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The Paris System for urine cytology in upper tract urothelial specimens: A comparative analysis with biopsy and surgical resection

Zheng, X; Si, Q; Du, D; Harshan, M; Zhang, Z; Haines, K; Shi, W; Chhieng, D C
INTRODUCTION:The Paris System (TPS) has recently been used in classification of urinary tract cytological specimens. Upper urinary tract (UUT) specimens are cytologically challenging. The utility of TPS was investigated in evaluating UUT specimens and its correlation with subsequent histological follow-up. METHOD:From 2014 to 2017, 324 cytology cases of UUT from 179 patients were retrieved. Concurrent or subsequent biopsy or resection within a 2-month period was available in 125 cases from 74 patients. RESULT:None of the cases with a cytology of low-grade urothelial neoplasm was found to have a high-grade urothelial carcinoma (HGUC) on biopsy. Among the 19 atypical urothelial cells (AUC) cytology cases, the histology is heterogeneous (seven benign, one atypia, five low-grade lesion, and six HGUC). The risk of HGUC for each cytological diagnostic category are 0% for non-diagnostic/unsatisfactory, 6% for negative for HGUC, 27.3% for AUC, 0% for low-grade urothelial neoplasm, 48% for suspicious for HGUC and 95% for positive HGUC. When we considered cytology cases with suspicious or positive for HGUC interpretations as positive, the performance of TPS in predicting high grade urothelial carcinoma on histology had values of: 78.6% sensitivity, 86% specificity, 80.5% positive predictive value and 84.5% negative predictive value. CONCLUSION:More than one-third of the UUT cytological cases were classified as AUC and approximately 1/15 as suspicious or positive for HGUC. Based on UUT cytology specimens, the risk of malignancy of each cytological diagnostic category of TPS was comparable to those reported in the literature. The use of TPS in evaluating UUT cytology specimens was specific and sensitive in identifying patients with HGUC by histology.
PMID: 29251368
ISSN: 1365-2303
CID: 5515712

A randomized study of local anesthesia for pain control during intra-articular corticosteroid injection in children with arthritis

Weiss, Jennifer E; Haines, Kathleen A; Chalom, Elizabeth C; Li, Suzanne C; Walco, Gary A; Nyirenda, Themba L; Edelheit, Barbara; Kimura, Yukiko
BACKGROUND: Intra-articular corticosteroid injections (IACI) are routinely used by pediatric rheumatologists in the treatment of chronic arthritis. Frequently, topical anesthetics are used to control procedural pain, but their relative efficacy has not been reported. In this study, we evaluated the level of pain associated with different anesthetic methods, Numby(R) 900 Iontophoretic Drug Delivery System, or EMLA(R) cream, with or without subcutaneous buffered lidocaine (SQBL), during IACI of the knee in children with arthritis. METHODS: We conducted a prospective study of patients, ages 4 to 21 years old, followed at three pediatric rheumatology centers who were undergoing IACI of a knee joint. Patients were randomized into two treatment groups: 1) topical anesthetic only (EMLA(R) or Numby(R) (E/N)), or 2) topical anesthetic (E/N) and SQBL. Pain was assessed at baseline, during topical anesthetic placement, and following the IACI (post-procedure). The Faces Pain Scale-Revised (FPS-R), the Face, Leg, Activity, Cry, Consolability (FLACC) behavioral scale and the parental global assessment (PGA) (0 = best experience, 10 = worst experience) were determined. RESULTS: Sixty-three patients (44 females) with a median [IQR] age of 10.8 [IQR = (8.2-14.4)] years (range 4.7-20 years) with active knee arthritis were consented. FPS-R post-procedure (P = 0.03), FLACC (P = 0.02) and PGA (P = 0.01) scores were significantly lower in females treated with E/N plus SQBL compared to patients treated with E/N only. Females in the E/N only group had a significant worsening of their baseline pain (p < 0.0004) and a greater magnitude of change in their baseline FPS-R scores (p < 0.001) from the procedure compared to females in the E/N plus SQBL group who had no worsening of their baseline pain. No significant change in pain level or PGA score was found among males in either treatment group. Pain scores overall were similar to the oligoarthritis patients, a more homogeneous group of patients. Both EMLA(R) (n = 33) and Numby(R) (n = 29) were equally well tolerated with no significant difference in median FPS-R administration scores overall. CONCLUSION: Our results suggest that a topical anesthetic plus SQBL is more effective for injection pain control than topical anesthesia only. Further studies addressing pain and anxiety will help determine the optimal method of pain control for IACI.
PMCID:4550066
PMID: 26310855
ISSN: 1546-0096
CID: 1745662

Vitamin D deficiency is common and associated with increased C-reactive protein in children and young adults with lupus: an Atherosclerosis Prevention in Pediatric Lupus Erythematosus substudy

Robinson, Angela Byun; Tangpricha, Vin; Yow, Eric; Gurion, Reut; McComsey, Grace A; Schanberg, Laura E; Ardoin, Stacy; Dewitt, Esi Morgan; Rabinovich, C Egla; Ellis, Janet; Mieszkalski, Kelly; Wootton, Janet; Chira, Peter; Hsu, Joyce; Lee, Tzielan; Sandborg, Christy; Perea, Jan; Gottlieb, Beth; Irigoyen, Patricia; Luftig, Jennifer; Siddiqi, Shaz; Ni, Zhen; Orlando, Marilynn; Pagano, Eileen; Eichenfield, Andrew; Imundo, Lisa; Levy, Deborah; Kahn, Philip; Batres, Candido; Cabral, Digna; Haines, Kathleen A; Kimura, Yukiko; Li, Suzanne C; Weiss, Jennifer; Riordan, Mary Ellen; Vaidya, Beena; von Scheven, Emily; Mietus-Snyder, Michelle; Silverman, Earl; Ng, Lawrence; Bowyer, Suzanne; Ballinger, Susan; Klausmeier, Thomas; Hinchman, Debra; Hudgins, Andrea; Punaro, Marilynn; Henry, Shirley; Zhang, Shuzen; Singer, Nora G; Brooks, Elizabeth B; Miner, Stacy; Szabo, Nancy; Scalzi, Lisabeth; Sherry, David; Dorfeld, Libby; Wilson, Sarajane; Tress, Jenna; McCurdy, Deborah; Hernandez, Tatiana; Vitale, Jyotsna; Klein-Gitelman, Marisa; Kress, Angela; Lowe, Nicole; Patel, Falguni; Wallace, Carol; Hamilton, Stephanie; Silver, Richard; Caldwell, Katie; Kamen, Diane; Wagner-Weiner, Linda; Puplava, Becky; Lonchev, Atanas; Higgins, Gloria; Bacani, Monica; Brunner, Hermine; Rutherford, Cynthia; Meyers-Eaton, Jamie; Nelson, Shannen; Grom, Alexei; Jung, Larry; Conway, Teresa; Frank, Lacey; Kuss, Lori; Soep, Jenny; Senz, Hazel; Reed, Ann; Mason, Thomas; Jaquith, Jane; Paepke-Tollefsrud, Diana E
OBJECTIVE: Epidemiological associations suggest vitamin D may play a role in inflammation and atherosclerosis. Using frozen serum and data from the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we assessed associations between 25-hydroxyvitamin D [25(OH)D] and measures of systemic lupus erythematosus (SLE) disease activity and cardiovascular risk. METHODS: Baseline APPLE serum samples were used to measure 25(OH)D levels. Logistic regression models for vitamin D deficiency [25(OH)D levels <20 ng/mL] were constructed using baseline variables collected as part of the trial, including race, season, latitude, disease duration, disease activity, high-sensitivity C-reactive protein (hsCRP), proteinuria, fasting lipids and carotid intima medial thickness (CIMT). RESULTS: Samples were available from 201 of 221 APPLE subjects; 61/201 (30%) had vitamin D deficiency at baseline. In univariable analysis, baseline vitamin D deficiency was associated with season (p<0.01), minority status (p<0.01), body mass index (p=0.04), duration of SLE (p<0.01), SLICC damage index (p=0.04), hsCRP (p<0.01), mean-max CIMT (p=0.01), LDL-cholesterol (p=0.03) and timed urine protein (p=0.03). In multivariable modelling, vitamin D deficiency was associated with age, latitude, season, minority status, proteinuria and hsCRP. CONCLUSIONS: Vitamin D deficiency is common in paediatric lupus and is independently associated with elevated hsCRP, a marker of inflammation that predicts cardiovascular disease risk. Although association is not proof of causation, this association is novel in the paediatric SLE population and suggests that vitamin D deficiency may contribute to heightened inflammation and cardiovascular risk in this population. TRIAL REGISTER NUMBER: NCT00065806.
PMCID:4225734
PMID: 25396060
ISSN: 2053-8790
CID: 1349432

Vitamin D status is a determinant of atorvastatin effect on carotid intima medial thickening progression rate in children with lupus: an Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) substudy

Robinson, Angela Byun; Tangpricha, Vin; Yow, Eric; Gurion, Reut; Schanberg, Laura E; McComsey, Grace A; Ardoin, Stacy; Dewitt, Esi Morgan; Rabinovich, C Egla; Ellis, Janet; Mieszkalski, Kelly; Wootton, Janet; Chira, Peter; Hsu, Joyce; Lee, Tzielan; Sandborg, Christy; Perea, Jan; Gottlieb, Beth; Irigoyen, Patricia; Luftig, Jennifer; Siddiqi, Shaz; Ni, Zhen; Orlando, Marilynn; Pagano, Eileen; Eichenfield, Andrew; Imundo, Lisa; Levy, Deborah; Kahn, Philip; Batres, Candido; Cabral, Digna; Haines, Kathleen A; Kimura, Yukiko; Li, Suzanne C; Weiss, Jennifer; Riordan, Mary Ellen; Vaidya, Beena; von Scheven, Emily; Mietus-Snyder, Michelle; Silverman, Earl; Ng, Lawrence; Bowyer, Suzanne; Ballinger, Susan; Klausmeier, Thomas; Hinchman, Debra; Hudgins, Andrea; Punaro, Marilynn; Henry, Shirley; Zhang, Shuzen; Singer, Nora G; Brooks, Elizabeth B; Miner, Stacy; Szabo, Nancy; Scalzi, Lisabeth; Sherry, David; Dorfeld, Libby; Wilson, Sarajane; Tress, Jenna; McCurdy, Deborah; Hernandez, Tatiana; Vitale, Jyotsna; Klein-Gitelman, Marisa; Kress, Angela; Lowe, Nicole; Patel, Falguni; Wallace, Carol; Hamilton, Stephanie; Silver, Richard; Caldwell, Katie; Kamen, Diane; Wagner-Weiner, Linda; Puplava, Becky; Lonchev, Atanas; Higgins, Gloria; Bacani, Monica; Brunner, Hermine; Rutherford, Cynthia; Meyers-Eaton, Jamie; Nelson, Shannen; Grom, Alexei; Jung, Larry; Conway, Teresa; Frank, Lacey; Kuss, Lori; Soep, Jenny; Senz, Hazel; Reed, Ann; Mason, Thomas; Jaquith, Jane; Paepke-Tollefsrud, Diana E
OBJECTIVE: Epidemiological associations suggest that vitamin D status may play a role in inflammation and progression of atherosclerosis. Using frozen serum, carotid intima medial thickness (CIMT) measurements and other existing data from the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we assessed interactions between serum 25-hydroxyvitamin D (25(OH)D), atorvastatin randomisation and CIMT progression rate. METHODS: Participants in the 3-year APPLE trial were randomised to placebo or atorvastatin and CIMT progression rate was measured. Baseline frozen serum was used to measure 25(OH)D concentrations. Mixed effect longitudinal models for CIMT progression at 3 years were used to evaluate interaction between vitamin D deficiency (serum 25(OH)D <20 ng/mL) at baseline and atorvastatin or placebo treatment, adjusting for key systemic lupus erythematosus disease variables and cardiovascular risk factors. RESULTS: 201/221 APPLE participants had available samples and were included in this analysis; 61/201 (30%) had vitamin D deficiency at baseline. In adjusted longitudinal modelling, there was significant interaction between baseline vitamin D deficiency and atorvastatin randomisation in 3-year progression of mean-max CIMT. In four out of six carotid segments, there was a greater decrease in mean-max CIMT progression rate in subjects who were treated with atorvastatin compared with placebo if they had baseline serum 25(OH)D levels >/=20 ng/mL. CONCLUSIONS: Subjects with serum 25(OH)D >/=20 ng/mL had less mean-max CIMT progression following 3 years of atorvastatin treatment. Results from secondary analyses must be interpreted cautiously, but findings suggest that underlying vitamin D deficiency may be involved in response to atorvastatin in atherosclerosis prevention. TRIAL REGISTRATION NUMBER: NCT00065806.
PMCID:4225736
PMID: 25396067
ISSN: 2053-8790
CID: 1349442

Consensus Treatment Plans for Induction Therapy in Childhood Proliferative Lupus Nephritis-Status of Use in Daily Clinical Care [Meeting Abstract]

von Scheven, Emily; Punaro, Marilynn; Ardoin, Stacy P; Brunner, Hermine; Hsu, Joyce J; Mehta, Jay; Wagner-Weiner, Linda; Klein-Gitelman, Marisa; Stevens, Kelly Rouster; Haines, Kathleen A; Schanberg, Laura; Eberhard, BAnne
ISI:000349950900023
ISSN: 2326-5205
CID: 1882942

Cancer risk in childhood-onset systemic lupus

Bernatsky, Sasha; Clarke, Ann E; Labrecque, Jeremy; von Scheven, Emily; Schanberg, Laura E; Silverman, Earl D; Brunner, Hermine I; Haines, Kathleen A; Cron, Randy Q; O'Neil, Kathleen M; Oen, Kiem; Rosenberg, Alan M; Duffy, Ciaran M; Joseph, Lawrence; Lee, Jennifer L; Kale, Mruganka; Turnbull, Elizabeth M; Ramsey-Goldman, Rosalind
INTRODUCTION: The aim of this study was to assess cancer incidence in childhood-onset systemic lupus erythematosus (SLE). METHODS: We ascertained cancers within SLE registries at 10 pediatric centers. Subjects were linked to cancer registries for the observational interval, spanning 1974 to 2009. The ratio of observed to expected cancers represents the standardized incidence ratio (SIR) or relative cancer risk in childhood-onset SLE, versus the general population. RESULTS: There were 1020 patients aged <18 at cohort entry. Most (82%) were female and Caucasian; mean age at cohort entry was 12.6 years (standard deviation (SD) = 3.6). Subjects were observed for a total of 7,986 (average 7.8) patient-years. Within this interval, only three invasive cancers were expected. However, 14 invasive cancers occurred with an SIR of 4.7, 95% confidence interval (CI) 2.6 to 7.8. Three hematologic cancers were found (two non-Hodgkin's lymphoma, one leukemia), for an SIR of 5.2 (95% CI 1.1 to 15.2). The SIRs stratified by age group and sex, were similar across these strata. There was a trend for highest cancer occurrence 10 to 19 years after SLE diagnosis. CONCLUSIONS: These results suggest an increased cancer risk in pediatric onset SLE versus the general population. In absolute terms, this represents relatively few events. Of note, risk may be highest only after patients have transferred to adult care.
PMCID:3978586
PMID: 24267155
ISSN: 1478-6354
CID: 921242

Consensus treatments for moderate Juvenile Dermatomyositis: Beyond the first two months. Results of the Second Childhood Arthritis and Rheumatology Research Alliance Consensus Conference

Huber, Adam M; Robinson, Angela B; Reed, Ann M; Abramson, Leslie; Bout-Tabaku, Sharon; Carrasco, Ruy; Curran, Megan; Feldman, Brian M; Gewanter, Harry; Griffin, Thomas; Haines, Kathleen; Hoeltzel, Mark F; Isgro, Josephine; Kahn, Philip; Lang, Bianca; Lawler, Patti; Shaham, Bracha; Schmeling, Heinrike; Scuccimarri, Rosie; Shishov, Michael; Stringer, Elizabeth; Wohrley, Julie; Ilowite, Norman T; Wallace, Carol
OBJECTIVE: To use consensus methods and the considerable expertise contained within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) organization to extend the 3 previously developed treatment plans for moderate juvenile dermatomyositis (DM) to span the full course of treatment. METHODS: A consensus meeting was held in Chicago on April 23-24, 2010, involving 30 pediatric rheumatologists and 4 lay participants. Nominal group technique was used to achieve consensus on treatment plans that represented typical management of moderate juvenile DM. A preconference survey of CARRA, completed by 151 (56%) of 272 members, was used to provide additional guidance to the discussion. RESULTS: Consensus was reached on timing and rate of steroid tapering, duration of steroid therapy, and actions to be taken if patients were unchanged, worsening, or experiencing medication side effects or disease complications. Of particular importance, a single consensus steroid taper was developed. CONCLUSION: We were able to develop consensus treatment plans that describe therapy for moderate juvenile DM throughout the treatment course. These treatment plans can now be used clinically, and data collected prospectively regarding treatment effectiveness and toxicity. This will allow comparison of these treatment plans and facilitate the development of evidence-based treatment recommendations for moderate juvenile DM.
PMCID:3315594
PMID: 22076847
ISSN: 2151-464x
CID: 164402

Treatment of pediatric localized scleroderma: results of a survey of North American pediatric rheumatologists

Li, Suzanne C; Feldman, Brian M; Higgins, Gloria C; Haines, Kathleen A; Punaro, Marilynn G; O'Neil, Kathleen M
OBJECTIVE: We surveyed pediatric rheumatologists (PR) in North America to learn how they treat pediatric localized scleroderma (LS), a disease associated with significant morbidity for the growing child. METHODS: A Web-based survey was sent to the 195 PR members of the pediatric rheumatology research alliance CARRA (Childhood Arthritis and Rheumatology Research Alliance). Members were asked which medications they use to treat LS and which factors modify their treatment strategies. Clinical vignettes were provided to learn the specific treatment regimens used. RESULTS: A total of 158 PR from over 70 clinical centers in the United States and Canada participated in the survey, representing 81% of the CARRA membership. These PR saw over 650 patients with LS in the prior year. Nearly all respondents treated LS with methotrexate (MTX) and corticosteroids; most of them intensify treatment for lesions located on the face or near a joint, and about half intensify treatment for recent disease onset (< 6 months). Most PR reserve topical medications for limited treatment situations. Clinical vignettes showed that PR use a broad range of treatment doses and durations for MTX and corticosteroids. CONCLUSION: Most PR in North America treat localized scleroderma with a combination of MTX and corticosteroids. However, there is no consensus on specific treatment regimens. There is a need for controlled treatment trials to better determine optimal therapy for this potentially disabling disease.
PMID: 19918041
ISSN: 0315-162x
CID: 921232

Neutrophil gelatinase-associated lipocalin is a predictor of the course of global and renal childhood-onset systemic lupus erythematosus disease activity

Hinze, Claas H; Suzuki, Michiko; Klein-Gitelman, Marisa; Passo, Murray H; Olson, Judyann; Singer, Nora G; Haines, Kathleen A; Onel, Karen; O'Neil, Kathleen; Silverman, Earl D; Tucker, Lori; Ying, Jun; Devarajan, Prasad; Brunner, Hermine I
OBJECTIVE: To determine whether neutrophil gelatinase-associated lipocalin (NGAL) can predict worsening of global and renal disease activity in childhood-onset systemic lupus erythematosus (SLE). METHODS: One hundred eleven patients with childhood-onset SLE were enrolled in a longitudinal, prospective study with quarterly study visits and had at least 3 study visits. At each visit, global disease activity was measured using 3 external standards: the numerically converted British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index 2000 update score, and the physician's assessment of global disease activity. Renal and extrarenal disease activity were measured by the respective domain scores. The disease course over time was categorized at the most recent visit (persistently active, persistently inactive, improved, or worsening). Plasma and urinary NGAL levels were measured by enzyme-linked immunosorbent assay, and urinary NGAL levels were standardized to the urinary creatinine concentration. The longitudinal changes in NGAL levels were compared with the changes in SLE disease activity using mixed-effect models. RESULTS: Significant increases in standardized urinary NGAL levels of up to 104% were detected up to 3 months before worsening of lupus nephritis (as measured by all 3 external standards). Plasma NGAL levels increased significantly by as much as 26% up to 3 months before worsening of global SLE disease activity as measured by all 3 external standards. Plasma NGAL levels increased significantly by 26% as early as 3 months prior to worsening of lupus nephritis as measured by the BILAG renal score. CONCLUSION: Serial measurement of urinary and plasma NGAL levels may be valuable in predicting impending worsening of global and renal childhood-onset SLE disease activity.
PMCID:3064260
PMID: 19714584
ISSN: 0004-3591
CID: 921222

Neutrophil gelatinase-associated lipocalin as a biomarker of disease activity in pediatric lupus nephritis

Suzuki, Michiko; Wiers, Kristina M; Klein-Gitelman, Marisa S; Haines, Kathleen A; Olson, Judyann; Onel, Karen B; O'Neil, Kathleen; Passo, Murray H; Singer, Nora G; Tucker, Lori; Ying, Jun; Devarajan, Prasad; Brunner, Hermine I
We hypothesized that neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of disease activity in lupus nephritis. NGAL in serial plasma (PNGAL) and urine (UNGAL) samples was measured by enzyme-linked immunosorbent assay (ELISA) in 85 participants with pediatric systemic lupus erythematosus (pSLE), healthy children (n = 50), and children with juvenile idiopathic arthritis (JIA) (n = 30). Disease activity was measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Plasma and urinary NGAL were significantly increased in subjects with pSLE compared with those with JIA or with healthy controls (all p < 0.03), and unrelated to subjects' age, weight, or height. Plasma and urinary NGAL were stable in pSLE subjects with unchanged disease activity. The pSLE subjects with worsening global or renal disease activity had a mean +/- standard error (SE) increase of UNGAL (in ng/ml) of 11.5 +/- 6.4 or 36.6 +/- 12.1 (p < 0.01), corresponding to a 156% or 380% increase, respectively. PNGAL increased with worsening disease but to a much lesser degree than UNGAL [global disease activity (mean +/- SE): 7.3 +/- 6.2 or 21%; renal disease activity: 20.2 +/- 6.0 or 51%; both p = not significant]. In conclusion, NGAL in urine but not in plasma represents a novel biomarker for renal disease activity in pSLE
PMID: 18202859
ISSN: 0931-041x
CID: 96584