Phenotype, genotype, and outcome of 25 Palestinian patients with hereditary tyrosinemia type 1.

BACKGROUND: Tyrosinemia type 1 (hepatorenal tyrosinemia, HT1) is a rare autosomal recessive inborn error of tyrosine metabolism caused by deficiency of the last enzyme in the tyrosine catabolic pathway, fumarylacetoacetate hydrolase (FAH) leading to severe hepatic, renal and peripheral nerve damage if left untreated. Early treatment may prevent acute liver failure, renal dysfunction, liver cirrhosis, hepatocellular carcinoma (HCC) and improves survival. MATERIAL AND METHODS: A retrospective single center study was carried out based on the clinical and biochemical presentation, therapy and outcome of 25 Palestinian patients with HT1 diagnosed during the last 25 years. RESULTS: HT1 is not included in newborn screening program in Palestine. The mean age at diagnosis was 8 months and the main clinical manifestations were coagulopathy, hepatomegaly, splenomegaly and renal tubular dysfunction. The main biochemical abnormalities were elevated plasma tyrosine, serum transaminases and prothrombin time, and low serum phosphorous with elevated alkaline phosphatase compatible with hypophosphatemic rickets secondary to renal tubular dysfunction. All patients were treated with nitisinone. The mean duration of nitisinone treatment was 74 months and the mean dosage was 0.89 mg/kg/day. None developed HCC or neurological crisis. CONCLUSIONS: Most patients present with liver failure and renal tubular dysfunction. Nitisinone treatment was effective therapy in all patients and improved both short- and long-term prognosis of HT1. Renal tubular dysfunction improved in all patients within the first week of starting nitisinone. Early diagnosis is necessary because delay in the treatment increases the risk of progressive liver failure HCC, progressive renal disease and neuropathy.

The Application of Posttransfer Free Flap Expansion for Management of Severe Foot Crush Injury with Extensive Soft Tissue Loss: A Case Report.

Reconstruction of posttraumatic soft tissue defects has been revolutionized after the application of microvascular free flaps. However, standard flaps are limited in size and may not completely cover the defect. Flap expansion which is indicated in large defects with extensive soft tissue loss or shortage of donor tissue enables tension-free closure of large defects, minimal donor site morbidity, and better aesthetic outcomes. The literature review revealed a higher complication rate in the expansion of free flaps implanted in the extremities. A 7-year-old Palestinian girl presented with right foot crush injury and open multiple metatarsal and tarsal bone fractures with significant soft tissue loss. She underwent free latissimus dorsi flap transfer and overlying skin graft island application followed months later by expander implantation within the flap. This flap was serially expanded once a week for 4 months, until its dimension was declared to be large enough to cover the foot defect. We successfully transferred a free flap to a foot with extensive tissue loss. The overlying skin island contracted and minimized the defect size. The flap was serially expanded until completely covered the defect. No features of vascular compromise or other complications occurred; the flap remained viable with good aesthetic outcome. Posttransfer free flap expansion in lower limb defects can be utilized with meticulous care and follow-up for reconstruction of large defects.

Modulation of Cathepsin L Expression in the Coronary Arteries of Atherosclerotic Swine.

INTRODUCTION: Neointimal hyperplasia (NIH) and restenosis after percutaneous transluminal coronary angioplasty (PTCA) and intravascular stenting remain a problem on a long-term basis by causing endothelial denudation and damage to the intima and media. Vascular sterile inflammation has been attributed to the formation of NIH. Cathepsin L (CTSL), a lysosome protease, is associated with diet-induced atherogenesis. Vitamin D regulates the actions and regulatory effects of proteases and protease inhibitors in different cell types. Objectives of this study are to evaluate the modulatory effect of vitamin D on CTSL activity in post-PTCA coronary arteries of atherosclerotic swine. METHODS: Yucatan microswine were fed with high-cholesterol atherosclerotic diets. The swine were stratified to receive three diets: (1) vitamin D-deficient diet, (2) vitamin D-sufficient diet, and (3) vitamin D-supplement diet. After 6 mo, PTCA was performed in the left circumflex coronary artery (LCx). After 1 y, angiography and optical coherence tomography imaging were performed, and swine was euthanized. Coronary arteries were embedded in paraffin. Tissue sections were stained with hematoxylin and eosin. Expression of Ki67 and CTSL were evaluated by immunofluorescence. RESULTS: Increased number of Ki67 + cells were observed in the postangioplasty LCx in vitamin D-deficient compared with vitamin D-sufficient or vitamin D-supplemented swine. Notably, the expression of CTSL was significantly increased in postangioplasty LCx of vitamin D-deficient swine compared with the vitamin D-sufficient or vitamin D-supplemented animal groups. CONCLUSIONS: Increased expression of CTSL correlates with the formation of NIH in the PTCA-injured coronary arteries. However, in the presence of sufficient or supplemented levels of vitamin D in the blood, CTSL expression was significantly reduced.

Vitamin B12 status among pregnant women and Its association with obesity and gestational diabetes

Background: pregnant women in resource-poor areas are at risk of multiple micronutrient deficiencies, and diets that are low in animal products place women at increased risk of vitamin B12 deficiency. Aim of the Work: to investigate the vitamin B12 status of pregnant women in Egypt and its relationship with obesity and gestational diabetes mellitus (GDM). Patients and Methods: this clinical observational prospective study has been conducted at Bab Al-Shaaria University Hospital Obstetrics and Gynecological Department from April 2018 to January 2019. To assess vitamin B12 status among pregnant woman and its association with obesity and gestational diabetes. 80 pregnant women attended to out-patient clinic were included in the study. The evaluation included data collection through: history taking, examination, anthropometric measurement, maternal blood vitamin B12 level estimation at second and third trimester and blood glucose level. Results: vitamin B12 deficiency in pregnancy is common particularly in obese women and those with GDM. Conclusion: vitamin B12 deficiency is silent and common in general population. Causes of vitamin B12 deficiencies are multifactorial and associated with many health problems. Also, obesity is common and its prevalence is increasing in the world. Therefore, both health problems have gained importance in family medicine practice in the last decades

Free Flap Transfer with Arteriovenous Loop Establishment for Upper Limb Salvage in a Crush Injury.

Constructing arteriovenous (AV) loops saves a crushed limb when healthy recipient vessels are unavailable at the site of injury by supporting a transferred free flap. Literature about using AV loops in the upper limb defect is scarce. We present a case with a devastating upper limb crush injury that was successfully managed with fibula flap transfer preceded by AV loop construction. A 38-year-old woman was admitted to our hospital with severe crushing trauma to her right forearm and hand. There was significant skin loss with injuries to blood vessels and tendons. She underwent multiple staged operations beginning with repair of the ulnar artery, debridement of necrotic tissue, and placement of 2 K-wires to stabilize the bones. Thereafter, a long saphenous AV loop was constructed between the brachial artery and the basilic vein. Finally, transfer of the fibula flap to the forearm. We used the staged procedure to provide adequate time for the AV loop maturation and adaptation. At around the patient's 7-month follow-up visit, her forearm and hand were stable, no complications related to the AV loop or the transferred fibula flap were noted. Utilizing AV loops to support transferred free flaps upper limb defects showed a promising successful outcome.