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51


Lipoprotein(a): a Case for Universal Screening in Youth

Alankar, Aparna; Brar, Preneet C; Kohn, Brenda
PURPOSE OF REVIEW/OBJECTIVE:Lipoprotein(a) has emerged as a strong independent risk factor for cardiovascular disease. Targeted screening recommendations for Lp(a) measurement exist for adults and youth known to be at high-risk. However, Lp(a) measurements are not included in universal screening guidelines in the US; hence, most families in the US with high Lp(a) levels who are at risk of future atherosclerotic heart disease, stroke, or aortic stenosis are not recognized. Lp(a) measurement included as part of routine universal lipid screening in youth would identify those children at risk of ASCVD and enable family cascade screening with identification and early intervention for affected family members. RECENT FINDINGS/RESULTS:Lp(a) levels can be reliably measured in children as young as two years of age. Lp(a) levels are genetically determined. The Lp(a) gene is inherited in a co-dominant fashion. Serum Lp(a) attains adult levels by two years of age and is stable for the lifetime of the individual. Novel therapies that aim to specifically target Lp(a) are in the pipeline, including nucleic acid-based molecules such as antisense oligonucleotides and siRNAs. Inclusion of a single Lp(a) measurement performed as part of routine universal lipid screening in youth (ages 9-11; or at ages 17-21) is feasible and cost effective. Lp(a) screening would identify youth at-risk of ASCVD and enable family cascade screening with identification and early intervention for affected family members.
PMID: 37405555
ISSN: 1534-6242
CID: 5539212

Can Surrogate Markers Help Define Cardiovascular Disease in Youth?

Brar, Preneet Cheema
PURPOSE OF REVIEW:Non-invasive measurements such as arterial stiffness serve as proxy surrogates for detection of early atherosclerosis and ASCVD risk stratification. These surrogate measurements are influenced by age, gender, and ethnicity and affected by the physiological changes of puberty and somatic growth in children and adolescents. RECENT FINDINGS:There is no consensus of the ideal method to measure surrogate markers in youth (< 18 years of age), nor standardized imaging protocols for youth. Currently, pediatric normative data are available but not generalizable. In this review, we provide rationale on how currently used surrogates can help identify subclinical atherosclerosis in youth and affirm their role in identifying youth at risk for premature CVD.
PMID: 37148462
ISSN: 1534-6242
CID: 5545042

Update on management of paediatric dyslipidaemia

Bansal, Nidhi; Kumar, Seema; Brar, Preneet Cheema
PURPOSE OF REVIEW/OBJECTIVE:Atherosclerosis and associated cardiovascular risk factors originate in childhood; hence, early management of dyslipidaemia is vital. However, hypercholesterolemia remains untreated or undertreated in many youths. We review current therapies, drugs under investigation and consider potential future directions for the management of paediatric dyslipidaemia to highlight the recent evidence and new therapeutic options for future use. RECENT FINDINGS/RESULTS:Cardiovascular disease (CVD) risk factors in childhood, including dyslipidaemia, are associated with CVD risk and clinical CVD events in adulthood. Recent data show that initiation of statin therapy in childhood in children with familial hypercholesterolemia reduces the risk of CVD in adulthood. Several well tolerated and efficacious treatment options have become available in recent times for the management of dyslipidaemia in youth. Many new lipid-lowering drugs are under investigation to widen the available choices. Some of these drugs are now available for use in paediatrics, while some remain targets for future use. SUMMARY/CONCLUSIONS:We review available treatment options for paediatric dyslipidaemia management, discuss potential limitations and propose future directions. We also acknowledge the need for continued research in paediatrics for optimal paediatric dyslipidaemia management.
PMID: 36541082
ISSN: 1752-2978
CID: 5394662

Visceral adiposity is related to insulin sensitivity and inflammation in adolescents with obesity and mild sleep disordered breathing

Vajravelu, Mary Ellen; Kindler, Joseph M; Zemel, Babette S; Jawad, Abbas; Koren, Dorit; Brar, Preneet; Brooks, Lee J; Reiner, Jessica; Levitt Katz, Lorraine E
OBJECTIVES/OBJECTIVE:To evaluate the relationships between adipose tissue distribution, insulin secretion and sensitivity, sleep-disordered breathing, and inflammation in obese adolescents. METHODS:; non-REM sleep duration), and inflammation (high-sensitivity C-reactive protein, hsCRP). RESULTS:Subjects (55% female) were mean (SD) 14.4 (2.1) years, with BMI Z-score of 2.3 (0.4). AHI was >5 in 10 (18%) subjects and 1< AHI ≤5 in 22 (39%). Visceral adipose tissue area (VAT) was positively correlated with OGTT 1 and 2 h insulin and 1 h glucose, and hsCRP (r=0.3-0.5, p≤0.007 for each). VAT was negatively correlated with sensitivity to insulin (r=-0.4, p=0.005) and SpO2 nadir (r=-0.3, p=0.04) but not with other sleep measures. After adjustment for BMI-Z, sex, population ancestry, age, and sleep measures, VAT remained independently associated with insulin measures and 1 h glucose, but no other measures of glycemia. SAT was not associated with measures of glycemia or insulin resistance. CONCLUSIONS:Among adolescents with obesity, visceral adiposity was associated with insulin resistance, SpO2 nadir, and inflammation. The independent association of visceral adiposity with insulin resistance highlights the potential role of VAT in obesity-related chronic disease.
PMID: 35822712
ISSN: 2191-0251
CID: 5279882

Impact of Environmental and Psychosocial stressors on Precocious Puberty seen in Girls during the COVID-19 Pandemic [Meeting Abstract]

Baby, M; Ilkowitz, J; Joseph, V; Gonzalez, J; Brar, P
Objectives The COVID-19 pandemic caused stress, social isolation and physical inactivity in many. We proposed to review anthropometric/biochemical profiles in girls seen for precocious puberty (PP) (ages 5-8 years) during the pandemic (3/2020- 3/2021) compared to girls seen in the prior 2 years (2/2018-2/2020) and look at environmental and psychosocial impacts. Methods A retrospective chart review of the girls prepandemic (Pre-PD) were compared to those seen during the pandemic (PD). Criteria for PP: luteinizing hormone (LH range: 0.02-0.3 mIU/L, ECLIA, Esoterix) with >0.3 defined as pubertal; estradiol (range <36 pg/ml for age 7-9 years, LCMS, ARUP) with >=36.0 pg/ml defined as pubertal; follicle stimulating level (FSH 0.4- 6.5 IU/L ECLIA, ARUP). Girls with isolated adrenarche were excluded. Pelvic ultrasound with ovarian volumes (OVs>1cc considered pubertal) and MRI pituitary were done as indicated. Bone age/chronological age ratio (BA/CA) >1 was considered advanced. A Covid-19 impact survey was sent via a HIPAA compliant REDCap link to assess activity, sleep, and psychosocial stressors, distress on 0-10 scale (mild 0-4, moderate 5-7, severe 8-10) to families. T-tests and bivariate correlations were run (SPSS Ver 21). Results In total 56 subjects were included (pre-PD=23 vs. PD=33). A 30% increase in puberty referrals was noted during the pandemic. Weight (mean+ SD: Pre-PD vs. PD: 26.8+/-5 vs. 26.9+/-5.7 kg) and BMI (17.3+/-2.3 vs.16.8+/-2.3kg/m2). Estradiol (9.7+/-7.5 vs.21.9+/-16.6 pg/ml; p-value =0.006), random LH (1 vs. 15) were pubertal. OVs (1.75+/-1.1 vs. 2.75 cc) and BA/CA (1.1+/- 0.4 vs. 1.0+/-0.5) were seen in the two groups respectively. There was a correlation between estradiol levels and OVs in PD group (r= 0.5; p=.05). Survey results showed 61% of subjects used remote learning, 55% spent >4 hours on social media (Tik Tok, WhatsApp, etc.), 50% reported no exercise and 33% reported no social interaction. Stress was moderate with a parental report of 5.4/10, (50%essential workers, 18% lost jobs) & children reported stress level of 4.8/10. Conclusions We report an increased incidence of PP during the pandemic (perhaps due to a delay in evaluation) and a more advanced puberty (higher estradiol levels and greater OVs) compared to Pre-PD patients. Though weight gain, potentially due to inactivity, did not appear to contribute, we believe that stress, excessive social media use and/or isolation could be factors which contributed to the increased incidence of PP during the pandemic
EMBASE:640122390
ISSN: 1663-2826
CID: 5510092

Genotype - phenotype correlation in an adolescent girl with pathogenic PPARy genetic variation that caused severe hypertriglyceridemia and early onset type 2 diabetes [Case Report]

Gutierrez Alvarez, Ana; Yachelevich, Naomi; Kohn, Brenda; Brar, Preneet Cheema
Severe hypertriglyceridemia (HTG) (>885 mg/dL) can be caused by familial partial lipodystrophy type 3 (FPLD3), an autosomal dominant disorder caused by loss of function of the peroxisome proliferator-activated receptor gamma (PPARG), characterized by abnormal distribution of fat and metabolic derangements. This case reports a 16-year-old female (body mass index, 23.5 kg/m2) hospitalized twice for pancreatitis (triglycerides [TG] level >2,200 mg/dL). Her treatment management included bowel rest, insulin infusion, and plasmapheresis. A low-fat diet with 10 g of fat daily and 160 mg of fenofibrate daily decreased fasting TG to 411 mg/dL (range, 0-149 mg/dL). The patient had a normal leptin level. Panel testing of genes that impact TG metabolism revealed a known pathogenic variant in the PPARG gene (c.452A>G p.Tyr151Cys). A second variant detected in this gene, c.1003G>C (p.Val335Leu), is considered benign. Her glycosylated hemoglobin of 6.6% and 2-hour oral glucose tolerance test confirmed type 2 diabetes mellitus (T2DM). This study reports the earliest detection of T2DM in an adolescent with a pathogenic variant of PPARG. PPARG-related FPLD3 should be considered in lean children that present with severe HTG and insulin resistance, and subsequent treatment with proliferator-activated receptor gamma agonists, specifically thiazolidinediones, should be considered.
PMID: 34991302
ISSN: 2287-1012
CID: 5107322

An endocrine perspective on menstrual suppression for adolescents: achieving good suppression while optimizing bone health

Lahoti, Amit; Yu, Christine; Brar, Preneet Cheema; Dalgo, Austin; Gourgari, Evgenia; Harris, Rebecca; Kamboj, Manmohan K; Marks, Seth; Nandagopal, Radha; Page, Laura; Raman, Vandana; Reynolds, Danielle G; Sarafoglou, Kyriakie; Terrell, Carrie; Stanley, Takara L
Suppression of menstruation and/or ovarian function in adolescent girls may be desired for a variety of reasons. Numerous medical options exist. The choice of the appropriate modality for an individual patient depends on several factors based on differences in the efficacy of achieving menstrual suppression as well as in their side effect profiles. Adolescence is also a period of bone mass accrual in girls, and several of these modalities may negatively influence peak bone mass. This review focuses on the efficacy of achieving menstrual suppression and the effect on bone health of the various options through an overview of the current literature and also highlights areas in need of further research.
PMID: 34388330
ISSN: 2191-0251
CID: 5011502

Case Studies in Pediatric Lipid Disorders and Their Management [Case Report]

Ashraf, Ambika P; Sunil, Bhuvana; Bamba, Vaneeta; Breidbart, Emily; Brar, Preneet Cheema; Chung, Stephanie; Gupta, Anshu; Khokhar, Aditi; Kumar, Seema; Lightbourne, Marissa; Kamboj, Manmohan K; Miller, Ryan S; Patni, Nivedita; Raman, Vandana; Shah, Amy S; Wilson, Don P; Kohn, Brenda
CONTEXT:Identification of modifiable risk factors, including genetic and acquired disorders of lipid and lipoprotein metabolism, is increasingly recognized as an opportunity to prevent premature cardiovascular disease (CVD) in at-risk youth. Pediatric endocrinologists are at the forefront of this emerging public health concern and can be instrumental in beginning early interventions to prevent premature CVD-related events during adulthood. AIM:In this article, we use informative case presentations to provide practical approaches to the management of pediatric dyslipidemia. CASES:We present 3 scenarios that are commonly encountered in clinical practice: isolated elevation of low-density lipoprotein cholesterol (LDL-C), combined dyslipidemia, and severe hypertriglyceridemia. Treatment with statin is indicated when the LDL-C is ≥190 mg/dL (4.9 mmol/L) in children ≥10 years of age. For LDL-C levels between 130 and 189 mg/dL (3.4-4.89 mmol/L) despite dietary and lifestyle changes, the presence of additional risk factors and comorbid conditions would favor statin therapy. In the case of combined dyslipidemia, the primary treatment target is LDL-C ≤130 mg/dL (3.4 mmol/L) and the secondary target non-high-density lipoprotein cholesterol <145 mg/dL (3.7 mmol/L). If the triglyceride is ≥400 mg/dL (4.5 mmol/L), prescription omega-3 fatty acids and fibrates are considered. In the case of triglyceride >1000 mg/dL (11.3 mmol/L), dietary fat restriction remains the cornerstone of therapy, even though the landscape of medications is changing. CONCLUSION:Gene variants, acquired conditions, or both are responsible for dyslipidemia during childhood. Extreme elevations of triglycerides can lead to pancreatitis. Early identification and management of dyslipidemia and cardiovascular risk factors is extremely important.
PMID: 34363474
ISSN: 1945-7197
CID: 5107702

Hyperosmolar diabetic ketoacidosis-- review of literature and the shifting paradigm in evaluation and management

Brar, Preneet Cheema; Tell, Shoshana; Mehta, Shilpa; Franklin, Bonita
BACKGROUND:Hyperosmolar diabetic ketoacidosis (H-DKA), a distinct clinical entity, is the overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). AIM/OBJECTIVE:We describe the clinical presentation, metabolic aberrations, and associated morbidity/mortality of these cases with H-DKA. We highlight the problem areas of medical care which require particular attention when caring for pediatric diabetes patients presenting with H-DKA. METHODS:In our study we reviewed the literature back to 1963 and retrieved twenty-four cases meeting the criteria of H-DKA: glucose >600 mg/dL, pH < 7.3, bicarbonate <15 mEq/L, and serum osmolality >320 mOsm/kg, while adding three cases from our institution. RESULTS:Average age of presentation of H-DKA was 10.2 years ± 4.5 years in females and 13.3 years ± 4 years in males, HbA1c was 13%. Biochemical parameters were consistent with severe dehydration: serum osmolality = 394.8±55 mOsm/kg, BUN = 48±22 mg/dL, creatinine = 2.81±1.03 mg/dL. Acute kidney injury, present in 12 cases, was the most frequent end-organ complication. CONCLUSION/CONCLUSIONS:Multi-organ involvement with AKI, rhabdomyolysis, pancreatitis, neurological and cardiac issues such as arrhythmias, are common in H-DKA. Aggressive fluid management, insulin therapy and supportive care can prevent acute and long term adverse outcomes in children and adolescents.
PMID: 34731818
ISSN: 1878-0334
CID: 5038192

Lymph node metastases in pediatric medullary thyroid carcinoma

Oliver, Jamie R; Patel, Kepal N; Chang, Clifford M; Baldwin, Chelsey K; Brar, Preneet C; Morris, Luc G T; Givi, Babak
BACKGROUND:Unlike medullary thyroid carcinoma in adults, the vast majority of pediatric medullary thyroid carcinoma is hereditary. Pediatric medullary thyroid carcinoma is known to have different genetic alterations driving tumorigenesis, but it is not known if pediatric medullary thyroid carcinoma has different clinicopathologic features. This study aims to identify which pediatric medullary thyroid carcinoma patients might warrant elective neck dissection. METHODS:We selected all patients ages 0 to 19 diagnosed with clinically evident medullary thyroid carcinoma in the National Cancer Database between 2004 to 2016. Clinicopathologic factors, treatments, and outcomes were analyzed and compared between this cohort and adults (ages ≥20) with medullary thyroid carcinoma. RESULTS:One hundred twenty-five pediatric medullary thyroid carcinoma (median age: 13) and 5,086 adult medullary thyroid carcinoma (median age: 57) patients were identified. Pediatric patients had smaller tumors (median diameter: 1.2 cm vs 2.0 cm; P < .001), lower rates of nodal metastases (n = 31, 36.9% vs 1,689, 50.4%; P = .02) but double the incidence of multifocal tumors (n = 70, 59.3%, vs 1,412, 29.9%; P < .001) compared with adults. Multifocal tumors conferred a significantly increased risk of nodal metastases in adult medullary thyroid carcinoma (64.4% vs 43.2%; P < .001) but not pediatric medullary thyroid carcinoma (37.7% vs 35.7%; P = .85). Nodal metastases were more frequent among older children (0-5 years: 0.0%, 6-12: 40.7%, 13-19: 41.7%; P = .04). However, rates of occult nodal metastases were similar between older children (6-19 years: n = 12, 21.4%) and adults (557, 25.8% P = .56). CONCLUSION/CONCLUSIONS:Pediatric medullary thyroid carcinoma has lower rates of lymph node metastases compared with adults. The risk of nodal disease was low among the youngest children, but older children ages 6 to 19 were at considerable risk for occult metastases. These findings could guide clinicians in selecting pediatric patients considered for elective lymph node dissection.
PMID: 33838880
ISSN: 1532-7361
CID: 4842142