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Real-world data on the effectiveness and safety of tildrakizumab, an interleukin 23p19 inhibitor, in Switzerland is limited. The objectives of this analysis were to assess the effectiveness and safety of tildrakizumab in patients with moderate-to-severe plaque psoriasis in Switzerland. Twenty-eight adults from the Swiss Dermatology Network for Targeted Therapies registry (SDNTT), who were on tildrakizumab treatment and had at least 3 months' follow-up, were enrolled in this prospective, multicentre study. No missing data imputation was performed. The median Psoriasis Area and Severity Index (PASI) decreased from 9.5 at baseline to 2.1 and 0.3 (both p < 0.001) after 3 and 18 months, respectively, of tildrakizumab treatment. After 3 months, 76.9%/30.8% patients reached an absolute PASI <  3/ < 1. These rates increased to 85.7%/57.1% after 18 months of treatment. The proportions of patients achieving PASI 90/100 responses were 47.8%/30.4% at month 6 and 42.9%/14.3% at month 18. A significant improvement in quality of life up to 18 months of follow-up was observed as measured by the Dermatology Life Quality Index. There were no treatment discontinuations due to adverse events. This real-world registry provides robust evidence supporting the long-term effectiveness and favourable safety profile of tildrakizumab in treating patients with moderate-to-severe psoriasis.

Background: The increased proliferation of Demodex mites in the pilosebaceous unit can be the cause of rosacea flare-ups on the face. Signs and symptoms of the scalp (e.g., itching, dandruff) have sometimes been reported in patients with papulopustular rosacea of face; they may be due to a proliferation of Demodex mites on the scalp., Methods: To study the Demodex mites count, a standardized skin surface biopsy was performed on the cheek and on the scalp. Microscopic examination and molecular identification of Demodex were performed. Pearson's χ 2 Test or Fisher's Exact Test were used to test for any association between categorical variables and outcome., Results: Patients affected by papulopustular rosacea had a greater frequency of Demodex-positive standardized skin surface biopsy than controls at the scalp (35.0% vs. 0%, P=0.033), at the face and/or at the scalp (50% vs. 10%, P=0.032). Demodex positive patients with a Demodex-positive face sample were more frequently found to have a Demodex-positive scalp sample (P=0.035). The predominant species was found to be Demodex folliculorum (92.6% of samples); the species Demodex brevis was identified only in 7.4% of samples., Conclusions: Demodex folliculorum is more frequently found on the scalp and face of patients with rosacea than controls, even though it is not statistically associated with scalp symptoms. The scalp may be a reservoir area for Demodex mites which could migrate on the face again after an acaricidal treatment.

Herpes zoster (HZ) is a condition caused by the reactivation of varicella-zoster virus (VZV), the virus responsible for chickepox, which is the clinical manifestation of the primary infection. Congenital or acquired immune system deficiencies, as well as the physiological decline in immune response occurring in the elderly, known as immune senescence, can allow VZV reactivation and, consequently, HZ. One out of 3 people develops HZ during their lifetime. Moreover, thirty percent of the affected subjects develop post-herpetic neuralgia, the most frequent complication after HZ skin rash. Patients with dermatological conditions characterized by alteration of the immune system, such as systemic lupus erythematosus, psoriasis, atopic dermatitis, bullous diseases, and cutaneous lymphomas, are at higher risk of developing HZ and post-herpetic neuralgia, even when their disease is in remission. In the present work, we described the currently available vaccinations against HZ and provided recommendations for the vaccination against HZ in patients with dermatological diseases.

Background: Trypanophobia or "needle phobia" represents a potential hindrance to the effective management of chronic diseases whenever an injectable therapy might be required, especially in case of frequent administrations. Psoriasis, a chronic dermatologic disease, can be effectively treated with biologic drugs administered subcutaneously. Thankfully, anti-IL-23 drugs require few administrations per year and are available in prefilled pens that hide the needle, thus representing a convenient option in patients with trypanophobia., Methods: An observational multicentric study was conducted on patients with moderate-to-severe psoriasis who were treated with 75 mg × 2 risankizumab prefilled syringe therapy for more than 6 months and reported a loss of efficacy measured by the Psoriasis Area and Severity Index (PASI) from PASI 90 to PASI 75 attributed to a reduction of adherence due to trypanophobia. The patients were switched to 1 prefilled pen of risankizumab 150 mg and asked to fill out the Self-Injection Assessment Questionnaire (SIAQ) before and after the injection at week 0 and at the following administration after 12 weeks. Subjects scored each item of the SIAQ on a 5-point scale, scores were later transformed from 0 (worst experience) to 10 (best experience)., Results: Twenty-two patients were enrolled. The mean SIAQ predose domain scores were 5.5 for feelings about injection, 6.2 for self-confidence, and 6.4 for satisfaction with self-injection. After dose scores were higher (> 8.5) for each of the six domains at Week 0 and even higher after 12 weeks (> 9.0)., Conclusions: User-friendly devices, such as prefilled pens, and a lower number of injections improved patient satisfaction in a group of patients with psoriasis on treatment with biologic drugs. We believe that treatment adherence could be positively influenced by such changes in the way of administration of a biologic treatment., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Background: Severe and/or symptomatic hypocalcemia due to hypoparathyroidism is the main contraindication for discharge in patients who have undergone thyroid surgery. Hypomagnesemia may contribute to the onset of hypoparathyroidism and is frequently observed after thyroid surgery in hypocalcemic patients. The impact of prophylactic and postoperative Magnesium supplementation on postoperative hypocalcemia and hypomagnesemia was prospectively evaluated by comparing patients undergoing prophylactic supplementation to a control group of patients who had only received magnesium after evidence of postoperative hypomagnesemia., Methods: One hundred and twenty patients who underwent a total thyroidectomy participated in the study. Seventy-three patients were included in the study group, 47 in the control group. Prior to surgery, patients in the study group were given magnesium orally for 5 days; postoperatively, calcium and magnesium was administered to all patients who displayed hypocalcemia and hypomagnesemia., Results: Postoperative biochemical hypocalcemia (serum calcium <8.5 mg/dL, regardless of its clinical severity) was found in 60 patients (50%) on D1 and in 58 patients (48.4%) on D2. Among hypocalcemic patients, hypomagnesemia was recorded in 29 at D1 (48%), and in 46 at D2 (79%). A significant positive correlation was found between magnesium, calcium, and parathyroid hormone in the first two postoperative days, while a significant inverse correlation occurred for these same parameters and length of hospital stay (P<0.001). One hundred and five patients (87.5%) were discharged as expected on the second postoperative day (65 in the study group, 40 in the control group, P=0.724), whereas 15 patients (12.5%) required prolonged hospitalization (eight in the study group, seven in the control group, P=0.721). The Study group only showed significantly higher magnesium levels on the first postoperative day (P=0.03)., Conclusions: Although magnesium and calcium levels showed the same trend after thyroidectomy, neither Magnesium prophylaxis nor Magnesium treatment influenced the clinical course of postoperative hypocalcemia.

Introduction: Genital involvement is observed in approximately 60% of patients with psoriasis, presenting clinicians with formidable challenges in treatment. While new biologic drugs have emerged as safe and effective options for managing psoriasis, their efficacy in challenging-to-treat areas remains inadequately explored. Intriguingly, studies have shown that interleukin (IL)-17 inhibitors exhibit effectiveness in addressing genital psoriasis., Objectives: We aimed to determine the effectiveness profile of bimekizumab in patients affected by moderate-to-severe plaque psoriasis with involvement of genitalia., Methods: Bimekizumab, a dual inhibitor of both IL-17A and IL-17F, was the focus of our 16-week study, demonstrating highly favorable outcomes for patients with genital psoriasis. The effectiveness of bimekizumab was evaluated in terms of improvement in Static Physician Global Assessment of Genitalia (sPGA-G) and Psoriasis Area and Severity Index., Results: Sixty-five adult patients were enrolled. Remarkably, 98.4% of our participants achieved a clear sPGA-G score (s-PGA-g = 0) within 16 weeks. Moreover, consistent improvements were observed in Psoriasis Area and Severity Index scores, accompanied by a significant reduction in the mean Dermatology Life Quality Index, signifying enhanced quality of life. Notably, none of the patients reported a severe impairment in their quality of life after 16 weeks of treatment. In our cohort of 65 patients, subgroup analyses unveiled that the effectiveness of bimekizumab remained unaffected by prior exposure to other biologics or by obesity., Conclusions: Our initial findings suggest that bimekizumab may serve as a valuable treatment option for genital psoriasis. Nevertheless, further research with larger sample sizes and longer-term follow-up is imperative to conclusively validate these results.

Background: In assisted reproductive cycles (ART), the fine balance of controlling corpus luteum function is severely disrupted. To challenge this iatrogenic deficiency, clinicians aim to provide exogenous support. Several reviews have investigated progesterone route of administration, dosage and timing., Methods: A survey about luteal phase support (LPS) after ovarian stimulation was conducted among doctors in charge in Italian II-III level ART centers., Results: With regards to the general approach to LPS, 87.9% doctors declare to diversify the approach; the reasons for diversifying (69.7%) were based on the type of cycle. For all the most important administration routes (vaginal, intramuscular, subcutaneous) it appears that in frozen cycles there is a shift towards higher dosages. The 90.9% of the centers use vaginal progesterone, and when a combined approach is required, in 72.7% of cases vaginal administration is combined with injective route of administration. When Italian doctors were asked about the beginning and duration of LPS, 96% of the centers start the day of the pickup or the day after, while 80% of the centers continue LPS until week 8-12. The rate of participation of the centers confirms the low perceived importance of LPS among Italian ART centers, while may be considered quite surprising the relatively higher percentage of centers that measures P level. Tailorization to women's needs is the new objective of LPS: self-administration, good tolerability are the main aspects for Italian centers., Conclusions: In conclusion, results of Italian survey are consistent to results of main international surveys about LPS.

Introduction: Immunomodulating therapies harness the power of the immune system to combat disease. In advanced melanoma, immune checkpoint inhibitors have significantly improved survival outcomes by activating the immune system to recognize and eliminate cancer cells. In psoriasis, interleukin inhibitors effectively suppress inflammation and improve disease symptoms., Areas Covered: We provide a meta-opinion-based consensus paper on the analogies and differences in treatment mechanisms, duration, frequency between immunotherapy for advanced melanoma and biologics for psoriasis. Combining the current scientific evidence with expert insights, we provide valuable guidance for future research and decision-making processes., Expert Opinion: The development of immunological treatments in melanoma and psoriasis has revolutionized dermatology, but the quest for tailored therapies that maximize efficacy continues. Managing cutaneous exacerbations during melanoma immunotherapy in psoriatic patients remains challenging. Similarly, treating oncologic psoriasis patients resistant to traditional therapies requires individualized approaches. Research is needed to identify response predictors in both conditions and address the sustainability of healthcare systems due to the high cost of biologics. Drug delay studies for psoriasis and longer follow-up evaluations after immunotherapy discontinuation in melanoma are essential for optimizing treatment outcomes and resource allocation.

Introduction: Patients with psoriasis who have failed multiple biologic drugs have been defined as "multi-failure," although there are no clear data on the characteristics, comorbidities, and best treatment strategies for this population. Nowadays, given the next generation and the number of biologics available, patients are considered multi-failure when ≥4 biologics fail to achieve a good response., Methods: Demographic characteristics and efficacy of anti-interleukin drugs in multi-failure patients were compared to a cohort of general psoriatic patients treated with IL-23 or IL-17 inhibitors., Results: In total 97 multi-failure patients (≥4 lines of biologics) were compared with 1,057 patients in the general cohort. The current drugs in the multi-failure group were risankizumab (34), ixekizumab (23), guselkumab (21), brodalumab (7), tildrakizumab (5), ustekinumab (4), secukinumab (2), and certolizumab pegol (1). A significant difference was found in the multi-failure cohort for age of psoriasis onset (mean 29.7 vs. 35.1, P < 0.001), concurrent psoriatic arthritis (45.4 vs. 26.9%, P < 0.001), diabetes mellitus (30.9 vs. 10.9%, P < 0.001), and cardiovascular comorbidity (54.6 vs. 39.8%, P = 0.005). In multi-failure patients, current biological therapy showed a good initial response (PASI 90 and 100 of 41.24 and 27.84%, respectively, at 16 weeks); the response tended to decline after 40 weeks. Anti-IL-17 agents showed clinical superiority over IL-23 agents in terms of achieving PASI90 at 28 weeks (P < 0.001) and 40 weeks (P = 0.007), after which they reached a plateau. In contrast, IL-23 agents showed a slower but progressive improvement that was maintained for up to 52 weeks. A similar trend was also seen for PASI100 (28 weeks P = 0.032; 40 weeks P = 0.121)., Conclusions: The multi-failure patient is characterized by many comorbidities and longstanding inflammatory disease that frequently precedes the introduction of systemic biologic therapy. Further studies are needed to identify more specific criteria that could be applied as a guideline by clinicians., (© 2024 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Background: Evidence-based indications for intracranial pressure (ICP) monitoring in patients with traumatic brain injury (TBI) are lacking. The aim of this study was to analyze the main factors that guided the decision-making of invasive ICP monitoring in a large cohort of TBI patients from our institution., Methods: This is a retrospective, single centre, observational study including adult TBI patients consecutively admitted to our Neurointensive Care Unit over 20 years. Logistic regression analyses were performed to identify potential factors associated with the decision for ICP monitor insertion. A decision tree was developed to identify the combination of factors with the highest statistical power to predict the decision for ICP monitor insertion., Results: A total of 857 adult patients were included in the analysis. The decision to monitor ICP was strongly related to different factors, including Glasgow Coma Scale (GCS), computed tomography (CT) scan classification, pupils' reactivity, and patients' prognosis at the admission calculated by the International Mission on Prognosis in Traumatic Brain Injury (IMPACT) score (P<0.01). Results from the decision tree showed an overall ability of the 72% in the prediction of ICP monitoring and that, among the factors analyzed, CT findings had the primarily and strongest discrimination power., Conclusions: The decision to insert an invasive ICP monitoring in patients with TBI is multifactorial. Among the different factors analysed in our cohort of TBI patients, prognostication factors as for IMPACT score and in particular CT findings could potentially explain the decision making for ICP monitoring.

Aims: Patients with Crohn's disease (CrD) have an elevated risk for the development of small bowel adenocarcinomas (SBAs). Actionable isocitrate dehydrogenase 1 (IDH1) mutations have been reported to be more frequent in CrD-SBAs than in sporadic SBAs. The present study aimed to investigate the clinicopathological and immunophenotypical features, as well as methylation profiles, of IDH1-mutated CrD-SBAs., Methods and Results: An international multicentre series of surgically resected CrD-SBAs was tested for IDH1 mutation. Clinicopathological features, immunophenotypical marker expression and O6-methylguanine-DNA methyltransferase (MGMT) and long interspersed nuclear element-1 (LINE-1) methylation were compared between IDH1-mutated and IDH1 wild-type CrD-SBAs. Ten (20%) of the 49 CrD-SBAs examined harboured an IDH1 mutation and all the mutated cancers harboured the R132C variant. Compared to IDH1 wild-type cases, IDH1-mutated CrD-SBAs showed significantly lower rates of cytokeratin 7 expression (P = 0.005) and higher rates of p53 overexpression (P = 0.012) and MGMT methylation (P = 0.012). All three dysplastic growths associated with IDH1-mutated SBAs harboured the same IDH1 variant (R132C) of the corresponding invasive cancer, and all were of non-conventional subtype (two serrated dysplastic lesions and one goblet cell-deficient dysplasia). In particular, non-conventional serrated dysplasia was significantly associated with IDH1-mutated CrD-SBAs (P = 0.029). No significant cancer-specific survival difference between IDH1-mutated CrD-SBA patients and IDH1 wild-type CrD-SBA patients was found (hazard ratio = 0.55, 95% confidence interval = 0.16-1.89; P = 0.313)., Conclusions: IDH1-mutated CrD-SBAs, which represent approximately one-fifth of total cases, are characterised by distinctive immunophenotypical features and methylation profiles, with potential therapeutic implications. Moreover, IDH1-mutated non-conventional, serrated dysplasia is likely to represent a precursor lesion to such CrD-SBAs., (© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Introduction: The development of several effective biological drugs for moderate-to-severe plaque psoriasis has dramatically changed the lives of patients. Despite the wide use of interleukin (IL) inhibitors, limited data are available to date regarding long-term treatment persistence., Method: This multicenter retrospective real-world study evaluated 5932 treatment courses across 5300 patients, all treated with interleukin inhibitors. Drug survival was expressed by using the Kaplan-Meier estimator for each biological drug at 6, 12, 24, 36 and 48 months. We also stratified by discontinuation associated with primary or secondary ineffectiveness., Results: In our study, the most prescribed drugs were secukinumab (1412), ixekizumab (1183), and risankizumab (977). After four years of follow-up, risankizumab emerged as the treatment with the highest drug survival overall, as 91.6% of patients were still on treatment. The overall probability of drug survival at four years was comparable for tildrakizumab (83.5%), ixekizumab (82.6%), guselkumab (82.4%) and brodalumab (81.8%). When evaluating only patients who discontinued the treatment because of ineffectiveness, once again risankizumab was the molecule with the highest drug survival at 4 years (93.4%), this time followed by ixekizumab (87%). Our study, in which all IL inhibitors were adequately represented, confirmed a slightly better treatment persistence for IL-23 inhibitors, consistent with other real-world studies., Conclusion: Our experience showed that IL-23 inhibitors, and risankizumab in particular, had a higher probability of drug survival overall during a 4-year follow-up. Risankizumab and ixekizumab were less likely to be discontinued because of ineffectiveness after four years., Competing Interests: LG has been a consultant for Almirall. LI has been a consultant for Almirall. PM has been a speaker for AbbVie, Lilly, Novartis, Janssen-Cilag, Celgene, Leopharma and Almirall. AB has received honoraria for participation in advisory boards, meetings or as speaker for AbbVie, Celgene, Janssen-Cilag, Eli Lilly, Novartis Pharma, Pfizer, Sanofi-Genzyme and UCB Pharma. FB has been a consultant advisor and clinical study investigator for Eli Lilly, Abbvie, Novartis, Leo Pharma, Sandoz, Bristol Myers, Abiogen-Pharma, Celgene and Janssen. MB has acted as a speaker and consultant for AbbVie, Janssen, Amgen, Novartis, Eli Lilly and UCB Pharma. CC has served as a board participant or speaker for Abbvie, Lilly, Janssen, Novartis, Celgene, Almirall and Leopharma. GD served as consultant and/or speaker for AbbVie, Almirall, Bristol-Meyers Squibb, LeoPharma, Novartis, Pfizer, Sanofi and UCB and received unrestricted grants from Pfizer and Almirall. PD has been a speaker for Novartis, Abbvie, Sanofi, UCB, Janssen, Lilly and LeoPharma. FG acted as a speaker or consultant for Novartis, Abbvie, Eli Lilly, Celgene, LeoPharma and Almirall. GG served as consultant and/or speaker for AbbVie, Almirall, Amgen, Biogen, Boehringer-Ingelheim, Bristol-Meyers Squibb, Eli-Lilly, LeoPharma, Novartis, Pfizer, Samsung, Sanofi and UCB. CG has been a scientific consultant/speaker/clinical study investigator for Abbvie, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, Sanofi, Almirall and LEO Pharma. CL declares a conflict of interest with Abbvie, Novartis, Lilly and Almirall. FL served on advisory boards and/or received honoraria for lectures from Abbvie, Janssen-Cilag, Novartis, Lilly and Sanofi. AM reports consultancy/advisory boards disease-relevant honoraria from AbbVie, Boehringer-Ingelheim, Novartis, Pfizer, Sanofi and UCB. MM acted as a speaker or consultant for Abbvie, Eli Lilly, Janssen, Leo-Pharma, UCB and Novartis. AC has served as an advisory board member, consultant and has received fees and speaker’s honoraria or has participated in clinical trials for Abbvie, Almirall, Biogen, LEO Pharma, Lilly, Janssen, Novartis, Pfizer, Sanofi Genzyme and UCB-Pharma. AN has served on advisory boards, received honoraria for lectures and research grants from Almirall, Abbvie, Leo Pharma, Celgene, Eli Lilly, Janssen, Novartis, Sanofi-Genzyme, Amgen and Boehringer Ingelheim. The remaining 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., (Copyright © 2024 Gargiulo, Ibba, Malagoli, Balato, Bardazzi, Burlando, Carrera, Damiani, Dapavo, Dini, Gaiani, Girolomoni, Guarneri, Lasagni, Loconsole, Marzano, Megna, Mercuri, Travaglini, Costanzo and Narcisi.)

Background: This review aims to understand the present circumstances on the provision of prehospital trauma care in low- and middle-income countries (LMICs), particularly scoping the challenges experienced by LMICs in this regard. The objective is to systematically evaluate the currently available evidence on this topic. Based on the themes and challenges identified in the provision of prehospital trauma care in LMICs, we provide a series of recommendations and a knowledge base for future research in the field., Methods: A systematic database search was conducted of original articles that explored and reported on prehospital trauma care in LMIC in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to March 2022. All original articles reporting on prehospital trauma care from 2010 to 2022 in LMICs were assessed, excluding case reports, small case series, editorials, abstracts, and pre-clinical studies; those with data inconsistencies that impede data extraction; and those with study populations fewer than ten., Results: The literature search identified 2,128 articles, of which 29 were included in this review, featuring 27,848 participants from LMICs countries. Four main areas of focus within the studies were identified: (1) exploring emergency service systems, frameworks, and interconnected networks within the context of prehospital trauma care; (2) transportation of patients from the response site to hospital care; (3) medical education and the effects of first responder training in LMICs; and (4) cultural and social factors influencing prehospital trauma care-seeking behaviors. Due to overarching gaps in social and health care systems, significant barriers exist at various stages of providing prehospital trauma care in LMICs, particularly in injury identification, seeking treatment, transportation to hospital, and receiving timely treatment and post-intervention support., Conclusion: The provision of prehospital trauma care in LMICs faces significant barriers at multiple levels, largely dependent on wider social, geographic, economic, and political factors impeding the development of such higher functioning systems within health care. However, there have been numerous breakthroughs within certain LMICs in different aspects of prehospital trauma care, supported to varying degrees by international initiatives, that serve as case studies for widespread implementation and targets. Such experiential learning is essential due to the heterogenous landscapes that comprise LMICs.

Background: The first two causes of liver cirrhosis and hepatocellular carcinoma are alcoholic and dysmetabolic. In the early stages alcohol related liver disease (ALD) is silent. For this reason, more efforts should be made to identify early individuals with hazardous/harmful alcohol consumption (AC). Alcohol use disorder identification test (AUDIT) is a validated test., Methods: ASL3 (Ligurian Local Health Company 3) has included the AUDIT renamed Glu-Glu Test on its institutional website dedicated to citizens. The renaming was carried out to bring citizens closer to the test with greater ease, especially younger citizens. At the end of the compilation of the test, the calculator provides the citizen with his score: in relation to his possible risk band, provides him with the appropriate advice. In case of a score higher than 7, ultrasonography and elastography (2D-SWE) are proposed., Results: From December 15, 2021, to July 15, 2022, 270 asymptomatic subjects requested a medical examination autonomously, without the indication of a health worker. In 167 patients the score found hazardous AC, in 65 harmful AC and in 38 alcohol addiction. In case of hazardous AC, fibrosis grade 1-2 was evidenced in 16.7%, fibrosis grade 3 in 4.8% and fibrosis grade 4 in 3.6% of subjects. In case of harmful AC fibrosis grade 1-2 was evidenced in 37%, grade 3 in 9%, grade 4 in 6%. In this group an HCC nodule was diagnosed. In case of alcohol addiction, fibrosis grade 1-2 was evidenced in 73.6%, grade 3 in 10.5% and grade 4 in 10.5%., Conclusions: This preliminary experience clearly tells us that it is possible to make an early diagnosis of fibrosis and HCC starting from the AC reported autonomously by citizens.

Background: According to the new criteria in the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V), the prevalence of alcohol use disorders (AUDs) is 20-30% in men and 10-15% in women worldwide. 2,3 The anticraving therapy/psychotherapy combination is currently used routinely in clinical practice. However, the results after one year are unsatisfactory. Meta-analytic studies found failure rates of 57 to 75%. These percentages vary in relation to the intensity and length of the treatment. In addition, the abstinence rates gradually decrease over time. In this study, the clinical outcome of alcohol related liver disease (ALD) patients who spontaneously attended self-help groups (SHGs) (club of alcoholics in treatment - multi-family community/ alcoholics anonymous) regularly versus those who did not want to start the path or did not complete it was evaluated., Methods: From January 2005 to December 2010, 1337 alcohol use disorder patients affected by compensated alcohol related liver disease, were prospectively followed and retrospectively assessed. Two hundred thirty-one patients were enrolled: 74 attended self-help groups assiduously, 27 attended sporadically and 130 refused participation in SHGs., Results: Constant attendance at SHGs compared to non-attendance allows for a significant increase (<0.0001) in the period of sobriety found in the median of distribution. Frequent attendance at SHGs is effectively "preventive," reducing the fraction of relapses by about 30%. The percentage of cases of cirrhosis is significantly different (P=0.0007) between those who have regularly attended SHG meetings (about 1% of patients) and those who have never attended or only occasionally (various percentages between 21 and 31% of patients); in both groups the incidence of new cases would seem to be 0.014 cases/ year. Similar difference in percentages regarding the onset of hepatocellular carcinomas (HCCs), although with a lower level of significance (P=0.017) among those who attended regularly, 4% of patients with an incidence of 0.006 cases/ year, compared to those who have never attended or only occasionally: over 14% of patients with an incidence of 0.022 cases/year., Conclusions: This study suggests the importance of attending SHGs not only for the long-term achievement of alcoholic abstention, but also in positively influencing the course of alcohol-related diseases.

In the present experience we have evaluated the link alcohol consumption/alcohol use disorder (AUD) and organ transplantation (OT) in order to provide adequate suggestions. The data used for the preparation of these recommendations are based on a detailed analysis of the scientific literature published before August 31, 2022 (Web of Science, Scopus, Google Scholar). Furthermore, in the process of developing this work, we consulted the guidelines/position papers of the scientific societies. With regard to the liver transplantation, there are position papers/guidelines that clearly define indications and contraindications for including the AUD patient in the transplant list. One of the major difficulties in this area is psychosocial assessment which can be influenced by stigma. To solve this problem, it is necessary to use objective tools. However, this assessment should be carried out after providing the patient and family adequate tools to be able to create or recreate reliable socio-family support. This behavior should also be used in the case of other OTs. For the latter, however, adequate guidelines must be created which at the moment do not exist or if there are, as in the case of heart transplantation, they are not sufficient. Even in the absence of obvious alcohol addiction, it is recommended to use alcohol use disorder identification test and to include the addiction specialist in the multidisciplinary transplant team. Besides, providing family members with the tools necessary to better support the patient is essential. They are patients with alcohol use disorder/ possible presence of psychopathological manifestations and alcohol-related pathology (cirrhosis, cardiomyopathy, liver-kidney disfunction, etc.). A cardiovascular and oncologic surveillance post-OT is recommended. For the selection of patients to be included in the list for non-LT (heart, lung, kidney, multivisceral, etc.) it is mandatory to include the diagnosis and treatment of AUDs in the guidelines. What has already been indicated for LT may be useful. Timing of alcoholic abstention in relation to clinical severity, optimal psychosocial activity, anticraving therapy in relation to the type of underlying disease and clinical severity. Close collaboration between scientific societies is required to better manage AUD patients who need OT.

Background: Postoperative pulmonary complications (PPCs) significantly contribute to postoperative morbidity and mortality. We conducted a study to determine the incidence of PPCs after major elective abdominal surgery and their association with early and 1-year mortality in patient without pre-existing respiratory disease., Methods: We conducted a multicenter observational prospective clinical study in 40 Italian centers. 1542 patients undergoing elective major abdominal surgery were recruited in a time period of 14 days and clinically managed according to local protocol. The primary outcome was to determine the incidence of PPCs. Further, we aimed to identify independent predictors for PPCs and examine the association between PPCs and mortality., Results: PPCs occurred in 12.6% (95% CI 11.1-14.4%) of patients with significant differences among general (18.3%, 95% CI 15.7-21.0%), gynecological (3.7%, 95% CI 2.1-6.0%) and urological surgery (9.0%, 95% CI 6.0-12.8%). PPCs development was associated with known pre- and intraoperative risk factors. Patients who developed PPCs had longer length of hospital stay, higher risk of 30-days hospital readmission, and increased in-hospital and one-year mortality (OR 3.078, 95% CI 1.825-5.191; P<0.001)., Conclusions: The incidence of PPCs in patients without pre-existing respiratory disease undergoing elective abdominal surgery is high and associated with worse clinical outcome at one year after surgery. General surgery is associated with higher incidence of PPCs and mortality compared to gynecological and urological surgery.

Background: Small bowel adenocarcinoma (SBA) is a rare cancer with an aggressive behavior. No study has specifically addressed the putative prognostic role of mismatch repair status in stage III SBAs., Aims: We aimed to investigate whether mismatch repair deficiency is associated with cancer-specific survival in a Western cohort of patients with stage III SBAs., Methods: In this retrospective multicentric international cohort study, we enrolled 70 patients who underwent surgically resection for stage III SBAs and we analyzed the frequency of mismatch repair deficiency, tested by immunohistochemistry for mismatch repair proteins and by polymerase chain reaction for microsatellite instability, and its association with cancer-specific survival and other clinic-pathologic factors., Results: We found sixteen (23%) patients with mismatch repair deficient adenocarcinoma, without discordance between immunohistochemical and polymerase chain reaction for microsatellite instability analyses. Mismatch repair deficiency proved to be associated with a better outcome both at univariable analysis (hazard ratio: 0.28, 95% confidence interval: 0.08-0.91, p: 0.035) and in bivariable models adjusted for patient age or gender, tumor site, pT4 stage, tumor budding, and perineural invasion., Conclusion: This study highlights the importance of testing mismatch repair status to improve prognostic stratification in stage III SBAs., Competing Interests: Conflict of Interest The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Bimekizumab is a monoclonal antibody that targets Interleukin-17 A and F, approved for the treatment of moderate-to-severe plaque psoriasis. While bimekizumab has been evaluated in several phase-III clinical trials, real-world evidence is still very limited., Method: This multicenter retrospective study included patients affected by plaque psoriasis treated with bimekizumab from May 1, 2022 to April 30, 2023, at 19 Italian referral hospitals. Patients affected by moderate-to-severe plaque psoriasis eligible for systemic treatments were included. The effectiveness of bimekizumab was evaluated in terms of reduction in psoriasis area and severity index (PASI) compared with baseline at weeks 4 and 16. The main outcomes were the percentages of patients achieving an improvement of at least 75% (PASI75), 90% (PASI90) and 100% (PASI100) in PASI score., Results: The study included 237 patients who received at least one injection of bimekizumab. One hundred and seventy-one patients and 114 reached four and 16 weeks of follow-up, respectively. Complete skin clearance was achieved by 43.3% and 75.4% of patients at weeks 4 and 16, respectively. At week 16, 86.8% of patients reported no impact on their quality of life. At week 16, there were no significant differences between bio-naïve and bio-experienced patients in terms of PASI75, PASI90 and PASI100. The most commonly reported adverse events (AEs) were oral candidiasis (10.1%). No severe AEs or AEs leading to discontinuation were observed throughout the study., Conclusion: Our experience supports the effectiveness and tolerability of bimekizumab in a real-world setting with similar results compared with phase-III clinical trials., Competing Interests: LG has been a consultant for Almirall. PM has been a speaker for AbbVie, Lilly, Novartis, Janssen-Cilag, Celgene, Leopharma, and Almirall. AB has received honoraria for participation in advisory boards, meetings, or as speaker for AbbVie, Celgene, Janssen-Cilag, Eli Lilly, Novartis Pharma, Pfizer, Sanofi-Genzyme, and UCB Pharma. LB has received honoraria as a speaker or consultant for AbbVie, Janssen, Almirall Eli-Lilly, Leopharma, Novartis, Sanofi, Pfizer, and UCB Pharma. GC reports consulting fees or honorarium and payment for lectures from Lilly and Novartis. CD reports consulting fees or honorarium from Abbvie, Amgen, Novartis, Celgene, Sanofi, UCB Pharma, Janssen, and Lilly and payment for lectures from Abbvie, Lilly, Novartis, UCB Pharma, and Celgene. PG has been a consultant and/or speaker for Abbvie, Almirall, Amgen, Janssen, Leo-Pharma, Eli-Lilly, Novartis, Pierre Febre, Sandoz, Sanofi, and UCB. MB has acted as a speaker and consultant for AbbVie, Janssen, Amgen, Novartis, Eli Lilly, and UCB Pharma. CC has served as a board participant or speaker for Abbvie, Lilly, Janssen, Novartis, Celgene, Almirall, and Leopharma. PD has been a speaker for Novartis, Abbvie, Sanofi, UCB, Janssen, Lilly, and LeoPharma. FG acted as a speaker or consultant for Novartis, Abbvie, Eli Lilly, Celgene, LeoPharma, and Almirall. AG received grants or is an investigator for Biogen and Lilly; and is a consultant/advisory board/speaker for AbbVie, Almirall, Celgene, Janssen, Leo Pharma, Eli Lilly, Merck Sharpe Dohme, Novartis, Pfizer, Sandoz, and UCB. FL served on advisory boards and/or received honoraria for lectures from Abbvie, Janssen-Cilag, Novartis, Lilly, Sanofi. AM reports consultancy/advisory boards disease-relevant honoraria from AbbVie, Boehringer-Ingelheim, Novartis, Pfizer, Sanofi, and UCB. MMe acted as a speaker or consultant for Abbvie, Eli Lilly, Janssen, Leo-Pharma, UCB, and Novartis. AO acted as a speaker and consultant for Abbvie, Eli Lilly, Novartis, Celgene, Sanofi, Galderma, Leo Pharma, and Pierre Fabre. MV served as a speaker or advisory board member for Abbvie, Almirall, Amgen, Eli-Lilly, Galderma, Leo Pharma, Novartis, Pierre Fabre, and UCB Pharma. ACo has served as an advisory board member, consultant and has received fees and speaker’s honoraria or has participated in clinical trials for Abbvie, Almirall, Biogen, LEO Pharma, Lilly, Janssen, Novartis, Pfizer, Sanofi Genzyme, and UCB-Pharma. AN has served on advisory boards, received honoraria for lectures and research grants from Almirall, Abbvie, Leo Pharma, Celgene, Eli Lilly, Janssen, Novartis, Sanofi-Genzyme, Amgen, and Boehringer Ingelheim. The remaining 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., (Copyright © 2023 Gargiulo, Narcisi, Ibba, Balato, Bianchi, Brianti, Buononato, Burlando, Caldarola, Campanati, Campione, Carrera, Carugno, Cristaudo, Cusano, Dapavo, Dattola, De Simone, Gaiani, Gisondi, Giunta, Loconsole, Maione, Mortato, Marzano, Maurelli, Megna, Mercuri, Offidani, Orsini, Parodi, Pellacani, Potestio, Quaglino, Richetta, Romano, Sena, Venturini, Malagoli and Costanzo.)

Background: Autoimmune blistering diseases (AIBD), are a heterogeneous group. Despite their pathogenesis is not completely understood, autoantibodies against directed adhesion molecules of the skin and adjacent mucous membranes could play a key role. The leukocyte-associated-Ig-like-receptor (LAIR) family is a small group of immunoreceptor-tyrosine-based-inhibition-motif-containing inhibitory receptors, recognizing collagens. LAIR-1 is a transmembrane glycoprotein expressed on human-peripheral-blood-leukocytes. LAIR-2 is a secreted receptor mainly produced by CD4 + T-lymphocytes, and is able to regulate the inhibitory potential of LAIR-1. Both LAIRs have been associated with several autoimmune diseases and inflammatory responses., Methods: We evaluated circulating LAIRs in patients with different blistering skin diseases by ELISA., Results: A significant increase of serum LAIR-2, and to a lesser extent of sLAIR-1 (with the exception of Pemphigus vulgaris), in the whole group of patients with bullous diseases, irrespective of the pathogenesis, compared to healthy controls was evident., Conclusions: Although the pathophysiological meaning of LAIR is not completely elucidated, the presence of increased concentration of LAIR proteins can somehow modulate the cascade of inflammatory phenomenon occurring in bullous skin diseases, in different way depending upon specific skin disease considered.

Background: The upfront treatment of metastatic renal cell carcinoma (mRCC) has been revolutionized by the introduction of immune-based combinations. The role of cytoreductive nephrectomy (CN) in these patients is still debated. The ARON-1 study (NCT05287464) was designed to globally analyze real-world data of mRCC patients receiving first-line immuno-oncology combinations. This sub-analysis is focused on the role of upfront or delayed partial or radical CN in three geographical areas (Western Europe, Eastern Europe, America/Asia)., Methods: We conducted a multicenter retrospective observational study in mRCC patients treated with first-line immune combinations from 55 centers in 19 countries. From 1152 patients in the ARON-1 dataset, we selected 651 patients with de novo mRCC. 255 patients (39%) had undergone CN, partial in 14% and radical in 86% of cases; 396 patients (61%) received first-line immune-combinations without previous nephrectomy., Results: Median overall survival (OS) from the diagnosis of de novo mRCC was 41.6 months and not reached (NR) in the CN subgroup and 24.0 months in the no CN subgroup, respectively (P<0.001). Median OS from the start of first-line therapy was NR in patients who underwent CN and 22.4 months in the no CN subgroup (P<0.001). Patients who underwent CN reported longer OS compared to no CN in all the three geographical areas., Conclusions: No significant differences in terms of patients' outcome seem to clearly emerge, even if the rate CN and the choice of the type of first-line immune-based combination varies across the different Cancer Centers participating in the ARON-1 project.

Introduction: A Doppler ultrasound (US) of the scrotum is commonly used to improve the diagnostic confidence for testicular torsion in an emergency setting. However, the sensitivity of this investigation to identify torsion varies largely. This is due, in part, to a lack of guidelines on how-to perform the US and therefore training is necessary., Evidence Acquisition: The Scrotal and Penile Imaging Working Group of the European Society of Urogenital Radiology (ESUR-SPIWG) and the Section of Urological Imaging of the European Association of Urology (ESUI) established a joint panel of experts to standardize Doppler US investigation of patients with testicular torsion. The panel reviewed the available literature, identified accumulated knowledge and limitations, and released recommendations on how-to perform Doppler US in patients with acute scrotal pain., Evidence Synthesis: Diagnosis of testicular torsion is based on clinical evaluation and investigation of the cord, the testis, and the paratesticular structures. A preliminary clinical evaluation, including history and palpation, is necessary. Grey scale US, color Doppler US and spectral analysis must be performed by a sonologist with at least level 2 competence. Modern equipment with adequate grey-scale and Doppler capabilities are required., Conclusions: Standardization of Doppler US in suspicious testicular torsion is presented, with the aim to obtain comparable results among different centres, prevent unnecessary operations, and improve patient management.

Cervical spondylotic myelopathy (CSM) is a progressively growing pathology to afford by a spinal surgeon due to the aging of the population, associated with better treatment management and the best diagnosis and treatment solutions are greatly discussed. Nowadays that scientific literature is progressively increasing to identify the gold standard in diagnosis and treatment can be very challenging. This is particularly evident in spinal surgery with many different indications not only in different countries but also in the same local reality. In this scenario, many neurosurgical societies works to identify some guideline or recommendations to help spinal surgeons in daily practice. Furthermore, in an era in which legal issues are increasingly present in clinical practice to have some indications globally accepted can be very useful. World Federation of Neurosurgical Societies (WFNS) few years ago starts this process creating a list of recommendations originating from a worldwide steering committee to respect all the local reality. The spinal section of Italian Neurosurgical Society decides to adopt the WFNS recommendations with some revision basing on Italian scenario. The steering committee of the Spinal Section of Italian Neurosurgical Society identify 7 groups to review the literature of the last 10 years about different topics on CSM and to analyses the WFNS recommendations to adapt it to the Italian daily practice. The statements were discussed and voted in 2 sessions to obtain the final version. A list of recommendations on natural course and clinical presentation; diagnostic tests; conservative and surgical treatment; anterior, posterior and combined surgical treatment; role of neurophysiological monitoring and follow-up and outcome was created with only few new or revised statements respect the ones of WFNS. The Spine Section of Italian Neurosurgical Society create a list of recommendations that represent the more contemporary treatment concepts for CSM as presented in the highest quality clinical literature and best clinical practices available on this subject.

Background: Guselkumab is a fully human monoclonal antibody that binds selectively to the p19 subunit of interleukin-23, which has shown efficacy in patients with previous incomplete response to ustekinumab in the NAVIGATE clinical trial. [Correction added on [28-02-2023], after first online publication: 'humanized monoclonal antibody' has been changed to 'fully human monoclonal antibody' in the preceding sentence.] OBJECTIVES: We conducted a 104-week multicenter retrospective study to assess the effectiveness and safety of guselkumab in patients affected by plaque psoriasis with an inadequate response to ustekinumab in a real-life setting., Methods: Our retrospective study included 233 adults affected by moderate-to-severe plaque psoriasis, enrolled in 14 different Italian centres, and treated with guselkumab after failing therapy with ustekinumab. Patient characteristics and PASI (Psoriasis Area and Severity Index) score at each visit (baseline, weeks 16, 52 and 104) were recorded. The percentages of patients achieving 75%, 90% and 100% (PASI 75, PASI 90 and PASI 100) improvement in PASI, compared with baseline, were registered., Results: At week 52, PASI 75 was reached by 89.88% of patients, PASI 90 by 71.43%, PASI 100 by 58.83% and absolute PASI ≤2 by 90.48%. At week 104, similar effectiveness results were observed. Compared to the NAVIGATE trial, we observed higher rates of PASI 75/90/100. Patients with the involvement of difficult-to-treat areas were significantly less likely to achieve PASI90 and PASI100 at week 16. Obese patients had significantly lower rates of PASI75 and PASI ≤2 at week 52. At week 104, comparable responses were observed among all patients' subgroups, regardless of BMI status, involvement of difficult-to-treat areas, presence of cardiometabolic comorbidities and concomitant psoriatic arthritis. No significant safety findings were reported throughout the study., Conclusion: Our data suggest that the efficacy of guselkumab in patients with inadequate response to ustekinumab for plaque psoriasis in 'real-life' clinical practice is comparable with NAVIGATE study with higher percentages of patients achieving PASI90 and PASI100 at weeks 16, 52 and 104., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Technetium-99m is the workhorse of diagnostic nuclear medicine. The aim of the work is to analyze the technetium-99m patents since 2000 to photograph its innovation. QUESTEL's ORBIT Intelligence system was used for the collection of technetium inventions disclosed in patents and patent applications in more than 96 countries in the period 2000-2022; 2768 patent documents were analyzed. Patent counting and analysis have shown that SPECT imaging using technetium-99m radiopharmaceuticals is still robust. The introduction of new technetium-99m radiopharmaceuticals into clinical routine goes beyond successful trials. In eastern economies, such as China and other emerging markets, patent applications are on the rise, while those in developed western countries are stagnating, with some exceptions for the United States. But despite the difficulties, academic and industrial research on these tracers remains essential for the development of nuclear medicine.

Introduction: Composite endpoints are pivotal when assessing rare outcomes over relatively short follow-ups. Most randomized controlled trials (RCTs) comparing percutaneous coronary intervention (PCI) with stent implantation to optimal medical therapy (OMT) in chronic coronary syndromes (CCS) patients included both hard and soft outcomes in their primary endpoint, with periprocedural myocardial infarctions (MIs) systematically allocated to the PCI arm. We meta-analyzed the above RCTs for composite hard endpoints, with and without periprocedural MIs., Evidence Acquisition: This study is registered in PROSPERO CRD42020166754 and follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Collaboration reporting. Patients had inducible ischemia, no left main disease nor severe left ventricular dysfunction., Evidence Synthesis: Six RCTs involving 10,751 patients followed for a mean of 4.4 years were included. PCI+OMT versus OMT alone was associated with no difference in the two co-primary composite endpoints of all-cause death/MI/stroke and cardiovascular death/MI including all-MIs (IRR 0.99; 95% CI 0.90-1.08 and IRR 0.95; 95% CI 0.83-1.08 respectively). After inclusion of spontaneous rather than all-MIs (i.e., excluding periprocedural MIs), the odds showed benefit of PCI+OMT for both co-primary endpoints (IRR 0.88; 95% CI 0.80-0.97, P<0.01 and IRR 0.81; 95% CI 0.69-0.95, P=0.01 respectively) with numbers needed to treat of 42 in both cases., Conclusions: Among CCS patients with inducible myocardial ischemia without severely reduced ejection fraction or left main disease, adding PCI to OMT reduces hard composite outcomes only after exclusion of periprocedural MIs. Continued efforts to define periprocedural MIs reproducibly, to assess their prognostic relevance and to prevent them are warranted.

Background: To understand padel tennis injuries occurrence in Liguria, Italy. Paddle is a well know racquet sport, similar to tennis. padel tennis has been widely adopted in Liguria only in the last 4 years, however sport practice was largely reduced by the worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: A questionnaire (N.=19 questions) was sent to all members of the Italian Federation of Tennis involved in official tournaments of padel tennis. We collected data on the number of injuries, the most frequent injuries, their distribution, type, location, the moment at which these occurred, and the diagnostic modality used to make the diagnosis., Results: A total of 800 Italian padel tennis players took part in the survey (mean age: 49±22 years). In total, 85 injuries were registered in 2020/2021 up to 1/6/2021. The majority of lesion was located on the lower limb N.=49/85 with the knee N.=16/49 highly affected. Then, the majority of lesion of the upper limb were localized al the elbow N.=22/36, the majority epicondylitis., Conclusions: Padel tennis injuries resulted more common in the lower limb and the elbow was the most affected area at the upper limb.

Background: Xerosis is an extremely common condition, especially in the elderly population. It is the most common cause of pruritus in the older adult. Since xerosis is generally caused by a lack of epidermal lipids, the use of leave-on skin care products is the mainstay treatment. The aim of this open prospective analytical observational study was to investigate the clinical and self-reported hydrating efficacy of a moisturizer formulation containing a synergy between amino-inositol and urea (INOSIT-U 20) in patients with psoriasis and xerosis., Methods: Twenty-two patients with psoriasis successfully treated with biologic therapy, and who presented xerosis, were recruited. Each patient was instructed to apply the topical with a frequency of two applications per die on the identified skin area. Corneometry values and a VAS itch questionnaire were measured at baseline (T0) and after 28 days (T4). To evaluate the cosmetic efficacy, the volunteers also completed a self-assessment questionnaire., Results: Comparing Corneometry values at T0 and T4, a statistically significant increase value was observed in the area subjected to topical treatment (P<0.0001). A significant decrease in itch (P=0.001) was also observed. Moreover, the patients' ratings of the cosmetic properties of the moisturizer showed significant confirmation rates., Conclusions: This study provides preliminary evidence that INOSIT-U20 provides a good hydrating effect on xerosis, further reducing self-reported itch.

Background: The COVID-19 pandemic severely impacted global health. The aim of this study was to compare predictors of symptoms-to-emergency-call timing delay in acute coronary syndrome (ACS) and their impact on mortality before and during the COVID-19 outbreak., Methods: We collected sociodemographic, clinical data, procedural features, preadmission and intra-hospital outcomes of consecutive patients admitted for ACS in seventeen Italian centers from March to April 2018, 2019, and 2020., Results: In 2020, a 32.92% reduction in ACS admissions was observed compared to 2018 and 2019. Unstable angina, typical and atypical symptoms, and intermittent angina were identified as significant predictors of symptoms-to-emergency-call timing delay before and during the COVID-19 pandemic (P<0.005 for all the items). Differently from 2018-2019, during the pandemic, hypertension and dyspnea (P=0.002 versus P=0.490 and P=0.001 vs. P=0.761 for 2018-2019 and 2020, respectively) did not result as predictors of delay in symptoms-to-emergency-call timing. Among these predictors, only the atypical symptoms (HR 3.36; 95% CI: 1.172-9.667, P=0.024) in 2020 and the dyspnea (HR 2.64; 95% CI: 1.345-5.190, P=0.005) in 2018-2019 resulted significantly associated with higher mortality. Finally, the family attendance at the onset of the symptoms resulted in a reduction in symptoms-to-emergency-call timing (in 2020 P<0.001; CI: -1710.73; -493.19) and in a trend of reduced mortality (HR 0.31; 95% CI: 0.089-1.079, P=0.066) in 2020., Conclusions: During the COVID-19 outbreak, atypical symptoms and family attendance at ACS onset were identified, respectively, as adverse and favorable predictors of symptoms-to-emergency-call timing delay and mortality.