Early pulmonary rehabilitation of COVID-19 patients in an isolation ward and intensive care unit.

When patient with coronavirus disease 2019 (COVID-19) are hospitalized, the limited space for activity, disease itself causes fever, muscle aches, fatigue, respiratory failure with mechanical ventilation, or medications such as steroids or neuromuscular blocking can cause muscle dysfunction. Pulmonary rehabilitation (PR) should be arranged for these patients with COVID-19. However, the literature on early PR within 1 week of admission on patients with COVID-19 are limited. This review focuses on early PR in COVID-19 patients admitted to isolation wards or intensive care units. The essential components of early PR programs include education, breathing exercise, airway clearance, and physical activity training. Breathing exercises, including diaphragmatic and pursed-lip breathing, are known to improve lung function in chronic obstructive pulmonary disease and are also recommended for COVID-19 patients. Poor airway clearance can further aggravate pneumonia. Airway clearance techniques help patients to clear sputum and prevent the aggravation of pneumonia. Early physical activity training allows patients to maintain limb muscle function during hospitalization. It is recommended to design appropriate indoor exercise training for patients with frequency 1-2 times a day, and intensity should not be too high (dyspnea Borg Scale ≤3) in the acute stage. In order to achieve safe training, criteria for selecting stable patients and training termination are important. Early PR may help reduce the length of hospital stay, maintain functional status, improve symptoms of dyspnea, relieve anxiety, and maintain health-related quality of life in these patients after discharge.

Prediction of Contaminated Areas Using Ultraviolet Fluorescence Markers for Medical Simulation: A Mobile Phone Application Approach.

The use of ultraviolet fluorescence markers in medical simulations has become popular in recent years, especially during the COVID-19 pandemic. Healthcare workers use ultraviolet fluorescence markers to replace pathogens or secretions, and then calculate the regions of contamination. Health providers can use bioimage processing software to calculate the area and quantity of fluorescent dyes. However, traditional image processing software has its limitations and lacks real-time capabilities, making it more suitable for laboratory use than for clinical settings. In this study, mobile phones were used to measure areas contaminated during medical treatment. During the research process, a mobile phone camera was used to photograph the contaminated regions at an orthogonal angle. The fluorescence marker-contaminated area and photographed image area were proportionally related. The areas of contaminated regions can be calculated using this relationship. We used Android Studio software to write a mobile application to convert photos and recreate the true contaminated area. In this application, color photographs are converted into grayscale, and then into black and white binary photographs using binarization. After this process, the fluorescence-contaminated area is calculated easily. The results of our study showed that within a limited distance (50-100 cm) and with controlled ambient light, the error in the calculated contamination area was 6%. This study provides a low-cost, easy, and ready-to-use tool for healthcare workers to estimate the area of fluorescent dye regions during medical simulations. This tool can promote medical education and training on infectious disease preparation.

Human Papillomavirus Infections and Increased Risk of Incident Osteoporosis: A Nationwide Population-Based Cohort Study.

Patients with viral infections are susceptible to osteoporosis. This cohort study investigated the correlation between human papillomavirus (HPV) infections and the risk of osteoporosis via 12,936 patients with new-onset HPV infections and propensity score-matched non-HPV controls enrolled in Taiwan. The primary endpoint was incident osteoporosis following HPV infections. Cox proportional hazards regression analysis and the Kaplan-Meier method was used to determine the effect of HPV infections on the risk of osteoporosis. Patients with HPV infections presented with a significantly high risk of osteoporosis (adjusted hazard ratio, aHR = 1.32, 95% CI = 1.06-1.65) after adjusting for sex, age, comorbidities and co-medications. Subgroup analysis provided that populations at risk of HPV-associated osteoporosis were females (aHR = 1.33; 95% CI = 1.04-1.71), those aged between 60 and 80 years (aHR = 1.45, 95% CI = 1.01-2.08 for patients aged 60-70; aHR = 1.51; 95% CI = 1.07-2.12 for patients aged 70-80), and patients with long-term use of glucocorticoids (aHR = 2.17; 95% CI = 1.11-4.22). HPV-infected patients who did not receive treatments for HPV infections were at a greater risk (aHR = 1.40; 95% CI = 1.09-1.80) of osteoporosis, while the risk of osteoporosis in those who received treatments for HPV infections did not reach statistical significance (aHR = 1.14; 95% CI = 0.78-1.66). Patients with HPV infections presented with a high risk of subsequent osteoporosis. Treatments for HPV infections attenuated the risk of HPV-associated osteoporosis.

Non-pharmaceutical interventions for COVID-19 reduced the incidence of infectious diseases: a controlled interrupted time-series study.

BACKGROUND: Non-pharmaceutical interventions (NPIs) have been implemented worldwide to suppress the spread of coronavirus disease 2019 (COVID-19). However, few studies have evaluated the effect of NPIs on other infectious diseases and none has assessed the avoided disease burden associated with NPIs. We aimed to assess the effect of NPIs on the incidence of infectious diseases during the COVID-19 pandemic in 2020 and evaluate the health economic benefits related to the reduction in the incidence of infectious diseases. METHODS: Data on 10 notifiable infectious diseases across China during 2010-2020 were extracted from the China Information System for Disease Control and Prevention. A two-stage controlled interrupted time-series design with a quasi-Poisson regression model was used to examine the impact of NPIs on the incidence of infectious diseases. The analysis was first performed at the provincial-level administrative divisions (PLADs) level in China, then the PLAD-specific estimates were pooled using a random-effect meta-analysis. RESULTS: A total of 61,393,737 cases of 10 infectious diseases were identified. The implementation of NPIs was associated with 5.13 million (95% confidence interval [CI] 3.45‒7.42) avoided cases and USD 1.77 billion (95% CI 1.18‒2.57) avoided hospital expenditures in 2020. There were 4.52 million (95% CI 3.00‒6.63) avoided cases for children and adolescents, corresponding to 88.2% of total avoided cases. The top leading cause of avoided burden attributable to NPIs was influenza [avoided percentage (AP): 89.3%; 95% CI 84.5‒92.6]. Socioeconomic status and population density were effect modifiers. CONCLUSIONS: NPIs for COVID-19 could effectively control the prevalence of infectious diseases, with patterns of risk varying by socioeconomic status. These findings have important implications for informing targeted strategies to prevent infectious diseases.

Quality of care in the course of subcutaneous versus intravenous trastuzumab administration in patients with breast cancer: an integrated time-motion study with mixed-methods research.

OBJECTIVES: This study aimed to compare the time required and concerns raised by various perspectives of participants regarding administering subcutaneous and intravenous trastuzumab for patients with breast cancer (BC). DESIGN: This observational time-motion study design with mixed-methods research (cross-sectional surveys and semistructured interviews) was conducted. The time spent on preparing or administering trastuzumab by different healthcare professionals (HCPs) was recorded. The data were analysed by descriptive/inferential statistical analyses, followed by thematic analyses. SETTING: Outpatient and inpatient administration units of a single medical centre in Taiwan. PARTICIPANTS: The study included patients with early-stage BC who received subcutaneous or intravenous trastuzumab (n=93), and HCPs including two attending physicians, a nurse practitioner, two pharmacists and two nurses. RESULT: Based on the perspectives of patients and HCPs, the subcutaneous form of trastuzumab was more efficient, less expensive and produced less discomfort in outpatient units than inpatient units. More participants preferred the subcutaneous form over the intravenous form in both outpatient and inpatient units. Pharmacists and nurse practitioners spent threefold more time on patients when preparing and administering the intravenous form in both outpatient and inpatient units. The concerns raised by patients and HCPs varied in certain aspects, including the injection skills, speed, mental distress (eg, needle phobia) and pain associated with the subcutaneous form. Almost all patients preferred receiving the subcutaneous form in outpatient units after the initial COVID-19 outbreak. CONCLUSION: Patients with early-stage BC preferred receiving subcutaneous trastuzumab in outpatient units rather than inpatient units or the intravenous form before and after the COVID-19 outbreak. Such findings may serve as real-world evidence to facilitate better quality of care regarding administration of subcutaneous or intravenous trastuzumab in medical settings, and its feasible resolutions to balance the quality, concerns and efficiency of anticancer administration during the COVID-19 pandemic.

Totally-green cellulosic fiber with prominent sustained antibacterial and antiviral properties for potential use in spunlaced non-woven fabric production.

The worldwide spread of COVID-19 has put a higher requirement for personal medical protective clothing, developing protective clothing with sustained antibacterial and antiviral performance is the priority for safe and sustaining application. For this purpose, we develop a novel cellulose based material with sustained antibacterial and antiviral properties. In the proposed method, the chitosan oligosaccharide (COS) was subjected to a guanylation reaction with dicyandiamide in the presence of Scandium (III) triflate; because of the relatively lower molecular weight and water solubility of the COS, GCOS (guanylated chitosan oligosaccharide) with high substitution degree (DS) could be successfully synthetized without acid application. In this instance, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the GCOS were only 1/8 and 1/4 of that of COS. The introduction of GCOS onto the fiber endowed the fiber with extremely high antibacterial and antiviral performance, showing 100% bacteriostatic rate against Staphylococcus aureus and Escherichia coli and 99.48% virus load reduction of bacteriophage MS2. More importantly, the GCOS modified cellulosic fibers (GCOS-CFs) exhibit excellent sustained antibacterial and antiviral properties; namely, 30 washing cycles had negligible effect on the bacteriostatic rate (100%) and inhibition rate of bacteriophage MS2 (99.0%). Moreover, the paper prepared from the GCOS-CFs still exhibited prominent antibacterial and antiviral activity; inferring that the sheeting forming, press, and drying process have almost no effect on the antibacterial and antiviral performances. The insensitive of antibacterial and antiviral activity to water washing (spunlace) and heat (drying) make the GCOS-CFs a potential material applicable in the spunlaced non-woven fabric production.

Candida parapsilosis infection after double-lung transplantation in a patient with pulmonary fibrosis caused by COVID-19.

Pulmonary fibrosis is a complication in patients with coronavirus disease 2019 (COVID-19). Extensive pulmonary fibrosis is a severe threat to patients' life and lung transplantation is last resort to prolong the life of patients. We reported a case of critical type COVID-19 patient, though various treatment measures were used, including anti-virus, anti-infection, improving immunity, convalescent plasma, prone position ventilation, and airway cleaning by fiber-optic bronchoscope, although his COVID-19 nucleic acid test turned negative, the patient still developed irreversible extensive pulmonary fibrosis, and respiratory mechanics suggested that lung compliance could not be effectively recovered. After being assisted by ventilator and extracorporeal membrane oxygenation for 73 days, he finally underwent double-lung transplantation. On the 2nd day after the operation, the alveolar lavage fluid of transplanted lung was examined by cytomorphology, and the morphology of alveolar epithelial cells was intact and normal. On the 20th day post-transplantation, the chest radiograph showed a large dense shadow in the middle of the right lung. On the 21st day, the patient underwent fiber-optic bronchoscopy, yeast-like fungal spores were found by cytomorphological examination from a brush smear of the right bronchus, which was confirmed as Candida parapsilosis infection by fungal culture. He recovered well due to the careful treatment and nursing in our hospital. Until July 29, 96 days after transplantation, the patient was recovery and discharged from hospital.

The COVIDTW study: Clinical predictors of COVID-19 mortality and a novel AI prognostic model using chest X-ray.

BACKGROUND: There is a lack of published research on the impact of the first wave of the COVID-19 pandemic in Taiwan. We investigated the mortality risk factors among critically ill patients with COVID-19 in Taiwan during the initial wave. Furthermore, we aim to develop a novel AI mortality prediction model using chest X-ray (CXR) alone. METHOD: We retrospectively reviewed the medical records of patients with COVID-19 at Taipei Tzu Chi Hospital from May 15 to July 15 2021. We enrolled adult patients who received invasive mechanical ventilation. The CXR images of each enrolled patient were divided into 4 categories (1st, pre-ETT, ETT, and WORST). To establish a prediction model, we used the MobilenetV3-Small model with "Imagenet" pretrained weights, followed by high Dropout regularization layers. We trained the model with these data with Five-Fold Cross-Validation to evaluate model performance. RESULT: A total of 64 patients were enrolled. The overall mortality rate was 45%. The median time from symptom onset to intubation was 8 days. Vasopressor use and a higher BRIXIA score on the WORST CXR were associated with an increased risk of mortality. The areas under the curve of the 1st, pre-ETT, ETT, and WORST CXRs by the AI model were 0.87, 0.92, 0.96, and 0.93 respectively. CONCLUSION: The mortality rate of COVID-19 patients who receive invasive mechanical ventilation was high. Septic shock and high BRIXIA score were clinical predictors of mortality. The novel AI mortality prediction model using CXR alone exhibited a high performance.

Immunothrombosis biomarkers as potential predictive factors of acute respiratory distress syndrome in moderate-to-critical COVID-19: A single-center, retrospective cohort study.

BACKGROUND: Immunothrombosis, a process of inflammation and coagulation, is involved in sepsis-induced acute respiratory distress syndrome formation (ARDS). However, the clinical correlation between immunothrombosis biomarkers (including tissue factor [TF] and von Willebrand factor [vWF]) and coronavirus disease 2019 (COVID-19)-related ARDS is unknown. This study investigated ARDS development following moderate-to-critical COVID-19 and examined immunothrombosis biomarkers as ARDS predictors. METHODS: This retrospective cohort study included patients with moderate-to-critical COVID-19 (n = 165) admitted to a northern teaching hospital during the 2021 pandemic in Taiwan, who had no COVID-19 vaccinations. Immunothrombosis biomarkers were compared between COVID-19 patients with and without ARDS (no-ARDS) and a control group consisting of 100 healthy individuals. RESULTS: The study included 58 ARDS and 107 no-ARDS patients. In multivariable analysis, TF (aOR=1.031, 95% CI: 1.009-1.053, p = 0.006); and vWF (aOR=1.053, 95% CI: 1.002-1.105, p = 0.041) were significantly associated with ARDS episodes, after adjusting for other confounding factors. vWF and TF predicted ARDS with the area under the curve of 0.870 (95% CI: 0.796-0.945). Further mechanical ventilation analysis found TF to be correlated significantly with pCO2 and ventilatory ratio. CONCLUSIONS: TF and vWF levels potentially predicted ARDS development within 7 days of admission for COVID-19 after adjusting for traditional risk factors. TF correlated with ventilation impairment in COVID-19 ARDS but further prospective studies are needed.

Association between heme oxygenase one and sepsis development in patients with moderate-to-critical COVID-19: a single-center, retrospective observational study.

BACKGROUND: Heme oxygenase one (HO-1) is considered a poor prognostic factor for survival in patients with severe-to-critical coronavirus disease (COVID-19), but the clinical correlation between heme catabolism biomarkers and COVID-19-related sepsis is unknown. The etiopathogenetic hypothesis of HO-1 response during sepsis in patients with poor prognosis should be clarified. This study aimed to investigate sepsis development within 48 h following moderate-to-critical COVID-19 and examined heme/HO-1 catabolism biomarkers associated with sepsis. We also studied the HO-1 and traditional prognostic factors for predicting survival in patients with COVID-19. METHODS: This retrospective observational study included patients unvaccinated for COVID-19 with moderate-to-critical COVID-19 (n = 156) who had been admitted to Taipei Tzu Chi Hospital in 2021. All COVID-19 patients were diagnosed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase polymerase chain reaction. For analysis of heme catabolism in SARS-CoV-2-induced sepsis, we excluded patients with co-infection and severe anemia. Heme catabolism biomarkers were compared between groups of patients with COVID-19 and sepsis (sepsis) and those with COVID-19 without sepsis (no sepsis), and a control group comprising 100 healthy individuals. All clinical and laboratory data were collected retrospectively and blood specimens were collected from Biobank. Multivariable logistic regression analysis was used to compare all variables between the sepsis and no-sepsis groups. Cox regression analysis was used to determine predictors of survival in patients with COVID-19. RESULTS: There were 71 and 85 patients with and without sepsis, respectively. Heme and HO-1 levels differed significantly between the sepsis, no sepsis, and control groups. In multivariate analysis, confusion, blood urea nitrogen, respiration, blood pressure in patients aged > 65 years (CURB-65) (adjusted odds ratio [aOR] 5.331, 95% confidence interval [CI] 2.587-10.987; p < 0.001), albumin (aOR 0.139, 95% CI 0.003-0.636; p = 0.01), D-dimer (aOR 1.001, 95% CI 1.000-1.002; p = 0.032), and HO-1 (aOR 1.116, 95% CI 1.055-1.180; p < 0.001) were significantly associated with 48-h sepsis episodes after adjusting for other confounding factors. HO-1 levels were also significantly associated with 48-h Sequential Organ Failure Assessment Score (SOFA) scores. However, HO-1 did not significantly increase the hazard of in-hospital mortality in moderate-to-critical COVID-19 by Cox regression analysis. CONCLUSIONS: HO-1 levels increased with sepsis development within 48 h of admission for COVID-19 after adjusting for other risk factors, but no significant association was observed between HO-1 and COVID-19 mortality. We suppose that HO-1 may have protective effect in early sepsis, but further clinical multicenter prospective studies are needed.

Immune Responses to COVID-19 Vaccines in Patients with Chronic Kidney Disease and Lead Exposure.

Literature data regarding the response rate to COVID-19 vaccination in chronic kidney disease (CKD) patients remain inconclusive. Furthermore, studies have reported a relationship between lead exposure and susceptibility to viral infections. This study examined immune responses to COVID-19 vaccines in patients with CKD and lead exposure. Between October and December 2021, 50 lead-exposed CKD patients received two doses of vaccination against COVID-19 at Chang Gung Memorial Hospital. Patients were stratified into two groups based on the median blood lead level (BLL): upper (≥1.30 µg/dL, n = 24) and lower (<1.30 µg/dL, n = 26) 50th percentile. The patients were aged 65.9 ± 11.8 years. CKD stages 1, 2, 3, 4 and 5 accounted for 26.0%, 20.0%, 22.0%, 8.0% and 24.0% of the patients, respectively. Patients in the lower 50th percentile of BLL had a lower proportion of CKD stage 5 than patients in the upper 50th percentile BLL group (p = 0.047). The patients in the lower 50th percentile BLL group also received a higher proportion of messenger RNA vaccines and a lower proportion of adenovirus-vectored vaccines than the patients in the upper 50th percentile BLL group (p = 0.031). Notably, the neutralizing antibody titers were higher in the lower 50th percentile than in the upper 50th percentile BLL group. Furthermore, the circulating levels of granulocyte-colony stimulating factor, interleukin-8, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1α were higher in the upper 50th percentile than in the lower 50th percentile BLL group. Therefore, it was concluded that lead-exposed CKD patients are characterized by an impaired immune response to COVID-19 vaccination with diminished neutralizing antibodies and augmented inflammatory reactions.

Short-term effect of internet-delivered mindfulness-based stress reduction on mental health, self-efficacy, and body image among women with breast cancer during the COVID-19 pandemic.

Background and aim: During the COVID-19 pandemic, an Internet-Mindfulness-Based Stress Reduction (iMBSR) program was delivered and may be better than an in-person approach. Our study evaluated the effects of iMBSR intervention on mental health, self-efficacy, and body image in women with breast cancer in Taiwan. Materials and methods: Sixty-seven women with breast cancer were allocated to a 6-week iMBSR (n = 41) program or a waitlist control group (n = 26), without heterogeneity between group characteristics. Patients from both groups were measured at baseline and postintervention using three scales: Depression, Anxiety, and Stress Scale (DASS-21), General self-efficacy scale, and Body Image Scale. Descriptive dataset analysis, paired t-test, and Student's t-test were used to evaluate the data. Results: Although iMBSR did not significantly improve depression and stress between groups, iMBSR could improve anxiety (Δmean: -2.0 vs. -0.4, p = 0.041) with medium effect sizes. Significant benefits were found for body image (Δmean: -3.6 vs. 0.9, p = 0.003) and self-efficacy (Δmean: 4.2 vs. 1.5, p = 0.004), with large effect sizes (Cohen's d = 0.73). Conclusion: Our preliminary study supports iMBSR as a program that can improve mental health, body image, and self-efficacy in women with breast cancer. During the COVID-19 pandemic, medical professionals can use Internet-based clinical health education.

Perceived COVID-19 risk exposure and adoption of preventive behaviors: Social media information consumption as a moderator

Increasing preventive behaviors is critical to mitigating the rapid spread of COVID-19, but this can be challenging as some people are reluctant to practice these behaviors. We explored the mediating role of threat appraisal in the link between perception of COVID-19 risk exposure and preventive behavior, and the moderating effect of COVID-19 information consumption through social media. We recruited 577 people in China to complete a survey. The results show that perception of COVID-19 risk exposure was positively associated with preventive behaviors and that threat appraisal partially mediated this relationship. Moreover, COVID-19 information consumption on social media moderated the mediating effect. These results provide theoretical and practical implications to increase individuals' preventive behaviors during the COVID-19 pandemic. [ FROM AUTHOR] Copyright of Social Behavior & Personality: an international journal is the property of Society for Personality Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Long-term improvement of air quality associated with lung function benefits in Chinese young adults: A quasi-experiment cohort study.

INTRODUCTION: Long-term exposure to air pollution is associated with lung function impairment. However, whether long-term improvements in air quality could improve lung function is unclear. OBJECTIVES: To examine whether the reduction of long-term air pollution was associated with lung function improvement among Chinese young adults. METHODS: We conducted a prospective quasi-experiment cohort study with 1731 college students in Shandong, China from September 2019 to September 2020, covering COVID-19 lockdown period. Data on air pollution concentrations were obtained from China Environmental Monitoring Station. Lung function indicators included forced vital capacity (FVC), forced expiratory volume in 1st second (FEV1) and forced expiratory flow at 50 % of FVC (FEF50%). We used linear mixed-effects model to examine the associations between the change of air pollutants concentrations and the change of lung function, and additional adjustments for indoor air pollution (IAP) source. We also conducted stratified analysis by sex. RESULTS: Compared with 2019, the mean FVC, FEV1 and FEF50% were elevated by 414.4 ml, 321.5 ml, and 28.4 ml/s respectively in 2020. Every 5 µg/m3 decrease in annual average PM2.5 concentrations was associated with 36.0 ml [95 % confidence interval (CI):6.0, 66.0 ml], 46.1 ml (95 % CI:16.7, 75.5 ml), and 124.2 ml/s (95 % CI:69.5, 178.9 ml/s) increment in the FVC, FEV1, and FEF50%, respectively. Similar associations were found for PM10. The estimated impact was almost unchanged after adjusting for IAP source. There was no significant effect difference between males and females. CONCLUSION: Long-term improvement of air quality can improve lung function among young adults. Stricter policies on improving air quality are needed to protect human health.

A weekly-diary study of students' schoolwork motivation and parental support.

BACKGROUND: Parental support plays an important role in children's schoolwork motivation and may have been even more important during the first UK COVID-19 pandemic lockdown because all schoolwork was completed at home. When examining the effect of parental support on children's schoolwork motivation, research has typically focused on comparing families with each other (i.e., difference between families). In reality, however, the effect unfolds as a transactional, bidirectional process between parents and children over time (i.e., a within family process). This research trend can result in imprecise conclusions about the association between parental support and schoolwork motivation. OBJECTIVES: We examined bidirectional effects of parental schoolwork support and children's schoolwork motivation at both the between-family and within-family level. METHODS: This study reports findings from a weekly-diary study conducted during the first UK COVID-19 school lockdown. Cross-lagged within and between multilevel modelling was used to analyse data from UK secondary school students (N = 98) in Years 7-9. RESULTS: Between-family results show no evidence of association between motivation and parental support. Within-family results indicate that higher motivation (assessed as higher expectations of success) predicted more support from parents. However, in contrast with predictions, weekly levels of parental support did not predict children's weekly fluctuations in motivation. CONCLUSIONS: Within-family results were not consistent with between-family results. This study is novel in showing that child-driven effects appear to be important in eliciting parental support within families over time.

Early detection of circulating tumor DNA and successful treatment with osimertinib in thr790met-positive leptomeningeal metastatic lung cancer: A case report.

BACKGROUND: Patients diagnosed with non-small-cell lung cancer with activated epidermal growth factor receptor mutations are more likely to develop leptomeningeal (LM) metastasis than other types of lung cancers and have a poor prognosis. Early diagnosis and effective treatment of leptomeningeal carcinoma can improve the prognosis. CASE SUMMARY: A 55-year-old female with a progressive headache and vomiting for one month was admitted to Peking University First Hospital. She was diagnosed with lung adenocarcinoma with osseous metastasis 10 months prior to admittance. epidermal growth factor receptor (EGFR) mutation was detected by genomic examination, so she was first treated with gefitinib for 10 months before acquiring resistance. Cell-free cerebrospinal fluid (CSF) circulating tumor DNA detection by next-generation sequencing was conducted and indicated the EGFR-Thr790Met mutation, while biopsy and cytology from the patient's CSF and the first enhanced cranial magnetic resonance imaging (MRI) showed no positive findings. A month later, the enhanced MRI showed linear leptomeningeal enhancement, and the cytology and biochemical examination in CSF remained negative. Therefore, osimertinib (80 mg/d) was initiated as a second-line treatment, resulting in a good response within a month. CONCLUSION: This report suggests clinical benefit of osimertinib in LM patients with positive detection of the EGFR-Thr790Met mutation in CSF and proposes that the positive findings of CSF circulating tumor DNA as a liquid biopsy technology based on the detection of cancer-associated gene mutations may appear earlier than the imaging and CSF findings and may thus be helpful for therapy. Moreover, the routine screening of chest CT with the novel coronavirus may provide unexpected benefits.

Deciphering the role of damage-associated molecular patterns and inflammatory responses in acute lung injury.

Acute lung injury (ALI) is characterized by diffuse pulmonary infiltrates and causes great mortality. ALI presents with overproduction of proinflammatory cytokines, cell death, destruction of alveoli-endothelial barriers, and neutrophil infiltration in lung tissues. Damage-associated molecular patterns (DAMPs) are molecules released from damaged cells due to infection, trauma, etc. DAMPs activate innate and adaptive immunity, trigger inflammatory responses, and are important in the initiation and development of ALI. We reviewed the literatures on DAMPs in ALI. Alveolar macrophages (AMs), neutrophils, and epithelial cells (AECs) are important in the pathogenesis of ALI. We comprehensively analyzed the interaction between DAMPs and AMs, alveolar neutrophils, and AECs. During the initial stage of ALI, ruptured cell membranes or destroyed mitochondria release DAMPs. DAMPs activate the inflammasome in nearby sentinel immune cells, such as AMs. AMs produce IL-1ß and other cytokines. These mediators upregulate adhesion molecules of the capillary endothelium that facilitate neutrophil recruitment. The recruited neutrophils detect DAMPs using formyl peptide receptors on the membrane, guiding their migration to the injured site. The accumulation of immune cells, cytokines, chemokines, proteases, etc., results in diffuse alveolar damage and pulmonary hyperpermeability with protein-rich fluid retention. Some clinical studies have shown that patients with ALI with higher circulating DAMPs have higher mortality rates. In conclusion, DAMPs are important in the initiation and progression of ALI. The interactions between DAMPs and AMs, neutrophils, and AECs are important in ALI. This review comprehensively addresses the mechanisms of DAMPs and their interactions in ALI.

Maternal psychological distress during the COVID-19 pandemic and structural changes of the human fetal brain.

Background: Elevated maternal psychological distress during pregnancy is linked to adverse outcomes in offspring. The potential effects of intensified levels of maternal distress during the COVID-19 pandemic on the developing fetal brain are currently unknown. Methods: We prospectively enrolled 202 pregnant women: 65 without known COVID-19 exposures during the pandemic who underwent 92 fetal MRI scans, and 137 pre-pandemic controls who had 182 MRI scans. Multi-plane, multi-phase single shot fast spin echo T2-weighted images were acquired on a GE 1.5 T MRI Scanner. Volumes of six brain tissue types were calculated. Cortical folding measures, including brain surface area, local gyrification index, and sulcal depth were determined. At each MRI scan, maternal distress was assessed using validated stress, anxiety, and depression scales. Generalized estimating equations were utilized to compare maternal distress measures, brain volume and cortical folding differences between pandemic and pre-pandemic cohorts. Results: Stress and depression scores are significantly higher in the pandemic cohort, compared to the pre-pandemic cohort. Fetal white matter, hippocampal, and cerebellar volumes are decreased in the pandemic cohort. Cortical surface area and local gyrification index are also decreased in all four lobes, while sulcal depth is lower in the frontal, parietal, and occipital lobes in the pandemic cohort, indicating delayed brain gyrification. Conclusions: We report impaired fetal brain growth and delayed cerebral cortical gyrification in COVID-19 pandemic era pregnancies, in the setting of heightened maternal psychological distress. The potential long-term neurodevelopmental consequences of altered fetal brain development in COVID-era pregnancies merit further study.

Single-cell transcriptome profiling of the immune space-time landscape reveals dendritic cell regulatory program in polymicrobial sepsis.

Rationale: Evident immunosuppression has been commonly seen among septic patients, and it is demonstrated to be a major driver of morbidity. Nevertheless, a comprehensive view of the host immune response to sepsis is lacking as the majority of studies on immunosuppression have focused on a specific type of immune cells. Methods: We applied multi-compartment, single-cell RNA sequencing (scRNA-seq) to dissect heterogeneity within immune cell subsets during sepsis progression on cecal ligation and puncture (CLP) mouse model. Flow cytometry and multiplex immunofluorescence tissue staining were adopted to identify the presence of 'mature DCs enriched in immunoregulatory molecules' (mregDC) upon septic challenge. To explore the function of mregDC, sorted mregDC were co-cultured with naïve CD4+ T cells. Intracellular signaling pathways that drove mregDC program were determined by integrating scRNA-seq and bulk-seq data, combined with inhibitory experiments. Results: ScRNA-seq analysis revealed that sepsis induction was associated with substantial alterations and heterogeneity of canonical immune cell types, including T, B, natural killer (NK), and myeloid cells, across three immune-relevant tissue sites. We found a unique subcluster of conventional dendritic cells (cDCs) that was characterized by specific expression of maturation- and migration-related genes, along with upregulation of immunoregulatory molecules, corresponding to the previously described 'mregDCs' in cancer. Flow cytometry and in stiu immunofluorescence staining confirmed the presence of sepsis-induced mregDC at protein level. Functional experiments showed that sepsis-induced mregDCs potently activated naive CD4+ T cells, while promoted CD4+ T cell conversion to regulatory T cells. Further observations indicated that the mregDC program was initiated via TNFRSF-NF-κB- and IFNGR2-JAK-STAT3-dependent pathways within 24 h of septic challenge. Additionally, we confirmed the detection of mregDC in human sepsis using publicly available data from a recently published single-cell study of COVID-19 patients. Conclusions: Our study generates a comprehensive single-cell immune landscape for polymicrobial sepsis, in which we identify the significant alterations and heterogeneity in immune cell subsets that take place during sepsis. Moreover, we find a conserved and potentially targetable immunoregulatory program within DCs that associates with hyperinflammation and organ dysfunction early following sepsis induction.

Global, regional, and national burden of mortality associated with short-term temperature variability from 2000-19: a three-stage modelling study.

BACKGROUND: Increased mortality risk is associated with short-term temperature variability. However, to our knowledge, there has been no comprehensive assessment of the temperature variability-related mortality burden worldwide. In this study, using data from the MCC Collaborative Research Network, we first explored the association between temperature variability and mortality across 43 countries or regions. Then, to provide a more comprehensive picture of the global burden of mortality associated with temperature variability, global gridded temperature data with a resolution of 0·5°â€ˆ× 0·5° were used to assess the temperature variability-related mortality burden at the global, regional, and national levels. Furthermore, temporal trends in temperature variability-related mortality burden were also explored from 2000-19. METHODS: In this modelling study, we applied a three-stage meta-analytical approach to assess the global temperature variability-related mortality burden at a spatial resolution of 0·5°â€ˆ× 0·5° from 2000-19. Temperature variability was calculated as the SD of the average of the same and previous days' minimum and maximum temperatures. We first obtained location-specific temperature variability related-mortality associations based on a daily time series of 750 locations from the Multi-country Multi-city Collaborative Research Network. We subsequently constructed a multivariable meta-regression model with five predictors to estimate grid-specific temperature variability related-mortality associations across the globe. Finally, percentage excess in mortality and excess mortality rate were calculated to quantify the temperature variability-related mortality burden and to further explore its temporal trend over two decades. FINDINGS: An increasing trend in temperature variability was identified at the global level from 2000 to 2019. Globally, 1 753 392 deaths (95% CI 1 159 901-2 357 718) were associated with temperature variability per year, accounting for 3·4% (2·2-4·6) of all deaths. Most of Asia, Australia, and New Zealand were observed to have a higher percentage excess in mortality than the global mean. Globally, the percentage excess in mortality increased by about 4·6% (3·7-5·3) per decade. The largest increase occurred in Australia and New Zealand (7·3%, 95% CI 4·3-10·4), followed by Europe (4·4%, 2·2-5·6) and Africa (3·3, 1·9-4·6). INTERPRETATION: Globally, a substantial mortality burden was associated with temperature variability, showing geographical heterogeneity and a slightly increasing temporal trend. Our findings could assist in raising public awareness and improving the understanding of the health impacts of temperature variability. FUNDING: Australian Research Council, Australian National Health & Medical Research Council.