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Background: Esophagectomy in locally advanced esophageal adenocarcinoma is challenging and carries risk. The value of esophagectomy in locally advanced esophageal adenocarcinoma is not well-defined., Study Design: The National Cancer Database was used to identify patients with cT4 esophageal adenocarcinoma from 2004 to 2020. Multivariable regression was used to identify factors associated with use of esophagectomy. Cox modeling was used to identify factors associated with all-cause mortality. Patients undergoing esophagectomy were 1:1 propensity score-matched to patients treated nonsurgically. Kaplan-Meier analysis was used to compare 5-year overall survival (OS)., Results: A total of 3,703 patients met inclusion criteria. Of those, 541 (15%) underwent esophagectomy, and 3,162 (85%) did not. Age 65 years or less (adjusted odds ratio [aOR] 1.69, 95% CI 1.33 to 2.14), White race (aOR 2.98, 95% CI 2.24 to 3.96), treatment in academic centers (aOR 1.64, 95% CI 1.33 to 2.02), private insurance (aOR 1.88, 95% CI 1.50 to 2.36), and tumors less than 6 cm (aOR 1.86, 95% CI 1.44 to 2.40) were associated with use of esophagectomy. Government of lack of insurance (hazard ratio [HR] 1.23, 95% CI 1.12 to 1.35), income <$46,000 (HR 1.11, 95% CI 1.03 to 1.20), treatment in nonacademic centers (HR 1.16, 95% CI 1.07 to 1.25), Charlson-Deyo Comorbidity Index 1 or more (HR 1.22, 95% CI 1.12 to 1.32), and tumors 6 cm or more (HR 1.20, 95% CI 1.09 to 1.32) were associated with risk of all-cause mortality. Esophagectomy (HR 0.50, 95% CI 0.44 to 0.56) and systemic therapy (HR 0.40, 95% CI 0.37 to 0.43) were associated with decreased risk of all-cause mortality. Patients undergoing esophagectomy had higher rates of 5-year OS (27.4% vs 13.2%, p < 0.0001) and longer median OS (24.71 vs 10.09 months, p < 0.0001). Among cT4b patients, those who underwent esophagectomy had higher rates of 5-year OS (24.5% vs 12.3%, p < 0.0001) and longer median OS (25.53 vs 11.01 months, p < 0.0001)., Conclusions: In cT4 esophageal adenocarcinoma, esophagectomy is associated with improved rates of 5-year OS compared with nonsurgical treatment., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: The value of palliative surgery in pancreatic cancer is not well-defined., Methods: We queried the National Cancer Database for patients undergoing curative-intent resection, palliative surgery or medical palliation for clinical stage cT4N0-2M0 pancreatic cancer. Cohorts were 1:1:1 propensity-score-matched for comorbidities and stage. Kaplan-Meier method was used to compare overall survival for matched cohorts., Results: 9,107 patients met inclusion criteria: 3,567 (39 ​%) underwent curative intent surgery, 1608 (18 ​%) surgical palliation, 3932 (43 ​%) medical palliation. Patients undergoing resection and surgical palliation had significant hospitalizations (11.0 ​± ​0.4 vs. 10.0 ​± ​0.3 days; p ​= ​0.821) and rates of readmission (8.1 ​% vs. 2.0 ​%; p ​< ​0.001). Patients undergoing surgical palliation demonstrated marginal increases in survival relative to those undergoing medical palliation (8.54 vs. 7.36 months; p ​< ​0.0001)., Conclusion: In patients undergoing care for locally advanced pancreatic cancer, palliative surgery is associated with marginal improvement in survival but significant lengths of hospitalization and risk of readmission., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Prior studies evaluating the efficacy of local excision compared to radical resection in the treatment of rectal adenocarcinoma lacked sufficient power to identify differences in outcomes for patients with cT2 disease but low-risk histopathology. We compared the outcomes of local excision and radical resection for low-risk histopathology and high-risk histology of patients with cT2N0M0 rectal adenocarcinoma to assess their outcomes., Methods: We queried the National Cancer Database for patients presenting with cT2N0M0 rectal adenocarcinoma between 2004 and 2019 and categorized them as low-risk histopathology or high-risk histology. We used the Cox proportional hazards model to identify factors associated with the risk of all-cause mortality. We 1:1 propensity-matched patients who underwent local excision to patients who underwent radical resection and used the Kaplan-Meier method to compare overall survival for matched cohorts., Results: Of the 4,446 patients selected, we classified 1,206 (27%) as high-risk histology and 3,240 (73%) as low-risk histopathology. Among the patients with high-risk histology, 121 (10%) underwent local excision and 1,085 (90%) underwent radical resection. Among the patients with low-risk histopathology, 340 (10%) underwent local excision and 2,900 (90%) radical resections. Whereas radical resection was associated with decreased risk of all-cause mortality and increased overall survival for patients with high-risk histology, it was not for patients with low-risk histopathology., Conclusion: The overall survival of patients with low-risk histopathology with cT2N0M0 rectal adenocarcinoma who undergo local excision is similar to those of patients with low-risk histopathology who undergo radical resection, suggesting local excision is a reasonable approach for these patients. In contrast, radical resection provides a significant survival advantage for patients with high-risk histology and should remain their treatment of choice., (Copyright © 2023. Published by Elsevier Inc.)

Background: Studies comparing approaches to managing rectal neuroendocrine tumors are underpowered by institutional series. The efficacy of expectant management relative to local excision and radical resection is poorly defined., Methods: We queried the National Cancer Database to identify patients presenting with non-metastatic rectal neuroendocrine tumors between 2004 and 2019. Multivariable regression was used to identify factors associated with expectant management. Cox modeling was used to identify factors associated with all-cause mortality. Patients undergoing expectant management were 1:1:1 propensity score matched for demographics and comorbid disease to those undergoing radical resection and local excision. The Kaplan-Meier method was used to compare overall survival profiles for matched cohorts., Results: A total of 6,316 patients met the inclusion criteria. Of these, 5,211 (83%) underwent local excision, 600 (9.5%) radical resection, and 505 (8%) expectant management. On multivariable regression, factors associated with expectant management included Black race, government insurance, and tumor size <2.0 centimeters. On Cox modeling, factors associated with mortality included age >65 years, male sex, government insurance, comorbidity score >0, tumor size >2 centimeters, and poorly differentiated histology. On comparison of matched cohorts: patients undergoing radical resection had longer hospitalizations and higher readmission rates than those undergoing local excision; there was no difference in overall survival between cohorts in patients with stage 1 disease; in stage 2 and 3 diseases, patients undergoing local excision and radical resection demonstrated improved rates of overall survival relative to those undergoing expectant management., Conclusion: Expectant management is a reasonable approach for patients with stage 1 rectal neuroendocrine tumors. Local excision should be the preferred treatment option for those presenting with stage 2/3 disease., (Copyright © 2023. Published by Elsevier Inc.)

Background: Malrotation with bowel ischemia is classically thought of as a disease of infants. However, the true prevalence of malrotation in both the pediatric and adult population is unknown due to the unclear number of asymptomatic patients., Case Presentation: A previously healthy 84-year-old man with no prior abdominal surgeries presented with an acute abdomen and was found on CT to have small bowel located in the right hemiabdomen and an abnormal SMA-SMV relationship suggestive of intestinal malrotation, as well as pneumatosis intestinalis. He underwent an exploratory laparotomy, where he was found to have a paraduodenal space which did not contain any bowel but was the likely source of an internal hernia. His duodenojejunal flexure was located to the right of the spinal column, the cecum in the left lower quadrant, a thick congenital band at the proximal jejunum, and multiple Ladd's bands at the level of the duodenum. The bowel appeared viable and a Ladd's procedure was performed. The patient had an uneventful post-operative course., Conclusions: There is a lack of guidelines regarding screening for and management of asymptomatic malrotation in older children and adults. However, the traditional thinking is that asymptomatic malrotation diagnosed after two years of age poses minimal risk. This case illustrates the potential risk of an internal hernia in the setting of malrotation at any time during one's lifetime., (© 2022. The Author(s).)

Background: Iliac arterial stenting is performed both in the operating room (OR) and the catheterization lab (CL). To date, no analysis has compared resource utilization between these locations., Methods: Consecutive patients (n = 105) treated at a single center were retrospectively analyzed. Patients included adults with chronic, symptomatic iliac artery stenosis with a minimum Rutherford classification (RC) of 3, treated with stents. Exclusion criteria were prior stenting, acute ischemia, or major concomitant procedures. Immediate and two-year outcomes were observed. Patient demographics, perioperative details, physician billings, and hospital costs were recorded. Multivariable regression was used to adjust costs by patient and perioperative cost drivers., Results: Fifty-one procedures (49%) were performed in the OR and 54 (51%) in the CL. Mean age was 57, and 44% were female. Severe cases were more often performed in the OR (RC ≥ 4; 42% vs. 11%, P < 0.001) and were associated with increased total costs (P < 0.01). OR procedures more often utilized additional stents (stents ≥ 2; 61% vs. 46%, P = 0.214), thrombolysis (12% vs. 0%, P = 0.011), cut-down approach (8% vs. 0%, P = 0.052), and general anesthesia (80% vs. 0%, P < 0.001): these were all associated with increased costs (P < 0.05). After multivariable regression, location was not a predictor of procedure room or total costs but was associated with increased professional fees. Same-stay (5%) and post-discharge reintervention (33%) did not vary by location., Conclusions: The OR was associated with increased length of stay, more ICU admissions, and increased total costs. However, OR patients had more severe disease and therefore often required more aggressive intervention. After controlling for these differences, procedure venue per se was not associated with increased costs, but OR cases incurred increased professional fees due to dual-provider charges. Given the similar clinical results between venues, it seems reasonable to perform most stenting in the CL or utilize conscious sedation in the OR., (Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

The American Heart Association recommends therapeutic hypothermia for comatose patients with return of spontaneous circulation after out-of-hospital ventricular fibrillation cardiac arrest. While there is a growing body of evidence for the general efficacy of therapeutic hypothermia, the individualized benefit of therapy is not currently predictable. Ninety-one consecutive patients, from April 2011 to July 2014, were treated at the University of Kentucky Medical Center with the therapeutic hypothermia protocol. Medical records were reviewed retrospectively. Data, such as preexisting comorbidities, cardiac arrest characteristics, and hospital course, were used to compose a multivariate logistic regression with mortality serving as the primary endpoint. The overall in-hospital mortality was 64% (n = 58) in this group. The arrest was considered cardiac etiology in 84% (n = 76) of patients, of which 49% (n = 45) were classed as ventricular fibrillation and 9% (n = 8) as ventricular tachycardia. The presence of a shockable rhythm, as well as shorter duration of cardiac arrest, was associated with increased survival, whereas time to target temperature was not. The presence of a preexisting neurologic disease was associated with a 10-fold increase in estimated odds of mortality. Age, serum lactate, ionized calcium, arterial pH, estimated glomerular filtration rate, and APACHE score were all predictors of mortality. Cardiac arrest is a devastating condition with a high mortality rate. Given the limited resources of the resuscitation community, the ability to predict survivors based on routinely obtained measures upon admission would be of tremendous value. In this study, we show a series of admission parameters that demonstrate predictive ability in identifying patients more likely to survive with therapeutic hypothermia.

Background: Obesity is a risk factor for cardiovascular disease. There is evidence of impaired left ventricular (LV) function associated with obesity, which may relate to cardiovascular mortality, but some studies have reported no dysfunction. Ventricular function data are generally acquired under resting conditions, which could mask subtle differences and potentially contribute to these contradictory findings. Furthermore, abnormal ventricular mechanics (strains, strain rates, and torsion) may manifest prior to global changes in cardiac function (i.e., ejection fraction) and may therefore represent more sensitive markers of cardiovascular disease. This study evaluated LV mechanics under both resting and stress conditions with the hypothesis that the LV mechanical dysfunction associated with obesity is exacerbated with stress and manifested at earlier stages of disease compared to baseline., Methods: C57BL/6J mice were randomized to a high-fat or control diet (60 %, 10 % kcal from fat, respectively) for varying time intervals (n = 7 - 10 subjects per group per time point, 100 total; 4 - 55 weeks on diet). LV mechanics were quantified under baseline (resting) and/or stress conditions (40 μg/kg/min continuous infusion of dobutamine) using cine displacement encoding with stimulated echoes (DENSE) with 7.4 ms temporal resolution on a 7 T Bruker ClinScan. Peak strain, systolic strain rates, and torsion were quantified. A linear mixed model was used with Benjamini-Hochberg adjustments for multiple comparisons., Results: Reductions in LV peak longitudinal strain at baseline were first observed in the obese group after 42 weeks, with no differences in systolic strain rates or torsion. Conversely, reductions in longitudinal strain and circumferential and radial strain rates were seen under inotropic stress conditions after only 22 weeks on diet. Furthermore, stress cardiovascular magnetic resonance (CMR) evaluation revealed supranormal values of LV radial strain and torsion in the obese group early on diet, followed by later deficits., Conclusions: Differences in left ventricular mechanics in obese mice are exacerbated under stress conditions. Stress CMR demonstrated a broader array of mechanical dysfunction and revealed these differences at earlier time points. Thus, it may be important to evaluate cardiac function in the setting of obesity under stress conditions to fully elucidate the presence of ventricular dysfunction.

Background: Cardiovascular magnetic resonance using displacement encoding with stimulated echoes (DENSE) is capable of assessing advanced measures of cardiac mechanics such as strain and torsion. A potential hurdle to widespread clinical adoption of DENSE is the time required to manually segment the myocardium during post-processing of the images. To overcome this hurdle, we proposed a radical approach in which only three contours per image slice are required for post-processing (instead of the typical 30-40 contours per image slice). We hypothesized that peak left ventricular circumferential, longitudinal and radial strains and torsion could be accurately quantified using this simplified analysis., Methods and Results: We tested our hypothesis on a large multi-institutional dataset consisting of 541 DENSE image slices from 135 mice and 234 DENSE image slices from 62 humans. We compared measures of cardiac mechanics derived from the simplified post-processing to those derived from original post-processing utilizing the full set of 30-40 manually-defined contours per image slice. Accuracy was assessed with Bland-Altman limits of agreement and summarized with a modified coefficient of variation. The simplified technique showed high accuracy with all coefficients of variation less than 10% in humans and 6% in mice. The accuracy of the simplified technique was also superior to two previously published semi-automated analysis techniques for DENSE post-processing., Conclusions: Accurate measures of cardiac mechanics can be derived from DENSE cardiac magnetic resonance in both humans and mice using a simplified technique to reduce post-processing time by approximately 94%. These findings demonstrate that quantifying cardiac mechanics from DENSE data is simple enough to be integrated into the clinical workflow.

Purpose: To test the hypothesis that magnitude images from cine displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) can accurately quantify left ventricular (LV) volumes, mass, and ejection fraction (EF)., Materials and Methods: Thirteen mice (C57BL/6J) were imaged using a 7T ClinScan MRI. A short-axis stack of cine T2-weighted black blood (BB) images was acquired for calculation of LV volumes, mass, and EF using the gold standard sum-of-slices methodology. DENSE images were acquired during the same imaging session in three short-axis (basal, mid, apical) and two long-axis orientations. A custom surface fitting algorithm was applied to epicardial and endocardial borders from the DENSE magnitude images to calculate volumes, mass, and EF. Agreement between the DENSE-derived measures and BB-derived measures was assessed via coefficient of variation (CoV)., Results: 3D surface reconstruction was completed on the order of seconds from segmented images, and required fewer slices to be segmented. Volumes, mass, and EF from DENSE-derived surfaces matched well with BB data (CoVs ≤11%)., Conclusion: LV mass, volumes, and EF in mice can be quantified through sparse (five slices) sampling with DENSE. This consolidation significantly reduces the time required to assess both mass/volume-based measures of cardiac function and advanced cardiac mechanics., (© 2013 Wiley Periodicals, Inc.)

Background: Obesity affects a third of adults in the US and results in an increased risk of cardiovascular mortality. While the mechanisms underlying this increased risk are not well understood, animal models of obesity have shown direct effects on the heart such as steatosis and fibrosis, which may affect cardiac function. However, the effect of obesity on cardiac function in animal models is not well-defined. We hypothesized that diet-induced obesity in mice reduces strain, torsion, and synchrony in the left ventricle (LV)., Methods: Ten 12-week-old C57BL/6 J mice were randomized to a high-fat or low-fat diet. After 5 months on the diet, mice were imaged with a 7 T ClinScan using a cine DENSE protocol. Three short-axis and two long-axis slices were acquired for quantification of strains, torsion and synchrony in the left ventricle., Results: Left ventricular mass was increased by 15% (p = 0.032) with no change in volumes or ejection fraction. Subepicardial strain was lower in the obese mice with a 40% reduction in circumferential strain (p = 0.008) a 53% reduction in radial strain (p = 0.032) and a trend towards a 19% reduction in longitudinal strain (p = 0.056). By contrast, subendocardial strain was modestly reduced in the obese mice in the circumferential direction by 12% (p = 0.028), and no different in the radial (p = 0.690) or longitudinal (p = 0.602) directions. Peak torsion was reduced by 34% (p = 0.028). Synchrony of contraction was also reduced (p = 0.032) with a time delay in the septal-to-lateral direction., Conclusions: Diet-induced obesity reduces left ventricular strains and torsion in mice. Reductions in cardiac strain are mostly limited to the subepicardium, with relative preservation of function in the subendocardium. Diet-induced obesity also leads to reduced synchrony of contraction and hypertrophy in mouse models.

Background: Advanced measures of cardiac function are increasingly important to clinical assessment due to their superior diagnostic and predictive capabilities. Cine DENSE cardiovascular magnetic resonance (CMR) is ideal for quantifying advanced measures of cardiac function based on its high spatial resolution and streamlined post-processing. While many studies have utilized cine DENSE in both humans and small-animal models, the inter-test and inter-observer reproducibility for quantification of advanced cardiac function in mice has not been evaluated. This represents a critical knowledge gap for both understanding the capabilities of this technique and for the design of future experiments. We hypothesized that cine DENSE CMR would show excellent inter-test and inter-observer reproducibility for advanced measures of left ventricular (LV) function in mice., Methods: Five normal mice (C57BL/6) and four mice with depressed cardiac function (diet-induced obesity) were imaged twice, two days apart, on a 7T ClinScan MR system. Images were acquired with 15-20 frames per cardiac cycle in three short-axis (basal, mid, apical) and two long-axis orientations (4-chamber and 2-chamber). LV strain, twist, torsion, and measures of synchrony were quantified. Images from both days were analyzed by one observer to quantify inter-test reproducibility, while inter-observer reproducibility was assessed by a second observer's analysis of day-1 images. The coefficient of variation (CoV) was used to quantify reproducibility., Results: LV strains and torsion were highly reproducible on both inter-observer and inter-test bases with CoVs ≤ 15%, and inter-observer reproducibility was generally better than inter-test reproducibility. However, end-systolic twist angles showed much higher variance, likely due to the sensitivity of slice location within the sharp longitudinal gradient in twist angle. Measures of synchrony including the circumferential (CURE) and radial (RURE) uniformity of strain indices, showed excellent reproducibility with CoVs of 1% and 3%, respectively. Finally, peak measures (e.g., strains) were generally more reproducible than the corresponding rates of change (e.g., strain rate)., Conclusions: Cine DENSE CMR is a highly reproducible technique for quantification of advanced measures of left ventricular cardiac function in mice including strains, torsion and measures of synchrony. However, myocardial twist angles are not reproducible and future studies should instead report torsion.

Background: Children with renal diseases who are treated with glucocorticoids are at increased risk of developing osteoporosis and fractures. However, there is no common strategy for prevention of corticosteroid-induced osteoporosis. The present systematic review was performed to determine whether prevention of bone loss by calcium (Ca), vitamin D (vit D) and/or bisphosphonates is justified, safe and efficacious in children treated with steroids for various renal diseases., Data Sources: Medline, Embase, Central were searched from 1961 up to 2012. Randomized controlled trials (RCTs) and observational studies concerning children ≤18 years with renal diseases requiring steroids were included., Results: The search strategy retrieved 2482 studies. Four RCTs including 166 patients and one observational study including 100 children met our eligibility criteria. One RCT and the observational study concerned treatment with Ca/vit D, one RCT with bisphosphonates and two RCTs with a combination of both therapies. All described a significant improvement in bone mineral density (BMD) in the treatment group compared with the control group., Conclusions:  Ca combined with vit D is recommended to prevent bone disease in children with renal diseases treated with steroids. Because of side effects, bisphosphonates should be reserved for the treatment of severe osteoporosis when Ca and/or vit D supplementation has failed.

Clinically relevant mature cartilage cells (chondrocytes) present challenges for use in cartilage tissue engineering applications, given their low capacity for cell division and tissue production. Since the in situ environment of chondrocytes is hypertonic relative to standard culture medium conditions, in this study we tested the hypothesis that using culture medium of a hypertonic, more physiologic osmolarity during both two-dimensional (2D) expansion of mature bovine chondrocytes (MBCs) and their subsequent encapsulation culture in three-dimensional (3D) agarose hydrogel constructs produces improved engineered tissue construct mechanical and biochemical properties. Results demonstrate that 2D expansion of MBCs in hypertonic (NaCl) medium before encapsulation yielded improved construct mechanical properties. However, 3D encapsulation culture of cells in hypertonic (NaCl) medium yielded poorer construct mechanical properties. Osmolarity-related differences in construct biochemical content and organization may have contributed to differences in mechanical properties, as construct glycosaminoglycan content correlated moderately with construct mechanical properties, and construct collagen distribution varied between 3D osmotic culture groups. Results of this study suggest that application of hypertonic (NaCl) medium during 2D mature chondrocyte expansion, but not 3D encapsulated chondrocyte culture, may serve as a convenient and inexpensive method for improving mechanical properties of expanded cell-seeded constructs.

A fully automated, random access method for the determination of cannabinoids (UTHC) was developed for the Dimension AR and XL clinical chemistry systems. The method utilizes Abuscreen ONLINE reagents and a multianalyte liquid calibrator containing 11-nor-Delta(9)-THC-9-carboxylic acid. Within-run and total reproducibility, determined using NCCLS protocol EP5- T2, was less than 0.6% and 1.6% CV, respectively, at all concentrations. Calibration stability was retained for at least 30 days. An extensive evaluation of non-structurally related drugs and various physiological substances indicated lack of interference in the method. No sample carry-over was observed following a specimen containing 1886 ng/ml 11-nor-Delta(9)-THC-9-carboxylic acid. A 99.1% agreement (N = 445 samples) was found between an EMIT based method on the aca discrete clinical analyser and the Dimension UTHC method.Dimension clinical chemistry system and aca discrete clinical analyser are registered trademarks of Dade International.

Variations of the symbolic delayed-matching-to-sample procedure were used to study a pigeon's memory for a small number of pecks. In the first experiment a choice of a left or right sidekey after a delay or retention interval was reinforced if a bird had not pecked at all or had pecked exactly once, before the delay, respectively. In the second experiment a choice of a red or green sidekey, regardless of its position, was reinforced if a bird had not pecked at all or had pecked exactly twice, respectively. In the first experiment a bird could orient toward the correct choice during the delay, whereas it could not in the second experiment. In a third experiment a feature-probing method was used to study a pigeon's memory for a number of pecks in the context of certain other pecks. The results showed that a pigeon can remember a small number of pecks for one-half to one minute or more and that the percent correct is a decreasing function of the log retention interval. When a second number of pecks is different from the first number, memory for the first number lasts only a few seconds. When a second number is the same, memory lasts considerably longer. The more recent number of pecks is remembered better. The results are interpreted in terms of a theory which holds that a reinforcer, in general, may act on a subjects' memory for recent behavior to generate patterns of behavior.