Real-world effectiveness of elexacaftor/tezacaftor/ivacaftor on the burden of illness in adolescents and adults with cystic fibrosis.

Background: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and efficacious in people with cystic fibrosis (CF) aged ≥2 years. Here, we describe results from an observational study assessing change in burden of illness following initiating ELX/TEZ/IVA in real-world settings. Methods: This US-based, multicenter, observational study used data from electronic medical records to evaluate real-world burden of illness before and after ELX/TEZ/IVA initiation in people with CF aged ≥12 years heterozygous for F508del and a minimal function mutation (F/MF) or an uncharacterized CFTR mutation. Endpoints included absolute change from baseline in percent predicted forced expiratory volume in 1 s (ppFEV1), body mass index (BMI) and BMI-for-age z-score, glycated hemoglobin (HbA1c), and numbers of pulmonary exacerbations (PEx). Results: Overall, 206 people with CF were enrolled (mean [SD] age 22.5 [11.1] years; 192 [93.2%] with F/MF genotype). Mean follow-up was 15.6 (SD, 1.6) months. Improvements in ppFEV1 (7.3 [95% CI: 5.7, 8.8] percentage points) were observed from baseline through follow-up. Increases in BMI (1.40 [95% CI: 1.07, 1.77] kg/m2) and BMI-for-age z-score (0.14 [95% CI: 0.00, 0.28]) were also observed from baseline at 12 months. The estimated annualized rate of any PEx was 1.31 at baseline and 0.61 over follow-up (rate ratio 0.47 [95% CI: 0.39, 0.55]), with annualized rates of PEx requiring antibiotics and hospitalizations of 0.55 and 0.88 in the baseline period and 0.12 and 0.36 over follow-up (rate ratios 0.22 [95% CI: 0.15, 0.31] and 0.41 [95% CI: 0.32, 0.51]), respectively. Absolute change in HbA1c was -0.22 (95% CI: -0.38, -0.06) from baseline through follow-up. Conclusions: ELX/TEZ/IVA treatment was associated with improved lung function, increased BMI, reduced frequency of PEx, and improved (i.e., reduced) HbA1c. These results confirm the broad clinical benefits of ELX/TEZ/IVA seen in clinical trials and show the potential for ELX/TEZ/IVA to improve markers of glucose metabolism.

Ventilation arrangement evaluation and proactive goaf inertisation for spontaneous combustion and gas explosion management during longwall panel sealing-off process.

When a longwall face approaches the finish-off line, 1 month is normally required to relocate the longwall equipment and seal the longwall panel, during which time the goaf gas atmosphere changes and the risk of spontaneous combustion and gas explosion considerably increases. To minimise the occurrence of these hazards, an improved insight into gas flow dynamics within the longwall panel is essential during the panel sealing-off process. Based on mining conditions of an Australian underground coal mine, three-dimensional computational models were developed and calibrated with onsite gas monitoring data, allowing for evaluating ventilation arrangements and understanding methane dispersion in the longwall workings during the six-stage panel sealing-off process with confidence. The simulation results indicate that nitrogen should be injected on the travel road side at a distance of 120 m behind the longwall face at a rate of 0.75 m3/s and the rear of the travel road should be tightly sealed at the final sealing-off stage, resulting in oxygen levels lowering than 5% in the longwall workings and producing desired panel sealing-off performance. In addition, gas sensors should be employed and positioned at the appropriate locations to reliably monitor goaf atmosphere change. This study sheds improved insights into evaluating ventilation arrangements and understanding gas flow dynamics during the panel sealing-off process and provides critical knowledge of effective proactive goaf inertisation strategies, thus minimising the risk of spontaneous heating and gas explosion and reducing environmental pollution induced by these hazards.

Underutilization of Transcatheter Aortic Valve Replacement in Northern Plains American Indians with Severe Aortic Stenosis.

INTRODUCTION: Transcatheter aortic valve replacement (TAVR) has overtaken surgical aortic valve replacement and revolutionized the treatment strategy for aortic valve replacement. Little is known on the disparities among minorities, especially American Indians (AI), undergoing this procedure. We explore TAVR outcomes to identify disparities at our institution. METHODS: Retrospective chart review was completed on patients who underwent TAVR at a North Dakota community hospital between 2012 and 2021. There were 1133 non-AI and 20 AI patients identified (n = 1153). AI patients were identified by enrollment in nationally recognized tribes, Indian Health Service (IHS), or who self-identified as AI. Patient demographics, preoperative characteristics, procedural information, and outcomes were collected. United States 2020 census data was used for state-wide population racial percentages. Unpaired two tail t test assuming unequal variance and chi-squared tests were used to evaluate data and identify disparities between AI and non-AI. RESULTS: AI presented at an earlier age (71 vs. 79; p = .001) with higher rates of diabetes (60% vs. 35%; p = .018) and history of smoking (100% vs. 60%; p ≤ .001) than Caucasian/white (C/W). The Society of Thoracic Surgery (STS) risk scores (3.2% vs. 4.6%; p = .054) and aortic valve mean gradients were lower among AI (42.8 mmHg vs. 47.5 mmHg; p = .010). For those deceased, AI had significantly shorter lifespans post-TAVR compared to C/W (374 days vs. 755 days; p = .004). AI from North Dakota had fewer TAVR procedures performed than expected (4 actual vs. 32 expected; p < .001). CONCLUSIONS: AI undergoing TAVR presented earlier, with higher rates of diabetes and smoking, lower STS risk scores, and lesser aortic valve gradients than C/W. The number of TAVR procedures performed on AI from North Dakota was lower than anticipated despite a nearly 10-year period and the disparities experienced by AI who could have otherwise benefited from TAVR.

Six-Month Deep Vein Thrombosis Outcomes by Chronicity: Analysis of the Real-World ClotTriever Outcomes Registry.

PURPOSE: To analyze the first 250 patients from the prospective, multicenter, industry-sponsored ClotTriever Outcomes (CLOUT) registry, assessing the safety and effectiveness of mechanical thrombectomy for acute, subacute, and chronic deep vein thrombosis (DVT). MATERIALS AND METHODS: Real-world patients with lower extremity DVT were treated with the ClotTriever System (Inari Medical, Irvine, California). Adjuvant venoplasty, stent placement, or both were performed at the physician's discretion. Thrombus chronicity was determined by visual inspection of removed thrombus, categorizing patients into acute, subacute, and chronic subgroups. Serious adverse events (SAEs) were assessed through 30 days. Clinical and quality-of-life (QoL) outcomes are reported through 6 months. RESULTS: Thrombus chronicity was designated for 244 of the 250 patients (acute, 32.8%; subacute, 34.8%; chronic, 32.4%) encompassing 254 treated limbs. Complete or near-complete (≥75%) thrombus removal was achieved in 90.8%, 81.9%, and 83.8% of the limbs with acute, subacute, and chronic thrombus, respectively. No fibrinolytics were administered, and 243 (99.6%) procedures were single sessions. One (0.4%) patient in the subacute group experienced a device-related SAE, a fatal pulmonary embolism. On comparing baseline and 6-month data, improvements were demonstrated in median Villalta scores (acute, from 10 to 1; subacute, from 9 to 1; chronic, from 10 to 3; for all, P < .0001) and mean EuroQol group 5-dimension (EQ-5D) self-report questionnaire scores (acute, 0.58 to 0.89; subacute, 0.65 to 0.87; chronic, 0.58 to 0.88; for all, P < .0001). There were no significant differences in outcomes across the subgroups. CONCLUSIONS: Mechanical thrombectomy using the ClotTriever System with adjunctive venoplasty and stent placement is safe and similarly effective for acute, subacute, and chronic DVT.

Percutaneous mechanical thrombectomy in a real-world pulmonary embolism population: Interim results of the FLASH registry.

OBJECTIVES: The FlowTriever All-Comer Registry for Patient Safety and Hemodynamics (FLASH) is a prospective multi-center registry evaluating the safety and effectiveness of percutaneous mechanical thrombectomy for treatment of pulmonary embolism (PE) in a real-world patient population (NCT03761173). This interim analysis reports outcomes for the first 250 patients enrolled in FLASH. BACKGROUND: High- and intermediate-risk PEs are characterized by high mortality rates, frequent readmissions, and long-term sequelae. Mechanical thrombectomy is emerging as a front-line therapy for PE that enables immediate thrombus reduction while avoiding the bleeding risks inherent with thrombolytics. METHODS: The primary endpoint is a composite of major adverse events (MAE) including device-related death, major bleeding, and intraprocedural device- or procedure-related adverse events at 48 h. Secondary endpoints include on-table changes in hemodynamics and longer-term measures including dyspnea, heart rate, and cardiac function. RESULTS: Patients were predominantly intermediate-risk per ESC guidelines (6.8% high-risk, 93.2% intermediate-risk). There were three MAEs (1.2%), all of which were major bleeds that resolved without sequelae, with no device-related injuries, clinical deteriorations, or deaths at 48 h. All-cause mortality was 0.4% at 30 days, with a single death that was unrelated to PE. Significant on-table improvements in hemodynamics were noted, including an average reduction in mean pulmonary artery pressure of 7.1 mmHg (22.2%, p < 0.001). Patient symptoms and cardiac function improved through follow-up. CONCLUSIONS: These interim results provide preliminary evidence of excellent safety in a real-world PE population. Reported outcomes suggest that mechanical thrombectomy can result in immediate hemodynamic improvements, symptom reduction, and cardiac function recovery.

Interim outcomes of mechanical thrombectomy for deep vein thrombosis from the All-Comer CLOUT Registry.

OBJECTIVES: The multicenter, prospective, single arm CLOUT registry assesses the safety and effectiveness of the ClotTriever System (Inari Medical, Irvine, CA) for the treatment of acute and nonacute lower extremity deep vein thrombosis (DVT) in all-comer patients. Reported here are the outcomes of the first 250 patients. METHODS: All-comer patients with lower extremity DVT were enrolled, including those with bilateral DVT, those with previously failed DVT treatment, and regardless of symptom duration. The primary effectiveness end point is complete or near-complete (≥75%) thrombus removal determined by independent core laboratory-adjudicated Marder scores. Safety outcomes include serious adverse events through 30 days and clinical outcomes include post-thrombotic syndrome severity, symptoms, pain, and quality of life through 6 months. RESULTS: The median age was 62 years and 40% of patients had contraindications to thrombolytics. A range of thrombus chronicity (33% acute, 35% subacute, 32% chronic) was observed. No patients received thrombolytics and 99.6% were treated in a single session. The median thrombectomy time was 28 minutes. The primary effectiveness end point was achieved in 86% of limbs. Through 30 days, one device-related serious adverse event occurred. At 6 months, 24% of patients had post-thrombotic syndrome. Significant and sustained improvements were observed in all clinical outcomes, including the Revised Venous Clinical Severity Score, the numeric pain rating scale, and the EuroQol Group 5-Dimension Self-Report Questionnaire. CONCLUSIONS: The 6-month outcomes from the all-comer CLOUT registry with a range of thrombus chronicities demonstrate favorable effectiveness, safety, and sustained clinical improvements.

Pediatric asthma hospitalization: individual and environmental characteristics of high utilizers in South Texas.

Objective: Few studies have examined factors affecting the high frequency of hospitalization for pediatric asthma. This study identifies individual and environmental characteristics of children with asthma from a low-income community with a high number of hospitalizations.Methods: The study population included 902 children admitted at least once to a children's hospital in South Texas because of asthma from 2010 to 2016. The population was divided into three groups by utilization frequency (high: ≥4 times, medium: 2-3 times, or low: 1 time). Individual-level factors at index admission and environmental factors were included for the analysis. Unadjusted and adjusted multivariate ordered logistic regression models were applied to identify significant characteristics of high hospital utilizers.Results: The high utilization group comprised 2.4% of total patients and accounted for substantial hospital resource utilization: 10.8% of all admissions and 13.5% of days stayed in the hospital. Patients in the high utilization group showed longer length of stay (LOS) and shorter time between admissions on average than the other two groups. The multivariate ordered logistic regression models revealed that age of 5-11 years (OR = 0.57, 95%CI = 0.35-0.93), longer LOS (2 days: OR = 1.80, 95%CI = 1.15-2.84; ≥3 days: OR = 3.38, 95%CI = 2.10-5.46), warm season at index admission (OR = 1.49, 95%CI = 1.01-2.20), and higher average ozone level in children's residential neighborhoods (OR = 1.78, 95%CI = 1.01-3.14) were significantly associated with a higher number of asthma hospitalizations.Conclusions: The findings suggest the importance of monitoring high hospital utilizers and establishing strategies for such patients based on their characteristics to reduce repeated hospitalizations and to increase optimal use of hospital resources.

Cardiopulmonary Arrest and Pulmonary Hypertension in an Infant with Pertussis Case Report.

Pertussis is a vaccine-preventable disease with an incidence that has been trending upwards in the United States over the last two decades. This is evident by an increase in the incidence from 10,100 cases in 1974 to a peak of >48,000 cases noted in the last decade. Pertussis disease severity ranges from mild to severe, with resultant complications capable of causing significant morbidity and mortality. We report a case of pertussis in a 5-week-old female infant who presented with fever, paroxysms of cough, apnea, and seizures leading to cardiopulmonary arrest. Cardiopulmonary resuscitation lasted 11 minutes before the return of spontaneous circulation. She was transferred to our tertiary facility and admitted to the pediatric intensive care unit. Complete blood count revealed significant leukocytosis, chest X-ray revealed bilateral pulmonary edema with pleural effusion, and echocardiogram demonstrated pulmonary hypertension. Bordetella pertussis infection was confirmed on respiratory polymerase chain reaction. She was treated with antibiotics, ventilatory management, and other supportive care. She was discharged on room air after a hospital course of 7 weeks with care coordination between her primary care provider, pulmonologist, and neurologist. Despite the positive outcome in this case, it is important to note that managing severe pertussis involves multidisciplinary care, and the morbidity and cost implications can be mitigated on a population scale through vaccine optimization strategies.

Effect of Ambient Air Pollution on Hospital Readmissions among the Pediatric Asthma Patient Population in South Texas: A Case-Crossover Study.

Few studies have evaluated the association between ambient air pollution and hospital readmissions among children with asthma, especially in low-income communities. This study examined the short-term effects of ambient air pollutants on hospital readmissions for pediatric asthma in South Texas. A time-stratified case-crossover study was conducted using the hospitalization data from a children's hospital and the air pollution data, including particulate matter 2.5 (PM2.5) and ozone concentrations, from the Centers for Disease Control and Prevention between 2010 and 2014. A conditional logistic regression analysis was performed to investigate the association between ambient air pollution and hospital readmissions, controlling for outdoor temperature. We identified 111 pediatric asthma patients readmitted to the hospital between 2010 and 2014. The single-pollutant models showed that PM2.5 concentration had a significant positive effect on risk for hospital readmissions (OR = 1.082, 95% CI = 1.008-1.162, p = 0.030). In the two-pollutant models, the increased risk of pediatric readmissions for asthma was significantly associated with both elevated ozone (OR = 1.023, 95% CI = 1.001-1.045, p = 0.042) and PM2.5 concentrations (OR = 1.080, 95% CI = 1.005-1.161, p = 0.036). The effects of ambient air pollutants on hospital readmissions varied by age and season. Our findings suggest that short-term (4 days) exposure to air pollutants might increase the risk of preventable hospital readmissions for pediatric asthma patients.

Association between Ambient Air Pollution and Hospital Length of Stay among Children with Asthma in South Texas.

Although hospital length of stay (LOS) has been identified as a proxy measure of healthcare expenditures in the United States, there are limited studies investigating the potentially important association between outdoor air pollution and LOS for pediatric asthma. This study aims to examine the effect of ambient air pollution on LOS among children with asthma in South Texas. It included retrospective data on 711 children aged 5-18 years old admitted for asthma to a pediatric tertiary care hospital in South Texas between 2010 and 2014. Air pollution data including particulate matter (PM2.5) and ozone were collected from the U.S. Centers for Disease Control and Prevention. The multivariate binomial logistic regression analyses were performed to determine the association between each air pollutant and LOS, controlling for confounders. The regression models showed the increased ozone level was significantly associated with prolonged LOS in the single- and two-pollutant models (p < 0.05). Furthermore, in the age-stratified models, PM2.5 was positively associated with LOS among children aged 5-11 years old (p < 0.05). In conclusion, this study revealed a concerning association between ambient air pollution and LOS for pediatric asthma in South Texas.

DUX4 Immunohistochemistry Is a Highly Sensitive and Specific Marker for CIC-DUX4 Fusion-positive Round Cell Tumor.

The histologic differential diagnosis of pediatric and adult round cell tumors is vast and includes the recently recognized entity CIC-DUX4 fusion-positive round cell tumor. The diagnosis of CIC-DUX4 tumor can be suggested by light microscopic and immunohistochemical features, but currently, definitive diagnosis requires ancillary genetic testing such as conventional karyotyping, fluorescence in situ hybridization, or molecular methods. We sought to determine whether DUX4 expression would serve as a fusion-specific immunohistochemical marker distinguishing CIC-DUX4 tumor from potential histologic mimics. A cohort of CIC-DUX4 fusion-positive round cell tumors harboring t(4;19)(q35;q13) and t(10;19)(q26;q13) translocations was designed, with additional inclusion of a case with a translocation confirmed to involve the CIC gene without delineation of the partner. Round cell tumors with potentially overlapping histologic features were also collected. Staining with a monoclonal antibody raised against the C-terminus of the DUX4 protein was applied to all cases. DUX4 immunohistochemistry exhibited diffuse, crisp, strong nuclear staining in all CIC-DUX4 fusion-positive round cell tumors (5/5, 100% sensitivity), and exhibited negative staining in nuclei of all of the other tested round cell tumors, including 20 Ewing sarcomas, 1 Ewing-like sarcoma, 11 alveolar rhabdomyosarcomas, 9 embryonal rhabdomyosarcomas, 12 synovial sarcomas, 7 desmoplastic small round cell tumors, 3 malignant rhabdoid tumors, 9 neuroblastomas, and 4 clear cell sarcomas (0/76, 100% specificity). Thus, in our experience, DUX4 immunostaining distinguishes CIC-DUX4 tumors from other round cell mimics. We recommend its use when CIC-DUX4 fusion-positive round cell tumor enters the histologic differential diagnosis.

Community health screenings can complement public health outreach to minority immigrant communities.

OBJECTIVES: We sought to provide culturally competent, community-based respiratory health screening and education in minority communities with high concentrations of Latino immigrants on Long Island and to assess the impact of this intervention on their decision to seek medical care. METHODS: Seven health care screenings were performed in communities with high concentrations of immigrants from Latin America. A subgroup of participants who identified themselves as Hispanic/Latino were analyzed. After completion of a respiratory health questionnaire and spirometry, screening scores were calculated, education provided, and recommendations were made for medical evaluation in those who screened positive. A positive screen was defined as abnormal respiratory symptoms, abnormal spirometry, or both. Follow-up contacts were made at 1, 6, and 12 months to assess compliance with the recommendation to seek care in those who screened positive. RESULTS: High positive screening rates for both men (64%) and women (61%) were found. Of the participants who screened positive and were advised to seek medical care, 52% did so. Compliance with the recommendation to seek care was associated with the presence of an identified medical provider at baseline. Of those who screened positive and who did not comply with team's recommendation, 75% were unable to identify a health care provider. CONCLUSIONS: A significant number of participants who screened positive could not identify a health care provider and did not follow-up with the recommendation to seek medical evaluation. Community-based screenings provide an opportunity to access at-risk immigrant populations for health screening and education, and to facilitate referral and access to medical services.

Association between parapneumonic effusion and pericardial effusion in a pediatric cohort.

OBJECTIVE: Associations between pleural and pericardial effusions have been described in malignancy and autoimmune disorders. Bacterial pneumonia is the most frequent cause of parapneumonic effusion; however, knowledge of the relationship between parapneumonic effusion and the presence of pericardial fluid in children is limited. We examined this relationship. METHODS: We performed a retrospective chart review of pediatric patients who were admitted to our institution during a 6-year period with a diagnosis of either parapneumonic effusion or empyema and who had undergone an echocardiogram, a computed tomography scan of the thorax, or both. All demographic, clinical, radiographic, and laboratory data of these patients were collected, and statistical analysis was done with Student's t tests and chi2 analyses. RESULTS: We reviewed the charts of 59 children with parapneumonic effusions. Forty-eight underwent 2-dimensional echocardiography, chest computed tomography scan, or both. Of these 48 patients, 54.2% (n=26) were found to have a concomitant pericardial effusion. The majority of patients with pericardial effusions had left-sided pleural disease. Patients with pericardial effusions had more symptomatic days before hospitalization, lower pleural fluid albumin levels, elevated serum white blood cell counts, elevated pleural fluid white blood cell and absolute neutrophil counts, and an increased incidence of surgical intervention. One patient had evidence of hemodynamic compromise that required pericardiocentesis. CONCLUSIONS: We found a high incidence of pericardial effusions in pediatric patients with parapneumonic effusions. Leukocytosis, higher pleural fluid leukocyte and neutrophil counts, and a propensity for surgical intervention suggest a prognostic relationship between pericardial effusions and more severe parapneumonic disease. The majority of these pericardial collections resolve with treatment of the underlying pleural disease.

Lymphomatoid granulomatosis in a pediatric patient.

We report the radiology and pathology of a pediatric patient with lymphomatoid granulomatosis (LG) and review the literature, with an emphasis on the radiological findings and on the small subset of pediatric patients with this rare condition.

Lack of evidence for functional ADP-activated human P2X1 receptors supports a role for ATP during hemostasis and thrombosis.

Purine nucleotides acting through P2 receptors play key roles in platelet signaling. The P2X1 receptor is an adenosine triphosphate (ATP)-gated ion channel that mediates a rapid calcium influx signal, but can also synergize with subsequent adenosine diphosphate (ADP)-evoked P2Y1 receptor-mediated responses and thus may contribute to platelet activation during hemostasis. Recent studies have shown that P2X1 receptors contribute to the formation of platelet thrombi, particularly under conditions of high shear stress. Based on intracellular Ca2+ measurements a previous report has suggested that a splice variant of the P2X1 receptor, P2X1del, is expressed in platelets and, in contrast to the full-length P2X1WT receptor, is activated by ADP. In the present study we show that the P2X1del receptor fails to form functional ion channels and is below the limit of detection in human platelets. Furthermore, ADP does not contribute to the rapid ionotropic P2X receptor-mediated response in platelets. These results support the notion that ATP is the principal physiologic agonist at P2X1 receptors and that it plays a role in the activation of platelets.