Learning from precedent: how the British Brexit experience shapes nationalist rhetoric outside the UK.

The liberal international order has recently come under increasing nationalist pressure, evidenced by a rise in nationalist demands to withdraw from international institutions. A growing literature examines the domestic economic, social, and political origins of this nationalist backlash against international institutions. However, less is known about the extent to which precedents of withdrawals of one country affect nationalist pressures for future withdrawals elsewhere. In this paper, we argue that initial withdrawal episodes provide new information about the feasibility and desirability of withdrawals to nationalist elites in other countries. Hence, we expect nationalists abroad to be either encouraged or deterred to follow a similar path - depending on the success of these precedents. We explore this argument in the context of the British withdrawal from the European Union (Brexit), which arguably marks the most significant withdrawal from an international institution to date. Based on a quantitative analyses of media reports in ten European countries, we show we show that nationalist parties in Europe increased or moderated the aggressiveness about their EU-related rhetoric as the ups and downs of the Brexit-drama unfolded. Our results suggest that precedents of nationalist withdrawals shape domestic politics well beyond the concerned countries themselves.

Epidemiology, therapy and outcome of hepatocellular carcinoma between 2010 and 2019 in Piedmont, Italy.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second leading cause of cancer deaths worldwide. It is often diagnosed at an advanced stage and therefore its prognosis remains poor with a low 5-year survival rate. HCC patients have increasingly complex and constantly changing characteristics, thus up-to-date and comprehensive data are fundamental. AIM: To analyze the epidemiology and main clinical characteristics of HCC patients in a referral center hospital in the northwest of Italy between 2010 and 2019. METHODS: In this retrospective study, we analyzed the clinical data of all consecutive patients with a new diagnosis of HCC recorded at "Santa Croce e Carle" Hospital in Cuneo (Italy) between 1 January 2010 and 31 December 2019. To highlight possible changes in HCC patterns over the 10-year period, we split the population into two 5-year groups, according to the diagnosis period (2010-2014 and 2015-2019). RESULTS: Of the 328 HCC patients who were included (M/F 255/73; mean age 68.9 ± 11.3 years), 154 in the first period, and 174 in the second. Hepatitis C virus infection was the most common HCC risk factor (41%, 135 patients). The alcoholic etiology rate was 18%, the hepatitis B virus infection etiology was 5%, and the non-viral/non-alcoholic etiology rate was 22%. The Child-Pugh score distribution of the patients was: class A 75%, class B 21% and class C 4%. The average Mayo end-stage liver disease score was 10.6 ± 3.7. A total of 55 patients (17%) were affected by portal vein thrombosis and 158 (48%) by portal hypertension. The average nodule size of the HCC was 4.6 ± 3.1 cm. A total of 204 patients (63%) had more than one nodule < 3, and 92% (305 patients) had a non-metastatic stage of the disease. The Barcelona Clinic Liver Cancer (BCLC) staging distribution of all patients was: 4% very early, 32% early, 23% intermediate, 34% advanced, and 7% terminal. Average survival rate was 1.6 ± 0.3 years. Only 20% of the patients underwent treatment. Age, presence of ascites, BCLC stage and therapy were predictors of a better prognosis (P < 0.01). A comparison of the two 5-year groups revealed a statistically significant difference only in global etiology (P < 0.05) and alpha-fetoprotein (AFP) levels (P < 0.01). CONCLUSION: In this study analyzing patients with a new diagnosis of HCC between 2010-2019, hepatitis C virus infection was the most common etiology. Most patients presented with an advanced stage disease and a poor prognosis. When comparing the two 5-year groups, we observed a statistically significant difference only in global etiology (P < 0.05) and AFP levels (P < 0.01).

Convergence and divergence in Kawasaki disease and multisystem inflammatory syndrome in children: results from the COVASAKI survey.

OBJECTIVES: To compare Kawasaki disease (KD) and multisystem inflammatory syndrome (MIS-C) in children. METHODS: Prospective collection of demographics, clinical and treatment data. Assessment of type 1 interferon (IFN) score, CXCL9, CXCL10, Interleukin (IL)18, IFNγ, IL6, IL1b at disease onset and at recovery. RESULTS: 87 patients (43 KD, 44 MIS-C) were included. Age was higher in MIS-C compared to KD group (mean 31±23 vs. 94±50 months, p<0.001). Extremities abnormalities (p=0.027), mucosal involvement (p<0.001), irritability (p<0.001), gallbladder hydrops (p=0.01) and lymphadenopathy (p=0.07) were more often recorded in KD. Neurological findings (p=0.002), gastrointestinal symptoms (p=0.013), respiratory involvement (p=0.019) and splenomegaly (p=0.026) were more frequently observed in MIS-C. Cardiac manifestations were higher in MIS-C (p<0.001), although coronary aneurisms were more frequent in KD (p=0.012). In the MIS-C group, the multiple linear regression analysis revealed that a higher IFN score at onset was related to myocardial disfunction (p<0.001), lymphadenopathy (p=<0.001) and need of ventilation (p=0.024). Both CXCL9 and CXCL10 were related to myocardial disfunction (p<0.001 and p=0.029). IL18 was positively associated to PICU admission (0.030) and ventilation (p=004) and negatively associated to lymphadenopathy (0.004). IFNγ values were related to neurological involvement and lymphadenopathy (p<0.001), IL1b to hearth involvement (0.006). A negative correlation has been observed between IL6 values, heart involvement (p=0.013) and PICU admission (p<0.001). CONCLUSIONS: The demographic and clinical differences between KD e MIS-C cohorts confirm previous reported data. The assessment of biomarkers levels at MIS-C onset could be useful to predict a more severe disease course and the development of cardiac complications.

Four-Component Recombinant Protein-Based Vaccine Effectiveness Against Serogroup B Meningococcal Disease in Italy.

Importance: Population-based data on the 4-component recombinant protein-based (4CMenB) vaccine effectiveness and reduction in incidence rate ratios (IRRs) are continuously needed to assess vaccine performance in the prevention of serogroup B invasive meningococcal disease (IMD). Objective: To assess the effectiveness and reduction in IRRs associated with the 4CMenB vaccine in the pediatric population in 6 regions in Italy. Design, Setting, and Participants: This retrospective cohort screening study and case-control study included data from children aged younger than 6 years in 6 highly populated Italian regions from January 1, 2006, to January 1, 2020. Participants included children younger than 6 years diagnosed with serogroup B IMD without predisposing factors. Data were collected from regional surveillance and vaccination registries and were analyzed from September 2021 to January 2022. Exposures: Routine 4CMenB vaccination, per regional vaccination programs. Main Outcomes and Measures: The main outcome was the effectiveness of the 4CMenB vaccine in the prevention of serogroup B IMD in the population of children aged younger than 6 years in 6 Italian regions. The percentages of vaccine effectiveness (VE) were obtained through the concomitant use of a screening method and a case-control study. Secondary outcomes were the comparison of effectiveness results obtained using the 2 different computational methods, the description of serogroup B IMD incidence rates, and reduction in IRRs before and after 4CMenB introduction, as a proxy for vaccine impact. Results: The cohort screening study included a resident population of 587 561 children younger than 6 years in 3 regions with similar surveillance protocols, and the matched-case controls study assessed a resident population of 1 080 620 children younger than 6 years in 6 regions. Analyses found that 4CMenB VE in fully immunized children was 94.9% (95% CI, 83.1%-98.4%) using the screening method and 91.7% (95% CI, 24.4%-98.6%) using the case-control method. Overall reduction in IRR was 50%, reaching 70% in regions with early-start vaccination schedules. The case-control method involving 6 highly-populated Italian regions included 26 cases and 52 controls and found an estimated VE of 92.4% (95% CI, 67.6%-97.9%) in children old enough for the first vaccine dose and 95.6% (95% CI, 71.7%-99.1%) in fully immunized children. VE was more than 90% for partially immunized children. Even in regions where the first dose was administered at age 2 months, almost 20% of unvaccinated cases were among infants too young to receive the first 4CMenB dose. Conclusions and Relevance: This screening cohort study and matched case-controls study found high effectiveness of 4CMenB vaccination and greater reduction in IRR for early-start vaccination schedules in preventing invasive serogroup B meningococcal disease. The high proportion of children too young to be vaccinated among unvaccinated cases suggests that starting the vaccination even earlier may prevent more cases. Screening and case-control methods provided similar estimates of VE: either method may be used in different study settings, but concomitant use can provide more robust estimates.

Comparison of two 2-D numerical models for snow avalanche simulation.

Snow avalanches are gravitational processes characterised by the rapid movement of a snow mass, threatening inhabitants and damaging infrastructure in mountain areas. Such phenomena are complex events, and for this reason, different numerical models have been developed to reproduce their dynamics over a given topography. In this study, we focus on the two-dimensional numerical simulation tools RAMMS::AVALANCHE and FLO-2D, aiming to compare their performance in predicting the deposition area of snow avalanches. We also aim to assess the employment of the FLO-2D simulation model, normally used in water flood or mud/debris flow simulations, in predicting the motion of snow avalanches. For this purpose, two well-documented avalanche events that occurred in the Province of Bolzano (IT) were analyzed (Knollgraben, Pichler Erschbaum avalanches). The deposition area of each case study was simulated with both models through back-analysis processes. The simulation results were evaluated primarily by comparing the simulated deposition area with the observed one through statistical indices. Subsequently, the maximum flow depth, velocity and deposition depth were also compared between the simulation results. The results showed that RAMMS::AVALANCHE generally reproduced the observed deposits better compared to FLO-2D simulation. FLO-2D provided suitable results for wet and dry snow avalanches after a meticulous calibration of the rheological parameters, since they are not those typically considered in avalanche rheology studies. The results showed that FLO-2D can be used to study the propagation of snow avalanches and could also be adopted by practitioners to define hazard areas, expanding its field of application.

The role of general practitioners in the EU: time to draw lessons from a too wide range?

Although the role played by general practitioners (GPs) is historically consolidated, continuous changes have been recently introduced in Europe because of the increasing multimorbidity and complexity of patients. Here we try to compare the roles played by GPs in the four major countries of Europe. In France GPs are self-employed medical doctors, and their remuneration consists of a payment scheme for the services provided. The weekly opening hours of French GPs are on average approximately 48. In Germany primary care is mainly provided by GPs and outpatient internists, and patients are free to choose the facility and the professional. German GPs are self-employed professionals mainly remunerated for each consultation, who work for an average of 50 opening hours per week. In Italy GPs are self-employed professionals mainly paid on per capita basis, who have their own list of patients and must guarantee a minimum number of clinical opening hours per week, which has often become the average number in practice. Accordingly, the patients' weekly access to Italian GPs' clinics is very limited. In Spain GPs are civil servants who work in multifunctional facilities with multi-professional teams. The weekly hours worked by Spanish GPs are 38 hours, as for any other civil servant. Trying to draw positive lessons from the comparison, the Spanish facilities seem to be the most advanced examples of horizontal-integrated organizations able to fulfil the expectations of a growing population of ageing people. The range of generalist professionals could be enlarged beyond GPs, as the German example shows.

Human herpes virus 8-negative effusion-based lymphoma in a patient with persistent serous effusions.

Diffuse large B-cell lymphoma is the most common histologic diagnosis among the aggressive lymphomas, accounting for 30% of all lymphomas. Human herpes virus 8-negative effusion-based lymphoma (HHV8-negative EBL) is a rare form of lymphoma, under recognized and still not well characterized in the literature. In contrast to primary effusion lymphoma (PEL), HHV8-negative EBL is characterized by malignant effusion in essentially serous body cavity with no detectable contiguous tumor masses and is no associated with human immunodeficiency virus and HHV8 infections. The presence of comorbid medical conditions can hide this type of lymphoma and made diagnosis more challenging. Here, we describe a rare case of an 82-year-old male suffering from peritoneal and pleural effusion and Hepatitis B virus related cirrhosis diagnosed with HHV8-negative EBL.

[The European mosaic of specialty training programmes in general practice.] / Il mosaico europeo dei programmi di formazione specialistica in medicina generale.

During last decades, general practice has been internationally recognized as an independent and essential medical specialization, with specific skills and tasks. This inevitably created the need to widely implement an organized specialty training programmes to allow future general practitioners to acquire all the skills and knowledge necessary to work within the world of primary care. However, this process has not led to homogeneous applications in European countries, mainly due to the profound and structural differences of each national health system. In our contribution we have tried to make a synoptic comparison of specialty training programmes in general practice in the main European countries (England, Italy, Spain, France and Germany).

Wunderlich syndrome, an unexpected urological complication in a patient with coronavirus disease 2019 (COVID-19): A case report.

We describe the first case of Wunderlich syndrome as a hemorrhagic complication in a patient with severe acute respiratory syndrome coronavirus 2 infection and acute respiratory distress syndrome. The possible underlying pathophysiological mechanisms have been extensively discussed. Emergency management included selective angioembolization of the upper polar arterial branches of the left kidney and discontinuation of thromboprophylaxis. The patient was discharged after 18 days. No other localizations or local recurrence of bleeding occurred during the hospitalization. Our report suggests a broad spectrum of clinical manifestations in patients with coronavirus disease 2019. As observed in our clinical case, in addition to thrombotic complications, bleeding is a significant cause of morbidity in coronavirus disease 2019 patients. Further studies should determine whether these urological bleeding sequelae are a direct manifestation of the infection or an indirect effect of thromboprophylaxis.

[The European enigma of pharmaceutical pricing: still solvable?] / L'enigma europeo dei prezzi dei farmaci: è ancora risolvibile?

The attempt to regulate pharmaceutical pricing has a long tradition in Western European countries and various solutions have been experienced in recent decades to try to control public pharmaceutical spending. Nonetheless, drug prices have become increasingly out of control and unsustainable even in the richest European countries. In a situation of "market failure" such as the pharmaceutical one, in fact, two totally opposite needs collide: the main objective of the health authorities of universal access to essential drugs, versus the aim of the pharmaceutical industry to maximize turnover in order to guarantee high returns on investments. We are therefore convinced that the growing threat of drug prices that are too high must be solved with drastic solutions. The goal of this contribution is therefore to first summarize the current situation of pharmaceutical pricing in Western European countries, then debate the main issues currently discussed and finally propose a radically alternative scenario that moves from prices to the budget.

Boswellia resin extract and propolis derived polyphenols in patients with type III chronic prostatitis/chronic pelvic pain syndrome: An Italian prospective multicenter study.

Objective: To assess the efficacy and safety of a treatment regimen based on rectal administration of Boswellia resin extract and propolis derived polyphenols in patients with type IIIa and type IIIb chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS). Methods: Patients with type IIIa and type IIIb CP/CPPS received one rectal suppository a day for 15 days per month for 3 consecutive months. Participants were evaluated with National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), the International Prostate Symptom Scores (IPSS), International Index of Erectile Function (IIEF), four-glass test, uroflowmetry, and prostate-specific antigen assessments at baseline and at Week 4, and Week 12. Primary endpoints were improvement in pain domain of NIH-CPSI and improvement of NIH-CPSI total score. Secondary outcomes included improvement of micturition and quality of life (QoL) domains of NIH-CPSI questionnaire. Results: A total of 61 males were enrolled. No adverse events were reported. Significant improvements from baseline to Day 30 were reported for NIH-CPSI total score (mean difference: -9.2; p<0.01), NIH-CPSI pain domain (mean difference: -5.5; p<0.01), NIH-CPSI micturition domain, NIH-CPSI QoL domain, and IPSS total score (mean difference: -5.6; p<0.01). No significant changes from baseline in terms of IIEF score or maximum flow rate were observed. At final follow-up (Day 90), further significant improvements in terms of NIH-CPSI total score (mean difference: -12.2; p<0.01), NIH-CPSI pain domain (mean difference: -6.6; p<0.01), NIH-CPSI micturition domain, NIH-CPSI QoL domain, and IPSS total score were reported. Conclusion: Rectal administration of Boswellia resin extract and propolis derived polyphenols is well tolerated and delivers a significant symptomatic improvement in most patients with type IIIa and type IIIb CP/CPPS.