Spontaneous breathing trial and post-extubation work of breathing in morbidly obese critically ill patients

Figure S5. difference in the work of breathing expressed in J/l between each test and the post-extubation period. Dashed line represents the absence of difference between the test and the post-extubation period. (JPG 44 kb

Renal hypoperfusion and impaired endothelium-dependent vasodilation in an animal model of VILI: the role of the peroxynitrite-PARP pathway

Introduction: Mechanical ventilation (MV) can injure the lungs and contribute to an overwhelming inflammatory response, leading to acute renal failure (ARF). We previously showed that poly(adenosine diphosphate-ribose) polymerase (PARP) is involved in the development of ventilator-induced lung injury (VILI) and the related ARF, but the mechanisms underneath remain unclear. In the current study we therefore tested the hypothesis that renal blood flow and endothelial, functional and tissue changes in the kidney of rats with lipopolysaccharide (LPS)-induced lung injury aggravated by MV, is caused, in part, by activation of PARP by peroxynitrite.Methods: Anesthetized Sprague Dawley rats (n = 31), were subjected to intratracheal instillation of lipopolysaccharide at 10 mg/kg followed by 210 min of mechanical ventilation at either low tidal volume (6 mL/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (19 mL/kg) with zero positive end-expiratory pressure in the presence or absence of a peroxynitrite decomposition catalyst, WW85 or a PARP inhibitor, PJ-34. During the experiment, hemodynamics and blood gas variables were monitored. At time (t) t = 0 and t = 180 min, renal blood flow was measured. Blood and urine were collected for creatinine clearance measurement. Arcuate renal arteries were isolated for vasoreactivity experiment and kidneys snap frozen for staining.Results: High tidal volume ventilation resulted in lung injury, hypotension, renal hypoperfusion and impaired renal endothelium-dependent vasodilation, associated with renal dysfunction and tissue changes (leukocyte accumulation and increased expression of neutrophil gelatinase-associated lipocalin). Both WW85 and PJ-34 treatments attenuated lung injury, preserved blood pressure, attenuated renal endothelial dysfunction and maintained renal blood flow. In multivariable analysis, renal blood flow improvement was, independently from each other, associated with both maintained blood pressure and endothelium-dependent vasodilation by drug treatment. Finally, drug treatment improved renal function and reduced tissue changes.Conclusions: The peroxynitrite-induced PARP activation is involved in renal hypoperfusion, impaired endothelium-dependent vasodilation and resultant dysfunction, and injury, in a model of lung injury

Osteopontin at the Crossroads of Inflammation and Tumor Progression.

Complex interactions between tumor and host cells regulate systemic tumor dissemination, a process that begins early at the primary tumor site and goes on until tumor cells detach themselves from the tumor mass and start migrating into blood or lymphatic vessels. Metastatic cells colonize target organs and are capable of surviving and growing at distant sites. In this context, osteopontin (OPN) appears to be a key determinant of the cross-talk between cancer cells and the host microenvironment, which in turn modulates immune evasion. OPN is overexpressed in several human carcinomas and has been implicated in inflammation, tumor progression, and metastasis. Thus, it represents one of the most attracting targets for cancer therapy. Within the tumor mass, OPN is secreted in various forms either by the tumor itself or by stroma cells, and it can exert either pro- or anti-tumorigenic effects according to cell type and tumor microenvironment. Thus, targeting OPN for therapeutic purposes needs to take into account the heterogeneous functions of the multiple OPN forms with regard to cancer formation and progression. In this review, we will describe the role of systemic, tumor-derived, and stroma-derived OPN, highlighting its pivotal role at the crossroads of inflammation and tumor progression

Clinical Outcomes in Patients Aged 80 Years or Older Receiving Non-Invasive Respiratory Support for Hypoxemic Acute Respiratory Failure Consequent to COVID-19

: As the clinical outcome of octogenarian patients hospitalised for COVID-19 is very poor, here we assessed the clinical characteristics and outcomes of patients aged 80 year or older hospitalised for COVID-19 receiving non-invasive respiratory support (NIRS). A multicentre, retrospective, observational study was conducted in seven hospitals in Northern Italy. All patients aged ≥80 years with COVID-19 associated hypoxemic acute respiratory failure (hARF) undergoing NIRS between 24 February 2020, and 31 March 2021, were included. Out of 252 study participants, 156 (61.9%) and 163 (64.6%) died during hospital stay and within 90 days from hospital admission, respectively. In this case, 228 (90.5%) patients only received NIRS (NIRS group), while 24 (9.5%) were treated with invasive mechanical ventilation (IMV) after NIRS failure (NIRS+IMV group). In-hospital mortality did not significantly differ between NIRS and NIRS+IMV group (61.0% vs. 70.8%, respectively; p = 0.507), while survival probability at 90 days was significantly higher for NIRS compared to NIRS+IMV patients (0.379 vs. 0.147; p = 0.0025). The outcome of octogenarian patients with COVID-19 receiving NIRS is quite poor. Caution should be used when considering transition from NIRS to IMV after NIRS failure

High tidal volume mechanical ventilation-induced lung injury in rats is greater after acid instillation than after sepsis-induced acute lung injury, but does not increase systemic inflammation: an experimental study

<p>Abstract</p> <p>Background</p> <p>To examine whether acute lung injury from direct and indirect origins differ in susceptibility to ventilator-induced lung injury (VILI) and resultant systemic inflammatory responses.</p> <p>Methods</p> <p>Rats were challenged by acid instillation or 24 h of sepsis induced by cecal ligation and puncture, followed by mechanical ventilation (MV) with either a low tidal volume (Vt) of 6 mL/kg and 5 cm H₂O positive end-expiratory pressure (PEEP; LVt acid, LVt sepsis) or with a high Vt of 15 mL/kg and no PEEP (HVt acid, HVt sepsis). Rats sacrificed immediately after acid instillation and non-ventilated septic animals served as controls. Hemodynamic and respiratory variables were monitored. After 4 h, lung wet to dry (W/D) weight ratios, histological lung injury and plasma mediator concentrations were measured.</p> <p>Results</p> <p>Oxygenation and lung compliance decreased after acid instillation as compared to sepsis. Additionally, W/D weight ratios and histological lung injury scores increased after acid instillation as compared to sepsis. MV increased W/D weight ratio and lung injury score, however this effect was mainly attributable to HVt ventilation after acid instillation. Similarly, effects of HVt on oxygenation were only observed after acid instillation. HVt during sepsis did not further affect oxygenation, compliance, W/D weight ratio or lung injury score. Plasma interleukin-6 and tumour necrosis factor-α concentrations were increased after acid instillation as compared to sepsis, but plasma intercellular adhesion molecule-1 concentration increased during sepsis only. In contrast to lung injury parameters, no additional effects of HVt MV after acid instillation on plasma mediator concentrations were observed.</p> <p>Conclusions</p> <p>During MV more severe lung injury develops after acid instillation as compared to sepsis. HVt causes VILI after acid instillation, but not during sepsis. However, this differential effect was not observed in the systemic release of mediators.</p

Outcomes of COVID-19 patients treated with continuous positive airway pressure outside ICU

Aim We aim at characterizing a large population of Coronavirus 19 (COVID-19) patients with moderate-to-severe hypoxemic acute respiratory failure (ARF) receiving CPAP outside intensive care unit (ICU), and ascertaining whether the duration of CPAP application increased the risk of mortality for patients requiring intubation. Methods In this retrospective, multicentre cohort study, we included COVID-19 adult patients, treated with CPAP outside ICU for hypoxemic ARF from March 1 st to April 15th, 2020. We collected demographic and clinical data, including CPAP therapeutic goal, hospital length of stay (LOS), and 60- day in-hospital mortality. Results The study includes 537 patients with a median age of 69 (IQR, 60-76) years. Males were 391 (73%). According to predefined CPAP therapeutic goal, 397 (74%) patients were included in full treatment subgroup, and 140 (26%) in the do-not intubate (DNI) subgroup. Median CPAP duration was 4 (IQR, 1-8) days, while hospital LOS 16 (IQR, 9-27) days. Sixty-day in-hospital mortality was overall 34% (95%CI, 0.304-0.384), and 21% (95%CI, 0.169-0.249) and 73% (95%CI, 0.648-0.787) for full treatment and DNI subgroups, respectively. In the full treatment subgroup, in-hospital mortality was 42% (95%CI, 0.345-0.488) for 180 (45%) CPAP failures requiring intubation, while 2% (95%CI, 0.008- 0.035) for the remaining 217 (55%) patients who succeeded. Delaying intubation was associated with increased mortality [HR, 1.093 (95%CI, 1.010-1.184)]. Conclusions We described a large population of COVID-19 patients treated with CPAP outside ICU. Intubation delay represents a risk factor for mortality. Further investigation is needed for early identification of CPAP failures

Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial

: As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63-1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70-1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk