Genomic profiling informs diagnoses and treatment in vascular anomalies.

Vascular anomalies are malformations or tumors of the blood or lymphatic vasculature and can be life-threatening. Although molecularly targeted therapies can be life-saving, identification of the molecular etiology is often impeded by lack of accessibility to affected tissue samples, mosaicism or insufficient sequencing depth. In a cohort of 356 participants with vascular anomalies, including 104 with primary complex lymphatic anomalies (pCLAs), DNA from CD31+ cells isolated from lymphatic fluid or cell-free DNA from lymphatic fluid or plasma underwent ultra-deep sequencing thereby uncovering pathogenic somatic variants down to a variant allele fraction of 0.15%. A molecular diagnosis, including previously undescribed genetic causes, was obtained in 41% of participants with pCLAs and 72% of participants with other vascular malformations, leading to a new medical therapy for 63% (43/69) of participants and resulting in improvement in 63% (35/55) of participants on therapy. Taken together, these data support the development of liquid biopsy-based diagnostic techniques to identify previously undescribed genotype-phenotype associations and guide medical therapy in individuals with vascular anomalies.

An evaluation of preference stability within MSWO preference assessments for children with autism.

Previous research has commonly evaluated preference stability over time and across multiple preference assessment administrations. No studies have evaluated shifts in preference across consecutive rounds of a single preference assessment, where rounds refer to each time the experimenter resets the stimulus-presentation array. The purpose of the present study was to examine the stability of stimulus selections across successive rounds of a multiple-stimulus-without-replacement (MSWO) preference assessment with different classes of stimuli for children with autism. The study involved a secondary data analysis and calculation of preference stability across consecutive rounds using Spearman rank-order correlation coefficients (Spearman's ρ ) for 17 participants across 40 MSWO preference assessments. Patterns of preference stability were observed in 24 out of the 40 assessments (60%) indicating that children's preferences in this study were slightly more likely to be classified as stable than other observed patterns of responding.

COVID-19 in pediatrics: Genetic susceptibility.

The uptick in SARS-CoV-2 infection has resulted in a worldwide COVID-19 pandemic, which has created troublesome health and economic problems. We performed case-control meta-analyses in both African and European ethnicity COVID-19 disease cases based on laboratory test and phenotypic criteria. The cases had laboratory-confirmed SARS-CoV-2 infection. We uniquely investigated COVID infection genetics in a pediatric population. Our cohort has a large African ancestry component, also unique to our study. We tested for genetic variant association in 498 cases vs. 1,533 controls of African ancestry and 271 cases vs. 855 controls of European ancestry. We acknowledge that the sample size is relatively small, owing to the low prevalence of COVID infection among pediatric individuals. COVID-19 cases averaged 13 years of age. Pediatric genetic studies enhance the ability to detect genetic associations with a limited possible environment impact. Our findings support the notion that some genetic variants, most notably at the SEMA6D, FMN1, ACTN1, PDS5B, NFIA, ADGRL3, MMP27, TENM3, SPRY4, MNS1, and RSU1 loci, play a role in COVID-19 infection susceptibility. The pediatric cohort also shows nominal replication of previously reported adult study results: CCR9, CXCR6, FYCO1, LZTFL1, TDGF1, CCR1, CCR2, CCR3, CCR5, MAPT-AS1, and IFNAR2 gene variants. Reviewing the biological roles of genes implicated here, NFIA looks to be the most interesting as it binds to a palindromic sequence observed in both viral and cellular promoters and in the adenovirus type 2 origin of replication.

Rare copy number variants in over 100,000 European ancestry subjects reveal multiple disease associations.

Copy number variants (CNVs) are suggested to have a widespread impact on the human genome and phenotypes. To understand the role of CNVs across human diseases, we examine the CNV genomic landscape of 100,028 unrelated individuals of European ancestry, using SNP and CGH array datasets. We observe an average CNV burden of ~650 kb, identifying a total of 11,314 deletion, 5625 duplication, and 2746 homozygous deletion CNV regions (CNVRs). In all, 13.7% are unreported, 58.6% overlap with at least one gene, and 32.8% interrupt coding exons. These CNVRs are significantly more likely to overlap OMIM genes (2.94-fold), GWAS loci (1.52-fold), and non-coding RNAs (1.44-fold), compared with random distribution (P < 1 × 10-3). We uncover CNV associations with four major disease categories, including autoimmune, cardio-metabolic, oncologic, and neurological/psychiatric diseases, and identify several drug-repurposing opportunities. Our results demonstrate robust frequency definition for large-scale rare variant association studies, identify CNVs associated with major disease categories, and illustrate the pleiotropic impact of CNVs in human disease.

An Evaluation of Patient and Student Experience at a Longstanding Student-run Free Clinic in Cape Town, South Africa.

Background Student-run free clinics (SRFCs) combine medical student learning with the provision of free health care. A comprehensive evaluation of patient experience at SRFCs is needed to ensure a balance between valuable clinical experience for students and enhancement of patient care. The aim of this study was to describe patient and medical student perception of care at a longstanding SRFC at the University of Cape Town (UCT). Methods We conducted an observational study at the Students' Health and Welfare Centres Organisation (SHAWCO), a student-run free clinic at UCT. Trained study staff observed clinical encounters between consenting medical students and patients. We surveyed patients on their demographic characteristics, overall satisfaction, and impressions of medical students and physicians at SHAWCO. We surveyed medical students on their level of training, motivation for volunteering, and future career plans. We linked all data from each clinical encounter by a study-generated identification number. Results We surveyed a total of 34 patients and 52 medical students on their experience at SHAWCO. All patients either strongly agreed (88%) or agreed (12%) that they were satisfied with care. Patient satisfaction did not vary with the parameters of care included in multivariable analysis. Patients rated medical students higher than physicians on listening skills, and equally to physicians on all other clinical skills rated. Medical students reported a strong desire to go into primary care and work in underserved settings both before and after volunteering at SHAWCO. Discussion We found a high level of patient satisfaction at SHAWCO, consistent with other studies. Our findings indicate that medical student involvement in care at SRFCs is not a detriment to patient satisfaction.

Surgical management of transitional cell carcinoma of the lacrimal sac: Is it time for a new treatment algorithm?

Transitional cell carcinoma (TCC) arising in the lacrimal sac is a rare neoplasm. Despite radical surgery and radiotherapy, these tumors generally have a poor prognosis due to an often late diagnosis, high rate of loco-regional recurrence and mortality. There are only a relatively small number of documented cases of TCC when compared to other epithelial malignancies of the lacrimal drainage system. As would be anticipated, there are currently no evidence-based clinical practice guidelines for the treatment of these lesions. We present an illustrative case and consider the literature in relation to current surgical management of these tumors. We propose an alternate management consideration for these tumors.