Overcoming barriers to lung cancer screening using a systemwide approach with additional focus on the non-screened.

BACKGROUND: The lung cancer screening program at St Elizabeth Healthcare (Kentucky, USA) began in 2013. Over 33,000 low-dose computed tomography lung cancer screens have been performed. From 2015 through 2021, 2595 lung cancers were diagnosed systemwide. A Screening Program with Impactful Results from Early Detection, reviews that experience; 342 (13.2%) were diagnosed by screening and 2253 (86.8%) were non-screened. As a secondary objective, the non-screened cohort was queried to determine how many additional individuals could have been screened, identifying barriers and failures to meet eligibility. METHODS: Our QlikSense database extracted the lung cancer patients from the Cancer Patient Data and Management System, and identified and categorized them separately as screened or non-screened populations. Stage distribution was compared in screened and non-screened groups. Those meeting age criteria, with any smoking history, were further queried for screening eligibility, accessing the electronic medical record smoking history and audit trail, and determining if enough information was available to substantiate screening eligibility. The same methodology was applied to CMS 2015 and USPSTF 2021 criteria. RESULTS: The screened and non-screened patients were accounted for in a stage migration chart demonstrating clear shift to early stage among screened lung cancer patients. Additionally, analysis of non-screened individuals is presented. CONCLUSION: Of the St Elizabeth Healthcare eligible patients attributed to primary care providers, 49.6% were screened in 2021. Despite this level of success, this study highlighted a sizeable pool of additional individuals that could have been screened. We are shifting focus to the non-screened pool of patients that meet eligibility, further enhancing the impact on our community.

A silver bullet: elemental silver as an efficient reducing agent for atom transfer radical polymerization of acrylates.

Elemental silver was used as a reducing agent in the atom transfer radical polymerization (ATRP) of acrylates. Silver wire, in conjunction with a CuBr(2)/TPMA catalyst, enabled the controlled, rapid preparation of polyacrylates with dispersity values down to D = 1.03. The silver wire in these reactions was reused several times in sequential reactions without a decline in performance, and the amount of copper catalyst used was reduced to 10 ppm without a large decrease in control. A poly(n-butyl acrylate)-block-poly(tert-butyl acrylate) diblock copolymer was synthesized with a molecular weight of 91 400 and D = 1.04, demonstrating good retention of chain-end functionality and a high degree of livingness in this ATRP system.

Iron complexes derived from {nacnac-(CH2py)2}- and {nacnac-(CH2py)(CHpy)}n ligands: stabilization of iron(II) via redox noninnocence.

Nacnac-based tetradentate chelates, {nacnac-(CH2py)2}(-) ({nn(PM)2}(-)) and {nacnac-(CH2py)(CHpy)}(n) ({nn(PM)(PI)}(n)) have been investigated in iron complexes. Treatment of Fe{N(TMS)2}2(THF) with {nn(PM)2}H afforded {nn(PM)2}FeN(TMS)2 [1-N(TMS)2], which led to {nn(PM)2}FeCl (1-Cl) from HCl and to {nn(PM)2}FeN3 (1-N3) upon salt metathesis. Dehydroamination of 1-N(TMS)2 was induced by L (L = PMe3, CO) to afford {nn(PM)(PI)}Fe(PMe3)2 [2-(PMe3)2] and {nn(PM)(PI)}FeCO (3-CO). Substitution of 2-(PMe3)2 led to {nn(PM)(PI)}Fe(PMe3)CO [2-(PMe3)CO], and exposure to a vacuum provided {nn(PM)(PI)}Fe(PMe3) (3-PMe3). Metathesis routes to {nn(PM)(PI)}FeL2 (2-L2; L = PMe3, PMe2Ph) and {nn(PM)(PI)}FeL (3-L; L = PMePh2, PPh3) from [{nn(PM)(PI)}(2-)]Li2 and FeBr2(THF)2 in the presence of L proved feasible, and 1e(-) and 2e(-) oxidation of 2-(PMe3)2 afforded 2(+)-(PMe3)2 and 2(2+)-(PMe3)2 salts. Mössbauer spectroscopy, structural studies, and calculational assessments revealed the dominance of iron(II) in both high-spin (1-X) and low-spin (2-L2 and 3-L) environments, and the redox noninnocence (RNI) of {nn(PM)(PI)}(n) [2-L2, 3-L, n = 2-; 2(+)-(PMe3)2, n = 1-; 2(2+)-(PMe3)2, n = 0]. A discussion regarding the utility of RNI in chemical reactivity is proffered.

C-C bond formation and related reactions at the CNC backbone in (smif)FeX (smif = 1,3-di-(2-pyridyl)-2-azaallyl): dimerizations, 3 + 2 cyclization, and nucleophilic attack; transfer hydrogenations and alkyne trimerization (X = N(TMS)2, dpma = (di-(2-pyridyl-methyl)-amide)).

Molecular orbital analysis depicts the CNC(nb) backbone of the smif (1,3-di-(2-pyridyl)-2-azaallyl) ligand as having singlet diradical and/or ionic character where electrophilic or nucleophilic attack is plausible. Reversible dimerization of (smif)Fe{N(SiMe3)2} (1) to [{(Me3Si)2N}Fe]2(µ-κ(3),κ(3)-N,py2-smif,smif) (2) may be construed as diradical coupling. A proton transfer within the backbone-methylated, and o-pyridine-methylated smif of putative ((b)Me2(o)Me2smif)FeN(SiMe3)2 (8) provides a route to [{(Me3Si)2N}Fe]2(µ-κ(4),κ(4)-N,py2,C-((b)Me,(b)CH2,(o)Me2(smif)H))2 (9). A 3 + 2 cyclization of ditolyl-acetylene occurs with 1, leading to the dimer [{2,5-di(pyridin-2-yl)-3,4-di-(p-tolyl-2,5-dihydropyrrol-1-ide)}FeN(SiMe3)2]2 (11), and the collateral discovery of alkyne cyclotrimerization led to a brief study that identified Fe(N(SiMe3)2(THF) as an effective catalyst. Nucleophilic attack by (smif)2Fe (13) on (t)BuNCO and (2,6-(i)Pr2C6H3)NCO afforded (RNHCO-smif)2Fe (14a, R = (t)Bu; 14b, 2,6-(i)PrC6H3). Calculations suggested that (dpma)2Fe (15) would favorably lose dihydrogen to afford (smif)2Fe (13). H2-transfer to alkynes, olefins, imines, PhN═NPh, and ketones was explored, but only stoichiometric reactions were affected. Some physical properties of the compounds were examined, and X-ray structural studies on several dinuclear species were conducted.

A heterobimetallic complex with an unsupported uranium(III)-aluminum(I) bond: (CpSiMe3)3U-AlCp* (Cp* = C5Me5).

A heterobimetallic complex with the first unsupported bond between an actinide and a group 13 element, (CpSiMe3)3U-AlCp* (Cp* = C5Me5) (1), was synthesized by reaction of (CpSiMe3)3U and 1/4(Cp*Al)4 in toluene. Density functional theory calculations indicate that the U-Al bond exhibits some covalent character resulting from a Cp*Al-->U charge-transfer.

Esophagectomy for high grade dysplasia is safe, curative, and results in good alimentary outcome.

BACKGROUND: The increasing adoption of endoscopic therapies and expectant surveillance for patients with high grade dysplasia (HGD) in Barrett's esophagus has created considerable controversy regarding the ideal treatment choice. Confusion may be due, in part, to a limited understanding of the outcomes associated with surgical resection for HGD and extrapolation of data derived from patients undergoing an esophagectomy for invasive cancer. The purpose of our study was to document the perioperative and symptomatic outcomes and long-term survival after esophagectomy for HGD of the esophagus. MATERIAL AND METHODS: The study population consisted of 38 patients who underwent esophagectomy for biopsy-proven HGD between 10/1999 and 6/2005. Three patients were excluded from analysis due to obvious tumor on upper endoscopy. Patients were evaluated regarding ten different foregut symptoms and administered a ten-question appraisal of eating and bowel habits. Outcome measures included postoperative morbidity and mortality, the prevalence of invasive cancer in the esophagectomy specimens, symptomatic and functional alimentary results, patient satisfaction, and long-term survival. Median follow-up was 32 months (range, 7-83). RESULTS: Thirty-day postoperative and in-hospital mortality was zero. Complications occurred in 37% (13/35), and median length of stay was 10 days. Occult adenocarcinoma was found in 29% (10/35) of surgical specimens (intramucosal in four; submucosal in five; and intramuscular in one with a single positive lymph node.) Patients consumed a median of three meals per day, most (76%, 26/34) had no dietary restrictions, and two-thirds (23/34) considered their eating pattern to be normal or only mildly impacted. Meal size, however, was reported to be smaller in the majority (79%, 27/34) of patients. Median body mass index (BMI) decreased slightly after surgery (28.6 vs 26.6, p>0.05), but no patient's BMI went below normal. The number of bowel movements/day was unchanged or less in a majority (82%) of patients after surgery. Fifteen of 34 (44%) patients reported loose bowel movements, which occurred less often than once per week in 10 of the 15. One patient had symptoms of dumping. Mean symptom severity scores improved for all symptoms except dysphagia and choking. Four patients developed foregut symptoms that occurred daily. Most patients (82%) required at least one postoperative dilation for dysphagia. Almost all (97%) patients were satisfied. Disease-free survival was 100%, and overall survival was 97% (34/35) at a median of 32 months. CONCLUSION: Esophagectomy is an effective and curative treatment for HGD and can be performed with no mortality, acceptable morbidity, and good alimentary outcome. These data provide a gold standard for comparison to alternative therapies.

Pathogenesis of Barrett esophagus: deoxycholic acid up-regulates goblet-specific gene MUC2 in concert with CDX2 in human esophageal cells.

HYPOTHESIS: Bile acid exposure can induce caudal-related homeobox 2 (CDX2) messenger RNA (mRNA) expression, a transcription factor that plays a crucial role in the development of Barrett esophagus. We investigated mucin 2 (MUC2) and CDX2 mRNA expression before and after treatment with deoxycholic acid in 4 human esophageal cell lines. DESIGN, SETTING, AND PARTICIPANTS: Four human esophageal cell lines-(1) normal squamous cells immortalized by SV40 (Het-1A), (2) adenocarcinoma (SEG-1), and (3 and 4) squamous cell carcinoma (HKESC-1 and HKESC-2)-were exposed in culture for 1 to 24 hours to 100 microM to 1000 microM deoxycholic acid. Total RNA was extracted before and after bile acid treatment and reverse transcribed to complementary DNA. MAIN OUTCOME MEASURE: MUC2 and CDX2 mRNA expression as determined by semiquantitative reverse transcription-polymerase chain reaction. RESULTS: MUC2 mRNA expression was absent before deoxycholic acid exposure in all 4 cell lines. MUC2 expression increased in a dose- and time-dependent manner with deoxycholic acid in all cell lines. Deoxycholic acid activated MUC2 up-regulation, which correlated directly with CDX2 up-regulation in all 4 cell lines. CONCLUSIONS: Bile acids up-regulate both intestinal differentiation factor CDX2 and goblet cell-specific gene MUC2 in normal esophageal and cancer cell lines. Further, bile acid-stimulated MUC2 up-regulation correlates directly with CDX2 up-regulation. The simultaneous up-regulation of both CDX2 and MUC2 after bile acid exposure provides molecular evidence of the role of bile acid in the pathogenesis of Barrett esophagus.

The pathogenesis of Barrett's esophagus: secondary bile acids upregulate intestinal differentiation factor CDX2 expression in esophageal cells.

INTRODUCTION: Clinical evidence strongly suggests that bile acids are important in the development of Barrett's esophagus, although the mechanism remains unknown. Caudal-related homeobox 2 (CDX2) is a transcription factor recently implicated in early differentiation and maintenance of normal intestinal epithelium and is suggested to play a key role in the pathogenesis of intestinal metaplasia in Barrett's esophagus. OBJECTIVE: The aim of this study was to investigate the effect of primary and secondary bile acids on CDX2 mRNA expression in human esophageal cells. METHODS: Human esophageal cells: (1) squamous, immortalized by SV40 (Het-1A); (2) adenocarcinoma (SEG-1); and (3) squamous cell carcinoma (HKESC-1 & HKESC-2), were exposed in cell culture for 1-24 h to 100-1,000 microM deoxycholic, chenodeoxycholic, and glycocholic acids. Total RNA was extracted before and after bile acid treatment and reverse transcribed to cDNA. CDX2 mRNA expression was determined by both quantitative real-time and reverse transcription PCR (RT-PCR). RESULTS: CDX2 mRNA expression was absent before bile acid exposure in all cell lines. CDX2 expression increased in a dose- and time-dependent fashion with deoxycholic and chenodeoxycholic, but not glycocholic, acid in all four cell lines. The maximal induction of CDX2 expression was seen in SEG-1 adenocarcinoma cells. Expression in Het-1A cells also increased significantly as did expression in HKESC-1,2 cells, although to a lesser extent than in adenocarcinoma. CONCLUSIONS: These findings show that secondary bile acid stimulation upregulates CDX2 gene expression in both normal and cancer cell lines. They further support the role of bile acids in the pathogenesis of Barrett's esophagus and link the clinical evidence of a high prevalence of luminal bile acids in Barrett's to expression of the gene thought to be responsible for the phenotypic expression of intestinal metaplasia.

Gastrectomy as a remedial operation for failed fundoplication.

The decision for, and choice of, a remedial antireflux procedure after a failed fundoplication is a challenging clinical problem. Success depends upon many factors including the primary symptom responsible for failure, the severity of underlying anatomic and physiologic defects, and the number and type of previous remedial attempts. Satisfactory outcomes after reoperative fundoplication have been reported to be as low as 50%. Consequently, the ideal treatment option is not clear. The purpose of this study was to evaluate the outcome of gastrectomy as a remedial antireflux procedure for patients with a failed fundoplication. The study population consisted of 37 patients who underwent either gastrectomy (n = 12) with Roux-en-Y reconstruction or refundoplication (n = 25) between 1997-2005. Average age, M/F ratio, and preoperative BMI were not significantly different between the two groups. Outcome measures included perioperative morbidity, relief of primary and secondary symptoms, and the patients' overall assessment of outcome. Mean follow up was 3.5 and 3.3 years in the gastrectomy and refundoplication groups, respectively (p = 0.43). Gastrectomy patients had a higher prevalence of endoscopic complications of GERD (58% vs 4%, p = 0.006) and of multiple prior fundoplications than those having refundoplication (75% vs 24%, p = 0.004). Mean symptom severity scores were improved significantly by both gastrectomy and refundoplication, but were not significantly different from each other. Complete relief of the primary symptom was significantly greater after gastrectomy (89% vs 50%, p = 0.044). Overall patient satisfaction was similar in both groups (p = 0.22). In-hospital morbidity was higher after gastrectomy than after refundoplication (67% vs 20%, p = 0.007) and new onset dumping developed in two gastrectomy patients. In select patients with severe gastroesophageal reflux disease (GERD) and multiple previous fundoplications, primary symptom resolution occurs significantly more often after gastrectomy than after repeat fundoplication. Gastrectomy, however, is associated with higher morbidity. Gastrectomy is an acceptable treatment option for recurrent symptoms particularly when another attempt at fundoplication is ill advised, such as in the setting of multiple prior fundoplications or failed Collis gastroplasty.

Adenocarcinoma of the gastroesophageal junction: benefits of an extended lymphadenectomy.

The incidence of esophageal adenocarcinoma is rising faster the any other cancer in the United States. Studies from around the world strongly suggest that for early cancers of the lower esophagus and cardia, en bloc esophagogastrectomy results in significantly better survival rates than does transhiatal esophagogastrectomy.

Magnetic resonance imaging in combination with helical computed tomography provides a safe and efficient method of cervical spine clearance in the obtunded trauma patient.

BACKGROUND: Assessment of the cervical spine (c-spine) in the obtunded blunt trauma patient remains a diagnostic dilemma. In 2002, our institution implemented a new c-spine clearance guideline utilizing c-spine computed tomography (CT) and magnetic resonance imaging (MRI). This study evaluates the safety and efficacy of this guideline. METHODS: Obtunded blunt trauma patients admitted over a 1-year period, who underwent both a c-spine CT and a c-spine MRI, were identified. Records were reviewed for demographics, mechanism, diagnostic evaluations, injuries, and outcome. RESULTS: Fifty-two patients met inclusion criteria. On average, patients underwent a c-spine CT on postinjury day 0.4 and MRI on postinjury day 4. Forty-four patients had a negative c-spine CT, of whom 13 (30%) had a positive MRI for ligamentous injury (p < 0.01). Thirty-one patients had both a negative CT and a negative MRI. All patients (n = 8) with positive CTs had positive MRIs. The average Injury Severity Score, Abbreviated Injury Score head and neck, length of stay, and outcome was not significantly different for patients with a c-spine injury. No missed c-spine injuries and no areas of cervical collar-related skin breakdown were seen in follow up. CONCLUSIONS: In the obtunded patient, expeditious c-spine evaluation is important. Both missed injuries and prolonged unnecessary immobilization can result in adverse outcomes. This study confirms that c-spine CT, when used in combination with MRI, provides a safe and efficient method for c-spine clearance in this patient population. CT alone misses a statistically significant number of c-spine injuries.