Computational modeling of pancreatic cancer reveals kinetics of metastasis suggesting optimum treatment strategies.

Pancreatic cancer is a leading cause of cancer-related death, largely due to metastatic dissemination. We investigated pancreatic cancer progression by utilizing a mathematical framework of metastasis formation together with comprehensive data of 228 patients, 101 of whom had autopsies. We found that pancreatic cancer growth is initially exponential. After estimating the rates of pancreatic cancer growth and dissemination, we determined that patients likely harbor metastases at diagnosis and predicted the number and size distribution of metastases as well as patient survival. These findings were validated in an independent database. Finally, we analyzed the effects of different treatment modalities, finding that therapies that efficiently reduce the growth rate of cells earlier in the course of treatment appear to be superior to upfront tumor resection. These predictions can be validated in the clinic. Our interdisciplinary approach provides insights into the dynamics of pancreatic cancer metastasis and identifies optimum therapeutic interventions.

Indoor environmental exposures and obstructive lung disease phenotypes among children with asthma living in poor urban neighborhoods.

BACKGROUND: Air trapping is an obstructive phenotype that has been associated with more severe and unstable asthma in children. Air trapping has been defined using pre- and postbronchodilator spirometry. The causes of air trapping are not completely understood. It is possible that environmental exposures could be implicated in air trapping in children with asthma. OBJECTIVE: We investigated the association between indoor exposures and air trapping in urban children with asthma. METHODS: Children with asthma aged 5 to 17 years living in Baltimore and enrolled onto the Environmental Control as Add-on Therapy for Childhood Asthma study were evaluated for air trapping using spirometry. Aeroallergen sensitization was assessed at baseline, and spirometry was performed at 0, 3, and 6 months. Air trapping was defined as an FVC z score of less than -1.64 or a change in FVC with bronchodilation of ≥10% predicted. Logistic normal random effects models were used to evaluate associations of air trapping and indoor exposures. RESULTS: Airborne and bedroom floor mouse allergen concentrations were associated with air trapping but not airflow limitation (odds ratio 1.19, 95% confidence interval 1.02-1.37, P = .02 per 2-fold increase in airborne mouse allergen; odds ratio 1.23, 95% confidence interval 1.07-1.41, P = .003 per 2-fold increase in bedroom floor mouse allergen). Other indoor exposures (cockroach, cat, dog, dust mite, particulate matter, and nicotine) were not associated with air trapping or airflow limitation. CONCLUSION: Mouse allergen exposure, but not other indoor exposure, was associated with air trapping in urban children with asthma.

Comprehensive home environmental intervention did not reduce allergen concentrations or controller medication requirements among children in Baltimore.

OBJECTIVE: To determine if the addition of home environmental control strategies (ECSs) to controller medication titration reduces asthma controller medication requirements and in-home allergen concentrations among children with persistent asthma in Baltimore City. METHODS: 155 children ages 5-17 with allergen-sensitized asthma were enrolled in a 6-month randomized clinical trial of multifaceted, individually-tailored ECS plus asthma controller medication titration compared to controller medication titration alone. Participants had to meet criteria for persistent asthma and have had an exacerbation in the previous 18 months. Allergen sensitization (mouse, cockroach, cat, dog, dust mite) was assessed at baseline and home dust allergen concentrations were measured at baseline, 3 and 6 months. ECS was delivered 3-4 times over the trial. Asthma controller medication was titrated using a guidelines-based algorithm at baseline, 2, 4, and 6 months. The primary outcome was controller medication treatment step at 6 months (0-6, as-needed albuterol to high-dose ICS + LABA). RESULTS: The population was predominately Black (90%), on public insurance (93%), and male (61%). The mean age was 10.1 years (SD 3.3). More than 70% were sensitized to a rodent, >50% to cockroach, and 70% were polysensitized. At 6 months, there were no differences in either treatment step (3.8 [SD 1.4] vs. 3.7 [SD 1.5]) or allergen concentrations between groups. CONCLUSION: Among this predominantly low-income, Black pediatric asthma population, the addition of ECS to controller medication titration reduced neither indoor allergen concentrations nor controller medication requirements compared to controller medication titration alone.

Home Dust Allergen Exposure Is Associated with Outcomes among Sensitized Individuals with Chronic Obstructive Pulmonary Disease.

Rationale: Environmental exposures have been associated with adverse outcomes in chronic obstructive pulmonary disease (COPD). Approximately one-third of individuals with COPD have allergic sensitization, but it is unknown whether exposure to allergens in the home is associated with outcomes. Objectives: To determine the prevalence and associations of allergen sensitization with exposure to common indoor allergens with symptoms and exacerbation risk in COPD. Methods: Allergen sensitization to five common indoor allergens was assessed in former smokers with COPD. Home settled dust was assessed for presence of corresponding allergens. Sensitization and exposure status was determined and associations evaluated in adjusted models with longitudinal outcomes including symptoms, lung function, and exacerbations. Interactions were assessed between sensitization/exposure status and lung function. Measurements and Main Results: One hundred eighty-three individuals studied were on average 67.3 years of age (SD, 8.22) with average FEV1 of 53.2% (SD, 17.6%). Seventy-seven percent of participants were exposed to at least one tested allergen, and 17% had sensitization with corresponding allergen exposure. After adjustment, sensitization with exposure was associated with lower lung function (ß, -8.29; 95% confidence interval [CI], -14.80 to -1.77), higher St. George's Respiratory Questionnaire Total Score (ß, 6.71; 95% CI, 0.17 to 13.25), and higher exacerbation risk (odds ratio, 2.31; 95% CI, 1.11 to 4.79). Associations appeared to be more pronounced among individuals with lower lung function. Conclusions: Allergen exposures are common in COPD and associated with adverse outcomes among those with concomitant allergen sensitization. This study establishes allergens as an important home exposure that potentially could be addressed with comprehensive home environmental modification strategies to improve COPD outcomes.

Randomized Clinical Trial of Air Cleaners to Improve Indoor Air Quality and Chronic Obstructive Pulmonary Disease Health: Results of the CLEAN AIR Study.

Rationale: Indoor particulate matter is associated with worse chronic obstructive pulmonary disease (COPD) outcomes. It remains unknown whether reductions of indoor pollutants improve respiratory morbidity. Objectives: To determine whether placement of active portable high-efficiency particulate air cleaners can improve respiratory morbidity in former smokers. Methods: Eligible former smokers with moderate-to-severe COPD received active or sham portable high-efficiency particulate absolute air cleaners and were followed for 6 months in this blinded randomized controlled trial. The primary outcome was 6-month change in St. George's Respiratory Questionnaire (SGRQ). Secondary outcomes were exacerbation risk, respiratory symptoms, rescue medication use, and 6-minute-walk distance (6MWD). Intention-to-treat analysis included all subjects, and per-protocol analysis included adherent participants (greater than 80% use of air cleaner). Measurements and Main Results: A total of 116 participants were randomized, of which 84.5% completed the study. There was no statistically significant difference in total SGRQ score, but the active filter group had greater reduction in SGRQ symptom subscale (ß, -7.7 [95% confidence interval (CI), -15.0 to -0.37]) and respiratory symptoms (Breathlessness, Cough, and Sputum Scale, ß, -0.8 [95% CI, -1.5 to -0.1]); and lower rate of moderate exacerbations (incidence rate ratio, 0.32 [95% CI, 0.12-0.91]) and rescue medication use (incidence rate ratio, 0.54 [95% CI, 0.33-0.86]) compared with sham group (all P < 0.05). In per-protocol analysis, there was a statistically significant difference in primary outcome between the active filter versus sham group (SGRQ, ß -4.76 [95% CI, -9.2 to -0.34]) and in moderate exacerbation risk, Breathlessness, Cough, and Sputum Scale, and 6MWD. Participants spending more time indoors were more likely to have treatment benefit. Conclusions: This is the first environmental intervention study conducted among former smokers with COPD showing potential health benefits of portable high-efficiency particulate absolute air cleaners, particularly among those with greater adherence and spending a greater time indoors.

A single-center experience of 30-day perioperative and one year clinical outcomes of transcarotid artery revascularization in 100 consecutive patients.

BACKGROUND: Transcarotid Artery Revascularization (TCAR) using the ENROUTE system (Silk Road) has been proposed as a safe and effective alternative to both carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TF-CAS). Two large registries (ROADSTER 1 and ROADSTER 2) have shown that TCAR has acceptable/low rates of perioperative stroke/death. This study will analyze the 30-day perioperative and 1-year clinical outcomes from a single-center. PATIENT POPULATION AND METHODS: This is a retrospective analysis of prospectively collected data from SVS/VQI TCAR surveillance project (TSP) of 100 consecutive patients (102 TCAR procedures) done in our institution. These procedures were done for high-risk patients for CEA, which included anatomical (previous CEA, high cervical lesion, neck radiation, stoma, arch type, etc.), physiological (CHF, severe coronary artery disease, COPD on O2 therapy, etc.) and combined anatomical/physiological reasons. These procedures were done by vascular surgeons after receiving the appropriate training. The perioperative stroke, death, and MI rates were analyzed. Kaplan Meyer analysis was used to estimate rate of freedom from stroke/death and the incidence of ≥50% and ≥80% in-stent restenosis at 1 year. RESULTS: 100 consecutive high-risk patients for CEA included: 38% anatomical, 44% physiological, and 18% combined anatomical and physiological reasons. The mean age was 72.5 years (range 52-90 years). Indications for TCAR were 34% for symptomatic lesions (TIA/stroke) and 66% for asymptomatic lesions. Mean ipsilateral treated stenosis was 80.4%. Contralateral ≥50% stenosis/occlusion was present in 31% of patients. Technical success rate was 100%. 92% had pre-stenting PTA and 26% had post-stenting PTA. The mean flow reversal time was 8.5 min (range 3-26 min). The 30-day perioperative stroke rate was 2.9% (1/67, 1.5% for asymptomatic patients), the stroke/death rate was 2.9%, and stroke/death and MI rate was 3.9% (4/102). Other perioperative complications included cranial nerve injury 3/102 (2.9%), carotid artery dissection (2%), and major hematoma (necessitated operation evacuation) (5.9%). Freedom from stroke rates and stroke/death rates at 1 year were: 90% and 89%. Freedom from ≥50% and ≥80% in-stent restenosis rates at 1 year were 82% and 90%, respectively. None of these restenosis were symptomatic except two (2/13). Freedom from reintervention rate at 1 year was 98%. CONCLUSION: Although the perioperative events were somewhat higher than what has been reported in previous registries, TCAR for patients who are high-risk for CEA has a low perioperative stroke and stroke/death rates with satisfactory outcome at 1 year. Further long-term data is probably needed to verify long-term outcome.

Association of a Housing Mobility Program With Childhood Asthma Symptoms and Exacerbations.

Importance: Structural racism has been implicated in the disproportionally high asthma morbidity experienced by children living in disadvantaged, urban neighborhoods. Current approaches designed to reduce asthma triggers have modest impact. Objective: To examine whether participation in a housing mobility program that provided housing vouchers and assistance moving to low-poverty neighborhoods was associated with reduced asthma morbidity among children and to explore potential mediating factors. Design, Setting, and Participants: Cohort study of 123 children aged 5 to 17 years with persistent asthma whose families participated in the Baltimore Regional Housing Partnership housing mobility program from 2016 to 2020. Children were matched to 115 children enrolled in the Urban Environment and Childhood Asthma (URECA) birth cohort using propensity scores. Exposure: Moving to a low-poverty neighborhood. Main Outcomes: Caregiver-reported asthma exacerbations and symptoms. Results: Among 123 children enrolled in the program, median age was 8.4 years, 58 (47.2%) were female, and 120 (97.6%) were Black. Prior to moving, 89 of 110 children (81%) lived in a high-poverty census tract (>20% of families below the poverty line); after moving, only 1 of 106 children with after-move data (0.9%) lived in a high-poverty tract. Among this cohort, 15.1% (SD, 35.8) had at least 1 exacerbation per 3-month period prior to moving vs 8.5% (SD, 28.0) after moving, an adjusted difference of -6.8 percentage points (95% CI, -11.9% to -1.7%; P = .009). Maximum symptom days in the past 2 weeks were 5.1 (SD, 5.0) before moving and 2.7 (SD, 3.8) after moving, an adjusted difference of -2.37 days (95% CI, -3.14 to -1.59; P < .001). Results remained significant in propensity score-matched analyses with URECA data. Measures of stress, including social cohesion, neighborhood safety, and urban stress, all improved with moving and were estimated to mediate between 29% and 35% of the association between moving and asthma exacerbations. Conclusions and Relevance: Children with asthma whose families participated in a program that helped them move into low-poverty neighborhoods experienced significant improvements in asthma symptom days and exacerbations. This study adds to the limited evidence suggesting that programs to counter housing discrimination can reduce childhood asthma morbidity.

Risk factors for meticillin-resistant Staphylococcus aureus (MRSA) carriage in MRSA-exposed household pets.

BACKGROUND: Household pets can carry meticillin-resistant Staphylococcus aureus (MRSA) introduced to the home by their human companions. Specific factors promoting pet carriage of this pathogen have not been fully elucidated. OBJECTIVE: This study evaluated MRSA cultured from pets and the home environment in households where a human infected with MRSA had been identified, and aimed to determine potential risk factors for pet MRSA carriage. MATERIALS AND METHODS: Humans diagnosed with community-associated MRSA (CA-MRSA) skin or soft-tissue infection (SSTI) in the mid-Atlantic United States were identified. One hundred forty-two dogs and cats from 57 affected households were identified of which 134 (94.4%) pets and the household environment were sampled for bacterial culture, PCR confirmation and spa-typing for MRSA strain determination. Samples were obtained 3 months later from 86 pets. RESULTS: At baseline, 12 (9.0%) pets carried MRSA. Potential risk factors associated with carriage included pet bed (environmental) MRSA contamination, flea infestation and prior antimicrobial use in the pet. Pets tended to carry human-adapted MRSA strains and spa-types of MRSA isolates cultured from pets were concordant with strains cultured from the home environment in seven of eight homes (87.5%) at baseline. CONCLUSIONS AND CLINICAL RELEVANCE: Results may inform risk-based veterinary clinical recommendations and provide evidence for selective pet testing as a possible alternative to early removal of pets from the homes of humans infected with MRSA. MRSA contamination of the home environment is likely an important risk factor for pet MRSA carriage, and household interventions should be considered to reduce risk of MRSA carriage in exposed pets.

Critical analysis of vertebral artery flow patterns/subclavian steal detected by cerebrovascular duplex ultrasound examinations and its clinical implications.

BACKGROUND: The prevalence of subclavian steal (defined as retrograde/bidirectional vertebral artery flow) in the general population and in patients undergoing cerebrovascular duplex ultrasound (CDUS) examinations is variable. This is the largest study to date to analyze the incidence of duplex-suggested subclavian steal in 5615 CDUS examinations over a 1-year period and to examine its clinical implications. PATIENT POPULATION AND METHODS: All consecutive CDUS examinations performed over a 1-year period were analyzed for the presence of subclavian steal. Indications of testing, presence of posterior cerebral circulation/subclavian steal symptoms, and any interventions for subclavian steal were analyzed. RESULTS: A total of 171 of 5615 (3.1%) CDUS examinations were found to have subclavian steal (duplex-suggested). One hundred seventeen (2.1%) had retrograde flow and 54 (1%) had bidirectional flow. Of 171, 104 (60.8%) were left sided. Indications for CDUS were post-carotid endarterectomy/carotid artery stenting surveillance in 39 patients (22.8%), surveillance for progression of carotid stenosis in 76 patients (44.4%), transient ischemic attack/stroke in 26 patients (15%), asymptomatic screening/carotid bruit in 18 patients (10.5%), and isolated posterior cerebral circulation symptoms in 12 patients (7%). A total of 63% patients had associated >50% carotid stenosis. The mean arm Doppler pressure gradient was 32.2 mm Hg for asymptomatic patients vs 37 mm Hg for patients with posterior circulation symptoms (P = .3254). There were significant differences between the mean systolic arm pressure for patients with retrograde vs antegrade vs bidirectional flow (105 mm Hg vs 146 mm Hg vs 134 mm Hg, respectively, P < .0001). All patients with retrograde flow had >50% subclavian stenosis or occlusion (100 of 117 had subtotal/total occlusion) except for one patient. Meanwhile, 52 of 54 patients with bidirectional flow had >50% subclavian stenosis (6 of 54 with subtotal/total occlusion), whereas two patients were normal/<50% stenosis (P < .0001). Overall, 26 of 171 patients (15.2%) had interventions for disabling symptoms. Eleven of 26 of all interventions were for disabling arm claudication, and only 10 of 171 patients (5.8%) were intervened for disabling posterior circulation symptoms with complete resolution of symptoms in all except one. At a late follow-up with a mean of 18 months (range: 1-37 months), there was no late major stroke with only two lacunar infarcts (not subclavian steal related). There were also seven late deaths, none stroke related. CONCLUSIONS: The incidence of subclavian steal in patients who undergo CDUS is relatively rare. Most of these patients are asymptomatic and can be treated conservatively, and only a few may need intervention for disabling symptoms with good symptom resolution.

Clinical Outcome of Drug-Eluted Stenting (Zilver PTX) in Patients With Femoropopliteal Occlusive Disease a Single Center Experience.

BACKGROUND: Few industry sponsored trials reported satisfactory outcomes in the use of drug-eluting stents (DES) for treatment of femoropopliteal arterial disease. This study analyzed the early/late clinical outcome from a real world single center. PATIENT POPULATIONS/METHODS: A total of 115 limbs treated with Zilver PTX were analyzed for: major adverse limb event (MALE: above ankle limb amputation/major intervention at 1 year), major adverse events (MAEs; death, amputation, and target lesion thrombosis/reintervention), primary patency (based on duplex ultrasound ± ankle brachial indexes), limb salvage, and amputation free survival rates (AFS) at 1 and 2 years. RESULTS: Indications included claudication in 32% and critical limb threatening ischemia (CLTI) in 68%. Lesions treated included: superficial femoral artery (SFA) 66%, both SFA and popliteal artery (PA) 19% and PA 15%. Mean lesion length was 21 cm and 68% had total occlusion. 45% were Trans-Atlantic Inter-Society Consensus (TASC) TASC II D lesions and 55% A-C lesions. Mean follow-up was 18.4 months (1-76 months). Perioperative major morbidity rate was 8.7% with 0% mortality. MALE rate at 1 year was 17% (13.5% for claudication vs 19.2% for CLTI, p=0.4499). MAE rate was 30% for claudication versus 52% for CLTI (p=0.0392). Overall primary patency rates at 1 and 2 years were 75% and 54% (86% and 71% for claudication vs 70% and 46% for CLTI, respectively, p=0.0213). Primary patency rates at 1 and 2 years were 94% and 88% for TASC A-C lesions versus 50% and 16% for TASC D lesions (p<0.0001). Overall freedom from MALE rate at 1 and 2 years were 85% and 79% (86% and 86% for claudication vs 84% and 74% for CLTI, p=0.2391). These rates were 96% and 93% for TASC A-C lesions versus 70% and 50% for D lesions, respectively (p<0.0001). Limb salvage rates at 1 and 2 years were 93% and 86% (100% and 100% for claudication vs 89% and 78% for CLTI, p=0.012). Overall AFS rates at 1 and 2 years were 79% and 71% (93% and 82% for TASC A-C vs 59% and 59% for D lesions, p=0.001). CONCLUSION: Clinical outcomes after DES (Zilver PTX) in femoropopliteal arterial lesions were satisfactory for TASC A-C lesions but inferior/unsatisfactory for TASC D lesions.

Microbiome alterations associated with phthalate exposures in a US-based sample of Latino workers.

Low-wage service sector jobs are largely occupied by racial/ethnic minority workers who often experience an increased risk of elevated chemical exposures, including chemicals like phthalates, compared to the general public. Phthalates have been linked with adverse health effects, including increased risk of atopy and asthma. An important etiological component in respiratory disease, including asthma, is the role of the upper respiratory microbiota in atopic disease development. However, it is unclear how the upper respiratory microbiome is affected by chemical exposures, and how this may impact respiratory outcomes. As Latino workers are often disproportionately exposed to increased concentrations of chemicals and Hispanics have higher rates of adverse respiratory health conditions such as asthma, the aim of this pilot study was to evaluate the effects of 10 unique phthalate urinary biomarkers on the 16S rRNA nasal microbiome. Nasal and urinary samples were collected from 20 facility workers (plumbers, landscapers, electricians) and 20 custodial workers. Our analysis revealed altered microbial composition and diversity according to phthalate urinary biomarker concentration within the two worker groups. Higher urinary biomarker concentrations of select phthalates (MBP, MBIP, and ∑DEHP) were associated with increased Moraxella relative abundance, which has been positively associated with asthma. Within-sample alpha diversity levels were decreased in facility workers and were generally inversely associated with most phthalate urinary biomarker concentrations. Our research suggests that exposure to chemicals in this vulnerable worker group may impact the respiratory microbiome, which may increase risk of development of adverse health conditions. Further research is warranted to refine the mechanistic pathways that underpin the relationships between phthalate exposures and respiratory microbial communities to provide key insights on respiratory pathologies and, most importantly, to identify modifiable risk factors that can be used to direct mitigation efforts aimed at ameliorating the harmful effects of chemical exposures in this understudied occupational population.

Microbiome alterations from volatile organic compounds (VOC) exposures among workers in salons primarily serving women of color.

Salon workers, especially those serving an ethnically and racially diverse clientele (i.e., Black/Latina), may experience disparately high levels of workplace exposures to respiratory irritants, including volatile organic compounds (VOCs). Salon workers are also reported to have a greater risk of developing respiratory conditions compared to the general population. Emerging evidence suggests that occupational chemical exposures may alter the human microbiome and that these alterations may be an important mechanism by which workplace VOC exposures adversely impact respiratory health. This preliminary research investigated the potential effects of 28 VOC urinary biomarkers on the 16S rRNA nasal microbiome in 40 workers from salons primarily serving women of color (Black and Dominican salons) compared to office workers. Our exploratory analysis revealed significant differences in microbial composition by worker group; namely dissimilar levels of Staphylococcus species (S. epidermidis and S. aureus, specifically) in salon workers compared to office workers, and higher alpha diversity levels in workers in Dominican salons compared to workers in Black salons. Within-sample alpha diversity levels tended to be decreased with higher VOC urinary biomarker concentrations, significantly for carbon disulfide, acrolein, acrylonitrile, crotonaldehyde, and vinyl chloride biomarkers. Our research highlights that occupational exposures, particularly to chemicals like VOCs, can impact the respiratory microbiome in the vulnerable salon worker group. Further understanding of the potential effects of chemical mixtures on microbial composition may provide key insights to respiratory health and other adverse health outcomes, as well as direct prevention efforts in this largely historically understudied occupational population.

Application of Markov models to predict changes in nasal carriage of Staphylococcus aureus among industrial hog operations workers.

Industrial hog operation (IHO) workers can be occupationally exposed to Staphylococcus aureus and may carry the bacteria in their nares. Workers may persistently carry S. aureus or transition between different states of nasal carriage over time: no nasal carriage, nasal carriage of a human-associated strain, and nasal carriage of a livestock-associated strain. We developed a mathematical model to predict the proportion of IHO workers in each nasal carriage state over time, accounting for IHO worker mask use. We also examined data sufficiency requirements to inform development of models that produce reliable predictions. We used nasal carriage data from a cohort of 101 IHO workers in North Carolina, sampled every 2 weeks for 4 months, to develop a three-state Markov model that describes the transition dynamics of IHO worker nasal carriage status over the study period and at steady state. We also stratified models by mask use to examine their impact on worker transition dynamics. If conditions remain the same, our models predicted that 49.1% of workers will have no nasal carriage of S. aureus, 28.2% will carry livestock-associated S. aureus, and 22.7% will carry human-associated S. aureus at steady state. In stratified models, at steady state, workers who reported only occasional mask (<80% of the time) use had a higher predicted proportion of individuals with livestock-associated S. aureus nasal carriage (39.2%) compared to workers who consistently (≥80% of the time) wore a mask (15.5%). We evaluated the amount of longitudinal data that is sufficient to create a Markov model that accurately predicts future nasal carriage states by creating multiple models that withheld portions of the collected data and compared the model predictions to observed data. Our data sufficiency analysis indicated that models created with a small subset of the dataset (approximately 1/3 of observed data) perform similarly to models created using all observed data points. Markov models may have utility in predicting worker health status over time, even when limited longitudinal data are available.

Transmission of Antimicrobial-Resistant Staphylococcus aureus Clonal Complex 9 between Pigs and Humans, United States.

Transmission of livestock-associated Staphylococcus aureus clonal complex 9 (LA-SA CC9) between pigs raised on industrial hog operations (IHOs) and humans in the United States is poorly understood. We analyzed whole-genome sequences from 32 international S. aureus CC9 isolates and 49 LA-SA CC9 isolates from IHO pigs and humans who work on or live near IHOs in 10 pig-producing counties in North Carolina, USA. Bioinformatic analysis of sequence data from the 81 isolates demonstrated 3 major LA-SA CC9 clades. North Carolina isolates all fell within a single clade (C3). High-resolution phylogenetic analysis of C3 revealed 2 subclades of intermingled IHO pig and human isolates differing by 0-34 single-nucleotide polymorphisms. Our findings suggest that LA-SA CC9 from pigs and humans share a common source and provide evidence of transmission of antimicrobial-resistant LA-SA CC9 between IHO pigs and humans who work on or live near IHOs in North Carolina.

Use of drug-eluting stents in patients with critical limb ischemia and infrapopliteal arterial disease: a real-world single-center experience.

BACKGROUND: Although no drug-eluting stent (DES) has been approved by the Food and Drug Administration to treat infrapopliteal arterial disease, several industry-sponsored trials have reported the outcomes with the use of paclitaxel or sirolimus DESs. To the best of our knowledge, only one study to date has reported on the use of everolimus DESs for infrapopliteal arterial disease. In the present study, we analyzed the clinical outcomes with everolimus DESs in our real-world, single-center experience. METHODS: A total of 107 limbs with critical limb threatening ischemia (98 patients; 118 lesions) treated with DESs (Xience; Abbott Vascular, Santa Clara, Calif) were analyzed. The postoperative early outcomes, major adverse limb events (above the ankle limb amputation or major intervention at 1 year), and major adverse events (death, amputation, target lesion thrombosis or reintervention) were analyzed. Kaplan-Meier analysis was used to estimate the primary patency rates (using duplex ultrasound), amputation-free rates, and amputation-free survival rates. RESULTS: Of the 118 lesions treated, 33% were in the anterior tibial artery, 28% were in the tibioperoneal (TP) artery, 21% were in the posterior tibial artery, 8% were in the peroneal artery, 5% were in the TP/posterior tibial artery, 4% were in the TP artery/PA, and 1% were in the TP/anterior tibial artery. The mean lesion length was 41 mm, and 59% were totally occluded (41% stenotic). The mean follow-up was 18.5 months (range, 1-70 months). The overall postoperative complication rate was 11% (2% major amputations), with 2% mortality. Late symptom improvement of one or more Rutherford category was obtained in 71%. The major adverse events rate at 30 days and 1 year was 12% and 45%, respectively. The major adverse limb events rate at 1 year was 15%. The overall primary patency rate was 42%. The primary patency rate at 1, 2, and 3 years was 57%, 45%, and 33%, respectively. The major amputation-free and overall amputation-free survival rates were 87%, 80%, and 77% and 76%, 65%, and 61% at 1, 2, and 3 years, respectively. CONCLUSIONS: The clinical outcomes after DES (Xience; Abbott Vascular) for infrapopliteal lesions were somewhat satisfactory at 1 year but inferior to the previously reported outcomes, especially at 3 years. Further data with long-term follow-up are needed.

Personal protective equipment use during industrial hog operation work activities and acute lung function changes in a prospective worker cohort, North Carolina 2014-2015.

INTRODUCTION: Occupational activities related to industrial hog operation (IHO) worker lung function are not well defined. Therefore, we aimed to identify IHO work activities associated with diminished respiratory function and the effectiveness, if any, of personal protective equipment (PPE) use on IHOs. METHODS: From 2014 to 2015, 103 IHO workers were enrolled and followed for 16 weeks. At each biweekly visit, work activities and PPE use were self-reported via questionnaire and lung function measurements were collected via spirometry. Generalized linear and linear fixed-effects models were fitted to cross-sectional and longitudinal data. RESULTS: Increasing years worked on an IHO were associated with diminished lung function, but baseline and longitudinal work activities were largely inconsistent in direction and magnitude. Unexpectedly, a -0.3 L (95% confidence interval: -0.6, -0.04) difference in forced expiratory volume in the first second (FEV1 ) was estimated when workers wore PPE consistently (≥80% of the time at work) versus those weeks they did not. In post-hoc analyses, we found that coveralls and facemasks were worn less consistently when workers experienced worse barn conditions and had more contact with pigs, but coveralls were worn more consistently as cleaning activities increased. CONCLUSIONS: Similar to past studies, baseline estimates were likely obscured by healthy worker effect bias, but showed decrements in worker lung function as years of work increased. A challenge to disentangling the effect of work activities on lung function was the discovery that IHO workers used PPE differently according to the work task. These data suggest that interventions may be targeted toward improving barn conditions so that workers can consistently utilize IHO-provided PPE.

Self-reported work activities, eye, nose, and throat symptoms, and respiratory health outcomes among an industrial hog operation worker cohort, North Carolina, USA.

INTRODUCTION: Respiratory disease among industrial hog operation (IHO) workers is well documented; however, it remains unclear whether specific work activities are more harmful and if personal protective equipment (PPE), as used by workers, can reduce adverse health outcomes. METHODS: IHO workers (n = 103) completed baseline and up to eight bi-weekly study visits. Workers reported typical (baseline) and transient (bi-weekly) work activities, PPE use, and physical health symptoms. Baseline and longitudinal associations were assessed using generalized logistic and fixed-effects logistic regression models, respectively. RESULTS: At baseline, reports of ever versus never drawing pig blood, applying pesticides, and increasing years worked at any IHO were positively associated with reports of eye, nose, and/or throat irritation. Over time, transient exposures, associated with dustiness in barns, cleaning of barns, and pig contact were associated with increased odds of sneezing, headache, and eye or nose irritation, particularly in the highest categories of exposure. When PPE was used, workers had lower odds of symptoms interfering with sleep (odds ratio [OR]: 0.1; 95% confidence interval [CI]: 0.01-0.8), and eye or nose irritation (OR: 0.1; 95% CI: 0.02-0.9). Similarly, when they washed their hands eight times or more per shift (median frequency) versus less frequently, the odds of any respiratory symptom were reduced (OR: 0.3; 95% CI: 0.1-0.8). CONCLUSIONS: In this healthy volunteer worker population, increasingly unfavorable IHO activities were associated with self-reported eye, nose, throat, and respiratory health symptoms. Strong protective associations were seen between PPE use and handwashing and the odds of symptoms, warranting further investigation.

External Societal Costs of Antimicrobial Resistance in Humans Attributable to Antimicrobial Use in Livestock.

Antimicrobial use (AMU) in animal agriculture contributes to antimicrobial resistance (AMR) in humans, which imposes significant health and economic costs on society. Economists call these costs negative externalities, societal costs that are not properly reflected in market prices. We review the relevant literature and develop a model to quantify the external costs of AMU in animal agriculture on AMR in humans. Parameters required for this estimate include (a) the health and economic burden of AMR in humans,(b) the impact of AMU in animal agriculture on AMR in animals, (c) the fraction of AMR in humans attributable to animal agriculture, and (d) AMU in animals. We use a well-documented historic case to estimate an externality cost of about US$1,500 per kilogram of fluoroquinolones administered in US broiler chicken production. Enhanced data collection, particularly on the third and fourth parameters, is urgently needed to quantify more fully the externalities of AMU in animal agriculture.

Contribution of Time, Taxonomy, and Selective Antimicrobials to Antibiotic and Multidrug Resistance in Wastewater Bacteria.

The use of nontherapeutic broad-spectrum antimicrobial agents triclosan (TCS) and benzalkonium chloride (BC) can contribute to bacterial resistance to clinically relevant antibiotics. Antimicrobial-resistant bacteria within wastewater may reflect the resistance burden within the human microbiome, as antibiotics and pathogens in wastewater can track with clinically relevant parameters during perturbations to the community. In this study, we monitored culturable and resistant wastewater bacteria and cross-resistance to clinically relevant antibiotics to gauge the impact of each antimicrobial and identify factors influencing cross-resistance profiles. Bacteria resistant to TCS and BC were isolated from wastewater influent over 21 months, and cross-resistance, taxonomy, and monthly changes were characterized under both antimicrobial selection regimes. Cross-resistance profiles from each antimicrobial differed within and between taxa. BC-isolated bacteria had a significantly higher prevalence of resistance to "last-resort antibiotic" colistin, while isolates resistant to TCS exhibited higher rates of multidrug resistance. Prevalence of culturable TCS-resistant bacteria decreased over time following Food and Drug Administration (FDA) TCS bans. Cross-resistance patterns varied according to sampling date, including among the most clinically important antibiotics. Correlations between strain-specific resistance profiles were largely influenced by taxonomy, with some variations associated with sampling date. The results reveal that time, taxonomy, and selection by TCS and BC impact features of cross-resistance patterns among diverse wastewater microorganisms, which could reflect the variety of factors influencing resistance patterns relevant to a community microbiome.

In Utero Exposure to Bisphenol a Promotes Mammary Tumor Risk in MMTV-Erbb2 Transgenic Mice Through the Induction of ER-erbB2 Crosstalk.

Bisphenol A (BPA) is the most common environmental endocrine disrupting chemical. Studies suggest a link between perinatal BPA exposure and increased breast cancer risk, but the underlying mechanisms remain unclear. This study aims to investigate the effects of in utero BPA exposure on mammary tumorigenesis in MMTV-erbB2 transgenic mice. Pregnant mice were subcutaneously injected with BPA (0, 50, 500 ng/kg and 250 µg/kg BW) daily between gestational days 11-19. Female offspring were examined for mammary tumorigenesis, puberty onset, mammary morphogenesis, and signaling in ER and erbB2 pathways. In utero exposure to low dose BPA (500 ng/kg) induced mammary tumorigenesis, earlier puberty onset, increased terminal end buds, and prolonged estrus phase, which was accompanied by proliferative mammary morphogenesis. CD24/49f-based FACS analysis showed that in utero exposure to 500 ng/kg BPA induced expansion of luminal and basal/myoepithelial cell subpopulations at PND 35. Molecular analysis of mammary tissues at PND 70 showed that in utero exposure to low doses of BPA induced upregulation of ERα, p-ERα, cyclin D1, and c-myc, concurrent activation of erbB2, EGFR, erbB-3, Erk1/2, and Akt, and upregulation of growth factors/ligands. Our results demonstrate that in utero exposure to low dose BPA promotes mammary tumorigenesis in MMTV-erbB2 mice through induction of ER-erbB2 crosstalk and mammary epithelial reprogramming, which advance our understanding of the mechanism associated with in utero exposure to BPA-induced breast cancer risk. The studies also support using MMTV-erbB2 mouse model for relevant studies.