Abstract Objective There are few studies evaluating whether to proceed with planned resection when a patient with non–small cell lung cancer (NSCLC) unexpectedly is found to have N2 disease at the ...time of thoracoscopy or thoracotomy. To help guide management of this clinical scenario, we evaluated outcomes for patients who were upstaged to pN2 after lobectomy without induction therapy using the National Cancer Data Base (NCDB). Methods Survival of NSCLC patients treated with lobectomy for clinically unsuspected mediastinal nodal disease (cT1-cT3 cN0-cN1, pN2 disease) from 1998-2006 in the NCDB was compared with “suspected” N2 disease patients (cT1-cT3 cN2) who were treated with chemotherapy with or without radiation followed by lobectomy, using matched analysis based on propensity scores. Results Unsuspected pN2 disease was found in 4.4% of patients (2047 out of 46,691) who underwent lobectomy as primary therapy for cT1-cT3 cN0-cN1 NSCLC. The 5-year survival was 42%, 36%, 21%, and 28% for patients who underwent adjuvant chemotherapy (n = 385), chemoradiation (n = 504), radiation (n = 300), and no adjuvant therapy (n = 858), respectively. Five-year survival of the entire unsuspected pN2 cohort was worse than survival of 2302 patients who were treated with lobectomy after induction therapy for clinical N2 disease (30% vs 40%; P < .001), although no significant difference in 5-year survival was found in a matched-analysis of 655 patients from each group (37% vs 37%; P = .95). Conclusions This population-based analysis suggests that, in the setting of unsuspected pN2 NSCLC, proceeding with lobectomy does not appear to compromise outcomes if adjuvant chemotherapy with or without radiation therapy can be administered following surgery.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Abstract Objective Lobectomy is considered optimal therapy for early-stage non–small cell lung cancer, but sublobar wedge resection and stereotactic body radiation therapy are alternative treatments. ...This study compared outcomes between wedge resection and stereotactic body radiotherapy. Methods Overall survival of patients with cT1N0 and tumors ≤2 cm who underwent stereotactic body radiotherapy or wedge resection in the National Cancer Data Base from 2008 to 2011 was assessed via a Kaplan-Meier and propensity score–matched analysis. A center-level sensitivity analysis that used observed/expected mortality ratios was conducted to identify an association between center use of stereotactic body radiotherapy and mortality. Results Of the 6295 patients included, 1778 (28.2%) underwent stereotactic body radiotherapy, and 4517 (71.8%) underwent wedge resection. Stereotactic body radiotherapy was associated with significantly reduced 5-year survival compared with wedge resection in both unmatched analysis (30.9% vs 55.2%, P < .001) and after adjustment for covariates (31.0% vs 49.9%, P < .001). Stereotactic body radiotherapy also was associated with worse overall survival than wedge resection after 2 subgroup analyses of propensity-matched patients ( P < .05 for both). Centers that used stereotactic body radiotherapy more often as opposed to surgery for patients with cT1N0 patients with tumors <2 cm were more likely to have an observed/expected mortality ratio > 1 for 3-year mortality ( P = .034). Conclusions In this national analysis, wedge resection was associated with better survival for stage IA non–small cell lung cancer than stereotactic body radiotherapy.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Summary Background The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such ...patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging. Methods A 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I–III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC). Findings Kaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71·4% (95% CI 60·5–80·0) in low-risk, 58·3% (48·9–66·6) in intermediate-risk, and 49·2% (42·2–55·8) in high-risk patients (ptrend =0·0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74·1% (66·0–80·6) in low-risk, 57·4% (48·3–65·5) in intermediate-risk, and 44·6% (40·2–48·9) in high-risk patients (ptrend <0·0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0·0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages. Interpretation Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection. Funding UCSF Thoracic Oncology Laboratory and Pinpoint Genomics.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
The yeast Saccharomyces cerevisiae is powerful for studying human G protein-coupled receptors as they can be coupled to its mating pathway. However, some receptors, including the mu opioid receptor, ...are non-functional, which may be due to the presence of the fungal sterol ergosterol instead of cholesterol. Here we engineer yeast to produce cholesterol and introduce diverse mu, delta, and kappa opioid receptors to create sensitive opioid biosensors that recapitulate agonist binding profiles and antagonist inhibition. Additionally, human mu opioid receptor variants, including those with clinical relevance, largely display expected phenotypes. By testing mu opioid receptor-based biosensors with systematically adjusted cholesterol biosynthetic intermediates, we relate sterol profiles to biosensor sensitivity. Finally, we apply sterol-modified backgrounds to other human receptors revealing sterol influence in SSTR5, 5-HTR4, FPR1, and NPY1R signaling. This work provides a platform for generating human G protein-coupled receptor-based biosensors, facilitating receptor deorphanization and high-throughput screening of receptors and effectors.
The purpose of this study was to identify risk factors and outcome implications for 30-day hospital readmission in lung transplant recipients.
We conducted a retrospective cohort study of lung ...transplant cases from a single, high-volume lung transplant program between January 2000 and March 2012. Demographic and health data were reviewed for all patients. Risk factors for 30-day readmission (defined as readmission within 30 days of discharge from index lung transplant hospitalization) were modeled using logistic regression, with selection of parameters by backward elimination.
The sample comprised 795 patients after excluding scheduled readmissions and in-hospital deaths. Overall 30-day readmission rate was 45.4% (n = 361). Readmission rates were similar across different diagnosis categories and procedure types. By univariate analysis, post-operative complications that predisposed to 30-day readmission included pneumonia, any infection, and atrial fibrillation (all p < 0.05). In the final multivariate model, occurrence of any post-transplant complication was the most significant risk factor for 30-day readmission (odds ratio = 1.764; 95% confidence interval, 1.259-2.470). Even for patients with no documented perioperative complication, readmission rates were still >35%. Kaplan-Meier analysis and multi-variate regression modeling to assess readmission as a predictor of long-term outcomes showed that 30-day readmission was not a significant predictor of worse survival in lung recipients.
Occurrence of at least 1 post-transplant complication increases risk for 30-day readmission in lung transplant recipients. In this patient population, 30-day readmission does not predispose to adverse long-term survival. Quality indicators other than 30-day readmission may be needed to assess hospitals that perform lung transplantation.
Objective To evaluate the clinical safety of antenatal and postnatal N-acetylcysteine (NAC) as a neuroprotective agent in maternal chorioamnionitis in a randomized, controlled, double-blinded trial. ...Study design Twenty-two mothers >24 weeks gestation presenting within 4 hours of diagnosis of clinical chorioamnionitis were randomized with their 24 infants to NAC or saline treatment. Antenatal NAC (100 mg/kg/dose) or saline was given intravenously every 6 hours until delivery. Postnatally, NAC (12.5-25 mg/kg/dose, n = 12) or saline (n = 12) was given every 12 hours for 5 doses. Doppler studies of fetal umbilical and fetal and infant cerebral blood flow, cranial ultrasounds, echocardiograms, cerebral oxygenation, electroencephalograms, and serum cytokines were evaluated before and after treatment, and 12, 24, and 48 hours after birth. Magnetic resonance spectroscopy and diffusion imaging were performed at term age equivalent. Development was followed for cerebral palsy or autism to 4 years of age. Results Cardiovascular measures, cerebral blood flow velocity and vascular resistance, and cerebral oxygenation did not differ between treatment groups. Cerebrovascular coupling was disrupted in infants with chorioamnionitis treated with saline but preserved in infants treated with NAC, suggesting improved vascular regulation in the presence of neuroinflammation. Infants treated with NAC had higher serum anti-inflammatory interleukin-1 receptor antagonist and lower proinflammatory vascular endothelial growth factor over time vs controls. No adverse events related to NAC administration were noted. Conclusions In this cohort of newborns exposed to chorioamnionitis, antenatal and postnatal NAC was safe, preserved cerebrovascular regulation, and increased an anti-inflammatory neuroprotective protein. Trial registration ClinicalTrials.gov : NCT00724594.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
A finite-element model of the interaction of an elastic–plastic asperity junction based on cylindrical or spherical asperities is used to predict sliding friction coefficients. The modelling differs ...from previous work by permitting greater asperity overlaps, enforcing an interface adhesional shear strength, and allowing material failure. The results of the modelling were also used to predict friction coefficients for a stochastic rough surface. The asperities were based on the titanium alloy Ti-6Al-4V, and the magnitudes of the predicted friction coefficients were generally representative of experimental measurements of sliding friction. The results suggest that friction arises from both plasticity and tangential interface adhesion.
► Model of sliding friction based on elastic–plastic asperities using finite-element analysis. ► Higher asperity overlaps, tangential adhesion, and asperity failure allow realistic friction predictions. ► Model based on Ti6/4: tests reveal friction coefficients within the range of model predictions. ► Explanation of sliding friction based on plastic deformation and tangential interface adhesion. ► Some level of tangential interface adhesion seems necessary to generate realistic friction.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SBCE, SBJE, UPUK
The present paper describes an experimental technique to accurately measure the tangential contact stiffness between two rough contacting surfaces manufactured from the titanium alloy Ti–6Al–4V. The ...digital image correlation method is employed to measure the local displacement field. The effect of normal contact pressure, nominal contact area and fretting wear on tangential contact stiffness is investigated. The experiments indicate that the tangential contact stiffness is approximately proportional to the nominal contact area and the normal pressure raised to the power of 0.64. Multiple experiments with the same parameters show good repeatability given the number of variables involved.
► Digital image correlation for accurate measurement of tangential contact stiffness. ► We use flat pads with rounded corners clamped against the flat surface of a specimen. ► Effect of contact pressure, contact area and wear on stiffness is investigated. ► Using the same experimental parameters, the repeatability of results is investigated.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SBCE, SBJE, UPUK
To evaluate the mechanical properties of gastrointestinal (GI) tissue segments and to compare them with the urinary bladder for urinary tract reconstruction.
Urinary bladders and GI tissue segments ...were sourced from porcine models (n = 6, 7 months old 5 male; 1 female). Uniaxial planar tension tests were performed on bladder tissue, and Cauchy stress-stretch ratio responses were compared with stomach, jejunum, ileum, and colonic GI tissue.
The biomechanical properties of the bladder differed significantly from jejunum, ileum, and colonic GI tissue. Young modulus (kPa—measure of stiffness) of the GI tissue segments was on average 3.07-fold (±0.21 standard error) higher than bladder tissue (P < .01), and the strain at Cauchy stress of 50 kPa for bladder tissues was on average 2.27-fold (±0.20) higher than GI tissues. There were no significant differences between the averaged stretch ratio and Young modulus of the horizontal and vertical directions of bladder tissue (315.05 ± 49.64 kPa and 283.62 ± 57.04, respectively, P = .42). However, stomach tissues were 1.09- (±0.17) and 0.85- (±0.03) fold greater than bladder tissues for Young modulus and strain at 50 kPa, respectively.
An ideal urinary bladder replacement biomaterial should demonstrate mechanical equivalence to native tissue. Our findings demonstrate that GI tissue does not meet these mechanical requirements. Knowledge on the biomechanical properties of bladder and GI tissue may improve development opportunities for more suitable urologic reconstructive biomaterials.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
Our purpose was to establish the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in asymptomatic patients scheduled to receive radiation therapy and its effect on ...management decisions.
Between April 2020 and July 2020, patients without influenza-like illness symptoms at four radiation oncology departments (two academic university hospitals and two community hospitals) underwent polymerase chain reaction testing for SARS-CoV-2 before the initiation of treatment. Patients were tested either before radiation therapy simulation or after simulation but before treatment initiation. Patients tested for indications of influenza-like illness symptoms were excluded from this analysis. Management of SARS-CoV-2-positive patients was individualized based on disease site and acuity.
Over a 3-month period, a total of 385 tests were performed in 336 asymptomatic patients either before simulation (n = 75), post-simulation, before treatment (n = 230), or on-treatment (n = 49). A total of five patients tested positive for SARS-CoV-2, for a pretreatment prevalence of 1.3% (2.6% in north/central New Jersey and 0.4% in southern New Jersey/southeast Pennsylvania). The median age of positive patients was 58 years (range, 38-78 years). All positive patients were white and were relatively equally distributed with regard to sex (2 male, 3 female) and ethnicity (2 Hispanic and 3 non-Hispanic). The median Charlson comorbidity score among positive patients was five. All five patients were treated for different primary tumor sites, the large majority had advanced disease (80%), and all were treated for curative intent. The majority of positive patients were being treated with either sequential or concurrent immunosuppressive systemic therapy (80%). Initiation of treatment was delayed for 14 days with the addition of retesting for four patients, and one patient was treated without delay but with additional infectious-disease precautions.
Broad-based pretreatment asymptomatic testing of radiation oncology patients for SARS-CoV-2 is of limited value, even in a high-incidence region. Future strategies may include focused risk-stratified asymptomatic testing.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
