Helmi, Haytham

AbstractPrimary care physicians (PCPs) are commonly approached with concerns involving patient genetics. This is a challenge because most PCPs lack expertise in genetic testing compared to their genetic counselor counterparts. Currently, the recommended best practice is to refer patients for genetic testing based on cancer‐related family history questionnaires with a genetic counseling referral to discuss their results and any implications. However, the extent to which PCPs are using these questionnaires for this purpose remains poorly understood. In this cross‐sectional study, PCPs were presented with the American Cancer Society's seven recommended family history questions to determine the percentage who consider each to be an indicator for referral to a genetics specialist. Questionnaires were completed by 88 of 260 attending PCPs at a national primary care review conference. The main outcome was the percentage of PCPs who identified each question as a trigger for genetic testing. Secondary outcomes included correlations with years of practice, genetics training, and methods used to obtain patient family history. Only two of the seven questions were considered triggers by most PCPs (range, 76–83%). The remaining five had lower percentages (range, 22–55%). Years of practice did not influence the number of triggers identified (Spearman correlation coefficient test: r = 0.05, p = 0.68). Few PCPs (3.4%) felt they had good to excellent genetics training during residency. Only 44.3% had genetics specialists available for referral. Overall, low percentages of PCPs consider the American Cancer Society questions to be triggers for genetic testing referrals. Furthermore, many do not have a genetics specialist or counselor available for referral. Addressing these concerns may help PCPs understand the basics of genetic testing and use standardized questionnaires to make appropriate referrals to genetic specialists, thereby reducing inappropriate referrals and improving appointment access to this precious resource for those who truly need it.

We describe the phenotype of a patient with extensive aortic, carotid, and abdominal dissections. The proband was found to have a heterozygous deletion of exons 21–34 inMYLK, which is a rare finding, as deletions in this gene have been infrequently reported. We describe this finding following detection in a proband with an extensive history of aortic, carotid, and abdominal dissections. Neoteric molecular modeling techniques to help determine the impact of this deletion on protein function indicated loss of function due to lack of any kinase domain. We also provide the electrostatics calculations from the wild type and mutant variant. Through a combined multiomic approach of clinical, functional, and protein informatics, we arrive at a data fusion for determination of pathogenicity embedded within the genetic code for this particular genetic variant, which, as a platform, continues to broaden its scope across the field of variants of uncertain significance classification.

Pulmonary arterial hypertension (PAH) is a devastating disease with significant morbidity and mortality. There are many psychosocial and financial implications of this disease; however, little is known how this affects the treatment of PAH patients. A questionnaire-based prospective cohort study was performed on 106 PAH patients from a Pulmonary Hypertension Center and the Pulmonary Hypertension Association national conference in 2018. The demographic, treatment, psychosocial, employment, financial impact on treatment data was obtained. The majority of patients had cardiopulmonary symptoms despite treatment. The symptoms affected their social and work lives, with about one in three applying for disability because of their PAH. The majority of PAH patients had insurance coverage, but still noted a significant financial burden of the disease, with nearly a half who needed financial assistance to pay for their PAH medications. Thirty (28.3%; 95% CI, 20.6–37.5%) patients mentioned they changed their medication regimen, with some skipping doses outright (28 [26.4%; 95% CI, 19–35.6%]) in order to save money. PAH continues to cause significant psychosocial and financial burden on patients despite advances in medications. This impact ranged from dissatisfaction with quality of life, to unemployment, to altering their medication regimen to save money.

Background Artificial Intelligent Virtual Assistants (AIVA) is a segment of artificial intelligence that is rapidly developing. However, its utilization to address patients' frequently asked questions remains unexplored. Methods We developed an AIVA to answer questions related to 10 frequent topics asked by plastic surgery patients in our institution. Between July 27, 2018, and August 10 of 2018, we recruited subjects with administrative positions at our health care institution to chat with the virtual assistant. They asked, with their own words, 1 question for each topic and filled out a satisfaction questionnaire. Postsurvey analysis of questions and answers allowed assessment of the virtual assistant's accuracy. Results Thirty participants completed the survey. The majority was female (70%), and the mean age was 27.76 years (SD, 8.68 [19–51] years). The overall accuracy of the plastic surgery AIVA was 92.3% (277/294 questions), and participants considered the answer correct in 83.3% of the time (250/294 answers). Most of the participants considered the AIVA easy to use, answered adequately, and could be helpful for patients. However, when asked if this technology could replace a human assistant, they stayed neutral.

Background. The ATP-binding cassette, subfamily D, member 1 (ABCD1) protein is a peroxisomal half-transporter that allows for very long chain fatty acid (VLCFA) degradation. Pathogenic variants of ABCD1 cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype. For example, the Addison-only form of X-ALD has no neurological impact, while the cerebral form of X-ALD often causes severe sensory loss, motor function impairment, cognitive decline, and death. Methods. A newly characterized and suspected pathogenic variant in ABCD1 was analyzed using our protein informatics platform (PIP). Personalized protein-level molecular studies were completed on genetic testing data, complementing the analysis and clinical study. Results. A case of adult onset adrenomyeloneuropathy (AMN) and a novel ABCD1 variant are presented. The unique ABCD1 protein is discussed, and the proband’s case is compared to existing reports of AMN. Conclusions. Data fusion from multiple sources was combined in a comprehensive approach yielding an enriched assessment of the patient’s disease and prognosis. Molecular modeling was performed on the variant to better characterize its clinical significance and confirm pathogenicity.

Abstract Background Bacteremia due to Staphylococcus aureus is a known complication of liver transplantation (LT). Studies have shown that LT recipients are more predisposed to S. aureus infections than other solid-organ transplant patients; however, these studies have been limited in scope and mostly based out of single centers. Methods This is a retrospective cohort study using 2012–2016 NIS, the largest public inpatient database in the United States. All patients with ICD9-10CM procedural codes for LT were included. The cohort was stratified into two groups depending on whether they had MSSA or MRSA infection. The odds of inpatient mortality in both groups of patients undergoing LT were determined. The inpatient mortality odds were then compared with those of patients undergoing LT without associated S. aureus infection. Other outcomes included inpatient morbidity, resource utilization, hospital length of stay (LOS), and inflation-adjusted total hospital costs and charges. Multivariate regression analyses were used to adjust for demographic variables and Charlson Comorbidity Index. Results A total of 26,415 patients underwent LT in the study period, of which 180 had MSSA and 160 had MRSA infection reported. The mean age was 51.5 years and 35.6% were female. Patients with MSSA and MRSA displayed significantly higher inpatient mortality rates (11.1% and 9.4%, respectively) compared with non-MSSA/MRSA patients (3.4%) who underwent LT (P < 0.01). After adjusting for confounders, patients with MSSA infection displayed higher mortality odds (aOR: 4.45, P < 0.01), while patients with MRSA infection had non-statistically significant higher inpatient mortality odds (aOR: 3.10, P = 0.12) compared with patients without MSSA/MRSA infection. Both MSSA and MRSA cohorts displayed higher mortality odds if the infection resulted in sepsis (aOR: 9.92 and 5.70, respectively; P < 0.01). Conclusion There is a direct correlation between S. aureus bacteremia and increased mortality rates and incidence of sepsis and shock in LT recipients. Patients with S. aureus bacteremia spent more days in hospital and had higher cost of healthcare. Preventing and aggressively treating S. aureus infections in the immediate post-LT setting is key to reducing mortality, morbidity and resource utilization in patients undergoing LT. Disclosures All authors: No reported disclosures.

Background and objectives: Loeys–Dietz syndrome 3, also known as aneurysms-–osteoarthritis syndrome, is an autosomal dominant genetic connective tissue disease caused by pathogenic variants in SMAD3, a transcription factor involved in TGF-β signaling. This disorder is characterized by early-onset osteoarthritis and arterial aneurysms. Common features include scoliosis, uvula abnormalities, striae, and velvety skin. Materials and Methods: The pathogenicity of a variant of uncertain significance in the SMAD3 gene was evaluated (variant c.220C > T) through personalized protein informatics and molecular studies. Results: The case of a 44-year-old male, who was originally presumed to have Marfan syndrome, is presented. An expanded gene panel determined the probable cause to be a variant in SMAD3, c.220C > T (p.R74W). His case was complicated by a history of stroke, but his phenotype was otherwise characteristic for Loeys–Dietz syndrome 3. Conclusion: This case emphasizes the importance of comprehensive genetic testing to evaluate patients for connective tissue disorders, as well as the potential benefit of utilizing a protein informatics platform for the assessment of variant pathogenicity.