[ANMCO/SIMEU Consensus document on the use of reversal agents of antithrombotic therapies in patients with active bleeding or at high-risk of major bleeding events]. / Documento di consenso ANMCO/SIMEU sull'impiego degli agenti di reversione delle terapie antitrombotiche nei pazienti con sanguinamento in atto o ad alto rischio di eventi emorragici.

In recent decades, an incredible evolution in antithrombotic therapies for the treatment of patients suffering from atherosclerosis, atrial fibrillation and venous thromboembolism occurred, leading to the availability of increasingly safe drugs. However, bleeding complications associated with these drugs still have an important health, social and economic impact. Recently, with the aim of improving the acute management of patients with or at risk of major bleeding events, specific reversal agents of antithrombotic drugs have been developed. Although these agents have demonstrated their effectiveness in small pharmacodynamic studies or clinical trials, it is important to consider that the benefit of reversal of an antiplatelet or anticoagulant drug must always be counterbalanced by the possible prothrombotic effect caused by the removal of antithrombotic protection as well as by prothrombotic mechanisms related to bleeding, major surgery or trauma.In this ANMCO/SIMEU consensus document we summarize the main characteristics and efficacy studies of the currently available reversal agents and present practical flow-charts in which we suggest their possible use in patients with active bleeding or at high risk of major bleeding events.

Pain Management at the End of Life in the Emergency Department: A Narrative Review of the Literature and a Practical Clinical Approach.

Access to pain management is a fundamental human right for all people, including those who are at the end of life (EOL). In end-stage patients, severe and uncontrolled pain is a common cause of admission to the emergency department (ED), and its treatment is challenging due to its complex, often multifactorial genesis. The aim of this narrative review was to identify the available literature on the management of severe EOL pain in the ED. The MEDLINE, SCOPUS, EMBASE, and CENTRAL databases were searched from inception to 1 April 2023 including randomised controlled trials, observational studies, systemic or narrative reviews, case reports, and guidelines on the management of EOL pain in the ED. A total of 532 articles were identified, and 9 articles were included (5 narrative reviews, 2 retrospective studies, and 2 prospective studies). Included studies were heterogeneous on the scales used and recommended for pain assessment and the recommended treatments. No study provided evidence for a better approach for EOL patients with pain in the ED. We provide a narrative summary of the findings and a review of the management of EOL pain in clinical practice, including (i) the identification of the EOL patients and unmet palliative care needs, (ii) a multidimensional, patient-centred assessment of the type and severity of pain, (iii) a multidisciplinary approach to the management of end-of-life pain, including an overview of non-pharmacological and pharmacological techniques; and (iv) the management of special situations, including rapid acute deterioration of chronic pain, breakthrough pain, and sedative palliation.

ANMCO-SIMEU consensus document: appropriate management of atrial fibrillation in the emergency department.

Atrial fibrillation (AF) accounts for 2% of the total presentations to the emergency department (ED) and represents the most frequent arrhythmic cause for hospitalization. It steadily increases the risk of thromboembolic events and is often associated with several comorbidities that negatively affect patient's quality of life and prognosis. AF has a considerable impact on healthcare resources, making the promotion of an adequate and coordinated management of this arrhythmia necessary in order to avoid clinical complications and to implement the adoption of appropriate technological and pharmacological treatment options. AF management varies across regions and hospitals and there is also heterogeneity in the use of anticoagulation and electric cardioversion, with limited use of direct oral anticoagulants. The ED represents the first access point for early management of patients with AF. The appropriate management of this arrhythmia in the acute setting has a great impact on improving patient's quality of life and outcomes as well as on rationalization of the financial resources related to the clinical course of AF. Therefore, physicians should provide a well-structured clinical and diagnostic pathway for patients with AF who are admitted to the ED. This should be based on a tight and propositional collaboration among several specialists, i.e. the ED physician, cardiologist, internal medicine physician, anesthesiologist. The aim of this ANMCO-SIMEU consensus document is to provide shared recommendations for promoting an integrated, accurate, and up-to-date management of patients with AF admitted to the ED or Cardiology Department, in order to make it homogeneous across the national territory.

Uncovering the Benefits of the Ketamine-Dexmedetomidine Combination for Procedural Sedation during the Italian COVID-19 Pandemic.

This retrospective observational study evaluated the safety and efficacy of the ketamine and dexmedetomidine combination (keta-dex) compared to ketamine or dexmedetomidine alone for sedation of patients with acute respiratory distress due to COVID-19 pneumonia who require non-invasive ventilation. The following factors were assessed: tolerance to the ventilation, sedation level on the Richmond Agitation-Sedation Scale (RASS), hemodynamic and saturation profile, adverse effects, and discontinuation or mortality during ventilation. The study included 66 patients who underwent sedation for non-invasive ventilation using keta-dex (KETA-DEX group, n = 22), ketamine (KET group, n = 22), or dexmedetomidine (DEX group, n = 22). The DEX group showed a slower sedation rate and a significant reduction in blood pressure compared to the KETA-DEX group (p < 0.05). An increase in blood pressure was recorded more frequently in the KET group. No reduction in oxygen saturation and no deaths were observed in any of the groups. None of the patients discontinued ventilation due to intolerance. The mean duration of sedation was 28.12 h. No cases of delirium were observed in any of the groups. Overall, keta-dex was associated with faster sedation rates and better hemodynamic profiles compared to dexmedetomidine alone. Keta-dex is effective and safe for sedation of uncooperative patients undergoing non-invasive ventilation.

Narrative Review: Low-Dose Ketamine for Pain Management.

Pain is the leading cause of medical consultations and occurs in 50-70% of emergency department visits. To date, several drugs have been used to manage pain. The clinical use of ketamine began in the 1960s and it immediately emerged as a manageable and safe drug for sedation and anesthesia. The analgesic properties of this drug were first reported shortly after its use; however, its psychomimetic effects have limited its use in emergency departments. Owing to the misuse and abuse of opioids in some countries worldwide, ketamine has become a versatile tool for sedation and analgesia. In this narrative review, ketamine's role as an analgesic is discussed, with both known and new applications in various contexts (acute, chronic, and neuropathic pain), along with its strengths and weaknesses, especially in terms of psychomimetic, cardiovascular, and hepatic effects. Moreover, new scientific evidence has been reviewed on the use of additional drugs with ketamine, such as magnesium infusion for improving analgesia and clonidine for treating psychomimetic symptoms. Finally, this narrative review was refined by the experience of the Pain Group of the Italian Society of Emergency Medicine (SIMEU) in treating acute and chronic pain with acute manifestations in Italian Emergency Departments.

Intranasal Fentanyl for Acute Pain Management in Children, Adults and Elderly Patients in the Prehospital Emergency Service and in the Emergency Department: A Systematic Review.

This systematic review examined the efficacy and safety of intranasal fentanyl (INF) for acute pain treatment in children, adults, and the elderly in prehospital emergency services (PHES) and emergency departments (ED). ClinicalTrials.gov, LILACS, PubMed, SCOPUS, EMBASE, Google Scholar and Cochrane databases were consulted until 31 December 2022. A total of 23 studies were included: 18 in children (1 PHES, 17 ED), 5 in adults (1 PHES, 4 ED) and 1 in older people (1 PHES subgroup analysis). In children, INF was effective in both settings and as effective as the comparator drugs, with no differences in adverse events (AEs); one randomised controlled trial (RCT) showed that INF was more effective than the comparator drugs. In adults, one study demonstrated the efficacy of INF in the PHES setting, one study demonstrated the efficacy of INF in the ED setting, two RCTs showed INF to be less effective than the comparator drugs and one RCT showed INF to be as effective as the comparator, with no difference in AEs reported. In older people, one study showed effective pain relief and no AEs. In summary, INF appears to be effective and safe in children and adults in PHES and ED. More high-quality studies are needed, especially in PHES and older people.

Unfavorable Outcome and Long-Term Sequelae in Cases with Severe COVID-19.

Emerging evidence shows that individuals with COVID-19 who survive the acute phase of illness may experience lingering symptoms in the following months. There is no clear indication as to whether these symptoms persist for a short time before resolving or if they persist for a long time. In this review, we will describe the symptoms that persist over time and possible predictors in the acute phase that indicate long-term persistence. Based on the literature available to date, fatigue/weakness, dyspnea, arthromyalgia, depression, anxiety, memory loss, slowing down, difficulty concentrating and insomnia are the most commonly reported persistent long-term symptoms. The extent and persistence of these in long-term follow-up is not clear as there are still no quality studies available. The evidence available today indicates that female subjects and those with a more severe initial disease are more likely to suffer permanent sequelae one year after the acute phase. To understand these complications, and to experiment with interventions and treatments for those at greater risk, we must first understand the physio-pathological mechanisms that sustain them.

[ANMCO-SIMEU Consensus document: Appropriate management of atrial fibrillation in the emergency department]. / Documento di consenso ANMCO-SIMEU: Gestione appropriata della fibrillazione atriale in Pronto Soccorso.

Atrial fibrillation (AF) accounts for 2% of the total presentations to the emergency department (ED) and represents the most frequent arrhythmic cause for hospitalization. It steadily increases the risk of thromboembolic events and is often associated with several comorbidities that negatively affect patient's quality of life and prognosis. AF has a considerable on healthcare resources, making the promotion of an adequate and coordinated management of this arrhythmia necessary in order to avoid clinical complications and to implement the adoption of appropriate technological and pharmacological treatment options. AF management varies across regions and hospitals and there is also heterogeneity in the use of anticoagulation and electric cardioversion, with limited use of direct oral anticoagulants. The ED represents the first access point for early management of patients with AF. The appropriate management of this arrhythmia in the acute setting has a great impact on improving patient's quality of life and outcomes as well as on rationalization of the financial resources related to the clinical course of AF. Therefore, physicians should provide a well-structured clinical and diagnostic pathway for patients with AF who are admitted to the ED. This should be based on a tight and propositional collaboration among several specialists, i.e. the ED physician, cardiologist, internal medicine physician, anesthesiologist. The aim of this ANMCO-SIMEU consensus document is to provide shared recommendations for promoting an integrated, accurate, and up-to-date management of patients with AF admitted to the ED or Cardiology Department, so as to make it homogeneous across the national territory.

Fast and reliable real life data on COVID-19 triaging with ID NOW.

In the context of SARS-CoV-2 pandemic, rapid and easy-to-perform diagnostic methods are essential to limit the spread of the virus and for the clinical management of COVID-19 patients. Although real-time polymerase chain reaction remains the "gold standard" to diagnose acute infections, this technique is expensive, requires trained personnel, well-equipped laboratory and is time-consuming. A prospective evaluation of the Abbott ID NOW COVID-19 point-of-care testing that uses isothermal nucleic acid amplification for the qualitative detection of SARS-CoV-2 RdRp gene was run in the Emergency Department during the third wave of COVID-19 pandemic. ID-NOW significantly simplified SARS-CoV-2 identification and COVID-19 patient triaging, being highly valuable in rapidly locating febrile patients in or out of COVID-19 areas, and can be considered as a first-line diagnostic test in the Emergency Room setting.

How to communicate with families living in complete isolation.

IMPORTANCE: During the SARS-CoV-2 pandemic, a complete physical isolation has been worldwide introduced. The impossibility of visiting their loved ones during the hospital stay causes additional distress for families: in addition to the worries about clinical recovery, they may feel exclusion and powerlessness, anxiety, depression, mistrust in the care team and post-traumatic stress disorder. The impossibility of conducting the daily meetings with families poses a challenge for healthcare professionals. OBJECTIVE: This paper aims to delineate and share consensus statements in order to enable healthcare team to provide by telephone or video calls an optimal level of communication with patient's relatives under circumstances of complete isolation. EVIDENCE REVIEW: PubMed, Cochrane Database of Systematic Reviews, Database of Abstracts and Reviews of Effectiveness and the AHCPR Clinical Guidelines and Evidence Reports were explored from 1999 to 2019. Exclusion criteria were: poor or absent relevance regarding the aim of the consensus statements, studies prior to 1999, non-English language. Since the present pandemic context is completely new, unexpected and unexplored, there are not randomised controlled trials regarding clinical communication in a setting of complete isolation. Thus, a multiprofessional taskforce of physicians, nurses, psychologists and legal experts, together with some family members and former intensive care unit patients was established by four Italian national scientific societies. Using an e-Delphi methodology, general and specific questions were posed, relevant topics were argumented, until arriving to delineate position statements and practical checklist, which were set and evaluated through an evidence-based consensus procedure. FINDINGS: Ten statements and two practical checklists for phone or video calls were drafted and evaluated; they are related to who, when, why and how family members must be given clinical information under circumstances of complete isolation. CONCLUSIONS AND RELEVANCE: The statements and the checklists offer a structured methodology in order to ensure a good-quality communication between healthcare team and family members even in isolation, confirming that time dedicated to communication has to be intended as a time of care.

Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19.

OBJECTIVES: No agent has yet been proven to be effective for the treatment of patients with severe COVID-19. METHODS: We conducted a pilot prospective open, single-arm multicentre study on off-label use of tocilizumab (TCZ) involving 63 hospitalised adult patients (56 males, age 62.6±12.5) with severe COVID-19. Clinical and laboratory parameters were prospectively collected at baseline, day 1, 2, 7 and 14. No moderate-to-severe adverse events attributable to TCZ were recorded. RESULTS: We observed a significant improvement in the levels of ferritin, C-reactive protein, D-dimer. The ratio of the partial pressure of oxygen (Pa02) to the fraction of inspired oxygen (Fi02) improved (mean±SD Pa02/Fi02 at admission: 152±53; at day 7: 283.73±115.9, at day 14: 302.2±126, p<0.05). The overall mortality was 11%; D-dimer level at baseline, but not IL-6 levels were predictors of mortality. TCZ administration within 6 days from admission in the hospital was associated with an increased likelihood of survival (HR 2.2 95%CI 1.3-6.7, p<0.05). CONCLUSIONS: In hospitalised adult patients with severe COVID-19, TCZ could be a safe option. An improvement in respiratory and laboratory parameters was observed. Future controlled trials in patients with severe illness are urgently needed to confirm the definite benefit with IL-6 target therapy.

The development of a Consensus Conference on Pediatric Procedural Sedation in the Emergency Department in Italy: from here where to?

BACKGROUND: In Italy, as in many European countries, Pediatric Emergency Medicine is not formally recognized as a pediatric subspecialty, hindering nation-wide adoption of standards of care, especially in the field of procedural sedation and analgesia (PSA) in the Emergency Department (ED). For this reason PSA in Italy is mostly neglected or performed very heterogeneously and by different providers, with no reference standard. We aimed to describe the procedures and results of the first multidisciplinary and multi-professional Consensus Conference in Italy on safe and effective pediatric PSA in Italian EDs. METHODS: The preparation, organization and conduct of the Consensus Conference, held in Florence in 2017, followed the recommended National methodological standards. Professionals from different specialties across the country were invited to participate. RESULTS: Overall 86 recommendations covering 8 themes (pre-sedation evaluation, pharmacologic agents, monitoring, equipment and discharge checklists, training, non-pharmacologic techniques, the adult ED setting, impact on hospitalizations) were developed, taking into account the Italian training system and healthcare organization characteristics. CONCLUSION: The results of the first multidisciplinary and multi-professional Consensus Conference in Italy are meant to provide up-to-date national guidance to improve the standard of care of children undergoing painful and stressful procedures in the ED. The recommendations will be periodically updated as new relevant evidence is published.

Cyanide poisoning by fire smoke inhalation: a European expert consensus.

Smoke inhalation is a common cause of cyanide poisoning during fires, resulting in injury and even death. In many cases of smoke inhalation, cyanide has increasingly been recognized as a significant toxicant. The diagnosis of cyanide poisoning remains very difficult, and failure to recognize it may result in inadequate or inappropriate treatment. Findings suggesting cyanide toxicity include the following: (a) a history of enclosed-space fire; (b) any alteration in the level of consciousness; (c) any cardiovascular changes (particularly inexplicable hypotension); and (d) elevated plasma lactate. The feasibility and safety of empiric treatment with hydroxocobalamin for fire smoke victims have been reported in the literature. On the basis of a literature review and a panel discussion, a group of European experts has proposed emergency management protocols for cyanide toxicity in fire smoke victims.

[High and low grade gastric epithelial dysplasia: clinical management, endoscopic assessment of p53]. / Displasia epiteliale gastrica a basso e ad alto grado: comportamento clinico, presentazione endoscopicae valutazione della p53.

Epithelial dysplasia is considered the only one true histological marker of gastric cancer. In the present study we have evaluated the real clinical importance of epithelial dysplasia divided into low-grade (70 patients, mean age 59.2 years) and high-grade (50 patients, mean age 58 years) dysplasia. Furthermore, it has been made a comparison with the corresponding endoscopic picture and an evaluation of the real meaning of p53 positivity. The clinical outcome subdivision of epithelial dysplasia was effected according to the criteria of Rugge: association with or progression to gastric cancer, persistence or regression. The endoscopic patterns have been divided into ulcerous lesions and non-ulcerous lesions. The immunohistochemical study has been carried out with the utilization of a p53 antibody (Dako, Glostrup, Denmark). From the analysis of the data it comes out that low-grade dysplasia is associated with or progressed to gastric cancer in a low percentage of cases (about 8.5%), while high-grade dysplasia is associated with or progressed to gastric cancer in a high percentage of cases (about 74%), by this proving itself to be a real histological marker of gastric cancer. The cases of epithelial dysplasia associated with or progressed to gastric cancer are significantly associated with an endoscopic picture of gastric ulcer (ulcer-cancer). Nonetheless, the cases of epithelial dysplasia in correspondence of non-ulcerous lesions have been noticed to be associated with or progressed to advanced gastric cancer. The evaluation of p53 did not positively correlate with the clinical progression of the epithelial dysplasia and with TNM classification in case of gastric cancer. Therefore, the evaluation of p53 does not represent a useful marker in the clinical practice.

Interferon therapy does not prevent hepatocellular carcinoma in HCV compensated cirrhosis.

BACKGROUND/AIMS: Recent experiences suggest that interferon may significantly decrease the incidence of hepatocellular carcinoma. We conducted a randomized study with interferon versus no therapy in hepatitis C virus Child A cirrhosis with abnormal alanine aminotransferase and HCV-RNA positive serum with the aim to investigate the incidence of hepatocellular carcinoma, worsening of cirrhosis's stage and death or orthotopic liver transplantation. METHODOLOGY: A cohort of 122 patients prospectively followed was analyzed retrospectively to assess the effect of interferon therapy (mean follow-up: 96 +/- 18.3 months). We only chose patients with hepatitis C virus infection who had undergone blood transfusion before 1980. Hepatitis C virus serotype was determined by hepatitis C virus serotyping 1-6 assay (Murex Biothec Limited Temple Hill, Dartford, Kent, UK). HCV-RNA level was determined by bDNA, Chiron Corporation Emeryville, CA. Diagnosis of hepatocellular carcinoma was made on the basis of the appearance of local lesions at periodic ultrasound examination of the liver and confirmed with spiral computed tomography. Fine needle biopsy under sonographic guidance was effected. Fifty-nine patients (mean age: 55.3 +/- 7) received interferon (3MU three times a week for 12 months), 8 stopped therapy for side effects, 71 did not receive interferon (mean age: 56.8 +/- 8). Baseline characteristics were similar. RESULTS: It emerges how interferon does not reduce the risk of hepatocellular carcinoma in compensated cirrhosis. In interferon treated patients an improvement in relation with worsening and death/orthotopic liver transplantation has been noted. CONCLUSIONS: The use of the interferon seems to be scarcely useful when structural alterations of the cirrhotic kind show up, as cirrhosis represents by itself a risk factor for hepatocellular carcinoma. Nevertheless, in relation to the worsening of cirrhosis's stage the interferon therapy can be useful in compensated cirrhosis.

Is it possible with an immunophenotypic study to foresee the oncologic risk of epithelial gastric dysplasia?

BACKGROUND/AIMS: Epithelial gastric dysplasia is considered the only true marker of gastric cancer. High-grade dysplasia is a surgical therapy needing lesion and low-grade dysplasia is considered a lesion with a low oncologic risk. The aim of this experience was to verify whether there are any immunohistochemical evaluations which may enable one to foresee more precisely the evolution of epithelial gastric dysplasia. METHODOLOGY: Immunophenotypic evaluation was effected in 70 cases of low-grade dysplasia (41 males, average age: 57.4) and in 50 cases of high-grade dysplasia (31 males, average age: 58). These cases were retrospectively selected and the studied samples are represented by gastric biopsies obtained in the course of endoscopy performed for dyspepsia. Epithelial gastric dysplasia diagnosis was done according to Goldstein and Lewin and the clinical subdivision was effected using the criteria of Rugge et al. Four antigens were studied using Abs against pepsinogen C, gastric foveolar M1, intestinal CAR-5 and pancreatic DU-PAN-2 Ags. RESULTS: Epithelial gastric dysplasia is characterized by a progressive reduction of gastric markers with a progressive expression of enteropancreatic antigens. Low-grade dysplasia is characterized by a frequent gastro-enteropancreatic coexpression, and high-grade dysplasia by a frequent enteropancreatic coexpression or by no markers expression. Low-grade dysplasia with greater enteropancreatic markers progresses frequently towards gastric cancer; high-grade dysplasia with enteropancreatic markers only is associated/progresses to gastric cancer, while high-grade dysplasia with gastric markers or gastric-enteropancreatic markers is included in the group with persistent or regressed cases. CONCLUSIONS: If confirmed in further studies, such results could modify the evaluation of epithelial gastric dysplasia, not only in terms of histochemical techniques, but also of immunohistochemical techniques.