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Vascular thrombosis, both arterial and venous, is a condition associated with significant morbidity and mortality. There are multiple risk factors for thrombosis, both congenital and acquired, and in the majority of cases, these risk factors are not modifiable. Over the past 2 decades, multiple drugs (both illegal and legal) have been associated with increased risk of thrombosis. However, due to limited scientific literature regarding the prothrombotic tendencies of these drugs, there is a concomitant limited understanding of the pathophysiology of drug-induced thrombosis. As drugs are one of the few modifiable risk factors for thrombosis, further study and dissemination of knowledge regarding drug-associated and drug-induced thrombosis are essential and have the potential to lead to decreased future incidence of thrombosis. The mechanisms at the basis of the thrombophilic activity of these drugs are variable and sometimes still ill recognized. Increased levels of clotting factors, reduction in coagulation natural inhibitors, decreased fibrinolysis, activated clotting factors, increased blood viscosity, endothelial damage, and increased platelet number and activation are the most frequent causes. Arterial steal or coronary arteries no flow has also been implicated. In some cases due to the intake of several drugs, more than one mechanism is present in a given patient. The purpose of the present review is to analyze all the drugs demonstrated to be potentially thrombotic. It is hoped that a prudent use or nonuse of these drugs might result in a reduction of thrombosis-associated diseases. [ABSTRACT FROM AUTHOR]

Objectives: The waning of humoral immunity after COVID-19 vaccine booster (third dose) has not yet been fully evaluated. This study updates data on anti-SARS-CoV-2 spike protein receptor binding domain (S-RBD) binding antibodies (bAb) and neutralizing antibodies (NAb) levels in individuals with homologous vaccination 3-4 months after receiving the booster dose., Methods: Fifty-five healthcare workers (HCW) from Padova University-Hospital were asked to collect serum samples for determining antibodies (Ab) at 12 (t 12 ) and 28 (t 28 ) days, at 6 months (t 6m ) after their first Comirnaty/BNT162b2 inoculation, and 3-4 months after receiving the 3rd homologous booster dose. HCW were monitored weekly for SARS-CoV-2 infection. Ab titers were measured by two chemiluminescent immunoassays, one targeting the S-RBD immunoglobulin G (IgG), and one surrogate viral neutralization test (sVNT), measuring NAb., Results: Twenty of the HCW had natural COVID-19 infection (COVID+) at different times, before either the first or the second vaccination. Median S-RBD IgG and NAb levels and their interquartile ranges 3-4 months after the 3rd dose were 1,076 (529-3,409) kBAU/L and 15.8 (11.3-38.3) mg/L, respectively, for COVID-, and 1,373 (700-1,373) kBAU/L and 21 (12.8-53.9) mg/L, respectively, for COVID+. At multivariate regression analyses, with age and gender included as covariates, S-RBD IgG bAb and sVNT NAb levels were closely associated with the time interval between serological determination and the 3rd vaccine dose (log 10 β coeff =-0.013, p=0.012 and log 10 β coeff =-0.010, p=0.025) for COVID+, whereas no such association was found in COVID- individuals., Conclusions: The third booster dose increases anti-SARS-CoV-2 Ab levels, elevated levels persisting for up to 3-4 months. Waning of Ab levels appears to be less pronounced for COVID+ individuals., (© 2022 Andrea Padoan et al., published by De Gruyter, Berlin/Boston.)

Objectives: mRNA vaccines, including Comirnaty (BNT162b2 mRNA, BioNTech-Pfizer), elicit high IgG and neutralizing antibody (NAb) responses after the second dose, but the progressive decrease in serum antibodies against SARS-CoV-2 following vaccination have raised questions concerning long-term immunity, decreased antibody levels being associated with breakthrough infections after vaccination, prompting the consideration of booster doses., Methods: A total number of 189 Padua University-Hospital healthcare workers (HCW) who had received a second vaccine dose were asked to collect serum samples for determining Ab at 12 (t 12 ) and 28 (t 28 ) days, and 6 months (t 6m ) after their first Comirnaty/BNT162b2 inoculation. Ab titers were measured with plaque reduction neutralization test (PRNT), and three chemiluminescent immunoassays, targeting the receptor binding domain (RBD), the trimeric Spike protein (trimeric-S), and surrogate viral neutralization tests (sVNT)., Results: The median percentages (interquartile range) for decrease in antibodies values 6 months after the first dose were 86.8% (67.1-92.8%) for S-RBD IgG, 82% (58.6-89.3%) for trimeric-S, 70.4% (34.5-86.4%) for VNT-Nab, 75% (50-87.5%) for PRNT 50 and 75% (50-93.7%) for PRNT 90 . At 6 months, neither PRNT titers nor VNT-Nab and S-RBD IgG bAb levels correlated with age (p=0.078) or gender (p=0.938), while they were correlated with previous infection (p<0.001)., Conclusions: After 6 months, a method-independent reduction of around 90% in anti-SARS-CoV-2 antibodies was detected, while no significant differences were found between values of males and females aged between 24 and 65 years without compromised health status. Further efforts to improve analytical harmonization and standardization are needed., (© 2021 Andrea Padoan et al., published by De Gruyter, Berlin/Boston.)

Background: Studies evaluating neutralizing antibody (NAb) after BNT162b2 vaccine are scarce. We therefore compared NAb using the plaque reduction neutralization test (PRNT) in vaccinated subjects, with those from five chemiluminescent (CLIA) assays, two targeting ACE and S-RBD interaction., Methods: Sera from 174 completely Comirnaty/BNT162b2 vaccinated healthcare workers (HCW) were evaluated at t 12 and t 28 . NAb titers at low (PRNT 50 ) or high (PRNT 90 ) stringency were compared with: Liaison SARS-CoV-2 Trimeric-S IgG, Elecsys S-RBD Ab, Maglumi SARS-CoV-2 S-RBD IgG and SARS-CoV-2 Nab; iFlash 2019-nCoV NAb., Results: Neither PRNT 50 nor PRNT 90 correlated with age (range, 24-65 years); no significant differences were found for gender. PRNT 50 and PRNT 90 seropositive titers (≥1:20) were 43 (24.7%) and 15 (8.6%) at t 12 and 167 (95.9%) and 149 (85.6%) at t 28 . CLIA results at t 28 were uncorrelated with age, apart from Elecsys S-RBD Ab (r = -0.164, p = 0.046). Gender differences were found for Maglumi SARS-CoV-2 S-RBD IgG (p = 0.037) and Maglumi NAb (p = 0.046). Considering PRNT 50 at thresholds of 1:20 (or 1:40) and 1:160 (or 1:320), corresponding to different immune protective levels, CLIA cut-offs have been identified., Conclusions: Comirnaty/BNT162b2 elicits strong NAb production, especially 28 days after first inoculum. Differences in correlation between Nab titers and circulating antibodies measured by 5 immunoassays have been found, being stronger the correlation for Maglumi Nab., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In western countries, about half of the hospitalized patients are anemic. Generally, these patients are old, often with multiple diseases, and anemia worsens the prognosis, finally increasing the risk of death. We describe a monocentric observational study that evaluates 249 consecutive adult patients (160 women and 89 men) with anemia admitted in the internal medicine department over five months. They represent 71.5% of all patients admitted in the study period. Demographic, historical, and clinical data, laboratory tests, duration of hospitalization, readmission at 30 days, and death were recorded. Patients were stratified by age (75-84=old, >85 years=oldest-old), anemia severity, and etiology of anemia. Anemia was found in 67.5% of old and in 77.2% of oldest-old patients. In 37% of old and 32% of oldest-old patients, anemia was mild, in 43% old and 59% of oldest-old moderate and in 20% old and 9% of oldest-old severe in agreement with WHO criteria. Moderate anemia was significantly more common in the oldest-old (p=0.01). The causes of anemia were iron deficiency in 10.6% of patients, other deficiencies in 2.8%, chronic diseases in 38.2%, hematologic neoplasms in 6.1%, multifactorial in 24.1%, and undetermined in 19.9%. The oldest-old have a higher frequency of multifactorial anemia (p=0.04), while hematologic neoplasms were more common in old patients (p=0.03). Most patients with undetermined anemia had mild/moderate forms. An anti-anemic treatment, mainly blood transfusion, was adopted in 100% of oldest-old patients and in 60% of old (p= 0.04). Anemia (and/or its treatment) was reported in the discharge letter in 19% of old and in 28.2% of oldestold patients. From a general point of view, physicians seem to disregard anemia in the context of more important pathologic conditions. In oldest-old patients, multifactorial anemia seems to be considered only "one more cause of disability." When borderline anemia occurs, even if it can represent a relevant adverse condition in frailty, it is poorly considered., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Anemia is extremely common in hospitalized patients who are old and often with multiple diseases. We evaluated 435 consecutive patients admitted in the internal medicine department of a hub hospital and 191 (43.9%) of them were anemic. Demographic, historic and clinical data, laboratory tests, duration of hospitalization, re-admission at 30 days and death were recorded. Patients were stratified by age (<65, 65-80, >80 years), anemia severity, and etiology of anemia. The causes of anemia were: iron deficiency in 28 patients, vitamin B 12 and folic acid deficiencies in 6, chronic inflammatory diseases in 80, chronic kidney disease in 15, and multifactorial in 62. The severity of the clinical picture at admission was significantly worse ( p < 0.001), length of hospitalization was longer ( p < 0.001) and inversely correlated to the Hb concentration, re-admissions and deaths were more frequent ( p 0.017) in anemic compared to non-anemic patients. A specific treatment for anemia was used in 99 patients (36.6%) (transfusions, erythropoietin, iron, vitamin B 12 and/or folic acid). Anemia (and/or its treatment) was red in the discharge letter only 54 patients. Even if anemia is common, in internal medicine departments scarce attention is paid to it, as it is generally considered a "minor" problem, particularly in older patients often affected by multiple pathologies. Our data indicate the need of renewed medical attention to anemia, as it may positively affect the outcome of several concurrent medical conditions and the multidimensional loss of function in older hospitalized patients.

Background: This study investigated whether work ability is associated with the duration of unemployment, heart rate variability (HRV), and the level of physical activity., Methods: Thirty-four unemployed persons (mean 55.7 ± standard deviation 33.3 years, 22 female, 12 male, unemployed: range 1-22.5 years) participated in the cross-sectional study. The Work Ability Index (WAI) and International Physical Activity Questionnaire (IPAQ) were applied. Short-term (five minutes) resting HRV (Low Frequency (LF), High Frequency (HF), Total Power (TP)) was collected., Results: Work ability was positively associated with the HRV: LF (r = 0.383; p = 0.025), HF (r = 0.412; p = 0.015) and TP (r = 0.361; p = 0.036). The WAI showed a positive linear correlation with the amount of total physical activity (r = 0.461; p = 0.006) as well as with the amount of moderate to vigorous physical activity (r = 0.413; p = 0.015). No association between the WAI and the duration of unemployment occurred., Conclusions: the relation between self-perceived work ability, health-associated parameters, the HRV and the level of physical activity points out the relevance of health-care exercise and the need of stress-reducing interventions to improve perceived work ability. Our results point out the need for the further and more holistic development of healthcare for the unemployed.

Myeloproliferative Neoplasms (MPN) course can be complicated by thrombosis involving unusual sites as the splanchnic veins (SVT). Their management is challenging, given their composite vascular risk. We performed a retrospective, cohort study in the framework of the International Working Group for MPN Research and Treatment (IWG-MRT), and AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM). A total of 518 MPN-SVT cases were collected and compared with 1628 unselected, control MPN population, matched for disease subtype. Those with MPN-SVT were younger (median 44 years) and enriched in females compared to controls; PV (37.1%) and ET (34.4%) were the most frequent diagnoses. JAK2V617F mutation was highly prevalent (90.2%), and 38.6% of cases had an additional hypercoagulable disorder. SVT recurrence rate was 1.6 per 100 patient-years. Vitamin K-antagonists (VKA) halved the incidence of recurrence (OR 0.48), unlike cytoreduction (OR 0.96), and were not associated with overall or gastrointestinal bleeding in multivariable analysis. Esophageal varices were the only independent predictor for major bleeding (OR 17.4). Among MPN-SVT, risk of subsequent vascular events was skewed towards venous thromboses compared to controls. However, MPN-SVT clinical course was overall benign: SVT were enriched in PMF with lower IPSS, resulting in significantly longer survival than controls; survival was not affected in PV and slightly reduced in ET. MPN-U with SVT (n = 55) showed a particularly indolent phenotype, with no signs of disease evolution. In the to-date largest, contemporary cohort of MPN-SVT, VKA were confirmed effective in preventing recurrence, unlike cytoreduction, and safe; the major risk factor for bleeding was esophageal varices that therefore represent a major therapeutic target., (© 2019 Wiley Periodicals, Inc.)

Vitamin K-dependent clotting factors are commonly divided into prohemorrhagic (FII, FVII, FIX, and FX) and antithrombotic (protein C and protein S). Furthermore, another protein (protein Z) does not seem strictly correlated with blood clotting. As a consequence of this assumption, vitamin K-dependent defects were considered as hemorrhagic or thrombotic disorders. Recent clinical observations, and especially, recent advances in molecular biology investigations, have demonstrated that this was incorrect. In 2009, it was demonstrated that the mutation Arg338Leu in exon 8 of FIX was associated with the appearance of a thrombophilic state and venous thrombosis. The defect was characterized by a 10-fold increased activity in FIX activity, while FIX antigen was only slightly increased (FIX Padua). On the other hand, it was noted on clinical grounds that the thrombosis, mainly venous, was present in about 2% to 3% of patients with FVII deficiency. It was subsequently demonstrated that 2 mutations in FVII, namely, Arg304Gln and Ala294Val, were particularly affected. Both these mutations are type 2 defects, namely, they show low activity but normal or near-normal FVII antigen. More recently, in 2011-2012, it was noted that prothrombin defects due to mutations of Arg596 to Leu, Gln, or Trp in exon 15 cause the appearance of a dysprothrombinemia that shows no bleeding tendency but instead a prothrombotic state with venous thrombosis. On the contrary, no abnormality of protein C or protein S has been shown to be associated with bleeding rather than with thrombosis. These studies have considerably widened the spectrum and significance of blood coagulation studies.

The story of factor X (FX) Friuli. Factor X Friuli was discovered in 1969 to 1970. However, the story of that disease was an international event since patients with this defect were studied in France and in Italy, and different diagnoses were reached-FVII; FX; combined prothrombin complex; and combined FII, FVII, and FX deficiencies. The diagnostic difficulties were due to the peculiar clotting pattern presented by these patients, namely, prolonged partial thromboplastin time, prolonged prothrombin time but normal Russell viper venom clotting time. Only suitable anti-FX antisera clarified the pattern. Altogether 12 homozygotes and 102 heterozygotes have been followed during 4 decades. Six homozygotes died, 2 of them due to HIV infection and 1 due to hepatitis B liver cirrhosis. The other 3 died of nontransfusion-related morbidity. Bleeding tendency has been moderate in agreement with the extrinsic or intrinsic system assay results-FX level of 4% to 5% is considered normal. Heterozygotes may present occasional bleeding manifestations usually during surgery or delivery. Molecular analysis have shown that the mutation responsible for the defect is a Pro343Ser substitution in exon 8. Chimeric FX Friuli mice have been useful in studying the effect of FX levels on embryonic or natal mortality of these animals. No new homozygote but several heterozygotes have been recently seen. The study of FX Friuli has revolutionized the diagnostic approach to FX deficiencies. The FX should be assayed by all assay systems. The FX Friuli has never been described in any other country, and all patients studied come from the Friuli Meduna River Valley.

: To investigate the prevalence of bleeding in heterozygotes for prothrombin deficiencies. Homozygotes or compound heterozygotes with Factor II (FII) levels of less than 10% of normal are always severely symptomatic.On the contrary little is known about the heterozygous population who have FII levels around 40-50% of normal.Forty-four patients heterozygous for this defect, in comparison with age and sex matched 44 unaffected family members, have been followed during a mean observational period of 22.5 years (range 4-35 years). The study was carried out in Padua between the years 1971 and 2010.The mean prothrombin activity was 0.49 IU/dl (range 0.38-0.62) and 0.91 IU/dl (range 0.81-1.10) in the heterozygotes and in the normal counterparts, respectively.In total, 14 patients showed bleeding manifestations vs. only three among the controls. Bleeding was sometimes spontaneous but more frequently occurred after tooth extractions, surgery, or delivery.Some heterozygous patients had also to be given replacement therapy to control the bleeding. No substitution therapy was ever needed for the normal counterparts.The prothrombin activity levels in the patients who were symptomatic tended to be lower than in those who remained asymptomatic.The difference in the frequency of bleeding and in the bleeding score between patients and unaffected family members was statistically significant (P = 0.007 and 0.0007).Prothrombin levels of about 40-50% of normal may not represent well tolerated hemostatic levels in case of surgical procedures, tooth extraction, or delivery. These data may have general clinical significance even for patients who have acquired defects.

Objectives: The main objective of the study was to evaluate the incidence of bleeding manifestations in heterozygotes for FX deficiency vs. unaffected family members. Secondary objective was to compare the prevalence of arterial or venous diseases found in the two groups., Patients and Methods: A total of 128 heterozygote patients for FX deficiency were investigated. A total of 102 patients had FX Friuli; 26 patients had other forms of FX deficiency. At time of diagnosis, each patient was paired with an unaffected family member, matched by gender and age (±5). Patients and their normal counterparts were checked every 1-2 yr for a mean period of 23.5 yr. The occurrence of bleeding manifestations was recorded and scored. The occurrence of arterial diseases and venous thrombosis was also recorded as a secondary finding., Results: A total of 38 heterozygote patients (29.7%) had one or more than one bleeding manifestation. The most frequent one was bleeding after tooth extraction or surgery. On the contrary, only three control subjects (2.3%) had documented hemorrhagic symptoms. There was a good correlation between bleeding and FX levels. Arterial disease (acute coronary syndromes, ischemic stroke, stable angina, peripheral arteries disease) was found in eight patients (6.3%) with FX deficiency and in seven unaffected subjects (5.5%). On the contrary, no venous thrombosis was seen in the affected group, whereas three cases (2.3%) of documented venous thrombosis were observed in the control group (two deep veins and one superficial vein)., Conclusions: Heterozygotes FX deficiency may be accompanied by a mild bleeding tendency. This has important implications to assure a safe FX level in case of surgery or invasive procedures. Furthermore, mild FX deficiency seems to have no protective effect on arterial disease but does seem to protect from venous thrombosis., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To investigate all cases of isolated factor VII (FVII) deficiency as gathered from personal files or by a PubMed search., Patients and Methods: Personal files dealing with patients studied in Padua during the years 1970 to 2010 were reevaluated. The PubMed search was time unlimited and was carried on 2 occasions during 2014. Cross-checking of the references, listed in every article, was also carried out to avoid omissions. Inclusion criteria were isolated FVII defect of less than 40% of normal, negative coagulation pattern in the family, normal level of other vitamin K-dependent clotting factors, and normalization of the clotting factor after the therapeutic procedures, unless the patient died., Results: Twenty-nine patients met the inclusion criteria (18 male and 9 female, in 2 cases gender was unreported). This number included 1 personal case. Mean age was 37.9 (range 3-80). Underlying diseases were the following: neoplasia, infections, polytrauma, penicillin administration, nephrotic syndrome Wiskott Aldrich syndrome, and left heart failure (1 case, each); 2 patients had no underlying disease. Bleeding was variable but usually mild. There were 11 fatalities., Conclusions: Isolated FVII deficiency is a rare defect, which appears to be a finding associated with several morbid conditions, especially sepsis and tumors. This indicates the need for a careful investigation of even a mild prolongation of prothrombin time, especially when fibrinogen and partial thromboplastin time are normal., (© The Author(s) 2015.)

Background: True essential thrombocythemia (ET) may carry one of the known driver mutations (JAK2, MPL and CALR) or none of them [in triple-negative (3NEG) cases]. The patients' mutational status seems to delineate the clinical manifestations of ET., Materials and Methods: We report the data of 183 patients diagnosed with ET strictly according to the WHO 2008 criteria and with a full molecular diagnosis, including the following: 114 patients (62·3%) with JAK2V617F; 25 (13·7%) with CALR type 1 and 19 (10·4%) with CALR type 2; 3 (1·6%) with MPL; 22 (12%) who were 3NEG. Thrombotic risk was assessed by means of the IPSET-thrombosis score (IPSET-T)., Results: CALR and 3NEG patients had lower haemoglobin levels and leucocyte count than JAK2 patients. CALR patients, and those with type 2 in particular, had higher mean platelet counts and had extreme thrombocytosis more often than any of the other groups. Based on their IPSET-T stratification, 3NEG- and CALR-mutated patients belonged more frequently to the low-risk group and had a significant more favourable thrombosis-free survival rate than those with JAK2 mutation., Conclusion: These findings indicate that the three different molecular markers have a significant impact on the clinical course of true ET, giving rise to different phenotypes of the same disease., (© 2016 Stichting European Society for Clinical Investigation Journal Foundation.)

Idiopathic erythrocytosis (IE) is an absolute erythrocytosis with no known cause, diagnosed by exclusion of primary and secondary erythrocytosis. Familial erythrocytosis (FE) is a rare disease and as the rare patients with JAK2-wild-type polycythemia vera (PV) may be misdiagnosed as IE. We compared 78 patients with IE, 21 with FE and 136 with PV in the effort to identify simple features capable of discriminating between them. FE patients were younger at diagnosis either than IE and PV (p < 0.001); IE and FE had lower WBC, platelet counts and higher serum EPO levels, and had splenomegaly and thrombotic events less frequently than PV patients. Phlebotomies to obtain a haematocrit lower than 45 % induce platelet count increase in 70 % of PV but not in IE. Mainly in men, normal spleen, normal platelet counts and no history of thrombosis at diagnosis argue against PV; diagnosis of IE could be supported by means of a cycle of venesection to see how it affects their platelet count. No simple data capable of distinguishing between IE and FE were identified; therefore, a case of sporadic erythrocytosis in a young patient should be investigated as a possible genetic cause.

Factor VII (FVII) deficiency is one of the two congenital coagulation disorders that was not discovered by the description of a new bleeding patient whose clotting pattern did not fit the blood coagulation knowledge of the time (the other is factor XIII deficiency). The existence of an additional factor capable of accelerating the conversion of prothrombin into thrombin was suspected before 1951, the year in which the first family with FVII deficiency was discovered. As several investigators were involved in the discovery of FVII deficiency from both sides of the Atlantic, several different names were tentatively suggested to define this entity, namely stable factor (in contrast with labile factor or FV), cothromboplastin, proconvertin, serum prothrombin conversion accelerator, prothrombin acceleration, and autoprothrombin I. The last term was proposed by those who denied the existence of this new entity, which was instead considered to be a derivate of prothrombin activation, namely autoprothrombin. The description of several families, from all over the world, of the same defect, however clearly demonstrated the singularity of the condition. Factor VII was then proposed to define this protein. In subsequent years, several variants were described with peculiar reactivity toward tissue thromboplastins of different origin. Molecular biology techniques demonstrated several gene mutations, usually missense mutations, often involving exon 8 of the FVII gene. Later studies dealt with the relation of FVII with tissue factor and activated FVII (FVIIa). The evaluation of circulating FVIIa was made possible by the use of a truncated form of tissue factor, which is only sensitive to FVIIa present in the circulation. The development of FVII concentrates, both plasma derived and recombinant, has facilitated therapeutic management of FVII-deficient patients. The use of FVIIa concentrates was noted to be associated with the occasional occurrence of thrombotic events, mainly venous. Total or partial liver transplants have been performed with success in these patients and have "cured" their deficiencies. Prenatal diagnosis has also been performed and recent research involves the development of inhibitors of FVII + tissue factor complex or of FVIIa. This approach, if successful, could provide another antithrombotic therapeutics tool. The story of FVII well summarizes the efforts of both theoretical and clinical approaches in the characterization of a coagulation disorder, that is, among the rare bleeding conditions, most frequently encountered in clinical practice., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Heat shock protein 70 (Hsp70) is a family of proteins with key roles in regulating malignancy. Cancer cells rely on Hsp70 to inhibit apoptosis, regulate senescence and autophagy, and maintain the stability of numerous onco-proteins. Despite these important biological functions in cancer, robust chemical tools that enable the analysis of the Hsp70-regulated proteome in a tumor-by-tumor manner are yet unavailable. Here we take advantage of a recently reported Hsp70 ligand to design and develop an affinity purification chemical toolset for potential use in the investigation of the endogenous Hsp70-interacting proteome in cancer. We demonstrate that these tools lock Hsp70 in complex with onco-client proteins and effectively isolate Hsp70 complexes for identification through biochemical techniques. Using these tools we provide proof-of-concept analyses that glimpse into the complex roles played by Hsp70 in maintaining a multitude of cell-specific malignancy-driving proteins.

Background: Aims of this study were to investigate whether hepatitis C virus infection influences the incidence and natural history of intrahepatic cholestasis of pregnancy (ICP) and whether ICP has different characteristics in hepatitis C virus (HCV) positive women from ICP in HCV negative women., Methods: A prospective study for the prevalence of the HCV infection and for the incidence of ICP was carried out in the 5840 patients admitted to the Prenatal Department of Padua University, Italy, between January 1996 and January 1999. Testing was done for HCV by the enzyme linked immunosorbent assay (ELISA 3), recombinant immuno blot assay (RIBA 3) and polymerase chain reaction (PCR). The diagnosis of ICP was made on clinical grounds based on the occurence of pruritus with onset during pregnancy, persisting up to the time of delivery and disappearing after delivery, supported by demonstrating an elevation of both serum ALT and total serum bile acids. The Student's t-test, one way anova and chi-square tests were used for statistical analysis., Results: During the study period, 56 of 5840 patients developed ICP (0.96%). Of these, 12 were also HCV-RNA positive. The rate of ICP was observed more commonly in HCV-RNA positive women than in HCV-RNA negative women (20.33% or 12/59 versus 0.78% or 44/5767, P = 0.001, Conclusions: Occurrence of ICP during the third trimester should be an indication to investigate the HCV status of the patient. Although the diagnosis of ICP is not confirmed by specific tests, we confirmed a higher risk of HCV infection in this condition. Therefore, occurence of ICP during the third trimester should be an indication to investigate the HCV status of the patient. Broader studies are necessary to assess the impact of infection on the perinatal outcome of ICP.

The prevalence of HCV-RNA positivity in pregnant women goes from 1.2% to 4.5% in different countries. The aim of our study is to show pregnancy outcome, vertical/perinatal transmission rate, the viral load and the tramnsaminases trend during pregnancy and after delivery. The study involved 11,681 pregnant women screened in the Obstetric Department for High Risk Pregnancy at the University of Padua between 1992 and 1999. We evaluated the markers of HCV, HBV, HIV, the viral load and genotype and AST/ALT in the mothers and positivity and viral load of HCV-RNA in the newborns at birth and at 3rd, 6th, 9th, 12th month. Of the 11,681 pregnant women, 135 (1.15%) tested positive for the presence of anti-HCV antibodies and of the 135 anti-HCV antibody-positive mothers, 80 were found to be positive for HCV-RNA. Of 80 pregnancies that were HCV-RNA positive, 4 termined in abortion, 1 in stillborn, 1 in neonatal death, 18 in preterm delivery and 56 were carried to term. We came to the conclusion that HCV infection does not increase the risk of obstetric complications and does not influence the fetal-neonatal status at delivery; the pregnancy evolution may be complicated by the onset of cholestatsis in the 2nd and 3rd trimester; vertical transmission of the infection develops in few cases (4.8%), more likely at delivery.

The clinical cases of three patients affected respectively by Eisenmerger's syndrome, Marfan syndrome, coarctation of the aorta are described. All patients belonged to NYHA class I or II. During pregnancy contact with cardiologists, anaesthetists, neonatologists was maintained and this allowed accurate management. Both pregnancy and delivery evolved without any complication and with a positive outcome for mother and newborn.

Abdominal pregnancies are very uncommon; in the United States they are seen once every 10,000 births and consist of approximately 1% ectopic gestations. We report one case with a primary pelvic-peritoneal ectopic pregnancy, diagnosed by chance at 11 gestational weeks complicated by hemoperitoneum and acute abdomen. This case is interesting because the early diagnosis of abdominal pregnancy is frequently difficult. In fact the clinical history, physical examination, laboratory and ultrasonographic findings are non specific. The physical examination is inconclusive in most patients. Findings such as abdominal tenderness, a closed uneffaced cervix, palpation of a pelvic mass distinct from the uterus are described as being suggestive of the abdominal pregnancy. Once the diagnosis of abdominal pregnancy is made, management of these patients requires a careful and further evaluation. Most clinicians agree that immediate operative intervention is indicated for those pregnancies prior to 23 to 24 weeks, because of the high incidence of maternal morbidity with significant risks of maternal mortality, in light of the poor prognosis for the fetus. In patients who present after 24 weeks, debate has arisen in the literature concerning the appropriateness of a more conservative approach.

The HELLP syndrome (HS) belongs to the list of obstetric complications believed to be associated with coagulation disorders. It was formerly thought that chronic intravascular clotting (DIC) in the placental vessels was the main cause. A hypercoagulable state has been reported in cases of severe HS associated with microvascular abnormalities that may involve cerebral, placental, hepatic and renal vessels. A case of acute pancreatitis and DVT of inferior cava in a pregnant woman, presenting with HS at 29 weeks, who was found to have a R506Q mutation, is reported. Preeclampsia-associated pancreatitis and DVT have rarely been reported. It is hypothesized that APC-R and Factor V Leiden mutation may prove to be new and more important markers capable of predicting a more significant maternal morbidity associated with HS. Thrombosis prophylaxis may be considered during pregnancy in order to reduce hazardous multiorgan failure (MOF) in women who are heterozygous for Factor V Leiden mutation.

Marfan syndrome is usually inherited as an autosomal dominant trait with high degree of penetrance. It is caused by an abnormal fibrillin gene located on chromosome 15q. Cardiovascular involvement in Marfan syndrome has been overstressed, although very little attention has been given to obstetric complications. Marfan syndrome may be responsible of cervical incompetence, abnormal placental site and post partum haemorrhagic complications. A 22-year-old woman with Marfan syndrome had mitral regurgitation since childhood. In addition aortic root dilatation was documented over six years by means of echocardiography and had been followed up regularly in a district hospital. Echocardiography six months before pregnancy had shown minimal mitral and aortic regurgitation and aortic root dilatation of 4.1 cm; left ventricular function was normal. Repeat echocardiography evaluations during pregnancy confirmed an aortic root dilatation. Routine booking and screening investigations were all within normal limits. At the 25th week, admission was necessary following a vaginal bleeding, without pain contraction. Echography showed a placenta praevia and cervical dilatation 2.8 cm of diameter. Bed rest and intravenous thocolitic therapy were immediately enhanced. A cervical cerclage, as described by McDonald, was placed. At the 37th week the patient was admitted and cerclage removed before the caesarean section. A healthy female of 2900 g was born. The postoperative period was favourable and patient was discharge after 7 days. In the present case, it is suggested that cervical incompetence and placenta praevia may be caused by an alteration of microfibrillar fibers.