Utility of bronchoalveolar lavage for COVID-19: a perspective from the Dragon consortium.

Diagnosing COVID-19 and treating its complications remains a challenge. This review reflects the perspective of some of the Dragon (IMI 2-call 21, #101005122) research consortium collaborators on the utility of bronchoalveolar lavage (BAL) in COVID-19. BAL has been proposed as a potentially useful diagnostic tool to increase COVID-19 diagnosis sensitivity. In both critically ill and non-critically ill COVID-19 patients, BAL has a relevant role in detecting other infections or supporting alternative diagnoses and can change management decisions in up to two-thirds of patients. BAL is used to guide steroid and immunosuppressive treatment and to narrow or discontinue antibiotic treatment, reducing the use of unnecessary broad antibiotics. Moreover, cellular analysis and novel multi-omics techniques on BAL are of critical importance for understanding the microenvironment and interaction between epithelial cells and immunity, revealing novel potential prognostic and therapeutic targets. The BAL technique has been described as safe for both patients and healthcare workers in more than a thousand procedures reported to date in the literature. Based on these preliminary studies, we recognize that BAL is a feasible procedure in COVID-19 known or suspected cases, useful to properly guide patient management, and has great potential for research.

SSRIs in the course of COVID-19 pneumonia: Evidence of effectiveness of antidepressants on acute inflammation. A retrospective study.

INTRODUCTION: Relationships between inflammation and mood have been observed in terms of pro-inflammatory effects induced by depressive conditions and, in parallel, by an antidepressant-induced favorable effect on the recovery of inflammatory states. Selective serotonin reuptake inhibitor (SSRI) drugs were hypothesized to improve the prognosis of COVID-19 pneumonia, a typical acute inflammation, in terms of decreased mortality rate and pro-inflammatory cytokine serum levels. METHODS: The medical records of COVID-19 pneumonia inpatients at Careggi University Hospital (Florence) were analyzed for prognosis and Interleukin 6 (IL-6) after admission for over a period of 22 months. Medical records of patients treated at admission and not discontinued until discharge with an SSRI or with vortioxetine were identified. Two groups, one treated with antidepressants, the other not treated, were evaluated according to the mentioned parameters. Multiple linear regression and logistic regression were performed. RESULTS: The entire sample composed of 1236 records (recovered patients 77.1%, deceased patients 22.9%). The treated group (n = 107) had a better prognosis than the untreated group in spite of age and comorbidity both being greater than in the untreated group. Correspondingly, IL-6 levels in the treated group were significantly lower (p < 0.01) than the levels in the untreated group, in every comparison. CONCLUSIONS: Outcomes of this study support the hypothesis of the favorable influence of some antidepressants on the prognosis of COVID-19, possibly mediated by IL-6 modulation. Reduction in acute inflammation induced by the action of antidepressants was confirmed.

Microbiota and Glucidic Metabolism: A Link with Multiple Aspects and Perspectives.

The global prevalence of overweight and obesity has dramatically increased in the last few decades, with a significant socioeconomic burden. In this narrative review, we include clinical studies aiming to provide the necessary knowledge on the role of the gut microbiota in the development of diabetic pathology and glucose-metabolism-related disorders. In particular, the role of a certain microbial composition of the fermentative type seems to emerge without a specific link to the development in certain subjects of obesity and the chronic inflammation of the adipose tissues, which underlies the pathological development of all the diseases related to glucose metabolism and metabolic syndrome. The gut microbiota plays an important role in glucose tolerance. Conclusion. New knowledge and new information is presented on the development of individualized therapies for patients affected by all the conditions related to reduced glucose tolerance and insulin resistance.

Can selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitor antidepressants decrease the "cytokine storm" in the course of COVID-19 pneumonia?

BACKGROUND: Lots of research has been conducted to fight COVID-19 since the outbreak of the pandemic in 2020. The role of "cytokine storm" in the pathogenesis of COVID-19 pneumonia is well known. Relationship between interleukins and depression is still subject matter of the research, but a correlation between interleukin-6 and depressive disorders is proven by now. The aim of this study is to verify differences among interleukin-6 blood levels of inpatients treated with selective serotonin reuptake inhibitors and/or serotonin and norepinephrine reuptake inhibitor before and during hospitalization and of inpatients not treated with these drugs. METHODS: This is an observational study performed during the first wave of SARS Cov-2 pandemic in Italy for three months. The hospitalized patients of Internal Medicine wards and Infectious and Tropical Diseases ward of Azienda Ospedaliero-Universitaria Careggi of Florence for COVID-19 pneumonia have been divided into two subgroups (treated / not treated with antidepressants). Patients admitted to Intensive Care Unit previously have been excluded. Each patient has been evaluated concerning demographic, clinical and therapeutic features. The first dosage of interleukin-6 detected during hospitalization has been noticed. RESULTS: The entire sample included 402 patients and 8.5% (N.=34) had been treated with an antidepressant of the two considered categories before admission until discharge from hospital. Significant lower levels of interleukin-6 of recovered patients of the treated subgroup have been highlighted as compared to recovered patients of not-treated subgroup (12.1 vs. 25.4 P<0.001). These results have been pointed out in spite of higher mean age and more serious comorbidities of the treated subgroup. Nevertheless, the incidence of severe acute respiratory distress syndrome is significantly lower in the subgroup of patients with antidepressant treatment (20.6% vs. 43.2% P<0.02) as well as endotracheal intubation employment (0.0% vs. 11.7% P<0.04). The rate of deceased patients of treated-subgroup is not significantly lower than the rate of not-treated subgroup (23.5% vs. 26.4% P=0.13). CONCLUSIONS: During COVID-19 pneumonia, the production of interleukin-6 seems to be modulated in presence of antidepressant therapy. Further proofs and broader surveys are necessary.

Influence of Gender in Diabetes Mellitus and Its Complication.

In medicine, there is growing evidence that gender differences are important and lead to variations in the pathophysiology and treatment of many diseases with traits that appear to be particularly relevant in influencing the outcomes of many morbid forms. Today, the inclusion of gender in biomedical research, to improve the scientific quality and scientific relevance of knowledge, of technology is an increasingly present element precisely due to the practical implications that derive from it. Gender differences describe the biological variability between women and men, which is, in turn, related to differences in the information contained in sex chromosomes, the specific gene expression of autosomes linked to sex, the different number and quality of sex hormones, and their different effects on systems and organs, without neglecting the fact that each of the sexes has different target organs on which these hormones act. Additionally, both genders undergo metabolic changes throughout their lives, and this is especially true for women who show more dramatic changes due to their role in reproduction. Gender differences are not only the result of our genetic makeup but are also mixed with socio-cultural habits, behaviors, and lifestyles, differences between women and men, exposure to specific environmental influences, different food and lifestyle styles or stress, or different attitude in compliance with treatments and disease prevention campaigns. Gender differences also affect behavior throughout life, and physical changes can have implications for lifestyle, social roles, and mental health. Therefore, determinism and therapeutic outcome in chronic diseases are influenced by a complex combination of biological and environmental factors, not forgetting that there are many interactions of social and biological factors in women and men. This review will address the role of gender differences in the management of various forms of diabetes and its complications considering the different biological functions of hormones, the difference in body composition, physiological differences in glucose and fat metabolism, also considering the role of the microbiota. intestinal, as well as the description of gestational diabetes linked to possible pathophysiological events typical of reproduction.

Clinical Implications of Multi-Drug Resistant Organisms' Gastrointestinal Colonization in an Internal Medicine Ward: The Pandora's Box.

Background: Multi-drug resistant organisms (MDRO) are an emerging health problem with an important impact on clinical outcome in Intensive Care Units (ICUs) and immunocompromised patients. Conversely, the role of MDRO colonization in Internal Medicine is less clear. The objective of our study is to evaluate the clinical impact (namely sepsis development, in-hospital and 30-days mortality, and re-hospitalization) of MDRO colonization in Internal Medicine. Methods: Patients admitted to our Internal Medicine Unit between January 2019 and March 2020 were potentially includible. Outcomes in patients with a positive rectal swab for MDRO (RS+) and in patients without a RS+ were compared. Results of the multivariate analyses were expressed as Odds Ratios (ORs) and the corresponding 95% Confidence Interval (CI). Results: In a cohort of 2147 patients, 77 patients with RS+ were consecutively identified; 377 patients with a rectal swab negative for MDRO were randomly selected from the same cohort (five for each patient with RS+). At the multivariate analysis, RS+ was associated with an increased risk of sepsis development during hospitalization (OR 4.18; 95% CI, 1.99-8.78) and with death or re-hospitalization at 30 days (OR 4.79; 95% CI, 2.79-8.23), whereas RS+ did not appear to be associated with death during hospitalization or need for ICU transfer. Conclusions: Our results suggest for the first time a prognostic role for RS+ in Internal Medicine. Thus, assessment of rectal swab at hospital admission appears useful even in this setting. However, larger prospective studies and a cost-benefit analysis are needed to confirm our preliminary findings.

Correlation of SpO2/FiO2 and PaO2/FiO2 in patients with symptomatic COVID-19: An observational, retrospective study.

Some patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experience acute hypoxemic respiratory failure progressing toward atypical acute respiratory distress syndrome (ARDS). The aim of the study is to evaluate whether a correlation between ratio of peripheral saturation of oxygen (SpO2) and fraction of inspired oxygen (S/F) and ratio of arterial partial pressure of oxygen and fraction of inspired oxygen (P/F) exists in COVID-19-related ARDS as already known in classical ARDS. In this multicenter, retrospective, observational study, consecutive, adult (≥ 18 years) patients with symptomatic coronavirus disease 2019 (COVID-19) admitted to different COVID-19 divisions in Italy between March and December 2020 were included. Patients with SpO2 > 97% or missing information were excluded. We included 1,028 patients (median age 72 years, prevalence of males [62.2%]). A positive correlation was found between P/F and S/F (r = 0.938, p < 0.0001). A receiver operating characteristic (ROC) curve analysis showed that S/F accurately recognizes the presence of ARDS (P/F ≤ 300 mmHg) in COVID-19 patients, with a cut-off of ≤ 433% showing good sensitivity and specificity. S/F was also tested against P/F values ≤ 200 and ≤ 100 mmHg (suggestive for moderate and severe ARDS, respectively), the latter showing great accuracy for S/F ≤ 178%. S/F was accurate in predicting ARDS for SpO2 ≥ 92%. In conclusion, our findings support the routine use of S/F as a reliable surrogate of P/F in patients with COVID-19-related ARDS.

Clinical nutrition in internal medicine: An Italian survey by the scientific societies FADOI and SINPE.

OBJECTIVES: Patients hospitalized in internal medicine are frequently malnourished or at risk for malnutrition. The aim of this study, conducted by the Federation of Associations of Hospital Internists (FADOI) and the Italian Society of Artificial Nutrition and Metabolism (SINPE) was to assess the nutritional management of internal medicine inpatients in Italy, to identify critical issues and formulate practical proposals to improve nutritional treatment. METHODS: From February to April 2021, FADOI and SINPE conducted a national web-based survey, including a 13 multiple-choice item questionnaire related to three key areas: screening and assessment of malnutrition and associated/overlapping sarcopenia and dysphagia; specialist consultations; and management of nutritional support. RESULTS: Responding to the questionnaire were 266 physicians among FADOI members (10.76%). Screening for malnutrition is performed with validated tests, within standardized care pathways, or routinely, only by 22% of participants. Global Leadership Initiative on Malnutrition criteria for diagnosis of malnutrition are little used (20%). Screening for sarcopenia was insufficient as the systematic use of assessment tools (handgrip/chair test) was minimal (3%). Screening for dysphagia is not a routine procedure for at-risk patients according to 33% of participants. Systematic involvement of clinical nutrition services/units in the management of malnourished/sarcopenic patients was reported by only 17% of internists. CONCLUSIONS: To overcome the critical issues that emerged from the present study, FADOI and SINPE experts proposed practical solutions to promote the application of the most recent guidelines and to improve awareness and sensitivity to nutritional management in internal medicine real-life settings.

Hospitalization and mortality for acute exacerbation of asthma: an Italian population-based study.

Asthma is an ever-increasing disease with a highly variable prevalence among different ethnic groups. Information on hospital admission for acute exacerbation of asthma in adult patients and data regarding short-term prognosis of these patients are limited. We, thus, performed an epidemiological study on hospital admission for asthma acute exacerbation in Italy using hospital discharge database records derived from all Italian hospitals. Patients > 15 years old were identified using clinical Modification (ICD-9-CM) codes. Information on baseline characteristics, vital status at discharge, duration of hospitalization, and up to five secondary discharge diagnoses was collected. Comorbidity was evaluated using the Charlson comorbidity index (CCI). During the observation period (2013-2014), 20,056 patients with asthma acute exacerbation were hospitalized. Median length of hospitalization was 7.9 days (interquartile range 4-10) and mean in-hospital mortality was 0.8%. In-hospital mortality and length of hospitalization varied among different regions (from 0 to 2.9% and from 6.5 to 8.9 days, respectively). Old age, invasive and non-invasive mechanical ventilation, and CCI resulted as significantly associated with higher in-hospital mortality. Our study results, on a large sample of patients, confirm that hospitalization for asthma acute exacerbation is not uncommon among Italian current population. Older age, high CCI, and use of ventilator support were associated with a higher mortality rate. These findings should be analyzed to set up appropriate health care policies on patients with asthma.

Ferritin as prognostic marker in COVID-19: the FerVid study.

BACKGROUND: In COVID-19 patients the progressive clinical deterioration seems secondary to the activation of a cytokine storm. Ferritin is considered a direct mediator of the immune system and some evidences suggested a shared physio-pathogenic basis between COVID-19 and 'Hyperferritinemic Syndromes.' The aim of our study was to evaluate the prognostic role of ferritin in COVID-19 patients. METHODS: We retrospectively studied consecutive COVID-19 patients admitted to four Italian Internal Medicine Units. Role of potential prognostic markers was evaluated with binary logistic regression analysis and results were expressed as odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). Poor outcome was defined as death or need to transfer in the intensive care unit. RESULTS: Two hundred patients were included (mean age 68.75 ± 13.22 years). Ferritin value was highly elevated (>3000 ng/mL) in 8% of our population; 13% of patients were transferred to intensive care units and 12% of patients died. At multivariate analysis, highly elevated ferritin levels (OR 16.67 C.I. 4.89-57.57 p < 0.001) and hemoglobin < 10 g/dL (OR 8.88 C.I. 2.02-39.09 p = 0.004) were independently associated with a bad outcome.Patients with ferritin values > 3000 ng/ml appeared to have an inflammatory activation with elevated values of CRP and D-dimer and low values of lymphocyte count. CONCLUSION: Our results confirm the prognostic role of ferritin in hospitalized COVID-19 patients. Patients with high ferritin levels should be considered critically ill and treated in an adequate setting. Furthermore, COVID-19 seems to share some characteristics with hyperferritinemic syndromes with potential therapeutic implications.

High-dose dexamethasone treatment for COVID-19 severe acute respiratory distress syndrome: a retrospective study.

Low-dose dexamethasone reduces mortality in patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). We retrospectively analyzed the efficacy of high-dose dexamethasone in patients with COVID-19-related ARDS and evaluated factors affecting the composite outcome (death or invasive mechanical ventilation). From March 4th to April 1st 2020, 98 patients with COVID-19 pneumonia were included. Those who after at least 7 days from symptom onset presented a worsening of the respiratory function or of inflammatory biomarkers were started on intravenous high-dose dexamethasone (20 mg daily for 5 days, followed by 10 mg daily for 5 days). Most patients were males (62%) with a mean age of 69 years. Hypertension and cardiovascular disease (CVD) were prevalent. Following dexamethasone treatment, a significant improvement in PaO2/FiO2 (277.41 [178.5-374.8] mmHg vs. 146.75 [93.62-231.16] mmHg, p < 0.001), PaO2 (88.15 [76.62-112.0] mmHg vs. 65.65 [57.07-81.22] mmHg, p < 0.001), and SpO2 (96 [95-98]% vs. 94 [90-96]%, p < 0.001) was observed. A concomitant decrease in C-reactive protein and ferritin levels was found (132.25 [82.27-186.5] mg/L vs. 7.3 [3.3-24.2] mg/L and 1169 [665-2056] ng/mL vs. 874.0 [569.5-1434] ng/mL, respectively; p < 0.001 for both vs. baseline). CVD was found to increase the risk of the composite outcome (RR 7.64, 95% CI 1.24-47.06, p = 0.028). In hospitalized patients with COVID-19-related ARDS, high-dose dexamethasone rapidly improves the clinical status and decreases inflammatory biomarkers. CVD was found to increase the risk of the composite outcome. These data support the importance of randomized clinical trials with high-dose dexamethasone in COVID-19 patients.

Immune system and COVID-19 by sex differences and age.

In COVID-19 disease, are reported gender differences in relation to severity and death. The aim of this review is to highlight gender differences in the immune response to COVID-19. The included studies were identified using PubMed, until 30 October 2020. The search included the following keywords: SARS-CoV-2, COVID-19, gender, age, sex, and immune system. Literature described that females compared to males have greater inflammatory, antiviral, and humoral immune responses. In female, estrogen is a potential ally to alleviate SARS-COV-2 disease. In male, testosterone reduces vaccination response and depresses the cytokine response. In the older patients, and in particular, in female older patients, it has been reported a progressive functional decline in the immune systems. Differences by gender were reported in infection diseases, including SARS-CoV-2. These data should be confirmed by the other epidemiological studies.

The challenge of prognostic markers in acute pancreatitis: internist's point of view.

Acute pancreatitis, the most frequent hospitalization reason in internal medicine ward among gastrointestinal diseases, is burdened by high mortality rate. The disease manifests mainly in a mild form, but about 20-30% patients have a severe progress that requires intensive care. Patients presenting with acute pancreatitis should be clinically evaluated for organ failure signs and symptoms. Stratifying patients in the first days from symptoms onset is essential to determine therapy and care setting. The aim of our study is to evaluate prognostic factors for acute pancreatitis patients, hospitalized in internal medicine wards, and moreover, understanding the role of various prognostic scores validated in intensive care setting in predicting in-hospital mortality and/or admission to intensive care unit. We conducted a retrospective study enrolling all patients with diagnosis of acute pancreatitis admitted took an internal medicine ward between January 2013 and May 2019. Adverse outcome was considered in-hospital mortality and/or admission to intensive care unit. In total, 146 patients (137 with positive outcome and 9 with adverse outcome) were enrolled. The median age was (67.89 ± 16.44), with a slight prevalence of male (55.1%) compared to female (44.9%). C protein reactive (p = 0.02), creatinine (p = 0.01), sodium (p = 0.05), and troponin I (p = 0.013) after 48 h were significantly increased in patients with adverse outcome. In our study, progression in SOFA score independently increases the probability of adverse outcome in patients hospitalized with acute pancreatitis. SOFA score > 5 is highly predictive of in-hospital mortality (O.R. 32.00; C.I. 6.73-152.5; p = 0.001) compared to other scores. The use of an easy tool, validated in intensive care setting such as SOFA score, might help to better stratify the risk of in-hospital mortality and/or clinical worsening in patients hospitalized with acute pancreatitis in internal medicine ward.

Oxygen Therapy in Headache Disorders: A Systematic Review.

BACKGROUND: The global active prevalence of migraines is approximately 14.7%. Oxygen therapy may reduce the use of non-steroidal anti-inflammatory drugs (NSAIDs) which often have various negative side effects. The purpose of this systematic review is to analyze the literature on the efficacy of high flow oxygen for the management of headache disorders, compared to placebo treatment. METHODS: Studies were identified by PubMed, Web of Science and Scopus database from 1980 to the 30 October 2020. The search included the following terms: "oxygen therapy" and "headache" and "migraine". Studies were included if high flow oxygen was used in the treatment of headache disorders. All selected studies were qualitatively analyzed. RESULTS: Our literature search identified 71 studies, of which 65 were discarded and 6 were included in the meta-analysis. The random effect model did not show a pooled significant resolution of headache disorders (OR 2.08 (95% CI 0.92-4.70), p < 0.0001) in the oxygen therapy group compared to the placebo group. CONCLUSION: In our systematic review of six studies, there were no significant differences between high flow oxygen and placebo treatment groups.

Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study.

Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus high-flow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.

Gender in acute kidney disease: A narrative review.

Acute kidney injury (AKI) occurs in 3.2 - 9.6% of hospital admissions and in 2.1 - 22.1% of prevalent intensive care unit patients, worldwide. There is a sexual dimorphism in the AKI evolution with implications of sex hormones, endothelin etc. We provide a mini-review on the gender-related differences in the AKI evolution.

Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile. Objective: To evaluate the effect of early tocilizumab administration vs standard therapy in preventing clinical worsening in patients hospitalized with COVID-19 pneumonia. Design, Setting, and Participants: Prospective, open-label, randomized clinical trial that randomized patients hospitalized between March 31 and June 11, 2020, with COVID-19 pneumonia to receive tocilizumab or standard of care in 24 hospitals in Italy. Cases of COVID-19 were confirmed by polymerase chain reaction method with nasopharyngeal swab. Eligibility criteria included COVID-19 pneumonia documented by radiologic imaging, partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2/Fio2) ratio between 200 and 300 mm Hg, and an inflammatory phenotype defined by fever and elevated C-reactive protein. Interventions: Patients in the experimental arm received intravenous tocilizumab within 8 hours from randomization (8 mg/kg up to a maximum of 800 mg), followed by a second dose after 12 hours. Patients in the control arm received supportive care following the protocols of each clinical center until clinical worsening and then could receive tocilizumab as a rescue therapy. Main Outcome and Measures: The primary composite outcome was defined as entry into the intensive care unit with invasive mechanical ventilation, death from all causes, or clinical aggravation documented by the finding of a Pao2/Fio2 ratio less than 150 mm Hg, whichever came first. Results: A total of 126 patients were randomized (60 to the tocilizumab group; 66 to the control group). The median (interquartile range) age was 60.0 (53.0-72.0) years, and the majority of patients were male (77 of 126, 61.1%). Three patients withdrew from the study, leaving 123 patients available for the intention-to-treat analyses. Seventeen patients of 60 (28.3%) in the tocilizumab arm and 17 of 63 (27.0%) in the standard care group showed clinical worsening within 14 days since randomization (rate ratio, 1.05; 95% CI, 0.59-1.86). Two patients in the experimental group and 1 in the control group died before 30 days from randomization, and 6 and 5 patients were intubated in the 2 groups, respectively. The trial was prematurely interrupted after an interim analysis for futility. Conclusions and Relevance: In this randomized clinical trial of hospitalized adult patients with COVID-19 pneumonia and Pao2/Fio2 ratio between 200 and 300 mm Hg who received tocilizumab, no benefit on disease progression was observed compared with standard care. Further blinded, placebo-controlled randomized clinical trials are needed to confirm the results and to evaluate possible applications of tocilizumab in different stages of the disease. Trial Registration: ClinicalTrials.gov Identifier: NCT04346355; EudraCT Identifier: 2020-001386-37.

Diagnostic accuracy of computerized tomography (CT) angiography in detecting non-variceal gastrointestinal bleeding (NVGIB): a sistematic review.

INTRODUCTION: The American Society for Gastrointestinal Endoscopy (ASGE) has produced numerous algorithms for the management of gastrointestinal bleeding (GIB) in which endoscopy plays a major role. The aim of this Systematic Review was to evaluate the diagnostic accuracy of computerized tomography (CT) angiography in detecting non-variceal gastrointestinal bleeding (NVGIB). METHODS: Studies were identified on PubMed, Web of Science and Scopus databases from 2009 to 2019. The search performed included the following terms: "digestive" and "bleeding" as well as "acute bleeding gastrointestinal" or "acute bleeding digestive". Studies were included if enrolled adult patients and included measures of diagnostic accuracy (sensibility and specificity) of CT angiography in detecting GIB. Studies on variceal bleeding were excluded. First, a bivariate diagnostic randomeffects meta-analysis was fitted through REML (Restricted maximum likelihood approach) method, with the estimation of pooled sensitivity, specificity and SROC curve. Then, an univariate model was fitted for the 11 studies, with the estimation of pooled Diagnostic Odds Ratio and Cochrane's Q for heterogeneity. RESULTS: Eleven studies were eligible for inclusion criteria and so included in the analysis. The pooled sensitivity is 85% [75%, 92%], the pooled specificity 93% [89%, 96%]. The pooled DOR is 94.35 [37.91, 234.82]. Q for heterogeneity is not significant (p=0.377). CONCLUSIONS: CT angiography showed a good sensibility and specificity in detecting NVGIB. Therefore, it would be useful to consider CT angiography use also in the suspicion of NVGIB, especially when endoscopy is not immediately available and there are signs and symptoms of bleeding in progress.