Stimulating olfactory epithelium mitigates mechanical ventilation-induced hippocampal inflammation and apoptosis.

Mechanical ventilation (MV), as a life-saving procedure in critical patients, is a risk factor to develop of neurocognitive dysfunction and triggers of inflammation and apoptosis in the brain. Since diversion of breathing route to the tracheal tube diminishes brain activity entrained by physiological nasal breathing, we hypothesized that simulating nasal breathing using rhythmic air-puff (AP) into the nasal cavity of mechanically ventilated rats can reduce hippocampal inflammation and apoptosis in association with restoring respiration-coupled oscillations. We found that stimulating olfactory epithelium through applying rhythmic nasal AP, in association with reviving respiration-coupled brain rhythm, mitigates MV-induced hippocampal apoptosis and inflammation involving microglia and astrocytes. The current translational study opens a window for a novel therapeutic approach to reduce neurological complications induced by MV.

Effectiveness of different vaccine platforms in reducing mortality and length of ICU stay in severe and critical cases of COVID-19 in the Omicron variant era: A national cohort study in Iran.

Various severe acute respiratory syndrome coronavirus 2 vaccines with different platforms have been administered worldwide; however, their effectiveness in critical cases of COVID-19 has remained a concern. In this national cohort study, 24 016 intensive care unit (ICU) coronavirus disease-2019 (COVID-19) admissions were included from January to April 2022. The mortality and length of ICU stay were compared between the vaccinated and unvaccinated patients. A total of 9428 (39.25%) patients were unvaccinated, and 14 588 (60.75%) patients had received at least one dose of the vaccine. Compared with the unvaccinated, the first, second, and third doses of vaccine resulted in 8%, 20%, and 33% lower risk of ICU mortality in the adjusted model, with risk ratio (RR): 0.92, 95% confidence interval (CI): 0.84-1.001, RR: 0.80, 95% CI: 0.77-0.83, and RR: 0.67, 95% CI: 0.64-0.71, respectively. The mean survival time was significantly shorter in the unvaccinated versus the fully vaccinated patients (hazard ratio [HR]: 0.84, 95% CI: 0.80-0.88); p < 0.001). All vaccine platforms successfully decreased the hazard of ICU death compared with the unvaccinated group. The duration of ICU stay was significantly shorter in the fully vaccinated than in unvaccinated group (MD, -0.62, 95% CI: -0.82 to -0.42; p < 0.001). Since COVID-19 vaccination in all doses and platforms has been able to reduce the risk of mortality and length of ICU-stay, universal vaccination is recommended based on vaccine availability.

Role of apoptosis and autophagy in mediating tramadol-induced neurodegeneration in the rat hippocampus.

BACKGROUND: Tramadol (TRA) is an analgesic prescribed for treating mild to moderate pains, the abuse of which has increased in recent years. Chronic tramadol consumption produces neurotoxicity, although the mechanisms are unclear. The present study investigated the involvement of apoptosis and autophagy signaling pathways and the mitochondrial system in TRA-induced neurotoxicity. MATERIALS AND METHODS: Sixty adult male Wistar rats were divided into five groups that received standard saline or TRA in doses of 25, 50, 75, 100, or 150 mg/kg intraperitoneally for 21 days. On the 22nd day, the Open Field Test (OFT) was conducted. Jun N-Terminal Kinase (JNK), B-cell lymphoma-2 (Bcl-2), Beclin1, and Bcl-2-like protein 4 (Bax) proteins and tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) were measured in rat hippocampal tissue. RESULTS: TRA at doses 75, 100, and 150 mg/kg caused locomotor dysfunction in rats and increased total and phosphorylated forms of JNK and Beclin-1, Bax, and Caspase-3. TRA at the three higher doses also increased the phosphorylated (inactive) form of Bcl-2 level while decreasing the unphosphorylated (active) form of Bcl-2. Similarly, the protein levels of TNF-α and IL-1ß were increased dose-dependently. The mitochondrial respiratory chain enzymes were reduced at the three higher doses of TRA. CONCLUSION: TRA activated apoptosis and autophagy via modulation of TNF-α or IL-1ß/JNK/Bcl-2/Beclin1 and Bcl-2/Bax signaling pathways and dysfunction of mitochondrial respiratory chain enzymes.

Neural signature of attention impairment in allergic asthma: an ERP study.

Background Cognitive impairments are linked to poor treatment response and disease control in allergic asthma. However, there are no studies exploring attention-related functional brain alterations in allergic asthma. Here, we explore attention deficit and its association with clinical characteristics and common neuropsychiatric disorders in patients with allergic asthma.Methods We recruited 38 participants, equally distributed into healthy and asthma groups. Behavioral, neurophysiological, and lung function assessment tools were used in this study.Results Our behavioral data show that allergic asthma induces attention impairment. Additionally, the event-related potentials (ERP) analysis reveals that this attention deficit is associated with a disruption in cognitive processing capability in frontal brain areas. These behavioral and neurophysiological abnormalities were strongly correlated with disease severity and neuropsychiatric comorbidities of asthmatic patients.Conclusion Together, here we propose that disrupted neurophysiological responses in frontal brain areas might lead to attention impairments in patients with allergic asthma. These findings could help characterizing the neuro-pathophysiology of cognitive disorders in allergic asthma, possibly opening the way for development of novel treatment strategies.

Nasal Air Puff Promotes Default Mode Network Activity in Mechanically Ventilated Comatose Patients: A Noninvasive Brain Stimulation Approach.

OBJECTIVES: Coma state and loss of consciousness are associated with impaired brain activity, particularly gamma oscillations, that integrate functional connectivity in neural networks, including the default mode network (DMN). Mechanical ventilation (MV) in comatose patients can aggravate brain activity, which has decreased in coma, presumably because of diminished nasal airflow. Nasal airflow, known to drive functional neural oscillations, synchronizing distant brain networks activity, is eliminated by tracheal intubation and MV. Hence, we proposed that rhythmic nasal air puffing in mechanically ventilated comatose patients may promote brain activity and improve network connectivity. MATERIALS AND METHODS: We recorded electroencephalography (EEG) from 15 comatose patients (seven women) admitted to the intensive care unit because of opium poisoning and assessed the activity, complexity, and connectivity of the DMN before and during the nasal air-puff stimulation. Nasal cavity air puffing was done through a nasal cannula controlled by an electrical valve (open duration of 630 ms) with a frequency of 0.2 Hz (ie, 12 puff/min). RESULTS: Our analyses demonstrated that nasal air puffing enhanced the power of gamma oscillations (30-100 Hz) in the DMN. In addition, we found that the coherence and synchrony between DMN regions were increased during nasal air puffing. Recurrence quantification and fractal dimension analyses revealed that EEG global complexity and irregularity, typically seen in wakefulness and conscious state, increased during rhythmic nasal air puffing. CONCLUSIONS: Rhythmic nasal air puffing, as a noninvasive brain stimulation method, opens a new window to modifying the brain connectivity integration in comatose patients. This approach may potentially influence comatose patients' outcomes by increasing brain reactivity and network connectivity.

National Plan for Chronic Respiratory Diseases Prevention and Control in Iran.

Background: Lower respiratory tract infections, chronic obstructive pulmonary disease (COPD), tuberculosis, and lung cancer are among the leading 10 causes of death worldwide. The Board of Respiratory Diseases Research Network (RDRN), a sub-committee of the Iranian Non-Communicable Diseases Committee (INCDC) is particularly concerned that there should be a coordinated National strategy to address the burden caused by chronic respiratory diseases. Methods: Iranian Ministry of Health and Medical Education (MoHME) has decided to give promotion to the establishment of research networks and use them as the milestones for research management, particularly for the national health priorities. Results: National Service Framework (NSF), which was designed for Chronic Respiratory Diseases, is one of the main outcomes of the chronic respiratory diseases sub-committee of INCDC. The main seven strategies were represented by the Steering Committee in 2010 for a period of 10 years. Successful development and implementation of our goals provide the CRDs sub-committee of INCDC with the opportunity to develop a paradigm to prevent chronic respiratory diseases. Conclusion: A stronger national plan for controlling chronic respiratory diseases will ensure stronger advocacy to support respiratory health at national, sub-national, and regional levels.

Decreased neutrophil-mediated bacterial killing in COVID-19 patients.

The coronavirus disease COVID-19 was first described in December 2019. The peripheral blood of COVID-19 patients have increased numbers of neutrophils which are important in controlling the bacterial infections observed in COVID-19. We sought to evaluate the cytotoxic capacity of neutrophils in COVID-19 patients. 34 confirmed COVID-19 patients (29 severe, five mild disease), and nine healthy controls were recruited from the Masih Daneshvari Hospital (Tehran, Iran) from March to May 2020. Polymorphonuclear (PMN) cells were isolated from whole blood and incubated with green fluorescent protein (GFP)-labelled methicillin-resistant Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). Bacterial growth was determined by measuring the florescence of co-cultures of bacteria and neutrophils and reported as the lag time before exponential growth. The number of viable bacteria was determined after 70 hours as colony-forming units (CFU). The immunophenotype of tested cells was evaluated by flow cytometry. Isolated neutrophils have higher surface expression of CD16 and CD62L with negative markers for PMN-MDSC. Bacterial growth in the presence of SA (22 ± 0.9 versus 9.2 ± 0.5 h, P < .01) and PA (12.4 ± 0.6 versus 4.5 ± 0.22, P < .01) was significantly reduced in COVID-19 patients. After 70 h incubation of PMN with bacteria (SA and PA), CFUs were significant increased in COVID-19 patients SA (2.6 ± 0.09 × 108 CFU/mL-severe patients and 1.4 ± 0.06 × 108 CFU/mL-mild patients, P < .001) and PA (2.2 ± 0.09 × 109 CFU/mL-severe patients and 1.6 ± 0.03 × 109 CFU/mL-mild patients, P < .001). Gentamycin proliferation assays confirmed the presence of intracellular bacteria. Reduced bacterial killing by neutrophils from COVID-19 patients may be responsible for the high bacterial yield seen in these patients.

The effects of pressure- versus volume-controlled ventilation on ventilator work of breathing.

BACKGROUND: Measurement of work of breathing (WOB) during mechanical ventilation is essential to assess the status and progress of intensive care patients. Increasing ventilator WOB is known as a risk factor for ventilator-induced lung injury (VILI). In addition, the minimization of WOB is crucial to facilitate the weaning process. Several studies have assessed the effects of varying inspiratory flow waveforms on the patient's WOB during assisted ventilation, but there are few studies on the different effect of inspiratory flow waveforms on ventilator WOB during controlled ventilation. METHODS: In this paper, we analyze the ventilator WOB, termed mechanical work (MW) for three common inspiratory flow waveforms both in normal subjects and COPD patients. We use Rohrer's equation for the resistance of the endotracheal tube (ETT) and lung airways. The resistance of pulmonary and chest wall tissue are also considered. Then, the resistive MW required to overcome each component of the respiratory resistance is computed for square and sinusoidal waveforms in volume-controlled ventilation (VCV), and decelerating waveform of flow in pressure-controlled ventilation (PCV). RESULTS: The results indicate that under the constant I:E ratio, a square flow profile best minimizes the MW both in normal subjects and COPD patients. Furthermore, the large I:E ratio may be used to lower MW. The comparison of results shows that ETT and lung airways have the main contribution to resistive MW in normals and COPDs, respectively. CONCLUSION: These findings support that for lowering the MW especially in patients with obstructive lung diseases, flow with square waveforms in VCV, are more favorable than decelerating waveform of flow in PCV. Our analysis suggests the square profile is the best choice from the viewpoint of less MW.

Silent hypoxia: higher NO in red blood cells of COVID-19 patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has spread to almost 100 countries, infected over 31 M patients and resulted in 961 K deaths worldwide as of 21st September 2020. The major clinical feature of severe COVID-19 requiring ventilation is acute respiratory distress syndrome (ARDS) with multi-functional failure as a result of a cytokine storm with increased serum levels of cytokines. The pathogenesis of the respiratory failure in COVID-19 is yet unknown, but diffuse alveolar damage with interstitial thickening leading to compromised gas exchange is a plausible mechanism. Hypoxia is seen in the COVID-19 patients, however, patients present with a distinct phenotype. Intracellular levels of nitric oxide (NO) play an important role in the vasodilation of small vessels. To elucidate the intracellular levels of NO inside of RBCs in COVID-19 patients compared with that of healthy control subjects. METHODS: We recruited 14 COVID-19 infected cases who had pulmonary involvement of their disease, 4 non-COVID-19 healthy controls (without pulmonary involvement and were not hypoxic) and 2 hypoxic non-COVID-19 patients subjects who presented at the Masih Daneshvari Hospital of Tehran, Iran between March-May 2020. Whole blood samples were harvested from patients and intracellular NO levels in 1 × 106 red blood cells (RBC) was measured by DAF staining using flow cytometry (FACS Calibour, BD, CA, USA). RESULTS: The Mean florescent of intensity for NO was significantly enhanced in COVID-19 patients compared with healthy control subjects (P ≤ 0.05). As a further control for whether hypoxia induced this higher intracellular NO, we evaluated the levels of NO inside RBC of hypoxic patients. No significant differences in NO levels were seen between the hypoxic and non-hypoxic control group. CONCLUSIONS: This pilot study demonstrates increased levels of intracellular NO in RBCs from COVID-19 patients. Future multi-centre studies should examine whether this is seen in a larger number of COVID-19 patients and whether NO therapy may be of use in these severe COVID-19 patients.

Correction to: Silent hypoxia: higher NO in red blood cells of COVID-19 patients.

An amendment to this paper has been published and can be accessed via the original article.

Effect of passive exposure to cigarette smoke on blood pressure in children and adolescents: a meta-analysis of epidemiologic studies.

BACKGROUND: Hypertension is an emerging disease in children and adolescents resulting in future morbidities. Cigarette smoking is one of the most studied contributing factors in this regard; however, there are contradictory results among different studies. Therefore, the present meta-analysis tends to assess the relationship between passive exposure to cigarette smoke and blood pressure in children and adolescents. METHOD: Medline, Embase, Scopus, EBSCO, and Web of Sciences were systematically reviewed for observational studies up to May, 2017, in which the relationship between cigarette smoking and hypertension were assessed in children and adolescents. The meta-analysis was performed with a fixed effect or random effects model according to the heterogeneity. RESULTS: Twenty-nine studies were included in present meta-analysis incorporating 192,067 children and adolescents. Active smoking (pooled OR = 0.92; 95% CI: 0.79 to 1.05) or passive exposure to cigarette smoke (pooled OR = 1.01; 95% CI: 0.93 to 1.10) were not associated with developing hypertension in the study population. Despite the fact that active cigarette smoking did not significantly affect absolute level of systolic and diastolic blood pressure, it was shown that passive exposure to cigarette smoke leads to a significant increase in absolute level of systolic blood pressure (pooled coefficient = 0.26; 95% CI: 0.12 to 0.39). CONCLUSION: Both active and passive cigarette smoking were not associated with developing hypertension in children and adolescents. However, passive cigarette smoke was associated with higher level of systolic blood pressure in children and adolescents.

Identification of antigens from nosocomial Acinetobacter baumannii clinical isolates in sera from ICU staff and infected patients using the antigenome technique.

Nosocomial infections with a bacterial origin are considered one of the most dangerous threats to global health. Among the causes of these infections, Acinetobacter baumannii is playing a significant role, and the present study aimed to determine the immunogenic proteins of this bacteria. Clinical isolates of A. baumannii were obtained from positive sputum cultures of intensive care unit (ICU) patients confirmed by Polymerase chain reaction (PCR) of the OXA-51 gene, and sera was obtained from 20 colonized patients. In addition, 20 and 30 serum samples were collected from ICU nurses and healthy controls, respectively. All the samples were screened in the presence of antibodies against A. baumannii by enzyme-linked immunosorbent assay (ELISA). IgG purified from the serum samples by affinity chromatography was used to isolate the bacteria by the Magnetic-activated cell sorting (MACS) procedure. After the bacteria were cultured, the identified antigen proteins were studied by western blotting and Mass spectrometry (MS). The MS results were analyzed with MASCOT software and revealed a 35 KD protein, which corresponds to outer membrane protein A (OmpA) of A. baumannii, a 25 KD band, which is a carbapenem-associated resistance protein precursor, and a 60 KD protein band, identified as a stress-induced bacterial acidophilic repeat motif protein. According to the properties of immunogen antigens and bio informatics tools, the outer membrane proteins (OMPs) can be used as a vaccine candidate in animal models.

Effect of the Cardio First Angel™ device on CPR indices: a randomized controlled clinical trial.

BACKGROUND: A number of cardiopulmonary resuscitation (CPR) adjunct devices have been developed to improve the consistency and quality of manual chest compressions. We investigated whether a CPR feedback device would improve CPR quality and consistency, as well as patient survival. METHODS: We conducted a randomized controlled study of patients undergoing CPR for cardiac arrest in the mixed medical-surgical intensive care units of four academic teaching hospitals. Patients were randomized to receive either standard manual CPR or CPR using the Cardio First Angel™ CPR feedback device. Recorded variables included guideline adherence, CPR quality, return of spontaneous circulation (ROSC) rates, and CPR-associated morbidity. RESULTS: A total of 229 subjects were randomized; 149 were excluded; and 80 were included. Patient demographics were similar. Adherence to published CPR guidelines and CPR quality was significantly improved in the intervention group (p < 0.0001), as were ROSC rates (72 % vs. 35 %; p = 0.001). A significant decrease was observed in rib fractures (57 % vs. 85 %; p = 0.02), but not sternum fractures (5 % vs. 17 %; p = 0.15). CONCLUSIONS: Use of the Cardio First Angel™ CPR feedback device improved adherence to published CPR guidelines and CPR quality, and it was associated with increased rates of ROSC. A decrease in rib but not sternum fractures was observed with device use. Further independent prospective validation is warranted to determine if these results are reproducible in other acute care settings. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02394977 . Registered on 5 Mar 2015.

The comparison of extemporaneous preparations of omeprazole, pantoprazole oral suspension and intravenous pantoprazole on the gastric pH of critically ill-patients.

BACKGROUND: Stress-related mucosal disease occurs in many critically ill-patients within 24 h of admission. Proton pump inhibitor therapy has been documented to produce more potent inhibition of gastric acid secretion than histamine 2 receptor antagonists. This study aimed to compare extemporaneous preparations of omeprazole, pantoprazole oral suspension and intravenous (IV) pantoprazole on the gastric pH in intensive care unit patients. MATERIALS AND METHODS: This was a randomized single-blind-study. Patients of ≥ 16 years of age with a nasogastric tube, who required mechanical ventilation for ≥ 48 h, were eligible for inclusion. The excluded patients were those with active gastrointestinal bleeding, known allergy to omeprazole and pantoprazole and those intolerant to the nasogastric tube. Fifty-six patients were randomized to treatment with omeprazole suspension 2 mg/ml (40 mg every day), pantoprazole suspension 2 mg/ml (40 mg every day) and IV pantoprazole (40 mg every day) for up to 14 days. Gastric aspirates were sampled before and 1-2.5 h after the drug administration for the pH measurement using an external pH meter. Data were analyzed using SPSS (version 21.0). RESULTS: In this study, 56 critically ill-patients (39 male, 17 female, mean age: 61.5 ± 15.65 years) were followed for the control of the gastric pH. On each of the 14 trial days the mean of the gastric pH alteration was significantly higher in omeprazole and pantoprazole suspension-treated patients than in IV pantoprazole-treated patients (P < 0.001). CONCLUSION: Omeprazole and pantoprazole oral suspension are more effective than IV pantoprazole in increasing the gastric pH.

Assessment of the EuroSCORE risk scoring system for patients undergoing coronary artery bypass graft surgery in a group of Iranian patients.

BACKGROUND AND AIMS: Previous studies around the world indicated validity and accuracy of European System for Cardiac Operative Risk Evaluation (EuroSCORE) risk scoring system we evaluated the EuroSCORE risk scoring system for patients undergoing coronary artery bypass graft (CABG) surgery in a group of Iranian patients. MATERIALS AND METHODS: In this cohort 2220 patients more than 18 years, who were performed CABG surgery in Massih Daneshvari Hospital, from January 2004 to March 2010 were recruited. Predicted mortality risk scores were calculated using logistic EuroSCORE and Acute Physiology and Chronic Health Evaluation II (APACHE II) and compared with observed mortality. Calibration was measured by the Hosmer-Lemeshow (HL) test and discrimination by using the receiver operating characteristic (ROC) curve area. RESULTS: Of the 2220 patients, in hospital deaths occurred in 270 patients (mortality rate of 12.2%). The accuracy of mortality prediction in the logistic EuroSCORE and APACHE II model was 89.1%; in the local EuroSCORE (logistic) was 91.89%; and in the local EuroSCORE support vector machines (SVM) was 98.6%. The area under curve for ROC curve, was 0.724 (95% confidence interval [CI]: 0.57-0.88) for logistic EuroSCORE; 0.836 (95% CI: 0.731-0.942) for local EuroSCORE (logistic); 0.978 (95% CI: 0.937-1) for Local EuroSCORE (SVM); and 0.832 (95% CI: 0.723-0.941) for APACHE II model. The HL test showed good calibration for the local EuroSCORE (SVM), APACHE II model and local EuroSCORE (logistic) (P = 0.823, P = 0.748 and P = 0.06 respectively); but there was a significant difference between expected and observed mortality according to EuroSCORE model (P = 0.033). CONCLUSION: We detected logistic EuroSCORE risk model is not applicable on Iranian patients undergoing CABG surgery.

Evaluation of the Tracheal Stenosis Effects on Airway Resistance and Work of Breathing Using Computational Fluid Dynamics.

Background: Bronchoscopy is one of the most accurate procedures to diagnose airway stenosis which is an invasive procedure. However, a quick and noninvasive estimation of the percent area of obstruction (%AO) of the lumen is helpful in decision-making before performing a bronchoscopy procedure. We hypothesized that there is a relationship between %AO and tracheal resistance against fluid flow. Materials and Methods: By measuring airway resistance, %AO could be estimated before the procedure. Using computational fluid dynamics (CFD), this study simulates the fluid flow through trachea models with web-liked stenosis using CFD. A cylindrical segment was inserted into the trachea to represent cross-sectional areas corresponding to 20%, 40%, 60%, and 80% AO. The fluid flow and pressure distribution in these models were studied. Our CFD simulations revealed that the tracheal resistance is exponentially increased by %AO. Results: The results showed a 130% and 55% increase in lung airway resistance and resistive work of breathing for an 80% AO, respectively. Moreover, a curve-fitted relationship was obtained to estimate %AO based on the measured airway resistance by body plethysmography or forced oscillation technique. Conclusion: This pre-estimation is very useful in diagnostic evaluation and treatment planning in patients with tracheal stenosis.

Effect of bromhexine in hospitalized patients with COVID-19.

BACKGROUND: Bromhexine is a potent inhibitor of transmembrane serine protease 2 and appears to have an antiviral effect in controlling influenza and parainfluenza infection; however, its efficacy in COVID-19 is controversial. METHODS: A group of hospitalized patients with confirmed COVID-19 pneumonia were randomized using 1:1 allocation to either standard treatment lopinavir/ritonavir and interferon beta-1a or bromhexine 8 mg four times a day in addition to standard therapy. The primary outcome was clinical improvement within 28 days, and the secondary outcome measures were time to hospital discharge, all-cause mortality, duration of mechanical ventilation, the temporal trend in 2019-nCoV reverse transcription-polymerase chain reaction positivity and the frequency of adverse drug events within 28 days from the start of medication. RESULTS: A total of 111 patients were enrolled in this randomized clinical trial and data from 100 patients (48 patients in the treatment arm and 52 patients in the control arm) were analyzed. There was no significant difference in the primary outcome of this study, which was clinical improvement. There was no significant difference in the average time to hospital discharge between the two arms. There were also no differences observed in the mean intensive care unit stay, frequency of intermittent mandatory ventilation, duration of supplemental oxygenation or risk of death by day 28 noted between the two arms. CONCLUSION: Bromhexine is not an effective treatment for hospitalized patients with COVID-19. The potential prevention benefits of bromhexine in asymptomatic postexposure or with mild infection managed in the community remain to be determined.