P122 SEX DIFFERENCES IN STATURAL GROWTH IMPAIRMENT IN PEDIATRIC CROHN’S DISEASE: EARLY FINDINGS FROM THE GROWTH STUDY

Abstract Background Statural growth impairment is both a marker and complication of poorly controlled Crohn’s disease (CD), and occurs more commonly in males than females. The specific molecular mechanisms responsible for this sex difference in growth impairment in CD remain poorly characterized. Methods We are conducting a prospective multicenter longitudinal study (Growth Study) examining sex differences in statural growth impairment in school-age children with CD with growth potential based on bone age (BA) [females (BA 4 yrs, 2 mos to 12 years, 0 months) and males (BA 5 years, 0 months to 14 yrs, 0 mos)]. We have enrolled 118 (65% male) patients. Variable Z scores calculated based on BA are denoted as Variable BA-Z scores; those calculated based on chronological age (CA) are denoted as Variable CA-Z scores. Height Z score difference was calculated as Height CA-Z score minus Height BA-Z score. We analyzed the concentration of selected cytokines in serum in 54 patients (56% male), using a V-Plex kit (Meso Scale Discovery, Rockville, MD). Serum hormone levels were analyzed at Esoterix Endocrinology (Calabasas Hills, CA). We used t-test and Chi-squared test to examine the sex difference for continuous variables and categorical variables respectively. We assessed the association between cytokines and hormones via linear regression. Results The mean height Z score difference was -0.4 ± 1.0 (SD) [range: -3.9 to 2.0] in males and -1.1 ± 1.1 [-3.9 to 0.9] in females (Figure). The absolute value of the mean height Z score difference was significantly lower in males (P= 0.021). The mean BA Z score was (0.0 ± .04 [-0.7 to 0.9]) in males and (0.0 ± 0.2 [-0.4 to 0.5]) in females (P= 0.952). Race/ethnicity [76% White], Tanner stage [63% pre/early puberty; 37% mid/late puberty], mean disease duration [2.3 ± 1.9 (SD) (range: 0.1 to 8.3) years], medication use [65% infliximab; 39% methotrexate; 13% azathioprine/6-mercaptopurine; 9% adalimumab], and mean disease activity indices (indicated remission) did not differ by sex (P= NS for all). TNF-α, IL-4, IL-6, IL-10, and IL-12 were significantly negatively associated with hormones important in growth in males, while IL-13 was significantly negatively associated with hormones important in growth in females (Table). Conclusions Statural growth remains compromised in males compared with females in a novel contemporary cohort of children with CD. Our early data suggest that the higher frequency of growth impairment in males appears to be due to less standardized height gain with skeletal maturation, rather than advanced BA progression. BA does not appear to be significantly delayed in this cohort. Furthermore, our preliminary data suggest that systemic inflammation exerts a greater negative impact on hormone levels important in growth in males, and that different molecular pathways lead to growth impairment in males versus females. We are further investigating these preliminary findings in the ongoing prospective multicenter longitudinal Growth Study.

Download Full-text

Introduction to and Screening Visit Results of the Multicenter Pediatric Crohn’s Disease Growth Study

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa023 ◽

2020 ◽

Vol 26 (12) ◽

pp. 1945-1950 ◽

Cited By ~ 2

Author(s):

Neera Gupta ◽

Robert H Lustig ◽

Howard Andrews ◽

Francisco Sylvester ◽

David Keljo ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Bone Age ◽

Skeletal Maturation ◽

Delayed Puberty ◽

Z Score ◽

Growth Study ◽

Score Difference ◽

Z Scores ◽

The Mean

Abstract Background Statural growth impairment is more common in males with Crohn’s disease (CD). We assessed sex differences in height Z score differences and bone age (BA) Z scores and characterized age of menarche in a novel contemporary cohort of pediatric CD patients undergoing screening for enrollment in the multicenter longitudinal Growth Study. Methods Crohn’s disease patients (females with chronological age [CA] 5 years and older and younger than 14 years; males with CA 6 years and older and younger than 16 years) participated in a screening visit for the Growth Study. Height BA-Z scores are height Z scores calculated based on BA. Height CA-Z scores are height Z scores calculated based on CA. The height Z score difference equals height CA-Z score minus height BA-Z score. Results One hundred seventy-one patients (60% male) qualified for this analysis. Mean CA was 12.2 years. Mean height CA-Z score was −0.4, and mean height BA-Z score was 0.4 in females. Mean height CA-Z score was −0.1, and mean height BA-Z score was 0.2 in males. The absolute value of the mean height Z score difference was significantly greater in females (0.8) than males (0.3; P = 0.005). The mean BA-Z score in females (−1.0) was significantly lower than in males (−0.2; P = 0.002). The median CA at menarche was 13.6 (95% CI, 12.6–14.6) years. Conclusions Our screening visit data suggest that standardized height gain is lower in males with skeletal maturation and delayed puberty is common in females in CD. We are investigating these findings in the ongoing Growth Study.

Download Full-text

Clinical Variables Associated With Statural Growth in Pediatric Crohn’s Disease Differ by Sex (The Growth Study)

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa220 ◽

2020 ◽

Author(s):

Neera Gupta ◽

Robert H Lustig ◽

Howard Andrews ◽

Ranjana Gokhale ◽

Alka Goyal ◽

...

Keyword(s):

Symptom Onset ◽

Z Score ◽

Growth Study ◽

Growth Impairment ◽

Clinical Variables ◽

Female Patients ◽

Height Gain ◽

Male Patients ◽

The Mean ◽

Initial Classification

Abstract Background Statural growth impairment is more common in male patients with Crohn’s disease (CD). We identified clinical variables associated with height z score differences by sex in children participating in the Growth Study, a prospective multicenter longitudinal study examining sex differences in growth impairment in pediatric CD. Methods Patients with CD (female patients with bone age [BA] ≥4 years 2 months and ≤12 years; male patients with BA ≥5 years and ≤14 years at screening) who had completed study visit 1 qualified. The height z score difference was computed as height z score based on chronological age minus height z score based on BA. Results One hundred thirteen patients with CD (36% female) qualified. The mean chronological age was 12.0 ± 1.8 (SD) years. The magnitude of the mean height z score difference was significantly greater in female patients (–0.9 ± 0.8) than in male patients (–0.5 ± 0.9; P = 0.021). An initial classification of inflammatory bowel disease as CD (P = 0.038) and perianal disease behavior at diagnosis (P = 0.009) were associated with higher standardized height gain with BA progression, and arthralgia at symptom onset (P = 0.016), azathioprine/6-merpcaptopurine (P = 0.041), and probiotics (P ≤ 0.021) were associated with lower standardized height gain with BA progression in female patients. Patient-reported poor growth at symptom onset (P = 0.001), infliximab (P ≤ 0.025), biologics (P ≤ 0.015), methotrexate (P = 0.042), and vitamin D (P ≤ 0.010) were associated with higher standardized height gain with BA progression, and initial classification as CD (P = 0.025) and anorexia (P = 0.005) or mouth sores (P = 0.004) at symptom onset were associated with lower standardized height gain with BA progression in male patients. Conclusions Different clinical variables were associated with statural growth in male patients vs female patients, suggesting that sex-specific molecular pathways lead to statural growth impairment in CD.

Download Full-text

Mo1899 SEX DIFFERENCES IN STATURAL GROWTH IMPAIRMENT IN PEDIATRIC CROHN'S DISEASE: EARLY FINDINGS GROM THE GROWTH STUDY

Gastroenterology ◽

10.1016/s0016-5085(20)33096-1 ◽

2020 ◽

Vol 158 (6) ◽

pp. S-969-S-970

Author(s):

Neera Gupta ◽

Robert Lustig ◽

Howard F. Andrews ◽

Francisco Sylvester ◽

David J. Keljo ◽

...

Keyword(s):

Sex Differences ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Growth Study ◽

Growth Impairment

Download Full-text

Trials of the Automated Particle Counter for laboratory rearing of mosquito larvae

PLoS ONE ◽

10.1371/journal.pone.0241492 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0241492

Author(s):

Mark Q. Benedict ◽

Priscila Bascuñán ◽

Catherine M. Hunt ◽

Erica I. Aviles ◽

Rachel D. Rotenberry ◽

...

Keyword(s):

Light Intensity ◽

Z Score ◽

Target Number ◽

Water Stream ◽

Throughput Rate ◽

Laboratory Rearing ◽

Particle Counter ◽

Type Device ◽

Z Scores ◽

The Mean

As a means of obtaining reproducible and accurate numbers of larvae for laboratory rearing, we tested a large-particle flow-cytometer type device called the ‘Automated Particle Counter’ (APC). The APC is a gravity-fed, self-contained unit that detects changes in light intensity caused by larvae passing the detector in a water stream and controls dispensing by stopping the flow when the desired number has been reached. We determined the accuracy (number dispensed compared to the target value) and precision (distribution of number dispensed) of dispensing at a variety of counting sensitivity thresholds and larva throughput rates (larvae per second) using < 1-day old Anopheles gambiae and Aedes aegypti larvae. All measures were made using an APC algorithm called the ‘Smoothed Z-Score’ which allows the user to define how many standard deviations (Z scores) from the baseline light intensity a particle’s absorbance must exceed to register a count. We dispensed a target number of 100 An. gambiae larvae using Z scores from 2.5–8 and observed no difference among them in the numbers dispensed for scores from 2.5–6, however, scores of 7 and 8 under-counted (over-dispensed) larvae. Using a Z score ≤ 6, we determined the effect of throughput rate on the accuracy of the device to dispense An. gambiae larvae. For rates ≤ 98 larvae per second, the accuracy of dispensing a target of 100 larvae was - 2.29% ± 0.72 (95% CI of the mean) with a mode of 99 (49 of 348 samples). When using a Z score of 3.5 and rates ≤ 100 larvae per second, the accuracy of dispensing a target of 100 Ae. aegypti was - 2.43% ± 1.26 (95% CI of the mean) with a mode of 100 (6 of 42 samples). No effect on survival was observed on the number of An. gambiae first stage larvae that reached adulthood as a function of dispensing.

Download Full-text

Bone Mineral Density in Transfusion Independent Thalassemia Patients.

Blood ◽

10.1182/blood.v108.11.3353.3353 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3353-3353

Author(s):

Zahra Pakbaz ◽

Zhe Zhang ◽

Ellen Fung ◽

Nancy Sweeters ◽

Sylvia Singer ◽

...

Keyword(s):

Bone Mineral Density ◽

Family History ◽

Bone Mineral ◽

Z Score ◽

Low Bone Mass ◽

Mineral Density ◽

Patients Âgés ◽

Z Scores ◽

History Of ◽

The Mean

Abstract Low bone mineral density (BMD) is commonly seen in regularly transfused thalassemia patients; however, there have been few reports for bone mineral density assessment in transfusion independent thalassemia patients. The present report includes the results of BMD assessments in patients with transfusion independent thalassemia who were referred to the bone density clinic through 2002–2006. BMD was evaluated by dual energy x-ray absorptiometry (DXA, Hologic Delphi A). A convenience sample of 24 patients (Females=15) with transfusion independent thalassemia were measured with a mean age of 22.1 ± 13.8 years. Subjects younger than 10 yrs old (n = 7) underwent scans for Lumbar spine (LS; L1-L4) and whole body (WB), patients ages 10–20 (n = 5) were assessed for LS, WB, and non-dominant hip, and for patients older than 20 (n = 12), LS and hip scans were completed. Z-scores specific for age and gender were generated using Zemel BS et al.(J. Bone Min Res 2004) database. Z-scores less than −2.0 were considered as low bone density. Calcium intake was assessed by a brief food frequency questionnaire. Past medical history, medications, history of fractures, and family history of osteoporosis were obtained by chart review and patient interview. Data is presented as Mean ± SD. T-test was used to assess differences in continuous variables. The mean LS Z-score (n = 24) was −1.5 ± 1.0 and the mean hip Z-score (n = 17) was −0.5 ± 1.1. Mean WB Z-score (n = 10) was −2.0 ± 1.2. There was a significant (p<0.001) difference between spine and hip Z-scores. Overall 46% had a Z-score less than −2.0. Thirty-three percent of patients have spine Z-scores of less than −2.0 and 25% spine Z-scores between −2.0 and −1.0. Average spine Z-score in patients younger than 10 years old (n=7) was −1.6 ± 0.5. In WB scans, 50% of the patients had WB Z-scores worse than −2.0. None of the young patients (5–9 yrs; n = 7) consumed inadequate intake of calcium (< 2/3 of RDA age specific) while 75% of patients ages 10–20 (n = 4) years old consumed inadequate intake of calcium (dietary + supplement). Neither spine nor hip Z-score was related to patients’ gender, age, and calcium intake. Two patients reported fractures in the past and two reported family history of osteoporosis. Six patients had delayed puberty and one has hypogonadism. Seven patients have short stature. This data suggests that low bone mass is not only a problem in transfused thalassemia patients, but is also observed in non-transfused patients. The significance and pathophysiology of low bone mass should be studied further in non-transfused patient population, especially in younger children.

Download Full-text

152 Sex Differences in IGF-1 Z Scores May Contribute to Sex Differences in Growth Impairment in Pediatric Patients With Crohn's Disease (CD)

Gastroenterology ◽

10.1016/s0016-5085(10)60135-7 ◽

2010 ◽

Vol 138 (5) ◽

pp. S-29

Author(s):

Neera Gupta ◽

Robert H. Lustig ◽

Michael Kohn ◽

Marjorie F. McCracken ◽

Eric Vittinghoff

Keyword(s):

Sex Differences ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Pediatric Patients ◽

Growth Impairment ◽

Z Scores

Download Full-text

Telomere Length in Inherited Bone Marrow Failure Syndromes

Blood ◽

10.1182/blood.v124.21.1609.1609 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1609-1609

Author(s):

Blanche P. Alter ◽

Neelam Giri ◽

Sharon A Savage ◽

Philip S. Rosenberg

Keyword(s):

Bone Marrow ◽

T Cells ◽

Bone Marrow Failure ◽

Canonical Variate ◽

Dna Repeats ◽

Z Score ◽

Essentially Normal ◽

Bone Marrow Failure Syndromes ◽

Z Scores ◽

The Mean

Abstract Background: Telomeres are short DNA repeats and a protein complex at chromosome ends that are essential for genome integrity. Telomeres are very short in patients with dyskeratosis congenita (DC) due to germline mutations in telomere biology genes. Telomere lengths (TL) were reported to be “short” in a few small studies of patients with other inherited bone marrow failure syndromes (IBMFS), specifically Fanconi anemia (FA), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS), although their relation to the very short TL seen in DC was not clear, and various analytic methods were used. Objectives: 1) To compare TL in a cohort of patients with FA, DBA, and SDS, with TL in DC. 2) To determine whether any individuals with non-DC IBMFS had TL as short as in DC. Methods: Blood was obtained from 100 patients with DC, 30 FA, 34 DBA, and 14 SDS enrolled in the NCI IBMFS Cohort Study. TL was measured by flow cytometry with fluorescence in situ hybridization (flow-FISH) in 6 leukocyte subsets: granulocytes, total lymphocytes, CD45RA-positive/CD20-negative naïve T cells, CD45RA-negative memory T cells, CD20-positive B cells, and CD57-positive NK/NKT cells. “Very short” TL was below the 1st percentile for age (defined by 400 normal controls). The diagnosis of DC required very short TL in 3 of 4 lymphocyte lineages including total lymphocytes. Z-scores were used to adjust for age; a Z-score of -2.3 equals the 1st percentile. Canonical Variate Analysis (CVA) including all 6 Z-score measurements was used for group comparisons and outlier identification. Results: Two patients with FA and 1 each with DBA and SDS had TL slightly below the 1st percentile in 3 or more lymphocyte lineages. In univariate analysis, the mean of the DC TL Z-scores was approximately -4, versus approximately -0.5 in FA, DBA, and SDS. Most individual DC Z-score measurements were well below -2.3, and all were below zero (the mean for the control data). Seventy percent of the FA, DBA and SDS lymphocyte TL Z-scores clustered in the bottom half of the normal range (i.e. -2.3 to 0, p <0.001), compared with the expected 50% if the non-DC patients had essentially normal TLs. In addition, short lymphocyte TL correlated with severity of marrow failure in DC; there was a non-significant trend in FA and no trend in DBA or SDS. Further refinement of interpretation utilized the CVA analysis. The first canonical variate captured 89.7% of the total variance, and separated DC widely from the other three IBMFS. The second canonical variate captured 10% of the variance, and separated DBA, FA, and SDS. In the CVA analysis, only 2 patients with FA and 1 each with DBA and SDS had results closer to the mean for DC patients than to the mean for their own disorder. Conclusions: Only 5% of individuals with FA, DBA, or SDS had TL in the DC range, and thus non-DC IBMFS in general do not have “very short” TL. However, 70% of non-DC IBMFS patients did have average TLs below the average for normal individuals. Thus disorders of DNA repair or ribosome biogenesis may result in TL changes, but the deficit in TL is not nearly as extreme as in DC itself. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Subgroup Analysis of Sex Difference on the Vandenberg-Kuse Mental Rotation Test

Perceptual and Motor Skills ◽

10.2466/pms.2003.96.1.197 ◽

2003 ◽

Vol 96 (1) ◽

pp. 197-200 ◽

Cited By ~ 6

Author(s):

Kázmér Karádi ◽

Árpád Csathó ◽

Beatrix Kovács ◽

Péter Kosztolányi

Keyword(s):

Sex Differences ◽

Mental Rotation ◽

Sex Difference ◽

Spatial Ability ◽

Subgroup Analysis ◽

Mental Rotation Test ◽

Men And Women ◽

Large Sample ◽

Rotation Test ◽

The Mean

A large sex difference has been elicited on the Vandenberg-Kuse mental rotation test. Prior research emphasizes the biological root of this sex difference. In recent experiments we confirmed this viewpoint. A large sample was administered the test, and the distributions of scores for men and women ( N = 138; 68 men and 70 women; ages 19 to 23 years). The mean scores were used as cut-off points to group the men and the women in different subgroups (Low/Women, High/Women, Low/Men, High/Men). There were large differences among all subgroups, reinforcing Kimura's testosterone hypothesis for sex differences in spatial ability.

Download Full-text

P122 SEX DIFFERENCES IN STATURAL GROWTH IMPAIRMENT IN PEDIATRIC CROHN'S DISEASE: EARLY FINDINGS FROM THE GROWTH STUDY

Gastroenterology ◽

10.1053/j.gastro.2019.11.188 ◽

2020 ◽

Vol 158 (3) ◽

pp. S74

Author(s):

Neera Gupta ◽

Robert Lustig ◽

Howard Andrews ◽

Francisco Sylvester ◽

David Keljo ◽

...

Keyword(s):

Sex Differences ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Growth Study ◽

Growth Impairment

Download Full-text

Changes in bone mineral density over 10 years in patients with early rheumatoid arthritis

RMD Open ◽

10.1136/rmdopen-2019-001142 ◽

2020 ◽

Vol 6 (1) ◽

pp. e001142

Author(s):

Lisa Theander ◽

Minna Willim ◽

Jan Åke Nilsson ◽

Magnus Karlsson ◽

Kristina E Åkesson ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Bone Mineral Density ◽

Lumbar Spine ◽

Femoral Neck ◽

Z Score ◽

Mineral Density ◽

Early Ra ◽

Z Scores ◽

The Mean

ObjectivesTo investigate changes in bone mineral density (BMD) in patients with early rheumatoid arthritis (RA) over a 10-year period.MethodsConsecutive patients with early RA (symptom duration <12 months) were followed according to a structured programme and examined with dual-energy X-ray absorptiometry (DXA) at inclusion and after 2, 5 and 10 years. Mean Z-scores over the study period were estimated using mixed linear effect models. Changes in Z-scores between follow-up visits were analysed using paired T-tests.ResultsAt inclusion, 220 patients were examined with DXA. At the femoral neck, the mean Z-score over 10 years was −0.33 (95 % CI −0.57 to −0.08) in men and −0.07 (−0.22 to 0.08) in women. Men had significantly lower BMD at the femoral neck than expected by age at inclusion (intercept Z-score value −0.35; 95 % CI −0.61 to −0.09), whereas there was no such difference in women. At the lumbar spine, the mean Z-score over the study period for men was −0.05 (−0.29 to 0.19) and for women 0.06 (−0.10 to 0.21). In paired comparisons of BMD at different follow-up visits, femoral neck Z-scores for men decreased significantly from inclusion to the 5-year follow-up. After 5 years, no further reduction was seen.ConclusionsIn this observational study of a limited sample, men with early RA had reduced femoral neck BMD at diagnosis, with a further significant but marginal decline during the first 5 years. Lumbar spine BMD Z-scores were not reduced in men or women with early RA. Data on 10-year follow-up were limited.

Download Full-text