Genome-guided purification of high amounts of the siderophore ornibactin and detection of potentially novel burkholdine derivatives produced by Burkholderia catarinensis 89T.

AIM: The increased availability of genome sequences has enabled the development of valuable tools for the prediction and identification of bacterial natural products. Burkholderia catarinensis 89T produces siderophores and an unknown potent antifungal metabolite. The aim of this work was to identify and purify natural products of B. catarinensis 89T through a genome-guided approach. MATERIALS AND METHODS: The analysis of B. catarinensis 89T genome revealed 16 clusters putatively related to secondary metabolism and antibiotics production. Of particular note was the identification of a nonribosomal peptide synthetase (NRPS) cluster related to the production of the siderophore ornibactin, a hybrid NRPS-polyketide synthase Type 1 cluster for the production of the antifungal glycolipopeptide burkholdine, and a gene cluster encoding homoserine lactones (HSL), probably involved in the regulation of both metabolites. We were able to purify high amounts of the ornibactin derivatives D/C6 and F/C8, while also detecting the derivative B/C4 in mass spectrometry investigations. A group of metabolites with molecular masses ranging from 1188 to 1272 Da could be detected in MS experiments, which we postulate to be new burkholdine analogs produced by B. catarinensis. The comparison of B. catarinensis BGCs with other Bcc members corroborates the hypothesis that this bacterium could produce new derivatives of these metabolites. Moreover, the quorum sensing metabolites C6-HSL, C8-HSL, and 3OH-C8-HSL were observed in LC-MS/MS analysis. CONCLUSION: The new species B. catarinensis is a potential source of new bioactive secondary metabolites. Our results highlight the importance of genome-guided purification and identification of metabolites of biotechnological importance.

Fate of the unoperated ascending thoracic aortic aneurysm: three-decade experience from the Aortic Institute at Yale University.

AIMS: This study aims to outline the 'true' natural history of ascending thoracic aortic aneurysm (ATAA) based on a cohort of patients not undergoing surgical intervention. METHODS AND RESULTS: The outcomes, risk factors, and growth rates of 964 unoperated ATAA patients were investigated, over a median follow-up of 7.9 (maximum of 34) years. The primary endpoint was adverse aortic events (AAE), including dissection, rupture, and aortic death. At aortic sizes of 3.5-3.9, 4.0-4.4, 4.5-4.9, 5.0-5.4, 5.5-5.9, and ≥6.0 cm, the average yearly risk of AAE was 0.2%, 0.2%, 0.3%, 1.4%, 2.0%, and 3.5%, respectively (P < 0.001), and the 10-year survival free from AAE was 97.8%, 98.2%, 97.3%, 84.6%, 80.4%, and 70.9%, respectively (P < 0.001). The risk of AAE was relatively flat until 5 cm of aortic size, at which it began to increase rapidly (P for non-linearity <0.001). The mean annual growth rate was estimated to be 0.10 ± 0.01 cm/year. Ascending thoracic aortic aneurysms grew in a very slow manner, and aortic growth over 0.2 cm/year was rarely seen. Multivariable Cox regression identified aortic size [hazard ratio (HR): 1.78, 95% confidence interval (CI): 1.50-2.11, P < 0.001] and age (HR: 1.02, 95% CI: 1.00-1.05, P = 0.015) as significant independent risk factors for AAE. Interestingly, hyperlipidemia (HR: 0.46, 95% CI: 0.23-0.91, P = 0.025) was found to be a significant protective factor for AAE in univariable Cox regression. CONCLUSION: An aortic size of 5 cm, rather than 5.5 cm, may be a more appropriate intervention criterion for prophylactic ATAA repair. Aortic growth may not be an applicable indicator for intervention.

p53-Abnormal "Fields of Dysplasia" in Human Papillomavirus-Independent Vulvar Squamous Cell Carcinoma Impacts Margins and Recurrence Risk.

Abnormal p53 (p53abn) immunohistochemical (IHC) staining patterns can be found in vulvar squamous cell carcinoma (VSCC) and differentiated vulvar intraepithelial neoplasia (dVIN). They can also be found in the adjacent skin that shows morphology that falls short of the traditional diagnostic threshold for dVIN. Vulvectomy specimens containing human papillomavirus-independent p53abn VSCC with margins originally reported as negative for invasive and in situ disease were identified. Sections showing the closest approach by invasive or in situ neoplasia to margins were stained with p53 IHC stains. We evaluated the following: (1) detection of morphologically occult p53abn in situ neoplasia, (2) rates of margin status change after p53 IHC staining, and (3) effect of p53abn IHC staining at margins on the 2-year local recurrence rates. Seventy-three human papillomavirus-independent p53abn VSCCs were included. Half (35/73, 48%) had documented an in situ lesion in the original report. The use of p53 IHC staining identified 21 additional cases (29%) with the p53abn in situ lesions that were originally unrecognized. The histology of in situ lesions in the p53abn "field" varied and became more subtle (morphologically occult) farther away from the VSCC. Fifteen (21%) cases had a morphologically occult and previously unrecognized p53abn in situ lesion present at a resection margin, which conferred an increased risk of local recurrence (5/7 [71.4%] vs 6/22 [27.3%], P = .036). The p53abn in situ lesions at a margin were confirmed to have TP53 mutations by sequencing. p53 IHC staining identified morphologically occult p53abn in situ lesions surrounding human papillomavirus-independent VSCC. p53abn IHC staining at a margin was associated with a 3-fold increased risk of local recurrence.

Classification of Vulvar Squamous Cell Carcinoma and Precursor Lesions by p16 and p53 Immunohistochemistry: Considerations, Caveats, and an Algorithmic Approach.

There is emerging evidence that vulvar squamous cell carcinoma (VSCC) can be prognostically subclassified into 3 groups based on human papillomavirus (HPV) and p53 status: HPV-associated (HPV+), HPV-independent/p53 wild-type (HPV-/p53wt), or HPV-independent/p53 abnormal (HPV-/p53abn). Our goal was to assess the feasibility of separating VSCC and its precursors into these 3 groups using p16 and p53 immunohistochemistry (IHC). A tissue microarray containing 225 VSCC, 43 usual vulvar intraepithelial neoplasia (uVIN/HSIL), 10 verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN), and 34 differentiated VIN (dVIN), was stained for p16 and p53. Noncomplementary p16 and p53 patterns were resolved by repeating p53 IHC and HPV RNA in situ hybridization (ISH) on whole sections, and sequencing for TP53. Of 82 p16-positive VSCC, 73 (89%) had complementary p16 and p53 patterns and were classified into the HPV+ group, 4 (4.9%) had wild-type p53 staining, positive HPV ISH and were classified into the HPV+ group, whereas 5 (6.1%) had p53 abnormal IHC patterns (1 null, 4 overexpression), negativity for HPV ISH, and harbored TP53 mutations (1 splice site, 4 missense); they were classified as HPV-/p53abn. Of 143 p16-negative VSCC, 142 (99.3%) had complementary p53 and p16 patterns: 115 (80.4%) HPV-/p53abn and 27 (18.9%) HPV-/p53wt. One had a basal-sparing p53 pattern, positivity for HPV ISH and was negative for TP53 mutations-HPV+ category. The use of IHC also led to revised diagnoses-HSIL to dVIN (3/43), dVIN to vaVIN (8/34), and dVIN to HSIL (3/34). Overall, 215/225 VSCC (95.6%) could be easily classifiable into 3 groups with p16 and p53 IHC. We identified several caveats, with the major caveat being that "double-positive" p16/p53 should be classified as HPV-/p53abn. We propose an algorithm that will facilitate the application of p16 and p53 IHC to classify VSCC in pathology practice.

Technical Feasibility and Safety of a Snare-Less, EVAR-First Technique for Iliac Branch Endoprosthesis.

OBJECTIVE: The purpose of this study was to evaluate the technical feasibility, safety, and early outcomes of a snare-less, endovascular abdominal aortic aneurysm repair (EVAR)-first technique (SET) for iliac branch endoprosthesis (IBE) placement. METHODS: We retrospectively reviewed all patients who received IBEs between July 2018 and March 2022. Patients were divided into 2 categories based on method of IBE deployment: SET or Standard. Primary endpoints were technical success, major adverse events, mortality, reintervention, internal iliac artery (IIA) patency, and freedom from IIA branch instability. Technical success was defined by successful deployment of both the EVAR and the IBE with maintained patency of the IIA and no stent graft migration. RESULTS: There were 20 patients (90% male, median age 72 [65.4-74.5] years) who underwent IBE placement. Among these, 5 (33.3%) underwent SET to treat 5 common iliac artery (CIA)/IIA aneurysms, while the remaining 15 (66.7%) underwent standard IBE deployment with through-and-through femoral access (n=13) or trans-brachial access (n=2) to treat 19 CIA/IIA aneurysms. Overall median renal to iliac bifurcation length was 169 (152-177) mm, with 9 patients falling short of the minimum of 165 mm for on-label IBE placement. Median contrast used was 148 (120-201) mL, fluoroscopy time 42.8 (35.0-49.8) minutes, estimated blood loss 200 (100-275) mL, and procedure time 192 (167-246) minutes, with no significant differences between the 2 groups. Technical success was achieved in 100% of cases. At 30 days, there were no mortalities or major adverse events in either group; there were 100% IIA patency, no IIA instability, and no reinterventions in both groups. Median follow-up in the SET group was 5.7 (5.5-6.2) months, with 1 death at 6 months and 1 type 1B endoleak at 6 months requiring reintervention. Median follow-up for the Standard group was 1.6 (0.8-2.1) years with 2 non-aneurysm-related deaths and no reinterventions at 1 year. CONCLUSIONS: SET for IBE is a safe and effective approach that decreases technical complexity and mitigates anatomic barriers to IBE placement. CLINICAL IMPACT: SET for IBE is a safe and effective approach to IBE placement that decreases technical complexity. A critical component to this technique is a large bore sheath with a stiff steerable tip. Importantly, this approach also mitigates anatomic barriers to IBE placement, expanding applicability of IBE technology to patients who may be otherwise ineligible.

Outcome Measurement in Children With a History of Disorders of Consciousness After Severe Brain Injury: Telephone Administration of the Vineland Adaptive Behavior Scales, Third Edition, and Glasgow Outcome Scale-Extended Pediatric Revision.

OBJECTIVES: Examine initial feasibility and utility of a battery of measures administered via telephone interview with a caregiver for describing long-term outcomes in individuals with a history of disorders of consciousness (DoC) after pediatric acquired brain injury (ABI). DESIGN: Cross-sectional. SETTING: Caregiver interview administered via telephone. PATIENTS: Convenience sample admitted to an inpatient pediatric neurorehabilitation unit with DoC after ABI at least 1 year prior to assessment (n = 41, 5-22 yr old at assessment). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Vineland Adaptive Behavior Scales, Third Edition (Vineland-3), and Glasgow Outcome Scale-Extended Pediatric Revision (GOS-E Peds) were examined. Administration time of the Vineland-3 ranged from 13 to 101 minutes (m = 50) and the GOS-E Peds ranged from 2 to 10 minutes (m = 3). Vineland-3 Adaptive Behavior Composite (ABC) ranged from standard scores (SSs) of 20 (exceptionally low) to 100 (average) and GOS-E Peds scores ranged from 3 (i.e., upper moderate disability) to 7 (vegetative state). Lower adaptive functioning on the Vineland-3 ABC was strongly associated with greater disability on the GOS-E Peds (r = -0.805). On the Vineland-3 ABC, 19.5% earned the lowest possible score, whereas 12.2% obtained the lowest possible score for survivors on the GOS-E Peds; only 7.3% earned lowest scores on both measures. CONCLUSIONS: The Vineland-3 and GOS-E Peds were feasibly administered by telephone and were complementary in this cohort; the GOS-E provided a quick and easy measure of gross functional outcome, whereas the Vineland-3 took longer to administer but provided a greater level of detail about functioning. When both measures were used together, the range and variability of scores were maximized.

Predictors of Audio-Only Versus Video Telehealth Visits During the COVID-19 Pandemic.

BACKGROUND: Most health insurance organizations reimbursed both video and audio-only (i.e., phone) visits during the COVID-19 pandemic, but may discontinue phone visit coverage after the pandemic. The impact of discontinuing phone visit coverage on various patient subgroups is uncertain. OBJECTIVE: Identify patient subgroups that are more probable to access telehealth through phone versus video. DESIGN: Retrospective cohort. PATIENTS: All patients at a U.S. academic medical center who had an outpatient visit that was eligible for telehealth from April through June 2020. MAIN MEASURES: The marginal and cumulative effect of patient demographic, socioeconomic, and geographic characteristics on the probability of using video versus phone visits. KEY RESULTS: A total of 104,204 patients had at least one telehealth visit and 45.4% received care through phone visits only. Patient characteristics associated with lower probability of using video visits included age (average marginal effect [AME] -6.9% for every 10 years of age increase, 95%CI -7.8, -4.5), African-American (AME -10.2%, 95%CI -11.4, -7.6), need an interpreter (AME -19.3%, 95%CI -21.8, -14.4), Medicaid as primary insurance (AME -12.1%, 95%CI -13.7, -9.0), and live in a zip code with low broadband access (AME -7.2%, 95%CI -8.1, -4.8). Most patients had more than one factor which further reduced their probability of using video visits. CONCLUSIONS: Patients who are older, are African-American, require an interpreter, use Medicaid, and live in areas with low broadband access are less likely to use video visits as compared to phone. Post-pandemic policies that eliminate insurance coverage for phone visits may decrease telehealth access for patients who have one or more of these characteristics.

Elucidating the Role of the AFX2 Endograft in Endovascular Treatment of Aortic Pathology.

BACKGROUND: The purpose of this study is to elucidate the role of the AFX2 platform in the endovascular treatment of aortic pathology. METHODS: All procedures by a single surgeon resulting in implantation of a bifurcated unibody stent graft were reviewed retrospectively. Indications for selection of the AFX2 endograft in each case were evaluated. Aortic anatomy was determined via review of pre-operative computed tomography (CT) scans. Cumulative event probabilities for endoleak, reintervention, and mortality were estimated. Patient and procedural details were described using mean, standard deviation, medians, and interquartile range (IQR). Kaplan-Meier survival analysis estimated freedom from mortality and reintervention. Cumulative incidence probabilities were calculated as one minus the Kaplan-Meier estimator. RESULTS: Between March 2018 and December 2020, the author (NN) used 142 aortic endografts in 142 patients. Of these, 46 (32.4%) were AFX2 endografts and the remaining were modular bifurcated devices, predominantly Medtronic Endurant II and Terumo Treo. No AFX-Strata or AFX-Duraply devices were placed. Amongst the patients who received an AFX2, mean age was 71.3 +/- 9.8 years with 84.8% male. Median operative time was 116 (86-166) min, with contrast dose of 79 (41-120) milliliters and fluoroscopy time of 12 (8.6-18) min. Overall, 78.3% (n = 36) of AFX2 devices were placed in aortas with maximum true lumen diameter <5.0 cm. Median postoperative follow-up was 1.7 years (IQR 1.0-2.4 years), with a maximum follow-up of 3.6 years. There was 1 patient lost to follow-up at 5 months. The 2-year incidence of type II endoleak, reintervention, and all-cause mortality was 12.7% (95% confidence interval CI, 0-29.6%), 2.2% (95% CI, 0-6.3%), and 11.3% (95% CI, 0.1-2.1.2%), respectively. There were no type I or III endoleaks. CONCLUSIONS: The AFX2 endograft plays a safe and effective role in treatment of infrarenal aortic pathologies that may be otherwise more technically challenging for traditional modular, bifurcated devices.

Surgery for complications after thoracic endovascular aortic repair with arch vessel debranching: Role of imaging in preoperative planning.

We describe here a series of patients who presented with failed hybrid arch and descending thoracic aortic aneurysm repairs, while highlighting the instrumental role that advanced medical imaging played in formulating an operative plan. Each case involved persistent 1A endoleaks and aneurysm sac growth after hybrid arch repairs tackled by arch debranching followed by thoracic endovascular aortic repair. Two open cases were described as well as one endovascular case. Imaging played a key role in elucidating the site of endoleak and in operative planning. These cases highlight the importance of multidisciplinary input between cardiac surgery, vascular surgery and radiology in management of complex aortic patients.

Very Long-Term Outcomes in Children Admitted in a Disorder of Consciousness After Severe Traumatic Brain Injury.

OBJECTIVES: To investigate functional outcomes and state of consciousness at 1 year and ≥2 years postinjury in children who sustained a traumatic brain injury and were in a disorder of consciousness (DOC), either vegetative state (VS) or minimally conscious state (MCS), upon admission to inpatient rehabilitation. DESIGN: Retrospective chart review. SETTING: Pediatric inpatient rehabilitation unit. PARTICIPANTS: Children aged 2-18 years (N=37) who were admitted to inpatient rehabilitation with admission scores <30 on the Cognitive and Linguistic Scale (CALS). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Glasgow Outcome Scale- Extended, Pediatric Revision (GOS-E Peds), and state of consciousness based on previously established guidelines. RESULTS: At admission, 16 children were in VS (43.2%) and 21 (56.8%) were in MCS. Children admitted in VS had a significantly longer time from injury to inpatient rehabilitation admission, lower CALS admission scores, were more likely to be in a DOC ≥28 days, and had greater disability at both follow-up time points. At the 1-year follow-up, 3 patients were in VS, 7 were in MCS, and 27 had emerged from MCS. By the time of the most recent follow-up (≥2y), 2 more patients had emerged from MCS. Across the cohort, GOS-E Peds scores at 1 year ranged from VS (GOS-E Peds, 7) to upper moderate disability (GOS-E Peds, 3). Most patients were functioning in the lower severe disability category (GOS-E Peds, 6) at 1 year (43.2%) and at the time of the most recent follow-up (43.2%). Twenty-seven patients (73.0%) showed stable GOS-E Peds scores between the 2 time points, 6 (16.2%) improved, and 4 (10.8%) were deceased. CONCLUSIONS: Although a majority of patients emerged from a DOC by 1 year postinjury, most continued to demonstrate notable functional impairment at the 1-year follow-up that persisted to the most recent follow-up. A small subset demonstrated important improvements between 1 year and the most recent follow-up (2 patients emerged, 6 patients showed improvement in GOS-E Peds scores).

Alternative Endograft Aortoiliac Reconstruction for Iliac Branch Endoprostheses.

BACKGROUND: Endovascular treatment of complex common iliac artery (CIA) and internal iliac artery (IIA) aneurysms using iliac branch endoprostheses (IBE) has proven safe and effective. Instructions for use (IFU) require deployment of current IBE technology with the corresponding manufacturer's modular bifurcated aortic endograft. Concomitant aortoiliac occlusive disease, inadequate renal artery-iliac bifurcation length, and unfavorable aortic anatomy preclude on-label IBE deployment. This study aimed to evaluate the technical feasibility and safety of Alternative Endograft Aortoiliac Reconstruction (AEGAR) for branched endovascular treatment of complex iliac artery aneurysms. METHODS: In 7 consecutive patients with CIA or IIA aneurysms, computed tomography angiography (CTA) and center-line reconstruction revealed aortoiliac anatomy incompatible with the current IBE IFU due to inadequate proximal CIA landing zone (n = 7), inadequate renal artery to iliac bifurcation length (n = 2), compromised aortic anatomy (n = 3), or short infrarenal neck <15 mm (n = 1), either alone or in combination. To overcome these restrictions and facilitate IBE deployment, aortoiliac reconstruction was performed using the Endologix AFX, Endologix Ovation limbs or the Medtronic Endurant II platforms (AEGAR technique). All internal iliac artery reconstructions and external iliac artery extensions were performed using the Gore VBX or Viabahn stent grafts. Technical success was defined as successful delivery of all endograft components without migration or endoleak. RESULTS: The mean patient age was 69 years (range 52-82 years; 6 male). Four patients had bilateral CIA aneurysms and 3 patients had unilateral CIA aneurysms (mean diameter 4.3cm; range 2.2-7 cm). There were 13 IIA VBX stent grafts used for a total of 9 IIAs treated with IBE (bilateral IBE = 2 patients). The mean fluoroscopy time was 38.8 min (range 21.3-64.3 min) and the mean contrast volume was 168.5 mL (range 122-226 mL). Technical success was achieved in all patients and there were no perioperative complications. Mean hospital-stay was 2.2 days (range 1-3 days). Follow-up ranged from 82-957 days (mean = 487 days). At last follow-up, all patients were alive without cardiovascular morbidity; and CTA revealed stable or decreased aneurysm size, patent endografts, and no evidence of endoleak or migration. CONCLUSIONS: The AEGAR technique can be used to safely and effectively overcome certain aortoiliac anatomic constraints that preclude use of current IBE technology. We encourage broader use of these alternative endografts in pertinent anatomic configurations.

New Nocobactin Derivatives with Antimuscarinic Activity, Terpenibactins A-C, Revealed by Genome Mining of Nocardia terpenica IFM 0406.

We report a genomics-guided exploration of the metabolic potential of the brasilicardin producer strain Nocardia terpenica IFM 0406. Bioinformatics analysis of the whole genome sequence revealed the presence of a biosynthetic gene cluster presumably responsible for the generation of formerly unknown nocobactin derivatives. Mass spectrometry-assisted isolation led to the identification of three new siderophores, terpenibactins A (1), B (2) and C (3), which belong to the class of nocobactins. Their structures were elucidated by employing spectroscopic techniques. Compounds 1-3 demonstrated inhibitory activity towards the muscarinic M3 receptor, while exhibiting only a low cytotoxicity.

p53 Immunohistochemical patterns in HPV-related neoplasms of the female lower genital tract can be mistaken for TP53 null or missense mutational patterns.

We have recently encountered p53 immunohistochemical (IHC) patterns in human papillomavirus (HPV)-associated carcinomas of the gynecologic tract, which were confused with absent (null) or overexpression TP53 mutational staining. We therefore evaluated p53 and p16 IHC in 25 squamous cell carcinomas (SCC) (16 vulva, 4 Bartholin's gland, and 5 cervix), 20 endocervical adenocarcinomas (EDAC), 14 high-grade squamous intraepithelial lesions (HSIL), 2 adenocarcinoma in situ (AIS), all of which exhibited morphologic features of HPV. Only cases showing diffuse/strong block-like p16 staining were included for further study. All EDACs underwent TP53 sequencing and HPV in situ hybridization (ISH) was performed in selected cases. p53 IHC staining fell into two main patterns. The most common was designated as "markedly reduced (null-like)" (absence or significantly attenuated staining in >70% of cells), which could be confused with true null mutational pattern. This was present in 14/25 (56%) SCCs, 7/14 (50%) HSILs, and 18/20 (90%) EDACs. The second notable pattern was "mid-epithelial (basal sparing)" (distinct absence of staining in basal cells juxtaposed with strong staining in parabasal cells), seen in 10/25 (40%) SCC, 7/14 (50%) HSIL, and none of the EDACs. There was scattered weak to moderate p53 staining (conventional wild type) in 1/25 (4%) SCC and 2/20 (10%) EDAC. No cases showed strong/diffuse overexpression. One EDAC had a TP53 missense mutation and exhibited "markedly reduced (null-like)" staining. HPV ISH revealed an inverse relationship with p53, cells positive for HPV mRNA were negative for p53. Knowledge of these patterns can help pathologists avoid misinterpreting p53 status in the setting of HPVA cancers.

Major p53 immunohistochemical patterns in in situ and invasive squamous cell carcinomas of the vulva and correlation with TP53 mutation status.

The recent literature has shown that vulvar squamous cell carcinoma (VSCC) can be stratified into two prognostically relevant groups based on human papillomavirus (HPV) status. The prognostic value of p53 for further sub-stratification, particularly in the HPV-independent group, has not been agreed upon. This disagreement is likely due to tremendous variations in p53 immunohistochemical (IHC) interpretation. To address this problem, we sought to compare p53 IHC patterns with TP53 mutation status. We studied 61 VSCC (48 conventional VSCC, 2 VSCC with sarcomatoid features, and 11 verrucous carcinomas) and 42 in situ lesions (30 differentiated vulvar intraepithelial neoplasia [dVIN], 9 differentiated exophytic vulvar intraepithelial lesions [deVIL], and 3 high-grade squamous intraepithelial lesions or usual vulvar intraepithelial neoplasia [HSIL/uVIN]). IHC for p16 and p53, and sequencing of TP53 exons 4-9 were performed. HPV in situ hybridization (ISH) was performed in selected cases. We identified six major p53 IHC patterns, two wild-type patterns: (1) scattered, (2) mid-epithelial expression (with basal sparing), and four mutant patterns: (3) basal overexpression, (4) parabasal/diffuse overexpression, (5) absent, and (6) cytoplasmic expression. These IHC patterns were consistent with TP53 mutation status in 58/61 (95%) VSCC and 39/42 (93%) in situ lesions. Cases that exhibited strong scattered staining and those with a weak basal overexpression pattern could be easily confused. The mid-epithelial pattern was exclusively observed in p16-positive lesions; the basal and parabasal layers that had absent p53 staining, appeared to correlate with the cells that were positive for HPV-ISH. This study describes a pattern-based p53 IHC interpretation framework, which can be utilized as a surrogate marker for TP53 mutational status in both VSCC and vulvar in situ lesions.

A review of prognostic factors in squamous cell carcinoma of the vulva: Evidence from the last decade.

Squamous cell carcinoma of the vulva is a rare gynecologic cancer that is associated with significant patient morbidity and mortality, particularly for recurrent disease. This review summarizes the evidence and continued challenges, regarding the traditional clinicopathologic factors used to prognosticate vulvar squamous cell carcinoma. Articles published within the last 10 years (2010-2020) were identified. Relevant articles concerning the following fifteen prognostic factors were reviewed: HPV/p16 status, vulvar intraepithelial neoplasia, patient age, tumor stage, tumor grade, tumor size, depth of invasion, stromal changes, histologic patterns of invasion, lymphovascular space invasion (LVSI), perineural invasion, lymph node metastases, tumour focality, margin status and lichen sclerosus (LS). The relationship between each prognostic factor and progression-free survival (PFS) and overall survival (OS), including hazard ratios, 95% confidence intervals and p-values, were extracted.

Intraoperative retrograde TEVAR to control endoleak after emergent total arch replacement and frozen elephant trunk repair for ruptured Kommerell's diverticulum.

We report an emergent complex hybrid repair of a type A intramural hematoma with a tear of the aortic arch at the site of Kommerell's diverticulum and an aberrant right subclavian artery. We identified a type IA endoleak intraoperatively, which was managed immediately with proximal extension. Performing this operation in the hybrid operating room facilitated optimal surgical management.

Practice patterns of dual antiplatelet therapy after lower extremity endovascular interventions.

Antiplatelet therapy is commonly prescribed following endovascular interventions. However, there is limited data regarding the regimen and duration of antiplatelet therapy following lower extremity endovascular interventions. The aim of this study was to investigate the practice patterns of dual antiplatelet therapy (DAPT) after lower extremity endovascular interventions. We identified all patients who received an endovascular intervention in the Vascular Study Group of New England (VSGNE) registry from 2010 through 2018. The antiplatelet regimen was examined at the time of discharge and follow-up. Variables predicting discharge antiplatelet therapy and duration of antiplatelet therapy were investigated. There were 13,510 (57.69%) patients discharged on DAPT, 8618 (36.80%) patients discharged on single antiplatelet therapy, and 1292 (5.51%) patients discharged without antiplatelet therapy. Patients with coronary artery disease (CAD), prior vascular bypass and endovascular intervention, preoperative statin use, stent placement compared with angioplasty, and femoropopliteal and tibial treatment were associated with higher odds of being discharged with DAPT compared with no antiplatelet therapy and single antiplatelet therapy. Of the patients discharged on DAPT who were followed up at 9-12 months and 21-24 months, 56.49% and 49.63% remained on DAPT, respectively. Only a narrow margin of the patient majority undergoing endovascular interventions was discharged with DAPT, suggesting that only a small proportion of patients undergoing endovascular intervention remain on DAPT long-term. As the number of peripheral vascular interventions continues to grow, further studies are crucial to identify the optimal duration of DAPT.

An Ecological Momentary Assessment of Cigarette and Cigar Dual Use Among African American Young Adults.

Introduction: The dual use of cigarettes and cigars among African American young adults is a significant public health issue. Patterns of and reasons for dual use are difficult to capture using traditional self-report methods. This study used ecological momentary assessment (EMA) to characterize patterns of dual smoking and examine the personal and environmental predictors of cigarette and cigar smoking among African American young adult dual users (ages 18-29) in real-time. Methods: For 14 days, 64 participants smoked ad libitum and were prompted four times daily to record their smoking, craving, emotions, social smoking, and environment via text message on their mobile phones. The odds of single product and dual use were examined using adjusted generalized estimating equations. Results: Participants smoked an average of 7.9 cigarettes and 4.2 cigars per day. Cigarettes and cigars were smoked as frequently during periods of dual use as they were during periods of single product use. Cigarette craving was positively associated with cigarette-only smoking (OR: 1.07), whereas cigar craving was positively associated with cigar-only smoking (OR: 1.43) and dual use (OR: 1.08). Cigars had the greatest odds of dual use when with others (OR: 4.69) and in others' homes (OR: 4.33). Cigarettes had the greatest odds of being smoked while alone (OR: 1.57). Conclusions: EMA was useful for capturing variable smoking patterns and predictors. In this study population, cigarettes and cigars appeared to be smoked additively, and cigars smoked socially. These findings can inform future interventions addressing dual use in this high priority population. Implications: This is the first study to use EMA to examine naturalistic patterns and predictors of multiple tobacco use in real-time. African American young adults smoked cigarettes and cigars during periods of dual use as frequently as during periods of single product use. This suggests that most use was additive (one product smoked in addition to another) and less often as substitution (one product smoked instead of another). Social smoking and craving were strongly associated with cigar smoking in single and dual use periods. This study suggests the need for cessation messaging specifically targeted to reduce dual use in this population.

Receipt of tobacco direct mail/email discount coupons and trajectories of cigarette smoking behaviours in a nationally representative longitudinal cohort of US adults.

BACKGROUND: We assessed whether receipt of coupons-via direct mail or e-mail-was prospectively related to trajectories of smoking behaviours. METHODS: Data were from a cohort of US adults (n=26 447) who participated in wave 1 (2013-2014) and wave 2 (2014-2015) of the Population Assessment of Tobacco and Health Study. Participants reported receipt of tobacco direct mail/email coupons in the past 6 months in wave 1 and their smoking status in both waves. Weighted multiple logistic regressions were used to examine demographic correlates of receiving tobacco direct mail/email coupons at wave 1 and to examine the prospective effect of receiving tobacco coupons on trajectories of smoking behaviours. FINDINGS: At wave 1, 10.7% of never smokers, 13.9% of experimental smokers, 37.1% of current smokers and 16.5% of former smokers reported receiving tobacco direct mail/email coupons. Lower education and higher poverty adults and non-Hispanic white current smokers were more likely to have received these coupons (p<0.05). Receiving tobacco direct mail/email coupons at wave 1 was associated with increased odds of smoking initiation among never smokers (adjusted odds ratio (AOR)=2.28, 95% CI 1.36 to 3.83), becoming established smokers among experimenters (AOR=1.62, 95% CI 1.29 to 2.04), becoming daily smokers among non-daily smokers (AOR=1.56, 95% CI 1.23 to 1.99) and smoking relapse among former smokers between waves (AOR=1.91, 95% CI 1.39 to 2.65). Receiving these coupons at wave 1 was associated with reduced odds of smoking cessation ≥6 months among current smokers (AOR=0.71, 95% CI 0.58 to 0.88). CONCLUSIONS: Tobacco direct mail/email coupons encourage and sustain smoking and disproportionately affect lower socioeconomic populations.

Flavored E-cigarette Use and Cigarette Smoking Reduction and Cessation-A Large National Study among Young Adult Smokers.

BACKGROUND: E-cigarette use prevalence has increased drastically among young adult cigarette smokers in recent years. OBJECTIVES: This study seeks to understand which e-cigarette flavors-sweet and fruity or tobacco and menthol/mint-are more likely to be associated with smoking reduction and cessation among young adults. METHODS: Longitudinal data (waves 1 and 2) of the Population Assessment of Tobacco and Health (PATH) Study from young adult (aged 18-34) cigarette smokers (n = 4,645) at wave 1 and current e-cigarette users (n = 844) at wave 2 were used. Univariate and multivariate regressions were conducted to examine the associations between past-year smoking reduction and cessation and current e-cigarette flavor use at wave 2. RESULTS: At wave 2, 25.9% of respondents either reduced or quit smoking, and 6.7%, 5.2%, and 6.3% of them reported currently using e-cigarettes with tobacco/menthol (TM) flavors, one non-tobacco/non-menthol (NTM) flavor, and multiple NTM flavors, respectively. E-cigarette users with one (AOR = 2.5, p < 0.001) and multiple NTM flavors (AOR = 3.0, p < 0.001) were more likely to have reduced or quit smoking over the past year compared to non-e-cigarette users. NTM flavor use was positively associated with e-cigarette use of a higher frequency and larger amount. CONCLUSIONS: The positive association between past-year smoking reduction and cessation and current NTM flavored e-cigarette use may be explained by young adults' escalated e-cigarette use with NTM flavors. Public health professionals should prevent and reduce multiple tobacco use through enhanced education about the harm of vaping NTM flavors and by advising young adult smokers to quit tobacco altogether using evidence-based methods.