Reviews on Recent Clinical Trials - Volume 15, Issue 4, 2020

Background: Non-invasive ventilation (NIV) is increasingly being used to treat episodes of acute respiratory failure not only in critical care and respiratory wards, but also in emergency departments. Aim: Aim of this review is to summarize the current indications for the management of NIV for respiratory failure. Methods: Current literature about the topic was reviewed and critically reported to describe the rationale and physiologic advantages of NIV in various situations of respiratory failure. Results: Early NIV use is commonly associated with the significant decrease in endotracheal intubation rate, the incidence of infective complications (especially ventilatory associated pneumonia), Intensive Care Units and the length of hospital stay and, in selected conditions, also in mortality rates. Severe acute exacerbation of chronic obstructive pulmonary disease (pH<7.35 and relative hypercarbia) and acute cardiogenic pulmonary oedema are the most common NIV indications; in these conditions NIV advantages are clearly documented. Not so evident are the NIV benefits in hypoxaemic respiratory failure occurring without prior chronic respiratory disease (De novo respiratory failure). One recent randomized control trial reported in hypoxaemic respiratory failure a survival benefit of high-flow nasal cannulae over standard oxygen therapy and bilevel NIV. Evidence suggests the advantages of NIV also in respiratory failure in immunocompromised patients or chest trauma patients. Use during a pandemic event has been assessed in several observational studies but remains controversial; there also is not sufficient evidence to support the use of NIV treatment in acute asthma exacerbation. Conclusion: NIV eliminates morbidity related to the endotracheal tube (loss of airway defense mechanism with increased risk of pneumonia) and in selected conditions (COPD exacerbation, acute cardiogenic pulmonary edema, immunosuppressed patients with pulmonary infiltrates and hypoxia) is clearly associated with a better outcome in comparison to conventional invasive ventilation. However, NIV is associated with complications, especially minor complications related to interface. Major complications like aspiration pneumonia, barotrauma and hypotension are infrequent.

Background: In symptomatic patients, admitted in emergency department for acute chest pain and dyspnea, who require an urgent treatment, a rapid diagnosis and prompt management of massive pleural effusion or hemothorax can be lifesaving. Aim: The aim of this review was to summarize the current diagnostic and therapeutic approaches for the management of the main types of pleural effusions that physicians can have in an emergency department setting. Methods: Current literature about the topic was reviewed and critically reported, adding the experience of the authors in the management of pleural effusions in emergency settings. Results: The paper analyzed the main types of pleural effusions that physicians can have to treat. It illustrated the diagnostic steps by the principal radiological instruments, with a particular emphasis to the role of ultrasonography, in facilitating diagnosis and guiding invasive procedures. Then, the principal procedures, like thoracentesis and insertion of small and large bore chest drains, are indicated and illustrated according to the characteristics and the amount of the effusion and patient clinical conditions. Conclusion: The emergency physician must have a systematic approach that allows rapid recognition, clinical cause identification and definitive management of potential urgent pleural effusions.

Background: In the last years, ultrasound technology has entered clinical practice as a tank and today, it has also allowed no-cardiologists to extend their medical examination without needing to call the consultant and having a good profile of diagnostic accuracy. The ultrasound bedside does not replace the consultant, but it allows not to perform inappropriate consultations with more savings for hospitals. Objective: The aim was to review the recently published literature to inform the clinician about the most up to date management of use bedside echography in the emergency setting. In this short review, we focused on two types of syndromes, no traumatic- hypotension and dyspnea, common to the three holistic disciplines of medicine, showing the main and basic questions and answers that ultrasound can give us for rapid identification of the problems. Methods: We conducted a systematic review using Pubmed/Medline, Ovid/Willey and Cochrane Library, combining key terms such as “cardiac ultrasound, “cardiac diseases”, “emergency medicine”, “pocus”, “dyspnea”, “hypotension”. We selected the most relevant clinical trials and review articles (excluding case reports) published in the last 19 years and in our opinion, 59 publications appeared to be the best choice according to the PRISMA statement. In additional papers identified from individual article reference lists were also included. Conclusion: Recent studies have shown a promise in establishing best practices for evaluation of heart, lung abdomen and deep vessels At the moment, bedside US is widely used in an integrated ultrasound vision just like the holistic view have internal medicine, intensive care and emergency medicine and many medical schools in Europe and the USA are inserting ultrasonography into the core curriculum, but we still have to find a standard method for the training program for minimum competence acquisition.

Background: Diabetic Ketoacidosis (DKA) is one of the most commonly encountered diabetic complication emergencies. It typically affects people with type 1 diabetes at the onset of the disease. It can also affect people with type 2 diabetes, although this is uncommon. Methods: Research and online content related to diabetes online activity is reviewed. DKA is caused by a relative or absolute deficiency of insulin and elevated levels of counter-regulatory hormones. Results: Goals of therapy are to correct dehydration, acidosis, and to reverse ketosis, gradually restoring blood glucose concentration to near normal. Conclusion: It is essential to monitor potential complications of DKA and, if necessary, to treat them and any precipitating events.

Background: Sepsis is a life-threatening organ dysfunction with high mortality and morbidity rate and with the disease progression many alterations are observed in different organs. The gastrointestinal tract is often damaged during sepsis and septic shock and main symptoms are related to increased permeability, bacterial translocation and malabsorption. These intestinal alterations can be both cause and effect of sepsis. Objective: The aim of this review is to analyze different pathways that lead to intestinal alteration in sepsis and to explore the most common methods for intestinal permeability measurement and, at the same time to evaluate if their use permit to identify patients at high risk of sepsis and eventually to estimate the prognosis. Material and Methods: The peer-reviewed articles analyzed were selected from PubMed databases using the keywords “sepsis” “gut alteration”, “bowel permeability”, “gut alteration”, “bacterial translocation”, “gut permeability tests”, “gut inflammation”. Among the 321 papers identified, 190 articles were selected, after title - abstract examination and removing the duplicates and studies on pediatric population,only 105 articles relating to sepsis and gut alterations were analyzed. Results: Integrity of the intestinal barrier plays a key role in the preventing of bacterial translocation and gut alteration related to sepsis. It is obvious that this dysfunction of the small intestine can have serious consequences and the early identification of patients at risk - to develop malabsorption or already malnourished - is very recommended to increase the survivor rate. Until now, in critical patients, the dosage of citrullinemia is easily applied test in clinical setting, in fact, it is relatively easy to administer and allows to accurately assess the functionality of enterocytes. Conclusion: The sepsis can have an important impact on the gastrointestinal function. In addition, the alteration of the permeability can become a source of systemic infection. At the moment, biological damage markers are not specific, but the dosage of LPS, citrulline, lactulose/mannitol test, FABP and fecal calprotectin are becoming an excellent alternative with high specificity and sensitivity.

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.

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.

Background: Hereditary hemorrhagic telangiectasia (HHT, or Rendu-Osler-Weber disease) is a rare inherited syndrome, characterized by artero-venous malformations (AVMs or telangiectasia) with autosomal dominant transmission. AVMs can occur in any organ of the body but most commonly it occurs in the nose, pulmonary, hepatic and cerebral circulations. In patients with HHT, we report teleangectasia of mucosa of the gastrointestinal tract. Methods: Research and online content related to HHT online activity is reviewed, and DOC writing excerpts are used to illustrate key themes. Results: Patients with HHT have a high rate of complications related to bleeding; of them gastrointestinal bleeding accounts for 10.8%. Several therapies, both medical and endoscopic, were utilized to reduce the need for transfusions and hospitalization. Conclusion: A combination of medical and endoscopic therapy is probably the best option.

Introduction: Disk Battery Ingestion (DBI) is a cause of access to the emergency department (ED), especially in pediatric age. This problem, if not well managed, may lead to serious injuries, with several complications involving the gastrointestinal and respiratory tract. Objective: The aim of this review is to analyze the literature of the last 25 years to make a decisional flow-chart that may help the emergency physician. Methods: For this review, 36 articles have been analyzed (8 articles and 28 case reports), from 1995 to 2019. Data considered from each study included year of publication, type of study, population studied, type of battery, timing of ingestion, treatment, outcomes, complications. Results: A decisional flow-chart has been configured. X-ray should be performed as the first step in every stable patient, meanwhile CT scan should be performed in unstable patients. When the battery is still localized in the esophagus, endoscopy should be performed as soon as possible, meanwhile, when the battery is beyond the esophagus, its diameter should be noted before taking a decision. Conclusion: The use of the flow-chart proposed may reduce the risk of worse consequences and severe injuries for the patients, helping the emergency physician in his decisional process.

Background and Aims: Liver cirrhosis (LC) of any origin has always been a source of several emergencies for physicians working at the Emergency Department (ER). LC patients can present with several complications that are sometimes difficult to recognize and treat. Thus, we reviewed the literature evidence for the diagnosis and management of several LC related emergencies. Methods: We conducted a search on the main medical databases for papers, reviews, metanalyses, case series, and RCTs using the following keywords and their associations: liver cirrhosis, variceal hemorrhage, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepato-renal syndrome, emergency. Results: Main LC emergencies are upper gastrointestinal hemorrhage, decompensated ascites and spontaneous bacterial peritonitis, hepatic encephalopathy, hepato-renal syndrome. Their management is partly medical and interventional. Very often, the final cure of some complications, such as hepato-renal syndrome, is represented by liver transplantation. Conclusion: Although LC prevalence is going to fall in the following years, due to HBV and HCV optimized treatments, its complications represent a significant admission percentage at the ER and challenge for physicians’ skills.

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.

Background: Critical hypoxia in this COVID-19 pandemic results in high mortality and economic loss worldwide. Initially, this disease’ pathophysiology was poorly understood and interpreted as a SARS (Severe Acute Respiratory Syndrome) pneumonia. The severe atypical lung CAT scan images alerted all countries, including the poorest, to purchase lacking sophisticated ventilators. However, up to 88% of the patients on ventilators lost their lives. It was suggested that COVID-19 could be similar to a High-Altitude Pulmonary Edema (HAPE). New observations and pathological findings are gradually clarifying the disease. Methods: As high-altitude medicine and hypoxia physiology specialists working and living in the highlands for over 50 years, we perform a perspective analysis of hypoxic diseases treated at high altitudes and compare them to Covid-19. Oxygen transport physiology, SARS-Cov-2 characteristics, and its transmission, lung imaging in COVID-19, and HAPE, as well as the causes of clinical signs and symptoms, are discussed. Results: High-altitude oxygen transport physiology has been systematically ignored. COVID-19 signs and symptoms indicate a progressive and irreversible failure in the oxygen transport system, secondary to pneumolysis produced by SARS-Cov-2’s alveolar-capillary membrane “attack”. HAPE’s pulmonary compromise is treatable and reversible. COVID-19 is associated with several diseases, with different individual outcomes, in different countries, and at different altitudes. Conclusions: The pathophysiology of High-altitude illnesses can help explain COVID-19 pathophysiology, severity, and management. Early diagnosis and use of EPO, acetylsalicylic-acid, and other anti-inflammatories, oxygen therapy, antitussives, antibiotics, and the use of Earth open-circuit- astronaut-resembling suits to return to daily activities, should all be considered. Ventilator use can be counterproductive. Immunity development is the only feasible long-term survival tool.

Backround: Oral mucositis (OM) consists of a major side effect of radiotherapy (RT) in head and neck (H-N) cancer patients and natural honey is gaining more and more scientific interest due to its beneficial effects in tissue repair. Objective: The aim of this review is to better clarify the preventive/therapeutic role of honey in the management of OM in patients with H-N cancer undergoing RT with or without chemotherapy (CT). Methods: We used the PubMed database to retrieve journal articles and the inclusion criteria were only reviews and meta-analyses that illustrated the effective use of honey for either the prevention or treatment of OM in H-N cancer patients receiving either RT alone or in combination with CT. Results: Our search resulted in 92 citations, of which 12 eventually fulfilled the inclusion criteria of our study. Decreased incidence and severity of OM, extended time of occurrence of mucositis, less weight loss and less treatment interruptions were occasionally documented with conventional honey use in the included reviews and meta-analyses. In contrast to conventional honey, manuka honey proved to be weak in improving OM management in the small number of included reviews in our search. Conclusion: Conventional honey might constitute a highly promising natural product against OM attracting much scientific interest due to its easy accessibility and low financial cost. Hence, the lack of studies with high evidence requires further advanced research to enhance the existing knowledge about the potential value of honey in radiation-induced OM in H-N cancer patients.