Immune Dysregulation in Myelodysplastic Syndromes: Pathogenetic-Pathophysiologic Aspects and Clinical Consequences

Myelodysplastic syndromes are clonal hematopoietic stem cell disorders, in which the immune system plays a substantial pathogenetic role. Patients manifest frequent infections, mainly attributed to neutropenia, but sometimes opportunistic pathogens are isolated in non-neutropenic patients. They also exhibit autoimmune diseases or syndromes with a background of immune activation and various “abnormalities” of T-lymphocytes, B-lymphocytes, and NK cells. The most typical profile includes reduced total T lymphocytes (mainly CD4+ helper T-cells, resulting in decrease or inversion of the CD4/CD8 cell ratio) and impaired NK cell function. Many TH1 direction cytokines, and particularly sIL-2R, IL-6, and TNF-α are usually found increased in the serum and bone marrow, which have been strongly associated with advanced disease, anemia, and other disease-related features. Clonal origin of lymphocytes has been confirmed only in few cases. Mixed lymphocyte cultures and genomic assays have shown severely impaired immunoregulatory abnormalities, probably induced by the hematopoietic cells. In a minority of patients, immune activation is capable to prevent or delay clonal expansion, but these patients have more profound hematopoietic impairment. Immunosuppressive treatment may not only relieve the autoimmune manifestations but also improve hematopoiesis. However, this kind of treatment is not well tolerated, is associated with severe infections, and in some cases may enhance AML evolution

Impact of Foreign Direct Investment on Economic Growth of the SAARC Countries

Empirical evidence suggests FDI has both growth enhancing and growth diminishing impact on the economic growth. The endogenous growth model supports the view that FDI has significant impact on improving human capital, managerial skills, research and development which in effect improve economic growth. However, “The dependency school theory” argues that importing foreign capital from developed countries is harmful in the long-run for the developing economies. This in effect causes distortion, hinders growth, and increases income inequality in developing countries. In this context, the impact of FDI on economic growth of SAARC and its member states has been investigated. For the purpose of investigation positivism philosophy, deductive approach and cross-sectional research design has been employed. Secondary data for the period of 2000-2014 for FDI (independent variable) and GDP, Total export, Inflation (dependent variables) has been collected from UNCTADstat database and analysed using correlation and regression analysis. The finding shows that FDI has significant impact on economic growth of SAARC region. For individual member states FDI is also found to be a significant factor for accelerating economic growth for all the countries with exception for Afghanistan and Pakistan. Therefore, this research recommends taking more initiative by the individual countries to attract more FDI through making FDI friendly policies, reducing tax and tariffs to accelerate economic growth. Keywords: Foreign Direct Investment, Economic growth, SAARC econom

Cystic Dilatations of the Common Bile Duct in Adults

Cystic dilatations of the common bile duct are believed to be of congenital etiology with most cases presenting in childhood. During the last 20 years, 10 patients with cystic dilatations of the bile duct were treated in our Department. There were 5 men and 5 women with an age range of 35–81 years. Clinical presentation consisted of right hypohondrial pain, nausea, vomiting and a history of obstructive jaundice. Diagnosis was established by ultrasound, cholangiography and ERCP in most cases. According to the Todani classification system, 5 patients had type I cysts, 4 had type II and one had type III. At the time of surgery, main associated diseases were choledocholithiasis in 3 cases and cholangitis in 2 cases. One patient (type III) underwent endoscopic sphincterotomy; 4 patients underwent internal drainage and 2 of them developed mild cholangitis postoperatively; 5 patients underwent excision of the cyst and a biliary-enteric bypass and developed no main complications. Patients remained in good health during long-term follow-up. We conclude that cyst excision is the treatment ofchoice for adults in order to reduce postoperative morbidity and the potential risk of malignancy

Cyclin D(1 )and Rb protein expression and their correlation with prognosis in patients with colon cancer

BACKGROUND: Cyclin D1 plays a major role as a potential contributor to the multistep process of oncogenesis; nevertheless its prognostic significance in colon cancer has already been examined in a few studies and needs to be further delineated. The aim of this study was to assess the expression of cyclin D1 and pRb and to correlate them with tumor histological stage and grade, proliferative capacity (Ki-67 labeling index) and clinical parameters, in order to delineate their impact on prognosis. METHODS: One hundred and eleven patients, who underwent surgical resection of the colon for colon cancer constituted the group of our study. The immunohistochemical expression of cyclin D1, Rb and Ki-67 proteins was examined and correlated with clinico-pathological parameters and survival. RESULTS: The 5-years survival rate of patients presenting cyclin D1 positive tumors was 54%, while that of cyclin D1 negative ones was 67% (P = > 0.05). The survival rate of patients with pRb positive tumors was similar to that of pRb negatine ones. Significant association was observed between Ki-67 and cyclin D1 positivity (P = 0.045). Univariate analysis revealed worse survival in advanced stage patients presenting cyclin D1 positive tumors (P = 0.025). Additionally, the survival of patients aging less than 70 years old was correlated to cyclin D1 positivity (P = 0.009). Multivariate survival analysis revealed statistical significance for stage and hepatic metastasis. CONCLUSION: Even though cyclin D1 and pRb have not disclosed any clear association with shorter survival, cyclin D1 positivity may be a useful predictor of subgroup patients with colon cancer being in advanced stage and early age

Immunological HCV-Associated Thrombocytopenia: Short Review

Infection with Hepatitis C virus (HCV) is affecting about 3% of the world's population, leading to liver damage, end-stage liver disease, and development of hepatocellular carcinoma, being thus the first indication for liver transplantation in the USA. Apart from the cirrhotic-liver-derived clinical signs and symptoms several conditions with immunological origin can also arise, such as, glomerulonephritis, pulmonary fibrosis, and thrombocytopenia. HCV-related autoimmune thrombocytopenia shows specific pathogenetic characteristics as well as symptoms and signs that differ in severity and frequency from symptoms in patients that are not HCV infected. Aim of this short paper is to estimate the epidemiological characteristics of the disease, to investigate the pathogenesis and clinical manifestation, and to propose treatment strategies according to the pertinent literature

Optimization of Cannula Visibility during Ultrasound-Guided Subclavian Vein Catheterization, via a Longitudinal Approach, by Implementing Echogenic Technology

Objective. One limitation of ultrasound-guided vascular access is the technical challenge of visualizing the cannula during insertion into the vessel. We hypothesized that the use of an echogenic vascular cannula (EC) would improve visualization when compared with a nonechogenic vascular cannula (NEC) during real-time ultrasound-guided subclavian vein (SCV) cannulation in the ICU. Material and Methods. Eighty mechanically ventilated patients were prospectively enrolled in a randomized study that was conducted in a medical-surgical ICU. Forty patients underwent EC and 40 patients were randomized to NEC. The procedure was ultrasound-guided SCV cannulation via the infraclavicular approach on the longitudinal axis. Results. The EC group exhibited increased cannula visibility as compared to the NEC group (92%±3% versus 85 ± 7%, resp., P < 0.01). There was strong agreement between the procedure operators and independent observers (k = 0.9, 95% confidence intervals assessed by bootstrap analysis = 0.87 to 0.93; P < 0.01). Access time (12.1 s ± 6.5 versus 18.9 s ± 10.9) and the perceived technical difficulty of the ultrasound method (4.5 ± 1.5 versus 7.5 ± 1.5) were both decreased in the EC group compared to the NEC group (P < 0.05). Conclusions. Echogenic technology significantly improved cannula visibility and decreased access time and technical complexity optimizing thus real-time ultrasound-guided SCV cannulation via a longitudinal approach

Patient-reported outcomes from a randomized phase II study of the deferasirox film-coated tablet in patients with transfusion-dependent anemias

Background: Adherence to long-term chelation therapy in transfusion-dependent patients is critical to prevent iron overload-related complications. Once-daily deferasirox dispersible tablets (DT) have proven long-term efficacy and safety in patients ≥2 years old with chronic transfusional iron overload. However, barriers to optimal adherence remain, including palatability, preparation time, and requirements for fasting state. A new film-coated tablet (FCT) formulation was developed, swallowed once daily (whole/crushed) with/without a light meal. Methods: The open-label, Phase II ECLIPSE study evaluated patient-reported outcomes (PROs) in transfusion-dependent thalassemia or lower-risk myelodysplastic syndromes patients randomized 1:1 to receive deferasirox DT or FCT over 24 weeks as a secondary outcome of the study. Three PRO questionnaires were developed to evaluate both deferasirox formulations: 1) Modified Satisfaction with Iron Chelation Therapy Questionnaire; 2) Palatability Questionnaire; 3) Gastrointestinal (GI) Symptom Diary. Results: One hundred seventy three patients were enrolled; 87 received the FCT and 86 the DT formulation. FCT recipients consistently reported better adherence (easier to take medication, less bothered by time to prepare medication and waiting time before eating), greater satisfaction/preference (general satisfaction and with administration of medicine), and fewer concerns (less worry about not swallowing enough medication, fewer limitations in daily activities, less concern about side effects). FCT recipients reported no taste or aftertaste and could swallow all their medicine with an acceptable amount of liquid. GI summary scores were low for both formulations. Conclusions: These findings suggest a preference in favor of the deferasirox FCT formulation regardless of underlying disease or age group. Better patient satisfaction and adherence to chelation therapy may reduce iron overload-related complications. Trial registration: ClinicalTrials.gov identifier: NCT02125877; registered April 26, 2014