Long peripheral catheters for intravenous infusions of iloprost or alprostadil therapy in rheumatologic outpatients.

BACKGROUND: Long peripheral catheters (LPCs) role in Difficult IntraVenous Access (DIVA) patients admitted to the emergency department has already been studied, resulting in a rapid, safe, and cost-effective procedure. Although their use in outpatient settings is established, there is a lack of studies assessing their benefits. In particular, rheumatologic outpatients affected by scleroderma, especially those affected by digital ulcers, are often treated with intravenous infusions of prostaglandin I2 (PGI2) analog (IV-PGI2A). OBJECTIVE AND METHODS: From 1 October 2021 to 31 March 2024, we conducted a prospective study enrolling DIVA outpatients affected by systemic sclerosis or undifferentiated connective tissue disease who needed IV-PGI2A therapy at L. Sacco Hospital in Milan (Italy). Each treatment cycle consisted of four consecutive days of infusion of iloprost or alprostadil. The primary aim was to assess the efficacy and potential complications associated with LPCs for IV-PGI2A. RESULTS: Twenty-six patients were enrolled 23 were females (88.5%), and the median age was 72 years (IQR 56-78.7). In total, 97 LPCs were inserted, with a mean number of insertions per patient/year of 2.3. An increase in LPCs insertion during the 30 months of the enrollment period was observed. Eighteen patients required more than one LPC placement, and in 61% of them, the second venipuncture was executed at a different site. No procedural complications were registered (accidental puncture of the brachial artery, accidental median nerve puncture, bleeding) nor late complications (Catheter-Related Thrombosis, Catheter-Related Bloodstream Infections, Accidental Removal). CONCLUSIONS: Our experience shows that LPCs could be valuable and safe for rheumatologic outpatients. The increased number of insertions and new and total patients enrolled each year defines the satisfaction of patients and health care professionals.

Immunological Profiles in Parry-Romberg Syndrome: A Case-Control Study.

Background: Parry-Romberg syndrome (PRS) is a rare craniofacial disorder. The aim of this study is to provide information on the immunological profile of this pathology. Since PRS can be included in a wider spectrum of sclerodermic diseases, we propose a case-control study comparing a patient affected by PRS with one with a diagnosis of scleroderma, herein used as control (CTR). Methods: B lymphocyte, T lymphocyte, and monocyte phenotypes and functions were assessed by flow cytometry in influenza (Flu)- or anti cluster differentiation (CD)3/CD28-stimulated peripheral blood mononuclear cells (PBMCs). Cytokine concentration was evaluated as well in PBMC supernatants, plasma, and saliva by Luminex assay. Results: T and B lymphocytes were similarly activated in unstimulated PRS and CTR cells but differed following antigen stimulation. T helper (Th)17 lymphocytes were expanded in PRS compared to CTR; this increase correlated with higher interleukin (IL)-17 concentration. Conclusions: Our case-control study is the first to compare the immunological profiles of PRS and scleroderma patients. The higher percentage of Th17 cells in PRS suggests the use of anti-IL17 receptor monoclonal antibody in this rare disease; however, further studies with larger numbers of patients are needed to confirm our findings.

A mathematical model to assess the effects of COVID-19 on the cardiocirculatory system.

Impaired cardiac function has been described as a frequent complication of COVID-19-related pneumonia. To investigate possible underlying mechanisms, we represented the cardiovascular system by means of a lumped-parameter 0D mathematical model. The model was calibrated using clinical data, recorded in 58 patients hospitalized for COVID-19-related pneumonia, to make it patient-specific and to compute model outputs of clinical interest related to the cardiocirculatory system. We assessed, for each patient with a successful calibration, the statistical reliability of model outputs estimating the uncertainty intervals. Then, we performed a statistical analysis to compare healthy ranges and mean values (over patients) of reliable model outputs to determine which were significantly altered in COVID-19-related pneumonia. Our results showed significant increases in right ventricular systolic pressure, diastolic and mean pulmonary arterial pressure, and capillary wedge pressure. Instead, physical quantities related to the systemic circulation were not significantly altered. Remarkably, statistical analyses made on raw clinical data, without the support of a mathematical model, were unable to detect the effects of COVID-19-related pneumonia in pulmonary circulation, thus suggesting that the use of a calibrated 0D mathematical model to describe the cardiocirculatory system is an effective tool to investigate the impairments of the cardiocirculatory system associated with COVID-19.

Venous Thromboembolism Management throughout the COVID-19 Era: Addressing Acute and Long-Term Challenges.

Background: COVID-19 increases the risk of venous thromboembolism (VTE) through a complex interplay of mechanisms collectively referred to as immunothrombosis. Limited data exist on VTE challenges in the acute setting throughout a dynamic long-term follow-up of COVID-19 patients compared to non-COVID-19 patients. The aim of the study was to investigate acute and long-term management and complications in VTE patients with and without COVID-19. Methods: A prospective, observational, single-center cohort study on VTE patients followed from the acute care stage until 24 months post-diagnosis. Results: 157 patients, 30 with COVID-19-associated VTE and 127 unrelated to COVID-19, were enrolled. The mean follow-up was 10.8 (±8.9) months. COVID-19 patients had fewer comorbidities (1.3 ± 1.29 vs. 2.26 ± 1.68, p < 0.001), a higher proportion of pulmonary embolism at baseline (96.7% vs. 76.4%, p = 0.01), and had a lower probability of remaining on anticoagulant therapy after three months (p < 0.003). The most used initial therapy was low-molecular-weight heparin in 130/157 cases, followed by long-term treatment with direct oral anticoagulants in 123/157. Two (6.7%) COVID-19 vs. three (2.4%) non-COVID-19 patients (p = 0.243) had major hemorrhagic events, all of them within the first three months. Four (3.1%) non-COVID-19 patients had VTE recurrence after six months. Three (2.4%) non-COVID-19 patients developed chronic thromboembolic pulmonary hypertension. There were no fatalities among patients with COVID-19, compared to a mortality of 12/127 (9.4%) in the non-COVID-19 subgroup (p = 0.027). Discussion: Our study offers a comprehensive overview of the evolving nature of VTE management, emphasizing the importance of personalized risk-based approaches, including a limited course of anticoagulation for most COVID-19-associated VTE cases and reduced-dose extended therapy for high-risk subsets.

Brachial Tunneled Peripherally Inserted Central Catheters and the Risk of Catheter Complications: A Systematic Review and Meta-Analysis.

INTRODUCTION: Situations involving increased workloads and stress (i.e., the COVID-19 pandemic) underline the need for healthcare professionals to minimize patient complications. In the field of vascular access, tunneling techniques are a possible solution. This systematic review and meta-analysis aimed to compare the effectiveness of tunneled Peripherally Inserted Central Catheters (tPICCs) to conventional Peripherally Inserted Central Catheters (cPICCs) in terms of bleeding, overall success, procedural time, and late complications. METHODS: Randomized controlled trials without language restrictions were searched using PUBMED®, EMBASE®, EBSCO®, CINAHL®, and the Cochrane Controlled Clinical Trials Register from August 2022 to August 2023. Five relevant papers (1238 patients) were included. RESULTS: There were no significant differences in overall success and nerve or artery injuries between the two groups (p = 0.62 and p = 0.62, respectively), although cPICCs caused slightly less bleeding (0.23 mL) and had shorter procedural times (2.95 min). On the other hand, tPICCs had a significantly reduced risk of overall complications (p < 0.001; RR0.41 [0.31-0.54] CI 95%), catheter-related thrombosis (p < 0.001; RR0.35 [0.20-0.59] IC 95%), infection-triggering catheter removal (p < 0.001; RR0.33 [0.18-0.61] IC 95%), wound oozing (p < 0.001; RR0.49 [0.37-0.64] IC 95%), and dislodgement (p < 0.001; RR0.4 [0.31-0.54] CI 95%). CONCLUSIONS: The tunneling technique for brachial access appears to be safe concerning intra-procedural bleeding, overall success, and procedural time, and it is effective in reducing the risk of late complications associated with catheterization.

Comorbidities in Angioedema Due to C1-Inhibitor Deficiency: An Italian Survey.

BACKGROUND: Hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency is characterized by unpredictable recurrent episodes of swelling affecting the skin and the mucosa tissues, including gastrointestinal tract and/or oropharyngeal-laryngeal mucosae. Long-term prophylaxis (LTP) is used to prevent attacks. OBJECTIVE: Because C1-INH plays a pivotal role in several biological pathways, we investigated the possible association of comorbidities with C1-INH deficiency and the use of LTP with attenuated androgens (AA) or tranexamic acid (TXA). METHODS: This retrospective cohort study involved adult patients with HAE referred to Milan and Padua angioedema centers in the period 1979-2021. A qualitative comparison was performed to analyze comorbidities versus general population. The incidence of comorbidities was evaluated during LTP with AA or TXA versus patients without LTP. RESULTS: A total of 446 patients were studied. A greater prevalence among patients was found for heart diseases (9.6% vs 4.8%), acute myocardial infarction (5.6% vs 1.4%), hepatitis C virus infection (10.5% vs 2.5%), and appendectomy (15.9% vs 4.3%). In patients taking AA, a greater incidence was found for hypertension (22.8% vs 10.8%; odds ratio [OR]: 2.02), hypercholesterolemia (19.5% vs 5.3%; OR: 3.97), diabetes mellitus (5% vs 1.4%; OR: 3.21), hepatic angioma (4.4% vs 0.7%; OR: 8.35), and focal nodular hyperplasia (2.5% vs 0.4%; OR: 6.9). No association between TXA and comorbidities was found. CONCLUSION: In this large patient population with a rare disease followed for up to a 43-year period, we found a greater prevalence of comorbidities hitherto unreported in the literature and an association between comorbidities and LTP with AA.

Integrated short peripheral intravenous cannulas and risk of catheter failure: A systematic review and meta-analysis.

BACKGROUND: Short peripheral catheters (SPCs) are used to provide intravenous therapies in hospitalized patients. Recently, the category of SPC has become more complex, with the introduction in clinical practice of "integrated" SPCs (ISPCs), renewed regarding the material (polyurethane rather than polytetrafluoroethylene) and design (large wing; pre-assembled extension; preassembled needle-free connector (NFC)). METHODS: This systematic review and meta-analysis aimed to analyze randomized controlled trials (RCTs) and quasi-randomized studies in hospitalized patients, analyzing the risk of overall catheter failure as well as the risk of each type of complication (occlusion, infiltration, thrombophlebitis, and dislodgement) for ISPCs compared to non-integrated SPCs. These systematic review and meta-analysis were registered on PROSPERO (CRD42022322970). DATA SOURCES: We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical Trials register from April to November 2022. RESULTS: INCLUDED STUDIES: The research identified 1260 articles. After the abstract review, 13 studies were included for full manuscript review and, after that, six papers (4727 patients) were included in the meta-analysis. DESCRIPTION OF THE EFFECT: We found a significantly reduced risk of catheter failure (pooling all complications) for ISPCs compared to SPCs (p = 0.002 RR 0.65; 95% CI 0.63-0.9). A significant reduction in the risks of occlusion (p = 0.007 RR 0.72; 95% CI 0.56-0.92) was observed. As regards the risk of infiltration, thrombophlebitis, and dislodgement, the analysis showed a trend in favor of ISPCs, though not statistically significant (respectively p = 0.2 RR 0.84; 95% CI 0.64-1.1; p = 0.25 RR 0.91; 95% CI 0.78-1.07; p = 0.06 RR 0.72; 95% CI 0.52-1.01). CONCLUSIONS: ISPCs significantly reduce the risks of catheter failure (overall complications) and occlusion. More RCTs are needed to understand if the preassembled ISPC is better than the composted closed system (non-integrated SPC + extension line + NFC).

Unlocking endothelial barrier restoration: FX06 in systemic capillary leak syndrome and beyond.

Increased vascular permeability is a prevalent feature in a wide spectrum of clinical conditions, but no effective treatments to restore the endothelial barrier are available. Idiopathic systemic capillary leak syndrome (ISCLS) is a life-threatening Paroxysmal Permeability Disorder characterized by abrupt, massive plasma extravasation. This condition serves as a robust model for investigating therapeutic approaches targeting interendothelial junctions. We conducted a single-center, interventional in vitro study at the Referral Center for ISCLS in Italy, involving four diagnosed ISCLS patients, aiming at investigating the effects of FX06, a Bß15-42 fibrin-derived peptide binding to VE-Cadherin, on endothelial barrier exposed to intercritical and acute ISCLS sera. The Transwell Permeability Assay was used to assess the permeability of human umbilical vein endothelial cells (HUVECs) exposed to ISCLS sera with or without FX06 (50 µg/ml). Acute ISCLS serum was also tested in a three-dimensional microfluidic device. Nitric oxide (NO), VE-Cadherin localization, and cytoskeletal organization were also assessed. In two and three-dimensional systems, ISCLS sera increased endothelial permeability, with a more pronounced effect for acute sera. Furthermore, acute sera altered VE-Cadherin localization and cytoskeletal organization. NO levels remained unchanged. FX06 restored the endothelial barrier function by influencing cellular localization rather than VE-Cadherin levels. In conclusion, FX06 prevents and reverts the hyperpermeability induced by ISCLS sera. These preliminary yet promising results provide initial evidence of the in vitro efficacy of a drug targeting the underlying pathophysiological mechanisms of ISCLS. Moreover, this approach may hold potential for addressing hyperpermeability in a spectrum of clinical conditions beyond ISCLS.

Low-molecular-weight heparin for the prevention of clinical worsening in severe non-critically ill COVID-19 patients: a joint analysis of two randomized controlled trials.

Coronavirus disease 2019 (COVID-19) carries a high risk of vascular thrombosis. However, whether a specific anticoagulation intensity strategy may prevent clinical worsening in severe COVID-19 patients is still debated. We conducted a joint analysis of two randomized controlled trials, COVID-19 HD (NCT044082359) and EMOS-COVID (NCT04646655), to assess the efficacy and safety of two anticoagulant regimens in hospitalized severe COVID-19 patients. Subjects with COVID-19-associated respiratory compromise and/or coagulopathy were randomly assigned to low (4000 IU qd) or high (70 IU Kg-1 every 12 h) enoxaparin dose. The primary efficacy endpoint was clinical worsening within 30 days, defined as the occurrence of at least one of the following events, whichever came first: in-hospital death, evidence of arterial or venous thromboembolism, acute myocardial infarction, need for either continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) in patients receiving standard oxygen therapy or none at randomization, and need for mechanical ventilation in any patient. The safety endpoint was major bleeding. We estimated the relative risk (RR) and its 95% confidence interval (CI) for the outcomes. Among 283 patients included in the study (144 in the low-dose and 139 in the high-dose group), 118 (41.7%) were on NIV or CPAP at randomization. 23/139 (16.5%) patients in the high-dose group reached the primary endpoint compared to 33/144 (22.9%) in the low-dose group (RR 0.72, 95% CI 0.45-1.17). No major bleeding was observed. No significant differences were found in the clinical worsening of hospitalized COVID-19 patients treated with high versus low doses of enoxaparin.

Disinfectant caps in vitro effectiveness.

Background: Catheter-related bloodstream infections (CRBSIs) are a major cause of morbidity and mortality among hospitalized patients. Different studies suggest that the use of disinfectant caps (DCs) significantly reduces the rate of CRBSIs. The first purpose of this study is to analyze, through an in-vitro-model, the antiseptic effect of DCs produced by two manufacturers; the second aim is to assess potential differences in terms of effectiveness between the two manufacturers' products. Methods: A know concentration of thirteen different microorganisms was incubated with the sponge drenched in antimicrobial fluid inside DCs and cultured through several assays to investigate the disinfectant effectiveness of some commercially available caps. Disinfectant properties were evaluated under two different conditions: baseline (DCs placed on the needle-free connectors (NFCs) and stress test (DCs directly applied to the catheter hub). Results: Both manufacturers overcame the basal tests (fourteen different assays). Regarding stress tests: the only significant bacterial load was found for Serratia marcescens (104 CFU/mL in ICU Medical™), both at 90 and 180 minutes after incubation; due to the low load, MDR Acinetobacter baumannii was not considered significant (<103 CFU/mL in BD PureHub™). Conclusions: Our results confirm what was reported in BD PureHub™ datasheet and add data not previously shown by ICU Medical™. Moreover, no difference was observed between the two manufacturers products: the use of both DCs on NFCs was able to reclaim the catheter lumen. These findings support the routine use of DCs with NFCs, as part of a structured bundle of interventions, to reduce the incidence of CRBSIs.

Physicochemical Characteristics of Antimicrobials and Practical Recommendations for Intravenous Administration: A Systematic Review.

Most antimicrobial drugs need an intravenous (IV) administration to achieve maximum efficacy against target pathogens. IV administration is related to complications, such as tissue infiltration and thrombo-phlebitis. This systematic review aims to provide practical recommendations about diluent, pH, osmolarity, dosage, infusion rate, vesicant properties, and phlebitis rate of the most commonly used antimicrobial drugs evaluated in randomized controlled studies (RCT) till 31 March 2023. The authors searched for available IV antimicrobial drugs in RCT in PUBMED EMBASE®, EBSCO® CINAHL®, and the Cochrane Controlled Clinical trials. Drugs' chemical features were searched online, in drug data sheets, and in scientific papers, establishing that the drugs with a pH of <5 or >9, osmolarity >600 mOsm/L, high incidence of phlebitis reported in the literature, and vesicant drugs need the adoption of utmost caution during administration. We evaluated 931 papers; 232 studies were included. A total of 82 antimicrobials were identified. Regarding antibiotics, 37 reach the "caution" criterion, as well as seven antivirals, 10 antifungals, and three antiprotozoals. In this subgroup of antimicrobials, the correct vascular access device (VAD) selection is essential to avoid complications due to the administration through a peripheral vein. Knowing the physicochemical characteristics of antimicrobials is crucial to improve the patient's safety significantly, thus avoiding administration errors and local side effects.

Safety of mid-thigh exit site venous catheters in multidrug resistant colonized patients.

INTRODUCTION: Venous catheters inserted in superficial femoral vein and with mid-thigh exit site have emerged as a feasible and safe technique for central or peripheral tip's venous access, especially in agitated, delirious patients. The spread of multidrug-resistant bacterial (MDR) strains is an emerging clinical problem and more and more patients are being colonized by these types of bacteria. The aim of this study is to evaluate the incidence of central line associated bloodstream infections (CLABSI) or catheter related bloodstream infections (CRBSI) in mid-thigh catheters in patients with positive rectal swabs to evaluate the safety of this procedure and the real infection risk. METHODS: In this retrospective observational study, we analyzed data on patients with mid-tight catheters inserted from May 2021 to November 2022. All surveillance rectal swabs were recorded. In addition, to collect data on CLABSI and CRBSI, the results of all blood and catheter tip cultures performed during the hospital stay were acquired. RESULTS: Six hundred two patients were enrolled, 304 patients (50.5%) had a rectal swab; 128 (42.1%) swabs were positive for MDR. Nine CLABSI (only two in patients with a positive rectal swab) and three CRBSI were detected. No statistical difference in the absolute number of CLABSI and CRBSI and in the number of infections per 1000 catheter days emerged between the overall population and patients with positive rectal swabs (respectively p = 0.45 and p = 0.53). Similarly, no statistical difference in the number of CLABSI and CRBSI was found among patients with a negative swab and patients with a positive one (respectively p = 0.43 and p = 0.51). CONCLUSIONS: According to our data, cannulation of the superficial femoral vein represents a safe location in patients with positive rectal swabs.

Use of non-invasive respiratory supports in high-intensity internal medicine setting during the first two waves of the COVID-19 pandemic emergency in Italy: a multicenter, real-life experience.

During the first two waves of the COVID-19 emergency in Italy, internal medicine high-dependency wards (HDW) have been organized to manage patients with acute respiratory failure (ARF). There is heterogeneous evidence about the feasibility and outcomes of non-invasive respiratory supports (NIRS) in settings outside the intensive care unit (ICU), including in patients deemed not eligible for intubation (i.e., with do-not-intubate, DNI status). Few data are available about the different NIRS modalities applied to ARF patients in the newly assembled internal medicine HDW. The main aim of our study was to describe a real-life experience in this setting of cure, focusing on feasibility and outcomes. We retrospectively collected data from COVID-19 patients with ARF needing NIRS and admitted to internal medicine HDW. Patients were treated with different modalities, that is high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), or non-invasive mechanical ventilation (NIMV). Switching among different NIRS during the hospitalization and the success rate (weaning with the same NIRS) or failure (endotracheal intubation-ETI or in-hospital death) were recorded. Three hundred thirty four ARF patients (median age 74 years), of which 158 (54%) had a DNI status, were included. CPAP, NIMV, and HFNC's success rates were 54, 33, and 13%, respectively. Although DNI status was strongly associated with death (Gehan-Breslow-Wilcoxon test p < 0.001), an acceptable success rate was observed in these patients using CPAP (47%). Multivariate regression models showed older age (odds ratio-OR 4.74), chronic ischemic heart disease (OR 2.76), high respiratory rate after 24 h (OR 7.13), and suspected acute respiratory distress syndrome-ARDS (OR 21.1) as predictors of mortality risk or ETI. Our real-life experience shows that NIRS was feasible in internal medicine HDW with an acceptable success rate. Although DNI patients had a worse prognosis, the use of NIRS represented a reasonable chance of treatment.

Multicentric Observational Study on Safety and Tolerability of COVID-19 Vaccines in Patients with Angioedema with C1 Inhibitor Deficiency: Data from Italian Network on Hereditary and Acquired Angioedema (ITACA).

Angioedema due to C1 inhibitor deficiency (AE-C1-INH) is a rare disease characterized by recurrent and unpredictable attacks of angioedema. Multiple trigger factors, including trauma, emotional stress, infectious diseases, and drugs, could elicit angioedema attacks. The aim of this study was to collect data on the safety and tolerability of COVID-19 vaccines in a population of patients affected by AE-C1-INH. Adult patients with AE-C1-INH, followed by Reference Centers belonging to the Italian Network for Hereditary and Acquired Angioedema (ITACA), were enrolled in this study. Patients received nucleoside-modified mRNA vaccines and vaccines with adenovirus vectors. Data on acute attacks developed in the 72 h following COVID-19 vaccinations were collected. The frequency of attacks in the 6 months after the COVID-19 vaccination was compared with the rate of attacks registered in the 6 months before the first vaccination. Between December 2020 and June 2022, 208 patients (118 females) with AE-C1-INH received COVID-19 vaccines. A total of 529 doses of the COVID-19 vaccine were administered, and the majority of patients received mRNA vaccines. Forty-eight attacks of angioedema (9%) occurred within 72 h following COVID-19 vaccinations. About half of the attacks were abdominal. Attacks were successfully treated with on-demand therapy. No hospitalizations were registered. There was no increase in the monthly attack rate following the vaccination. The most common adverse reactions were pain at the site of injection and fever. Our results show that adult patients with angioedema due to C1 inhibitor deficiency can be safely vaccinated against SARS-CoV-2 in a controlled medical setting and should always have available on-demand therapies.

A decision-making algorithm proposal for PICCs and midlines insertion in patients with advanced kidney disease: A pilot study.

INTRODUCTION: Kidney Disease Outcomes Quality Initiative clinical practice guidelines recommend avoiding placement of peripherally inserted vascular access devices in patients with an estimated glomerular filtration rate (eGFR) <45 ml/min. On the other hand, many patients with severe chronic kidney disease (CKD) have poor prognosis.This study carried out a global assessment of mortality at 2 years through Charlson Comorbidity Index (CCI) and Beclap score in patients with PICCs or Midlines, assuming that in those with an estimated high mortality rate at 2 years, it could be acceptable to implant a peripheral vascular access device (PVAD) despite the presence of CKD. METHODS: We analyzed data on patients with PICCs or Midlines inserted from October 2018 to November 2019. CCI, Beclap score, and eGFR were calculated for each patient at the time of the catheter insertion. We then followed patients for 2 years to assess 2-year mortality for each. RESULTS: One hundred and thirty-one patients were enrolled, 49 (37.4%) had eGFR<45 ml. The 2-year mortality rate was 57.3%. The cut off derived from ROC curve analysis of 15 for Beclap score and 5 for CCI, showed good sensitivity and specificity in predicting mortality of the total population, patients without an oncological disease and patients with eGFR<45 ml/min. CONCLUSION: CCI and Beclap score are good predictors of mortality at 2 years.Physicians and nurses can use these tools in the evaluation of patients at risk for future dialysis, instead of relying exclusively on renal function to decide whether implanting PICCs, Midlines, or other vascular access devices.

The use of lung ultrasound in COVID-19.

This review article addresses the role of lung ultrasound in patients with coronavirus disease 2019 (COVID-19) for diagnosis and disease management. As a simple imaging procedure, lung ultrasound contributes to the early identification of patients with clinical conditions suggestive of COVID-19, supports decisions about hospital admission and informs therapeutic strategy. It can be performed in various clinical settings (primary care facilities, emergency departments, hospital wards, intensive care units), but also in outpatient settings using portable devices. The article describes typical lung ultrasound findings for COVID-19 pneumonia (interstitial pattern, pleural abnormalities and consolidations), as one component of COVID-19 diagnostic workup that otherwise includes clinical and laboratory evaluation. Advantages and limitations of lung ultrasound use in COVID-19 are described, along with equipment requirements and training needs. To infer on the use of lung ultrasound in different regions, a literature search was performed using key words "COVID-19", "lung ultrasound" and "imaging". Lung ultrasound is a noninvasive, rapid and reproducible procedure; can be performed at the point of care; requires simple sterilisation; and involves non-ionising radiation, allowing repeated exams on the same patient, with special benefit in children and pregnant women. However, physical proximity between the patient and the ultrasound operator is a limitation in the current pandemic context, emphasising the need to implement specific infection prevention and control measures. Availability of qualified staff adequately trained to perform lung ultrasound remains a major barrier to lung ultrasound utilisation. Training, advocacy and awareness rising can help build up capacities of local providers to facilitate lung ultrasound use for COVID-19 management, in particular in low- and middle-income countries.

Remdesivir-induced bradycardia in patients hospitalized with SARS-CoV2 infection: a possible vagally-mediated mechanism.

Recently, case series studies on patients with SARS-CoV-2 infection reported an association between remdesivir (RDV) administration and incidental bradycardia. However, the phenomenon has not yet been described in detail. We conducted a retrospective case-control study to evaluate the occurrence of RDV-related bradycardia in patients hospitalized for SARS-CoV2 pneumoniae. We retrospectively evaluated 71 patients, hospitalized in six internal medicine wards of the Milan area, affected by mild-to-moderate COVID-19 who received RDV (RDV group) and 54 controls, matched for sex, age and disease severity on admission (CTR group). The mean heart rate value recorded during the first two days of hospitalization was considered as baseline heart rate (HRb). Heart rate values relative to the 5-days treatment and the 5-days post-treatment were extracted for RDV group, while heart rate values relative to 10 days of hospitalization were considered for the CTR group. ΔHR values were calculated as maximum HR drop versus HRb. Possible associations between ΔHR and clinical-demographic factors were assessed through regression analysis. The RDV group experienced a significantly higher incidence of bradycardia compared to the CTR group (56% vs 33%, OR 2.6, 95% CI 1.2-5.4, p value = 0.011). Moreover, the RDV group showed higher ΔHR values than the CTR group. The HR progressively decreased with daily administration of RDV, reaching the maximun drop on day six (-8.6±1.9 bpm). In RDV group, patients who experienced bradycardia had higher drop in HR, higher alanine aminotransferase (ALT) values at the baseline (bALT) and during the RDV administration period. ΔHR was positively associated with HRb (ß = 0.772, p < 0.001) and bALT (ß = 0.245, p = 0.005). In conclusion, our results confirmed a significant association between RDV administration and development of bradycardia. This effect was proportional to baseline HR and was associated with higher levels of baseline ALT, suggesting a possible interaction between RDV liver metabolism and a vagally-mediated effect on HR due to increased availability of RDV metabolites.