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Allergic rhinitis and asthma are closely linked. A progression from rhinitis to overt asthma is common. FEF25-75 is a spirometry parameter that could reflect small airways patency and could reliably predict early bronchial involvement in allergic rhinitis patients. MEF50 very strongly correlates with FEF25-75. The aim of this study was to evaluate possible spirometry change in two groups of children suffering from AR over time. The first group took a course of a nutraceutical (Lertal®) before the observation (active group, AG); a second one was considered as control (control group, CG). The children were visited at baseline, at the end of the nutraceutical course, and after 1 year. FEV1, FVC, and MEF50 were the primary outcomes. After one year, children in AG had significantly higher MEF50 than CG children (p=0.009). In conclusion, the present study showed that a course with a multicomponent nutraceutical could prevent the MEF50 decline in children with allergic rhinoconjunctivitis. (www.actabiomedica.it)

Nutraceuticals represent interesting therapeutic options in clinical practice. In this regard, a new compound has been designed: Lertal®. It contains quercetin, perilla extract, and vitamin D3. These agents exert anti-allergic and anti-inflammatory activities. This article reports and discusses the results of four clinical studies conducted in adult and paediatric patients suffering from AR. Outcomes provided evidence that Lertal® may significantly prevent clinical worsening when prescribed as add-on to continuous antihistaminic treatment and also prevent clinical exacerbations, such as the need of rescue medication, when used alone as preventive strategy in AR patients. (www.actabiomedica.it)

To determine antenatal factors that may predict successful vaginal birth after Caesarean section (VBAC), to develop a relevant antenatal scoring system and a nomogram for prediction of vaginal birth after caesarean delivery. A non recurring indication for previous Caesarean section (CS), such as breech presentation or foetal distress, is associated with a much higher successful VBAC rate than recurrent indications, such as cephalopelvic disproportion (CPD). Prior vaginal deliveries are excellent prognostic indicators of successful VBAC, especially if the vaginal delivery follows the prior CS. A low vertical uterine incision does not seem to adversely affect VBAC success rates as compared to a low transverse incision. Maternal obesity and diabetes mellitus adversely affect VBAC outcomes. Foetal macrosomia does not appear to be a contraindication to VBAC, as success rates exceeding 50% are achieved and uterine rupture rates are not increased. An inter-pregnancy interval of

Background: Parathyroid hormone related peptide (PTHrP) is widely expressed in a variety of normal fetal and adult tissues. Aim of work: Review of these normal physiologic functions of PTHrP in each of these tissues. Method: Performed literature search on pubmed on articles related to PTHrP and physiologic roles. Results: PTHrP is expressed in wide range of sites in the body with roles including relaxation of vessels and smooth muscle cells, and regulation of development. PTHrP also mediates humoral hypercalcemia of malignancy. PTHrP can be falsely elevated in benign conditions. Lastly, PTHrP has a pharmacological role in osteoporosis treatment. Conclusions: PTHrP has many various physiological roles besides mediating humoral hypercalcemia of malignancy. (www.actabiomedica.it)

The Fontan operation has been the final palliation for patients born with congenital heart defects with a functional single ventricle for more than 4 decades. The “normal” Fontan physiology is characterized by the loss of the sub-pulmonary ventricle with consequent elevated pressure in the caval system, non-pulsatile blood flow in the pulmonary circulation and at least mild reduction of the systemic output. When successful, this procedure is associated with a range of benefits including improved arterial saturation and abolishment of chronic volume overload, allowing a fairly normal life to the majority of patients through early adulthood. As we enter the 5th decade of caring for patients palliated with the Fontan procedure, it is evident that adult survivors face significant morbidity due to multiorgan dysfunction, early mortality and need for heart transplantation. Several late complications may occur: ventricular dysfunction, arrhythmia, cyanosis, exercise intolerance, elevated pulmonary vascular resistance, protein-losing enteropathy, plastic bronchitis, hepatic and renal complications. The mechanism of late Fontan failure is multifactorial and not completely understood, it depends on interactions between the ventricle, the pulmonary vascular bed, the venous and lymphatic compartments. Conclusions: the aim of this review is to describe the pathophysiology of Fontan circulation and the clinical and hemodynamic characteristics of early and late failing Fontan survivors, their association with morbidity and mortality, and the strategies for their management. (www.actabiomedica.it).

Background: Hantaviruses can cause serious human diseases including hemorrhagic fever with renal syndrome (HFRS) and Hantavirus Cardiopulmonary Syndrome (HCPS). European Hantavirus are usually associated with HFRS, and their geographical distribution mirrors the ecology of reservoir host species. Epidemiology of HFRS is well-studied in Western Europe, but data from Italy are fragmentary. Methods: We searched into two different databases (PubMed and EMBASE), focusing on studies reporting the prevalence of Hantaviruses in Italy. Data were extracted using a standardized assessment form, and results of the analyses were systematically reported, summarized and compared. Results: We identified a total of 18 articles, including 12 reports (total population: 5,336 subjects, 1981-2019) and 6 case reports (1984-2019). In total, 200 subjects exhibited some degree of seropositivity, with a pooled seroprevalence of 1.7% (95% confidence interval 0.7%-4.0%) in the general population. Higher occurrence was reported in selected subgroups, i.e. acute (28.7%, 95%CI 22.1-36.2) and chronic (6.6%, 95%CI 4.7-9.1) renal failure, forestry workers (3.0%, 95%CI 1.4-6.5, actual range 0.0 to 10.8%). Conclusions: In the last decade, no human cases of hantavirus infection have been officially reported in Italy. However, our analysis stresses the actual occurrence of Hantavirus among general population and in selected population groups. Further studies on hantavirus infection rates in reservoir host species (rodents, shrews, and bats) and virus transmission to humans are needed to prevent outbreaks in the future.

Introduction: Nigeria like many African countries has tried to start the newborn screening for congenital hypothyroidism and many failed. Since sickle cell disease is more common in Nigeria, the hypothesis is that incorporating it into a screening programme for congenital hypothyroidism will improve the uptake of the programme by parents and government. Methods: Different aspects of newborn screening with difficulties and challenges in running newborn screening were identified and discussed. Result: Identifying that for newborn screening to be successful, several key factors have to be put in place including but not limited to organizational structure, system thinking, finance, legislative and political will. A proper recall system for test positives and diagnostic/confirmatory test must be put in place before the programme starts. Since several other screening programmes like sickle cell disease, cervical and breast cancer have run successfully in Nigeria, incorporating one of them into the newborn screening for CH can make the programme succeed as there will be better uptake by the population and the policy makers. Conclusion: The difficulty in establishing a newborn screening programme in Nigeria stem from health care financing, organizing the programme from screening through to recall and treatment, and ultimately, prevention of diseases. (www.actabiomedica.it)

Food-dependent exercise-induced anaphylaxis (FDEIA) is an IgE-mediated allergy resulting from the combination of the ingestion of an offending food and physical exercise. According literature, oral food challenge (OFC) followed by physical exercise (OFCPE) should be considered the diagnostic gold standard. In the absence of adverse reactions, other cofactors should be added (e.g. acetylsalicylic acid, alcohol in adulthood), one at a time. But many other factors increase patient's reactivity. This could reduce the sensitivity of the OFCPE and, consequently, make instructions for patients less reliable. On the other hand, the addition of cofactors not reported by the patient may reduce test specificity. With the help of two exemplary stories, that present opposite outcomes, diagnostic difficulties of FDEIA are discussed.

Background and Aim: Job burnout is the psychosocial judgement of the physical and psychological tiredness result to the prolongation emotional pressure associated to the job. The World Health Organization (WHO) also promotes care safety culture and awareness, by publishing the “Multi-professional Patient Safety Curriculum Guide” to guarantee patient safety education in universities, schools and professional institutions in the dental, medical, obstetric, nursing and pharmaceutical sectors. Hence, this study highlights correlations existed between burnout levels and patient safety perceptions among Italian nurses who work in different contexts. Method: Data were collected in July and August 2019. Burnout was assessed by the Italian version of the 22-item Maslach Burnout Inventory Human Service Survey. The patient safety perception was assessed to the “Hospital Survey on Patient Safety Culture” (HSOPSC) questionnaire. Results: 300 Italian nurses voluntary participated in this study. Questionnaire were administered by Google Forms application, were all Italian nurses could voluntary participate. Conclusion: Emotional Exhaustion (EE) is the most representative dimension of burnout. This outcome becomes more acute with greater age and seniority in the position, due to the stress and monotony encountered and/or job dissatisfaction. Moreover, our results showed strong and moderate values on different fields of the HSOPSC questionnaire. (www.actabiomedica.it)

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality for women. This review summarizes the relationship between alcohol consumption and common CVDs in women and highlights potential differences from men. Except for risk of hypertension, no sex-related effects of alcohol consumption on the risk for coronary heart disease and stroke have been reported, and data on the sex-related effects on risk for peripheral arterial disease are limited. For women, alcohol consumption has a J-shaped relationship with hypertension. About 1 to 2 standard drinks per day is associated with lower risk for the development of hypertension, whereas for men, the relationship is relatively linear. In the area of alcoholic cardiomyopathy, the prevalence is greater for men, but women may develop alcoholic cardiomyopathy at a lower lifetime level of alcohol consumption. Overall, data support that 1 to 2 standard drinks per day for women and men is associated with a lower risk of CVD, and higher daily amounts may increase the risk of CVD.

The following article aims to clarify the guidelines needed for the gaining of informed consent in surgery treatments. Legal dispositions in the provisions of law n. 219/2017, written according to the regulatory mechanism uphold by the Italian Supreme Court and medical code of practice have been properly analyzed in order answer the questions unanswered by the law. Who is supposed to inform the patient? About which risks? Does the patient's characteristics affect information obligation? Is necessary to add more information than those required by the law? How do emergency and urgency affect information obligation? Can the patient give consent in advance to an additional operation during the undergoing surgery, if needed? The answers provided by the law and by the Italian Supreme Court picture a state of obligation, where the single physician risks to encounter several responsibilities. It's important to face this problem inside sanitary facilities, creating a suitable informed consent form and planning surgeries to allow the usage of personal data according to the patient's need.

Women with alcohol use disorder (AUD) experience more barriers to AUD treatment and are less likely to access treatment than men with AUD. A literature review identified several barriers to women seeking help: low perception of a need for treatment; guilt and shame; co-occurring disorders; employment, economic, and health insurance disparities; childcare responsibilities; and fear of child protective services. Women entering treatment present with more severe AUD and more complex psychological, social, and service needs than men. Treatment program elements that may reduce barriers to AUD treatment include provision of childcare, prenatal care, treatment for co-occurring psychological problems, and supplemental social services. Research has suggested that outcomes for women are best when treatment is provided in women-only programs that include female-specific content. To date, research on treatments tailored to the individual needs of women is limited, but research on mechanisms of change has suggested the importance of targeting anxiety and depression, affiliative statements in treatment, abstinence self-efficacy, coping skills, autonomy, and social support for abstinence. Future research should focus on early interventions, linkages between primary care or mental health clinics and AUD treatment settings, and integrated treatments for co-occurring AUD and other disorders. Further research should also explore novel treatment delivery approaches such as digital platforms and peer support groups.

Allergic rhinoconjunctivitis (AR) is the most common IgE-mediated disease. A type2 immune response is involved in AR pathogenesis. Allergic inflammation is characterized by eosinophilic infiltrate and mediators release. AR treatment is usually based on medication prescription, including antihistamines and intranasal corticosteroids. However, medications may be prescribed for long periods and sometimes may be scarcely effective, thus aggressive strategy should be used. Therefore, complementary medicine is becoming attractive for patients at present. Nutraceuticals represent interesting therapeutic options in clinical practice. In this regard, a new compound has been designed containing Vitamin D3, Perilla extract, and quercetin. (www.actabiomedica.it)

Sleep disturbance is common among individuals with alcohol use disorder (AUD). Insomnia not only is a pathway toward alcohol consumption but also is related to increased risk of relapse, psychosocial impairment, decreased quality of life, and suicidal ideation in individuals with AUD. Few studies examining sleep disturbance and alcohol use have explored how this relationship differs between men and women. Historically, studies of AUD have included few, if any, women in their samples. However, women are increasingly consuming alcohol at an earlier age and at higher rates, and the effect of alcohol on women’s mental and physical health is expected to rise. This narrative review consolidates findings from studies that have reported the effects of acute and chronic alcohol use on sleep among women. Additional research is needed to investigate sex differences in this area. Such research should consider the modifying effects of age, lifetime alcohol use, and psychiatric co-occurrence, as well as the effectiveness of combined interventions for AUD and sleep disturbance.

Alcohol, tobacco, and cannabis are the substances most frequently used during pregnancy, and opioid-exposed pregnancies have increased fourfold. The purpose of this review is to describe the prevalence and consequences of prenatal exposure to alcohol, tobacco, cannabis, and opioids. Currently available screening questionnaires for prenatal substance use are summarized and contrasted with the measures available for prenatal alcohol use. Because screening for prenatal alcohol and substance use is but the prelude to efforts to mitigate the potential adverse consequences, attempts for the modification of these consequences are briefly reviewed. In addition, areas of future research related to the criminalization of prenatal substance use, which may inhibit both inquiry and disclosure, are discussed. Indeed, the full potential of effective interventions has yet to be realized.

Globally, more than 2 million new cases of breast cancer are reported annually. The United States alone has more than 496,000 new cases every year. The worldwide prevalence is approximately 6.8 million cases. Although many risk factors for breast cancer are not modifiable, understanding the role of the factors that can be altered is critical. Alcohol consumption is a modifiable factor. Studies of alcohol in relation to breast cancer incidence have included hundreds of thousands of women. Evidence is consistent that intake, even intake of less than 10-15 grams per day, is associated with increased risk of this disease. In addition, evidence, although less extensive, shows that possible early indicators of risk, such as benign breast disease and increased breast density, are associated with alcohol consumption. Evidence is less strong for differences based on geographic region, beverage type, drinking pattern, or breast cancer subtype. Some studies have examined the association between alcohol and recurrence or survival after a breast cancer diagnosis. These findings are less consistent. Public awareness of alcohol as a risk factor for breast cancer is low, and public health measures to increase that awareness are warranted.

Antihistamines are the cornerstone treatment of allergic rhinitis (AR). To quantify the antihistaminic consume is particularly relevant in clinical practice, since a remarkable use is usually associated with severe symptoms. The aim of the study was to measure the use of antihistamines in two groups of children suffering from AR. The first group took a course of a nutraceutical (Lertal®) before the observation (active group, AG); a second one was considered as control (control group, CG). Both groups took antihistamines on demand. The children were visited at baseline and after 1 year. The number of days of antihistaminic use was the primary outcome. Children in AG had a significant reduced number of antihistamines use in comparison with CG (p=0.008). In conclusion, the current study showed that a course with a multicomponent nutraceutical could reduce the use of symptomatic antihistamines in children with allergic rhinoconjunctivitis. (www.actabiomedica.it)

Alcohol-related liver disease generally has been ascribed to men because men reportedly consume alcohol at an increased rate and quantity as compared to women. Recent literature has reported, however, that rates of liver disease attributed to alcohol use by women have increased, largely due, in part, to the increased number of women who consume alcohol regularly. This increase is a paramount concern, as women are more susceptible than men to the effects of alcohol-related liver injury. Health care providers should make efforts to counsel women on the risks of excess alcohol consumption to prevent further increase in alcohol-related liver disease and its associated complications.

Injection drugs are the greater source for HCV infection. About 60% of drug users and about 20-30% of convicts are infected with HCV. HCV infection is often associated with behavioral disorders and drug use. At present, few subjects with HCV belonging to risk groups have been treated with Direct-Acting Antivirals (DAAs). SerDs and prisons should implement the screening for HCV. HCV populations at risk can be successfully treated with DAAs. The primary objective of the linkage to care is the holistic and integrated treatment, and the prevention of reinfections is a priority and essential part of the treatment goals. The removal of the barriers to treatment is a primary goal of the linkage-to-care models and integrated systems; the main action to be undertaken for the linkage to care of the HCV population at risk are screening, referral, treatment and prevention of reinfection. All HCV RNA+ patients may be eligible for treatment, and those with the clinical criteria for starting treatment should be treated with DAAs. All patients should receive a structured harm-reduction program (with skill training). The prevention of the infection is of paramount importance in the linkage to care of the HCV population at risk and is an element which should always be associated with the drug treatment. (www.actabiomedica.it)

Cough is a natural defense mechanism that protects the respiratory tract from inhaling foreign bodies and by clearing excessive bronchial secretions. As a spontaneous reflex arc, it involves receptors, an afferent pathway, a center processing information, an efferent pathway and effectors. The determinant factor of cough efficacy is the operational volume of the lung, which in turn relies on the strength and coordination of respiratory and laryngeal muscles as well as on lung mechanics. Respiratory muscle weakness and dysfunction as well as expiratory flow limitation and lung hyperinflation may occur in some neuromuscular disorders and in obstructive airway diseases, respectively. Accordingly, all these diseases may show an ineffective cough. In this brief overview, we deal with the determinants of the cough efficacy and the clinical conditions affecting cough efficacy as well as the cough’s efficacy measurements in clinical setting. (www.actabiomedica.it)

Total knee replacement is a common treatment for advanced knee osteoarthritis. The most common and widespread method is cemented arthroplasty. As in the prosthetic hip a gradual transition from cemented to uncemented fixation techniques occurred over time, increasing interest is growing also around cementless knee fixation, with the theoretical advantages of preserving the bone stock and obtaining a biological fixation avoiding cement fragmentation. On the basis of the actual knowledge, the uncemented knee prosthesis represents an interesting alternative especially for the patient under 65 years of age, with viable bone quality, in which a biological bone-prosthesis fixation is desirable, while avoiding the drawbacks of cement fragmentation and of the possible future revision of a cemented implant. However the weak link remains the tibial fixation, so that technical tips are important to avoid micromovements with subsequent lack of osteointegration. In our experience, gap balancing, mobile bearings and no haemostatic tourniquet well combine with this kind of implant. (www.actabiomedica.it)

In 1783, the work of Ferdinand de la Boissiere, Letters above the certainty of death signs with various observations and experiences over the drowned, was published in Rome. Manuscript is a translation of the French work of Antoine Louis, Lettres sur la certitude des signes de la mort, printed in France in 1752 and in which the surgeon discussed on the certain diagnosis of death. The Louis’s work represented an important contribute of medicine especially because in the 18th century only the appearance of the first putrefactive processes was recognized as the indisputable sign of death. In the debate of the time, the treaty of Antoine Louis (1723-1792) overtaken the believed that the only indisputable sign of death was the appearance the first putrefaction processes. Our paper is limit to offering some author’s account around the characteristic signs of death, which dispense from putrefaction of the bodies or the rigidity of the limbs and the collapse and softness of the eye. The book boasted a great meaning in the medical association of the time, especially because it discussed with contemporary criteria the signs of certain death. (www.actabiomedica.it)

Research on associations of suicidal behavior, including suicide and suicide attempt, with alcohol use disorder (AUD) and acute use of alcohol (AUA) are discussed, with an emphasis on data from meta-analyses. Based on psychological autopsy investigations, results indicate that AUD is prevalent among individuals who die by suicide. Results also indicate that AUD is a potent risk factor for suicidal behavior. Risk estimates are higher for individuals with AUD in treatment settings, when compared to individuals in the community who have AUD. Also, although rates of suicide and prevalence of AUD remain higher in men, they have increased more among women in recent decades. Based on postmortem blood alcohol concentrations, AUA was commonly present among those who died by suicide. AUA is a potent proximal risk factor for suicidal behavior, and the risk increases with the amount of alcohol consumed, consistent with a dose-response relationship. Research indicates that AUA increases risk for suicidal behavior by lowering inhibition and promoting suicidal thoughts. There is support for policies that serve to reduce alcohol availability in populations with high rates of AUD and suicide, that promote AUD treatment, and that defer suicide risk assessments in intoxicated patients to allow the blood alcohol concentration to decrease.

This paper describes the design and testing of a gripper developed for handling of delicate and flexible tissues during minimally invasive surgery. The device operates on the Bernoulli principle for generating hight-speed flow between the gripper and product surface threby creating vacuum which lifted the product. The Bernoulli gripper, which is widely employed in automated production lines, is a pneumatic manipulator capable of non contact gripping. This study experimentally investigates the applicable of Bernoulli gripper in minimally invasive surgery. The gripper allow tissues to be lifted with minimal contact thereby reducing the possibility of damaging the object. Most of the roobot grippers are not easily applicable in minimal invasive surgery due to the tissues are often delicate, easily damaged, adhesive and slippery. Due to surgeons can not gauging the force exerted on the grasped tissue during laparoscopic grasping, excessive grasp forces may lead to tissue damage. Although Minimally invasive surgery has many benefit, force feedback or touch sensation is limited during th operation in the currently available tools, creating the potential for excessive force application and unintended tissue injury. To overcome such problems, this paper proposes a concept to enable the use of non-contact grippers instead of traditional grippers. In this paper, an innovative approach of a gripper for grasping variable in sizes, shape and weight of chicken tissues are presented. The experimental results show that the Bernoulli principle gripper can be used to lift tissues of different texture and shape without damage. The main objective of this study is to highlights the importance of a non-contact end effector in Minimally invasive surgery and develop a gripper to grasp different tissues. A novel gripper such as the tested prototype has the potential to be used as grasper instrument in minimally invasive surgery. The results will be valuable for literature and future works. (www.actabiomedica.it)

The College Alcohol Intervention Matrix (CollegeAIM) is a user-friendly, interactive decision tool based on a synthesis of the substantial and growing literature on campus alcohol use prevention. It includes strategies targeted at both the individual and environmental levels. Commissioned by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), CollegeAIM reflects the collective knowledge of 16 separate experts in the field, which makes it unique relative to other summaries of the science. CollegeAIM is designed to help college stakeholders compare and contrast different evidence-based prevention strategies to select a mix of individual and environmental strategies that will work best on and around their campuses. CollegeAIM is a living document, which will be updated to keep pace with the science. Colleges are therefore encouraged to ensure that evaluations of individual- or environmental-focused strategies on their campuses or in their communities make it into the published literature.

Allergen avoidance, allergen immunotherapy, IgE antagonists, biological medications, prevention and treatment of respiratory infections, probiotics, adapted formula, vitamins, and oligo-elements have been investigated as strategies in the prevention of allergic diseases. Promising findings were obtained. To prevent allergic diseases could be a dream that will be soon realized in clinical practice. (www.actabiomedica.it)

Allergic children with respiratory infections (RI) are a demanding challenge for the paediatrician. Antibiotic prescription represents a critical problem, mainly concerning the growing issue of resistance. To prevent RI would be therefore a goal in clinical practice. In this regard, modulation of immune system may have a critical role. The aim of the present study was to measure the number of respiratory infections and the use of antibiotics in two groups of children suffering from allergic rhinoconjunctivitis. The first group took a course of a nutraceutical (Lertal®) before the observation (active group, AG); a second one was considered as control (control group, CG). The children were visited at baseline and after 1 year. The number of RI and of antibiotic courses was the primary outcomes. Children in AG reported a significant reduced number of RI and of antibiotic course in comparison with CG (p=0.01 and 0.002 respectively). In conclusion, the current study showed that a course with a multicomponent nutraceutical could reduce the number of respiratory infections and consequently the use of antibiotics in children with allergic rhinoconjunctivitis. (www.actabiomedica.it)

The article addresses the increasingly important issue of organizational ethics in healthcare. Assuming that the governance of organizational change consists of a seriousness of continuous choices and of objectives to be determined and achieved, a possible definition of this new discipline is then deepened, and its fields of application are identified. In the discussion therefore emerge the close link between ethical choice in organization and legality, passing through transparency and prevention of corruptive phenomena. After a focus on the strategic role played by the Medical Doctor of the healthcare management team, in conclusion, the need arises to support a strengthened supervisory and evaluation system and a culture of the ethical organizational choice of health managers, a rooting of the sense of identity and belonging to the healthcare organization and its mission by Professionals. Also governing this last aspect is the new challenge for the management of public healthcare enterprises. (www.actabiomedica.it)

Background and aim: Medical deontology is increasingly important, owing to the interests and rights which the medical profession involves. This paper focuses on the relationships of the Italian Code of Medical Deontology (CMD) with both the ethical and legal dimensions, in order to clarify the role of medical ethics within the medical profession, society and the overall system of the sources of law. Methods: The authors analyze the CMD from an ethical perspective and through the new doctrinal guidelines and current trends in the Italian law courts. Results: From an ethical point of view, moral philosophical analysis scarcely seems to address professional medical ethics. Nonetheless, the CMD needs to undergo careful ethical analysis. From a legal perspective, the Italian CMD contains provisions which do not have an official legal nature. However, they are directly binding for medical practitioners, and therefore could be understood as a supplement to the general rules of the legal system. Conclusions: At an ethical level, rigorous debate on the CMD is indispensable, in order to update its specific principles and to make it a real moral normative document. At a legislative level, there is a possible contradiction between a legal system that does not take into account the CMD, but which then attributes significant importance to the violation of its rules. (www.actabiomedica.it)

Major orthopedic surgery, mainly entailing hip fracture surgery, hip and knee arthroplasty, is associated with significant morbidity and mortality, which are especially attributable to the high risk of postoperative VTE. Such a considerable risk is mainly due to a procoagulant state sustained by several important mechanisms, including massive release of procoagulants from tissue and bone damage, blood vessel injury, reduced venous emptying, perioperative immobilization and cement polymerization, among others. The risk of VTE during and after major orthopedic surgery approximates 50-80% in patients with no thromboprophylaxis, and persists for up 3 to 6 months after surgery. The anticoagulant or antithrombotic armamentarium entails several anticoagulants such as heparin, coumarins, fondaparinux, and the recently developed DOACs inhibiting either activated factor Xa (i.e., rivaroxaban, apixaban, edoxaban) or thrombin (i.e., dabigatran), as well as aspirin, i.e., the oldest antiplatelet drug to be ever discovered and used in clinical practice. The current guidelines are not in complete agreement regarding the choice of the ideal thromboprophylaxis, since some consider aspirin, and some discourage it. Recent evidence seems to support the use of aspirin in selected situations and in selected protocols. Therefore, we believe that consideration should be made about increasing the use of this old but still effective drug for perioperative prophylaxis of VTE, especially in patients for whom the administration of DOACs may be challenging. (www.actabiomedica.it)

Background: The aim of the study was to assess safety and efficacy of pre-operative assessment for internal mucosal rectal prolapse (IMRP) in internal hemorrhoids, in order to achieve a tailored transanal stapled surgery. Methods: All consecutive patients (January 2011 to December 2014; age 18-80 years), affected by prolapses with II-IV degrees hemorrhoids that underwent Longo procedure with EEA® Auto Suture stapler (Covidien) were included in the present study. Results: A total of 100 consecutive patients (38 females) were enrolled in the study. Preoperative Visual Analogue Scale pain assessment was 7.33±2.68. The mean duration of the procedure was 34.1±17.8 min, and the median hospital stay was 2 days (range 2-6). No major complication occurred, including relapses of mucosal prolapse. Preoperative prolapse measurement with EEA® EEA® Auto Suture stapler (2.3±0.5 cm) was well correlated direct assessment (2.4±0.6, p

The excessive use of alcohol is a global problem causing many adverse pathological health effects and a significant financial health care burden. This review addresses the effect of alcohol consumption on the microbiota in the gastrointestinal tract (GIT). Although data are limited in humans, studies highlight the importance of changes in the intestinal microbiota in alcohol-related disorders. Alcohol-induced changes in the GIT microbiota composition and metabolic function may contribute to the well-established link between alcohol-induced oxidative stress, intestinal hyperpermeability to luminal bacterial products, and the subsequent development of alcoholic liver disease (ALD), as well as other diseases. In addition, clinical and preclinical data suggest that alcohol-related disorders are associated with quantitative and qualitative dysbiotic changes in the intestinal microbiota and may be associated with increased GIT inflammation, intestinal hyperpermeability resulting in endotoxemia, systemic inflammation, and tissue damage/organ pathologies including ALD. Thus, gut-directed interventions, such as probiotic and synbiotic modulation of the intestinal microbiota, should be considered and evaluated for prevention and treatment of alcohol-associated pathologies.

HIV disease and alcohol independently influence the human immune system, so it stands to reason that, together, their influence may be additive. Here, we review the evidence that alcohol can exacerbate HIV's influence on the immune system, thereby affecting disease progression and transmission. We focus particularly on alcohol's effect on the mucosal immune system in the tissues of the gastrointestinal tract, the genital tract and the lungs, all of which play a role in transmission and progression of HIV disease.

Both alcohol abuse and infection with hepatitis viruses can lead to liver disease, including chronic hepatitis. Alcohol and hepatitis viruses have synergistic effects in the development of liver disease. Some of these involve the cellular membranes and particularly their functionally active domains, termed lipid rafts, which contain many proteins with essential roles in signaling and other processes. These lipid rafts play a central role in the lifecycles of hepatitis viruses. Alcohol's actions at the lipid rafts may contribute to the synergistic harmful effects of alcohol and hepatitis viruses on the liver and the pathogenesis of liver disease.

Adolescence represents a vulnerable period for developing youth. Alcohol use and misuse are especially problematic behaviors during this time. Adolescents are more sensitive to alcohol and less tolerant of its detrimental effects than are adults. Research in humans and animals has revealed that early alcohol consumption can result in delayed pubertal development. Animal studies have shown that alcohol detrimentally affects neuroendocrine systems within the hypothalamic region of the brain that are associated with the normal, timely onset of the pubertal process. To effectively restore development and shorten recovery time associated with the adverse effects of alcohol on puberty, researchers must first understand the molecular and physiological mechanisms by which alcohol interferes with critical hypothalamic functions.

“Health” is a positive multi-dimensional concept involving a variety of features, ranging from ability to integrity, from fitness to well-being. According to the first principle of the constitution of the World Health Organization “Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity”. This constitution was adopted by the International Health Conference held in New York in June-July 1946 and became operative in April 1948. This classical, seventy-year old definition of the World Health Organization is nowadays considered a historical one and it stands as a fundamental milestone of a diachronic track beginning, in Western medicine, with the definition of health proposed by Hippocrates and his School. For Hippocrates health was the state of equilibrium of four humours. This philosophical-naturalistic definition has been flanked in the history of Western medicine by various concepts of health and disease, alternatively based, according to different scientists and in different medical contexts and periods, on epidemiological, anatomical, physiological, functional, social and molecular perspectives. Since biomedical definitions are always prone to integration and updating, depending on the continuous achievements of medical science and bioethics, the fascinating journey through the concepts of health and disease, the fundamental milestones of which are here briefly proposed, is still in progress. (www.actabiomedica.it)

Patients with diverticulosis who develop persistent abdominal pain, bloating and changes in bowel habits not associated with overt inflammation may have symptomatic uncomplicated diverticular disease (SUDD). The severity and frequency of SUDD symptoms may have an impact on daily activities and severely affect quality of life. Effective management of SUDD should follow a three part strategy: divert, tackle and maintain. Divert to make the correct diagnosis: several symptoms of SUDD are common to other conditions that require different therapeutic approaches. However, several key differences should be used to diagnose SUDD. Pain in SUDD is normally in the iliac fossa, persistent, often lasting more than 24 hrs, and is not relieved by bowel movement, as is often the case with irritable bowel syndrome. Another difference is in the timing: the prevalence of SUDD increases with age, and patients under the age of 40 years are less likely to have diverticula. It is useful to establish whether a patient has diverticulosis, especially if the patient is relatively young; lack of diverticula excludes SUDD. Cross-sectional imaging is indicated; however, recent archival image data or ultrasonography may be useful alternatives. Laboratory tests should be ordered to exclude overt inflammation. Once the diagnosis of SUDD is made, the patient should receive effective therapy to tackle the condition. This should include dietary fibre supplementation and cyclic treatment with rifaximin 400 mg twice daily for 7 days per month. Once symptom control is achieved, it should be maintained by continuing therapy for at least 12 months. (www.actabiomedica.it)

Acute and chronic pain have an important socio-economical impact. In order to help physicians to choose the appropriate drug, especially for cancer pain, in 1986 WHO has developed a three-step analgesic “ladder” for cancer pain relief in adults. Later it has also been used for acute pain and chronic non-cancer pain. In step I nonsteroidal anti-inflammatory drugs (NSAIDs) are considered with or without adjuvants, in step II the use of weak opioids for mild-moderate pain, with or without NSAIDs and adjuvant, is suggested, while the step III is reserved to strong opioids for moderate-severe pain with or without non-opioids or adjuvants. In the last two decades, a better pathophysiology knowledge has improved pain management shifting our view from the pain ladder to a modern pain pyramid, in which drugs are selected not only on the basis of pain intensity, but mainly according to mechanisms underlying pain, including peripheral and spinal sensitization which is the main trigger of chronic pain. The best pharmacological approach has become multimodal, in which drugs belonging to different steps should be combined, matching the mechanisms of action with the type of pain. An important corollary of combining analgesic drugs with different mechanism of action is that proper matching achieves the same effect with lower doses, better outcome and fewer adverse effects. In this new perspective, fixed-dose pharmaceutical combinations of different drugs are very useful to fulfil pharmacodynamics, pharmacokinetics and adherence criteria, enriching the pain pyramid of half-steps between the first and second step and between the second and third step. Hence, a new fixed combination of a NSAID with peripheral and central anti-infilammatory activities, such as dexketoprofen, and a weak opioid, such as tramadol, with double analgesic activity in the spinal cord as an opioid and, at the same time, on the descending modulatory pathways, is expected to cover a wide range of acute and recurrent painful conditions, ranging from nociceptive inflammatory pain to neuropathic pain of moderate/severe intensity. In this review we evaluate the rationale that justifies its use as new class of pharmacological modality to treat pain accordingly also to a more update view of WHO pain ladder. (www.actabiomedica.it)

Introduction: Total knee replacement (TKR) is one of the most frequent orthopaedic procedures performed every year. At the same time 20% of patients who underwent TKR are not satisfied with the outcome. The reasons are unknown; we think that a mechanical alignment beyond 3° of varus-valgus can represent the most important cause of failure of TKR and consequently patient dissatisfaction. Materials and Methods: Neutral mechanical alignment is the main goal in every TKR: this can be achieved through different tools, such as extramedullary and intramedullary guides, patient-specific instrumentation (PSI) and computer-assisted surgery (CAS). The aim of this review is to compare the different alignment techniques in TKR, to describe CAS procedure and CAS results in recent literature. Results: Regarding the intramedullary guide, there is an increased risk of fatty embolism; there are great limitations on its use, or even impossibility, in cases of bone deformity and sequelae of trauma. Regarding the extramedullary guide, it becomes more difficult to use in cases of great obesity or increased soft-tissue volume around the tibia. PSI for TKR has been introduced to improve alignment, reduce outliers, operation time and the risk of fatty embolism by avoidance of intramedullary canal violation. Recent randomized controlled trials and meta-analysis proved no advantage of PSI in improving mechanical axis and implant survivorship. Discussion: CAS has provided to be a useful tool in assisting the surgeon to achieve more accurate post-operative mechanical axis through precise and reproducible bone cuts and ligament balancing. Two meta-analyses definitively proved that CAS technique improves mechanical axis and implant survivorship and one recent meta-analysis demonstrated that CAS provides better mechanical alignment and higher functional scores at short-term follow-up. (www.actabiomedica.it)

Background: The current lack of scientific validation of non-conventional treatments in medicine, whose epistemological foundations lie in scientific evidence and experimentation, raises a significant questions regarding the costs and benefits of alternative-treatment forms. Nonetheless, in the last few decades non-conventional treatments have been increasingly recognised by the Italian medical profession, with one regional healthcare administration adopting some non-conventional practices as part of its conventional healthcare services. Aims: The Authors aim to analyse non-conventional treatments in medicine from an epistemological, cultural, ethical, political and economic point of view, in order to highlight criticalities and incongruities, especially when these treatments are approved by a public healthcare system, which should be grounded on the “evidence-based medicine” principle. Conclusions: Non-conventional treatments in medicine are constituted by meta-theories, i.e. philosophical, religious and ideological concepts that conflict with contemporary rational, empirical medicine. In the interest of patients and society, the paper stresses the incongruity of a healthcare system which, despite being grounded on the “evidence-based medicine” principle, allows the development of non conventional treatments. Having said that, medical science should address not only the biological domain of illness but also its existential implications. Awareness and respect for the individual experience can undoubtedly lead to a new medical model that allows for a more effective therapeutic intervention. (www.actabiomedica.it)

The law on medically assisted procreation in Italy, from its entering into force, has undergone numerous amendments. This has been due to the fact that those citizens, directly affected by its imposed prohibitions, have not given in, bringing their requests before the courts, both nationally and internationally. Over the years, the courts through numerous rulings have significantly changed a law clearly incapable of protecting the rights of those involved. Currently Italy has an acceptable law on M.A.P. which is the result of the strong willing of citizens affected by problems of sterility or infertility. The aim of this paper is to present an historical summary of the troubled path which the issue, from every perspective, has faced and is still facing today. As well, it will document how, in Italy, the case-law and, therefore, the law’s interpretation and application by the judges have contributed, in the end, to shaping a positive legislation. (www.actabiomedica.it)

Background and aim: In recent years, archaeologists and anthropologists involved in the study of human remains have had to take into consideration ethical issues, which have come to the fore. The aim of this study is to illustrate the ethical and religious issues involved in relation to the positions of researchers. Method: Ethical issues involve the different study phases of human remains: archaeological excavation, anthropological analysis and, finally, museum display. Results: Osteoarchaeological remains may find a place in museums. However, in recent years, even the display of human remains museum has had to face new important ethical issue involving previously ignored or neglected aspect. The adoption of Native American Grave Protection Act in 1990 in the United States and the Human Tissue Act in 2004 in England, has created new scenarios relating to the storage of human remains in museum. Conclusion: All this caused a series of changes in the study of human remains, but many issues remain open to debate. (www.actabiomedica.it)

Recent studies have suggested that macrophages have a critical role in the development of alcohol-induced inflammation in the liver. To define the precise pathogenic function of these cells during alcoholic liver disease (ALD), it is extremely important to conduct extensive studies in clinical settings that further elucidate the phenotypic diversity of macrophages in the context of ALD. Research to date already has identified several characteristics of macrophages that underlie the cells’ actions, including macrophage polarization and their phenotypic diversity. Other analyses have focused on the contributions of resident versus infiltrating macrophages/monocytes, as well as on the roles of macrophage mediators, in the development of ALD. Findings point to the potential of macrophages as a therapeutic target in alcoholic liver injury. Future studies directed toward understanding how alcohol affects macrophage phenotypic switch in the liver and other tissues, whether the liver microenvironment determines macrophage function in ALD, and if targeting of macrophages alleviates alcoholic liver injury, will provide promising strategies to manage patients with alcoholic hepatitis.

Evidence from research in humans and animals suggest that ingesting alcohol during pregnancy can disrupt the fetal immune system and result in an increased risk of infections and disease in newborns that may persist throughout life. Alcohol may have indirect effects on the immune system by increasing the risk of premature birth, which itself is a risk factor for immune-related problems. Animal studies suggest that alcohol exposure directly disrupts the developing immune system. A comprehensive knowledge of the mechanisms underlying alcohol’s effects on the developing immune system only will become clear once researchers establish improved methods for identifying newborns exposed to alcohol in utero.

Considering that the prostate cancer radioresistance occurs in a significant percentage – as 20–40% of prostate cancer (PCa) patients undergone external beam radiation therapy developing, within ten years, recurrent and more aggressive tumor – the resort to customized radiosensitizer measures, focusly targeting PCa radioresistance-linked individual molecular aberrations, can increase the successful outcomes of PCa radiotherapy.

Bowel intussusception is rare in adults but common in children. Almost 90% of adult intussusceptions are secondary to a pathologic condition and the clinical picture can be very aspecific and challenging. In this review we discuss the symptoms, location, etiology, characteristics, diagnostic methods and treatment strategies of this rare and enigmatic clinical entity in adults. We have to highlight the high index of suspicion that is necessary for the operating surgeon, when dealing with acute, subacute or chronic abdominal pain in adults, because any misinterpretation may result in unfavorable outcomes.

Malpractice is the responsible for the greatest number of legal claims. At the present time, legal actions against physicians in Italy are 15,000 per year, and a stunning increase about costs to refund patients injured by therapeutic and diagnostic errors is expected. The method for the medical prevention is “Risk Management”, that is the setting-up of organizational instruments, methods and actions that enable the measurement or estimation of medical risk; it allows to develop strategies to govern and reduce medical error. In the present work, the reconstruction about the history of risk management in Italy was carried out. After then the latest initiatives undertaken by Italy about the issue of risk management were examined.