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The consumption of energy drinks (ED) has become a growing public health issue, since potentially ED-related serious adverse cardiovascular events, including arrhythmias, myocardial infarction, cardiomyopathies, and sudden cardiac death, have been reported in recent years. The substances contained in ED include caffeine, taurine, sugars, B group vitamins and phyto-derivatives, which, especially if taken in large quantities and in a short amount of time, could cause serious side effects through various mechanisms of action, such as increased blood pressure and QT interval prolongation. Although there are still many open questions on ED that require further specific investigations, there is an urgent need for information and educational plans to the population, as well as for regulatory actions, particularly regarding transparency of substances and possible adverse effects.

A unique case of severe measles complicated by multiple features of gas accumulation is described, on the ground of the available literature evidences. Complications from measles have been reported in every organ system and they may vary by age and underlying conditions. Pneumomediastinum is usually associated with subcutaneous emphysema and pneumopericardium, but rarely associated with pneumothorax. We report extremely rare simultaneous occurrence of self-limiting pneumomediastinum, pneumopericardium, subcutaneous neck and chest region emphysema, and pneumothorax, in a 19-year-old girl with measles. A review of the literature has documented only one previous report of spontaneous pneumomediastinum, subcutaneous emphysema and pneumothorax in the course of measles, and no previous cases reported the association of pneumomediastinum, subcutaneous emphysema, pneumopericardium and pneumothorax complicating measles.

Two recent cases of extremely severe thrombocytopenic purpura related to a concomitant cytomegalovirus infection, either associated or not with an underlying immunosuppression, draw our attention on this intriguing pathologic association, on the ground of an updated literature review.

Backgrounds: Two recent randomized controlled trials (RCTs), the PROTECT-AF and the PREVAIL, showed that in atrial fibrillation (AF) patients, left atrial appendage closure (LAAC) is comparable to oral anticoagulants (OAC) in the prevention of stroke and could also possibly reduce mortality. Nevertheless, this net clinical benefit was not confirmed in the most recent RCT comparing LAAC vs. OAC, the PRAGUE-17 trial., Aim: aim of the present study was to evaluate the efficacy and safety of LAAC compared with OAC among available high-quality studies., Methods: A systematic search of electronic databases (Medline, Scopus, Embase and the Cochrane Library) was performed to identify eligible RCTs and observational studies with propensity score matching (PSM) analysis. PRISMA guidelines were used for abstracting data and assessing data quality and validity. Outcomes of interest were the occurrence of cardiovascular death (CVD), all-cause death, all-type stroke, and major bleedings., Results: A total of 3 RCTs and 7 PMS studies involving 25,700 patients were identified. 12,961 patients received LAAC while 12,739 received OAC therapy. After a median follow-up of 2.6 years (IQR 2-4.4), patients who received LAAC had lower risk of CVD (RR = 0.62; 95%CI, 0.51-0.74, I 2  = 0%), all-cause death (RR = 0.67; 95% CI, 0.57-0.78, I 2 68%) and major bleedings (RR = 0.68; 95%CI, 0.48-0.95 I 2  = 87%) compared with patients on OAC. No difference was found between the two groups regarding strokes incidence (RR = 0.94; 95% CI, 0.77-1.15, I 2  = 0%)., Conclusions: According to this meta-analysis, LAAC has comparable efficacy in the prevention of stroke compared with OAC and a reduced risk of major bleedings, all-cause death and CVD that may be even larger with longer follow-up., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=269768, identifier CRD42021269768., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Franchin, Piroli, Demola, Mantovani, Iannaccone, Manfredi, D'Ascenzo, Fortuni, Ugo, Meucci, Navazio and Boccuzzi.)

Acute heart failure is a heterogeneous clinical syndrome and is the first cause of unplanned hospitalization in people >65 years. Patients with heart failure may have different clinical presentations according to clinical history, pre-existing heart disease, and pattern of intravascular congestion. A comprehensive assessment of clinical, echocardiographic, and laboratory data should aid in clinical decision-making and treatment. In some cases, a more accurate evaluation of patient haemodynamics via a pulmonary artery catheter may be necessary to undertake and guide escalation and de-escalation of therapy, especially when clinical, echo, and laboratory data are inconclusive or in the presence of right ventricular dysfunction. Similarly, a pulmonary artery catheter may be useful in patients with cardiogenic shock undergoing mechanical circulatory support. With the subsequent de-escalation of therapy and haemodynamic stabilization, the implementation of guideline-directed medical therapy should be pursued to reduce the risk of subsequent heart failure hospitalization and death, paying particular attention to the recognition and treatment of residual congestion., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

An intriguing case of lethal rickettsiosis caused by Rickettsia conorii complicated by brain involvement and the presence anti-phospholipid antibodies is presented and discussed, on the ground of recent literature evidences.

A unique report of Schönlein-Henoch purpura (SHP) associated with a recent Giardia lamblia enteric infection is described and discussed on the ground of the available literature. Tinidazole plus an appropriate probiotic therapy, including Lactobacillus reuteri and vitamin D, proved to be effective in the condition. SHP is an immunocomplex-mediated disorder characterised by a number of differently associated signs and symptoms, leading to the possible involvement of the skin, joints, abdomen and kidneys. Recent bacterial, viral, or protozoan infections may trigger the disease onset in patients of all ages. The paper describes the first case of SHP triggered by a giardiasis. Tinidazole plus an appropriate probiotic therapy, i.e. L. reuteri and vitamin D proved to be effective in this condition. To our knowledge, this is the first reported case of lambliasis-associated SHP described in an international traveller.

Angina is the main symptom of ischemic heart disease; mirroring a mismatch between oxygen supply and demand. Epicardial coronary stenoses are only responsible for nearly half of the patients presenting with angina; whereas in several cases; symptoms may underlie coronary vasomotor disorders; such as microvascular dysfunction or epicardial spasm. Various medications have been proven to improve the prognosis and quality of life; representing the treatment of choice in stable angina and leaving revascularization only in particular coronary anatomies or poorly controlled symptoms despite optimal medical therapy. Antianginal medications aim to reduce the oxygen supply-demand mismatch and are generally effective in improving symptoms; quality of life; effort tolerance and time to ischemia onset and may improve prognosis in selected populations. Since antianginal medications have different mechanisms of action and side effects; their use should be tailored according to patient history and potential drug-drug interactions. Angina with non-obstructed coronary arteries patients should be phenotyped with invasive assessment and treated accordingly. Patients with refractory angina represent a higher-risk population in which some therapeutic options are available to reduce symptoms and improve quality of life; but robust data from large randomized controlled trials are still lacking.

Messenger RNA (mRNA) coronavirus disease of 2019 (COVID-19) vaccines have been recently associated with acute myocarditis, predominantly in healthy young males. Out of 231,989 vaccines administrated in our region (Marche, Italy), we report a case series of six healthy patients (four males and two females, 16.5 years old (Q1, Q3: 15, 18)) that experienced mRNA-COVID-19-vaccines side effects. All patients were hospitalized due to fever and troponins elevation following the second dose of an mRNA-based COVID-19 vaccine. Cardiovascular magnetic resonance (CMR) was performed 72-96 h after vaccination. All patients were treated with colchicine and ibuprofen. Myocarditis was prevalent in males. It was characterized by myocardial edema and late gadolinium enhancement (LGE) in the lateral wall of the left ventricle (LV). One patient showed sole right ventricular involvement, while the females presented with myopericarditis (myocarditis + pericardial effusion). All patients in our series had preserved LV ejection fraction and remained clinically stable during a relatively short inpatient hospital stay. One case presented with atrial tachycardia. At the follow-up, no significant CMR findings were documented after a three-month medical treatment. According to other recently published case series, our report suggests a possible association between acute myocarditis and myopericarditis with mRNA COVID-19 vaccination in healthy young adults and pediatric patients. Not only males are involved, while some arrhythmic manifestations are possible, such as atrial tachycardia. Conversely, we here highlight the benign nature of such complications and the absence of CMR findings after a three-month medical treatment with colchicine and ibuprofen.

The historical-medical and anthropological studies, regarding Mesoamerica and South America, have been mainly focused on the great empires (Inca, Atzec, Maya), while other civilizations have been less investigated and only recently are gaining interest. In general, the paleopathological research provides interesting data to know the type of nutrition and the general environmental conditions as well as to point out some ritual mutilation practices, which were relatively frequent in the pre-Columbian cultures. A lot of civilizations flourished in the South America before the arrival of the Spanish Conquistadores in the new world. In the last years it is progressively increasing the interest for the study of the Moche culture as well as for a deeper knowledge of pathocenosis of infectious diseases in the Moche society. Human infectious diseases are known to have a frequent animal origin, in particular from domesticated species, although the species domesticated in the pre-Columbian era were a small number. The purpose of our paper has been to examine the archeological findings suggestive of infectious diseases in artistic ceramic pots, dating back to the Moche period. We examined the iconography of ceramic pots belonging to the collection of the Larco Museum in Lima and reproducing body signs suggestive of infectious diseases. We identified 8 handworks with very interesting features by a medical point of view. In these handworks there are signs and lesions possibly associated with infectious diseases: risus sardonicus, orbital edema, facial nerve palsy, dorsal kyphosis, face and skin lesions. These features are compatible with some infectious diseases, including: syphilis, Bartonella bacilliformis, leishmaniasis, Pott's disease and Chagas disease. A wide discussion about these handworks is provided., Competing Interests: Conflicts of interest None to declare., (Copyright © 2016 - 2021 InfezMed.)

Long term survival and its determinants after Percutaneous Coronary Intervention (PCI) on Unprotected Left Main Coronary Artery (ULMCA) remain to be appraised. In 9 European Centers 470 consecutive patients performing PCI on ULMCA between 2002 and 2005 were retrospectively enrolled. Survival from all cause and cardiovascular (CV) death were the primary end points, while their predictors at multivariate analysis the secondary ones. Among the overall cohort 81.5% of patients were male and mean age was 66 ± 12 years. After 15 years (IQR 13 to 16), 223 patients (47%) died, 81 (17.2%) due to CV etiology. At multivariable analysis, older age (HR 1.06, 95%CI 1.02 to 1.11), LVEF < 35% (HR 2.97, 95%CI 1.24 to 7.15) and number of vessels treated during the index PCI (HR 1.75, 95%CI 1.12 to 2.72) were related to all-cause mortality, while only LVEF <35% (HR 4.71, 95%CI 1.90 to 11.66) to CV death. Repeated PCI on ULMCA occurred in 91 (28%) patients during the course of follow up and did not significantly impact on freedom from all-cause or CV mortality. In conclusion, in a large, unselected population treated with PCI on ULMCA, 47% died after 15 years, 17% due to CV causes. Age, number of vessels treated during index PCI and depressed LVEF increased risk of all cause death, while re-PCI on ULMCA did not impact survival., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Hiatal hernia repair (HHR) is a complex surgical procedure and its management is not standardized. Several meta-analyses have compared cruroplasty with hiatus reinforcement with mesh, and crura augmentation appears to have better outcomes. However, heterogeneity in type of mesh and placement techniques has differed significantly. Materials and Methods: A systematic review and network meta-analysis were carried out. An electronic systematic research was carried out throughout Pubmed, CENTRAL, and Web of Science, of articles analyzing HHR with cruroplasty, nonabsorbable mesh (NAM), and absorbable mesh (AM) reinforcement. Results: Seventeen articles based on 1857 patients were enrolled in this article. The point estimation showed that when compared against the control group (NAM), the HH recurrence risk in AM and cruroplasty group was higher (relative ratio [RR] 2.3; CrI 0.8-6.3, RR 3.6; CrI 2.0-8.3, respectively). Postoperative complication rates were alike in all groups. The prevalence of mesh erosion after HHR is low. Conclusions: This network meta-analysis showed that prosthetic reinforcement significantly reduced HH recurrence when compared with cruroplasty alone. However, there is not enough evidence to compare different mesh compositions.

Background: This study aims to consolidate all available articles on this topic and evaluate MSA effectiveness in the management of gastroesophageal reflux disease (GERD). Matherials and Methods: We conducted an electronic systematic search using MEDLINE databases (PubMed), EMBASE, and Web of Science. An electronic systematic search of articles comparing preoperative and postoperative health-related quality of life (GERD-HRQL) scores in patients who underwent MSA placement for management of GERD following bariatric surgery was performed. Three retrospective studies totaling 33 patients met the inclusion criteria and were included in this meta-analysis. Results: The pooled mean difference in change from preoperative GERD-HRQL score was 17.5 (95% CrI; -22.88 to -12.20) and it was statistically significant. The between-study variability is 3.621 (95% HPD; 1.39 4.99) with low heterogeneity ( I 2  = 15%; 95% HPD; 2.1 26.2%). Conclusions: MSA for refractory GERD following bariatric surgery appears feasible. Prospective randomized controlled with standardized surgical technique and objective follow-up evaluation is needed to better assess short- and long-term efficacy.

Background: Clinical benefits of FFR (Fraction Flow Reserve) driven CABG (Coronary Artery Bypass Graft) remain to be established., Methods: All randomized controlled trials (RCTs) and observational studies with multivariable adjustement were included. MACE (Major Adverse Cardiac Events) was the primary end point, while its single components (death, myocardial infarction, and total vessel revascularization [TVR]) along with number of anastomoses, on pump procedures and graft occlusion at angiographic follow-up were the secondary ones. Each analysis was stratified for RCTs versus observational studies., Results: Four studies (two RCTs and two observational) were included, enrolling 983 patients, 542 angio-guided and 441 FFR-guided. Mean age was 68.45 years, 79% male, with a mean EuroSCORE I of 2.7. Coronary lesions were located in 37% of patients in the left anterior descending artery, 32% in the circumflex artery, and 26% in the right coronary artery. After a mean follow-up of 40 months, risk of MACE did not differ (OR 0.86 [0.63-1.18]) as that of all cause death (OR 0.86 [0.59-1.25]), MI (OR 0.57 [0.30-1.11]) and TVR (OR 1.10 [0.65-1.85]). FFR-driven CABG reduced on-pump procedures (OR 0.58 [0.35-0.93]) and number of anastomoses (-0.40 [-0.80: -0.01]) while incidence of graft occlusion at follow-up did not differ (OR 0.59 [0.30-1.15], all CI 95%)., Conclusion: Fraction flow reserve driven CABG reduced the number of anastomoses and of on-pump procedures without increasing risk of MACE and without reducing graft occlusion at angiographic follow-up. ID CRD42020211945., (© 2020 Wiley Periodicals LLC.)

Background: Cardiovascular disease (CVD) is still the leading cause of death worldwide, responsible for an estimated 17.8 million deaths globally in 2017, accounting for 31.8% of all deaths. In this review, we aim to provide an updated overview of CVD burden from an Italian and a global perspective., Methods: Crude and age-standardized incidence and prevalence, as well as age-standardized mortality rate and morbidity rate (expressed as disability-adjusted life years - DALYs), of different cardiovascular conditions, derived from the Global Burden of Disease Injuries, and Risk Factors Study (GBD) 2017, were reported and compared between Italy and the world., Results: Crude prevalence of CVD in Italy is nearly twofold higher than global prevalence (12.9% vs. 6.6%), while age-standardized estimates are similar (6.2% vs. 6.3%). Mortality and morbidity from CVD are reduced in Italy, as compared to worldwide estimates (age-standardized mortality rate 113/100,000 vs. 233/100,000; age-standardized rate of DALYs lost 1764/100,000 vs. 4598/100,000). Of the evaluated cardiovascular conditions, the most important CVD burden is due to ischemic heart disease, which show a crude prevalence of 3.6% in Italy (age-standardized: 1.7%), doubling the corresponding crude global estimate (1.7%; age-standardized: 1.6%)., Conclusions: This latest update on the epidemiology of CVD within Italy and the world summarizes the burden of major cardiovascular conditions. CVD, especially ischemic heart disease, is still an important cause of mortality and morbidity. The impact of increasing life-expectancy is a key determinant of CVD epidemiology in Italy, if compared to worldwide data, since older age is one of the major risk factors for CVD.

In the year 1630, similarly to other cities of Northern Italy, Bologna was affected by a plague epidemic. It occurred after the arrival of Lansquenet troops, engaged by the Emperor Frederick II in the siege of Mantua city. The human losses have been calculated by the historian demographer Bellettini in the terms of around 15,000 people, so that the number of inhabitants in Bologna declined from 62,000 to 47,000 units in the time span of 7-8 months. Initially, during the winter and the early spring, although the plague epidemic had been known after that it involved many cities close to Bologna (i.e. Turin, Milan, Venice, Genoa and Verona), the population tried to keep the epidemic hidden, being afraid that commerce exchanges could be affected by this event. Later, starting from the month of May, under the guidance of cardinal Bernardino Spada, cooperating with the numerous religious orders and in particular with the one of the Camillians, the city reacted, launching an organization effort which significantly aided in the containment of the plague epidemic. A number of Lazarettos were organized outside of the city walls and relevant sums supported the clean operation of over 3,000 houses. The city Senate sustained the poor population with a sum of 700,000 lire and grain donations. Even if the loss of human lives was high, it resulted not so dramatic, compared with that paid by other Italian cities. From a cultural point of view, according to the belief of the scientific knowledge of that time, the miasmatic theories were still considered satisfactory, although in the common practice the people who could leave the city escaped from Bologna, in order to avoid the contagion. We can argue that the impact of the epidemic was reduced by means of the organizational approach with strict isolation measures for sick persons, the closing of the city walls in the urban areas more affected by the plague, and finally a sanctionatory and punitive approach for individuals, who disregarded the applied rules.

In December 2019, a novel human-infecting coronavirus, named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), was recognised to cause a pneumonia epidemic outbreak with different degrees of severity in Wuhan, Hubei Province in China. Since then, this epidemic has spread worldwide; in Europe, Italy has been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, few studies about SARS-CoV-2 concerning its immunopathogenesis and treatment are available. On the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82 % of genome homology) and that its characteristics, like the modality of transmission or the type of the immune response it may stimulate, are still poorly known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analysed: (1) the structure of SARS-CoV-2 and SARS-CoV; (2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the cytokine release syndrome; (3) the modification of the cell microRNome and of the immune response in patients with SARS infection; and (4) the possible role of some fat-soluble compounds (such as vitamins A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.

Background: In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a "public health emergency of international concern". A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins., Methods: We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function., Results: SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection., Conclusions: Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.

In the year 1527, following the invasion of Italy by Landsknechts, who were headed by Georg von Frundsberg, the bubonic plague appeared in the country. These soldiers were part of an army that Charles V sent to invade Italy in order to subjugate the Italian states which had adhered to the League of Cognac. In Bologna during the year 1527 believers held a procession from the Sanctuary of the Madonna del Soccorso, through the city, as far as the Church of San Rocco. The reason for this practice was linked with the plague epidemic. After some cases of plague observed in the Borgo di San Pietro district the miracle of the interruption of the epidemics, thanks to the intervention of Our Lady, was narrated by the faithfuls. Later, after several decades, it was reported by several authors from Bologna, who were not witnesses to the facts, that the epidemic had involved 12,000 out of a total population of around 60,000 inhabitants at that time. We re-evaluated this situation starting from the demographic data concerning the citizens in Bologna during the 15th, 16th and 17th centuries. Furthermore, we performed a search in the State Archives in the city of Bologna in order to find any public notices from the city authorities in the year 1527 aiming to counteract a plague epidemic. Our investigation found no elements to support the outbreak of this disease. Throughout the 16th century, until 1590, the population grew significantly, and no public notices were issued or specific laws enacted to deal with the plague until the year 1557. However, it remains possible that in the area in question, some episodes of plague occurred, but it was fortunately a micro-epidemic, which involved a very poor area of the city. Then this disease was self-limited. However, in our opinion, this episode proved very important, since in this district of Bologna, and around a wooden image of the Madonna del Soccorso, a confraternity took place, and its activities continued until the year 1798. This group of citizens also played a major role in many charitable activities to aid the inhabitants of Bologna, during a difficult historical period, namely the Protestant Reformation, and contributed to strengthen the faith of Catholic believers.

A 21-year-old patient has been treated in emergency with venovenous extracorporeal membrane oxygenation after severe thoracic trauma causing severe air leak and haemothorax. The extracorporeal assistance was managed without heparin for 10 days till the full recovery of the lung, and no side-effect was recorded.

The living conditions of Italian prisoners during the First World War were extremely difficult. At the end of the conflict, the treatment of Italian soldiers in Austro-Hungarian POW camps and in those of the German territories was recognized as particularly harsh in comparison with that of other prisoners. The reasons may be ascribed to three main factors. The Italian prisoners paid the price of being considered traitors, since Italy was allied with the Austro-Hungarian Empire and with Germany until 1914, subsequently switching to the side of France, the United Kingdom and Russia. The Italian government and the Italian High Command considered their soldiers poorly inclined to engage in a war which became over time increasingly costly in terms of human sacrifice. The strategy pursued by the General-in-Chief Luigi Cadorna was very aggressive and showed little care for the life conditions of his troops, who were frequently thrown into the fray and exposed to potential slaughter. Due to this negative judgement on their troops' willingness to fight, the government did not help, and even hindered, the despatch of packages of food and clothes to prisoners in the Austro-Hungarian and German camps via the Red Cross. The idea of a better life in the trenches compared with that expected in the camps as prisoners was widespread. Thirdly, the maritime blockade of the Adriatic Sea over time reduced to starvation the populations of Austria, Hungary and Germany, which obviously had grave repercussions on prisoners. It was estimated that around 100,000 Italians lost their lives in POW camps; after the defeat at Caporetto, when over 250,000 prisoners were captured, the number of deaths rose. The main causes of death were: tuberculosis, pneumonia, malnutrition and typhoid fever. At the end of the war, when coming back to Italy, former POWs were interned for months in camps (located predominantly in the Emilia region) and had to face interrogation and trials to demonstrate they were not deserters and were free to go back home. In the meantime, many lost their lives due to "Spanish" flu, pneumonia and other infectious diseases. Only the mobilization both of families and public opinion forced the Italian government to close the camps at the end of the year 1919.

During the Great War, which involved Italy from May 1915 until November 1918, the Italian Army paid an extremely high price in terms of suffering; around 600,000 soldiers died. About 100,000 of these deaths were caused by diseases, mainly infectious ones. The casualties accounted for over one million cases. Epidemics of cholera and petechial typhus were recorded as well as an increase in morbidity due to tuberculosis and malaria, which had shown some minor epidemiological reduction in several regions of Italy during the years preceding the Great War. A large number of soldiers acquired respiratory tract and brain infections. Severe limb infections were due to war wounds, but also to a novel disorder called "trench foot", In a context of general hygienic decay, death and stress linked to massive bombing, severe psychiatric disorders were observed. They were called "shell shock" in English (and known in Italy as "the wind of the howitzer"). The patients suffering from the above psychiatric disorders were considered simulators by the great majority of psychiatrists, who largely believed such soldiers wanted to avoid active combat. They were subjected to electric shocks and later sent back to the war front or to a mental hospital in the most severe cases. In some dramatic occurrences, like at the time of the Caporetto defeat, a substantial number of soldiers were dealt rough justice in front of firing squads under the suspicion of desertion. Yet World War I, with its dramatic load of suffering, forced the medical environment to develop extremely innovative techniques and research applied to clinical practice. During the decades to follow, such efforts yielded major results in the field of pharmacology: studies which led to the discovery of the first antibiotics were set in motion.

In past centuries, epidemics, the scourge of humankind, caused pain, anger, uncertainty of the future, social as well as economic disorder and a significant impact on their victims, involving also their spiritual sphere. The latter effect led to undoubted effects on participation in the religious and social life of communities. The custom of preparing artistic votive expressions has been lost in the mists of time and evidence of ex voto gifts, offered by believers to pagan gods, has been found in prehistoric archaeological sites. Furthermore, several finds from the Ancient Greek and Roman worlds may be observed in our museums. These remains are generally ceramic and metal artifacts, reproducing limbs and other body parts which had been healed. These elements, according to the belief of those making the offerings, had benefited from the miraculous intervention of a thaumaturgical deity. With the advent of Christianity, some pre-existing religious practices were endorsed by the new religion. Believers continued to demonstrate their gratitude in different ways either to miracle-working saints or to the Virgin Mary, because they thought that, thanks to an act of faith, their own health or that of a family member would benefit from the direct intervention of the divine entities to whom they had prayed. In the Ancient Greek world, it was believed that the god Asclepius could directly influence human events, as testified by the popularity of shrines and temples to the god, especially at Epidaurus. In the Christian world as well, particular places have been detected, often solitary and secluded in the countryside or in the mountains, where, according to tradition, direct contact was established between the faithful and Saints or the Virgin Mary Herself. Manifestations occurred by means of miracles and apparitions, thereby creating a direct link between the supernatural world and believers. Religious communities, in these extraordinary places, responded to the call through the building of shrines and promotion of the cult. Over time, the faithful reached these places of mystery, performing pilgrimages with the aim of strengthening their religious faith, but also with the purpose of seeking intercession and grace. In this case, the request for clemency assumed spiritual characteristics and also became a profession of faith. Accordingly, the shrines in the Christian world are places where supernatural events may occur. In these environments the believer resorted to faith, when medicine showed its limits in a tangible way. For the above reasons, while epidemics were occurring, the requests for clemency were numerous and such petitions were both individual and collective. In particular, by means of votive offerings (ex voto) the believers, both individually and collectively, gave the evidence of the received grace to the thaumaturgical Saint. Through the votive act, a perpetual link between the believer and the Saints or Holy Virgin was forged and a strong request for communion was transmitted. The aim of the present study is to describe the role played by votive tablets (ex voto) in the last 500-600 years, as visible evidence of human suffering. From this perspective, these votive expressions may assume the role of markers because, in accordance with the expressions of popular faith, they allow us to follow the most important outbreaks that have caused distress to Christian communities.

Background: Hyperlipidaemia is a risk factor for the progression of chronic kidney disease (CKD), which is a frequent comorbidity in patients with HIV-1 infection, but the renal effects of statins remain unclear., Methods: We performed an observational, prospective study of HIV-infected patients on suppressive antiretroviral therapy, with CKD and hyperlipidaemia, and starting a lipid-lowering treatment with rosuvastatin, atorvastatin or omega-3 fatty acids. CKD was defined as an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m 2 for >3 months., Results: As a whole, 69 patients (53 men, 58 Caucasian, median age 56.2 years) were enrolled. Overall, 25 patients started rosuvastatin (10 mg daily, group A), 23 patients atorvastatin (20 mg daily, group B), and 21 started omega-3 fatty acids (3 g daily, group C). At baseline, median eGFR was 54.4 mL/min/1.73 m 2 , and the eGFR ranged between 50 and 60 mL/min/1.73 m 2 in 87% of patients. After 12 months, the median eGFR decline was significantly lower in group A (-0.84 mL/min/1.73 m 2 ) and in group B (-0.91 mL/min/1.73 m 2 ) in comparison with the group C (-1.53 mL/min/1.73 m 2 ; p < 0.001 for both comparisons). The median decrease in prevalence of proteinuria and high-sensitivity C-reactive protein was also significantly greater in groups A and B than in group C, while the incidence of treatment discontinuations was comparable across the three groups., Conclusion: In our study, rosuvastatin and atorvastatin showed a significant protective effect on the renal function compared to omega-3 fatty acids in HIV-1-infected patients with CKD and dyslipidaemia.

Introduction: Synthetic materials have traditionally been used for tissue reconstruction in thoracic surgery. New biomaterials have been tested in other areas of surgery with good results. Non-cross-linked swine dermal collagen prosthesis has been used to reconstruct musculofascial defects in the trunk with low infection and herniation rate., Material and Methods: Retrospectively, we analyze our initial experience of chest wall reconstruction on large defects using a non-cross-linked swine dermal collagen matrix mesh with a thickness of 1.4 mm. A total of 11 consecutive patients were included. Preoperative, intraoperative, and postoperative data were taken into consideration., Results: Eleven sarcoma patients with a mean age of 58.25 ± 12.9 years underwent chest wall resections. Complete thoracic wall defects ranged from 6 · 9 to 16 · 25 cm in size. In all cases, we used a porcine collagen matrix mesh, and in all patients, it was covered by transposition of myocutaneous flap. The complications occurred in 5 (45%) patients, 1 (9%) pneumonia, 1 atrial fibrillation (9%), and 3 (27%) wound healing difficulty because of hematoma or infection. There was no respiratory impairment, and the pulmonary function (total lung capacity, vital capacity, and forced expiratory volume in 1 second) was not statistically different before and after surgery. The 30-day mortality was 0%, 1-year mortality and 2-year mortality was 27.2%. The collagen material resulted in a durable and good to excellent chest wall stability in clinical follow-ups, and on computer tomography scans spanning over 2 years., Conclusion: Non-cross-linked acellular porcine dermal collagen matrix is a feasible and reliable biological patch material for reconstruction of the thoracic wall. Excellent wound healing, long-term stability, low complication, and good pulmonary function are achieved even in large defects.

In the late nineteenth century, with industrial growth and the resulting mass urbanisation, tuberculosis represented a plague mainly among the poor social classes. The outdated and crowded Italian prisons (formerly old monasteries) during the early 1900s were insufficient to "host" the multitude of inmates condemned or waiting for judgment. Italian prisoners were beset by hunger and poor hygiene facilities. Clothes did not differ between winter and summer. The Criminal Sanatorium of Pianosa was officially inaugurated in 1907, but from the 1860s it had been set up to host an agricultural penal colony. Here we report the excellent results obtained between 1907 and 1909 in the management of tuberculosis among prisoners in Pianosa, where surgery was also available. In those times, climate therapy with an enriched and varied nutrition was the only effective treatment for tuberculosis. Overall, of the 913 prisoners housed in Pianosa in that period and according to the acknowledged scientific criteria, the following results were achieved: complete cure in 182, improvement in 416, mild amelioration in 94, worsening in 80, no change in 20. The number of prisoners who died or were transferred to another prison is unknown. The case series of the prison hospital in Pianosa may be reconstructed thanks to data published by the Director Roberto Passini. The better outcome of the prisoners in Pianosa, in comparison with inmates of other Italian institutions, was due both to treatment standards (climate, nutritional, hygienic, and surgical) and to the proportionally longer period of stay in Pianosa for prisoners with already confirmed detention periods.

Background: We reviewed our experience with patients presenting with trauma and peritonitis who underwent an open abdomen (OA) procedure, and compared outcomes between Negative Pressure Wound Therapy (NPWT) and a modified Barker Vacuum Pack (mBVP) technique., Methods: In this descriptive study, we retrospectively analyzed data regarding all patients who underwent OA for intra-abdominal sepsis or abdominal trauma at our Centre from January 2012 to December 2015. Demographic data, co-morbidities, indications to surgery, intra-operative details and Björck classification grade were considered. Outcomes included were: time to closure in days, fascial closure rates, ICU and hospital stay, in-hospital and overall mortality, and entero-atmospheric fistula rate., Results: A total of 83 cases were considered. Mean closure time was 6 days versus 6.5 days (p = 0.71) in NPWT and mBVP groups, respectively; the fascial closure rate was 75.4% versus 93.8% (p = 0.10). At multivariate analysis, in-hospital and overall mortality were significantly higher within the mBVP, as compared to NPWT (OR 3.8, 95% CI 1.1 to 13.1, p = 0.02 - OR 4.2, 95% CI 1.2 to 14.1, p = 0.01). Entero-atmospheric fistula rate was 2.6% in the two groups., Conclusions: NPWT as a temporary abdominal closure technique, as compared to mBVP, appears to be associated with better outcomes in terms of mortality.

Nucleoside reverse transcriptase inhibitor (NRTI)- and protease inhibitor (PI)-sparing antiretroviral regimens may be useful in selected human immune deficiency virus (HIV)-infected patients with resistance or intolerance to these drug classes. This was an observational prospective study of patients on suppressive antiretroviral therapy containing two NRTIs plus one ritonavir-boosted PI who switched to a dual regimen containing raltegravir plus etravirine. Patients were required not to have prior virological failure to raltegravir and to have efficacy of etravirine shown through the genotypic resistance assay in case of prior non-nucleoside reverse transcriptase inhibitor (NNRTI) virological failure. As a whole, 38 patients were enrolled. The mean duration of current regimen was 4.3 years, and the reason for simplification was toxicity in 29 patients and resistance to NRTIs in 9 patients. After switching, the percentage of patients with HIV RNA <20 copies/ml at week 48 was 81.6% in the intent-to-treat-exposed analysis. The switch led to a significant reduction in the mean serum triglyceride levels (-81.2 mg/dl), in the mean total cholesterol levels (-44.3 mg/dl), and in the prevalence of tubular proteinuria (-30.2%), with a significant increase in the mean phosphoremia (+0.52 mg/dl) and in both mean lumbar and femoral neck bone mineral density (+6.5% and +4.7%, respectively). Two patients (5.2%) had virological failure due to suboptimal adherence, and five subjects (13.1%) discontinued treatment due to adverse events. In our study, simplification to the dual-therapy raltegravir plus etravirine was associated with a good efficacy and tolerability, in addition to a favorable effect on kidney, bone, and serum lipids.

A 30-year-old man was admitted to hospital after complaining of a retrosternal burning pain, radiating to the jugular region, and to both upper limbs. An electrocardiography examination showed a ST segment elevation involving the lower-lateral leads. A trans-thoracic ultrasonography showed findings compatible with an acute myopericarditis. All performed serological testings excluded other recent infections with cardiac tropism. Among screening tests, a peripheral lymphocyte subset analysis was performed and an inversion of the CD4/CD8 ratio was found. Therefore, HIV testing was performed and proved positive for HIV-1 antibodies. The discovery of a primary HIV infection with involvement of a vital organ led us to start HAART. On day 20, our patient underwent a right heart catheterization and endomyocardial biopsy. During the following days, the clinical conditions of our patient improved, and a further heart ultrasonography documented a mild pericardial thickening as a result of the recent myopericarditis. Also the evolving changes of ECG were compatible with a benign evolution of myopericarditis. The histopathologic studies revealed a mild fibrosis of the myocardial right ventricular tissue, and inflammatory findings compatible with a recent myocarditis. At the real-time PCR analysis on bioptic sample, only HHV6 DNA and HIV-DNA were reactive. An immunofluorescence staining was performed to highlight the HIV p24 protein and a positive signal was detected in myocardial tissue. Considering the low avidity level of the anti-HIV IgG antibodies and the positivity of HIV-DNA in the endomyocardial tissue, we believe that the clinical manifestation presented can be referred to the recent primary HIV-infection.

Complex pelvic injuries are among the most dangerous and deadly trauma related lesions. Different classification systems exist, some are based on the mechanism of injury, some on anatomic patterns and some are focusing on the resulting instability requiring operative fixation. The optimal treatment strategy, however, should keep into consideration the hemodynamic status, the anatomic impairment of pelvic ring function and the associated injuries. The management of pelvic trauma patients aims definitively to restore the homeostasis and the normal physiopathology associated to the mechanical stability of the pelvic ring. Thus the management of pelvic trauma must be multidisciplinary and should be ultimately based on the physiology of the patient and the anatomy of the injury. This paper presents the World Society of Emergency Surgery (WSES) classification of pelvic trauma and the management Guidelines.

The introduction of potent combination antiretroviral therapy (cART) has had a remarkable impact on the natural history of HIV infection, leading to a dramatic decline in the mortality rate and a considerable increase in the life expectancy of HIV-positive people. However, cART use is frequently associated with several metabolic complications, mostly represented by lipid metabolism alterations, which are reported very frequently among persons treated with antiretroviral agents. In particular, hyperlipidaemia occurs in up to 70%-80% of HIV-positive subjects receiving cART and is mainly associated with specific antiretroviral drugs belonging to three classes of antiretroviral agents: NRTIs, NNRTIs and PIs. The potential long-term consequences of cART-associated dyslipidaemia are not completely understood, but an increased risk of premature coronary heart disease has been reported in HIV-infected patients on cART, so prompt correction of lipid metabolism abnormalities is mandatory in this population. Dietary changes, regular aerobic exercise and switching to a different antiretroviral regimen associated with a more favourable metabolic profile are the first steps in clinical management, but lipid-lowering therapy with fibrates or statins is often required. In this case, the choice of hypolipidaemic drugs should take into account the potential pharmacokinetic interactions with many antiretroviral agents., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Advanced Trauma Life Support (ATLS) guidelines are widely accepted for use in initial management of trauma patients. The application of ATLS guidelines and introduction of management by means of trauma team (TT) both took place in April 2011. The aim of the present study was to evaluate related effects on mortality in the shock room (SR) and at 24 hours after admission., Methods: Data were retrieved by administrative software based on patient admission for trauma of at least 48 hours. Study period was from April 2011 to December 2012, and control period was from January 2007 to March 2011. All admitted patients were identified by first diagnosis (ICD 9-CM), excluding traumatic brain injuries, and only patients admitted to the general intensive care, general surgery, and orthopedics units were included., Results: The control group (CG) included 198 patients; the study group (SG) included 141. Differences were determined in patient age, which was mean 45.2 years (SD: 19.2) in the CG and mean 49.3 years (SD±18.3) in the SG (p=0.03). Differences were not found regarding gender, length of hospital stay, or Injury Severity Score (ISS). Among the patients who died, no differences were found in terms of systolic blood pressure, metabolic acidosis, or packed red blood cell consumption. Mortality was significantly higher in the CG, compared to the SG (14.1% vs 7.1%, respectively; p=0.033; confidence interval [CI]: 0.21-0.95). Mortality in the shock room was significantly lower in the SG, compared to the CG (0.7% vs 7.1%, respectively; p=0.002; CI: 0.004-0.592)., Conclusion: The introduction of ATLS guidelines and TT had a positive impact on mortality in the first 24 hours, both in the SR and after admission.

Background: Acute calcolous cholecystitis (ACC) is a very common pathology in western countries. The aim of our work was to assess the epidemiology of ACC and its treatment in Bergamo, a northern Italy province, during the last seventeen years., Methods: A restrospective analysis, covering 1997 to 2013, was performed based on the administrative register of the province Health System. Only patients admitted for ACC were selected. From 1997 to 2013 were collected 8959 cases of ACC, mean age was 61.28, 51.5% were male., Results: The incidence of ACC was 48/100.000 per year; the operation rate was 66%. Overall mortality was 0.7%, mean hospitalization time was 9.7 days. The treatment of ACC in Bergamo Province seemed to be acceptable and comparable to literature results. Over the last years, laparoscopy has become the standard treatment., Conclusions: This study outlined some criticisms on the selection's methodology sourcing data from administrative registers, raising questions about truthfulness of results and usefulness for health policy issues.

Background: Systemic response to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) causes the activation of endocrine, metabolic, hemodynamic and inflammatory processes. The aim of this work is to describe and analyze the time course of the inflammatory markers concentration during CRS+HIPEC in plasma and peritoneal fluids and the association with hemodynamic and metabolic parameters., Methods: Pre-, intra- and postoperative data were collected. Tumor necrosis factor (TNF), interleukine 6 (IL-6), pro-calcitonin (PCT), cancer antigen 125 (CA-125) in blood and in peritoneal fluids were evaluated., Results: Thirty-eight patients were included, 29 (76.3%) of them were female. Mean/median PCI was 9.2/5, primary malignancy was 5 colorectal cancer (13.2%), 5 gastric cancer (13.2%), 23 ovarian cancer (60.5%) and 5 other malignancies (13.2%). Combined clinical risk 0-1 was reached in all patients. Cardiac index, heart rate and central venous pressure increased during the procedure, while stroke volume variation showed a decrease. Mean arterial pressure and superior vena cava oxygenation were stable throughout the whole procedure. TNF and CA-125 were steady during the whole procedure; IL-6 had a relevant increase from baseline to start of perfusion (P<0.01); PCT had a steady increase at every time point. Peritoneal sampling showed a statistically significant increase (P<0.01) between start and end of the perfusion phase for all markers but TNF. Serum and peritoneal marker concentration were similar for TNF, PCT and CA-125. IL-6 showed a sharp difference., Conclusions: The most significant variations were in IL-6 and PCT levels. The cytokines level parallels the hemodynamic derangements. Treatment during HIPEC should mimic the established treatment during sepsis and septic shock.

Background: Nucleoside reverse transcriptase inhibitor (NRTI)-sparing antiretroviral therapies may be useful in HIV-infected patients with resistance or intolerance to this class., Methods: We performed an observational study of patients on suppressive antiretroviral therapy containing two NRTIs plus one ritonavir-boosted protease inhibitor who switched to a dual regimen containing raltegravir (400 mg twice daily) and darunavir/ritonavir (800/100 mg once daily) and were followed-up for 48 weeks., Results: As a whole, 82 patients were enrolled. Mean duration of current regimen was 4.6 years and mean duration of plasma HIV RNA < 50 copies/mL before the switch was 46.2 months. Reason for simplification was toxicity in 76 patients and resistance to NRTIs in 13. After switching, the percentage of patients with HIV RNA < 50 copies/mL at week 48 was 92.7% in the intent-to-treat-exposed analysis and 97.6% in the per-protocol analysis. The switch led to a significant reduction in the mean triglyceride value (-85.2 mg/dL), in the prevalence of tubular proteinuria (-56%) and in the mean level of interleukin-6 (-0.94 pg/mL), with a significant increase in the mean phosphoremia (+0.58 mg/dL). Mean trough concentrations of both raltegravir and darunavir were within the therapeutic range. Two patients (2.4%) had virological failure due to suboptimal adherence and 4 subjects (4.9%) discontinued treatment due to adverse events, but no patients experienced Grade 3 or 4 adverse events., Conclusion: In our study, simplification to a dual therapy containing raltegravir plus darunavir/ritonavir after 48 weeks maintained viral suppression in more than 90% of patients and showed a good tolerability with a favourable effect on proteinuria, ipophosphoremia, and lipid metabolism.

Background: Acute appendicitis (AA) is one of the most common diseases affecting especially young but also older people. A systematic evaluation of bacteriology of AA has been frequently conducted in children but is not well known and discussed in adult population., Study Design: The study has been obtained from two multicenter prospective observational studies (CIAO and CIAOW studies). The aim of the study is to analyze the intra-abdominal bacteriology in AA and its relation with clinical outcomes., Results: Patients included were 1431, 806 male (56.3%). The mean/median age was 38.9 (SD ± 18.4) and 35 (range 18-94). Clinical condition at the admission was sepsis in 623 patients (43.5%), severe sepsis and septic shock in 29 (2%) and 10 (0.7%). Peritonitis was localized in 1107 patients (77.4%) and generalized in 324 (22.6%). Adequate source-control and empirical antimicrobial therapy were reported in 95.2% and 88.7% of the patients. 47 isolated bacteria (6.8%) were resistant. Two (4.2%) were health-care-associated infections and 45 (95.7%) were community-acquired infections. Univariate analysis showed factor associated to resistant bacteria was the inadequacy of the empiric antimicrobial therapy (p = 0.013); at multivariated analysis factors associated with mortality were age>70 years (p = 0.003) and severe sepsis at the admission (p = 0.02); factors associated to ICU admission were: severe sepsis (p < 0.0001), generalized peritonitis (p < 0.0001), malignancy (p < 0.0001) and cardiovascular disease (p < 0.0001)., Conclusion: The evolution of antimicrobial resistance, in common community-acquired infections, combined with lack of new antibiotics development are strictly linked to clinical outcomes. Adequate empirical antimicrobial therapy is fundamental to counteract bacterial resistance., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Hyperthermic intraperitoneal chemotherapy (HIPEC) is currently delivered after cytoreductive surgery in patients with several kinds of peritoneal surface malignancies. Different methods for delivering HIPEC have been proposed all of them being variations between two modalities: the open technique and the closed technique. The open technique assures optimal distribution of heat and cytotoxic solution, with the disadvantage of heat loss and leakage of cytotoxic drugs. The closed technique prevents heat loss and drug spillage, increases drug penetration, but does not warrant homogeneous distribution of the perfusion fluid. A novel procedure that combines the advantages of the two techniques by means of laparoscopy is herein presented.

Background: A part of damage-control laparotomy is to leave the fascial edges and the skin open to avoid abdominal compartment syndrome and allow further explorations. This condition, known as open abdomen (OA), although effective, is associated with severe complications. Our aim was to develop evidence-based recommendations to define indications for OA, techniques for temporary abdominal closure, management of enteric fistulas, and methods of definitive wall closure., Methods: The literature from 1990 to 2014 was systematically screened according to PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-analyses] protocol. Seventy-six articles were reviewed by a panel of experts to assign grade of recommendations (GoR) and level of evidence (LoE) using the GRADE [Grading of Recommendations Assessment, Development, and Evaluation] system, and an international consensus conference was held., Results: OA in trauma is indicated at the end of damage-control laparotomy, in the presence of visceral swelling, for a second look in vascular injuries or gross contamination, in the case of abdominal wall loss, and if medical treatment of abdominal compartment syndrome has failed (GoR B, LoE II). Negative-pressure wound therapy is the recommended temporary abdominal closure technique to drain peritoneal fluid, improve nursing, and prevent fascial retraction (GoR B, LoE I). Lack of OA closure within 8 days (GoR C, LoE II), bowel injuries, high-volume replacement, and use of polypropylene mesh over the bowel (GoR C, LoE I) are risk factors for frozen abdomen and fistula formation. Negative-pressure wound therapy allows to isolate the fistula and protect the surrounding tissues from spillage until granulation (GoR C, LoE II). Correction of fistula is performed after 6 months to 12 months. Definitive closure of OA has to be obtained early (GoR C, LoE I) with direct suture, traction devices, component separation with or without mesh. Biologic meshes are an option for wall reinforcement if bacterial contamination is present (GoR C, LoE II)., Conclusion: OA and negative-pressure techniques improve the care of trauma patients, but closure must be achieved early to avoid complications.

Background: The objective of the study was to assess plasma concentrations of efavirenz, darunavir/ritonavir and raltegravir in patients with human immunodeficiency virus-hepatitis C virus (HIV-HCV)-coinfection without liver cirrhosis., Methods: In this observational, open-label study, adult HIV-infected outpatients treated with tenofovir/emtricitabine plus efavirenz (600 mg daily), darunavir/ritonavir (800/100 mg daily) or raltegravir (400 mg twice daily) for at least 4 weeks were asked to participate. Subjects with liver cirrhosis were excluded. The trough concentration (C trough) of darunavir/ritonavir and raltegravir and the mid-dose concentration (C12h) of efavirenz were assessed at steady state by a validated high-performance liquid chromatography (HPLC)-tandem mass spectrometry method., Results: A total of 96 HIV-positive patients were enrolled into the study. Thirty-four patients were treated with efavirenz, 33 with darunavir/ritonavir and 29 with raltegravir. The geometric mean plasma C trough [coefficient of variation (%)] of darunavir was comparable between HIV+/HCV+ and HIV+/HCV- subjects: 2644 ng/ml (155%) and 2491 ng/ml (139%), respectively (geometric mean ratio (GMR) = 0.81; 95% confidence interval (CI) = 0.79-1.56; p = 0.69). These values were comparable for raltegravir: 108 ng/ml (149%) in the HIV+/HCV+ group and 96 ng/ml (161%) in the HIV+/HCV- group (GMR = 0.84; 95% CI = 0.61-1.44; p = 0.72). On the contrary, the geometric mean plasma C12h of efavirenz was significantly higher among the 15 HIV+/HCV+ patients (1915 ng/ml, 159%) than among the 19 HIV+/HCV- patients (1505 ng/ml, 167%; GMR = 1.41; 95% CI = 1.19-1.71; p = 0.009)., Conclusions: The mean plasma concentration of efavirenz was significantly higher in HCV-positive than in HCV-negative patients without liver cirrhosis, while the mean plasma levels of darunavir/ritonavir and raltegravir were comparable in both groups.

Background: Treatment option and timing for surgery in case of acute calculous cholecystitis (ACC) is still a matter of discussion. Tokyo Guidelines (TG13) offers some rules but they don't reflect entirely the information of Evidence Based Medicine (EBM). This study aimed to draw some consideration from our practice in the application of the guidelines and put forward the clinical, economic and organizational effect of it., Methods: The study is a single center retrospective study based on administrative database formed by gathering information from clinical registry. Data were collected between January 1st, 2008 and April 30th, 2013. A cutoff point was established on May 15th, 2010 when we moved from a single surgeon method to a shared EBM method to treat ACC. The economic aspect was developed considering health service reimburse and hospital costs., Results: Five hundred and two patients were selected, 203 patients before the organizational change (Group 0) and 299 after (Group 1). In Group 0, 24.63% of the patients were treated with early laparoscopic cholecystectomy (ELC) and 39.4% received surgery delayed in second admission (DLC). After the change, 57.5% of the patients were treated with ELC while 13% were treated with DLC. Median length of stay (LOS) was significantly lower after the change (9.5 vs. 7.3, p<0.0001), and no difference in terms of complication was noticed., Conclusion: Application of evidence based medicine in clinical practice resulted in better results. Economically, the clinical change resulted in a proper use of resources with a positive gap between the costs and refund to the hospital.

Introduction: Postoperative complications for cholecystitis and cholelithiasis are important causes of intra-abdominal infections (IAIs). There have been no previous reports on intra-abdominal bacteriology in complicated IAIs due to acute cholecystitis (AC)., Material and Methods: The data came from two prospective multicenter observational cohort studies (CIAO: the "Complicated Intra-Abdominal infection Observational" study and CIAOW: the "Complicated Intra-Abdominal infection Observational World" study) which involved 116 medical institutions worldwide with consecutive patients who underwent surgery, interventional drainage or conservative treatment for AC., Results: Of 567 patients, there were 291 males (51.3%). The mean and median age were 62.5 and 64 years respectively. 546 (96.3%) had community-acquired and 21 (3.7%) patients had health-care-associated infections. 267 bacteria were isolated, 21 (7.8%) were resistant bacteria. No resistant Fungi or Anaerobes were isolated. 4 out of the 21 resistant bacteria were health-care-associated. Multivariate analysis demonstrated health-care associated infection (p = 0.03), inadequacy of empiric antimicrobial therapy (p = 0.003) and recent antimicrobial therapy (p < 0.0001) to be factors associated with resistant bacteria. The factors associated with mortality were presence of generalized peritonitis (p < 0.0001) and inadequate source control (p = 0.018). The factors associated with ICU admission were severe sepsis (p < 0.0001), generalized peritonitis (p = 0.001), concomitant malignancy (p = 0.037), inadequate source control (p = 0.025), delay in initial intervention (p < 0.0001) and age over 70 years (p = 0.025)., Conclusion: The number of infection caused by Extended Spectrum Beta-Lactamase bacteria (ESBL+) and Klebsiella pneumoniae Carbapenemase-producer bacteria (KPC+) were common in acute cholecystitis and in community-acquired infections. An adequate empirical antimicrobial therapy was fundamental to reduce bacterial resistance and to improve outcomes., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Aim: To investigate the role of laparoscopy in diagnosis and treatment of intra abdominal infections., Methods: A systematic review of the literature was performed including studies where intra abdominal infections were treated laparoscopically., Results: Early laparoscopic approaches have become the standard surgical technique for treating acute cholecystitis. The laparoscopic appendectomy has been demonstrated to be superior to open surgery in acute appendicitis. In the event of diverticulitis, laparoscopic resections have proven to be safe and effective procedures for experienced laparoscopic surgeons and may be performed without adversely affecting morbidity and mortality rates. However laparoscopic resection has not been accepted by the medical community as the primary treatment of choice. In high-risk patients, laparoscopic approach may be used for exploration or peritoneal lavage and drainage. The successful laparoscopic repair of perforated peptic ulcers for experienced surgeons, is demonstrated to be safe and effective. Regarding small bowel perforations, comparative studies contrasting open and laparoscopic surgeries have not yet been conducted. Successful laparoscopic resections addressing iatrogenic colonic perforation have been reported despite a lack of literature-based evidence supporting such procedures. In post-operative infections, laparoscopic approaches may be useful in preventing diagnostic delay and controlling the source., Conclusion: Laparoscopy has a good diagnostic accuracy and enables to better identify the causative pathology; laparoscopy may be recommended for the treatment of many intra-abdominal infections.

The liver is the most injured organ in abdominal trauma. Road traffic crashes and antisocial, violent behavior account for the majority of liver injuries. The present position paper represents the position of the World Society of Emergency Surgery (WSES) about the management of liver injuries.

Actually the most common indications for Open Abdomen (OA) are trauma, abdominal sepsis, severe acute pancreatitis and more in general all those situations in which an intra-abdominal hypertension condition is present, in order to prevent the development of an abdominal compartment syndrome. The mortality and morbidity rate in patients undergone to OA procedures is still high. At present many studies have been published about the OA management and the progresses in survival rate of critically ill trauma and septic surgical patients. However several issues are still unclear and need more extensive studies. The definitions of indications, applications and methods to close the OA are still matter of debate. To overcome this lack of high level of evidence data about the OA indications, management, definitive closure and follow-up, the World Society of Emergency Surgery (WSES) promoted the International Register of Open Abdomen (IROA). The register will be held on a web platform (Clinical Registers®) through a dedicated web site: www.clinicalregisters.org. This will allow to all surgeons and physicians to participate from all around the world only by having a computer and a web connection. The IROA protocol has been approved by the coordinating center Ethical Committee (Papa Giovanni XXIII hospital, Bergamo, Italy). IROA has also been registered to ClinicalTrials.gov (ClinicalTrials.gov Identifier: NCT02382770).

Introduction: Both natural history and epidemiological trend of HIV infection have been deeply modified by the introduction of highly active antiretroviral therapy (HAART), around twenty years ago., Methods: However, despite a rapid drop of the incidence of the large majority of opportunistic infections, a slow, but continued increase of malignancies occurred, with particular evidence focused on cancers which are not strictly related to the definition of full blown AIDS (the so called non-AIDS-defining malignancies)., Results: The unique clinical occurrence of HIV infection complicated by even four non-AIDS-defining cancers prompted us to re-discuss the epidemiology and the possible pathogenesis, the clinical presentation, and the differential diagnosis of this pathologic presentation., Conclusions: On the ground of our experience in this field, and the available literature evidences, we discuss how this clinical occurrence is acting on HIV infection presentation during the HAART era of the third millennium. These changes need broad scale studies, and promise relevant consequences on etiopathogenetic, prevention, therapeutic, and management aspects of HIV disease in the next future.