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SummaryWithout thromboprophylaxis, knee arthroscopy (KA) carries a low to moderate risk of venous thromboembolism. Over 5 million arthroscopies are performed worldwide yearly. It was our study objective to assess the efficacy and safety of rivaroxaban for thromboprophylaxis after therapeutic KA. Patients undergoing KA in nine Italian teaching or community hospitals were allocated to once-daily rivaroxaban (10 mg) or placebo for seven days in a phase II, multicentre, double-blind, placebo-controlled randomised trial. The primary efficacy outcome was a composite of all-cause death, symptomatic thromboembolism and asymptomatic proximal DVT at three months; major bleeding represented the primary safety outcome. All patients underwent whole-leg ultrasonography at day 7(+1), or earlier if symptomatic. A total of 241 patients were randomised (122 rivaroxaban, 119 placebo), and 234 completed the study. The primary efficacy outcome occurred in 1/120 of the rivaroxaban group and in 7/114 of the placebo group (0.8% vs 6.1%, respectively, p=0.03; absolute risk difference, −5.3%, 95% CI, −11.4 to −0.8; crude relative risk 0.14, 95% CI, 0.02 to 0.83; number-needed-to-treat=19). No major bleedings were observed. We found no association between different arthroscopic procedures and thrombotic events. Small sample size, high exclusion rate, and low number of anterior cruciate ligament reconstruction procedures are the main limitations of our study. In conclusion, a seven-day course of 10-mg rivaroxaban may be safely employed for thromboprophylaxis after KA. Whether prophylaxis after KA should be given to all patients, or to selected “high-risk” subjects, remains to be determined. A larger trial to verify our preliminary results is warranted.

Summary - The animal and plant biodiversity of the Italian territory is known to be one of the richest in the Mediterranean basin and Europe as a whole, but does the genetic diversity of extant human populations show a comparable pattern? According to a number of studies, the genetic structure of Italian populations retains the signatures of complex peopling processes which took place from the Paleolithic to modern era. Although the observed patterns highlight a remarkable degree of genetic heterogeneity, they do not, however, take into account an important source of variation. In fact, Italy is home to numerous ethnolinguistic minorities which have yet to be studied systematically. Due to their difference in geographical origin and demographic history, such groups not only signal the cultural and social diversity of our country, but they are also potential contributors to its bio-anthropological heterogeneity. To fill this gap, research groups from four Italian Universities (Bologna, Cagliari, Pisa and Roma Sapienza) started a collaborative study in 2007, which was funded by the Italian Ministry of Education, University and Research and received partial support by the Istituto Italiano di Antropologia. In this paper, we present an account of the results obtained in the course of this initiative. Four case-studies relative to linguistic minorities from the Eastern Alps, Sardinia, Apennines and Southern Italy are first described and discussed, focusing on their micro-evolutionary and anthropological implications. Thereafter, we present the results of a systematic analysis of the relations between linguistic, geographic and genetic isolation. Integrating the data obtained in the course of the long-term study with literature and unpublished results on Italian populations, we show that a combination of linguistic and geographic factors is probably responsible for the presence of the most robust signatures of genetic isolation. Finally, we evaluate the magnitude of the diversity of Italian populations in the European context. The human genetic diversity of our country was found to be greater than observed throughout the continent at short (0-200 km) and intermediate (700-800km) distances, and accounted for most of the highest values of genetic distances observed at all geographic ranges. Interestingly, an important contribution to this pattern comes from the “linguistic islands” (e.g. German speaking groups of Sappada and Luserna from the Eastern Italian Alps), further proof of the importance of considering social and cultural factors when studying human genetic variation.

Recent genetic studies of the Tuareg have begun to uncover the origin of this semi-nomadic northwest African people and their relationship with African populations. For centuries they were caravan traders plying the trade routes between the Mediterranean coast and south-Saharan Africa. Their origin most likely coincides with the fall of the Garamantes who inhabited the Fezzan (Libya) between the 1st millennium BC and the 5th century AD. In this study we report novel data on the Y-chromosome variation in the Libyan Tuareg from Al Awaynat and Tahala, two villages in Fezzan, whose maternal genetic pool was previously characterized. High-resolution investigation of 37 Y-chromosome STR loci and analysis of 35 bi-allelic markers in 47 individuals revealed a predominant northwest African component (E-M81, haplogroup E1b1b1b) which likely originated in the second half of the Holocene in the same ancestral population that contributed to the maternal pool of the Libyan Tuareg. A significant paternal contribution from south-Saharan Africa (E-U175, haplogroup E1b1a8) was also detected, which may likely be due to recent secondary introduction, possibly through slavery practices or fusion between different tribal groups. The difference in haplogroup composition between the villages of Al Awaynat and Tahala suggests that founder effects and drift played a significant role in shaping the genetic pool of the Libyan Tuareg.

We investigated the behavior of prothrombin fragment F1+2 and thrombin-antithrombin complexes in 70 patients treated with chronic anticoagulant therapy. Moreover, in a longitudinal study 37 patients were evaluated twice and 16 patients three times. Twenty-eight age-and sex-matched healthy subjects were also studied as a control group. Prothrombin fragment F1+2 and thrombinantithrombin complexes were significantly higher in controls than in patients on anticoagulants. There were no differences in prothrombin fragment F1+2 or thrombinantithrombin values among patients with different International Normalized Ratios, nor in the same patients studied two or three times. Our results confirm that oral anticoagulant treatment can effectively reduce thrombin activity. However, strong anticoagulation does not induce a further significant decrease in fragment F1+2 values. Therefore, we feel measurement of fragment F1+2 might be less useful than thought in optimizing oral anticoagulant therapy.

In 1959 a modified PT was introduced for monitorig oral anticoagulant therapy, the so-called Thrombotest (l). Thrombotest reagent is made of a brain thromboplastin together with bovine adsorbed plasma with constant amount of factor V and fibrinogen. The test can be performed using whole blood employing the manual tilt tube tecnique. Since only a thermostatic bath, rnicropipettes and a stop-watch are neede.d, “Thrombotest method” still represents a cheap and easy way for monitoring oral anticoagulant therapy. This means that the management of small groups of patients could be done even in country side out-patients Thrombosis Services without a more complex laboratory equipment such as centrifuge and coagulometer. We think that the matter is of interest since many patients encounter difficulties in coming periodically to city-centres. This problem is particularly relevant for the elderly. In fact they have oilen not prescribed oral anticoagulants since they live too far born the main centres, being of course impossible a correct monitoring of therapy. The aim of this study was to investigate whether the “old manual thrombotest tecnique” shows an agreement with the new adopted fast automated PT tecnique performed with a coagulometer in main hospital laboratories.

Esterase D (ESD), glyoxalase 1 (GLO1), phosphogluconate dehydrogenase (PGD) and phosphoglucomutase 1 and 2 (PGM1 and PGM2) systems have been studied in the Salerno province (Campania, Southern Italy). The mean weighted frequencies for the Campania region were calculated. These frequencies show a general similarity to those reported for the other Italian regions.

Surnames of parents and grandparents were collected from 1993 children in the primary schools of the thirteen Italo-Greco communes that lie in two areas, four communes in Reggio Calabria in the "toe" of Italy and nine in Lecce in the "heel." The coefficients of relationship by isonymy show almost no relationship between the two areas. The smaller area in Reggio Calabria Province has consistently larger coefficients of relationship between communes than the larger area in Lecce Province. The difference can be ascribed to greater accumulated random isonymy in the smaller area. These populations are not genetic isolates, but each area shows a degree of cohesiveness with respect to surnames that suggests that they are genetically somewhat distinct. Contiguous pairs of communes tend to have higher coefficients of relationship than pairs of communes separated by intervening communes.

We have performed the BT test in 55 patients undergoing oral anticoagulant therapy monitored by means of Thrombotest (TT). Patients in steady state of anticoagulation showed longer BT than normal controls; patients in overdose phase had longer BT values than either controls or patients in steady state. After recovery the overdose phase patients showed BT values not different from those of the controls. Moreover we were able to find in our patients a significant linear correlation between BT and TT. Impairment in primary haemostasis could be due either to a scarce fibrin deposition in the haemostatic plug or to deficiency of a possible vitamin K dependent vascular "bleeding factor".

Phenotype and gene frequencies of twelve genetic markers (ABO, RH, MNS, ACP1, ESD, PGD, PGM1, PGM2, HB, ALB, CP and HP) of the three Croatian communities (Acquaviva Collecroce, Montemitro and S. Felice del Molise) living in Southern Italy are reported. From the comparison with the surrounding Italian population and with Balkan populations, some instances of still incomplete genetic admixture can be inferred (ABO*A and O, ESD, PGD and PGM1).

In the present paper we report on new data of the frequency of common and rare variants in the Italian population for ADA, AK-1, 6-PGD, EsA, EsB, EsD, PGM-1, PGM-2, SOD-A, AcP, GPT, and PGI. Moreover we present a comprehensive review of the available data on the electrophoretic variants of red cell enzymes in Italians. We find a considerable degree of genetic heterogeneity between the various populations living in the Peninsula and between the population of the Peninsula and of Sardinia. We also find that the estimates of the average heterozygosity are considerably smaller for the population of Sardinia as compared to Peninsula and Sicily. Finally, we report on the occurrence of several uncommon enzyme variants, which overall frequency is very similar to previously reported estimates for North European populations (Harris et al. 1974).

A random sample of 686 unrelated subjects from Bari (Southern Italy) and Genoa (Northern Italy) provinces was studied for HP polymorphism. The correlation between the HP*1 frequencies and geographical coordinates was studied for the populations of Italy, Europe, Middle East and Mediterranean basin. The results reveal the existence of a gradient of declining HP*1 frequencies from north-west to south-east across Europe and the Middle East.

The aim of our study was to investigate the effect of a diet with a known vitamin K content on the monitor test for oral anticoagulant therapy. We studied 10 poorly controlled patients (7 women and 3 men, mean age 48+15 years) in therapy with acenocoumarol for at least 1 year. Another group of 10 poorly controlled patients was considered as a control group. After a baseline period, during which a free diet was allowed, patients were administered a diet with a controlled vitamin K content; in the same period, control subjects were not subjected to any dietary restriction. Thrombotest (Nyegaard, Oslo) was employed for monitoring oral anticoagulant therapy, with a therapeutic range between 2.3 and 4.8 INR. We found a significant difference by thrombotest between the percentages within the therapeutic range obtained before and during dietary treatment (p = 0.0001). The difference in percentages was -0.31 and the 95% CI, of the difference ranged from -0.45 to -0.17. No significant difference was shown in the control group in the same periods. Our data suggest that a diet with a controlled vitamin K content is effective in increasing the percentage of tests within the therapeutic range in patients with poorly controlled anticoagulation.

Prostate and breast cancer are major causes of death worldwide, mainly due to patient relapse upon disease recurrence through formation of metastases. Chemokines are small proteins with crucial roles in the immune system, and their regulation is finely tuned in early inflammatory responses. They are key molecules during inflammatory processes, and many studies are focusing on their regulatory functions in tumor growth and angiogenesis during metastatic cell seeding and spreading. Bindarit is an anti-inflammatory indazolic derivative that can inhibit the synthesis of MCP-1/CCL2, with a potential inhibitory function in tumor progression and metastasis formation. We show here that in vitro, bindarit can modulate cancer-cell proliferation and migration, mainly through negative regulation of TGF-beta and AKT signaling, and it can impair the NF-kappa B signaling pathway through enhancing the expression of the NF-kappa B inhibitor IkB-alpha. In vivo administration of bindarit results in impaired metastatic disease in prostate cancer xenograft mice (PC-3M-Luc2 cells injected intra-cardially) and impairment of local tumorigenesis in syngeneic Balb/c mice injected under the mammary gland with murine breast cancer cells (4T1-Luc cells). In addition, bindarit treatment significantly decreases the infiltration of tumor-associated macrophages and myeloid-derived suppressor cells in 4T1-Luc primary tumors. Overall, our data indicate that bindarit is a good candidate for new therapies against prostate and breast tumorigenesis, with an action through impairment of inflammatory cell responses during formation of the tumor-stroma niche microenvironment.