Acute Respiratory Insufficiency Research Articles

Outcome of high-flow nasal cannula (HFNC) therapy in respiratory failure due to lower respiratory tract infections in PICU - a single center experience in Karachi, Pakistan.

Objective: To evaluate the outcome of high-flow nasal cannula (HFNC) therapy by ROX index in critically ill children with acute respiratory failure due to lower respiratory tract infections in pediatric intensive care unit (PICU). Study Design: Analytical, Observational, Cross-sectional study. Setting: The PICU of the Indus Hospital, Karachi, Pakistan. Period: November 2022 to October 2023. Methods: We enrolled children of either gender, aged above 1 month up to 16 years and presenting with acute respiratory insufficiency due to lower respiratory tract infections. The use of HFNC was monitored for 72-hours. HFNC failure was characterized by requiring either noninvasive mechanical ventilation or invasive mechanical ventilation due to an unstable state. Results: In a total of 62 children, 39 (62.9%) were male. The mean age was 27.01±30.96 months. The most common diagnosis at the time of admission were pneumonia, and bronchiolitis noted in 25 (40.3%), and 33 (53.2%) children, respectively. Gradual improvement in ROX index was observed among children with HFNC success while a declining ROX index predicted HFNC failure. Outcome of HFNC was successful in 45 (72.6%) children. Mortality was observed in 12 (19.4%) children. Presence of comorbidity was significantly associated with unsuccessful HFNC outcomes. Conclusion: ROX index was found to be a good predictor of HFNC outcome. Overall, HFNC therapy in PICU demonstrated 72.6% success rate. HFNC outcomes are hampered particularly in cases involving comorbidities highlighting the need for tailored interventions.

Outcomes of bailout use of continuous positive airway pressure in patients with severe COVID-19 respiratory failure

During the first wave of the Coronavirus-19 (COVID-19) pandemic, due to an overflow of patients in the ICU, continuous positive airway pressure (CPAP) was used as a last resort to mechanical ventilation. The purpose of this study is to evaluate prognostic factors in COVID-19 severe respiratory failure patients treated with helmet CPAP. We reviewed the medical records of COVID-19 respiratory failure patients treated with H-CPAP at the Emergency Department from February 23rd to March 14th, 2020. A total of 202 (40%) patients admitted for respiratory failure due to COVID-19 pneumonia were considered. 129 (64%) patients received H-CPAP, while 73 (36%) required endotracheal intubation and invasive mechanical ventilation despite initial H-CPAP. 99 patients (49%) died. The mortality rate in the IMV group was 37%, compared to 56% in the group that received only H-CPAP (p= 0.004). The age and comorbidities of patients in the two groups differed significantly (p < 0.001). Age and PaO2/FiO2 were identified as the only independent risk factors for death. Identifying these independent predictors of mortality in patients with acute respiratory insufficiency may help clinicians optimize treatment escalation.

Liquid respiratory desaturation. The first experience of application on large biological objects

Introduction. This article is a continuation of the publication of the experimental studies results of prevention of acute decompression sickness (aDCS) in laboratory animals by the method of liquid respiratory desaturation (LRDS). LRDS is a method of preventing decompression disorders by the excretion of metabolically indifferent gases (in particular nitrogen) from the body during spontaneous respiration with liquid or artificial liquid lung ventilation (ALLV), by dissolved gas concentration gradient "from tissues to respiratory fluid". The method allows to provide rapid desaturation of the body from metabolically indifferent gases in the process of liquid respiration before and/or during decompression, thereby creating conditions for application of ultra-fast decompression profiles without the risk of decompression disorders.
 The aim of the study was to confirm the possibility of LRDS being a method of DCS prevention on large laboratory animals (minipigs).
 Materials and methods. The studies were performed on Wiessenau minipigs (n=8) — male and female, aged 4–5.5 months and weighing 7.1–11.2 kg. Animals of the control (n=4) and experimental (n=4) groups were subjected by compression by keeping in an air environment under high pressure (absolute 0.5 MPa for 60 minutes) to saturate tissues with indifferent gas (nitrogen). After compression experimental group was exposed to 30-minute ALLV with a liquid (perfluorodecalin) saturated with an oxygen under normobaric conditions. Air environment pressure during procedure of artificial lung ventilation was kept at 0.5 MPa. Decompression of the control and experimental groups was carried out in non-stop manner for 80 and 40 seconds respectively. The investigation of severity of clinical manifestations of DCS (changes in hemodynamic and respiratory parameters) including ultrasonic examination of gas bubbles in the heart and large vessels of the liver and as well as survival of animals in groups and pathoanatomical changes was performed.
 Results of the study. Clinical manifestations, ultrasonic scanning of the heart and venous vessels of the liver, as well as morphological examination data indicated the development of severe acute post-decompression disorders (PDD) in animals of the control group, which caused deaths in 100% of cases. Meanwhile all animals in experimental group survived and their state was stable. According to ultrasonic examination, the presence of small number of gas bubbles in the right-side heart chambers and liver's venous vessels being noted, but they disappeared after several hours. Deviations of the respiration's parameters function from background values (shortness of breath of a mixed type with the participation of auxiliary muscles, etc.) observed from the 2nd to the 4th day after ALLV, as well as compensatory reactions from the cardiovascular system (heart rate variability and instability of hemodynamic parameters) were caused by ALLV.
 Conclusions. Compressed air exposure 0.5 MPa for 60 minutes followed by 80 seconds of non-stop decompression allows to provoke the severe acute PDD minipigs model, manifested by pronounced intravascular gas formation, the development of acute respiratory and cardiovascular insufficiency causing the development of adverse outcomes.
 The ultrasound method of visual assessment of intravascular gas formation severity, adapted for minipigs, together with the dynamics of changes in the indicators of respiratory and cardiovascular systems makes possible to assess not only state of animal under anesthesia, but also the effectiveness of PDD prevention measures.
 The usage of ALLV with PFC liquid completely saturated with 100% oxygen under normobaric conditions makes possible partial removal of indifferent gas (nitrogen) dissolved in tissues of experimental animals during exposition in a compressed air environment before decompression and thereby carry out the prevention of DCS by LRDS method. It makes possible to implement successfully ultra-fast decompression profiles, incompatible with life in the control group.
 The state of animals from experimental group after LRDS is characterized by lung impairment caused by ALLV in hyperbaric conditions accompanied by temporary changes of external respiration function and compensatory reactions of cardiovascular system, observed during first 4 days.
 Ethics. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki. The Clinical Study Protocol was approved by local Ethics Committee of The Federal State Budgetary Scientific Institution «Izmerov Research Institute of Occupational Health».

Excretion of SARS-CoV-2 RNA in feces has no prognostic benefit in the outcome of COVID-19: A clinical and immunological study

This study explores the correlation between immunological and clinical characteristics in coronavirus disease 2019 (COVID-19) patients with detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in feces, analyzing data from 251 patients admitted to Mostar University Clinical Hospital from December 2021 to January 2022. Methods involved reverse transcription quantitative polymerase chain reaction (RT-qPCR) from nasopharyngeal swabs and feces, alongside serological tests for anti-SARS-CoV-2 spike IgGs. Demographic and clinical data were collected through questionnaires and medical records. The data analyses were performed using SPSS statistical software. Death occurred in 53 patients (21.1%, P < 0.001), mostly in the elderly (47/53, 88.7%, P = 0.001) and immunocompromised (19/53, 35.8%, P = 0.05), particularly those developing acute respiratory insufficiency (ARI) (46/53, 86.8%, P = 0.004), and severe/critical disease (46/53, 86.8%, P = 0.002). Among the patients with positive anti-SARS-CoV-2 IgG antibodies (86/251, 34.3%, P < 0.001), 41 (47.7%) were vaccinated and 45 (52.3%) unvaccinated (P = 0.666), showing no significant differences in clinical outcomes or mortality. Unvaccinated patients with a negative antibody titer had a higher incidence of ARI (96/123, 78%, P = 0.029) and intensive care unit admission (22/123, 17.9%, P = 0.026), than those with a positive antibody titer. Forty-seven (62.7%) patients, out of the 75 hospitalized who provided a feces sample, were positive for SARS-CoV-2 RNA (P = 0.028), without statistical differences between fecal SARS-CoV-2 positive and negative groups regarding vaccination status (15/47, 31.9%, P = 0.493), antibody status (18/47, 38.3%, P = 0.628) or death outcome (5/47, 10.6%, P = 0.706). In conclusion, unvaccinated hospitalized patients with a severe COVID-19 presentation and a negative anti-spike SARS-CoV-2 IgG titer had adverse outcomes more frequently. This suggests cautious consideration for the diagnostic use of fecal samples compared to nasopharyngeal swabs.

Effects of the PI3K/Akt/HO-1 pathway on autophagy in a sepsis-induced acute lung injury mouse model

Sepsis-induced lung injury is an acute hypoxic respiratory insufficiency caused by systemic infectious factors that results in alveolar epithelial cell and capillary endothelial cell injury, diffuse pulmonary interstitial edema, and alveolar edema. Heme oxygenase (HO)-1 is usually associated with inflammation and has anti-inflammatory effects. Autophagy is a degradation pathway that eliminates cellular metabolic waste and plays an important protective role during stress. The phosphatidylinositol 3-kinase/ protein kinase B (PI3K/Akt) signaling pathway plays a key role in mediating cellular responses to inflammatory reactions. Therefore, we hypothesized that HO-1 is associated with autophagy and regulated by the PI3K/Akt signaling pathway in mice with sepsis-induced lung injury. Sepsis-induced lung injury was induced in mice using cecal ligation and puncture (CLP). Hemin or Sn-protoporphyrin IX (SnPP) was administered via intraperitoneal injection before surgery. Survival rates were observed during days 1–7 after the surgery; lung histology was discerned 24 h after the surgery; pro-inflammatory and anti-inflammatory factors in plasma and lung tissue were measured using enzyme-linked immunosorbent assay (ELISA); HO-1, Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B)-II, p62 and lysosome associated membrane protein (LAMP)2 protein expression levels were measured 24 h after the surgery; HO-1 and LC3B-II protein expression levels were observed using immunofluorescence 24 h after the surgery; and autophagosomes were detected using electron microscopy 24 h after the surgery. Furthermore, when PI3K inhibitors LY294002, PI3K activators Recilisib and hemin were administered before the surgery, Akt, p-Akt, HO-1, and LC3-II levels were measured 24 h post-surgery. We found that HO-1 overexpression increased the survival rate and inhibited sepsis-induced lung injury. HO-1 overexpression attenuated the levels of proinflammatory cytokines (TNF-α, IL-1β) and increased the anti-inflammatory cytokine (IL-10, HO-1) overexpression. Moreover, HO-1 overexpression was also associated with increased expression of Beclin-1, LC3B-II and LAMP2 protein expression; decreased p62 protein expression; and significantly increased autophagosome formation. The results for HO-1-downregulated mice contrasted with those mentioned above. LY294002 inhibited p-Akt/Akt, HO-1, and LC3B-II protein expression; and hemin reversed the inhibitory effect of LY294002. The protective effect of HO-1 was involved in the mediation of autophagy, which may be regulated by the PI3K/Akt signaling pathway during sepsis-induced lung injury in mice.

Non-invasive Mechanical Ventilation in Acute Respiratory Failure. Clinical Practice Guidelines - on behalf of the German Society of Pneumology and Ventilatory Medicine

The guideline update outlines the advantages as well as the limitations of NIV in the treatment of acute respiratory failure in daily clinical practice and in different indications.Non-invasive ventilation (NIV) has a high value in therapy of hypercapnic acute respiratory failure, as it significantly reduces the length of ICU stay and hospitalization as well as mortality.Patients with cardiopulmonary edema and acute respiratory failure should be treated with continuous positive airway pressure (CPAP) and oxygen in addition to necessary cardiological interventions. This should be done already prehospital and in the emergency department.In case of other forms of acute hypoxaemic respiratory failure with only mild or moderately disturbed gas exchange (PaO2/FiO2 > 150 mmHg) there is no significant advantage or disadvantage compared to high flow nasal oxygen (HFNO). In severe forms of ARDS NIV is associated with high rates of treatment failure and mortality, especially in cases with NIV-failure and delayed intubation.NIV should be used for preoxygenation before intubation. In patients at risk, NIV is recommended to reduce extubation failure. In the weaning process from invasive ventilation NIV essentially reduces the risk of reintubation in hypercapnic patients. NIV is regarded useful within palliative care for reduction of dyspnea and improving quality of life, but here in concurrence to HFNO, which is regarded as more comfortable. Meanwhile NIV is also recommended in prehospital setting, especially in hypercapnic respiratory failure and pulmonary edema.With appropriate monitoring in an intensive care unit NIV can also be successfully applied in pediatric patients with acute respiratory insufficiency.

TREATMENT OF SEVERE EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE IN HOSPITAL SETTING

The main goal of treating chronic obstructive disease (COPD) is the prevention of acute and serious exacerbations, that is, the timely application of effective therapy when an exacerbation occurs. As a nonpharmacological strategy for the treatment of acute exacerbations of COPD associated with acute respiratory insufficiency, the importance of applying respiratory support in the form of oxygen therapy and non-invasive ventilation is emphasized. The goal of the work: Analysis of patient characteristics, length of hospitalization, type of respiratory support and outcome of treatment. Material and methods: This retrospective study included a group of 408 patients who, in the period from January 1, 2022. until December 31, 2022. were treated in the Clinic for Pulmonary Diseases of the University Hospital of the Republic of Srpska, due to an acute exacerbation of COPD associated with acute respiratory insufficiency. The necessary parameters (age, sex, diagnosis of COPD, length of hospitalization, comorbidities) were taken from the medical records of each individual patient and were processed using methods from the domain of descriptive statistics. Results: Out of the total number of 408 patients, 266 (65.2%) were male and 142 (38.8%) were female. A total of 358 patients have at least one significant comorbidity associated with them, which is relatively 87.75% of all patients with severe exacerbation of COPD. The average age of the mentioned patients is 70 years, while the average duration of hospitalization was 8.87 days. A total of 370 patients (90.68%) were discharged from the Clinic for Pulmonary Diseases cured, while 38 patients (9.32%) ended with a fatal outcome. Out of 408, 304 patients (74.5%) were treated only with oxygen therapy, while 104 patients (25.5%) required intermittent use of non-invasive ventilation. Patients who required the application of non-invasive ventilation survived the exacerbation in 83.65% of cases and were discharged home, while 16.35% of patients ended fatally. Conclusion: Timely and adequate application of oxygen therapy and non-invasive ventilation leads to improvement of gas exchange, reduces work of breathing and the need for intubation, and reduces mortality and length of hospitalization

Mortality Rate and Acute Kidney Injury Prevalence Reduction in COVID-19 Critical Patients Treated with Hemoperfusion.

Coronavirus disease 2019 (COVID-19) induces organic damage mainly through the patient's immune overreaction. Hemoperfusion (HPF) can remove inflammatory cytokines and can reduce the negative effects of cytokine storm in COVID-19. We compared the mortality rate, inflammatory response, and acute kidney injury (AKI) prevalence among patients suffering from respiratory insufficiency secondary to COVID-19 treated with and without HPF with HA330 cartridge. Mortality rate, serum creatinine, and ferritin values were compared between patients suffering from respiratory insufficiency secondary to COVID-19 who received conventional treatment and another group of patients who additionally received four sessions of HPF with HA330. Of 116 patients suffering from acute respiratory insufficiency secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), one group (n: 84) received support treatment and the other group (n: 32) additionally received HPF with HA330 cartridge. Both groups had no renal disease and similar age and comorbidities at admission, except for obesity and mechanical ventilation requirement, which were significantly higher in the HPF group. Mortality rate (61% vs. 31%, P: 0.008), serum creatinine (1.4 vs. 0.5 mg/dl, P < 0.001), and post-HPF serum ferritin (2868 vs. 1675, P < 0.001) were significantly lower in the HPF group. Mortality rate, serum ferritin, and AKI were significantly reduced in critical COVID-19 patients who received HPF with HA330 cartridge than in those who did not receive it. These results were obtained despite the HPF group risk factors, such as obesity and mechanical ventilation, worsening its prognosis.

Long non-coding RNA PFI inhibits apoptosis of alveolar epithelial cells to alleviate lung injury via miR-328-3p/Creb1 axis

Acute lung injury (ALI), a common clinical type of critical illness, is an acute hypoxic respiratory insufficiency caused by the damage of alveolar epithelial cells and capillary endothelial cells. In a previous study, we reported a novel lncRNA, lncRNA PFI, which could protect against pulmonary fibrosis in pulmonary fibroblasts. The present study demonstrated that lncRNA PFI was downregulated in alveolar epithelial cell of mice injury lung tissues, and further investigated the role of lncRNA PFI in regulating inflammation-induced alveolar epithelial cell apoptosis. Overexpression of lncRNA PFI could partially abrogated bleomycin induced type II AECs injured. Subsequently, bioinformatic prediction revealed that lncRNA PFI might directly bind to miR-328-3p, and further AGO-2 RNA binding protein immunoprecipitation (RIP) assay confirmed their binding relationship. Furthermore, miR-328-3p promoted apoptosis in MLE-12 cells by limiting the activation of the Creb1, a protein correlated with cell apoptosis, whereas AMO-328-3p ablated the pro-apoptosis effect of silencing lncRNA PFI in MLE-12 cells. While miR-328-3p could also ablate the function of lncRNA PFI in bleomycin treated human lung epithelial cells. Enhanced expression of lncRNA PFI reversed the LPS-induced lung injury in mice. Overall, these data reveal that lncRNA PFI mitigated acute lung injury through miR-328-3p/Creb1 pathway in alveolar epithelial cells.

Beneficial or detrimental activity of regulatory T cells, indoleamine 2,3-dioxygenase, and heme oxygenase-1 in the lungs is influenced by the level of virulence of Mycobacterium tuberculosis strain infection.

Tuberculosis (TB) caused by the complex Mycobacterium tuberculosis (Mtb) is the main cause of death by a single bacterial agent. Last year, TB was the second leading infectious killer after SARS-CoV-2. Nevertheless, many biological and immunological aspects of TB are not completely elucidated, such as the complex process of immunoregulation mediated by regulatory T cells (Treg cells) and the enzymes indoleamine 2,3-dioxygenase (IDO) and heme oxygenase 1 (HO-1). In this study, the contribution of these immunoregulatory factors was compared in mice infected with Mtb strains with different levels of virulence. First Balb/c mice were infected by intratracheal route, with a high dose of mild virulence reference strain H37Rv or with a highly virulent clinical isolate (strain 5186). In the lungs of infected mice, the kinetics of Treg cells during the infection were determined by cytofluorometry and the expression of IDO and HO-1 by RT-PCR and immunohistochemistry. Then, the contribution of immune-regulation mediated by Treg cells, IDO and HO-1, was evaluated by treating infected animals with specific cytotoxic monoclonal antibodies for Treg cells depletion anti-CD25 (PC61 clone) or by blocking IDO and HO-1 activity using specific inhibitors (1-methyl-D,L-tryptophan or zinc protoporphyrin-IX, respectively). Mice infected with the mild virulent strain showed a progressive increment of Treg cells, showing this highest number at the beginning of the late phase of the infection (28 days), the same trend was observed in the expression of both enzymes being macrophages the cells that showed the highest immunostaining. Animals infected with the highly virulent strain showed lower survival (34 days) and higher amounts of Treg cells, as well as higher expression of IDO and HO-1 one week before. In comparison with non-treated animals, mice infected with strain H37Rv with depletion of Treg cells or treated with the enzymes blockers during late infection showed a significant decrease of bacilli loads, higher expression of IFN-g and lower IL-4 but with a similar extension of inflammatory lung consolidation determined by automated morphometry. In contrast, the depletion of Treg cells in infected mice with the highly virulent strain 5186 produced diffuse alveolar damage that was similar to severe acute viral pneumonia, lesser survival and increase of bacillary loads, while blocking of both IDO and HO-1 produced high bacillary loads and extensive pneumonia with necrosis. Thus, it seems that Treg cells, IDO and HO-1 activities are detrimental during late pulmonary TB induced by mild virulence Mtb, probably because these factors decrease immune protection mediated by the Th1 response. In contrast, Treg cells, IDO and HO-1 are beneficial when the infection is produced by a highly virulent strain, by regulation of excessive inflammation that produced alveolar damage, pulmonary necrosis, acute respiratory insufficiency, and rapid death.

An observational study on factors associated with ICU mortality in Covid-19 patients and critical review of the literature

The novel pandemic caused by SARS-CoV-2 has been associated with increased burden on healthcare system. Recognizing the variables that independently predict death in COVID-19 is of great importance. The study was carried out prospectively in a single ICU in northern Greece. It was based on the collection of data during clinical practice in 375 adult patients who were tested positive for SARS-CoV-2 between April 2020 and February 2022. All patients were intubated due to acute respiratory insufficiency and received Invasive Mechanical Ventilation. The primary outcome was ICU mortality. Secondary outcomes were 28-day mortality and independent predictors of mortality at 28 days and during ICU hospitalization. For continuous variables with normal distribution, t-test was used for means comparison between two groups and one-way ANOVA for multiple comparisons. When the distribution was not normal, comparisons were performed using the Mann–Whitney test. Comparisons between discrete variables were made using the x2 test, whereas the binary logistic regression was employed for the definition of factors affecting survival inside the ICU and after 28 days. Of the total number of patients intubated due to COVID-19 during the study period, 239 (63.7%) were male. Overall, the ICU survival was 49.6%, whereas the 28-day survival reached 46.9%. The survival rates inside the ICU for the four main viral variants were 54.9%, 50.3%, 39.7% and 50% for the Alpha, Beta, Delta and Omicron variants, respectively. Logistic regressions for outcome revealed that the following parameters were independently associated with ICU survival: wave, SOFA @day1, Remdesivir use, AKI, Sepsis, Enteral Insufficiency, Duration of ICU stay and WBC. Similarly, the parameters affecting the 28-days survival were: duration of stay in ICU, SOFA @day1, WBC, Wave, AKI and Enteral Insufficiency. In this observational cohort study of critically ill COVID-19 patients we report an association between mortality and the wave sequence, SOFA score on admission, the use of Remdesivir, presence of AKI, presence of gastrointestinal failure, sepsis and WBC levels. Strengths of this study are the large number of critically ill COVID-19 patients included, and the comparison of the adjusted mortality rates between pandemic waves within a two year-study period.

Positive End-Expiratory Pressure Levels in Adult Patients With Acute Lung Injury and Acute Respiratory Distress Syndrome

Positive End-Expiratory Pressure Levels in Adult Patients With Acute Lung Injury and Acute Respiratory Distress Syndrome

Hyperoxemia During Cardiac Surgery Is Associated With Postoperative Pulmonary Complications.

Retrospective cohort study. We analyzed intraoperative data from five hospitals within the Multicenter Perioperative Outcomes Group between January 1, 2014, and December 31, 2019. We assessed intraoperative oxygenation of adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Hyperoxemia pre and post CPB was quantified as the area under the curve (AUC) of Fio2 above 0.21 in minutes when the corresponding peripheral oxygen saturation was greater than 92% measured by pulse oximetry. We quantified hyperoxemia during CPB as the AUC of Pao2 greater than 200 mm Hg measured by arterial blood gas. We analyzed the association of hyperoxemia during all phases of cardiac surgery with the frequency of postoperative pulmonary complications within 30 days, including acute respiratory insufficiency or failure, acute respiratory distress syndrome, need for reintubation, and pneumonia. Twenty-one thousand six hundred thirty-two cardiac surgical patients. None. During 21,632 distinct cardiac surgery cases, 96.4% of patients spent at least 1 minute in hyperoxemia (99.1% pre-CPB, 98.5% intra-CPB, and 96.4% post-CPB). Increasing exposure to hyperoxemia was associated with an increased risk of postoperative pulmonary complications throughout three distinct surgical periods. During CPB, increasing exposure to hyperoxemia was associated with an increased odds of developing postoperative pulmonary complications (p < 0.001) in a linear manner. Hyperoxemia before CPB (p < 0.001) and after CPB (p = 0.02) were associated with increased odds of developing postoperative pulmonary complications in a U-shaped relationship. Hyperoxemia occurs almost universally during cardiac surgery. Exposure to hyperoxemia assessed continuously as an AUC during the intraoperative period, but particularly during CPB, was associated with an increased incidence of postoperative pulmonary complications.

Rhabdomyolysis Associated with Recent SARS-COV-2 Infection in a Patient with Carnitine Palmitoyltransferase II Deficiency.

Carnitine palmitoyltransferase II deficiency (CPT II) is an autosomal recessive inherited disorder of long-chain fatty acid oxidation in the mitochondrial matrix, resulting in an inability to utilize fat for energy in cells. The most frequent myopathic form occurs in young adults and is associated with recurrent episodes of exercise-induced rhabdomyolysis. The myopathic form is caused by the Ser113Leu mutation of the CPT II gene. Rarely, massive rhabdomyolysis could be complicated by acute kidney injury (AKI), cardiomyopathy, and respiratory insufficiency. We present a case of an 18-year old male with myalgia, muscular weakness, and dark-colored urine after prolonged exercise and a recent mildSARS-CoV-2infection. Massive rhabdomyolysis was diagnosed with markedly increased serum concentrations of myoglobin and creatine kinase, with normal kidney function. The patient experienced two similar episodes in the years 2017 and 2018, with rhabdomyolysis and AKI treated with hemodialysis. After excluding autoimmune and infectious diseases as causes of recurrent rhabdomyolysis, the patient was genetically tested and Ser113Leu mutation of the CPT II gene was confirmed. When a patient presents with myalgia and dark-colored urine triggered by minor physical activities, genetic testing for possible CPT II deficiency should be initiated. TheSARS-CoV-2infection could be a factor that triggers the occurrence of rhabdomyolysis and aggravates the severity of the attack in patients with CPT II deficiency.

A population-based cohort study of sex and risk of severe outcomes in covid-19

There is a male sex disadvantage in morbidity and mortality due to COVID-19. Proposed explanations to this disparity include gender-related health behaviors, differential distribution of comorbidities and biological sex differences. In this study, we investigated the association between sex and risk of severe COVID-19 while adjusting for comorbidities, socioeconomic factors, as well as unmeasured factors shared by cohabitants which are often left unadjusted. We conducted a total-population-based cohort study (n = 1,854,661) based on individual-level register data. Cox models was used to estimate the associations between sex and risk for severe COVID-19. We additionally used a within-household design and conditional Cox models aiming to account for unmeasured factors shared by cohabitants. A secondary aim was to compare the risk of COVID-19 related secondary outcomes between men and women hospitalized due to COVID-19 using logistic regression. Men were at higher risk for hospitalization (HR = 1.63;95%CI = 1.57–1.68), ICU admission (HR = 2.63;95%CI = 2.38–2.91) and death (HR = 1.81;95%CI = 1.68–1.95) due to COVID-19, based on fully adjusted models. However, the effect of sex varied significantly across age groups: Among people in their 50s, men had > four times higher risk of COVID-19 death. The within-household design did not provide any further explanation to the sex disparity. Among patients hospitalized due to COVID-19, men had an increased risk for viral pneumonia, acute respiratory distress syndrome, acute respiratory insufficiency, acute kidney injury, and sepsis which persisted in fully adjusted models. Recognition of the combined effect of sex and age on COVID-19 outcomes has implications for policy strategies to reduce the adverse effects of the disease.

Proposing an Intelligent Monitoring System for Early Prediction of Need for Intubation among COVID-19 Hospitalized Patients

Introduction: Predicting acute respiratory insufficiency due to coronavirus disease 2019 (COVID-19) can diminish the severe complications and mortality associated with the disease. This study aimed to develop an intelligent system based on machine learning (ML) models for frontline clinicians to effectively triage high-risk patients and prioritize who needs mechanical intubation (MI).&#x0D; Materials and Methods: In this retrospective-design study, the data regarding 482 COVID-19 hospitalized patients from February 9, 2020, to July 20, 2021, was analyzed by six ML classifiers. The most critical clinical variables were identified by a minimal-redundancy-maximal-relevance (mRMR) feature selection technique. In the next step, the models' performance was assessed using confusion matrix criteria and, finally, the best model was adopted.&#x0D; Results: Proposed models were implemented using 23 confirmed variables. Results of comparing six selected ML algorithms indicated the extreme gradient boosting (XGBoost) classifier with 84.7% accuracy, 76.5 % specificity, 90.7% sensitivity, 85.1% f-measure, 87.4% Kappa statistic, and 85.3% for receiver operating characteristic (ROC) had the best performance in the intubation prediction.&#x0D; Conclusion: It is found that ML enables a satisfactory accuracy level in calculating intubation risk in COVID-19 patients. Therefore, using the ML-based intelligent models, notably the XGBoost algorithm, actually enables recognizing high-risk cases and advising correct therapeutic and supportive care by the clinicians.

Effects of Physiotherapy on Rehabilitation and Quality of Life in Patients Hospitalized for COVID-19: A Review of Findings from Key Studies Published 2020-2022.

The estimated percentage of individuals with COVID-19 due to infection with SARS-CoV-2 in need of hospitalization mostly increases proportionally with age, reaching almost 10% for those older than 60 years. Among hospitalized patients, one-fifth require treatment in the intensive care unit (ICU) due to acute respiratory distress syndrome, multiorgan failure, or hypoxemic respiratory insufficiency. Patients with moderate and severe COVID-19 who were hospitalized during the early stages of the pandemic and who continue to be hospitalized report fatigue, muscle weakness, joint stiffness, reduced mobility, increased risk of falls, and impaired quality of life. Physiotherapy is recognized to be important in the rehabilitation of COVID-19 patients requiring hospitalization. The current physiotherapy guidelines and recommendations for individuals with COVID-19, which include treatment methods and outcome measures for evaluation of the effects on respiratory and physical function and quality of life, are those established from the pre-COVID-19 era. The available extant scientific literature mainly reported the effect of physiotherapy in patients with COVID-19 in the acute, hospitalization courses of the disease, while there is a lack of quality primary, experimental studies on the effects of physiotherapy in rehabilitation of post-COVID-19 patients after hospitalization. This review aims to present an update on the effects of physiotherapy on rehabilitation and quality of life in patients hospitalized for COVID-19 and the findings from key studies published between 2020 and 2022.

Analysis of risk factors for the failure of respiratory support with high-flow nasal cannula oxygen therapy in children with acute respiratory dysfunction: A case-control study.

BackgroundEvidence-based clinical practice guidelines regarding high-flow nasal cannula (HFNC) use for respiratory support in critically ill children are lacking. Therefore, we aimed to determine the risk factors for early HFNC failure to reduce the failure rate and prevent adverse consequences of HFNC failure in children with acute respiratory dysfunction.MethodsDemographic and laboratory data were compared among patients, admitted to the pediatric intensive care unit between January 2017 and December 2018, who were included in a retrospective cohort study. Univariate and multivariate analyses were performed to determine risk factors for eventual entry into the predictive model for early HFNC failure and to perform an external validation study in a prospective observational cohort study from January to February 2019. Further, the association of clinical indices and trends pre- and post-treatment with HFNC treatment success or failure in these patients was dynamically observed.ResultsIn total, 348 pediatric patients were included, of these 282 (81.0%) were included in the retrospective cohort study; HFNC success was observed in 182 patients (64.5%), HFNC 0–24 h failure in 74 patients (26.2%), and HFNC 24–48 h failure in 26 patients (9.2%). HFNC 24 h failure was significantly associated with the pediatric risk of mortality (PRISM) III score [odds ratio, 1.391; 95% confidence interval (CI): 1.249–1.550], arterial partial pressure of carbon dioxide-to-arterial partial pressure of oxygen (PaCO2/PaO2) ratio (odds ratio, 38.397; 95% CI: 6.410–230.013), and respiratory rate-oxygenation (ROX) index (odds ratio, 0.751; 95% CI: 0.616–0.915). The discriminating cutoff point for the new scoring system based on the three risk factors for HFNC 24 h failure was ≥ 2.0 points, with an area under the receiver operating characteristic curve of 0.794 (95% CI, 0.729–0.859, P < 0.001), sensitivity of 68%, and specificity of 79%; similar values were noted on applying the model to the prospective observational cohort comprising 66 patients (AUC = 0.717, 95% CI, 0.675–0.758, sensitivity 83%, specificity 44%, P = 0.009). In this prospective cohort, 11 patients with HFNC failure had an upward trend in PaCO2/PaO2 ratio and downward trends in respiratory failure index (P/F ratio) and ROX index; however, opposite directions of change were observed in 55 patients with HFNC success. Furthermore, the fractional changes (FCs) in PaCO2/PaO2 ratio, P/F ratio, percutaneous oxygen saturation-to-fraction of inspired oxygen (S/F) ratio, and ROX index at 2 h post-HFNC therapy onset were statistically significant between the two groups (all, P < 0.05).ConclusionIn the pediatric patients with acute respiratory insufficiency, pre-treatment PRISM III score, PaCO2/PaO2 ratio, and ROX index were risk factors for HFNC 24 h failure, and the direction and magnitude of changes in the PaCO2/PaO2 ratio, P/F ratio, and ROX index before and 2 h after HFNC treatment were warning indicators for HFNC 24 h failure. Further close monitoring should be considered for patients with these conditions.

Mucopenetration study of solid lipid nanoparticles containing magneto sensitive iron oxide

In most chronic respiratory diseases, excessive viscous airway secretions oppose a formidable permeation barrier to drug delivery systems (DDSs), with a limit to their therapeutic efficacy for the targeting epithelium. Since mucopenetration of DDSs with slippery technology (i.e. PEGylation) has encountered a reduction in the presence of sticky and complex airway secretions, our aim was to evaluate the relevance of magnetic PEGylated Solid Lipid Nanoparticles (mSLNs) for pulling them through chronic obstructive pulmonary disease (COPD) airway secretions. Thus, COPD sputum from outpatient clinic, respiratory secretions aspirated from high (HI) and low (LO) airways of COPD patients in acute respiratory insufficiency, and porcine gastric mucus (PGM) were investigated for their permeability to mSLN particles under a magnetic field. Rheological tests and mSLN adhesion to airway epithelial cells (AECs) were also investigated. The results of mucopenetration show that mSLNs are permeable both in COPD sputum and in PGM, while HI and LO secretions are always impervious. Parallel rheological results show a different elastic property, which can be associated with different mucus mesostructures. Finally, adhesion tests confirm the role of the magnetic field in improving the interaction of SLNs with AECs. Overall, our results reveal that mesostructure is of paramount importance in determining the mucopenetration of magnetic SLNs.

Thromboembolic Complications in COVID-19 Patients Hospitalized in Italian Ordinary Wards: Data from the Multicenter Observational START-COVID Register.

Background Coronavirus disease 2019 (COVID-19) infection causes acute respiratory insufficiency with severe interstitial pneumonia and extrapulmonary complications; in particular, it may predispose to thromboembolic disease. The reported incidence of thromboembolic complications varies from 5 to 30% of cases. Aim We conducted a multicenter, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe the clinical characteristics of patients at admission and bleeding and thrombotic events occurring during the hospital stay. Results The number of hospitalized patients included in the START-COVID-19 Register was 1,135, and the number of hospitalized patients in ordinary wards included in the study was 1,091, with 653 (59.9%) being males and 71 years (interquartile range 59–82 years) being the median age. During the observation, two (0.2%) patients had acute coronary syndrome episodes and one patient (0.1%) had an ischemic stroke; no other arterial thrombotic events were recorded. Fifty-nine patients had symptomatic venous thromboembolism (VTE) (5.4%) events, 18 (30.5%) deep vein thrombosis (DVT), 39 (66.1%) pulmonary embolism (PE), and 2 (3.4%) DVT+PE. Among patients with DVT, eight (44.4%) were isolated distal DVT and two cases were jugular thrombosis. Among patients with PE, seven (17.9%) events were limited to subsegmental arteries. No fatal PE was recorded. Major bleeding events occurred in nine (1.2%) patients and clinically relevant nonmajor bleeding events in nine (1.2%) patients. All bleeding events occurred among patients receiving thromboprophylaxis, more frequently when treated with subtherapeutic or therapeutic dosages. Conclusion Our findings confirm that patients admitted to ordinary wards for COVID-19 infection are at high risk for thromboembolic events. VTE recorded among these patients is mainly isolated PE, suggesting a peculiar characteristic of VTE in these patients.