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PubMedDate not supplied

Smoking status and psychosocioeconomic outcomes of functional restoration in patients with chronic spinal disability.

BACKGROUND CONTEXT: Studies have revealed smoking to have a negative impact on spinal surgery. It is assumed that this is the result of the negative impact of nicotine on revascularization of damaged tissue. However, there is a paucity of research on the role of smoking with regard to nonsurgical rehabilitation, but there exists a clear bias for believing that smoking is strongly associated with poor socioeconomic and psychosocial outcome. PURPOSE: This study was designed to examine the relationship between smoking and outcomes in a chronically disabled work-related spinal disorder (CDWRSD) cohort undergoing functional restoration. STUDY DESIGN: A prospective comparison cohort study investigating the effects of smoking status on functional restoration treatment outcomes. PATIENT SAMPLE: A cohort of 1,141 consecutive CDWRSD patients were divided into four groups: Group A, patients who did not smoke (n=710); Group B, patients who smoked less than one cigarette pack/day (n=157); Group C, patients who smoked 1.0 to 1.9 packs/day (n=218); Group D, patients who smoked 2.0 or more packs/day (n=56). OUTCOME MEASURES: Before the start of functional restoration, and upon its completion, patients received a standard psychosocial assessment battery and were assessed on a variety of physical factors. A structured clinical interview examining socioeconomic outcomes was conducted 1 year after the program. METHODS: Patients underwent an intensive functional restoration chronic pain management rehabilitation program consisting of quantitatively directed exercise progression and a multimodal disability management program for CDWRSD. The program consisted of four phases, the most significant of which involved a 3-week full-day intensive phase after preparatory preprogram phases and before a work transition phase. RESULTS: Analysis revealed that the percent of males increased as the smoking level increased (Group A=51.8% vs Group D=73.2%; p<.001). Also, as smoking increased, the level of education significantly decreased. In addition, as smoking level increased, the percent of patients completing the rehabilitation program decreased (from 86.3% to 75%; p=.03). No significant differences in 1-year posttreatment socioeconomic outcomes of work status, health utilization, recurrent injury or case closure were related to smoking except work retention, which decreased with more smoking (85 to 71%, p<.05). Surprisingly, the physical cumulative score at posttreatment increased as smoking frequency increased (p<.01). This finding indicates that those who smoked more performed at a higher level on physical measures. Those who smoked more frequently before treatment also appeared more depressed (p<.001), but after treatment, these differences disappeared. Self-reported pain intensity differed only after treatment, and posttreatment disability ratings showed a significant linear trend. CONCLUSIONS: Contrary to popular belief, CDWRSD patients who smoke do not differ significantly in socioeconomic or psychosocial outcomes relative to those who do not. Although this study does indicate that those who smoke more evidence lower rehabilitation completion rates, those who completed the program had identical 1-year posttreatment outcomes of socioeconomic importance except in retraining work at year end as those who did not smoke. Smokers had slightly higher posttreatment self-reported pain and disability ratings mixed and limited. Overall, there is evidence for the widely held belief that smoking negatively affects tertiary rehabilitation.

Adult↗

PubMed2005

External imaging of CCND1, MYC, and KRAS oncogene mRNAs with tumor-targeted radionuclide-PNA-peptide chimeras.

In 2005, breast cancer will kill approximately 40,410 women in the U.S., and pancreatic cancer will kill approximately 31,800 men and women in the U.S. Clinical examination and mammography, the currently accepted breast cancer screening methods, miss almost half of breast cancers in women younger than 40 years, approximately one-quarter of cancers in women aged 40-49 years, and one-fifth of cancers in women over 50 years old. Pancreatic cancer progresses rapidly, with only 1% of patients surviving more than 5 years after diagnosis. However, if the disease is diagnosed when it is localized, the 5-year survival is approximately 20%. It would be beneficial to detect breast cancer and pancreatic cancer at the earliest possible stage, when multimodal therapy with surgery, radiotherapy, and chemotherapy have the greatest chance of prolonging survival. Human estrogen receptor-positive breast cancer cells typically display elevated levels of Myc protein due to overexpression of MYC mRNA, elevated cyclin D1 protein due to overexpression of CCND1 mRNA, and elevated insulin-like growth factor 1 receptor (IGF1R) due to overexpression of IGF1R mRNA. We hypothesized that scintigraphic detection of MYC or CCND1 peptide nucleic acid (PNA) probes with an IGF1 peptide loop on the C-terminus, and a Tc-99m-chelator peptide on the N-terminus, could measure levels of MYC or CCND1 mRNA noninvasively in human IGF1R-overexpressing MCF7 breast cancer xenografts in immunocompromised mice. Similarly, human pancreatic cancer cells typically display elevated levels of KRAS mRNA and elevated IGF1R. Hence, we also hypothesized that a KRAS Tc-99m-chelator PNA-peptide probe could detect overexpression of KRAS mRNA in pancreatic cancer xenografts by scintigraphic imaging, or by positron emission tomography (PET) with a KRAS Cu-64-chelator PNA-peptide. Human MCF7 breast cancer xenografts in immunocompromised mice were imaged scintigraphically 4-24 h after tail-vein administration of MYC or CCND1 Tc-99m-chelator PNA-peptides, but not after administration of mismatch controls. Similarly, human Panc-1 pancreatic cancer cells xenografts were imaged scintigraphically 4 and 24 h after tail-vein administration of a KRAS Tc-99m-chelator PNA-peptide, and AsPC1 xenografts were imaged by PET 4 and 24 h after tail-vein adminstration of a KRAS Cu-64-chelator PNA-peptide. The radioprobes distributed normally to the kidneys, livers, tumors, and other tissues. External molecular imaging of oncogene mRNAs in solid tumors with radiolabel-PNA-peptide chimeras might in the future provide additional genetic characterization of pre-invasive and invasive breast cancers.

Animals↗

PubMed2026

Aflibercept With Versus Without Reduced-Fluence Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: Optical Coherence Tomography Angiographic Changes From a Randomized Clinical Trial.

OBJECTIVES: To report the longitudinal optical coherence tomography angiography (OCTA) changes in polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept monotherapy or in combination with reduced-fluence PDT. DESIGN: Image analysis of a double-masked, sham-controlled, randomized clinical trial. SUBJECTS: 55 eyes of 55 treatment-naïve participants with symptomatic macular PCV completing 52 weeks of follow-up. METHODS: Participants underwent protocolized, multimodal imaging, including OCT, OCTA, fluorescein angiography, and indocyanine green angiography at baseline, week 12, and week 52. Quantitative OCTA parameters included total lesion area, branching neovascular network (BNN) area, and BNN vessel density (VD). Qualitative features included trunk vessel presence and OCTA signal within the polypoidal lesion (PL). Eyes were categorized by treatment arm and PL closure at week 52. MAIN OUTCOME MEASURES: Longitudinal OCTA changes and predictors of PL closure at week 52. RESULTS: We included 55 eyes (28 combination therapy and 27 monotherapy). Total lesion area decreased at week 12 but returned toward baseline at week 52 (combination: 3.72 ± 3.01mm2 at baseline, 2.86 ± 2.50mm2 at week 12, 3.59 ± 3.26mm2 at week 52; monotherapy: 3.77 ± 2.23mm2 at baseline, 3.27 ± 2.36mm2 at week 12, and 3.47 ± 2.58mm2 at week 52). BNN area decreased at week 12 and remained reduced at week 52 in both treatment arms (combination: 2.29 ± 2.08 mm2 at baseline, 1.46 ± 1.36mm2 at week 12, and 1.53 ± 1.32mm2 at week 52; monotherapy: 2.39 ± 1.85mm2 at baseline, 1.87 ± 1.68mm2 at week 12, and 1.82 ± 1.38mm2 at week 52). BNN VD reduction was greater in the combination arm at week 12 (-10 ± 15% vs - 3 ± 12%, P = .02). The proportion of eyes with trunk vessels increased over time in both arms (combination: 35.7% at baseline, 59.3% at week 12, and 67.8% at week 52; monotherapy: 25.9% at baseline, 44.4% at week 12, and 71.4% at week 52). In multivariable analysis, baseline BCVA predicted BCVA change at week 52 (β=-0.96 [-1.21 to -0.72], P < .01), and baseline CST predicted CST change (β=0.93 [0.75 to 1.10], P < .01). Greater reduction in BNN VD at week 12 was independently associated with PL closure at week 52 (OR 0.62 [0.39 to 0.97], P = .03). CONCLUSIONS: Early reduction in BNN vessel density, rather than reduction in lesion size, was associated with subsequent PL closure. OCTA-derived vascular changes may serve as noninvasive biomarkers for predicting treatment response in PCV.

Humans↗