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One in 10 infants are born with a vascular birthmark each year. Some vascular birthmarks, such as infantile hemangiomas, are common, while vascular malformations, such as capillary, lymphatic, venous, and arteriovenous malformations, are less so. Diagnosing uncommon vascular birthmarks can be challenging, given the phenotypic heterogeneity and overlap among these lesions. Both sporadic and germline variants have been detected in various genes associated with vascular birthmarks. Identification of these genetic variants offers insight into both diagnosis and underlying molecular pathways and can be fundamental in the discovery of novel therapeutic approaches. The PIK3/AKT/mTOR and RAS/MEK/ERK signaling pathways, which mediate cell growth and angiogenesis, are activated secondary to genetic variations in vascular malformations. Somatic variants in TEK (TIE2) and PIK3CA cause venous malformations. Variants in PIK3CA also cause lymphatic malformations as well as a number of overgrowth syndromes associated with vascular anomalies. Variants in GNAQ and GNA11 have been identified in both so-called "congenital" hemangiomas and capillary malformations. RASA1 and EPHB4 variants are associated with capillary malformation-arteriovenous malformation syndrome. This review discusses the genetics of vascular birthmarks, including the various phenotypes, genetic variants, pathogenesis, associated syndromes, and new diagnostic techniques.

Objectives:\ud COVID-19 is associated with significant morbidity and mortality. This study aims to synthesize evidence to assess the cost-effectiveness of remdesivir (RDV) for the treatment of hospitalized patients with COVID-19 in England and Wales.\ud \ud Methods:\ud A probabilistic cost-effectiveness analysis was conducted informed by 2 large trials and uses a partitioned survival approach to assess short- and long-term clinical consequences and costs associated with COVID-19 in a hypothetical cohort of hospitalized patients requiring supplemental oxygen at the start of treatment. Given that it is uncertain whether RDV reduces death, 2 analyses are presented, assuming RDV either reduces death or does not. Published sources were used for long-term clinical, quality of life, and cost parameters.\ud \ud Results:\ud Under the assumption that RDV reduces death, the incremental cost-effectiveness ratio for RDV is estimated at £11 881 per quality-adjusted life-year gained compared with standard of care (SoC) (probabilistic incremental cost-effectiveness ratio £12 400). The probability for RDV to be cost-effective is 74% at a willingness-to-pay threshold of £20 000 per quality-adjusted life-year gained. RDV was no longer cost-effective when the hazard ratio for overall survival compared with SoC was >0·915.\ud \ud Conclusions:\ud Results from this study suggest that using RDV for the treatment of hospitalized patients with COVID-19 is likely to represent a cost-effective use of National Health Service resources at current willingness-to-pay threshold in England and Wales, only if it prevents death. Results needs to be interpreted caution as vaccination was introduced and the SoC and evidence available have also evolved considerably since the analysis is conducted.

Transport of bile acids within the enterohepatic circulation from the liver to the intestines via the gallbladder and back to the liver via the portal vein plays a critical role in bile acid regulation and homeostasis. Deficiency of fibroblast growth factor 19 (FGF19), a hormone whose role is to suppress de novo hepatic bile acid synthesis to maintain homeostatic levels, results in bile acid diarrhea (BAD). FGF19 also modulates gallbladder motility so that bile acids are concentrated in the gallbladder until postprandial contraction. To assess bile acid transport and diagnose ailments like BAD that are associated with altered bile acid synthesis and transport, we created bile acid conjugates with nitroxide radicals. Because nitroxides are paramagnetic and can promote proton relaxation, we reasoned that these paramagnetic conjugates should act as contrast agents in in vivo magnetic resonance imaging (MRI). We tested substrate capability by assessing the inhibitory potential of these novel agents against taurocholate uptake by the apical sodium dependent bile acid transporter (ASBT) and the Na

© 2019, American Association of Colleges of Pharmacy. All rights reserved. Objective. To assess final-year pharmacy students’ performance on and evaluate their experience with a “flipped examination” vs a traditional examination for an advanced clinical pharmacy course. Methods. Students devised multiple-choice questions for the flipped examination. The Biggs revised 2-factor Study Process Questionnaire was administered before and after the examination to assess any possible changes in the students’ perceptions of their level of engagement in the learning process. Focus group discussions also were conducted to further gauge the students’ feedback and insights into the flipped examination experience. Results. Changes in mean total study process scores at the deep and surface levels of learning were significant. The flipped examination experience was enjoyable, facilitated a less-stressful learning environment, and improved the students’ learning satisfaction, knowledge, and assessment grades. Conclusion. The flipped examination model is an innovative instructional approach that can bring about significant educational gains if designed well pedagogically.

PHACE syndrome represents the association of large infantile hemangiomas of the head and neck with brain, cerebrovascular, cardiac, ocular, and ventral or midline defects. Cardiac and cerebrovascular anomalies are the most common extracutaneous features of PHACE, and they also constitute the greatest source of potential morbidity. Congenital heart disease in PHACE is incompletely described, and this study was conducted to better characterize its features. This study of the International PHACE Syndrome Registry represents the largest central review of clinical, radiologic, and histopathologic data for cardiovascular anomalies in patients with PHACE to date. Sixty-two (41%) of 150 subjects had intracardiac, aortic arch, or brachiocephalic vessel anomalies. Aberrant origin of a subclavian artery was the most common cardiovascular anomaly (present in 31 (21%) of150 subjects). Coarctation was the second most common anomaly, identified in 28 (19%) of 150 subjects, and can be missed clinically in patients with PHACE because of the frequent association of arch obstruction with aberrant subclavian origin. Twenty-three (37%) of 62 subjects with cardiovascular anomalies required procedural intervention. A greater percentage of hemangiomas were located on the left side of the head and neck in patients with coarctation (46% vs 39%); however, hemangioma distribution did not predict the presence of cardiovascular anomalies overall. In conclusion, PHACE is associated with a high risk of congenital heart disease. Cardiac and aortic arch imaging with detailed assessment of arch patency and brachiocephalic origins is essential for any patient suspected of having PHACE. Longitudinal investigation is needed to determine the long-term outcomes of cardiovascular anomalies in PHACE.

Infantile myofibromatosis (IM) is a disorder of mesenchymal proliferation characterized by the development of nonmetastasizing tumors in the skin, muscle, bone, and viscera. Occurrence within families across multiple generations is suggestive of an autosomal-dominant (AD) inheritance pattern, but autosomal-recessive (AR) modes of inheritance have also been proposed. We performed whole-exome sequencing (WES) in members of nine unrelated families clinically diagnosed with AD IM to identify the genetic origin of the disorder. In eight of the families, we identified one of two disease-causing mutations, c.1978C>A (p.Pro660Thr) and c.1681C>T (p.Arg561Cys), in PDGFRB. Intriguingly, one family did not have either of these PDGFRB mutations but all affected individuals had a c.4556T>C (p.Leu1519Pro) mutation in NOTCH3. Our studies suggest that mutations in PDGFRB are a cause of IM and highlight NOTCH3 as a candidate gene. Further studies of the crosstalk between PDGFRB and NOTCH pathways may offer new opportunities to identify mutations in other genes that result in IM and is a necessary first step toward understanding the mechanisms of both tumor growth and regression and its targeted treatment.

Introduction The number of persons receiving renal replacement therapy (RRT) is estimated at more than 2.5 million worldwide, and is growing by 8% annually. Registries in the developing world are not up to standards compared to the United States Renal Data System (USRDS). Herein we examine the causes, progression, and magnitude of end-stage kidney disease (ESKD) over 3 decades in Oman. Methods We examined ESKD data from 1983 to 2013. Data from 1998 to 2013 were obtained through an Information Management System. Data before 2008 were collected from patients’ files. A questionnaire based on USRDS form 2728 was completed by nephrologists once a citizen reached ESKD. Results A total of 4066 forms were completed, with a response rate of 90% (52% male). The mean (SD) age was 50.1 (14.0) years. By 31 December 2013, there were 2386 patients alive on RRT, of whom 1206 were on hemodialysis (50.5%), 1080 were living with a functioning kidney transplant (45.3%), and 100 were receiving peritoneal dialysis (4.2%). The incidence of ESKD on RRT was 21, 75, and 120 per million population in 1983, 2001, and 2013, respectively. Similarly, the prevalence of ESKD was 49, 916, and 2386 in 1983, 2001, and 2013 respectively. Among patients with ESKD on RRT, a progressive rise was seen in diabetic nephropathy, with 5.8%, 32.1%, and 46% in 1983, 2001, and 2013 respectively. Discussion The incidence and prevalence of ESKD has increased progressively over last 30 years. This is anticipated to continue at an even higher rate in view of the progressive rise in noncommunicable diseases. Continuous improvement in registries is required to improve capturing of ESKD patients for providing accurate data to health authorities, and enhancing public awareness of the magnitude, future trends, treatments, and outcomes regarding ESKD.

Objective To prospectively evaluate a cohort of patients with infantile hemangioma in the midline lumbosacral region for spinal anomalies to determine the positive predictive value of infantile hemangioma for occult spinal anomalies and to make evidence-based recommendations for screening. Study design A multicenter prospective cohort study was performed at 9 Hemangioma Investigator Group sites. Results Intraspinal abnormalities were detected in 21 of 41 study participants with a lumbosacral infantile hemangioma who underwent a magnetic resonance imaging evaluation. The relative risk for all patients with lumbosacral infantile hemangiomas for spinal anomalies was 640 (95% confidence interval [CI], 404-954), and the positive predictive value of infantile hemangioma for spinal dysraphism was 51.2%. Ulceration of the hemangioma was associated with a higher risk of having spinal anomalies. The presence of additional cutaneous anomalies also was associated with a higher likelihood of finding spinal anomalies; however, 35% of the infants with isolated lumbosacral infantile hemangiomas had spinal anomalies, with a relative risk of 438 (95% CI, 188-846). The sensitivity for ultrasound scanning to detect spinal anomalies in this high-risk group was poor at 50% (95% CI, 18.7%-81.3%), with a specificity rate of 77.8% (95% CI, 40%-97.2%). Conclusions Infants and children with midline lumbosacral infantile hemangiomas are at increased risk for spinal anomalies. Screening magnetic resonance imaging is recommended for children with these lesions. (J Pediatr 2010; 157:789-94).

Non-involuting congenital haemangioma (NICH) is a rare cutaneous vascular tumour about which little is known. Fully formed at birth, NICH enlarges proportionally with age but fails to involute as most infantile haemangiomas do. In addition to this unique clinical character, NICH demonstrates several distinct features. Doppler and magnetic resonance imaging (MRI) studies reveal persistent high-flow arterial feeders and a tumour-like capillary blush; however, NICH fails to demonstrate early venous opacification in contrast to arteriovenous malformation (AVM). NICH lesions also contain microscopic dermal arteriovenous fistulas as well as prominent interlobular veins. Here, we present the first known case of NICH-related high-output cardiomyopathy in a 2-year-old boy.