Citations

AbstractBackgroundThe aim of the study was to describe a novel technique for reinforcement of salvage laryngectomy closure using a bipedicled musculofascial submental flap.MethodsA retrospective cohort study design identified patients who underwent salvage laryngectomy reinforcement with a bipedicled submental hammock flap between January 2008 and December 2016 were compared to salvage laryngectomy patients treated with primary closure of the neopharynx during the same time period. Pharyngocutaneous fistula rates were compared between groups.ResultsPharyngocutaneous fistula rate in the submental hammock group (2/31, 6.5%) was significantly lower compared to the primary closure group (14/45, 31%, P < .05).ConclusionThe bipedicled musculofascial submental hammock flap is a viable method for reinforcement of salvage laryngectomy defects. It has a favorable pharyngocutaneous fistula rate compared to primary closure alone and has unique advantages over conventional methods of reinforcement.

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Abstract Purpose: We aimed to assess the concordance of colorectal cancer–associated methylated DNA markers (MDM) in primary and metastatic colorectal cancer for feasibility in detection of distantly recurrent/metastatic colorectal cancer in plasma. Experimental Design: A panel of previously discovered colorectal cancer–associated MDMs was selected. MDMs from primary and paired metastatic colorectal cancer tissue were assayed with quantitative methylation-specific PCR. Plasma MDMs were measured blindly by target enrichment long-probe quantitative-amplified signal assays. Random forest modeling was used to derive a prediction algorithm of MDMs in archival plasma samples from primary colorectal cancer cases. This algorithm was validated in prospectively collected plasma samples from recurrent colorectal cancer cases. The accuracy of the algorithm was summarized as sensitivity, specificity, and area under the curve (AUC). Results: Of the 14 selected MDMs, the concordance between primary and metastatic tissue was considered moderate or higher for 12 MDMs (86%). At a preset specificity of 95% (91%–98%), a panel of 13 MDMs, in plasma from 97 colorectal cancer cases and 200 controls, detected stage IV colorectal cancer with 100% (80%–100%) sensitivity and all stages of colorectal cancer with an AUC of 0.91 (0.87–0.95), significantly higher than carcinoembryonic antigen [AUC, 0.72 (0.65–0.79)]. This panel, in plasma from 40 cases and 60 healthy controls, detected recurrent/metastatic colorectal cancer with 90% (76%–97%) sensitivity, 90% (79%–96%) specificity, and an AUC of 0.96 (0.92–1.00). The panel was positive in 0.30 (0.19–0.43) of 60 patients with no evidence of disease in post-operative patients with colorectal cancer. Conclusions: Plasma assay of novel colorectal cancer–associated MDMs can reliably detect both primary colorectal cancer and distantly recurrent colorectal cancer with promising accuracy.

Background: Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability. Methods: We performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls. We then used mendelian randomization to examine the causal effects of blood pressure on AAA. We examined the association of AAA risk variants with aneurysms in the lower extremity, cerebral, and iliac arterial beds, and derived a genome-wide polygenic risk score (PRS) to identify a subset of the population at greater risk for disease. Results: Through a genome-wide association study, we identified 14 novel loci, bringing the total number of known significant AAA loci to 24. In our mendelian randomization analysis, we demonstrate that a genetic increase of 10 mm Hg in diastolic blood pressure (odds ratio, 1.43 [95% CI, 1.24–1.66]; P =1.6×10 −6 ), as opposed to systolic blood pressure (odds ratio, 1.06 [95% CI, 0.97–1.15]; P =0.2), likely has a causal relationship with AAA development. We observed that 19 of 24 AAA risk variants associate with aneurysms in at least 1 other vascular territory. A 29-variant PRS was strongly associated with AAA (odds ratio PRS , 1.26 [95% CI, 1.18–1.36]; P PRS =2.7×10 −11 per SD increase in PRS), independent of family history and smoking risk factors (odds ratio PRS+family history+smoking , 1.24 [95% CI, 1.14–1.35]; P PRS =1.27×10 −6 ). Using this PRS, we identified a subset of the population with AAA prevalence greater than that observed in screening trials informing current guidelines. Conclusions: We identify novel AAA genetic associations with therapeutic implications and identify a subset of the population at significantly increased genetic risk of AAA independent of family history. Our data suggest that extending current screening guidelines to include testing to identify those with high polygenic AAA risk, once the cost of genotyping becomes comparable with that of screening ultrasound, would significantly increase the yield of current screening at reasonable cost.

AbstractBackgroundConsensus definitions for transfusion‐related acute lung injury (TRALI) and transfusion‐associated circulatory overload (TACO) have recently been revised; however, pulmonary transfusion reactions remain difficult to diagnose. We hypothesized that N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels could have utility in the identification and classification of pulmonary transfusion reactions.Study design and methodsWe performed a secondary analysis of a case‐control study of pulmonary transfusion reactions at four academic hospitals. We evaluated clinical data and measured NT‐proBNP levels prior to and following transfusion in patients with TACO (n = 160), transfused acute respiratory distress syndrome (ARDS) [n = 51], TRALI [n = 12], TACO/TRALI [n = 7], and controls [n = 335]. We used Wilcoxon Rank‐Sum tests to compare NT‐proBNP levels, and classification and regression tree (CART) algorithms to produce a ranking of covariates in order of relative importance for differentiating TACO from transfused controls.ResultsPre‐transfusion NT‐proBNP levels were elevated in cases of transfused ARDS and TACO (both P < .001) but not TRALI (P = .31) or TACO/TRALI (P = .23) compared to transfused controls. Pre‐transfusion NT‐proBNP levels were higher in cases of transfused ARDS or TRALI with a diagnosis of sepsis compared to those without (P < .05 for both). CART analyses resulted in similar differentiation of patients with TACO from transfused controls for models utilizing either NT‐proBNP levels (AUC 0.83) or echocardiogram results (AUC 0.80).ConclusionsNT‐proBNP levels may have utility in the classification of pulmonary transfusion reactions. Prospective studies are needed to test the predictive utility of pre‐transfusion NT‐proBNP in conjunction with other clinical factors in identifying patients at risk of pulmonary transfusion reactions.

AbstractCarotid artery atherosclerotic disease (CAAD) is a risk factor for stroke. We used a genome‐wide association (GWAS) approach to discover genetic variants associated with CAAD in participants in the electronic Medical Records and Genomics (eMERGE) Network. We identified adult CAAD cases with unilateral or bilateral carotid artery stenosis and controls without evidence of stenosis from electronic health records at eight eMERGE sites. We performed GWAS with a model adjusting for age, sex, study site, and genetic principal components of ancestry. In eMERGE we found 1793 CAAD cases and 17,958 controls. Two loci reached genome‐wide significance, on chr6 in LPA (rs10455872, odds ratio [OR] (95% confidence interval [CI]) = 1.50 (1.30–1.73), p = 2.1 × 10−8) and on chr7, an intergenic single nucleotide variant (SNV; rs6952610, OR (95% CI) = 1.25 (1.16–1.36), p = 4.3 × 10−8). The chr7 association remained significant in the presence of the LPA SNV as a covariate. The LPA SNV was also associated with coronary heart disease (CHD; 4199 cases and 11,679 controls) in this study (OR (95% CI) = 1.27 (1.13–1.43), p = 5 × 10−5) but the chr7 SNV was not (OR (95% CI) = 1.03 (0.97–1.09), p = .37). Both variants replicated in UK Biobank. Elevated lipoprotein(a) concentrations ([Lp(a)]) and LPA variants associated with elevated [Lp(a)] have previously been associated with CAAD and CHD, including rs10455872. With electronic health record phenotypes in eMERGE and UKB, we replicated a previously known association and identified a novel locus associated with CAAD.

AbstractBackgroundMost injection techniques utilizing hyaluronic acid–based soft tissue fillers have predictable outcomes at the location injected. However, the temporal region has been identified to have aesthetic effects beyond the temple.AimsTo identify and quantify the panfacial aesthetic effects of three different temporal injection techniques.Patients/MethodsThe medical records of nine female and five male Caucasian patients with a mean age of 50.9 ± 11.9 years were retrospectively reviewed for the effects of these techniques: supraperiosteal, interfascial, and subdermal. Panfacial effects were evaluated by the semiquantitative assessment of aesthetic scores for the temple volume, the temporal crest visibility, the lateral orbital rim visibility, the position of the eyebrows, the severity of lateral canthal lines, the midfacial volume, and the contour of the jawline.ResultsThe supraperiosteal injection technique had the greatest influence on improving the temporal volume (25.0%), the temporal crest (33.3%), and the lateral orbital rim visibility (31.0%) scales but had no effects in other facial regions. The interfascial injection technique revealed good effects on improving temporal hollowing (23.3%) but had an even greater effect on the crow's feet (26.8%) and on the position of the eyebrow (33.3%). The subdermal injection technique had its greatest effects in the lower face by improving the contour of the jawline (26.8%) followed by the improvement of the lower cheek fullness scale (14.3%).ConclusionFuture injection algorithms could utilize all three injection techniques together as one multi‐layer injection approach with a tailored proportion of each technique based on the aesthetic needs of the patient.