A systematic review and meta-analysis on the influence of sociodemographic factors on amputation in patients with peripheral arterial disease.

OBJECTIVE: To identify disparities in sociodemographic factors that are associated with major lower limb amputation in patients with peripheral arterial disease (PAD). METHODS: A systematic review of the literature was performed to identify studies that reported major lower limb amputation rates in patients with PAD among different sociodemographic groups. Data that compared amputation rates on the basis of sex, race, ethnicity, income, insurance, geography, and hospital type were collected and described. Outcomes were then aggregated and standardized, and a meta-analysis was performed to synthesis data into single odds ratios (ORs). RESULTS: Forty-one studies were included in the review. There was no association found between males and females (OR, 0.95; 95% confidence interval [CI], 0.90-1.00). Compared with Whites, higher rates of amputation were seen among Blacks/African Americans (OR, 2.02; 95% CI, 1.81-2.26) and Native Americans (OR, 1.22; 95% CI, 1.04-1.45). No significant association was found between Whites and Asians, Native Hawaiians, or Pacific Islanders (OR, 1.15; 95% CI, 1.00-1.33). Hispanics had higher rates of amputation compared with non-Hispanics (OR, 1.36; 95% CI, 1.22-1.52). Compared with private insurance, higher rates of amputation were seen among Medicare patients (OR, 1.38; 95% CI, 1.27-1.50), Medicaid patients (OR, 1.59; 95% CI, 1.44-1.76), and noninsured patients (OR, 1.41; 95% CI, 1.02-1.95). Compared with the richest income quartile, higher rates of amputation were seen among the second income quartile (OR, 1.10; 95% CI, 1.05-1.15), third income quartile (OR, 1.20; 95% CI, 1.07-1.35), and bottom income quartile (OR, 1.36; 95% CI, 1.24-1.49). There was no association found between rural and urban populations (OR, 1.35; 95% CI, 0.92-1.97) or between teaching and nonteaching hospitals (OR, 1.01; 95% CI, 0.91-1.12). CONCLUSIONS: Our study has identified a number of disparities and quantified the influence of sociodemographic factors on major lower limb amputation rates owing to PAD between groups. We believe these findings can be used to better target interventions aimed at decreasing amputation rates, although further research is needed to better understand the mechanisms behind our findings.

Can remote endarterectomy expand access to kidney transplantation in patients with severe iliac calcification?

Severe iliac artery calcification in patients with end-stage renal disease is a common barrier to listing for kidney transplant. While few surgical solutions to iliac calcification have been reported, improving treatment may thus improve access to transplant care. Here we present two cases of a novel application of remote endarterectomy of the external iliac artery to facilitate listing for renal transplant. Both patients were listed following remote endarterectomy, followed by successful renal transplants using the treated vessels.

Genetic contributions to variation in human stature in prehistoric Europe.

The relative contributions of genetics and environment to temporal and geographic variation in human height remain largely unknown. Ancient DNA has identified changes in genetic ancestry over time, but it is not clear whether those changes in ancestry are associated with changes in height. Here, we directly test whether changes over the past 38,000 y in European height predicted using DNA from 1,071 ancient individuals are consistent with changes observed in 1,159 skeletal remains from comparable populations. We show that the observed decrease in height between the Early Upper Paleolithic and the Mesolithic is qualitatively predicted by genetics. Similarly, both skeletal and genetic height remained constant between the Mesolithic and Neolithic and increased between the Neolithic and Bronze Age. Sitting height changes much less than standing height-consistent with genetic predictions-although genetics predicts a small post-Neolithic increase that is not observed in skeletal remains. Geographic variation in stature is also qualitatively consistent with genetic predictions, particularly with respect to latitude. Finally, we hypothesize that an observed decrease in genetic heel bone mineral density in the Neolithic reflects adaptation to the decreased mobility indicated by decreased femoral bending strength. This study provides a model for interpreting phenotypic changes predicted from ancient DNA and demonstrates how they can be combined with phenotypic measurements to understand the relative contribution of genetic and developmentally plastic responses to environmental change.

A geometric morphometric assessment of shape variation in adult pelvic morphology.

OBJECTIVES: In humans, the pelvis is the most sexually dimorphic skeletal element and is often utilized in aging and sexing remains. The pelvis has become greatly relied upon in anthropological research (e.g., forensics, demographics, obstetrics, evolutionary history); however, pelvis morphology is highly variable, and very little is known about the nature, sources, patterning, and interpretation of this variation. This study aims to quantify pelvis shape variation, document sexual shape variation, and estimate the plasticity of morphology. This will ultimately give greater ability to interpret modern, archaeological, and evolutionary patterns to gain deeper insight into processes which shape human anatomy. MATERIALS AND METHODS: Using a sample of 129 Medieval Danish skeletons, shape variation is documented in the greater sciatic notch (GSN), iliac crest (IC), arcuate line (AL), and sub-pubic angle (SPA) using 3D geometric morphometrics. The landmarking method applied here has the advantage of being applicable to fragmentary remains, rather than requiring whole bones. This allows it to be easily applied to archaeological samples and for the interpretation of separate bone features. Differences in shape were statistically analyzed by principle component analysis, linear discriminate analysis, and morphological disparity. Relationships between maximum femur length, body mass, and shape centroid size were also test by allometric regression. RESULTS: Results quantify the sexual dimorphism and shape variation present in these features. The GSN shape is the most variable, while the AL is the least. Similarly, the IC is the only feature which shows almost no dimorphism in shape, and instead best reflects lifestyle/activity patterns. Evidence of dimorphism in the IC is likely a result of cultural labor patterns rather than genetic and hormonal influence. Finally, the shapes of the GSN, AL, and SPA are more related to body mass than to femur length, such that individuals with increased mass exhibit more classically "male" shapes and those with less mass have more "female" shapes. DISCUSSION: The results have important implications for the evolution of pelvic anatomy, and sexual dimorphism, but also highlight the plasticity inherent in pelvic morphology. Analyzing pelvis features separately in a clearly defined, relatively genetically homogenous population gives insight into the determinants of bone morphology, which are not readily observable by other means. The relationship between body mass and shape suggests dimorphism in body size and composition may affect bone shape.

"Voice your choice": a study of women's choice of surgery for primary stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: This was an observational study aiming to determine factors which influence women's choice of surgery for primary stress urinary incontinence (SUI). METHODS: Two hundred twelve women undergoing a primary SUI procedure were recruited to this study from 12 hospitals in the north of England. After choosing a procedure, women were asked to complete a standardized semi-structured questionnaire about their health, demographics and a free text box to record factors important to them when choosing their procedure. Statistical analysis was performed to determine the impact of demographic, lifestyle or healthcare factors on women's decision-making. Thematic analysis of the free text data was performed to identify factors important for women when choosing a surgical procedure. RESULTS: Sixty-four percent of women chose urethral bulking. There was no significant difference among age, BMI, smoking status or previous laparotomy between women choosing the four types of surgery. Women were less likely to choose urethral bulking if seen in a tertiary centre compared with a secondary centre (p < 001). Major themes in decision-making were efficacy, invasiveness, recovery, risk of complications, use of mesh, the clinician, the media, hierarchy of treatments and type of anaesthetic. Some women expressed a hierarchical approach to treatment. CONCLUSIONS: Our findings suggest decision-making is not influenced by patient factors such as age, BMI, smoking status or previous laparotomies. Women's choices are a complex mix of factors and not simply related to efficacy.

A process for prioritising systematic reviews in tinnitus.

Objective: To develop an innovative prioritisation process to identify topics for new or updated systematic reviews of tinnitus research.Design: A two-stage prioritisation process was devised. First, a scoping review assessed the amount of randomized controlled trial-level evidence available. This enabled development of selection criteria for future reviews, aided the design of template protocol and suggested the scale of work that would be required to conduct these reviews. Second, using the pre-defined primary and secondary criteria, interventions were prioritised for systematic review.Study sample: Searches identified 1080 records. After removal of duplicates and out of scope works, 437 records remained for full data charting.Results: The process was tested, using subjective tinnitus as the clinical condition and using Cochrane as the systematic review platform. The criteria produced by this process identified three high priority reviews: (1) Sound therapy using amplification devices and/or sound generators; (2) Betahistine and (3) Cognitive behaviour therapy. Further secondary priorities were: (4) Gingko biloba, (5) Anxiolytics, (6) Hypnotics, (7) Antiepileptics and (8) Neuromodulation.Conclusions: A process was developed which successfully identified priority areas for Cochrane systematic reviews of interventions for subjective tinnitus. This technique could easily be transferred to other conditions and other types of systematic reviews.

Update on Neoadjuvant Regimens for Patients with Operable Oesophageal/Gastrooesophageal Junction Adenocarcinomas and Squamous Cell Carcinomas.

Survival outcomes following multimodal treatment of operable oesophageal and gastrooesophageal cancer remain disappointingly poor. Although an appreciation of the impact of both tumour location and histological subtype is now shaping the design of clinical trials, there has been a lack of consensus of the optimal neoadjuvant treatment strategy. This update article will review recent advances in the use of both neoadjuvant chemotherapy and chemoradiotherapy. The emerging role of PET imaging to direct appropriate neoadjuvant treatment regimens and the additive benefit of biological agents are also discussed.

A Defined Protocol to Resolving Cannulation Failure during Endovenous Ablation Procedures.

During endovenous ablation for the treatment of insufficient veins, failure to cannulate the entirety of the refluxing vein with the treatment catheter prevents technically successful ablation. In this technique report, we describe a defined protocol to overcome cannulation failure of axial veins for endovenous ablation. This protocol utilizes commonly available adjunctive techniques including ultrasound-guided digital compression, the use of a guidewire, the use of a guide catheter, and placement of a second puncture site in a step-wise fashion to overcome varying degrees of tortuosity or obstruction. The sequential application of these techniques as described in this report allows endovenous ablation to be applied to patients with challenging venous anatomy.

Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations.

BACKGROUND: Atherosclerosis is thought to be a disease of modern human beings and related to contemporary lifestyles. However, its prevalence before the modern era is unknown. We aimed to evaluate preindustrial populations for atherosclerosis. METHODS: We obtained whole body CT scans of 137 mummies from four different geographical regions or populations spanning more than 4000 years. Individuals from ancient Egypt, ancient Peru, the Ancestral Puebloans of southwest America, and the Unangan of the Aleutian Islands were imaged. Atherosclerosis was regarded as definite if a calcified plaque was seen in the wall of an artery and probable if calcifications were seen along the expected course of an artery. FINDINGS: Probable or definite atherosclerosis was noted in 47 (34%) of 137 mummies and in all four geographical populations: 29 (38%) of 76 ancient Egyptians, 13 (25%) of 51 ancient Peruvians, two (40%) of five Ancestral Puebloans, and three (60%) of five Unangan hunter gatherers (p=NS). Atherosclerosis was present in the aorta in 28 (20%) mummies, iliac or femoral arteries in 25 (18%), popliteal or tibial arteries in 25 (18%), carotid arteries in 17 (12%), and coronary arteries in six (4%). Of the five vascular beds examined, atherosclerosis was present in one to two beds in 34 (25%) mummies, in three to four beds in 11 (8%), and in all five vascular beds in two (1%). Age at time of death was positively correlated with atherosclerosis (mean age at death was 43 [SD 10] years for mummies with atherosclerosis vs 32 [15] years for those without; p<0·0001) and with the number of arterial beds involved (mean age was 32 [SD 15] years for mummies with no atherosclerosis, 42 [10] years for those with atherosclerosis in one or two beds, and 44 [8] years for those with atherosclerosis in three to five beds; p<0·0001). INTERPRETATION: Atherosclerosis was common in four preindustrial populations including preagricultural hunter-gatherers. Although commonly assumed to be a modern disease, the presence of atherosclerosis in premodern human beings raises the possibility of a more basic predisposition to the disease. FUNDING: National Endowment for the Humanities, Paleocardiology Foundation, The National Bank of Egypt, Siemens, and St Luke's Hospital Foundation of Kansas City.

Socio-cultural practices may have affected sex differences in stature in Early Neolithic Europe.

The rules and structure of human culture impact health as much as genetics or environment. To study these relationships, we combine ancient DNA (n = 230), skeletal metrics (n = 391), palaeopathology (n = 606) and dietary stable isotopes (n = 873) to analyse stature variation in Early Neolithic Europeans from North Central, South Central, Balkan and Mediterranean regions. In North Central Europe, stable isotopes and linear enamel hypoplasias indicate high environmental stress across sexes, but female stature is low, despite polygenic scores identical to males, and suggests that cultural factors preferentially supported male recovery from stress. In Mediterranean populations, sexual dimorphism is reduced, indicating male vulnerability to stress and no strong cultural preference for males. Our analysis indicates that biological effects of sex-specific inequities can be linked to cultural influences at least as early as 7,000 yr ago, and culture, more than environment or genetics, drove height disparities in Early Neolithic Europe.

Isotopic evidence for human mobility in late antique Bulla Regia (Tunisia).

This paper represents the first isotopic study on late antique human mobility in North Africa, using the urban site of Bulla Regia in Tunisia as a case study. We also present the first values for bioavailable 87Sr/86Sr in northern Tunisia, analysing 63 plant and snail samples, as well as a simple method for the pre-processing of plants in the field to facilitate their export. Bulla Regia was a prominent Roman and late antique town situated on an important axis of transport and communication in North Africa and is therefore an ideal site to explore mobility in the region during this time period. Strontium (87Sr/86Sr) and oxygen (δ18OCarb) isotopic analysis of 22 late antique individuals from a Christian church and cemetery identified at least seven or eight non-locals, while comparative analysis of five Roman individuals from a funerary enclosure on the same site classified all but one of them as potential locals. Most non-local individuals exhibit 87Sr/86Sr values that match various areas of northern Tunisia, which supports regional mobility rather than long-distance migration, although when combined with the oxygen results, inter-regional mobility from an area with a warmer climate may be hypothesised for some individuals. Examination of the spatial distribution of non-local individuals in their cemetery setting reveals that they were privileged individuals, thus they may reflect the mobility of wealthier town-dwellers in late antiquity, particularly perhaps along the Carthage-Hippo route.

Impact of deviations in target volume delineation - Time for a new RTQA approach?

The international radiotherapy community has recognised that non-adherence to RT protocols can influence trial endpoints. However this conclusion is based on studies predominantly assessing the impact of deviations in dosimetric or treatment delivery protocol parameters rather than target volume delineation (TVD). This review evaluates the assessment of TVD within Radiation Therapy Quality Assurance (RTQA) programmes in clinical trials and the clinical impact of TVD protocol deviations. The implications for RTQA programmes are discussed. MEDLINE, PreMEDLINE, Embase, Cochrane Library, Web of Science, OpenGrey, WHO International Clinical Trials Registry Platform portal and ClinicalTrials.gov were searched. Full-length articles and conference abstracts were included to avoid publication bias. 5864 abstracts were screened for relevance; 94 full-length articles were reviewed and 5 relevant trials identified. Various classification systems were used to assess protocol deviations; 'unacceptable' or 'major' deviations in TVD occurred in 2.9-13.4% of assessed RT plans (when reported). It was often not possible to establish deviation rates specifically related to TVD as these were frequently combined with other types of protocol deviations. Details on the nature of unacceptable deviations was also not routinely reported and difficulties in establishing a 'consensus' for appropriate TVD for on-trial patients highlighted. Results suggest that deviations in TVD were associated with poorer outcomes for overall survival, local control and treatment-related toxicity; however the data were heterogeneous. RTQA of TVD was retrospective and feedback on the quality of TVD to recruiting centres was not standard. In summary, few trials have published outcomes on the impact of assessing the quality of TVD in trials. We propose that a new approach is now required. Unacceptable TVD deviations must be clearly defined at the time of protocol development to minimise interobserver variation, thereby promoting consistency in RTQA feedback. Prospective TVD reviews should be implemented for trials involving novel or complex RT techniques to identify deviations that require modification prior to treatment delivery. Furthermore, the consistent reporting of RTQA programme outcomes, both within and across trial groups, is of paramount importance to accelerate the evidence-base for the best RTQA approach when assessing TVD and to enable the impact on clinical outcomes within RT trials to be assessed.

Resuscitative endovascular balloon occlusion of the aorta for non-traumatic intra-abdominal hemorrhage.

BACKGROUND: Hemorrhagic shock is the second leading cause of death in blunt trauma and a significant cause of mortality in non-trauma patients. The increased use of resuscitative endovascular balloon occlusion of the aorta (REBOA) as a bridge to definitive control for massive hemorrhage has provided promising results in the trauma population. We describe an extension of this procedure to our hemodynamically unstable non-trauma patients. METHODS: This is a retrospective review of patients requiring REBOA for end stage non-traumatic abdominal hemorrhage from our tertiary care facility. After excluding patients with trauma, supradiaphragmatic bleed and thoracic/abdominal aortic aneurysms, demographics, etiology of bleed, REBOA placement specifics, complications and outcomes were reviewed. RESULTS: From August 2013 to August 2016, 11 patients were identified requiring REBOA placement for hemodynamic instability from non-traumatic abdominal hemorrhage. Average patient age was 54.9 (SD 15.2). Sixty-four percent suffered cardiac arrest prior to REBOA, with mean shock index of 1.29. Average time from diagnosis of shock (MAP ≤ 65) or signs of bleeding to placement of REBOA was 177 min. The leading etiologies of hemorrhage were ruptured visceral aneurysm and massive upper gastrointestinal bleed. REBOA was placed by both acute care and vascular surgeons. The procedure was mainly completed in the operating room in 82% of the patients and at the bedside in 18%. One patient expired before operative repair. Definitive surgical control of the source of bleeding was obtained by open surgical approach (n = 6) and combined surgical and endovascular approach (n = 4). In-hospital survival was 64%. There were no local complications related to REBOA placement. CONCLUSION: Similar to the trauma population, REBOA is an adjunctive technique for proximal control of bleeding as well as resuscitation in end stage non-traumatic intra-abdominal hemorrhage. We propose an algorithmic approach to REBOA use in this population and a larger prospective review is necessary to determine both the timing of REBOA placement and which non-traumatic patients may benefit from this technique. LEVEL OF EVIDENCE: V. STUDY TYPE: Brief report.

Management of Chronic Massive Traumatic Popliteal Artery Pseudoaneurysm: A Case Series With Different Treatment Strategies.

Giant traumatic popliteal artery (PA) pseudoaneurysms (PSA) are rare but limb threatening if untreated. Management can be challenging, as no standardized approach exists. This report evaluates our experience with 3 cases treated differently. Treatment is individualized based on patient disease and comorbidities. Endovascular and local patch arterial repair are safe alternatives to graft bypass when feasible.

Double prepuncture as a valuable adjunctive technique for complex endovenous ablation.

OBJECTIVE: The objective of this study was to characterize the technique and to report the results of double prepuncture used during complex radiofrequency ablation (RFA) in cases of treating multiple incompetent veins or encountering focal obstruction to catheter advancement. METHODS: A double prepuncture technique was applied in patients requiring endovascular ablation of multiple veins and patients with great saphenous vein cannulation failure. We treated 13 limbs in 12 patients during a 24-month period with RFA in which the double prepuncture technique was used. Clinical history, operative reports, outcomes, and follow-up were reviewed. RESULTS: RFA was performed with the double puncture technique on, collectively, 10 great saphenous veins, 5 small saphenous veins, and 5 anterior accessory saphenous veins. Mean preoperative Clinical, Etiology, Anatomy, and Pathophysiology score was 4.38 ± 1.6. Three limbs required prepuncture because of difficulty in advancing the catheter cephalad through tortuosity and focal obstruction after failure with techniques such as a guidewire, a guide catheter, and manual compression with ultrasound guidance. Ten limbs received planned double prepuncture for multiple adjacent incompetent veins, for which venipuncture and cannulation of the second target vein would be difficult after tumescent application to the first vein. Postoperative ultrasound demonstrated successful closure of all target veins in which the double prepuncture technique was used. One patient had a deep venous thrombosis (7.7%) that resolved without complications. CONCLUSIONS: Double prepuncture is a useful technical adjunct both for simultaneous endovenous ablation of multiple adjacent incompetent veins and when catheter passage is impeded. This technique aids in efficient and successful application of endovenous ablation to complex venous anatomy.

The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy.

BACKGROUND AND PURPOSE: The derived neutrophil-lymphocyte ratio (dNLR) is a validated prognostic biomarker for cancer survival but has not been extensively studied in locally-advanced oesophageal cancer treated with definitive chemoradiotherapy (dCRT). We aimed to identify the prognostic value of dNLR in patients recruited to the SCOPE1 trial. MATERIALS AND METHODS: 258 patients were randomised to receive dCRT±cetuximab. Kaplan-Meier's curves and both univariable and multivariable Cox regression models were calculated for overall survival (OS), progression free survival (PFS), local PFS inside the radiation volume (LPFSi), local PFS outside the radiation volume (LPFSo), and distant PFS (DPFS). RESULTS: An elevated pre-treatment dNLR≥2 was significantly associated with decreased OS in univariable (HR 1.74 [95% CI 1.29-2.35], p<0.001) and multivariable analyses (HR 1.64 [1.17-2.29], p=0.004). Median OS was 36months (95% CI 27.8-42.4) if dNLR<2 and 18.4months (95% CI 14.1-24.9) if dNLR≥2. All measures of PFS were also significantly reduced with an elevated dNLR. dNLR was prognostic for OS in cases of squamous cell carcinoma with a non-significant trend for adenocarcinoma/undifferentiated tumours. CONCLUSIONS: An elevated pre-treatment dNLR may be an independent prognostic biomarker for OS and PFS in oesophageal cancer patients treated with definitive CRT. dNLR is a simple, inexpensive and readily available tool for risk-stratification and should be considered for use in future oesophageal cancer clinical trials. The SCOPE1 trial was an International Standard Randomised Controlled Trial [number 47718479].

Southern Elephant Seals Replenish Their Lipid Reserves at Different Rates According to Foraging Habitat.

Assessing energy gain and expenditure in free ranging marine predators is difficult. However, such measurements are critical if we are to understand how variation in foraging efficiency, and in turn individual body condition, is impacted by environmentally driven changes in prey abundance and/or accessibility. To investigate the influence of oceanographic habitat type on foraging efficiency, ten post-breeding female southern elephant seals Mirounga leonina (SES) were equipped and tracked with bio-loggers to give continuous information of prey catch attempts, body density and body activity. Variations in these indices of foraging efficiency were then compared between three different oceanographic habitats, delineated by the main frontal structures of the Southern Ocean. Results show that changes in body density are related not only to the number of previous prey catch attempts and to the body activity (at a 6 day lag), but also foraging habitat type. For example, despite a lower daily prey catch attempt rate, SESs foraging north of the sub-Antarctic front improve their body density at a higher rate than individuals foraging south of the sub-Antarctic and polar fronts, suggesting that they may forage on easier to catch and/or more energetically rich prey in this area. Our study highlights a need to understand the influence of habitat type on top predator foraging behaviour and efficiency when attempting a better comprehension of marine ecosystems.

A Critical Look at Mummy CT Scanning.

Computed tomography scanning of mummies has been conducted for almost 40 years, and has become an increasingly popular method of mummy study in the 21st century. However, most CT scan analyses published today still do little more than praise the technique's non-destructive, non-invasive properties. Despite the wealth of information contained within a modern, high definition scan, most researchers have yet to fully exploit the full potential of this technology. In addition, those that have utilized CT scanning in ancient remains continue to interpret mummified tissues as though they were living, without investigating how taphonomy and mummification could have effected the tissue images that are produced. Because of this, there is very limited information available for clear interpretation of mummy CT's. This article presents a critical assessment of the development of mummy CT scanning and presents the results of two Egyptian mummies CT'ed at the Penn Museum as an example of the potentials and pitfalls of high-resolution scanning.