Anthony Haddad

β-Thalassemia Intermedia: A Bird's-Eye View.

Beta-thalassemia is due to a defect in the synthesis of the beta-globin chains, leading to alpha/beta imbalance, ineffective erythropoiesis, and chronic anemia. The spectrum of thalassemias is wide, with one end comprising thalassemia minor, which consists of a mild hypochromic microcytic anemia with no obvious clinical manifestations, while on the other end is thalassemia major, characterized by patients who present in their first years of life with profound anemia and regular transfusion requirements for survival. Along the spectrum lies thalassemia intermedia, a term developed to describe patients with manifestations that are neither mild enough nor severe enough to be classified in the spectrum’s extremes. Over the past decade, our understanding of β-thalassemia intermedia has increased tremendously with regards to molecular information as well as pathophysiology. It is now clear that β-thalassemia intermedia has a clinical presentation as well as complications associated with the disease that are different from those of β-thalassemia major. This review is designed to tackle issues related to β-thalassemia intermedia from the basic definition of the disease to paramedical issues, namely the quality of life in these patients. Genetics and pathophysiology are revisited, as well as the complications specific to this disease. These complications include effects on several organ systems, including the cardiovascular, hepatic, endocrine, renal, brain, and skeletal systems. Extramedullary hematopoiesis is also discussed in this article. Risk factors are highlighted and cutoffs are identified to minimize morbidities in β-thalassemia intermedia. Several treatment modalities are considered by shining a light on the pros and cons of each modality, as well as the role of special pharmacological agents in the progress of the disease and its morbidities. Finally, health-related quality of life is discussed in these patients with a direct comparison to the more severe β-thalassemia major.

Skin Substitutes and Bioscaffolds : Temporary and Permanent Coverage

Advancements in surgical wound treatment have led to skin substitutes and bioscaffolds as temporary and permanent coverage for burn wounds. Skin substitutes are used to improve wound coverage and restore the functional and aesthetic qualities of skin, and help to prevent wound infection and maintain a moist wound healing environment. Although allografts are preferred when autografts are not possible, high costs and limited availability have led to the use of xenografts and the development of skin substitutes and bioscaffolds. Despite constant evolution in the development of these skin substitutes and bioscaffolds, no single product stands out as the gold standard.

Preventing Thalassemia in Lebanon: Successes and Challenges in a Developing Country

Abstract Thalassemia continues to be a major health burden. The chronicity of the disease and the high cost of life-long treatment make prevention strategies crucial in the management of this disease. In this article, we revisit different successful prevention strategies, and underline the Lebanese model. The Chronic Care Center (CCC), Beirut, is the only specialized center in Lebanon for the treatment and prevention of thalassemia. The current number of patients registered up to August 2013 was 724, representing cases from all over Lebanon. In 1994, the center launched a national prevention program following the World Health Organization (WHO) recommendations. The major activities of the program include awareness campaigns, screening for thalassemia carriers in the general population and high risk groups, registry of new cases and follow-up on the mandatory premarital law (established at the same time). Screening programs showed a carrier rate of around 2.3% in the general population, and 4.0–41.0% in high risk groups. The major pitfall in the law is that only persons with a mean corpuscular volume (MCV) of >70.0 fL are asked to perform further hemoglobin (Hb) testing. A significant decrease in the number of new cases of thalassemia patients in Lebanon reflects the efforts deployed in the prevention of the disease. However, some limitations are faced in reaching a complete eradication of the disease, mainly due to the fact that abortion is illegal and due to pitfalls and incorrect implementation of the premarital law.

Novel approach to reactive oxygen species in nontransfusion-dependent thalassemia.

The term Nontransfusion dependent thalassaemia (NTDT) was suggested to describe patients who had clinical manifestations that are too severe to be termed minor yet too mild to be termed major. Those patients are not entirely dependent on transfusions for survival. If left untreated, three main factors are responsible for the clinical sequelae of NTDT: ineffective erythropoiesis, chronic hemolytic anemia, and iron overload. Reactive oxygen species (ROS) generation in NTDT patients is caused by 2 major mechanisms. The first one is chronic hypoxia resulting from chronic anemia and ineffective erythropoiesis leading to mitochondrial damage and the second is iron overload also due to chronic anemia and tissue hypoxia leading to increase intestinal iron absorption in thalassemic patients. Oxidative damage by reactive oxygen species (generated by free globin chains and labile plasma iron) is believed to be one of the main contributors to cell injury, tissue damage, and hypercoagulability in patients with thalassemia. Independently increased ROS has been linked to a myriad of pathological outcomes such as leg ulcers, decreased wound healing, pulmonary hypertension, silent brain infarcts, and increased thrombosis to count a few. Interestingly many of those complications overlap with those found in NTDT patients.

Moderate-intensity Intermittent External Volume Expansion Optimizes the Soft-tissue Response in a Murine Model.

Background: Intermittent external volume expansion using suction enhances the vascular network of soft tissues, possibly increasing fat graft survival. However, the optimal kinetics of application have not been determined. Based on their previous experience, the authors hypothesized that moderate-intensity intermittent external volume expansion application may further enhance both the angiogenic and adipogenic potential. Methods: Fifty 12-week-old wild-type mice were assigned to five experimental groups (n = 10 per group) and underwent five different intermittent applications of external volume expansion (i.e., single-application control, low-intensity, moderate-intensity, and two groups of high-intensity). Five days after the final stimulation, skin biopsy specimens were obtained from stimulated and contralateral nonstimulated areas. Microscopic sections were analyzed for angiogenesis, skin remodeling, and adipogenesis. Results: Moderate-intensity intermittent stimulation (0.5 hour, 6 times/day for 5 days at −25 mmHg suction) almost doubled cutaneous vascular density (1.9-fold increase), induced skin thickening (1.9-fold increase), and expanded the subcutaneous tissue (2.3-fold increase) compared with control. External volume expansion kinetics did not affect tissue inflammation at 5 days after treatment. High-intensity intermittent stimulations also increased the density of blood vessels (1.6-fold increase compared with controls) but caused tissue damage, whereas low-intensity external volume expansion did not induce significant changes. Conclusion: Application of moderate-intensity intermittent external volume expansion optimizes induction of angiogenesis and adipogenesis in soft tissues without tissue damage, holding potential for time-effective recipient-site preconditioning before fat grafting.

Hyperspectral Imaging Provides Early Prediction of Random Axial Flap Necrosis in a Preclinical Model

Background: Necrosis remains a significant complication in cutaneous flap procedures. Monitoring, and ideally prediction, of vascular compromise in the early postoperative period may allow surgeons to limit the impact of complications by prompt intervention. Hyperspectral imaging could be a reliable, effective, and noninvasive method for predicting flap survival postoperatively. In this preclinical study, the authors demonstrate that hyperspectral imaging is able to correlate early skin perfusion changes and ultimate flap survival in a preclinical model. Methods: Thirty-one hairless, immunocompetent, adult male mice were used. Random pattern dorsal skin flaps were elevated and sutured back into place with a silicone barrier. Hyperspectral imaging and digital images were obtained 30 minutes, 24 hours, or 72 hours after flap elevation and before sacrifice on postoperative day 7. Results: Areas of high deoxygenated hemoglobin change (124; 95 percent CI, 118 to 129) seen at 30 minutes after surgery were associated with greater than 50 percent flap necrosis at postoperative day 7. Areas demarcated by high deoxygenated hemoglobin at 30 minutes postoperatively had a statistically significant correlation with areas of macroscopic necrosis on postoperative day 7. Analysis of images obtained at 24 and 72 hours did not show similar changes. Conclusions: These findings suggest that early changes in deoxygenated hemoglobin seen with hyperspectral imaging may predict the region and extent of flap necrosis. Further clinical studies are needed to determine whether hyperspectral imaging is applicable to the clinical setting.

Priapism, an emerging complication in β-thalassemia intermedia patients.

Abstract The increase in survival rate of β-thalassemia (β-thal) patients allowed for the appearance and manifestation of several complications in almost every organ system. Priapism in β-thal patients is rarely reported in the literature. We herein report and investigate the occurrence of two cases of priapism in two young patients with β-thal intermedia (β-TI). The potential mechanisms are due to either a cellular mechanism involving a thrombus obstructing the efferent venules of the corpora cavernosa leading to priapism, or a recently elucidated functional mechanism that causes alteration of nitric oxide (NO) response of the penis, ultimately causing priapism. This should incite clinicians for a close follow-up and monitoring of high risk patients who are susceptible to developing priapism.

Preclinical Optimization of a shelf-ready, human-derived, decellularized Allograft Adipose Matrix

IMPACT STATEMENT Trauma, disease, surgery, or congentital defects can cause soft tissue losses in patients, leading to disfigurement, functional impairment, and a low quality of life. In the lack of available effective methods to reconstruct these defects, acellular adipose matrices could provide a novel therapeutic solution to such challenge.

Injectable Shape-Memorizing 3D Hyaluronic Acid Cryogels (3D MA-HA) for Skin Sculpting and Soft Tissue Reconstruction.

INTRODUCTION Hyaluronic acid (HA)-based fillers are used for various cosmetic procedures. However, due to filler migration and degradation, reinjections of the fillers are often required. Methacrylated HA (MA-HA) can be made into injectable shape-memorizing fillers (three-dimensional [3D] MA-HA) aimed to address these issues. In this study, shape retention, firmness, and biocompatibility of 3D MA-HA injected subcutaneously in mice were evaluated. MATERIALS AND METHODS Fifteen mice, each receiving two subcutaneous injections in their back, were divided into four groups receiving HA, MA-HA, 3D MA-HA, or saline, respectively. Digital imaging, scanning electron microscope (SEM) and in vivo imaging system (IVIS), durometry, and histology were utilized to evaluate in vitro/vivo degradation and migration, material firmness, and the angiogenic (CD31) and immunogenic (CD45) response of the host tissue toward the injected materials. RESULTS Digital imaging, SEM, and IVIS revealed that 3D MA-HA fillers maintained their predetermined shape for at least 30 days in vitro and in vivo. Little volume effects were noted in the saline and other control groups. There were no differences in skin firmness between the groups or over time. Histology showed intact skin architecture in all groups. Three-dimensional MA-HA maintained its macroporous structure with significant angiogenesis at the 3D MA-HA/skin interfaces and throughout the 3D MA-HA. There was no significant inflammatory response to any of the injected materials. CONCLUSION 3D MA-HA showed remarkable tissue compatibility, compliance, and shape predictability, as well as retention, and thus might be suitable for various skin sculpting and soft tissue reconstruction purposes.

Post-partum ovarian vein thrombosis: combined effect of infection and factor v leiden mutation.

To the Editor, Ovarian vein thrombosis (OVT) is a rare complication of pregnancy that mainly affects women in their 3rd or 4th decade. Numerous etiologies have been proposed, including ones of idiopathic origin. Early therapy with anticoagulants can be lifesaving; hence, a high index of suspicion is important in order to avoid serious complications such as pulmonary embolism (14%), sepsis, and death [1]. In this letter, an attempt at uncovering one of the etiologies to further solidify our understanding of the disease is made. A 34-year-old female, gravida 3, para 3, presented on the fifth day after an uncomplicated normal vaginal delivery with right lower quadrant pain, fever, and chills. She had been diagnosed with Behcet’s disease 8 years ago and was maintained on colchicine and steroids for 2 years, which were stopped later. The patient denied previous episodes of deep vein thrombosis (DVT), as well as family history of hypercoagulable diseases. The course of her pregnancy was uneventful except for a positive rectovaginal culture for beta-hemolytic group B streptococci, for which she received Post-Partum Ovarian Vein Thrombosis: Combined Effect of Infection and Factor V Leiden Mutation Post-Partum Yumurtalik Ven Trombozu: Enfeksiyon ve Faktor V Leiden Mutasyonunun Birlesik Etkisi