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Abstract Lung cancer remains the leading cause of cancer-related deaths in Europe, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. NSCLC is a heterogeneous disease encompassing various oncogenic alterations. Among them, EGFR exon 20 insertion mutations, constituting 0.3–2.2% of NSCLC cases, rank as the third most common EGFR alteration after exon 19 deletions and the L858R point mutation in exon 21, also known as “typical” EGFR alterations. Recent advancements in understanding the molecular pathogenesis of NSCLC have led to significant breakthroughs in targeted therapies, revolutionizing treatment options for patients with specific genetic alterations. This article presents the outcomes of a Virtual Meeting conducted on the online platform (provided Within3©) from September 19 to October 30, 2022. The meeting focused on addressing the challenges in the diagnosis and treatment of NSCLC patients with EGFR exon 20 insertion mutations. The participants consisted of healthcare professionals from ten Central and Eastern European countries who shared their experiences and opinions on various aspects, including epidemiology, treatment options, and diagnostic approaches employed in their respective healthcare institutions. The discussions were facilitated through open-ended and multiple-choice questions. The primary objective of this article is to provide an overview of the identified challenges associated with the diagnosis and treatment of this heterogeneous disease, based on the assessments of the meeting participants. Among the major emerging challenges discussed, the reimbursement issues concerning next-generation sequencing (NGS), a recommended method in NSCLC molecular diagnosis, and the availability of approved targeted treatments to enhance patient outcomes were of paramount importance. Furthermore, fostering community awareness of lung cancer and promoting harmonized lung cancer care were identified as areas deserving greater attention. Notably, the rapidly evolving treatment landscape, particularly with NGS for NSCLC patients with genomic alterations like EGFR, ALK, RET, MET, NTRK, and ROS1, necessitates prioritizing the development of new drugs, even for the relatively smaller subgroup with exon 20 insertion mutations.

In the process of tertiary migration of crude oil, the phase that occurs after the cessation of primary exploitation of petroleum fluid deposits, the deposit is characterized by a state of maximum discontinuity of microscale phases and their abnormal gravitational positioning. This is precisely why it is necessary to discuss the blocking/unblocking mechanisms of wetting phase and non-wetting phase plugs in/out of capillary microtraps. The article presents for the first time a microfluidic behavior of crude oil through cores, with the analysis of polymer flow through rock pores and their filling with petroleum fluids.

Coiled tubing is used in oil and gas well production with the aim of increasing oil field production. The efficiency of this process is reproduced in this material, with practical applications in carbonate rocks, also presenting the conditions of applicability of the method (the maximum friction coefficient, the optimal depth of the intervention zone, the working conditions during the operations to increase the recovery). The surface weight variation graphs with depth are also shown (Theoretical lockup and Predicted surface weight during CT-RIH and CT-POOH considering default values for the coefficients of friction for 8.5-in OH section and 6-in OH section). The 55% increase in well productivity after using this technique makes the coiling tube useful at over 1000m depth.

The reduction of greenhouse gases is an assumed objective of the European Community. Thus, in the future, natural gas transport and distribution pipelines will also have to deal with ensuring the transport of mixtures formed between hydrogen, biomethane and natural gas from fossil resources. Considering the increase in the amount of biomethane and the increase in the amount of green hydrogen produced, these fuels’s use in natural gas distribution networks is expected. The article presents an analysis of hydrogen production methods as well as numerical models of hydrogen transportation and mixing with natural gas. Also, there are presented the results obtained at the international level regarding the thresholds for the use of hydrogen in the fossil fuel of natural gas type, as well as the effects produced by the presence of this gas on the transport and supply systems. Numerical models of mixing and dynamic behavior of the new fuel obtained are also analyzed.

Many reservoirs comprised of relatively young sediments are so poorly consolidated that sand will be produced along with the reservoir fluids unless the rate is restricted significantly. The mathematical modelling of the flow of the sanded well uses the continuity equation written in cylindrical coordinates, Darcy's law admitting its availability and the solutions of these equations obtained for the boundary conditions in the case of a crude oil well that produces sand floods. In this article we have created a numerical model based on the variation of fluid flow from the productive layer, depending on the pressure drop between the productive layer and the wellbore, as well as the permeability of the layer. As a function of the flows extracted from the well, we rewrote the flow variation equations as polynomial relations of order 5, the error being a maximum of 0.04%. After determining the flow through the two relationships and confronting the reality in the field, the article confirms the type of flow through sand.

In Romania, the oil refineries were designed to process the crude oil extracted from the deposits located in their immediate vicinity (Suplacu de Barcău Refinery, 1 Mai Refinery, Câmpina Refinery, Vega Refinery and Dărmănești Refinery), to process crude oil imported from external oil basins (Onești Refinery, Brazi Refinery, Teleajen Refinery, Midia Refinery and Pitești Refinery) and to process crude oil from the Muntenia and Oltenia oil basins (Brazi Refinery and Pitești refinery). The closing of some refineries after 1990, the reduction of crude oil imports and especially the tightening of the quality conditions of the delivered petroleum products (the need to reduce the sulphur content of petroleum products, the use of bio-fuels) led to the reconsideration of deliveries to the refineries that remained in operation, through the creation of mixtures of crude oils extracted from Romania (for the Brazi Refinery) and the import of crude oil mixtures for the Teleajen and Midia Refineries, which would ensure the new quality conditions of finished petroleum products. The article describe how to create crude oil blends according to refinery requirements, using both classical estimation methods and genetic algorithms to determine the variation in the properties of these blends.

Formation evaluation in thin bed lamination is challenging and classic petrophysical workflow would results in underestimation of true hydrocarbon pore thickness and consequently underestimation of hydrocarbon in place in oil and gas fields. Due to deficiency of conventional well logs to detect thin bed shale sand laminations, they appear as non- hydrocarbon bearing low resistivity interval on well logs. True log response cannot be recorded in thin bed shale sand lamination intervals since thickness of these layers is lower than logging tool resolution. Logging tools can only record the average log response of shale and sand together – rather than true response of sand - anywhere the thickness of each lamination falls below vertical resolution of logging tools. Forward modeling and inversion workflow was applied in a thinly laminated shaly sand reservoir to calculate true hydrocarbon pore thickness. The process of forward modeling and inversion was optimized by using Genetic Algorithm approach by developing a computer code. A new workflow for formation evaluation was proposed for formation evaluation in thin bed shale sand laminations and verified successfully. The result was fully integrated and verified with core, well log and production data. True hydrocarbon pore thickness was increased, and new perforation interval was suggested based on the findings.

IntroductionSurgical lighting systems have to be re-adjusted manually during surgery by the medical personnel. While some authors suggest that interaction with a surgical lighting system in the operating room might be a distractor, others support the idea that manual interaction with the surgical lighting system is a hygiene problem as pathogens might be present on the handle. In any case, it seems desirable to develop a novel approach to surgical lighting that minimizes the need for manual interaction during a surgical procedure.MethodesWe investigated the effect of manual interaction with a classical surgical lighting system and simulated a proposed novel design of a surgical lighting system in a virtual reality environment with respect to performance accuracy as well as cognitive load (measured by electroencephalographical recordings).ResultsWe found that manual interaction with the surgical lights has no effect on the quality of performance, yet for the price of a higher mental effort, possibly leading to faster fatigue of the medical personnel in the long run.DiscussionOur proposed novel surgical lighting system negates the need for manual interaction and leads to a performance quality comparable to the classical lighting system, yet with less mental load for the surgical personnel.

IntroductionIn demanding work situations (e.g., during a surgery), the processing of complex soundscapes varies over time and can be a burden for medical personnel. Here we study, using mobile electroencephalography (EEG), how humans process workplace-related soundscapes while performing a complex audio-visual-motor task (3D Tetris). Specifically, we wanted to know how the attentional focus changes the processing of the soundscape as a whole.MethodParticipants played a game of 3D Tetris in which they had to use both hands to control falling blocks. At the same time, participants listened to a complex soundscape, similar to what is found in an operating room (i.e., the sound of machinery, people talking in the background, alarm sounds, and instructions). In this within-subject design, participants had to react to instructions (e.g., “place the next block in the upper left corner”) and to sounds depending on the experimental condition, either to a specific alarm sound originating from a fixed location or to a beep sound that originated from varying locations. Attention to the alarm reflected a narrow attentional focus, as it was easy to detect and most of the soundscape could be ignored. Attention to the beep reflected a wide attentional focus, as it required the participants to monitor multiple different sound streams.Results and discussionResults show the robustness of the N1 and P3 event related potential response during this dynamic task with a complex auditory soundscape. Furthermore, we used temporal response functions to study auditory processing to the whole soundscape. This work is a step toward studying workplace-related sound processing in the operating room using mobile EEG.

Breast cancer is the most common cancer among women. In Bosnia and Herzegovina, accurate data on the status of breast cancer are lacking due to the absence of a central registry. Multiple international guidelines imply that institutions that monitor breast cancer patients should have optimal therapeutic options for treatment. In addition, there have been several international consensus guidelines written on the management of breast cancer. Application of consensus guidelines has previously been demonstrated to have a positive influence on breast cancer care. The importance of specialty breast centers has previously been reported. As part of the 2021 Bosnian-Herzegovinian American Academy of Arts and Sciences (BHAAAS) conference in Mostar, a round table of multidisciplinary specialists from Bosnia and Herzegovina and the diaspora was held. All were either members of BHAAAS or regularly participate in collaborative projects. The focus of the consortium was to write the first multidisciplinary guidelines for the general management of breast cancer in Bosnia and Herzegovina. Guidelines were developed for each area of breast cancer treatment and management. These guidelines will serve as a resource for practitioners managing breast cancer in the Bosnia and Herzegovina region. This might also be of benefit to the ministry of health and any future investors interested in developing breast cancer care policies in this region of the world.

The most common type of renal cell carcinoma (RCC) is clear cell renal cell carcinoma (ccRCC), which has a high metastatic potential. Even though the International Metastatic RCC Database Consortium (IMDC) risk model is conventionally utilized for selection and stratification of patients with metastatic RCC (mRCC), there remains an unmet demand for novel prognostic and predictive markers. The goal of this study was to analyze the expression of Vascular endothelial growth factor (VEGF), Cluster of Differentiation 31 (CD31) to determine microvessel density, and Angiopoietin-1 (Ang-1) in primary kidney tumors, as well as their predictive and prognostic value in patients with metastatic ccRCC (mccRCC) who were treated with first-line sunitinib. The study included 35 mccRCC patients who were treated with first-line sunitinib in period between 2009 and 2019. Immunofluorescence was used to examine biomarker expression in tissue specimens of the primary tumor and surrounding normal kidney tissue. Median disease-free survival (DFS) was longer in patients with negative and low tumor VEGF score than in patients with medium tumor VEGF score (p=0.02). Those with low tumor CD31 expression had a longer median DFS than patients with high tumor CD31 expression (p=0.019). There was no correlation between Ang-1 expression and DFS. The expression of biomarkers in normal kidney tissue was significantly lower than in tumor tissue (p

Malignancy is one of the major public health problems in Bosnia and Herzegovina. Along with breakthroughs in specific oncological therapy, improving the quality of life of cancer patients and management of therapy-induced side effects need to be recognized as a priority in the comprehensive cancer patient care. Fertility loss after cancer treatment is a field requiring special attention due to its various consequences on patients themselves. Although oncofertility is well-recognized area of oncology, low- to middle-income countries are facing issues with its implementation in everyday practice. Increased awareness about fertility preservation is of high priority for all specialists who participate in the medical care of cancer patients. The absence of a systemic solution and lack of expertise led to the founding of Fertility Preservation Working Group of the Oncology Association of Bosnia and Herzegovina. We have made recommendationsas an expert consensus with the ultimate goal of making the first step towards enhancement of oncofertility implementation in Bosnia and Herzegovina.

Extracted oils and gases have different physical and chemical properties, depending on oil structures. Thus, it is beneficial to create mixtures of oils by combining cheaper crude oils with variants that have better properties (Brent type). This will result, in a reduced cost of acquisition. Mixing crude oil (obtaining blend crude oil) is a process in constant development, so that new ways for improving crude oil properties can be surfaced and to create new ways for transport and storage with lower costs. As an example, by mixing crude oil we can ensure viscosities and freezing conditions for certain transport systems. The aim of this paper is to present the techniques for mixing crude oil, the study of technologies, equipment needed for it and the numerical models for obtaining optimal mixing rates.

The catalytic cracking plant is one of the most important facilities in the refinery, due to ensuring the conversion of heavy oil fractions into gasoline, diesel and olefin-rich gases. The catalytic cracking process is a complex process of automatic conduction, due to the strong interactions between the process variables. That is why the mathematical modeling of this process is difficult to achieve, given the nonlinear nature of the system.This complexity increases with the increasingly restrictive requirements regarding the products obtained, the modernization of the installation and especially the reduction of operating costs. The present paper aims to present the techniques of hierarchical management of the catalytic cracking process and the numerical simulation models of this installation.

Additive manufacturing is a modern technique to produce parts with a complex geometry. However, the choice of the printing parameters is a time-consuming and costly process. In this study, the parameter optimization for the laser powder bed fusion process was investigated. Using state-of-the art multi-objective Bayesian optimization, the set of the most-promising process parameters (laser power, scanning speed, hatch distance, etc.), which would yield parts with the desired hardness and porosity, was established. The Gaussian process surrogate model was built on 57 empirical data points, and through efficient sampling in the design space, we were able to obtain three points in the Pareto front in just over six iterations. The produced parts had a hardness ranging from 224–235 HV and a porosity in the range of 0.2–0.37%. The trained model recommended using the following parameters for high-quality parts: 58 W, 257 mm/s, 45 µm, with a scan rotation angle of 131 degrees. The proposed methodology greatly reduces the number of experiments, thus saving time and resources. The candidate process parameters prescribed by the model were experimentally validated and tested.

Inguinal hernia repair is a common surgical procedure with an acceptably low complication rate. However, complications with potentially life-threating consequences may occur in rare cases. These complications might be very challenging to manage, even more in laparo-endoscopic interventions compared to open repair. One of these challenges can be the treatment of an intraoperative injury to the iliac vein. To the best of our knowledge, a lesion of the iliac vein during TEP (totally endoscopic preperitoneal) for inguinal hernia repair, and a safe technique for its management have not been reported yet. We report the case of a 75-year-old male patient with previous abdominal surgery scheduled for TEP repair of an inguinal hernia. During surgery, the iliac vein was damaged. If we had performed a laparotomy in this situation, the potentially life-threatening condition of the patient could have deteriorated further. Instead, to avoid a potential CO2 associated embolism, the preperitoneal pressure was gradually reduced, and the positive end expiratory pressure (PEEP) was increased in the manner that a balance between excessive bleeding and potential development of a CO2 embolism was achieved. The injured vein was sutured endoscopically, and in addition a hemostatic patch was applied. We then continued with the planned surgical procedure. Thrombosis of the sutured vein was prevented by prophylactic administration of low molecular weight heparin until the 14th postoperative day. We conclude that in case of major vein injury during TEP, which might happen irrespective of prior abdominal surgery, the preperitoneal pressure and PEEP adjustment can be used to handle the complication.

The HERe2Cure project, which involved a group of breast cancer experts, members of multidisciplinary tumor boards from healthcare institutions in Bosnia and Herzegovina, was initiated with the aim of defining an optimal approach to the diagnosis and treatment of HER2 positive breast cancer. After individual multidisciplinary consensus meetings were held in all oncology centers in Bosnia and Herzegovina, a final consensus meeting was held in order to reconcile the final conclusions discussed in individual meetings. Guidelines were adopted by consensus, based on the presentations and suggestions of experts, which were first discussed in a panel discussion and then agreed electronically between all the authors mentioned. The conclusions of the panel discussion represent the consensus of experts in the field of breast cancer diagnosis and treatment in Bosnia and Herzegovina. The objectives of the guidelines include the standardization, harmonization and optimization of the procedures for the diagnosis, treatment and monitoring of patients with HER2-positive breast cancer, all of which should lead to an improvement in the quality of health care of mentioned patients. The initial treatment plan for patients with HER2-positive breast cancer must be made by a multidisciplinary tumor board comprised of at least: a medical oncologist, a pathologist, a radiologist, a surgeon, and a radiation oncologist/radiotherapist.

The analysis of the corrosion phenomenon of the installations of the largest refinery in Romania confirmed the existence of its conditions, in the atmospheric distillation plants of crude oil, in the heat exchangers, and in the petrol and diesel hydrofining plants. However, the slightest effect of this phenomenon was found in the dome, the plates, and the exhaust pipes at the top of the distillation column, as well as in the reflux vessel of the atmospheric distillation plant. The main cause of the corrosion phenomenon and the increase in the corrosion areas of the material of the crude oil refining installations is the presence of hydrochloric acid, obtained after incorrect desalination (hydrolysis of calcium and magnesium chloride). To prevent this phenomenon, in laboratory conditions, we tested an antacid inhibitor (alkyl phenol) and a residual product (undistilled polyamine), with the role of supplementing the commercial inhibitor with a cheap product. The effectiveness of these additives was evaluated by introducing specimens made from the material taken from the refining column and from the reflux vessel into a solution of hydrochloric acid of various concentrations (5–15%). This solution was treated with the two corrosion inhibitors, the analysis of their effectiveness being performed at concentrations ranging between 0.05 and 0.2%. In addition, in this article, we deduced the equations of variation of the corrosion rate, depending on the working temperature of the refinery.

Drivers need lifting device jack with notch fits in place under the vehicle in the proper location during changing tires, also in workshops or maintenance centers jacks required for maintenance and refurbishment of parts, this device made the job faster and easy. Traditional car trailers use a mechanical feature to allow the human to raise the vehicle by manual force, by using the screw thread power or hydraulic jack which uses hydraulic power. The other way for lifting cars are pneumatic air bags, these bags are highly effective in industrial, maintenance applications and construction. In order to study this modern technology development and obtain good air bag design, which can lift and sustain the weight of more than 1200 kg estimated car weight, Solid works software used to analyze the weak points of pneumatic airbag. In this paper pressure used 249809.6 N/m^2 by imposing a weight of 1250 kg, Using natural rubber an as air bag material with two cases of thickness 1 mm, 3 mm, three behaviors of air bag tested (Von Mises stress, Strain and Deformation in two directions) analyzed, the results shows that the 1 mm thickness cannot sustain the load and pressure and weakest area lays between connection natural rubber and metal cast iron which contact the body of the car.

When crude oil is produced from an oil field well, it is generally accompanied with variable proportions of water, which makes the separation of water from crude oil commercially difficult. In this research it was found the best alternative demulsifier (belongs to the researchers) from the demulsifiers (unknown chemical formula) that is used in the wet oil treatment. Which is highly effective and less costly in economic terms of their counterparts. The crude oil that we made our research is taken from Jamboor field in Iraq. (Specific gravity = 0.6417) and the water quantity 0.18 ml, if we used organic component Benzene with demulsifier (special formula belongs to researchers), we will see that the quantity of water in crude 0il is (0.17 ml).

For decades respiratory chain and photosystems were the main firing field of the studies devoted to mechanisms of electron transfer in proteins. The concept of conjugated lateral electron and transverse proton transport during cellular respiration and photosynthesis, which was formulated in the beginning of 1960-s, has been confirmed by thousands of experiments. However, charge transfer in recently discovered bacterial nanofilaments produced by various electrogenic bacteria is regarded currently outside of electron and proton conjugation concept. Here we report the new study of charge transfer within nanofilaments produced by Shewanella oneidensis MR-1 conducted in atmosphere of different relative humidity (RH). We utilize impedance spectroscopy and DC (direct current) transport measurements to find out the peculiarities of conductivity and Raman spectroscopy to analyze the nanofilaments' composition. Data analysis demonstrates that apparent conductivity of nanofilaments has crucial sensitivity to humidity and contains several components including one with unusual behavior which we assign to electron transport. We demonstrate that in the case of Shewanella oneidensis MR-1 charge transfer within these objects is strongly mediated by water. Basing on current data analysis of conductivity we conclude that the studied filaments of Shewanella oneidensis MR-1 are capable of hybrid (conjugated) electron and ion conductivity.

Computer systems in the pipeline oil transporting that the greatest amount of data can be gathered, analyzed and acted upon in the shortest amount of time. Most operators now have some form of computer based monitoring system employing either commercially available or custom developed software to run the system. This paper presented the SCADA systems to oil pipeline in concordance to the Romanian environmental regulations.

Leak detection systems range from simple, visual line walking and checking ones to complex arrangements of hard-ware and software. No one method is universally applicable and operating requirements dictate which method is the most cost effective. The aim of the paper is to review the basic techniques of leak detection that are currently in use. The advantages and disadvantages of each method are discussed and some indications of applicability are outlined.

Adverse drug reactions still pose an important clinical problem. Dihydropyrimidine dehydrogenase (DPD) is an enzyme that regulates 5-FU quantities available for anabolic processes and hence affects its pharmacokinetics, toxicity and efficacy. There are several studies describing a hereditary (pharmacogenetic) disorder in which individuals with absent or significantly reduced DPD activity may even develop a life-threatening toxicity following exposure to 5-FU. The most common mutation is known as the DPYD*2A or as the splice-site mutation (IVS14 + 1G A) leading to creation of a dysfunctional protein. An objective behind the study was to ascertain existence of the IVS14+ 1G A mutation among the population of Bosnia and Herzegovina. Our research has undeniably attested to existence of one heterozygote for the DPYD gene mutation, i.e. one heterozygote for IVS14 + 1 G > A, DPYD*2A mutation.

Background. Myeloid sarcoma is an extramedullary neoplasm of immature myeloid cells. Our study reports a presentation of myeloid sarcoma which presented with severe leukemoid reaction as a secondary malignancy in a patient who was treated for acute lymphoblastic leukemia previously. The case emphasizes the difficulties in diagnosis of patients who do not have concomitant leukemia. Case Presentation. A 6-year-old girl who was treated for acute lymphoblastic leukemia previously presented with fatigue, paleness, and hepatosplenomegaly. Peripheral blood smear and bone marrow aspirate examination did not demonstrate any blasts in spite of severe leukemoid reaction with a white cell count 158000/mm(3). FDG/PET CT revealed slight uptake in cervical and supraclavicular lymph nodes. Excisional lymph node biopsy was performed from these lymph nodes and it showed myeloid sarcoma. Conclusion. Myeloid sarcoma can develop as a secondary malignancy in children who are treated for acute lymphoblastic leukemia. It can be associated with severe leukemoid reaction and diagnosis may be difficult if there is not concomitant leukemia. PET/CT is helpful in such cases.

Background. Neutropenic enterocolitis is one of the most common gastrointestinal complications seen in patients who are receiving chemotherapy for leukemia. Severe neutropenia is the main underlying factor of this pathology. It is characterized by fever and abdominal pain. Case Presentation. Herein, we report a case of neutropenic enterocolitis which presented with intestinal perforation in an afebrile patient who was diagnosed with acute lymphoblastic leukemia and was receiving induction chemotherapy. Conclusion. We aimed to emphasize the importance of enterocolitis and increase awareness against such severe complications which could have unexpected presentations.

Objective: T-cell acute lymphoblastic leukemia (T-ALL) is associated with recurrent chromosomal aberrations andabnormal ectopic gene expression during T-cell development. In order to gain insight into the pathogenesis of T-ALLthis study aimed to measure the level of expression of 7 T-cell oncogenes (LMO2, LYL1, TAL1, TLX1, TLX3, BMI1, andCALM-AF10) in pediatric T-ALL patients Material and Methods: LMO2, LYL1, TLX1, TLX3, BMI1, TAL1, and CALM-AF10 expression was measured usingquantitative real-time PCR in 43 pediatric T-ALL patients., Results: A high level of expression of LMO2, LYL1, TAL1, and BMI1 genes was observed in a large group of T-ALL.Several gene expression signatures indicative of leukemic arrest at specific stages of normal thymocyte development(LYL1 and LMO2) were highly expressed during the cortical and mature stages of T-cell development. Furthermore,upregulated TAL1 and BMI1 expression was observed in all phenotypic subgroups. In all, 6 of the patients had TLX1and TLX3 proto-oncogene expression, which does not occur in normal cells, and none of the patients had CALM-AF10fusion gene transcription. Expression of LYL1 alone and LMO2-LYL1 co-expression were associated with mediastinalinvolvement; however, high-level oncogene expression was not predictive of outcome in the present pediatric T-ALLpatient group, but there was a trend towards a poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 protooncogeneexpression., Conclusion: Poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 proto-oncogene expression indicate the needfor extensive study on oncogenic rearrangement and immunophenotypic markers in T-ALL, and their relationship totreatment outcome., Conflict of Interest: None declared.

Objective: To identify the well-known common translocations and FLT3 mutations in childhood acute myelogenousleukemia (AML) patients in Turkey., Material and Methods: The study included 50 newly diagnosed patients in which t(15;17), t(8;21), and inv(16)chromosomal translocations were identified using real-time PCR and FLT3 gene mutations were identified via direct PCR amplification PCR-RE analysis., Results: In all, t(15;17) chromosomal aberrations were observed in 4 patients (8.0%), t(8;21) chromosomal aberrationswere observed in 12 patients (24.0%), inv(16) chromosomal aberrations were observed in 3 patients (6.0%), and FLT3-ITD mutations were observed in 2 patients (4.0%); FLT3-D835 point mutation heterozygosity was observed in only 1patient (2.0%) patient., Conclusion: Despite of the known literature, a patient with FLT3-ITD and FLT3-D835 double mutation shows a bettersurvival and this might be due to the complementation effect of the t(15;17) translocation. The reportedmutation ratein this article (4%) of FLT3 gene seems to be one of the first results for Turkish population.

Objective: To retrospectively evaluate the clinical findings, laboratory data, management, and outcome in a group ofTurkish children diagnosed with rare coagulation deficiencies (RCDs) between January 1999 and June 2009., Material and Methods: The Turkish Society of Pediatric Hematology-Hemophilia-Thrombosis-Hemostasissubcommittee designed a Microsoft Excel-based questionnaire for standardized data collection and sent it to participatinginstitutions., Results: In total, 156 patients from 12 pediatric referral centers were included in the study. The cost common RCDswere as follows: FVII (n = 53 [34%]), FV (n = 24 [15.4%]), and FX (n = 23 [14.7%]) deficiency. The most common initialfinding in the patients was epistaxis, followed by ecchymosis, and gingival bleeding., Conclusion: Initial symptoms were mucosal bleeding, and fresh frozen plasma (FFP) and tranexamic acid werethe most commonly used treatments. We think that prophylactic treatment used for hemophilia patients should beconsidered as an initial therapeutic option for patients with rare factor deficiencies and a severe clinical course, and forthose with a factor deficiency that can lead to severe bleeding.

The NOTCH signaling pathway plays important role in the development of multicellular organisms, as it regulates cell proliferation, survival, and differentiation. In adults, it is essential for the T- or B-lymphocyte lineage commitment. NOTCH1 and FBXW7 mutations both lead the activation of the NOTCH1 pathway and are found in the majority of T-ALL patients. In this study, the mutation analysis of NOTCH1 and FBXW7 genes was performed in 87 pediatric T-ALLs who were treated on the ALL-BFM protocols. In 19 patients (22%), activating NOTCH1 mutations were observed either in the heterodimerization domain or in the PEST domain and 7 cases (10%) demonstrated FBXW7 mutations (2 cases had both NOTCH1 and FBXW7 mutations). We also analyzed the relationship of the mutation data between the clinical and biological data of the patients. NOTCH1 and FBXW7, NOTCH1 alone were found correlated with lower initial leucocyte counts which was independent from the sex and T- cell immunophenotype. However, NOTCH1 and FBXW7 mutations were not predictive of outcome in the overall cohort of pediatric T-ALLs.