Time-series analysis of satellite-derived fine particulate matter pollution and asthma morbidity in Jackson, MS.

In order to examine associations between asthma morbidity and local ambient air pollution in an area with relatively low levels of pollution, we conducted a time-series analysis of asthma hospital admissions and fine particulate matter pollution (PM2.5) in and around Jackson, MS, for the period 2003 to 2011. Daily patient-level records were obtained from the Mississippi State Department of Health (MSDH) Asthma Surveillance System. Patient geolocations were aggregated into a grid with 0.1° × 0.1° resolution within the Jackson Metropolitan Statistical Area. Daily PM2.5 concentrations were estimated via machine-learning algorithms with remotely sensed aerosol optical depth and other associated parameters as inputs. Controlling for long-term temporal trends and meteorology, we estimated a 7.2% (95% confidence interval 1.7-13.1%) increase in daily all-age asthma emergency room admissions per 10 µg/m3 increase in the 3-day average of PM2.5 levels (current day and two prior days). Stratified analyses reveal significant associations between asthma and 3-day average PM2.5 for males and blacks. Our results contribute to the current epidemiologic evidence on the association between acute ambient air pollution exposure and asthma morbidity, even in an area characterized by relatively good air quality.

Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study.

BACKGROUND: Results from retrospective studies indicate that selecting individuals for low-dose CT lung cancer screening on the basis of a highly predictive risk model is superior to using criteria similar to those used in the National Lung Screening Trial (NLST; age, pack-year, and smoking quit-time). We designed the Pan-Canadian Early Detection of Lung Cancer (PanCan) study to assess the efficacy of a risk prediction model to select candidates for lung cancer screening, with the aim of determining whether this approach could better detect patients with early, potentially curable, lung cancer. METHODS: We did this single-arm, prospective study in eight centres across Canada. We recruited participants aged 50-75 years, who had smoked at some point in their life (ever-smokers), and who did not have a self-reported history of lung cancer. Participants had at least a 2% 6-year risk of lung cancer as estimated by the PanCan model, a precursor to the validated PLCOm2012 model. Risk variables in the model were age, smoking duration, pack-years, family history of lung cancer, education level, body-mass index, chest x-ray in the past 3 years, and history of chronic obstructive pulmonary disease. Individuals were screened with low-dose CT at baseline (T0), and at 1 (T1) and 4 (T4) years post-baseline. The primary outcome of the study was incidence of lung cancer. This study is registered with ClinicalTrials.gov, number NCT00751660. FINDINGS: 7059 queries came into the study coordinating centre and were screened for PanCan risk. 15 were duplicates, so 7044 participants were considered for enrolment. Between Sept 24, 2008, and Dec 17, 2010, we recruited and enrolled 2537 eligible ever-smokers. After a median follow-up of 5·5 years (IQR 3·2-6·1), 172 lung cancers were diagnosed in 164 individuals (cumulative incidence 0·065 [95% CI 0·055-0·075], incidence rate 138·1 per 10 000 person-years [117·8-160·9]). There were ten interval lung cancers (6% of lung cancers and 6% of individuals with cancer): one diagnosed between T0 and T1, and nine between T1 and T4. Cumulative incidence was significantly higher than that observed in NLST (4·0%; p<0·0001). Compared with 593 (57%) of 1040 lung cancers observed in NLST, 133 (77%) of 172 lung cancers in the PanCan Study were early stage (I or II; p<0·0001). INTERPRETATION: The PanCan model was effective in identifying individuals who were subsequently diagnosed with early, potentially curable, lung cancer. The incidence of cancers detected and the proportion of early stage cancers in the screened population was higher than observed in previous studies. This approach should be considered for adoption in lung cancer screening programmes. FUNDING: Terry Fox Research Institute and Canadian Partnership Against Cancer.

Probability of cancer in pulmonary nodules detected on first screening CT.

BACKGROUND: Major issues in the implementation of screening for lung cancer by means of low-dose computed tomography (CT) are the definition of a positive result and the management of lung nodules detected on the scans. We conducted a population-based prospective study to determine factors predicting the probability that lung nodules detected on the first screening low-dose CT scans are malignant or will be found to be malignant on follow-up. METHODS: We analyzed data from two cohorts of participants undergoing low-dose CT screening. The development data set included participants in the Pan-Canadian Early Detection of Lung Cancer Study (PanCan). The validation data set included participants involved in chemoprevention trials at the British Columbia Cancer Agency (BCCA), sponsored by the U.S. National Cancer Institute. The final outcomes of all nodules of any size that were detected on baseline low-dose CT scans were tracked. Parsimonious and fuller multivariable logistic-regression models were prepared to estimate the probability of lung cancer. RESULTS: In the PanCan data set, 1871 persons had 7008 nodules, of which 102 were malignant, and in the BCCA data set, 1090 persons had 5021 nodules, of which 42 were malignant. Among persons with nodules, the rates of cancer in the two data sets were 5.5% and 3.7%, respectively. Predictors of cancer in the model included older age, female sex, family history of lung cancer, emphysema, larger nodule size, location of the nodule in the upper lobe, part-solid nodule type, lower nodule count, and spiculation. Our final parsimonious and full models showed excellent discrimination and calibration, with areas under the receiver-operating-characteristic curve of more than 0.90, even for nodules that were 10 mm or smaller in the validation set. CONCLUSIONS: Predictive tools based on patient and nodule characteristics can be used to accurately estimate the probability that lung nodules detected on baseline screening low-dose CT scans are malignant. (Funded by the Terry Fox Research Institute and others; ClinicalTrials.gov number, NCT00751660.).

Remembering Dr. Frederick Griffith Pearson.

SUMMARY: Canada has lost a remarkable surgeon and leader. Dr. Frederick Griffith "Griff" Pearson, aged 90, died in Kitchener, Ont., on Aug. 10, 2016, surrounded by his wife, Hilppa Pearson, and his family.

Acute bacterial skin and skin structure infections (ABSSSI): practice guidelines for management and care transitions in the emergency department and hospital.

BACKGROUND: Acute bacterial skin and skin structure infections (ABSSSI), formally referred to as complicated skin and soft tissue infections, include infections with resistance to previously effective antimicrobials. Increasing dramatically in incidence, they have become a challenging medical problem associated with high direct and indirect costs to both the medical system and society. OBJECTIVES: To describe the burden of ABSSSI and to explore multidisciplinary approaches to its management and new treatments that can be initiated in the emergency department. DISCUSSION: We offer a best practice model aimed at providing risk-stratified and convenient care for ABSSSI at the lowest possible cost, while minimizing complications, readmissions, and inappropriate antibiotic use. In doing so, we focus on the care provided by emergency physicians and hospitalists and the transition of management between them for inpatient care, as well as the facilitation of observation or direct-to-outpatient care for suitable patients. CONCLUSIONS: A standard, consistent, and multidisciplinary approach to ABSSSI can streamline care, reduce admissions, support antimicrobial stewardship, and improve clinical and resource consumption outcomes.

Alveolar macrophage proteinase/antiproteinase expression in lung function and emphysema.

Alveolar macrophages play an important role in chronic obstructive pulmonary disease via production of matrix metalloproteinases (MMPs) and cathepsins as well as their inhibitors, tissue inhibitors of metalloproteinases and cystatin C. We hypothesised that expression levels of these molecules by alveolar macrophages at baseline and after stimulation would be influenced by genotype and associated with chronic obstructive pulmonary disease phenotypes. Quantitative PCR and ELISAs/gelatine zymography were used to investigate expression levels of mRNA and protein, respectively. The relationships of expression with genotype, pulmonary function and emphysema were analysed. The results showed that basal expression level of MMP12 mRNA was inversely related to the diffusing capacity of the lung for carbon monoxide/alveolar volume and to forced expiratory volume in 1 s/forced vital capacity after correction for multiple comparisons. The expression level of MMP12 protein stimulated with lipopolysaccharide was also inversely related to the diffusing capacity of the lung for carbon monoxide/alveolar volume and was positively related to the extent of emphysema. The basal expression of MMP1 mRNA was positively correlated with the extent of emphysema. Cathepsin L protein level was positively associated with forced expiratory volume in 1 s % predicted. We conclude that increased MMP12 and MMP1 expression may play a role in the pathogenesis of emphysema. Cathepsin L and MMP9 may be involved in the development of airflow limitation.

Daptomycin-induced rhabdomyolysis and acute liver injury.

Daptomycin use is a known cause of rhabdomyolysis; its role in liver injury is less certain. We report a case of daptomycin-induced rhabdomyolysis with liver injury. This report indicates a role for liver function monitoring while receiving daptomycin, as well as the importance of promptly considering drug toxicities in acute and emergency care settings.

Expression of matrix metalloproteinase-1 in alveolar macrophages, type II pneumocytes, and airways in smokers: relationship to lung function and emphysema.

BACKGROUND: An imbalance between proteolytic enzymes and their inhibitors is thought to be involved in the pathogenesis of chronic obstructive pulmonary disease. Matrix metalloproteinase-1, also known as interstitial collagenase, has been implicated as a potentially important proteinase in the genesis of chronic obstructive pulmonary disease and, more specifically, emphysema. METHODS: We performed quantitative immunohistochemical assessment of matrix metalloproteinase-1 expression in the resected lung of 20 smokers/ex-smokers who had varying severity of airflow obstruction and emphysema and compared this with the lungs of 5 nonsmokers. Emphysema was measured using a morphometric measure of the lungs' surface area/volume ratio and with qualitative and quantitative computed tomography (CT) measures of emphysema. RESULTS: There were significantly more matrix metalloproteinase-1-expressing alveolar macrophages and type II pneumocytes as well as a greater percentage of small airways that stained positively for matrix metalloproteinase-1 in the lungs of smokers than in those of nonsmokers (p < 0.0001, p < 0.0001, and p = 0.0003, respectively). The extent of staining of type II pneumocytes and airways for matrix metalloproteinase-1 was significantly related to the extent of smoking (p = 0.012 and p = 0.013, respectively). In addition, the extent of matrix metalloproteinase-1 staining of alveolar macrophages was related to the lung surface area/volume ratio and to qualitative estimates of emphysema on CT. CONCLUSION: These findings suggest that cigarette smoking increases expression of matrix metalloproteinase-1 in alveolar macrophages as well as in alveolar and small airway epithelial cells. Smokers who develop emphysema have increased alveolar macrophage expression of matrix metalloproteinase-1.

Donepezil-associated bradyarrhythmia in a patient with dementia with Lewy bodies (DLB).

Dementia with Lewy bodies (DLB) is a neurodegenerative condition that results in loss of mesopontine cholinergic neurons and sympathetic deinnervation. Although acetylcholinesterase inhibitors have been shown to improve cognitive and behavioral deficits in DLB, these patients may be more susceptible to bradyarrhythmic side effects from this class of drugs due to the autonomic insufficiency associated with the disease. We present a patient who experienced a dose-dependent, symptomatic sinus bradyarrhythmia with donepezil doses at and greater than 5 mg. Owing to underlying autonomic dysfunction, patients with DLB may be at increased risk of bradyarrhythmia resulting from treatment with acetylcholinesterase inhibitors.

Lung nodules: CT-guided placement of microcoils to direct video-assisted thoracoscopic surgical resection.

PURPOSE: To prospectively assess the safety and effectiveness of computed tomography (CT)-guided placement of fiber-coated microcoils used to guide video-assisted thoracoscopic surgical (VATS) excision of small peripheral lung nodules, with successful excision as the primary outcome and successful CT-guided microcoil placement and procedural complications as secondary outcomes. MATERIALS AND METHODS: The institutional review board approved the study protocol. Informed consent was obtained from all 69 enrolled patients (30 men, 39 women; mean age, 60.7 years +/- 10.1 [standard deviation]) with 75 nodules. At CT, one end of an 80-mm long, 0.018-inch-diameter fiber-coated microcoil was placed deep to the small peripheral lung nodule, and the other end was coiled in the pleural space. VATS excision of lung tissue, nodules, and the microcoil was performed with fluoroscopic guidance. RESULTS: Seventy-three (97%) 4-24-mm nodules were successfully removed at fluoroscopically guided VATS excision; two nodules could not be removed. CT-guided microcoil placement was successful in all cases; however, two (3%) of 75 coils were displaced at VATS excision. Pneumothorax requiring chest tube placement occurred in two (3%) patients, and asymptomatic hemothorax occurred in one (1%) patient. The microcoil did not impede intraoperative frozen-section histopathologic analysis, which facilitated accurate clinical management in all patients. For 19 (28%) patients, the preoperative treatment plan based on bronchoscopy, needle biopsy, and positron emission tomography findings changed after VATS excision. CONCLUSION: Microcoil localization of small peripheral lung nodules enabled fluoroscopically guided VATS resection of 97% of the nodules, with a low rate of intervention (3%) for procedural complications.

Strategic faculty recruitment increases research productivity within an academic university division.

BACKGROUND: Research is an important mandate for academic surgical divisions. However, there is widespread concern that the current health care climate is leading to a decline in research activity. A University of British Columbia (UBC) academic surgical division attempted to address this concern by strategically recruiting PhD research scientists to prioritize research and develop collaborative research programs. The objective of our study was to determine whether this strategy resulted in increased research productivity. METHODS: We reviewed the UBC Department of Surgery database to assess research funding obtained by the Division of General Surgery for the years 1994-2004. We searched MEDLINE for peer-reviewed publications by faculty members during this period. RESULTS: Research funding increased from a mean of Can$417,292 per year in the 5 years (1994/95-1998/99) before the recruitment of dedicated PhD scientists to a mean of Can$1.3 million per year in the 5 years following the recruitment strategy (1999/2000-2003/04; p = 0.012). Funding for the initial 5 years was Can$2.1 million, including 1 Canadian Institutes of Health Research (CIHR) grant. Funding increased to Can$6.8 million, including 22 CIHR grants over the subsequent 5 years (p < 0.001). Collaborative research led to the awarding of multidisciplinary grants exceeding Can$4 million with divisional members as principle or coprinciple investigators. From 1994/05 to 1998/99, the total number of peer-reviewed publications was 116 (mean 23.2, standard deviation [SD] 7 per year), increasing to 144 from 1999/2000 to 2003/04 (mean 28.8, SD 13 per year). The trend was for publications in journals with higher impact factors in the latter 5-year period. CONCLUSION: Strategic recruitment resulted in increased and sustained research productivity. Interactions between research scientists and clinicians resulted in successful program grant funding support. These results have implications for sustaining the research mission within academic departments of surgery.

Microcoil-Guided Video-Assisted Thoracoscopic Excision of Nodules Suspicious for Metastasis in Patients With Extra-Thoracic Malignancies.

The purpose of this study is to determine the utility of preoperative CT-guided microcoil localization followed by fluoroscopy guided video-assisted thoracoscopic resection in the diagnosis and management of small peripheral pulmonary nodules in patients with extra-thoracic malignancies. This study is a retrospective analysis of prospectively collected data between August 2003 and September 2013. Fifty patients with extra-thoracic malignancies underwent preoperative localization of small indeterminate pulmonary nodules using CT-guided microcoil localization. Nodules were then resected by video-assisted thoracoscopic resection wedge excision and intraoperative fluoroscopy guidance. Univariate and multivariate logistic regression analysis were conducted. Fifty patients with a history of 14 different extra-thoracic cancers (57% female, mean age 62 years) had 55 nodules resected (mean size = 12 mm, depth from visceral pleura = 22 mm). Histology of resected nodules showed metastasis (25 of 50 patients), benign (10 of 50), and (15 of 50) early stage primary lung cancer. Smokers were found 6 times more likely to present with primary lung cancer than metastasis (P < 0.009). CT-guided microcoil localization procedure was successful in all patients with a mean time of 31(10) minutes and allowed successful wedge resection in all cases with no major complications. The mean operative time and fluoroscopy time were 27(12) minutes and 3(5) minutes, respectively. Microcoil-guided thoracoscopic wedge resection was effective in achieving early definitive diagnosis and changed management in 50% of patients with presumed metastasis with minimal morbidity.

Rickettsia parkeri rickettsiosis and its clinical distinction from Rocky Mountain spotted fever.

BACKGROUND: Rickettsia parkeri rickettsiosis, a recently identified spotted fever transmitted by the Gulf Coast tick (Amblyomma maculatum), was first described in 2004. We summarize the clinical and epidemiological features of 12 patients in the United States with confirmed or probable disease attributable to R. parkeri and comment on distinctions between R. parkeri rickettsiosis and other United States rickettsioses. METHODS: Clinical specimens from patients in the United States who reside within the range of A. maculatum for whom an eschar or vesicular rash was described were evaluated by > or =1 laboratory assays at the Centers for Disease Control and Prevention (Atlanta, GA) to identify probable or confirmed infection with R. parkeri. RESULTS: During 1998-2007, clinical samples from 12 patients with illnesses epidemiologically and clinically compatible with R. parkeri rickettsiosis were submitted for diagnostic evaluation. Using indirect immunofluorescence antibody assays, immunohistochemistry, polymerase chain reaction assays, and cell culture isolation, we identified 6 confirmed and 6 probable cases of infection with R. parkeri. The aggregate clinical characteristics of these patients revealed a disease similar to but less severe than classically described Rocky Mountain spotted fever. CONCLUSIONS: Closer attention to the distinct clinical features of the various spotted fever syndromes that exist in the United States and other countries of the Western hemisphere, coupled with more frequent use of specific confirmatory assays, may unveil several unique diseases that have been identified collectively as Rocky Mountain spotted fever during the past century. Accurate assessments of these distinct infections will ultimately provide a more valid description of the currently recognized distribution, incidence, and case-fatality rate of Rocky Mountain spotted fever.

Practical approaches to the surgical management of achalasia.

Achalasia is a primary motor disorder of the esophagus characterized by an abnormal hypertensive, nonrelaxing lower esophageal sphincter (LES) and nonfunctioning, aperistaltic esophageal body resulting in significant regurgitation and dysphagia. The primary goal of treatment is palliation of symptoms. At present, all treatment techniques are directed at relieving the functional obstruction at the level of the LES by disruption or paralysis of the esophageal muscle constituting the LES. Destruction of the LES function also places the patient at risk for pathologic gastroesophageal reflux disease. Therefore, the treatment of patients with achalasia must strike a balance between the relief of dysphagia and potential creation of pathologic gastroesophageal reflux. The advent of laparoscopic esophageal myotomy for the treatment of achalasia over the past decade has resulted in most patients with the disease being referred to surgeons for definitive treatment. At the time of consultation the patient may present with a myriad of symptoms, investigative results, and previous treatments. Based on our experience of over 300 patients treated with surgery at our institution between 1990 and 2007, this review will address the practical problems encountered in the surgical management of achalasia.

Dalbavancin Use for the Treatment of Methicillin-resistant Staphylococcus aureus Pneumonia.

Dalbavancin is a lipoglycopeptide with a long half-life that allows infrequent dosing. It is indicated for the treatment of acute bacterial skin and skin structure infections caused by susceptible organisms, including Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). Although this agent has been used off-label clinically, there are minimal data in infections outside the current indications. We report a case of a 28-year-old nonadherent male with HIV presenting with pneumonia due to MRSA that was treated with dalbavancin. The patient was admitted to the hospital with classic pneumonia symptoms, and sputum cultures and bronchoalveolar lavage grew MRSA. Other infections were ruled out. The patient was initially treated with vancomycin, but subtherapeutic concentrations prompted a change to dalbavancin upon discharge. The patient was readmitted 11 days later with the complaints of hemoptysis and shortness of breath, with unchanged imaging. However, no evidence of MRSA was found at this time. Utility of dalbavancin for other disease states has profound implications, particularly in patients with poor medication adherence.

CT-Directed microcoil localization of small peripheral lung nodules: a feasibility study in pigs.

Platinum microcoils were placed in porcine lungs to determine the feasibility for use as a lung nodule marker. Using computed tomography (CT) guidance, the microcoils were successfully deployed in 17 out of 19 attempts. Coil deployment depth ranged from 7 mm to 34 mm below the pleural surface. Moderate pneumothorax was detected after 3 of 19 microcoil insertions. No hemothorax or significant pulmonary hemorrhage was noted. Fluoroscopic guided thoracoscopic resection was successful in 10 of 12 attempts. Platinum microcoils can be safely and easily deployed into the lung parenchyma with minimal complication risk, and can be used to guide subsequent thoracoscopic wedge resection.

Preoperative computed tomography-guided microcoil localization of small peripheral pulmonary nodules: a prospective randomized controlled trial.

OBJECTIVES: Growing, small, peripheral, pulmonary nodules in patients at high risk for lung cancer lead to requests for video-assisted thoracoscopic (VATS) resection for pathologic diagnosis. The purpose of this randomized controlled trial was to determine if preoperative localization using percutaneously placed computed tomography (CT)-guided platinum microcoils decreases the need for thoracotomy or VATS anatomic resection (segmentectomy/lobectomy) for diagnosis. METHODS: Patients with undiagnosed nodules of 15 mm or less were randomized to either no localization or preoperative microcoil localization. Coils were placed with the distal end deep to the nodule and the superficial end coiled on the visceral pleural surface with subsequent visualization by intraoperative fluoroscopy and VATS. Nodules were removed by VATS wedge excision using endostaplers. The primary outcome was a VATS wedge excision for pathologic diagnosis of the nodule without the need for either thoracotomy or VATS anatomic resection. RESULTS: Sixty patients were randomized and 56 underwent surgery between March 2010 and June 2012. Twenty-nine underwent microcoil localization and 27 did not. The baseline characteristics (age, sex, forced expiratory volume in the first second of expiration, nodule size/depth) were similar. The coil group had a higher rate of successful diagnosis with VATS wedge resection alone (27/29 vs 13/27; P < .001), decreased operative time to nodule excision (37 ± 39 vs 100 ± 67 minutes; P < .001), and reduced stapler firings (3.7 ± 2.0 vs 5.9 ± 31; P = .003) with no difference in total costs. Pathologic diagnoses included 14 benign nodules, 32 primary lung malignancies, and 10 metastases. There were no clinically significant complications related to the coil placement or wedge resection. CONCLUSIONS: Preoperative CT-guided microcoil localization decreases the need for thoracotomy or VATS anatomic resection for the diagnosis of small peripheral pulmonary nodules.

Trichomonas vaginalis: characterization of a family of P-type ATPase genes.

P-type ATPases are ion-transporting pumps that enable organisms to control cellular functions and survive changing environmental conditions by regulating internal ion concentrations. Eight P-type ATPases were identified in the amitochondriate protist Trichomonas vaginalis using polymerase chain reaction (PCR) amplification with oligonucleotide primers that recognize conserved motifs present in all P-type ATPases, the ATP phosphorylation site (DKTGTLT) and the ATP binding site (TGDGVND). Phylogenetic analysis and the presence of conserved motifs in predicted peptide sequences identify the Trichomonas ATPases as a sarcoplasmic-endoplasmic reticulum calcium pump (TVCA1); three additional Ca(2+) transporting pumps (TVCA2-4), three phospholipid translocases (TVAPLT1-3), and one P-type ATPase of unknown transport specificity (TVPATP8). Southern blot analyses indicate that the P-type ATPase genes are not linked and are present in single copy, except TVCA2 and TVCA4 which contain additional copies or closely related homologues within the genome. Transcripts of 3.1 kb for TVCA1, 3.0 kb for TVCA2, 2.9 kb for TVCA3, 4.0 kb for TVAPLT1, 4.2 kb for TVAPLT2, 3.9 kb for TVAPLT3, and 3.1 kb for TVPATP8 were detected by Northern blot analysis. No TVCA4 transcript was observed, however, RT-PCR amplification of a transcript product indicates that TVCA4 is expressed. RNA expression of the Trichomonas ATPases, except TVCA3, was constitutive over a range of environmental conditions. TVCA1, TVAPLT3 and TVPATP8 had the highest levels of RNA expression while TVAPLT1 and TVAPLT2 expression was the lowest.