Positive airway pressure therapy adherence and outcomes in obstructive sleep apnea: An exploratory longitudinal retrospective randomized chart review.

Background: Positive airway pressure (PAP) therapy is prescribed to patients with obstructive sleep apnea (OSA). A commonly used definition for PAP therapy adherence is based upon the minimum requirements to receive Medicare coverage in the US, defined as PAP usage of four or more hours per night on 70 percent of nights for at least 30 consecutive days. However, little evidence exists to support this definition for PAP therapy adherence. Therefore, the present study sought to determine the efficacy of the present definition of PAP therapy adherence on longitudinal outcomes in patients with OSA, using objectively measured PAP device usage time. Methods: An exploratory longitudinal, retrospective, randomized chart review was done to assess clinical outcomes between patients with OSA who were defined as PAP therapy adherent (n=50) and non-adherent (n=50) during an eight-year observation period. Results: No significant differences were shown between groups for mortality, hospitalizations, or development of co-morbidities during the observation period. However, logistic regression showed significantly higher odds of adherence in male patients compared to female patients (OR=8.519; 95%CI=1.301-55.756; p=0.025) and significantly lower odds of adherence in patients with higher normal (OR=0.039; 95%CI=0.005-0.392; p=0.003), mild excessive (OR=0.039; 95%CI=0.003-0.517; p=0.014), and severe excessive (OR=0.088; 95%CI=0.012-0.635; p=0.016) daytime sleepiness compared to patients with lower normal daytime sleepiness. An increasing number of hospitalizations also corresponded with a significant decrease in odds of being adherent (OR=0.741; 95%CI=0.551-0.995; p=0.046). Conclusion: The present study supports a steadily growing body of literature calling for more consideration and evidence to support a definition of PAP therapy adherence that is clinically meaningful.

Profiling Immunological Phenotypes in Individuals During the First Year After Traumatic Spinal Cord Injury: A Longitudinal Analysis.

Abstract Individuals with SCI are severely affected by immune system changes, resulting in increased risk of infections and persistent systemic inflammation. While recent data support that immunological changes after SCI differ in the acute and chronic phases of living with SCI, only limited immunological phenotyping in humans is available. To characterize dynamic molecular and cellular immune phenotypes over the first year, we assess RNA (bulk-RNA sequencing), protein, and flow cytometry (FACS) profiles of blood samples from 12 individuals with SCI at 0-3 days and at 3, 6, and 12 months post injury (MPI) compared to 23 uninjured individuals (controls). We identified 967 differentially expressed (DE) genes in individuals with SCI (FDR <0.001) compared to controls. Within the first 6 MPI we detected a reduced expression of NK cell genes, consistent with reduced frequencies of CD56bright, CD56dim NK cells present at 12 MPI. Over 6MPI, we observed increased and prolonged expression of genes associated with inflammation (e.g. HMGB1, Toll-like receptor signaling) and expanded frequencies of monocytes acutely. Canonical T-cell related DE genes (e.g. FOXP3, TCF7, CD4) were upregulated during the first 6 MPI and increased frequencies of activated T cells at 3-12 MPI. Neurological injury severity was reflected in distinct whole blood gene expression profiles at any time after SCI, verifying a persistent 'neurogenic' imprint. Overall, 2876 DE genes emerge when comparing motor complete to motor incomplete SCI (ANOVA, FDR <0.05), including those related to neutrophils, inflammation, and infection. In summary, we identify a dynamic immunological phenotype in humans, including molecular and cellular changes which may provide potential targets to reduce inflammation, improve immunity, or serve as candidate biomarkers of injury severity.

The Beginning of the AI-Enabled Preventative PAP Therapy Era: A First-in-Human Proof of Concept Interventional Study.

Positive Airway Pressure (PAP) therapy is the most common and efficacious treatment for Obstructive Sleep Apnea (OSA). However, it suffers from poor patient adherence due to discomfort and may not fully alleviate all adverse consequences of OSA. Identifying abnormal respiratory events before they have occurred may allow for improved management of PAP levels, leading to improved adherence and better patient outcomes. Our previous work has resulted in the successful development of a Machine-Learning (ML) algorithm for the prediction of future apneic events using existing airflow and air pressure sensors available internally to PAP devices. Although researchers have studied the use of ML for the prediction of apneas, research to date has focused primarily on using external polysomnography sensors that add to patient discomfort and has not investigated the use of internal-to-PAP sensors such as air pressure and airflow to predict and prevent respiratory events. We hypothesized that by using our predictive software, OSA events could be proactively prevented while maintaining patients' sleep quality. An intervention protocol was developed and applied to all patients to prevent OSA events. Although the protocol's cool-down period limited the number of prevention attempts, analysis of 11 participants revealed that our system improved many sleep parameters, which included a statistically significant 31.6% reduction in Apnea-Hypopnea Index, while maintaining sleep quality. Most importantly, our findings indicate the feasibility of unobtrusive identification and unique prevention of each respiratory event as well as paving the path to future truly personalized PAP therapy by further training of ML models on individual patients.

Making It to Sustainability: Evaluating Billing Strategies for Collaborative Care.

The collaborative care model (CoCM) is an effective strategy to manage common mental disorders in primary care. Despite the growing adoption of newer CoCM billing codes to support these programs, few studies have investigated the use of these codes. This column evaluated the implementation of CoCM billing codes by comparing clinics using different billing strategies and assessed the impact of CoCM code implementation on revenue and on clinical and process-of-care outcomes. Qualitative data were obtained to understand provider perspectives. The results indicate that CoCM billing code implementation is operationally feasible, does not adversely affect the delivery of patient care or revenue, and is acceptable to providers.

High Frequency-Low Amplitude Oscillometry: Continuous Unobtrusive Monitoring of Respiratory Function on PAP Machines.

Oscillometry or Forced Oscillation Technique, traditionally used in intermittent clinical measurements, has recently gained substantial attention from its application as a continuous monitoring tool for large and small airways. However, low frequency (<8 Hz) continuous oscillometry faces high breathing noise, and hence requires high oscillation amplitudes to maintain an acceptable signal-to-noise ratio. Therefore, PAP machines that utilize low frequency oscillometry do so intermittently to distinguish airway patency several seconds after a breathing pause has occurred. We hypothesized that high frequency and low amplitude (HFLA) oscillometry may be as sensitive and applicable for monitoring upper airway patency to distinguish between central and obstructive apnea and hypopnea events, and for monitoring respiratory impedance. An inline oscillometry prototype device was developed and connected to commercial PAP machines to test whether oscillometry at 17, 43, and 79 Hz are as sensitive to airway patency as oscillometry at 4 Hz. Analysis of 11 patients with 171 apneas and hypopneas showed that all frequency oscillometry inputs were equally sensitive in distinguishing between central and obstructive apneas, while 17 Hz and 43 Hz oscillometry were most sensitive in distinguishing between central and obstructive hypopneas. Observations during normal breathing also showed the same periodicity and cross-correlation between impedance measurements from HFLA oscillometry compared to 4 Hz. Our findings provide an unobtrusive means of distinguishing airway patency during sleep and a means of continuous monitoring of respiratory function, with the potential for detection and prediction of developing respiratory diseases and significantly richer context for data analytics.

Elevated levels of IgA and IgG2 in individuals with chronic spinal cord injury.

OBJECTIVES: To determine circulating levels of antibodies (IgA, IgM, IgG1-4) in individuals with SCI as compared to uninjured individuals. STUDY DESIGN: Prospective, observational study. SETTING: Outpatient clinic of a Department of Physical Medicine and Rehabilitation and research institute in an academic medical center. PARTICIPANTS: Individuals with chronic (≥ 1 year from injury) SCI and uninjured individuals. OUTCOME MEASURES: Serum antibody titers were determined by commercial multiplex ELISA. RESULTS: Blood samples were collected from individuals with chronic SCI (N = 29, 83% males) and uninjured individuals (N = 25, 64% males). Among participants with SCI, the distribution of American Spinal Injury Association Impairment Scale (AIS) grades was: A (n = 15), B (n = 2), C (n = 4), D (n = 8). Neurological levels of injury were: cervical (n = 17), thoracic (n = 10), and lumbar (n = 2). IgA levels were significantly elevated in participants with SCI compared to uninjured participants (median: 1.98 vs. 1.21 mg/ml, P < 0.0001), with levels most elevated in individuals with motor complete injuries compared to uninjured participants (P < 0.0003). IgG2 antibodies were also significantly elevated in participants with SCI compared to uninjured participants (median: 5.98 vs. 4.37 mg/ml, P < 0.018). CONCLUSIONS: To our knowledge, this study provides the first evidence of elevated IgA, the antibody type most prevalent at respiratory, genitourinary and gastrointestinal tracts, common sites of infections in individuals with SCI. IgG2 levels were also elevated in individuals with SCI. These data support further investigations of IgA and other antibody types in individuals with chronic SCI, which may be increasingly important in the context of emerging novel infectious diseases such as SARS-CoV-2.

Systemic gene expression profiles according to pain types in individuals with chronic spinal cord injury.

Pain affects most individuals with traumatic spinal cord injury (SCI). Major pain types after SCI are neuropathic or nociceptive, often experienced concurrently. Pain after SCI may be refractory to treatments and negatively affects quality of life. Previously, we analyzed whole blood gene expression in individuals with chronic SCI compared to able-bodied (AB) individuals. Most participants with SCI reported pain (N = 19/28). Here, we examined gene expression of participants with SCI by pain status. Compared to AB, participants with SCI with pain had 468 differentially expressed (DE) genes; participants without pain had 564 DE genes (FDR < 0.05). Among DE genes distinct to participants with SCI with pain, Gene Ontology Biological Process (GOBP) analysis showed upregulated genes were enriched in categories related to T cell activation or inflammation; downregulated genes were enriched in categories related to protein proteolysis and catabolism. Although most participants with pain reported multiple pain types concurrently, we performed a preliminary comparison of gene expression by worst pain problem type. Compared to AB, participants with SCI who ranked neuropathic (N = 9) as worst had one distinct DE gene (TMEM156); participants who ranked nociceptive (N = 10) as worst had 61 distinct DE genes (FDR < 0.05). In the nociceptive group, the GOBP category with the lowest P-value identified among upregulated genes was "positive regulation of T cell activation"; among downregulated genes it was "receptor tyrosine kinase binding". An exploratory comparison of pain groups by principal components analysis also showed that the nociceptive group was enriched in T-cell related genes. A correlation analysis identified genes significantly correlated with pain intensity in the neuropathic or nociceptive groups (N = 145, 65, respectively, Pearson's correlation r > 0.8). While this pilot study highlights challenges of identifying gene expression profiles that correlate with specific types of pain in individuals with SCI, it suggests that T-cell signaling should be further investigated in this context.

The effects of sample handling on proteomics assessed by reverse phase protein arrays (RPPA): Functional proteomic profiling in leukemia.

Reverse phase protein arrays (RPPA) can assess protein expression and activation states in large numbers of samples (n > 1000) and evidence suggests feasibility in the setting of multi-institution clinical trials. Despite evidence in solid tumors, little is known about protein stability in leukemia. Proteins collected from leukemia cells in blood and bone marrow biopsies must be sufficiently stable for analysis. Using 58 leukemia samples, we initially assessed protein/phospho-protein integrity for the following preanalytical variables: 1) shipping vs local processing, 2) temperature (4 °C vs ambient temperature), 3) collection tube type (heparin vs Cell Save (CS) preservation tubes), 4) treatment effect (pre- vs post-chemotherapy) and 5) transit time. Next, we assessed 1515 samples from the Children's Oncology Group Phase 3 AML clinical trial (AAML1031, NCT01371981) for the effects of transit time and tube type. Protein expression from shipped blood samples was stable if processed in ≤72 h. While protein expression in pre-chemotherapy samples was stable in both heparin and CS tubes, post-chemotherapy samples were stable in only CS tubes. RPPA protein extremes is a successful quality control measure to identify and exclude poor quality samples. These data demonstrate that a majority of shipped proteins can be accurately assessed using RPPA. SIGNIFICANCE: RPPA can assess protein abundance and activation states in large numbers of samples using small amounts of material, making this method ideal for use in multi-institution clinical trials. However, there is little known about the effect of preanalytical handling variables on protein stability and the integrity of protein concentrations after sample collection and shipping. In this study, we used RPPA to assess preanalytical variables that could potentially affect protein concentrations. We found that the preanalytical variables of shipping, transit time, and temperature had minimal effects on RPPA protein concentration distributions in peripheral blood and bone marrow, demonstrating that these preanalytical variables could be successfully managed in a multi-site clinical trial setting.

Plasma Zonulin Levels in Childhood Nephrotic Syndrome.

Objective: We conducted this study to test the hypothesis that plasma zonulin levels are elevated in pediatric patients with nephrotic syndrome compared to healthy controls. Study Design: Plasma zonulin levels were measured by ELISA in 114 children enrolled in the NEPTUNE study. Clinical and laboratory data were retrieved from the NEPTUNE database. Results: The median age of the patients was 10 (IQR = 5 to 14) years, 59 were male, 64 had minimal change disease, 47 focal segmental glomerulosclerosis, median eGFR was 96 (IQR = 80 to 114) ml/min/1.73 m2, and median urine protein:creatinine ratio was 0.5 (IQR = 0.1 to 3.4) (g:g). The plasma zonulin level was 14.2 ± 5.0 vs. 10.2 ± 2.5 ng/ml in healthy adults in a report using the same assay kit, P = 0.0025. These findings were confirmed in an independent cohort of children with nephrotic syndrome compared to healthy age-matched controls, P = 0.01. Zonulin concentrations did not differ in children with minimal change disease vs. focal segmental glomerulosclerosis, frequently relapsing vs. steroid-dependent vs. steroid-resistant clinical course, and were not influenced by the immunosuppressive treatment regimen. There was no relationship between plasma zonulin levels and the absolute or percentage change in proteinuria from enrollment until the time of the zonulin assay. Conclusion: Plasma zonulin levels are elevated in childhood nephrotic syndrome regardless of level of proteinuria or specific treatment. The cause of the high plasma zonulin levels and whether zonulin contributes to glomerular injury requires further study.

Melamine and cyanuric acid exposure and kidney injury in US children.

BACKGROUND: Melamine and cyanuric acid, which are currently used in a variety of common consumer products and present in foods, have been implicated in the development of urolithiasis and acute kidney injury in Chinese children. To determine whether US children have measurable concentrations of these chemicals in their bodies and whether they are at greater risk of acute kidney injury, we measured melamine and cyanuric acid exposure in a cohort of US children and determined their relationship with markers of kidney injury. METHODS: We measured urinary melamine and cyanuric acid in a convenience sample of 109 children (4 months - 8 years) from Seattle, WA and New York City, NY using liquid chromatography with tandem mass spectrometry. We measured several urinary markers of kidney injury: fatty acid binding protein 3 (FABP3), kidney injury molecule 1 (KIM1), neutrophil gelatinase-associated lipocalin (NGAL) using Luminex xMAP methods, and urine urea was measured using standard laboratory methods. We described urinary melamine and cyanuric acid concentrations and assessed predictors of the exposures. We used multivariable linear regression to assess relationships between melamine/cyanuric acid and kidney injury markers in unadjusted and adjusted (creatinine, age, sex) analyses. RESULTS: Melamine and cyanuric acid were above the limit of detection (LOD) in 78% and 95% of all samples, respectively. The mean concentrations (SD) for melamine and cyanuric acid were 27.4 ng/ml (141.9 ng/ml) and 35.3 ng/ml (42.4 ng/ml). In unadjusted analyses, we observed statistically significant increases in the percentages of FABP3 and KIM1 in relation to a one log unit change in melamine and cyanuric acid, respectively. In adjusted analyses, we observed a 55% (95% CI 0, 141) increase in KIM1 in relation to a one log unit increase in cyanuric acid. CONCLUSIONS: US children have detectable concentrations of melamine and cyanuric acid in urine, and these concentrations are higher than those reported in children from other countries. This is a novel finding that improves upon previous exposure estimates using questionnaires only and suggests widespread exposure in the population. Cyanuric acid is associated with increased KIM 1 concentrations, suggesting kidney injury. Given the potential widespread exposure, future analyses should examine melamine and cyanuric acid in relation to chronic kidney disease and markers of kidney injury in a larger cohort that is representative of the general population.

Modifying maternal sleep position in the third trimester of pregnancy with positional therapy: a randomised pilot trial.

OBJECTIVE: To evaluate whether the percentage of time spent supine during sleep in the third trimester of pregnancy could be reduced using a positional therapy device (PrenaBelt) compared with a sham device. DESIGN: A double-blind, randomised, sham-controlled, cross-over pilot trial. SETTING: Conducted between March 2016 and January 2017, at a single, tertiary-level centre in Canada. PARTICIPANTS: 23 participants entered the study. 20 participants completed the study. Participants were low-risk, singleton, third-trimester pregnant women aged 18 years and older with body mass index <35 kg/m2 at the first antenatal appointment for the index pregnancy and without known fetal abnormalities, pregnancy complications or medical conditions complicating sleep. INTERVENTIONS: A two-night, polysomnography study in a sleep laboratory. Participants were randomised by computer-generated, one-to-one, simple randomisation to receive either a PrenaBelt or a sham-PrenaBelt on the first night and were crossed over to the alternate device on the second night. Allocation concealment was by unmarked, security-tinted, sealed envelopes. Participants, the recruiter and personnel involved in setting up, conducting, scoring and interpreting the polysomnogram were blinded to allocation. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the percentage of time spent supine during sleep. Secondary outcomes included maternal sleep architecture, respiration, self-reported sleep position and feedback. RESULTS: The median percentage of sleep time supine was reduced from 16.4% on the sham night to 3.5% on the PrenaBelt night (pseudomedian=5.8, p=0.03). We were unable to demonstrate differences in sleep architecture or respiration. Participants underestimated the time they spent sleeping supine by 7.0%, and six (30%) participants indicated they would make changes to the PrenaBelt. There were no harms in this study. CONCLUSIONS: This study demonstrates that the percentage of sleep time supine during late pregnancy can be significantly reduced via positional therapy. TRIAL REGISTRATION NUMBER: NCT02377817; Results.

Distinct Patterns of Hyperpnea During Cheyne-Stokes Respiration: Implication for Cardiac Function in Patients With Heart Failure.

STUDY OBJECTIVES: In heart failure (HF), we observed two patterns of hyperpnea during Cheyne-Stokes respiration with central sleep apnea (CSR-CSA): a positive pattern where end-expiratory lung volume remains at or above functional residual capacity, and a negative pattern where it falls below functional residual capacity. We hypothesized the negative pattern is associated with worse HF. METHODS: Patients with HF underwent polysomnography. During CSR-CSA, hyperpnea, apnea-hyperpnea cycle, and lung to finger circulation times (LFCT) were measured. Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration and left ventricular ejection fraction (LVEF) were assessed. RESULTS: Of 33 patients with CSR-CSA (31 men, mean age 68 years), 9 had a negative hyperpnea pattern. There was no difference in age, body mass index, and apnea-hypopnea index between groups. Patients with a negative pattern had longer hyperpnea time (39.5 ± 6.4 versus 25.8 ± 5.9 seconds, P < .01), longer cycle time (67.8 ± 15.9 versus 51.7 ± 9.9 seconds, P < .01), higher NT-proBNP concentrations (2740 [6769] versus 570 [864] pg/ml, P = .01), and worse New York Heart Association class (P = .02) than those with a positive pattern. LFCT and LVEF did not differ between groups. CONCLUSIONS: Patients with HF and a negative CSR-CSA pattern have evidence of worse cardiac function than those with a positive pattern. Greater positive expiratory pressure during hyperpnea is likely generated during the negative pattern and might support stroke volume in patients with worse cardiac function. COMMENTARY: A commentary on this article appears in this issue on page 1227. CLINICAL TRIAL REGISTRATION: The trial is registered with Current Controlled Trials (www.controlled-trials.com; ISRCTN67500535) and Clinical Trials (www.clinicaltrials.gov; NCT01128816).

Design of the effect of adaptive servo-ventilation on survival and cardiovascular hospital admissions in patients with heart failure and sleep apnoea: the ADVENT-HF trial.

INTRODUCTION: Both types of sleep-disordered breathing (SDB), obstructive and central sleep apnoea (OSA and CSA, respectively), are common in patients with heart failure and reduced ejection fraction (HFrEF). In such patients, SDB is associated with increased cardiovascular morbidity and mortality but it remains uncertain whether treating SDB by adaptive servo-ventilation (ASV) in such patients reduces morbidity and mortality. AIM: ADVENT-HF is designed to assess the effects of treating SDB with ASV on morbidity and mortality in patients with HFrEF. METHODS: ADVENT-HF is a multicentre, multinational, randomized, parallel-group, open-label trial with blinded assessment of endpoints of standard medical therapy for HFrEF alone vs. with the addition of ASV in patients with HFrEF and SDB. Patients with a history of HFrEF undergo echocardiography and polysomnography. Those with a left ventricular ejection fraction ≤45% and SDB (apnoea-hypopnoea index ≥15) are eligible. SDB is stratified into OSA with ≥50% of events obstructive or CSA with >50% of events central. Those with OSA must not have excessive daytime sleepiness (Epworth score of ≤10). Patients are then randomized to receive or not receive ASV. The primary outcome is the composite of all-cause mortality, cardiovascular hospital admissions, new-onset atrial fibrillation requiring anti-coagulation but not hospitalization, and delivery of an appropriate discharge from an implantable cardioverter-defibrillator not resulting in hospitalization during a maximum follow-up time of 5 years. CONCLUSION: The ADVENT-HF trial will help to determine whether treating SDB by ASV in patients with HFrEF improves morbidity and mortality.

Exposure to bisphenols and phthalates and association with oxidant stress, insulin resistance, and endothelial dysfunction in children.

BACKGROUND: The health effects of bisphenol A (BPA) and di-(2-ethylhexyl) phthalate (DEHP) have been studied extensively in children. The impact of other chemicals in these two classes has not been investigated as fully. METHODS: We conducted a cross-sectional pilot study of 10-13 y old healthy children. We assessed descriptive, univariable, and multivariable associations of urinary metabolites of bisphenols and phthalates with oxidant stress, insulin resistance, body mass, and endothelial dysfunction. Possible associations with brachial artery distensibility, pulse wave velocity (markers of vascular stiffness), and serum endothelial cell-derived microparticle levels were also assessed. RESULTS: We enrolled 41 participants, 12.1 ± 1.0 y, most of whom were Mexican Americans (42%) or other Hispanics (34%). Increased BPA levels were associated with increased levels of F2-isoprostane (ng/ml) (P = 0.02), with a similar trend for DEHP metabolites. Each log unit increase of high molecular weight (HMW) phthalate metabolites was associated with a 0.550 increase in Homeostatic Model Assessment of insulin resistance (HOMA-IR) units (P = 0.019) and altered circulating levels of activated endothelial cell-derived microparticles (% per ml) (P = 0.026). Bisphenol S (BPS), a replacement for BPA, was associated with increased albumin (mg):creatinine (g) ratio (P = 0.04). Metabolites of HMW phthalates were also associated with decreased brachial artery distensibility (P = 0.047). CONCLUSION: Exposure to bisphenols and phthalates, including a BPA replacement, is associated with increased oxidant stress, insulin resistance, albuminuria, as well as disturbances in vascular function in healthy children.

Blood Eosinophils and World Trade Center Exposure Predict Surgery in Chronic Rhinosinusitis. A 13.5-Year Longitudinal Study.

RATIONALE: The World Trade Center (WTC) collapse generated caustic airborne particulates that caused chronic rhinosinusitis in exposed Fire Department of New York firefighters. Surgery was performed when symptoms remained uncontrolled despite medical management. OBJECTIVES: To identify predictors of surgical intervention for chronic rhinosinusitis in firefighters exposed to airborne irritants at the WTC collapse site. METHODS: We assessed in 8,227 firefighters with WTC exposure between September 11, 2001 (9/11), and September 25, 2001, including WTC-site arrival time, months of rescue and recovery work, and eosinophil concentration measured between 9/11 and March 10, 2003. We assessed the association of serum cytokines and immunoglobulins with eosinophil concentration and surgery for rhinosinusitis in 112 surgical cases and 376 control subjects with serum available from the first 6 months after exposure to the WTC collapse site. MEASUREMENTS AND MAIN RESULTS: Between 9/11 and March 10, 2015, the surgery rate was 0.47 cases per 100 person-years. In the first 18 months post-9/11, surgical patients had higher mean blood eosinophil levels than study cohort patients (219 ± 155 vs. 191 ± 134; P < 0.0001). Increased surgery risk was associated with increasing blood eosinophil counts (hazard ratio [HR], 1.12 per 100 cells/µl; 95% confidence interval [CI], 1.07-1.17; P < 0.001); arriving at the WTC site on 9/11 or September 12, 2001 (HR, 1.43; 95% CI, 1.04-1.99; P = 0.03); and working 6 months or longer at the WTC site (HR, 1.48; 95% CI, 1.14-1.93; P < 0.01). Median blood eosinophil levels for surgical patients were above levels for the cohort in all 18-month intervals March 11, 2000, through March 10, 2015, using 51,163 measurements representing 97,733 person-years of observation. Increasing age, increasing IL-17A, and low IgA in serum from 2001 to 2002 predicted blood eosinophil concentration in surgical patients but not in control subjects (R(2) = 0.26, P < 0.0001; vs. R(2) = 0.008, P = 0.56). CONCLUSIONS: Increasing blood eosinophil concentration predicts surgical intervention for chronic rhinosinusitis, particularly in those with intense acute and prolonged exposure to airborne irritants. WTC-exposed Fire Department of New York firefighters who underwent irritant-associated sinus surgery are immunologically different from the cohort. Surgical patients have a higher blood eosinophil levels that is associated with mediators of mucosal immunity.

Technique for office-based, ultrasonography-guided percutaneous biopsy of renal cortical neoplasms using a novel transducer for facilitated ultrasound targeting.

OBJECTIVES: To help clarify which small renal cortical neoplasms (RCNs) require surgery by using office-based, ultrasonography-guided percutaneous renal biopsy. PATIENTS AND METHODS: Biopsies were performed using facilitated ultrasound targeting (FUT) technology, which incorporates a needle guide and onscreen beam-steered technology to permit highly precise needle deployment. Patient and tumour characteristics, procedure time, complications and biopsy efficacy were documented. Wong-Baker pain levels were obtained before, during and 1 h after the procedure. RESULTS: Seven patients underwent biopsy, six for RCNs and one for medical renal disease. The mean (range) patient age was 68.5 (54-79) years, and the mean (range) tumour diameter was 2.55 (2.0-2.9) cm. Mean pain levels before, during and 1 h after the procedure were 0, 1.6 and 0.5, respectively. There were no intra- or post-procedural complications. Biopsy results were diagnostic in five of the six RCN cases and in the single case of medical renal disease. CONCLUSIONS: Our preliminary experience shows that office-based percutaneous renal biopsy using a novel transducer for FUT is safe and effective. An international multicentre study is planned to confirm these preliminary results.