Among patients suffering from coronavirus disease 2019 (COVID-19) syndrome, one of the worst possible scenarios is represented by the critical lung damage caused by the severe acute respiratory ...syndrome coronavirus-2 (SARS-CoV-2)-induced cytokine storm, responsible for a potentially very dangerous hyperinflammatory condition. Within such a context, interleukin-6 (IL-6) plays a key pathogenic role, thus being a suitable therapeutic target. Indeed, the IL-6-receptor antagonist tocilizumab, already approved for treatment of refractory rheumatoid arthritis, is often used to treat patients with severe COVID-19 symptoms and lung involvement. Therefore, the aim of this review article is to focus on the rationale of tocilizumab utilization in the SARS-CoV-2-triggered cytokine storm, as well as to discuss current evidence and future perspectives, especially with regard to ongoing trials referring to the evaluation of tocilizumab's therapeutic effects in patients with life-threatening SARS-CoV-2 infection.
Asthma is a very frequent chronic airway disease that includes many different clinical phenotypes and inflammatory patterns. In particular, eosinophilic bronchial inflammation is often associated ...with allergic as well as nonallergic asthma. The most important cytokine involved in the induction, maintenance, and amplification of airway eosinophilia in asthma is interleukin-5 (IL-5), released by both T helper 2 (Th2) lymphocytes and group 2 innate lymphoid cells (ILC2). Hence, IL-5 and its receptor are suitable targets for selective biologic drugs which can play a key role in add-on treatment of severe eosinophilic asthma refractory to corticosteroids. Within such a context, the anti-IL-5 monoclonal antibodies mepolizumab and reslizumab have been developed and approved for biological therapy of uncontrolled eosinophilic asthma. In this regard, on the basis of several successful randomized controlled trials, the anti-IL-5 receptor benralizumab has also recently obtained the approval from US Food and Drug Administration (FDA).
During flexible fiberoptic bronchoscopy (FOB) the arterial partial pressure of oxygen can drop, increasing the risk for respiratory failure. To avoid desaturation episodes during the procedure ...several oxygenation strategies have been proposed, including conventional oxygen therapy (COT), high flow nasal cannula (HFNC), continuous positive airway pressure (CPAP) and non-invasive ventilation (NIV). By a review of the current literature, we merely describe the clinical practice of oxygen therapies during FOB. We also conducted a pooled data analysis with respect to oxygenation outcomes, comparing HFNC with COT and NIV, separately. COT showed its benefits in patients undergoing FOB for broncho-alveolar lavage (BAL) or brushing for cytology, in those with peripheral arterial oxyhemoglobin saturation < 93% prior to the procedure or affected by obstructive disorder. HFNC is preferable over COT in patients with mild to moderate acute respiratory failure (ARF) undergoing FOB, by improving oxygen saturation and decreasing the episodes of desaturation. On the opposite, CPAP and NIV guarantee improved oxygenation outcomes as compared to HFNC, and they should be preferred in patients with more severe hypoxemic ARF during FOB.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the ...short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO
clearance after 2 h of treatment.
We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25-7.35, PaCO
≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO
from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO
at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes.
Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO
reduction from baseline to 2 h were - 6.8 mmHg (± 8.7) in the HFNT and - 9.5 mmHg (± 8.5) in the NIV group (p = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO
reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p = 0.0003). Both treatments had a significant effect on PaCO
reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis.
HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO
after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD.
The study was prospectively registered on December 12, 2017, in ClinicalTrials.gov (NCT03370666).
Despite an apparent effective vaccination, some patients are admitted to the hospital after SARS-CoV-2 infection. The role of adaptive immunity in COVID-19 is growing; nonetheless, differences in the ...spike-specific immune responses between patients requiring or not hospitalization for SARS-CoV-2 infection remains to be evaluated. In this study, we aim to evaluate the spike-specific immune response in patients with mild-moderate or severeSARS-CoV-2 infection, after breakthrough infection following two doses of BNT162b2 mRNA vaccine.
We included three cohorts of 15 cases which received the two BNT162b2 vaccine doses in previous 4 to 7 months: 1) patients with severe COVID-19; 2) patients with mild-moderate COVID-19 and 3) vaccinated individuals with a negative SARS-CoV-2 molecular pharyngeal swab (healthy subjects). Anti-S1 and anti-S2 specific SARS-CoV-2 IgM and IgG titers were measured through a chemiluminescence immunoassay technology. In addition, the frequencies of IFNγ-releasing cells were measured by ELISpot.
The spike-specific IFNγ-releasing cells were significantly lower in severe patients (8 0; 26 s.f.c.×106), as compared to mild-moderate patients (135 64; 159 s.f.c.×106; p<0.001) and healthy subjects (103 50; 188 s.f.c.×106; p<0.001). The anti-Spike protein IgG levels were similar among the three cohorts of cases (p = 0.098). All cases had an IgM titer below the analytic sensitivity of the test. The Receiver Operating Curve analysis indicated the rate of spike-specific IFNγ-releasing cells can discriminate correctly severe COVID-19 and mild-moderate patients (AUC: 0.9289; 95%CI: 0.8376-1.000; p< 0.0001), with a diagnostic specificity of 100% for s.f.c. > 81.2 x 106.
2-doses vaccinated patients requiring hospitalization for severe COVID-19 show a cellular-mediated immune response lower than mild-moderate or healthy subjects, despite similar antibody titers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND:Assessing the volemic status of patients undergoing surgery is part of the routine management for the anesthesiologist. This assessment is commonly performed by means of dynamic indexes ...based on the cardiopulmonary interaction during mechanical ventilation (if available) or by administering a fluid challenge (FC). The FC is used during surgery to optimize predefined hemodynamic targets, the so-called Goal-Directed Therapy (GDT), or to correct hemodynamic instability (non-GDT).
METHODS:In this systematic review, we considered the FC components in studies adopting either GDT or non-GDT, to assess whether differences exist between the 2 approaches. In addition, we performed a meta-analysis to ascertain the effectiveness of dynamic indexes pulse pressure variation (PPV) and stroke volume (SV) variation (SVV), in predicting fluid responsiveness.
RESULTS:Thirty-five non-GDT and 33 GDT studies met inclusion criteria, including 5017 patients. In the vast majority of non-GDT and GDT studies, the FC consisted in the administration of colloids (85.7% and 90.9%, respectively). In 29 non-GDT studies, the colloid infused was the 6% hydroxyethyl starch (6% HES; 96.6% of this subgroup). In 20 GDT studies, the colloid infused was the 6% HES (66.7% of this subgroup), while in 5 studies was a gelatin (16.7% of this subgroup), in 3 studies an unspecified colloid (10.0% of this subgroup), and in 1 study albumin (3.3%) or, in another study, both HES 6% and gelatin (3.3%). In non-GDT studies, the median volume infused was 500 mL; the time of infusion and hemodynamic target to assess fluid responsiveness lacked standardization. In GDT studies, FC usually consisted in the administration of 250 mL of colloids (48.8%) in 10 minutes (45.4%) targeting an SV increase >10% (57.5%). Only in 60.6% of GDT studies, a safety limit was adopted. PPV pooled area under the curve (95% confidence interval CI) was 0.86 (0.80–0.92). The mean (standard deviation) PPV threshold predicting fluid responsiveness was 10.5% (3.2) (range, 8%–15%), while the pooled (95% CI) sensitivity and specificity were 0.80 (0.74–0.85) and 0.83 (0.73–0.91), respectively. SVV pooled area under the curve (95% CI) was 0.87 (0.81–0.93). The mean (standard deviation) SVV threshold predicting fluid responsiveness was 11.3% (3.1) (range, 7.5%–15.5%), while the pooled (95% CI) sensitivity and specificity were 0.82 (0.75–0.89) and 0.77 (0.71–0.82), respectively.
CONCLUSIONS:The key components of FC including type of fluid (colloids, often 6% HES), volume (500 and 250 mL in non-GDT studies and GDT studies, respectively), and time of infusion (10 minutes) are quite standardized in operating room. However, pooled sensitivity and specificity of both PPV and SVV are limited.
Abstract
Background
Besides airway suctioning, patients undergoing invasive mechanical ventilation (iMV) benefit of different combinations of chest physiotherapy techniques, to improve mucus removal. ...To date, little is known about the clearance effects of oscillating devices on patients with acute respiratory failure undergoing iMV. This study aimed to assess (1) the effects of high-frequency chest wall oscillation (HFCWO) on lung aeration and ventilation distribution, as assessed by electrical impedance tomography (EIT), and (2) the effect of the association of HFCWO with recruitment manoeuvres (RM).
Methods
Sixty critically ill patients, 30 classified as normosecretive and 30 as hypersecretive, who received ≥ 48 h of iMV, underwent HFCWO; patients from both subgroups were randomized to receive RM or not, according to two separated randomization sequences. We therefore obtained four arms of 15 patients each. After baseline record (T0), HFCWO was applied for 10 min. At the end of the treatment (T1) or after 1 (T2) and 3 h (T3), EIT data were recorded. At the beginning of each step, closed tracheobronchial suctioning was performed. In the RM subgroup, tracheobronchial suctioning was followed by application of 30 cmH
2
O to the patient’s airway for 30 s. At each step, we assessed the change in end-expiratory lung impedance (ΔEELI) and in tidal impedance variation (ΔTIV), and the center of gravity (COG) through EIT. We also analysed arterial blood gases (ABGs).
Results
ΔTIV and COG did not differ between normosecretive and hypersecretive patients. Compared to T0, ΔEELI significantly increased in hypersecretive patients at T2 and T3, irrespective of the RM; on the contrary, no differences were observed in normosecretive patients. No differences of ABGs were recorded.
Conclusions
In hypersecretive patients, HFCWO significantly improved aeration of the dorsal lung region, without affecting ABGs. The application of RM did not provide any further improvements.
Trial registration
Prospectively registered at the Australian New Zealand Clinical Trial Registry (
www.anzctr.org.au
; number of registration: ACTRN12615001257550; date of registration: 17th November 2015).
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Prostaglandin D2 (PGD2) is a pleiotropic mediator, significantly involved in the pathogenesis of type 2 (T2) asthma because of its biologic actions exerted on both immune/inflammatory ...and airway structural cells. In particular, the pro-inflammatory and pro-remodelling effects of PGD2 are mainly mediated by stimulation of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). This receptor is the target of the oral competitive antagonist fevipiprant, which on the basis of recent phase II studies is emerging as a potential very promising anti-asthma drug. Indeed, fevipiprant appears to be safe and effective, especially in consideration of its ability to inhibit eosinophilic bronchial inflammation and improve forced expiratory volume in one second (FEV1). Further ongoing phase III trials will definitely clarify if fevipiprant can prospectively become a valid option for an efficacious add-on treatment of moderate-to-severe T2-high asthma.
In individuals diagnosed with obstructive sleep apnea syndrome (OSAS), variations in craniofacial structure have been inconsistently documented, showing differing degrees of alteration between obese ...and nonobese patients. In addition, sleep disturbance has also been shown to induce disequilibrium in this population of patients. This pilot observational study aimed to assess craniofacial values in obese and nonobese subpopulations of patients with OSAS and their correlation and association with the severity of OSAS. We also assessed whether OSAS patients are characterized by an impaired equilibrium in relation to and associated with the severity of OSAS.
We included all consecutive adult patients with OSAS. Through cephalometry, we assessed the upper (UPa-UPp) and lower (LPa-LPp) pharynx diameters, superior anterior facial height (Sor-ANS), anterior facial height (ANS-Me), anterior vertical dimension (Sor-Me), posterior facial height (S-Go) and craniovertebral angle (CVA). Furthermore, we analyzed postural equilibrium through a stabilometric examination.
Forty consecutive OSAS patients (45% female with a mean age of 56 ± 8.2 years) were included. The subgroup of nonobese patients had a reduced UPa-UPp (p = 0.02). Cephalometric measurements were correlated with the severity of OSAS in nonobese patients, whereas only Sor-ANS was correlated with the severity of OSAS in the obese subpopulation. In the overall population, altered craniofacial values are associated with severe OSAS. Although there are differences in equilibrium between obese and nonobese OSAS patients, the stabilometric measurements were not correlated or associated with OSAS severity.
Altered craniofacial values and compromised equilibrium in OSAS patients are linked to OSAS severity. Therefore, the management of OSAS should be tailored not only to weight management but also to craniofacial and postural rehabilitation to enhance patient outcomes.
Since its first documentation, a novel coronavirus (SARS-CoV-2) infection has emerged worldwide, with the consequent declaration of a pandemic disease (COVID-19). Severe forms of acute respiratory ...failure can develop. In addition, SARS-CoV-2 may affect organs other than the lung, such as the liver, with frequent onset of late cholestasis. We here report the histological findings of a COVID-19 patient, affected by a tardive complication of acute ischemic and gangrenous cholecystitis with a perforated and relaxed gallbladder needing urgent surgery.
A 59-year-old Caucasian male, affected by acute respiratory failure secondary to SARS-CoV-2 infection was admitted to our intensive care unit (ICU). Due to the severity of the disease, invasive mechanical ventilation was instituted and SARS-CoV-2 treatment (azithromycin 250 mg once-daily and hydroxychloroquine 200 mg trice-daily) started. Enoxaparin 8000 IU twice-daily was also administered subcutaneously. At day 8 of ICU admission, the clinical condition improved and patient was extubated. At day 32, patient revealed abdominal pain without signs of peritonism at examination, with increased inflammatory and cholestasis indexes at blood tests. At a first abdominal CT scan, perihepatic effusion and a relaxed gallbladder with dense content were detected. The surgeon decided to wait and see the evolution of clinical conditions. The day after, conditions further worsened and a laparotomic cholecystectomy was performed. A relaxed and perforated ischemic gangrenous gallbladder, with a local tissue inflammation and perihepatic fluid, was intraoperatively met. The gallbladder and a sample of omentum, adherent to the gallbladder, were also sent for histological examination. Hematoxylin-eosin-stained slides display inflammatory infiltration and endoluminal obliteration of vessels, with wall breakthrough, hemorrhagic infarction, and nerve hypertrophy of the gallbladder. The mucosa of the gallbladder appears also atrophic. Omentum vessels also appear largely thrombosed. Immunohistochemistry demonstrates an endothelial overexpression of medium-size vessels (anti-CD31), while not in micro-vessels, with a remarkable activity of macrophages (anti-CD68) and T helper lymphocytes (anti-CD4) against gallbladder vessels. All these findings define a histological diagnosis of vasculitis of the gallbladder.
Ischemic gangrenous cholecystitis can be a tardive complication of COVID-19, and it is characterized by a dysregulated host inflammatory response and thrombosis of medium-size vessels.
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