Histone locus regulation by the Drosophila dosage compensation adaptor protein CLAMP.

The conserved histone locus body (HLB) assembles prior to zygotic gene activation early during development and concentrates factors into a nuclear domain of coordinated histone gene regulation. Although HLBs form specifically at replication-dependent histone loci, the cis and trans factors that target HLB components to histone genes remained unknown. Here we report that conserved GA repeat cis elements within the bidirectional histone3-histone4 promoter direct HLB formation in Drosophila In addition, the CLAMP (chromatin-linked adaptor for male-specific lethal [MSL] proteins) zinc finger protein binds these GA repeat motifs, increases chromatin accessibility, enhances histone gene transcription, and promotes HLB formation. We demonstrated previously that CLAMP also promotes the formation of another domain of coordinated gene regulation: the dosage-compensated male X chromosome. Therefore, CLAMP binding to GA repeat motifs promotes the formation of two distinct domains of coordinated gene activation located at different places in the genome.

Extended thoracic endovascular aortic repair is optimal therapy in acute complicated type B dissection.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) represents optimal therapy for complicated acute type B aortic dissection (aTBAD). Persistent knowledge gaps remain, including the optimal length of aortic coverage, impact on distal aortic remodeling, and fate of the dissected abdominal aorta. METHODS: Review of the Emory Aortic Database identified 92 patients who underwent TEVAR for complicated aTBAD from 2012 to 2018. Standard TEVAR covered aortic zones 3 and 4 (from the left subclavian to the mid-descending thoracic aorta). Extended TEVAR fully covered aortic zones 3 though 5 (from the left subclavian to the celiac artery). Long-term imaging, clinical follow-up, and overall and aortic-specific mortality were reviewed. RESULTS: Extended TEVAR (n = 52) required a greater length of coverage vs standard TEVAR (n = 40) (240 ± 32 mm vs 183 ± 23 mm; P < .01). In-hospital mortality occurred in 5.4% of patients (7.7% vs 2.5%; P = .27) owing to mesenteric malperfusion (n = 3) or rupture (n = 2). The overall incidences of postoperative stroke, transient paraparesis, paraplegia, and dialysis were 5.4% (3.9% vs 7.5%; P = .38), 3.2% (5.8% vs 0%; P = .18), 0%, and 0% respectively, equivalent between groups. Follow-up was 96.6% complete to a mean of 6.1 years (interquartile range, 3.5-8.6 years). There were significantly higher rates of complete thrombosis or obliteration of the entire thoracic false lumen after Extended TEVAR (82.2% vs 51.5%; P = .04). Distal aortic reinterventions were less frequent after extended TEVAR (5.8% vs 20%; P = .04). Late aorta-specific survival was 98.1% after extended TEVAR vs 92.3% for standard TEVAR (P = .32). CONCLUSIONS: Extended TEVAR for complicated aTBAD is safe, results in a high rate of total thoracic false lumen thrombosis/obliteration, and reduces distal reinterventions. Longer-term follow-up will be needed to demonstrate a survival benefit compared to limited aortic coverage.

Acute Type B Intramural Hematoma: Novel Insights in the Endovascular Era.

BACKGROUND: The pathophysiology and behavior of acute type B intramural hematoma (TBIMH) is poorly understood. The purpose of this study is to characterize the pathophysiology, fate, and outcomes of TBIMH in the endovascular era. METHODS: A retrospective analysis of a US Aortic Database identified 70 patients with TBIMH from 2008 to 2022. Patients were divided into groups and analyzed based upon subsequent management: early thoracic endovascular aortic repair (TEVAR; Group 1) or hospital discharge on optimal medical therapy (OMT) (Group 2). RESULTS: Of 70 total patients, 43% (30/70) underwent TEVAR (Group 1) and 57% (40/70) were discharged on OMT (Group 2). There were no significant differences in age, demographics, or comorbidities between groups. Indications for TEVAR in Group 1 were as follows: 1) Penetrating atheroscletoic ulcer (PAU) or ulcer-like projection (n = 26); 2) Descending thoracic aortic aneurysm (n = 3); or 3) Progression to type B aortic dissection (TBAD) (n = 2). Operative mortality was zero. No patient suffered a stroke or spinal cord ischemia. During the follow-up period, 50% (20/40) of Group 2 patients required delayed surgical intervention, including TEVAR in 14 patients and open repair in 6 patients. Indications for surgical intervention were as follows: 1) Development of a PAU / ulcer-like projection (n = 13); 2) Progression to TBAD (n = 3), or 3) Concomitant aneurysmal disease (n = 4). Twenty patients did not require surgical intervention. Of the initial cohort, 71% of patients required surgery, 9% progressed to TBAD, and 19% had regression or stability of TBIMH with OMT alone. CONCLUSIONS: The most common etiology of TBIMH is an intimal defect. Progression to TBAD and intramural hematoma regression without an intimal defect occurs in a small percentage of patients. An aggressive strategy with endovascular therapy and close surveillance for TBIMH results in excellent short-term and long-term outcomes.

Efficacy of Grignard Pure to Inactivate Airborne Phage MS2, a Common SARS-CoV-2 Surrogate.

Grignard Pure (GP) is a unique and proprietary blend of triethylene glycol (TEG) and inert ingredients designed for continuous antimicrobial treatment of air. TEG has been designated as a ″Safer Chemical" by the US EPA. GP has already received approval from the US EPA under its Section 18 Public Health Emergency Exemption program for use in seven states. This study characterizes the efficacy of GP for inactivating MS2 bacteriophage─a nonenveloped virus widely used as a surrogate for SARS-CoV-2. Experiments measured the decrease in airborne viable MS2 concentration in the presence of different concentrations of GP from 60 to 90 min, accounting for both natural die-off and settling of MS2. Experiments were conducted both by introducing GP aerosol into air containing MS2 and by introducing airborne MS2 into air containing GP aerosol. GP is consistently able to rapidly reduce viable MS2 bacteriophage concentration by 2-3 logs at GP concentrations of 0.04-0.5 mg/m3 (corresponding to TEG concentrations of 0.025 to 0.287 mg/m3). Related GP efficacy experiments by the US EPA, as well as GP (TEG) safety and toxicology, are also discussed.

Bumblebee family lineage survival is enhanced in high-quality landscapes.

Insect pollinators such as bumblebees (Bombus spp.) are in global decline. A major cause of this decline is habitat loss due to agricultural intensification. A range of global and national initiatives aimed at restoring pollinator habitats and populations have been developed. However, the success of these initiatives depends critically upon understanding how landscape change affects key population-level parameters, such as survival between lifecycle stages, in target species. This knowledge is lacking for bumblebees, because of the difficulty of systematically finding and monitoring colonies in the wild. We used a combination of habitat manipulation, land-use and habitat surveys, molecular genetics and demographic and spatial modelling to analyse between-year survival of family lineages in field populations of three bumblebee species. Here we show that the survival of family lineages from the summer worker to the spring queen stage in the following year increases significantly with the proportion of high-value foraging habitat, including spring floral resources, within 250-1,000 m of the natal colony. This provides evidence for a positive impact of habitat quality on survival and persistence between successive colony cycle stages in bumblebee populations. These findings also support the idea that conservation interventions that increase floral resources at a landscape scale and throughout the season have positive effects on wild pollinators in agricultural landscapes.

NRX-101, a Rapid-Acting Anti-Depressant, Does Not Cause Neurotoxicity Following Ketamine Administration in Preclinical Models.

Agents that act at the N-methyl-D-aspartate receptor (NMDAR), such as ketamine, have gained increasing attention as rapid-acting antidepressants; however, their use has been limited by potential neurotoxicity. Recent FDA guidance requires a demonstration of safety on histologic parameters prior to the initiation of human studies. D-cycloserine (DCS) is a partial NMDA agonist that, along with lurasidone, is being investigated as a treatment for depression. The current study was designed to investigate the neurologic safety profile of DCS. To this end, female Sprague Dawley rats (n = 106) were randomly divided into 8 study groups. Ketamine was administered via tail vein infusion. DCS and lurasidone were administered via oral gavage in escalating doses to a maximum of 2000 mg/kg DCS. To ascertain toxicity, dose escalation with 3 different doses of D-cycloserine/lurasidone was given in combination with ketamine. MK-801, a known neurotoxic NMDA antagonist, was administered as a positive control. Brain tissue was sectioned and stained with H&E, silver, and Fluoro-Jade B stains. No fatalities were observed in any group. No microscopic abnormalities were found in the brain of animal subjects given ketamine, ketamine followed by DCS/lurasidone, or DCS/lurasidone alone. Neuronal necrosis, as expected, was seen in the MK-801 (positive control) group. We conclude that NRX-101, a fixed-dose combination of DCS/lurasidone, when administered with or without prior infusion of IV ketamine was tolerated and did not induce neurotoxicity, even at supratherapeutic doses of DCS.

Diverse Genome Topologies Characterize Dosage Compensation across Species.

Dosage compensation is the process by which transcript levels of the X chromosome are equalized with those of autosomes. Although diverse mechanisms of dosage compensation have evolved across species, these mechanisms all involve distinguishing the X chromosome from autosomes. Because one chromosome is singled out from other chromosomes for precise regulation, dosage compensation serves as an important model for understanding how specific cis-elements are identified within the highly compacted 3D genome to co-regulate thousands of genes. Recently, multiple genomic approaches have provided key insights into the mechanisms of dosage compensation, extending what we have learned from classical genetic studies. In the future, newer genomic approaches that require little starting material show great promise to provide an understanding of the heterogeneity of dosage compensation between cells and how it functions in nonmodel organisms.

Female gender is associated with increased late luminal narrowing within the stent graft after thoracic endovascular aortic repair.

BACKGROUND: Luminal narrowing, suspected secondary to thrombus, occurs within stent grafts at an unclear incidence after thoracic endovascular aortic repair (TEVAR). The significance of this phenomenon has not been determined, nor have the risk factors for development of intragraft luminal narrowing. Small graft diameter is hypothesized to be a risk factor for the development of ingraft stenosis. METHODS: A retrospective analysis was performed of a multicenter healthcare system including all patients who underwent TEVAR between July 2011 and July 2019 with at least 1 year of subsequently available surveillance contrast-enhanced computed tomography imaging. Standard demographic, preoperative, intraoperative, and postoperative variables were collected. Measurements were obtained via direct off-line images from computed tomography scans. Patent intragraft diameters were compared with baseline and interval change values were normalized to time to follow-up. The primary outcome measure was annual rate of intragraft luminal narrowing. RESULTS: There were 208 patients who met the inclusion criteria (94 women, 114 men) with a median follow-up of 822 days. The mean annual rate of percent intragraft diameter reduction was 10.5 ± 7.7% for women and 7.6 ± 5.6% for men (P = .0026). Multivariate analysis demonstrated female gender (P = .0283), preoperative diagnosis of hypertension (P = .0449), and need for coverage of the left subclavian artery (P = .0328) were all significant predictors of intragraft luminal narrowing. Small aortic diameters were not found to be associated independently with ingraft luminal narrowing nor was the concomitant use of antiplatelet or anticoagulation medications. Significant amounts of ingraft luminal narrowing, defined as a greater than 20% intragraft diameter decrease, were associated with an increased need for any reintervention, including for malperfusion, endoleak, and symptomatic aneurysm (P = .0249). Kaplan-Meier estimates demonstrated a significant gender-associated difference in high rates of intragraft luminal narrowing (P = .00189). CONCLUSIONS: In this analysis, female gender is shown to be a significant nonmodifiable risk factor for intragraft luminal narrowing after TEVAR. The development of this phenomenon is not benign; as such, these findings were associated with an increased need for reintervention. This finding may be attributable to differences in aortic compliance or gender-associated differences in coagulation pathways and merits further investigation. Surveillance after thoracic stent grafting must account for patient-specific variations in complication risk.

Learning curve and proficiency metrics for transcarotid artery revascularization.

BACKGROUND: When introduced to a new procedure, physicians improve their performance and reduce their procedural adverse event rates rapidly during the initial cases and then improvement slows, signaling that proficiency has been achieved. Determining when they have acquired proficiency has important implications for procedural innovation, education, credentialing, and patient safety. We analyzed the worldwide experience with transcarotid artery revascularization (TCAR), a hybrid approach to carotid revascularization, to identify the (1) procedural performance measures associated with clinical and technical adverse events; (2) target levels of performance measures that minimize adverse event rates; and (3) number of TCAR cases needed to achieve the target levels for the performance measures. METHODS: The patient, lesion, and physician characteristics were collected for each TCAR procedure performed by each physician worldwide in an international quality assurance database. Four procedural performance measures were recorded for each procedure: flow-reversal time, fluoroscopy time, contrast volume, and total skin-to-skin time. Composite clinical adverse events (ie, transient ischemic attack, stroke, myocardial infarction, death) and composite technical adverse events (ie, aborted procedure, conversion to surgery, bleeding, dissection, cranial nerve injury, device failure), occurring within 24 hours were also recorded. Correlations between each performance measure and the clinical and technical adverse event rates were computed. The inflection points in the performance measures were identified at which no further improvements occurred in the adverse event rates. Finally, the minimum number of TCAR cases required to achieve the target performance measure levels was computed. RESULTS: A total of 18,240 procedures performed by 1273 physicians were analyzed. Of the 18,240 patients, 34.9% were women and 62.5% were asymptomatic. The flow-reversal time correlated with clinical adverse events adjusted for age, sex, and symptomatic status (R2 = 0.91; P < .0001) and adjusted technical adverse events (R2 = 0.86; P < .0001). The skin-to-skin time correlated with adjusted technical adverse events (R2 = 0.92; P < .0001). A reduction in flow-reversal times to <13.1 minutes and the skin-to-skin time to <81 minutes did not translate into further improvements in the adverse event rates. A minimum of 26 TCAR cases was required to achieve the target flow-reversal time, and a minimum of 15 cases was required to achieve the target skin-to-skin time. CONCLUSIONS: The flow-reversal time and skin-to-skin time are appropriate performance measures for establishing the level of expertise of physicians as they acquire skills to perform TCAR. A target time of ≤13.1 minutes for flow-reversal and 81 minutes for skin-to-skin time minimized the adverse event rates. Familiarity with the steps involved in performing TCAR was achieved after ≥15 cases, and minimizing clinical adverse events occurred after ≥26 cases.

Long-term outcomes of the conformable TAG thoracic endoprosthesis in a prospective multicenter trial.

BACKGROUND: The Gore conformable TAG thoracic endoprosthesis (CTAG) was engineered to enhance conformability in the thoracic aorta and has demonstrated greater deployment accuracy and wall apposition than the original TAG device. The Food and Drug Administration approved the CTAG in 2011 based on the 1-year results of the pivotal trial for the CTAG device. In the present report, we have documented the outcomes for those patients through 5 years. METHODS: The CTAG aneurysm study was a prospective, multicenter trial that assessed the safety and effectiveness of the CTAG device as treatment of descending thoracic aortic aneurysms. Follow-up imaging assessments consisted of radiographs and computed tomography at annual intervals through 5 years. A core imaging laboratory was used to assess the aneurysm size, device integrity, and endoleaks. RESULTS: A total of 66 patients were enrolled (51 pivotal arm patients and 15 continued access patients) from October 2009 through September 2011. The baseline characteristics, procedural characteristics, and outcomes through 2 years were reported previously. Through 5 years, five patients (7.6%) had required device-related reintervention (one type Ia endoleak or contained rupture of the descending thoracic aorta, one type Ib endoleak, two indeterminate endoleaks, and one thoracic aortic pseudoaneurysm). Four patients (6.1%) had died of aneurysm-related causes, with one death occurring within 30 days of the index procedure. A total of 24 patients (36.3%) had died during the 5-year study period. Seven patients (10.6%) had experienced stroke or transient ischemic attack through 5 years, with one early stroke (postoperative day 28). Prosthesis or intercomponent migration was observed in six patients (9.1%) through 5 years; however, no patient had developed a type III junctional endoleak. No stent-graft fracture or compression was observed through 5 years. At 5 years, 14 patients (50.0%) showed sac regression, 5 (17.9%) showed sac expansion, and 9 (32.1%) showed sac stability using on a 5-mm threshold for change. CONCLUSIONS: Thoracic endovascular aortic repair with the CTAG device was associated with low rates of aneurysm-related mortality and reintervention through 5 years. Proximal endoleak was rare, and most patients showed sac regression or stability at 5 years after the initial thoracic endovascular aortic repair.

Influence of baseline kidney dysfunction on perioperative renal outcomes after endovascular aneurysm repair with suprarenal fixation.

BACKGROUND: Conflicting evidence exists regarding the comparative effects of endovascular aneurysm repair (EVAR) with and without suprarenal fixation. We compare outcomes in patients treated by EVAR with baseline normal kidney function and moderate and severe chronic kidney disease. METHODS: Patients with normal kidney function (glomerular filtration rate [GFR] ≥60 mL/min/1.73 m2) or moderate (GFR = 30-59 mL/min/1.73 m2) or severe (GFR <30 mL/min/1.73 m2) kidney disease who underwent EVAR (N = 5534) were identified from the American College of Surgeons National Surgical Quality Improvement Program targeted database (2011-2015). Groups were determined by the presence (Cook Zenith [Cook Medical, Bloomington, Ind] or Medtronic Endurant [Medtronic, Minneapolis, Minn]) or absence (Gore Excluder [W. L. Gore & Associates, Flagstaff, Ariz]) of a suprarenal fixation system. Postoperative renal complications, defined as rise in creatinine concentration of >2 mg/dL without dialysis or new dialysis requirements, were analyzed within the first 30 days with results stratified by degree of kidney disease. RESULTS: A total of 5534 patients underwent EVAR, with 3225 (58.3%) receiving a device using a suprarenal fixation system. Suprarenal fixation systems were less commonly used for symptomatic patients (11.0% vs 13.7%; P = .002) and patients with ruptured abdominal aortic aneurysm (4.5% vs 6.3%; P = .01). There was no difference in baseline kidney function between groups. EVAR with suprarenal fixation was associated with more renal complications (1.40% vs 0.65%; P = .008). In subgroup analysis, patients with moderate kidney dysfunction (n = 1780) had more renal complications (2.2% vs 0.8%; P = .02) with suprarenal fixation systems. No differences were seen in patients with normal kidney function (0.4% vs 0.2%; P = .32; n = 3597) or severe kidney dysfunction (14.3% vs 10.2%; P = .45; n = 157). This difference was driven mostly by postoperative elevation of creatinine concentration (0.6% vs 0.2%; P = .03) without requirements for new dialysis (0.8% vs 0.4%; P = .08). After adjustments with multivariate logistic regression models, EVAR with suprarenal fixation was associated with more renal complications (odds ratio, 2.65; 95% confidence interval, 1.32-5.34). CONCLUSIONS: In our study, EVAR with suprarenal fixation devices was associated with more perioperative renal complications in patients with moderate kidney dysfunction. Long-term evaluation of these patients undergoing EVAR should be considered.

Remodeling of Abdominal Aortic Angulation and Curvature After Endovascular Aneurysm Repair in Patients With vs Without Late Type Ia Endoleak or Endograft Migration.

PURPOSE: To investigate aortic remodeling of the supra- and infrarenal aorta from preoperative to 1 month and midterm follow-up after endovascular aneurysm repair (EVAR) by analyzing changes in angulation and curvature in patients with vs without late type Ia endoleak or device migration. MATERIALS AND METHODS: From a multicenter database, 35 patients (mean age 76±5 years; 31 men) were identified with late (>1 year) type Ia endoleak or endograft migration (≥10 mm) and defined as the complication group. The control group consisted of 53 patients (mean age 75±7 years; 48 men) with >1-year computed tomography angiography (CTA) follow-up and no evidence of endoleaks. Suprarenal and infrarenal angles were measured on centerline reconstructions of the preoperative, 1-month, and midterm CTA scans. The value and location relative to baseline of maximum suprarenal and infrarenal curvature were determined semiautomatically using dedicated software. Changes were determined at 1 month compared with the preoperative CTA and at midterm compared with 1 month. RESULTS: Preoperative suprarenal angulation was significantly greater in the complication group compared to the controls (34°±18° vs 24°±17°, p=0.008). It decreased significantly at 1 month in the complication group (29°±16°, p=0.011) and at midterm follow-up in the controls (20°±19°, p<0.001). Preoperative infrarenal angulation was not significantly different (57°±15° vs 49°±24°, p=0.114). This measurement increased significantly through midterm follow-up in the complication group (63°±23°, p<0.001) but remained stable in the controls (46°±22°). Preoperative suprarenal curvature was not significantly different (38±22 m-1 vs 29±25 m-1, p=0.115). This variable increased significantly through midterm follow-up in the complication group (44±22 m-1) but remained constant in the controls (28±22 m-1). Preoperative infrarenal curvature was significantly greater in the complication group (77±29 m-1 vs 65±28 m-1, p=0.047) and decreased significantly in both groups during midterm follow-up (50±17 m-1 vs 41±19 m-1 p=0.033). The location of the maximum curvature with regard to baseline shifted significantly distally in the complication group (54±43 to 72±41 mm, p<0.001), while it remained stable in the controls (46±33 to 48±31 mm). CONCLUSION: At midterm follow-up, significant differences in supra- and infrarenal angulation and curvature were observed between patients with vs without type Ia endoleak or migration. The location of the maximum curvature shifted distally in patients with complications. The aortic morphology is more stable during midterm follow-up in the patients without endoleaks.

Stent Graft Oversizing is Associated with an Increased Risk of Long-Term Left Ventricular Wall Thickening in Young Patients Following Thoracic Endovascular Aortic Repair.

BACKGROUND: Left ventricular (LV) wall thickening occurs in patients following thoracic endovascular aortic repair (TEVAR). Clinical consequences of cardiovascular (CV) remodeling may be more significant younger patients with longer anticipated life spans. Risk factors for CV remodeling following TEVAR are unknown but may be related to graft size. METHODS: A retrospective analysis was performed of a multicenter healthcare system including patients aged ≤60 who underwent TEVAR between 2011 and 2019 with at least 1 year follow-up computed tomography angiography imaging available. Standard perioperative variables, native aortic diameter, and stent graft specifications were collected. Graft oversizing was calculated by dividing proximal graft diameter by proximal aortic diameter on preoperative imaging. Posterior LV wall thickness was measured at baseline and interval increases were normalized to time-to-follow-up. Primary outcome was annual rate of posterior LV wall thickening. RESULTS: One hundred one patients met inclusion criteria with a mean (SD) follow-up time of 1270 (693) days. Overall mean (SD) rate of LV wall thickness change was 0.534 (0.750) mm per year. Mean (SD) absolute LV wall thickness at most recent follow-up was 10.97 (2.85) mm for men, 9.69 (2.03) mm for women. Multivariate analysis demonstrated that higher rates of LV wall thickening were associated with narrower graft diameters (P = 0.0311). Greater absolute LV wall thickness at follow-up was associated with narrower grafts (P= 0.0155) and greater graft oversizing (P= 0.0376). Logistic regression demonstrated individuals who met criteria for LV hypertrophy were more likely to have narrower stent-grafts (P= 0.00798) and greater graft oversizing (P= 0.0315). CONCLUSIONS: LV wall thickening occurred to a greater degree in individuals with narrower stent-grafts and higher rates of graft oversizing. This has significant implications for long-term cardiovascular health in younger patients may undergo TEVAR for atypical indications. Particular attention should be paid to long-term effects of stent-graft oversizing when selecting grafts in such populations.

Factors associated with adherence to follow-up calls in cancer patients receiving care at a community oncology practice.

BACKGROUND: Follow-up calls in the oncology setting are frequently used to augment care and encourage oral antineoplastic adherence. However, limited data are available on patient populations that would benefit from this intervention versus populations that may require alternative interventions. The purpose of this study was to identify characteristics among patients on oral antineoplastic agents that influence their likelihood to respond to follow-up calls. METHODS: Patients receiving care from one of the eight community oncology clinics within the same branch were analyzed. Patients were included if they were ≥18 years, received a new oral antineoplastic agent that was electronically prescribed between August 2018-October 2018, and picked up their first fill from their pharmacy of choice. Patients received up to six follow-up calls after picking up their first prescription. Calls were categorized as adherent (≥3 monthly interactions) or non-adherent (<3 monthly interactions). Logistic regression models were used to evaluate factors associated with follow-up call adherence. Factors included demographics, cancer stage, marital status, employment, pharmacy setting (internal pharmacy versus external pharmacy), and insurance used by the patient. Descriptive analysis was performed to analyze response rates, cancer diagnosis, and to determine the best time and day patients responded to follow-up calls. RESULTS: Data from 125 patients were analyzed, of which 65 patients (52%) were adherent to follow-up calls and the mean response rate over six months was 45% (range: 35% -- 54%). High success rates for follow-up calls were seen between 12-3 pm and on Tuesdays and Thursdays. After adjusting for covariates, patients with stage III-IV were 89% less likely to respond to follow-up calls compared to those with stage 0-II (95% CI: 0.02-0.64; p = 0.01), patients with commercial insurance were 79% less likely to adhere to follow-up calls compared to those on government insurance (95% CI: 0.06-0.71; p = 0.01), and patients using an external pharmacy had a 2.8 times increase odds of being adherent (95% CI 0.98-8.34; p = 0.05). All other factors were not significant. CONCLUSIONS: For patients taking oral antineoplastics, non-adherence to follow-up calls was observed in more than 45% of patients receiving care from a community oncology clinic. Findings demonstrated that those with advanced stages of cancer, on commercial insurance, and going to an internal pharmacy were at higher risk for not adhering to follow up calls. Therefore, alternative methods for managing adherence and side effects in these populations are warranted.

Prevalence and predictors of patients reporting adverse drug reactions to health care providers during oral targeted cancer treatment.

BACKGROUND: Pharmacovigilance is a critical component to facilitate clinicians' decision-making to alter or discontinue therapy. However, self-administration of oral targeted therapy (OTT) requires fewer clinical visits than parenteral infusions, potentially leading to an increase in the under-reporting of adverse drug reactions (ADRs). OBJECTIVE(S): To identify factors associated with patients reporting ADRs to their health care provider (HCP) and to identify the prevalence of unreported ADRs while on OTT. METHODS: Patients aged ≥18 years who received care from a community oncology clinic and newly prescribed an OTT between August 1, 2018, and October 31, 2018, were included. Six-monthly follow-up calls were conducted by the pharmacy staff to assess for gradable ADRs-validated by the NCI Common Terminology Criteria for Adverse Events-and ungradable ADRs. Descriptive analysis was used to analyze the prevalence of unreporting ADRs, and a multivariate logistic regression model was utilized to evaluate predictors of reporting ADRs to an HCP. Predictors included sociodemographic factors, severity of ADRs, insurance type, pharmacy setting, type of OTT, and the number of prescribed medications RESULTS: Of the 76 patients analyzed, the mean age was 63.32 ±11.55 years, 84.2% were women, 68.8% were non-Hispanic white, and 76.3% had breast cancer. During the follow-up calls, 306 ADRs were identified and 22.2% were not previously reported to an HCP. Of the unreported gradable ADRs, 63.2% were grade 1, 19.3% were grade 2, and 17.5% were grade 3. We found that for every 1-year increase in age, there was a 5% decrease in the likelihood of reporting ADRs (95% CI, 0.91-0.99), and men were 11.4 times more likely to report ADRs (95% CI, 1.29-100.8). CONCLUSION: Follow-up calls served as an outlet to collect pharmacovigilance data by identifying over 20% of unreported ADRs to HCPs, in which over one-third were moderate to severe. However, future studies are needed to further understand the statistically significant differences found in under-reporting for women and the older population.

Diabetes, dysglycemia, and vascular surgery.

BACKGROUND: Abnormalities in glucose metabolism are common in patients with arterial disease. Chronic hyperglycemia and insulin resistance contribute to the complexity of vascular disorders. They also overlap with the effects of perioperative hyperglycemia on adverse perioperative outcomes. We provide an overview of the pathophysiologic consequences of dysglycemia and the evidence behind glycemic control in patients undergoing vascular surgery. METHODS: We searched the literature for major studies evaluating the pathophysiology of hyperglycemia in microvascular and macrovascular beds, randomized trials in perioperative populations, and meta-analyses. The literature was summarized to guide therapy in the population of vascular patients and for the perioperative period. RESULTS: National standards for glycemic control after vascular interventions were not identified. Mounting evidence exists for the long-term consequences of poor glycemic control on the progression of vascular disease. Similarly, there is a large body of evidence supporting tight control of hyperglycemia after general and cardiac surgery during the critical perioperative period. The absolute glucose target remains controversial. Randomized controlled studies are lacking in vascular surgery patients, but the current evidence can be extrapolated to guide management after vascular interventions. Glycated hemoglobin is a biomarker for increased mortality and vascular morbidity after vascular surgery. CONCLUSIONS: Hyperglycemia contributes to poor outcome in the vascular patient. Further vascular focused studies are required to determine the proper perioperative serum glucose target and the long-term glycated hemoglobin range.

Clinical competence statement of the Society for Vascular Surgery on training and credentialing for transcarotid artery revascularization.

As the practice of medicine grows in complexity, the process of defining the expertise required for the competent execution of specific procedures has also become complex. The Society for Vascular Surgery therefore constituted a task force to provide informed recommendations on the knowledge, technical skills, resources, and infrastructure required to obtain and to maintain privileges for the safe and effective performance of transcarotid artery revascularization (TCAR). The TCAR procedure is being adopted rapidly, and it is therefore important that informed guidance be available expeditiously. Formal training in the pathophysiology and diagnosis of carotid occlusive disease and all management options is essential. Appropriate diagnostic, imaging, endovascular, surgical, and monitoring infrastructure is required, as are resources to maintain quality control. Credentialing and privileging require a combination of both open surgical and endovascular skills. As such, physicians must have hospital privileges to perform carotid endarterectomy. They should attend an appropriate program for education and simulated training in TCAR. In addition, physicians must have performed ≥25 endovascular procedures as the primary operator using low-profile rapid-exchange platforms plus ≥5 TCAR procedures as the primary operator (pathway 1); or they may have acquired ≥25 endovascular procedures as the primary operator using low-profile rapid-exchange platforms and a supplement of 5 TCAR procedures under proctored guidance if they have not performed sufficient TCAR procedures (pathway 2); or a team of two physicians can collaborate, combining the endovascular and surgical requirements plus at least 5 TCAR procedures under proctored guidance (pathway 3).

Economic burden and clinical impact of preoperative opioid dependence for patients undergoing lower extremity bypass surgery.

OBJECTIVE: Surgeons' prescription practices and the opioid epidemic have received significant attention in the media. Limited data exist, however, on the impact of prior or coexistent opioid use on vascular surgery outcomes. This study aimed to quantify the incidence, economic burden, and clinical impact of pre-existing opioid dependency in patients undergoing lower extremity bypass (LEB) surgery. METHODS: Data were collected from 1,132,645 weighted (230,858 unweighted) patient admissions for LEB in the National Inpatient Sample for the years 2002 to 2015. Patients with a concomitant diagnosis of opioid abuse or dependency were identified using International Classification of Diseases, Ninth Revision codes. Matched cohorts of patients with (n = 606 unweighted) and without (n = 32,343 unweighted) opioid dependence were created using coarsened exact matching to control for patient demographics. Linear regression was used to control for hospital-level factors and to identify differential outcomes for patients with opioid dependency. Our primary end points were hospital cost and length of stay. Our secondary end points were surgical complications and in-hospital mortality. RESULTS: There were 1,132,645 (230,858 unweighted) patient admissions for LEB in the National Inpatient Sample during 2002 to 2015. There were 3190 (0.3%) patients (643 unweighted) who had a diagnosis of pre-existing opioid dependency. The incidence of opioid dependency rose over time (2002, 0.13%; 2015, 0.63%; R2 = 0.90; P < .001). Before matching, opioid-dependent patients were younger (53.9 ± 12.3 years vs 66.7 ± 12.1 years; P < .001) and more likely to be male (65.2% vs 61.9%; P < .001), to be nonwhite (37.9% vs 24.1%; P < .001), to pay with Medicaid (29.6% vs 7.4%; P < .001), and to fall in the lowest income quartile based on ZIP code (39.6% vs 27.5%; P < .001). After matching, opioid-dependent patients (n = 606 unweighted vs n = 32,343 unweighted nonopioid-dependent patients) were at increased risk of surgical site infections (odds ratio [OR], 1.61; P = .006), major bleeding (OR, 1.56; P = .04), acute kidney injury (OR, 1.46; P = .02), and deep venous thrombosis (OR, 2.53; P = .005). Linear regression of matched cohorts revealed that opioid-dependent patients had an increased length of hospital stay (11.76 days vs 9.80 days; P < .001) and an increased mean inflation-adjusted in-hospital cost of U.S. $7032 ($37,522 vs $30,490; P < .001). CONCLUSIONS: The incidence of pre-existing opioid dependency in patients undergoing LEB continues to rise. Patients with opioid use disorder undergoing LEB surgery have substantial increases in length of hospital stay and costs. These findings highlight the importance of early preoperative recognition of this disorder in vascular surgery patients and open the opportunity for early intervention in that cohort.

CT-Derived Pretreatment Thoracic Sarcopenia Is Associated with Late Mortality after Thoracic Endovascular Aortic Repair.

BACKGROUND: Frailty, characterized by physiologic depletion, predicts postoperative morbidity and mortality in vascular surgery patients. CT-derived sarcopenia is a valuable method for objectively staging frailty preoperatively. PURPOSE: With prior analyses primarily measuring psoas cross-sectional area on CT, we compared a method of measuring thoracic sarcopenia to existing techniques of lumbar sarcopenia and assessed the association with long-term survival and outcomes post-Thoracic Endovascular Aortic Repair (TEVAR). METHODS: Prospectively collected data of 217 patients undergoing TEVAR from 2009 to 2012 were reviewed. Thoracic sarcopenia was quantified by measuring total area of the rectus abdominis, latissimus dorsi, intercostal, erector spinae, and external and internal oblique muscles at the T12 vertebral level. Total psoas area at the L3 was used to measure lumbar sarcopenia. RESULTS: 200 patients had preoperative imaging enabling measurements of thoracic sarcopenia, 186 of these patients were also assessed for lumbar sarcopenia. Thoracic sarcopenic patients were older, had lower body mass indices, were more commonly female, and most commonly being treated for aneurysms. Thoracic sarcopenic patients had significantly higher rates of congestive heart failure, hypertension, prior vascular intervention, and TEVAR-related adverse events. Thoracic sarcopenia was associated with significantly higher mortality at 2 and 5 years post-TEVAR (2-year mortality: 19% vs 8%, P = 0.02; 5-year mortality: 31% vs 18%, P = 0.03). Lumbar sarcopenia was not associated with increased mortality at any time point. Patients whose muscle mass degraded over 48-month follow-up did not experience significantly higher rates of adverse events. CONCLUSIONS: CT-derived thoracic sarcopenia, but not lumbar sarcopenia, is significantly associated with 5-year mortality post-TEVAR.