Reported Family History Research Articles

Whole aorta imaging shows increased risk for thoracic aortic aneurysms and dilatations in relatives of abdominal aortic aneurysm patients

ObjectiveFor relatives of abdominal aortic aneurysm (AAA) patients, guidelines recommend abdominal imaging aimed at early detection and management of AAA, and do not include screening for thoracic aortic aneurysms (TAA). We aimed to investigate if TAA occur in undiagnosed relatives of AAA patients without a known genetic susceptibility for aneurysms, similar to families with identified genetic susceptibilities for aneurysms like in Marfan and Loeys-Dietz syndrome, where both AAA and TAA occur. MethodsRelatives of AAA patients were invited for non-contrast whole aorta CT screening. Systematic measurements of the CT scans were used to detect aneurysms and dilatations. Classification into familial and non-familial was based on reported family histories. In addition, aneurysm gene panel testing of AAA index cases was used for the classification of high vs unknown genetic risk (high genetic risk: familial aneurysm or a (likely) pathogenic variant (P/LP) in an aneurysm gene; unknown genetic risk: no family history or P/LP). ResultsWhole aorta imaging of 301 relatives of 115 abdominal aortic aneurysm index-patients with non-contrast CT scans showed a 28-fold increase in thoracic aortic aneurysms in relatives (1.7%, p<0.001 versus the age adjusted population) and a high frequency of thoracic dilatations in 18% of the relatives. Thoracic aneurysms and dilatations in relatives occurred even when index patients were unaware of familial aneurysms. AAA was increased in the relatives compared to the age adjusted population (8%, p<0.001). ConclusionsAn increased risk for thoracic aneurysms and dilatations was detected by whole aorta imaging of relatives of AAA index patients, even when index patients were unaware of familial aneurysms.These results indicate -still unknown- shared genetic susceptibilities for thoracic and abdominal aneurysms. Therefore, imaging of the whole aorta of relatives of all abdominal aneurysm patients, will improve early detection of aortic aneurysms in relatives of all AAA patients.

Pre-school hearing screening is necessary to detect childhood hearing loss after the newborn period: a study exploring risk factors, additional disabilities, and referral pathways

Objective To explore strategies for detecting childhood hearing loss, aside from newborn hearing screening. Design A retrospective review of medical records on the modes of detection of hearing loss, risk factors for late-onset hearing loss, hearing loss degree, aetiology, additional disabilities, and timelines from referral to intervention. Study sample Children, born 2006 to 2015, enrolled for intervention whose hearing loss was detected up to age 7 years but not from newborn hearing screening (n = 326). Results Universal pre-school hearing screening detected 38% of the cohort at 4–5 years of age. Risk factors for late-onset hearing loss were present in 36% of children, 80% of whom had a reported family history. Sixty-nine percent had mild bilateral or unilateral hearing loss. Children with additional disabilities faced significantly longer delays from referral to intervention. Children self-referred due to parent concern had more severe degree of hearing loss than those referred from screening. Conclusion Most children with hearing loss detected after the newborn period do not have any known risk factors for late-onset hearing loss. Pre-school hearing screening is needed for comprehensive detection of hearing loss in early childhood. More work is needed towards improving timely diagnosis and intervention for children with additional disabilities.

Prevalence and correlates of alcohol and drug harms to others: Findings from the 2020 U.S. National Alcohol Survey.

Measure prevalence and overlap of secondhand harms from other people's use of alcohol, cannabis, opioid, or other drugs and examine sociodemographic and other correlates of these secondhand harms. This cross-sectional analysis used data from 7,799 respondents (51.6% female; 12.9% Black, 15.6% Hispanic/Latiné; mean age: 47.6) in the 2020 U.S. National Alcohol Survey. Secondhand harms included family/marriage difficulties, traffic accidents, vandalism, physical harm, and financial difficulties. Weighted prevalence estimates provided nationally representative estimates of these harms. Logistic regression assessed associations between individual characteristics and secondhand harms. Lifetime prevalence of secondhand harms from alcohol, cannabis, opioid, or other drugs was 34.2%, 5.5%, 7.6%, and 8.3%, respectively. There was substantial overlap among lifetime harms: almost 30% of those reporting secondhand alcohol harms also reported secondhand drug harms. Significant correlates of secondhand substance harms included female sex (alcohol, other drug); white (alcohol, opioid), American Indian/Alaska Native (opioid), and Black (cannabis) race/ethnicity; and separated/divorced/widowed marital status (opioid). Those reporting family history of alcohol problems had significantly higher odds of reporting secondhand harms across substance types. Individuals who reported frequent cannabis use had higher odds of reporting secondhand alcohol and opioid harms compared to those with no cannabis use, (aOR=1.55; aOR=2.38), but lower odds of reporting secondhand cannabis harms (aOR=0.51). Although less prevalent than secondhand alcohol harms, 14% of participants reported secondhand harms from someone else's drug use and frequently experienced secondhand harms attributed to multiple substances. Population-focused interventions are needed to reduce the total burden of alcohol and drug use.

Clinical Interpretation of Genetic Variants in the Evaluation and Management of Thoracic Aortic Aneurysm and Dissection

BackgroundWe aimed to elucidate clinical implications of genetic variant interpretation in assessing disease severity and progression in thoracic aortic aneurysm and dissection (TAAD) patients. MethodsConsecutive TAAD patients with aortic root and/or ascending aortic aneurysms seen between 2011 and 2020 were included. Serial echocardiography, family history of TAAD, and management information were retrospectively collected and analyzed. Patients were classified into gene-positive (Gen-P), variants of uncertain significance, and gene-negative (Gen-N) groups. ResultsA total of 407 patients were included: mean age 53.7 ± 15.4 years, 64.4% men, and 38% with reported family history of TAAD. Thirty-seven (9.1%) were Gen-P; 147 (36.1%) had a variant of uncertain significance. The maximal aneurysm diameter was 4.78 mm larger in Gen-P than the other groups (P < .001). In 162 unoperated TAAD patients with serial echocardiographic measurements, aneurysms enlarged at a significantly higher rate in the Gen-P (1.36 mm/year, 95% CI: 0.77-1.95) than variants of uncertain significance and Gen-N groups (0.83 mm/year vs 0.89 mm/year, respectively; P < .001). Aneurysms were 20% more likely to require surgical intervention for every millimeter increase in diameter. When considered on an individual basis, the highest growth rates were found in the variants of uncertain significance group. ConclusionsWhile aneurysms linked to variants of uncertain significance demonstrate average growth rates comparable to those in Gen-N, close follow-up and genetic counseling in the variants of uncertain significance group are recommended for assessment of pathogenicity on a case-by-case basis. Early familial gene testing in TAAD is important to develop individualized preventive and therapeutic criteria.

Awareness of Common Eye Diseases Among College Students at A Saudi University

Introduction: Many eye conditions, including cataract, glaucoma, and diabetic retinopathy, are among the major causes of blindness in the world. There were many studies on the subject worldwide but fewer in the Middle East; hence, the subject needs more investigation. This research is significant as it fills the gap in the literature on the awareness of common eye diseases in Saudi Arabia. This study was carried out to assess the awareness of common eye diseases among college students at a Saudi University. Methodology: This was a cross-sectional study, including college students at Prince Sattam bin Abdulaziz University (PSAU), Saudi Arabia. Data was collected using a self-administered questionnaire and was analyzed using the SPSS program. Results: Our study included 579 participants. 62.7% of participants reported no family history of eye diseases, and among those who did, dry eye was the most frequently mentioned condition, with 27.8%. Cataract, glaucoma, and diabetic retinopathy had lower reported family histories at 12.3%, 5.9%, and 3.5%, respectively. Concerning awareness, 60.3% of participants were aware of dry eye, followed by cataract (38.7%) and glaucoma (33.3%). However, 26.9% reported no awareness of any eye disease. The internet emerged as the most significant source of information (46.7%), while family, friends, and relatives were also prominent sources (35.4%). Regarding knowledge of specific eye diseases, there were varying awareness levels. For example, 58.4% recognized cataract as treatable, and 42.5% knew glaucoma could cause blindness. Conclusion: A significant proportion of participants exhibited awareness of conditions like dry eye, cataract, and glaucoma; there is room for improvement. Study findings underscore the importance of educational interventions aimed at enhancing awareness, especially for students in non-medical disciplines.

Clinical presentation and delay to diagnosis and treatment in Mexican patients with gastric cancer.

291 Background: Gastric cancer is the fifth leading cause of cancer-related deaths in Mexico. Diagnosis is often made at advanced stages, resulting in a poor prognosis. The delay from the onset of the first symptom to diagnosis and treatment could influence the poor prognosis of gastric cancer patients (pts) in our country. In Mexico, information on this topic is limited. We aim to investigate the time delay between the onset of symptoms, histological diagnosis, and initiation of oncological treatment in pts with gastric adenocarcinoma. Methods: We conducted a retrospective review of the clinical records at our institution of all pts with confirmed histological diagnosis of gastric adenocarcinoma (GC) treated between Jan 2005 and Dec 2017. Overall Survival (OS) was estimated using the Kaplan-Meier method. Groups were compared using Log-Rank test. Results: We included 270 pts with confirmed histopathological diagnosis of GC, 53.3% (n=144) women, median age 58 years (IQR 25-75); 44% (n=121) reported family history of cancer, 39.6% (n=107) smoking, H. pylori infection was documented in 22% (n=61). Symptoms before diagnosis were present in 98.5% (n=266) of pts, most common were: weight loss 77.4% (n=209), fatigue 51.9% (n=140), early satiety 51.1% (n=138), nausea 48.9% (n=132), vomiting 48.1% (n=130), dysphagia 21.5% (n=58), and gastrointestinal bleeding 37.8% (n=102). The most common method for histological diagnosis was endoscopy with biopsy in 86.7% (n=234). The median time between the onset of symptoms and histopathological diagnosis was 4.21 (IQR 2.25–8.48) months (m), between the onset of symptoms and the initiation of oncological treatment 5.28 (IQR 2.86–9.52) m, and between histopathological diagnosis and oncological treatment 0.60 (IQR 0.13–1.21) m. 72.6% (n=196) of cases were stage IV, 14.1% (n=38) stage III, 8.1% (n=22) stage II, 4.8% (n=13) and stage 0 or I. The median OS for the entire cohort was 7.2 m, 3.7 m for stage IV, 17.3 m for stage III, and 84 m for stage I. Median OS for stage II was not reached, and it was 58% at 5 years. Symptoms associated with worse or better survival are shown in table. Conclusions: Reducing delays in histopathological diagnosis from symptom onset could lead to earlier detection and curative treatments. Identifying alarm signs and appropriate patient navigation would enable earlier diagnosis and early treatment. [Table: see text]

Assessment of genetic familiarity and genetic knowledge among Palestinian university students

Background and aimsGenetic knowledge and familiarity among the population represent the lane toward effective participation in social decisions regarding genetic issues. This cross sectional research aimed to assess genetic knowledge and familiarity among university students in Palestine.MethodsThe familiarity with genetics was evaluated using the Genetic Literacy and Comprehension instrument (GLAC), and genetic knowledge was measured using a 16-item scale of prevalent genetic concepts.ResultsAmong the 624 participants, 59.5% were females. 38.8% reported family history of genetic diseases. The genetic familiarity mean score was 4.83 and the genetic knowledge mean total score was 11.5. Students’ genetic familiarity was high for the terms chromosome and genetic while it was low for the terms sporadic and vulnerability. Genetic knowledge was highest for gene definition while it was the lowest regarding the number of human genes. The age group, year of study, and learning genetic courses were the significant predictors of familiarity among medical students. The year of study, family history of genetic diseases, parental consanguinity, and learning genetic courses were the significant variables associated with genetic knowledge among medical students. Regarding the non-medical group of participants, all study variables were significant for both familiarity and knowledge scores except for age group with familiarity.ConclusionGenetic familiarity and knowledge among Palestinian university students are inadequate. Consanguinity and hereditary disorders are prevalent in Palestine. These findings encourage university stakeholders to take action to improve genetic knowledge and familiarity among students through both appropriate pedagogical and non-pedagogical interventions.

Community Knowledge, Attitude, and Practices Related to Strabismus and Strabismus Treatment and Surgery in Al-Jouf Region, Saudi Arabia.

Strabismus is the misalignment of the visual axis of both eyes caused by abnormalities in binocular vision or anomalies of neuromuscular control of ocular motility.This study aimed to assess the community knowledge, attitude, and practices related to strabismus and strabismus treatment and surgery in the Al-Jouf region of Saudi Arabia. This study utilized a quantitative cross-sectional design. The consented volunteering adult participants were randomly selected through sequential enrollment to the completion of the target sample size from five population groups constituting the Al-Jouf region of Saudi Arabia. The data were collected through an online validated self-administered questionnaire. The collected data were analyzed using descriptive and inferential statistics. The study included 340 participants; 67.6% of them were females and 32.4% were males. Only 66.8% of participants correctly defined strabismus. Symptoms of strabismus were identified as double vision (58.5%), blurred vision (48.2%), headache (31.8%), eye fatigue (41.5%), and difficulty reading (47.1%). Regarding risk factors of strabismus, 48.5% reported family history, 39.4% reported uncorrected refractive errors, and 23.2% reported long screen time. Complications of untreated strabismus were reported as low self-confidence (39.1%), vision loss (27.6%), poor interpersonal relationships (25.9%), amblyopia (42.6%), and cosmetic stigma (14.1%). Only 45.6% of the participants agreed to marry someone with strabismus or allow their relatives to do so. The majority of participants (72.6%) would advise a strabismus patient to visit an ophthalmologist. Despite a higher knowledge regarding strabismus among females, younger agers, higher education, single persons, workers/students, and those inhabiting the capital city of the region, such association did not reach significance. The study shows a moderate level of knowledge, attitude, and practices among the general population of Al-Jouf Saudis towardstrabismus. There was no significant relationship between knowledge of strabismus and any of the demographic characteristics of the participants. This might prove detrimental to the early detection and treatment of strabismus to prevent its complications and improve its outcomes and the quality of patients' lives. Institution of correlation plans are mandated by the Ministry of Health and interested stakeholders.

Novel Double Fusion (βδβ) Hemoglobin Variant with Comparison to Lepore Hemoglobins

Lepore hemoglobins (Hbs) such as Hb Lepore-Boston-Washington [δ(1-87) β(116-146)], Hb Lepore-Baltimore [δ(1-50) β(86-146)], Hb Lepore-Hollandia [δ(1-22) β(50-146)] are δβ gene fusion/deletion variants (ε- Gγ- Aγ-[δβ] v )(Figure 1). They are controlled by the weak δ-globin gene promoter and synthesized at approximately 10-15% of hemoglobin fractions. This results in a similar phenotype as β +-thalassemia (microcytosis and hypochromia ± mild anemia). Anti-Lepore hemoglobins such as Hb P-Nilotic (β(1-22) δ(50-146) are βδ gene fusion/duplication variants (ε- Gγ- Aγ-δ-[βδ] v-β) associated with normal CBC values. Herein we describe a novel βδβ double fusion variant (ε- Gγ- Aγ-δ-[βδβ] v). Due to high homology between the δ and β genes, this double fusion event encodes an identical protein to Hb Lepore-Hollandia, albeit linked to the β-promoter and therefore expressed at ~40% of hemoglobin fractions, which would be expected to enhance any intrinsic properties of the variant. This novel hemoglobin variant is named Hb Lepore Rochester-MN. Two cases have been identified (Table 1). Case 1 was a 10-month-old Caucasian/Native American infant referred for an abnormal newborn screen and a reported family history of Hb G-Coushatta (β22, GAA&amp;gt;GCA, Glu&amp;gt;Ala; HGVS: c.68A&amp;gt;C, p.E23A). Case 2 was a 3-month-old infant referred for an abnormal newborn screen. CBCs were normal for age including MCV. Cation-exchange high performance liquid chromatography (HPLC) showed a shouldered peak in the Hb A 2 window typical for Hb Lepore (elution time: 3.41-3.46 mins), although the variant percentage was higher than expected, mimicking Hb G-Coushatta (expected elution time: 3.33 mins). Capillary electrophoresis identified a peak in the D zone (Z(D) zone), which is expected for Hb Lepore or Hb G-Coushatta. Intact mass spectrometry was consistent with Hb Lepore-Hollandia at 15836 amu, differing from Hb G-Coushatta (Glu&amp;gt;Ala, 15809 amu). Multiplex ligand probe amplification (MLPA) was normal because the highly variable fusion regions are unsuitable for probe placement. Sanger sequencing of the β-globin gene identified multiple single base substitutions which were challenging to interpret but matched the sequence expected for a complex double crossover event (NM_000518.4:c.28_68delins41 (p.Ser10_Glu23delins14TAVNALWGKVNVDA). The first crossover is located between c.-29 and c.9, the second crossover is located between c.69 and c.92+17. Long-read sequencing was performed (Sequel, Pacific Biosciences) which detected the multiple missense mutations in cis conformation, as was corroborated by the mass spectrometry data. In summary, Hb Lepore Rochester-MN represents a novel double fusion [βδβ] variant class that will pose a diagnostic challenge for laboratories. Although it is likely a result of sequential crossover events (deletion and duplication) between Lepore and anti-Lepore variants, MLPA analysis is normal due to technical constraints and high homology. DNA sequencing (both Sanger and long read methods) yielded complex results that require sophisticated analysis and correlation with protein data including intact mass spectrometry. HPLC and CE data including variant percentage are very similar to Hb G-Coushatta. In addition, although resulting in an identical protein, the variant should not be mistaken for Hb Lepore-Hollandia, which is produced at lower levels and causes a thalassemic phenotype. Hb Lepore Rochester-MN is controlled by the β-promoter and therefore is associated with approximately 40% variant and apparently normal CBC values in the two infants.

A Novel Variant of the CYCS Gene Alters Apoptosis of Megakaryocytes in a Family with Thrombocytopenia

Introduction: In humans, the CYCS gene encodes Cytochrome c, a protein important for the respiratory electron transport chain in mitochondria and for apoptosis. The clinical features of known CYCS pathogenic variants have been reported to be linked with thrombocytopenia. Herein, we present a novel variant of CYCS gene found in a Greek family with thrombocytopenia and its effects in apoptosis. Patients: A 1 year-old patient (Patient 1) with moderate thrombocytopenia (platelets=42×10 3/μl, MCV=76fL) and reported family history of thrombocytopenia has been referred to “Aghia Sophia” Children's Hospital for Whole Exome Sequencing. A 28 year-old female (Patient 2) and her 52 year-old mother (Patient 3) have been referred to the Hematology Unit of Attikon University General Hospital due to chronic grade III thrombocytopenia with no evidence of hemorrhagic diathesis. A thorough hematological examination of these two adult patients, including peripheral blood - bone marrow morphology, functional platelet assays, marrow cytogenetics and NGS, has detected no abnormalities. A trial of gamma globulin and steroids has been performed with no platelet response. Family history revealed more family members with thrombocytopenia on the side of the mother. In total five family members with moderate thrombocytopenia and four members with normal platelet counts have been tested with Sanger sequencing. Methods: Whole Exome Sequencing has been performed on Patient 1 and Sanger sequencing/Segregation analysis in nine members of the family. Florescence Activated Cell Sorting (FACS) has been performed in bone marrow mononuclear cells of Patient 2, Patient 3 and eight healthy controls. The antibody panel used included PE anti-human CD42a, PE/Cyanine7 anti-human CD42b, APC/Cyanine7 anti-human CD31 and APC anti-human CD71 antibodies. The stained cells (immature and mature megakaryocytes) have been sorted on a FACS Aria IIu (BD Biosciences) and subsequently stained with Annexin V FITC/7-AAD, to allow the detection of early-stage and late-stage cell apoptosis. Results: A novel missense variant of unknown significance (VUS) in the CYCS gene ( CYCS(NM_018947.6):c.292T&amp;gt;C (p.Tyr98His)) has been identified using whole exome sequencing in Patient 1. Segregation analysis of the variant in the family showed complete genotype-phenotype correlation (five family members with moderate thrombocytopenia, four members with normal platelet counts) (Figure 1A). The variant has been found to be heterozygous in all family members tested. To investigate the functional role of the novel variant and its potential link to the thrombocytopenic phenotype FACS has been performed to isolate immature and mature megakaryocytes (positive for CD42a, CD42b, CD31 and medium positive for CD71) followed by analysis of apoptosis in Patient 2, Patient 3 and healthy controls. Cells undergoing early apoptosis have stained positive for Annexin V, while late apoptotic cells have been characterized by positive staining for both Annexin V and 7-AAD. Our preliminary results show increased numbers of apoptotic cells in the patients compared to controls (Figure 1B). We are currently validating this finding by inserting the CYCS gene variant in the megakaryocytic cell line DAMI, using the CRISPR-Cas9 system. Conclusions: A novel missense variant in the CYCS gene has been identified in a Greek family with thrombocytopenia, where the phenotype is mild with isolated thrombocytopenia, no hemorrhagic diathesis and no any other organ dysfunction. FACS analysis of two variant carriers has revealed increased apoptosis of immature and mature megakaryocytes compared to controls. This study will delineate the molecular mechanisms underlying thrombocytopenia in the family and it is expected that the findings will be translated in novel therapeutic management strategies for patients with thrombocytopenic related pathologies. Figure 1. A novel missense variant in the CYCS gene increases apoptosis in megakaryocytes. A. Segregation analysis of the family: Thrombocytopenia phenotype is marked with pink and carriers of the variant with dot. B. FACS analysis of megakaryocytes stained with Annexin V/7-AAD: Percentages of total apoptotic cells (early and late) are shown on the chart. Values represent mean ± SE, N=2 for patients and N=8 for controls (three FACS experiments have been performed for patient 2, two for patient 3 and one for each control).

OR34-03 Defining Clinical Characteristics Of Patients With Severe Hypoglycemia After Roux-en-Y Gastric Bypass: How Do They Differ From Asymptomatic Patients?

Abstract Disclosure: A. Grover: None. A.L. Sheehan: None. C. Cummings: None. M. Farahmandsadr: None. H. Saeed: None. A.M. Puleio: None. D.C. Simonson: Stock Owner; Self; Phase V Technologies, GI Windows. M. Patti: Consulting Fee; Self; AstraZeneca, MBX-Biosciences, Hanmi Pharmaceutical. Other; Self; DSMB: Fractyl Health, Inc. Introduction: Post-bariatric hypoglycemia (PBH) is a severe, disabling complication of Roux-en-Y gastric bypass (RYGB). We aimed to identify clinical characteristics distinguishing patients with severe PBH vs. post-RYGB patients without symptomatic hypoglycemia (RYGB non-hypo) to help elucidate PBH pathophysiology and potential risk factors. Methods: Adults aged 18-70, without diabetes mellitus (DM), were recruited into 3 groups: (1) PBH with neuroglycopenia (n=33); (2) RYGB non-hypo (n=16); (3) non-surgical weight-matched controls (n=17). Detailed history of hypoglycemia, medical/surgical/family history, medications, Dumping Symptom Rating Scale (DSRS), and Rome IV diagnostic criteria for Irritable Bowel Syndrome (IBS) was completed. Differences between PBH and RYGB non-hypo were evaluated by unpaired t-tests and chi-square analysis as indicated. Results: PBH participants were 90% female, mean age 53±2 y, BMI 32±1 kg/m2, 39±2% body fat, with similar data for RYGB non-hypo (100% female, age 54±2 y, BMI 33±2 kg/m2, 40±2% fat), and controls (65% female, age 45±4 y, BMI 31±2 kg/m2, 35±3% fat). 90% of PBH reported level 3 hypoglycemia, with ER visits in 29% and motor vehicle accidents in 7%. Reduced awareness of hypoglycemia was reported by 80% of PBH, with hypoglycemia awareness at mean glucose of 57±2 mg/dL. 29% of PBH reported hypoglycemic symptoms occurring preoperatively, and 20% reported family history of hypoglycemia. The majority of PBH reported depression, change in driving habits, and adverse impact on employment. When compared with RYGB non-hypo, PBH participants had no difference in postoperative weight loss trajectories but had higher prevalence of revisional surgeries (p&amp;lt;0.05). PBH participants also had a higher score on DSRS (p&amp;lt;0.05) and higher prevalence of IBS (48 vs. 7% meeting Rome IV criteria, p&amp;lt;0.05). Higher rates of orthostatic hypotension, intestinal dysmotility, and vitamin B12 deficiency requiring treatment were reported by PBH (p&amp;lt;0.05 for all). Additionally, PBH participants reported greater gabapentin, PPI, and hormonal contraceptive use (p&amp;lt;0.05 for all); there were no differences in SSRI/SNRI use. Conclusion: PBH participants reported high rates of hypoglycemia unawareness, a likely contributor to hypoglycemia severity, recurrence, and adverse effects on safety and personal life. High rates of IBS, dumping symptoms, and orthostatic hypotension suggest possible disordered autonomic regulation in the pathophysiology of PBH. Self-reported preoperative symptoms and family history of hypoglycemia suggest possible differences in glucose metabolism prior to surgery in at-risk individuals. Preoperative assessment of these and other factors, together with longitudinal follow-up studies to determine incidence of PBH, will be required to identify risk factors for development of post-bariatric hypoglycemia. Presentation: Sunday, June 18, 2023

THU236 Mild Asymptomatic Hypercalcemia Secondary To A Novel Calcium-sensing Receptor Mutation

Abstract Disclosure: J. Tarkoff: None. Background: Familial hypocalciuric hypercalcemia (FHH) is a rare cause of mild hypercalcemia that is usually secondary to heterozygous mutations of the calcium-sensing receptor (CaSR) with autosomal dominant inheritance. The distinction between this entity and primary hyperparathyroidism can be difficult. Clinical Case: A 15-year-old female presented to the endocrinology clinic for an incidentally found elevated total calcium of 10.9 mg/dl (8.9-10.4) and elevated ionized calcium 5.5 mg/dl (4.8-5.3 mg/dl). Her labs at that time also showed a PTH of 29 pg/mL (12-71) and phosphorus 3.5 mg/dl (2.5-4.5 mg/dl). She denied any symptoms of hypercalcemia and there is no reported family history of mineral disorders or fractures. She does not take any medications. Her physical exam was unremarkable. Our evaluation showed calcium 10.5 mg/dl, phosphorus 4 mg/dl, magnesium 2.2 mg/dl (1.5-2.5 mg/dl) 25-hydroxyvitamin D 32 ng/ml (30-100 ng/ml), fractional excretion of calcium (FeCa) based upon spot urine sample = 0.0104, TSH 1.29 mIU/L (0.5-4.3 mIU/L), alkaline phosphatase 79 U/L (45-150 U/L), and normal renal function. Given her spot FeCa being &amp;lt;0.02, sequencing of the CASR gene was offered to the family because of potential overlap of her FeCa with primary hyperparathyroidism for which the treatment would be surgical (1). Commercial genetic testing was notable for a previously unreported heterozygous nonsense mutation, c.3001C&amp;gt;T (p.Gln1001X). It is expected to disrupt the final 78 amino acids of the protein in its intracellular domain and may play a role in preventing downstream signaling. At follow-up without treatment, her calcium has ranged between 10-10.9 mg/dl and she remains asymptomatic. Clinical lesson/conclusion: Hypocalciuria in the setting of hypercalcemia should raise the suspicion of FHH even without family history. Genetic testing of the CaSR is a crucial step in facilitating the diagnosis of FHH, especially given the importance of distinguishing it from primary hyperparathyroidism. Reference: (1) Christensen, S.E., Nissen, P.H., Vestergaard, P., Heickendorff, L., Brixen, K. and Mosekilde, L. (2008), Discriminative power of three indices of renal calcium excretion for the distinction between familial hypocalciuric hypercalcemia and primary hyperparathyroidism: a follow-up study on methods. Clinical Endocrinology, 69: 713-720. Presentation: Thursday, June 15, 2023

An investigation of knowledge and attitudes towards antidepressants: a cross-sectional survey of Jordan’s six medical schools

ObjectiveDepression is Jordan’s most ravaging mental illness. Despite the growth of antidepressant use, only a handful of studies examine the factors affecting antidepressant knowledge among healthcare workers or medical students. Therefore, we aimed to explore the knowledge and attitudes towards antidepressants across Jordan’s six medical schools.MethodsUsing a cross-sectional design, we investigated the knowledge and attitudes towards antidepressants through the Drug Attitude Inventory and a literature-validated knowledge domain. Clinical students from Jordan’s six medical schools were recruited. Differences in knowledge and attitudes scores were examined by year of study, medical school among other factors. A multivariate linear regression model was utilized to assess predictors of knowledge.ResultsWe included a total of 1,234 participants representing Jordan’s six major schools of medicine. About 14.9% of participants had a personal history of antidepressant use while 20.5% reported family history of psychiatric disease. The majority of students demonstrated favorable attitudes towards antidepressants (74.1%). Students demonstrated an average understanding of antidepressants’ mechanism of action, side effects, but not indications in special populations. Senior medical students, higher GPA, higher family income, personal history of antidepressants, and family history of psychiatric illnesses were associated with significantly higher knowledge scores (all p-values < 0.001). In addition to attitudes scores, the aforementioned were positive predictors of knowledge scores in the multivariate model.ConclusionMedical students’ knowledge towards antidepressants leaves room for significant improvement. Yet, it is evident that significant differences for both attitudes and knowledge exist across medical schools which may indicate a gap in either training or teaching methodology.

E37 Clinical and demographic criteria of Juvenile primary systemic vasculitis in Libyan Children

Abstract Introduction Primary vasculitis syndromes are rare in childhood. The clinical manifestations depend on the vessels involved and can lead to significant mortality and morbidity. Aim To study demographic and clinical characteristics of patients with diagnosed with vasculitis other than Kawazaki disease and Henoch-Schonlein purpora (HSP) and to report the outcome of the patients. Materials and methods This is a case series conducted by reviewing the files of patients diagnosed with vasculitis and followed up at the pediatric rheumatology unit of the Tripoli Children Hospital, Libya from year 2000–2022. Data regarding patients’ demography, time of diagnosis, clinical features, laboratory results, treatment and complications were retrieved. Results A total of 37 cases included in the study. 17 (45.9%) were males and 20 (54%) were females followed up for a mean period of 4.48 ± 4.21. Mean age at diagnosis was 8.39 ± 3.84 years. Regarding the diagnosis, there were 3 (8.1%) patients with Takayasu arteritis, 5 (13.5%) patients with polyarteritis nodosa, 2 (5.4%) patients with cutaneous polyarthritis nodosa, 1 (2.7%) patients with granulomatosis with polyahgitis, 1 (2.7%) patient with microscopic polyangiitis, 3 (8.1%) patients with Chrug-Strauss disease, 16 (43.2%) patients with Behcet disease, 1 (2.7%) patients with cogan syndrome, 3(8.1%) patients with urticarial vasculitis, 1 (2.7%) patient with hypocomplementaemic vasculitis, and 1 (2.7%) patient with DADA2. Mean period between the start of symptoms and diagnosis was 1.4 ± 2.8 years. In 6 (16.2%) of the patients there was family history of vasculitis and in 11 (29.7%) the parents are consanguineous. Angiography revealed abnormalities in 5 (13.5%) of the patients. Skin biopsy was done in 4 (10.8%) patients [2 patients with polyarthritis nodosa and 2 patients with urticarial vasculitis] and renal biopsy was done in 1 (2.7%) patient. Steroid was used in 24 (64.9%), Azathioprine in 4 (10.8%) patients. Cellcept was used in 10 (27%) of the patients. Ciclosporin was used 1(2.7%) patient, cyclophosphamide in 3 (8.1%) patients and Immunoglobulin in 6 (16.2%) of patients. Biologics were used in six patients, adalimumab in one patient which was discontinued because of recurrent abscess. In the two patients who used infliximab, treatment was effective. Three patients were treated with tocilizumab, it was ineffective in two, therefore discontinued. However, tocilizumab was effective in one patient with Takayasu arteritis. Complications developed in 23 (62.2%). Muscle atrophy in 1, deforming arthritis in 1, osteoporosis in 1, mouth ulcers in 2, hypertension in 2, hearing loss in 1, chronic sinusitis in 1, cardiovascular accident in 1, cataract in 1, visual impairment in 3, proteinuria in 2, pulmonary fibrosis in 1, chronic asthma in 3, impaired renal function in 1. Conclusion This is the first report of pediatric vasculitis cases in Libya. It showed a heterogeneous spectrum of vasculitis with high rate of consanguinity and low rate of reported family history of vasculitis. Hopefully this report will increase awareness among clinicians of vasculitis and more cases will be diagnosed.

Exploring the natural and treatment history of vitiligo: patient and healthcare professional perceptions from the global VALIANT study.

Vitiligo is a chronic autoimmune disease affecting melanocytes, resulting in depigmentation of skin. Patients with vitiligo often have reduced quality of life and comorbid autoimmune conditions and have reported a lack of available treatments for their vitiligo. The Vitiligo and Life Impact Among International Communities (VALIANT) study is the first global survey to explore the natural history and management of vitiligo from the perspectives of patients and healthcare professionals (HCPs). The survey recruited adults (≥18 years) diagnosed with vitiligo and HCPs treating patients with vitiligo via an online panel in 17 countries. Patients were queried regarding clinical characteristics and vitiligo treatment. HCPs were queried regarding diagnosis and management of patients with vitiligo. Included in the analysis were 3541 patients and 1203 HCPs. Nearly half (45.2%) of patients had >5% affected body surface area; 57.1% reported family history. Patients obtained formal diagnosis after a mean (SD) of 2.4 (4.1) years; 44.9% reported previous misdiagnosis. Many patients (56.7%) reported being told that vitiligo could not be treated; 53.9% of HCPs believed patients who never treated their vitiligo were told that vitiligo could not be treated. One-quarter of HCPs (26.3%) did not believe an effective therapy for vitiligo exists; 44.6% of patients reported giving up on finding an effective therapy. Top treatment goals for patients and HCPs, respectively, were reduction/cessation of spread (24.7%/18.5%) and repigmentation (22.5%/37.2%). Patient perception of effective care was similar for treatment by dermatologists (66.9%) and primary care HCPs (67.0%). Patients with vitiligo and HCPs reported similar treatment goals and expressed frustration with lack of effective therapies. Patients reported high rates of initial misdiagnosis; many ceased seeking healthcare because they perceived that vitiligo could not be treated. Findings highlight the need for earlier diagnosis and improved disease management for vitiligo.

Assessment of health status and cardiovascular risk factors in a Roma population sample from South Bulgaria.

Roma population is one of the major ethnic groups in the Central and Eastern Europe, having high rates of chronic diseases and associated risk factors related to their poor social conditions, unhealthy lifestyle and low educational level. The purpose of our study was to assess the health status of Roma from South Bulgaria by means of blood indicators and determine the prevalence of some cardiovascular (CV) risk factors in the Roma population sample. The study group consisted of 60 Roma (23 men and 37 women), mean age 53.7 ± 15.9 years, and the control group consisted of 68 non-Roma from the majority population (29 men and 38 women), mean age 45.8 ± 12.2 years. The data were collected via questionnaire, anthropometric measures, and venous blood samples analyses after an overnight fasting. The Roma population subjects were slightly but significantly older compared to the non-Roma group and both study groups included more women. The fasting glucose, body mass index (BMI), triglycerides (TG), total cholesterol (TC), and LDL-cholesterol (LDL-C) levels were significantly higher, and HDL-cholesterol (HDL-C) levels were significantly lower in Roma compared to the control non-Roma group. The values of cardiovascular risk markers such as TC/HDL-C and TG/HDL-C ratios, atherogenic index of plasma (AIP) and lipoprotein combine index (LCI) were significantly higher in Roma compared to non-Roma subjects. The prevalence of obesity in Roma was 35%, diabetes mellitus was recorded in 16.7% of the entire Roma sample, and hyperglycaemia in non-diabetics was recorded in 32%. Hypercholesterolaemia was found in 90% and hypertriglyceridaemia was found in 88.3%. The prevalence of cardiovascular diseases (CVD) was high and was encountered in 71.7% of the Roma participants and most of the subjects (96.7%) reported family history of CVD. The studied population showed high smoking rates with 33.3% active smokers. Our study confirmed high prevalence of CV risk factors among Roma population, such as abnormal lipid profile parameters, obesity and heavy smoking and very high cardiovascular morbidity rate. Therefore, adequate measures and healthcare programmes aiming at the early identification, treatment and prevention of CVD risks among Roma are necessary.

Prevalence of EGFR mutations in patients with resected stage I-III non-squamous NSCLC: Results from the EARLY-EGFR study.

8531 Background: The prevalence of EGFR mutations ( EGFRm) in resected stage I-III NSCLC remains controversial as prior research studies were retrospective in nature. EARLY-EGFR is the first prospective, international study to determine the prevalence of EGFRm and treatment patterns in patients (pts) with early-stage NSCLC. Methods: EARLY-EGFR (NCT04742192), a non-interventional real-world study, captured data on EGFRm status, treatment patterns, demographic, clinical and pathological characteristics in consecutively enrolled pts with surgically resected stage IA-IIIB (AJCC 8th) non-squamous NSCLC (Mar 2021 – Oct 2022). The primary endpoint was prevalence of EGFRm and secondary endpoints included prevalence of EGFRm subtypes and treatment patterns. Results: Of 601 pts (median [range] age: 62 [30-86] yrs) enrolled at 33 centers across Middle East and Africa (n=16), Latin America (n=80), and Asia (n=505), 317 (52.7%) were females, 354 (58.9%) were never smokers. The majority had stage IA-IB NSCLC (64.1%) involving right lung (62.9%), no nodal involvement (81.5%), T1a-T2b tumor (82.7%), adenocarcinoma histology (98.7%), and 105/420 (25.0%) tumors were poorly differentiated. About 23.3% (130/559) were diagnosed through a screening program; 60/539 (11.1%) reported family history of lung cancer. The overall prevalence of EGFRm was 50.7% (300/592). Exon-19 deletions accounted for 50.3%, L858R mutations for 35.7%, and compound mutations for 2.3% of mutations. EGFRm tumors were found to be PD-L1 positive in 38.5% of cases (15/39). Women had higher EGFRm rate than men (63.6% vs 36.2%). Compared with EGFR wild type (wt), pts with EGFRm were more likely to be never smokers (39.5% vs 60.5%) and have stage I/II NSCLC (46.5% vs 53.5%) (Table). Of 216 stage II/III NSCLC pts, only 51.4% received systemic adjuvant therapy. Significantly higher EGFRm rates in stages I and II than in stage III NSCLC (p&lt;0.001 and p=0.050) were found, while no significant difference was found between stages I and II NSCLC (p=0.158). Conclusions: In this first prospective, real-world study of EGFRm prevalence in resected NSCLC, stage III and smoking were independent predictors associated with decreased odds of EGFRm. The results highlight the need to adhere to ASCO adjuvant chemotherapy guidelines, as only half of stage II/III NSCLC pts received adjuvant systemic therapy. Clinical trial information: NCT04742192 . [Table: see text]

Description of the ARMADA (assessing reliable measurement in Alzheimer’s disease) general population study cohorts

AbstractBackgroundGiven the growing population of aging adults, and subsequently individuals with dementia, there is a need for instruments that can detect cognitive impairment in early stages. The NIH Toolbox® for Assessment of Neurological and Behavioral Function (NIHTB) is a computerized battery of assessments measuring multiple domains cognition, emotion, sensation, and motor abilities. The goal of the ARMADA study is to validate the NIHTB in individuals with mild cognitive impairment (MCI) and dementia of the Alzheimer type (DAT). Here, we describe the demographic and clinical characteristics of participants ages 65 to 85 from the general population sample.MethodNormal control (NC), MCI, and DAT groups racially proportional to the US population were recruited from existing cohorts across nine Alzheimer’s Disease Research Centers and sites with cognitive aging studies. Diagnoses were based on the Uniform Data Set methodology, and included multiple clinical and cognitive assessments. Participants completed the NIH Toolbox at baseline, 12‐, and 24‐month visits.ResultGroups were matched with respect to multiple demographic characteristics. There were some differences in age and sex, such that the NC group had more female participants and was the youngest. Dementia severity levels differed as expected, with the DAT group demonstrating greater cognitive and functional impairment compared to the MCI group, and the NC group demonstrating minimal cognitive or functional symptoms. Additionally, the DAT group reported more neuropsychiatric symptoms compared to the NC and MCI groups. There was no difference in reported family history of cognitive impairment across groups. Many participants across groups had at least one Alzheimer biomarker collected.ConclusionThe study cohorts included in the ARMADA study accurately reflect their respective clinical syndromes for validating the NIHTB across the cognitive aging spectrum. The goals for the ARMADA study include comparing performance on all four modules of the NIHTB across groups, evaluating the relationship between Alzheimer biomarkers and NIHTB measures, and measuring changes in performance longitudinally. Special emphasis groups, including individuals over age 85, African American participants, and Spanish‐Speaking participants, were also recruited and are reported elsewhere.

Coping strategies in bipolar patients: A comparative study with siblings and healthy controls

IntroductionData regarding coping strategies used by bipolar patients to deal with psychosocial stress and their consequences in adaptational outcomes are scant. Moreover, family studies have reported the presence of several similarities between bipolar patients and their relatives regarding genetics, biology, personality traits, temperaments and stressful lived life experiences. Bipolar patients and their siblings had significantly higher global score of life events and more events in the field of work, socio-family events and health than control subjects. This might suggest that patients with bipolar disorder would be distinguished from their family members by the coping strategies they use to deal with stress.ObjectivesIn this study, we aimed to compare perceived stress and coping strategies of remitted bipolar I patients with those of their siblings and controls.MethodsA descriptive and comparative study of case-control type was conducted. Were included 46 bipolar I patients, 46 siblings and 50 controls. The three groups were matched for age and sex. Assessments of perceived stress and coping strategies were performed using the 10-item Perceived Stress Scale (PSS) and the 28-item Brief COPE respectively.ResultsMean age of bipolar I patients was 39 ± 13 years. Thirty-one patients (67%) reported family history of one or more psychiatric disorders.Mean duration of bipolar disorder was 11.83 ± 9.92 years.There was no significant difference between the three groups on PSS scores. Bipolar patients and siblings were more likely to use emotion-focused coping strategies than controls (p=0.001). Controls used problem-focused coping strategies more than bipolar patients (p = 0.02). Compared to controls, bipolar patients were less likely to use active coping and planning, but they showed higher scores in the dimensions of humor, religion and behavioral disengagement with intergroup p value: 0.02; 0.019; 0.002 respectively.ConclusionsOur findings suggest that bipolar I patients were more likely to use maladaptive coping strategies to deal with stress than their siblings. Based on this observation, it seems advisable to study coping strategies used by bipolar patients, in order to reinforce adaptive strategies and to reduce maladaptive ones.Disclosure of InterestNone Declared

Metabolic syndrome in people living with antiretroviral therapy: A cross-sectional investigation from Pune, India.

Improved longevity of people living with HIV on highly active antiretroviral therapy and accelerated aging processes are considered contributory to Metabolic Syndrome. The current study investigated metabolic syndrome (MetS) in people living with HIV (PLH) who were receiving antiretroviral therapy (ART) under the ongoing National AIDS Control Program. Clinic attendees (n = 3088) who were on ART for more than 6 months constituted the sampling frame, from which 378 study participants were randomly drawn and included in the analysis following the eligibility check. One hundred and fifty-nine clinic attendees, initiated on ART in ≤6 months, provided an opportunity to estimate the prevalence of MetS in them. Sixty-two PLH from this smaller group were enrolled. MetS was found among 19% (73/378; 95% confidence interval [CI] 15.5%-23.7%) PLH who were on ART >6 months compared with 24% (15/62; 95% CI 14.2%-36.7%) in those who were on ART for ≤6 months based on harmonization criteria for the Asian population; the confidence intervals overlapped and apparently observed difference was not statistically significant. Adjusted for age, body mass index (BMI), protease inhibitor (PI)-based ART regimen, duration of ART, insulin resistance (IR), reported family history of hypertension and residential setting, factors independently associated with MetS were PI containing ART regimen, IR, duration of ART intake and BMI. In the adjusted model, the odds of MetS were three times higher among PLH on PI containing ART regimen (95% CI of adjusted odds ratio; aOR 1.27-8.51) and those having IR (95% CI of aOR 1.48-5.07). The odds of MetS among PLH with BMI ≥23 kg/m2 was 4 (95% CI of aOR 2.08-6.81) times higher than those with lower BMI. MetS in PLH requires the attention of health-care workers in India. Appropriate screening would help initiate early management.