Skeletal Muscle Bioenergetics in Critical Limb Ischemia and Diabetes.

INTRODUCTION: Mitochondrial dysfunction is implicated in the metabolic myopathy accompanying peripheral artery disease (PAD) and critical limb ischemia (CLI). Type-2 diabetes mellitus (T2DM) is a major risk factor for PAD development and progression to CLI and may also independently be related to mitochondrial dysfunction. We set out to determine the effect of T2DM in the relationship between CLI and muscle mitochondrial respiratory capacity and coupling control. METHODS: We studied CLI patients undergoing revascularization procedures or amputation, and non-CLI patients with or without T2DM of similar age. Mitochondrial respiratory capacity and function were determined in lower limb permeabilized myofibers by high-resolution respirometry. RESULTS: Fourteen CLI patients (65 ± 10y) were stratified into CLI patients with (n = 8) or without (n = 6) T2DM and were compared to non-CLI patients with (n = 18; 69 ± 5y) or without (n = 19; 71 ± 6y) T2DM. Presence of CLI but not T2DM had a marked impact on all mitochondrial respiratory states in skeletal muscle, adjusted for the effects of sex. Leak respiration (State 2, P < 0.025 and State 4o, P < 0.01), phosphorylating respiration (P < 0.001), and maximal respiration in the uncoupled state (P < 0.001), were all suppressed in CLI patients, independent of T2DM. T2DM had no significant effect on mitochondrial respiratory capacity and function in adults without CLI. CONCLUSIONS: Skeletal muscle mitochondrial respiratory capacity was blunted by ∼35% in patients with CLI. T2DM was not associated with muscle oxidative capacity and did not moderate the relationship between muscle mitochondrial respiratory capacity and CLI.

Factors associated with access and approach to esophagectomy for cancer: a National Cancer Database study.

BACKGROUND: Minimally invasive esophagectomy (MIE) for esophageal cancer has been associated with decreased pain, less blood loss, and shorter hospital stay with comparable survival to open surgery. To date, there is minimal information regarding what factors are associated with access to MIE. METHODS: The National Cancer Database (NCDB) was used to compare rates of MIE (either robotic or laparoscopic) and open esophagectomy (OE) by demographic and clinical factors. Continuous variables were compared using a linear trend test, and categorical variables were compared using Mantel-Haenszel tests. Binomial regression was performed to examine significant factors after adjusting for confounding variables. RESULTS: There were 18,366 patients included in the analysis. Of all esophagectomies performed in the US, 49% were performed by OE and 51% were performed by MIE. Patients who had undergone MIE were more likely to live in the Eastern US as compared with the Midwest [odds ratio (OR) 1.72; 95% confidence interval (CI) 1.58, 1.88] or the South (OR 1.31; 95% CI 1.19, 1.44). They were also more likely to be treated at an academic center (OR 1.64; 95% CI 1.53, 1.75) rather than a community hospital, and to be of White race as compared with Asian race (OR 1.46; 95% CI 1.10, 1.92). There was not a significant difference in the rates of MIE between White and Black patients (OR 1.12; 95% CI 0.96, 1.32). MIE was more likely with each passing year, and higher TNM stages of cancer were less likely to be treated with MIE (P < 0.001 for all). CONCLUSION: While MIE is evolving, OE is still considered standard of care with robotic approaches representing a minority of MIE. While there are several factors associated with access to MIE, including race, facility type and geographic location, these factors should be further explored to help increase access to MIE.

Predicting Transcarotid Artery Revascularization Adverse Outcomes by Imaging Characteristics.

BACKGROUND: Approximately 20-30% of ischemic strokes are caused by internal carotid artery stenosis. Stroke is the leading cause of disability and the second leading cause of death in the United States. Second generation transcarotid arterial revascularization (TCAR) stenting, using the ENROUTE flow reversal technology to prevent embolic stroke during the stenting process, has demonstrated stroke and death outcomes equivalent to carotid endarterectomy with reduced cranial nerve injury. However, at present, it is not known whether imaging characteristics obtained preoperatively can predict outcomes of TCAR procedures. METHODS: This retrospective cohort study included patients who underwent TCAR with flow reversal at three hospitals within a single hospital network who had computed tomography angiography, magnetic resonance imaging angiography, or preoperative diagnostic angiogram to determine whether carotid and lesion characteristics could predict patients who experienced major adverse critical events (MACE) versus those who did not. MACE was defined as myocardial infarction at 30 days, restenosis/persistent stenosis (peak systolic velocity within the stent >230 cm/sec by postoperative ultrasound), stroke within any time of follow-up, or death within 1 year of TCAR. Student's t-tests and Chi-squared tests were used to compare imaging characteristics, such as presence of pinpoint stenosis, calcification within the common carotid artery at the take-off from the aorta, and plaque length in millimeters. Binomial logistic regression was used to examine the likelihood that imaging characteristics were associated with MACE. RESULTS: Of 220 patients who underwent TCAR in our network, seven were excluded because flow reversal was not used or appropriate imaging had not been performed prior to TCAR. Of the 213 patients who were included in analysis, the median length of follow-up was 10.8 months (interquartile range: 3.4-33.1 months). Twelve percent (26/213) experienced MACE and a model based on imaging characteristics was statistically significant in predicting MACE with 68% accuracy (P = 0.005). The presence of pinpoint stenosis was highly predictive of MACE (hazards ratio: 3.34, confidence interval: 1.2 to 9.3, P = 0.021). A shorter clavicle to carotid bifurcation distance was associated with an increased likelihood of experiencing MACE (P = 0.009) but it was weakly predictive (hazards ratio: 1.03, confidence interval: 1.01 to 1.05). CONCLUSIONS: Preoperative imaging characteristics, such as pinpoint stenosis and clavicle to carotid bifurcation distance, can be used to predict adverse outcomes in TCAR placement.

T6SS and ExoA of flesh-eating Aeromonas hydrophila in peritonitis and necrotizing fasciitis during mono- and polymicrobial infections.

An earlier report described a human case of necrotizing fasciitis (NF) caused by mixed infection with 4 Aeromonas hydrophila strains (NF1-NF4). While the NF2, NF3, and NF4 strains were clonal and possessed exotoxin A (ExoA), the NF1 strain was determined to be phylogenetically distinct, harboring a unique type 6 secretion system (T6SS) effector (TseC). During NF1 and NF2 mixed infection, only NF1 disseminated, while NF2 was rapidly killed by a contact-dependent mechanism and macrophage phagocytosis, as was demonstrated by using in vitro models. To confirm these findings, we developed 2 NF1 mutants (NF1ΔtseC and NF1ΔvasK); vasK encodes an essential T6SS structural component. NF1 VasK and TseC were proven to be involved in contact-dependent killing of NF2 in vitro, as well as in its elimination at the intramuscular injection site in vivo during mixed infection, with overall reduced mouse mortality. ExoA was shown to have an important role in NF by both NF1-exoA (with cis exoA) and NF2 during monomicrobial infection. However, the contribution of ExoA was more important for NF2 than NF1 in the murine peritonitis model. The NF2∆exoA mutant did not significantly alter animal mortality or NF1 dissemination during mixed infection in the NF model, suggesting that the ExoA activity was significant at the injection site. Immunization of mice to ExoA protected animals from NF2 monomicrobial challenge, but not from polymicrobial infection because of NF2 clearance. This study clarified the roles of T6SS and ExoA in pathogenesis caused by A. hydrophila NF strains in both mouse peritonitis and NF models in monomicrobial and polymicrobial infections.

Reduced Postburn Hypertrophic Scarring and Improved Physical Recovery With Yearlong Administration of Oxandrolone and Propranolol.

BACKGROUND: Massive burns induce a hypermetabolic response that leads to total body wasting and impaired physical and psychosocial recovery. The administration of propranolol or oxandrolone positively affects postburn metabolism and growth. The combined administration of oxandrolone and propranolol (OxProp) for 1 year restores growth in children with large burns. Here, we investigated whether the combined administration of OxProp for 1 year would reduce scarring and improve quality of life compared with control. STUDY DESIGN: Children with large burns (n = 480) were enrolled into this institutional review board-approved study; patients were randomized to control (n = 226) or administration of OxProp (n = 126) for 1 year postburn. Assessments were conducted at discharge and 6, 12, and 24 months postburn. Scar biopsies were obtained for histology. Physical scar assessments and patient reported outcome measures of physical and psychosocial function were obtained. RESULTS: Reductions in cellularity, vascular structures, inflammation, and abnormal collagen (P < 0.05) occurred in OxProp-treated scars. With OxProp, scar severity was attenuated and pliability increased (both P < 0.05). Analyses of patient-reported outcomes showed improved general and emotional health within the OxProp-treated group (P < 0.05). CONCLUSIONS: Here, we have shown improvements in objective and subjective measures of scarring and an increase in overall patient-reported physical function. The combined administration of OxProp for up to a year after burn injury should be considered for the reduction of postburn scarring and improvement of long-term psychosocial outcomes in children with massive burns.

Machine learning applications for the differentiation of primary central nervous system lymphoma from glioblastoma on imaging: a systematic review and meta-analysis.

OBJECTIVEGlioblastoma (GBM) and primary central nervous system lymphoma (PCNSL) are common intracranial pathologies encountered by neurosurgeons. They often may have similar radiological findings, making diagnosis difficult without surgical biopsy; however, management is quite different between these two entities. Recently, predictive analytics, including machine learning (ML), have garnered attention for their potential to aid in the diagnostic assessment of a variety of pathologies. Several ML algorithms have recently been designed to differentiate GBM from PCNSL radiologically with a high sensitivity and specificity. The objective of this systematic review and meta-analysis was to evaluate the implementation of ML algorithms in differentiating GBM and PCNSL.METHODSThe authors performed a systematic review of the literature using PubMed in accordance with PRISMA guidelines to select and evaluate studies that included themes of ML and brain tumors. These studies were further narrowed down to focus on works published between January 2008 and May 2018 addressing the use of ML in training models to distinguish between GBM and PCNSL on radiological imaging. Outcomes assessed were test characteristics such as accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC).RESULTSEight studies were identified addressing use of ML in training classifiers to distinguish between GBM and PCNSL on radiological imaging. ML performed well with the lowest reported AUC being 0.878. In studies in which ML was directly compared with radiologists, ML performed better than or as well as the radiologists. However, when ML was applied to an external data set, it performed more poorly.CONCLUSIONSFew studies have applied ML to solve the problem of differentiating GBM from PCNSL using imaging alone. Of the currently published studies, ML algorithms have demonstrated promising results and certainly have the potential to aid radiologists with difficult cases, which could expedite the neurosurgical decision-making process. It is likely that ML algorithms will help to optimize neurosurgical patient outcomes as well as the cost-effectiveness of neurosurgical care if the problem of overfitting can be overcome.

Body Composition Changes in Severely Burned Children During ICU Hospitalization.

OBJECTIVES: Prolonged hospitalization due to burn injury results in physical inactivity and muscle weakness. However, how these changes are distributed among body parts is unknown. The aim of this study was to evaluate the degree of body composition changes in different anatomical regions during ICU hospitalization. DESIGN: Retrospective chart review. SETTING: Children's burn hospital. PATIENTS: Twenty-four severely burned children admitted to our institution between 2000 and 2015. INTERVENTIONS: All patients underwent a dual-energy x-ray absorptiometry within 2 weeks after injury and 2 weeks before discharge to determine body composition changes. No subject underwent anabolic intervention. We analyzed changes of bone mineral content, bone mineral density, total fat mass, total mass, and total lean mass of the entire body and specifically analyzed the changes between the upper and lower limbs. MEASUREMENTS AND MAIN RESULTS: In the 24 patients, age was 10 ± 5 years, total body surface area burned was 59% ± 17%, time between dual-energy x-ray absorptiometries was 34 ± 21 days, and length of stay was 39 ± 24 days. We found a significant (p < 0.001) average loss of 3% of lean mass in the whole body; this loss was significantly greater (p < 0.001) in the upper extremities (17%) than in the lower extremities (7%). We also observed a remodeling of the fat compartments, with a significant whole-body increase in fat mass (p < 0.001) that was greater in the truncal region (p < 0.0001) and in the lower limbs (p < 0.05). CONCLUSIONS: ICU hospitalization is associated with greater lean mass loss in the upper limbs of burned children. Mobilization programs should include early mobilization of upper limbs to restore upper extremity function.

Examination of near-wall hemodynamic parameters in the renal bridging stent of various stent graft configurations for repairing visceral branched aortic aneurysms.

OBJECTIVE: This study examined the flow behavior of four stent graft configurations for endovascular repair of complex aneurysms of the descending aorta. METHODS: Computational fluid dynamics models with transient boundary conditions and rigid wall simplifying assumptions were developed and used with four distinct geometries to compare various near-wall hemodynamic parameters. RESULTS: Graphic plots for time-averaged wall shear stress, oscillating shear index, and relative residence time were presented and compared among the four stent graft configurations of interest. CONCLUSIONS: Abrupt 90° and 180° changes in stent geometry (particularly in the side branches) cause a high momentum change and thus increased flow separation and mixing, which has significant implications in blood flow characteristics near the wall. By comparison, longer bridging stents provide more gradual changes in momentum, thus allowing blood flow to develop before reaching the target vessel.

Associations of urban versus rural patient residence on outcomes after burn: A national inpatient sample database study.

INTRODUCTION: Burn patients in rural areas may encounter poorer outcomes associated with barriers to care; however, residence has not been studied in a large sample. The association between rural-versus-urban residence and outcomes after burn was examined using the National Inpatient Sample (NIS) database. METHODS: Using the 2019 NIS database, patients over 18 years with a primary diagnosis of burn or corrosive injury were included. Level of urbanization was categorized into six groups. Outcomes after burn such as in-hospital mortality, multifactorial shock, prolonged mechanical ventilation, length of stay, and total costs were analyzed after adjusting for demographic factors and hospital characteristics. RESULTS: We included 4671 records, which represented a weighted population of 23,085 patients. Rural residence was associated with higher percentage of prior transfer but not in-hospital mortality. Compared to the most urbanized counties, encounters from the most rural counties were associated with higher odds of shock (aOR:2.62, 99% CI: 1.04-6.56, p = 0.007). CONCLUSION: Burn encounters from less urbanized counties did not experience differences in mortality, rates of skin grafting, prolonged mechanical ventilation, length of stay, or overall costs. However, odds of shock were higher among the least urbanized counties. Despite improved triage and transportation systems across the US, disparities and challenges exist for burn patients from rural residence.

Kidney Injury in Critically Ill Patients Treated with Vancomycin and Zosyn or an Alternative: A Systematic Review and Meta-Analysis.

Background: Zosyn® (piperacillin-tazobactam; Pfizer Medical, New York, NY), a valuable antibiotic against gram-negative bacteria, combined with vancomycin (Z+V) is known for its high incidence of acute kidney injury (AKI), particularly in the intensive care unit (ICU), leading to the frequent use of alternatives for gram-negative coverage (Alt+V). Because there are limited data describing AKI on these alternative antibiotic agents, a systematic review and meta-analysis was conducted to determine if these regimens were indeed associated with decreased rates of AKI. Patients and Methods: A literature review was performed electronically from its inception to November 1, 2018, screening for relevant literature by title, abstract and full text according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines within the following databases: PubMed/Medline, CINAHL, Scopus, and Cochrane Central Register of Controlled Trials. Studies were included if they contained adults who had been admitted to the ICU for treatment and had received a combination of intravenous Z + V or Alt+V as well as had AKI measured during administration of these antibiotic agents. Studies were excluded if they represented pediatric populations, did not receive care in an ICU during their hospital admission, only received monotherapy for antibiotic treatment or received antibiotic treatment for less than 48 hours. Independent extraction was performed by two reviewers. Risk of bias was assessed using the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) methodology for retrospective studies. Random-effects models were used to calculate any differences between rates of AKI after Z + V or Alt + V. Results: Fourteen articles (totaling 30,399 patients) were included. All studies available were retrospective in design. Compared with Alt + V, Z + V was associated with a higher risk ratio of AKI (1.79; 95% confidence interval [CI], 1.46-2.19; p < 0.001). Cefepime (C + V) was the most common alternative to Zosyn, and Z + V was associated with higher rates of kidney injury compared with C + V (1.70; 95% CI, 1.36-2.12; p < 0.00001). However, there was substantial heterogeneity in the data collected as well as high risk of bias. Conclusions: Zosyn plus vancomycin is associated with more risk of AKI compared with Alt+V coverage in ICU adult populations. However, the conclusions were limited by the retrospective nature of the studies, high bias of included articles, and heterogeneity of the included studies.

Heart Rate Variability Can Detect Blunt Traumatic Brain Injury Within the First Hour.

INTRODUCTION: In patients with multi-organ system trauma, the diagnosis of coinciding traumatic brain injury can be difficult due to injuries from the hemorrhagic shock that confound clinical and radiographic signs of traumatic brain injury. In this study, a novel technique using heart rate variability was developed in a porcine model to detect traumatic brain injury early in the setting of hemorrhagic shock without the need for radiographic imaging or clinical exam. METHODS: A porcine model of hemorrhagic shock was used with an arm of swine receiving hemorrhagic shock alone and hemorrhagic shock with traumatic brain injury. High-resolution heart rate frequencies were collected at different time intervals using waveforms based on voltage delivered from the heart rate monitor. Waveforms were analyzed to assess statistically significant differences between heart rate variability parameters in those with hemorrhagic shock and traumatic brain injury versus those with only hemorrhagic shock. Stochastic analysis was used to assess the validity of results and create a model by machine learning to better assess the presence of traumatic brain injury. RESULTS: Significant differences were found in several heart rate variability parameters between the two groups. Additionally, significant differences in heart rate variability parameters were found in swine within 1 hour of inducing hemorrhage in those with traumatic brain injury versus those without. These results were confirmed with stochastic analysis and machine learning was used to generate a model which determined the presence of traumatic brain injury in the setting of hemorrhage shock with 91.6% accuracy. CONCLUSIONS:  Heart rate variability represents a promising diagnostic tool to aid in the diagnosis of traumatic brain injury within 1 hour of injury.

Robotic enucleation of a biliary adenofibroma.

A 69-year-old man was referred to the hepatobiliary surgeons for mild enlargement of an asymptomatic cystic liver lesion found on routine screening in 2017 that measured 3.7×3.6×4.3 cm. Work-up with MRI revealed a complex multilocular cyst that had enlarged to 6.6×5.5×4.6 cm. Other work-up was unremarkable. He had a Eastern Cooperative Oncology Group score of 1; therefore, a surgical excision was planned due to the possibility for malignancy. A robotic approach with enucleation of the lesion was undertaken, with plans for return for a wider resection if pathological examination revealed malignancy. The lesion was noted to be a biliary adenofibroma, an exceptionally rare lesion that is thought to be benign, but requires excision due to potential malignant degeneration. The patient was discharged home the following day and has had minimal pain in his postoperative course.

Supervised Resistance Training on Functional Capacity, Muscle Strength and Vascular Function in Peripheral Artery Disease: An Updated Systematic Review and Meta-Analysis.

Supervised resistance training appears to be a promising alternative exercise modality to supervised walking in patients with peripheral artery disease (PAD). This meta-analysis examined the efficacy of supervised RT for improving walking capacity, and whether adaptations occur at the vascular and/or skeletal muscle level in PAD patients. We searched Medline, CINAHL, Scopus, and Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) in PAD patients testing the effects of supervised RT for ≥4 wk. on walking capacity, vascular function, and muscle strength. Pooled effect estimates were calculated and evaluated using conventional meta-analytic procedures. Six RCTs compared supervised RT to standard care. Overall, supervised RT prolonged claudication onset distance during a 6-min walk test (6-MWT) (101.7 m (59.6, 143.8), p < 0.001) and improved total walking distance during graded treadmill walking (SMD: 0.67 (0.33, 1.01), p < 0.001) and the 6-MWT (49.4 m (3.1, 95.6), p = 0.04). Five RCTS compared supervised RT and supervised intermittent walking, where the differences in functional capacity between the two exercise modalities appear to depend on the intensity of the exercise program. The insufficient evidence on the effects of RT on vascular function and muscle strength permitted only limited exploration. We conclude that RT is effective in prolonging walking performance in PAD patients. Whether RT exerts its influence on functional capacity by promoting blood flow and/or enhancing skeletal muscle strength remains unclear.

The impact of catecholamines on skeletal muscle following massive burns: Friend or foe?

Profound skeletal muscle wasting in the setting of total body hypermetabolism is a defining characteristic of massive burns, compromising the patient's recovery and necessitating a protracted period of rehabilitation. In recent years, the prolonged use of the non-selective beta-blocker, propranolol, has gained prominence as an effective tool to assist with suppressing epinephrine-dependent burn-induced hypermetabolism and by extension, blunting muscle catabolism. However, synthetic ß-adrenergic agonists, such as clenbuterol, are widely associated with the promotion of muscle growth in both animals and humans. Moreover, experimental adrenodemedullation is known to result in muscle catabolism. Therefore, the blunting of muscle ß-adrenergic signaling via the use of propranolol would be expected to negatively impair muscle protein homeostasis. This review explores these paradoxical observations and identifies the manner by which propranolol is thought to exert its anti-catabolic effects in burn patients. Moreover, we identify potential avenues by which the use of beta-blocker therapy in the treatment of massive burns could potentially be further refined to promote the recovery of muscle mass in these critically ill patients while continuing to ameliorate total body hypermetabolism.

A systematic review and meta-analysis of valued obstetric and gynecologic (OB/GYN) procedures in resource-poor areas.

BACKGROUND: Obstetric and gynecologic procedures are valuable in rural settings. Data identifying common procedures may better prepare surgeons to meet patient needs in remote settings. MATERIALS AND METHODS: A literature review using key MeSH terms was performed according to methods described by the Cochrane Collaboration and PRISMA on studies that described obstetric and gynecologic surgery in rural high-income countries or any setting in middle- to low-income countries. Meta-analysis was performed using random effects modeling for odds ratios of cesarean delivery and hysterectomy as proportions of total surgical volume. RESULTS: A total of 195 studies were included for qualitative synthesis and 22 for quantitative analysis. Obstetric and gynecologic procedures made up a 19% of all surgical cases. As compared to other obstetric and gynecologic surgical procedures, cesarean delivery was the most common procedure with odds ratio of 2.39 (95% confidence interval 1.48-3.86), and hysterectomy was the second most common procedure with odds ratio of 1.60 (1.57-1.64). However, heterogeneity between the studies was extremely high and risk of bias was high, limiting quality of findings. CONCLUSION: Greater provision of surgical care can be enhanced by defining which procedures are most needed, which include many obstetric and gynecologic procedures, most commonly cesarean delivery and hysterectomy.

Novel Technique for Laparoscopic Common Bile Duct Exploration Using Endovascular Instrumentation.

Treatment of choledocholithiasis is sometimes a two-step process involving both surgeons and gastroenterologists. Common bile duct (CBD) exploration can be performed at the same time as cholecystectomy but often requires the use of rigid tools, increasing the risk of CBD damage. Here, we report the case of a 64-year-old man who presented with epigastric pain and a positive Murphy's sign. Ultrasonography revealed cholecystitis with cholelithiasis. Gangrenous cholecystitis was visualized upon surgical exploration, and an intraoperative cholangiogram diagnosed likely choledocholithiasis. Cholecystectomy was completed, and CBD exploration was performed by the manipulation of endovascular equipment using a trans-cystic approach through to the ampulla of Vater, and the patient made a complete recovery without complications. The substantial flexibility, gentleness, and durability of endovascular instruments allow for minimal tension on structures during the removal of gallstones from the CBD, providing safe, definitive treatment for choledocholithiasis during cholecystectomy.