Significant Risk Factor For Progression Research Articles

DOP41 Low-grade dysplasia prognosis and predictive factors for advanced neoplasia progression in the 21st century: A large multi-centre retrospective cohort study

Abstract Background Recent advances in ulcerative colitis (UC) endoscopic surveillance such as high-definition imaging and greater chromoendoscopy (CE) use have led to an increase in detection and resection of visible dysplasia. An updated study of prognosis of low-grade dysplasia (LGD) is needed to address uncertainty as to the accuracy of progression rates based on historical studies. Methods This retrospective cohort study involved four UK IBD centres. Hospital and endoscopy pathology databases were searched between 1 January 2001 and 30 December 2018 to identify adult patients with UC who had their first LGD diagnosis diagnosed within the extent of colitis. Only patients followed up with at least one colonoscopy or colectomy by 30 August 2019 were included. The study endpoint was time to high-grade dysplasia (HGD) or cancer (CRC), i.e. advanced neoplasia (AN), or end of follow-up. Survival analyses were performed using Kaplan–Meier estimation and Cox proportional hazards (PH) models. Results In total, 460 patients met the inclusion criteria and were followed up for a median of 4.1 years (IQR 6), equating to 2,232 patient-years. A mean of 3.7 (range 0–17) subsequent colonoscopies was performed per patient. Seventy-seven per cent of patients had CE surveillance. Complete endoscopic resection was achieved in 94% and 64% of the polypoid and non-polypoid LGD, respectively. There was progression to AN in 88 cases (19%) during follow-up. There was no significant difference in AN progression between centres. Unresectable non-polypoid or invisible LGD carried the greatest risk of AN development (Figure 1). On univariate Cox PH analysis, CE use was protective against AN progression (HR 0.5; 95% CI 0.3–1.0; p = 0.04). However, only highly significant predictors of LGD progression to AN on univariate analysis (Bonferroni adjusted p < 0.003), were entered into the multivariate model: Cumulative risk of AN increased with the number of risk factors (Figure 2). Conclusion This is the largest study examining prognosis of LGD, based on endoscopic features, in this century. Five-year cumulative incidence of AN is low after complete endoscopic resection of visible LGD without surrounding dysplasia. Lesion size of 1 cm or more, invisibility, multifocality and unresectability of LGD are significant risk factors for progression to AN. These factors should be taken into consideration when discussing management options with patients.

Differences between Risk Factors for Sepsis and Septic Shock in Obstructive Urolithiasis.

BackgroundComplicated acute pyelonephritis (APN) is a life-threatening condition that requires immediate intervention. This study examined the characteristics of APN occurring as a complication of ureteral stone.MethodsWe retrospectively reviewed 85 patients diagnosed with APN complicated by ureteral stone between December 2006 and July 2017 at our institution. Patients with concomitant renal stone, multiple ureteral stones, ureteral strictures, ureteral cancer, and urogenital anomalies, including vesicoureteral reflux were excluded. Clinical characteristics including age, sex, underlying disease, medical history, stone characteristics, initial laboratory data, and the procedure used to correct urinary obstruction were summarized, and the risk factors associated with sepsis and septic shock were analyzed.ResultsSepsis was diagnosed at initial presentation in 62 patients, 17 of whom suffered from septic shock. Disease-related death did not occur in any patient. Previous history of stone (P = 0.015), leukocytosis (P < 0.001), elevated C-reactive protein levels (P = 0.006), and low albumin (P = 0.038) were significant risk factors for progression to sepsis. The absence of hypertension (P = 0.047), thrombocytopenia (P = 0.006), decreased erythrocyte sedimentation rate (ESR) (P = 0.003), elevated blood urea nitrogen (P = 0.016), and positive blood culture (P = 0.018) were significant predictors for progression to septic shock. Multivariate analysis revealed that previous history of stone (P = 0.015) was an independent risk factor for sepsis, while the absence of hypertension (P = 0.047), thrombocytopenia (P = 0.013), and decreased ESR (P = 0.009) were risk factors for shock.ConclusionThe risk factors associated with the progression from APN to sepsis differed from those associated with the progression from sepsis to septic shock. Various factors should be considered while selecting treatment options based on the severity of APN associated with ureteral stone. It should be managed with aggressive treatment and close observation, especially in the presence of risk factors.

The significance of genetic mutations and their prognostic impact on patients with incidental finding of isolated del(20q) in bone marrow without morphologic evidence of a myeloid neoplasm

Patients with a sole del(20q) chromosomal abnormality and without morphologic features of a myeloid neoplasm (MN) have shown variable clinical outcomes. To explore the potential risk stratification markers in this group of patients, we evaluated their genetic mutational landscape by a 35-gene MN-focused next-generation sequencing (NGS) panel and examined the association of mutations to progression of MNs. Our study included 56 patients over a 10-year period with isolated del(20q), of whom 23 (41.1%) harbored at least one mutation. With a median follow-up of 32.6 months (range: 0.1−159.1), 9 of 23 patients with mutation(s) progressed to MNs, while all 33 patients without mutations did not progress to MN. Kaplan−Meier survival analysis demonstrated the presence of mutation(s) as a significant risk factor for progression to MN (P < 0.0001). MN progression was strongly associated with the presence of non-DNMT3A/TET2/ASXL1 epigenetic modifiers and nonspliceosome mutations (P = 0.003). There was no significant difference among patients with and without MN progression with respect to the number of mutations, variant allele frequency, percentage of del(20q), and other clinical/laboratory variables. This study illustrates the underlying genetic heterogeneity and complexity of isolated del(20q), and underscores the prognostic value of NGS mutational analysis in these cases.

Delaying haematopoietic stem cell transplantation in children with viral respiratory infections reduces transplant-related mortality.

SummaryViral respiratory infections (VRIs) contribute to the morbidity and transplant‐related mortality (TRM) after allogeneic haematopoietic stem cell transplantation (HSCT) and strategies to prevent and treat VRIs are warranted. We monitored VRIs before and after transplant in children undergoing allogeneic HSCT with nasopharyngeal aspirates (NPA) and assessed the impact on clinical outcome. Between 2007 and 2017, 585 children underwent 620 allogeneic HSCT procedures. Out of 75 patients with a positive NPA screen (12%), transplant was delayed in 25 cases (33%), while 53 children started conditioning with a VRI. Patients undergoing HSCT with a positive NPA screen had a significantly lower overall survival (54% vs. 79%) and increased TRM (26% vs. 7%) compared to patients with a negative NPA. Patients with a positive NPA who delayed transplant and cleared the virus before conditioning had improved overall survival (90%) and lower TRM (5%). Pre‐HSCT positive NPA was the only significant risk factor for progression to a lower respiratory tract infection and was a major risk factor for TRM. Transplant delay, whenever feasible, in case of a positive NPA screen for VRIs can positively impact on survival of children undergoing HSCT.

HIV Infection Is Associated With Downregulation of BTLA Expression on Mycobacterium tuberculosis-Specific CD4 T Cells in Active Tuberculosis Disease.

Nearly a quarter of the global population is infected with Mycobacterium tuberculosis (Mtb), with 10 million people developing active tuberculosis (TB) annually. Co-infection with human immunodeficiency virus (HIV) has long been recognized as a significant risk factor for progression to TB disease, yet the mechanisms whereby HIV impairs T cell-mediated control of Mtb infection remain poorly defined. We hypothesized that HIV infection may promote upregulation of inhibitory receptors on Mtb-specific CD4 T cells, a mechanism that has been associated with antigen-specific T cell dysfunction in chronic infections. Using cohorts of HIV-infected and HIV-uninfected individuals with latent Mtb infection (LTBI) and with active TB disease, we stimulated peripheral blood mononuclear cells (PBMC) for 6 hours with Mtb peptide pools and evaluated co-expression profiles of the inhibitory receptors BTLA, CTLA-4, and PD-1 on IFN-γ+/TNF-α+ Mtb-specific CD4 T cells. Mtb-specific CD4 T cells in all participant groups expressed predominately either one or no inhibitory receptors, unlike cytomegalovirus- and HIV-specific CD4 T cells circulating in the same individuals, which were predominately CTLA-4+PD-1+. There were no significant differences in inhibitory receptor expression profiles of Mtb-specific CD4 T cells between HIV-uninfected and HIV-infected individuals with LTBI. Surprisingly, BTLA expression, both alone and in combination with CTLA-4 and PD-1, was markedly downregulated on Mtb-specific CD4 T cells in HIV-infected individuals with active TB. Together, these data provide novel evidence that the majority of Mtb-specific CD4 T cells do not co-express multiple inhibitory receptors, regardless of HIV infection status; moreover, they highlight a previously unrecognized role of BTLA expression on Mtb-specific CD4 T cells that could be further explored as a potential biomarker of Mtb infection status, particularly in people living with HIV, the population at greatest risk for development of active TB disease.

Incidence and Risk Factors for a Partial Anterior Cruciate Ligament Tear Progressing to a Complete Tear After Nonoperative Treatment in Patients Younger Than 30 Years.

Background:Partial anterior cruciate ligament (ACL) tears are observed in 10% to 27% of isolated ACL tears. There is currently no consensus on diagnosis and treatment protocols, and the outcomes of nonoperative treatment remain undefined.Purpose:To assess the incidence and risk factors for the progression of partial ACL tears to complete ruptures after nonoperative treatment in active patients younger than 30 years.Study Design:Case-control study; Level of evidence, 3.Methods:A total of 41 patients, all younger than 30 years and active in sports, were diagnosed with a partial ACL tear, with no associated meniscal or chondral lesions on magnetic resonance imaging (MRI). All were assigned to a nonoperative treatment program. The Lachman test, ≤4-mm side-to-side difference in laxity by Rolimeter, and MRI were utilized for the diagnosis. Tegner and International Knee Documentation Committee (IKDC) scores were assessed before and after the first lesion, and the Anterior Cruciate Ligament Return to Sport After Injury (ACL-RSI) score was assessed at last follow-up. Postinjury Tegner and IKDC scores were assessed before the second injury for patients progressing to a complete ACL tear and at last follow-up for patients without progression.Results:At a mean of 43 months (range, 24-96 months), the partial ACL injury progressed to a complete ACL tear in 16 (39%) patients. In the remaining 25 patients without progression, the mean Tegner and IKDC scores were 7.0 and 96.0 before the injury and 5.9 and 85.7, respectively, at last follow-up. The mean ACL-RSI score was 69.3. The Tegner and IKDC scores were significantly lower at final follow-up (P = .0002 and P < .0001, respectively). Only 18 (44%) patients returned to their preinjury level of sports activities. A significantly increased risk of progression to a complete ACL tear was seen in patients ≤20 years (odds ratio, 5.19; P = .037) or patients practicing pivoting contact sports (odds ratio, 6.29; P = .026). Meniscal lesions were found in 50% of patients with a partial tear that progressed to a complete ACL tear.Conclusion:A partial ACL injury progressed to a complete ACL tear in 39% of young active patients treated conservatively, with half of the complete tears presenting with a concomitant meniscal lesion at the time of reconstruction. Age ≤20 years and participation in pivoting contact sports were identified as significant risk factors for progression to a complete tear.

Prognosis of young patients with monoclonal gammopathy of undetermined significance.

8049 Background: Monoclonal gammopathy of undetermined significance (MGUS) is rare in young patients (pts; age &lt;40 years at diagnosis), with a prevalence of &lt; 0.3%, representing approximately 2% of all patients with MGUS. We hypothesized that MGUS detected in pts &lt;40 years of age may be associated with a higher risk of progression. Methods: We identified 249 pts with MGUS &lt;40 yrs old, evaluated at Mayo Clinic, Rochester from 1997 to 2016. The endpoint was time to progression assessed by Kaplan-Meier method. Results: 119 were male, 130 were female. Most (n= 179, 72%) were diagnosed between the ages of 30-39. The type of MGUS was IgG 69%, IgA 10%, IgM 15%, and other 5%. 135 pts (54%) had concurrent immune-related conditions, including autoimmune, inflammatory, and infectious disorders at the time of diagnosis of MGUS. Pts without immune-related conditions tend to have higher M protein compared to pts with immune-related conditions (mean, 0.36 gm/dl VS 0.20 gm/dl, p =0.057). During follow up, the M protein resolved in 36 patients. The M protein was more likely to resolve in pts with immune-related conditions compared with pts without immune-related conditions (RR 1.91, 95% CI 1.02-3.59). Progression was seen in 16 pts: 9 smoldering multiple myeloma (SMM), 4 multiple myeloma (MM), 1 macroglobulinemia, 2 non-Hodgkin’s lymphoma. The rate of progression to SMM, MM, or related disorder at 5 and 10 years was 6.0% and 13.8%, respectively. The size of M protein was a significant risk factor for progression (HR 4.23, 95% CI 2.17-7.91) The risk of progression at 5 and 10 years for pts with immune-related conditions concurrently present when MGUS was first diagnosed was 1.5% and 10.1% respectively; corresponding rate in pts without immune-related conditions at the time of diagnosis was higher at 12.3% and 18.9%, respectively (p =0.016), (HR 2.36, 95% CI 0.85-6.52). Similar results were seen when patients in whom the M protein resolved were excluded. Conclusions: Young patients with MGUS may have a higher risk of progression, 1.4% per year; approximately 50% are diagnosed in the setting of immune-related disorders. When occurring in the setting of immune related disorders, the M protein is smaller, more likely to resolve, and may have a lower risk of progression than in pts in whom MGUS is detected without concurrent immune-related disorder.

Significance of dynamic contour tonometry in evaluation of progression of glaucoma in patients with a history of laser refractive surgery

AimsIn this study, we tested the hypothesis that intraocular pressure (IOP) parameters measured by dynamic contour tonometry (DCT) would be more relevant in progression of glaucoma when there is a...

Increasing Bovine leukemia virus (BLV) proviral load is a risk factor for progression of Enzootic bovine leucosis: A prospective study in Japan

Bovine leukemia virus (BLV) belongs to the genus Deltaretrovirus in the family Retroviridae, and is etiologically associated with Enzootic Bovine Leukosis (EBL). The majority of BLV-infected cattle remain asymptomatic throughout their productive lives, whereas approximately 5%–10% of infected cattle develop EBL. Data accumulated recently indicate that whole blood proviral load (PVL) levels of BLV-infected cattle could be an indicator of disease progression in the field. However, a few cross-sectional studies have been reported. Here, we prospectively evaluated 866 cattle enrolled between August 2015 and December 2015, and followed until November 2018, identifying 407 asymptomatic BLV-infected cattle. There were no significant differences in the median PVL level among the category of herd seroprevalence (p = 0.57), herd size (p = 0.19), nor among the category of past EBL history in the herd (p = 0.31). During the study period, 12 cattle developed EBL. The PVL levels of EBL cattle at the time of enrollment were significantly higher than that of cattle that did not progress to EBL (median, 90,695 vs 39,139 copies/105 cells, p = 0.0005). Moreover, the adjusted hazard ratio for the increase in PVL was 2.61 (95% CI, 1.51–4.53) as estimated by the Cox proportional hazards frailty model. These results indicate that a high PVL level is a significant risk factor for progression to EBL, and could potentially be used as an indicator for the identification of cattle to be culled from the herd long before the progression of EBL. This knowledge might be useful to design a strategy for decreasing economic loss from EBL or even eradicating it from herds.

ASSOCIATION BETWEEN NEUROPSYCHIATRIC SYMPTOM TRAJECTORY AND PROGRESSION TO ALZHEIMER'S DISEASE

Introduction Objective: Neuropsychiatric symptoms (NPS) are a key characteristic and known biomarker of Alzheimer's disease (AD). Our study investigates the potential of NPS as measured by the Neuropsychiatric Inventory score (NPI) to predict progression from Mild Cognitive Impairment (MCI) to AD. In addition, we have analyzed the trajectory of NPS in comparison to global cognitive scores. Introduction NPS are common in MCI and based on prior studies they are a significant risk factor for progression to AD. Working memory and episodic memory are also known to decline with progression of AD. Cognitive tests such as MMSE have been utilized to track patients’ level of cognition and the decline in these cognitive tests is a well-known predictor of dementia. However, how NPI scores relate to cognitive test scores in predicting progression to AD is still unknown. We propose to analyze NPI (total score and sub scores) longitudinally for 6 years and to compare scores between MCI- converters (MCI-C) and MCI- non converters (MCI-NC). We hypothesize that converters may have higher scores compared to non-converters. In addition, we expect that MMSE score should correlate inversely with NPI score. Symptoms associated with progression to AD that are prevalent in our study should match those that are shown in previous studies (depression, delusion, agitation, and apathy.) Methods We selected 150 subjects from Alzheimer's Disease Neuroimaging Initiative phase 3 (36 MCI-C and 114 MCI-NC). The only inclusion criteria were that subjects must have NPI scores at two or more time points. Gender, age, and education were matched across all subjects. To measure NPI scores longitudinally, subjects were divided into two groups, MCI-C and MCI-NC. We also grouped subjects according to their NPI scores to measure their cognition using MMSE: healthy (N=55), mild (NPI score= 1-9, N=65), and severe (NPI score= 10 and above, N=30). The NPI total score and MMSE were measured across 6 years and compared at 12-month intervals. All statistical analyses were performed using SPSS 25. Analyses of variance (ANOVA) were used to compare MCI-C and MCI-NC group differences. If the assumption of homogeneity was violated, Brown-Forsythe Test p-value was reported instead. Post-hoc analyses was done by using Gabriel and Dunnett's T3 test. The 12 NPI sub scores were also counted as percentage to analyse the progression of NPS. Results The NPI total scores at all time points for the duration of 6 years were significantly different between MCI-C and MCI-NC (p Conclusions Our study has confirmed previous findings that NPI scores increased with progression of clinical symptoms from MCI to AD in MCI-C relative to MCI-NC. In addition, MMSE scores varied between NPI groups at all time points after baseline. Both of the scores showed a deteriorating trend in their respective scale in MCI-C relative to MCI-NC. This research was funded by Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.

Frequency of Acquired Genetic Mutations and Their Prognostic Impact on Patients with Incidental Finding of Isolated 20q- in Bone Marrow without Morphologic Evidence of a Myeloid Neoplasm

IntroductionMyelodysplastic syndromes (MDS) are heterogeneous myeloid disorders characterized by dysplasia in one or more hematopoietic cell lines, peripheral cytopenia(s), and distinct cytogenetic abnormalities. The presence of certain cytogenetic abnormalities [e.g. 7/del(7q), -5/del(5q), 13/del(13q), i(17p)], in the setting of unexplained persistent cytopenia, has been considered presumptive evidence of MDS, despite definitive morphologic features of MDS. Conversely, chromosomal abnormalities such as isolated 20q- are not considered definitive evidence for MDS, in the absence of dysplasia. Based on our previous findings, patients with isolated 20q- without morphologic features of a myeloid neoplasm have varied clinical outcomes (Jawad MD et al. Am J Hematol.2016). In this study, we investigate the frequency of recurrent somatic gene mutations in these patients, and their relationship to progression to a myeloid neoplasm.MethodsWe retrospectively reviewed the bone marrow pathology reports of patients evaluated at our institution from 01/2005 to 09/2015 who had isolated 20q- in at least 2 of 20 metaphases. Patients with isolated 20q- and without myeloid neoplasms were included in the study, along with medical record review. A 35-gene next generation sequencing (NGS) panel (OncoHeme) targeting myeloid neoplasms was performed on available archived bone marrow aspirate pellets. Statistical analyses were performed using JMP Pro software version 13. Parametric (t-test) or nonparametric tests such as the Fisher-exact test, chi-square test, or Wilcoxon rank-sum test, were utilized as appropriate for test variables. Statistical significance was based on a 2-sided significance level of .05. Kaplan-Meier analysis was used for analyzing time to progression to myeloid neoplasms and progression-free survival (i.e. time to progression to myeloid neoplasms or death from any cause).ResultsFifty-six (42 males, 14 females) patients with isolated 20q- were identified. The average percentage of 20q- was 38.5 % (±29.3). The median age was 68 years (range: 44-90) and the median hemoglobin (Hb), absolute neutrophil count (ANC) and platelet count (Plt) were 11.7 g/dL (range: 8.3-15.1), 2.7 x 10(9)/L (range: 0.6-9.4) and 138 x 10(9)/L (range: 16-392), respectively. The indications for bone marrow biopsies ranged from cytopenia (21), multiple myeloma (20), non-Hodgkin lymphoma (10), amyloidosis (2), CLL (2) and transplant donor evaluation (1). Twenty-three patients harbored pathogenic mutations (15 had one mutation, 1 had two mutations and 7 had three mutations). The identified pathogenic mutations included ASXL1 (8), TET2 (8), SRSF2(3),PHF6 (2), SF3B1 (2), CBL (2), U2AF1 (2), IDH1 (1), IDH2 (1), BCOR (1), JAK2 (1), PTPN11(1), TP53 (1) and RUNX1 (1). Nine patients (16.1%) progressed to myeloid neoplasms (5 MDS, 2 acute myeloid leukemia, 2 chronic myeloid neoplasm-not otherwise specified) at a median follow-up of 36.7 months (range: 1.9-57.4). Of these 9 patients, 5 had one mutation (BCOR, TET2, DNM3TA, CBL, IDH2), 1 had two mutations (SF3B1/CBL) and 3 had three mutations (ASXL1/IDH1/SRSF2,DNM3TA/PTPN11/TET2, PHF6/TET2/TET2). In contrast, only 29.8% of non-progressed cases showed at least 1 mutation. Kaplan-Meier analysis demonstrated the presence of genetic mutations in patients with isolated 20q- carried significantly higher chance of progression to myeloid neoplasms (p<.05, Figure 1A and 1B). However, the number of genetic mutations was not predictive of progression in our relatively small study cohort (p=.66). There was no significant difference between those who did and did not progress with respect to age, gender, Hb, ANC, Plt, 20q- or mutational allele burden.ConclusionsMost of the patients with isolated 20q- and without morphologic features of a myeloid neoplasm did not harbor myeloid neoplasm associated gene mutations and further did not develop a myeloid neoplasm during the course of our study. Among patients with pathogenic mutations, nearly one-third showed progression to a myeloid neoplasm. Of the clinical and laboratory variables, the presence of genetic mutation is a significant risk factor for progression to a myeloid neoplasm. This study revealed the underlying molecular heterogeneity of isolated 20q- in the absence of morphologic features of a myeloid neoplasm, and underscored the prognostication value of genetic mutation analysis in these cases. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Steatohepatitis Is Not Associated with an Increased Risk for Fibrosis Progression in Nonalcoholic Fatty Liver Disease.

Introduction Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease globally. The majority of NAFLD patients have fatty liver without inflammation (nonalcoholic fatty liver, NAFL), whereas a minority develop steatohepatitis (nonalcoholic steatohepatitis, NASH). Only NASH and not NAFL has been considered to increase the risk for fibrosis progression. The present study investigates risk factors for fibrosis progression in patients with NAFLD, and if fibrosis progression associates with subsequent mortality. Material and Methods All patients with at least two liver biopsies more than a year apart at our hospital between 1971 and 2016 were identified. Data on plausible risk factors for fibrosis progression were collected. Biopsies were scored for the presence of NASH and fibrosis stage. Regression models were used to investigate the association between baseline NASH and fibrosis progression and fibrosis progression with future mortality. Results 60 patients had undergone serial biopsies (median interval between biopsies 8.4 years, range 1–33 years), with 26 patients (43%) having fibrosis progression. We found no significant risk factors for progression of fibrosis except time between biopsies. Among patients with fibrosis progression, 54% had NAFL and 46% had NASH at baseline. There was a trend for an association between fibrosis progression per se and increased mortality (hazard ratio 2.83, 95% CI 1.0–8.1, p = 0.05). Conclusions In this study on NAFLD, baseline steatohepatitis was not associated with an increased risk for fibrosis progression. NAFLD patients without steatohepatitis may develop progressive fibrosis, and those with progressive fibrosis appear to have a higher mortality risk irrespective of baseline NASH status.

Assessment of Endovascular Treatment of Tibial Artery Occlusion in Diabetic Patients

Background: Globally, over 170 million people have diagnosed DM, and by the year 2030, the prevalence is estimated to raise 2.5-fold. Diabetes mellitus (DM) is one of the strongest predictors of peripheral arterial occlusive disease and a significant risk factor for progression of asymptomatic disease or claudication into critical limb ischaemia (CLI). Critical limb ischaemia is the most advanced stage of peripheral arterial occlusive disease. The prognosis is poor, with amputation rates up to been 30% and mortality up to 25 % after 1 year. Aim of the Work: The aim of this work is to evaluate the role of endovascular treatment of tibial artery occlusive disease in diabetic patients, as regard to efficacy, safety, as well as complications. Patients and Methods: This is prospective cohort study, diabetic patients with peripheral arterial occlusive disease (affecting tibial arteries), it is the study of 20 patients, Al-Azhar University Hospitals. Patients with Critical limb ischaemia (CLI) with Computerized Topographic Angiography (CTA) evidence of significant isolated tibial artery occlusive disease (anterior or posterior or both). Patients with generally adequate state of cardiac, respiratory and renal conditions that allow the procedure. Results: The present study was conducted on 20 diabetic patients, 11 males (55%) and 9 females (45%). Their age ranged between 50 years and 87 years with a mean age of 66.7  12.35. All 20 diabetic patients had tibial disease which ranges from segmental stenosis to total occlusion. The procedure time was estimated from the time of infiltration of local anaesthesia to the end of the procedure; It ranged from 45 min to 120 minutes with mean ± SD (88.920. min).The hospital stay ranged from 1 to 21 days with mean ± SD (5.5 ±6.8). Conclusion: Tibial angioplasty demonstrated its feasibility, safety and effectiveness in the treatment of diabetic patients with CLI. Limb salvage should be the main goal in patients with CLI due to infrapopliteal occlusive disease. With a prompt diagnosis, treatment can be started early and serious consequences may be avoided. Revascularisation that can prevent amputation is the ultimate treatment strategy.

Prognostic model for high-tumor-burden follicular lymphoma integrating baseline and end-induction PET: a LYSA/FIL study

AbstractBoth total metabolic tumor volume (TMTV), computed on baseline positron emission tomography (PET), and end of induction (EOI) PET are imaging biomarkers showing promise for early risk stratification in patients with high-tumor-burden follicular lymphoma. A model was built incorporating these 2 factors in 159 patients from three prospective trials: 2 Lymphoma Study Association (LYSA) studies and 1 Fondazione Italiana Linfomi (FIL) trial. Median follow up was 64 months. High TMTV (>510 cm3) and positive EOI PET were independent, significant risk factors for progression. Their combination stratified the population into 3 risk groups: patients with no risk factors (n = 102; 64%) had a 5-year progression-free survival (PFS) of 67% vs 33% (hazard ratio [HR], 2.9; 95% confidence interval [CI], 1.8-4.9) for patients with 1 risk factor (n = 44; 27%) and only 23% (HR, 4.6; 95% CI, 2.3-9.2) for patients with both risk factors (n = 13; 8%). 2-year PFS was respectively 90% vs 61% (HR, 4.8; 95% CI, 2.2-10.4) and 46% (HR, 8.1; 95%CI, 3.1-21.3). This model enhances the prognostic value of PET staging and response assessment, identifying a subset of patients with a very high risk of progression and early treatment failure at 2 years.

MP08-03 ABSENCE OF INCHWORM SIGN ON DWI: A PREDICTIVE MARKER FOR PROGRESSION IN PT1 BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Non-invasive I1 Apr 2018MP08-03 ABSENCE OF INCHWORM SIGN ON DWI: A PREDICTIVE MARKER FOR PROGRESSION IN PT1 BLADDER CANCER shugo yajima, Soichiro Yoshida, Taro Takahara, Minato Yokoyama, Junichiro Ishioka, Yoh Matsuoka, Kazutaka Saito, Kazunori Kihara, and Yasuhisa Fujii shugo yajimashugo yajima More articles by this author , Soichiro YoshidaSoichiro Yoshida More articles by this author , Taro TakaharaTaro Takahara More articles by this author , Minato YokoyamaMinato Yokoyama More articles by this author , Junichiro IshiokaJunichiro Ishioka More articles by this author , Yoh MatsuokaYoh Matsuoka More articles by this author , Kazutaka SaitoKazutaka Saito More articles by this author , Kazunori KiharaKazunori Kihara More articles by this author , and Yasuhisa FujiiYasuhisa Fujii More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.308AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The utility of diffusion-weighted MRI (DWI) in the management of bladder cancer (BC) has been increasingly reported. The high signal intensity (SI) of BC with a low SI submucosal stalk shows an arch-like shape, which represents the papillary structure of the BC. This characteristic finding is called the “inchworm sign”, and is used as a criterion for T staging in NMIBC (T1 or less) (Takeuchi M, et al. Radiology 251:112-21, 2009). We evaluated the significance of the inchworm sign for recurrence and progression in the treatment course of T1 BC. METHODS Of the BC patients who were diagnosed with pT1 urothelial carcinoma between September 2007 and June 2016, 149 patients who underwent MRI examination including DWI (b-values of 0 and 1000 s/mm2) before TUR were retrospectively evaluated. A DWI image of the dominant BC was reviewed at a b value of 1000 s/mm2, and the presence of the inchworm sign was analyzed along with anatomic information from T2WI. The association of the presence of the inchworm sign or other clinical variables with progression at recurrence was evaluated. RESULTS Of the 149 included patients, we excluded 19 patients who had BC smaller than 10 mm on T2WI, 14 patients in whom muscle sampling was not performed, and 27 patients whose preoperative MRI could not be fully analyzed. The remaining 89 patients were eligible for the analysis. All tumors showed a high signal intensity on DWI. Of the 89 tumors, 60 (67%) were positive for the inchworm sign (IS), and 29 (33%) were negative for the inchworm sign (non-IS). During the median follow-up period of 27 months (range, 1–110 months), 24 IS patients (40%) and 14 non-IS patients (48%) experienced BC recurrence. At the time of recurrence, 1 (4%) and 7 (50%) BCs progressed to pT2 or greater in IS and non-IS patients, respectively. While the inchworm sign was not associated with recurrence, the progression rate was significantly higher in non-IS patients compared with IS patients (p = 0.0004) (Fig.). A negative inchworm sign and histological grade 3 were independent significant risk factors for progression (hazard ratio (HR) 9.7, p = 0.0018; HR 5.5, p=0.0191, respectively). CONCLUSIONS Absence of the inchworm sign in pT1 cancer predicts a high risk for progression at recurrence. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e96-e97 Advertisement Copyright & Permissions© 2018MetricsAuthor Information shugo yajima More articles by this author Soichiro Yoshida More articles by this author Taro Takahara More articles by this author Minato Yokoyama More articles by this author Junichiro Ishioka More articles by this author Yoh Matsuoka More articles by this author Kazutaka Saito More articles by this author Kazunori Kihara More articles by this author Yasuhisa Fujii More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Incidence and progression of myopia and associated factors in urban school children in Delhi: The North India Myopia Study (NIM Study).

AimTo evaluate the incidence and progression of myopia and factors associated with progression of myopia in school going children in Delhi.MethodsProspective longitudinal study of 10,000 school children aged 5 to 15 years screened after an interval of 1 year to identify new myopes (Spherical Equivalent≤ -0.5D) and progression of myopia in previously diagnosed myopic children. Association between risk factors and progression was analyzed using adjusted odds ratio.ResultsOf the 9,616 children re-screened (97.3% coverage), annual incidence of myopia was 3.4%with mean dioptric change of -1.09 ± 0.55. There was a significant higher incidence of myopia in younger children compared to older children (P = 0.012) and among girls compared to boys (P = 0.002). Progression was observed in 49.2%children with mean dioptric change of -0.27 ± 0.42 diopters. The demographic and behavioral risk factors were analyzed for children with progression (n = 629) and adjusted odds ratio values were estimated. Hours of reading-writing/week (p<0.001), use of computers/ video games (P<0.001) and watching television (P = 0.048) were significant risk factors for progression of myopia. Outdoor activities / time spent outdoors> 2 hours in a day were protective with an inverse association with progression of myopia (P< 0.001).ConclusionMyopia is an important health issue in India and is associated with long hours of reading and screen time with use of computers and video games. An annual eye vision screening should be conducted, and outdoor activities be promoted to prevent the increase of myopia among school children.

Risk factors for visual field progression of normal-tension glaucoma in patients with myopia

ObjectiveTo identify risk factors for visual field progression of normal-tension glaucoma (NTG) in patients with myopia. DesignLongitudinal, observational study. ParticipantsFifty-one eyes of 51 NTG patients with myopia (less than −0.75D based on spherical equivalence) who had undergone visual field (VF) testing at least once per year for ≥6 years between November 2005 and December 2013. MethodsProgression was defined using event-based guided progression analysis. Risk factors were analyzed using the Cox proportional hazards model and further tested for independence in a multivariate model. ResultsThe mean observation period was 7.0 ± 1.3 years, and 16 of 51 subjects showed progression. In the univariate analysis, abnormal retinal nerve fibre layer (RNFL) colour codes (yellow or red sector) at the 11, 10, and 7 o’clock positions on optical coherence tomography showed significant associations with the VF progression (p = 0.03, 0.03, and 0.01, respectively). In the final multivariate models, the abnormal RNFL colour code of the 7 o’clock sector (inferotemporal sector) was the only significant risk factor for progression (hazard ratio = 4.07 and 4.37; 95% CI, 1.11–14.92 and 1.27–15.04; p = 0.03 and 0.02, respectively). ConclusionsInferotemporal RNFL thinning could be a risk factor for progression in NTG patients with myopia.

Effect of Autoantibodies to Erythropoietin Receptor in Systemic Lupus Erythematosus with Biopsy-proven Lupus Nephritis.

We examined the clinical significance of autoantibodies to the erythropoietin receptor (EPOR) in patients with systemic lupus erythematosus (SLE) who had biopsy-proven lupus nephritis (LN). Forty-six Japanese patients with SLE with LN who had undergone renal biopsy during 1993-2014 were enrolled in this study and followed for a mean of 83 months. Sera from those patients were screened for anti-EPOR antibodies using ELISA. Anti-EPOR antibodies were detected in 18 (39%) of the 46 patients with SLE with anemia. Anti-EPOR antibodies were associated with low hemoglobin concentrations and reticulocytopenia. In addition, anti-EPOR antibodies were positively correlated with SLE disease activity, even though serum levels of the complement factors 3 and 4 did not differ between the 2 groups. In patients with International Society of Nephrology/Renal Pathology Society 2003 class IV LN, anti-EPOR antibodies were associated with active lesions including cellular crescents in glomeruli. Decrease in renal function was more frequently observed in patients without complete or partial renal response than in patients with it, and serum levels of the antibodies as well as renal response to treatment were significant risk factors for progression of renal dysfunction. The present study suggests that anti-EPOR antibodies might be involved in overall disease activity and active renal lesions, as well as in the impaired erythropoiesis in patients with SLE with LN. Further, the levels of anti-EPOR antibodies may be an additional predictor for renal injury.

MP13-02 IS RE-RESECTION NECESSARY? RE-RESECTION OF NON-MUSCLE INVASIVE BLADDER CANCER AT A TERTIARY CARE CENTER

You have accessJournal of UrologyBladder Cancer: Non-Invasive I1 Apr 2016MP13-02 IS RE-RESECTION NECESSARY? RE-RESECTION OF NON-MUSCLE INVASIVE BLADDER CANCER AT A TERTIARY CARE CENTER Rano Matta, Ashraf Al Matar, Bimal Bhindi, Alexander Zlotta, Neil Fleshner, Michael Jewett, Robert Hamilton, Antonio Finelli, and Girish Kulkarni Rano MattaRano Matta More articles by this author , Ashraf Al MatarAshraf Al Matar More articles by this author , Bimal BhindiBimal Bhindi More articles by this author , Alexander ZlottaAlexander Zlotta More articles by this author , Neil FleshnerNeil Fleshner More articles by this author , Michael JewettMichael Jewett More articles by this author , Robert HamiltonRobert Hamilton More articles by this author , Antonio FinelliAntonio Finelli More articles by this author , and Girish KulkarniGirish Kulkarni More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2483AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Re-staging transurethral resection (re-TUR) of T1 bladder tumors provides more accurate staging, and is associated with better local control. Re-TUR has been included in guidelines for management of non-muscle invasive bladder cancer since 2007. However, in practice, re-TUR has been questioned in the setting of perceived complete resection at initial TUR, amongst other patient and surgeon specific factors. We aimed to understand the practice patterns of re-TUR of T1 urothelial carcinoma at our center and its predictors. We also determined outcomes associated with re-TUR at a Canadian tertiary care center. METHODS We retrospectively identified 358 consecutive patients with pT1 high grade urothelial carcinoma of the bladder who were treated at the University Health Network, Toronto, from 2000 to 2012. We excluded those who had metastatic disease on diagnosis, those treated primarily with cystectomy or chemotherapy/radiation after TURBT. Those treated with early cystectomy or chemotherapy/radiation after re-TUR were not included in the final cohort. Patients who did not undergo immediate/early cystectomy were offered adjuvant BCG therapy. The remaining 270 patients were included in the final analysis. We compared re-TUR rates in the pre- (2000-2008) and post-guideline (2009-2012) era. End points were time to recurrence, time to progression (defined as stage T2 or higher), and mortality. Univariate and multivariate analyses were used to determine any significant effect of patient specific factors (age, gender) and disease specific factors (associated CIS, muscle sampled, immediate chemotherapy) on proceeding for re-TUR. We also performed Cox-proportional hazard models to determine risk factors for recurrence, progression, and survival. RESULTS The median age of the cohort was 68.9 years (18-97) with a mean follow up 3.3 years (0.08-13.3 years). Re-TUR was performed in 109 patients (40%). The average re-TUR rate increased after 2008 from 31.6% to 51.3% (p=0.038). There was residual tumor in 70% of re-TUR cases. Upstaging to T2 disease on re-TUR was seen in 16.5% of patients. There was residual pT1 in 29.4% of cases. Residual T1 disease at re-TUR was a significant risk factor for progression (HR 38.1; CI 5.9-246.6). Re-TUR was not a significant risk factor for recurrence, progression or mortality. CONCLUSIONS Overall, re-TUR is an important therapy, decision-making and prognostication tool in NMIBC. However, in terms of the effectiveness of re-TUR on recurrence and progression, further prospective studies will provide more definitive information. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e134 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Rano Matta More articles by this author Ashraf Al Matar More articles by this author Bimal Bhindi More articles by this author Alexander Zlotta More articles by this author Neil Fleshner More articles by this author Michael Jewett More articles by this author Robert Hamilton More articles by this author Antonio Finelli More articles by this author Girish Kulkarni More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Long-term (>8 years) evaluation of progression in patients with low-pressure glaucoma.

To describe the long-term clinical course of patients with low-pressure glaucoma (LPG) and to assess the risk factors for disease progression. The Wills Eye Glaucoma Research Center retrospectively reviewed the charts of LPG patients with documented follow-up of &gt;8 years between 2000 and 2013. Medical records were evaluated for systemic diseases, family history of glaucoma, best-corrected visual acuity, refractive error, treatments, central corneal thickness (CCT), intraocular pressure (IOP), IOP change after pupil dilation, optic disc evaluation, visual field (VF) mean deviation (MD), VF grading, and time to progression. Progression was determined when both disc and VF appeared to have worsened. From 850 charts classified as LPG between 2000 and 2013, 49 eyes of 49 patients were included in our analysis. The mean ( ± SD) follow-up time was 9.3 ( ± 1.9) years. Glaucoma progressed in 25 eyes and remained stable in 24 eyes over the follow-up period. Eyes with progression had higher peak IOP (p = 0.043). There was a trend towards progression in patients with thinner CCT (p = 0.085) and disc hemorrhage (p = 0.098). Estimated annual change in MD was -0.57 dB in the progressing group and -0.10 dB in the stable group (p&lt;0.0001). Nearly half of the patients with LPG showed glaucoma progression despite treatment after &gt;8 years. High peak IOP was a significant risk factor for progression. Identifying patients at risk may warrant closer follow-up and more aggressive treatment in order to preserve visual function in patients with LPG.