Goran Marjanovic

Polymorphisms of tumor-necrosis factor-α−308 and lymphotoxin-α + 250: Possible modulation of susceptibility to apoptosis in chronic lymphocytic leukemia and non-Hodgkin lymphoma mononuclear cells

Tumor necrosis factor alpha (TNF-α) and lymphotoxin alpha (LT-α) have been shown to play an important role in the pathogenesis of limphoproliferative disease. Both cytokines regulate cell-survival and cell-death in leukemic cells. TNF-α and LT-α are highly produced in chronic lymphotic leukemia (CLL) and non-Hodgkin lymphoma (NHL) patients. Genetic polymorphism within regulatory regions of these cytokine genes can alter their expression levels. This study investigates an influence of TNF-α−308 and LT-α + 250 polymorphisms on the activity of alkaline DNase in mononuclear cells of both patient groups as a potent biochemical marker of DNA fragmentation in the terminal phase of apoptosis. Study was performed on mononuclear cells of CLL and NHL patients. SNP were obtained by PCR-RFLP method. The activity of alkaline DNase was measured by spectrophotometric method. The study provided evidence of the influence of TNFG/A genotype and A alleles in the susceptibility to NHL, since the association of LT-αG/G genotype with CLL was observed. High-producing TNF-α−308/LT-α + 250 heterozygous haplotype is associated with high NHL incidence. The investigated SNP influence the activity of alkaline DNase in CLL and NHL patients. The observed polymorphisms may modulate susceptibility of leukemic cells to apoptosis by way of DNase activity.

Somatostatine analogue in nonoperative treatment of posttraumatic pancreatic pseudocyst in a child: a case report

Pancreatic pseudocyst is a complication of pancreatic trauma. We describe improved nonoperative treatment of patient with posttraumatic pancreatic pseudocyst with somatostatin analogue. A 9-year-old girl was admitted to our hospital after blunt abdominal trauma with handlebar. Three weeks after abdominal trauma, pancreatic pseudocyst developed. Nonoperative treatment of posttraumatic pancreatic pseudocyst (the largest dimensions 70 × 55 × 65 mm) with somatostatin analogue, octreotide acetate, was applied for the next 52 days. The patient was followed up for 24 months after the discontinuation of octreotide and there were no recurrence of pancreatic pseudocyst. Somatostatin analogue could be usefull in the nonoperative treatment of posttraumatic pancreatic pseudocysts in children.

The incidence and risk factors of ventilator-associated pneumonia in patients with severe traumatic brain injury

INTRODUCTION Patients with severe traumatic brain injury are at a risk of developing ventilator-associated pneumonia. The aim of this study was to describe the incidence, etiology, risk factors for development of ventilator-associated pneumonia and outcome in patients with severe traumatic brain injury. MATERIAL AND METHODS A retrospective study was done in 72 patients with severe traumatic brain injury, who required mechanical ventilation for more than 48 hours. RESULTS Ventilator-associated pneumonia was found in 31 of 72 (43.06%) patients with severe traumatic brain injury. The risk factors for ventilator-associated pneumonia were: prolonged mechanical ventilation (12.42 vs 4.34 days, p < 0.001), longer stay at intensive care unit (17 vs 5 days, p < 0.001) and chest injury (51.61 vs 19.51%, p < 0.009) compared to patients without ventilator-associated pneumonia. The mortality rate in the patients with ventilator-associated pneumonia was higher (38.71 vs 21.95%, p = 0.12). CONCLUSION The development of ventilator-associated pneumonia in patients with severe traumatic brain injury led to the increased morbidity due to the prolonged mechanical ventilation, longer stay at intensive care unit and chest injury, but had no effect on mortality.

Serum biomarkers and clinical characteristics of patients with Hodgkin lymphoma

Background/Aim. In classical Hodgkin’s lymphoma (cHL) the existing prognostic scoring systems do not include markers that adequately reflect the interaction of malignant Hodgkin and Reed-Sternberg (HRS) cells and tumor environment. The aim of this study was to determine the relationship between serum Galectin-1 (Gal-1) and soluble CD163 (sCD163) and the clinical status of patients with cHL, with special emphasis on the presence of relapse, progression, or resistance to the therapy applied. Methods. The research included 79 patients of whom 63 were patients with cHL, and the control group of 16 healthy volunteers. The study group of 63 patients with cHL included a subgroup of newly diagnosed patients without therapy, newly diagnosed patients with therapy, patients with relapse and progression of the disease and primary refractory patients during 2014 and 2015. Results. Analysis of the levels of sCD163 and Gal-1 within a group of patients suffering from cHL showed that the values of both molecules were higher in relapsed patients and the subgroup with progressive disease comparing to the subgroup of newly diagnosed patients without therapy or patients with therapy onset. Conclusion. Determination of Gal-1 and sCD163 levels is simple and reliable analysis that can contribute to the identification of high-risk patients with cHL and deserves inclusion in current prognostic scoring systems.

Current Issues in Histology, Biology and Prognosis of Hodgkin Lymphoma

Summary High risk Hodgkin lymphoma patients may occasionally have borderline characteristics similar to gray zone lymphomas and T-cell/histiocyte rich B cell lymphomas. These entities require different and more aggressive treatment modalities. Aggressive behavior is often associated with disturbances caused by Epstein Barr virus, or immune evasion caused by overexpression of check point inhibitors PDL-1 and PDL-2 coupled with the lack of expression of Class I and II MHC molecules. Galectin-1, TARC, sCD163 and other surrogate markers of immunosuppression in Hodgkin lymphoma may be useful for the assessment of treatment response. The improvements in lymphoma management diminished the importance of prognostic factors unified in the International Prognostic Scoring system, reducing them from 7 to 3 factors that remained relevant. Interim PET analysis is the only method able to identify resistant patients while chemotherapy is ongoing, thus enabling adjustment of treatment according to the treatment response. Efforts for stratification of patients according to disease histology, biology, microenvironment, clinical scoring systems and PET scan are ongoing. Current breakthroughs have set strong background for novel therapies with monoclonal antibodies and check point inhibitors that will result in improvement of management of high risk patients.

Preparation of patients with hemophilia A for oral surgery

Hemophilia A is an inherited disease characterized by deficiency of coagulation factor VIII and bleeding tendency. It is transmitted through the X chromosome. Hemophilia A is characterized by excessive bleeding in various tissues of the body, including soft tissue hematomas and hemarthrosis. In formulating the diagnosis of hemophilia A, in addition to a well-taken medical history and physical examination, laboratory tests should also be carried out and analyzed. Tooth extraction is the most common surgical procedures in patients with hemophilia. Hematological preparation implies the application of a concentrated factor VIH for one to two days prior to the intervention to achieve a desired level of factor VIII needed for the operation. In tooth extraction, this level has to be 50% before and after the tooth extraction for 5 days, with the application of antifibrinolytic agents. In oral surgical interventions the desired level of factor VIII is 50-80% preoperatively, 30-80% for 5 days after surgery, and 30% up to 14 days, also with the use of antifibrinolytic therapy. Patients with hemophilia and inhibitors are prepared for intervention through the application of recombinant FVIIa at the dose of 120mcg/kg, repeated every 2 hours for the period of 7-10 days after the intervention. It is necessary to apply antifibrinolytic agents and local hemostatic measures. Measures of local hemostasis are unavoidable in the case of oral surgical interventions in patients with hemophilia A. Implementation of these procedures in oral surgery has the role of minimizing the possibility of intra- and postoperative bleeding in patients with hemophilia A. For this purpose, the following are mostly used: absorbable suture thread, preparations of collagen, oxycellulose, gelatin, fibrin glue, with topical application of tranexamic or epsilon aminocaproic acid. Conclusion: Close cooperation between hematologists and oral surgeons is essential in order to minimize unwanted complications in patients with hemophilia A.