Publications by authors named "Corradi F"

157 Publications

Association between preoperative evaluation with lung ultrasound and outcome in frail elderly patients undergoing orthopedic surgery for hip fractures: study protocol for an Italian multicenter observational prospective study (LUSHIP).

Ultrasound J 2021 Jun 7;13(1):30. Epub 2021 Jun 7.

Department of Medicine, University of Udine, Via Colugna no. 50, 33100, Udine, Italy.

Background: Hip fracture is one of the most common orthopedic causes of hospital admission in frail elderly patients. Hip fracture fixation in this class of patients is considered a high-risk procedure. Preoperative physical examination, plasma natriuretic peptide levels (BNP, Pro-BNP), and cardiovascular scoring systems (ASA-PS, RCRI, NSQIP-MICA) have all been demonstrated to underestimate the risk of postoperative complications. We designed a prospective multicenter observational study to assess whether preoperative lung ultrasound examination can predict better postoperative events thanks to the additional information they provide in the form of "indirect" and "direct" cardiac and pulmonary lung ultrasound signs.

Methods: LUSHIP is an Italian multicenter prospective observational study. Patients will be recruited on a nation-wide scale in the 12 participating centers. Patients aged  >  65 years undergoing spinal anesthesia for hip fracture fixation will be enrolled. A lung ultrasound score (LUS) will be generated based on the examination of six areas of each lung and ascribing to each area one of the four recognized aeration patterns-each of which is assigned a subscore of 0, 1, 2, or 3. Thus, the total score will have the potential to range from a minimum of 0 to a maximum of 36. The association between 30-day postoperative complications of cardiac and/or pulmonary origin and the overall mortality will be studied. Considering the fact that cardiac complications in patients undergoing hip surgery occur in approx. 30% of cases, to achieve 80% statistical power, we will need a sample size of 877 patients considering a relative risk of 1.5.

Conclusions: Lung ultrasound (LU), as a tool within the anesthesiologist's armamentarium, is becoming increasingly widespread, and its use in the preoperative setting is also starting to become more common. Should the study demonstrate the ability of LU to predict postoperative cardiac and pulmonary complications in hip fracture patients, a randomized clinical trial will be designed with the scope of improving patient outcome. Trial registration ClinicalTrials.gov, NCT04074876. Registered on August 30, 2019.
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http://dx.doi.org/10.1186/s13089-021-00230-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184059PMC
June 2021

μBrain: An Event-Driven and Fully Synthesizable Architecture for Spiking Neural Networks.

Front Neurosci 2021 19;15:664208. Epub 2021 May 19.

Ultra-Low-Power Systems for Internet of Things (IoT), Stichting Interuniversitair Micro-Elektronica Centrum (IMEC) Nederland, Eindhoven, Netherlands.

The development of brain-inspired neuromorphic computing architectures as a paradigm for Artificial Intelligence (AI) at the edge is a candidate solution that can meet strict energy and cost reduction constraints in the Internet of Things (IoT) application areas. Toward this goal, we present μBrain: the first digital yet fully event-driven without clock architecture, with co-located memory and processing capability that exploits event-based processing to reduce an always-on system's overall energy consumption (μW dynamic operation). The chip area in a 40 nm Complementary Metal Oxide Semiconductor (CMOS) digital technology is 2.82 mm including pads (without pads 1.42 mm). This small area footprint enables μBrain integration in re-trainable sensor ICs to perform various signal processing tasks, such as data preprocessing, dimensionality reduction, feature selection, and application-specific inference. We present an instantiation of the μBrain architecture in a 40 nm CMOS digital chip and demonstrate its efficiency in a radar-based gesture classification with a power consumption of 70 μW and energy consumption of 340 nJ per classification. As a digital architecture, μBrain is fully synthesizable and lends to a fast development-to-deployment cycle in Application-Specific Integrated Circuits (ASIC). To the best of our knowledge, μBrain is the first tiny-scale digital, spike-based, fully parallel, non-Von-Neumann architecture (without schedules, clocks, nor state machines). For these reasons, μBrain is ultra-low-power and offers software-to-hardware fidelity. μBrain enables always-on neuromorphic computing in IoT sensor nodes that require running on battery power for years.
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http://dx.doi.org/10.3389/fnins.2021.664208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170091PMC
May 2021

The Targeting of MRE11 or RAD51 Sensitizes Colorectal Cancer Stem Cells to CHK1 Inhibition.

Cancers (Basel) 2021 Apr 19;13(8). Epub 2021 Apr 19.

Italian Institute for Genomic Medicine (IIGM), c/o IRCSS, 10060 Candiolo, Italy.

Cancer stem cells (CSCs) drive not only tumor initiation and expansion, but also therapeutic resistance and tumor relapse. Therefore, CSC eradication is required for effective cancer therapy. In preclinical models, CSCs demonstrated high capability to tolerate even extensive genotoxic stress, including replication stress, because they are endowed with a very robust DNA damage response (DDR). This favors the survival of DNA-damaged CSCs instead of their inhibition via apoptosis or senescence. The DDR represents a unique CSC vulnerability, but the abrogation of the DDR through the inhibition of the ATR-CHK1 axis is effective only against some subtypes of CSCs, and resistance often emerges. Here, we analyzed the impact of druggable DDR players in the response of patient-derived colorectal CSCs (CRC-SCs) to CHK1/2 inhibitor prexasertib, identifying RAD51 and MRE11 as sensitizing targets enhancing prexasertib efficacy. We showed that combined inhibition of RAD51 and CHK1 (via B02+prexasertib) or MRE11 and CHK1 (via mirin+prexasertib) kills CSCs by affecting multiple genoprotective processes. In more detail, these two prexasertib-based regimens promote CSC eradication through a sequential mechanism involving the induction of elevated replication stress in a context in which cell cycle checkpoints usually activated during the replication stress response are abrogated. This leads to uncontrolled proliferation and premature entry into mitosis of replication-stressed cells, followed by the induction of mitotic catastrophe. CRC-SCs subjected to RAD51+CHK1 inhibitors or MRE11+CHK1 inhibitors are eventually eliminated, and CRC-SC tumorspheres inhibited or disaggregated, via a caspase-dependent apoptosis. These results support further clinical development of these prexasertib-based regimens in colorectal cancer patients.
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http://dx.doi.org/10.3390/cancers13081957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073980PMC
April 2021

Comparison of diuretic strategies in diuretic-resistant acute heart failure: a systematic review and network meta-analysis.

Eur Rev Med Pharmacol Sci 2021 Apr;25(7):2971-2980

Department of Medicine, University of Udine, Udine, Italy.

Objective: Up to 50% of patients hospitalized for acute heart failure (AHF) show resistance to diuretics. This condition contributes to a prolonged hospital length of stay and a higher risk of death. This review aimed to investigate whether a diuretic therapeutic approach more effective than furosemide alone exists for patients with diuretic-resistant AHF.

Materials And Methods: We identified all randomized controlled trials (RCTs) evaluating diuretic therapy in patients with diuretic-resistant AHF. We searched Pubmed, BioMed Central, and Cochrane CENTRAL databases.

Results: Six RCTs were identified, involving a total of 845 patients. The P-score ranges from 0.6663 for furosemide to 0.2294 for the tolvaptan-furosemide. We found no significant differences in efficacy for any drug comparison.

Conclusions: None of the diuretics considered in RCTs performed to date (tolvaptan, metolazone, hydrochlorothiazide, indapamide) appear to be more effective than furosemide therapy alone for the treatment of patients with diuretic-resistant AHF.
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http://dx.doi.org/10.26355/eurrev_202104_25550DOI Listing
April 2021

Arterial and Venous Cerebral Blood Flow Velocities in Healthy Volunteers.

Acta Neurochir Suppl 2021 ;131:131-134

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Transcranial Doppler ultrasound (TCD) enables assessment of brain hemodynamics through insonation of cerebral arteries and veins. Few studies have investigated whether the normal ranges of flow velocities in both arterial and venous compartments may be affected by age and sex.The purpose of this study was to determine the normal blood flow velocities across different sex and age subgroups in a cohort of healthy volunteers by studying the middle cerebral arteries (MCAs) and the straight sinus (SS).A total of 122 healthy volunteers undergoing preanesthetic assessment were recruited at Galliera Hospital in Genoa, Italy. The cohort was stratified for sex (males and females) and for age (18-44 years, 45-64 years, and ≥65 years). Data on systolic, diastolic, and mean flow velocities (FVs, FVd, and FVm, respectively) in the MCA and peak venous flow velocity in the SS (FVVs) were collected from each volunteer.The arterial FVs and FVm were significantly higher in males than in females; FVs, FVm, FVd, and FVVs increased across the age spectrum, especially in the elderly female population.Our findings suggest that there are differences in cerebrovascular flow velocities due to age and sex, which may be correlated to hormonal variations during the lifespan.
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http://dx.doi.org/10.1007/978-3-030-59436-7_27DOI Listing
June 2021

Variability of the Optic Nerve Sheath Diameter on the Basis of Sex and Age in a Cohort of Healthy Volunteers.

Acta Neurochir Suppl 2021 ;131:121-124

Brain Physics Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Many studies have demonstrated that the optic nerve sheath diameter (ONSD) is a good indicator of intracranial pressure (ICP). There are uncertainties regarding the optimal ONSD threshold, considering age and sex differences in the healthy population, and these differences could lead to uncertainties in evaluation of ONSD in pathological conditions.The aim of this prospective observational study was to investigate if age and sex could influence ONSD in a cohort of healthy Italian volunteers recruited during preanesthetic assessment for low-risk surgical procedures.The population was stratified for sex (males versus females) and for age (18-44 years, 45-64 years, and ≥65 years). The axial and longitudinal ONSD diameters were measured by two trained investigators.A significant difference in ONSD between males and females was found (median 4.2 (interquartile range 3.9-4.6) versus 4.1 (interquartile range 3.6-4.2) mm, P = 0.01), and a positive correlation between ONSD and age was found (R = 0.50, P < 0.0001).It was concluded that ONSD increases with age and is significantly larger in the healthy male population. These discrepancies should be taken into consideration when ONSD measurement is performed.
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http://dx.doi.org/10.1007/978-3-030-59436-7_25DOI Listing
June 2021

Quantitative Lung Ultrasound: Technical Aspects and Clinical Applications.

Anesthesiology 2021 06;134(6):949-965

Lung ultrasound is increasingly used in emergency departments, medical wards, and critical care units-adult, pediatric, and neonatal. In vitro and in vivo studies show that the number and type of artifacts visualized change with lung density. This has led to the idea of a quantitative lung ultrasound approach, opening up new prospects for use not only as a diagnostic but also as a monitoring tool. Consequently, the multiple scoring systems proposed in the last few years have different technical approaches and specific clinical indications, adaptable for more or less time-dependent patients. However, multiple scoring systems may generate confusion among physicians aiming at introducing lung ultrasound in their clinical practice. This review describes the various lung ultrasound scoring systems and aims to clarify their use in different settings, focusing on technical aspects, validation with reference techniques, and clinical applications.
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http://dx.doi.org/10.1097/ALN.0000000000003757DOI Listing
June 2021

Lung ultrasound for the early diagnosis of COVID-19 pneumonia: an international multicenter study.

Intensive Care Med 2021 Apr 20;47(4):444-454. Epub 2021 Mar 20.

Emergency Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Purpose: To analyze the application of a lung ultrasound (LUS)-based diagnostic approach to patients suspected of COVID-19, combining the LUS likelihood of COVID-19 pneumonia with patient's symptoms and clinical history.

Methods: This is an international multicenter observational study in 20 US and European hospitals. Patients suspected of COVID-19 were tested with reverse transcription-polymerase chain reaction (RT-PCR) swab test and had an LUS examination. We identified three clinical phenotypes based on pre-existing chronic diseases (mixed phenotype), and on the presence (severe phenotype) or absence (mild phenotype) of signs and/or symptoms of respiratory failure at presentation. We defined the LUS likelihood of COVID-19 pneumonia according to four different patterns: high (HighLUS), intermediate (IntLUS), alternative (AltLUS), and low (LowLUS) probability. The combination of patterns and phenotypes with RT-PCR results was described and analyzed.

Results: We studied 1462 patients, classified in mild (n = 400), severe (n = 727), and mixed (n = 335) phenotypes. HighLUS and IntLUS showed an overall sensitivity of 90.2% (95% CI 88.23-91.97%) in identifying patients with positive RT-PCR, with higher values in the mixed (94.7%) and severe phenotype (97.1%), and even higher in those patients with objective respiratory failure (99.3%). The HighLUS showed a specificity of 88.8% (CI 85.55-91.65%) that was higher in the mild phenotype (94.4%; CI 90.0-97.0%). At multivariate analysis, the HighLUS was a strong independent predictor of RT-PCR positivity (odds ratio 4.2, confidence interval 2.6-6.7, p < 0.0001).

Conclusion: Combining LUS patterns of probability with clinical phenotypes at presentation can rapidly identify those patients with or without COVID-19 pneumonia at bedside. This approach could support and expedite patients' management during a pandemic surge.
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http://dx.doi.org/10.1007/s00134-021-06373-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980130PMC
April 2021

Continuous infusion versus intermittent administration of meropenem in critically ill patients (MERCY): A multicenter randomized double-blind trial. Rationale and design.

Contemp Clin Trials 2021 May 6;104:106346. Epub 2021 Mar 6.

University Hospital O.O.R.R. Foggia, Foggia, Italy.

Objective: Meropenem is a β-lactam, carbapenem antibacterial agent with antimicrobial activity against gram-negative, gram-positive and anaerobic micro-organisms and is important in the empirical treatment of serious infections in Intensive Care Unit (ICU) patients. Multi-drug resistant gram-negative organisms, coupled with scarcity of new antibiotic classes, forced healthcare community to optimize the therapeutic potential of available antibiotics. Our aim is to investigate the effect of continuous infusion of meropenem against bolus administration, as indicated by a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens in a population of ICU patients.

Design: Double blind, double dummy, multicenter randomized controlled trial (1:1 allocation ratio).

Setting: Tertiary and University hospitals.

Interventions: 600 ICU patients with sepsis or septic shock, needing by clinical judgment antibiotic therapy with meropenem, will be randomized to receive a continuous infusion of meropenem 3 g/24 h or an equal dose divided into three daily boluses (i.e. 1g q8h).

Measurements: The primary endpoint will be a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens. Secondary endpoints will be death from any cause at day 90, antibiotic-free days at day 28, ICU-free days at day 28, cumulative SOFA-free (Sequential Organ Failure Assessment) score from randomization to day 28 and the two, separate, components of the primary endpoint. We expect a primary outcome reduction from 52 to 40% in the continuous infusion group.

Conclusions: The trial will provide evidence for choosing intermittent or continuous infusion of meropenem for critically ill patients with multi-drug resistant gram-negative infections.
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http://dx.doi.org/10.1016/j.cct.2021.106346DOI Listing
May 2021

Low diaphragm muscle mass predicts adverse outcome in patients hospitalized for COVID-19 pneumonia: an exploratory pilot study.

Minerva Anestesiol 2021 04 17;87(4):432-438. Epub 2021 Feb 17.

Department of Surgical, Medical, Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy.

Background: The aim of this study was to evaluate whether measurement of diaphragm thickness (DT) by ultrasonography may be a clinically useful noninvasive method for identifying patients at risk of adverse outcomes defined as need of invasive mechanical ventilation or death.

Methods: We prospectively enrolled 77 patients with laboratory-confirmed COVID-19 infection admitted to our intermediate care unit in Pisa between March 5 and March 30, 2020, with follow-up until hospital discharge or death. Logistic regression was used identify variables potentially associated with adverse outcomes and those P<0.10 were entered into a multivariate logistic regression model. Cumulative probability for lack of adverse outcomes in patients with or without low baseline diaphragm muscle mass was calculated with the Kaplan-Meier product-limit estimator.

Results: The main findings of this study are that: 1) patients who developed adverse outcomes had thinner diaphragm than those who did not (2.0 vs. 2.2 mm, P=0.001); and 2) DT and lymphocyte count were independent significant predictors of adverse outcomes, with end-expiratory DT being the strongest (ß=-708; OR=0.492; P=0.018).

Conclusions: Diaphragmatic ultrasound may be a valid tool to evaluate the risk of respiratory failure. Evaluating the need of mechanical ventilation treatment should be based not only on PaO2/FiO2, but on a more comprehensive assessment including DT because if the lungs become less compliant a thinner diaphragm, albeit free of intrinsic abnormality, may become exhausted, thus contributing to severe respiratory failure.
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http://dx.doi.org/10.23736/S0375-9393.21.15129-6DOI Listing
April 2021

Is surgery on patients recently recovered from COVID-19 safe?

Minerva Anestesiol 2021 05 16;87(5):615-617. Epub 2021 Feb 16.

Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy.

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http://dx.doi.org/10.23736/S0375-9393.21.15259-9DOI Listing
May 2021

Percutaneous Tracheostomy in COVID-19 Critically Ill Patients: Experience from 30 Consecutive Procedures.

Int Arch Otorhinolaryngol 2021 Jan 1;25(1):e135-e140. Epub 2021 Feb 1.

Cardiothoracic and Vascular Anesthesia and Intensive Care, Department of Anesthesia and Critical Care Medicine, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.

 Percutaneous tracheostomy (PT) in the intensive care unit (ICU) is a well-established practice that shows a reduced risk of wound infection compared with surgical tracheostomy, thus facilitating mechanical ventilation, nursing procedures, reduction in sedation and early mobilization.  This is an observational case-control study that compares the results of PT in ICU patients with coronavirus disease 2019 (COVID-19) prospectively enrolled to a similar group of subjects, retrospectively recruited, without COVID-19.  Ninety-eight consecutive COVID-19 patients admitted to the ICU at Pisa Azienda Ospedaliero Universitaria Pisana between March 11th and May 20 , 2020 were prospectively studied. Thirty of them underwent PT using different techniques. Another 30 non-COVID-19 ICU patients were used as a control-group. The main outcome was to evaluate the safety and feasibility of PT in COVID-19 patients. We measured the rate of complications.  Percutaneous tracheostomy was performed with different techniques in 30 of the 98 COVID-19 ICU patients admitted to the ICU. Tracheostomy was performed on day 10 (mean 10 ± 3.3) from the time of intubation. Major tracheal complications occurred in 5 patients during the procedure. In the control group of 30 ICU patients, no differences were found with regards to the timing of the tracheostomy, whereas a statistically significant difference was observed regarding complications with only one tracheal ring rupture reported.  Percutaneous tracheostomy in COVID-19 patients showed a higher rate of complications compared with controls even though the same precautions and the same expertise were applied. Larger studies are needed to understand whether the coronavirus disease itself carries an increased risk of tracheal damage.
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http://dx.doi.org/10.1055/s-0040-1718528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851370PMC
January 2021

Control of replication stress and mitosis in colorectal cancer stem cells through the interplay of PARP1, MRE11 and RAD51.

Cell Death Differ 2021 Jul 2;28(7):2060-2082. Epub 2021 Feb 2.

IIGM - Italian Institute for Genomic Medicine, c/o IRCSS, Candiolo, Italy.

Cancer stem cells (CSCs) are tumor subpopulations driving disease development, progression, relapse and therapy resistance, and their targeting ensures tumor eradication. CSCs display heterogeneous replication stress (RS), but the functionality/relevance of the RS response (RSR) centered on the ATR-CHK1 axis is debated. Here, we show that the RSR is efficient in primary CSCs from colorectal cancer (CRC-SCs), and describe unique roles for PARP1 and MRE11/RAD51. First, we demonstrated that PARP1 is upregulated in CRC-SCs resistant to several replication poisons and RSR inhibitors (RSRi). In these cells, PARP1 modulates replication fork speed resulting in low constitutive RS. Second, we showed that MRE11 and RAD51 cooperate in the genoprotection and mitosis execution of PARP1-upregulated CRC-SCs. These roles represent therapeutic vulnerabilities for CSCs. Indeed, PARP1i sensitized CRC-SCs to ATRi/CHK1i, inducing replication catastrophe, and prevented the development of resistance to CHK1i. Also, MRE11i + RAD51i selectively killed PARP1-upregulated CRC-SCs via mitotic catastrophe. These results provide the rationale for biomarker-driven clinical trials in CRC using distinct RSRi combinations.
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http://dx.doi.org/10.1038/s41418-020-00733-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257675PMC
July 2021

Acute cardiovascular events in patients with community acquired pneumonia: results from the observational prospective FADOI-ICECAP study.

BMC Infect Dis 2021 Jan 25;21(1):116. Epub 2021 Jan 25.

Medical Department, Hospital "Buon Consiglio-Fatebenefratelli", Naples, Italy.

Background: The burden of cardiovascular (CV) complications in patients hospitalised for community-acquired pneumonia (CAP) is still uncertain. Available studies used different designs and different criteria to define CV complications. We assessed the cumulative incidence of acute of CV complications during hospitalisation for CAP in Internal Medicine Units (IMUs).

Methods: This was a prospective study carried out in 26 IMUs, enrolling patients consecutively hospitalised for CAP. Defined CV complications were: newly diagnosed heart failure, acute coronary syndrome, new onset of supraventricular or ventricular arrhythmias, new onset hemorrhagic or ischemic stroke or transient ischemic attack. Outcome measures were: in-hospital and 30-day mortality, length of hospital stay and rate of 30-day re-hospitalisation.

Results: A total of 1266 patients were enrolled, of these 23.8% experienced at least a CV event, the majority (15.5%) represented by newly diagnosed decompensated heart failure, and 75% occurring within 3 days. Female gender, a history of CV disease, and more severe pneumonia were predictors of CV events. In-hospital (12.2% vs 4.7%, p < 0.0001) and 30-day (16.3% vs 8.9%, p = 0.0001) mortality was higher in patients with CV events, as well as the re-hospitalisation rate (13.3% vs 9.3%, p = 0.002), and mean hospital stay was 11.4 ± 6.9 vs 9.5 ± 5.6 days (p < 0.0001). The occurrence of CV events during hospitalisation significantly increased the risk of 30-day mortality (HR 1.69, 95% CI 1.14-2.51; p = 0.009).

Conclusion: Cardiovascular events are frequent in CAP, and their occurrence adversely affects outcome. A strict monitoring might be useful to intercept in-hospital CV complications for those patients with higher risk profile.

Trial Registration: NCT03798457 Registered 10 January 2019 - Retrospectively registered.
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http://dx.doi.org/10.1186/s12879-021-05781-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830042PMC
January 2021

Role of Low-Molecular-Weight Heparin in Hospitalized Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia: A Prospective Observational Study.

Open Forum Infect Dis 2020 Dec 19;7(12):ofaa563. Epub 2020 Nov 19.

Infectious Disease Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Background: This study was conducted to evaluate the impact of low-molecular-weight heparin (LMWH) on the outcome of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia.

Methods: This is a prospective observational study including consecutive patients with laboratory-confirmed SARS-CoV-2 pneumonia admitted to the University Hospital of Pisa (March 4-April 30, 2020). Demographic, clinical, and outcome data were collected. The primary endpoint was 30-day mortality. The secondary endpoint was a composite of death or severe acute respiratory distress syndrome (ARDS). Low-molecular-weight heparin, hydroxychloroquine, doxycycline, macrolides, antiretrovirals, remdesivir, baricitinib, tocilizumab, and steroids were evaluated as treatment exposures of interest. First, a Cox regression analysis, in which treatments were introduced as time-dependent variables, was performed to evaluate the association of exposures and outcomes. Then, a time-dependent propensity score (PS) was calculated and a PS matching was performed for each treatment variable.

Results: Among 315 patients with SARS-CoV-2 pneumonia, 70 (22.2%) died during hospital stay. The composite endpoint was achieved by 114 (36.2%) patients. Overall, 244 (77.5%) patients received LMWH, 238 (75.5%) received hydroxychloroquine, 201 (63.8%) received proteases inhibitors, 150 (47.6%) received doxycycline, 141 (44.8%) received steroids, 42 (13.3%) received macrolides, 40 (12.7%) received baricitinib, 13 (4.1%) received tocilizumab, and 13 (4.1%) received remdesivir. At multivariate analysis, LMWH was associated with a reduced risk of 30-day mortality (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.21-0.6;  < .001) and composite endpoint (HR, 0.61; 95% CI, 0.39-0.95;  = .029). The PS-matched cohort of 55 couples confirmed the same results for both primary and secondary endpoint.

Conclusions: This study suggests that LMWH might reduce the risk of in-hospital mortality and severe ARDS in coronavirus disease 2019. Randomized controlled trials are warranted to confirm these preliminary findings.
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http://dx.doi.org/10.1093/ofid/ofaa563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717381PMC
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.

Ospedale Niguarda C' Grande, Milan, Italy.

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

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

Diaphragmatic thickening fraction as a potential predictor of response to continuous positive airway pressure ventilation in Covid-19 pneumonia: A single-center pilot study.

Respir Physiol Neurobiol 2021 02 13;284:103585. Epub 2020 Nov 13.

Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Italy.

Background: In a variable number of Covid-19 patients with acute respiratory failure, non-invasive breathing support strategies cannot provide adequate oxygenation, thus making invasive mechanical ventilation necessary. Factors predicting this unfavorable outcome are unknown, but we hypothesized that diaphragmatic weakness may contribute.

Methods: We prospectively analyzed the data of 27 consecutive patients admitted to the general Intensive Care Unit (ICU) from March 19, 2020, to April 20, 2020 and submitted to continuous positive airway pressure (CPAP) before considering invasive ventilation. Diaphragmatic thickening fraction (DTF) inferred by ultrasound was determined before applying CPAP.

Results: Eighteen patients recovered with CPAP, whereas nine required invasive mechanical ventilation with longer stay in ICU (p < 0.001) and hospital (p = 0.003). At univariate logistic regression analysis, CPAP failure was significantly associated with low DTF [β: -0.396; OR: 0.673; p < 0.001] and high respiratory rate [β: 0.452; OR: 1.572; p < 0.001] but only DTF reached statistical significance at multivariate analysis [β: -0.384; OR: 0.681; p < 0.001]. The DTF best threshold predicting CPAP failure was 21.4 % (AUC: 0.944; sensitivity: 94.4 %, specificity: 88.9 %).

Conclusions: In critically ill patients with Covid-19 respiratory failure admitted to ICU, a reduced DTF could be a potential predictor of CPAP failure and requirement of invasive ventilation.
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http://dx.doi.org/10.1016/j.resp.2020.103585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664482PMC
February 2021

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

Circummaxillary Sutures in Patients With Apert, Crouzon, and Pfeiffer Syndromes Compared to Nonsyndromic Children: Growth, Orthodontic, and Surgical Implications.

Cleft Palate Craniofac J 2021 03 10;58(3):299-305. Epub 2020 Aug 10.

Department of Cranio-Maxillo-Facial Surgery, 9265San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.

Objective: To evaluate patency of circummaxillary sutures in children with Apert, Crouzon, and Pfeiffer Syndromes and to compare it to a nonsyndromic matched control group.

Design: Case-control study.

Setting: Tertiary care public hospital.

Materials And Methods: Thirty-eight computed tomography (CT) scans of patients affected by syndromic craniofacial synostosis (13 patients with Apert syndrome, 20 patients with Crouzon syndrome, and 5 patients with Pfeiffer syndrome), average age 5 ± 2.8 years, range 1.9 to 12 years, were compared to age- and sex-matched control CTs of 38 nonsyndromic children. Computed tomography scans of the study group had to be performed prior to any midfacial surgery.

Main Outcome Measures: Midpalatal suture, zygomaticomaxillary sutures, and pterigomaxillary sutures were evaluated and scored.

Results: The syndromic group showed a significant earlier ossification of all sutures compared to the nonsyndromic group. Significant differences were already present in early childhood and continued through adolescence.

Conclusions: Based on the differences in terms of maxillary sutural ossification identified, midfacial hypoplasia does not seem to be only secondary to premature cranial base ossification, but also to primary synostosis of facial sutures, thus providing new insights into the pathogenesis of midface deficiency in children with craniofacial-synostosis. Care should be taken when planning any maxillary orthopedics, such as expansion or maxillary protraction, given the high frequency of early fusion of circummaxillary sutures.
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http://dx.doi.org/10.1177/1055665620947616DOI Listing
March 2021

Quantitative Lung Ultrasound: Time for a Consensus?

Chest 2020 08;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

When data interpretation should not rely on the magnitude of P values: the example of ANDROMEDA SHOCK trial.

Ann Transl Med 2020 Jun;8(12):802

Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy.

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http://dx.doi.org/10.21037/atm.2020.01.49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333159PMC
June 2020

Lung, Heart, Vascular, and Diaphragm Ultrasound Examination of COVID-19 Patients: A Comprehensive Approach.

J Cardiothorac Vasc Anesth 2021 06 11;35(6):1866-1874. Epub 2020 Jun 11.

Department of Medicine, Anesthesia and Intensive Care Clinic, University of Udine, Udine, Italy; Department of Anesthesia and Intensive care, University-Hospital of Udine, Italy, Udine, Italy.

Lung ultrasound (LU) has a multitude of features and capacities that make it a useful medical tool to assist physicians contending with the pandemic spread of novel coronavirus disease-2019 (COVID-19) caused by coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, an LU approach to patients with suspected COVID-19 is being implemented worldwide. In noncritical COVID-19 patients, 2 new LU signs have been described and proposed, the "waterfall" and the "light beam" signs. Both signs have been hypothesized to increase the diagnostic accuracy of LU for COVID-19 interstitial pneumonia. In critically ill patients, a distinct pattern of LU changes seems to follow the disease's progression, and this information can be used to guide decisions about when a patient needs to be ventilated, as occurs in other disease states similar to COVID-19. Furthermore, a new algorithm has been published, which enables the automatic detection of B-lines as well as quantification of the percentage of the pleural line associated with lung disease. In COVID-19 patients, a direct involvement of cardiac function has been demonstrated, and ventilator-induced diaphragm dysfunction might be present due to the prolonged mechanical ventilation often involved, as reported for similar diseases. For this reason, cardiac and diaphragm ultrasound evaluation are highly important. Last but not least, due to the thrombotic tendency of COVID-19 patients, particular attention also should be paid to vascular ultrasound. This review is primarily devoted to the study of LU in COVID-19 patients. The authors explain the significance of its "light and shadows," bearing in mind the context in which LU is being used-the emergency department and the intensive care setting. The use of cardiac, vascular, and diaphragm ultrasound is also discussed, as a comprehensive approach to patient care.
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http://dx.doi.org/10.1053/j.jvca.2020.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289113PMC
June 2021

Wearable Monitoring and Interpretable Machine Learning Can Objectively Track Progression in Patients during Cardiac Rehabilitation.

Sensors (Basel) 2020 Jun 26;20(12). Epub 2020 Jun 26.

Mobile Health Unit, Faculty of Medicine and Life Sciences, Hasselt University, 3500 Hasselt, Belgium.

Cardiovascular diseases (CVD) are often characterized by their multifactorial complexity. This makes remote monitoring and ambulatory cardiac rehabilitation (CR) therapy challenging. Current wearable multimodal devices enable remote monitoring. Machine learning (ML) and artificial intelligence (AI) can help in tackling multifaceted datasets. However, for clinical acceptance, easy interpretability of the AI models is crucial. The goal of the present study was to investigate whether a multi-parameter sensor could be used during a standardized activity test to interpret functional capacity in the longitudinal follow-up of CR patients. A total of 129 patients were followed for 3 months during CR using 6-min walking tests (6MWT) equipped with a wearable ECG and accelerometer device. Functional capacity was assessed based on 6MWT distance (6MWD). Linear and nonlinear interpretable models were explored to predict 6MWD. The t-distributed stochastic neighboring embedding (t-SNE) technique was exploited to embed and visualize high dimensional data. The performance of support vector machine (SVM) models, combining different features and using different kernel types, to predict functional capacity was evaluated. The SVM model, using chronotropic response and effort as input features, showed a mean absolute error of 42.8 m (±36.8 m). The 3D-maps derived using the t-SNE technique visualized the relationship between sensor-derived biomarkers and functional capacity, which enables tracking of the evolution of patients throughout the CR program. The current study showed that wearable monitoring combined with interpretable ML can objectively track clinical progression in a CR population. These results pave the road towards ambulatory CR.
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http://dx.doi.org/10.3390/s20123601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349532PMC
June 2020

Arterial and Venous Cerebral Blood Flow Velocities and Their Correlation in Healthy Volunteers and Traumatic Brain Injury Patients.

J Neurosurg Anesthesiol 2020 Jun 16. Epub 2020 Jun 16.

Brain Physics Laboratory.

Background: Few studies have explored the cerebral venous compartment or the correlation between venous and arterial cerebral blood flows. We aimed to correlate cerebral blood flow velocities in the arterial (middle cerebral artery) and venous (straight sinus) compartments in healthy volunteers and traumatic brain injury (TBI) patients. In addition, we determined the normative range of these parameters.

Materials And Methods: A total of 122 healthy volunteers and 95 severe TBI patients of both sexes were included and stratified into 3 age groups as follows: group 1 (aged, 18 to 44 y); group 2 (aged, 45 to 64 y); group 3 (older than 65 y). Transcranial Doppler systolic cerebral blood flow velocity, diastolic cerebral blood flow velocity, and mean cerebral blood flow velocity (FVs, FVd, FVm, respectively) were measured in the middle cerebral artery and peak cerebral venous blood flow velocity (FVVs) was measured in the straight sinus. The arteriovenous correlation was assessed on the basis of a positive relationship between FVs and FVVs.

Results: There was an arteriovenous correlation (FVs vs. FVVs) in healthy volunteers (R=0.39, P<0.0001). We found no arteriovenous correlation in the TBI cohort overall, but FVs and FVVs were correlated in age group 1 (R=0.28, P=0.05) and in males (R=0.29, P=0.01). In healthy volunteers, FVs and FVm were significantly higher in males compared with females; and FVs, FVm, FVd, FVVs all increased across the age spectrum. There were no significant differences in any of these parameters in TBI patients.

Conclusions: There are age and sex differences in arterial and venous cerebral blood flow velocities in healthy volunteers. Arteriovenous correlation is present in healthy volunteers but absent in TBI patients.
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http://dx.doi.org/10.1097/ANA.0000000000000704DOI Listing
June 2020

Why, when, and how to use lung ultrasound during the COVID-19 pandemic: enthusiasm and caution.

Eur Heart J Cardiovasc Imaging 2020 09;21(9):941-948

Department of Medical Biotechnologies, Division of Cardiology, University of Siena, Siena, Italy.

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http://dx.doi.org/10.1093/ehjci/jeaa163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314093PMC
September 2020
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