Associations of mid-to-late-life inflammation with late-life mobility and the influences of chronic comorbidities, race, and social determinants of health: The Atherosclerosis Risk in Communities Study.

BACKGROUND: Relationships of midlife inflammation with late-life mobility and influences of chronic health conditions, race, and social determinants of health (SDoH) on these relationships are poorly understood. METHODS: Among 4758 community-dwelling participants (41% men, 20% Black), high-sensitivity C-reactive protein (hsCRP) was measured over 20+ years: in midlife at study visit 2 (V2: 1990-1992, 47-68 years); at V4 (1996-1998, 53-74 years); and with concurrent late-life 4-m gait speed at V5 (2011-2013, 67-88 years, mean 75 years). SDoH measures included race, the national-rank area deprivation index, education, and income. We examined associations of late-life gait speed with midlife hsCRP (V2 continuous and clinically high ≥3 mg/L), with 20-year hsCRP history from midlife (V2-V5 average continuous hsCRP and clinically high ≥3 mg/L) and with inflammation accumulation (visits and years with high hsCRP). Regression models adjusted for demographic, cardiovascular, and SDoH measures; effect modification by the presence of other common chronic conditions (obesity, diabetes, hypertension) and race were examined, with and without accounting for SDoH. RESULTS: High midlife hsCRP was associated with slower late-life gait speed, even among those without chronic conditions in midlife: -4.6 cm/s (95% CI: -6.4, -2.8). Importantly, sustained high hsCRP was associated with a 20-year slowing of -10.0 cm/s (-14.9, -5.1) among those who never experienced obesity, diabetes, or hypertension over the 20-year period. Associations were similar between Black participants, -3.8 cm/s (-6.9, -0.7) and White participants -3.3 (-4.5, -2.2) per interquartile range of midlife hsCRP; effect modifications by chronic conditions and race were unsupported throughout. Results were robust to accounting for SDoH or otherwise; however, worse SDoH was associated with higher inflammation and slower gait speed in both Black and White participants. CONCLUSIONS: Inflammation in midlife may contribute to clinically meaningful late-life slowing of gait speed, even among otherwise healthy-appearing adults and regardless of race and socioeconomic disadvantage. Regular monitoring and interventions for inflammation may be warranted from midlife.

Paragangliomas Arising From the Laryngeal Paraganglia: Thyroid and Laryngeal Paragangliomas With Radiology-Pathology Correlation.

Paragangliomas are neuroendocrine tumors that arise from the embryonic neural crest cells of the extra-adrenal chromaffin and non-chromaffin cellular system. Paragangliomas arising from the laryngeal paraganglia, which occur in the thyroid and larynx, are a rare subset of paragangliomas compared to the more common locations of the carotid body, vagale, jugular, and tympanic paragangliomas. The preoperative diagnosis of both thyroid and laryngeal paragangliomas may pose a challenge due to cytological, pathological, and imaging non-specificity that overlaps with many other neoplasms. These lesions may be associated with significant intraoperative bleeding and complicated excision with adherence to nearby structures, including the recurrent laryngeal nerve. This article discusses the imaging appearance, pathological features, clinical and operative considerations and manifestations, and management of head and neck paragangliomas, as seen in two patients at our institution.

Delivery of multipotent adult progenitor cells via a functionalized plasma polymerized surface accelerates healing of murine diabetic wounds.

Introduction: Stem cell therapies have been investigated as potential treatment modalities for chronic wounds however there has been limited success to date. Multipotent Adult Progenitor Cells (MAPCs©) have been identified as having potential as an allogenic stem cell product due to their high population doubling number and their characteristic dampening of T-cell proliferation. This helps to prevent autoimmunity and graft/cell rejection. Methods: We have developed a dressing, consisting of medical grade silicone coated with a heptylamine plasma polymer, which supports the growth and transfer of MAPCs to skin. To determine if the dressing can deliver functional stem cells into diabetic wounds, they were loaded with MAPCs and then placed over excisional wounds in both normal and diabetic mice. Results and discussion: Accelerated healing was observed in both the normal and diabetic wounds with wound gape being significantly smaller at day 3 when compared to controls. Wound analysis showed that treatment with the MAPC dressings dampened the inflammatory response with reduced numbers of neutrophils and macrophages observed. Additionally, an increase in pro-angiogenic VEGF and CD31 positive endothelial cells was observed indicating improved new blood vessel formation. The MAPC dressings had no effect on fibrosis with collagen I and III being equally affected in both control and treated wounds. Overall, the functionalized MAPC dressings improve healing responses particularly in diabetic mice with impaired healing responses and therefore, show potential for development as an advanced therapeutic approach for the treatment of chronic diabetic wounds.

Endurance and gait speed relationships with mild cognitive impairment and dementia.

INTRODUCTION: Slower mobility is associated with mild cognitive impairment (MCI) and dementia. We examined the interaction of endurance with gait speed on prevalent MCI and dementia. METHODS: Cross-sectional multinomial regression in the ARIC cohort (n = 2844 participants; 71 to 94 years; 44% men; 18% Black persons) with cognitive status (normal/MCI/dementia), 4 m gait speed, and endurance (2 minute walk [2MW]). RESULTS: Faster gait speed (up to but not above 1 m/s) and better 2MW were separately associated with lower dementia risk. Good performance in both (2MW = 200 m, gait speed = 1.2 m/s) was associated with 99% lower dementia (Relative Prevalence Ratio [RPR] = 0.01 [95% CI: 0.0 to 0.06]) and 73% lower MCI, RPR = 0.27 (0.15 to 0.48) compared to poor performance in both (2MW = 100 m, gait speed = 0.8 m/s). Models incorporating a gait speed-by-2MW interaction term outperformed gait speed-only models (P < .001). DISCUSSION: Gait speed relationships with dementia diminish at faster gait speeds. Combining endurance with gait speed may yield more sensitive markers of MCI and dementia than gait speed alone.

Relationships of Clinical and Computed Tomography-Imaged Adiposity with Cognition in Middle-Aged and Older African Americans.

Background: Adiposity depots may differentially affect cognition. African Americans (AA) have higher rates of obesity and dementia but lower visceral adipose tissue (VAT) than whites, yet are underrepresented in studies of adiposity and cognition. Our study compared relations of cognitive function to clinical adiposity measures and computed tomography (CT)-imaged abdominal adiposity in AA. Methods: CT-imaged subcutaneous adipose tissue (SAT) and VAT measurements were obtained in the AA cohort of the Genetic Epidemiology Network of Arteriopathy Study (N = 652, mean age 68 ± 8.4 years, 74% females, 59% obese, 82% hypertensive). Clinical adiposity measures included waist circumference (WC) and body mass index (BMI). Global cognition was operationalized as a global cognitive z-score generated from the average of four cognitive domain z-scores. Generalized estimating equations were used to examine cross-sectional associations between individual standardized adiposity measures and cognition, accounting for age, sex, education, smoking status, and familial clustering. A collective model was constructed including multiple supported adiposity measures and age-by-adiposity interactions. Results: In the collective model, higher WC was associated with worse global cognition, ß = -0.12 (95%CI: -0.21, -0.03); higher SAT was associated with better cognition, ß = 0.09 (0.01, 0.18); higher BMI was associated with worse cognition at younger ages with attenuation at older ages (BMI-by-age-interaction p = .004). VAT was not significantly associated with global cognition, ß = -0.03 (-0.07, 0.02). Conclusions: WC may be the simplest and most efficient measure of adiposity to assess with respect to cognition in clinical settings, although studies to determine mechanistic effects of subcutaneous and other adiposity depots on cognition are warranted.

The association of pre-operative home accelerometry with cardiopulmonary exercise variables.

We investigated the association of pre-operative activity, reported by the Duke Activity Score Index, Short Form-12 and measured by an accelerometer worn at home, with five cardiopulmonary exercise variables: peak power; peak oxygen consumption; anaerobic threshold; and ventilatory equivalents for oxygen and carbon dioxide. Fifty patients scheduled for major surgery underwent a standard pre-operative cardiopulmonary exercise test and wore a chest-mounted triaxial accelerometer for a mean (SD) duration of 3.2 (0.4) days. The Duke Activity Score Index and six accelerometer variables were significantly correlated with all five cardiopulmonary exercise variables, Pearson correlation coefficients 0.5-0.7, p = 0.02 to p < 0.001. Our results can guide future studies that measure physical activity for pre-operative assessment and interventions.

The Birmingham experience of high-pressure methylene blue dye test during primary and revisional bariatric surgery: A retrospective cohort study.

INTRODUCTION: Leak following bariatric surgery continues to be associated with morbidity and rarely mortality. With improvement in surgical techniques and stapler design, leak rates have reduced drastically. Intra-operative high pressure Methylene blue leak test (HPMB) is one of the techniques employed to confirm integrity of anastomoses and staple lines. Despite this, evidence for its use remains limited. We evaluated the role of HPMB in detecting and preventing leaks. METHODS: A retrospective cohort of consecutive patients who underwent primary or revisional Laparoscopic Sleeve Gastrectomy (SG) or Laparoscopic Roux-en-Y Gastric bypass (RYGB) under the care of five surgeons in three centres across Birmingham, UK, between 2012 and 2016 were assessed. All patients had routine HPMB at the end of the procedure. Demographics, HPMB positivity, and post operative leaks were recorded. RESULTS: 924 patients underwent bariatric surgery: 696(75.3%) RYGB, and 225(24.3%) SG. 85(9.2%) were revisional procedures. Two HPMB were positive, which necessitated staple or suture line reinforcement with sutures intra-operatively. The patients had an uneventful recovery. 5 patients had postoperative leaks, all of whom had negative intraoperative HPMB: 3 SG patients; and 2 RYGB patients (gastro-jejunostomy anastomotic leaks). There was no statistically significant relationship between positive HPMB and anastomotic leak (Fishers exact test; p = 1). CONCLUSION: Despite routine use of methylene blue dye test in 924 patients, there were only two positive tests. Whilst HPMB may demonstrate technical failure, this study suggests that there is no role for its routine use in primary bariatric surgery. Discontinuation of this practice would reduce risk of anaphylaxis to the dye, cost, and intra-operative time.

Superior mesenteric artery syndrome: a single centre experience of laparoscopic duodenojejunostomy as the operation of choice.

INTRODUCTION The superior mesenteric artery (SMA) syndrome, or Wilkie's syndrome, is a rare cause of postprandial epigastric pain, vomiting and weight loss caused by compression of the third part of the duodenum as it passes beneath the proximal superior mesenteric artery. The syndrome may be precipitated by sudden weight loss secondary to other pathologies, such as trauma, malignancy or eating disorders. Diagnosis is confirmed by angiography, which reveals a reduced aorto-SMA angle and distance, and contrast studies showing duodenal obstruction. Conservative management aims to increase intra-abdominal fat by dietary manipulation and thereby increase the angle between the SMA and aorta. Where surgery is indicated, division of the ligament of Treitz, anterior transposition of the third part of the duodenum and duodenojejunostomy have been described. METHODS We present four cases of SMA syndrome where the intention of treatment was laparoscopic duodenojejunostomy. The procedure was completed successfully in three patients, who recovered quickly with no short-term complications. A fourth patient underwent open gastrojejunostomy (complicated by an anastomotic bleed) when dense adhesions prevented duodenojejunostomy. CONCLUSIONS The superior mesenteric artery syndrome should be considered in patients with epigastric pain, prolonged vomiting and weight loss. Laparoscopic duodenojejunostomy is a safe and effective operation for management of the syndrome. A multi-speciality team approach including gastrointestinal, vascular and radiological specialists should be invoked in the management of these patients.

Feasibility of Intraoperative Breast MRI and the Role of Prone Versus Supine Positioning in Surgical Planning for Breast-Conserving Surgery.

We assessed the feasibility of supine intraoperative MRI (iMRI) during breast-conserving surgery (BCS), enrolling 15 patients in our phase I trial between 2012 and 2014. Patients received diagnostic prone MRI, BCS, pre-excisional supine iMRI, and postexcisional supine iMRI. Feasibility was assessed based on safety, sterility, duration, and image-quality. Twelve patients completed the study; mean duration = 114 minutes; all images were adequate; no complications, safety, or sterility issues were encountered. Substantial tumor-associated changes occurred (mean displacement = 67.7 mm, prone-supine metric, n = 7). We have demonstrated iMRI feasibility for BCS and have identified potential limitations of prone breast MRI that may impact surgical planning.

Associations of Brain Structure With Adiposity and Changes in Adiposity in a Middle-Aged and Older Biracial Population.

BACKGROUND: Studies of adiposity and brain pathology in African Americans (AA) are sparse despite higher rates of obesity, dementia, and dementia-associated brain pathology in AA. This study examined relations of adiposity to white matter hyperintensities (WMH) and total brain volume (TBV) in AA and non-Hispanic whites (NHW). METHODS: Waist circumference (WC) and body mass index (BMI) were measured in the Genetic Epidemiology Network of Arteriopathy study at Visits 1 (mean age 57 [±11]) and 2 (mean age 61 [±10], mean 5.2 years later). Brain MRIs were obtained shortly after Visit 2 in 1,702 participants (64% women, 48% AA). Multilevel linear regression using generalized estimating equation estimated associations of adiposity (cross-sectional) or adiposity changes with WMH (accounting for intracranial size) or TBV adjusting for demographics, cardiovascular risk factors, and incorporating adiposity-by-race interactions. Adiposity-by-age interactions were examined. RESULTS: Concurrent TBV was inversely associated with BMI (ß = -2.76 [95% confidence interval (CI): -4.99, -0.53]) and WC (ß = -2.19 [CI: -4.04, -0.34]). Concurrent WMH were negatively associated with BMI (ß = -0.04 [CI: -0.06, -0.01]) and, among NHW, with WC (ß = -0.04 [CI: -0.06, -0.02]) but not with changes in BMI or WC. BMI increases were associated with lower TBV (ß = -16.20, [CI: -30.34, -2.06]) in AA but not in NHW (ß = -2.76 [CI: -14.02, 8.51]), although race-by-adiposity interactions were not supported. WC increases were not associated with MRI outcomes. CONCLUSION: Greater measures of obesity and increases in measures of obesity, which are common in mid-life, could be detrimental to brain health, particularly in AA.

Scaffold-cell bone engineering in a validated preclinical animal model: precursors vs differentiated cell source.

The properties of osteoblasts (OBs) isolated from the axial skeleton (tOBs) differ from OBs of the orofacial skeleton (mOBs) due to the different embryological origins of the bones. The aim of the study was to assess and compare the regenerative potential of allogenic bone marrow-derived mesenchymal progenitor cells with allogenic tOBs and allogenic mOBs in combination with a mPCL-TCP scaffold in critical-sized segmental bone defects in sheep tibiae. After 6 months, the tibiae were explanted and underwent biomechanical testing, micro-computed tomography (microCT) and histological and immunohistochemical analyses. Allogenic MPCs demonstrated a trend towards a better outcome in biomechanical testing and the mean values of newly formed bone. Biomechanical, microCT and histological analysis showed no significant differences in the bone regeneration potential of tOBs and mOBs in our in vitro study, as well as in the bone regeneration potential of different cell types in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

Smart stylet: the development and use of a bedside external ventricular drain image-guidance system.

BACKGROUND: Placement accuracy of ventriculostomy catheters is reported in a wide and variable range. Development of an efficient image-guidance system may improve physician performance and patient safety. OBJECTIVE: We evaluate the prototype of Smart Stylet, a new electromagnetic image-guidance system for use during bedside ventriculostomy. METHODS: Accuracy of the Smart Stylet system was assessed. System operators were evaluated for their ability to successfully target the ipsilateral frontal horn in a phantom model. RESULTS: Target registration error across 15 intracranial targets ranged from 1.3 to 4.6 mm (mean 3.1 mm). Using Smart Stylet guidance, a test operator successfully passed a ventriculostomy catheter to a shifted ipsilateral frontal horn 20/20 (100%) times from the frontal approach in a skull phantom. Without Smart Stylet guidance, the operator was successful 4/10 (40%) times from the right frontal approach and 6/10 (60%) times from the left frontal approach. In a separate experiment, resident operators were successful 2/4 (50%) times when targeting the shifted ipsilateral frontal horn with Smart Stylet guidance and 0/4 (0%) times without image guidance using a skull phantom. CONCLUSIONS: Smart Stylet may improve the ability to successfully target the ventricles during frontal ventriculostomy.

Factors associated with external ventricular drain placement accuracy: data from an electronic health record repository.

BACKGROUND: We evaluated external ventricular drain placement for factors associated with placement accuracy. Data were acquired using an electronic health record data requisition tool. METHOD: Medical records of all patients who underwent ventriculostomy from 2003 to 2010 were identified and evaluated. Patient demographics, diagnosis, type of guidance and number of catheter passes were searched for and recorded. Post-procedural hemorrhage and/or infection were identified. A grading scale was used to classify accuracy of catheter placements. A multiple logistic regression model was developed to assess features associated with accurate catheter placement. RESULTS: One hundred nine patients who underwent 111 ventriculostomies from 2003 to 2010 were identified. Patient diagnoses were classified into vascular (63 %), tumor (21 %), trauma (14 %), and cyst (2 %). Procedures were performed freehand in 90 (81 %), with the Ghajar guide in 17 (15 %), and with image guidance in 4 (4 %) patients. Eighty-eight (79 %) catheters were placed in the correct location. Trauma patients were more likely to have catheters misplaced (p = 0.007) whereas patients in other diagnostic categories were not significantly associated with misplaced catheters. Post-procedural hemorrhage was noted in 2 (1.8 %) patients on post-procedural imaging studies. Five (4.5 %) definite and 6 (5.4 %) suspected infections were identified. CONCLUSIONS: External ventricular drain placement can be performed accurately in most patients. Patients with trauma are more likely to have catheters misplaced. Further development is required to identify and evaluate procedure outcomes using an electronic health record repository.

On mixed reality environments for minimally invasive therapy guidance: systems architecture, successes and challenges in their implementation from laboratory to clinic.

Mixed reality environments for medical applications have been explored and developed over the past three decades in an effort to enhance the clinician's view of anatomy and facilitate the performance of minimally invasive procedures. These environments must faithfully represent the real surgical field and require seamless integration of pre- and intra-operative imaging, surgical instrument tracking, and display technology into a common framework centered around and registered to the patient. However, in spite of their reported benefits, few mixed reality environments have been successfully translated into clinical use. Several challenges that contribute to the difficulty in integrating such environments into clinical practice are presented here and discussed in terms of both technical and clinical limitations. This article should raise awareness among both developers and end-users toward facilitating a greater application of such environments in the surgical practice of the future.

Statistical Learning Algorithm for in situ and invasive breast carcinoma segmentation.

Dynamic Contrast Enhanced MRI (DCE-MRI) has proven to be a highly sensitive imaging modality in diagnosing breast cancers. However, analyzing the DCE-MRI is time-consuming and prone to errors due to the large volume of data. Mathematical models to quantify contrast perfusion, such as the black box methods and pharmacokinetic analysis, are inaccurate, sensitive to noise and depend on a large number of external factors such as imaging parameters, patient physiology, arterial input function, and fitting algorithms, leading to inaccurate diagnosis. In this paper, we have developed a novel Statistical Learning Algorithm for Tumor Segmentation (SLATS) based on Hidden Markov Models to auto-segment regions of angiogenesis, corresponding to tumor. The SLATS algorithm has been trained to identify voxels belonging to the tumor class using the time-intensity curve, first and second derivatives of the intensity curves ("velocity" and "acceleration" respectively) and a composite vector consisting of a concatenation of the intensity, velocity and acceleration vectors. The results of SLATS trained for the four vectors has been shown for 22 Invasive Ductal Carcinoma (IDC) and 19 Ductal Carcinoma In Situ (DCIS) cases. The SLATS trained for the velocity tuple shows the best performance in delineating the tumors when compared with the segmentation performed by an expert radiologist and the output of a commercially available software, CADstream.

Surgery, virtual reality, and the future.

MMVR has provided the leading forum for the multidisciplinary interaction and development of the use of Virtual Reality (VR) techniques in medicine, particularly in surgical practice. Here we look back at the foundations of our field, focusing on the use of VR in Surgery and similar interventional procedures, sum up the current status, and describe the challenges and opportunities going forward.

Comparative study of NOTES alone versus NOTES guided by a new image registration system for navigation in the mediastinum: a study in a porcine model.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) mediastinoscopy (MED) through the esophagus has proved to be feasible in the animal model. However, injury of the adjacent pleura and pneumothorax has been reported as a frequent adverse event when using a blind access. OBJECTIVE: To assess the utility and safety of a CT-based image registration system (IRS) for navigation in the mediastinum. DESIGN: Prospective, randomized, controlled trial in 30 Yorkshire pigs. Thirty-minute MEDs were performed: 15 MEDs were performed with IRS guidance (MED-IRS), and 15 MEDs were performed with a blind access. SETTING: Animal research laboratory. INTERVENTIONS: In both groups, the mediastinum was accessed through a 10-cm submucosal tunnel in the esophageal wall. Timed exploration was performed with identification of 8 mediastinal structures. MAIN OUTCOME MEASUREMENTS: Technical feasibility, adverse events, and the number of mediastinal structures identified. RESULTS: Thirty animals weighing 31.5 ± 3.5 kg were included in this study. MED was not possible in 2 animals in the "MED with blind access" group but was possible in all MEDs performed with IRS. The mean number of identified organs was slightly higher in "with IRS-MED" (6.13 ± 1.3) than with MED with blind access (4.7 ± 2.3; P = .066). Moreover, the right atrium and vena cava were identified in more cases with IRS-MED than in MED with blind access (13 vs 3 and 15 vs 11, P = .000 and P = .03, respectively). There were 3 (23%) adverse events with IRS-MED and 4 (27%) with "MED with blind access" (P = not significant), with pneumothorax being the most frequent (2 and 3, respectively). LIMITATIONS: Nonsurvival animal study. CONCLUSIONS: This study demonstrates that the IRS system appears feasible in natural orifice transluminal endoscopic surgery MED and suggests that IRS guidance might be useful for selected procedures.

Transcending scale dependence in identifying habitat with resource selection functions.

Multi-scale resource selection modeling is used to identify factors that limit species distributions across scales of space and time. This multi-scale nature of habitat suitability complicates the translation of inferences to single, spatial depictions of habitat required for conservation of species. We estimated resource selection functions (RSFs) across three scales for a threatened ungulate, woodland caribou (Rangifer tarandus caribou), with two objectives: (1) to infer the relative effects of two forms of anthropogenic disturbance (forestry and linear features) on woodland caribou distributions at multiple scales and (2) to estimate scale-integrated resource selection functions (SRSFs) that synthesize results across scales for management-oriented habitat suitability mapping. We found a previously undocumented scale-specific switch in woodland caribou response to two forms of anthropogenic disturbance. Caribou avoided forestry cut-blocks at broad scales according to first- and second-order RSFs and avoided linear features at fine scales according to third-order RSFs, corroborating predictions developed according to predator-mediated effects of each disturbance type. Additionally, a single SRSF validated as well as each of three single-scale RSFs when estimating habitat suitability across three different spatial scales of prediction. We demonstrate that a single SRSF can be applied to predict relative habitat suitability at both local and landscape scales in support of critical habitat identification and species recovery.

The effect of alcohol on surgical skills.

INTRODUCTION: The General Medical Council states 'a surgeon must not work when their health state is adversely influenced by fatigue, disease, drugs or alcohol'. However, there are no defined criteria for acceptable blood alcohol levels when operating. The aim of this study was to measure the effect of varying amounts of alcohol on surgical dexterity, cognitive abilities and the social interactions required to ensure patient safety during a routine ear, nose and throat (ENT) operation. METHODS: ENT surgeons were asked to perform a microlaryngoscopy with excision of a predetermined glottic lesion on a validated laryngeal model. The procedure was repeated four times over a period of four hours with varying doses of alcohol (no alcohol control, one glass, three glasses and six glasses of wine). The parameters recorded included theatre etiquette, surgical time, operative skills and patient safety. Scores were adjudicated by two independent observers. RESULTS: The more glasses of wine consumed, the more detrimental the effect was on the surgical performance of all participants. There was a global reduction in ability of 7.25% after three glasses and 19.25% after six glasses of alcohol. No domain showed an improvement following sequential increase in blood alcohol concentration. CONCLUSIONS: This study suggests that there are no deleterious effects on surgical performance following the consumption of one glass of wine 45 minutes prior to microlaryngoscopy among ENT surgeons of varying experience. However, there is clear evidence that with three or more glasses of wine there is an adverse effect on performance, with decreased surgical dexterity, cognition functions and professionalism.