Citations

Background: The expansion of adipose mass requires adipocyte precursor cells that originate from multipotent mesenchymal stem cells (MSC). The inflammatory milieu in obesity often involves high levels of tumor necrosis factor (TNF)-α in adipose tissue, but whether this affects MSC function remains unknown. We tested the hypothesis that microenvironmental changes during the evolution of obesity affect MSC function, which may in turn promote obesity. Methods: Domestic pigs were fed with an adipogenic (n=7) or normal (n=7) diet for 16 weeks. Abdominal adipose tissue biopsies were collected at 8, 12, and 16 weeks for histology and MSC culture. Adipose tissue inflammation and MSC levels were evaluated in situ using immunohistochemistry staining for TNF-α, CD34, and Von Willebrand factor (vWF). The adipogenic propensity of MSC was tested in vitro using appropriate differentiation media, with or without supplementation of TNF-α or anti-TNF-α antibody for 3 weeks. Results: Obese pigs had increased body weight and abdominal fat mass (by CT) compared with lean pigs. TNF-α expression in adipose tissue (Figure 1A) was upregulated in obese pigs at 12 and 16 weeks, accompanied by increased numbers of MSC (CD34 + /vWF - ) at 16 weeks. In vitro, MSC derived from obese adipose tissue at 16weeks showed enhanced adipogenesis, which was abolished by anti-TNF-α treatment. Similarly, in lean MSC TNF-α treatment enhanced adipogenesis (Figure 1B). Conclusion: Obesity-induced adipose tissue inflammation may stimulate MSC differentiation into adipocytes, which further increase the adipose tissue mass. Our results support development of anti-inflammatory strategies for obesity management.

Objectives: Signet-ring cells (SRCs) in effusion specimens represent a diagnostic challenge. In this study, a consecutive series of pleural and peritoneal effusions with benign SRCs are examined and compared with malignant SRCs. Material and Methods: We reviewed consecutive Wright-stained serous effusion slides and searched for cases with SRCs. Corresponding ThinPrep slides and clinical histories were reviewed. Cytology cases with known signet-ring adenocarcinoma were retrieved and reviewed. Results: Four hundred Wright-stained serous effusions were reviewed. Eighteen cases were identified with SRC-like cells. Thirteen patients had liver cirrhosis, three patients had end-stage renal disease, one patient had a history of pancreatic adenocarcinoma, and one patient had endometrioid carcinoma. For the latter two patients, the primary tumor showed no histologic findings of signet-ring features. In all cases, no SRCs were found on the corresponding ThinPrep slides. Five cytology cases with malignant SRCs were reviewed. Benign SRCs have a uniformly pale and markedly distended cytoplasm, and the nuclei are thin and curved. The malignant SRCs showed larger non-curved nuclei and bubbly mucin-containing cytoplasm. Conclusion: Mesothelial cells and histiocytes can mimic signet-ring adenocarcinoma cells on Wright-stained slides. Correlation with ThinPrep specimens is necessary before reporting, as the SRCs typically are not present in ThinPrep preparations.

AbstractBackgroundCenters discard high kidney donor profile index (KDPI) allografts, potentially related to delayed graft function and prolonged hospital use by kidney transplant recipients (KTR). We sought to determine whether high KDPI KTRs have excess health care utilization.MethodsWe conducted a retrospective cohort study from a high‐volume center analyzing KTRs from January 3, 2011 to April 12, 2015 (n = 652). We measured differences in hospital use, emergency visits, and outpatient visits within the first 90 days between low (≤85%) versus high KDPI (>85%) KTRs, as well as long‐term graft function and patient survival.ResultsHigh (n = 107) and low KDPI (n = 545) KTRs had similar length of stay (median = 3 days, P = .66), and readmission rates at 7, 30, and 90 days after surgery (all, P > .05). High KDPI kidneys were not associated with excess utilization of the hospital, emergency services, outpatient transplant clinics, or ambulatory infusion visits on univariate or multivariate analysis (all, P > .05). Low KDPI KTRs had significantly better eGFR at 2 years (Low vs. High KDPI: 60.35 vs. 41.54 ml/min, P < .001), but similar 3‐year patient and graft survival (both, P > .09).ConclusionsHigh and low KDPI KTRs demonstrated similar 90‐day risk‐adjusted health care utilization, which should encourage use of high KDPI kidneys.

482 Background: Prostate radiotherapy is associated with worse oncologic outcomes in patients with bladder cancer. This is thought to be secondary to microvascular damage resulting in propagation of inflammation. There is sparse data on the effect of prior radiotherapy on the efficacy of intravesical Bacillus Calmette-Guerin (BCG) in patients with non-muscle invasive bladder cancer (NMIBC). We sought to evaluate BCG response and outcomes in NMIBC patients who have previously undergone prostate radiotherapy compared to patients with no prior history of pelvic radiotherapy. Methods: This is a retrospective cohort study that includes patients who received intravesical BCG for NMIBC at our institution from 2001 to 2019. Data were collected on patient and pathologic characteristics. Patients were stratified into three cohorts: prior radiotherapy (RT), radical prostatectomy (RP), and no prostate cancer (No PCa). Wilcoxon rank sum test and Chi-squared test were used for comparison between groups. The primary endpoints included recurrence at one-year, progression to MIBC and progression to metastatic disease. Results: In 199 total patients who underwent BCG for NMIBC, 23 had a prior history of radiotherapy treatment for prostate cancer, while 17 underwent prior radical prostatectomy. Overall, 41.2% of patients had recurrence at one year. There was no difference in recurrence at one year between the cohorts: 42.8% No PCa, 29.4% RP and 39.1% RT; p = 0.56. There was also no difference in progression to MIBC (6.9% No PCA, 0% RP, and 8.7% RT) or progression to metastatic disease (6.9% No PCA, 5.9% RP and 4.3% RT) with p = 0.50 and 0.89 respectively. Conclusions: The efficacy of intravesical BCG does not appear to be modified by prior radiation treatment for prostate cancer in patients with NMIBC.[Table: see text]

Objective: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma. Summary Background Data: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization. Methods: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics. Results: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients. Conclusions: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.

Abstract Background the Xiangya Hospital circuit training (X-CircuiT), was developed to reverse pre-frailty in Chinese older adults and determine potential mechanisms through which pre-frailty is reversed. Methods this randomised controlled trial was performed at Xiangya Hospital, Changsha, China from September 2020 to May 2021. Forty-eight pre-frail older adults were enrolled. Participants were randomly assigned (1:1) to X-CircuiT (46 min/session, three supervised sessions/week for 3 months at a community health centre) or control (1-time advice on physical activity without supervised exercise). The primary outcome was the proportion of participants with pre-frailty after 3-month intervention. The secondary outcomes included absolute risk reduction (ARR), number needed to treat (NNT), and the changes in senior fitness, body composition and clinical measures. Results among 48 participants (mean age, 72 years; women [65%]), 22 participants in the X-CircuiT (92%) and 21 participants in the control (88%) completed the study. After 3 months, the proportion of pre-frailty was significantly lower in the X-CircuiT group than the control (14% versus 95%, P &lt; 0.001). The ARR and NNT were 82% [95% CI, 65–99] and 1 [1–2], respectively. X-CircuiT was associated with significant improvements in senior fitness indicators and body composition. No significant difference in blood chemistry, carotid ultrasound and echocardiography parameters was found between groups. No significant interaction was detected between sex, BMI, baseline peak oxygen consumption and study groups. Conclusion this study demonstrates that X-CircuiT could significantly reverse pre-frailty in Chinese older adults. The underlying mechanisms may involve X-CircuiT-induced improvements in body composition and senior fitness. The trial is registered at Chictr.org.cn. Number: ChiCTR2100048125.

Background: DPP4 (dipeptidyl peptidase-4) inhibitors comprise a class of oral diabetes medication that have the potential for off-target cardiovascular effects. We previously showed that DPP4 inhibition attenuates the hypotensive effect of acute ACE (angiotensin-converting enzyme) inhibition and increases norepinephrine. Here, we investigated the effects of DPP4 during sustained ACE inhibition compared with during therapy with an ARB (angiotensin receptor blocker) or calcium channel blocker (neutral comparator) in a randomized, double-blinded crossover study. Methods: We enrolled 106 adults with type 2 diabetes and hypertension and 100 received intervention. Subjects were randomized to one of 3 blood pressure arms: ramipril, valsartan, or amlodipine for a total of 15 weeks and received 3 one-week crossover therapies in random order: placebo + placebo, sitagliptin + placebo, and sitagliptin + aprepitant separated by 4-week washout. Results: We found that DPP4 inhibition increased norepinephrine during ramipril but did not increase blood pressure. Aprepitant, a NK1 (substance P) receptor blocker, lowered standing heart rate during renin-angiotensin-aldosterone system blockade with ramipril or valsartan. Conclusions: Increased catecholamines during concurrent ACE and DPP4 inhibition may contribute to cardiovascular complications in patients predisposed to heart failure.

AbstractWhile the COVID-19 pandemic has catalyzed the expansion of telemedicine into nearly every specialty of medicine, few articles have summarized current practices and recommendations for integrating virtual care in the practice of neuro-oncology. This article identifies current telemedicine practice, provides practical guidance for conducting telemedicine visits, and generates recommendations for integrating virtual care into neuro-oncology practice. Practical aspects of telemedicine are summarized including when to use and not use telemedicine, how to conduct a virtual visit, who to include in the virtual encounter, unique aspects of telehealth in neuro-oncology, and emerging innovations.

AbstractModern fluoroscopes used for image guidance have become quite complex. Adding to this complexity are the many regulatory and accreditation requirements that must be fulfilled during acceptance testing of a new unit. Further, some of these acceptance tests have pass/fail criteria, whereas others do not, making acceptance testing a subjective and time‐consuming task. The AAPM Task Group 272 Report spells out the details of tests that are required and gives visibility to some of the tests that while not yet required are recommended as good practice. The organization of the report begins with the most complicated fluoroscopes used in interventional radiology or cardiology and continues with general fluoroscopy and mobile C‐arms. Finally, the appendices of the report provide useful information, an example report form and topics that needed their own section due to the level of detail.

AbstractPurposeTo reduce the likelihood of errors in organ delineations used for radiotherapy treatment planning, a knowledge‐based quality control (KBQC) system, which discriminates between valid and anomalous delineations is developed.Method and MaterialsThe KBQC is comprised of a group‐wise inference system and anomaly detection modules trained using historical priors from 296 locally advanced lung and prostate cancer patient computational tomographies (CTs). The inference system discriminates different organs based on shape, relational, and intensity features. For a given delineated image set, the inference system solves a combinatorial optimization problem that results in an organ group whose relational features follow those of the training set considering the posterior probabilities obtained from support vector machine (SVM), discriminant subspace ensemble (DSE), and artificial neural network (ANN) classifiers. These classifiers are trained on nonrelational features with a 10‐fold cross‐validation scheme. The anomaly detection module is a bank of ANN autoencoders, each corresponding with an organ, trained on nonrelational features. A heuristic rule detects anomalous organs that exceed predefined organ‐specific tolerances for the feature reconstruction error and the classifier's posterior probabilities. Independent data sets with anomalous delineations were used to test the overall performance of the KBQC system. The anomalous delineations were manually manipulated, computer‐generated, or propagated based on a transformation obtained by imperfect registrations. Both peer‐review–based scoring system and shape similarity coefficient (DSC) were used to label regions of interest (ROIs) as normal or anomalous in two independent test cohorts.ResultsThe accuracy of the classifiers was 99.8%, and the minimum per‐class F1‐scores were 0.99, 0.99, and 0.98 for SVM, DSE, and ANN, respectively. The group‐wise inference system reduced the miss‐classification likelihood for the test data set with anomalous delineations compared to each individual classifier and a fused classifier that used the average posterior probability of all classifiers. For 15 independent locally advanced lung patients, the system detected 79% of the anomalous ROIs. For 1320 auto‐segmented abdominopelvic organs, the anomaly detection system identified anomalous delineations, which also had low Dice similarity coefficient values with respect to manually delineated organs in the training data set.ConclusionThe KBQC system detected anomalous delineations with superior accuracy compared to classification methods that judge only based on posterior probabilities.