One step further: randomised single-centre trial comparing the direct and afterload techniques of embryo transfer.

STUDY QUESTION: What are the differences in ease of use between two different embryo transfer (ET) techniques: the preload direct approach and the afterload approach. SUMMARY ANSWER: The afterload technique seems to reduce the rate of difficult ETs. WHAT IS KNOWN ALREADY: Numerous published trials now document that the ET procedure has an impact on pregnancy and delivery rates after IVF. Difficult transfers should be avoided, as they reduce implantation and pregnancy rates. Preload direct ETs with soft catheters under ultrasound guidance is currently considered the best procedure. However, when using soft catheters, it is not known which technique is preferable or which one should be implemented to reduce the operator factor. STUDY DESIGN, SIZE, DURATION: This prospective randomised unblinded controlled clinical trial, included 352 ultrasound-guided ETs assigned to either direct ET or afterload ET, between September 2017 and March 2019. The sample size was calculated based on the historical rate of difficult ETs encountered between 2014 and 2015 with a direct ET procedure. PARTICIPANTS/MATERIALS, SETTING, METHODS: The inclusion criteria were women 18-38 years old, with BMI between 18 and 28, receiving a single-thawed blastocyst transfer. The exclusion criteria were use of testicular sperm and preimplantation genetic testing (PGT) cycles. The primary outcome was the rate of difficult or suboptimal transfers defined as: advancement of the outer sheath (specific for the direct transfer), multiple attempts, use of force, required manipulation, use of a stylet or tenaculum, dilatation, or use of a different catheter. The secondary outcome was clinical pregnancy rate. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 352 frozen ETs were randomised, with 176 patients in each group. The two arms were homogeneous for female and male age, female BMI, duration of infertility, secondary infertility, previous deliveries or miscarriages, myomas, previous surgery to the uterine cavity, cycle day at ovulation trigger, freeze all cycles, first transfers, indication for treatment, endometrial preparation protocol and duration, endometrial thickness, and blastocyst grade at vitrification. Across the entire population, 85 (24.1%) ETs were defined as difficult. The rate of difficult transfers was significantly higher in the direct ET group than in the afterload group: 68 (38.6%) versus 17 (9.7%), respectively (OR 0.17, 95% CI 0.09-0.30, P < 0.001). The mean percentage in the rate of difficult transfers per operator was 22.5% (SD ± 14.5%), of which 36.1% (SD ± 23.4%) were in the direct group compared with 8.6% (± 8.2%) in the afterload group (P < 0.001). The difficult transfer rate among operators varied from 0 to 43.8% (0-77.8% in the direct group and 0 to 25.0% in the afterload group). The clinical pregnancy rates (42.0% vs 48.3%, P = 0.239 in the direct and afterload groups, respectively) were not significantly different between the groups. LIMITATIONS, REASONS FOR CAUTION: There were 18 experienced operators who participated in the trial. Conclusions about the pregnancy rate should not be generalised, since the sample analysis was not performed on this outcome and, although clinically relevant, the difference was not significantly different. WIDER IMPLICATIONS OF THE FINDINGS: The rate of difficult transfers was significantly higher in the direct ET group compared with the afterload ET group, although a wide variation was observed among operators. Further studies regarding the association between transfer technique and ART outcomes are required. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was sought and there are no competing interests. TRIAL REGISTRATION NUMBER: NCT03161119. TRIAL REGISTRATION DATE: 5 April 2017. DATE OF FIRST PATIENT'S ENROLMENT: 26 September 2017.

[Digitization and Virtual Healthcare in a teaching hospital (Pisa, Italy) during COVID-19 emergency]. / Digitalizzazione e Virtual Healthcare nell'Azienda Ospedaliero Universitaria Pisana (AOUP) ai tempi dell'emergenza COVID-19.

The initial phases of COVID-19 emergency in Italy highlighted the technical delay that the national health system has accumulated in health services digitalization. Italian hospitals rapidly applied a demand systems for virtual health services based on tele-triage, tele-consultation and tele-visits procedures. This led, in the following months, the integration of virtual healthcare services applicable to the Azienda Ospedaliero Universitaria Pisa (AOUP). In particular, BCure system represents an important technological investment for the remote management of care protocols and the analysis of the complete use of health services. This is a unique system for sharing information between specialists, general practitioners and patients.

[Skills tracing and activation of multi-professional teams in response to COVID-19 pandemic]. / Mappatura delle competenze ed attivazione di equipe multi professionali in risposta ad emergenza pandemica COVID-19.

The rapid spread of Covid-19 epidemic led to a change in the organizational strategies of all Italian healthcare facilities. From January 31, 2020 (starting date of the state of national health emergency) Asst Valle Olona has prepared a reorganization of the supply units passing from a traditional division system to a structure that foresees the presence of traditional wards and a set of areas dedicated exclusively to the of Covid 19 treatments.The study aims to represent the method used for the redistribution of human capital in the new areas for identified, mapped, evaluated and reordered skills. The method may guarantee assistance to Covid-19 patients with the greatest number of human resources available and adequately trained.

The human factor: does the operator performing the embryo transfer significantly impact the cycle outcome?

STUDY QUESTION: Is Ongoing Pregnancy Rate (OPR) operator-dependent, and can experience improve embryo transfer efficiency? SUMMARY ANSWER: OPR is influenced by the operators who perform the embryo transfer (ET), and experience does not assure proficiency for everyone. WHAT IS KNOWN ALREADY: ET remains the critical step in assisted reproduction. Although many other factors such as embryo quality and uterine receptivity impact embryo implantation, the proper ET technique is clearly an operator-dependent variable and as such it should be objectively standardized. STUDY DESIGN, SIZE, DURATION: Retrospective comparative analysis including all fresh ETs performed between January 1996 and December 2016 at the Humanitas Fertility Center after IVF-ICSI cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: IVF/ICSI fresh ETs performed by 32 operators, 19 824 cycles in all, were analyzed. All transfers consisting of freehand insertion of a preloaded soft catheter into the uterine cavity under transabdominal ultrasound guidance were considered. Two different statistical analyses were performed. First, a logistic regression model with a random intercept for the operator was used to estimate the heterogeneity of the rate of success among operators, accounting for woman age, FSH, number of oocytes retrieved, fertilization rate, year of the procedure, number and stage of transferred embryos and operator's experience. Second, the relationship between experience and pregnancy rate was estimated separately for each operator by logistic regression, and operator-specific results were combined and compared in a random-effects meta-analysis. In both analyses, the operator's experience at time t was measured in terms of number of embryo transfers performed before t. MAIN RESULTS AND THE ROLE OF CHANCE: The heterogeneity among operators was highly significant (P value <0.001) and explained 44.5% of the total variability. The odds ratio of success of the worst operator in respect to the mean was equal to 0.84. For the best operator, the odds ratio of success was equal to 1.13 in respect to the mean. Based on the meta-analysis of the relationship between operator's experience and success rate, it resulted that, on average, the operators' performance did not improve with additional transfers. LIMITATIONS, REASONS FOR CAUTION: At our center, operators become independent for ET's after performing between 30 and 50 transfers under supervision. It is also possible that other relevant factors, such as embryologists on duty for the ET, have not been included in the present analysis and this may represent a potential bias. Among these, it should be mentioned that the embryologists on duty for the ET were not taken into consideration. WIDER IMPLICATIONS OF THE FINDINGS: Continued performance analysis and the use of a digital simulator could help operators to test their expertise over time and either correct poor performance or avoid doing transfers. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: NCT03561129.

Survey on Energy Drinks consumption and related lifestyle among students of two Italian high schools.

BACKGROUND: The European Food Safety Authority (EFSA) has identified some risk factors for the occurrence of side effects linked to energy drinks (EDs) consumption by young people. EDs consumption has been evaluated in a sample of students in Italy together with some aspects of their lifestyle. METHODS: The survey was performed in two high schools from September 2016 to June 2017. 583 students between 14 to 18 years were recruited and a standard questionnaire (EFSA checklist) was used to collect information on responders characteristics, beverages consumption, EDs with alcohol, and EDs and sports. RESULTS: Despite 350 out of 583 responders (60%) consumed EDs, only 146 out of 583 (25%) were EDs-alcohol consumers. Moreover, 208 out of 379 (55%) of all physically active adolescents reported frequent EDs consumption before sport trainings. CONCLUSIONS: Study results highlight the need for primary prevention measures in communication campaigns and training delivered by school to limit potential health threats related to excess of EDs consumption.

Knowledge, experiences, and attitudes toward Mantoux test among medical and health professional students in Italy: a cross-sectional study.

BACKGROUND: The World Health Organization's Action Framework for tuberculosis elimination in low-tuberculosis incidence countries includes the screening for active and latent tuberculosis in selected high-risk groups, including health care workers. In this context, medical and health profession students, exposed to nosocomial tuberculosis transmission during training and clinical rotations, are target populations for tuberculosis screening. No updated data are available on tuberculosis screening practice and knowledge of medical and health profession students in Italy. METHODS: Within the activities Italian Study Group on Hospital Hygiene of the Italian Society of Hygiene, Preventive Medicine and Public Health, we carried out a multicentre cross-sectional study to assess knowledge, attitude and practices on tuberculosis prevention and control among Medical, Dentistry, Nursing and other health professions' students. Students were enrolled in the study on a voluntary basis and were administered a previously piloted structured questionnaire. Logistic regression models were applied to explore knowledge on tuberculosis prevention by selected socio-demographic variables and University-based tuberculosis prevention practice. RESULTS: Students of seventeen Universities across Italy participated in the study, and 58.2% of them received compulsory tuberculin skin test either at enrollment or while attending clinical practice. A total of 5,209 students filled the questionnaire. 37.7% were medicine and dentistry students (Group 1), 44.9% were nursing students (Group 2) and 17.4% were other health professions' students (Group 3). Age and gender had different distributions by groups, as well as knowledge and practice on tuberculin skin test. 84.4% of the study population (95% CI = 83.3-85.3) was aware of the existence of the tuberculin skin test, 74.4% (95% CI = 73.2-75.6) knew what is the first-level screening test for latent tuberculosis and only 22.5% (95% CI = 21.4-23.6) knew how to proceed after a positive tuberculin skin test result. Overall, knowledge on tuberculosis prevention was higher in Group 2 and lower Group 3, as compared to Group 1. CONCLUSION: In Italy, the knowledge on tuberculosis screening among University students is generally good. To reduce some of the criticalities found among the different study courses, it would be appropriate to harmonize both the regulations on tuberculosis screening practices for admission to University courses, and the educational activities on the topic of tuberculosis, to be extended to all workers involved in health care setting.

Colonization by Legionella spp. of water networks in residential buildings of the Province of Pisa, Italy.

BACKGROUND: Despite the increase of community acquired cases of legionellosis in Italy over the last years, the Italian guidelines do not give indications for prevention and control of Legionella in the hot water networks (or centralized conditioning systems) of residential buildings. We performed a survey on eight medium sized apartment buildings in the Pisa district to assess the prevalence of Legionella spp. in the water network and the respondance to drinking water requisites at the point of use, according to the Italian norms. METHODS: For each building two hot water and three cold water samples (located at water entrance from the aqueduct network into the building pipework, at the exit from pressure autoclave, and at a remote tap) were collected. RESULTS: Legionella was detected in 20% of residential buildings, mostly in those with a central hot water production system. CONCLUSIONS: The study highlights a condition of potential risk for susceptible population subgroups and supports the need for measures of risk assessment and control.

Five years (2004-2009) of a restrictive law-regulating ART in Italy significantly reduced delivery rate: analysis of 10,706 cycles.

STUDY QUESTION: Was the delivery rate of ART cycles negatively affected by the enactment of the Law 40/2004 by the Italian Parliament which imposed a long list of restrictions for ART procedures? SUMMARY ANSWER: This large and extensive comparative analysis of ART outcomes prior to and after the introduction of the Law 40 revealed a significant reduction in pregnancy and delivery rates per cycle, independent of age or other clinical variables, once the law went into effect. WHAT IS KNOWN ALREADY: Several studies have been published on the effect of Law 40/2004 on ART outcomes, some authors demonstrating a negative impact of the Law in relation to specific etiologies of infertility, other authors showing opposite conclusions. STUDY DESIGN, SIZE, DURATION: Retrospective clinical study of 3808 patients treated prior to the enactment of the Law, September 1996-March 2004 (Group I) and 6898 treated during the Law, March 2004-May 2009 (Group II). PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 10 706 ART cycles were analysed, 3808 performed before and 6898 after the application of the Law. An intention-to-treat statistical analysis was performed to detect pregnancy and delivery rates (pregnancies ≥ 24 weeks) per started cycle. A P value of <0.05 was considered statistically significant. We analysed different outcomes: differences in fertilization, pregnancy and delivery rate, multiple pregnancies and miscarriage rates between the two time periods. MAIN RESULTS AND THE ROLE OF CHANCE: The delivery rate for started cycle was 20% before and 16.0% after the introduction of the Law representing a 25% reduction (P < 0.001). The multivariate analysis, corrected by female age of >38 years, duration of infertility, basal FSH level and number of retrieved oocytes, showed a 16% lower delivery rate (odds ratio: 0.84; confidence interval: 0.75-0.94). This statistical approach removed the risk that the observed effects were due to chance and confirmed unequivocally that the Law was an independent factor responsible for the reduced likelihood of a successful outcome. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study. A prospective randomized study, with patients treated in the same time period and randomized to restrictions or not, would have minimized potential limitations due to differences in years of treatments. WIDER IMPLICATIONS OF THE FINDINGS: Our findings based on the analysis of such a large number of cycles proved clearly and unequivocally that imposing restrictions on the practice of ART penalized patients. These data represent a relevant clinical contribution for countries still debating the enactment of restrictive limitations of ART.

Solvent detergent vs. fresh frozen plasma in cirrhotic patients undergoing liver transplant surgery: a prospective randomized control study.

BACKGROUND: Although orthotopic liver transplantation (OLT) is nowadays considered standard practice at experienced centres, it can still be affected by a significant risk of massive bleeding and its related complications. Solvent/detergent plasma (S/D Plasma) has been proposed as an alternative to fresh frozen plasma (FFP) to curtail such complications. This study aimed at evaluating the efficacy of S/D Plasma in OLT patients by comparing it to FFP. MATERIALS AND METHODS: Sixty-three OLT patients were randomized into two groups depending on whether they were transfused with FFP or S/D plasma. A thromboelastography-based protocol aimed at achieving and maintaining predetermined coagulation goals was used to guide plasma transfusions. At the beginning and the end of surgery, standard laboratory coagulation tests were performed together with the assessment of the VII, VIII, V, XII factors and S protein blood levels. RESULTS: The two study groups equally achieved the thromboelastography goals but with a reduced amount of transfusions in the S/D plasma group (P < 0.0001). At the end of surgery, factors V and XII and S protein blood levels were lower in the S/D plasma patients who also showed lower INR, aPTT and antithrombin III levels. CONCLUSION: In cirrhotic patients undergoing OLT, the use of S\D plasma associated with thromboelastography allows the same clinical results but with a significant reduction in the amount of plasma transfusions.

Trends in hospital acquired New Delhi metallo-beta-lactamase-producing Enterobacterales in Tuscany (Italy) from 2019 to 2021: impact of the COVID-19 pandemic.

OBJECTIVES: In Tuscany, Italy, New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE) in hospitalized patients has increasingly been observed since 2018, leading in 2019 to the implementation of enhanced control measures successfully reducing transmission. We describe the NDM-CRE epidemiology during the COVID-19 pandemic in Tuscany. METHODS: Data on NDM-CRE patients hospitalized in five Tuscan hospitals were collected from January 2019 to December 2021. Weekly rates of NDM-CRE cases on hospital days in medical and critical-care wards were calculated. In March-December 2020, NDM-CRE rates were stratified by COVID-19 diagnosis. Multi-variate regression analysis was performed to assess outcomes' differences among two periods analysed and between COVID-19 populations. RESULTS: Since March 2020, an increase in NDM-CRE cases was observed, associated with COVID-19 admissions. COVID-19 patients differed significantly from non-COVID-19 ones by several variables, including patient features (age, Charlson index) and clinical history and outcomes (NDM-CRE infection/colonization, intensive care unit stay, length of stay, mortality). During the pandemic, we observed a higher rate of NDM-CRE cases per hospital day in both non-COVID-19 patients (273/100,000) and COVID-19 patients (370/100,00) when compared with pre-pandemic period cases (187/100,00). CONCLUSIONS: Our data suggest a resurgence in NDM-CRE spread among hospitalized patients in Tuscany during the COVID-19 pandemic, as well as a change in patients' case-mix. The observed increase in hospital transmission of NDM-CRE could be related to changes in infection prevention and control procedures, aimed mainly at COVID-19 management, leading to new challenges in hospital preparedness and crisis management planning.

Minimally invasive video assisted thyroidectomy versus endoscopic thyroidectomy via the areola approach: a retrospective analysis of safety, postoperative recovery, and patient satisfaction.

AIM: Minimally invasive video-assisted thyroidectomy (MIVAT) and endoscopic thyroidectomy through areola (ETA) access are among the endoscopic approaches for thyroidectomy that have been perfected, but reports comparing the two are lacking. This study evaluated the safety, postoperative recovery, and patient satisfaction of MIVAT compared with ETA. METHODS: This study included 119 patients undergoing MIVAT and 42 patients undergoing ETA from January 2006 to October 2009. Operative time, complications, postoperative recovery, cosmetic result, and patient satisfaction were analyzed. RESULTS: The ETA group had a higher percentage of women (100% vs. 78.2%, P<0.05) and was younger (33.5 vs. 39 years, P<0.05). Thyroid volume (24.5 vs. 14.5 mL, P<0.001) and nodular diameter (26 vs. 22 mm, P<0.05) were larger in ETA group. The MIVAT group had a shorter operative time (28.2 vs. 112.8 minutes) and a lower rate of intraoperative (7.2 vs. 21.2 mL) and postoperative (0 vs. 80 mL, P<0.0001) blood loss. Rates of conversion and complications were similar. Postoperative pain at 12 hours was 1.9 in MIVAT vs. 3.1 in ETA (P<0.0001). Hospitalization was 1 day in the MIVAT group vs. 3.5 days in ETA (P<0.0001). Patient satisfaction was similar. CONCLUSION: MIVAT and ETA showed similar results for safety, although ETA might be considered more invasive than MIVAT. Patients of both groups were equally satisfied with the cosmetic result. Differently from ETA, MIVAT allows total thyroidectomy to be performed also for malignant diseases. Although different, the two approaches were safe and reliable and both are valid options. Choice might depend on the surgeon's preference, thyroid size, type of disease, and the patient's expectation about cosmesis.

[Study on the efficacy of personal protective equipment for skin against nicotine absorption through the skin route in tobacco workers]. / Verifica dell'efficacia protettiva dei dispositivi di protezione individuale per la cute, nei confronti dell'esposizione per via cutanea a nicotina, in operatori addetti alla lavorazione del tabacco.

During a previous assessment on the efficacy of some recently installed general dust extraction systems in a tuscan cigar manufacture line, both environmental and biologic monitoring were performed. Although the analysis of environmental samples supported the efficacy of the new general protection implant, these data did not parallel the results from the biologic monitoring, suggesting that nicotine skin absorption needed to be further investigated. We, therefore, carried out a study aimed at evaluating the efficacy of three different kind of PPE for skin (two nitrile gloves of different thickness and one latex glove), to be used by tobacco workers. The results of this study showed that the performance of these three materials in stopping nicotine transfer through the gloves was significantly different. The 0.22 mm thick nicotine gloves resulted, by far, the best gloves in protecting the workers' skin against nicotine exposure.

[Preliminary study to evaluate the meaning of GGT fractions analysis in a population of workers previously exposed to asbestos]. / Studio preliminare volto all'inquadramento del significato preventive del dosaggio di frazioni di GGT in una popolazione di lavoratori ex-esposti ad Amianto.

The GGT enzyme, considered for years only as a marker of liver disease and alcohol abuse, has now revealed a risk of death for many causes. Through a molecular exclusion chromatography on FPLC system (Fast Protein Liquid Chromatography), it is possible to discriminate four fractions of GGT, defined according to the molecular weight: big-GGT, medium-GGT, small-GGT and free-GGT. The objective was to study the preventing meaning of GGT fractions for asbestos-related diseases. This study was conducted on 129 workers previously exposed to asbestos, 22 patients affected by Malignant Pleural Mesothelioma and 107 healthy workers. Our data demonstrated a statistical significant correlation between the fraction free-GGT with the presence of MPM, suggesting a possible role for this molecule as a biomarker for MPM diagnosis. However, being a preliminary study, further studies are warranted to confirm our results.

Italian Constitutional Court modifications of a restrictive assisted reproduction technology law significantly improve pregnancy rate.

BACKGROUND: In May 2009, the Italian Constitutional Court banned most of the limitations of a restrictive law regulating assisted reproduction technology on the grounds that it limited a couple's right to have access to the best possible medical treatment and reduce any possible higher risk of complications. The aim of the study was to compare our results in fresh cycles before and after this change. MATERIALS AND METHODS: We analysed retrospectively 3274 IVF cycles: 2248 before and 1026 after the law was modified. RESULTS: There was no significant difference between the two groups in terms of age, basal FSH levels, years of infertility, the number of previous cycles or the number of oocytes retrieved but the number of oocytes used (2.7 ± 0.6 versus 4.6 ± 1.8; P = <0.001), the number of embryos obtained (2.0 ± 0.9 versus 3.3 ± 1.8; P = <0.001) and transferred (2.2 ± 0.7 versus 2.3 ± 0.7; P = <0.001) were all higher after the removal of the previous restrictions, as was the pregnancy rate per started cycle (23.49% versus 20.42%; P = 0.047). Before modification of the law, the pregnancies were single in 74.11% of the cases (versus 71.43% afterwards), twins in 23.44% (versus 26.89%; P = 0.318) and triplets in 2.46% (versus 1.68%; P = 0.594). CONCLUSIONS: Our preliminary results after the removal of the previous legal restrictions show a higher pregnancy rate per started cycle (3.7% represents a 15% difference) and a positive (albeit non-significant) trend towards a reduction in the number of multiple pregnancies.

Mini-invasive video-assisted surgery of the thyroid and parathyroid glands: a 2011 update.

Thyroid surgery during the last century was characterized by a development of Kocher's concepts: through a relentless work of surgeons from all over the world thyroidectomy reached a standard of quality in terms of overall results which was unimaginable in the first half of the XX century. The flattering data collected in the literature until the 90's were all concordant in assuming that there would be little space for a real improvement in the quality standard of thyroid surgery. The introduction of laparoscopic surgery, though, changed very quickly the attitude of surgeons towards their operative behavior and countless new mini-invasive techniques were soon proposed for almost any field of surgery. In 1994, Gagner published the first series of laparoscopic adrenalectomies. Soon after, parathyroid adenomas seemed to offer an ideal field of application of these new surgical concepts. The first report of an endoscopic parathyroidectomy was in 1996. One year later other videoscopic procedures were described whose results seemed quite encouraging so as to push surgeons to try the same access and the same technique also for operations on thyroid. During the following decade several endoscopic or video-assisted approaches were proposed for the removal of thyroid gland. This paper aims to evaluate the results of minimally invasive thyroid and parathyroid surgery through an extensive review of the literature, in particular as far as minimally invasive video-assisted thyroidectomy is concerned.

Hypoxic liver perfusion with mitomycin-C for treating multifocal metastases and unresectable primary tumours: a single-centre series of 42 patients.

PURPOSE: The purpose of our study was to retrospectively evaluate the feasibility, toxicity and impact on overall (OS) and disease-free (DFS) survival of intra-arterial liver perfusion with mitomycin-C (MMC) [hypoxic liver perfusion with MMC (HLPM)] in patients with multifocal liver metastases or with unresectable primary liver tumours. MATERIALS AND METHODS: Forty-two patients underwent 56 intra-arterial liver infusions with MMC between June 2001 and May 2009. The patients presented specific characteristics, i.e. they were all refractory to locoregional (LR) and/or systemic treatments. HLPM consists of selective catheterisation of the common hepatic artery, permanent occlusion of the gastroduodenal artery at its origin using metal coils, an inflated balloon catheter placement at the origin of the proper hepatic artery to block blood flow and induce hypoxia for around 10 min, MMC infusion and vascular-bed occlusion through injection of an absorbable haemostatic agent. During the procedure, the patients received anaesthesiological monitoring. Biochemical and morphological responses were evaluated, as were haematological, hepatic and systemic toxicity. RESULTS: Patients were hospitalised for 10 days on average (range 7-15). Side effects were liver toxicity in all cases, acute pancreatitis in one case and liver failure in one case. Computed tomography performed at 30 days documented a partial response (PR) in 29%, stable disease (SD) in 45% and progressive disease (PD) in 26% of patients. The response lasted 4 months on average (range 3-6). Mean overall survival (OS) was 20 months for all patients, reaching 30 months in those with colorectal carcinoma. CONCLUSIONS: The procedure is feasible, and treatmentrelated toxicity and mortality rates are acceptable. It may be considered a palliative treatment option in patients with advanced liver disease in centres with adequately experienced medical teams.

[Assessment of urinary cotinine in a group occupationally exposed to nicotine]. / Valutazione della cotinina urinaria in un gruppo di esposti professionalmente alla nicotina.

In a Tobacco processing company, located in central Italy, both air nicotine and, one of its metabolites, the urinary cotinine were assessed, as part of the evaluation of the effectiveness of recently implemented technical preventive controls. Urinary cotinine measurements ranged from 9,63 to 234,09 microg/gr creat. in non-smokers and from 178,79 to 2476,19 microg/gr creat. in smokers. Urinary cotinine proved useful as an exposure biological index especially in terms of population monitoring. On the contrary, the meaning of the measured values were less clear in single workers, because of significant both intra- and inter-individual variability.

Mutations in GDI1 and X-linked non-specific mental retardation.

Mental retardation (MR) is a complex phenotype characterized by suboptimal functioning of the central nervous system (CNS). It is estimated that from 1 to 3% of the general population is affected with MR. MR or "intellectual disability" can be caused by genetic as well as environmental causes that act on the development and functioning of the CNS prenatally, perinatally or postnatally. Genetic causes of MR include chromosome aneusomies, chromosome structural abnormalities, genomic disorders and monogenic diseases. Amongst children, acute MR (QI < 50) is estimated at 0.4% and faint MR is about 2.5-3%. To determine the etiology of the MR, many diagnostic studies have been conducted and they show that MR is very heterogeneous and its etiology is not yet known in 20-50% of the group of patients with severe MR. This percentage increases up to 75-80% in the group of individuals with mild or "borderline" forms of MR. In light of the literature results, we tried to carry out a screening of 41 subjects with nonspecific MR for the detection of mutations in the gene GDI1 using the DHPLC methodology. This technique has the following advantages: low cost, high sensitivity (> 95%), and it can be done quickly. We have found 3 nucleotide (nt) substitutions: an intronic polymorphism at nt 107877 A --> C, a polymorphism in exon 3 at nt 109259 T --> C (Asn73Asn), and an intronic polymorphism at nt 110314 G --> C. The mutations in this gene are common and do not seem to influence the gene expression so as to cause a change in phenotype. These results therefore do not encourage the research of a diagnostic protocol designed for mutational analysis of the GDI1 human gene as the only responsible factor for a complex disease as Mental Retardation X-linked (MRX).

First trimester pregnancy outcomes in a large IVF center from the Lombardy County (Italy) during the peak COVID-19 pandemic.

At the beginning of 2020, the Italian Lombardy region was hit by an "epidemic tsunami" which was, at that point in time, one of the worst pandemics ever. At that moment the effects of SARS-COV 2 were still unknown. To evaluate whether the pandemic has influenced ART (Assisted Reproduction Techniques) outcomes in an asymptomatic infertile population treated at one of the major COVID-19 epicentres during the weeks immediately preceding lockdown. All ART procedures performed during two time periods were compared: November 1st, 2018 to February 28th, 2019 (non-COVID-19 risk) and November 1st, 2019 to February 29th, 2020 (COVID-19 risk). In total 1749 fresh cycles (883 non-COVID-19 risk and 866 COVID-19 risk) and1166 embryos and 63 oocytes warming cycles (538 and 37 during non-COVID and 628 and 26 during COVID-19 risk, respectively) were analysed. Clinical pregnancies per cycle were not different: 370 (25.38%) in non-COVID versus 415 (27.30%) (p = 0.237) during COVID-19 risk. There were no differences in biochemical pregnancy rates 52 (3.57%) versus 38 (2.50%) (p = 0.089) nor in ectopic pregnancies 4 (1.08%) versus 3 (0.72%) (p = 0.594), spontaneous miscarriages 84 (22.70%) versus 103 (24.82%) p = 0.487, nor in intrauterine ongoing pregnancies 282 (76.22%) versus 309 (74.46%) p = 0.569. A multivariate analysis investigating differences in spontaneous miscarriage rate showed no differences between the two timeframes. Our results support no differences in asymptomatic infertile couples' ART outcomes between the pre COVID and COVID-19 periods in one of the earliest and most severe pandemic areas.

[Incidence and socioeconomic burden of hip fractures in Italy: extension study 2003-2005]. / Incidenza e costi delle fratture di femore in Italia: studio di estensione 2003-2005.

OBJECTIVES: We aimed to analyze incidence and costs of hip fractures in Italy. METHODS: We analyzed the Italian Ministry of Health national hospitalization and DRGs databases concerning fractures occurred in people > or =65 between 2003 and 2005. We have estimated incidence and direct costs sustained by the National Health Service for hospitalization and treatment of hip fractures on the basis of the value of the Diagnosis Related Groups (DRGs) referring to hip fractures. The expenses of rehabilitation and indirect costs were based on regional estimations. RESULTS: Between 2003 and 2005 we registered almost 90,000 hospital admissions per year (corresponding to 75,000 patients) because of hip fractures in people aged > or =65. Women accounted for the majority of hospital admissions due to hip fractures (78.0%; n=214,519). Among women, 84.3% of fractures (n=180,861) occurred in patients > or =75, which is known to be the age group with the highest prevalence of osteoporosis. Hospitalizations of both men and women showed an increasing trend across all the examined period. Hospital costs increased up to 467 million euros in 2005, while rehabilitation costs rose up to 531 million in the same year. CONCLUSIONS: Hip fractures in the Italian population are increasing and represent a major public health challenge.