Effect of preoperative delay on prognosis for patients with early stage non-small cell lung cancer

AbstractObjective: Screening for lung cancer will discover many nodules of indeterminate pathology. Observation has the theoretic risk of permitting dissemination of a localized cancer and worsening prognosis, whereas immediate evaluation of benign conditions generates morbidity and cost. This study was conducted to assess the effect of delay in surgical intervention on survival for patients with early stage non-small cell lung cancer. Methods: Records for patients with resected pathologic stage I and II non-small cell lung cancer (1989-1999) were abstracted for patient age, race, sex, medical history, date of presentation, date and type of surgical treatment, pathologic stage, and date of death or last follow-up. Kaplan-Meier survival analysis was performed to test for the effect of delay (time from presentation to surgical intervention) on survival. Results: Eighty-four patients were identified. Median age was 66 years, median preoperative interval was 82 days (range, 1-641 days), and median follow-up was 3.3 years (range, 5 days-11.9 years). Median survival was 3.7 years. Overall 5-year survival was 40%; disease-specific 5-year survival was 63%. Log-rank analysis of the effect of delay on overall survival generated a P value of.54, with an estimated hazard ratio for a 90-day delay of 1.06 (95% confidence interval, 0.87-1.30). Conclusions: For this population, we were unable to detect a significant effect of delay on prognosis. Although these results suggest that the risk of judicious observation of indeterminate pulmonary nodules might be low, the 95% confidence interval is broad. Larger sample sizes are needed to reach definitive conclusions.J Thorac Cardiovasc Surg 2003;125:108-1

Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility.

Decreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment with doxycycline for two weeks after MI was associated with normalization of MMP-2 levels and improvement in ex-vivo contractile protein developed force in the myocardial border zone. The purpose of the current study was to determine if there is a sustained effect of short term treatment with doxycycline (Dox) on border zone function in a large animal model of antero-apical myocardial infarction (MI). Antero-apical MI was created in 14 sheep. Seven sheep received doxycycline 0.8 mg/kg/hr IV for two weeks. Cardiac MRI was performed two weeks before, and then two and six weeks after MI. Two sheep died prior to MRI at six weeks from surgical/anesthesia-related causes. The remaining 12 sheep completed the protocol. Doxycycline induced a sustained reduction in intracellular MMP-2 by Western blot (3649±643 MI+Dox vs 9236±114 MI relative intensity; p = 0.0009), an improvement in ex-vivo contractility (65.3±2.0 MI+Dox vs 39.7±0.8 MI mN/mm2; p<0.0001) and an increase in ventricular wall thickness at end-systole 1.0 cm from the infarct edge (12.4±0.6 MI+Dox vs 10.0±0.5 MI mm; p = 0.0095). Administration of doxycycline for a limited two week period is associated with a sustained improvement in ex-vivo contractility and an increase in wall thickness at end-systole in the border zone six weeks after MI. These findings were associated with a reduction in intracellular MMP-2 activity

Multiplanar strain quantification for assessment of right ventricular dysfunction and non-ischemic fibrosis among patients with ischemic mitral regurgitation

Background: Ischemic mitral regurgitation (iMR) predisposes to right ventricular (RV) pressure and volume overload, providing a nidus for RV dysfunction (RVDYS) and non-ischemic fibrosis (NIF). Echocardiography (echo) is widely used to assess iMR, but performance of different indices as markers of RVDYS and NIF is unknown. Methods: iMR patients prospectively underwent echo and cardiac magnetic resonance (CMR) within 72 hours. Echo quantified iMR, assessed conventional RV indices (TAPSE, RV-S’, fractional area change [FAC]), and strain via speckle tracking in apical 4-chamber (global longitudinal strain [RV-GLS]) and parasternal long axis orientation (transverse strain). CMR volumetrically quantified RVEF, and assessed ischemic pattern myocardial infarction (MI) and septal NIF. Results: 73 iMR patients were studied; 36% had RVDYS (EF<50%) on CMR among whom LVEF was lower, PA systolic pressure higher, and MI size larger (all p<0.05). CMR RVEF was paralleled by echo results; correlations were highest for RV-GLS (r = 0.73) and lowest for RV-S’ (r = 0.43; all p<0.001). RVDYS patients more often had CMR-evidenced NIF (54% vs. 7%; p<0.001). Whereas all RV indices were lower among NIF-affected patients (all p≤0.006), percent change was largest for transverse strain (48.3%). CMR RVEF was independently associated with RV-GLS (partial r = 0.57, p<0.001) and transverse strain (r = 0.38, p = 0.002) (R = 0.78, p<0.001). Overall diagnostic performance of RV-GLS and transverse strain were similar (AUC = 0.93[0.87–0.99]|0.91[0.84–0.99], both p<0.001), and yielded near equivalent sensitivity and specificity (85%|83% and 80%|79% respectively). Conclusion: Compared to conventional echo indices, RV strain parameters yield stronger correlation with CMR-defined RVEF and potentially constitute better markers of CMR-evidenced NIF in iMR

Prevalence of programmed death ligand-1 (PD-L1) by demographic, disease and sample characteristics in unresectable, stage III NSCLC (PACIFIC)

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Endoventricular patch plasty for dyskinetic anteroapical left ventricular aneurysm increases systolic circumferential shortening in sheep

ObjectiveEndoventricular patch plasty (Dor procedure) has gained favor as a surgical treatment for heart failure associated with large anteroapical myocardial infarction. We tested the hypotheses that the Dor procedure increases systolic circumferential shortening and longitudinal shortening in noninfarcted left ventricular regions in sheep.MethodsIn 6 male Dorsett sheep, the left anterior descending coronary artery and its second diagonal branch were ligated 40% of the distance from the apex to the base. Sixteen weeks after myocardial infarction, a Dor procedure was performed with a Dacron patch that was 50% of the infarct neck dimension. Two weeks before and 2 and 6 weeks after the Dor procedure, animals underwent magnetic resonance imaging with tissue tagging in multiple short-axis and long-axis slices. Fully three-dimensional strain analyses were performed. All 6 end-systolic strain components were compared in regions 1 cm, 2 cm, 3 cm, and 4 cm below the valves, as well as in the anterior, posterior, and lateral left ventricular walls and the interventricular septum.ResultsCircumferential shortening increased from before the Dor procedure to 6 weeks after repair in nearly every left ventricular region (13/16). The greatest regional change in circumferential shortening was found in the equatorial region or 2 cm below the base and in the posterior wall (from 9.0% to 18.4%; P < .0001). Longitudinal shortening increased 2 weeks after the Dor procedure but then returned near baseline by 6 weeks after the Dor procedure.ConclusionThe Dor procedure significantly increases systolic circumferential shortening in nearly all noninfarcted left ventricular regions in sheep

Evaluating the effectiveness of a large multi-use MPA in protecting Key Biodiversity Areas for marine predators

Marine protected areas can serve to regulate harvesting and conserve biodiversity. Within large multi‐use MPAs, it is often unclear to what degree critical sites of biodiversity are afforded protection against commercial activities. Addressing this issue is a prerequisite if we are to appropriately assess sites against conservation targets. We evaluated whether the management regime of a large MPA conserved sites (Key Biodiversity Areas, KBAs) supporting the global persistence of top marine predators