Patients undergoing total laryngectomy are at high risk for hospital readmission. Hospital readmissions are increasingly scrutinized because they are used as a metric of quality care and are subject ...to financial penalties.
To determine the rate of, reasons for, and risk factors that predict 30-day unplanned readmission for patients undergoing total laryngectomy.
Retrospective cohort study at a single academic tertiary referral medical center. The study population comprised 155 patients who underwent total laryngectomy with or without flap closure between January 2007 and December 2012 as either a primary treatment or salvage treatment for prior nonsurgical management.
Total laryngectomy.
Rate of 30-day unplanned readmission, readmission diagnoses, and risk factors for unplanned readmission. Univariable and multivariable logistic regression were performed to identify risk factors for unplanned readmission within 30 days of discharge.
The 30-day unplanned readmission rate for patients following discharge after total laryngectomy was 26.5% (41 of 155). The most common readmission diagnoses were pharyngocutaneous fistula (27% of readmissions; n = 11) and stomal cellulitis (16% of readmissions; n = 7). The median time to unplanned readmission was 7 days. Thirty-four percent of readmissions (14 of 41) occurred within 3 days of discharge. Significant predictors of 30-day unplanned readmission on multivariable analysis were postoperative complication after discharge (odds ratio OR, 11.50; 95% CI, 4.10-32.28), visit to the emergency department within 30 days after discharge (OR, 5.25; 95% CI, 1.84-14.99), salvage total laryngectomy (OR, 3.52; 95% CI, 1.56-13.12), and chyle fistula during the index hospitalization (OR, 5.25; 95% CI, 0.86-29.92). The discriminative ability of the model to predict unplanned readmission, as measured by the C statistic, was 0.88.
Patients undergoing total laryngectomy are an at-risk patient population with a high rate of unplanned readmission within 30 days of discharge. By identifying the risk factors that predict 30-day unplanned readmission, these data can be used to design and implement quality-improvement interventions to decrease readmissions.
Ras/MEK/ERK pathway activation is common in oral cavity squamous cell carcinoma (OCSCC). We performed a neoadjuvant (preoperative) trial to determine the biomarker and tumor response of OCSCC to MEK ...inhibition with trametinib.
Patients with stage II-IV OCSCC received trametinib (2 mg/day, minimum 7 days) prior to surgery. Primary tumor specimens were obtained before and after trametinib to evaluate immunohistochemical staining for p-ERK1/2 and CD44, the primary endpoint. Secondary endpoints included changes in clinical tumor measurements and metabolic activity maximum standardized uptake values (SUV
) by F-18 fluorodeoxyglucose positron emission tomography/CT), and in tumor downstaging. Drug-related adverse events (AE) and surgical/wound complications were evaluated.
Of 20 enrolled patients, 17 (85%) completed the study. Three patients withdrew because of either trametinib-related (
= 2: nausea, duodenal perforation) or unrelated (
= 1: constipation) AEs. The most common AE was rash (9/20 patients, 45%). Seventeen patients underwent surgery. No unexpected surgical/wound complications occurred. Evaluable matched pre- and posttrametinib specimens were available in 15 (88%) of these patients. Reduction in p-ERK1/2 and CD44 expression occurred in 5 (33%) and 2 (13%) patients, respectively. Clinical tumor response by modified World Health Organization criteria was observed in 11 of 17 (65%) evaluable patients (median 46% decrease, range 14%-74%). Partial metabolic response (≥25% reduction in SUV
) was observed in 6 of 13 (46%) evaluable patients (median 25% decrease, range 6%-52%). Clinical-to-pathologic tumor downstaging occurred in 9 of 17 (53%) evaluable patients.
Trametinib resulted in significant reduction in Ras/MEK/ERK pathway activation and in clinical and metabolic tumor responses in patients with OCSCC.
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Identify the risk factors that predict 30-day unplanned readmission in hospitalized otolaryngology patients.
Retrospective cohort study.
Single academic hospital.
All otolaryngology admissions for ...the 1-year period between January 1, 2011, and December 31, 2011, at an academic hospital were reviewed. Univariate logistic regression and multivariate logistic regression, employing a backward elimination stepwise approach, were performed to identify risk factors for unplanned readmission to the hospital within 30 days of discharge from the otolaryngology service.
There were 1058 patients that accounted for 1271 hospital admissions. The 30-day unplanned readmission rate for patients discharged from the otolaryngology service was 7.3% (93/1271). Significant predictors identified on univariate analysis were used to build a multivariable logistic regression model of risk factors for unplanned readmission. These risk factors included presence of a complication (odds ratio OR = 11.60, 95% confidence interval CI, 7.11-18.93), new total laryngectomy (OR = 4.72, 95% CI, 1.58-14.10), discharge destination of skilled nursing facility (OR = 2.70, 95% CI, 1.21-6.02), severe coronary artery disease or chronic lung disease (OR = 2.33, 95% CI, 1.38-3.93), and current illicit drug use (OR = 2.60, 95% CI, 1.27-5.34). The discriminative ability of the multivariate regression model to predict unplanned readmissions, as measured by the c-statistic, was 0.85.
Otolaryngology patients have unique risk factors that predict unplanned readmission within 30 days of discharge. These data identify specific patient characteristics and care processes that can be targeted with quality improvement interventions to decrease unplanned readmissions.
We have found a small molecule that specifically inhibits cleavage of a precursor to the oncogenic miRNA, miR-21, by the microprocessor complex of Drosha and DGCR8. We identified novel ligands for ...the apical loop of this precursor from a screen of 14,024 N-substituted oligoglycines (peptoids) in a microarray format. Eight distinct compounds with specific affinity were obtained, three having affinities for the targeted loop in the low micromolar range and greater than 15-fold discrimination against a closely related hairpin. One of these compounds completely inhibits microprocessor cleavage of a miR-21 primary transcript at concentrations at which cleavage of another miRNA primary transcript, pri-miR-16, is little affected. The apical loop of pri-miR-21, placed in the context of pri-miR-16, is sufficient for inhibition of microprocessor cleavage by the peptoid. This compound also inhibits cleavage of pri-miR-21 containing the pri-miR-16 apical loop, suggesting an additional site of association within pri-miR-21. The reported peptoid is the first example of a small molecule that inhibits microprocessor cleavage by binding to the apical loop of a pri-miRNA.
•Desialylation of glycans by neuraminidases can be detected by chemoselective labeling.•Chemoenzymatic labeling of unsialylated glycans can be performed on glass slides.•Three pneumococcal ...neuraminidases exhibit distinct glycan specificities.
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Neuraminidases hydrolytically remove sialic acids from glycoconjugates. Neuraminidases are produced by both humans and their pathogens, and function in normal physiology and in pathological events. Identification of neuraminidase substrates is needed to reveal their mechanism of action, but high-throughput methods to determine glycan specificity of neuraminidases are limited. Here we use two glycan labeling reactions to monitor neuraminidase activity toward glycan substrates. While both periodate oxidation and aniline-catalyzed oxime ligation (PAL) and galactose oxidase and aniline-catalyzed oxime ligation (GAL) can be used to monitor neuraminidase activity toward glycans in microtiter plates, only GAL accurately measured neuraminidase activity toward glycans displayed on a commercial glass slide microarray. Using GAL, we confirm known linkage specificities of three pneumococcal neuraminidases and obtain new information about underlying glycan specificity.
The optimal reconstruction of total glossectomy defects with or without total laryngectomy is controversial. Various pedicled and free tissue flaps have been advocated, but long-term data on ...functional outcomes are not available to date.
To compare various total glossectomy defect reconstructive techniques used by multiple institutions and to identify factors that may lead to improved long-term speech and swallowing function.
A multi-institutional, retrospective review of electronic medical records of patients undergoing total glossectomy at 8 participating institutions between June 1, 2001, and June 30, 2011, who had a minimal survival of 2 years.
Total glossectomy with or without total laryngectomy.
Demographic and surgical factors were compiled and correlated with speech and swallowing outcomes.
At the time of the last follow-up, 45% (25 of 55) of patients did not have a gastrostomy tube, and 76% (42 of 55) retained the ability to verbally communicate. Overall, 75% (41 of 55) of patients were tolerating at least minimal nutritional oral intake. Feeding tube dependence was not associated with laryngeal preservation or the reconstructive techniques used, including flap suspension, flap innervation, or type of flap used. Laryngeal preservation was associated with favorable speech outcomes, such as the retained ability to verbally communicate in 97% of those not undergoing total laryngectomy (35 of 36 patients) vs 44% (7 of 16) in those undergoing total laryngectomy (P < .001), as well as those not undergoing total laryngectomy achieving some or all intelligible speech in 85% (29 of 34 patients) compared with 31% (4 of 13) undergoing total laryngectomy achieving the same intelligibility (P < .001).
In patients with total glossectomy, feeding tube dependence was not associated with laryngeal preservation or the reconstructive technique, including flap innervation and type of flap used. Laryngeal preservation was associated with favorable speech outcomes such as the retained ability to verbally communicate and higher levels of speech intelligibility.
Abstract
Objectives
To review the indications, techniques, and outcomes for a series of patients in whom the lower trapezius flaps was used for repair of complex posterior scalp and neck defects ...after posterior occipital-cervical surgeries.
Design
Retrospective case series.
Setting
Tertiary academic hospital.
Participants
A retrospective review of cases that required complex occipital-cervical repair was performed to identify patients who underwent reconstruction using the lower trapezius flap. Data collected included demographics, clinical presentations, surgical anatomy, operative techniques, and outcomes with review of the pertinent literature.
Outcomes
Nine patients who underwent reconstruction using the lower trapezius flap were identified. Prior surgical interventions included five complex tumor resections, two patients with multiple instrumented cervical spine surgeries, one patient with a craniotomy for attempted extracranial to intracranial arterial bypass for a basilar aneurysm repair, and a posterior occipital-cervical decompression after trauma. During the median follow-up period of 7 months, all nine single-stage reconstructions resulted in successful healing without major surgical complications.
Conclusion
Lower trapezius island flaps provide a reliable option for the reconstruction of complex scalp and neck defects that develop after complex occipital-cervical surgeries.
Facile alcohol oxidation to aldehydes and ketones is achieved in stoichiometric reaction with Cp*Ru(NO)OTf2 complex, with generation of RuRu dimeric product. Alcohol binding pre-equilibrium step and ...kinetics of the oxidation reaction are investigated by NMR spectroscopy methods. Chelate-stabilized diol adduct is structurally characterized. Display omitted
Treatment of the complex 1 Cp*Ru(NO)(OTf)2 (OTf=OSO2CF3, Cp*=η5-C(CH3)5) with neat 2-propanol results in the rapid quantitative formation of the Ru(0) complex Cp*Ru(μ-NO)2 and (CH3)2CO. Formation of H2 and CHDCl2 is detected when the reaction between 1 and 2-propanol occurs in CDCl3, indicating possible formation of a short-lived metal hydride species. Similar results are observed upon treatment of 1 with ethanol and methanol, with formation of acetaldehyde and formaldehyde, respectively. The kinetics of the oxidation of 2-propanol by complex 1 is studied by 1H NMR spectroscopy in CH2Cl2 at variable temperatures and the reaction is found to be first-order in complex 1 and in 2-propanol. The kinetic isotope effect for the reaction of 1 with (CD3)2CD-OD at −11°C is determined to be kH/kD=2.0 (3). A mechanism for alcohol oxidation by electrophilic ruthenium (II) complexes via a β-hydrogen elimination step is proposed. The pre-equilibrium exchange step between complex Cp*Ru(NO)(OTf)2 (1) and alcohol-coordinated species is examined by 19F and 1H NMR spectroscopy in CH2Cl2 solution, where triflate substitution is found to be exothermic and entropically unfavorable. The synthesis and solid state structure of the chelate-stabilized complex diol salt Cp*Ru(NO)(HO–CH2CH2–OH)2OTf are discussed.
Papillomavirus E2 is a multifunctional viral protein that regulates many aspects of the viral life cycle including viral episome maintenance, transcriptional activation, and repression. E2 is ...degraded by the ubiquitin-proteasome pathway. Cellular bromodomain protein Brd4 has been implicated in the stabilization of the E2 protein. E2 normally shuttles between the cytoplasm and the nucleus. In this study, we demonstrate that E2 ubiquitylation mostly occurs in the cytoplasm. We also find that the interaction with Brd4 promotes nuclear retention of papillomavirus E2 proteins and contributes to their stabilization in the nucleus. Compared to wild type E2 proteins, nuclear-localization-defective mutants are rapidly degraded by the ubiquitin-proteasome pathway; however, co-expression of Brd4 redirects these mutants into the nucleus and significantly increases their stability. We further demonstrate that tethering E2 proteins to chromatin as either double-bromodomain fusion proteins or histone 2B (H2B) fusion proteins significantly stabilizes the E2 proteins. Our studies suggest that chromatin recruitment of the E2 protein via interaction with Brd4 prevents E2 ubiquitylation and proteasomal degradation in the cytoplasm, leading to its stabilization in the nucleus. These studies bring new insights for understanding Brd4-mediated E2 stabilization, and provide an additional mechanism by which the chromatin-associated Brd4 regulates E2 functions.
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