The Clinical and Prognostic Significance of Ribonucleotide Reductase Subunits RRM1 and RRM2 mRNA Levels in Patients with Chronic Lymphocytic Leukemia.

Ribonucleotide Reductase (RNR) converts ribonucleotides to deoxyribonucleotides required for DNA replication and repair. RNR consists of subunits M1 and M2. It has been studied as a prognostic factor in several solid tumors and in chronic hematological malignancies, but not in chronic lymphocytic leukemia (CLL). Peripheral blood samples were collected from 135 CLL patients. M1/M2 gene mRNA levels were measured and expressed as a RRM1-2/GAPDH ratio. M1 gene promoter methylation was studied in a patients' subgroup. M1 mRNA expression was higher in patients without anemia (p = 0.026), without lymphadenopathy (p = 0.005) and 17p gene deletion (p = 0.031). Abnormal LDH (p = 0.022) and higher Rai stage (p = 0.019) were associated with lower M1 mRNA levels. Higher M2 mRNA levels were found in patients without lymphadenopathy (p = .048), Rai stage 0 (p = 0.025) and Trisomy 12 (p = 0.025). The correlation between RNR subunits and clinic-biological characteristics in CLL patients demonstrate RNR's potential role as a prognostic factor.

Effect of prolonged storage on quality characteristics of recovered plasma: Is there an expiration date?

BACKGROUND: Although there are guidelines on industrial manufacture of plasma-derived medicinal products, there are no clear recommendations about plasma intended for fractionation, as there is no expiry time and the effect of prolonged storage on the activity of coagulation factors is unknown. STUDY AND DESIGN METHODS: A total of 237 units of plasma stored at -30°C in the National Blood Transfusion Centre for 1 year (62 units), 5 years (75 units), and 10 years (100 units) were studied. The effect of storage time was investigated by determining the activity of clotting factors FII, FV, FVII, FVIII, FIX, FX, FXI, FXII, FXIII using coagulometric methods and antithrombin III and fibrinogen with chromogenic assays, using System BCSR > XP (Siemens Healthcare diagnostics Marburg, Germany). Albumin was measured by Medilyzer (BX, Medicon). ABO blood group was recorded and correlated with the levels of FVIII. Comparison of values between one and five, 1 and 10 and 5 and 10 years of storage was performed via the SAS for Windows 9.4 software platform (SAS Institute Inc., NC, U.S.A.). RESULTS: Albumin, AT III, fibrinogen, FIX, FXI, FXII, and FXIII remain rather stable even after 10 years of storage. Levels of FII, FV, FVII, FVIII, and FX decreased after 5 years of storage. DISCUSSION: Our study is in agreement with all the previous studies and concludes that there is a putative usability of recovered plasma and some of its coagulation factors after many years of storage at the recommended temperature.

Bone marrow ribonucleotide reductase mRNA levels and methylation status as prognostic factors in patients with myelodysplastic syndrome treated with 5-Azacytidine.

Ribonucleotide Reductase (RNR) is a two-subunit (RRM1, RRM2) enzyme, responsible for the conversion of ribonucleotides to deoxyribonucleotides required for DNA replication. To evaluate RNR as a biomarker of response to 5-azacytidine, we measured RNR mRNA levels by a quantitative real-time PCR in bone marrow samples of 98 patients with myelodysplastic syndrome (MDS) treated with 5-azacytidine with parallel quantification of the gene promoter's methylation. Patients with low RRM1 levels had a high RRM1 methylation status (p = 0.005) and a better response to treatment with 5-azacytidine (p = 0.019). A next-generation sequencing for genes of interest in MDS was also carried out in a subset of 61 samples. Splicing factor mutations were correlated with lower RRM1 mRNA levels (p = 0.044). Our results suggest that the expression of RNR is correlated with clinical outcomes, thus its expression could be used as a prognostic factor for response to 5-azacytidine and a possible therapeutic target in MDS.

Successful Pregnancy and Persistent Polyclonal B Cell Lymphocytosis (PPBL): A Case Study of a Rare Co-Existence.

BACKGROUND Persistent polyclonal B cell lymphocytosis (PPBL) is a benign clinical condition, which is characterized by persistent absolute polyclonal B lymphocytosis (>4.0 K/µL), with the presence of circulating binucleated lymphocytes on the peripheral blood smear and an extra 3 chromosome long arm i(3q) in most cases. Immunophenotype reveals the polyclonal population of B cell lymphocytes with expression of CD19, CD20, and CD22 antigens, and kappa and lambda immunoglobulin light chains. Patients are mostly asymptomatic. Although PPBL has a benign clinical course and does not affect the survival expectancy of most patients, pregnancy seems to be extremely rare in these patients, as only 1 case reported so far. Although the real role of immunologic disorders, possibly PPBL, in recurrent pregnancy losses remains unclear, the rarity of successful pregnancy in PPBL patients could be attributed to the possible association of PPBL with infertility or recurrent miscarriages. CASE REPORT In the present study we present the second published case of a woman with a typical PPBL and recurrent pregnancy loss with a successful pregnancy outcome. Close clinical and laboratory monitoring in combination with the administration of thromboprophylaxis and the induction of mild immunosuppression with low-dose prednisolone may have contributed to the successful outcome of the pregnancy. CONCLUSIONS In conclusion and taking all these findings into consideration, pregnancy in patients with PPBL seems to be extremely rare and the contribution of PPBL to the 2 previous miscarriages in our case could not be excluded.

JAK2V617F positive polycythemia vera with paroxysmal nocturnal hemoglobinuria and visceral thromboses: a case report and review of the literature.

BACKGROUND: Polycythemia vera (PV) is characterized by red cell mass expansion in the peripheral blood and can be complicated with thrombosis, bleeding, evolution to acute myeloid leukemia (AML) or a fibrotic phase. Paroxysmal nocturnal hemoglobinuria (PNH) in an acquired clonal haematopoietic stem cell disorder associated with chronic intravascular hemolysis, venous thrombosis, defective hematopoiesis, frequent episodes of infection and, rarely, leukemic transformation. Herein, we report an interesting case of a patient with coexistence of PNH clones and a JAK2V617F positive PV, with unusual thromboses without hemolysis. CASE PRESENTATION: A 51-year-old woman presented with increased levels of hematocrit, multiple liver, spleen, and left kidney infarctions and ascites; further investigation revealed a JAK2V617F-positive polycythemia vera and the presence of a significant PNH population (more than 90% CD55- CD59- cells among both granulocytes and red blood cells). Interestingly, the patient has experienced severe thrombotic events without any signs or symptoms of hemolysis. CONCLUSIONS: This case raises questions over uncharted aspects of the PNH etiopathogenesis and its potential association with myeloproliferative neoplasms (MPN) and highlights the difficulty of diagnosing and managing patients with more than one potentially thrombophilic conditions, especially with established and severe thromboses.

The effect of 5-azacytidine treatment delays and dose reductions on the prognosis of patients with myelodysplastic syndrome: how to optimize treatment results and outcomes.

The regimen of 5-azacytidine for patients with myelodysplastic syndrome (MDS) has remained unchanged since its first approval. Although several modifications have since been made and delays and dose reductions are common especially during the first treatment cycles, there are minimal data on the prognostic effect of these modifications. In this study, based on data from 897 patients with MDS treated with 5-azacytidine recorded in a national registry, the effect of treatment delays and dose reductions on response, transformation to acute myeloid leukaemia, and survival (after 5-azacytidine initiation, OST ) were analysed. Delays during the first two cycles were noted in 150 patients (16·7%) and were found to adversely affect OST independently of the International Prognostic Scoring System score [hazard ratio (HR), 1·368; P = 0·033] or pre-existing neutropenia (HR, 1·42; P = 0·015). In patients achieving a response, delays before response achievement were correlated with its type (complete remission, 2·8 days/cycle; partial remission, 3·3 days/cycle; haematologic improvement, 5·6 days/cycle; P = 0·041), while delays after response achievement did not have any effect on retention of response or survival. Dose reductions were found to have no prognostic impact. Based on our results, treatment delays especially during the first cycles should be avoided, even in neutropenic patients. This strict strategy may be loosened after achieving a favourable response.

Genetic Polymorphisms Implicated in Major Pregnancy Complications: a Review.

Pregnancy short- or long-term complications may involve the mother's health, the fetus's health, or both. A systematic literature review was performed, including studies up to October 2018 from Medline (PubMed), Science Direct, Web of Science and Google Scholar. The following inclusion criteria were applied: studies published until 2018 concerning the genetic background of pregnancy complications such as high blood pressure, gestational diabetes, preeclampsia, pregnancy loss, endometrial death, placental abruption, premature labor, and intrauterine growth retardation which may render pregnancy a high risk condition.We identified 164 articles that met the inclusion criteria and reviewed and analyzed them. The results so far are contradictory and the pathogenicity of these pregnancy complications remains unclear. For most of the polymorphisms studied so far, data refer to small studies size but research is on-going.The identification of genetic polymorphisms with strong correlations with certain pregnancy complications could provide us with useful tools which could be incorporated in diagnostic algorithms that could facilitate early detection and treatment of major pregnancy complications.

Retrospective Study on Prevalence, Specificity, Sex, and Age Distribution of Alloimmunization in Two General Hospitals in Athens

Objective: Blood transfusion is a common lifesaving treatment but it is often complicated with alloimmunization. Previously studies in Greece have concentrated on alloimmunization in multiply transfused thalassemic patients or antenatal women. However, the relative frequency of red blood cell (RBC) alloantibodies in the general patient population has not been studied so far. The aim of the present retrospective study was to estimate the prevalence and specificity of RBC alloantibodies in a large cohort of patients in two general hospitals and their association with age, sex, and the patients' clinic of hospitalization. Materials and Methods: Data from 2012 to 2016 from the "Sismanogleio" and "Thriasio" general hospitals in Athens, Greece, were studied retrospectively. Statistical analysis was performed with SAS for Windows 9.4. Results: Six hundred twenty-six patients (626/53800, 1.16%) were alloimmunized for one or more alloantibodies. The mean age was 67.99±17.56 years. Most antibodies were found in women [62.66% (438/699) in women vs. 37.34% (261/699) in men (p=0.0007)], while the vast majority of antibodies (66.81%) were found in patients aged 61-90. The most frequent antibody was anti-Kell (26.61%), followed by anti-E (16.02%), anti-D (15.02%), anti-Jka (5.87%), and anti-M (5.72%). Anti-C (81.48%, n=27) and anti-Cw (54.17%, n=24) tended to be found more often in patients with multiple antibodies. Most alloimmunized cases were found in general surgery (42.65%) and internal medicine departments (38.66%). Conclusion: According to our results, the alloimmunization data in a general patient population in Greece were consistent with the majority of studies in the international literature. Whether a strategy at national level needs to be directed towards extending matching for the whole population or towards applying sensitive and compulsory indirect antiglobulin tests before any transfusions in order to efficiently prevent alloimmunization remains an issue of debate.

Emerging patterns of resistance in a cohort of Greek patients with recurrent UTIs: a pilot study.

Bacterial urogenital infections caused by multi-drug resistant organisms (MDROs), are increasingly becoming a severe public health issue. The purpose of the present study was to examine the epidemiology of recurrent UTIs along with antimicrobial resistance patterns in a cohort of patients followed as outpatients at an Infectious Disease clinic of a tertiary care center in Greece. One hundred, sequential patients suffering from recurrent UTIs and coming for clinical evaluation, follow-up and treatment were examined; microbiological urine culture results were analyzed. Patients were separated into Group A: patients with ≥3 urogenital infections during the last study year, and Group B: patients with ≤2 urogenital infections. Furthermore, antimicrobial resistance patterns and presence of MDROs in relation to the number of urogenital infections during a three years period was evaluated. Group A had a mean of 4.3 ± 1.7 urogenital infections during the last year of the study, while patients in Group B 1.9 ± 0.3 infections over a three years period. An age cut-off of 30 years was critical for higher UTI rates. Escherichia Coli was the predominant isolated pathogen in 96.2% of the patients. Patients with diabetes mellitus had a 3 fold-higher risk for ≥3 UTIs. Resistance to colistin and imipenem was associated with a history of more than 2 episodes of UTIs but observed in a small number of patients with comorbidities. In this pilot study MDRO detection in patients suffering from recurrent UTIs emphasizes the need for continuous epidemiological surveillance in order to improve our understanding of the evolution of resistance in a common community infection as well as to implement successful prevention strategies.

A Unique Case of Primary Extranodal Marginal Zone Lymphoma of the Anal Canal.

Marginal zone lymphomas represent approximately 10-12% of all B-cell lymphomas. Extranodal marginal zone lymphomas (EMZL) or mucosa-associated lymphoid tissue (MALT) lymphomas are the most common subtype. Almost half of all MALT lymphomas arise in the gastrointestinal (GI) tract and, while the stomach is the most common site of GI involvement, the small and large intestines can also be involved. Rare cases of MALT lymphoma involving the rectum have been reported; however, to our knowledge, involvement of the anal canal has never been reported in the literature. Here, we describe a unique case of MALT lymphoma of the anal canal. Infectious agents have been implicated in the pathogenesis of MALT lymphomas, possibly through persistent antigenic stimulation of the area; however, in our case no such infection was documented.

Health risk behaviors among high school and university adolescent students.

Tobacco, alcohol and drug abuse constitute a public health concern. Data regarding health risk behaviors among Greek youth are scarce. The aim of the present study was to investigate health risk behaviors of a large adolescent sample (730 adolescents, 294 males and 436 females), residing in different areas of Greece, trace perceived side effects and associate the findings with the adopted lifestyle. High school students and University newcomers, aged 14-21 years (17.8±4.5 years), self-reported health risk behaviors via an anonymous, closed-type, validated questionnaire. Simultaneous adoption of unhealthy habits, such as smoking and drug abuse, were not independent (χ2=38.668, P=0.01). Age was the most significant factor in the adoption of unhealthy behaviors; smoking (χ2=27.220, P=0.01), misuse of cannabis and recreational drugs (χ2=9.874, P=0.05) and combining alcohol and smoking with entertainment (χ2=8.708, P=0.05; χ2=317.309, P=0.05, respectively) were adopted more by the elder (18-20 years) than the younger (15-18 years) teenagers. Males were more prone to abuse of cannabis (χ2=8.844, P=0.01), whereas females combined drinking and smoking with loud music during entertainment (χ2=6.618, P=0.05). The majority (64%) reported driving after drinking alcohol and intense entertainment, especially in urban areas. Almost half of smokers (53.1%) and drug users (46.3%) first encountered smoking or drugs from friends. Educational institutions and entertainment venues were the main places of initiation of smoking (26%) or drug use (35.2%), respectively. Adolescents from touristic regions were more prone to smoking (33.9%, P=0.01) and drug abuse (53.7%, P=0.01). The lower the frequency of exercise, the higher the consumption of psychoactive substances (P=0.022). Youth engaging in unhealthy habits were also willing to use prohibited doping substances (56%, P=0.043). Health problems were the main reason to consider changing habits (72%). In conclusion, health risk behaviors were multifactorial and tended to cluster. Thus, preventive youth strategies should target negative peer influences, especially during late adolescence.

Pneumothorax: from definition to diagnosis and treatment.

Pneumothorax is an urgent situation that has to be treated immediately upon diagnosis. Pneumothorax is divided to primary and secondary. A primary pneumothorax is considered the one that occurs without an apparent cause and in the absence of significant lung disease. On the other hand secondary pneumothorax occurs in the presence of existing lung pathology. There is the case where an amount of air in the chest increases markedly and a one-way valve is formed leading to a tension pneumothorax. Unless reversed by effective treatment, this situation can progress and cause death. Pneumothorax can be caused by physical trauma to the chest or as a complication of medical or surgical intervention (biopsy). Symptoms typically include chest pain and shortness of breath. Diagnosis of a pneumothorax requires a chest X-ray or computed tomography (CT) scan. Small spontaneous pneumothoraces typically resolve without treatment and require only monitoring. In our current special issue we will present the definition, diagnosis and treatment of pneumothorax from different experts in the field, different countries and present different methods of treatment.

Human immunodeficiency virus infection and pneumothorax.

Pneumothorax is a serious and relatively frequent complication of human immunodeficiency virus (HIV) infection that may associate with increased morbidity and mortality and may prove difficult to manage, especially in patients with acquired immunodeficiency syndrome (AIDS).

The role for medical thoracoscopy in pneumothorax.

Pneumothorax is a life threatening situation that requires fast treatment. There are two major classifications: Primary and Secondary. Staging of pneumothorax is also very important for treatment. Treatment of pneumont can be performed either from thoracic surgeons, or pulmonary physicians. In our current work we provide up-to-date information regarding pneumothorax classification, staging and treatment from the point of view of expert pulmonary physicians.

Unusual causes of pneumothorax.

Pneumothorax is divided to primary and secondary. It is a situation that requires immediate treatment, otherwise it could have severe health consequences. Pneumothorax can be treated either by thoracic surgeons, or pulmonary physicians. In our current work, we will focus on unusual cases of pneumothorax. We will provide the etiology and treatment for each case, also a discussion will be made for each situation.

Bronchoscopic interventions for severe COPD.

Chronic obstructive pulmonary disease (COPD) causes severe handicap among smokers. Most patients have to remain under continuous oxygen therapy at home. Moreover, respiratory infections are very common among these patients and vaccination is obligatory against influenza. Emphysema and bronchiectasis are observed with computed tomography (CT) and in several situations these parenchymal damages are responsible for pneumothorax in one case and pseudomonas aeroginosa infection. Novel mini-invasive techniques are used currently for emphysema treatments which are described extensively throughout our current work.

Approach of the treatment for pneumothorax.

Pneumothorax can occur in several situations such as; chronic obstructive pulmonary disease (COPD) where emphysema is observed or due to a biopsy for malignancy suspicion. In any case it is a dangerous situation that requires immediate attention and treatment. Pneumothorax can be divided in primary and secondary. Staging of pneumothorax is also very important. In our current editorial we summarize etiology and treatment of pneumothorax from a panel of pulmonary physicians, oncologists and thoracic surgeons.

Pneumothorax: observation.

Pneumothorax based on the cause, it can be divided into two large categories; primary and secondary. The staging of pneumothorax plays a crucial role for treatment. Currently both thoracic surgeons and pulmonary physicians can handle efficiently treatment. Pulmonary physicians with the minimally medical thoracoscopy while thoracic surgeons with a more extensive intervention. Experience defines the outcome in most situations and not the method. In our current work we will present data regarding the observation of pneumothorax from a panel of experts.

Pneumothorax after transbronchial needle biopsy.

Currently there several diagnostic techniques that re used by radiologists and pulmonary physicians for lung cancer diagnostics. In several cases pneumothorax (PNTX) is induced and immediate action is needed. Both radiologists and pulmonary physicians can insert a chest tube for symptom relief. However; only pulmonary physicians and thoracic surgeons can provide a permanent solution for the patient. The final solution would be for a patient to undergo surgery for a final solution. In our current work we will provide all those diagnostic cases where PNTX is induced and treatment from the point of view of expert radiologists and pulmonary physicians.