[Appendix ... it's not just appendicitis: neuroendocrine tumors.] / L'appendice... non è solo appendicite: i tumori neuroendocrini.

Well-differentiated neuroendocrine tumors of the appendix (NETs) are rare in pediatric and adolescent age groups. However, they are the most common gastrointestinal epithelial tumor in this age group and the most common malignancy of the appendix in the general population. The classification of these tumors considers factors such as the proliferation index, size of the neoplasm, and the presence of perineural and/or lymphovascular invasion, which can contribute to distant metastases. Preoperative diagnosis is challenging, except in cases where patients exhibit symptoms of carcinoid syndrome or signs of metastatic disease, which are uncommon in pediatric and adolescent patients. For tumors smaller than 1 cm, appendectomy is usually curative, while larger tumors or those at risk of spreading may require right hemicolectomy with lymphadenectomy. We present a case of an adolescent with NET and provide a literature review on the diagnostic and therapeutic approaches that should be considered for this relatively rare condition.Key words. Adolescent age, appendix, neuroendocrine tumors, pediatric age.

Effectiveness and safety of filgotinib in rheumatoid arthritis: a real-life multicentre experience.

OBJECTIVES: We investigated the effectiveness and safety of filgotinib in a real-life multicentre cohort of rheumatoid arthritis (RA) patients. METHODS: RA patients were evaluated at baseline and after 12 and 24 weeks and were stratified based on previous treatments as biologic disease-modifying anti-rheumatic drug (bDMARD)-naive and bDMARD-insufficient responders (IR). Concomitant usage of methotrexate (MTX) and oral glucocorticoids (GC) was recorded. At each timepoint we recorded disease activity, laboratory parameters and adverse events. RESULTS: 126 patients were enrolled. 15.8% were bDMARD-naive (G0), while 84% were bDMARD-IR (G1). In G0, 45% of patients were in monotherapy (G2) and 55% were taken MTX (G3). In G1, 50% of patients were in monotherapy (G4) and 50% used MTX (G5).A significant reduction in all parameters at 12 weeks was observed; in the extension to 24 weeks the significant reduction was maintained for patient global assessment (PGA), examiner global assessment (EGA), visual analogue scale (VAS) pain, VAS fatigue, disease activity score (DAS)28- C-reactive protein (CRP) and CRP values. Filgotinib in monotherapy showed better outcomes in bDMARD-naive patients, with significant differences for patient reported outcomes (PROs) and DAS28-CRP. At 12 weeks, low disease activity (LDA) and remission were achieved in a percentage of 37.2 % and 10.7 % by simplified disease activity index (SDAI), 42.6 % and 5.7 % by clinical disease activity index (CDAI), 26.8 % and 25.2 % by DAS28-CRP, respectively. A significant decrease in steroid dose was evidenced in all patients. We observed a major adverse cardiovascular event in one patient and an increase in transaminase in another. No infections from Herpes Zoster were reported. CONCLUSIONS: Our real-world data confirm the effectiveness and safety of filgotinib in the management of RA, especially in bDMARD-naive patients.

Other-regarding preferences in pro-environmental behaviours: Empirical analysis and policy implications of organic and local food products purchasing in Italy.

This paper investigates the link between organic and local food products purchasing as pro-environmental behaviours, and "other-regarding preferences", such as altruism, intrinsic motivation and self-image, which is measured through individuals' environmental concerns, volunteering, participation in ecological associations and pro-social behaviours. Using the Italian data from the Multipurpose survey on households "Aspects of daily life" conducted in 2019, and bivariate probit models, this paper shows that environmental egoistic and altruistic concerns, volunteering in formal organizations and participation in ecological associations are positively correlated with the purchase of more organic and local food products. Higher pro-social behaviours correlate positively with the purchase of more local products and negatively with the purchase of more organic products. Furthermore, higher education and better household economic conditions are strongly correlated with the purchase of more organic products, while participation in cultural activities is positively associated with the purchase of more organic and local food products.

Microchimerism in multiple sclerosis: The association between sex of offspring and MRI features in women with multiple sclerosis.

Aims: During pregnancy, fetal cells can migrate to the mother via blood circulation. A percentage of these cells survive in maternal tissues for decades generating a population of fetal microchimeric cells (fMCs), whose biological role is unclear. The aim of this study was to investigate the association between the sex of offspring, an indirect marker of fMCs, and magnetic resonance imaging (MRI) features in women with multiple sclerosis (MS). Methods: We recruited 26 nulliparous MS patients (NPp), 20 patients with at least one male son (XYp), and 8 patients with only daughters (XXp). Each patient underwent brain MR scan to acquire 3D-T2w FLAIR FatSat and 3D-T1w FSPGR/TFE. Lesion Segmentation Tool (LST) and FreeSurfer were used to obtain quantitative data from MRI. Additional data were collected using medical records. Multiple regression models were applied to evaluate the association between sex of offspring and MS data. Results: Comparing NPp and XXp, we found that NPp had larger 4th ventricle volume (2.02 ± 0.59 vs. 1.70 ± 0.41; p = 0.022), smaller left entorhinal volume (0.55 ± 0.17 vs. 0.68 ± 0.25; p = 0.028), and lower thickness in the following cortical areas: left paracentral (2.34 ± 0.16 vs. 2.39 ± 0.17; p = 0.043), left precuneus (2.27 ± 0.11 vs. 2.34 ± 0.16; p = 0.046), right lateral occipital (2.14 ± 0.11 vs. 2.25 ± 0.08; p = 0.006). NPp also had lower thickness in left paracentral cortex (2.34 ± 0.16 vs. 2.46 ± 0.17; p = 0.004), left precalcarine cortex (1.64 ± 0.14 vs. 1.72 ± 0.12; p = 0.041), and right paracentral cortex (2.34 ± 0.17 vs. 2.42 ± 0.14; p = 0.015) when compared to XYp. Comparing XYp and XXp, we found that XYp had higher thickness in left cuneus (1.80 ± 0.14 vs. 1.93 ± 0.10; p = 0.042) and left pericalcarine areas (1.59 ± 0.19 vs. 1.72 ± 0.12; p = 0.032) and lower thickness in right lateral occipital cortex (2.25 ± 0.08 vs. 2.18 ± 0.13; p = 0.027). Discussion: Our findings suggested an association between the sex of offspring and brain atrophy. Considering the sex of offspring as an indirect marker of fMCs, we speculated that fMCs could accumulate in different brain areas modulating MS neuropathological processes.

Use of 18F-fluorodeoxyglucose positron emission tomography-computed tomography in patients affected by polymyalgia rheumatica and persistent increase of acute phase reactants.

Polymyalgia rheumatica (PMR) is an inflammatory disease affecting older adults characterized by aching pain and morning stiffness of the shoulder and pelvic girdles. Moreover, PMR can be associated with giant cell arteritis (GCA). Generally, PMR is highly responsive to steroids, reaching complete remission in the majority of cases. However, the possibility of occult diseases, including extra-cranial GCA, should be excluded. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is able to detect the presence of peri-/articular or vascular inflammation, which may be both present in PMR, thus representing a useful diagnostic tool, mainly in presence of extra-cranial GCA. We retrospectively evaluated all consecutive patients who received the diagnosis of PMR in our rheumatology clinic, classified according to the 2012 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria, in the period between April 2020 and May 2022. Among this case series, we selected the patients who underwent 18F-FDG-positron emission tomography (PET) because of the persistent increase of acute phase reactants (APR) besides the steroid therapy. Eighty patients were diagnosed with PMR. Nine out of them also presented arthritis of the wrists during the follow-up, whereas none showed signs of cranial GCA at the diagnosis. Seventeen out of eighty subjects (mean age 71.5 ± 7.5 years; M/F 2/15) presented persistent increase of erythrocyte sedimentation rate (mean ESR 44.2 ± 20.8 mm/h) and/or C-reactive protein (mean CRP 25.1 ± 17 mg/l), thus they underwent total body 18F-FDG-PET/CT. Large vessel 18F-FDG uptake indicating an occult GCA was found in 5/17 (29.4%) cases. Twelve out of seventeen (70.6%) patients showed persistence of peri-/articular inflammation, suggesting a scarce control of PMR or the presence of chronic arthritis. Finally, in 2 cases, other inflammatory disorders were found, namely an acute thyroiditis and a hip prosthesis occult infection. 18F-FDG-PET/CT in PMR patients with persistent increase of APR is a useful diagnostic technique in order to detect occult GCA, persistence of active PMR or other misdiagnosed inflammatory diseases.

Systemic Sclerosis and Idiopathic Portal Hypertension: Report of a Case and Review of the Literature.

The presence of liver involvement in systemic sclerosis (SSc) is considered atypical, besides the possible coexistence of other autoimmune hepatic disorders. However, the occurrence of portal hypertension and, more specifically, of the syndromes called idiopathic portal hypertension (IPH) and regenerative nodular hyperplasia (RNH) have been anecdotally reported in the literature for SSc patients. We described a case of SSc woman complicated by IPH; moreover, we reviewed the literature on the topic. A 61-year-old female SSc patient was admitted to our hospital because of the onset of ascites. SSc, as a limited skin subset of disease with anticentromere antibodies, was diagnosed 11 years previously, with no significant visceral involvement. We excluded possible causes of portal hypertension, namely chronic infections, autoimmune hepatic diseases, neoplasia, thrombosis of portal vein, and Budd-Chiari syndrome. Finally, IPH was diagnosed. A review of the literature identified a number of case reports or case series that described IPH in the course of SSc. No specific SSc pattern linked to IPH emerged, even though reports from the literature often described the limited skin subset. Coexistence of prothrombotic states and overlap with other hepatic diseases could facilitate IPH onset. Besides being a rare condition, the onset of IPH in SSc patients is an occurrence that should be taken into account.

The Impaired Elasticity of Large Arteries in Systemic Sclerosis Patients.

(1) Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by endothelial dysfunction and fibrosis of skin and visceral organs. In the last decade, attention has been focused on the macrovascular involvement of the disease. In particular, the observation of increased arterial stiffness represented an interesting aspect of the disease, as predictor of cardiovascular risk. (2) Methods: We recruited 60 SSc patients (52 ± 12 years old, 90% females) and 150 age/sex-matched healthy controls in order to evaluate both intima-media thickness of the right common carotid artery and arterial stiffness using the B-mode echography and the SphygmoCor system® tonometer. (3) Results: The carotid-femoral pulse wave velocity (PWV) was higher in SSc patients than in controls (8.6 ± 1.7 vs. 7.8 ± 1.5 m/s; p < 0.001), as was the carotid-radial PWV (7.8 ± 1.1 vs. 6.7 ± 1.4 m/s; p < 0.001). The intima-media thickness was higher in SSc than in controls (654 ± 108 vs. 602 ± 118 µm; p = 0.004). The other parameters measured at carotid (radial strain, Young's modulus, compliance and distensibility) all indicated that arterial stiffness in tension was more pronounced in SSc. Of interest, the direct correlation between PWV and age corresponded closely in SSc. Moreover, a significant difference between SSc and controls as regards the carotid parameters was evident in younger subjects. (4) Conclusions: SSc patients showed an increased arterial stiffness compared to healthy controls. In particular, an SSc-related pathologic effect was suggested by the more pronounced increase in PWV with age and lower values of carotid elasticity in younger SSc patients than in age-matched controls.

Clinical Onset and Multiple Sclerosis Relapse after SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with several neurological disorders including headache, facial palsy, encephalitis, stroke, demyelinating disorders. The present report will discuss cases of multiple sclerosis (MS) onset and relapse both beginning early after SARS-CoV-2 infection. In both cases, magnetic resonance imaging (MRI) showed widespread bilateral subcortical and periventricular active lesions. Serum IgG against SARS-CoV-2 Spike antigens confirmed seroconversion with titers that are considered not definitely protective against possible reinfection. We hypothesize that SARS-CoV-2 infection, as previously reported for other viruses, could drive an active inflammatory response that can contribute either to the onset of MS or its relapse. The presented data further support the importance of vaccination in individuals with MS.

The Role of Nutritional Lifestyle and Physical Activity in Multiple Sclerosis Pathogenesis and Management: A Narrative Review.

Studies on the role of nutritional factors and physical activity (PA) in the pathogenesis of multiple sclerosis (MS) go back a long time. Despite the intrinsic difficulty of studying their positive or negative role in MS, the interest of researchers on these topics increased during the last few decades, since the role of diet has been investigated with the perspective of the association with disease-modifying drugs (DMD). The association of DMD, diets, and PA might have an additive effect in modifying disease severity. Among the various diets investigated (low-carbohydrate, gluten-free, Mediterranean, low-fat, fasting-mimicking, and Western diets) only low-carbohydrate, Mediterranean, and fast-mimicking diets have shown both in animal models and in humans a positive effect on MS course and in patient-reported outcomes (PROs). However, the Mediterranean diet is easier to be maintained compared to fast-mimicking and low-carbohydrate diets, which may lead to detrimental side effects requiring careful clinical monitoring. Conversely, the Western diet, which is characterized by a high intake of highly saturated fats and carbohydrates, may lead to the activation of pro-inflammatory immune pathways and is therefore not recommended. PA showed a positive effect both in animal models as well as on disease course and PROs in humans. Training with combined exercises is considered the more effective approach.

Role of CT angiography in detecting acute pulmonary embolism associated with COVID-19 pneumonia.

PURPOSE: Recently coronavirus disease (COVID-19) caused a global pandemic, characterized by acute respiratory distress syndrome (ARDS). The aim of our study was to detect pulmonary embolism (PE) in patients with severe form of COVID-19 infection using pulmonary CT angiography, and its associations with clinical and laboratory parameters. METHODS: From March to December 2020, we performed a prospective monocentric study collecting data from 374 consecutive patients with confirmed SARS-CoV-2 infection, using real-time reverse-transcriptase polymerase-chain-reaction (rRT-PCR) assay of nasopharyngeal swab specimens. We subsequently selected patients with at least two of the following inclusion criteria: (1) severe acute respiratory symptoms (such as dyspnea, persistent cough, fever > 37.5 °C, fatigue, etc.); (2) arterial oxygen saturation ≤ 93% at rest; (3) elevated D-dimer (≥ 500 ng/mL) and C-reactive protein levels (≥ 0.50 mg/dL); and (4) presence of comorbidities. A total of 63/374 (17%) patients met the inclusion criteria and underwent CT angiography during intravenous injection of iodinated contrast agent (Iomeprol 400 mgI/mL). Statistical analysis was performed using Wilcoxon rank-sum and Chi-square tests. RESULTS: About, 26/60 patients (40%) were found positive for PE at chest CT angiography. In these patients, D-dimer and CRP values were significantly higher, while a reduction in SaO2 < 93% was more common than in patients without PE (P < 0.001). Median time between illness onset and CT scan was significantly longer (15 days; P < 0.001) in patients with PE. These were more likely to be admitted to the Intensive Care Unit (19/26 vs. 11/34 patients; P < 0.001) and required mechanical ventilation more frequently than those without PE (15/26 patients vs. 9/34 patients; P < 0.001). Vascular enlargement was significantly more frequent in patients with PE than in those without (P = 0.041). CONCLUSIONS: Our results pointed out that patients affected by severe clinical features of COVID-19 associated with comorbidities and significant increase of D-dimer levels developed acute mono- or bi-lateral pulmonary embolism in 40% of cases. Therefore, the use of CT angiography rather than non-contrast CT should be considered in these patients, allowing a better evaluation, that can help the management and improve the outcomes.

[Hepatic adenoma with high phlogosis indices: what relationship? Description of a pediatric clinical case.] / Adenoma epatico con alti indici di flogosi: quale relazione? Descrizione di un caso clinico pediatrico.

Hepatocellular adenoma is a benign neoplasm that accounts for 2-4% of pediatric liver tumors. The inflammatory variant of the adenoma can be expressed at the clinical level only with the evidence of persistent elevation of the inflammatory indices, since the hepatic mass is itself silent unless there are complications. The main complications relate to the bleeding risk, the chronic inflammatory state and the low risk of malignant evolution. The predictive marker of hemorrhagic complication is the size and in particular if the diameter is greater than 5 cm surgical treatment is recommended. We describe the case of a 9-year-old girl with a hepatocellular adenoma in the telangiectatic inflammatory variant, with a clinical presentation of loss of appetite and high inflammatory indices.

Cancer mortality rates and spillover effects among different areas: A case study in Campania (southern Italy).

The present study analyses the spatial distribution of cancer mortality rates in Campania (an Italian region with the highest population density), in which residents in several areas are exposed to major environmental health hazards. The paper has the methodological aims of verifying the existence, or otherwise, of a spatial correlation between mortality from different types of cancer and the occurrence of some specific area characteristics, using both Bayesian statistics and spatial econometrics. We show that the use of the Spatial Empirical Bayes Smoothed Rate, instead of the more commonly used Raw Rate, allows a more comprehensive analysis of the mortality rate, highlighting the existence of different cluster sizes throughout the region, according to the type of cancer mortality rate analysed. By using a Spatial Durbin model we verify that cancer mortality rates are related to the environmental characteristics of specific areas with spatial spillover effects. Our results validate the hypothesis that living along the coast by Mt Vesuvius and, to a lesser extent, along the Domitio-Flegreo coast NW of Naples and in more urbanised municipalities, increases the risk of dying of cancer. By contrast, living in less urbanised municipalities, with the presence of natural and historical attractions, has a positive effect on the residents' health, reducing their risk of disease. In both cases significant spillover effects (negative and positive) are found in municipalities close to the areas in question. Despite a number of reasonable limitations, our findings may provide useful information support for policy makers to foster knowledge, awareness and informed participation of citizens.

Knowledge assessment instrument on basic support of hip fractures in the elderly.

OBJECTIVE: To validate an instrument to determine the graduate students' knowledge level of health care on the basic support of life procedures, risk factors, damage and disorders in elderly patients with hip fractures. METHOD: A group of experts was asked to analyze the instrument in two steps. Firstly, the procedure was done subjectively and according to objective analysis using the Likert scale proposed by the Delphi method. After adjustment according to the suggestions, the version of the instrument was applied to 179 undergraduate students in the health area. RESULT: The instrument has achieved in its entirety and in parts (risk factors), the minimum criteria established for the Cronbach's alpha (i.e., ≥0.70). There was no change in the Cronbach's alpha (0.551) for the maintenance of initial items of the instrument, as well as the deletion of seven assessment items. CONCLUSION: The instrument developed has sufficient internal validity to determine the level of knowledge of undergraduate students in the health area on basic life support, damage, injuries and risk factors in elderly patients with hip fractures from falls. Level of Evidence III, Diagnostic Study.

Knowledge assessment instrument on basic support of hip fractures in the elderly

OBJECTIVE: To validate an instrument to determine the graduate students' knowledge level of health care on the basic support of life procedures, risk factors, damage and disorders in elderly patients with hip fractures. METHOD: A group of experts was asked to analyze the instrument in two steps. Firstly, the procedure was done subjectively and according to objective analysis using the Likert scale proposed by the Delphi method. After adjustment according to the suggestions, the version of the instrument was applied to 179 undergraduate students in the health area. RESULT: The instrument has achieved in its entirety and in parts (risk factors), the minimum criteria established for the Cronbach's alpha (i.e., ≥0.70). There was no change in the Cronbach's alpha (0.551) for the maintenance of initial items of the instrument, as well as the deletion of seven assessment items. CONCLUSION: The instrument developed has sufficient internal validity to determine the level of knowledge of undergraduate students in the health area on basic life support, damage, injuries and risk factors in elderly patients with hip fractures from falls. Level of Evidence III, Diagnostic Study,

Esophagogastric metaplasia relates to nodal metastases in adenocarcinoma of esophagus and cardia.

BACKGROUND: Immunohistochemical profiles of esophageal and cardia adenocarcinoma differ according to the presence or absence of Barrett's epithelium (BIM) and gastric intestinal metaplasia (GIM) in the fundus and antrum. Different lymphatic spreading has been demonstrated in esophageal adenocarcinoma. We investigated the correlation among the presence or absence of intestinal metaplasia in the esophagus and stomach and lymphatic metastases in patients who underwent radical surgery for esophageal and cardia adenocarcinoma. METHODS: The mucosa surrounding the adenocarcinoma and the gastric mucosa were analyzed. The BIM+ patients underwent subtotal esophagectomy and gastric pull up, and the BIM- patients underwent esophagectomy at the azygos vein, total gastrectomy, and esophagojejunostomy. The radical thoracic (station numbers 2, 3, 4R, 7, 8, and 9) and abdominal (station numbers 15 through 20) lymphadenectomy was identical in both procedures except for the greater curvature. RESULTS: One hundred ninety-four consecutive patients were collected in three major groups: BIM+/GIM-, 52 patients (26.8%); BIM-/GIM-, 90 patients (46.4%); BIM-/GIM+, 50 patients (25.8%). Two patients (1%) were BIM+/GIM+. A total of 6,010 lymph nodes were resected: 1,515 were recovered in BIM+, 1,587 in BIM-/GIM+, and 2,908 in BIM-/GIM- patients. The percentage of patients with pN+ stations 8 and 9 was higher in BIM+ (p=0.001), and the percentage of patients with pN+ perigastric stations was higher in BIM- (p=0.001). The BIM-/GIM- patients had a number of abdominal metastatic lymph nodes higher than did the BIM-/GIM+ patients (p=0.0001). CONCLUSIONS: According to the presence or absence of BIM and GIM in the esophagus and cardia, adenocarcinoma correspond to three different patterns of lymphatic metastasization, which may reflect different biologic and carcinogenetic pathways.

Juxta-anastomotic stenosis of native arteriovenous fistulas: surgical treatment versus percutaneous transluminal angioplasty.

PURPOSE: Juxta-anastomotic stenosis (JAS) is a complication of arteriovenous fistulas (AVFs). Both surgical revision (SR) and percutaneous transluminal angioplasty (PTA) may correct JAS. In this study we compare the results for SR treatment versus PTA. METHODS: From January 2005 until December 2008, 66 PTA and 68 SR were performed in 43 and 57 uremic pts with JAS of the native AVF, respectively. Efficacy of SR and PTA was evaluated measuring brachial arterial flow (BAF) by CDU. The Kaplan-Meier table of primary and assisted primary patency was analyzed. RESULTS: PTA was attempted in 50 patients. PTA failed in 7 patients and they were switched to SR. In 43 pts, PTA produced a favorable effect, with a mean increase of 99 ± 70% (p<0.001) in blood flow. Restenosis occurred in 17 pts: 2 were treated by SR and 15 by PTA. Restenosis occurred again in 6/15 pts: after second restenosis, 5/6 pts received a third PTA with stenting, 1 patient underwent SR. The failure of access occurred after 12-17 months in 3 pts. In 57/57 JAS treated by SR, a new well-functioning fistula was created upstream of the stenosis, with a mean increase of 102 ± 71% in blood flow (p<0.001). Restenosis occurred in 15 pts: 9 were treated by SR and 6 by PTA. Access failure occurred after 3-36 months in 9 pts. The Kaplan-Meier table showed a better primary patency for SR (p<0.05) without difference in assisted primary patency. CONCLUSIONS: SR showed a better primary patency then PTA, confirming the trend to stenosis relapse after PTA. So, as PTA does not exclude a later correction of the JAS, the similar assisted patency suggests to perform a PTA first, reserving SR for after its failure.