Global longitudinal strain is an informative index of left ventricular performance in neonates receiving intensive care.

Echocardiographic assessment of left ventricular function is crucial in NICU. The study aimed to compare the accuracy and agreement of global longitudinal strain (GLS) with conventional measurements. Real-life echocardiograms of neonates receiving intensive care were retrospectively reviewed. Shortening fraction (SF), ejection fraction (EF) and S' measurements were retrieved from health records. GLS was calculated offline from stored images. The association with stroke volume indexed for body weight (iSV) was evaluated by regression analysis. The diagnostic ability to identify uncompensated shock was assessed by ROC curve analysis. Cohen's κ was run to assess agreement. 334 echocardiograms of 155 neonates were evaluated. Mean ± SD gestational age and birth weight were 34.5 ± 4.1 weeks and 2264 ± 914 g, respectively. SF, EF, S' and GLS were associated with iSV with R2 of 0.133, 0.332, 0.252 and 0.633, (all p < .001). Including all variables in a regression model, iSV prediction showed an adjusted R2 of 0.667, (p < .001). GLS explained 73% of the model variance. GLS showed a better ability to diagnose uncompensated shock (AUC 0.956) compared to EF, S' and SF (AUC 0.757, 0.737 and 0.606, respectively). GLS showed a moderate agreement with EF (κ = .500, p < .001) and a limited agreement with S' and SF (κ = .260, p < .001, κ = .242, p < .001). GLS was a more informative index of left ventricular performance, providing the rationale for a more extensive use of GLS at the cotside.

Anti-CGRP and Anti-CGRP Receptor Monoclonal Antibodies for Migraine Prophylaxis: Retrospective Observational Study on 209 Patients.

BACKGROUND: Migraine is a neurological disorder characterized by attacks of head pain with prevalent unilateral localization, moderate to high intensity and specifically associated accompanying symptoms. METHODS: In this retrospective observational study, we analyzed data regarding 209 patients who had previously been diagnosed with migraine and who were prescribed, between 2019 and 2022, subcutaneous injections of anti-CGRP monoclonal antibodies (mAbs) fremanezumab or galcanezumab or anti-CGRP receptors mAb erenumab regardless of the concomitant assumption of any other acute-phase or prophylactic migraine medication. RESULTS: Regarding efficacy, in the 205 analyzed patients, the change from baseline in terms of MIDAS, HIT-6, MMDs and MAD scores was statistically significant for erenumab and galcanezumab, while for fremanezumab a statistical significance was not achieved likely due to the small sample size. In the treated population, 36 patients (17.5%) reported AEs (pain during injection, transient injection site erythema, nausea, constipation and fatigue). Only 5 patients (2.4%) discontinued the treatment for AEs while 15 patients (7.3%) left for lack of efficacy. CONCLUSIONS: this retrospective study comes out in favor of both significant efficacy and safety of anti-CGRP and anti-CGRP receptors mAbs in migraine patients. Further methodologically stronger studies are necessary to validate our observation.

Inhaled Pulmonary Vasodilators for the Treatment of Right Ventricular Failure in Cardio-Thoracic Surgery: Is One Better than the Others?

Right ventricular failure (RFV) is a potential complication following cardio-thoracic surgery, with an incidence ranging from 0.1% to 30%. The increase in pulmonary vascular resistance (PVR) is one of the main triggers of perioperative RVF. Inhaled pulmonary vasodilators (IPVs) can reduce PVR and improve right ventricular function with minimal systemic effects. This narrative review aims to assess the efficacy of inhaled nitric oxide and inhaled prostacyclins for the treatment of perioperative RVF. The literature, although statistically limited, supports the clinical similarity between them. However, it failed to demonstrate a clear benefit from the pre-emptive use of inhaled nitric oxide in patients undergoing left ventricular assist device implantation or early administration during heart-lung transplants. Additional concerns are related to cost safety and IPV use in pathologies associated with pulmonary venous congestion. The largest ongoing randomized controlled trial on adults (INSPIRE-FLO) is addressing whether inhaled Epoprostenol and inhaled nitric oxide are similar in preventing RVF after heart transplants and left ventricular assist device placement, and whether they are similar in preventing primary graft dysfunction after lung transplants. The preliminary analysis supports their equivalence. Several key points may be achieved by the present narrative review. When RVF occurs in the setting of elevated PVR, IPV should be the preferred initial treatment and they should be preventively used in patients at high risk of postoperative RVF. If severe refractory postoperative RVF occurs, IPVs should be combined with complementary pharmacology (inotropes and inodilators). If unsuccessful, right ventricular mechanical support should be established.

Tissue-Tracking Mitral Annular Displacement in Neonates: A Novel Index of Left Ventricular Systolic Function.

OBJECTIVES: To assess the feasibility, accuracy, and reproducibility of tissue-tracking mitral annular displacement (TMAD) compared with other measures of left ventricular systolic function in healthy preterm and term neonates in the transitional period. METHODS: This was a prospective observational study. Two echocardiograms were performed at 24 and 48 hours of life. TMAD, shortening fraction (SF), ejection fraction (EF), s', and global longitudinal strain (GLS) were measured offline. Accuracy to detect impaired GLS was tested by ROC curve analysis. DeLong test was used to compare AUCs. Intra and interobserver reproducibility of the off-line analysis was calculated. RESULTS: Mean ± SD gestational age and weight were 34.2 ± 3.8 weeks and 2162 ± 833 g, respectively. TMAD was feasible in 168/180 scans (93%). At 24 hours the AUC (95% CI) of SF, EF, s', and TMAD (%) was 0.51 (0.36-0.67), 0.68 (0.54-0.82), 0.63 (0.49-0.77), and 0.89 (0.79-0.99) respectively. At 48 hours the AUC (95% CI) of SF, EF, s', and TMAD (%) was 0.64 (0.51-0.77), 0.59 (0.37-0.80), 0.70 (0.54-0.86), and 0.96 (0.91-1.00), respectively. The AUC of TMAD was superior to the AUC of SF, EF, s', at both timepoints (P < .02). Intraclass correlation coefficients (95% CI) of intra and interobserver reproducibility of TMAD were 0.97 (0.95-0.99) and 0.94 (0.88-0.97), respectively. CONCLUSION: TMAD showed improved accuracy and optimal reproducibility in neonates in the first 48 hours of life.

Analysis of P(v-a)CO2/C(a-v)O2 Ratio and Other Perfusion Markers in a Population of 98 Pediatric Patients Undergoing Cardiac Surgery.

BACKGROUND: The so-called Low Cardiac Output Syndrome (LCOS) is one of the most common complications in pediatric patients with congenital heart disease undergoing corrective surgery. LCOS requires high concentrations of inotropes to support cardiac contractility and improve cardiac output, allowing for better systemic perfusion. To date, serum lactate concentrations and central venous oxygen saturation (ScVO2) are the most commonly used perfusion markers, but they are not completely reliable in identifying a state of global tissue hypoxia. The study aims to evaluate whether the venoarterial carbon dioxide difference/arterial-venous oxygen difference ratio [P(v-a)CO2/C(a-v)O2] can be a good index to predict the development of LCOS in the aforementioned patients, so as to treat it promptly. METHODS: This study followed a population of 98 children undergoing corrective cardiac surgery from June 2018 to October 2020 at the Department of Cardiac Surgery of University Hospital Integrated Trust and their subsequent admission at the Postoperative Cardiothoracic Surgery Intensive Care Unit. During the study, central arterial and venous blood gas analyses were carried out before and after cardiopulmonary bypass (CPB) (pre-CPB and post-CPB), at admission to the intensive care unit, before and after extubation, and at any time of instability or modification of the patient's clinical and therapeutic conditions. RESULTS: The data analysis shows that 46.9% of the children developed LCOS (in line with the current literature) but that there is no statistically significant association between the P(v-a)CO2/C(a-v)O2 ratio and LCOS onset. Despite the limits of statistical significance, however, a 31% increase in the ratio emerged from the pre-CPB phase to the post-CPB phase when LCOS is present. CONCLUSIONS: This study confirms a statistically significant association between the most used markers in adult patients (serum lactate concentration, ScVO2, and oxygen extraction ratio-ERO2) measured in the pre-CPB phase and the incidence of LCOS onset, especially in patients with hemodynamic instability before surgery.

Proof of concept study on coronary microvascular function in low flow low gradient aortic stenosis.

OBJECTIVES: We hypothesised that low flow low gradient aortic stenosis (LFLGAS) is associated with more severe coronary microvascular dysfunction (CMD) compared with normal-flow high-gradient aortic stenosis (NFHGAS) and that CMD is related to reduced cardiac performance. METHODS: Invasive CMD assessment was performed in 41 consecutive patients with isolated severe aortic stenosis with unobstructed coronary arteries undergoing transcatheter aortic valve implantation (TAVI). The index of microcirculatory resistance (IMR), resistive reserve ratio (RRR) and coronary flow reserve (CFR) were measured in the left anterior descending artery before and after TAVI. Speckle tracking echocardiography was performed to assess cardiac function at baseline and repeated at 6 months. RESULTS: IMR was significantly higher in patients with LFLGAS compared with patients with NFHGAS (24.1 (14.6 to 39.1) vs 12.8 (8.6 to 19.2), p=0.002), while RRR was significantly lower (1.4 (1.1 to 2.1) vs 2.6 (1.5 to 3.3), p=0.020). No significant differences were observed in CFR between the two groups. High IMR was associated with low stroke volume index, low cardiac output and reduced peak atrial longitudinal strain (PALS). TAVI determined no significant variation in microvascular function (IMR: 16.0 (10.4 to 26.1) vs 16.6 (10.2 to 25.6), p=0.403) and in PALS (15.9 (9.9 to 26.5) vs 20.1 (12.3 to 26.7), p=0.222). Conversely, left ventricular (LV) global longitudinal strain increased after TAVI (-13.2 (8.4 to 16.6) vs -15.1 (9.4 to 17.8), p=0.047). In LFLGAS, LV systolic function recovered after TAVI in patients with preserved microvascular function but not in patients with CMD. CONCLUSIONS: CMD is more severe in patients with LFLGAS compared with NFHGAS and is associated with low-flow state, left atrial dysfunction and reduced cardiac performance.

Epicardial adipose tissue volume and CT-attenuation as prognostic factors for pulmonary embolism and mortality in critically ill patients affected by COVID-19.

BACKGROUND/OBJECTIVES: The aim of this post-hoc analysis was to evaluate if epicardial adipose tissue (EAT) quantity and quality, as evaluated by computed tomography (CT), have a different role in the risk of mortality and pulmonary embolism in critically ill COVID-19 patients admitted to an intensive care unit (ICU). SUBJECTS/METHODS: CT derived EAT volume and density, as well as anthropometric and blood biomarkers, were evaluated in a sample of 138 subjects, 109 men and 29 women, for whom CT images and information on pulmonary embolism were available from a total of 313 subjects who were consecutively admitted to the ICU for COVID-19 from the REINSURE-ARDS prospective registry. RESULTS: A total of 28 patients (20.3%) died during the first 28 days after ICU admission. 26 subjects out of 138 had pulmonary embolism (18.8%). Age, weight, BMI, IL-6 levels and pulmonary embolism prevalence were significantly higher across EAT volume tertiles. Subjects who died in the first 28 days from ICU admission were older, had higher EAT volume, D-dimer, LDH and IL-6 level. After adjustment for age and gender, participants in tertile 3 of EAT volume had lower survival at 28 days from ICU admission as compared to subjects in the tertile 1, HR 2.95 (95% C.I. 1.02-8.49), but after adjusting for potential confounders the relation was no longer significant. No relation between EAT density and mortality was observed. From a binary logistic regression, subjects in tertile 3 of EAT volume and in tertile 1 of EAT density showed a 4 times and 3.6 times increased risk of pulmonary embolism, respectively. CONCLUSIONS: ICU subjects affected by severe COVID-19 with higher EAT volume and low EAT density should be carefully monitored and managed with a prompt and aggressive approach, to prevent serious and life-threatening consequences and the increase of hospital treatment costs.

Bipolar Spectrum Symptoms in Patients with Fibromyalgia: A Dimensional Psychometric Evaluation of 120 Patients.

BACKGROUND: Fibromyalgia Syndrome (FMS) is characterized by chronic widespread pain, fatigue, unrefreshing sleep and cognitive dysfunction. Depressive and manic symptoms are often reported in FMS patients' history. The aim of this study was to evaluate the prevalence of bipolar spectrum symptoms (BSS) and to correlate these with quality of life (QoL) scores and antidepressant treatment. METHODS: From October 2017 to July 2018, a battery of QoL questionnaires (FIQ, PSQI and SF-12) was administered to 120 FMS patients after a clinical examination. The MOODS-SR lifetime questionnaire was then remotely administered to the patients included in the study. RESULTS: The presence of depressive and manic lifetime symptoms was found, in line with the results of the available literature. A correlation was found between the history of depressive symptoms and the severity of FIQ and SF-12 scores. Despite a low statistical strength, a trend toward a correlation between a history of manic symptoms and SNRI treatment was detected. CONCLUSIONS: The correlation between the MOOD-depressive domains and poor QoL is in line with the available literature. Further studies are needed to corroborate these findings and to elucidate the relationship between manic symptoms and SNRI treatment.

The Effects of Temperature Management on Brain Microcirculation, Oxygenation and Metabolism.

PURPOSE: Target temperature management (TTM) is often used in patients after cardiac arrest, but the effects of cooling on cerebral microcirculation, oxygenation and metabolism are poorly understood. We studied the time course of these variables in a healthy swine model. METHODS: Fifteen invasively monitored, mechanically ventilated pigs were allocated to sham procedure (normothermia, NT; n = 5), cooling (hypothermia, HT, n = 5) or cooling with controlled oxygenation (HT-Oxy, n = 5). Cooling was induced by cold intravenous saline infusion, ice packs and nasal cooling to achieve a body temperature of 33-35 °C. After 6 h, animals were rewarmed to baseline temperature (within 5 h). The cerebral microvascular network was evaluated (at baseline and 2, 7 and 12 h thereafter) using sidestream dark-field (SDF) video-microscopy. Cerebral blood flow (laser Doppler MNP100XP, Oxyflow, Oxford Optronix, Oxford, UK), oxygenation (PbtO2, Licox catheter, Integra Lifesciences, USA) and lactate/pyruvate ratio (LPR) using brain microdialysis (CMA, Stockholm, Sweden) were measured hourly. RESULTS: In HT animals, cerebral functional capillary density (FCD) and proportion of small-perfused vessels (PSPV) significantly decreased over time during the cooling phase; concomitantly, PbtO2 increased and LPR decreased. After rewarming, all microcirculatory variables returned to normal values, except LPR, which increased during the rewarming phase in the two groups subjected to HT when compared to the group maintained at normothermia. CONCLUSIONS: In healthy animals, TTM can be associated with alterations in cerebral microcirculation during cooling and altered metabolism at rewarming.

Oxycodone-Naloxone Combination Hinders Opioid Consumption in Osteoarthritic Chronic Low Back Pain: A Retrospective Study with Two Years of Follow-Up.

Chronic low back pain (CLBP) due to osteoarthritis represents a therapeutic challenge worldwide. Opioids are extensively used to treat such pain, but the development of tolerance, i.e., less susceptibility to the effects of the opioid, which can result in a need for higher doses to achieve the same analgesic effect, may limit their use. Animal models suggest that ultra-low doses of opioid antagonists combined with opioid agonists can decrease or block the development of opioid tolerance. In this retrospective study, we tested this hypothesis in humans. In 2019, 53 patients suffering from CLBP were treated with either Oxycodone and Naloxone Prolonged Release (27 patients, OXN patients) or Oxycodone Controlled Release (26 patients, OXY patients). The follow-up period lasted 2 years, during which 10 patients discontinued the treatment, 5 out of each group. The remaining 43 patients reached and maintained the targeted pain relief, but at 18 and 24 months, the OXY patients showed a significantly higher oxycodone consumption than OXN patients to reach the same level of pain relief. No cases of respiratory depression or opioid abuse were reported. There were no significant differences in the incidence of adverse effects between the two treatments, except for constipation, more common in OXY patients. From our results, we can affirm that a long-term opioid treatment with oxycodone-naloxone combination, when compared with oxycodone only, may significantly hinder the development of opioid tolerance. We were also able to confirm, in our cohort, the well known positive effect of naloxone in terms of opioid-induced bowel dysfunction incidence reduction.

Comparative Prognostic Value of Parameters of Pulsatile Right Ventricular Afterload in Patients With Advanced Heart Failure Awaiting Heart Transplantation.

Right ventricular pulsatile afterload (RVPA) demonstrated a strong impact on survival of patients with advanced heart failure (HF) with reduced ejection fraction. The best prognostic parameter of RVPA is unknown. The aim of this work was to examine the prognostic relevance of pulmonary artery compliance (PAC), pulmonary artery elastance (PAE), and pulmonary artery pulsatile index (PAPi) in a consecutive cohort of patients with advanced HF evaluated for heart transplantation (HT). A total of 149 patients with end-stage HF underwent right-sided cardiac catheterization and were clinically followed up until death or any censoring events, including HT, left ventricular assist device, and hospitalization for acute HF. The primary endpoint occurred in 29 patients (19.5%) during a median follow-up time of 12 (interquartile range 3 to 34) months. This cohort presented a worse hemodynamic profile than event-free survivors. PAC <1.9 mL/mm Hg (hazard ratio 3, 95% confidence interval 1.3 to 6.0, p= 0.007) and PAE >0.9 mmHg/mL (hazard ratio 2.5, 95% confidence interval 1.1 to 5.2, p= 0.02) were associated with the adverse outcome. On the contrary, PAPi was not associated with the outcome. PAC demonstrated a superior predictive value for the composite adverse outcome compared with pulmonary vascular resistance (area under the curve comparison p= 0.019) and PAPi (p= 0.03) but similar compared with PAE (p= 0.19) and mean pulmonary arterial pressure (p= 0.51). PAC, but not PAE, showed incremental prognostic value compared with cardiac index (p= 0.02). In conclusion, hemodynamic indexes of RVPA are associated with worse survival in patients with end-stage HF. PAC and PAE demonstrated superior prognostic value compared with PAPi and pulmonary vascular resistance. Moreover, PAC showed incremental prognostic value compared with cardiac index in patients awaiting HT.

Optimal timing for percutaneous coronary intervention in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: The best timing to perform percutaneous coronary interventions (PCI) in patients undergoing TAVI is unknown. Most PCI are performed before TAVI, because of concerns about potential ischemic complications during valve implantation. In this study we aimed to compare short-and long-term outcomes of patients undergoing PCI before or after TAVI. METHODS: Patients undergoing TAVI and PCI from 2010 to 2021 were analyzed. PCI was defined as high-risk when involving unprotected left main, proximal left anterior descending, proximal dominant right coronary artery or 3-vessel disease. The primary endpoint was the cumulative incidence of any TAVI procedural complication and in-hospital adverse events (VARC-3 criteria). RESULTS: Out of 1162 patients, 144 underwent PCI, 68% after TAVI, 78.4% of which were at high-risk. The primary endpoint occurred in 28.4% of patients in PCI pre-TAVI group vs 21.4% in PCI post-TAVI group (p = 0.403) and in 34.4% vs 17.3% of patients respectively among high-risk patients (p = 0.075). A higher rate of stroke was observed in the PCI pre-TAVI group regardless of the PCI complexity (6.5% vs 0.0%, p = 0.031; 9.3% vs 0.0% p = 0.025 in the high-risk group). At 24 months, MACCE-free survival was lower in patients who underwent PCI before TAVI (84.4% vs 97.9%, adjusted HR 10.16, 95% CI 1.19-86.57, p = 0.019; and 84.4% vs 97.3%, adjusted HR 7.34 95% CI 0.78-62.28 p = 0.082 in the high-risk group). CONCLUSIONS: PCI performed after TAVI does not expose patients to higher risks of peri-procedural hazards and provides a trend towards favourable clinical outcome at mid-to-long term.

Persistent Idiopathic Facial Pain (PIFP) in Patients Referred to a Multidisciplinary Centre in Italy: A Retrospective Observational Study.

BACKGROUND: Persistent Idiopathic Facial Pain (PIFP), previously named Atypical Facial Pain (AFP) is a poorly understood condition, often diagnosed after several inconclusive investigations. The aim of this retrospective study was to evaluate the demographic and clinical characteristics of patients with PIFP referred to a Facial Pain Center. METHODS: Between May 2011 and September 2014, data on 41 PIFP patients were analyzed regarding temporal, topographical and descriptive pain features, including onset, localization, pain descriptors and intensity. Pharmacological pain treatments were also registered. Finally, the presence and type of previous minor oro-surgery procedures in the painful area were investigated. RESULTS: Demographic and clinical characterization were similar to PIFP patients reported in literature. The presence of previous minor oro-surgery procedures in the painful area was reported in most of these patients, in particular endodontic treatments and tooth extractions. CONCLUSIONS: This retrospective analysis showed a high prevalence of minor oro-surgery procedures in our population, while its role in PIFP pathophysiology remains unknown. A new classification of PIFP built around the main discriminant factor of presence of these procedures in the painful area could be considered while available data were still insufficient to define specific diagnostic criteria.

Fatal cytokine release syndrome by an aberrant FLIP/STAT3 axis.

Inflammatory responses rapidly detect pathogen invasion and mount a regulated reaction. However, dysregulated anti-pathogen immune responses can provoke life-threatening inflammatory pathologies collectively known as cytokine release syndrome (CRS), exemplified by key clinical phenotypes unearthed during the SARS-CoV-2 pandemic. The underlying pathophysiology of CRS remains elusive. We found that FLIP, a protein that controls caspase-8 death pathways, was highly expressed in myeloid cells of COVID-19 lungs. FLIP controlled CRS by fueling a STAT3-dependent inflammatory program. Indeed, constitutive expression of a viral FLIP homolog in myeloid cells triggered a STAT3-linked, progressive, and fatal inflammatory syndrome in mice, characterized by elevated cytokine output, lymphopenia, lung injury, and multiple organ dysfunctions that mimicked human CRS. As STAT3-targeting approaches relieved inflammation, immune disorders, and organ failures in these mice, targeted intervention towards this pathway could suppress the lethal CRS inflammatory state.

Efficacy of Pulsatile Flow Perfusion in Adult Cardiac Surgery: Hemodynamic Energy and Vascular Reactivity.

Background: The role of pulsatile (PP) versus non-pulsatile (NP) flow during a cardiopulmonary bypass (CPB) is still debated. This study's aim was to analyze hemodynamic effects, endothelial reactivity and erythrocytes response during a CPB with PP or NP. Methods: Fifty-two patients undergoing an aortic valve replacement were prospectively randomized for surgery with either PP or NP flow. Pulsatility was evaluated in terms of energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE). Systemic (SVRi) and pulmonary (PVRi) vascular resistances, endothelial markers levels and erythrocyte nitric-oxide synthase (eNOS) activity were collected at different perioperative time-points. Results: In the PP group, the resultant EEP was 7.3% higher than the mean arterial pressure (MAP), which corresponded to 5150 ± 2291 ergs/cm3 of SHE. In the NP group, the EEP and MAP were equal; no SHE was produced. The PP group showed lower SVRi during clamp-time (p = 0.06) and lower PVRi after protamine administration and during first postoperative hours (p = 0.02). Lower SVRi required a higher dosage of norepinephrine in the PP group (p = 0.02). Erythrocyte eNOS activity results were higher in the PP patients (p = 0.04). Renal function was better preserved in the PP group (p = 0.001), whereas other perioperative variables were comparable between the groups. Conclusions: A PP flow during a CPB results in significantly lower SVRi, PVRi and increased eNOS production. The clinical impact of increased perioperative vasopressor requirements in the PP group deserves further evaluation.

Outcomes of COVID-19 patients intubated after failure of non-invasive ventilation: a multicenter observational study.

The efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the intensive care unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: (1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and (2) assessing whether the length of NIV application affects patient survival. This observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February-April 2020), who underwent endotracheal intubation after NIV failure. Among the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60-76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06-4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04-1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. In-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality.

Heart, kidney and left ventricular assist device: a complex trio.

BACKGROUND: Heart failure (HF) is a complex syndrome affecting the whole body, kidneys included. The left ventricular assist device (LVAD) is a valid option for patients with very severe HF. Focusing on renal function, LVAD implantation could theoretically reverse the detrimental effects of HF syndrome on kidneys. However, implanting an LVAD is a high-risk surgical procedure, and LVAD patients have higher risk of bleeding, device thrombosis, strokes, renal impairment, multi-organ failure and infections. Furthermore, an LVAD has its own particular effects on the renal system. METHODS: In this review, we provide a comprehensive overview of the complex interaction between LVAD and the kidneys from the pathophysiological and clinical perspectives. An analysis of the different effects of pulsatile-flow and continuous-flow LVAD is provided. RESULTS: Despite their limitations, creatinine-based estimated glomerular filtration rate (eGFR) formulas help to stratify patients by their post-LVAD placement prognosis. Poor basal renal function, the onset of acute kidney injury or the need for renal replacement therapy after LVAD implantation negatively influences a patient's prognosis. LVAD can also prompt an improvement in renal function, however, with some counterintuitive effects on a patient's prognosis. CONCLUSION: It is still hard to say whether different trends in eGFR depend on different renal conditions before LVAD placement, on a patient's better overall status or on a particular patient management strategy before and/or after the device's implantation. Steps should be taken to solve this question because finding the best candidates for LVAD implantation is of paramount importance to ensure the best outcomes.

Impact on Renal Function and Hospital Outcomes of an Individualized Management of Cardiopulmonary Bypass in Congenital Heart Surgery: A Pilot Study.

During cardiopulmonary bypass (CPB), high flows can allow an adequate perfusion to kidneys, but, on the other hand, they could cause emboli production, increased vascular pressure, and a more intense inflammatory response, which are in turn causes of renal damage. Along with demographic variables, other intra-operative management and post-operative events, this might lead to Acute kidney injury (AKI) in infants undergoing cardiac surgery. The aim of our study was to investigate if a CPB strategy with flow requirements based on monitoring of continuous metabolic and hemodynamic parameters could have an impact on outcomes, with a focus on renal damage. Thirty-four consecutive infants and young children undergoing surgery requiring CPB, comparable as for demographic and patho-physiological profile, were included. In Group A, 16 patients underwent, for a variable period of 20 min, CPB aiming for the minimal flow that could maintain values of MVO2 > 70% and frontal NIRS (both left and right) > 45%, and renal NIRS > 65%. In Group B, 18 patients underwent nominal flows CPB. Tapered CPB allowed for a mean reduction of flows of 34%. No difference in terms of blood-gas analysis, spectroscopy trend, laboratory analyses, and hospital outcome were recorded. In patients developing AKI (20%), renal damage was correlated with demographic characteristics and with renal NIRS during the first 6 h in the ICU. A safe individualized strategy for conduction of CPB, which allows significant flow reduction while maintaining normal hemodynamic and metabolic parameters, does not impact on renal function and hospital outcomes.

Static compliance and driving pressure are associated with ICU mortality in intubated COVID-19 ARDS.

BACKGROUND: Pathophysiological features of coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) were indicated to be somewhat different from those described in nonCOVID-19 ARDS, because of relatively preserved compliance of the respiratory system despite marked hypoxemia. We aim ascertaining whether respiratory system static compliance (Crs), driving pressure (DP), and tidal volume normalized for ideal body weight (VT/kg IBW) at the 1st day of controlled mechanical ventilation are associated with intensive care unit (ICU) mortality in COVID-19 ARDS. METHODS: Observational multicenter cohort study. All consecutive COVID-19 adult patients admitted to 25 ICUs belonging to the COVID-19 VENETO ICU network (February 28th-April 28th, 2020), who received controlled mechanical ventilation, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1st day of controlled mechanical ventilation were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients. RESULTS: A total of 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: (1) Crs was not linearly associated with ICU mortality (p value for nonlinearity = 0.01), with a greater risk of death for values < 48 ml/cmH2O; (2) the association between DP and ICU mortality was linear (p value for nonlinearity = 0.68), and increasing DP from 10 to 14 cmH2O caused significant higher odds of in-ICU death (OR 1.45, 95% CI 1.06-1.99); (3) VT/kg IBW was not associated with a significant increase of the risk of death (OR 0.92, 95% CI 0.55-1.52). Multivariable analysis confirmed these findings. CONCLUSIONS: Crs < 48 ml/cmH2O was associated with ICU mortality, while DP was linearly associated with mortality. DP should be kept as low as possible, even in the case of relatively preserved Crs, irrespective of VT/kg IBW, to reduce the risk of death.

Intermuscular Adipose Tissue as a Risk Factor for Mortality and Muscle Injury in Critically Ill Patients Affected by COVID-19.

BACKGROUND: Muscular fatigue and injury are frequently observed in critically ill COVID-19 patients. The aim of this study was to determine whether different muscle adipose tissue depots are associated with mortality and muscle damage in patients affected by COVID-19 admitted to the ICU. METHODS: CT images were obtained in 153 ICU patients with COVID-19 (121 males and 32 females). Height, weight, body mass index (BMI), C-reactive protein, Creatine PhosphoKinase (CPK), muscle density, and intermuscular adipose tissue (IMAT) were measured. RESULTS: Participants in the highest tertile of IMAT/muscle had the shorter 28-day survival from ICU admission as compared to subjects in the first tertile. Estimates derived from the Cox proportional hazard models, after adjustment for age, sex, and BMI, confirmed the results of the survival analysis (HR 3.94, 95% CI: 1.03-15.09). Participants in the lowest tertile of muscle density had the shorter survival at 28 days from ICU admission as compared to subjects in the highest tertile (HR 3.27, 95% CI: 1.18-4.61), but the relationship was no longer significant when age was included in the model. Subjects in the second muscle density tertile did not show an increased risk.Participants in the highest tertile of IMAT/muscle and those in the lowest tertile of muscle density showed both significantly higher CPK adjusted for weight values as evaluated during the first 8 days of hospitalization. CONCLUSION: Our data seem to suggest that higher levels of IMAT/muscle and low muscle density are both associated with higher risk of ICU mortality and muscle injury as evaluated with CPK level.