Educational tools support informed decision-making for genetic carrier screening in a heterogenic Israeli population.

Reproductive genetic carrier screening (RGCS) aims to provide couples with information to make informed decisions. Since 2013, the Israeli Carrier Screening Program has been offered routinely and free of charge to all Israelis of reproductive age, personalized based on religion, ethnicity, and village/tribe where a disorder is frequent. This study evaluated the impact of two educational tools on an informed choice on RGCS uptake and satisfaction with counselling within a heterogeneous population in northern Israel. Participants from diverse sociodemographic population groups were randomly assigned to watch an animated film, read a booklet conveying the same information, or receive no information before counselling for RGCS, and asked to complete pre- and post-counselling questionnaires. A higher informed-decision rate was demonstrated in the film (n=93/141, 66%) and booklet (n=88/131, 67%) groups vs. the non-intervention group (n=62/143, 43%) (P<0.001), assessed by the Multidimensional Measure of Informed Choice. Multivariate logistic regression analysis revealed that allocation to an intervention group, Jewish ethnicity and higher education level, best predicted informed choice. Most participants expressed high levels of satisfaction with the counselling process, regardless of group assignment. While only a minority of participants reported seeking information prior to visiting the clinic, the pre-counselling information interventions were well accepted. Pre-counselling self-learning educational tools should be promoted, easily available, and adjusted linguistically and culturally to targeted populations, to avoid unwanted "automatic" compliance of tested individuals and maximize the potential of informed decision-making. Our study can be applied to other countries where majority and minority ethnic groups access genetic services.

The SARS-CoV-2 responsible for phlegmasia cerulea dolens: a case report.

Coronavirus disease 2019 (COVID-19) is a worldwide pandemic systemic infection that is responsible for serious coagulopathies similar to disseminated intravascular coagulation. Case Presentation: The authors report the case of a COVID-19 patient who presented with phlegmasia cerulea dolens (PCD) of the left lower limb, so he benefited from aponeurotomies of the internal and anterolateral muscular compartments. Clinical Discussion: The severe acute respiratory syndrome coronavirus 2 involves an inflammatory process in thrombotic events in COVID-19 patients, including a cytokine storm. PCD evolves in three semiological phases: venous stasis, weakening of the pulses, and the constitution of major ischemia. In the literature, the authors find many reports that have been published regarding increased thrombus formation in COVID-19 patients; these include DVT formation, pulmonary embolism, and stroke. Nevertheless, publications concerning PCD in COVID-19 patients remain rare. Conclusion: Although the severe acute respiratory syndrome coronavirus 2 remains a thrombogenic pathology, systematic anticoagulation is the subject of hypothesis. Hence the importance of regular monitoring of markers of vascular thrombosis.

Acute limb ischemia due to diclofenac sodium iatrogenic intra-arterial injection: a case report.

Diclofenac sodium is a nonsteroidal anti-inflammatory, the injection of which by the intra-arterial route can lead to serious vascular complications, including limb ischemia. Case presentation: We report the case of accidental intra-arterial injection of diclofenac sodium in the brachial artery leading to acute limb ischemia. Clinical discussion: Iatrogenic intra-arterial injection is rarely reported in the literature; however, it is toxic and can lead to limb amputation. Only two cases of intra-arterial injection of diclofenac have been reported in the literature. The proposed pathophysiological mechanism is vasospasm, intravascular thrombosis, and chemical endoarteritis. The most common anatomical location in accidental intra-arterial injection is the antecubital fossa, where branches of the ulnar and brachial arteries are more superficial. Conclusion: The injection of medication must be as careful as possible, since the intra-arterial injection can affect the functional prognosis of the organ.

Cannabis arteritis: A case report and brief review of the literature.

Introduction: Cannabis is commonly misused psychoactive drug which is known to be associated with a number of psychotic and somatic side-effects. Cannabis arteritis is a rare vascular disorder, since only about fifty cases have been reported in the literature. Case presentation: We report a case of a 40-year-old chronic cannabis user male, who was admitted for painful necrosis of the fifth toe of the right foot. The etiological investigation ruled out the main causes of juvenile arterial disease. Therefore cannabis was the only causative factor found in this patient. An amputation of the fifth toe was performed 20 days later of administrating Prostacyclin (Iloprost) , with a good postoperative improvement. Discussion: The main causes of juvenile arterial disease are: atheromatous arterial disease, thromboangiitis obliterans (Buerger's disease) , systemic or autoimmune diseases. The diagnosis of cannabis arteritis remains a diagnosis of exclusion. it remains a rare phenomenon which is responsible for various symptoms, which can go as far as the amputation of the limb. Several authors have classified cannabis arteritis as a clinical form of Buerger's disease, due to similar clinical semiology and similar appearance at arteriography. Nowadays, we don't know exactly the histopathologic patterns of this pathology. Conclusion: Although several therapeutic options exist, Cannabis weaning still the main part of cannabis arteritis treatment.

Concomitant variants in NF1, LZTR1 and GNAZ genes probably contribute to the aggressiveness of plexiform neurofibroma and warrant treatment with MEK inhibitor.

Neurofibromatosis 1 (NF1) is caused by germline mutations in the NF1 gene and manifests as proliferation of various tissues, including plexiform neurofibromas. The plexiform neurofibroma phenotype varies from indolent to locally aggressive, suggesting contributions of other modifiers in addition to somatic loss of NF1. In this study, we investigated a life-threatening plexiform neurofibroma in a 9-month-old female infant with NF1. Germline mutations in two RASopathy-associated genes were identified using whole-exome sequencing-a de novo pathogenic variant in the NF1 gene, and a known pathogenic variant in the LZTR1 gene. Somatic analysis of the plexiform neurofibroma revealed NF1 loss of heterozygosity and a variant in GNAZ, a gene encoding a G protein-coupled receptor. Cells expressing mutant GNAZ exhibited increased ERK 1/2 activation compared to those expressing wild-type GNAZ. Taken together, we suggest the variants in NF1, LZRT1 and GNAZ act synergistically in our patient, leading to MAPK pathway activation and contributing to the severity of the patient's plexiform neurofibromatosis. After treatment with the MEK inhibitor, trametinib, a prominent clinical improvement was observed in this patient. This case study contributes to the knowledge of germline and somatic non-NF1 variants affecting the NF1 clinical phenotype and supports use of personalized, targeted therapy.

Elevated anti-tissue transglutaminase antibodies in children newly diagnosed with type 1 diabetes do not always indicate coeliac disease.

AIM: Elevated levels of anti-tissue transglutaminase (anti-tTG) antibody may spontaneously normalise in children with newly diagnosed type 1 diabetes, even if they eat gluten. The prevalence of this phenomenon and predictors of a subsequent coeliac disease (CD) diagnosis were determined. METHODS: The medical records of children diagnosed with type 1 diabetes at Ha'Emek Medical Centre, Israel, from 2007 to 2015, were retrospectively reviewed for elevated anti-tTG antibody levels. Demographic, clinical, laboratory and histological findings were compared between CD patients and those with transient coeliac serology. RESULTS: Of 425 patients with new onset type 1 diabetes, 34 (8%) had elevated anti-tTG antibodies: CD was diagnosed in 14, anti-tTG normalisation occurred in 13 and duodenal biopsies did not suggest CD in seven without anti-tTG antibody normalisation. Protective factors for a subsequent CD diagnosis were older age (p = 0.009) and mildly elevated anti-tTG antibody levels at the time of the type 1 diabetes diagnosis (p = 0.007), and decreased anti-tTG levels within six months of diagnosis (p = 0.03). CONCLUSION: Serological follow-up of a diet containing gluten is recommended for children who have newly diagnosed type 1 diabetes and slightly elevated anti-tTG antibodies with no symptoms that suggest CD.

Clinical and Phenotypic Differences in Inflammatory Bowel Disease Among Arab and Jewish Children in Israel.

BACKGROUND: Data on inflammatory bowel disease (IBD) phenotypes among the Arab population in Israel or in the neighboring Arab countries is scarce. AIM: We aimed to assess differences in disease phenotype among Arab and Jewish children living in Israel. METHODS: We performed a retrospective chart review of pediatric IBD cases, which were diagnosed at the Schneider Children's Medical Center and Ha'Emek Medical Center in Israel between 2000 and 2014. Demographic, clinical, and phenotypic variables were compared between Arabs and Jews from Eastern (Sephardic) and Western (Ashkenazi) origin. RESULTS: Seventy-one Arab children with IBD were compared with 165 Ashkenazi and 158 Sephardic Jewish children. Age and gender did not differ between groups. Sephardic and Ashkenazi Jewish Crohn's disease (CD) patients had significantly more stenotic behavior (24 and 26 vs. 5%, p = 0.03) and less fistulzing perianal disease (15 and 11 vs. 31%, p = 0.014) compared with Arab patients. Arab children with ulcerative colitis (UC) had more severe disease at diagnosis compared to Sephardic and Ashkenazi Jews reflected by higher Pediatric UC Activity Index (45 vs. 35 and 35, respectively, p = 0.03). Arab patients had significantly lower proportion of anti-Saccharomyces cerevisiae antibodies positivity (in CD) and perinuclear anti-neutrophil cytoplasmic antibodies positivity (in UC) than both Sephardic and Ashkenazi Jewish children (23 vs. 53 and 65%, p = 0.002 and 35 vs. 60 and 75%, respectively, p = 0.002). CONCLUSION: Arab and Jewish children with IBD differ in disease characteristics and severity. Whether genetic or environmental factors are the cause for these differences is yet to be determined.