Acute Vascular Complications of VA-ECMO in COVID-19 Patients. Does COVID-19 Affect the Outcome?

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) through the femoral artery and vein can lead to significant vascular complications. We retrospectively studied the acute vascular complications of Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) in COVID-19 patients compared to non-COVID patients during the period from January 2020 to July 2023. RESULTS: Seventy-eight patients underwent VA-ECMO for various indications from January 2020 to July 2023. The studied patients had a mean age of 59.6 ± 6.9 years for non-COVID patients (38 patients), and 62.2 ± 7.6 years for COVID patients (40 patients), with a P = 0.268. In non-COVID patients, The baseline characteristics were similar in both groups. The primary indications for ECMO were cardiac diseases, followed by respiratory failure (78.9% vs 10.5%). Conversely, in COVID patients, respiratory failure due to COVID-19 infection was the main indication (45% vs 40%). The overall incidence of general complications, including cerebrovascular stroke, acute kidney injury, intracardiac thrombi, and wound infection, was comparable in both groups (31.6% vs 45%). The overall incidence of vascular complications in both groups was 33.3%. Ipsilateral acute lower limb ischemia occurred in 5.3% vs 10% of non-COVID and COVID patients, respectively. Thrombosis of the distal perfusion catheter (DPC) occurred in 10.5% vs 15%, respectively. CONCLUSION: During the COVID-19 pandemic, an increasing number of patients required VA-ECMO due to associated respiratory failure. Patients undergoing VA-ECMO are at high risk of developing various vascular complications. COVID-19 significantly increases the risk of acute limb ischemia and distal perfusion catheter thrombosis in both upper and lower limbs. However, other VA-ECMO-related vascular complications are comparable between COVID-19 and non-COVID patients.

Diagnostic Value of Chest Computed Tomography Scan for Identification of Foreign Body Aspiration in Children: A Systematic Review and Meta-analysis.

Introduction: Foreign body aspiration (FBA) is a common, life-threatening pediatric emergency and was shown to be associated with high risk of morbidity and mortality. This systematic review and meta-analysis aimed to investigate the diagnostic value of chest computed tomography (CT) scan for identification of FBA in children. Methods: From inception to May 2024, a systematic search was carried out across multiple databases including Medline, Scopus, and Web of Science, considering published papers in English language. Quality assessment of the included studies was performed using seven domains of Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Results: The systematic literature search yielded 7203 articles. The pooled sensitivity and specificity of chest CT scan for identification of FBA were 0.99 (95% CI: 0.98-0.99) and 0.97 (95% CI: 0.96-0.98), respectively. The pooled positive likelihood ratio was 10.12 (95% CI: 4.59-22.20), and pooled negative likelihood ratio was 0.05 (95% CI: 0.02-0.1). Furthermore, the area under the summarized receiver operating characteristic (SROC) curve was 0.98. Conclusion: Our meta-analysis revealed that despite high heterogeneity, in the diagnostic characteristics of chest CT scan among studies, it has high diagnostic value in identifying FBA in suspected pediatric cases.

Accuracy study of Angiotensin 1-7 composite index test to predict pulmonary fibrosis and guide treatment.

BACKGROUND: Pulmonary fibrosis can develop after acute respiratory distress syndrome (ARDS). The hypothesis is we are able to measure phenotypes that lie at the origin of ARDS severity and fibrosis development. The aim is an accuracy study of prognostic circulating biomarkers. METHODS: A longitudinal study followed COVID-related ARDS patients with medical imaging, pulmonary function tests and biomarker analysis, generating 444 laboratory data. Comparison to controls used non-parametrical statistics; p < 0·05 was considered significant. Cut-offs were obtained through receiver operating curve. Contingency tables revealed predictive values. Odds ratio was calculated through logistic regression. RESULTS: Angiotensin 1-7 beneath 138 pg/mL defined Angiotensin imbalance phenotype. Hyper-inflammatory phenotype showed a composite index test above 34, based on high Angiotensin 1-7, C-Reactive Protein, Ferritin and Transforming Growth Factor-ß. Analytical study showed conformity to predefined goals. Clinical performance gave a positive predictive value of 95 % (95 % confidence interval, 82 %-99 %), and a negative predictive value of 100 % (95 % confidence interval, 65 %-100 %). Those severe ARDS phenotypes represented 34 (Odds 95 % confidence interval, 3-355) times higher risk for pulmonary fibrosis development (p < 0·001). CONCLUSIONS: Angiotensin 1-7 composite index is an early and objective predictor of ARDS evolving to pulmonary fibrosis. It may guide therapeutic decisions in targeted phenotypes.

Method to Assess Immunosenescent CD8+ T Cells in Respiratory Viral Infections.

Immunosenescence is a well-characterized phenomenon that occurs with increasing age in all immune and somatic cells. In order to best study immunosenescence, it is imperative to develop methods to accurately identify immunosenescent cells. Elderly patients are known to have impaired immune responses to respiratory viruses, and it is hypothesized that this is due, in part, to immunosenescent, terminally exhausted CD8+ T cells. To test this hypothesis, we developed an aged mouse model and a flow cytometry protocol using the Cytek® Aurora to assess the CD8+ T-cell response during respiratory viral infection and identify immunosenescent CD8+ T cells. This protocol and our aged mouse model have great potential to be incredibly valuable for future studies elucidating how to rejuvenate and possibly reverse immunosenescent CD8+ T cells, which could improve the immune response to respiratory viruses in this at-risk population.

Establishment of a rapid detection method for Mycoplasma pneumoniae based on RPA-CRISPR-Cas12a technology.

Mycoplasma pneumoniae can cause respiratory infections and pneumonia, posing a serious threat to the health of children and adolescents. Early diagnosis of Mycoplasma pneumoniae infection is crucial for clinical treatment. Currently, diagnostic methods for Mycoplasma pneumoniae infection include pathogen detection, molecular biology techniques, and bacterial culture, all of which have certain limitations. Here, we developed a rapid, simple, and accurate detection method for Mycoplasma pneumoniae that does not rely on large equipment or complex operations. This technology combines the CRISPR-Cas12a system with recombinase polymerase amplification (RPA), allowing the detection results to be observed through fluorescence curves and immunochromatographic lateral flow strips.It has been validated that RPA-CRISPR/Cas12a fluorescence analysis and RPA-CRISPR/Cas12-immunochromatographic exhibit no cross-reactivity with other common pathogens, and The established detection limit was ascertained to be as low as 102 copies/µL.Additionally, 49 clinical samples were tested and compared with fluorescence quantitative polymerase chain reaction, demonstrating a sensitivity and specificity of 100%. This platform exhibits promising clinical performance and holds significant potential for clinical application, particularly in settings with limited resources, such as clinical care points or resource-constrained areas.

Evidence to support cultivated fruiting body of Ophiocordyceps sinensis (Ascomycota)'s role in relaxing airway smooth muscle.

ETHNOPHARMACOLOGICAL RELEVANCE: Ophiocordyceps sinensis (O. sinensis) is a genus of Ascomycete fungus that is endemic to the alpine meadows of the Tibetan Plateau and adjoining Himalayas. It has been used traditionally as a tonic to improve respiratory health in ancient China as well as to promote vitality and longevity. Bioactive components found in O. sinensis such as adenosine, cordycepin, 3-deoxyadenosine, L-arginine and polysaccharides have gained increasing interest in recent years due to their antioxidative and other properties, which include anti-asthmatic, antiviral, immunomodulation and improvement of general health. AIM OF THE STUDY: This study's primary aim was to investigate the effect of a cultivated fruiting body of O. sinensis strain (OCS02®) on airways patency and the secondary focus was to investigate its effect on the lifespan of Caenorhabditis elegans. MATERIALS AND METHODS: A cultivated strain, OCS02®, was employed and the metabolic profile of its cold-water extract (CWE) was analysed through liquid chromatography-mass spectrometry (LC-MS). Organ bath approach was used to investigate the pharmacological properties of OCS02® CWE when applied on airway tissues obtained from adult male Sprague-Dawley rats. The airway relaxation mechanisms of OCS02® CWE were explored using pharmacological tools, where the key regulators in airway relaxation and constriction were investigated. For the longevity study, age-synchronised, pos-1 RNAi-treated wild-type type Caenorhabditis elegans at the L4 stage were utilised for a lifespan assay. RESULTS: Various glycopeptides and amino acids, particularly a high concentration of L-arginine, were identified from the LC-MS analysis. In airway tissues, OCS02® CWE induced a significantly greater concentration-dependent relaxation when compared to salbutamol. The relaxation response was significantly attenuated in the presence of NG-Nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) and several K+ channel blockers. The longevity effect induced by OCS02® CWE (5 mg/mL and above) was observed in C. elegans by at least 17%. CONCLUSIONS: These findings suggest that the airway relaxation mechanisms of OCS02® CWE involved cGMP-dependent and cGMP-independent nitric oxide signalling pathways. This study provides evidence that the cultivated strain of OCS02® exhibits airway relaxation effects which supports the traditional use of its wild O. sinensis in strengthening respiratory health.

Prevalência de Influenza A, vírus sincicial respiratório eSARS-CoV-2 em pacientes com síndrome respiratóriaaguda grave em Passo Fundo, Rio Grande do Sul / Prevalence of Influenza A, respiratory syncytial virus andSARS-CoV-2 in patients with severe acute respiratorysyndrome in Passo Fundo, Rio Grande do Sul

A síndrome respiratória aguda grave (SRAG) é caracterizada por sintomas de febre alta, tosse e dispneia, e, na maioria dos casos, relacionada a uma quantidade reduzida de agentes infecciosos. O objetivo foi avaliar a prevalência dos vírus respiratórios Influenza A (FluA), vírus sincicial respiratório (RSV) e do novo coronavírus (SARS-CoV-2) em pacientes com internação hospitalar por SRAG. Estudo transversal, com pacientes em internação hospitalar com SRAG entre novembro de 2021 e maio de 2022. Dados sociodemográficos e clínicos e amostras da nasofaringe foram coletados/as, as quais foram submetidas à extração de RNA e testadas quanto à positividade para Influenza A, RSV e SARS-CoV-2 por meio da técnica de PCR em tempo real pelo método SYBR Green. Foram incluídos 42 pacientes, sendo 59,5% do sexo feminino, 57,1% idosos, 54,8% com ensino fundamental. A maior parte dos pacientes reportou hábito tabagista prévio ou atual (54,8%), não etilista (73,8%) e 83,3% deles apresentavam alguma comorbidade, sendo hipertensão arterial sistêmica e diabetes mellitus tipo 2 as mais prevalentes. Um total de 10,5% dos pacientes testou positivo para FluA, nenhuma amostra positiva para RSV e 76,3% positivos para SARS-CoV-2. Na população estudada, SRAG com agravo hospitalar foi observado em maior proporção, em mulheres, idosos e pessoas com comorbidades, embora sem significância estatística, sendo o novo coronavírus o agente etiológico mais relacionado, o que evidencia a patogenicidade desse agente e suas consequências ainda são evidentes após quase 2 anos de período pandêmico.

Severe acute respiratory syndrome (SARS) is characterized by symptoms of high fever, cough and dyspnea, and is in most cases related to a reduced amount of infectious agents. The objective was to assess the prevalence of respiratory viruses Influenza A (FluA), respiratory syncytial virus (RSV) and the new coronavirus (SARS-CoV-2) in patients hospitalized for SARS. Cross-sectional study, with patients hospitalized with SARS between November 2021 and May 2022. Sociodemographic and clinical data and nasopharyngeal samples were collected, which were subjected to RNA extraction and tested for positivity for Influenza A, RSV and SARS-CoV-2 using the real-time PCR technique using the SYBR Green method. 42 patients were included, 59.5% female, 57.1% elderly, 54.8% with primary education. Most patients reported previous or current smoking habits (54.8%), non-drinkers (73.8) and 83.3% of them had some comorbidity, with systemic arterial hypertension and type 2 diabetes mellitus being the most prevalent. A total of 10.5% of patients tested positive for FluA, no samples positive for RSV, and 76.3% positive for SARS-CoV-2. In the studied population, SARS with hospital injury was observed more frequently in women and the elderly, with associated comorbidities, with the new coronavirus being the most related etiological agent, which shows, although not statistically significant, that the pathogenicity of this agent and its consequences are still evident after almost 2 years of period pandemic.

Respiratory Syncytial Virus Risk Profile in Hospitalized Infants and Comparison with Influenza and COVID-19 Controls in Valladolid, Spain, 2010-2022.

INTRODUCTION: We aimed to describe the risk profile of RSV infections among children aged ≤ 24 months in Valladolid from January 2010 to August 2022 and to compare them with influenza and COVID-19 controls. METHODS: We conducted a retrospective cohort study of all laboratory-confirmed RSV, influenza, and COVID-19 infections. We analyzed risk factors for RSV hospitalization and severity (length-of-stay ≥ 8 days, intensive-care-unit admission, in-hospital death or readmission < 30 days) and compared severity between hospitalized RSV patients vs. influenza and COVID-19 controls using multivariable logistic regression models. RESULTS: We included 1507 patients with RSV (1274 inpatient), 32 with influenza, and 52 COVID-19 controls. Hospitalized RSV (mean age 5.3 months) and COVID-19 (4 months) were younger than influenza (9.1 months) patients. Sixteen percent of patients had RSV within the first month of life. Most infants did not have comorbidities (74% RSV, 56% influenza, and 69% COVID-19). Forty-one percent of patients with RSV and influenza were coinfected vs. 27% COVID-19 (p = 0.04). Among RSV, hospitalization risk factors were prematurity (adjusted OR 3.11 [95% CI 1.66, 4.44]) and coinfection (2.03 [1.45, 2.85]). Risks for higher severity were maternal smoking (1.89 [1.07, 3.33]), prematurity (2.31 [1.59, 3.34]), chronic lung disease (2.20 [1.06, 4.58]), neurodevelopmental condition (4.28 [2.10, 8.73]), and coinfection (2.67 [2.09, 3.40]). Breastfeeding was protective against hospitalization (0.87 [0.80, 0.95]) and severity (0.81 [0.74, 0.88]), while complete vaccination schedule was protective against severity (0.51 [0.27, 0.97]). RSV had 2.47 (1.03, 5.96) higher risk of experiencing any severe outcome compared to influenza and did not show significant differences vs. COVID-19. CONCLUSIONS: RSV hospitalizations were more frequent and severe than influenza, while severity was comparable to the early pandemic COVID-19. Currently, both influenza and COVID-19 vaccines are included in the maternal and childhood Spanish immunization schedule between the ages of 6 and 59 months. RSV monoclonal antibody is recommended for ≤ 6 months but a third of patients were aged 6-24 months. Maternal RSV vaccination can protect their children directly from birth and indirectly through breastfeeding.

Betulonic Acid Inhibits Type-2 Porcine Reproductive and Respiratory Syndrome Virus Replication by Downregulating Cellular ATP Production.

Porcine reproductive and respiratory syndrome (PRRS), caused by PRRS virus (PRRSV) infection, has been a serious threat to the pork industry worldwide and continues to bring significant economic loss. Current vaccination strategies offer limited protection against PRRSV transmission, highlighting the urgent need for novel antiviral approaches. In the present study, we reported for the first time that betulonic acid (BA), a widely available pentacyclic triterpenoids throughout the plant kingdom, exhibited potent inhibition on PRRSV infections in both Marc-145 cells and primary porcine alveolar macrophages (PAMs), with IC50 values ranging from 3.3 µM to 3.7 µM against three different type-2 PRRSV strains. Mechanistically, we showed that PRRSV replication relies on energy supply from cellular ATP production, and BA inhibits PRRSV infection by reducing cellular ATP production. Our findings indicate that controlling host ATP production could be a potential strategy to combat PRRSV infections, and that BA might be a promising therapeutic agent against PRRSV epidemics.

Integrated One-Step Fabrication of Protonic Sensing Devices for Respiratory Monitoring.

The development of direct fabrication routes with seamless integration of both the macro/micropatterning process and nanostructure synthesis is crucial for the commercial realization of cost-effective nanoscale sensor devices. This, if realized, can liberate us from the conventional limitations inherent in nanoscale device manufacturing. Specifically, such fabrication routes can, in principle, address the challenges such as the complexity, multistep nature, and substantial costs associated with existing technologies, which are not suitable for widespread market adoption in everyday-use devices. Herein, we propose a novel yet facile one-step fabrication approach that simultaneously accomplishes both patterning and nanostructure synthesis by employing low-power, cost-effective laser technology with a minimal environmental footprint. Versatile in nature, this approach can enable the incorporation of diverse functionalities spanning a broad spectrum of technologies, encompassing fields such as sensors, catalysts, photonics, energy storage, and biomedical monitoring devices. As a proof of concept, using our approach, we fabricated an ultra responsive, high-speed protonic sensing device for real-time respiratory monitoring. The enhanced temporal characteristics of our as-fabricated device, particularly in the relative humidity levels of interest in breath monitoring (typically over 55%), exhibited a superior response/recovery time in rapid humidity fluctuations. We envisage that the advantages brought by the presented fabrication approach can pave the way to establish a new method for inexpensive large-scale functional-material-based device fabrication.

Clinical Manifestations and Outcomes in Adults Hospitalized With Respiratory Syncytial Virus and Influenza a/B: A Multicenter Observational Cohort Study.

Background: Respiratory syncytial virus (RSV) and influenza cause significant health challenges, particularly for individuals with comorbid conditions and older adults. However, information on the clinical manifestations and outcomes of adults hospitalized with RSV in Europe remains limited. Methods: This multicenter observational cohort study of adults hospitalized with RSV or influenza A or B from March 2016 to April 2020 investigated the clinical manifestations, mortality risk factors, and association with 90-day mortality rates by logistic regression analysis after adjustment for covariates. Results: Of 988 patients hospitalized with either virus, 353 had RSV, 347 had influenza A, and 288 had influenza B infection. Patients with RSV, compared with those with influenza A or B, were more likely to have comorbid conditions (83% for RSV vs 72% for influenza A [P = .03] and 74% for influenza B [P = .001]) or pneumonia (41% vs 29% [P = .03] and 24% [P < .001], respectively). After adjustment for covariates, RSV infection was associated with an increased all-cause mortality rate within 90 days compared with influenza B (odds ratio, 2.16 [95% confidence interval, 1.20-3.87]; P = .01) but not influenza A (1.38 [.84-2.29]; P = .21). Increasing age and present pneumonia were identified as independent mortality risk factors in patients with RSV. Conclusions: Older adults hospitalized with RSV infections are at a higher risk of dying within 90 days of hospitalization than patients admitted with influenza B but at a similar risk as those admitted with influenza A, emphasizing the detrimental effects and severity of older patients being infected with RSV. Our findings underscore the need for strategic testing and vaccination approaches to mitigate the impact of RSV among older adults.

Revisiting ARDS Classification: Are We There Yet?

How to cite this article: Mishra S. Revisiting ARDS Classification: Are We There Yet? Indian J Crit Care Med 2024;28(10):899-900.

Respiratory Complications in the Immediate Postoperative Period after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Nowadays: An Observational Study.

Background and objectives: Several respiratory complications have been described after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Materials and methods: Patients admitted to intensive care unit (ICU) after CRS and HIPEC during 10 years. Data recorded were: Demographic characteristics; severity of illness; complete blood sample; chest radiographs; type of cancer and extension; HIPEC drug and temperature; ICU and hospital stay; and mortality. Results: Of the 124 patients included, 67 patients (54.0%) presented respiratory complications: 56 (83.6%) acute respiratory failure, 25 (37.3%) pleural effusion, 13 (19.4%) atelectasis, and 3 (4.5%) other; only 1 (3.0%) developed pneumonia. They had higher severity scores at ICU admission. 1 patient required initiation of invasive mechanical ventilation during ICU admission due to pneumonia, and 1 patient needed placement of a pleural chest tube due to symptomatic pleural effusion.Only the need for a high fluid balance during surgery was correlated to the development of respiratory complications on multivariate analysis.Median ICU stay was 5 (4.0-5.0) days. ICU mortality was 0.8.0%. Conclusion: In our study, 54% of patients treated with CRS and HIPEC developed respiratory complications during the postoperative period. However, the majority of these complications were not severe and did not significantly impact mortality rates or hospital stays. How to cite this article: Pintado MC, Oñoro A, Beltran D, Nevado E. Respiratory Complications in the Immediate Postoperative Period after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Nowadays: An Observational Study. Indian J Crit Care Med 2024;28(10):952-957.

Inconsistencies in the Indian Guidelines for the Prescription of Antibiotics for Critically Ill Patients.

The recently formulated guidelines by Khilnani GC et al. for the prescription of antibiotics for critically ill patients present an extensive compilation of evidence and recommendations. Despite their comprehensive nature, several inconsistencies need addressing. In this commentary, we delve into some of these discrepancies in the order in which they appeared in the guidelines, starting with the misrepresentation of "nonbronchoscopic bronchoalveolar lavage (BAL)" and "mini BAL" as different techniques when they are, in fact, identical. Secondly, the Centers for Disease Control and Prevention (CDC) in the year 2013 replaced the older, unreliable ventilator-associated pneumonia (VAP) definition with ventilator-associated events (VAE). This new VAE definition eliminates subjectivity in pneumonia diagnosis by focusing on objective criteria for ventilator support changes, avoiding dependence on potentially inaccurate chest X-rays and inconsistent medical record keeping. Thus, using the term VAP in the Indian guidelines seems regressive. Furthermore, the recommendation for routine anaerobic coverage in aspiration pneumonia is outdated and unsupported by current evidence. Lastly, while endorsing multiplex polymerase chain reaction (PCR) for pathogen identification, the guidelines fail to adequately address its limitations and the risk of overdiagnosis. How to cite this article: Raj N, Nath SS, Singh V, Agarwal J. Inconsistencies in the Indian Guidelines for the Prescription of Antibiotics for Critically Ill Patients. Indian J Crit Care Med 2024;28(10):908-911.

Oscillometry in Asthma: Respiratory Modeling and Analysis in Occupational and Work-Exacerbated Phenotypes.

Background: Asthma onset or worsening of the disease in adulthood may be associated with occupational asthma (OA) or work-exacerbated asthma (WEA). Oscillometry and respiratory modeling offer insight into the pathophysiology and contribute to the early diagnosis of respiratory abnormalities. Purpose: This study aims to compare the changes due to OA and WEA and evaluate the diagnostic accuracy of this method. Patients and Methods: Ninety-nine volunteers were evaluated: 33 in the control group, 33 in the OA group, and 33 in the WEA group. The area under the receiver operator characteristic curve (AUC) was used to describe diagnostic accuracy. Results: Oscillometric analysis showed increased resistance at 4 hz (R4, p<0.001), 20 hz (R20, p<0.05), R4-R20 (p<0.0001), and respiratory work (p<0.001). Similar analysis showed reductions in dynamic compliance (p<0.001) and ventilation homogeneity, as evaluated by resonance frequency (Fr, p<0.0001) and reactance area (p<0.0001). Respiratory modeling showed increased peripheral resistance (p<0.0001), hysteresivity (p<0.0001), and damping (p<0.0001). No significant changes were observed comparing OA with WEA in any parameter. For OA, the diagnostic accuracy analyses showed Fr as the most accurate among oscillometric parameters (AUC=0.938), while the most accurate from respiratory modeling was hysteresivity (AUC=0.991). A similar analysis for WEA also showed that Fr was the most accurate among traditional parameters (AUC=0.972), and hysteresivity was the most accurate from modeling (AUC=0.987). The evaluation of differential diagnosis showed low accuracy. Conclusion: Oscillometry and modeling have advanced our understanding of respiratory abnormalities in OA and WEA. Furthermore, our study presents evidence suggesting that these models could aid in the early diagnosis of these diseases. Respiratory oscillometry examinations necessitate only tidal breathing and are straightforward to conduct. Collectively, these practical considerations, coupled with the findings of our study, indicate that respiratory oscillometry in conjunction with respiratory modeling, may enhance lung function assessments in OA and WEA.

Parental Awareness of Antibiotic Use for Upper Respiratory Tract Infection in Children in Jazan Region, Saudi Arabia.

BACKGROUND: Upper respiratory tract infections are a prevalent cause of morbidity in children, often managed in primary care settings. These infections are predominantly viral, but antibiotics are sometimes inappropriately prescribed. This misuse, driven by parental pressure and misconceptions, contributes to the growing problem of antibiotic resistance. The impact of parental awareness on antibiotic use practices is significant, as gaps in knowledge can lead to inappropriate use. METHODS: This study used a cross-sectional design to assess parents' awareness of antibiotic use for upper respiratory tract infections in children in Jazan, Saudi Arabia. Data were collected via a self-administered online questionnaire distributed through social media platforms. Participants were parents aged 18 years and older residing in Jazan. A snowball sampling technique was employed. The questionnaire assessed knowledge, attitudes, and practices regarding antibiotics. RESULTS: The study included 398 participants, with a nearly equal gender distribution of 198 females (49.7%) and 200 males (50.3%). Participants' ages were as follows: 148 (37.2%) were 18-30 years old, 162 (40.7%) were 31-40 years old, and 88 (22.1%) were over 40 years old. Regarding educational attainment, 29 (7.3%) mothers and 36 (9.0%) fathers had primary school education; 117 (29.4%) mothers and 128 (32.2%) fathers had secondary school education; 22 (5.5%) mothers and 33 (8.3%) fathers had intermediate school education; 209 (52.5%) mothers and 175 (44.0%) fathers held a bachelor's degree; and 21 (5.3%) mothers and 26 (6.5%) fathers had a master's degree. Most participants had a moderate income level (270, 67.8%) and resided in Bish (202, 50.8%). The main sources of information about antibiotics were doctors (242, 60.8%) and the internet (90, 22.6%). Perceptions varied, with 147 (36.9%) agreeing and 84 (21.1%) strongly agreeing that antibiotics can prevent complications from infections. A significant proportion believed that inappropriate use could lead to antibiotic resistance (172, 43.2% agreed; 129, 32.4% strongly agreed). Regarding the use of leftover antibiotics, 197 (49.5%) disagreed with using them without consulting a doctor. Interaction with pediatricians showed that 212 (53.3%) always followed pediatrician advice and instructions, while 66 (16.6%) rarely did. CONCLUSION: The study highlights significant gaps in parental awareness regarding antibiotic use for upper respiratory tract infections in Jazan. Despite some understanding of antibiotic resistance, misconceptions about the efficacy and appropriate use of antibiotics persist. Addressing these gaps through targeted education and improving communication with healthcare providers could enhance antibiotic stewardship and reduce the risk of resistance.

Continuous Process Verification 4.0 application in upstream: adaptiveness implementation managed by AI in the hypoxic bioprocess of the Pichia pastoris cell factory.

The experimental approach developed in this research demonstrated how the cloud, the Internet of Things (IoT), edge computing, and Artificial Intelligence (AI), considered key technologies in Industry 4.0, provide the expected horizon for adaptive vision in Continued Process Verification (CPV), the final stage of Process Validation (PV). Pichia pastoris producing Candida rugosa lipase 1 under the regulation of the constitutive GAP promoter was selected as an experimental bioprocess. The bioprocess worked under hypoxic conditions in carbon-limited fed-batch cultures through a physiological control based on the respiratory quotient (RQ). In this novel bioprocess, a digital twin (DT) was built and successfully tested. The implementation of online sensors worked as a bridge between the microorganism and AI models, to provide predictions from the edge and the cloud. AI models emulated the metabolism of Pichia based on critical process parameters and actionable factors to achieve the expected quality attributes. This innovative AI-aided Adaptive-Proportional Control strategy (AI-APC) improved the reproducibility comparing to a Manual-Heuristic Control strategy (MHC), showing better performance than the Boolean-Logic-Controller (BLC) tested. The accuracy, indicated by the Mean Relative Error (MRE), was for the AI-APC lower than 4%, better than the obtained for MHC (10%) and BLC (5%). Moreover, in terms of precision, the same trend was observed when comparing the Root Mean Square Deviation (RMSD) values, becoming lower as the complexity of the controller increases. The successful automatic real time control of the bioprocess orchestrated by AI models proved the 4.0 capabilities brought by the adaptive concept and its validity in biopharmaceutical upstream operations.

The association of coronary artery disease with heart rate at anaerobic threshold and respiratory compensatory point.

Background: There is limited knowledge regarding the association between heart rate (HR) during different exercise phases and coronary artery disease (CAD). This study aimed to evaluate the relationship between four exercise-related HR metrics detected by cardiopulmonary exercise testing (CPET) and CAD. These metrics include HR at the anaerobic threshold (HRAT), HR at respiratory compensatory point (HRRCP), maximal HR (HRmax), and HR 60 s post-exercise (HRRec60s). Methods: The 705 participants included 383 with CAD and 322 without CAD in Beijing Hospital, who underwent CPET between January 2021 and December 2022. The Logistic regression analysis was applied to estimate the odds ratio and the 95% confidence interval. Additionally, the multivariable Logistic regression analyses with restricted cubic splines were conducted to characterize the dose-response association and explore whether the relationship was linear or nonlinear. Results: Our primary finding indicates that for each one-beat increase in HRAT, there is a 2.8% reduction in the adjusted risk of CAD in the general population. Similarly, a one-beat increase in HRRCP corresponds to a 2.6% reduction in the adjusted risk of CAD. Subgroup analyses revealed significant interactions between HRAT and factors such as sex, hypertension, and lung cancer, as well as between HRRCP and sex and hypertension, in relation to CAD. The dose-response analysis further confirmed that higher HRAT and HRRCP are associated with a reduced risk of CAD. Conclusion: These results are suggestive of a good association between HRAT, HRRCP, and CAD. The lower HRAT, and HRRCP are signs of poor HR response to exercise in CAD. HRAT and HRRCP are potentially good indicators of poor HR response to exercise without considering maximal effort.

Neonatal Cardiac and Respiratory Arrest During Linezolid Therapy: A Case Report.

Lactic acidosis is one of the severe adverse reactions of linezolid. Its clinical manifestations are non-specific, primarily including abdominal discomfort, nausea, vomiting, diarrhea, weakness, lethargy, rapid breathing, and tachycardia, with no reports of cardiac and respiratory arrest. In this case report, we present a 13-day-old male infant with omphalitis caused by methicillin-resistant Staphylococcus aureus (MRSA) infection, who was treated with linezolid. He had lactic acidosis before treatment, which was not severe and was likely related to the infection. After linezolid therapy, he experienced cardiac and respiratory arrest, and re-measurement showed an increase in lactate levels. After resuscitation, linezolid withdrawal, and symptomatic treatment, lactate levels decreased. However, due to hypoxic-ischemic encephalopathy and uncorrectable ventricular arrhythmia caused by post-cardiopulmonary resuscitation myocardial damage, the infant died. A comprehensive autopsy and genetic testing were performed after death, and no congenital diseases or inherited metabolic diseases were found. Given that this case was a sudden infant death without typical symptoms of lactic acidosis and linezolid is often mistakenly considered safer than vancomycin in the treatment of special populations, this paper analyzes and discusses this to draw attention to clinical treatment. More research is needed in the future to fully demonstrate its causal relationship and mechanism of action.

Effect of high-flow nasal oxygen therapy combined with ipratropium bromide on Th1/Th2 balance and inflammation in patients with chronic obstructive pulmonary disease and respiratory failure.

Objective: To investigate the effect of a combination of high-flow nasal oxygen therapy (HFNO) and ipratropium bromide (IB) on Th1/Th2 balance and inflammation in patients with chronic obstructive pulmonary disease (COPD) and respiratory failure (RF). Methods: A retrospective analysis was conducted on the clinical data of patients with COPD and RF admitted to the Affiliated Nanjing Brain Hospital of Nanjing Medical University from June 2021 to March 2023. A total of 162 patients were included, with 79 patients received respiratory support using HFNO (HFNO group) and 83 patients who were treated using combined HFNO/IB (combined group). Treatment effect, lung function, levels of Th1/Th2, and inflammatory state were compared before and after the treatment. Results: Total effeicacy of patients in the combined group was significantly higher than that of the HFNO group (P<0.05). After the treatment, pulmonary function levels of the two groups was higher than that before the treatment, and was significantly better in the combined group compared to the HFNO group (P<0.05). The treatment was associated with a significant increase in the levels of Th1/Th2 in both groups. Post-treatment levels of these indexes in the combined group were markedly higher compared to the HFNO group (P<0.05). After the treatment, the inflammatory response of the two groups decreased, and was lower in the combined group that in the HFNO group (P<0.05). Conclusions: In COPD patients with RF, HFNO combined with IB is efficient in alleviating the inflammatory state of patients, restoring Th1/Th2 balance, and improving lung function compared to HFNO alone.