Lesson by SARS-CoV-2 disease (COVID-19): whole-body CT angiography detection of "relevant" and "other/incidental" systemic vascular findings.

OBJECTIVES: Increasing evidence suggests that SARS-CoV-2 infection may lead to severe and multi-site vascular involvement. Our study aimed at assessing the frequency of vascular and extravascular events' distribution in a retrospective cohort of 42 COVID-19 patients. METHODS: Patients were evaluated by whole-body CT angiography between March 16 and April 30, 2020. Twenty-three out of the 42 patients evaluated were admitted to the intensive care unit (ICU). Vascular and extravascular findings were categorized into "relevant" or "other/incidental," first referring to the need for immediate patient care and management. Student T-test, Mann-Whitney U test, or Fisher exact test was used to compare study groups, where appropriate. RESULTS: Relevant vascular events were recorded in 71.4% of cases (n = 30). Pulmonary embolism was the most frequent in both ICU and non-ICU cases (56.5% vs. 10.5%, p = 0.002). Ischemic infarctions at several sites such as the gut, spleen, liver, brain, and kidney were detected (n = 20), with multi-site involvement in some cases. Systemic venous thrombosis occurred in 30.9% of cases compared to 7.1% of systemic arterial events, the first being significantly higher in ICU patients (p = 0.002). Among incidental findings, small-sized splanchnic arterial aneurysms were reported in 21.4% of the study population, with no significant differences in ICU and non-ICU patients. CONCLUSIONS: Vascular involvement is not negligible in COVID-19 and should be carefully investigated as it may significantly affect disease behavior and prognosis. KEY POINTS: • Relevant vascular events were recorded in 71.4% of the study population, with pulmonary embolism being the most frequent event in ICU and non-ICU cases. • Apart from the lung, other organs such as the gut, spleen, liver, brain, and kidneys were involved with episodes of ischemic infarction. Systemic venous and arterial thrombosis occurred in 30.9% and 7.1% of cases, respectively, with venous events being significantly higher in ICU patients (p = 0.002). • Among incidental findings, small-sized splanchnic arterial aneurysms were reported in 21.4% of the whole population.

Bronchoscopy in COVID-19 patients: When, how and why. Experience in clinical practice.

Severe Acute Respiratory Syndrome due to Coronavirus-19 (SARS-CoV-2) is caused by combined alveolar-capillary lung damage, with bilateral pneumonia and thrombosis, which often causes respiratory failure. Proper COVID-19 management requires high skills in airway control and the need to perform aerosol-generating procedures such as bronchoscopy, which can increase the possibility of virus spreading among healthcare professionals. In an epidemiologically delicate moment, the multidisciplinary decision on "WHEN, HOW and WHY" to perform bronchoscopies minimizing the risk of COVID-19 transmission, represented a great challenge for all specialists engaged in bronchoscopic procedures. In this work authors want to share all technical aspects of 87 videobronchoscopies performed in confirmed or suspected COVID-19 patients, from 3rd to 6th January 2020, describing the reason, the organizational and operational model and patients characteristics. Was also evaluated the impact of high-risk procedures such as bronchoscopy on the personnel involved. The disclosure of all technical details, represents, in the opinion of the authors, an important contribution, capable of providing support to all physicians engaged in bronchoscopy procedures in confirmed or suspected COVID-19 patients.

Early experience with remdesivir in SARS-CoV-2 pneumonia.

At present, there is no definitive antiviral treatment for coronavirus disease 2019 (COVID-19). We describe our early experience with remdesivir in four critically ill COVID-19 patients. Patients received a 200 mg loading dose, followed by 100 mg daily intravenously for up to 10 days. All patients had been previously treated with other antivirals before remdesivir initiation. One patient experienced a torsade de pointes requiring cardiac resuscitation and one died due to multiple organ failure. Three patients showed biochemical signs of liver injury. Lymphocyte count increased in all patients soon after remdesivir initiation. Nasal swab SARS-CoV-2 RNA became negative in three of four patients after 3 days of therapy. We observed an in vivo virological effect of remdesivir in four critically ill, COVID-19 patients, coupled with a significant burden of adverse events. Although limited by the low number of subjects studied, our preliminary experience may be relevant for clinicians treating COVID-19.

Right ventricular-arterial uncoupling independently predicts survival in COVID-19 ARDS.

AIM: To investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an Acute Respiratory Distress Syndrome (ARDS). METHODS: Ninety-four consecutive patients (mean age 64 years) admitted for acute respiratory failure on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio RESULTS: The majority of patients needed ventilatory support, which was noninvasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62 ± 13 vs. 68 ± 12 years, p = 0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO2)/fraction of inspired O2 (FIO2) ratio (270 ± 104 vs. 117 ± 57 mmHg, p < 0.001). In the non-survivors, PASP was increased (42 ± 12 vs. 30 ± 7 mmHg, p < 0.001), while TAPSE was decreased (19 ± 4 vs. 25 ± 4 mm, p < 0.001). Accordingly, the TAPSE/PASP ratio was lower than in the survivors (0.51 ± 0.22 vs. 0.89 ± 0.29 mm/mmHg, p < 0.001). At univariate/multivariable analysis, the TAPSE/PASP (HR: 0.026; 95%CI 0.01-0.579; p: 0.019) and PaO2/FIO2 (HR: 0.988; 95%CI 0.988-0.998; p: 0.018) ratios were the only independent predictors of mortality, with ROC-determined cutoff values of 159 mmHg and 0.635 mm/mmHg, respectively. CONCLUSIONS: COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO2/FIO2 in ARDS on COVID-19.

A case of intravascular large B cell lymphoma: New clinical and immunohistochemical findings.

Intravascular large B cell lymphoma (IVLBCL) is a rare extranodal non-Hodgkin lymphoma characterized by proliferation of malignant cells within the lumen of small vessels, with a predilection for the CNS and the skin. IVLBCL clinical course is highly aggressive, clinical signs and symptoms are not specific and may consist of neurological and cognitive impairment, fever of unknown origin and cutaneous lesions, lacking of a typical neuroimaging pattern. For all these reasons the diagnosis is commonly missed and the exitus is frequent, therefore post mortem evaluation is necessary to clarify the clinical history. We present a case of IVLBCL in a 62-year-old woman with unusual symptomatology, mimicking a vascular, multi-infarctual cerebropathy. Hachinski Ischemic Score was 7 suggesting a vascular dementia. Autopsy was unable to define the nature of the disease. Immunohistochemical analysis for cluster of differentiation 20 (CD20) revealed the ubiquitous presence of malignant lymphoid B-cells into the vessel of all organs analyzed, allowing the definitive diagnosis of IVLBCL. The atypical cells expressed high levels of anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and Galectin-3, and showed cellular myelocytomatosis (c-Myc) staining in <50% of tumor nuclei. Conversely, cells were immunonegative for multiple myeloma-1 (MUM1), CD3, CD44, CD30, CD34 and CD133. Fluorescent in situ hybridization analysis for MYC rearrangements was negative. The high expression of Galectin-3 provides new insights in the understanding of molecular pathogenesis of IVLBCL; indeed, such a finding represents a prognostic factor for other types of lymphoma and should, in the same way, be taken into account in IVLBCL.

Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial.

BACKGROUND: Extensively drug-resistant (XDR) Acinetobacter baumannii may cause serious infections in critically ill patients. Colistin often remains the only therapeutic option. Addition of rifampicin to colistin may be synergistic in vitro. In this study, we assessed whether the combination of colistin and rifampicin reduced the mortality of XDR A. baumannii infections compared to colistin alone. METHODS: This multicenter, parallel, randomized, open-label clinical trial enrolled 210 patients with life-threatening infections due to XDR A. baumannii from intensive care units of 5 tertiary care hospitals. Patients were randomly allocated (1:1) to either colistin alone, 2 MU every 8 hours intravenously, or colistin (as above), plus rifampicin 600 mg every 12 hours intravenously. The primary end point was overall 30-day mortality. Secondary end points were infection-related death, microbiologic eradication, and hospitalization length. RESULTS: Death within 30 days from randomization occurred in 90 (43%) subjects, without difference between treatment arms (P = .95). This was confirmed by multivariable analysis (odds ratio, 0.88 [95% confidence interval, .46-1.69], P = .71). A significant increase of microbiologic eradication rate was observed in the colistin plus rifampicin arm (P = .034). No difference was observed for infection-related death and length of hospitalization. CONCLUSIONS: In serious XDR A. baumannii infections, 30-day mortality is not reduced by addition of rifampicin to colistin. These results indicate that, at present, rifampicin should not be routinely combined with colistin in clinical practice. The increased rate of A. baumannii eradication with combination treatment could still imply a clinical benefit. CLINICAL TRIALS REGISTRATION: NCT01577862.

Postoperative pulmonary complications and mortality after major abdominal surgery. An observational multicenter prospective study.

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

Multidrug-Resistant Infections and Outcome of Critically Ill Patients with Coronavirus Disease 2019: A Single Center Experience.

Background: The aim of this study was to assess the drivers of multidrug-resistant (MDR) bacterial infection development in coronavirus disease 2019 (COVID-19) and its impact on patient outcome. Methods: Retrospective analysis on data from 32 consecutive patients with COVID-19, admitted to our intensive care unit (ICU) from March to May 2020. Outcomes considered were MDR infection and ICU mortality. Results: Fifty percent of patients developed an MDR infection during ICU stay after a median time of 8 [4-11] days. Most common MDR pathogens were carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii, causing bloodstream infections and pneumonia. MDR infections were linked to a higher length of ICU stay (p = 0.002), steroid therapy (p = 0.011), and associated with a lower ICU mortality (odds ratio: 0.439, 95% confidence interval: 0.251-0.763; p < 0.001). Low-dose aspirin intake was associated with both MDR infection (p = 0.043) and survival (p = 0.015). Among MDR patients, mortality was related with piperacillin-tazobactam use (p = 0.035) and an earlier onset of MDR infection (p = 0.042). Conclusions: MDR infections were a common complication in critically ill COVID-19 patients at our center. MDR risk was higher among those dwelling longer in the ICU and receiving steroids. However, MDR infections were not associated with a worse outcome.

Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial).

INTRODUCTION: In patients with septic shock, low levels of circulating immunoglobulins are common and their kinetics appear to be related to clinical outcome. The pivotal role of immunoglobulins in the host immune response to infection suggests that additional therapy with polyclonal intravenous immunoglobulins may be a promising option in patients with septic shock. Immunoglobulin preparations enriched with the IgM component have largely been used in sepsis, mostly at standard dosages (250 mg/kg per day), regardless of clinical severity and without any dose adjustment based on immunoglobulin serum titres or other biomarkers. We hypothesised that a personalised dose of IgM enriched preparation based on patient IgM titres and aimed to achieve a specific threshold of IgM titre is more effective in decreasing mortality than a standard dose. METHODS AND ANALYSIS: The study is designed as a multicentre, interventional, randomised, single-blinded, prospective, investigator sponsored, two-armed study. Patients with septic shock and IgM titres <60 mg/dL will be randomly assigned to an IgM titre-based treatment or a standard treatment group in a ratio of 1:1. The study will involve 12 Italian intensive care units and 356 patients will be enrolled. Patients assigned to the IgM titre-based treatment will receive a personalised daily dose based on an IgM serum titre aimed at achieving serum titres above 100 mg/dL up to discontinuation of vasoactive drugs or day 7 after enrolment. Patients assigned to the IgM standard treatment group will receive IgM enriched preparation daily for three consecutive days at the standard dose of 250 mg/kg. The primary endpoint will be all-cause mortality at 28 days. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committees of the coordinating centre (Comitato Etico dell'Area Vasta Emilia Nord) and collaborating centres. The results of the trial will be published within 12 months from the end of the study and the steering committee has the right to present them at public symposia and conferences. TRIAL REGISTRATION DETAILS: The trial protocol and information documents have received a favourable opinion from the Area Vasta Emilia Nord Ethical Committee on 12 September 2019. The trial protocol has been registered on EudraCT (2018-001613-33) on 18 April 2018 and on ClinicalTrials.gov (NCT04182737) on 2 December 2019.

Real-life experience with ceftobiprole in a tertiary-care hospital.

OBJECTIVES: Ceftobiprole is a new therapeutic option for bacterial pneumonia, with activity against most antimicrobial-resistant Gram-positive cocci, including methicillin-resistant Staphylococcus aureus. Data on the use of ceftobiprole in real life are limited. We evaluated the efficacy and safety of ceftobiprole in a context of a hospital practice. METHODS: In a single-centre, observational, retrospective clinical study, we collected data of 29 patients undergoing ceftobiprole therapy, with a focus on clinical outcomes and adverse events. RESULTS: There was a high burden of comorbidities in the study cohort, including kidney dysfunction (38%) and cancer (24%), and a high proportion of patients with sepsis/septic shock (72%), a central line (41%) or on mechanical ventilation (21%). Most infections were nosocomial (24, 82.8%). Ceftobiprole was mostly prescribed for pneumonia (17 patients, 58.6%), and bloodstream infections (10 patients, 34.5%), both empirically (9 cases, 31%) and as targeted therapy (20, 69%, with staphylococci as the dominant pathogens). It was the first-line drug in 15 cases (51.7%). Overall, a favourable clinical outcome was observed in the majority of cases (68.9%), with clinical cure in 3 (10.3%) and clinical improvement in 17 (58.6%). Failure of treatment occurred in seven cases (24.1%). Three patients experienced a definite ceftobiprole-related adverse event, with two cases of myoclonus. No major adverse effect on bone marrow, kidney or liver function was observed. CONCLUSIONS: Ceftobiprole, even outside current indications, may be a safe and effective treatment for resistant Gram-positive cocci infections where other drugs are inactive or poorly tolerated, and for salvage therapy.

Outcomes and biomarker analyses among patients with COVID-19 treated with interleukin 6 (IL-6) receptor antagonist sarilumab at a single institution in Italy.

BACKGROUND: The inflammatory pathology observed in severe COVID-19 disease caused by the 2019 novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by elevated serum levels of C reactive protein (CRP) and cytokines, including interferon gamma, interleukin 8 (IL-8), and interleukin 6 (IL-6). Initial reports from the outbreak in Italy, China and the USA have provided anecdotal evidence of improved outcomes with the administration of anti-IL-6 agents, and large-scale trials evaluating these therapies are ongoing. STUDY DESCRIPTION: In this retrospective case series, clinical outcomes and correlates of response to treatment with the IL-6 receptor antagonist sarilumab are described for 15 patients with COVID-19 from a single institution in Southern Italy. Among 10 patients whose symptoms improved after sarilumab treatment, rapid decreases in CRP levels corresponded with clinical improvement. Lower levels of IL-6 at baseline as well as lower neutrophil to lymphocyte ratio as compared with patients whose COVID-19 did not improve with treatment were associated with sarilumab-responsive disease. CONCLUSIONS: This observation may reflect a possible clinical benefit regarding early intervention with IL-6-modulatory therapies for COVID-19 and that CRP could be a potential biomarker of response to treatment.

Combined use of high doses of vasopressin and corticosteroids in a patient with Crohn's disease with refractory septic shock after intestinal perforation: a case report.

BACKGROUND: In this article, we present a clinical case of refractory septic shock resulting from intestinal perforation treated with high doses of vasopressin and hydrocortisone during emergency surgery. The use of such high doses of vasopressin for this type of shock is not described in the literature. CASE PRESENTATION: A 49-year-old white woman with grade III obesity, Crohn's disease, and an intestinal perforation presented with refractory septic shock. Initially, a low dose of vasopressin was used. Then, the dosage was increased to 0.4 U/minute; in the literature, this is defined as "salvage therapy." This therapy consists of an initial load followed by a continuous infusion of hydrocortisone. CONCLUSIONS: The significant increase in her cardiac index and stroke volume index resulted in an improvement in peripheral resistance, gas exchange, and urine output and a decrease in her heart rate, interleukin-6 level, and tumor necrosis factor-α level. The administration of high doses of vasopressin and corticosteroids was demonstrated to be safe for the immune system, to reduce the systemic inflammatory response, and to have direct cardiovascular effects. Further studies are required to examine the use of vasopressin as an initial vasopressor as well as its use in high dosages and in combination with corticosteroids.