Subsequent Exacerbation Research Articles

Fulminant myocarditis associated with human rhinovirus A66 infection: a case report

BackgroundHuman rhinoviruses (HRVs) are among the most common pathogens of upper respiratory infections, and they are responsible for the common cold. An increasing number of studies have shown that HRV is associated with more severe illness. However, HRV-associated fulminant myocarditis has rarely been reported.Patient presentationA previously healthy 8-year-old boy developed fever, fatigue, and vomiting for 3 days, with a subsequent exacerbation accompanied by confusion lasting for 9 h. The day before admission, the patient presented with oliguria, confusion, and hypotension, and he was suspected of having myocarditis. The patient was transferred to our hospital for further diagnosis and treatment. On admission, rough and moist rales were detected, and the heart sounds were muffled, accompanied by an irregular heart rhythm and a gallop. An electrocardiogram (EKG) revealed a wide QRS complex, ST-segment depression, premature ventricular contractions, and complete right bundle branch block. Laboratory tests revealed that brain natriuretic peptide (BNP), N-terminal pro BNP (NT-pro BNP), and cardiac biomarkers, such as troponin I, creatinine kinase (CK), and creatinine kinase-MB (CK-MB) were elevated. Additionally, echocardiography revealed an ejection fraction of approximately 28%. The child developed severe cardiac dysfunction and tissue hypoperfusion, and the cardiogenic shock could not be corrected despite active drug therapy. He had indications for ECMO implantation. A rarely reported rhinovirus, namely, A66, was detected in his bronchoalveolar lavage fluid and oropharyngeal swabs via metagenomic next-generation sequencing and a PCR assay. Bacterial culture of all the samples yielded negative results.ConclusionsThis case presents a patient with severe human rhinovirus A66 infection, which is likely responsible for fulminant myocarditis. This report facilitates prompt diagnosis and treatment of fulminant myocarditis. Clinicians should consider rhinovirus as a possible pathogen of fulminant myocarditis, especially when patients present with symptoms or signs of heart involvement.

Pain resilience dimensions and regional gray matter volume as risk factors for poor outcomes of chronic pain: a prospective cohort study.

Pain resilience and regional gray matter volume (rGMV) are established correlates of adaptation to chronic pain within cross-sectional studies. Extending such work, this prospective cohort study tested the status of baseline pain resilience dimension scores and rGMV as risk factors for subsequent exacerbations in chronic pain disability and intensity. 142 adults with chronic musculoskeletal pain completed an initial assessment comprising a structural magnetic resonance imaging scan and self-report measures of cognitive/affective positivity and behavioral perseverance pain resilience dimensions, disability, pain intensity, and demographics. Disability and pain intensity were outcomes re-assessed at a 6-month follow-up. The impact of pain resilience dimension scores and identified rGMV sites on follow-up outcomes was examined after controlling for other baseline correlates of outcomes. Mediating effects of identified rGMV sites on pain resilience dimension-follow-up outcome relations were also evaluated. Aside from the significant multivariate effect of lower behavioral perseverance and cognitive/affective positivity scores, augmented left precuneus, temporal pole, superior temporal gyrus (STG), and precentral gyrus rGMV combined to predict higher follow-up disability levels, independent of covariates. Higher left fusiform gyrus rGMV levels predicted follow-up exacerbations in pain intensity, but pain resilience dimension scores did not. Finally, left precuneus and left temporal pole STG rGMV partially mediated cognitive/affective positivity-follow-up disability relations. Findings underscore deficits in pain resilience and increased rGMV as potential risk factors for poorer subsequent outcomes of chronic musculoskeletal pain and provide foundations for further prospective extensions as well as targeted intervention research.

Impairment of neuronal tyrosine phosphatase STEP worsens post-ischemic inflammation and brain injury under hypertensive condition

Hypertension is associated with poor outcome and higher mortality in patients with ischemic stroke. The impairment of adaptive vascular mechanisms under hypertensive condition compromises collateral blood flow after arterial occlusion in patients with acute ischemic stroke resulting in hypoperfusion. The increased oxidative stress caused by hypoperfusion is thought to be a trigger for the rapid evolution of ischemic infarct volume under hypertensive condition. However, the cellular factors and pathways that contribute to the exacerbation of ischemic brain injury under hypertensive condition is not yet understood. The current study reveals that predisposition to hypertension leads to basal loss of function of the neuron-specific tyrosine phosphatase STEP, which plays a crucial role in neuroprotection against excitotoxic insult. The findings further show that a mild ischemic insult in hypertensive rats triggers an early onset and sustained activation of the neuronal extracellular signal regulated kinase (ERK MAPK), a member of the mitogen activated protein kinase family and a substrate of STEP. This leads to rapid increase in the activation of neuronal NF-κB, expression of neuronal cyclooxygenase-2 and subsequent biosynthesis of the pro-inflammatory mediator prostaglandin E2, resulting in rapid morphological transformation of microglia to the pro-inflammatory state and subsequent exacerbation of ischemic brain injury. Restoration of STEP signaling with intravenous administration of a STEP-derived peptide mimetic reduces the pro-inflammatory response in neurons, activation of microglia, and ischemic brain injury. The findings suggest that the basal loss of STEP function under hypertensive condition contributes to the exacerbation of ischemic brain injury by enhancing post-ischemic inflammatory response. The study not only presents a novel role of STEP in regulating neuroimmune communication but also highlights the therapeutic potential of a STEP-mimetic in mitigating ischemic brain damage under hypertensive condition.

Psychotic experiences and psychological distress in adolescents: an examination of longitudinal bidirectional effects across sex

BackgroundAlthough the co-occurrence of psychotic experiences (PEs) and psychological distress symptoms is growingly recognized in several previous studies, there is still a lack of literature, which clearly outlines how these two psychopathological entities affect each other over time. This study is intended to add to the literature by examining: (a) the longitudinal, bidirectional associations between PEs and psychological distress in a sample of Tunisian adolescents, and (b) whether these associations are moderated by sex.Methods510 adolescent students (mean age of 16.05 ± 1.01 years, 61.2% females) took part in a prospective longitudinal study. PEs and psychological distress were measured at three occasions over a one-year period. The cross-lagged panel modeling approach was adopted.ResultsThe current results showed that the experience of PEs at baseline tended to temporally precede prospective increases in psychological distress (at 6 months), which had in turn led to further exacerbation of psychological distress at 12 months of follow-up. Temporally primary psychological distress symptoms were not a significant predictor for the development of later psychotic symptoms in the whole sample. However, temporal patterns between adolescent distress and psychotic symptoms differed for girls and boys. Endorsing PEs at baseline was followed by greater psychological distress at 6 months, which was in turn associated with a significant increased risk of subsequent exacerbation of PEs at 12 months in boys, whereas psychological distress at 12-month follow-up was significantly predicted by pre-existing PEs in girls.ConclusionThese findings suggest that clinicians and support workers are recommended to take into account different social risk profiles for boys and girls when considering interventions to address PEs and distress in adolescents.

Exacerbation history and blood eosinophil count prior to diagnosis of COPD and risk of subsequent exacerbations.

Prior exacerbation history is used to guide initial maintenance therapy in COPD; however, the recommendations were derived from patients already diagnosed and treated. We assessed the rates of moderate (i.e. treated with antibiotics and/or systemic corticosteroids) and severe (i.e. hospitalised) exacerbations in the year following diagnosis in patients newly diagnosed with COPD according to their prior history of exacerbations, blood eosinophil count (BEC) and whether maintenance therapy was started. Data were extracted from the Optimum Patient Care Research Database. 73 189 patients were included. 61.9% had no exacerbations prior to diagnosis, 21.5% had 1 moderate, 16.5% had ≥2 moderate and 0.3% had ≥1 severe. 50% were started on maintenance therapy. In patients not started on maintenance therapy the rates of moderate exacerbations in the year after diagnosis in patients with no, 1 moderate, ≥2 moderate and ≥1 severe prior exacerbations were 0.34 (95% CI 0.33-0.35), 0.59 (95% CI 0.56-0.61), 1.18 (95% CI 1.14-1.23) and 1.21 (95% CI 0.73-1.69), respectively. Similar results were seen in patients started on maintenance therapy. BEC did not add significantly to the prediction of future exacerbation risk. A single moderate exacerbation in the year prior to diagnosis increases the risk of subsequent exacerbations, and more frequent or severe exacerbations prior to diagnosis are associated with a higher risk.

Porphyria in pregnancy with exacerbation after delivery due to COVID-19

We present a case of acute intermittent porphyria (AIP) diagnosed in a pregnant woman with subsequent exacerbation after delivery due to COVID-19 infection. The patient’s symptoms manifested with acute neurovisceral attacks - abdominal pain followed by flaccid quadriparesis, sensory disturbances, hypertension and disturbance in electrolyte levels. The blood plasma test and a 24-hour urine collection revealed increased levels of urine porphobilinogen, 5-aminolevulinic acid and uroporphyrins, which led to the diagnosis of AIP. The patient received i.v. human hemin with positive outcome. After delivery she was again admitted to the hospital due to abdominal pain and trunk hyperesthesia that occurred after a mild course of COVID-19 infection. The second administration of human hemin led to the improvement of the patient's condition. The aim of this case report is to indicate that even with severe risk factors of AIP such as infection and pregnancy, proper diagnostics can increase the chance of quick recovery.

The Balance N1 Is Larger in Children With Anxiety and Associated With the Error-Related Negativity

BackgroundThe error-related negativity (ERN) is a brain response evoked by mistakes on cognitive tasks that is enhanced with anxiety and can predict the subsequent onset or exacerbation of anxiety in children and adolescents. A physical disturbance to standing balance evokes a brain response called the balance N1 that resembles the ERN in scalp topography and in response to a variety of moderating factors. We recently found that the balance N1 and ERN correlate in amplitude across small adult samples. MethodsIn the current study, we tested the effect of anxiety on the balance N1 in children (ages 9–12 years) with and without diagnosed anxiety disorders (38 children with generalized anxiety, social anxiety, and/or obsessive-compulsive disorder and 50 children without these disorders). We measured the balance N1 in response to sudden release of support from a forward leaning posture, the ERN in response to mistakes on a Go/NoGo task, and anxiety symptoms using child- and parent-report forms of the Screen for Child Anxiety and Related Emotional Disorders. ResultsBoth the balance N1 and the ERN were larger in the anxious group. The balance N1 was also associated with both the ERN and parent report of child anxiety symptom severity across individuals. ConclusionsThe higher measurement reliability of the balance N1 than the ERN and greater experimental control over errors suggest that balance paradigms may provide a more powerful method for investigating individual differences in error-related brain activity related to anxiety.

COPD Subtypes Are Differentially Associated With Cardiovascular Events and COPD Exacerbations

The coronary artery calcium score (CACS) and ratio of the pulmonary artery to aorta diameters (PA:A ratio) measured from chest CT scans have been established as predictors of cardiovascular events and COPD exacerbations, respectively. However, little is known about the reciprocal relationship between these predictors and outcomes. Furthermore, the prognostic implications of COPD subtypes on clinical outcomes remain insufficiently characterized. How can these two chest CT scan-derived parameters predict subsequent cardiovascular events and COPD exacerbations in different COPD subtypes? Using COPDGene study data, we assessed prospective cardiovascular disease (CVD) and COPD exacerbation risk in patients with COPD (Global Initiative for Chronic Obstructive Lung Disease spirometric grades 2-4), focusing on CACS and PA:A ratio at study enrollment, with logistic regression models. These outcomes were analyzed in three COPD subtypes: 1,042 patients with non-emphysema-predominant disease (NEPD) (low attenuation area at-950 Hounsfield units [LAA-950]< 5%), 1,324 patients with emphysema-predominant disease (EPD) (LAA-950≥ 10%), and 465 patients with intermediate emphysema disease (5%≤ LAA-950< 10%). Our study indicated significantly higher overall risk for cardiovascular events in patients with higher CACS (≥ median; OR, 1.61; 95%CI, 1.30-2.00) and increased COPD exacerbations in those with higher PA:A ratios (≥ 1; OR, 1.80; 95%CI, 1.46-2.23). Notably, patients with NEPD showed a stronger association between these indicators and clinical events than those with EPD (with CACS/CVD, NEPD vsEPD: OR, 2.02 vs1.41; with PA:A ratio/COPD exacerbation, NEPD vsEPD: OR, 2.50 vs1.65); the difference in ORs between COPD subtypes was statistically significant for CACS/CVD. Two chest CT scan parameters, CACS and PA:A ratio, hold distinct predictive values for cardiovascular events and COPD exacerbations that are influenced by specific COPD subtypes. ClinicalTrials.gov; No.: NCT00608764; URL: www. gov.

Age-related effects of Mycoplasma pneumoniae infection and subsequent asthma exacerbation in children.

Mycoplasma pneumoniae causes community-acquired pneumonia in children and increases asthma risk, but large studies are lacking. To assess the link between M. pneumoniae infection and to asthma exacerbation, in children with allergies, and age of infection impact. This retrospective cohort study analyzed medical records of South Korean children between January 2002 and December 2017. The study's exposure was hospitalization with an M. pneumoniae-related diagnosis, and the outcome was defined as asthma exacerbation, confirmed by hospitalization at least 6 months after M. pneumoniae infection, with alternative validation using asthma diagnosis and systemic steroid prescription records. Hazard ratios (HRs) for asthma exacerbation risk were estimated for the matched cohort using a Cox proportional hazards model stratified by allergic comorbidities. Time-dependent covariates and age-stratified exposure groups were used to calculate odds ratios. The study included 84,074 children with M. pneumoniae infection and 336,296 unexposed children. Follow-up for 12.2 ± 2.3 years found the exposed group had a significant risk of asthma exacerbation (HR 2.86, 95% confidence interval [CI] 2.67-3.06) regardless of allergic comorbidities. The risk was highest (over threefold) in children infected between 24 and 71 months. Sensitivity analysis using an alternative definition of the outcome showed an HR of 1.38 (95% CI 1.35-1.42), further supporting the association between M. pneumoniae infection and asthma exacerbation. M. pneumoniae infection was significantly associated with an increased risk of subsequent asthma exacerbation regardless of allergic comorbidities. Further research needed for understanding and confirmation.

Autophagy-deficient macrophages exacerbate cisplatin-induced mitochondrial dysfunction and kidney injury via miR-195a-5p-SIRT3 axis

Macrophages (Mφ) autophagy is a pivotal contributor to inflammation-related diseases. However, the mechanistic details of its direct role in acute kidney injury (AKI) were unclear. Here, we show that Mφ promote AKI progression via crosstalk with tubular epithelial cells (TECs), and autophagy of Mφ was activated and then inhibited in cisplatin-induced AKI mice. Mφ-specific depletion of ATG7 (Atg7Δmye) aggravated kidney injury in AKI mice, which was associated with tubulointerstitial inflammation. Moreover, Mφ-derived exosomes from Atg7Δmye mice impaired TEC mitochondria in vitro, which may be attributable to miR-195a-5p enrichment in exosomes and its interaction with SIRT3 in TECs. Consistently, either miR-195a-5p inhibition or SIRT3 overexpression improved mitochondrial bioenergetics and renal function in vivo. Finally, adoptive transfer of Mφ from AKI mice to Mφ-depleted mice promotes the kidney injury response to cisplatin, which is alleviated when Mφ autophagy is activated with trehalose. We conclude that exosomal miR-195a-5p mediate the communication between autophagy-deficient Mφ and TECs, leading to impaired mitochondrial biogenetic in TECs and subsequent exacerbation of kidney injury in AKI mice via miR-195a-5p-SIRT3 axis.

A randomised trial of oral prednisone for cystic fibrosis pulmonary exacerbation treatment.

Elevated markers of systemic and pulmonary inflammation are associated with failure to recover lung function following pulmonary exacerbations in people with cystic fibrosis (pwCF). Our aim was to determine whether adjuvant oral prednisone treatment would improve recovery of forced expiratory volume in 1 s (FEV1) % pred in CF pulmonary exacerbations not responding to antibiotic therapy. This was a randomised, double-blind, placebo-controlled trial in pwCF treated with intravenous antibiotics for a pulmonary exacerbation. At day 7, those who had not returned to >90% baseline FEV1 % pred were randomised to adjuvant prednisone 1 mg·kg-1 twice daily (maximum 60 mg·day-1) or placebo for 7 days. The primary outcome was the difference in proportion of subjects who recovered >90% baseline FEV1 % pred at day 14 of i.v. antibiotic therapy. 173 subjects were enrolled, with 76 randomised. 50% of subjects in the prednisone group recovered baseline FEV1 on day 14 compared with 39% of subjects in the placebo group (difference of 11%, 95% CI -11-34%; p=0.34). The mean±sd change in FEV1 % pred from day 7 to day 14 was 6.8±8.8% predicted in the prednisone group and 4.6±6.9% predicted in the placebo group (mean difference 2.2% predicted, 95% CI -1.5-5.9%; p=0.24). Time to subsequent exacerbation was not prolonged in prednisone-treated subjects (hazard ratio 0.83, 95% CI 0.45-1.53; p=0.54). This study failed to detect a difference in FEV1 % pred recovery between adjuvant oral prednisone and placebo treatment in pwCF not responding at day 7 of i.v. antibiotic therapy for pulmonary exacerbations.

Association between blood procollagen III N-terminal propeptide, granulocyte-macrophage colony-stimulating factor and triple therapy in single inhaler efficacy for chronic obstructive pulmonary disease re-exacerbation prevention

Triple therapy with inhaled corticosteroid (ISC) / long-acting β2 agonist (LABA) / long-acting muscarinic antagonist (LAMA) in single inhaler expanded the possibilities for prevention of chronic obstructive pulmonary disease (COPD) exacerbations. Heterogeneity of COPD determines the needs in search of target population and efficacy markers for each existing therapy. Disease phenotype depends on a complex of factors, with respiratory viral infection among the most significant. Aim of the study was to assess the efficacy of triple therapy with ICS/LABA/LAMA in single inhaler for subsequent COPD exacerbations prevention and to search molecular markers of the efficacy depending the etiology of index exacerbation. Material and methods. It was a prospective observational study of three COPD patients’ strata: after COPD exacerbation required hospitalization with viral (n = 60), bacterial (n = 60) and viral-bacterial (n = 60) infection. Triple therapy in single inhaler (n = 104) or in free combinations (n = 76) were prescribed in real clinical practice. COPD was diagnosed according to spirography criteria. To establish the COPD exacerbation etiology the real time PCR of sputum or bronchoalveolar lavage fluid, standard cultural method, blood procalcitonin, as well as marker blood proteins, hyaluronic acid by ELISA measurement were done. Associations were revealed using Cox regression. Results. Triple therapy in single inhaler in comparison with free combinations decreased time to first re-exacerbation, hazard ratio (HR) in viral-associated index exacerbation strata was 0.38 (95% confidence interval (95% CI) 1.15–0.40), in bacterial – 0.47 (0.39–0.72), in viral-bacterial – 0.39 (0.14–0.39). In strata of COPD patients after viral and viral-bacterial exacerbations, in subgroups treated with triple therapy in single inhaler blood procollagen III N-terminal propeptide (PIIINP) (HR for group after viral index exacerbations was 1.03, 95 % CI 1.02–1.28, HR for group after viral-bacterial exacerbations was 1.04, 95 % CI 1.02–1.28), granulocyte-macrophage colony-stimulating factor (GM-CSF) (HR 1.03, 95 % CI 1.02–1.32, 1.01, 95 % CI 1.00–1.35, respectively) content was associated with time of re-exacerbations. Conclusions. Blood PIIINP and GM-CSF during COPD exacerbation are perspective markers of subsequent exacerbations within 1 year in patients after virus-associated or viral-bacterial index exacerbation. In these groups of patients triple therapy in single inhaler is more effective than free combination for subsequent exacerbations prevention.

Implications of Cardiopulmonary Risk for the Management of COPD: A Narrative Review.

Chronic obstructive pulmonary disease (COPD) constitutes a major global health burden and is the third leading cause of death worldwide. A high proportion of patients with COPD have cardiovascular disease, but there is also evidence that COPD is a risk factor for adverse outcomes in cardiovascular disease. Patients with COPD frequently die of respiratory and cardiovascular causes, yet the identification and management of cardiopulmonary risk remain suboptimal owing to limited awareness and clinical intervention. Acute exacerbations punctuate the progression of COPD in many patients, reducing lung function and increasing the risk of subsequent exacerbations and cardiovascular events that may lead to early death. This narrative review defines and summarises the principles of COPD-associated cardiopulmonary risk, and examines respiratory interventions currently available to modify this risk, as well as providing expert opinion on future approaches to addressing cardiopulmonary risk.

Association of device detected atrial and ventricular tachyarrhythmia with adverse events in patients with an implantable cardioverter-defibrillator.

Heart failure patients with a history of atrial fibrillation (AF) and ventricular tachycardia/ventricular fibrillation (VT/VF) are known to have worse outcomes. However, there are limited data on the temporal relationship between development of these arrhythmias and the risk of subsequent congestive heart failure (CHF) exacerbation and death. The study cohort comprised 5511 patients implanted with an implantable cardioverter-defibrillator (ICD) in landmark clinical trials (MADIT-II, MADIT-RISK, MADIT-CRT, MADIT-RIT, and RAID) who were in sinus rhythm at enrollment. Multivariate cox analysis was performed to evaluate the time-dependent association between development of in-trial device detected AF and VT/VF with subsequent CHF exacerbation and death. Multivariate analysis showed that AF occurrence and VT/VF occurrence were both associated with a similar magnitude of risk for subsequent CHF exacerbation (HR = 1.73 and 1.87 respectively, p < .001 for both). In contrast, only in-trial VT/VF was associated with a significant > two-fold increase in the risk of subsequent mortality (HR = 2.13, p < .001) whereas AF occurrence was not associated with a significant mortality increase after adjustment for in-trial VT/VF (HR = 1.36, p = .096). Our findings from a large cohort of ICD recipients enrolled in landmark clinical trials show that device detected AF and VT/VF can be used to identify patients with increased risk for CHF exacerbation and mortality. These findings suggest a need for early intervention in CHF patients who develop device-detected atrial and ventricular tachyarrhythmias.

The role of long-acting antipsychotics in illness relapse: an observational study

IntroductionIn patients affected by Schizophrenia and Bipolar Disorder disorders the use of antipsychotic drugs is essential in preventing the exacerbation of symptoms. The use of long-acting injectable (LAI) antipsychotics is considered an important treatment option. The aim of this study was to evaluate the incidence and predictors of relapse during antipsychotic treatment with LAIs in a sample of psychiatric outpatients up to a year after the start of long-acting therapy.ObjectivesThe study included 103 adult patients admitted to the psychiatric unit of Sant’Andrea University Hospital in Rome.MethodsWe evaluated duration of untreated illness, previous treatments, substance abuse, suicidal status, LAI dose, and use of other medicines for association with new episodes of illness or of symptomatic worsening as well as hospitalization, using bivariate and multivariate analyses.Results Seventy-three patients were diagnosed with schizophrenia spectrum and 30 with bipolar disorders. Age at study entry averaged 36.7 years (SD= 11.55). 40.8% of patients were women. The mean age at onset were 23.11 (SD= 7.0). All the other information were reported in Table 1. On 103 patients undergoing with LAI treatment for a year only 9 (8.7%) patients had a relapse during the study period. The two groups differed according to the presence of hospitalization during the 12 months before the LAI treatment (p = .022), in particular patients with relapse were more hospitalized than patients with no relapse (62.5% vs. 21.7%). Moreover, group with relapse were more at risk of suicide during the 12 months before the LAI treatment than the other group, for both suicidal ideation (11.1% vs. 4.3%; p= .015) and attempt (25.0% vs. 3.2%; p= .049). Finally, the two groups differed according to the side effects reported during the year of LAI treatment (χ² =38.48; p&lt; .001). Specifically, patients’ group with relapse reported more side effects caused by parkinsonism (25.0% vs. 1.1%) and tremor (25.0% vs. 0%). No differences were found for the other variables (See table 1).Image:ConclusionsIn conclusion, our observations confirm the importance of LAI therapy in real word. However, our results indicate that these drugs might not prevent subsequent exacerbations for a proportion of individuals whose illness is stabilised on continuous antipsychotic treatment. Extra pyramidal symptoms in particular might have pathophysiological implications for relapse.Disclosure of InterestNone Declared

Gaps in Care Among Uncontrolled Severe Asthma Patients in the United States

Understanding the implementation of key guideline recommendations is critical for managing severe asthma (SA) in the treatment of uncontrolled disease. To assess specialist visits and medication escalation in US patients with SA after events indicating uncontrolled disease (EUD) and associations with health outcomes and social disparity indicators. Patients with SA appearing in administrative claims data spanning 2015 to 2020 were indexed hierarchically on asthma-related EUD, including hospitalizations, emergency department visits with systemic corticosteroid treatment, or outpatient visits with systemic corticosteroid treatment. Patients with SA without EUD served as controls. Eligibility included age 12 or greater, 12 months enrollment before and after index, no biologic use, and no other major respiratory disease during the pre-period. Escalation of care in the form of specialist visits and medication escalation, health care resource use, costs, and disease exacerbations were assessed during follow-up. We identified 180,736 patients with SA (90,368 uncontrolled and 90,368 controls). Between 35% and 51% of patients with SA with an EUD had no specialist visit or medication escalation. Follow-up exacerbations ranged from 51% to 4% across EUD cohorts, compared with 13% in controls. Among uncontrolled patients with SA who were Black or Hispanic/Latino, 41% and 38%, respectively, had no specialist visit or medication escalation after EUD, compared with 33% of non-Hispanic White patients. A substantial proportion of uncontrolled patients with SA had no evidence of specialist visits or medication escalation after uncontrolled disease, and there was a clear relationship between uncontrolled disease and subsequent health care resource use and exacerbations. Findings highlight the need for improved guideline-based care delivery to patients with SA, particularly for those facing social disparities.

Relationship between exacerbating patellofemoral pain and dynamic knee valgus in females with patellofemoral pain after a patellofemoral joint loading protocol: A cross-sectional

ObjectiveThe aim of the present study is to 1) the effect of exacerbating patellofemoral pain (PFP) on dynamic knee valgus (DKV) 2) the relationship between exacerbating PFP and DKV in females with patellofemoral pain. DesignCross-sectional study. MethodsSixty women with PFP were recruited from the orthopedic clinics. We evaluated pain intensity and DKV in two conditions without (condition 1) and with (condition 2) PFJ loading during the single-leg squat (SLS) task. The MANOVA test was used to compare pain intensity and DKV angle between the two conditions. Furthermore, the Pearson correlation was used to examine the correlation between pain intensity with DKV angle. ResultsThe MANOVA analysis showed that pain intensity (P < 0.000, η2 = 0.623) and DKV angle (P < 0.000, η2 = 0.544) with a medium effect size significantly increased after PFJ loading. Furthermore, an excellent positive correlation was observed between an increase in pain intensity and DKV angle (P < 0.000, r = 0.840). ConclusionIt seems that after the PFJ loading protocol and the subsequent pain exacerbation, the neuromuscular biomechanics of the lower limb are deficits. As a result, the stabilizing muscles activation decreases and increases the lower limb movement in the frontal plane.

Risk of Death and Cardiovascular Events Following an Exacerbation of COPD: The EXACOS-CV US Study.

This study estimated the magnitude and duration of risk of cardiovascular events and mortality following acute exacerbations of chronic obstructive pulmonary disease (AECOPD), and whether risks varied by number and severity of exacerbation in a commercially insured population in the United States. This was a retrospective cohort study of newly diagnosed COPD patients ≥40 years old in the Healthcare Integrated Research Database from 2012 to 2019. Patients experiencing exacerbations comprised the "exacerbation cohort". Moderate exacerbations were outpatient visits with contemporaneous antibiotic or glucocorticoid administration; severe exacerbations were emergency department visits or hospitalizations for AECOPD. Follow-up started on the exacerbation date. Distribution of time between diagnosis and first exacerbation was used to assign index dates to the "unexposed" cohort. Cox proportional hazards models estimated risks of a cardiovascular event or death following an exacerbation adjusted for medical and prescription history and stratified by follow-up time, type of cardiovascular event, exacerbation severity, and rank of exacerbation (first, second, or third). Among 435,925 patients, 170,236 experienced ≥1 exacerbation. Risk of death was increased for 2 years following an exacerbation and was highest during the first 30 days (any exacerbation hazard ratio (HR)=1.79, 95% CI=1.58-2.04; moderate HR=1.22, 95% CI=1.04-1.43; severe HR=5.09, 95% CI=4.30-6.03). Risks of cardiovascular events were increased for 1 year following an AECOPD and highest in the first 30-days (any exacerbation HR=1.34, 95% CI=1.23-1.46; moderate HR=1.23 (95% CI 1.12-1.35); severe HR=1.93 (95% CI=1.67-2.22)). Each subsequent AECOPD was associated with incrementally higher rates of both death and cardiovascular events. Risk of death and cardiovascular events was greatest in the first 30 days and rose with subsequent exacerbations. Risks were elevated for 1-2 years following moderate and severe exacerbations, highlighting a sustained increased cardiopulmonary risk associated with exacerbations.

Real World Practices of Thrombopoietin Receptor Agonist Use and Discontinuation in Pediatric Patients with Immune Thrombocytopenia (ITP): A Single Center Retrospective Review

Introduction Thrombopoietin Receptor Agonists (TPO-RAs) are becoming widely used as second-line treatment in patients with immune thrombocytopenia (ITP). These can be weaned/discontinued in adults. There is a paucity of literature on weaning and discontinuation practices in pediatric ITP. Methods We performed a retrospective review of pediatric patients aged 0-18 years with ITP treated with TPO-RAs at our institution over an eight-year period (2015-2022). Weaning and discontinuation practices were compared between patients based on timing of TPO-RA initiation: &amp;lt;3 months from diagnosis (group A), ≥3 to &amp;lt;12 months from diagnosis (group B), &amp;lt;12 months from diagnosis (group AB) or ≥12 months from diagnosis (group C). Results There were 11, 12 and 32 patients in group A, B, and C respectively (table 1). As of last follow up, 10 patients successfully weaned and discontinued their TPO-RA. Eighteen patients were weaning their TPO-RA monotherapy and 15 continued a TPO-RA at maximal dose or required the addition of another agent, such as an immunosuppressant, to permit TPO-RA weaning. Five patients discontinued their TPO-RA due to poor response. Seven patients had stopped the TPO-RA due to an alternate reason (family preference, side effects, etc.). There was no difference in any of these outcomes based on timing of TPO-RA initiation. In patients whose platelet count responded to TPO-RAs, the dose was weaned at the provider's discretion. The dose was generally not weaned for a platelet count &amp;lt;50k. Among only patients in which the TPO-RA monotherapy was weaned, patients in group AB had a shorter duration of TPO-RA treatment than patients in group C (IQR 12.1-48.9 months vs 37.5-88.0 months; p=0.019). While not statistically significant, after the start of the TPO-RA dose weaning, patients in group A weaned their TPO-RA at a faster rate (IQR 4.7-20.5% of maximal dose per month) compared to patients in groups B and C (IQR 1.8-5.1% of maximal dose per month and 1.5-5.5% of maximal dose per month). The 10 patients who fully weaned their TPO-RA had a shorter duration of TPO-RA use compared to the 18 patients who partially weaned their TPO-RA monotherapy (IQR 11.5-38.6 months vs 27.6-82.1 months; p=0.018). Once the wean of TPO-RA dose was started, patients who fully weaned their TPO-RA did so at a faster rate than patients who partially weaned (IQR 5.6-29.6% of maximal dose per month vs 1.0-3.4% of maximal dose per month; p=0.017; figure 1). Seven patients who fully weaned their TPO-RA had follow up CBCs between one and three months after discontinuation. Of these, five patients had platelet counts &amp;gt;100k, while the other two had platelet counts &amp;gt;40k that continued to rise to &amp;gt;80k within a year of discontinuation without further treatment. Of the remaining three patients, two had CBCs more than three months post TPO-RA discontinuation with platelet counts &amp;gt;100k without additional treatment and one had no follow up CBC after TPO-RA discontinuation. Two patients with follow-up had transient ITP exacerbations with platelet counts &amp;lt;10k at 14 and 31 months after TPO-RA discontinuation that were treated with anti-D/steroids and IVIG respectively with subsequent sustained improvement in platelet counts that did not require any further intervention. There was no difference in the number of rescue medications (IVIG, anti-D, steroids) required between patient groups based on timing of TPO-RA initiation or type of agent used. Patients who were treated with both romiplostim and eltrombopag required adjunctive therapies (such as immunosuppressants) more than patients treated with either agent alone (p=0.022). Conclusion TPO-RAs were weaned and successfully discontinued in 10 of 55 (18.2%) pediatric patients with ITP in our small cohort with a low rate of subsequent ITP exacerbation. There was no difference in TPO-RA discontinuation rate in patients with a good platelet response based on timing of TPO-RA initiation. Patients who started a TPO-RA within 12 months of their ITP diagnosis had a shorter duration of TPO-RA use than patients who started a TPO-RA more than 12 months after diagnosis. Patients who started a TPO-RA within three months of diagnosis were able to wean their TPO-RA dose at a faster rate than patients who started a TPO-RA more than three months after diagnosis. TPO-RA dose was weaned at a faster rate in patients who fully weaned their TPO-RA compared to patients who were partially weaned. This data should be validated in a larger study.

Perinatal foodborne titanium dioxide exposure-mediated dysbiosis predisposes mice to develop colitis through life

BackgroundPerinatal exposure to titanium dioxide (TiO2), as a foodborne particle, may influence the intestinal barrier function and the susceptibility to develop inflammatory bowel diseases (IBD) later in life. Here, we investigate the impact of perinatal foodborne TiO2 exposure on the intestinal mucosal function and the susceptibility to develop IBD-associated colitis. Pregnant and lactating mother mice were exposed to TiO2 until pups weaning and the gut microbiota and intestinal barrier function of their offspring was assessed at day 30 post-birth (weaning) and at adult age (50 days). Epigenetic marks was studied by DNA methylation profile measuring the level of 5-methyl-2′-deoxycytosine (5-Me-dC) in DNA from colic epithelial cells. The susceptibility to develop IBD has been monitored using dextran-sulfate sodium (DSS)-induced colitis model. Germ-free mice were used to define whether microbial transfer influence the mucosal homeostasis and subsequent exacerbation of DSS-induced colitis.ResultsIn pregnant and lactating mice, foodborne TiO2 was able to translocate across the host barriers including gut, placenta and mammary gland to reach embryos and pups, respectively. This passage modified the chemical element composition of foetus, and spleen and liver of mothers and their offspring. We showed that perinatal exposure to TiO2 early in life alters the gut microbiota composition, increases the intestinal epithelial permeability and enhances the colonic cytokines and myosin light chain kinase expression. Moreover, perinatal exposure to TiO2 also modifies the abilities of intestinal stem cells to survive, grow and generate a functional epithelium. Maternal TiO2 exposure increases the susceptibility of offspring mice to develop severe DSS-induced colitis later in life. Finally, transfer of TiO2-induced microbiota dysbiosis to pregnant germ-free mice affects the homeostasis of the intestinal mucosal barrier early in life and confers an increased susceptibility to develop colitis in adult offspring.ConclusionsOur findings indicate that foodborne TiO2 consumption during the perinatal period has negative long-lasting consequences on the development of the intestinal mucosal barrier toward higher colitis susceptibility. This demonstrates to which extent environmental factors influence the microbial-host interplay and impact the long-term mucosal homeostasis.