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RSC Medicinal Chemistry Jun 2024Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of coronavirus disease (COVID-19) since its emergence in December 2019. As of...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of coronavirus disease (COVID-19) since its emergence in December 2019. As of January 2024, there has been over 774 million reported cases and 7 million deaths worldwide. While vaccination efforts have been successful in reducing the severity of the disease and decreasing the transmission rate, the development of effective therapeutics against SARS-CoV-2 remains a critical need. The main protease (Mpro) of SARS-CoV-2 is an essential enzyme required for viral replication and has been identified as a promising target for drug development. In this study, we report the identification of novel Mpro inhibitors, using a combination of deep reinforcement learning for drug design with 3D pharmacophore/shape-based alignment and privileged fragment match count scoring components followed by hit expansions and molecular docking approaches. Our experimentally validated results show that 3 novel series exhibit potent inhibitory activity against SARS-CoV-2 Mpro, with IC values ranging from 1.3 μM to 2.3 μM and a high degree of selectivity. These findings represent promising starting points for the development of new antiviral therapies against COVID-19.
PubMed: 38911172
DOI: 10.1039/d4md00106k -
Cureus May 2024Primitive neuroectodermal tumors (PNETs) are unprecedented threatening neoplasms beginning from primitive neuroectodermal cells. PNETs are reported as the predominant...
Primitive neuroectodermal tumors (PNETs) are unprecedented threatening neoplasms beginning from primitive neuroectodermal cells. PNETs are reported as the predominant incidence observed in children and young adults with a high mortality rate. These neuroectodermal tumors are quite aggressive with a life expectancy of eight months on average. PNETs belong to the family of small round cell tumors majorly affecting bones and soft tissues in different body parts such as the brain, lungs, spine, and pelvic region. Computed tomography (CT) and magnetic resonance imaging (MRI) play a major role in giving the size, extent, and resectability of the tumors. A confirmed diagnosis is then made by histopathology and immunohistochemistry markers. This report depicts a case of PNET found within the right lung of a 13-year-old female, enumerating the clinical introduction, demonstrative handle, treatment modalities, and results. The case underscores the significance of precise conclusions and multidisciplinary approaches in pediatric PNET cases. Once the provisional diagnosis of pleuropulmonary blastoma or PNET was given on CT, a conformational histopathological examination was carried out. Histopathological analysis confirmed the final diagnosis of PNET, and the patient underwent neoadjuvant therapy as the tumor was non-resectable due to its massive size.
PubMed: 38910629
DOI: 10.7759/cureus.60820 -
Allergy, Asthma & Immunology Research May 2024Current literature primarily delves into the relationship between bronchiectasis and severe asthma, and only a few studies have evaluated the impact of bronchiectasis in...
Current literature primarily delves into the relationship between bronchiectasis and severe asthma, and only a few studies have evaluated the impact of bronchiectasis in patients with non-severe asthma. Therefore, this study investigated the clinical impact of bronchiectasis in patients with non-severe asthma. A prospective observational study of 140 non-severe asthmatic patients with (bronchiectasis group) and without bronchiectasis (control group) was conducted between September 2012 and February 2022. The bronchiectasis and control groups were compared in terms of demographics, lung function, asthma control test (ACT) results, exacerbation history, and respiratory medications. Among 140 non-severe asthmatic subjects, approximately 15.7% (n = 22) had bronchiectasis. The most common type of bronchiectasis was cylindrical type (90.7%). The left lingular division was the most frequently involved lung lobe (20.4%). There were no significant differences in the demographics (age, sex, body mass index, smoking history, and comorbidities) or ACT results between the 2 groups. The bronchiectasis group used inhaled corticosteroids/long-acting β2-agonists ( = 0.074) and mucolytics ( < 0.001) more frequently than the control group. Compared to the control group, the bronchiectasis group had lower forced expiratory volume in 1 second (FEV1) (L) (1.9 ± 0.7 L vs. 2.3 ± 0.9 L, = 0.039) and FEV1%predicted (67.2 ± 22.2%predicted vs. 77.1 ± 20.0%predicted, = 0.038). The rate of hospital admission to a general ward in the preceding year was significantly higher in the bronchiectasis group compared to those of the control group (23.8% vs. 3.5%, = 0.005) with an adjusted odds ratio of 6.308 (95% confidence interval, 1.401-28.392). Patients with non-severe asthma and bronchiectasis had lower lung function and more frequent exacerbations requiring hospitalization than those without bronchiectasis. More attention is needed for asthmatic patients with bronchiectasis, even if the asthma is not severe.
PubMed: 38910286
DOI: 10.4168/aair.2024.16.3.291 -
Allergy, Asthma & Immunology Research May 2024Few studies have compared the clinical characteristics of severe asthma (SA) in elderly patients compared to that in nonelderly patients.
PURPOSE
Few studies have compared the clinical characteristics of severe asthma (SA) in elderly patients compared to that in nonelderly patients.
METHODS
We analyzed data from the Korean SA Registry, a nationwide, real-world observational study of SA in Korea. The baseline clinical characteristics, disease control status, and medication use of the patients were compared between elderly (≥ 65 years) and nonelderly groups.
RESULTS
Of the 864 patients with SA, 260 (30.1%) were in the elderly group. The elderly group had lower atopy rate, but had higher prevalence of chronic obstructive pulmonary disease (COPD), hypertension, and osteoporosis than did the nonelderly group. The elderly group had a lower rate of type 2 inflammation and lower levels of forced expiratory volume in 1 second (FEV1) (% predicted) and FEV1/forced vital capacity ratio than did the nonelderly group ( < 0.05 for all). However, asthma symptom scores and the frequency of asthma exacerbation were not significantly different between the 2 groups. Of controller medications, biologics were less frequently used in the elderly group ( < 0.05 for all).
CONCLUSIONS
SA in the elderly is characterized by lower lung function, less type 2-low airway inflammation, and comorbidity with COPD. These findings are being taken into consideration in the management of elderly patients with SA in real-world clinical practice.
PubMed: 38910284
DOI: 10.4168/aair.2024.16.3.267 -
Pilot and Feasibility Studies Jun 2024Adults with intellectual disabilities experience numerous health inequalities. Targeting unhealthy lifestyle behaviours, such as high levels of sedentary behaviour and...
Adults with intellectual disabilities experience numerous health inequalities. Targeting unhealthy lifestyle behaviours, such as high levels of sedentary behaviour and overweight/obesity, is a priority area for improving the health and adults with intellectual disabilities and reducing inequalities. Energy expenditure is a fundamental component of numerous health behaviours and an essential component of various free-living behaviour measurements, e.g. accelerometry. However, little is known about energy expenditure in adults with intellectual disabilities and no population-specific accelerometer data interpretation methods have been calibrated. The limited research in this area suggests that adults with intellectual disabilities have a higher energy expenditure, which requires further exploration, and could have significant impacts of device calibration. However, due to the complex methods required for measuring energy expenditure, it is essential to first evaluate feasibility and develop an effective protocol. This study aims to test the feasibility of a laboratory-based protocol to enable the measurement of energy expenditure and accelerometer calibration in adults with intellectual disabilities.We aimed to recruit ten adults (≥ 18 years) with intellectual disabilities. The protocol involved a total of nine sedentary, stationary, and physical activities, e.g. sitting, lying down, standing, and treadmill walking. Each activity was for 5 min, with one 10 min lying down activity to measure resting energy expenditure. Breath by breath respiratory gas exchange and accelerometry (ActiGraph and ActivPAL) were measured during each activity. Feasibility was assessed descriptively using recruitment and outcome measurement completion rates, and participant/stakeholder feedback.Ten adults (N = 7 female) with intellectual disabilities participated in this study. The recruitment rate was 50% and 90% completed the protocol and all outcome measures. Therefore, the recruitment strategy and protocol are feasible.This study addresses a significant gap in our knowledge relating to exercise laboratory-based research for adults with intellectual disabilities The findings from this study provide essential data that can be used to inform the development of future protocols to measure energy expenditure and for accelerometer calibration in adults with intellectual disabilities.
PubMed: 38909244
DOI: 10.1186/s40814-024-01512-5 -
BMC Anesthesiology Jun 2024There is a high incidence of pulmonary atelectasis during paediatric laparoscopic surgeries. The authors hypothesised that utilising a recruitment manoeuvre or using... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Comparison of the effect of two recruitment manoeuvres to conventional ventilation on lung atelectasis in paediatric laparoscopic surgery- a prospective randomised controlled trial.
BACKGROUND
There is a high incidence of pulmonary atelectasis during paediatric laparoscopic surgeries. The authors hypothesised that utilising a recruitment manoeuvre or using continuous positive airway pressure may prevent atelectasis compared to conventional ventilation.
OBJECTIVE
The primary objective was to compare the degree of lung atelectasis diagnosed by lung ultrasound (LUS) using three different ventilation techniques in children undergoing laparoscopic surgeries.
DESIGN
Randomised, prospective three-arm trial.
SETTING
Single institute, tertiary care, teaching hospital.
PATIENTS
Children of ASA PS 1 and 2 up to the age of 10 years undergoing laparoscopic surgery with pneumoperitoneum lasting for more than 30 min.
INTERVENTION
Random allocation to one of the three study groups: CG group: Inspiratory pressure adjusted to achieve a TV of 5-8 ml/kg, PEEP of 5 cm HO, respiratory rate adjusted to maintain end-tidal carbon dioxide (ETCO) between 30-40 mm Hg with manual ventilation and no PEEP at induction. RM group: A recruitment manoeuvre of providing a constant pressure of 30 cm HO for ten seconds following intubation was applied. A PEEP of 10 cm HO was maintained intraoperatively. CPAP group: Intraoperative maintenance with PEEP 10 cm HO with CPAP of 10 cm HO at induction using mechanical ventilation was done.
OUTCOME MEASURES
Lung atelectasis score at closure assessed by LUS.
RESULTS
Post induction, LUS was comparable in all three groups. At the time of closure, the LUS for the RM group (8.6 ± 4.9) and the CPAP group (8.8 ± 6.8) were significantly lower (p < 0.05) than the CG group (13.3 ± 3.8). In CG and CPAP groups, the score at closure was significantly higher than post-induction. The PaO/FiO ratio was significantly higher (p < 0.05) for the RM group (437.1 ± 44.9) and CPAP group (421.6 ± 57.5) than the CG group (361.3 ± 59.4) at the time of pneumoperitoneum.
CONCLUSION
Application of a recruitment manoeuvre post-intubation or CPAP during induction and maintenance with a high PEEP leads to less atelectasis than conventional ventilation during laparoscopic surgery in paediatric patients.
TRIAL REGISTRY
CTRI/2019/08/02058.
Topics: Humans; Pulmonary Atelectasis; Laparoscopy; Prospective Studies; Female; Male; Child, Preschool; Child; Respiration, Artificial; Infant; Positive-Pressure Respiration; Continuous Positive Airway Pressure; Ultrasonography
PubMed: 38909220
DOI: 10.1186/s12871-024-02596-5 -
Scientific Reports Jun 2024This study aimed to develop a new simple and effective prognostic model using artificial intelligence (AI)-based chest radiograph (CXR) results to predict the outcomes...
This study aimed to develop a new simple and effective prognostic model using artificial intelligence (AI)-based chest radiograph (CXR) results to predict the outcomes of pneumonia. Patients aged > 18 years, admitted the treatment of pneumonia between March 2020 and August 2021 were included. We developed prognostic models, including an AI-based consolidation score in addition to the conventional CURB-65 (confusion, urea, respiratory rate, blood pressure, and age ≥ 65) and pneumonia severity index (PSI) for predicting pneumonia outcomes, defined as 30-day mortality during admission. A total of 489 patients, including 310 and 179 patients in training and test sets, were included. In the training set, the AI-based consolidation score on CXR was a significant variable for predicting the outcome (hazard ratio 1.016, 95% confidence interval [CI] 1.001-1.031). The model that combined CURB-65, initial O requirement, intubation, and the AI-based consolidation score showed a significantly high C-index of 0.692 (95% CI 0.628-0.757) compared to other models. In the test set, this model also demonstrated a significantly high C-index of 0.726 (95% CI 0.644-0.809) compared to the conventional CURB-65 and PSI (p < 0.001 and 0.017, respectively). Therefore, a new prognostic model incorporating AI-based CXR results along with traditional pneumonia severity score could be a simple and useful tool for predicting pneumonia outcomes in clinical practice.
Topics: Humans; Artificial Intelligence; Male; Female; Prognosis; Aged; Pneumonia; Middle Aged; Radiography, Thoracic; Severity of Illness Index; Aged, 80 and over; Retrospective Studies
PubMed: 38909087
DOI: 10.1038/s41598-024-65488-1 -
Journal of Global Antimicrobial... Jun 2024Ceftolozane-tazobactam (C/T) is a combination of a cephalosporin and a β-lactamase inhibitor with activity against Gram-negative bacilli (GNB). The study aims were to...
In vitro activity of ceftolozane/tazobactam against Gram-negative bacilli isolated from pediatric patients: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART) 2017-2021, China.
OBJECTIVES
Ceftolozane-tazobactam (C/T) is a combination of a cephalosporin and a β-lactamase inhibitor with activity against Gram-negative bacilli (GNB). The study aims were to evaluate the activity of C/T in vitro vs. comparators against clinical GNB isolated from Chinese pediatric patients.
METHODS
From 2017-2021, 660 GNB isolates were collected from 20 hospitals across China. The minimum inhibitory concentrations were tested using a Trek Diagnostic System (Thermo Fisher Scientific). Susceptibility was determined by CLSI broth microdilution and the results were interpreted according to CLSI M100 (2021) breakpoints.
RESULTS
GNB isolates were obtained from pediatric patients < 18 years old, mainly from the bloodstream (n=146), intraperitoneal cavity (n=138), lower respiratory (n=278) and urinary tract (n=96). Overall, C/T was active against 76.6% of 436 Enterobacterales, with a descending susceptibility rate of 100.0% to S. marcescens, 92.2% to E. coli, 83.3% to K. oxytoca, 66.7% to K. aerogenes, 66.7% to P. mirabilis, 58.6% to K. pneumoniae and 57.1% to E. cloacae. The susceptibility of P. aeruginosa to C/T was 89.4%, which was the highest among the β-lactams and was second only to amikacin (92.9%). Isolates of respiratory tract infection (RTI) derived P. aeruginosa were highly susceptible (93.8%) to C/T, while < 75% of isolates of RTI derived P. aeruginosa were susceptible to the other β-lactams tested, except for ceftazidime-avibactam (91.2%).
CONCLUSION
GNBs collected from pediatric patients in China showed a high susceptibility to C/T making this drug combination an effective choice for treating the pediatric population, especially those infected with P. aeruginosa.
PubMed: 38908824
DOI: 10.1016/j.jgar.2024.05.017 -
Journal of Vascular and Interventional... Jun 2024To retrospectively investigate the safety and efficacy of percutaneous radiofrequency ablation (RFA) by analyzing results in patients with lung neoplasm accompanied by...
PURPOSE
To retrospectively investigate the safety and efficacy of percutaneous radiofrequency ablation (RFA) by analyzing results in patients with lung neoplasm accompanied by interstitial lung disease (ILD) on computed tomography (CT) in a multicenter study.
MATERIALS & METHODS
Patients with lung neoplasm accompanied by ILD who underwent RFA between April 2002 and October 2017 at seven institutions were investigated. Technical success rate, and local tumor progression (LTP) of ablated tumors were evaluated. Adverse events including acute exacerbation of ILD were also evaluated. Univariate analyses were performed to identify factors associated with acute exacerbation.
RESULTS
Forty-nine patients with 64 lung neoplasm (mean diameter, 22.6 mm; range, 4-58 mm) treated in 66 sessions were included. Usual interstitial pneumonia (UIP) pattern on CT was identified in 23 patients (47%). All patients underwent successful RFA. Acute exacerbations were seen in 5 sessions (8%: 7% with UIP pattern, 8% without) in 5 patients, all occurring on or after 8 days (median, 12 days; range, 8-30 days). Three of those 5 patients died of acute exacerbation. Treatment resulted in mortality after 5% of sessions, representing 6% of patients. Pleural effusion and fever ≥38°C after RFA were identified by univariate analysis (p = 0.0012, p = 0.02, respectively) as significant risk factors for acute exacerbation. The cumulative LTP rate was 43% at 1 year.
CONCLUSIONS
RFA appears feasible for patients with lung neoplasm complicated by ILD. Acute exacerbation occurred in 8% of patients with symptoms occurring more than 8 days post-ablation and was associated with a 45% mortality rate.
PubMed: 38908746
DOI: 10.1016/j.jvir.2024.06.010 -
Medicina 2024Despite improvements in health care, pneumonia-associated mortality remains high. The objective of this study was to analyze the factors associated with mortality in...
INTRODUCTION
Despite improvements in health care, pneumonia-associated mortality remains high. The objective of this study was to analyze the factors associated with mortality in bacteremic pneumonia caused by pneumococcus.
METHODS
Retrospective cohort study in adult patients with pneumonia diagnosis and isolation of pneumococcus in blood cultures, between January 2012 and May 2021, was carried out. Clinical and laboratory variables, radiological involvement, evolution and mortality during hospitalization were analyzed. The group of deceased patients was compared with that of survivors.
RESULTS
152 patients were included. Median age: 58 years; men: 58.9%; 33% presented a CURB-65 > than 2 at admission. Overall mortality: 34% (n=52). Deceased patients were more tachypneic on admission (respiratory rate 26 vs. 22; p=0.003), presented sensory alteration more frequently (58% vs. 14%; p< 0.001), PaO2/fraction of inspired oxygen ratio < 250 (58% vs. 22%; p<0.001), bilateral radiological compromise (50% vs. 32%; p=0.03), needed mechanical ventilation (50% vs 12%; p< 0.001), higher blood creatinine values (1.6 vs. 1.15; p=0.01), lower white blood cell count (10 900 vs 17 400; p=0.002), a lower glucose dosage (111 vs. 120; p=0.01), and fewer days of hospital stay (6 vs. 9; p=0.015). In logistic regression model, significant differences were maintained in the following factors associated with mortality: mechanical ventilation (OR=3.54), altered mental status (OR=5.95), chest X-ray with bilateral compromise (OR 3.20) and PAFI less than 250 (OR=3.62).
CONCLUSION
In our series, the factors related to mortality, despite the presence of bacteremia, do not differ from those published in the literature and which are part of the different prognostic scores used in routine practice.
Topics: Humans; Male; Retrospective Studies; Middle Aged; Female; Aged; Pneumonia, Pneumococcal; Risk Factors; Adult; Streptococcus pneumoniae; Hospital Mortality; Bacteremia
PubMed: 38907962
DOI: No ID Found