Epstein-Barr virus, Cytomegalovirus, and Herpes Simplex-1/2 reactivations in critically ill patients with COVID-19.

OBJECTIVES: To assess the incidences of Herpes Simplex-1 and 2 (HSV-1, HSV-2), Cytomegalovirus (CMV), Epstein-Barr Virus (EBV) reactivations in critically ill COVID-19 patients. To determine the association between viral reactivation and in-hospital mortality, Intensive Care Unit Bloodstream infection (ICU-BSI), ventilator-associated pneumonia (VAP). DESIGN: Observational retrospective cohort study. SETTING: COVID-19 Intensive Care Unit. PATIENTS: From November 2020 to May 2021, one hundred and twenty patients with COVID-19 severe pneumonia were enrolled and tested for HSV-1, HSV-2, CMV and EBV at the admission in ICU and weekly until discharge or death. The presence of VAP and ICU-BSI was evaluated according to clinical judgement and specific diagnostic criteria. MEASUREMENTS AND MAIN RESULTS: One hundred and twenty patients were enrolled. Multiple reactivations occurred in 75/120 (63%) patients, single reactivation in 27/120 patients (23%). The most reactivated Herpesvirus was EBV, found in 78/120 (65%) patients. The multivariate analysis demonstrated that viral reactivation is a strong independent risk factor for in-hospital mortality (OR = 2.46, 95% CI 1.02-5.89), ICU-BSI (OR = 2.37, 95% CI 1.06-5.29) and VAP (OR = 2.64, 95% CI 1.20-5.82). CONCLUSIONS: Human Herpesviruses reactivations in critically ill patients with COVID-19 severe Pneumonia are associated with mortality and with a higher risk to develop both VAP and ICU-BSI.

Extracorporeal Membrane Oxygenation in Acute Respiratory Failure due to Hemorrhagic Alveolitis in a Patient with Acute Myeloblastic Leukemia.

Introduction. Extracorporeal membrane oxygenation (ECMO) support for severe acute respiratory distress syndrome (ARDS) is nowadays widely used with notable results on the overall survival as reported in the ELSO registry near to 55% at 90 days. This is the reason why ECMO teams force the use of this extreme technique to several populations, even though there is still a lack of data about its use on hematological patients. Case Report. A 39-year-old woman without a history of previous diseases, but a new diagnosis of acute myeloblastic leukemia (AML) was admitted to intensive care unit (ICU) for worsening hypoxia and respiratory acidosis, presenting an ARDS with PaO2/FiO2 < 100 in spontaneous breathing treated with noninvasive ventilation via full-face mask. Meanwhile, chemotherapy was started leading to a severe bone marrow aplasia that was managed with multiple blood and platelet transfusions. These conditions did not allow physicians to start any invasive approaches. After 14 days, ARDS worsened whereas bone marrow recovered, making possible the beginning of an invasive mechanical ventilation, with low positive end-expiratory pressure and a low tidal volume. Moreover, an immediate extracorporeal CO2 removal (ECCO2R) therapy was added. Despite these efforts, no improvement was achieved, and that is why venovenous ECMO throughout femoral-jugular cannulation was applied. A full protective lung ventilation by ultralow tidal volumes was guaranteed. After 2 weeks of ECMO, a gradual weaning from ECMO support was started and completed after two days. No ECMO-related complications were registered. In the end, the patient started her weaning from the mechanical ventilation and reached 12 hours of spontaneous ventilation in oxygen therapy. Discussion. ECMO is used as a rescue therapy in patients affected by severe respiratory failure with life-threatening hypoxia and respiratory acidosis nonresponsive to other maneuvers. However, immunosuppression and coagulopathies of hematological malignancies are considered relative contraindications for ECMO, while long-lasting respiratory failure represents another relative contraindication to extracorporeal support. ECMO could be a valid option to improve the survival of hematological patients with severe ARDS and thrombocytopenia, and management could change case by case, even if high incidence of recurrency.

Safety and Efficacy of PCSK9 Inhibitors in Patients with Acute Coronary Syndrome Who Underwent Coronary Artery Bypass Grafts: A Comparative Retrospective Analysis.

Background. The in-hospital reduction in low-density lipoprotein cholesterol (LDL-C) levels following acute coronary syndrome (ACS) is recommended in the current clinical guidelines. However, the efficacy of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors in those patients undergoing coronary artery bypass graft (CABG) has never been demonstrated. Methods. From January 2022 to July 2023, we retrospectively analyzed 74 ACS patients characterized by higher LDL-C levels than guideline targets and who underwent coronary bypass surgery. In the first period (January 2022-January 2023), the patients increased their statin dosage and/or added Ezetimibe (Group STEZE, 43 patients). At a later time (February 2023-July 2023), the patients received not only statins and Ezetimibe but also Evolocumab 140 mg every 2 weeks starting as early as possible (Group STEVO, 31 patients). After one and three months post-discharge, the patients underwent clinical and laboratory controls with an evaluation of the efficacy lipid measurements and every adverse event. Results. The two groups did not differ in terms of preoperative risk factors and Euroscore II (STEVO: 2.14 ± 0.75 vs. STEZE: 2.05 ± 0.6, p = 0.29). Also, there was no difference between the groups in terms of ACS (ST-, Instable angina, or NSTE) and time of symptoms onset regarding total cholesterol, LDL-C, and HDL-C trends from the preprocedural period to 3-month follow-up, but there was a more significant reduction in LDL-C and total cholesterol in the STEVO group (p = 0.01 and p = 0.04, respectively) and no difference in HDL-C rise (p = 0.12). No deaths were reported. In three STEZE group patients, angina recurrence posed the need for percutaneous re-revascularization. No STEVO patients developed significant adverse events. The statistical difference in these serious events, 7% in STEZE vs. 0% in STEVO, was not significant (p = 0.26). Conclusions. Evolocumab initiated "as soon as possible" in ACS patients submitted to CABG with high-intensity statin therapy and Ezetimibe was well tolerated and resulted in a substantial and significant reduction in LDL-C levels at discharge, 1 month, and 3 months. This result is associated with a reduction but without a statistical difference between groups.

The Role of TAP/RS Block in Minor Gynecologic Laparoscopic Surgery: A Randomized Clinical Trial.

OBJECTIVES: The aim of the study was to compare, in patients undergoing minor gynecological laparoscopic procedures, the effects of ultrasound (US)-guided transversus abdominis plane (TAP) + rectus sheath (RS) block versus no TAP/RS block in terms of post-surgical pain control using the numeric pain rating scale (NRS) and the degree of patient satisfaction, according to the main goals of Early Recovery After Surgery (ERAS) programs. The primary outcome is to value the postoperative abdominal pain using NRS in both groups. Secondary outcomes are to evaluate blood values, presence of postoperative nausea and vomiting (PONV), postoperative ileus, level of patient expected satisfaction, time of discharge, length of stay (LOS), and the amounts of additional analgesics required. DESIGN: In this prospective randomized controlled trial, patients were randomly assigned to loco-regional anesthesia (LRA) group, who received TAP and RS block under US guidance, or no loco-regional anesthesia (N-LRA) group. Enrolled patients were randomized 1:1 to either receive bilateral TAP/RS block with ropivacaine or sham treatment (patches were applied on the abdominal wall of the patients under general anesthesia). PARTICIPANTS: All patients aged between 18 and 75 years, with ASA (American Society of Anesthesiologists) physical status 1-2, undergoing laparoscopic minor gynecological surgery, were enrolled. SETTING: The study was conducted to the University of Campus Bio-Medico Hospital of Rome. METHODS: Half an hour before surgery, all patients received gabapentin 300 mg per os. Once the patient underwent general anesthesia, US-guided bilateral TAP/RS block was performed by the anesthesiology team, while the uterine manipulator was positioned by a gynecology resident (not involved in the study). In the operative room, all patients received the same standardized anesthetic regimen. Postoperative abdominal pain was assessed at rest, after palpation, during movement, and after a cough by evaluating the patient at 6, 12, 18, 24, 36, 48, and 72 h after surgery, using the NRS from 0 to 10 in both groups. The amount of drug used for analgesia in the first 48 h after surgery was recorded. Moreover, hemoglobin, white blood cells, and c-reactive protein levels were recorded at 24, 48, and 72 h. The presence of PONV and the postoperative ileus was recorded throughout convalescence. The expected level of patient satisfaction at discharge and finally the LOS were assessed. LIMITATIONS: The major weakness of this study is that 60 mL of 0.5% ropivacaine was administered to each patient, without considering weight differences, yet contemporary literature rarely suggests volume/dose titration in fascial blocks. RESULTS: A total of 104 women, undergoing gynecological minor laparoscopic surgery, were enrolled and assigned to LRA group (53 pts) and N-LRA group (51 pts). Postoperative pain was significantly reduced in patients who received TAP/RS block. A reduction in the intake of non-steroidal anti-inflammatory drugs after surgery was registered in LRA group (p < 0.01). Moreover, a significant reduction of LOS (45.97 ± 9.87 vs. 65.08 ± 17.32 h; p < 0.01) and PONV was observed in the LRA group, as well as a better level of patient satisfaction at discharge (9.43 ± 0.94 vs. 8.26 ± 1.19; p < 0.01), compared to the N-LRA group. CONCLUSIONS: US-guided TAP and RS block significantly reduces postoperative pain after minor gynecologic laparoscopic surgery and improves patients' post-operative recovery.

High dose esomeprazole as an anti-inflammatory agent in sepsis: Protocol for a randomized controlled trial.

BACKGROUND: Sepsis is caused by dysregulated immune responses due to infection and still presents high mortality rate and limited efficacious therapies, apart from antibiotics. Recent evidence suggests that very high dose proton pump inhibitors might regulate major sepsis mediators' secretion by monocytes, which might attenuate excessive host reactions and improve clinical outcomes. This effect is obtained with doses which are approximately 50 times higher than prophylactic esomeprazole single daily administration and 17 times higher than the cumulative dose of a three day prophylaxis. We aim to perform a randomized trial to investigate if high dose esomeprazole reduces organ dysfunction in patients with sepsis or septic shock. METHODS: This study, called PPI-SEPSIS, is a multicenter, randomized, double blind, placebo-controlled clinical trial on critically ill septic patients admitted to the emergency department or intensive care unit. A total of 300 patients will be randomized to receive high dose esomeprazole (80 mg bolus followed by 12 mg/h for 72 h and a second 80 mg bolus 12 h after the first one) or equivolume placebo (sodium chloride 0.9%), with 1:1 allocation. The primary endpoint of the study will be mean daily Sequential Organ Failure Assessment (SOFA) score over 10 days. Secondary outcomes will include antibiotic-free days, single organ failure severity, intensive care unit-free days at day 28, and mortality. DISCUSSION: This trial aims to test the efficacy of high dose esomeprazole to reduce acute organ dysfunction in patients with septic shock. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov with the trial identification NCT03452865 in March 2018.

Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial.

Importance: Meropenem is a widely prescribed ß-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, Setting, and Participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and Relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial Registration: ClinicalTrials.gov Identifier: NCT03452839.

The specialized pro-resolving lipid mediator Protectin D1 affects macrophages differentiation and activity in Adult-onset Still's disease and COVID-19, two hyperinflammatory diseases sharing similar transcriptomic profiles.

Introduction: COVID-19 and autoinflammatory diseases, such as Adult-onset Still's Disease (AOSD), are characterized by hyperinflammation, in which it is observed massive production and uncontrolled secretion of pro-inflammatory cytokines. The specialized pro-resolving lipid mediators (SPMs) family is one the most important processes counteracting hyperinflammation inducing tissue repair and homeostasis restoration. Among SPMs, Protectin D1 (PD1) is able to exert antiviral features, at least in animal models. The aim of this study was to compare the transcriptome of peripheral blood mononuclear cells (PBMCs) from patients with AOSD and COVID-19 and to evaluate the role of PD1 on those diseases, especially in modulating macrophages polarization. Methods: This study enrolled patients with AOSD, COVID-19, and healthy donors HDs, undergoing clinical assessment and blood sample collection. Next-generation deep sequencing was performed to identify differences in PBMCs transcripts profiles. Plasma levels of PD1 were assessed by commercial ELISA kits. Monocyte-derived macrophages were polarized into M1 and M2 phenotypes. We analyzed the effect of PD1 on macrophages differentiation. At 10 days, macrophages were analyzed for surface expression of subtypes markers by flow cytometry. Cytokines production was measured in supernatants by Bio-Plex Assays. Results: In the transcriptomes from AOSD patients and COVID-19 patients, genes involved in inflammation, lipid catabolism, and monocytes activation were specifically dysregulated in AOSD and COVID-19 patients when compared to HDs. Patients affected by COVID-19, hospitalized in intensive care unit (ICU), showed higher levels of PD1 when compared to not-ICU hospitalized patients and HDs (ICU COVID-19 vs not-ICU COVID-19, p= 0.02; HDs vs ICU COVID-19, p= 0.0006). PD1 levels were increased in AOSD patients with SS ≥1 compared to patients with SS=0 (p=0.028) and HDs (p=0.048). In vitro treatment with PD1 of monocytes-derived macrophages from AOSD and COVID-19 patients induced a significant increase of M2 polarization vs control (p<0.05). Furthermore, a significant release of IL-10 and MIP-1ß from M2 macrophages was observed when compared to controls (p<0.05). Discussion: PD1 is able to induce pro-resolutory programs in both AOSD and COVID-19 increasing M2 polarization and inducing their activity. In particular, PD1-treated M2 macrophages from AOSD and COVID-19 patients increased the production of IL-10 and enhanced homeostatic restoration through MIP-1ß production.

The similar expression of both ferritin and scavenger receptors activation genes in patients with COVID19 and AOSD support their role in the pathogenesis of these diseases and identify a common mechanism at the basis of the "hyperferritinemic syndromes".

A role for COVID19 in "hyperferritinemic syndromes" has been proposed based on its clinical and serological characteristics and its similarities with AOSD. To better understand the molecular pathways responsible of these similarities, we evaluated in the PBMCs of 4 active AOSD patients, 2 COVID19 patients with ARDS, and 2 HCs the expression of genes associated with iron metabolisms, with monocyte/macrophages activation, and finally with NETs formation.

Ultrasound Guided Parasternal Block for Perioperative Analgesia in Cardiac Surgery: A Prospective Study.

Ultrasound guided parasternal block is a regional anaesthesia technique targeting the anterior branches of intercostal nerves, which supply the anterior thoracic wall. The aim of this prospective study is to assess the efficacy of parasternal block to manage postoperative analgesia and reduce opioid consumption in patients undergoing cardiac surgery throughout sternotomy. A total of 126 consecutive patients were allocated to two different groups, receiving (Parasternal group) or not (Control group) preoperative ultrasound guided bilateral parasternal block with 20 mL of 0.5% ropivacaine per side. The following data were recorded: postoperative pain expressed by a 0-10 numeric rating scale (NRS), intraoperative fentanyl consumption, postoperative morphine consumption, time to extubation and perioperative pulmonary performance at incentive spirometry. Postoperative NRS was not significantly different between Parasternal and Control groups with a median (IQR) of 2 (0-4.5) vs. 3 (0-6) upon awakening (p = 0.07); 0 (0-3) vs. 2 (0-4) at 6 h (p = 0.46); 0 (0-2) vs. 0 (0-2) at 12 h (p = 0.57). Postoperative morphine consumption was similar among groups. However, intraoperative fentanyl consumption was significantly lower in the Parasternal group [406.3 ± 81.6 mcg vs. 864.3 ± 154.4, (p < 0.001)]. Parasternal group showed shorter times to extubation [(191 ± 58 min vs. 305 ± 72 min, (p)] and better performance at incentive spirometer with a median (IQR) of 2 raised balls (1-2) vs. 1 (1-2) after awakening (p = 0.04). Ultrasound guided parasternal block provided an optimal perioperative analgesia with a significant reduction in intraoperative opioid consumption, time to extubation and a better postoperative performance at spirometry when compared to the Control group.

Continuous field flooding versus final one-shot CO2 insufflation in minimally invasive mitral valve repair.

BACKGROUND: Insufflation of carbon dioxide (CO2) into the operative field to prevent cerebral or myocardial damage by air embolism is a well known strategy in open-heart surgery. However, here is no general consensus on the best delivery approach. METHODS: From January 2018 to November 2021, we retrospectively collected data of one hundred consecutive patients undergoing minimally invasive mitral valve repair (MIMVR). Of these, fifty patients were insufflated with continuous CO2 1 min before opening the left atrium and ended after its closure, and fifty patients were insufflated with one shot CO2 10 min before the start of left atrium closure. The primary outcome of the study was the incidence of transient post-operative cognitive disorder, in particular agitation and delirium at discontinuation of anesthesia, mechanical ventilation (MV) duration and intensive care unit (ICU) length of stay. RESULTS: In all patients that received continuous field flooding CO2, correction of ventilation for hypercapnia during cardiopulmonary bypass (CPB) was applied with an increase of mean sweep gas air (2.5 L) and monitoring of VCO2 changes. One patient vs. 9 patients of control group reported agitation at discontinuation of anesthesia (p = 0.022). MV duration was 14 ± 3 h vs. 27 ± 4 h (p = 0.016) and ICU length of stay was 33 ± 4 h vs. 42 ± 5 h (p = 0.029). A significant difference was found in the median number of total micro-emboli recorded from release of cross-clamp until 20 min after end of CPB (154 in the continuous CO2 group vs. 261 in the one-shot CO2 control group; p < 0.001). Total micro-emboli from the first 15 min after the release of cross-clamp was 113 in the continuous CO2 group vs. 310 in the control group (p < 0.001). In the continuous CO2 group, the median number of detectable micro-emboli after CPB fell to zero 9 ± 5 min after CPB vs. 19 ± 3 min in the control group (p = 0.85). CONCLUSION: Continuous field flooding insufflation of CO2 in MIMVR is associated with a lower incidence of micro-emboli and of agitation at discontinuation of anesthesia, along with improved MV duration and ICU length of stay.

Specific theorical and practical education on mechanical chest compression during advanced life support training courses - Results from a local experience.

Specific training modules focusing on mechanical chest compression and device use might be considered in a structured manner during the standard advanced life support (ALS) courses. The aim of this study was to evaluate the impact of a specific brief 15 min training on the use of a specific mechanical CPR device during Advanced Cardiac Life Support courses on its correct use and on attendees' satisfaction.

Hybrid approach for long-standing persistent atrial fibrillation: immediate versus staged treatment.

BACKGROUND: The hybrid approach has become the most effective treatment option for restoring sinus rhythm and reducing the risk of atrial fibrillation (AF) recurrence. However, several issues remain to be clearly defined, including the appropriate timing of the staged procedure and the most effective strategy. METHODS: Over a 12-year period of activity, we performed 609 AF ablation procedures via a right mini-thoracotomy. From this general population, 60 patients underwent a hybrid procedure with catheter ablation performed at least 4 weeks after the surgical procedure to confirm if effective complete electrical isolation of pulmonary veins was achieved. In 20 patients, the second stage procedure was performed during the same hospitalization due to patient's electrical instability. The results obtained in immediate versus staged patients were compared. RESULTS: All patients were discharged after the first stage procedure in sinus rhythm. The 20 immediate patients had a shorter hospital stay compared with the staged patients, in whom the two hospitalizations resulted in a longer hospital stay (immediate 5.5 ± 1.6 days versus staged 8.7 ± 1.4, P < 0.001). A significantly higher number of immediate patients had an associated ablation of the Bachmann's bundle (n = 16 in the immediate group [80%] versus n = 14 in the staged group [45%]; P = 0.001). After a mean follow-up of 74 months, there was no significant difference in the risk of AF relapse between groups (immediate 1/20 [5%] versus staged 7/40 [17.5%]; P = 0.18). CONCLUSION: The hybrid approach for the treatment of AF was safe and effective in immediate restoring sinus rhythm and in its maintenance at follow-up. Our preliminary results show that both immediate and staged procedures show similar efficacy but this result is strongly influenced by the concomitant ablation of the Bachmann's bundle, which appears to be the most important component of the treatment strategy in order to reduce the risk of recurrent AF.

Pressure monitoring devices may undetect epidural space: a report on the use of Compuflo® system for epidural injection.

Lumbar epidural infiltration (EI) is a feasible procedure performed in pain therapy. Even though epidural analgesia is widely applied, it remains a blind technique, based on the operator's hand sensations, and it is associated with significant failure rate and several potential complications. Compuflo® (Compuflo, Milestone Scientific, Livingston, NJ) is a computerized injection pump which precisely detects the real time pressure at the tip of a Tuohy needle when placed in human tissues, thanks to a continuous fluid path. In our institution, we usually perform EI for chronic back pain guided by the Compuflo device, especially for expected difficult procedures. However, we report 6 false negative cases on a total number of 60 procedures in which the Compuflo system didn't meet the criteria of epidural space entry, even though the epidural space was actually reached. A mild pressure decrease (less than 50%) which lasted for more than 5 s was reported on the monitor, and the acoustic signal changed in a little bit lower sound, without a clear indication on stopping or not the needle advancement. This unspecific drop in monitored pressure gives false negatives using the Compuflo® system and may lead to excessive advancing of the needle. In conclusion, we consider the epidural pressure monitoring device Compuflo as a tool which may be able to ease the correct positioning of an epidural needle. The percentage of 10% false negative identifications of the epidural space in our case series however suggests more investigations on adequate or specific settings for this epidural system. In the meantime, in chronic pain patients, this anesthetic technique should only be used by experienced hands.