Scaling between cell cycle duration and wing growth is regulated by Fat-Dachsous signaling in Drosophila.

The atypical cadherins Fat and Dachsous (Ds) signal through the Hippo pathway to regulate growth of numerous organs, including the Drosophila wing. Here, we find that Ds-Fat signaling tunes a unique feature of cell proliferation found to control the rate of wing growth during the third instar larval phase. The duration of the cell cycle increases in direct proportion to the size of the wing, leading to linear-like growth during the third instar. Ds-Fat signaling enhances the rate at which the cell cycle lengthens with wing size, thus diminishing the rate of wing growth. We show that this results in a complex but stereotyped relative scaling of wing growth with body growth in Drosophila . Finally, we examine the dynamics of Fat and Ds protein distribution in the wing, observing graded distributions that change during growth. However, the significance of these dynamics is unclear since perturbations in expression have negligible impact on wing growth.

Energy metabolism modulates the regulatory impact of activators on gene expression.

Gene expression is a regulated process fueled by ATP consumption. Therefore, regulation must be coupled to constraints imposed by the level of energy metabolism. Here, we explore this relationship both theoretically and experimentally. A stylized mathematical model predicts that activators of gene expression have variable impact depending on metabolic rate. Activators become less essential when metabolic rate is reduced and more essential when metabolic rate is enhanced. We find that, in the Drosophila eye, expression dynamics of the yan gene are less affected by loss of EGFR-mediated activation when metabolism is reduced, and the opposite effect is seen when metabolism is enhanced. The effects are also seen at the level of pattern regularity in the adult eye, where loss of EGFR-mediated activation is mitigated by lower metabolism. We propose that gene activation is tuned by energy metabolism to allow for faithful expression dynamics in the face of variable metabolic conditions.

Impact of Housing Insecurity on Outcomes in Abdominal Aortic Aneurysm Repair Among Veterans.

BACKGROUND: Veterans are disproportionately affected by housing insecurity (HI), which can lead to adverse health outcomes and reduced life expectancy. We sought to examine the impact of HI on the outcomes of veterans who underwent abdominal aortic aneurysm (AAA) repair at our regional Veterans Affairs medical center. METHODS: Retrospective chart review was performed on patients who underwent AAA repair at our institution between January 1, 2000, and December 31, 2020. We examined medical history, procedure details, hospitalization course, and postoperative outcomes. Primary endpoints were a 30-day mortality and median survival. Secondary endpoints were hospital length of stay, readmission rate, and perioperative complications. Hypothesis testing was performed with t-test and chi-squared analysis. Survival analysis was conducted using Kaplan-Meier estimation. RESULTS: Of the 314 veterans that underwent AAA repair (mean age of 71.4 ± 7.8 years, 99.7% male) over the 21-year period, we identified 39 (12.4%) patients with a history of HI. The HI was associated with a positive smoking history (100% vs. 88.0%, P = 0.022), lower rate of hypertension diagnosis (69.2% vs. 84.0%, P = 0.024), and increased rate of surgical site infections (SSI) (10.3% vs. 1.8%, P = 0.016). The median postoperative survival was lower in the HI group (7.6 years [CI 6.0-11.2] vs. 8.9 [CI 6.9-10.3]). CONCLUSIONS: HI was associated with reduced median postoperative survival, greater readmission rate, and increased risk of SSI following AAA repair.

Frailty Among Veterans Undergoing Abdominal Aortic Aneurysm Repair.

BACKGROUND: Frailty is a known risk factor for adverse outcomes following surgery and affects at least 3 of every 10 US Veterans aged 65 years and older. We designed a study to characterize the association between frailty and complications after endovascular aneurysm repair (EVAR) compared to open aneurysm repair (OAR) at our regional Veterans Affairs Medical Center. METHODS: Veterans who underwent either OAR or EVAR at our institution between January 1, 2000 and December 31, 2020 were identified. We examined medical history, procedure characteristics, perioperative complications, and frailty as measured by the 5-factor modified frailty index (mFI-5). Frailty was defined as an mFI-5 score ≥2. Primary endpoints were postoperative complications, duration of surgery, and length of hospital stay. Tests of association were performed with t-test and chi-squared analysis. RESULTS: Over the 21-year period, we identified 314 patients that underwent abdominal aortic aneurysm (AAA) repair with 115 (36.6%) OAR and 199 EVAR (63.4%) procedures. Patients undergoing EVAR were older on average (72.1 years vs. 70.2 years) and had a higher average mFI-5 compared to the open repair group (1.49 vs. 1.23, P = 0.036). When comparing EVAR and OAR cohorts, patients undergoing OAR had a larger AAA diameter (6.5 cm, standard deviation [SD]: 1.5) compared to EVAR (5.5 cm, SD: 1.1 P < 0.0001). Fewer frail patients underwent OAR (n = 40, 34.8%) compared to EVAR (n = 86, 43.2%), and frail EVAR patients had higher AAA diameter (5.8 cm, SD: 1.0) compared to nonfrail EVAR patients (5.3 cm, SD 1.2), P = 0.003. Among OAR procedures, frail patients had longer operative times (296 min vs. 253 min, P = 0.013) and higher incidence of pneumonia (17.5% vs. 5.3%, P = 0.035). Among frail EVAR patients, operative time and perioperative complications including wound dehiscence, surgical site infection, and pneumonia were not significantly different than their nonfrail counterparts. Overall, frail patients had more early complications (n = 55, 43.7%) as compared to nonfrail patients (n = 48, 25.5%, P = 0.001). OAR patients had higher rates of postoperative complications including wound dehiscence (7.0% vs. 0.5%, P = 0.001), surgical site infections (7.0% vs. 1.0%, P = 0.003), and pneumonia (9.6% vs. 0.5%, P=<0.0001). Open repair was also associated with overall longer average intensive care unit stays (11.0 days vs. 1.6 days, P < 0.0001) and longer average hospitalizations (13.5 days vs. 2.4 days, P < 0.0001). CONCLUSIONS: Our findings demonstrate that frailty is associated with higher rates of adverse outcomes in open repair compared to EVAR. Patients who underwent open repair had higher rates of wound dehiscence, surgical site infection, and pneumonia, compared to those undergoing endovascular repair. Frailty was associated with larger AAA diameter in the EVAR cohort and longer operative times, with higher frequency of postoperative pneumonia in the OAR cohort. Frailty is a strong risk factor that should be considered in the management of aortic aneurysms.

When Healing Hands Hurt: Epidemiology of Thoracic Outlet Syndrome Among Physicians.

BACKGROUND: Thoracic outlet syndrome (TOS) is an infrequent condition which results in disability in use of upper extremity. While TOS is often associated with manual labor, industrial workers, and accidents, it has not been reported in a physician (MD) population. Given the investment of time and effort in training to become a MD, the impact of TOS may be devastating. Our objective is to report the presentation and outcome of TOS in MDs. METHODS: A prospectively surgical database was reviewed for MDs who sought care of disabling TOS between 1997 and 2022. Demographic, clinical, outcome and pathological data were reviewed. Outcomes were assessed based on Somatic Pain Scale (SPS), Quick Disabilities of Arm, Shoulder and Hand (DASH) scores, and Derkash scores. Results were also assessed based on return to employment. RESULTS: A total of 19 MDs were identified, from 1,687 TOS cases. The group included 13 (63%) men, 6 (31%) women, average age 45 years (range 27-57). Presentations included 1 (5.3%) arterial TOS (ATOS), 9 (47.4%) venous TOS (VTOS), and 9 (47.4) neurogenic TOS (NTOS). All patients were right-handed, and symptomatic side was dominant hand in 7 (37%) patients. Etiologies included repetitive motion injury, athletic injury, and congenital bony abnormalities. Repetitive motion was associated with 3/9 (33%) NTOS. Significant athletic activities were noted in 12 of 19 (63%) MDs, including 8/9 (89%) VTOS and 4/9 (44%) NTOS. Athletic activities associated with VTOS included triathletes (2), rock climbing (1), long distance swimming (2), and weightlifting (3). Of the 9 NTOS cases, 3 were associated with weightlifting and 1 with skiing. Congenital causes included 1 (5%) abnormal first rib and 1 (5%) cervical rib. Time from symptom onset to consultation varied significantly according to diagnosis: ATOS 6 days, VTOS 97 days, and NTOS 2,335 days (P < 0.05). All underwent first rib resection (FRR), and 4 (4) patients required contralateral FRR. Time from surgery to last follow-up averaged 1,005 days (range: 37-4,535 days). On presentation, 6 patients were work disabled and 13 patients were work restricted. Following surgery, 4 MDs remained work restricted with mild to moderate symptoms. After surgery, standardized outcomes (SPS, Quick DASH, and Derkash score) improved in all metrics. All who were initially disabled returned to work without restriction. Significant non-TOS related comorbidities were present in all who had residual restriction. Return to work was documented in all. CONCLUSIONS: Although it has not been reported, MDs are subject to developing TOS. Causes include repetitive motions, athletic injuries, and congenital bony abnormalities. Surgical decompression is beneficial with significant reduction in pain and disability. MDs are highly motivated and insightful; accordingly, they have a very high probability of successful work resumption, with all returning to their medical positions.

Effect of a Decision Aid on Agreement Between Patient Preferences and Repair Type for Abdominal Aortic Aneurysm: A Randomized Clinical Trial.

Importance: Patients with abdominal aortic aneurysm (AAA) can choose open repair or endovascular repair (EVAR). While EVAR is less invasive, it requires lifelong surveillance and more frequent aneurysm-related reinterventions than open repair. A decision aid may help patients receive their preferred type of AAA repair. Objective: To determine the effect of a decision aid on agreement between patient preference for AAA repair type and the repair type they receive. Design, Setting, and Participants: In this cluster randomized trial, 235 patients were randomized at 22 VA vascular surgery clinics. All patients had AAAs greater than 5.0 cm in diameter and were candidates for both open repair and EVAR. Data were collected from August 2017 to December 2020, and data were analyzed from December 2020 to June 2021. Interventions: Presurgical consultation using a decision aid vs usual care. Main Outcomes and Measures: The primary outcome was the proportion of patients who had agreement between their preference and their repair type, measured using χ2 analyses, κ statistics, and adjusted odds ratios. Results: Of 235 included patients, 234 (99.6%) were male, and the mean (SD) age was 73 (5.9) years. A total of 126 patients were enrolled in the decision aid group, and 109 were enrolled in the control group. Within 2 years after enrollment, 192 (81.7%) underwent repair. Patients were similar between the decision aid and control groups by age, sex, aneurysm size, iliac artery involvement, and Charlson Comorbidity Index score. Patients preferred EVAR over open repair in both groups (96 of 122 [79%] in the decision aid group; 81 of 106 [76%] in the control group; P = .60). Patients in the decision aid group were more likely to receive their preferred repair type than patients in the control group (95% agreement [93 of 98] vs 86% agreement [81 of 94]; P = .03), and κ statistics were higher in the decision aid group (κ = 0.78; 95% CI, 0.60-0.95) compared with the control group (κ = 0.53; 95% CI, 0.32-0.74). Adjusted models confirmed this association (odds ratio of agreement in the decision aid group relative to control group, 2.93; 95% CI, 1.10-7.70). Conclusions and Relevance: Patients exposed to a decision aid were more likely to receive their preferred AAA repair type, suggesting that decision aids can help better align patient preferences and treatments in major cardiovascular procedures. Trial Registration: ClinicalTrials.gov Identifier: NCT03115346.

Factors associated with preference of choice of aortic aneurysm repair in the PReference for Open Versus Endovascular repair of AAA (PROVE-AAA) study.

OBJECTIVE: Patients can choose between open repair and endovascular repair (EVAR) of abdominal aortic aneurysm (AAA). However, the factors associated with patient preference for one repair type over another are not well-characterized. Here we assess the factors associated with preference of choice for open or endovascular AAA repair among veterans exposed to a decision aid to help with choosing surgical treatment. METHODS: Across 12 Veterans Affairs hospitals, veterans received a decision aid covering domains including patient information sources and understanding preference. Veterans were then given a series of surveys at different timepoints examining their preferences for open versus endovascular AAA repair. Questions from the preference survey were used in analyses of patient preference. Results were analyzed using χ2 tests. A logistic regression analysis was performed to assess factors associated with preference for open repair or preference for EVAR. RESULTS: A total of 126 veterans received a decision aid informing them of their treatment choices, after which 121 completed all preference survey questions; five veterans completed only part of the instruments. Overall, veterans who preferred open repair were typically younger (70 years vs 73 years; P = .02), with similar rates of common comorbidities (coronary disease 16% vs 28%; P = .21), and similar aneurysms compared with those who preferred EVAR (6.0 cm vs 5.7 cm; P = .50). Veterans in both preference categories (28% of veterans preferring EVAR, 48% of veterans preferring open repair) reported taking their doctor's advice as the top box response for the single most important factor influencing their decision. When comparing the tradeoff between less invasive surgery and higher risk of long-term complications, more than one-half of veterans preferring EVAR reported invasiveness as more important compared with approximately 1 in 10 of those preferring open repair (53% vs 12%; P < .001). Shorter recovery was an important factor for the EVAR group (74%) and not important in the open repair group (76%) (P = .5). In multivariable analyses, valuing a short hospital stay (odds ratio, 12.4; 95% confidence interval, 1.13-135.70) and valuing a shorter recovery (odds ratio, 15.72; 95% confidence interval, 1.03-240.20) were associated with a greater odds of preference for EVAR, whereas finding these characteristics not important was associated with a greater odds of preference for open repair. CONCLUSIONS: When faced with the decision of open repair versus EVAR, veterans who valued a shorter hospital stay and a shorter recovery were more likely to prefer EVAR, whereas those more concerned about long-term complications preferred an open repair. Veterans typically value the advice of their surgeon over their own beliefs and preferences. These findings need to be considered by surgeons as they guide their patients to a shared decision.

Lower Extremity Amputations Among Veterans: Have Ambulatory Outcomes and Survival Improved?

BACKGROUND: We hypothesize among patients undergoing lower extremity amputation, access to pre-, and post operative rehabilitation services; as well as improved medical care, have led to higher rates of postoperative ambulation, and improved survival. METHODS: Retrospective single center review of all major lower extremity amputations performed at the Greater Los Angeles Veterans Affairs Healthcare System from 2000-2020 stratified into multiyear cohorts. We abstracted demographics, operative indication, comorbidities, preoperative medical management, perioperative complications, discharge location, and pre and postoperative ambulatory status. Odds of ambulation after amputation were analyzed using multivariate logistic regression. Survival was analyzed using multivariate logistic regression and Kaplan-Meier survival analysis. Multivariate logistic predictors were selected based on prior literature and clinical experience. RESULTS: We identified 654 operations in our study, noting fewer amputations performed in the latest 3 cohort years as compared to the initial cohort (2000-2004). Patients undergoing below-knee amputations (BKA) had 2.7 times (P < 0.05) greater odds of postoperative ambulation and 86% (P < 0.05) increased odds of survival compared to above-knee amputations (AKA). The odds of ambulation increased by 8.8% (P < 0.05) for each consecutive study year. Ambulation post-amputation conferred 13.2 times (P < 0.05) greater odds of survival. The odds of survival in "emergent" operations decreased by 48% (P < 0.05) compared to an "elective" operation. For each additional comorbidity, the odds of survival decreased by 18% (P < 0.05). Patients with any perioperative complication had a 48% (P < 0.05) lower odds of survival. Kaplan-Meier survival estimates demonstrated significant survival difference between patients by amputation level and postoperative ambulatory status (P < 0.05). CONCLUSIONS: Ambulatory status following distal amputation has improved over time and is significantly associated with increased survival post-amputation. Patients undergoing a BKA or discharged home were most likely to ambulate postoperatively. Amputation level, preoperative comorbidities, and perioperative complications remain strong predictors of survival.

Preoperative thrombolysis is associated with improved vein patency and functional outcomes after first rib resection in acute Paget-Schroetter syndrome.

INTRODUCTION: Most patients with acute Paget-Schroetter syndrome (PSS) present in one of two manners: (1) thrombosis managed initially with thrombolysis and anticoagulation and then referred for surgery, and (2) initial treatment with anticoagulation only and later referral for surgery. Definitive benefits of thrombolysis in the acute period (the first 2 weeks after thrombosis) over anticoagulation alone have not been well reported. Our goal was to compare patients managed with early thrombolysis and anticoagulation followed by first rib resection (FRR) and later postoperative venography with venoplasty (PTA) with those managed with anticoagulation alone followed by FRR and PTA using vein patency assessed with venography and standardized outcome measures. METHODS: We reviewed a prospectively collected database from 2000 to 2019. Two groups were compared: those managed with early thrombolysis at our institution (Lysis) and those managed with anticoagulation alone (NoLysis). All patients underwent FRR. Venography was routinely performed before and after FRR. Standardized outcome measures included Quick Disability of Arm, Shoulder, and Hand (QuickDASH) scores and Somatic Pain Scale. RESULTS: A total of 50 Lysis and 50 NoLysis patients were identified. Pre-FRR venography showed that thrombolysis resulted in patency of 98% of veins, whereas 78% of NoLysis veins were patent. After FRR, postoperative venography revealed that 46 (92%) patients in the Lysis group and 37 (74%) patients in the NoLysis group achieved vein patency. Thrombolysis was significantly associated with final vein patency (odds ratio: 17 [4-199]; P < .001). Lysis patients had a trend toward lower QuickDASH scores from pre-FRR to post-FRR compared with NoLysis patients with a mean difference of -16.4 (±19.7) vs -5.2 (±15.6) points (P = .13). The difference in reduction of Somatic Pain Scale scores was not statistically significant. CONCLUSIONS: Thrombolysis as initial management of PSS, combined with anticoagulation, followed by FFR and VenoPTA resulted in improved final vein patency and may lead to an improved functional outcome measured with QuickDASH scores. Therefore, clinical protocols using thrombolysis as initial management should be considered when planning the optimal treatment strategy for patients with acute PSS.

Telemedicine and Vascular Surgery: Expanding Access and Providing Care Through the COVID-19 Pandemic.

INTRODUCTION: Access to surgical service is limited by provider availability and geographic barriers. Telemedicine ensures that patients can access medical care. OBJECTIVE: The objective is to describe our use of telemedicine in delivering vascular surgery services to remote locations before and during the COVID-19 pandemic. METHODS: We conducted a retrospective chart review analyzing care delivered at six vascular surgery telemedicine clinics over a 22-month period. We examined vascular diagnoses, recommended interventions, referrals placed, and emergency department visits within 30 days of evaluation. We calculated travel distance saved for patients between their local clinic and our main hospital. RESULTS: We identified 94 patients and 144 telemedicine visits, with an average of 1.5 visits per patient (SD = 0.73). The most common referrals were for peripheral artery disease (20.2%) and abdominal aortic aneurysm (14.9%). Three patients were immediately referred to the emergency department due to concern for acute limb ischemia (2) or questionable symptomatic AAA (1). Telemedicine visit recommendations were distributed between no intervention (n = 30, 31.9%), medical management (n = 41, 43.6%), and surgical intervention (n = 23, 24.5%).The surgical intervention cohort was most commonly referred to arterial revascularization (n = 4), venous ablation (n = 4), and arteriovenous fistula procedures (n = 4). Fourteen patients came to our main hospital for surgery and four to local providers. Average travel distance saved per telemedicine visit was 104 miles (SD = 43.7). CONCLUSIONS: Telemedicine provided safe, efficient care during the COVID-19 pandemic and saved patients an average of 104 travel miles per visit.

The Impact of Work Status and Age in Choosing Type of Abdominal Aortic Aneurysm Repair.

INTRODUCTION: The PReferences for Open Versus Endovascular Repair of Abdominal Aortic Aneurysm (PROVE-AAA) trial aimed to determine the efficacy of a validated decision aid to enable better alignment between patient preference and their ultimate repair. We sought to determine the key factors influencing the decision-making of veterans for endovascular repair of abdominal aortic aneurysm (EVAR) or open surgical repair (OSR). METHODS: A total of 235 veterans in the PROVE-AAA trial were asked their information sources regarding repairs, employment status, and preferred intervention. Answers were coded and analyzed using conventional content analysis to generate nonoverlapping themes, then stratified by employment status. RESULTS: Forty-two patients (17.8% of enrollees) provided their source of information for OSR prior to using a decision aid. 81% of retired veterans were greater than 70 y old, while 58% of nonretired veterans were greater than 70 (P = 0.003). The most common information source was from a vascular surgeon/professional or unspecified MD/other health professionals (51.4%), while sources from outside this group made up the remaining 48.5%. The most preferred procedure was EVAR. However, nonretired individuals were more likely to prefer OSR. These data on information source and preferred procedure were similar in patients who provided their source for EVAR. CONCLUSIONS: Veterans in the PROVE-AAA study were more likely to be retired and more likely to rely on information from an unspecified MD/other health professionals for EVAR. Although both retired and nonretired veterans preferred EVAR the most, nonretired veterans were more likely to prefer OSR despite being younger.

Mechanochemical Endovenous Ablation of the Saphenous Vein: A Look at Contemporary Outcomes.

BACKGROUND: Endovenous ablation techniques have replaced greater saphenous vein (GSV) ligation and stripping for treatment of venous insufficiency. Our objective was to investigate our initial procedural experience and clinical presentation of patients undergoing mechanochemical ablation (MOCA) at a single institution. We hypothesized that closure level and success rate improved over time and were comparable to other endovenous ablation techniques. METHODS: We retrospectively reviewed all MOCA procedures performed at the Greater Los Angeles Veterans Affairs Hospital from 2015 - 2020. Variables included CEAP and VCSS scores, patient symptoms, post procedure duplex ultrasound, closure level, and need for anticoagulation. Success was defined as GSV thrombosis on initial post procedure duplex ultrasound. Procedure associated extension of thrombus into the deep veins was defined using the American Venous Forum (AVF) endothermal heat induced thrombosis (EHIT) classification. RESULTS: 104 venous ablation procedures were performed on 86 patients. Eleven (12.8%) patients received bilateral interventions, and six (7%) patients had asynchronous interventions on the same leg. The average age was 58.4 years (SD 12) and 93% were male. Pre-procedural symptoms included pain (102, 98.1%), varicose veins (87, 83.7%), edema (58, 55.8%), and active ulcers (19, 18.3%). A CEAP category of C2 was the most common indication (34.6%), followed by C3 (22.1%) and C6 (21.2%). Forty-five (43.2%) patients had deep system reflux, and 53% had concomitant phlebectomies. Average VCSS score was 7.5 (SD 3.5).We observed a GSV ablation rate of 92.7% (n = 89) in the 96 procedures which had post-procedure follow up, with no temporal evidence of a learning curve. On post procedure duplex of the 89 technically successful ablations, 77 (86.5%) patients had AVF EHIT level 1 closure, three (3.4%) had level 2 closure, eight (8.9%) had level 3 closure, and one had a level 4 closure. Fourteen (15.7%) patients were newly started on anticoagulation for an average of 33.2 days (SD 34.1). Of the 19 legs treated for active venous ulcers, 13 (68.4%) had improvement or resolution of their venous ulcers. No pulmonary embolic complications were reported. CONCLUSIONS: We observed a successful GSV thrombosis rate of 92.7% using MOCA without evidence of a learning curve and comparable to that reported in the literature. The rate of thrombus extension into the deep veins was 14.6%, with no adverse effects associated with anticoagulation or clinically significant sequelae of AVF EHIT level 2 or greater. Comparisons with MOCA associated thrombus extension into deep veins in the literature are limited as post procedure screening duplex are not standard of care. However, we demonstrated that MOCA ablation of the GSV is a safe procedure that may be performed with good technical success.

BERM: a Belowground Ecosystem Resiliency Model for estimating Spartina alterniflora belowground biomass.

Spatiotemporal patterns of Spartina alterniflora belowground biomass (BGB) are important for evaluating salt marsh resiliency. To solve this, we created the BERM (Belowground Ecosystem Resiliency Model), which estimates monthly BGB (30-m spatial resolution) from freely available data such as Landsat-8 and Daymet climate summaries. Our modeling framework relied on extreme gradient boosting, and used field observations from four Georgia salt marshes as ground-truth data. Model predictors included estimated tidal inundation, elevation, leaf area index, foliar nitrogen, chlorophyll, surface temperature, phenology, and climate data. The final model included 33 variables, and the most important variables were elevation, vapor pressure from the previous four months, Normalized Difference Vegetation Index (NDVI) from the previous five months, and inundation. Root mean squared error for BGB from testing data was 313 g m-2 (11% of the field data range), explained variance (R2 ) was 0.62-0.77. Testing data results were unbiased across BGB values and were positively correlated with ground-truth data across all sites and years (r = 0.56-0.82 and 0.45-0.95, respectively). BERM can estimate BGB within Spartina alterniflora salt marshes where environmental parameters are within the training data range, and can be readily extended through a reproducible workflow. This provides a powerful approach for evaluating spatiotemporal BGB and associated ecosystem function.

Primordial Follicle Formation - Some Assembly Required.

Formation of primordial follicles occurs when germ cell nests break apart and individual oocytes become surrounded by pregranulosa cells. Why mammalian germ cells develop in germ cell nests is not fully understood but recent work has provided evidence that some oocytes serve as nurse cells supporting other oocytes in the cyst. Headway has also been made in understanding interactions that occur between cyst cells that must change as individual oocytes separate to associate with pregranulosa cells. As germ cell nests undergo breakdown some oocytes are lost by programmed cell death that has been attributed to apoptosis, but newer studies have implicated autophagy in counteracting apoptosis to promote cell survival and maintain the ovarian reserve. Work in the past few years has added to already known pathways regulating primordial follicle formation and has identified new players including signaling molecules, transcription factors and RNA binding proteins.

Intravascular ultrasonography provides more sensitive detection of subclavian vein stenosis than venography in patients presenting with Paget-Schroetter syndrome.

OBJECTIVE: Spontaneous subclavian vein (SCV) thrombosis (Paget-Schroetter syndrome [PSS]) has been attributed to venous compression at the thoracic outlet and traditionally diagnosed using venography. Intravascular ultrasonography (IVUS) allows for a multidimensional view of vascular structures and might be more accurate in revealing venous compression. The goal of the present study was to compare venography and IVUS in patients presenting with PSS to assess the relative accuracy of each modality. METHODS: Patients presenting for evaluation of PSS from 2013 to 2019 were evaluated for SCV compression using venography and IVUS. Venography and IVUS measurements of stenosis were performed of the index and contralateral limbs in both neutral and stress (arm overhead) positions. The IVUS data included the SCV diameters in the anteroposterior (AP) plane, craniocaudal (CC) plane, and cross-sectional area (CSA). Stenosis was reported as the percentage of reduction from a reference point (lateral margin of the first rib) for the venography and IVUS data. RESULTS: For the 35 subjects, the average age was 35 years, 57% were women, 20% had presented with a documented pulmonary embolus, and 70% had initially been treated with thrombolysis. Venography demonstrated SCV occlusion in 3 patients (16%) with the index limb in the neutral position and in 18 patients (54%) with the limb in the stress position. The average stenosis in the index limbs was 41.5% (venography), and the average IVUS stenosis was 41.9% (CC), 61.8% (AP), and 74.5% (CSA; P < .05). A subset analysis revealed that in 10 of 35 patients (28%) in whom venography had identified no significant stenosis (average, 10%), IVUS had identified significant stenosis (33.5% CC, 54.3% AP, 68.7% CSA; P < .05). CONCLUSIONS: IVUS proved more sensitive than venography in detecting significant stenosis leading to SCV thrombosis. A reduction in the CSA was the most sensitive measure of stenosis. IVUS identified significant stenosis in patients in whom venography failed to do so. The greatest utility of IVUS is in the evaluation of patients with PSS in whom venography shows no evident compression.

Trauma and the content of hallucinations and post-traumatic intrusions in first-episode psychosis.

OBJECTIVE: Increasing evidence suggests experiences of childhood trauma may be causally related to the development of hallucinations. Cognitive theories of psychosis suggest post-traumatic intrusions to be a primary mechanism in this relationship. These theories predict that the content of hallucinations will be related to traumatic experiences; however, few studies have investigated this. This study examined the relationship between childhood trauma, the content of hallucinations, and the content of post-traumatic intrusions in a sample with first-episode psychosis. METHODS: Sixty-six young people aged 15-25 experiencing a first episode of psychosis were recruited from an early intervention service. Participants completed assessments of traumatic experiences, hallucination content, and post-traumatic intrusion content using a systematic coding frame. The coding frame assessed for three types of relationships between traumatic experiences, the content of hallucinations, and the content of post-traumatic intrusions: direct relationships (hallucination content exactly matching the trauma/intrusion), thematic relationships (hallucinations with the same themes as the trauma/intrusion), and no relationship (hallucination and trauma/intrusion content unrelated). RESULTS: Of those people who reported trauma and hallucinations (n = 36), 22 of these (61%) experienced post-traumatic intrusions, and of these, 16 (73%) experienced hallucinations that were directly or thematically related to their post-traumatic intrusions. Twelve people experienced hallucination content directly related to their trauma, six of whom (50%) also had intrusions relating to the same traumatic event as their hallucinations. CONCLUSIONS: The finding that some people experience hallucinations and post-traumatic intrusions relating to the same traumatic event supports theories proposing a continuum of memory intrusion fragmentation. These results indicate that early intervention services for young people with psychosis should provide assessment and intervention for trauma and PTSD and should consider the impact of past traumatic events on the content of current hallucinatory experience. PRACTITIONER POINTS: Trauma and post-traumatic stress disorder should be assessed in those experiencing a first episode of psychosis. Interventions for trauma should be offered in early intervention for psychosis services. In a notable proportion of people, hallucination content is related to traumatic experiences. Clinical assessment and formulation of hallucinations requires consideration of how past traumatic events may be contributing to hallucinatory experience. It is important for clinicians to have an understanding of the phenomenological differences between hallucinations and post-traumatic intrusions when conducting clinical assessments with people with comorbid psychosis and PTSD.

Design of the PReferences for Open Versus Endovascular Repair of Abdominal Aortic Aneurysm (PROVE-AAA) Trial.

For patients with abdominal aortic aneurysm (AAA), randomized trials have found endovascular AAA repair (EVAR) is associated with lower perioperative morbidity and mortality than open surgical repair (OSR). However, OSR has fewer long-term aneurysm-related complications, such as endoleak or late rupture. Patients treated with EVAR and OSR have similar survival rates within two years after surgery, and OSR does not require intensive surveillance. Few have examined if patient preferences are aligned with the type of treatment they receive for their AAA. Although many assume that patients may universally prefer the less-invasive nature of EVAR, our preliminary work suggests that patients who value the lower risk of late complications may prefer OSR. In this study, called The PReferences for Open Versus Endovascular Repair of Abdominal Aortic Aneurysm (PROVE-AAA) trial, we describe a cluster-randomized trial to test if a decision aid can better align patients' preferences and their treatment type for AAA. Patients enrolled in the study are candidates for either endovascular or open repair and are followed up at VA hospitals by vascular surgery teams who regularly perform both types of repair. In Aim 1, we will determine patients' preferences for endovascular or open repair and identify domains associated with each repair type. In Aim 2, we will assess alignment between patients' preferences and the repair type elected and then compare the impact of a decision aid on this alignment between the intervention and control groups. This study will help us to accomplish two goals. First, we will better understand the factors that affect patient preference when choosing between EVAR and OSR. Second, we will better understand if a decision aid can help patients be more likely to receive the treatment strategy they prefer for their AAA. Study enrollment began on June 1, 2017. Between June 1, 2017 and November 1, 2018, we have enrolled 178 of a total goal of 240 veterans from 20 VA medical centers and their vascular surgery teams across the country. We anticipate completing enrollment in PROVE-AAA in June 2019, and study analyses will be performed thereafter.

Prevalence and outcomes of young people with concurrent autism spectrum disorder and first episode of psychosis.

BACKGROUND: The intersect and blurring of boundaries between schizophrenia spectrum disorders and autism spectrum disorder (ASD) has long been an area of confusion, in both nosology and clinical practice. Individuals with a comorbid presentation of the two spectra can present with a distinct phenomenological profile to those with psychosis or ASD alone. AIMS: To examine the prevalence rates of ASD in a cohort of young people presenting with a first episode of psychosis (FEP) and compare the demographic and clinical characteristics and functional outcomes between individuals with concurrent FEP and ASD, and individuals with FEP only. METHODS: Young people aged 15 to 24 who presented with FEP to the Early Psychosis Prevention and Intervention Centre (EPPIC) between 1st January 2011 and 31st December 2013 were included in the study. RESULTS: Of the 544 individuals presenting with a FEP, 3.7% (N = 20) had a diagnosis of ASD. Individuals with a concurrent diagnosis of FEP and ASD were more likely to be male and less likely to have comorbid substance use issues. There was no difference found in the severity of psychotic symptoms or diagnoses between groups. Those with FEP and ASD were more likely to experience impairments in interpersonal skills and be more likely to be engaged in employment or education at time of discharge from service. CONCLUSIONS: Individuals with concurrent FEP and ASD can present with distinct clinical characteristics that require specialised assessment and treatment. Further large-scale studies with control groups could help to better understand the phenomenological specificity of this subgroup.

Patient information sources when facing repair of abdominal aortic aneurysm.

OBJECTIVE: Shared medical decision making is most important when there are competing options for repair such as in treatment of abdominal aortic aneurysm (AAA). We sought to understand the sources of patients' pre-existing knowledge about AAA to better inform treating physicians about patients' needs for preoperative counseling. METHODS: We performed a multicenter survey of patients facing AAA repair at 20 Veterans Affairs hospitals across the United States as part of the Preferences for Open Versus Endovascular Repair of AAA study. A validated survey instrument was administered to examine the sources of information available and commonly used by patients to learn about their repair options. The survey was administered by study personnel before the patient had any interaction with the vascular surgeon because survey data were collected before the vascular clinic visit. RESULTS: Preliminary analysis of data from 99 patients showed that our cohort was primarily male (99%) and elderly (mean age 73 years). Patients commonly had a history of hypertension (86%), prior myocardial infarction (32%), diabetes (32%), and were overweight (58%). Patients arrived at their surgeon's office appointment with limited information. A majority of patients (52%) reported that they had not talked to their primary care physician at all about their options for AAA repair, and one-half (50%) reported that their view of the different surgical options had not been influenced by anyone. Slightly less than one-half of patients reported that they did not receive any information about open surgical aneurysm repair and endovascular aortic aneurysm repair (41% and 37%, respectively). Few patients indicated using the internet as their main source of information about open surgical aneurysm repair and endovascular aortic aneurysm repair (10% and 11%, respectively). CONCLUSIONS: Patients are commonly referred for AAA repair having little to no information regarding AAA pathology or repair options. Fewer than one in five patients searched the internet or had accessed other sources of information on their own. Most vascular surgeons should assume that patients will present to their first vascular surgery appointment with minimal understanding of the treatment options available to them.