cobb angle of 72 degrees, mean progression of curves of +12 degrees, and mean rate of progression of +2.5 degrees per year: the group's postoperative figures were 92 degrees, +15 degrees, and +3 degrees per year, respectively. The epiphysiodesis and late Harrington rod group had a mean preoperative Cobb angle of 56 degrees, mean progression of +12 degrees, and a mean rate of progression of +5 degrees per year; the group's postoperative Cobb angle averaged 62 degrees, progression +6 degrees, and rate of progression +1 degree per year. The epiphysiodesis with simultaneous Harrington rod group had a preoperative mean Cobb angle of 60 degrees, mean progression of +18 degrees, and mean rate of progression of +6 degrees per years. After surgery, these improved to 58 degrees, correction of 2 degrees, and rate of correction of 0.5 degree per year. CONCLUSION: Combined anterior and posterior convex spinal growth arrest alone does not prevent progression of deformity in infantile idiopathic scoliosis. The addition of posterior instrumentation can slow or arrest deformity progression but not reverse it.

Bone Nails↗

PubMed1997

Transitional progressive multiple sclerosis: a clinical and imaging study.

OBJECTIVE: To study the prevalence and the natural course of transitional progressive multiple sclerosis (TPMS). This clinical form is defined by a progressive course beginning many years after an isolated bout. METHODS: 214 consecutive outpatients with definite or probable multiple sclerosis were studied. The prevalence of TPMS was established. Patients with TPMS were compared with patients with other progressive forms of multiple sclerosis according to the clinical course. A prospective one year follow up study was performed in a subgroup of patients to compare progression of the disease using clinical indices and MRI. RESULTS: In this clinical population of 214 outpatients with multiple sclerosis, 55 had secondary progressive multiple sclerosis (SPMS), 38 primary progressive multiple sclerosis (PPMS), and 12 TPMS. Retrospective analysis of the clinical data of these patients shows that TPMS is very similar to SPMS at the beginning of the disease (age at onset, time before progression, clinical symptoms at onset, progression index). In addition a cohort of patients was prospectively followed up clinically and by MRI for one year. CONCLUSIONS: The results did not show any significant differences between the three forms during this follow up. However, all data showed a concordant trend suggesting that at this progressive stage, TPMS is closer to PPMS in terms of progression of disability and new MRI lesions.

Brain↗

PubMed1999

Influence of methotrexate and azathioprine on radiologic progression in rheumatoid arthritis.

We investigated 43 patients with seropositive rheumatoid arthritis (RA) under a therapy with methotrexate (MTX) or azathioprine (AZA). All patients fulfilled the American Rheumatism Association criteria. It has been a retrospective study over 2.6 years (MTX: 26 patients, average age 54 +/- 14.6 years, female/male 19:7, AZA: 17 patients, average age 59.4 +/- 12.5 years, female/male 12:5). The mean duration of disease was 8 years (+/- 5.3) in the MTX-group and 7 years (+/- 7.3) in the AZA-group. The mean dose of MTX was 13. 3mg/week and of azathioprine 142.6mg/ daily. The drugs were administered orally. - Radiographs of hands, wrists and feet obtained at enrollment and at review were scored by a rheumatologist according to a modified Larsen score. Radiographic damages were counted in 25 joints of each hand and in 25 joints of each foot. The change in radiological score was calculated by subtracting the joint damage scores at follow up with first damage score at inclusion. The rate of radiological progression (YP) was calculated by dividing the change in radiological score by the number of years during the period of study. - Only 3 patients with MTX showed no radiologic progression. All other patients of both groups showed progressive radiological changes. - The study demonstrated no significant difference in the rate of radiologic progression between the different treatment-groups. However, there was a trend that MTX treated patients (YP 5 +/- 4.4) had a slower radiographic progression compared with those treated with AZA (YP 8.5 +/- 7.7). MTX may be more effective in patients at an earlier stage of rheumatoid arthritis. - When we started a therapy with AZA or MTX in a later period of disease we revealed a better influence of radiologic progression under AZA and a trend towards an increase of the radiologic progression under MTX. - Probably there is a decreasing effect of MTX in later periods of the disease. - The corticoid dose reduction was higher under AZA (AZA: Reduction about 58.6%, MTX: 25%) over the study duration. - Our investigation demonstrated a trend towards reduced radiological progression in MTX treated patients compared to AZA, however statistic analysis showed no significant difference in the rate of radiologic progression. At an earlier stage of the disease there is a better influence of MTX in radiologic progression, at the later stage we showed a slowing of radiological deterioration in AZA treated group.

Adult↗

PubMed2002

Risk factors and outcome of failure to progress during the first stage of labor: a population-based study.

BACKGROUND: One of the major indications for Cesarean section (CS) is failure of labor to progress. This study was aimed at defining obstetric risk factors for failure of labor to progress during the first stage, and to determine pregnancy outcome. METHODS: A population-based study comparing all singleton, vertex, term deliveries between the years 1988 and 1999 with an unscarred uterus, complicated with failure of labor to progress during the first stage with deliveries without non-progressive labor (NPL). Multiple logistic regression analysis was performed to investigate independent obstetric risk factors associated with failure of labor to progress during the first stage. RESULTS: Failure to progress during the first stage of labor complicated 1.3% (n = 1197) of all deliveries included in the study (n = 92 918), and resulted in CS. Independent risk factors for failure of labor to progress during the first stage, using a multivariable analysis, were premature rupture of membranes (PROM; OR = 3.8, 95% CI 3.2-4.5), nulliparity (OR = 3.8, 95% CI 3.3-4.3), labor induction (OR = 3.3, 95% CI 2.9-3.7), maternal age > 35 years (OR = 3.0, 95% CI 2.6-3.6), birth weight > 4 kg (OR = 2.2, 95% CI 1.8-2.7), hypertensive disorders (OR = 2.1, 95% CI 1.8-2.6), hydramnios (OR = 1.9, 95% CI 1.5-2.3), fertility treatment (OR = 1.8, 95% CI 1.4-2.4), epidural analgesia (OR = 1.6, 95% CI 1.4-1.8) and gestational diabetes (OR = 1.4, 95% CI 1.1-1.7). Although newborns delivered after failure of labor to progress during the first stage had significantly higher rates of Apgar scores lower than 7 at 1 and 5 min as compared with the controls (18.2% vs. 2.1%; P < 0.001 and 1.3% vs. 0.2%; P < 0.001, respectively), no significant differences were noted between the groups regarding perinatal mortality (0.3% vs. 0.4%; P = O.329). Maternal anemia and accordingly packed cells transfusion (47.4% vs. 22.8%; P < 0.001 and 5.6% vs. 1.0%; P < 0.001, respectively) were higher among pregnancies complicated with failure of labor to progress during the first stage as compared with the controls. CONCLUSIONS: Major risk factors for failure of labor to progress during the first stage were PROM, nulliparity, induction of labor and older maternal age. Indications for labor induction should be carefully evaluated in order to decrease the rate of operative deliveries.

Adolescent↗

PubMed1991

Analysis of viral and cellular gene expression during progression and suppression of the transformed phenotype in type 5 adenovirus-transformed rat embryo cells.

Transformation of secondary Sprague-Dawley rat embryo (RE) cells with type 5 adenovirus (Ad5) results in morphologically transformed cells which can undergo a series of sequential changes resulting in enhanced expression of the transformed phenotype, a process termed progression. Selection for a progressed phenotype often occurs after growth in agar or tumor formation in nude mice, and this process is reversible following treatment of cells with 5-azacytidine. In the present study we have analyzed a series of clonal populations of Ad5-transformed RE cells representing different stages in a defined progression lineage. Progression was not associated with alterations in the steady-state levels of mRNA produced by the viral transforming genes, E1A and E1B, or the cellular gene, c-myc. In addition, the tumor-promoting agent 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which induces expression of a progressed phenotype in Ad5-transformed RE cells, did not significantly alter the RNA transcription rates of the Ad5 E1A or E1B genes, the TPA-inducible gene TPA-S1 or the TPA-responsive genes Pro1 or protein kinase C. TPA did, however, increase by 1 h the steady-state level of c-fos mRNA, but this effect was similar in both progressed and unprogressed cells. Progression also did not involve a change in the RNA transcription rate of a number of cellular and viral genes, including actin, c-Ha-ras, c-myc, v-fos, erbB, TGF-alpha, TGF-beta, Pro-2, transin, TPA-R1, v-myb and c-mos, or other adenovirus genes in addition to E1A and E1B, including E2A and E4. Immunoblotting analysis using E1B polyclonal antiserum further indicated that progression was not associated with changes in the levels of an Mr 21,000 polypeptide encoded by E1B. Similarly, immunoprecipitation analysis with an Ad2 E1A monoclonal antibody indicated similar levels of the Mr 55,000 and 48,000 E1A polypeptides, as well as coprecipitated proteins of Mr 300,000, 107,000 and 105,000 [which is the retinoblastoma (Rb) protein], in E11 and E11-NMT cells. Immunoprecipitation of cell lysates with a monoclonal antibody specific for the Mr 105,000 Rb protein further demonstrated that progression also was not associated with a change in the level or state of phosphorylation of the Rb protein. However, transfection of a human Rb gene (also containing a neomycin resistance gene) into Ad5-transformed RE cells was more inhibitory, with respect to formation of G418-resistant colonies, in unprogressed than in progressed Ad5-transformed RE cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoviruses, Human↗

PubMed1994

[A radiographic study of the progression of ossification of the cervical posterior longitudinal ligament: the correlation between the ossification of the posterior longitudinal ligament and that of the anterior longitudinal ligament].

Progression of ossification of the posterior longitudinal ligament (OPLL) was evaluated in relation to that of ossification of the anterior longitudinal ligament (OALL). The subjects of this study were 68 patients with OPLL in the cervical spine. 47 of them underwent conservative treatment, and the remaining 21 underwent decompression surgery of the cervical spine (involving 11 cases of laminectomy and 10 of an enlargements of the spinal canal). All 68 patients were followed up for more than 5 years. Most of the continuous and most of the mixed types of OPLL exhibited advancement of the stage at the final examination, and showed much progression of OALL during the follow-up period. The progression of OALL tended to be more advanced in those cases in which the progression of OPLL was advanced. In most of the operated cases, OPLL was highly progressed after surgery in both the longitudinal direction and in the thickness, regardless of the ossification type. There was also evidence of progression of OALL in these patients, at each level of the cervical spine, with particularly advanced progression at the lower levels with a higher rate than in the conservative cases. These results indicate that the progressions of OPLL and OALL are closely correlated, and that the same precipitating factors may therefore be involved in both OPLL and OALL. A marked progression of the ossification after surgery suggested that local factors of the cervical spine played an important role in the progression.

Adult↗

PubMed2000

Relapses and progression of disability in multiple sclerosis.

BACKGROUND: The influence of the patterns of onset of multiple sclerosis and relapses of the disease on the time course of irreversible disability is controversial. METHODS: In 1844 patients with multiple sclerosis who were followed for a mean (+/- SD) of 11 +/- 10 years, we determined the time of the clinical onset of the disease, the initial course (relapsing-remitting or progressive) and the subsequent course (relapsing-remitting, secondary progressive, or primary progressive), the times of relapses, the time to the onset of irreversible disability, and the time course of progressive, irreversible disability. We used three scores on the Kurtzke Disability Status Scale (range, 0 to 10, with higher scores indicating more severe disability) as measures of the severity and progression of disability: a score of 4 (limited walking ability but able to walk for more than 500 m without aid or rest), a score of 6 (ability to walk with unilateral support no more than 100 m without rest), and a score of 7 (ability to walk no more than 10 m without rest while leaning against a wall or holding onto furniture for support). We used Kaplan-Meier analyses to determine the influence of relapses on the time to the onset of irreversible disability. RESULTS: The median times from the onset of multiple sclerosis to the assignment of a score of 4, a score of 6, and a score of 7 on the disability scale were longer among the 1562 patients with a relapsing-remitting onset of disease (11.4, 23.1, and 33.1 years, respectively) than among the 282 patients who had progressive disease from the onset (0.0, 7.1, and 13.4 years, respectively; P<0.001 for all comparisons). In contrast, the times from the assignment of a score of 4 to a score of 6 were similar in the two groups (5.7 and 5.4 years, P=0.74). The time course of progressive, irreversible disease among patients with the primary progressive type of multiple sclerosis was not affected by the presence or absence of superimposed relapses. CONCLUSIONS: Among patients with multiple sclerosis, relapses do not significantly influence the progression of irreversible disability.

Adolescent↗

PubMed2001

Increased frequency of JC virus type 2 and of dual infection with JC virus type 1 and 2 in Italian progressive multifocal leukoencephalopathy patients.

To verify the possibility of different role of JC virus genotypes in the etiology of progressive multifocal leukoencephalopathy, we analysed several JC virus isolates amplified from AIDS patients with and without progressive multifocal leukoencephalopathy and healthy controls by nucleotide sequencing. Cerebrospinal fluid (CSF), peripheral blood mononuclear cells (PBMCs) and urine from 52 AIDS patients suffering from various neurological diseases including 21 cases of progressive multifocal leukoencephalopathy, and PBMCs and urine from healthy subjects were evaluated by nested polymerase chain reaction (PCR) for the presence of DNA belonging to the highly conserved large T antigen (LT) of JC virus. The different JC virus subtypes were identified by nucleotide sequence analysis of the virion protein (VP1) genomic region. JC virus DNA was detected in all the CSF samples from the progressive multifocal leukoencephalopathy patients, but not in the CSF from non-progressive multifocal leukoencephalopathy cases, while the frequency of JC virus DNA detection in the PBMCs and urine did not differ among the three groups studied. JC virus type 2 was detected only in progressive multifocal leukoencephalopathy patients, and in particular in 52.4% of their CSF samples. Moreover, in the CSF of 19.0% of the progressive multifocal leukoencephalopathy cases, dual infection with both JC virus types 1 and 2 was found. The data obtained in this study indicate that the unexpected involvement of JC virus type 2, a strain not common in Italy, and the high frequency of dual infection with both JC virus types 1 and 2 in progressive multifocal leukoencephalopathy CSF, can be indications of risk factors for progressive multifocal leukoencephalopathy development.

Acquired Immunodeficiency Syndrome↗

PubMed2026

Transcriptomic profiling across stages of non-muscle-invasive bladder cancer identifies fibroblast activation protein-alpha as a stromal biomarker associated with progression.

BACKGROUND: T1 non-muscle-invasive bladder cancer (NMIBC) represents a biologically aggressive subgroup with substantial heterogeneity in recurrence and progression risk. Current clinicopathological risk stratification tools lack sufficient precision to identify patients at the highest risk of progression to muscle-invasive bladder cancer (MIBC). OBJECTIVE: To characterize transcriptomic differences between T1 and < T1 (Ta/Tis) NMIBC and to explore the association of fibroblast activation protein-α (FAP) gene expression with disease progression. METHODS: Transcriptomic profiling was performed on formalin-fixed paraffin-embedded (FFPE) tumor tissue from 66 patients with primary, treatment-naïve NMIBC and 5 patients with T2 disease (included for exploratory comparisons). Analyses included differential gene expression, gene set enrichment analysis (GSEA), molecular subtyping, immune cell deconvolution, and evaluation of FAP expression in relation to recurrence and progression. External validation of FAP was conducted in three independent NMIBC cohorts. RESULTS: T1 tumors demonstrated a distinct transcriptomic profile compared with < T1 tumors, characterized by enrichment of cell cycle-related and metabolic pathways and a higher prevalence of aggressive molecular subtypes. Despite these molecular differences, no statistically significant differences in recurrence-free, progression-free, cancer-specific, and overall survival were observed, likely reflecting limited event numbers. Among recurrent tumors, early recurrences (≤ 24 months) were associated with epithelial-mesenchymal transition signatures. FAP expression increased with tumor stage (p = 0.0005) and was associated with progression (p = 0.002) and mortality (p = 0.01). Patients with tumors in the highest quartile of FAP expression had worse progression-free survival. This association was consistently observed in three external NMIBC cohorts. CONCLUSIONS: T1 NMIBC exhibits distinct transcriptomic features suggestive of increased biological aggressiveness. Elevated FAP expression is reproducibly associated with progression risk across multiple cohorts, supporting its potential role as a biomarker of aggressive disease. Given the limited number of progression events, these findings should be considered hypothesis-generating and warrant prospective validation before clinical implementation.

Humans↗