Illuminating the dark spaces of healthcare with ambient intelligence.

Advances in machine learning and contactless sensors have given rise to ambient intelligence-physical spaces that are sensitive and responsive to the presence of humans. Here we review how this technology could improve our understanding of the metaphorically dark, unobserved spaces of healthcare. In hospital spaces, early applications could soon enable more efficient clinical workflows and improved patient safety in intensive care units and operating rooms. In daily living spaces, ambient intelligence could prolong the independence of older individuals and improve the management of individuals with a chronic disease by understanding everyday behaviour. Similar to other technologies, transformation into clinical applications at scale must overcome challenges such as rigorous clinical validation, appropriate data privacy and model transparency. Thoughtful use of this technology would enable us to understand the complex interplay between the physical environment and health-critical human behaviours.

Socially situated artificial intelligence enables learning from human interaction.

Regardless of how much data artificial intelligence agents have available, agents will inevitably encounter previously unseen situations in real-world deployments. Reacting to novel situations by acquiring new information from other people-socially situated learning-is a core faculty of human development. Unfortunately, socially situated learning remains an open challenge for artificial intelligence agents because they must learn how to interact with people to seek out the information that they lack. In this article, we formalize the task of socially situated artificial intelligence-agents that seek out new information through social interactions with people-as a reinforcement learning problem where the agent learns to identify meaningful and informative questions via rewards observed through social interaction. We manifest our framework as an interactive agent that learns how to ask natural language questions about photos as it broadens its visual intelligence on a large photo-sharing social network. Unlike active-learning methods, which implicitly assume that humans are oracles willing to answer any question, our agent adapts its behavior based on observed norms of which questions people are or are not interested to answer. Through an 8-mo deployment where our agent interacted with 236,000 social media users, our agent improved its performance at recognizing new visual information by 112%. A controlled field experiment confirmed that our agent outperformed an active-learning baseline by 25.6%. This work advances opportunities for continuously improving artificial intelligence (AI) agents that better respect norms in open social environments.

Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting.

The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERs) organized a daylong symposium at the 2024 annual meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research as well as debates on the mechanisms and management of eosinophilic gastrointestinal diseases. Updates on recent clinical trials and consensus guidelines were also presented. We summarize the updates on eosinophilic gastrointestinal diseases presented at the symposium.

The bacterial tyrosine kinase system CpsBCD governs the length of capsule polymers.

Many pathogenic bacteria are encased in a layer of capsular polysaccharide (CPS). This layer is important for virulence by masking surface antigens, preventing opsonophagocytosis, and avoiding mucus entrapment. The bacterial tyrosine kinase (BY-kinase) regulates capsule synthesis and helps bacterial pathogens to survive different host niches. BY-kinases autophosphorylate at the C-terminal tyrosine residues upon external stimuli, but the role of phosphorylation is still unclear. Here, we report that the BY-kinase CpsCD is required for growth in Streptococcus pneumoniae Cells lacking a functional cpsC or cpsD accumulated low molecular weight CPS and lysed because of the lethal sequestration of the lipid carrier undecaprenyl phosphate, resulting in inhibition of peptidoglycan (PG) synthesis. CpsC interacts with CpsD and the polymerase CpsH. CpsD phosphorylation reduces the length of CPS polymers presumably by controlling the activity of CpsC. Finally, pulse-chase experiments reveal the spatiotemporal coordination between CPS and PG synthesis. This coordination is dependent on CpsC and CpsD. Together, our study provides evidence that BY-kinases regulate capsule polymer length by fine-tuning CpsC activity through autophosphorylation.

Distinct CRTH2+CD161+ (peTh2) memory CD4+ T-cell cytokine profiles in food allergy and eosinophilic gastrointestinal disorders.

INTRODUCTION: Although IgE-mediated food allergy (FA) and eosinophilic gastrointestinal disorders (EGID) are clinically distinct and treated differently, pathogenic effector Th2 (peTh2) cells are implicated in the pathogenesis of both FA and EGID. The aim of this study was to better characterize peTh2 cells in the context of FA and EGID and the overlap between these two conditions. METHODS: Peripheral blood peTh2 cells (CD3+CD4+CD27-CD49d+CRTH2+CD161+) were profiled by intracellular cytokine flow cytometry in the following patient cohorts: patients with FA alone (n = 8), FA and food-triggered EGID (EGID+FA+FT, n = 7), food-triggered EGID alone (EGID+FT, n = 7), EGID without FA or specific food triggers (ONLY_EGID, n = 9), and healthy volunteers (HV, n = 7). Overnight peripheral blood mononuclear cell (PBMC) culture supernatants were assessed for cytokine production by multiplex analysis. RESULTS: CRTH2+CD161+ (peTh2) memory CD4+ T cells were significantly increased in both patients with FA and those with ALL_EGID (inclusive of EGID+FA+FT, EGID+FT and ONLY_EGID) when compared to HV. However, ALL_EGID patients, particularly those with EGID+FA+FT, had significantly elevated IL-5+IL-13+ peTh2 cells, whereas FA patients had significantly elevated IFN-γ or IL-17A-expressing peTh2 cells. This finding was supported by increased spontaneous IL-5 and IL-13 production in overnight cultures of PBMC from EGID+FA+FT patients compared to spontaneous IL-10 and IFN-γ production by PBMC from FA patients. FA patients had increased IL-9, IL-10, IL-17A, and IFN-γ production in overnight cultures of stimulated PBMC. CONCLUSIONS: EGID and IgE-mediated FA share a common cell subtype defined by specific surface markers and termed CRTH2+CD161+ (peTh2) memory CD4+ T cells. However, the cytokine profiles of these CRTH2+CD161+ (peTh2) memory CD4+ T cells are markedly different between the two disorders.

Drivers of habitat availability for terrestrial mammals: Unravelling the role of livestock, land conversion and intrinsic traits in the past 50 years.

The global decline of terrestrial species is largely due to the degradation, loss and fragmentation of their habitats. The conversion of natural ecosystems for cropland, rangeland, forest products and human infrastructure are the primary causes of habitat deterioration. Due to the paucity of data on the past distribution of species and the scarcity of fine-scale habitat conversion maps, however, accurate assessment of the recent effects of habitat degradation, loss and fragmentation on the range of mammals has been near impossible. We aim to assess the proportions of available habitat within the lost and retained parts of mammals' distribution ranges, and to identify the drivers of habitat availability. We produced distribution maps for 475 terrestrial mammals for the range they occupied 50 years ago and compared them to current range maps. We then calculated the differences in the percentage of 'area of habitat' (habitat available to a species within its range) between the lost and retained range areas. Finally, we ran generalized linear mixed models to identify which variables were more influential in determining habitat availability in the lost and retained parts of the distribution ranges. We found that 59% of species had a lower proportion of available habitat in the lost range compared to the retained range, thus hypothesizing that habitat loss could have contributed to range declines. The most important factors negatively affecting habitat availability were the conversion of land to rangeland and high density of livestock. Significant intrinsic traits were those related to reproductive timing and output, habitat breadth and medium body size. Our findings emphasize the importance of implementing conservation strategies to mitigate the impacts caused by human activities on the habitats of mammals, and offer evidence indicating which species have the potential to reoccupy portions of their former range if other threats cease to occur.

Bulk T-cell receptor sequencing confirms clonality in pediatric eosinophilic esophagitis and identifies a food-specific repertoire.

BACKGROUND: Eosinophilic esophagitis (EoE) involves a chronic immune-mediated response to dietary antigens. Recent work identifies T-cell clonality in children with EoE, however, it is unknown whether this is true in adults or whether there is a restricted food-specific T-cell repertoire. We sought to confirm T-cell receptor (TCR) clonality in EoE and assess for differences with specific food triggers. METHODS: Bulk TCR sequencing was performed on mRNA isolated from esophageal biopsies obtained from adults and children with EoE (n = 15) who had food triggers confirmed by endoscopic evaluation. Non-EoE adult and pediatric controls (n = 10) were included. Differences in TCR clonality by disease and treatment status were assessed. Shared and similar V-J-CDR3s were assessed based on specific food triggers. RESULTS: Active EoE biopsies from children but not adults displayed decreased unique TCRα/ß clonotypes and increased relative abundance of TCRs comprising >1% of the total compared to non-EoE controls and paired inactive EoE samples. Among patients in which baseline, post diet elimination, and food trigger reintroduction samples (n = 6) were obtained, we observed ~1% of TCRs were shared only between pre-diet elimination and trigger reintroduction. Patients with a shared EoE trigger (milk) had a greater degree of shared and similar TCRs compared to patients with differing triggers (seafood, wheat, egg, soy). CONCLUSION: We confirmed relative clonality in children but not adults with active EoE and identified potential food-specific TCRs, particularly for milk-triggered EoE. Further studies are needed to better identify the broad TCR repertoire relevant to food triggers.

Urine eosinophil-derived neurotoxin: A potential marker of activity in select eosinophilic disorders.

BACKGROUND: Biomarkers of eosinophilic disease activity, especially in the context of novel therapies that reduce blood eosinophil counts, are an unmet need. Absolute eosinophil count (AEC) does not accurately reflect tissue eosinophilia or eosinophil activation. Therefore, the aims of this study were to compare the reliability of plasma and urine eosinophil major basic protein 1, eosinophil cationic protein, eosinophil-derived neurotoxin (EDN), and eosinophil peroxidase measurement and to evaluate the usefulness of eosinophil granule protein (EGP) measurement for the assessment of disease activity in patients with eosinophil-associated diseases treated with mepolizumab, benralizumab, or dexpramipexole. METHODS: Eosinophil granule protein concentrations were measured in serum, plasma, and urine from healthy volunteers and patients with hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic asthma using a multiplex assay. RESULTS: Urine EGP concentrations remained stable, whereas serum and plasma EGP concentrations increased significantly with delayed processing. Plasma (p) EDN, but not urine (u) EDN, concentration correlated with AEC and negatively correlated with prednisone dose. Both pEDN and uEDN decreased significantly following treatment of HES patients with benralizumab and EGPA patients with mepolizumab. uEDN appeared to increase with clinical relapse in both patient groups. CONCLUSIONS: Measurement of EGP in urine is noninvasive and unaffected by cellular lysis. Although plasma and urine EDN concentrations showed a similar pattern following benralizumab and mepolizumab treatment, the lack of correlation between AEC or prednisone dose and uEDN concentrations suggests that measurement of uEDN may provide a potential biomarker of disease activity in patients with HES and EGPA.

False-Negative Testing for FIP1L1::PDGFRA by Fluorescence in situ Hybridization Is a Frequent Cause of Diagnostic Delay.

The imatinib-sensitive fusion gene FIP1L1::PDGFRA is the most frequent molecular abnormality identified in patients with eosinophilic myeloid neoplasms. Rapid recognition of this mutation is essential given the poor prognosis of PDGFRA-associated myeloid neoplasms prior to the availability of imatinib therapy. We report a case of a patient in whom delayed diagnosis resulted in cardiac transplantation for eosinophilic endomyocardial fibrosis. The delay in diagnosis was due, in part, to a false-negative result in fluorescence in situ hybridization (FISH) testing for FIP1L1::PDGFRA. To explore this further, we examined our cohort of patients presenting with confirmed or suspected eosinophilic myeloid neoplasms and found 8 additional patients with negative FISH results despite a positive reverse-transcriptase polymerase chain reaction test for FIP1L1::PDGFRA. More importantly, false-negative FISH results delayed the median time to imatinib treatment by 257 days. These data emphasize the importance of empiric imatinib therapy in patients with clinical features suggestive of PDGFRA-associated disease.

Effectiveness of microwave ablation for the treatment of hepatic hemangioma - meta-analysis and meta-regression.

BACKGROUND: The treatment of hepatic hemangioma includes surgical resection, radiofrequency ablation and Transarterial embolization. However, complications, mortality and compromised effectiveness limit their applications. Microwaves with effective heating generation and short ablation time become a promising treatment. The aim of this study is to conduct systematic review and meta-analyses to evaluate the effectiveness of Microwave Ablation (MWA) for the treatment of hepatic hemangioma. METHODS: A systematic literature review was conducted in PubMed. Main outcomes were defined as hemangioma decreases in diameters and volume changes post-MWA. Conventional random-effect meta-analysis technique was applied to analyze the pooled data, and meta-regression model was established to explore the association among factors. RESULTS: There were nine studies with a total of 501 patients retrieved. The pooled estimate of mean differences and 95% CI of hemangioma decreases after MWA treatment in diameter and in volume change (%) were 3.009 cm and (1.856, 4.161), and 53.169% and (51.274, 55.065), respectively. The pooled estimates of liver enzyme, ALT and AST, elevation were 219.905 with 95%CI (160.860, 278.949) and 315.679 with 95%CI (226.961, 404.397), respectively. Major complications were defined as acute kidney injury (AKI), pleural effusion, diaphragmatic hernia, and jaundice that needed to be treated, and the pooled incidence was 0.017 with 95% CI of (0.006, 0.029). No mortality related to MWA was reported. Meta-regression showed ablation time was associated with pre-operative lesion size (p = .001). CONCLUSION: MWA is effective and safe in treatment of hepatic hemangioma, and our study suggests that hemangioma size should be investigated in the future MWA pretreatment difficulty scoring system study.

Benralizumab for PDGFRA-Negative Hypereosinophilic Syndrome.

BACKGROUND: Hypereosinophilic syndrome is a group of diseases defined by marked eosinophilia in blood or tissue and eosinophil-related clinical manifestations. Benralizumab is a monoclonal antibody against interleukin-5 receptor α, which is expressed on human eosinophils. METHODS: In this randomized, double-blind, placebo-controlled, phase 2 trial, we administered a series of three monthly subcutaneous injections of either benralizumab (at a dose of 30 mg) or placebo in 20 symptomatic patients who had PDGFRA-negative hypereosinophilic syndrome and an absolute eosinophil count of at least 1000 cells per cubic millimeter; all the patients were receiving stable therapy (drugs or dietary changes) for this disease. This regimen was followed by an open-label phase, during which the patient's background therapy could be tapered as tolerated, and an extension phase. The primary end point of the randomized phase was a reduction of at least 50% in the absolute eosinophil count at week 12. RESULTS: During the randomized phase, the primary end point occurred in more patients in the benralizumab group than in the placebo group (9 of 10 patients [90%] vs. 3 of 10 patients [30%], P = 0.02). During the open-label phase, clinical and hematologic responses were observed in 17 of 19 patients (89%) and were sustained for 48 weeks in 14 of 19 patients (74%); in the latter group, in 9 of 14 patients (64%), background therapies could be tapered. Bone marrow and tissue eosinophilia were also suppressed with benralizumab therapy. The most common drug-related adverse events, headache and an elevated lactate dehydrogenase level, occurred in 32% of the patients after the first dose of benralizumab and resolved within 48 hours in all patients. Other adverse events occurred with similar frequency in the two groups. Of the many potential predictors of response that were examined, only clinical disease subtype appeared to be associated with the initial response or relapse. CONCLUSIONS: In this small phase 2 trial, patients with PDGFRA-negative hypereosinophilic syndrome who received benralizumab for 12 weeks had lower absolute eosinophil counts than those who received placebo. During the open-label phase, clinical and hematologic responses were sustained for 48 weeks in 74% of the patients. Adverse events did not limit treatment. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov numbers, NCT00001406 and NCT02130882.).

Trend in the incidence of hepatitis A in mainland China from 2004 to 2017: a joinpoint regression analysis.

BACKGROUND: China has experienced a continuous decreasing trend in the incidence of hepatitis A in recent years. Temporal trend analyses are helpful in exploring the reasons for the changing trend. Thus, this study aims to analyse the incidence trend of viral hepatitis A by region and age group in mainland China from 2004 to 2017 to evaluate the effectiveness of prevention and control measures. METHODS: Data on hepatitis A and population information were collected and analysed with a joinpoint regression model. Annual percentage changes (APCs) and average annual percentage changes (AAPCs) were estimated for the whole country and for each region and age group. RESULTS: From 2004 to 2017, the seasonality and periodicity of hepatitis A case numbers were obvious before 2008 but gradually diminished from 2008 to 2011 and disappeared from 2012-2017. The national incidence of hepatitis A (AAPC = - 12.1%) and the incidence rates for regions and age groups showed decreasing trends, with differences in the joinpoints and segments. Regarding regions, the hepatitis A incidence in the western region was always the highest among all regions, while a nonsignificant rebound was observed in the northeastern region from 2011 to 2017 (APC = 14.2%). Regarding age groups, the hepatitis A incidence showed the fastest decrease among children (AAPC = - 15.3%) and the slowest decrease among elderly individuals (AAPC = - 6.6%). Among all segments, the hepatitis A incidence among children had the largest APC value in 2007-2017, at - 20.4%. CONCLUSION: The national annual incidence of hepatitis A continually declined from 2004 to 2017 and the gaps in hepatitis A incidence rates across different regions and age groups were greatly narrowed. Comprehensive hepatitis A prevention and control strategies, including the use of routine vaccination during childhood in mainland China, especially the implementation of the national Expanded Program on Immunization (EPI) in 2008, resulted in substantial progress from 2004 to 2017. However, gaps remain. Regular monitoring and analysis of hepatitis A epidemic data and prompt adjustment of hepatitis A prevention and control strategies focusing on children, elderly individuals and those living in certain regions are recommended.

Responses to direct-to-consumer advertising in Australia: Comparing experience.

AbsractThis paper examines the potential effect of Direct-to-Consumer (DTC) advertising on consumers' behavioral intentions in relation to a medical issue. Using an online experiment, 1295 people were randomized to two information conditions. One group watched an advertisement for a hypothetical cold sore medicine, while a second (control) group did not view the advertisement, before both groups answered questions on symptoms. The responses were analyzed based on group allocation and the respondents' experience with cold sores. Results indicate that those who viewed the advertisement were more likely to choose the product, and the advertisement had larger effects based on consumer experience.

Biomimetic niches reveal the minimal cues to trigger apical lumen formation in single hepatocytes.

The symmetry breaking of protein distribution and cytoskeleton organization is an essential aspect for the development of apicobasal polarity. In embryonic cells this process is largely cell autonomous, while differentiated epithelial cells collectively polarize during epithelium formation. Here, we demonstrate that the de novo polarization of mature hepatocytes does not require the synchronized development of apical poles on neighbouring cells. De novo polarization at the single-cell level by mere contact with the extracellular matrix and immobilized cadherin defining a polarizing axis. The creation of these single-cell liver hemi-canaliculi allows unprecedented imaging resolution and control and over the lumenogenesis process. We show that the density and localization of cadherins along the initial cell-cell contact act as key triggers of the reorganization from lateral to apical actin cortex. The minimal cues necessary to trigger the polarization of hepatocytes enable them to develop asymmetric lumens with ectopic epithelial cells originating from the kidney, breast or colon.

Primary cardiac lymphoma: the management and outcome of a single-centre cohort of 22 patients.

BACKGROUND: The incidence of primary cardiac lymphoma (PCL) is increasing, but the optimal management approach remains unclear. We assessed the clinical characteristics of a single-centre cohort with the goal of determining the optimal management approach. The treatment outcomes and prognostic factors are reported. MATERIAL AND METHODS: All PCL patients were diagnosed via biopsy guided by whole-body imaging (positron emission tomography/computed tomography [PET/CT] and/or contrast-enhanced CT]. Curative therapy involved either surgery or prephase steroids followed by definitive immunochemotherapy, depending on the histological type. The primary outcomes were overall survival (OS) and progression-free survival (PFS); the secondary outcome was the treatment response. RESULTS: Twenty-two PCL patients (14 males, 8 females; age: 59.5 ± 14.7 years [mean ± S.D.]) were histologically confirmed to have diffuse large B-cell lymphoma (DLBCL; n = 17 [77.3%]), fibrin-associated DLBCL (FA-DLBCL) (n = 4 [18.2%]) and Burkitt lymphoma (n = 1 [4.5%]). Seven patients underwent cardiotomy (three for biopsy, four with curative intent). The median and longest follow-up periods were 16.3 and 180.0 months, respectively. The 16 patients who received curative therapy (complete response [CR], n = 15 [93.8%]; partial response [PR], n = 1 [6.2%]) showed better survival than those who did not (5-year OS: 83.0 ± 11.3% vs. 0%; hazard ratio [HR]: 0.025[95% confidence interval, CI: 0.003-0.187], p < 0.001); 5-year PFS: 78.7 ± 11.0% vs. 0%, HR= 0.010[0.001-0.093], p < 0.001). The left ventricular ejection fractions (LVEF) before and after definitive treatment was 63.6 ± 2.4% and 64.6 ± 4.5%, respectively (p = 0.275, power = 0.318). Extrapericardial lesions were associated with poorer survival (5-year OS: 40.0 ± 29.7% vs. 100%, p = 0.027; 5-year PFS:40.0 ± 21.9% vs. 100%, p = 0.010). CONCLUSIONS: Whole-body imaging is essential for diagnosis and prognosis. Curative therapy provided reasonable outcomes and survival; extrapericardial lesions were associated with a poorer treatment response.

Efficacy of exercise-based interventions in preventing falls among community-dwelling older persons with cognitive impairment: is there enough evidence? An updated systematic review and meta-analysis.

OBJECTIVE: Exercise prevents falls in the general older population, but evidence is inconclusive for older adults living with cognitive impairment. We performed an updated systematic review and meta-analysis to assess the potential effectiveness of interventions for reducing falls in older persons with cognitive impairment. METHODS: PubMed, EMBASE, CINAHL, Scopus, CENTRAL and PEDro were searched from inception to 10 November 2020. We included randomised controlled trials (RCTs) that evaluated the effects of physical training compared to a control condition (usual care, waitlist, education, placebo control) on reducing falls among community-dwelling older adults with cognitive impairment (i.e. any stage of Alzheimer's disease and related dementias, mild cognitive impairment). RESULTS: We identified and meta-analysed nine studies, published between 2013 and 2020, that included 12 comparisons (N = 1,411; mean age = 78 years; 56% women). Overall, in comparison to control, interventions produced a statistically significant reduction of approximately 30% in the rate of falls (incidence rate ratio = 0.70; 95% CI, 0.52-0.95). There was significant between-trial heterogeneity (I2 = 74%), with most trials (n = 6 studies [eight comparisons]) showing no reductions on fall rates. Subgroup analyses showed no differences in the fall rates by trial-level characteristics. Exercise-based interventions had no impact on reducing the number of fallers (relative risk = 1.01; 95% CI, 0.90-1.14). Concerns about risk of bias in these RCTs were noted, and the quality of evidence was rated as low. CONCLUSIONS: The positive statistical findings on reducing fall rate in this meta-analysis were driven by a few studies. Therefore, current evidence is insufficient to inform evidence-based recommendations or treatment decisions for clinical practice.PROSPERO Registration number: CRD42020202094.

Discrepancies between proxy estimates and patient reported, health related, quality of life: minding the gap between patient and clinician perceptions in heart failure.

PURPOSE: Health related quality of life (HRQoL) is rarely routinely measured in the clinical setting. In the absence of patient reported data, clinicians rely on proxy and informal estimates to support clinical decisions. This study compares clinician estimates (proxy) with patient reported HRQoL in patients with advanced heart failure and examines factors influencing discrepancies. METHODS: Seventy-five patients with heart failure, (22 females, 53 males) completed the EQ-5D-5L questionnaire. Thirty-nine clinicians (11 medical, 23 nursing, 5 allied health) completed the proxy version (V1) producing 194 dyads. Correlation was assessed using Spearman's rank tests, systematic bias was examined with Bland-Altman analyses. Inter-rater agreement at the domain level, was investigated using linear weighted Kappa statistics while factors influencing the IRG were explored using independent student t-tests, analysis of variance and regression. RESULTS: There was a moderate positive correlation between clinician HRQoL estimates and patient reported utility (r = 0.38; p < .0005). Mean clinician estimates were higher than patient reported utility (0.60 vs 0.54; p = 0.008), with significant underestimation of reported problems apparent in three of the five EQ-5D-5L domains. Patient sex (female), depressed mood and frailty were all associated with an increased inter-rater gap. CONCLUSION: Clinicians in this sample overestimated HRQoL. Factors affecting the inter-rater gap, including sex and depression, support formal HRQoL screening to enhance clinical conversations and decision making. The discrepancy also supports regulatory restriction on the use of expert opinion in the development of QALYs in health economic analysis.

COVID-19 vaccine-related presumed allergic reactions and second dose administration by using a two-step graded protocol.

Background: Acute allergic reactions to messenger RNA (mRNA) vaccines are rare but may limit public health immunization efforts. Objectives: To characterize suspected allergic reactions to the first dose of coronavirus disease 2019 (COVID-19) mRNA vaccine and to assess the safety and utility of a two-step graded-dose protocol for the second dose of the Pfizer-BioNTech vaccine in patients with a history of low suspicion of anaphylaxis to their first dose. Methods: This was a retrospective evaluation of referrals to the allergy and immunology clinic for a presumed allergic reaction to the first dose of the COVID-19 mRNA vaccine (Pfizer-BioNTech or Moderna) between December 17, 2020, and February 28, 2021. Recommendations for the second dose and outcomes were evaluated by trained board-certified allergists. Results: Seventy-seven patients presented with a Pfizer-BioNTech reaction (56 [72.7%]) or with a Moderna reaction (21 [27.3%]). Most patients (69.7%) had symptom onset within 4 hours. Most commonly reported symptoms were cutaneous (51.9%), cardiovascular (48.1%), and respiratory (33.8%) symptoms. Recommendations included to proceed with the single dose (70.1%), two-step graded dose (19.5%), or deferral (10.4%). Twelve of 15 patients completed the second dose with a graded-dose protocol. Of these patients, five reported at least one or more similar symptoms as experienced with their first dose. Conclusion: Of the patients with presumed allergic reactions to their first dose of COVID-19 mRNA vaccine, most were able to safely receive the second dose. For those with a low suspicion of anaphylaxis, the two-step graded protocol with the Pfizer-BioNTech vaccine was well tolerated. A graded-dose protocol could be an effective strategy for second-dose vaccination in those who may otherwise defer the second dose.

Prevalence and characterization of asthma in hospitalized and nonhospitalized patients with COVID-19.

BACKGROUND: The Centers for Disease Control and Prevention advises that patients with moderate to severe asthma belong to a high-risk group that is susceptible to severe coronavirus disease 2019 (COVID-19). However, the association between asthma and COVID-19 has not been well-established. OBJECTIVE: The primary objective was to determine the prevalence of asthma among patients with COVID-19 in a major US health system. We assessed the clinical characteristics and comorbidities in asthmatic and nonasthmatic patients with COVID-19. We also determined the risk of hospitalization associated with asthma and/or inhaled corticosteroid use. METHODS: Medical records of patients with COVID-19 were searched by a computer algorithm (March 1 to April 15, 2020), and chart review was used to validate the diagnosis of asthma and medications prescribed for asthma. All patients had PCR-confirmed COVID-19. Demographic and clinical features were characterized. Regression models were used to assess the associations between asthma and corticosteroid use and the risk of COVID-19-related hospitalization. RESULTS: Of 1526 patients identified with COVID-19, 220 (14%) were classified as having asthma. Asthma was not associated with an increased risk of hospitalization (relative risk, 0.96; 95% CI, 0.77-1.19) after adjusting for age, sex, and comorbidities. The ongoing use of inhaled corticosteroids did not increase the risk of hospitalization in a similar adjusted model (relative risk, 1.39; 95% CI, 0.90-2.15). CONCLUSIONS: Despite a substantial prevalence of asthma in our COVID-19 cohort, asthma was not associated with an increased risk of hospitalization. Similarly, the use of inhaled corticosteroids with or without systemic corticosteroids was not associated with COVID-19-related hospitalization.

Pivalopril improves anti-cancer efficiency of cDDP in breast cancer through inhibiting proliferation, angiogenesis and metastasis.

Breast cancer is the most common cancer type among female worldwide. Cisplatin (cDDP) is one of the most effective chemotherapies for the treatment of breast cancer. Nevertheless, there is an urgent requirement to reduce its systemic side effects and chemoresistance. In this present study, pivalopril (PP), a clinically used antihypertensive drug, has been verified as a chemosensitizer that extremely improves the sensitivity of breast cancer cells to cDDP. PP treatment markedly promoted the capacity of cDDP to reduce the proliferation of breast cancer cells. The combination of PP and cDDP significantly induced apoptosis and inhibited vascular endothelial growth factor (VEGF) expression in breast cancer cells, accompanied with reduced angiogenesis. Furthermore, PP plus cDDP effectively reduced the cell migration and invasion in breast cancer cells. The in vivo studies confirmed that the anti-metastatic effect of cDDP was further improved by PP, as evidenced by the markedly decreased number of metastatic nodules in lungs. Moreover, we confirmed that PP combined with cDDP cooperatively suppressed tumor growth in breast cancer xenograft mouse models without extra toxicity. Together, the present study provided the first evidence that PP greatly sensitized breast cancer cells to cDDP without additional toxicity, and the synergistic effect may be mainly through cooperatively inhibiting proliferation, angiogenesis, metastasis, and inducing apoptotic cell death.