Different Rates Of Progression Research Articles

Expression of matrix metalloproteinase-9 in gingival tissue biopsy in patients with slowly/ moderately and rapidly progressing periodontitis: An observational study.

Background:Matrix metalloproteinases (MMPs) are a group of host-derived zinc-dependent enzymes which mediates the destruction of the extracellular matrix. In periodontitis, there is excess production of MMPs associated with periodontal tissue destruction. The aim of this study was to estimate the level MMP-9 in both active and latent form in gingival tissue (GT) samples collected from periodontitis patients with different rates of progression and compare it with healthy individuals.Materials and Methods:Sixty patients were selected and divided into three groups, 20 each: Group A (slowly/moderately progressing periodontitis), Group B (rapidly progressing periodontitis), and Group C (clinical periodontal health). Plaque index, gingival index, periodontal probing depth (PPD), and clinical attachment level were recorded. GT samples were collected from all 60 patients and MMP-9 expressions were measured using gelatin zymography and western blotting.Results:Levels of active MMP-9 (aMMP-9) and latent MMP-9 (lMMP-9) were significantly high in both Group A (GA) (aMMP-9: 2.05 arbitrary unit [AU]/lMMP-9: 2.54 AU) and Group B (GB) (aMMP-9: 1.32 AU/lMMP-9: 1.74 AU) when compared to that of Group C (GC) (aMMP-9: 0.93/lMMP-9: 1.08 AU). In GA, levels of aMMP-9 showed a significant correlation with PPD values. No other correlations were found.Conclusion:The levels of aMMP-9 and lMMP-9 were increased in both the types of periodontitis when compared with periodontally healthy individuals. A significant correlation was found between PPD and activities of aMMP-9 in slowly/moderately progressing periodontitis patients. However, further studies are required to confirm these findings.

A narrative review of the role of fibroblasts in the growth and development of neurogenic tumors.

Neurogenic tumors, a group of tumors arising from neurogenic elements, could theoretically appear in every region of human bodies wherever nerves exist. Patients with these tumors suffer from both physical and psychological problems. However, as a relatively rare tumor type, therapies are relatively scarce for these tumors due to the limited understanding of the underlying mechanisms. Recently, a tailored tumor microenvironment containing multiple types of nonneoplastic cells has been considered to play an essential role in tumor survival, growth, and metastasis. Fibroblasts are a crucial constituent of the tumor microenvironment and have been found to promote tumor growth via multiple mechanisms. However, the understanding of the pivotal role of fibroblasts in the tumorigenesis and development of the neurogenic tumors is still incomplete, and studies in this area show differences in rates of progression among different neurogenic tumor subtypes. Nevertheless, all these neural crest-originated neoplasms show some similarities in the tumor microenvironment, indicating that studies of one subtype of neurogenic tumor might assist in clarifying the underlying mechanisms of other subtypes. This review aims to provide current studies showing the impacts of fibroblasts on major benign/malignant subtypes of neurogenic tumors, including neurofibromatosis type 1, neuroblastomas, pheochromocytomas, and malignant peripheral nerve sheath tumors. Multiple related mechanisms such as the fibroblasts regulating the tumor inflammation, angiogenesis, metabolism, and microenvironment establishment have been studied up to present. Consistently, we focus on how studies on various subtypes of these neurogenic tumors contribute to the establishment of potential future directions for further studies in this area. Clarifying the underlying mechanisms by which fibroblasts promote the growth and metastasis of neurogenic tumors will indicate new therapeutic targets for further clinical treatment.

Preablation three-dimensional ultrasonography can predict therapeutic effect and local tumor progression after radiofrequency ablation for hepatocellular carcinoma

PurposeTo assess the agreement between ablative margin (AM) predicted by preablation three-dimensional ultrasonography (3D-US) and AM measured on postablation computed tomography (CT)/magnetic resonance (MR) images. MethodsSixty patients with 73 hepatocellular carcinoma nodules were enrolled. 3D-US data were collected immediately after puncture by the electrode before ablation. The maximum distance from the electrode to the edge of the tumor in the plane perpendicular to the electrode (C-plane) was defined as “a” and the diameter of the ablation zone as “b”. We classified predicted AM into “0.5b − a” ≥0 mm as AM(+) or <0 mm as AM(−), and “0.5b − a” ≥3 mm or <3 mm. ResultsForty-eight nodules (66 %) were visualized in the C-plane. There was an agreement between the predicted and measured AMs for 39 (81 %) of the 48 nodules. Local tumor progression was observed in 3 (7%) of 43 nodules with predicted AM(+) and in 2 (40 %) of 5 nodules with predicted AM(−) but was not observed in any of 21 nodules with predicted AM ≥ 3 mm. The local tumor progression rate was significantly lower for nodules with predicted AM(+) compared with predicted AM(−)(p = 0.03), and for nodules with predicted AM ≥ 3 mm compared with predicted AM < 3 mm (p = 0.04). Local progression was detected in 2 (4.7 %) of 42 nodules with a sufficient AM (≥0 mm) on postablation CT/MR images and in 5 (83.3 %) of 6 nodules with an insufficient AM (<0 mm); the difference in progression rate was significant (p = 0.0008). Conclusion3D-US allows prediction of the AM before radiofrequency ablation.

Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial

AimsDespite the effects of statins in reducing cardiovascular events and slowing progression of coronary atherosclerosis, significant cardiovascular (CV) risk remains. Icosapent ethyl (IPE), a highly purified eicosapentaenoic acid ethyl ester, added to a statin was shown to reduce initial CV events by 25% and total CV events by 32% in the REDUCE-IT trial, with the mechanisms of benefit not yet fully explained. The EVAPORATE trial sought to determine whether IPE 4 g/day, as an adjunct to diet and statin therapy, would result in a greater change from baseline in plaque volume, measured by serial multidetector computed tomography (MDCT), than placebo in statin-treated patients.Methods and resultsA total of 80 patients were enrolled in this randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis as documented by MDCT (one or more angiographic stenoses with ≥20% narrowing), be on statin therapy, and have persistently elevated triglyceride (TG) levels. Patients underwent an interim scan at 9 months and a final scan at 18 months with coronary computed tomographic angiography. The pre-specified primary endpoint was change in low-attenuation plaque (LAP) volume at 18 months between IPE and placebo groups. Baseline demographics, vitals, and laboratory results were not significantly different between the IPE and placebo groups; the median TG level was 259.1 ± 78.1 mg/dL. There was a significant reduction in the primary endpoint as IPE reduced LAP plaque volume by 17%, while in the placebo group LAP plaque volume more than doubled (+109%) (P = 0.0061). There were significant differences in rates of progression between IPE and placebo at study end involving other plaque volumes including fibrous, and fibrofatty (FF) plaque volumes which regressed in the IPE group and progressed in the placebo group (P < 0.01 for all). When further adjusted for age, sex, diabetes status, hypertension, and baseline TG, plaque volume changes between groups remained significantly different, P < 0.01. Only dense calcium did not show a significant difference between groups in multivariable modelling (P = 0.053).ConclusionsIcosapent ethyl demonstrated significant regression of LAP volume on MDCT compared with placebo over 18 months. EVAPORATE provides important mechanistic data on plaque characteristics that may have relevance to the REDUCE-IT results and clinical use of IPE.

Focal Segmental Membranoproliferative Glomerulonephritis: A Histological Variant of Denys-Drash Syndrome.

Introduction: Denys-Drash Syndrome (DDS) consists of a triad of pseudohermaphroditism, Wilms’tumor and nephropathy. This condition may manifest as a complete triad or in an incomplete form; with either one or a combination of the above features. The characteristic glomerular abnormality in DDS is diffuse mesangial sclerosis (DMS). Case report: We report two cases of DDS with focal membranoproliferative glomerulonephritis (MPGN). Both of our cases were males with ambiguous genitalia. They had a similar heterozygous germline mutation in exon 9 of WT1, c.1180C>T, p.R394W; a known mutation hotspot for DDS. Case 1 had nephropathy at the age of 4 years and Case 2 at 2.5 years with different rates of progression to end-stage renal failure. Conclusion: Our findings, in combination with other reports, illustrate the clinicopathological heterogeneity of DDS. There are no universal recommendations for optimal management of patients with DDS due to the inability to accurately predict affected individuals’ progress.

Serum immunoglobulin A levels and alcohol-induced liver disease.

Recent data suggest intestinal immunity including immunoglobulin A (IgA) may contribute to the pathogenesis of alcohol-induced liver disease (ALD). We documented serum IgA levels in ALD patients and determined whether those with elevated levels of IgA (E-IgA) had similar, more, or less advanced disease and different rates of progression than those with normal levels of IgA (N-IgA). Standard liver function tests (bilirubin, international normalized ratio [INR], and albumin), model for end-stage liver disease (MELD), and Fibrosis-4 (FIB-4) scores were used as indicators of disease severity. From the study centre's clinical database, we identified 175 adult patients with ALD, 107 (61%) with E-IgA and 68 (39%) with N-IgA. Gender distribution and mean age of the two cohorts were similar. E-IgA patients had biochemical evidence of more advanced liver disease (higher serum bilirubin and INR and lower albumin levels) than N-IgA patients (ps < .05). E-IgA patients also had significantly higher median MELD and FIB-4 scores (ps < .01). A higher percentage of E-IgA patients had FIB-4 values in keeping with advanced fibrosis or cirrhosis (55% versus 28%, p = .02). After mean follow-up periods of approximately 4 years, liver biochemistry and MELD and FIB-4 scores changed to similar extents in the two cohorts. Serum IgA levels were increased in approximately 70% of ALD patients. Although these patients had biochemical and non-invasive indicators of more advanced disease, elevations in serum IgA levels do not predict disease progression; therefore, IgA is unlikely to be of importance in the pathogenesis of ALD.

3079Subclinical progression of biventricular cardiomyopathy in patients with systemic sclerosis

Abstract Background Systemic sclerosis (SSc) is a progressive autoimmune disease which has been proven to affect the heart. While it is widely known that the disease can cause pulmonary artery hypertension and therefore secondary right heart impairment, new studies have detected a subclinical heart involvement of both the left and right ventricles. The similar changes in myocardial deformation of both chambers assessed by speckle tracking imaging are consistent with the definition of SSc-related cardiomyopathy as a standalone entity with peculiar characteristics. Purpose The aim of the present study is to describe the progression of myocardial deformation as assessed through speckle tracking in patients with SSc and no pulmonary hypertension. Methods Prospective, longitudinal study on 48 patients affected by SSc. Patients with a history of heart failure, known structural heart disease, atrial fibrillation, and pulmonary hypertension were excluded. For every patient, standard echocardiographical and speckle-tracking derived variables for the systolic and diastolic function of the left ventricle (LV) and right ventricle (RV) were acquired at baseline and after 15±6 months. Results While common parameters of systolic function (Simpons's left ventricular ejection fraction, right ventricular fractional area change, TAPSE, tricuspidal S') did not change during follow-up, mean global longitudinal strain (GLS) significantly worsened for both left (from −19.1%±4.2% to −17.2%±5.0%) and right ventricle (from −17.9%±5.2% to −15.9%±4.8%) over 15 months. The increased impairment seen in SSc patients was homogeneous across endocardial layers (LV: from −21.8%±4.8% to −18.8%±5.2%; RV: from −20.6%±4.5% to −19.4%±4.9%), midventricular layers (LV: from −19.2%±4.5% to −17.7%±4.9%; RV: from −17.7%±4.7% to −16.7%±4.6%) and epicardial layers (LV: from −16.3%±4.7% to −16.0%±4.3%; RV: from −15.4%±5.0% to −14.6%±4.1%), as well as across myocardial segments (Figure 1). No difference in progression rate was seen between the diffuse and limited version of SSc, nor between different serotypes. Figure 1 Conclusions While traditional echocardiographical parameters are useless in order to follow the natural history of SSc-related cardiomyopathy during its early stages, GLS impairment progresses during a 15-month follow-up and involves similarly both the left and right ventricle. Whether, how, and how much the altered myocardial deformation contributes to the incidence of pulmonary arterial hypertension in these patients is still to be assessed. Acknowledgement/Funding Marche Polytechnic University

211-OR: Analysis of Longitudinal Autoantibody Profiles and the Progression Rates to Type 1 Diabetes

Clinical type 1 diabetes (T1D) is preceded by asymptomatic islet-autoimmunity (IA) with presence of islet autoantibodies (AAb). However, both AAb profiles (clusters) during IA phase and progression rate to T1D are heterogeneous. It is unclear if AAb profiles affect the progression to T1D similarly in different countries. We analyzed data from 3 prospective birth cohorts, DAISY (U.S.), DiPiS (Sweden), and DIPP (Finland), to address this question. We developed a similarity algorithm that considers subject-level temporal IA profiles (based on 4 AAbs - IAA, GADA, IA2A, and ZnT8A positivity or negativity), age at which AAb developed, and imbalance in AAb positivity by weighting positive AAb matches higher than negative ones. Using this subject-level similarity measure, we performed hierarchical clustering of AAb positive subjects having at least 3 visits. We used a log-rank test to identify the number of clusters in 1125 DIPP subjects (329 T1D cases), 309 DAISY subjects (70 cases), and 226 DiPiS subjects (33 cases). Each dataset was individually clustered. We identified three clusters in each dataset associated with different rate of progression from seroconversion to T1D - slow progressors (SP), moderate progressors (MP) and fast progressors (FP). These were distributed as follows: DIPP (654 SP with 3% 10-year T1D risk, 356 MP with 60% risk, 115 FP with 96% risk); DAISY (215 SP with 6% 10-year risk, 92 MP with 62% risk, 2 FP with 100% risk); and DiPiS (160 SP with 3% 10-year risk, 62 MP with 58% risk, 4 FP with 100% risk). Finally, we tested the generalizability of the clusters by 1) learning a clustering from one data set “learned clusters,” 2) classifying subjects from another (independent) data set with the “learned clusters,” and 3) measuring how often the subjects were assigned to the same cluster (SP, MP, FP) as the “internal” clustering. The average accuracy of cluster transfer was high (mean = 87.9%, sd = 1.1%) suggesting that the IA profile predicts progression rate to T1D independently of the population. Disclosure M. Ghalwash: None. V. Anand: None. B. Liu: None. E. Koski: None. K. Ng: None. J.L. Dunne: None. M. Lundgren: None. M. Rewers: None. R. Veijola: None. Funding JDRF

Pirfenidone Therapy for Familial Pulmonary Fibrosis: A Real-Life Study

Familial pulmonary fibrosis (FPF) is defined as an idiopathic diffuse parenchymal lung disease affecting two or more members of the same primary biological family. The aim of this study was to compare disease progression and tolerance to pirfenidone in a population of FPF patients who presented with radiological and/or histological evidence of UIP, and a group of idiopathic pulmonary fibrosis (IPF) patients. Seventy-three patients (19 with FPF and 54 with IPF) were enrolled and data were collected retrospectively at 6, 12 and 24months follow-up. FPF patients were statistically younger and more frequently females. A significantly greater decline in FVC and DLCO was recorded in FPF than in IPF patients at 24months follow-up. At the 6-min walking test, walked distance declined significantly in FPF patients than IPF at 24months. No statistically significant differences in drug tolerance or side effects were recorded between groups. Different rate of progression was observed in patients with IPF and FPF on therapy with pirfenidone; our findings may not be due to lack of effectiveness of therapy, but to the different natural history and evolution of these two conditions. Pirfenidone was well tolerated by FPF and IPF patients. Specific unbiased randomized clinical trials on larger populations to validate our preliminary exploratory results are needed.

Active Surveillance for T1bN0M0 Papillary Thyroid Carcinoma.

Prospective trials of active surveillance for asymptomatic papillary microcarcinoma (T1aN0M0) since the 1990s have shown progression rates of only 5-10%. Late rescue surgery after progression had no deleterious effects on mortality and morbidity. The 2015 American Thyroid Association guidelines approved active surveillance for very low-risk papillary thyroid carcinoma (PTC) as an alternative method to immediate surgery. However, there is no study that evaluates long-term active surveillance for T1b tumors. A prospective trial of active surveillance with 360 very low-risk PTC (T1aN0M0) patients has been conducted since 1995. Of the 392 T1bN0M0 patients, 61 selected active surveillance over surgery and eventually participated in this trial, while the remaining 331 patients underwent surgery. To find an appropriate management strategy for patients with T1bN0M0 PTC, the outcomes of active surveillance for T1bN0M0 to T1aN0M0 PTC were investigated and compared, and the outcomes of surgery for T1bN0M0 PTC were studied. After a mean of 7.4 years of active surveillance, 29 (8%) T1aN0M0 tumors and four (7%) T1bN0M0 tumors had increased in size (p = 0.69). Development of lymph node metastasis was seen in three (0.8%) patients and two (3%) patients, respectively (p = 0.10). No significant difference in progression rate was seen between groups. Among T1bN0M0 tumors, weak calcification and rich vascularity were risk factors for tumor-size increase, and younger age was a predictor for the development of lymph node metastasis. Mean initial tumor size was significantly greater in T1bN0M0 patients who underwent immediate surgery (14.5 ± 2.8 mm) than it was in patients who chose observation (11.7 ± 1.1 mm; p < 0.0001). No postoperative recurrence was seen in patients with tumor <15 mm in diameter. Active surveillance is an option for selected patients with T1bN0M0 PTC.

Progression and complications of canine cataracts for different stages of development and aetiologies.

To evaluate progression and complications of various cataract aetiologies and stages of development. In all, 447 eyes of 250 dogs with cataracts were monitored between 2012 and 2015. Breed, gender, age, vision, types of cataract, stage of cataract development (incipient, immature, mature and hypermature), complications of cataracts, ocular ultrasonography and electroretinography findings were recorded. Re-examinations were performed after a minimum of 1, 6 and 12 months. A relative rate of progression within 1 month was determined and progression was categorised as stationary, slow, moderate or rapid. Overall, 44∙7% cataracts progressed and 55∙3% remained stationary. Incipient, immature, mature and hypermature cataracts progressed in 34∙1, 72∙7, 66∙7 and 44∙6% of cases, respectively. Hereditary, congenital, diabetic, contusive trauma-related, perforating trauma-related, radiation-related, senile cataracts and cataracts secondary to concurrent ocular diseases progressed in 47∙1, 66∙7, 66∙7, 50, 44∙4, 0, 29∙9 and 48∙9% of cases, respectively. Rapid progression was identified in 13∙3% of diabetic and 4∙3% of hereditary cataracts. Complications were diagnosed in 43∙5% and occurred at any stage but more frequently the further the cataract had developed. Lens-induced uveitis was the most common complication. Diabetic, traumatic, secondary and hereditary cataracts were associated with more complications than senile cataracts. Stage of development and cataract aetiology are associated with different rates of progression and complications.

Different rates of progression and mortality in patients with chronic kidney disease at outpatient nephrology clinics across Europe

The incidence of renal replacement therapy varies across countries. However, little is known about the epidemiology of chronic kidney disease (CKD) outcomes. Here we describe progression and mortality risk of patients with CKD but not on renal replacement therapy at outpatient nephrology clinics across Europe using individual data from nine CKD cohorts participating in the European CKD Burden Consortium. A joint model assessed the mean change in estimated glomerular filtration rate (eGFR) and mortality risk simultaneously, thereby accounting for mortality risk when estimating eGFR decline and vice versa, while also correcting for the measurement error in eGFR. Results were adjusted for important risk factors (baseline eGFR, age, sex, albuminuria, primary renal disease, diabetes, hypertension, obesity and smoking) in 27,771 patients from five countries. The adjusted mean annual eGFR decline varied from 0.77 (95% confidence interval 0.45, 1.08) ml/min/1.73m2 in the Belgium cohort to 2.43 (2.11, 2.75) ml/min/1.73m2 in the Spanish cohort. As compared to the Italian PIRP cohort, the adjusted mortality hazard ratio varied from 0.22 (0.11, 0.43) in the London LACKABO cohort to 1.30 (1.13, 1.49) in the English CRISIS cohort. These results suggest that the eGFR decline showed minor variation but mortality showed the most variation. Thus, different health care organization systems are potentially associated with differences in outcome of patients with CKD within Europe. These results can be used by policy makers to plan resources on a regional, national and European level.

Fractographic Analysis of a Split Tooth Presenting Radiographically as a Horizontal Root Fracture in an Unrestored Mandibular Second Molar

IntroductionSpontaneously catastrophic fracture of intact unrestored molar teeth is not common. Nevertheless, cracks do occur that progress apically, resulting in the complete splitting of the tooth and root. This report describes a catastrophic fracture that occurred in an unrestored mandibular second molar resulting in a previously unreported combination of a longitudinal and horizontal root fracture, appearing radiographically as a single horizontal root fracture. MethodsTooth fragments were examined clinically, stereoscopically, and by scanning electron microscopy. Fractographic analysis was used to investigate the dynamics involved in fracture initiation, structural resistances encountered during progression of the fracture, and reasons for direction changes culminating in the unusual radiographic appearance. ResultThe uniqueness of this report is that it describes fractographic evidence of factors contributing to the initiation and progression of an in vivo crack. It shows fracture markings that are evidence of the energy dissipation mechanisms. The topographic location of these markings confirmed that cracks occur in vivo in stages with different rates of progression. ConclusionThis analysis helps to explain why split teeth are uncommon and highlights some of the multitude of factors that have to coincide for a tooth to catastrophically fracture. The report describes the mechanism of fracture and should stimulate clinicians and researchers to investigate cracking of teeth by undertaking fractographic analysis of extracted cracked teeth.

REM Sleep Behavior Disorder Is Not Associated with a More Rapid Cognitive Decline in Mild Dementia.

REM sleep behavior disorder (RBD) is associated with cognitive dysfunctions and is a risk factor for development of mild cognitive impairment and dementia. However, it is unknown whether RBD is associated with faster cognitive decline in already established dementia. The main goal of this study was to determine if patients with mild dementia with and without RBD differ in progression rate and in specific neuropsychological measures over 4-year follow-up. This longitudinal, prospective study based on data from the DemVest study compares neuropsychological measures in a mild dementia cohort. A diagnosis of probable RBD (pRBD) was made based on the Mayo Sleep Questionnaire. Neuropsychological domains were assessed by Mini Mental State Examination, total score and figure copying, California Verbal Learning Test-II, Visual Object and Space Perception Cube and Silhouettes, Boston Naming Test, Stroop test, Verbal Category Fluency, Trail Making Test A and B. Among the 246 subjects, 47 (19.1%) had pRBD at the baseline, and pRBD group was younger and with male predominance. During 4-year follow-up, we did not observe any significant differences in the rate of decline in neuropsychological measures. Patients with pRBD performed generally poorer in visuoconstructional, visuoperceptual, and executive/attention tests in comparison to RBD negative. We did not find any significant differences in progression rate of neurocognitive outcomes between dementia patients with and without RBD.

Challenging Assumptions About African American Participation in Alzheimer Disease Trials

The authors investigated potential effects of increased African American participation in Alzheimer disease (AD) and mild cognitive impairment (MCI) clinical trials by examining differences in comorbid conditions and treatment outcome affecting trial design. Using a meta-database of 18 studies from the Alzheimer's Disease Cooperative Study and the Alzheimer's Disease Neuroimaging Initiative, a cohort of 5,164 subjects were included for whom there were baseline demographic data and information on comorbid disorders, grouped by organ system. Meta-analysis was used to compare prevalence of comorbidities, dropouts, and rates of change on the cognitive subscale of the Alzheimer's Disease Assessment Scale by race. Clinical trial scenarios similar to recent therapeutic trials were simulated to determine effects of increased African American participation on statistical power. Approximately 7% of AD, 4% of MCI, and 11% of normal participants were African American. African American subjects had higher prevalence of cardiovascular disorders (odds ratio: 2.10; 95% confidence interval [CI]: 1.71-2.57) and higher rate of dropouts (odds ratio: 1.60; 95% CI: 1.15-2.21) compared with whites but lower rates of other disorders. There were no significant differences in rate of progression (-0.862 points/year; 95% CI: -1.89 to 0.162) by race and little effect on power in simulated trials with sample sizes similar to current AD trial designs. Increasing African American participation in AD clinical trials will require adaptation of trial protocols to address comorbidities and dropouts. However, increased diversity is unlikely to negatively affect trial outcomes and should be encouraged to promote generalizability of trial results.

P53 protein accumulation predicts malignant progression in Barrett's metaplasia: a prospective study of 275 patients.

The purpose of this study was to determine prospectively whether p53 protein accumulation in biopsies of Barrett's metaplasia (BM) is a predictor of malignant progression, without relying on dysplasia grading. Sections of formalin-fixed paraffin-embedded tissue from the initial biopsies of 275 patients with BM, who had no high-grade dysplasia (HGD) or oesophageal adenocarcinoma (EAC), were stained for p53 by immunohistochemistry. The mean follow-up was 41 months. p53-positive biopsies were divided into four groups: scattered positive cells, multifocal scattered positive cells, aggregates of positive cells, and multifocal aggregates of positive cells. Kaplan-Meier analysis with the log-rank test was used to determine the rate of progression to HGD/EAC. Of the 275 patients, 227 had initial biopsies that were completely negative for p53, and, of these, one (0.4%) progressed to HGD/EAC; none of 24 (0%) patients with scattered positive cells and none of four (0%) of patients with multifocal scattered positive cells progressed. In contrast, five of 16 (31.25%) patients with aggregates of positive cells and three of four (75%) of those with multifocal aggregates of positive cells progressed to HGD/EAC. Kaplan-Meier analysis with log-rank statistics showed the difference in progression rate between the five groups to be highly significant (P < 0.0001). We conclude that p53 protein accumulation, detected by immunohistochemistry in aggregates of cells, is a significant predictor of malignant progression in patients with BM.

Familial pulmonary fibrosis: Clinical and radiological characteristics and progression analysis in different high resolution-CT patterns

BackgroundFamilial pulmonary fibrosis (FPF) is defined as an idiopathic diffuse parenchymal lung disease affecting two or more members of the same primary biological family. The aim of the present study was to contribute to the clinical, functional and radiological characterisation of FPF with particular regards to disease progression and survival. MethodsBaseline clinical, functional and radiological data of a FPF population (n = 46 patients) were retrospectively collected and analysed according to the 2011 IPF guidelines HRCT classification. A PFT follow-up after 1-year and survival analysis was conducted among to different HRCT patterns. Results22 female and 24 male patients (age at diagnosis 58.5 ± 9.7 years-old), belonging to 30 families, were included in this study. Radiological analysis demonstrated the presence of a UIP pattern at HRCT in 54.3% of patients, Poss-UIP in 21.8% and Incon-UIP in 23.9%. Incon-UIP patients were younger and more frequently female. Pulmonary function tests showed a restrictive ventilatory defect in patients with UIP and Incon-UIP patterns, while Poss-UIP patients had normal volumes with only a mild reduction of DLCO. BAL composition revealed increased lymphocytes percentage in Incon-UIP patients. Respiratory functional 1-year follow-up showed a significant worsening in UIP patients only. HRCT pattern progression was only demonstrated from Poss-UIP to UIP (18% of patients). Median survival was not statistically different among the 3 HRCT groups, although Poss-UIP patients presented a better outcome. ConclusionsFPF has been confirmed to be a complex condition with poor prognosis. The present study firstly analysed functional and radiological follow-up data of patients with FPF, showing that it may manifests with several HRCT patterns with different rates of progression, in which Possible UIP and UIP could be considered phases of the same disease and Inconsistent UIP patients may represent a different clinical and radiological condition.

Pre-Post Demographic Study of Child-Centered Play Therapy for Students With Highly Disruptive Behavior in High-Poverty Schools

As a follow-up to a controlled comparison study of child-centered play therapy (CCPT) for students with highly disruptive behavior in high-poverty schools (Cochran & Cochran, in press), this study considers changes from pretreatment to posttreatment across nine school weeks of CCPT for all served students (regardless of control period), yielding evidence of significant improvement and large effect sizes, and a large enough sample to investigate possible demographic differences. While main effects were found for ethnicity and gender, with students from minority ethnicities in the data set (African American, Hispanic, and Native American) having higher means in externalizing behavior than students from the majority ethnicity in the data set (Caucasian), and girls having lower means in externalizing and higher means in internalizing than boys, no differences in rates of progress were found for ethnicity, gender, or age for each of the five dependent variables, supporting evidence of the wide ranging applicability and cultural sensitivity of CCPT.

Progression of kidney disease in elderly stage 3 and 4 chronic kidney disease patients.

The prevalence of chronic kidney disease (CKD) has been rising steadily in the elderly population. We studied the rate of progression of CKD in this population and the factors associated with progression of CKD to better identify patients who are likely to progress to ESRD. This was an observational study including 4562 patients older than 65years with two outpatient estimated glomerular filtration rates (eGFRs) of <60ml/min/1.73m2, at least 90days apart with no intervening eGFR >60ml/min/1.73m2 (March 1, 2001, and March 31, 2008) at VA healthcare facilities. Patients with eGFR <15ml/min/1.73m2 were excluded. Annual rate of decline of eGFR was studied and categorized as <1ml/min/1.73m2, 1-4ml/min/1.73m2, and >4ml/min/1.73m2. Mean age of the study participants was 77.2years. 24.3% were diabetics. 4.3% had proteinuria. In univariate comparison of different rates of progression, 54.2% patients had an annual rate of progression of <1ml/min/1.73m2. Multivariable mixed model analyses revealed that increasing age, body mass index, presence of cardiovascular disease, diabetes mellitus, and proteinuria were associated with significantly increased rate of progression of CKD. Serum albumin and hemoglobin level were inversely associated with progression of CKD. CKD progresses at a slower rate in the elderly population. We have identified risk factors associated with an increased risk of progression of CKD in the elderly. This may help to improve health care planning and resource utilization.

Valuing biodiversity and ecosystem services: a useful way to manage and conserve marine resources?

Valuation of biodiversity and ecosystem services (ES) is widely recognized as a useful, though often controversial, approach to conservation and management. However, its use in the marine environment, hence evidence of its efficacy, lags behind that in terrestrial ecosystems. This largely reflects key challenges to marine conservation and management such as the practical difficulties in studying the ocean, complex governance issues and the historically-rooted separation of biodiversity conservation and resource management. Given these challenges together with the accelerating loss of marine biodiversity (and threats to the ES that this biodiversity supports), we ask whether valuation efforts for marine ecosystems are appropriate and effective. We compare three contrasting systems: the tropical Pacific, Southern Ocean and UK coastal seas. In doing so, we reveal a diversity in valuation approaches with different rates of progress and success. We also find a tendency to focus on specific ES (often the harvested species) rather than biodiversity. In light of our findings, we present a new conceptual view of valuation that should ideally be considered in decision-making. Accounting for the critical relationships between biodiversity and ES, together with an understanding of ecosystem structure and functioning, will enable the wider implications of marine conservation and management decisions to be evaluated. We recommend embedding valuation within existing management structures, rather than treating it as an alternative or additional mechanism. However, we caution that its uptake and efficacy will be compromised without the ability to develop and share best practice across regions.