Serum Calprotectin in the Evaluation of Gastrointestinal Diseases: An Ace up Your Sleeve?

Background: Calprotectin (CP) is a calcium- and zinc-binding protein that plays a key role in innate immunity and in the recruitment of inflammatory cells. CP can be detected both in serum and in fecal samples. Serum CP (sCP) is more specific for autoimmune diseases, while fecal CP (fCP) has been well investigated for gastrointestinal diseases. Few studies have shown the clinical effectiveness of sCP as an acute-phase biomarker for gastrointestinal diseases. Aim: The aim of this narrative review is to discuss the role of sCP as a useful alternative biomarker of the acute-phase activity of gastrointestinal diseases and as a possible tool for screening and monitoring these diseases. Material and Methods: We searched original articles, abstracts, reviews, case reports, and clinical trials on PubMed®, Up-to-Date®, and Medscape® in the last ten years. Conclusion: We found that sCP could represent a useful biomarker in the evaluation of the inflammatory stage in patients with immune-mediated gastrointestinal diseases, but more studies are needed to promote its routine use in clinical practice as a diagnostic and prognostic biomarker as a replacement for fCP.

Emerging oral drug options for ulcerative colitis.

INTRODUCTION: Despite the availability of a variety of therapeutic compounds and improved management strategies, one-third of UC patients with moderate-to-severe disease do not benefit from the existing treatments or experience drug-related side effects. This has boosted intensive research focusing on the development of new drugs for UC therapy. This article aims to summarize the available evidence on oral drugs, which are now being explored in clinical trials or are ready to enter the clinics. AREAS COVERED: From May 15 to June 11, we searched on PubMed using the keywords 'oral drugs ulcerative colitis,' 'ulcerative colitis clinical trials,' 'UC phase 2 and 3 trials' excluding case reports, case series, phase 1 and 4 studies, and studies about approved therapies. EXPERT OPINION: The findings discussed in this article suggest that the future treatment of UC patients will be probably characterized by the possibility of using various small-molecule drugs. All these new compounds, even those belonging to the same class, differ in terms of efficacy and safety. Identification of predictors of response could help optimize the efficacy and safety of these treatments, thus improving resource allocation through a pretreatment stratification of patients.

Gastrointestinal Bleeding Due to NOACs Use: Exploring the Molecular Mechanisms.

Novel oral anticoagulants (NOACs) are drugs approved for the prevention and treatment of many thromboembolic cardiovascular conditions as a safer alternative to warfarin. We reviewed studies published in PubMed®, UpToDate®, Web of Science®, and Cochrane® about NOACs' risks and benefits in patients requiring anticoagulation, with a focus on gastrointestinal bleeding and on molecular and pathophysiological mechanisms underlying the risk of bleeding in patients treated with them. Apixaban resulted in a lower rate of gastrointestinal bleeding compared to dabigatran and rivaroxaban. However, data reported that gastrointestinal bleeding in patients treated with NOACs was less severe compared to warfarin. Studies show promising results on the increased and widespread use of NOACs in patients who require anticoagulation (for example-in case of atrial fibrillation or high risk of venous thromboembolism), reporting an overall lower risk of major bleeding events. The profile of NOACs was more effective and secure compared to warfarin, but a more careful medical prescription is required in patients who are at high risk of gastrointestinal bleeding.

Lactobacillus Reuteri DSM 17938 (Limosilactobacillus reuteri) in Diarrhea and Constipation: Two Sides of the Same Coin?

Background and Objectives: Lactobacillus reuteri DSM 17938 (L. reuteri) is a probiotic that can colonize different human body sites, including primarily the gastrointestinal tract, but also the urinary tract, the skin, and breast milk. Literature data showed that the administration of L. reuteri can be beneficial to human health. The aim of this review was to summarize current knowledge on the role of L. reuteri in the management of gastrointestinal symptoms, abdominal pain, diarrhea and constipation, both in adults and children, which are frequent reasons for admission to the emergency department (ED), in order to promote the best selection of probiotic type in the treatment of these uncomfortable and common symptoms. Materials and Methods: We searched articles on PubMed® from January 2011 to January 2021. Results: Numerous clinical studies suggested that L. reuteri may be helpful in modulating gut microbiota, eliminating infections, and attenuating the gastrointestinal symptoms of enteric colitis, antibiotic-associated diarrhea (also related to the treatment of Helicobacter pylori (HP) infection), irritable bowel syndrome, inflammatory bowel disease, and chronic constipation. In both children and in adults, L. reuteri shortens the duration of acute infectious diarrhea and improves abdominal pain in patients with colitis or inflammatory bowel disease. It can ameliorate dyspepsia and symptoms of gastritis in patients with HP infection. Moreover, it improves gut motility and chronic constipation. Conclusion: Currently, probiotics are widely used to prevent and treat numerous gastrointestinal disorders. In our opinion, L. reuteri meets all the requirements to be considered a safe, well-tolerated, and efficacious probiotic that is able to contribute to the beneficial effects on gut-human health, preventing and treating many gastrointestinal symptoms, and speeding up the recovery and discharge of patients accessing the emergency department.

Non-COVID Diseases during the Pandemic: Where Have All Other Emergencies Gone?

Background and objectives: the emergency department (ED) is frequently identified by patients as a possible solution for all healthcare problems, leading to a high rate of misuse of the ED, possibly causing overcrowding. The coronavirus disease 2019 (COVID-19) pandemic started in China; it then spread throughout Italy, with the first cases confirmed in Lombardy, Italy, in February 2020. This has totally changed the type of patients referred to EDs. The aim of this study was to analyze the reduction of ED admissions at a Second level urban teaching (Fondazione Policlinico Universitario Agostino Gemelli IRCCS) during the COVID-19 pandemic. Materials and Methods: in this retrospective observational cross-sectional study, we reviewed and compared clinical records of all the patients consecutively admitted to our ED over a 40-day period (21 February -31 March) in the last three years (2018-2019-2020). Mean age, sex, triage urgency level, day/night admission, main presentation symptom, and final diagnosis, according to different medical specialties, hospitalization, and discharge rate, were analyzed. Results: we analyzed 16,281 patient clinical records. The overall reduction in ED admissions in 2020 was 37.6% compared to 2019. In 2020, we observed an increase in triage urgency levels for ED admissions (the main presentation symptom was a fever). We noticed a significant drop in admissions for cardio-thoracic, gastroenterological, urological, otolaryngologic/ophthalmologic, and traumatological diseases. Acute neurological conditions registered only a slight, but significant, reduction. Oncology admissions were stable. Admissions for infectious diseases were 30% in 2020, compared to 5% and 6% in 2018 and 2019, respectively. In 2020, the hospitalization rate increased to 42.9% compared to 27.7%, and 26.4% in previous years. Conclusions: the drastic reduction of ED admissions during the pandemic may be associated with fear of the virus, suggesting that patients with serious illnesses did not go to the emergency room. Moreover, there was possible misuse of the ED in the previous year. In particular, worrisome data emerged regarding a drop in cardiology and neurology admissions. Those patients postponed medical attention, possibly with fatal consequences, just for fear of exposure to COVID-19, leading to unnecessary morbidity and mortality.

Proximal esophageal impedance baseline increases the yield of impedance-pH monitoring for GERD diagnosis and is associated with heartburn response to PPI.

BACKGROUND: Impairment of esophageal mucosal integrity as assessed by low mean nocturnal baseline impedance (MNBI) measured in the distal esophagus increases the diagnostic yield of impedance-pH in patients with inconclusive GERD diagnosis as defined by Lyon criteria. AIM: To assess the diagnostic yield of MNBI measurement in the proximal esophagus, and its relationship with PPI response. METHODS: Expert review of off-therapy impedance-pH tracings from consecutive patients with heartburn, 80 responders and 80 non-responders to label-dose PPI. Data were compared to those from 36 healthy controls using ROC analysis. Multivariate analysis was performed to measure the strength of association of MNBI with PPI response. RESULTS: A threshold value of 2665 Ω was defined for proximal MNBI by ROC analysis, affording 91.7% sensitivity and 86.5% specificity. Proximal and distal MNBI were significantly lower in non-responder cases as compared to responders. Adding proximal MNBI positivity to pathologic (>6%) acid exposure time (AET) and positive symptom-reflux association, the proportion of patients with abnormal impedance-pH findings increased from 74/160 (46%) to 106/160 (66.3%) (p = 0.0016). Among the 12 patients with pathologic proximal MNBI as the only positive impedance-pH finding, 9 cases (75%) were PPI responders. According to multivariate analysis, AET and pathological distal and proximal MNBI were significantly associated with PPI response, the strongest association observed for proximal MNBI. CONCLUSIONS: Impedance baseline assessment in the proximal esophagus may increase the diagnostic yield of impedance-pH monitoring. Heartburn response to PPI is directly related to ultrastructural mucosal damage in the distal and in the proximal esophagus as well.

Gut Microbiota Alteration and Its Modulation with Probiotics in Celiac Disease.

Celiac disease (CD) is a chronic inflammation of the small intestine triggered by gluten ingestion in genetically predisposed people. Recent literature studies highlight the possible role of the gut microbiota in the pathogenesis of this disease. The gut microbiota is a complex community of microorganisms that can interact with the innate and adaptative immune systems. A condition of dysbiosis, which refers to an alteration in the composition and function of the human gut microbiota, can lead to a dysregulated immune response. This condition may contribute to triggering gluten intolerance, favoring the development and/or progression of CD in genetically susceptible patients. Interestingly, studies on children and adults with CD showed a different microbiome profile in fecal samples, with a different degree of "activity" for the disease. From this point of view, our review aimed to collect and discuss modern evidence about the alteration of the gut microbiota and its modulation with probiotics, with possible future indications in the management of patients affected by CD.

Reversibility of Frail Phenotype in Patients with Inflammatory Bowel Diseases.

It was recently reported that frailty status can negatively influence the clinical course of patients with inflammatory bowel diseases (IBDs). Our recent study demonstrated that 20% of patients with an IBD are frail, and disease activity increases the risk of frailty. In the present study, we prospectively monitored this subgroup of frail patients, assessed whether the frailty status was reversible, and analyzed factors associated with frailty reversibility. Of the sixty-four frail patients with IBD enrolled, five (8%) were lost during the follow-up period and one (2%) underwent a colectomy. Eleven out of the fifty-eight (19%) patients maintained a frail phenotype during a median follow-up of 8 months (range 6-19 months), and thirty-five (60%) and twelve (21%) became pre-frail or fit, respectively. A comparison of the 58 patients at baseline and at the end of the study showed that frail phenotype reversibility occurred more frequently in patients who achieved clinical remission. A multivariate analysis showed that the improvement of the frail phenotype was inversely correlated with the persistence of clinically active disease (OR:0.1; 95% CI: 0.02-0.8) and a history of extra-intestinal manifestations (OR:0.1; 95% CI: 0.01-0.6) and positively correlated with the use of biologics (OR: 21.7; 95% CI: 3.4-263). Data indicate that the frail phenotype is a reversible condition in most IBD patients, and such a change relies on the improvement in disease activity.

Intestinal Damage, Inflammation and Microbiota Alteration during COVID-19 Infection.

BACKGROUND: The virus SARS-CoV-2 is responsible for respiratory disorders due to the fact that it mainly infects the respiratory tract using the Angiotensin-converting enzyme 2 (ACE2) receptors. ACE2 receptors are also highly expressed on intestinal cells, representing an important site of entry for the virus in the gut. Literature studies underlined that the virus infects and replicates in the gut epithelial cells, causing gastrointestinal symptoms such as diarrhea, abdominal pain, nausea/vomiting and anorexia. Moreover, the SARS-CoV-2 virus settles into the bloodstream, hyperactivating the platelets and cytokine storms and causing gut-blood barrier damage with an alteration of the gut microbiota, intestinal cell injury, intestinal vessel thrombosis leading to malabsorption, malnutrition, an increasing disease severity and mortality with short and long-period sequelae. CONCLUSION: This review summarizes the data on how SARS-CoV-2 effects on the gastrointestinal systems, including the mechanisms of inflammation, relationship with the gut microbiota, endoscopic patterns, and the role of fecal calprotectin, confirming the importance of the digestive system in clinical practice for the diagnosis and follow-up of SARS-CoV-2 infection.

Lower Gastrointestinal Bleeding in the Emergency Department: High- Volume vs. Low-Volume Peg Bowel Preparation for Colonoscopy: A Randomized Trial.

BACKGROUND: Lower Gastrointestinal Bleeding (LGIB) is a common cause of admission to the Emergency Department (ED). Early colonoscopy is the exam of choice for evaluating LGIB, and an adequate colon cleansing is essential. High-volume solution 4L-PEG is largely used, but it has some limitations. Low-volume solution 2L-PEG may improve patient's tolerability and compliance, reducing the time of administration and speeding up the exam. PATIENTS AND METHODS: We conducted a randomized 1:1, prospective observational monocentric study in 228 patients (144M/84F) with LGIB. 121 (69M/52F) received the High-Volume, while 107 (75M/32F) received Low-Volume. They completed a "satisfaction questionnaire" (taste and smell, mood, time of taking, general experience). We collected the results of the Boston Bowel Preparation Scale (BBPS) and the final diagnosis. The study was retrospectively registered on clinicaltrial.gov with protocol number NCT0536 2227. RESULTS: A mean value of BBPS 6,3 was achieved by both groups (p=0.57). Regarding smell, taste, mood and time of taking (1 to 5), we do not find any statistically differences. The overall satisfaction between the two preparations was 2.90 for low-volume compared to 3.17 for Highvolume (p=0.06). No side effects were reported. The proportion of patients without an evident source of bleeding was higher in High volume preparations compared to Low-volume (39% vs. 30%, respectively). CONCLUSION: Low volume bowel preparation showed the same efficacy and tolerability with better satisfaction compared with high volume. Low-volume could represent an effective and more desirable preparation for patients in the ED.

Randomized control trial on the efficacy of Limosilactobacillus reuteri ATCC PTA 4659 in reducing inflammatory markers in acute uncomplicated diverticulitis.

INTRODUCTION: Recent guidelines suggest treating acute uncomplicated diverticulitis (AUD) without antibiotics. We tested the efficacy of Limosilactobacillus reuteri ATCC PTA 4659 in AUD. Primary outcome was the reduction of abdominal pain and inflammatory markers [C-reactive protein (C-RP) and calprotectin]. Secondary outcome was the reduction of hours of hospitalization. PATIENTS AND METHODS: A double-blind, randomized controlled trial was conducted in 119 patients with AUD. The probiotic group (61 patients) was treated with fluids, bowel rest and L. reuteri/b.i.d. for 10 days. The placebo group (58 patients) was treated with the same therapy and placebo/b.i.d. for 10 days. All patients completed a daily visual analogue scale (VAS) for abdominal pain. RESULTS: Both groups showed a mean VAS score of 7 at enrolment and a reduction of 4 points after 3 days. C-RP value, after 72 h, decreased by 58.8% in the probiotic group and by only 40% in the placebo group (P < 0.05). Calprotectin levels, after 72 h, decreased by 17% in the probiotic group and by only 10.6% in the control group (P < 0.05). In the probiotic group, the hospitalization was done for 75.5 h compared to 83.5 in the placebo group. CONCLUSIONS: The supplementation with L. reuteri 4659 together with bowel rest and fluids significantly reduced both blood and faecal inflammatory markers compared to the placebo group.

Vitamin-K Antagonists vs. Direct Oral Anticoagulants on Severity of Upper Gastrointestinal Bleeding: A Retrospective Analysis of Italian and UK Data.

Background: Gastrointestinal bleeding (GIB) is one of most frequent and significant challenges for emergency physicians and gastroenterologists. Mortality for upper (U) GIB is high, especially in the elderly and comorbid patients. However, there is scant evidence in the literature concerning an assessment of warfarin (VKA) and direct oral anticoagulants (DOACs) in terms of upper gastrointestinal bleeding (UGIB) severity. Aims: Using data from two different settings (Italy and the UK), we aimed to compare the impact of VKA and DOACs on the severity of UGIB. Methods: Retrospective bicentric study on adult patients under VKA or DOACs admitted either to the emergency department at the Gemelli Hospital in Rome, Italy or University College Hospital in London, UK, with suspected UGIB from 01/01/2017 to 31/12/2018. Univariate analysis with Fisher's exact test, and analysis of variance (ANOVA) were used. Results: 106 patients (62 M/44 F; mean age 71.2 ± 16.9 yrs) were enrolled and divided into the VKA group (N = 57; M: 56%, mean age: 64.9 ± 21.3 yrs) and the DOAC group (N = 49; M: 61%; mean age: 77.6 ± 12.5 yrs). At univariate analysis, the VKA group presented two endoscopic diagnoses more frequently than the DOAC group (26% vs. 8%, p < 0.05), were more frequently endoscopically treated (44% vs. 22%, p < 0.05), rescoped (12% vs. 2%, p = 0.048) and hospitalized (79% vs. 53%, p = 0.01) with a longer length of stay, LOS (VKA: 58% > 5 days vs. DOAC: 68% < 5 days, p = 0.01). There was no difference in terms of hemoglobin level on admission, however the requirement of blood transfusions was higher in the VKA group (60% vs. 41%, p = 0.041). One third of the VKA group showed a lower platelet count than the DOAC group (33% vs. 8%, p = 0.01). No statistically significant differences for in-hospital mortality were observed. For the ANOVA, the type of anticoagulant used was the only significant predictor of need to rescope (p = 0.041) and a significant co-predictor for a LOS > 5 days (p = 0.009; as well as cirrhosis, p = 0.013 and age, p = 0.005). Conclusions: Our outcomes revealed a more severe UGIB in patients on VKA, but the impact of comorbidities (i.e., more cirrhotic patients in the VKA group) cannot be disregarded. DOAC subgroup descriptive analysis, even though on a little cohort, showed higher bleeding severity for rivaroxaban.

Viral Encephalitis in Adults: A Narrative Review.

Viral infections of the central nervous system cause frequent hospitalization. The pathogenesis of viral encephalitis involves both the direct action of invading pathogens and the damage generated by the inflammatory reaction they trigger. The type of signs and symptoms presented by the patient depends on the severity and location of the ongoing inflammatory process. Most of the viral encephalitides are characterized by an acute development, fever, variable alterations in consciousness (confusion, lethargy, even coma), seizures (focal and generalized) and focal neurologic signs. The specific diagnosis of encephalitis is usually based on lumbar puncture. Cerebrospinal fluid examination should be performed in all patients unless absolutely contraindicated. Also, electroencephalogram and neuroimaging play a prominent role in diagnosis. Airway protection, ventilatory support, the management of raised intracranial pressure and correction of electrolyte disorders must be immediately considered in a patient with altered mental status. The only therapy strictly recommended is acyclovir in HSV encephalitis. The use of adjunctive glucocorticoids has poor-quality evidence in HSV, EBV, or VZV encephalitis. The role of antiviral therapy in other types of viral encephalitis is not well defined.

Gut Microbiota and Acute Diverticulitis: Role of Probiotics in Management of This Delicate Pathophysiological Balance.

How can the knowledge of probiotics and their mechanisms of action be translated into clinical practice when treating patients with diverticular disease and acute diverticulitis? Changes in microbiota composition have been observed in patients who were developing acute diverticulitis, with a reduction of taxa with anti-inflammatory activity, such as Clostridium cluster IV, Lactobacilli and Bacteroides. Recent observations supported that a dysbiosis characterised by decreased presence of anti-inflammatory bacterial species might be linked to mucosal inflammation, and a vicious cycle results from a mucosal inflammation driving dysbiosis at the same time. An alteration in gut microbiota can lead to an altered activation of nerve fibres, and subsequent neuronal and muscular dysfunction, thus favoring abdominal symptoms' development. The possible role of dysbiosis and mucosal inflammation in leading to dysmotility is linked, in turn, to bacterial translocation from the lumen of the diverticulum to perivisceral area. There, a possible activation of Toll-like receptors has been described, with a subsequent inflammatory reaction at the level of the perivisceral tissues. Being aware that bacterial colonisation of diverticula is involved in the pathogenesis of acute diverticulitis, the rationale for the potential role of probiotics in the treatment of this disease becomes clearer. For this review, articles were identified using the electronic PubMed database through a comprehensive search conducted by combining key terms such as "gut microbiota", "probiotics and gut disease", "probiotics and acute diverticulitis", "probiotics and diverticular disease", "probiotics mechanism of action". However, the amount of data present on this matter is not sufficient to draw robust conclusions on the efficacy of probiotics for symptoms' management in diverticular disease.

Clinical Management of Infectious Diarrhea.

BACKGROUND: Infectious diarrhea is the most common cause of diarrhea worldwide and is responsible for more deaths than other gastrointestinal tract diseases such as gastrointestinal cancers, peptic ulcer disease or inflammatory bowel disease. Diarrheal disease still represents the 8th leading cause of death worldwide, with more than 1,6 million attributed fatalities in 2016 alone. The majority of cases can be divided into three principal clinical presentations: acute watery diarrhea lasting 5-10 days and normally self-limiting, bloody diarrhea (dysentery), and persistent diarrhea with or without intestinal malabsorption. METHODS: We performed an electronic search on PUBMED of the scientific literature concerning infectious diarrhea and its clinical management. AIM: In this review article, we analyze the most important causes of infectious diarrhea and their constellation of signs and symptoms, providing an update on the diagnostic tools available in today's practice and on the different treatment options. CONCLUSION: Even though the majority of intestinal infections are self-limiting in immunocompetent individuals, specific diagnosis and identification of the causative agent remain crucial from public health and epidemiological perspectives. Specific diagnostic investigation can be reserved for patients with severe dehydration, more severe illness, persistent fever, bloody stools, immunosuppression, and for cases of suspected nosocomial infection or outbreak and it includes complete blood count, creatinine and electrolytes evaluation, determination of leukocytes and lactoferrin presence in the stools, stool culture, together with C. difficile testing, PCR, ova and parasites' search, endoscopy and abdominal imaging. Since acute diarrhea is most often self-limited and caused by viruses, routine antibiotic use is not recommended for most adults with mild, watery diarrhea. However, when used appropriately, antibiotics are effective against shigellosis, campylobacteriosis, C. difficile colitis, traveler's diarrhea, and protozoal infections. Furthermore, antibiotics use should be considered in patients who are older than 65 years, immunocompromised, severely ill, or septic.

A Review on the Use of Reversal Agents of Direct Oral Anticogulant Drugs in Case of Gastrointestinal Bleeding.

BACKGROUND: Major bleeding is a life-threatening condition and a medical emergency with high mortality risk. It is often the complication of anticoagulant's intake. Anticoagulants are commonly used for the prevention and treatment of thrombotic events. The standard therapy with vitamin K antagonist (warfarin) has been frequently replaced by direct oral anticoagulants (DOACs). The latter agents (rivaroxaban, apixaban, edoxaban, dabigatran, and betrixaban) showed better efficacy and safety compared to standard warfarin treatment and they are recommended for the reduction of ischemic stroke. Literature data reported a high risk of gastrointestinal bleeding with DOACs, in particular with dabigatran and rivaroxaban. In case of life-threatening gastrointestinal bleeding, these patients could benefit from the use of reversal agents. METHODS: We performed an electronic search on PUBMED of the literature concerning reversal agents for DOACs and gastrointestinal bleeding in the Emergency Department from 2004 to 2020. AIM: This review summarizes the current evidence about three reversal agents idarucizumab, andexanet alfa and ciraparantag, and the use of the first two in the emergency setting in patients with active major bleeding or who need urgent surgery which physicians indicate for a better management approach in order to increase patient's safety. CONCLUSION: Although these agents have been marketed for five years (idarucizumab) and two years (andexanet alfa) respectively, and despite guidelines considering antidotes as first-line agents in treating life-threatening hemorrhage when available, these antidotes seem to gain access very slowly in the clinical practice. Cost, logistical aspects and need for plasma level determination of DOAC for an accurate therapeutic use probably have an impact on this phenomenon.. An expert multidisciplinary bleeding team should be established so as to implement international guidelines based on local resources and organization.

Management of Immunotherapy Adverse Events in Oncological Patients: Anti-CTLA-4, Anti-PD-1/PD-L1.

BACKGROUND: The widespread use of immunotherapy drugs in the oncological field has led to the spread of new toxicities compared to the more common chemotherapy treatments. This is because immunotherapy with anti-CTLA-4 (Cytotoxic T Lymphocytes-Associated Antigen 4), anti- PD-1 and anti-PD-L1 monoclonal antibodies has become the standard-of-care in a growing number of indications. Any organ or tissue can be involved, but more commonly, side effects are reported regarding skin, colon, endocrine glands, liver, lung and kidney. Other less frequent, but more serious, adverse events are neurological and myocarditis. METHODS: We performed an electronic search on PUBMED of the literature concerning immunotherapy- related toxicities and their management in oncological patients from 2007 to 2020, with particular attention to the most recent publications. AIM: To summarize the different types of immunotherapy-related toxicities, together with their incidence and diagnosis, and to simplify their management, especially in the emergency setting. CONCLUSION: Usually, for grade I toxicities, it is not recommended to stop immunotherapy; for most of grade II toxicities, immunotherapy should be postponed to when toxicity will have regressed to grade I, considering the possibility of corticosteroid treatment for most toxicities. The majority of grade III and IV require administration of high-dose corticosteroid intravenous therapy and suspension of immunotherapy. Mortality related to immune checkpoint inhibitors' toxicity, occurring at a rate of 0.3-1.3%, is well below fatality rates due to other oncologic interventions and should not discourage the promising results so far reached by immunotherapy.

Rapid Clinical Management of Leishmaniasis in Emergency Department: A Case Report with Clinical Review of Recent Literature.

Systemic or localized lympho-adenomegaly is a common cause of access to the emergency department (ED), and differential diagnosis is often complicated. The combination of anamnesis, physical examination, laboratory tests, and instrumental diagnosis are extremely important to orientate toward a rapid and correct therapy, even if a prompt discrimination of the etiology of this lymphadenomegaly is not often possible. Our aim with this review is to improve the management of a differential diagnosis between hematological and infective diseases as leishmaniasis in ED and suggest quick diagnostic techniques that might be useful for early identification. Together in the review, we describe a case report of a young man affected from visceral leishmaniasis who presented to our ED and was incorrectly addressed to the wrong ward for the study of his condition. Subsequently, we focus on the clinical presentation of visceral leishmaniasis and compare it to the most common differential diagnoses that are usually taken into account in the management of such patients.

Risk Management in First Aid for Acute Drug Intoxication.

Drug abuse (cannabis, cocaine, opiates, and synthetic drugs) is an increasing phenomenon, especially in the younger population, thus leading to more cases of intoxication requiring evaluation in the emergency department and subsequent hospitalization. In 2017, 34.2% of students reported having used an illegal psychoactive substance in their lifetime, while 26% reported having done so over the past year. We made a review about the effectiveness of the role of the temporary observation unit in the emergency department to improve management of acute drugs intoxication. We checked medical literature from the last 10 years (2009-2019). The following electronic databases were systematically searched: MEDLINE-PubMed, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials. Then, a systematic review was carried out according to the Preferred Reporting Items for Systematic Review standards. Intoxicated patients usually display a favorable medical course, few diagnostic and therapeutic interventions, a short stay in the hospital, and, when hospitalization is needed, semi-intensive therapy is a feasible solution; therefore, intoxicated patients are ideal candidates for a temporary observation unit. The emergency department is very important to manage intoxicated patients; however, the hospitalization of these patients is often not necessary.