Publications by authors named "Francesco Mojoli"

93 Publications

Lung ultrasound presentation of COVID-19 patients: phenotypes and correlations.

Intern Emerg Med 2021 Mar 1. Epub 2021 Mar 1.

Emergency Medicine Unit and Emergency Medicine Postgraduate Training Program, Internal Medicine, Vascular and Metabolic Disease Unit, Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, P.Le Golgi, 19, 27100, Pavia, Italy.

Bedside lung ultrasound (LUS) can play a role in the setting of the SarsCoV2 pneumonia pandemic. To evaluate the clinical and LUS features of COVID-19 in the ED and their potential prognostic role, a cohort of laboratory-confirmed COVID-19 patients underwent LUS upon admission in the ED. LUS score was derived from 12 fields. A prevalent LUS pattern was assigned depending on the presence of interstitial syndrome only (Interstitial Pattern), or evidence of subpleural consolidations in at least two fields (Consolidation Pattern). The endpoint was 30-day mortality. The relationship between hemogasanalysis parameters and LUS score was also evaluated. Out of 312 patients, only 36 (11.5%) did not present lung involvment, as defined by LUS score < 1. The majority of patients were admitted either in a general ward (53.8%) or in intensive care unit (9.6%), whereas 106 patients (33.9%) were discharged from the ED. In-hospital mortality was 25.3%, and 30-day survival was 67.6%. A LUS score > 13 had a 77.2% sensitivity and a 71.5% specificity (AUC 0.814; p < 0.001) in predicting mortality. LUS alterations were more frequent (64%) in the posterior lower fields. LUS score was related with P/F (R 0.68; p < 0.0001) and P/F at FiO = 21% (R 0.59; p < 0.0001). The correlation between LUS score and P/F was not influenced by the prevalent ultrasound pattern. LUS represents an effective tool in both defining diagnosis and stratifying prognosis of COVID-19 pneumonia. The correlation between LUS and hemogasanalysis parameters underscores its role in evaluating lung structure and function.
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http://dx.doi.org/10.1007/s11739-020-02620-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917171PMC
March 2021

Diagnostic accuracy of diaphragm ultrasound to predict weaning outcome: A systematic review and meta-analysis.

Int J Nurs Stud 2021 Jan 29;117:103890. Epub 2021 Jan 29.

LNC UMR1231, University of Bourgogne Franche-Comté, Dijon, France; Department of Anesthesiology and Intensive Care, University Hospital of Dijon, Dijon, France. Electronic address:

Background: The accuracy of diaphragm ultrasound for predicting weaning outcome is still debated, despite the publication of numerous studies evaluating this issue.

Objective: The aim of this systematic review and meta-analysis was to assess the diagnostic accuracy of diaphragm ultrasound for predicting weaning failure in critically ill patients.

Design And Data Sources: MEDLINE, Science direct, Cochrane Library, EMBASE and CENTRAL were searched. Two investigators independently selected studies that met the inclusion criteria, and three extracted data and performed a bias analysis using the Quality Assessment of Diagnostic Accuracy Studies-2 instrument. A bivariate model was used to estimate the pooled results for sensitivity, specificity and diagnostic odds ratio. Sources of heterogeneity were explored, and subgroup analyses were performed.

Results: Twenty-eight studies were included in the systematic review, from which 16 studies (816 patients in total) were included in the meta-analysis. The pooled sensitivity, specificity and area under the summary receiver operator characteristic curve were 0.70 (95% CI 0.57-0.80), 0.84 (95% CI 0.73-0.91), and 0.82 (95% Cl 0.78-0.85) for diaphragm thickening fraction, respectively, and 0.71 (95% CI 0.61-0.79), 0.80 (95% CI 0.73-0.86), and 0.82 (95% Cl 0.79-0.86) for diaphragm excursion, respectively. There was substantial heterogeneity among the studies. Meta-regression highlighted significant effects of prevalence of extubation failure, cut-off and risk of bias in flow and timing of the study on diaphragm ultrasound accuracy. By excluding outlier and influential studies, sensitivity was lower and specificity higher for diaphragm thickening fraction.

Conclusion: The specificity of diaphragm ultrasound for predicting the risk of extubation failure in critically ill patients was moderate-to-high. However, sensitivity was low because weaning is also affected by non-diaphragm-related factors. Further research in subgroups of critically ill patients applying a homogeneous definition of weaning and uniformly conducted measure is needed to assess the accuracy of diaphragm ultrasound.

Clinical Trial Registration: Registered on http://www.crd.york.ac.uk/PROSPERO as CRD42017058028. Tweetable abstract: Diaphragm ultrasound predicts extubation failure with high specificity. Absence of diaphragm dysfunction does not imply no risk of extubation failure.
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http://dx.doi.org/10.1016/j.ijnurstu.2021.103890DOI Listing
January 2021

Outcomes of COVID-19 patients treated with continuous positive airway pressure outside the intensive care unit.

ERJ Open Res 2021 Jan 25;7(1). Epub 2021 Jan 25.

Azienda Ospedaliero Universitaria "Maggiore della Carità", Anestesia e Terapia Intensiva, Novara, Italy.

Aim: We aimed to characterise a large population of coronavirus disease 2019 (COVID-19) patients with moderate-to-severe hypoxaemic acute respiratory failure (ARF) receiving continuous positive airway pressure (CPAP) outside the intensive care unit (ICU), and to ascertain whether the duration of CPAP application increased the risk of mortality for patients requiring intubation.

Methods: In this retrospective, multicentre cohort study, we included adult COVID-19 patients, treated with CPAP outside ICU for hypoxaemic ARF from 1 March to 15 April, 2020. We collected demographic and clinical data, including CPAP therapeutic goal, hospital length of stay and 60-day in-hospital mortality.

Results: The study included 537 patients with a median (interquartile range (IQR) age of 69 (60-76) years. 391 (73%) were male. According to the pre-defined CPAP therapeutic goal, 397 (74%) patients were included in the full treatment subgroup, and 140 (26%) in the do not intubate (DNI) subgroup. Median (IQR) CPAP duration was 4 (1-8) days, while hospital length of stay was 16 (9-27) days. 60-day in-hospital mortality was 34% (95% CI 0.304-0.384%) overall, and 21% (95% CI 0.169-0.249%) and 73% (95% CI 0.648-0.787%) for full treatment and DNI subgroups, respectively. In the full treatment subgroup, in-hospital mortality was 42% (95% CI 0.345-0.488%) for 180 (45%) CPAP failures requiring intubation, and 2% (95% CI 0.008-0.035%) for the remaining 217 (55%) patients who succeeded. Delaying intubation was associated with increased mortality (hazard ratio 1.093, 95% CI 1.010-1.184).

Conclusions: We described a large population of COVID-19 patients treated with CPAP outside ICU. Intubation delay represents a risk factor for mortality. Further investigation is needed for early identification of CPAP failures.
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http://dx.doi.org/10.1183/23120541.00541-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607967PMC
January 2021

Non-infective endocarditis in Crohn's disease: an anecdotal case of obstructive shock.

Eur Heart J Cardiovasc Imaging 2021 Jan 20. Epub 2021 Jan 20.

Anaesthesia and Intensive Care, Fondazione IRCCS Policlinico San Matteo, Anestesia e Rianimazione 1, DEA Piano -1, Viale Golgi 19, 27100 Pavia, Italy.

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http://dx.doi.org/10.1093/ehjci/jeab003DOI Listing
January 2021

Acute Thrombosis of Lower Limbs Arteries in The Acute Phase and after Recovery from COVID19.

Ann Surg 2021 Jan 7;Publish Ahead of Print. Epub 2021 Jan 7.

Vascular and Endovascular Surgery Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy Anesthesiology and Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy Infectious Diseases Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy Department of Medical, Surgical, Diagnostic and Pediatric Science, University of Pavia, Italy Sapienza University of Rome.

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http://dx.doi.org/10.1097/SLA.0000000000004700DOI Listing
January 2021

Noninvasive Ventilatory Support of COVID-19 Patients Outside the Intensive Care Units (WARd-COVID).

Ann Am Thorac Soc 2021 Jan 4. Epub 2021 Jan 4.

University of Milano-Bicocca, Milan, Italy , Department of Medicine and Surgery, Milano, Italy.

Rationale: Treatment with non-invasive ventilation (NIV) in COVID-19 is frequent. Shortage of Intensive care unit (ICU) beds led clinicians to deliver NIV also outside intensive care units (ICUs). Data about the use of NIV in COVID-19 is limited.

Objective: To describe the prevalence and clinical characteristics of patients with COVID-19 treated with NIV outside the ICUs. To investigate the factors associated with NIV failure (need for intubation or death).

Methods: In this prospective single day observational study, we enrolled adult COVID-19 patients, treated with NIV outside the ICU from thirty-one hospitals in Lombardy, Italy.

Results: We collected data on demographic, clinical characteristics, ventilatory management and patients' outcome. Of 8753 COVID-19 patients present in the hospitals on the study day, 909 (10%) were receiving NIV outside the ICU. 778/909 (85%) patients were treated with Continuous Positive Airway Pressure (CPAP), delivered by helmet in 617 (68%). NIV failed in 300 patients (37.6%), while 498 (62.4%) were discharged alive without intubation. Overall mortality was 25%. NIV failure occurred in 152/284 (53%) patients with a PaO2/FiO2 ratio < 150 mmHg. Higher C-reactive protein, lower PaO2/FiO2, and platelet counts were independently associated with increased risk of NIV failure.

Conclusions: The use of NIV outside the ICUs, in COVID-19 was common, with a predominant use of helmet CPAP, with a rate of success greater than 60% and close to 75% in full treatment patients. C-reactive protein, PaO2/FiO2, platelet counts were independently associated with increased risk of NIV failure. Clinical trial registered with ClinicalTrials.gov (NCT04382235).
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http://dx.doi.org/10.1513/AnnalsATS.202008-1080OCDOI Listing
January 2021

EBV DNA increase in COVID-19 patients with impaired lymphocyte subpopulation count.

Int J Infect Dis 2020 Dec 21;104:315-319. Epub 2020 Dec 21.

Molecular Virology Unit, Microbiology and VirologyDepartment, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy. Electronic address:

Objectives: The immunologic profile and opportunistic viral DNA increase were monitored in Italian patients with COVID-19 in order to identify markers of disease severity.

Methods: A total of 104 patients infected with SARS-CoV-2 were evaluated in the study. Of them, 42/104 (40.4%) were hospitalized in an intensive care unit (ICU) and 62/104(59.6%) in a sub-intensive care unit (SICU). Human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), Parvovirus B19 and Human Herpesvirus 6 virus reactivations were determined by real-time PCR, and lymphocyte subpopulation counts were determined by flow cytometry.

Results: Among opportunistic viruses, only EBV was consistently detected. EBV DNA was observed in 40/42 (95.2%) of the ICU patients and in 51/61 (83.6%) of the SICU patients. Comparing the two groups of patients, the EBV DNA median level among ICU patients was significantly higher than that observed in SICU patients. In parallel, a significant reduction of CD8 T cell and NK count in ICU patients as compared with SICU patients was observed (p<0.05). In contrast, B cell count was significantly increased in ICU patients (p=0.0172).

Conclusions: A correlation between reduced CD8 T cells and NK counts, EBV DNA levels and COVID-19 severity was observed. Other opportunistic viral infections were not observed. The relationship between EBV load and COVID-19 severity should be further evaluated in longitudinal studies.
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http://dx.doi.org/10.1016/j.ijid.2020.12.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833117PMC
December 2020

Multi-organ point-of-care ultrasound for COVID-19 (PoCUS4COVID): international expert consensus.

Crit Care 2020 12 24;24(1):702. Epub 2020 Dec 24.

King Abdulaziz Medical City, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.

COVID-19 has caused great devastation in the past year. Multi-organ point-of-care ultrasound (PoCUS) including lung ultrasound (LUS) and focused cardiac ultrasound (FoCUS) as a clinical adjunct has played a significant role in triaging, diagnosis and medical management of COVID-19 patients. The expert panel from 27 countries and 6 continents with considerable experience of direct application of PoCUS on COVID-19 patients presents evidence-based consensus using GRADE methodology for the quality of evidence and an expedited, modified-Delphi process for the strength of expert consensus. The use of ultrasound is suggested in many clinical situations related to respiratory, cardiovascular and thromboembolic aspects of COVID-19, comparing well with other imaging modalities. The limitations due to insufficient data are highlighted as opportunities for future research.
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http://dx.doi.org/10.1186/s13054-020-03369-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759024PMC
December 2020

Re-organization of the Vascular Surgery Department During the Acute Phase of the COVID19 Outbreak: Lessons Learned and Future Perspectives.

Ann Vasc Surg 2021 Jan 13. Epub 2021 Jan 13.

The Sapienza University of Rome, Rome, Italy.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represents a serious threat to public health because it leads to a wide spectrum of clinical manifestations. The region Lombardia (Italy) has suffered from severe problems during the acute phase of the outbreak in Italy (March-April 2020). The aim of our analysis is to report the experience of the Department of Vascular Surgery of Pavia, including the learned lessons and future perspectives, considering that the COVID-19 outbreak is in its acute phase in other continents.

Material And Methods: Single-center, retrospective, observational study based on extracted data from the medical records of all consecutive COVID-19 patients observed in our Vascular Department between March 1st and April 30th, 2020. We reviewed the records for demographic information, comorbidities, laboratory tests, and anticoagulation treatment at the time of hospital admission.

Results: We observed an important reduction in elective and urgent interventions compared to the same period of the previous year; in parallel, we observed an increase in the diagnosis of deep vein thrombosis (DVT) in hospitalized patients, especially with severe infection. In our department, four infections were reported among health workers.

Conclusions: The impact of the COVID19 pandemic on health-care delivery has been massive. A wave of vascular-related complications is expected. Regular SARS-CoV-2 screening, adequate protection, and quick reorganization of health-care resources are still needed.
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http://dx.doi.org/10.1016/j.avsg.2020.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832376PMC
January 2021

Second-order grey-scale texture analysis of pleural ultrasound images to differentiate acute respiratory distress syndrome and cardiogenic pulmonary edema.

J Clin Monit Comput 2020 Dec 12. Epub 2020 Dec 12.

Anaesthesia and Intensive Care Unit, E.O. Ospedali Galliera, Genoa, Italy.

Discriminating acute respiratory distress syndrome (ARDS) from acute cardiogenic pulmonary edema (CPE) may be challenging in critically ill patients. Aim of this study was to investigate if gray-level co-occurrence matrix (GLCM) analysis of lung ultrasound (LUS) images can differentiate ARDS from CPE. The study population consisted of critically ill patients admitted to intensive care unit (ICU) with acute respiratory failure and submitted to LUS and extravascular lung water monitoring, and of a healthy control group (HCG). A digital analysis of pleural line and subpleural space, based on the GLCM with second order statistical texture analysis, was tested. We prospectively evaluated 47 subjects: 16 with a clinical diagnosis of CPE, 8 of ARDS, and 23 healthy subjects. By comparing ARDS and CPE patients' subgroups with HCG, the one-way ANOVA models found a statistical significance in 9 out of 11 GLCM textural features. Post-hoc pairwise comparisons found statistical significance within each matrix feature for ARDS vs. CPE and CPE vs. HCG (P ≤ 0.001 for all). For ARDS vs. HCG a statistical significance occurred only in two matrix features (correlation: P = 0.005; homogeneity: P = 0.048). The quantitative method proposed has shown high diagnostic accuracy in differentiating normal lung from ARDS or CPE, and good diagnostic accuracy in differentiating CPE and ARDS. Gray-level co-occurrence matrix analysis of LUS images has the potential to aid pulmonary edemas differential diagnosis.
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http://dx.doi.org/10.1007/s10877-020-00629-1DOI Listing
December 2020

Correction to: Inhaled nitric oxide in patients admitted to intensive care unit with COVID-19 pneumonia.

Crit Care 2020 Nov 26;24(1):665. Epub 2020 Nov 26.

Department of Clinical-Surgical, Diagnostic and Paediatric Sciences, Unit of Anaesthesia and Intensive Care, University of Pavia, Pavia, Italy.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s13054-020-03390-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689390PMC
November 2020

Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome.

BMC Pulm Med 2020 Nov 16;20(1):301. Epub 2020 Nov 16.

University of Pavia and Pneumology Unit, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19.

Methods: Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n = 28) and to the Intermediate Medicine Ward (IMW) (n = 5). We analyze the differential cell count, ultrastructure of cells and Interleukin (IL)6, 8 and 10 levels.

Results: ICU patients showed a marked increase in neutrophils (1.24 × 10 ml, 0.85-2.07), lower lymphocyte (0.97 × 10 ml, 0.024-0.34) and macrophages fractions (0.43 × 10 ml, 0.34-1.62) compared to IMW patients (0.095 × 10 ml, 0.05-0.73; 0.47 × 10 ml, 0.28-1.01 and 2.14 × 10 ml, 1.17-3.01, respectively) (p < 0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p < 0.01, IL8 p < 0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p < 0.1) or antivirals (p < 0.05).

Conclusions: Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.
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http://dx.doi.org/10.1186/s12890-020-01343-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668012PMC
November 2020

Contextualizing cardiac dysfunction in critically ill patients with COVID-19.

Minerva Anestesiol 2020 12 11;86(12):1340-1345. Epub 2020 Nov 11.

Department of Cardiac Anesthesia and Intensive Care, Cardiocentro Ticino Foundation, Lugano, Switzerland.

Acute cardiac injury incidence in COVID-19 is about 13 times higher in the Intensive Care Unit (ICU)/severely ill than in less critical patients. Patients with cardiovascular comorbidities seem to be more prone to develop higher acuity of the infection, and myocardial injury has been reported amongst them in up to 15% of those hospitalized and up to 30% of ICU-admitted ones. The symptoms of over ischemia/heart failure may be challenging to distinguish as dyspnea and chest discomfort overlap with those due to COVID-19. Therefore, beside close monitoring with electrocardiography, biomarkers and, in case of demonstrated cardiac involvement, echocardiography, strategies to improve myocardial oxygen delivery should be promptly applied. The cytokine release with complement and iNO dysregulation are established mechanisms potentially leading to sepsis-related cardiomyopathy, making sepsis per se one of the potential mechanism leading to acute cardiac injury in COVID-19 patients. Moreover, the hyper-inflammation with endothelial dysfunction is likely be responsible of both pulmonary in-situ platelet aggregation and deep thrombosis potentially leading to severe pulmonary embolism and right ventricular failure. Besides the customary antithrombotic prophylaxis for critical patients, D-dimer levels and tighter coagulation monitoring are recommended and should guide the choice for anticoagulation treatment. We summarize the current knowledge regarding cardiovascular involvement in patient with COVID-19.
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http://dx.doi.org/10.23736/S0375-9393.20.14859-4DOI Listing
December 2020

Venous thromboembolism and COVID-19: a single center experience from an academic tertiary referral hospital of Northern Italy.

Intern Emerg Med 2020 Nov 8. Epub 2020 Nov 8.

Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy.

Preliminary evidence supports the notion that COVID-19 patients may have an increased susceptibility to develop venous thromboembolism (VTE). However, the magnitude of this association still needs to be defined. Furthermore, clinical predictors of thrombogenesis, and the relationship with the inflammatory status are currently unknown. On this basis, we conducted a retrospective, observational study on 259 consecutive COVID-19 patients admitted to an academic tertiary referral hospital in Northern Italy between March 19th and April 6th, 2020. Records of COVID-19 patients with a definite VTE event were reviewed for demographic information, co-morbidities, risk factors for VTE, laboratory tests, and anticoagulation treatment. Twenty-five cases among 259 COVID-19 patients developed VTE (9.6%), all of them having a Padua score > 4, although being under standard anticoagulation prophylaxis since hospital admission. In the VTE subcohort, we found a significant positive correlation between platelet count (PLT) and either C reactive protein (CRP) (p < 0.0001) or lactate dehydrogenase (LDH) (p = 0.0013), while a significant inverse correlation was observed between PLT and mean platelet volume (p < 0.0001). Platelet-to-lymphocyte ratio significantly correlated with CRP (p < 0.0001). The majority of VTE patients was male and younger compared to non-VTE patients (p = 0.002 and p = 0.005, respectively). No significant difference was found in D-dimer levels between VTE and non VTE patients, while significantly higher levels of LDH (p = 0.04) and IL-6 (p = 0.04) were observed in VTE patients in comparison to non-VTE patients. In conclusion, our findings showed a quite high prevalence of VTE in COVID-19 patients. Raised inflammatory indexes and increased serum levels of pro-inflammatory cytokines should raise the clinical suspicion of VTE.
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http://dx.doi.org/10.1007/s11739-020-02550-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648897PMC
November 2020

Acute arterial and deep venous thromboembolism in COVID-19 patients: Risk factors and personalized therapy.

Surgery 2020 12 22;168(6):987-992. Epub 2020 Sep 22.

Vascular and Endovascular Surgery Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Background: The Lombardy region suffered severely during the acute phase of the coronavirus disease 2019 outbreak in Italy (Mar-Apr 2020) with 16,000 diagnosed coronavirus disease 2019-related deaths (49% of the total coronavirus disease 2019-related deaths in Italy). In the area surrounding Pavia during the critical stage of the outbreak (Mar-Apr 2020), 1,225 of the documented 4,200 deaths were related to coronavirus disease 2019 infection, with a mortality rate of 181/100,000 inhabitants and an increase in deaths of 138% compared with the same period during previous years. Our aim was to report the experience of the Department of Vascular Surgery of Pavia (Lombardy, Italy), including the lessons learned and future perspectives regarding the management of coronavirus disease 2019 patients who developed severe acute ischemia with impending lower limb loss or deep vein thrombosis.

Materials And Methods: We carried out a retrospective data collection of coronavirus disease 2019 patients with severe acute ischemia of the lower limbs or deep vein thrombosis, which we observed in our department during the period March 1, 2020, to April 30, 2020. Primary outcomes of the analysis were postoperative mortality for all patients and amputation rates only in those coronavirus disease 2019 patients suffering from acute lower limb ischemia. Secondary outcomes were the prevalence of the disease among admitted coronavirus disease 2019 patients, and any possible correlation among inflammatory parameters, thrombolytic status, and the presence of acute ischemia or deep vein thrombosis.

Results: We observed 38 patients (28 male) with severe coronavirus disease 2019 infection (6 with lower limb arterial thrombosis and 32 with deep vein thrombosis). The median patient age was 64 years (range 30-94 y). In the arterial group, 3 had thrombosis on plaque and 3 on healthy arteries ("simple" arterial thrombosis). All underwent operative or hybrid (open/endo) revascularization; 1 patient died from major organ failure and 1 patient underwent major amputation. In the deep vein thrombosis group, 9 (28%) patients died from major organ failure, despite aggressive medical therapy. In patients with simple arterial thrombosis and those with deep vein thrombosis, we observed a decrease in inflammatory parameters (C-reactive protein) and in D-dimer and fibrinogen after aggressive therapy (P <.001).

Conclusion: Our study confirms that critically ill, coronavirus disease 2019 patients who develop arterial and deep vein thrombosis have a high risk of mortality, but, if treated properly, there is an improvement in overall survival, especially in patients of 60 years of age or younger.
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http://dx.doi.org/10.1016/j.surg.2020.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508538PMC
December 2020

Left ventricular diastolic dysfunction as a predictor of weaning failure from mechanical ventilation. Author's reply.

Intensive Care Med 2020 Nov 28;46(11):2123. Epub 2020 Sep 28.

Department of Anaesthesia and Intensive Care, Istituto di Ricovero e Cura a Carattere Scientifico, Policlinico San Matteo Foundation, Pavia, Italy.

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http://dx.doi.org/10.1007/s00134-020-06239-4DOI Listing
November 2020

Inpatient Mortality According to Level of Respiratory Support Received for Severe Acute Respiratory Syndrome Coronavirus 2 (Coronavirus Disease 2019) Infection: A Prospective Multicenter Study.

Crit Care Explor 2020 Sep 18;2(9):e0220. Epub 2020 Sep 18.

Baylor Heart and Vascular Institute, Dallas, TX.

Objectives: To describe patients according to the maximum degree of respiratory support received and report their inpatient mortality due to coronavirus disease 2019.

Design: Analysis of patients in the Coracle registry from February 22, 2020, to April 1, 2020.

Setting: Hospitals in the Piedmont, Lombardy, Tuscany, and Lazio regions of Italy.

Patients: Nine-hundred forty-eight patients hospitalized for coronavirus disease 2019.

Interventions: None.

Measurements And Main Results: Among 948 patients, 122 (12.87%) received invasive ventilation, 637 (67.19%) received supplemental oxygen only, and 189 (19.94%) received no respiratory support. The median (quartile 1-quartile 3) age was 65 years (54-76.59 yr), and there was evidence of differential respiratory treatment by decade of life ( = 0.0046); patients greater than 80 years old were generally not intubated. There were 606 men (63.9%) in this study, and they were more likely to receive respiratory support than women ( < 0.0001). The rate of in-hospital death for invasive ventilation recipients was 22.95%, 12.87% for supplemental oxygen recipients, and 7.41% for those who received neither ( = 0.0004). A sensitivity analysis of the 770 patients less than 80 years old revealed a lower, but similar mortality trend (18.02%, 8.10%, 5.23%; = 0.0008) among the 14.42%, 65.71%, and 19.87% of patients treated with mechanical ventilation, supplemental oxygen only, or neither. Overall, invasive ventilation recipients who died were significantly older than those who survived (median age: 68.5 yr [60-81.36 yr] vs 62.5 yr [55.52-71 yr]; = 0.0145).

Conclusions: Among patients hospitalized for coronavirus disease 2019, 13% received mechanical ventilation, which was associated with a mortality rate of 23%.
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http://dx.doi.org/10.1097/CCE.0000000000000220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505344PMC
September 2020

Lung ultrasound modifications induced by fibreoptic bronchoscopy may improve early bedside ventilator-associated pneumonia diagnosis: A case series.

Eur J Anaesthesiol 2020 Oct;37(10):946-949

From the Anaesthesia and Intensive Care, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy (FM, SM), Unit of Anaesthesia and Intensive Care, Department of Clinical-Surgical, Diagnostic and Paediatric Sciences, University of Pavia, Pavia, Italy (FM), Department of Anaesthesiology and Intensive Care, CHU Dijon (BB), Université Bourgogne Franche-Comté, LNC UMR866, Dijon, France, (BB) and Department of Emergency Medicine, San Luigi Gonzaga University Hospital, Torino, Italy (GV).

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http://dx.doi.org/10.1097/EJA.0000000000001254DOI Listing
October 2020

Acute deep vein thrombosis in COVID 19 hospitalized patients. Risk factors and clinical outcomes.

Phlebology 2021 Apr 14;36(3):240-242. Epub 2020 Sep 14.

Vascular and Endovascular Surgery Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

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http://dx.doi.org/10.1177/0268355520958598DOI Listing
April 2021

Inhaled nitric oxide in patients admitted to intensive care unit with COVID-19 pneumonia.

Crit Care 2020 08 17;24(1):508. Epub 2020 Aug 17.

Department of Clinical-Surgical, Diagnostic and Paediatric Sciences, Unit of Anaesthesia and Intensive Care, University of Pavia, Pavia, Italy.

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http://dx.doi.org/10.1186/s13054-020-03222-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429937PMC
August 2020

Ultrastructural Evidence of Direct Viral Damage to the Olfactory Complex in Patients Testing Positive for SARS-CoV-2.

JAMA Otolaryngol Head Neck Surg 2020 Aug 13. Epub 2020 Aug 13.

Medical Direction, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.

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http://dx.doi.org/10.1001/jamaoto.2020.2366DOI Listing
August 2020

Quantitative Lung Ultrasound: Time for a Consensus?

Chest 2020 Aug;158(2):469-470

Anaesthesia and Intensive Care, San Matteo Hospital, Pavia, Italy; Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, Unit of Anaesthesia and Intensive Care, University of Pavia, Pavia, Italy.

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http://dx.doi.org/10.1016/j.chest.2020.03.080DOI Listing
August 2020

Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy.

JAMA Intern Med 2020 10;180(10):1345-1355

Department of Anaesthesia and Intensive Care Medicine, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy.

Importance: Many patients with coronavirus disease 2019 (COVID-19) are critically ill and require care in the intensive care unit (ICU).

Objective: To evaluate the independent risk factors associated with mortality of patients with COVID-19 requiring treatment in ICUs in the Lombardy region of Italy.

Design, Setting, And Participants: This retrospective, observational cohort study included 3988 consecutive critically ill patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinating center (Fondazione IRCCS [Istituto di Ricovero e Cura a Carattere Scientifico] Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network from February 20 to April 22, 2020. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by real-time reverse transcriptase-polymerase chain reaction assay of nasopharyngeal swabs. Follow-up was completed on May 30, 2020.

Exposures: Baseline characteristics, comorbidities, long-term medications, and ventilatory support at ICU admission.

Main Outcomes And Measures: Time to death in days from ICU admission to hospital discharge. The independent risk factors associated with mortality were evaluated with a multivariable Cox proportional hazards regression.

Results: Of the 3988 patients included in this cohort study, the median age was 63 (interquartile range [IQR] 56-69) years; 3188 (79.9%; 95% CI, 78.7%-81.1%) were men, and 1998 of 3300 (60.5%; 95% CI, 58.9%-62.2%) had at least 1 comorbidity. At ICU admission, 2929 patients (87.3%; 95% CI, 86.1%-88.4%) required invasive mechanical ventilation (IMV). The median follow-up was 44 (95% CI, 40-47; IQR, 11-69; range, 0-100) days; median time from symptoms onset to ICU admission was 10 (95% CI, 9-10; IQR, 6-14) days; median length of ICU stay was 12 (95% CI, 12-13; IQR, 6-21) days; and median length of IMV was 10 (95% CI, 10-11; IQR, 6-17) days. Cumulative observation time was 164 305 patient-days. Hospital and ICU mortality rates were 12 (95% CI, 11-12) and 27 (95% CI, 26-29) per 1000 patients-days, respectively. In the subgroup of the first 1715 patients, as of May 30, 2020, 865 (50.4%) had been discharged from the ICU, 836 (48.7%) had died in the ICU, and 14 (0.8%) were still in the ICU; overall, 915 patients (53.4%) died in the hospital. Independent risk factors associated with mortality included older age (hazard ratio [HR], 1.75; 95% CI, 1.60-1.92), male sex (HR, 1.57; 95% CI, 1.31-1.88), high fraction of inspired oxygen (Fio2) (HR, 1.14; 95% CI, 1.10-1.19), high positive end-expiratory pressure (HR, 1.04; 95% CI, 1.01-1.06) or low Pao2:Fio2 ratio (HR, 0.80; 95% CI, 0.74-0.87) on ICU admission, and history of chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.28-2.19), hypercholesterolemia (HR, 1.25; 95% CI, 1.02-1.52), and type 2 diabetes (HR, 1.18; 95% CI, 1.01-1.39). No medication was independently associated with mortality (angiotensin-converting enzyme inhibitors HR, 1.17; 95% CI, 0.97-1.42; angiotensin receptor blockers HR, 1.05; 95% CI, 0.85-1.29).

Conclusions And Relevance: In this retrospective cohort study of critically ill patients admitted to ICUs in Lombardy, Italy, with laboratory-confirmed COVID-19, most patients required IMV. The mortality rate and absolute mortality were high.
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http://dx.doi.org/10.1001/jamainternmed.2020.3539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364371PMC
October 2020

Urinary Bladder Test Device to Integrate Basic Ultrasound Training for Nurses.

Ultrasound Med Biol 2020 Oct 10;46(10):2855-2860. Epub 2020 Jul 10.

Anaesthesia and Intensive Care, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Policlinico San Matteo Foundation, Pavia, Italy.

Ultrasound is a useful tool for integrating clinical assessment with a bedside reliable imaging technique, but it requires adequate training. Ultrasonographic training involves examination performed on human models, in which many pathologic findings are not always readily available for the trainee to observe. The possibility of creating test objects that reproduce pathologic images allows the provision of training courses with those elements that are not always available. Our aims were to describe how to create a urinary bladder test object and to test its image quality and usefulness. Thus, we compared computed volume with the actual filling volume for five different devices to assess their reliability in volume estimation. Moreover, we evaluated the image quality and teaching utility using a 5-point Likert-type questionnaire among a group of learners. Computed bladder volume had excellent correlation with actual filling volume (p < 0.001, R = 0.9874). Trainees judged the ultrasound exploration realistic and considered the device useful in understanding ultrasound images and improving ultrasound skills. In conclusion, our device contributes to ultrasound training by providing a realistic ultrasound image, improving image understanding and skill development and allowing reliable bladder volume estimation.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2020.06.011DOI Listing
October 2020

Prevalence of SARS-CoV-2 specific neutralising antibodies in blood donors from the Lodi Red Zone in Lombardy, Italy, as at 06 April 2020.

Euro Surveill 2020 06;25(24)

Department of Clinical Surgical Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.

We evaluated SARS-CoV-2 RNA and neutralising antibodies in blood donors (BD) residing in the Lodi Red Zone, Italy. Of 390 BDs recruited after 20 February 2020 - when the first COVID-19 case in Lombardy was identified, 91 (23%) aged 19-70 years were antibody positive. Viral RNA was detected in an additional 17 (4.3%) BDs, yielding ca 28% (108/390) with evidence of virus exposure. Five stored samples collected as early as 12 February were seropositive.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.24.2001031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315724PMC
June 2020

Lung- and Diaphragm-Protective Ventilation.

Am J Respir Crit Care Med 2020 10;202(7):950-961

Interdepartmental Division of Critical Care Medicine.

Mechanical ventilation can cause acute diaphragm atrophy and injury, and this is associated with poor clinical outcomes. Although the importance and impact of lung-protective ventilation is widely appreciated and well established, the concept of diaphragm-protective ventilation has recently emerged as a potential complementary therapeutic strategy. This Perspective, developed from discussions at a meeting of international experts convened by PLUG (the Pleural Pressure Working Group) of the European Society of Intensive Care Medicine, outlines a conceptual framework for an integrated lung- and diaphragm-protective approach to mechanical ventilation on the basis of growing evidence about mechanisms of injury. We propose targets for diaphragm protection based on respiratory effort and patient-ventilator synchrony. The potential for conflict between diaphragm protection and lung protection under certain conditions is discussed; we emphasize that when conflicts arise, lung protection must be prioritized over diaphragm protection. Monitoring respiratory effort is essential to concomitantly protect both the diaphragm and the lung during mechanical ventilation. To implement lung- and diaphragm-protective ventilation, new approaches to monitoring, to setting the ventilator, and to titrating sedation will be required. Adjunctive interventions, including extracorporeal life support techniques, phrenic nerve stimulation, and clinical decision-support systems, may also play an important role in selected patients in the future. Evaluating the clinical impact of this new paradigm will be challenging, owing to the complexity of the intervention. The concept of lung- and diaphragm-protective ventilation presents a new opportunity to potentially improve clinical outcomes for critically ill patients.
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http://dx.doi.org/10.1164/rccm.202003-0655CPDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710325PMC
October 2020