Endoscopic Management of Difficult Biliary Stones: An Evergreen Issue.

Choledocholithiasis is one of the most common indications for endoscopic retrograde cholangiopancreatography (ERCP) in daily practice. Although the majority of stones are small and can be easily removed in a single endoscopy session, approximately 10-15% of patients have complex biliary stones, requiring additional procedures for an optimum clinical outcome. A plethora of endoscopic methods is available for the removal of difficult biliary stones, including papillary large balloon dilation, mechanical lithotripsy, and electrohydraulic and laser lithotripsy. In-depth knowledge of these techniques and the emerging literature on them is required to yield the most optimal therapeutic effects. This narrative review aims to describe the definition of difficult bile duct stones based on certain characteristics and streamline their endoscopic retrieval using various modalities to achieve higher clearance rates.

Oncology Clinical Trials in Greece: Progress in the Past Decade.

Cancer is established as a major contributor to global burden as millions of deaths are reported every year. Advances in molecular, epidemiologic and clinical research have led to significant improvements in prevention, screening and treatment of tumors. The purpose of the study is to describe the progress of oncology clinical trials performed in Greece during the past decade and the obstacles that still need to be addressed in cancer research. A search was conducted in the public database EU Clinical Trials Register using the algorithm 'cancer AND Greece'. Results included relevant trials approved between 2010 and 2020. A total of 480 trials were approved for conduct in Greece from 2010 to 2020. The majority are multinational, phase III trials, exploring the efficacy and safety of agents in the management of lung cancer and multiple myeloma. A variety of small-molecules and monoclonal antibodies has and is being tested against key binding targets. Based on their promising effects on patients' responses and outcomes, many have been marketed for the treatment of several cancer types and are considered milestones in cancer discovery. It goes without saying that oncology research has made tremendous steps towards the development of potent and tolerable anticancer agents, with Greece having an active role. Current efforts focus on the use of alternative designs and tools aiming at further improving patients' survival and quality of life, while globalization of clinical research is also a matter of high importance.

Comparative performance and external validation of three different scores in predicting inadequate bowel preparation among Greek inpatients undergoing colonoscopy.

Background: Predictive scores aim to predict bowel preparation adequacy among hospitalized patients undergoing colonoscopy. We evaluated the comparative efficacy of these scores in predicting inadequate bowel cleansing in a cohort of Greek inpatients. Methods: We performed a post hoc analysis of data generated from a cohort of inpatients undergoing colonoscopy in 4 tertiary Greek centers to validate the 3 models currently available (models A, B and C). We used the Akaike information criterion to quantify the performance of each model, while Harrell's C-index, as the area under the receiver operating characteristics curve (AUC), verified the discriminative ability to predict inadequate bowel prep. Primary endpoint was the comparison of performance among models for predicting inadequate bowel cleansing. Results: Overall, 261 patients-121 (46.4%) female, 100 (38.3%) bedridden, mean age 70.7±15.4 years-were included in the analysis. Model B showed the highest performance (Harrell's C-index: AUC 77.2% vs. 72.6% and 57.5%, compared to models A and C, respectively). It also achieved higher performance for the subgroup of mobilized inpatients (Harrell's C-index: AUC 72.21% vs. 64.97% and 59.66%, compared to models A and C, respectively). Model B also performed better in predicting patients with incomplete colonoscopy due to inadequate bowel preparation (Harrell's C-index: AUC 74.23% vs. 69.07% and 52.76%, compared to models A and C, respectively). Conclusions: Predictive model B outperforms its comparators in the prediction of inpatients with inadequate bowel preparation. This model is particularly advantageous when used to evaluate mobilized inpatients.

Variations of the Median Nerve and Carpal Tunnel Syndrome: a Systematic Review of the Literature.

Objectives:The purpose of this systematic review is to examine the different variations of the median nerve (MN) and the diagnostic methods used to identify carpal tunnel syndrome (CTS), a common neuropathy resulting from the entrapment of the MN within the carpal tunnel. Understanding the different variations of the MN is crucial in order to prevent injuries during surgical treatment of the syndrome. Materials and methods:Data were extracted from studies published in PubMed. A detailed search in PubMed was performed for studies that reviewed the variations of the MN and CTS. Results:There are two main classifications of the MN, known as the Lanz and Amadio categories. Lanz's classification is the one being mostly used in the surgical literature, with group 3 (Bifid MN) being the main cause of the CTS. Additionally, there are branches and anastomosis of the MN that do not fit into either category, with the third common digital branch being the most injured nerve during carpal tunnel release surgery. Diagnostic techniques for CTS include physical examination combined with NCS tests, magnetic resonance imaging (MRI), ultrasound, or elastography. While NCS has been previously the most commonly used diagnostic method, the recent literature suggests that ultrasound and elastography are the most accurate techniques. Conclusions:In order to minimize injuries during carpal tunnel release surgery, it is crucial to have knowledge on the different variations of the MN that cause CTS. Additionally, this review emphasizes the significance of the current diagnostic methods, which not only make CTS more affordable but also facilitate easier recognition of the condition.

Modified endoscopic mucosal resection techniques for treating precancerous colorectal lesions.

Endoscopic mucosal resection (EMR) is a technique allowing efficacious and minimally invasive resection of precancerous lesions across the entire gastrointestinal tract. However, conventional EMR, involving injection of fluid into the submucosal space, is imperfect, given the high rate of recurrence of post-endoscopic resection adenoma, especially after piecemeal resection. In light of these observations, modifications of the technique have been proposed to overcome the weakness of conventional EMR. Some of them were designed to maximize the chance of en bloc resection-cap-assisted EMR, underwater EMR, tip-in EMR, precutting, assisted by ligation device-while others were designed to minimize the complications (cold EMR). In this review, we present their modes of action and summarize the evidence regarding their efficacy and safety.

Anti-Ro52 antibody is highly prevalent and a marker of better prognosis in patients with ovarian cancer.

BACKGROUND AND AIMS: Anti-Ro52 antibody (Ab) reactivity is highly prevalent in autoimmune rheumatic diseases (ARDs), mainly Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE), but also in other inflammatory disorders. Thorough assessment of the prevalence, clinical significance and epitope specificity of Ro52-autoAbs in cancerous diseases is still lacking. MATERIAL AND METHODS: Anti-Ro52 Ab reactivity was tested in a large cohort of 490 patients with various malignant diseases. Ro52-autoAb epitope mapping by an in house line immunoassay was carried out using 5 recombinant Ro52 polypeptides spanning Ro52. RESULTS: Anti-Ro52 abs were significantly more prevalent in patients with ovarian cancer (30%) compared to patients with 6 other malignant diseases (median 8.1%, range 5.9-15.8%). The presence of anti-Ro52 abs in patients with ovarian cancer was strongly associated with better overall survival. Ro52 epitope mapping of patients with ovarian cancer was dissimilar to that of SLE and SjS ARDs, less frequently recognizing Ro52-1 and Ro52-4 fragments compared to patients with SLE and SjS. CONCLUSION: We demonstrate for first time an unexpectedly high frequency of anti-Ro52 abs in patients with ovarian cancer, their presence indicating better overall survival. Their distinguishing epitope profile may suggest a non-SLE or SjS-related stimulus for autoAb production.

Clinical practice guidelines on diabetes mellitus and pregnancy: Ι. Pre-existing type 1 and type 2 diabetes mellitus.

Women with type 1 (T1DM) or type 2 diabetes (T2DM) diagnosed prior to pregnancy are classified as having pre-existing diabetes mellitus (DM). The prevalence of hyperglycemia in pregnancy has been estimated at 17% globally and 5.4% in Europe, differences existing among racial and ethnic groups, following the prevalence of type 2 diabetes. Only a minority (approximately 15%) of the cases of diabetes during pregnancy represent women with pre-existing diabetes. Because of the rising prevalence of obesity and limited screening for diabetes in young women, there has been, globally, an increase in the diagnosis of previously unknown overt diabetes early in pregnancy; these women should be treated as women with pre-existing diabetes, as they may already have unrecognized complications (e.g., nephropathy and retinopathy). The Hellenic Endocrine Society and the Hellenic Society of Maternal-Fetal Medicine commissioned an expert group to construct national guidelines on "Diabetes mellitus and pregnancy: Pre-existing type 1 and 2 diabetes mellitus". Following a search for the best available evidence and critical appraisal of the search results, the writing group generated a series of consensus recommendations regarding preconception counseling and care, care during pregnancy, and care after the pregnancy in cases of pre-existing T1DM and T2DM.

Clinical practice guidelines on diabetes mellitus and pregnancy: ΙI. Gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic disease of pregnancy and is associated with several perinatal complications. GDM is defined as diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation. In Europe, in 2016, the prevalence of GDM was estimated to be 5.4% (3.8-7.8). It varied depending on maternal age, year of data collection, country, area of Europe, week of gestation at testing, and diagnostic criteria. The Hellenic Endocrine Society and the Hellenic Society of Maternal-Fetal Medicine commissioned an expert group to construct national guidelines on "Diabetes mellitus and pregnancy: Gestational diabetes mellitus." Following a search for the best available evidence and critical appraisal of the results, the writing group generated a series of consensus recommendations regarding screening tests for the general population, monitoring and management, fetal monitoring, management of preterm labor, planning of labor and delivery, puerperium and breastfeeding, and long-term follow-up of GDM.

Dietary Intake and Cholelithiasis: A Review.

Gallbladder disease (GBD) is one of the most prevalent gastrointestinal disorders in western societies. Etiology is multifactorial and may follow complex interaction between genetic and environmental factors. Dietary intake has been considered as a potentially modifiable risk factor for GBD, because a number of dietary factors have been involved in cholelithiasis pathogenesis. In our aim to evaluate potential usefulness of diet pattern modification for GBD prevention, we perform a systematic review of related epidemiological studies. We define GBD as a disorder in which a patient bears gallstones and/or undergoes surgery for gallstones. We review English-language studies found in the Med-line database that occurred from 1973 to 2018. We searched for epidemiological evidence of the role of diet as a potential risk factor for gallstone formation. In particular, we thoroughly inspected intake of fatty acid, cholesterol, carbohydrate, protein, fiber, alcohol, nuts, and coffee and vegetarian eating-pattern effects. Our results show that simple sugar (simple carbohydrate) and saturated fat consumption suggests a positive association with the risk for gallstone formation. Protein, fiber, nuts, coffee, and moderate alcohol intake consistently reduces that probability. Different studies found that fat and cholesterol intake are variable risk factors for GBD; therefore, additional analyses are necessary to clarify their relevance in gallstone formation pathogenesis. GBD is a multifactorial disorder that can be affected both positively and negatively by diet. Although no specific dietary recommendations can be addressed to reduce risk for gallstone formation, healthy diet patterns can be expected to improve prospects for healthy gallbladder function.

Monitoring of colonoscopy quality indicators in an academic endoscopy facility reveals adherence to international recommendations.

BACKGROUND: We monitor colonoscopy service quality biannually, by measuring sedation administration, colonoscopy completion, adenoma detection and early complications rates (CR). We herein present our audit results for the years 2013 and 2015. METHODS: In our endoscopy facility, five rotating senior gastroenterologists perform colonoscopies, on a daily basis. We measured the quality indicators in three cohorts: A, intention for total colonoscopy cases; B, cohort A excluding bowel obstruction cases; C, colorectal cancer (CRC) screening cases. RESULTS: In 2015, overall sedation administration rate (SAR) was 93.0% (91.6-94.4%), achieving our target to give conscious sedation to >90% of patients undergoing colonoscopy in all three cohorts. Colonoscopy completion rate (CCR) increased significantly (P<0.0001) from 94.8% (93.4-96.2%) to 98.1% (97.3-98.9%) in cohort B and numerically from 96.6% (94.4-98.8%) to 98.6% (97.4-99.7%) in cohort C, at the same periods. In cohort C, adenoma detection rates (ADR) were similar-27.1% (21.7-32.5%) and 27% (22.7-31.3%)-in the two periods. There were only two serious early complications: one cardiorespiratory event and one perforation in 2013 and 2015, respectively. While significant variability regarding SAR (ranging from 80% to 100%) was detected among the participating endoscopists, all but one of them constantly achieved [judged by the lower confidence interval (CI) of the quality indicator] CCRs higher than the recommended by international guidelines. On the contrary ADR was variable among endoscopists during the studied periods. CONCLUSIONS: Although there is certain variability in endoscopists' performance, the overall colonoscopy quality indicators meet or exceed the internationally recommended standards, in our endoscopy facility.

A Girl with 10 Mb Distal Xp Deletion Arising from Maternal Pericentric Inversion: Clinical Data and Molecular Characterization.

BACKGROUND: Short arm deletions of the X-chromosome are challenging issues for genetic counseling due to their low penetrance in population. Female carriers of these deletions have milder phenotype than male ones, considering the intellectual ability and social skills, probably because of the X-chromosome inactivation phenomenon. CASE REPORT: A female patient with a 10Mb distal Xp deletion and an Xq duplication, showing mild intellectual disability, is described in this report. While the deletion arose from a maternal pericentric inversion, the duplication was directly transmitted from the mother who is phenotypically normal. CONCLUSION: This report underlines the usefulness of molecular cytogenetic technics in postnatal diagnosis.

Non-invasive prenatal screening versus prenatal diagnosis by array comparative genomic hybridization: a comparative retrospective study.

OBJECTIVE: To calculate the proportion of array comparative genomic hybridization (aCGH) pathogenic results, that would not be detectable by non-invasive prenatal screening (NIPS). METHODS: This is a comparative study using data from 2779 fetuses, which underwent invasive prenatal diagnosis, and the samples were analyzed using aCGH. The simulated NIPS assay would test for trisomies 21, 18, 13, monosomy X, 47, XXX, 47, XYY, and 47, XXY. Indications for invasive testing were grouped into categories and the absolute, relative rates of pathogenic/likely pathogenic results of aCGH analysis that would not be detectable by NIPS were calculated. RESULTS: The expected rate of aCGH-detected abnormalities that would not be detectable by NIPS was 28.0% (95% CI 14.3-47.6) for nuchal translucency (NT) 95 to 99th centile; 14.3% (95% 5.0-34.6) for NT > 99th centile; 34.2% (95% CI 21.1-50.1) for high-risk first-trimester results (regardless of NT); 52.4% (95% CI 32.4-71.7) for second-trimester markers; and 50.0% (95% CI 26.8-73.2) for advanced maternal age. The overall rate of aCGH pathogenic/likely pathogenic results was 5.0% and 44.0% (95% CI 36.0-52.2) of them would not be detected by NIPS. CONCLUSIONS: Approximately half of the abnormal aCGH results would not be detectable by standard NIPS assays, highlighting the necessity of pre-test counseling, and illustrating the limitations of NIPS. © 2017 John Wiley & Sons, Ltd.

A nationwide survey of training satisfaction and employment prospects among Greek gastroenterology fellows during the economic recession.

BACKGROUND: This study assessed Greek gastroenterology fellows' satisfaction regarding training, working conditions, quality of life and future employment perspectives. METHODS: Greek gastroenterology fellows completed an anonymous multiple-choice electronic questionnaire designed to rate their satisfaction using a five-step Likert scale in two major domains: 1) fellowship program (training, working conditions, research activity, acquisition of endoscopic competencies, quality of life); and 2) professional expectations. Pareto analysis was used to determine the factors that had the most negative effect on fellows' satisfaction. RESULTS: In 2016, over a two-month period, 121 invitations were distributed and 70 (58%) fellows responded. Overall, responders reported a low level of satisfaction with their training programs: the mean total satisfaction score was 42.94±11.55 (range 15-75). Pareto analysis revealed that the main factors negatively affecting satisfaction were financial remuneration, routine or menial work, and uncertainty about professional future (98.6%, 94.3% and 92.9% unfavorable answers, respectively). Of the total participants, 53% felt tired or very tired and 44.3% of them reported high levels of stress following a normal working day. Although the majority of the fellows did not regret choosing gastroenterology fellowship training, 34.4% of them would choose a different training environment, if possible. CONCLUSION: Our study revealed that Greek gastroenterology fellows are dissatisfied with their training programs and with their professional perspectives. It also detected the issues that contribute most to this unfavorable outcome.

Eradication of Helicobacter pylori Infection Restores ki67, p53, and Cyclin D1 Immunoreactivity in the Human Gastric Epithelium.

INTRODUCTION: We evaluated the effect of Helicobacter pylori (HP) eradication on p53, cyclin D1 expression, and cell proliferation in gastric mucosa. MATERIALS AND METHODS: We assessed p53, cyclin D1, and ki67 immunoexpression in gastric mucosa from 31 HP chronic gastritis patients and 12 controls. Reassessment was performed 6 months after successful HP eradication. RESULTS: Successful eradication resulted in significant decrease of p53 (1.53 ± 0.16 vs 0.83 ± 0.19, P = 0.01) and ki67 (9.84 ± 0.96 vs 4.77 ± 0.27, P < 0.001) staining in the antrum. Similarly, p53 immunoreactivity significantly decreased in the corpus (1.27 ± 0.20 vs 0.46 ± 0.15, P = 0.02), while there was a trend for decreased corpus cyclin D1 and ki67 expression (0.17 ± 0.07 vs 0.0, P = 0.08 and 8.71 ± 1.24 vs 5.85 ± 0.54, P = 0.09, respectively). Importantly, after successful HP eradication, the immunoreactivity of the studied parameters was similar to that of controls. CONCLUSION: Successful HP infection eradication restores p53, cyclin D1, and ki67 immunoreactivity in the gastric mucosa to the level of controls.

Long-term patient satisfaction of gastrointestinal endoscopic procedures.

BACKGROUND: We prospectively assessed patient satisfaction in a Greek Academic endoscopy facility. METHODS: Consecutive outpatients filled a satisfaction questionnaire right after their endoscopy (D1), 3 days (D3) and 3 months (M3) later. Overall patient satisfaction was measured by their willingness to repeat endoscopy in our facility and to further recommend it. Participant satisfaction regarding pre-procedural, procedural and post-procedural issues was measured using a five-step Likert scale in 19 items with 4 and 5 scores indicating favorable responses. Pareto analysis was used to determine service issues requiring improvement. Late adverse events were recorded at D3 and M3 assessments. RESULTS: Over six months, 501 patients participated (89.4% and 87.8% response rate at D3 and M3 assessments, respectively). More than 97% of the participants would repeat the procedure in our facility and would recommend our endoscopy service, at all three assessments. Pareto analysis identified waiting time until the appointment and on the day of the examination, discomfort during and after the endoscopy, time to obtain the pathology report and overall management of the patient problems as the issues requiring improvement. No predictor of high satisfaction score has been identified. No serious late adverse events were reported. CONCLUSION: Despite the overall high levels of patient satisfaction, management of patient discomfort and organizational issues need improvement.

Systematic analysis of the contribution of c-myc mRNA constituents upon cap and IRES mediated translation.

Fine tuning of c-MYC expression is critical for its action and is achieved by several regulatory mechanisms. The contribution of c-myc mRNA regulatory sequences on its translational control has been investigated individually. However, putative interactions have not been addressed so far. The effect of these interactions upon the translatability of monocistronic and bicistronic chimaeric mRNAs, carrying combinations of the c-myc mRNA 5'-untranlated region (UTR), 3'-UTR, and coding region instability element (CRD) was investigated on this study. The presence of the 5'-UTR induced an increase in translatability of 50%. The presence of the CRD element, when in frame, reduced translatability by approximately 50%, regardless of the expression levels of the wild type CRD- binding protein (CRD-BP/IMP1). Conversely, overexpression of a mutated CRD-BP/IMP1 (Y396F) further impeded translation of the chimaeric mRNAs carrying its cognate sequences. The presence of the c-myc 3'-UTR increased translatability by approximately 300% affecting both cap and c-myc internal ribosome entry site (IRES) mediated translation. In addition, 3'-UTR rescued the cap mediated translation in the presence of the polyadenylation inhibitor cordycepin. Furthermore, the 3'-UTR rescued cap mediated translation under metabolic stress conditions and this was enhanced in the absence of a long poly (A) tail.

Routine use of array comparative genomic hybridization (aCGH) as standard approach for prenatal diagnosis of chromosomal abnormalities. Clinical experience of 1763 prenatal cases.

OBJECTIVE: This study aims to evaluate the diagnostic yield of comparative genomic hybridization microarrays (aCGH) and compare it with conventional karyotype analysis of standard >5-Mb resolution. METHOD: A total of 1763 prenatal samples were analyzed by aCGH (CytoChip Focus Constitutional microarrays, BlueGnome, Cambridge). The diagnostic yield of chromosomal abnormalities detected by aCGH was assessed, compared with conventional karyotype analysis. RESULTS: The result was pathogenic/unknown penetrance in 125 cases (7.1%), and a variant of unknown significance (VOUS) was detected in 13 cases (0.7%). Out of the 125 cases with abnormal findings, 110 were also detected by conventional karyotype analysis. The aCGH increment in diagnostic yield was 0.9% (15/1763) and 1.6% when VOUS were included. Stratifying the sample according to indications for prenatal invasive testing, the highest values of diagnostic yield increment were observed for patients positive for second-trimester sonographic markers (1.5%) and for the presence of fetal structural anomalies (1.3%). In contrast, the incremental yield was marginal in patients with fetus with increased nuchal translucency (0.5%). CONCLUSION: The present study indicates that routine implementation of aCGH offers an incremental yield over conventional karyotype analysis, which is also present in cases with 'milder' indications, further supporting its use as a first-tier test.

D-dimer, factor VIII and von Willebrand factor predict a non-dipping pattern of blood pressure in hypertensive patients.

AIM: The aim of this study is to assess whether the haemostatic markers D-dimer, factor VIII (FVIII) and von Willebrand factor (VWF) are predictive of non-dipping status in treated hypertensive patients; so, as easy available laboratory data can predict non-dipping pattern and help with the selection of the patients whom circadian blood pressure should be re-examined. PATIENTS AND METHODS: Forty treated hypertensive patients with essential hypertension were included in the study. Twenty-four-hour ambulatory blood pressure monitoring was performed in all patients. Daytime and nocturnal average systolic, diastolic and mean blood pressures were calculated. Patients were characterised as "non-dippers" on the basis of a less than 10 % decline in nocturnal blood pressure (BP); either systolic or diastolic or mean (MAP). D-dimer as marker of fibrinolytic function, FVIII activity and VWF antigen as marker of endothelial dysfunction were measured on plasma. The predictive efficiency was analysed by receiver operating characteristic (ROC) curves. Youden index was used for the estimation of the cut-off points and the associated values for sensitivity and 1-specificity. RESULTS: Plasma levels of D-dimer, FVIII and VWF were significantly higher in non-dippers as compared with dippers, irrespective of the classification used (BP index); all P < 0.05. The ROC curves indicated a good diagnostic efficiency for D-dimer (AUC(ROC) = 0.697, 0.715 and 0.774), FVIII (AUC(ROC) = 0.714, 0.692 and 0.755) and VWF (AUC(ROC) = 0.706, 0.740 and 0.708) in distinguishing non-dipping pattern (systolic, diastolic or mean) in the study population; all P < 0.05. Among the three haemostatic markers, D-dimer presents the most satisfactory sensitivity/1-specificity for the differentiation of non-dippers, with a cut-off point >168 ng/ml (sensitivity/1-specificity for systolic BP non-dippers of 0.789/0.381, for diastolic BP non-dippers 0.923/0.444 and for MAP non-dippers 0.875/0.375). CONCLUSION: In conclusion, D-dimer has a good predictive value for non-dipping pattern and the decision for the 24-h ambulatory blood pressure re-monitoring among dippers could rely on its values.

Changes in haemostatic and platelet activation markers in non-dipper hypertensive patients.

BACKGROUND: Non-dipper hypertensive patients are at increased risk for cardiovascular disease. Coagulation and fibrinolysis activation factors are considered as risk factors for cardiovascular disease. The aim of this study was to examine the relationship between the haemostatic and platelet activation markers and the non-dipping pattern in treated hypertensive patients. PATIENTS AND METHODS: Seventy-one treated hypertensive patients (53 with essential and 18 with secondary hypertension, due to chronic kidney disease-stage 4), aged 33 to 81 years (30 men), were classified as dippers and non-dippers, according to the presence or absence, respectively, of a decline of nocturnal average systolic blood pressure (BP) by more than 10% of the diurnal BP (non-dipping pattern) on 24-hour ambulatory BP monitoring. Plasma levels of factors VIII and IX, fibrinogen, prothrombin fragment 1 + 2, thrombin-antithrombin complex, protein C, plasmin-alpha-2 antiplasmin complex, D-dimer and platelet factor 4 were measured in all patients. RESULTS: Thirty-seven patients were classified as dippers and 34 as non-dippers. The percentages of patients with essential and with secondary hypertension were similar in the dippers and in the non-dippers groups (both P = 0.754). Multivariate analysis of variance showed statistically significant differences in all measured variables between dippers and non-dippers (P = 0.043). Plasma levels of factors VIII and IX, fibrinogen, prothrombin fragment 1 + 2, protein C, plasmin-alpha-2-antiplasmin complex, and D-dimers were significantly higher in non-dippers when compared to dippers (P < 0.05 for all). In contrast, there were no significant differences in plasma levels of thrombin-antithrombin complex (P = 0.955) and platelet factor 4 (P = 0.431) between the two groups. CONCLUSION: This study provides evidence that non-dipper treated hypertensive patients exhibit alterations in haemostasis, which may affect their cardiovascular risk.

Dynamics of telomere's length and telomerase activity in Philadelphia chromosome negative myeloproliferative neoplasms.

Telomere exhaustion and increased telomerase activity are associated with the acquisition of aggressive molecular events in a variety of haematological malignancies. In Philadelphia chromosome negative myeloproliferative neoplasms (Ph(neg)MPN's), telomere dynamics during clonal evolution of these diseases have not yet been fully elucidated. Herein we demonstrated that telomere shortening is a global phenomenon in Ph(neg)MPN's, irrespective of disease phenotype, treatment administration and JAK2V617F mutational status but the presence of additional cytogenetic abnormalities further affects them. Consistent with the above finding, TA was upregulated in CD34+ haemopoietic progenitors from almost all Ph(neg)MPN subgroups compared to healthy donors. Moreover, TL below the cut-off value of 27% could predict disease progression in Ph(neg)MPN patients (PFS at 5 years 39% vs 81%). Thus, TL emerges as a new prognostic marker in Ph(neg)MPN, reflecting probably the genetic instability of highly proliferating MPN clones.