A Multipathway Phosphopeptide Standard for Rapid Phosphoproteomics Assay Development.

Recent advances in methodology have made phosphopeptide analysis a tractable problem for many proteomics researchers. There are now a wide variety of robust and accessible enrichment strategies to generate phosphoproteomes while free or inexpensive software tools for quantitation and site localization have simplified phosphoproteome analysis workflow tremendously. As a research group under the Association for Biomolecular Resource Facilities umbrella, the Proteomics Standards Research Group has worked to develop a multipathway phosphopeptide standard based on a mixture of heavy-labeled phosphopeptides designed to enable researchers to rapidly develop assays. This mixture contains 131 mass spectrometry vetted phosphopeptides specifically chosen to cover as many known biologically interesting phosphosites as possible from seven different signaling networks: AMPK signaling, death and apoptosis signaling, ErbB signaling, insulin/insulin-like growth factor-1 signaling, mTOR signaling, PI3K/AKT signaling, and stress (p38/SAPK/JNK) signaling. Here, we describe a characterization of this mixture spiked into a HeLa tryptic digest stimulated with both epidermal growth factor and insulin-like growth factor-1 to activate the MAPK and PI3K/AKT/mTOR pathways. We further demonstrate a comparison of phosphoproteomic profiling of HeLa performed independently in five labs using this phosphopeptide mixture with data-independent acquisition. Despite different experimental and instrumentation processes, we found that labs could produce reproducible, harmonized datasets by reporting measurements as ratios to the standard, while intensity measurements showed lower consistency between labs even after normalization. Our results suggest that widely available, biologically relevant phosphopeptide standards can act as a quantitative "yardstick" across laboratories and sample preparations enabling experimental designs larger than a single laboratory can perform. Raw data files are publicly available in the MassIVE dataset MSV000090564.

Digital: accelerating the pathway.

The Spherical Tokamak for Energy Production (STEP) programme is an ambitious but challenging endeavour to design and deliver a prototype fusion power plant. It is a rapid, fast-moving programme, designing a first of a kind device in a Volatile, Uncertain, Complex and Ambiguous (VUCA) environment, and digital tools play a pivotal role in managing and navigating this space. Digital helps manage the complexity and sheer volume of information. Advanced modelling and simulation techniques provide a platform for designers to explore various scenarios and iteratively refine designs, providing insights into the intricate interplay of requirements, constraints and design factors across physics, technology and engineering domains and aiding informed decision-making amidst uncertainties. It also provides a means of building confidence in the new scientific, technological and engineering solutions, given that a full-scale-integrated precursor test is not feasible, almost by definition. The digital strategy for STEP is built around a vision of a digital twin of the whole plant. This will evolve from the current digital shadow formed by system architecting codes and complex workflows and will be underpinned by developing capabilities in plasma, materials and engineering simulation, data management, advanced control, industrial cybersecurity, regulation, digital technologies and related digital disciplines. These capabilities will help address the key challenges of managing the complexity and quantity of information, improving the reliability and robustness of the current digital shadow and developing an understanding of its validity and performance.This article is part of the theme issue 'Delivering Fusion Energy - The Spherical Tokamak for Energy Production (STEP)'.

Absolute quantification of tumor antigens using embedded MHC-I isotopologue calibrants.

Absolute quantification measurements (copies per cell) of peptide major histocompatibility complex (pMHC) antigens are necessary to inform targeted immunotherapy drug design; however, existing methods for absolute quantification have critical limitations. Here, we present a platform termed SureQuant-IsoMHC, utilizing a series of pMHC isotopologues and internal standard-triggered targeted mass spectrometry to generate an embedded multipoint calibration curve to determine endogenous pMHC concentrations for a panel of 18 tumor antigens. We apply SureQuant-IsoMHC to measure changes in expression of our target panel in a melanoma cell line treated with a MEK inhibitor and translate this approach to estimate antigen concentrations in melanoma tumor biopsies.

The Association between Pediatric Readiness and Mortality for Injured Children Treated at US Trauma Centers.

OBJECTIVE: To use updated 2021 weighted Pediatric Readiness Score (wPRS) data to identify a threshold level of trauma center emergency department (ED) pediatric readiness. SUMMARY BACKGROUND DATA: Most children in the US receive initial trauma care at non-pediatric centers. The National Pediatric Readiness Project (NPRP) aims to ensure that all EDs are prepared to provide quality care for children. Trauma centers reporting the highest quartile of wPRS on the 2013 national assessment have been shown to have lower mortality. Significant efforts have been invested to improve pediatric readiness in the past decade. STUDY DESIGN: A retrospective cohort of trauma centers that completed the NPRP 2021 national assessment and contributed to the National Trauma Data Bank (NTDB) in 2019-21 was analyzed. Center-specific observed-to-expected mortality estimates for children (0-15y) were calculated using Pediatric TQIP models. Deterministic linkage was used for transferred patients to account for wPRS at the initial receiving center. Center-specific mortality odds ratios were then compared across quartiles of wPRS. RESULTS: 66,588 children from 630 centers with a median [IQR] wPRS of 79 [66-93] were analyzed. The average observed-to-expected odds of mortality (1.02 [0.97-1.06]) for centers in the highest quartile (wPRS≥93) was lower than any of the lowest three wPRS quartiles (1.19 [1.14-1.23](Q1), 1.29 [1.24-1.33](Q2), and 1.28 [1.19-1.36](Q3), all P <0.05). The presence of a pediatric-specific quality improvement plan was the domain with the strongest independent association with mortality (standardized beta -0.095 [-0.146--0.044]). CONCLUSION: Trauma centers should address gaps in pediatric readiness to include a pediatric-specific quality improvement plan and aim to achieve wPRS ≥93.

Pulmonary Cryoablation Outcomes in Octogenarians and Nonagenarians with Primary Lung Cancer.

PURPOSE: To characterize the effectiveness, safety, and length of stay (LOS) associated with pulmonary cryoablation for management of primary lung malignancies in patients aged ≥80 years. MATERIALS AND METHODS: A retrospective single-center database was compiled of all consecutive patients aged ≥80 years who underwent percutaneous computed tomography-guided cryoablation using modified triple-freeze protocol (1-3 ablation probes) for Stage IA-IIB primary lung malignancies between March 2017 and March 2020 (n = 19; 53% women; mean age, 85 years ± 3.5; range, 80-94 years). Follow-up imaging was assessed for local recurrence. Adverse events and LOS were recorded from chart review. Kaplan-Meier analysis was performed to assess both overall and local recurrence-free survival. RESULTS: Mean patient follow-up period was 21.6 months ± 10.8, and mean imaging follow-up period was 19.2 months ± 9.6. Overall survival at 3 years was 94% (95% CI, 81%-100%). Local recurrence-free survival was 100% throughout the imaging follow-up period. Intraprocedural pneumothorax occurred in 37% (7 of 19) of patients; pneumothorax risk was significantly associated with increased tumor distance from pleura (odds ratio, 1.2; P = .018). Sixty-three percent (12 of 19) of patients were discharged on the day of the procedure, with a mean LOS of 7.7 hours ± 1.6, whereas 37% of patients required overnight observation (2 of 19) or admission (5 of 19), with a mean LOS of 48.1 hours ± 19.4. Overall LOS for all patients was 22.6 hours ± 22.9. CONCLUSIONS: Percutaneous cryoablation of primary pulmonary malignancies can be performed in select octogenarians and nonagenarians with high 3-year overall and recurrence-free survival. Despite nonnegligible risk of pneumothorax, most patients are discharged on the day of the procedure.

Impact of Chronic Kidney Disease on In-Hospital Outcomes of Hospitalizations With Acute Limb Ischemia Undergoing Endovascular Therapy.

PURPOSE: Studies on outcomes related to endovascular treatment (EVT) in advanced stages of chronic kidney disease (CKD) and end-stage renal disease (ESRD) among hospitalizations with acute limb ischemia (ALI) are limited. METHODS: The Nationwide Inpatient Sample was quarried from October 2015 to December 2017 to identify the hospitalizations with ALI and undergoing EVT. The study population was subdivided into 3 groups based on their CKD stages: group 1 (No CKD, stage I, stage II), group 2 (CKD stage III, stage IV), and group 3 (CKD stage V and ESRD). The primary outcome was all-cause in-hospital mortality. RESULTS: A total of 51 995 hospitalizations with ALI undergoing EVT were identified. The in-hospital mortality was significantly higher in group 2 (OR = 1.17; 95% CI 1.04 - 1.32, p=0.009) and group 3 (OR = 3.18; 95% CI 2.74-3.69, p<0.0001) compared with group 1. Odds of minor amputation, vascular complication, atherectomy, and blood transfusion were higher among groups 2 and 3 compared with group 1. Group 2 had higher odds of access site hemorrhage compared with groups 1 and 3, whereas group 3 had higher odds of major amputation, postprocedural infection, and postoperative hemorrhage compared with groups 1 and 2. Besides, groups 2 and 3 had lower odds of discharge to home compared with group 1. Finally, the length of hospital stay and cost of care was significantly higher with the advancing CKD stages. CONCLUSION: Advanced CKD stages and ESRD are associated with higher mortality, worse in-hospital outcomes and higher resource utilization among ALI hospitalizations undergoing EVT. CLINICAL IMPACT: Current guidelines are not clear for the optimum first line treatment of acute limb ischemia, especially in patients with advanced kidney disease as compared to normal/mild kidney disease patients. We found that advanced kidney disease is a significant risk factor for worse in-hospital morbidity and mortality. Furthermore, patients with acute limb ischemia and advanced kidney disease is associated with significantly higher resource utilization as compared to patients with normal/mild kidney disease. This study suggests shared decision making between treating physician and patients when considering endovascular therapy for the treatment of acute limb ischemia in patients with advanced kidney disease.

Computed Tomography Evaluation of In Vivo Pulmonary Cryoablation Zone Sizes.

PURPOSE: To evaluate ablation zone sizes in patients undergoing pulmonary tumor cryoablation with 14-gauge cryoablation probes. MATERIALS AND METHODS: A single-center retrospective analysis of all consecutive patients who underwent cryoablation of pulmonary tumors with 1 or more 14-gauge probes (August 2017 to June 2020) was performed. Intraprocedural and 1-2-month postprocedural chest computed tomography (CT) scans were evaluated to characterize pulmonary lesions, ice balls, and ablation zones. Single-probe 14-gauge ablation zone volumes were compared with manufacturer reference isotherms and single- and 2-probe ablation zones from a prior investigation of 17-gauge probes. Overall survival and local recurrence-free survival were calculated to 3 years. RESULTS: Forty-seven pulmonary malignancies in 42 patients (women, 50%; mean age, 75.2 years ± 11.5) underwent cryoablation with 1 (n = 35), 2 (n = 10), or 3 (n = 2) cryoablation probes. One- to 2-month follow-up CT images were available for 30 of the 42 patients. The mean cryoablation zone volumes at 1-2 months when 1 (n = 21), 2 (n = 8), and 3 (n = 1) probes were used were 5.0 cm3 ± 2.3, 37.5 cm3 ± 20.5, and 28.4 cm3, respectively. The mean single-probe follow-up ablation zone volume was larger than that previously reported for 17-gauge probes (3.0 cm3 ± 0.3) (P < .001) but smaller than manufacturer-reported isotherms (11.6 cm3 for -40 °C isotherm) and the 2-probe ablation zone volume with 17-gauge devices (12.9 cm3 ± 2.4) (for all, P < 001). The 3-year overall survival and local recurrence-free survival were 69% (95% confidence interval [CI], 53%-89%) and 87% (95% CI, 74%-100%), respectively. CONCLUSIONS: Fourteen-gauge probes generate larger ablation volumes than those generated by 17-gauge probes. Manufacturer-reported isotherms are significantly larger than actual cryoablation zones. Cryoablation can attain low rates of local recurrence.

The extracellular matrix molecules versican and hyaluronan in urethral and vaginal tissues in stress urinary incontinence.

PURPOSE: Abnormal extracellular matrix (ECM) changes are correlated with stress urinary incontinence (SUI). The ECM components versican (Vcan) and hyaluronan (HA) play key roles in regulating tissue inflammation and maintaining connective tissue homeostasis. We analyzed the localization and expression of these ECM components in urethral and vaginal tissues from a rat model of urinary incontinence and from human clinical specimens. METHODS: Nulliparous rats underwent vaginal distension (VD), a rodent model of SUI, or a sham procedure. Tissues were harvested from six rats per group at days 1, 4, and 21 for immunohistochemistry and RNA expression analysis of ECM components. Periurethral vaginal samples from female patients with SUI were also examined. RESULTS: High-intensity staining for Vcan was observed 1 day after procedure in both control and VD animals. This level of abundance persisted at day 4 in VD compared to control, with concurrent reduced messenger RNA (mRNA) expression of the Vcan-degrading enzymes ADAMTS5 and ADAMTS9 and reduced staining for the Vcan cleavage epitope DPEAAE. Abundance of HA was not different between VD and control, however mRNA expression of the HA synthase Has2 was significantly reduced in VD tissues at day 4. Abundant Vcan staining was observed in 60% of SUI patient samples, which was strongest in regions of disrupted elastin. CONCLUSION: Reduction of Vcan-degrading enzymes and HA synthases at day 4 postsurgery indicates a potential delay in ECM turnover associated with SUI. Abundant Vcan is associated with inflammation and elastin fiber network disruption, warranting further investigation to determine its role in SUI pathogenesis.

Validating the European randomised study for screening of prostate cancer (ERSPC) risk calculator in a contemporary South African cohort.

INTRODUCTION: Numerous prostate cancer predictive tools have been developed to help with decision-making in men needing prostate biopsy. However, they have been modelled and validated almost exclusively in Caucasian cohorts, hence limiting their use in other population groups. The aim of this study was to assess the validity of the ERSPC risk calculator in a South African cohort. METHODS: Patients who have had a transrectal ultrasound (TRUS)-guided prostate biopsy at Groote Schuur Hospital from January 2008 to August 2017 were reviewed. Predictor variables were entered into the ERSPC risk calculator and results were compared with prostate biopsy pathology results. Predictive accuracy of the ERSPC risk calculator for these patients was derived using receiver operator characteristics (ROC) Area under the curve and is expressed as a percentage. RESULTS: 516 prostate biopsy sessions in 475 different men were analysed. The predictive accuracy of the ERSPC risk calculator was better than a PSA/DRE strategy for the presence of cancer-0.738 (95% CI 0.695-0.781) vs 0.686 (95% CI 0.639-0.732), and for significant PCa-0.833 (95% CI 0.789-0.876) vs 0.793 (95% CI 0.741-0.846). This translated into 50 less biopsies when compared to a PSA > 4/abnormal DRE strategy. Use of the ERSPC RC would have missed eight non-significant cancers [Significant cancer being defined as having a tumour stage T2b (> 1/2 lobe involved with prostate cancer) and/or a Gleason Score equal to or greater than 7]. CONCLUSION: Our results confirm the validity of the ERSPC RC in a South African cohort. Application of this calculator to the wider South African population would allow better selection of patients for prostate biopsy and spare a significant number its adverse consequences.

Mechanisms of Horizontal Cell-to-Cell Transfer of Wolbachia spp. in Drosophila melanogaster.

Wolbachia is an intracellular endosymbiont present in most arthropod and filarial nematode species. Transmission between hosts is primarily vertical, taking place exclusively through the female germ line, although horizontal transmission has also been documented. The results of several studies indicate that Wolbachia spp. can undergo transfer between somatic and germ line cells during nematode development and in adult flies. However, the mechanisms underlying horizontal cell-to-cell transfer remain largely unexplored. Here, we establish a tractable system for probing horizontal transfer of Wolbachia cells between Drosophila melanogaster cells in culture using fluorescence in situ hybridization (FISH). First, we show that horizontal transfer is independent of cell-to-cell contact and can efficiently take place through the culture medium within hours. Further, we demonstrate that efficient transfer utilizes host cell phagocytic and clathrin/dynamin-dependent endocytic machinery. Lastly, we provide evidence that this process is conserved between species, showing that horizontal transfer from mosquito to Drosophila cells takes place in a similar fashion. Altogether, our results indicate that Wolbachia utilizes host internalization machinery during infection, and this mechanism is conserved across insect species.IMPORTANCE Our work has broad implications for the control and treatment of tropical diseases. Wolbachia can confer resistance against a variety of human pathogens in mosquito vectors. Elucidating the mechanisms of horizontal transfer will be useful for efforts to more efficiently infect nonnatural insect hosts with Wolbachia as a biological control agent. Further, as Wolbachia is essential for the survival of filarial nematodes, understanding horizontal transfer might provide new approaches to treating human infections by targeting Wolbachia Finally, this work provides a key first step toward the genetic manipulation of Wolbachia.

Evaluation of [11C]TAZA for amyloid ß plaque imaging in postmortem human Alzheimer's disease brain region and whole body distribution in rodent PET/CT.

OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disease characterized by Aß plaques in the brain. The aim of this study was to evaluate the effectiveness of a novel radiotracer, 4-[(11) C]methylamino-4'-N,N-dimethylaminoazobenzene ([(11)C]TAZA), for binding to Aß plaques in postmortem human brain (AD and normal control (NC)). METHODS: Radiosyntheses of [(11)C]TAZA, related [(11)C]Dalene ((11)C-methylamino-4'-dimethylaminostyrylbenzene), and reference [(11)C]PIB were carried out using [(11)C]methyltriflate prepared from [(11) C]CO(2) and purified using HPLC. In vitro binding affinities were carried out in human AD brain homogenate with Aß plaques labeled with [(3) H]PIB. In vitro autoradiography studies with the three radiotracers were performed on hippocampus of AD and NC brains. PET/CT studies were carried out in normal rats to study brain and whole body distribution. RESULTS: The three radiotracers were produced in high radiochemical yields (>40%) and had specific activities >37 GBq/µmol. TAZA had an affinity, K(i) = 0.84 nM and was five times more potent than PIB. [(11)C]TAZA bound specifically to Aß plaques present in AD brains with gray matter to white matter ratios >20. [(11)C]TAZA was displaced by PIB (>90%), suggesting similar binding site for [(11)C]TAZA and [(11)C]PIB. [(11)C]TAZA exhibited slow kinetics of uptake in the rat brain and whole body images showed uptake in interscapular brown adipose tissue (IBAT). Binding in brain and IBAT were affected by preinjection of atomoxetine, a norepinephrine transporter blocker. CONCLUSION: [(11)C]TAZA exhibited high binding to Aß plaques in human AD hippocampus. Rat brain kinetics was slow and peripheral binding to IBAT needs to be further evaluated.

Preventable Complications Driving Rising Costs in Management of Patients with Critical Limb Ischemia.

BACKGROUND: This study aimed to identify factors that drive increasing health-care costs associated with the management of critical limb ischemia in elective inpatients. METHODS: Patients with a primary diagnosis code of critical limb ischemia (CLI) were identified from the 2001-2011 Nationwide Inpatient Sample. Demographics, CLI management, comorbidities, complications (bleeding, surgical site infection [SSI]), length of stay, and median in-hospital costs were reviewed. Statistical analysis was completed using Students' t-test and Mann-Kendall trend analysis. Costs are reported in 2011 US dollars corrected using the consumer price index. RESULTS: From 2001 to 2011, there were a total of 451,823 patients who underwent open elective revascularization as inpatients for CLI. Costs to treat CLI increased by 63% ($12,560 in 2001 to $20,517 in 2011, P < 0.001 in trend analysis). Endovascular interventions were 20% more expensive compared with open surgery ($19,566 vs. $16,337, P < 0.001). Age, gender, and insurance status did not affect the cost of care. From 2001 to 2011, the number of patient comorbidities (7.56-12.40) and percentage of endovascular cases (13.4% to 27.4%) increased, accounting for a 6% annual increase in total cost despite decreased median length of stay (6 to 5 days). Patients who developed SSI had total costs 83% greater than patients without SSIs ($30,949 vs. $16,939; P < 0.001). Patients who developed bleeding complications had total costs 41% greater than nonbleeding patients ($23,779 vs. $16,821, P < 0.001). Overall, there was a 32% reduction in SSI rates but unchanged rates of bleeding complications during this period. CONCLUSIONS: The cost of CLI treatment is increasing and driven by rising endovascular use, SSI, and bleeding in the in-patient population. Further efforts to reduce complications in this patient population may contribute to a reduction in health care-associated costs of treating CLI.

Racial/Ethnic variation in carotid artery revascularization utilization and outcomes: analysis from the National Cardiovascular Data Registry.

BACKGROUND AND PURPOSE: It is not known whether racial or ethnic disparities observed with other revascularization procedures are also seen with carotid artery stenting (CAS) and endarterectomy (CEA). METHODS: We compared the utilization and outcomes of CAS and CEA across racial/ethnic groups within the CARE Registry between May 2007 and December 2012. RESULTS: Between 2007 and 2012, of the 13 129 patients who underwent CAS, majority were non-Hispanic whites (89.3%), followed by blacks (4.4%), Hispanics (4.3%), and other groups (2.0%). A similar distribution was observed among the 10 953 patients undergoing CEA (non-Hispanic whites, 92.6%; blacks, 3.5%; Hispanics, 2.8%; and other groups, 1.1%). During this time period, a trend toward proportionate increase in CAS utilization was observed in non-Hispanic whites and other groups, whereas the opposite was observed among Hispanics and blacks. This trend persisted even when hospitals performing both CAS and CEA were exclusively analyzed. Adherence to antiplatelet and statin therapy was significantly lower among blacks post CEA. In-hospital major adverse cardiac and cerebrovascular events remained comparable across groups post CAS and CEA. At 30 days, the incidence of stroke (7.2%) and major adverse cardiac and cerebrovascular events (8.8%) was higher among blacks post CEA (P<0.05), after risk adjustment. CONCLUSION: During the study period, utilization of CAS and CEA was highest among non-Hispanic whites. There was a trend toward increased CAS utilization over time among non-Hispanic whites and other groups, and a trend toward increased CEA utilization among Hispanics and blacks. In-hospital major adverse cardiac and cerebrovascular events remained comparable between groups, whereas 30-day major adverse cardiac and cerebrovascular events were significantly higher in blacks.

Comparison of military and civilian popliteal artery trauma outcomes.

OBJECTIVE: Popliteal artery injury has historically led to high amputation rates in both the military and civilian setting. Military and civilian popliteal injury patterns differ in mechanism and severity of injury, prompting us to compare modern management and report differences in outcomes between these two patient groups. We hypothesized that whereas amputation rates may be higher in the military, this would correlate with worse overall injury severity. METHODS: Military casualties from 2003-2007 with a popliteal artery injury identified from the Joint Theater Trauma Registry were compared retrospectively with civilian patients presenting to a single level I institution from 2002-2009 with popliteal arterial injury. Demographics, mechanism of injury, coinjuries, Injury Severity Score (ISS), Mangled Extremity Severity Scores (MESS), interventions, and secondary amputation rates were reviewed. Descriptive statistics and unpaired t-tests were used to compare data. Statistical significance was P < .05. RESULTS: The study group of 110 patients consisted of 46 (41.8%) military and 64 (58.2%) civilians with 48 and 64 popliteal artery injuries, respectively. The military population was younger (28 vs 35 years; P < .004), entirely male (46 [100%] vs 51 [80%]; P < .0001), and had more penetrating injuries (44 [96%] vs 19 [30%]; P < .0001). ISS (18.7 vs 13.9; P < .005) and MESS (7.3 vs 5.1; P < .0001) were higher in the military group. Limb revascularizations in both military and civilian populations were mostly by autogenous bypass (65% vs 77%) followed by primary repair (26% vs 16%), covered stent (0% vs 6%), or other procedure (ligation and/or thrombectomy) (9% vs 1%). Fasciotomy (20 [42%] vs 37 [58%]; P = .14), compartment syndrome (10 [21%] vs 15 [23%]; P = .84), and concomitant venous repair rates (14 [29%] vs 15 [23%]; P = .42) were not different between cohorts. There was no difference in the fracture rate (26 [54%] vs 41 [64%]; P = .43), but the civilian group had a higher rate of dislocation (1 [2%] vs 19 [30%]; P < .0001). Secondary amputation rates were significantly higher in the military (14 [29%] vs 8 [13%]; P < .03). CONCLUSIONS: Although both civilian and military cohorts have high amputation rates for popliteal arterial injury, the rate of amputation appears to be higher in the military and is associated with a penetrating mechanism of injury primarily from improvised explosive devices resulting in a higher MESS and ISS.

Endovascular management of a traumatic renal-caval arteriovenous fistula in a pediatric patient.

Traumatic renal arteriovenous fistula involving the inferior vena cava (IVC) are exceptionally rare, but if left untreated can have devastating clinical consequences, including development of renovascular hypertension, cardiomegaly, and congestive heart failure. We report a rare, pediatric case of a renal-caval arteriovenous fistula that developed after a gunshot wound to the abdomen and its subsequent treatment with endovascular means. We review our case and the world literature on the evaluation and management of trauma-related renal-caval arteriovenous fistulae.

Carotid endarterectomy national trends over a decade: does sex matter?

BACKGROUND: The objective was to evaluate the difference in timing (if any) of in-hospital carotid endarterectomy (CEA) or outcomes of CEA based on sex among men and women hospitalized for carotid artery disease. METHODS: This was a retrospective cross-sectional study using the Nationwide Inpatient Sample Database. All patients from 2000-2009 who underwent CEA during their hospitalization were examined. International Classification of Diseases, 9th revision codes were used to identify patients who underwent CEA during hospitalization, stratify asymptomatic and symptomatic patients, determine time in days from admission to CEA, and examine in-hospital complications, including perioperative stroke, cardiac events, and death. Statistical analysis was performed with chi-squared and t-tests. Linear and logistic regression models were used to evaluate relationships between sex and outcomes. The main outcome measures were time from admission to surgery, in-hospital mortality, complications, mean duration of stay, and discharge disposition. RESULTS: Two hundred twenty-one thousand two hundred fifty three patients underwent CEA during hospitalization. More than 9% (9.2%) had symptomatic carotid artery disease. Among symptomatic patients, bivariate analysis found that women had a longer mean time from admission to surgery (2.8 vs. 2.6 days; P < 0.001) and a longer duration of hospital stay (6.4 vs. 5.9 days; P < 0.001) than their male counterparts. However, there was no difference between men and women with regard to rates of perioperative stroke, cardiac complications, myocardial infarction, or death. Among asymptomatic patients, women had a longer mean time from admission to surgery (0.53 vs. 0.48 days; P < 0.001) and a trend toward increased perioperative stroke (0.6% vs. 0.5%; P = 0.06), but a lower rate of cardiac complications (1.5% vs. 1.7%; P = 0.01) and in-hospital mortality (0.26% vs. 0.31%; P = 0.05). However, on multivariable analysis adjusting for differences in age, elective status, insurance, race, hospital location, hospital region, and hospital teaching status, there was no sex disparity in time from admission to surgery, regardless of symptomatic status. In addition, asymptomatic women were less likely than men to have a cardiac complication (odds ratio [OR]: 0.90; 95% confidence interval [CI]: 0.83-0.97) or in-hospital mortality (OR: 0.83; 95% CI: 0.70-0.98). Symptomatic women were also less likely than men to have a cardiac complication (OR: 0.78; 95% CI: 0.63-0.97). CONCLUSIONS: In this decade-long national population-based study of hospitalized patients undergoing CEA, women had lower perioperative cardiac morbidity and mortality rates than men. After adjusting for patient, clinical, and hospital factors, there is no discernible difference in timing of CEA based on sex.

Surgical site infections after lower extremity revascularization procedures involving groin incisions.

BACKGROUND: We sought to evaluate the incidence, epidemiology, and factors associated with surgical site infections (SSIs) after lower extremity revascularization procedures involving groin incisions and determine outcomes based on SSI status. METHODS: This is a single-institution, retrospective cohort study of 106 patients who underwent lower extremity revascularization procedures involving femoral artery exposure through a groin incision at a tertiary referral hospital. The primary outcome was occurrence of SSI at the groin wound. The duration of hospital stay, reoperation within 30 days, discharge disposition, and 30-day mortality were also evaluated. Independent variables included patient demographics and operative variables (i.e., procedure type, transfusion requirements, preoperative antibiotics, intraoperative vasopressors, and operative duration). Statistical analysis included chi-squared tests, t-tests, and multivariable regression analysis. RESULTS: Of the 106 patients who underwent a lower extremity revascularization procedure with a groin incision for femoral artery exposure, 62% were male, and the mean age was 62 years. Comorbidities included hypertension (93%), dyslipidemia (65%), statin use (63%), active smoker (50%), diabetes (24%), and chronic obstructive pulmonary disease (23%). All patients received preoperative antibiotics, 50% required intraoperative pressors, 21% received a blood transfusion, and the mean operative time was 296 min. The overall duration of stay was 10.7 days, the 30-day reoperation rate was 18%, and the 30-day mortality rate was 12%. Overall, 22% developed a seroma or hematoma, and 31% developed a SSI. Patients who developed an SSI compared with those who did not were more likely to have a postoperative seroma or hematoma (55% vs 5%) and to receive a blood transfusion (33% vs 15%), but less likely to be treated with a statin (47% vs 69%) or carry a diagnosis of dyslipidemia (50% vs 72%), respectively, all P < 0.05. Patients with an SSI had a longer duration of stay (14.5 vs 8.7 days) and a higher reoperative rate (49% vs 4%), but had a lower 30-day mortality (0% vs 18%) than those who did not develop an SSI (all P < 0.05). On multivariable regression analysis adjusting for differences in patient and operative variables, the occurrence of a wound seroma or hematoma remained an independent predictor for SSI (odd ratio: 27.6; 95% confidence interval: 5.4-139.6). CONCLUSIONS: The incidence of postoperative surgical site complications after lower extremity revascularization procedures involving a groin incision was 31% and was significantly associated with blood transfusion, postoperative seroma or hematoma, dyslipidemia, and statin usage. After adjusting for differences in patient and operative variables, postoperative seroma or hematoma was an independent predictor of SSI. Patients with a SSI have a longer duration of hospitalization and higher reoperative rate. Additional prospective cohort studies are warranted to delineate ways to decrease the rate of SSI.

Condylus tertius with atlanto-axial rotatory fixation: an unreported association.

The "condylus tertius" or the "third occipital condyle" is an embryological remnant of the proatlas sclerotome. Anatomically, it is attached to the basion and often articulates with the anterior arch of the atlas and the odontoid apex; hence, it is also called the "median occipital condyle". It is a rare anomaly of the cranio-vertebral junction (CVJ) that can lead to instability and compression of important surrounding neurovascular structures. We report a case of a 16-year-old boy who presented with suboccipital neck pain, torticollis and right sided hemiparesis. Plain radiographs revealed an increased atlanto-dental interspace (ADI) with a retroflexed odontoid. Open mouth view showed asymmetry of the articular processes of the atlas with respect to the dens. Computed tomography (CT) of the CVJ delineated the third occipital condyle. Furthermore, on dynamic CT study, a type 3 atlanto-axial rotatory fixation (AARF) was clearly demonstrated. Magnetic resonance imaging (MRI) of the CVJ revealed severe right-sided spinal cord compression by the retroflexed and rightward deviated dens. It also revealed disruption of the left alar and transverse ligaments. The patient was treated with 8 weeks of cranial traction and reasonable alignment was obtained. This was followed by C1-C2 lateral mass screw fixation and C1-C2 interlaminar wiring to maintain the alignment. A review of the literature did not reveal any cases of condylus tertius associated with non-traumatic AARF. An accurate knowledge of the embryology and imaging features of this rare CVJ anomaly is useful in the prompt diagnosis and management of such patients.

Pulmonary arterial hypertension: a clot in question.

Pulmonary arterial hypertension (PAH) is a group of disorders characterized by a progressive increase in pulmonary vascular resistance leading to right heart failure and premature death. We present an unusual case of PAH diagnosed initially as Idiopathic PAH (IPAH) after secondary causes were excluded which was successfully managed for a number of years with vasodilators and anticoagulation. Over the months after stopping anticoagulation (because of recurring small bowel hemorrhaging) patient developed progressive findings of right heart failure, which failed to respond to escalating doses of prostacyclin. The patient died and an autopsy revealed the surprising finding of extensive organized central pulmonary artery thrombi as is seen in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We discuss the question of whether these thrombi are generally embolic or develop in situ and recommend that clinicians have a high index of suspicion for central thrombi in patients with IPAH were anticoagulation is contraindicated.