Defining the optimal technique for endoscopic ultrasound shear wave elastography: a combined benchtop and animal model study with comparison to transabdominal shear wave elastography

Background/Aims@#Shear wave elastography (SWE) is used for liver fibrosis staging based on stiffness measurements. It can be performed using endoscopic ultrasound (EUS) or a transabdominal approach. Transabdominal accuracy can be limited in patients with obesity because of the thick abdomen. Theoretically, EUS-SWE overcomes this limitation by internally assessing the liver. We aimed to define the optimal technique for EUS-SWE for future research and clinical use and compare its accuracy with that of transabdominal SWE. @*Methods@#Benchtop study: A standardized phantom model was used. The compared variables included the region of interest (ROI) size, depth, and orientation and transducer pressure.Porcine study: Phantom models with varying stiffness values were surgically implanted between the hepatic lobes. @*Results@#For EUS-SWE, a larger ROI size of 1.5 cm and a smaller ROI depth of 1 cm demonstrated a significantly higher accuracy. For transabdominal SWE, the ROI size was nonadjustable, and the optimal ROI depth ranged from 2 to 4 cm. The transducer pressure and ROI orientation did not significantly affect the accuracy. There were no significant differences in the accuracy between transabdominal SWE and EUS-SWE in the animal model. The variability among the operators was more pronounced for the higher stiffness values. Small lesion measurements were accurate only when the ROI was entirely situated within the lesion. @*Conclusions@#We defined the optimal viewing windows for EUS-SWE and transabdominal SWE. The accuracy was comparable in the non-obese porcine model. EUS-SWE may have a higher utility for evaluating small lesions than transabdominal SWE.

Epidemiology of Eosinophilic Esophagitis in Patients with Cystic Fibrosis: A Population-Based 5-Year Study / 대한소아소화기영양학회지

Purpose@#The prevalence of eosinophilic esophagitis (EoE) has been on the rise since it was first described in the 1990s. Several diseases and exogenous factors have been associated with EoE. Our aim was to investigate the epidemiology of EoE in cystic fibrosis (CF) patients. @*Methods@#We identified individuals with CF from September 2014 to September 2019 within a database (IBM Explorys Solutions, Inc.). The prevalence of EoE in patients with CF was compared to the general population. @*Results@#The database included 36,111,860 patients during the 5-year study period: 12,950 with CF (0.036%) and 28,090 with EoE (0.078%). EoE prevalence was higher in CF patients than the general population (46 in 10,000 vs. 7.8 in 10,000, p<0.001). Patients with CF and EoE were more likely to be male (50% vs. 33.5%, p<0.008), children (33.3% vs. 16.5%, p<0.001), and non-Hispanic (100% vs. 88.7%, p<0.001) than CF patients without EoE. CF with EoE patients were more likely to be children than EoE only (33.3% vs. 10.5%, p<0.001). Allergic conditions were generally more prevalent in CF with EoE than CF only (83.3% vs.68.3%, p=0.01) and EoE only (83.3% vs. 69.3%, p=0.014). @*Conclusion@#EoE is nearly 6-times more prevalent in CF patients. Those patients had higher incidence of other atopic conditions. EoE must be considered in the differential diagnosis of patients with CF presenting with dysphagia, refractory gastroesophageal reflux, vomiting, and other esophagus-related symptoms.

CAR-T cells: Early successes in blood cancer and challenges in solid tumors

New approaches to cancer immunotherapy have been developed, showing the ability to harness the immune system to treat and eliminate cancer. For many solid tumors, therapy with checkpoint inhibitors has shown promise. For hematologic malignancies, adoptive and engineered cell therapies are being widely developed, using cells such as T lymphocytes, as well as natural killer (NK) cells, dendritic cells, and potentially others. Among these adoptive cell therapies, the most active and advanced therapy involves chimeric antigen receptor (CAR)-T cells, which are T cells in which a chimeric antigen receptor is used to redirect specificity and allow T cell recognition, activation and killing of cancers, such as leukemia and lymphoma. Two autologous CAR-T products have been approved by several health authorities, starting with the U.S. Food and Drug Administration (FDA) in 2017. These products have shown powerful, inducing, long-lasting effects against B cell cancers in many cases. In distinction to the results seen in hematologic malignancies, the field of using CAR-T products against solid tumors is in its infancy. Targeting solid tumors and trafficking CAR-T cells into an immunosuppressive microenvironment are both significant challenges. The goal of this review is to summarize some of the most recent aspects of CAR-T cell design and manufacturing that have led to successes in hematological malignancies, allowing the reader to appreciate the barriers that must be overcome to extend CAR-T therapies to solid tumors successfully.

First Occurrence and Population Dynamics of Blissus pulchellus (Hemiptera: Blissidae) in Brazil: a new pest of pastures in Roraima

ABSTRACT Cattle production is one of the main economic activities in the state of Roraima, and insect pest attacks in pastures have a negative effect on this sector in the region. Little is known about the species that cause damage to forage fields in the state. This study presents the first report of the occurrence of the chinch bug Blissus pulchellus Montandon (Hemiptera: Blissidae) in Roraima, Brazil and a description of the population dynamics of this pest in pasture areas in this state. Pasture areas were sampled in nine municipalities of Roraima to detect the insect. The population dynamics study was conducted for two years in Alto Alegre municipality, two of which have Brachiaria brizantha cv. Marandu and one of Megathrysus maximus cv. Mombaça (Poaceae) crops. Blissus pulchellus was found in all sampled areas, except in Rorainópolis and São João da Baliza. High densities of this bug were found in in Alto Alegre. This is the first report of B. pulchellus in Brazil. The factors that affect the population dynamics and the damage caused by this insect pest to pastures as well as the risk of dispersal of this pest in Brazil are discussed.

Response of the oxygen uptake efficiency slope to exercise training in patients with chronic kidney disease

Background@#Chronic kidney disease (CKD) patients have poor cardiorespiratory fitness. Although cardiopulmonary exercise testing (CPET) is a universal assessment of cardiorespiratory fitness, values taken at ‘peak’ effort are strongly influenced by motivation and the choice of test endpoint. The oxygen uptake efficiency slope (OUES) integrates cardiovascular, musculoskeletal, and respiratory function into a single index to provide a more pragmatic and safer alternative to maximal testing. No research has explored whether exercise can improve the OUES in CKD patients. @*Methods@#Thirty-two patients with non-dialysis CKD were recruited into a 12-week exercise program consisting of mixed aerobic and resistance training three times a week. CPET was conducted at baseline, and then, following a 6-week control period, at pre- and post-exercise intervention. Direct measurements of oxygen consumption (V̇O2) and ventilatory parameters were collected. The OUES was calculated as the relationship between V̇O2 and the log10 of minute ventilation (V̇E). @*Results@#No changes were observed in any variable during the control period, although modest increases in V̇O2peak were observed. No meaningful changes were observed as a result of exercise in any cardiorespiratory value obtained. The OUES calculated at 100%, 90%, 75%, and 50% of exercise duration did not change significantly after 12 weeks of exercise training. @*Conclusion@#Our results show that 12 weeks of exercise training had no beneficial effects on the OUES, which supports the modest change observed in V̇O2peak. The lack of change in the OUES and other parameters could indicate a dysfunctional cardiorespiratory response to exercise in patients with CKD, likely mediated by dysfunctional peripheral metabolic mechanisms.

The effect of individual-level factors in survival prognosis for colorectal cancer in Malaysia

Background: In Malaysia, colorectal cancer is the second most common type of cancer for both sexes, represents 10.2% of total cancer cases in Malaysia. This study aims to identify the effect of individual-level factors on survival prognosis for patients with colorectal cancer in Malaysia.Methods: The study involved 4412 of colorectal cancer patients in Malaysia with histologically verified primary colorectal cancer, diagnosed between 2008 and 2013 (ICD-10, C18-C20), recorded in the database of National Cancer Patient Registry- Colorectal Cancer (NCPR-CC) Malaysia. We investigated the effect of individual characteristics such as age, gender, education as well as clinical characteristics such as cancer staging, cancer site and treatment modalities on survival prognosis after a diagnosis of colorectal cancer using a Cox regression survival model.Results: Patients diagnosed at stage IV had an almost 6-fold greater risk of dying from colorectal cancer than those with stage I. Age, third-degree education, poor tumour differentiation, the presence of distant metastases and receiving ‘other’ treatments were the other factors that increased the risk of death for colorectal cancer patients in Malaysian population.Conclusions: Our analysis revealed that the severity of the disease lead to poor prognosis in colorectal cancer in the population after adjusting for other individual characteristics. Health education programs targeting high risk group and emphasizing the importance of early detection of cancer as well as knowledge on the importance of cancer treatment should be implemented. Formulation of a better screening program needs to be extended so that it is a genuinely national program.

Clinicopathological characteristics of surgically treated localized renal masses in patients previously exposed to chemotherapy

ABSTRACT Purpose: To explore the potential association between renal mass characteristics and a history of chemotherapy. Materials and methods: A retrospective review of records of patients surgically treated for a localized renal mass between 2000 and 2012 was undertaken following an institutional review board approval. Patients age and sex, renal mass clinical characteristics (radiological size and mode of presentation) and pathological characteristics (diagnosis, renal cell carcinoma subtype, Fuhrman grade and stage) were compared between patients with and without a history of chemotherapy, using Fisher's exact test, Student's t-test and Wilcoxon rank sum test. A multivariate logistic analysis was performed to evaluate the independent association of chemotherapy and tumor pathology. Results: Of the 1,038 eligible patients, 33 (3%) had a history of chemotherapy. The distribution of clinical stage, renal mass diagnosis, renal cell carcinoma subtype, Fuhrman grade, pathological stage, sex and median age were similar between the general population and the chemotherapy group. However, the latter had a higher rate of incidental presentation (P = 0.003) and a significantly smaller median radiological tumor size (P = 0.01). In a subset analysis of T1a renal cell carcinoma, the chemotherapy group presented an increased rate of high Fuhrman grade (P = 0.03). On multivariate analysis adjusted for radiological tumor size, sex and age the chemotherapy cohort had a 3.92 higher odds for high Fuhrman grade. Conclusion: Patients with a history of chemotherapy typically present with smaller renal masses that, if malignant, have higher odds of harboring a high Fuhrman grade and thus may not be suitable for active surveillance.

Enterourachal Fistula as an Initial Presentation in Crohn Disease / 대한소아소화기영양학회지

Crohn disease has a wide spectrum of clinical presentations and rarely can present with complications such as a bowel stricture or fistula. In this case report, we describe a 17-year-old male who presented with a history of recurrent anterior abdominal wall abscesses and dysuria. He was diagnosed with Crohn disease and also found to have a fistulous communication between the terminal ileum and a patent urachus. An ileocecectomy with primary anastomosis and complete resection of the abscess cavity was performed. He is on azathioprine for maintenance therapy and currently in remission. Clinicians should have a high index of suspicion for this complication in Crohn disease patients presenting with symptoms suggestive of urachal anomalies such as suprapubic abdominal pain, dysuria, umbilical discharge, and periumbilical mass.

On thin ice: barriers to adoption of surveillance for patients with stage I testicular seminoma. Survey of US radiation oncologists

ABSTRACT Purpose: Most men with stage I testicular seminoma are cured with surgery alone, which is a preferred strategy per national guidelines. The current pattern of practice among US radiation oncologists (ROs) is unknown. Materials and Methods: We surveyed practicing US ROs via an online questionnaire. Respondent's characteristics, self-rated knowledge, perceived patient compliance rates with observation were analyzed for association with treatment recommendations. Results: We received 353 responses from ROs, of whom 23% considered themselves experts. A vast majority (84%) recommend observation as a default strategy, however this rate drops to 3% if the patient is believed to be noncompliant. 33% of respondents believe that survival is jeopardized in case of disease recurrence, and among these respondents only 5% support observation. 22% of respondents over-estimate the likelihood of noncompliance with observation to be in the 50-80% range. Responders with a higher perceived noncompliance rate are more likely to recommend adjuvant therapy (Fisher's exact p<0.01). Only 7% of respondents recommend observation for stage IS seminoma and 45% administer adjuvant RT in patients with elevated pre-orchiectomy alpha-fetal protein levels. Conclusions: Many US ROs over-estimate the likelihood that stage I testicular seminoma patients will be noncompliant with surveillance and incorrectly believe that overall survival is jeopardized if disease recurs on surveillance. Observation is quickly dismissed for patients who are not deemed to be compliant with observation, and is generally not accepted for patients with stage IS disease. There is clearly an opportunity for improved physician education on evidence-based management of stage I testicular seminoma.

Reversal of Immunogenicity in Pediatric Inflammatory Bowel Disease Patients Receiving Anti-Tumor Necrosis Factor Medications / 대한소아소화기영양학회지

Loss of response to anti-tumor necrosis factor (anti-TNF) agents in the treatment of inflammatory bowel disease (IBD) is a major consideration to maintain sustained response. Reversal of immunogenicity can re-establish response and increase the durability of these agents. Strategies to reverse immunogenicity include dose-intensification and/or the addition of an immunomodulator. However, there is a relative paucity of data on the efficacy of such interventions in pediatric IBD patients. Available reports have not strictly utilized homogenous mobility shift assay, which reports on anti-drug antibodies even in the presence of detectable drug, whereas prior studies have been confounded by the use of drug sensitive assays. We report four pediatric inflammatory bowel disease patients with successful reversal of immunogenicity on an anti-TNF agent using dose intensification and/or addition of an immunomodulator.

Endoscopic Features of Mucous Cap Polyps: A Way to Predict Serrated Polyps

BACKGROUND/AIMS: The aims of the study were to identify whether a mucous-cap predicts the presence of serrated polyps, and to determine whether additional endoscopic findings predict the presence of a sessile serrated adenomas/polyp (SSA/P). METHODS: We analyzed 147 mucous-capped polyps with corresponding histology, during 2011–2014. Eight endoscopic features (presence of borders, elevation, rim of debris, location in the colon, size ≥10 mm, varicose vessels, nodularity, and alteration in mucosal folds) of mucous-capped polyps were examined to see if they can predict SSA/Ps. RESULTS: A total of 86% (n=126) of mucous-capped polyps were from the right sided serrated pathway (right-sided hyperplastic [n=83], SSA/Ps [n=43], traditional serrated adenoma [n=1]), 10% (n=15) were left-sided hyperplastic polyps, and 3% (n=5) were from the adenoma-carcinoma sequence. The presence of a mucous cap combined with varicose vessels was the only significant predictor for SSA/Ps. The other seven characteristics were not found to be statistically significant for SSA/Ps, although location in the colon and the presence of nodularity trended towards significance. CONCLUSIONS: Our study suggests that mucous-capped polyps have high predictability for being a part of the serrated pathway. Gastroenterologists should be alert for a mucous-capped polyp with varicose veins, as these lesions have a higher risk of SSA/P.

Normal Age-Adjusted Sagittal Spinal Alignment Is Achieved with Surgical Correction in Adolescent Idiopathic Scoliosis

STUDY DESIGN: Retrospective analysis. PURPOSE: Our hypothesis is that the surgical correction of adolescent idiopathic scoliosis (AIS) maintains normal sagittal alignment as compared to age-matched normative adolescent population. OVERVIEW OF LITERATURE: Sagittal spino-pelvic alignment in AIS has been reported, however, whether corrective spinal fusion surgery re-establishes normal alignment remains unverified. METHODS: Sagittal profiles and spino-pelvic parameters of thirty-eight postsurgical correction AIS patients ≤21 years old without prior fusion from a single institution database were compared to previously published normative age-matched data. Coronal and sagittal measurements including structural coronal Cobb angle, pelvic incidence, pelvic tilt, thoracic kyphosis, lumbar lordosis, sagittal vertical axis, C2–C7 cervical lordosis, C2–C7 sagittal vertical axis, and T1 pelvic angles were measured on standing full-body stereoradiographs using validated software to compare preoperative and 6 months postoperative changes with previously published adolescent norms. A sub-group analysis of patients with type 1 Lenke curves was performed comparing preoperative to postoperative alignment and also comparing this with previously published normative values. RESULTS: The mean coronal curve of the 38 AIS patients (mean age, 16±2.2 years; 76.3% female) was corrected from 53.6° to 9.6° (80.9%, p<0.01). None of the thoracic and spino-pelvic sagittal parameters changed significantly after surgery in previously hypo- and normo-kyphotic patients. In hyper-kyphotic patients, thoracic kyphosis decreased (p=0.003) with a reciprocal decrease in lumbar lordosis (p=0.01), thus lowering pelvic incidence-lumbar lordosis mismatch mismatch (p=0.009). Structural thoracic scoliosis patients had slightly more thoracic kyphosis than age-matched patients at baseline and surgical correction of the coronal plane of their scoliosis preserved normal sagittal alignment postoperatively. A sub-analysis of Lenke curve type 1 patients (n=24) demonstrated no statistically significant changes in the sagittal alignment postoperatively despite adequate coronal correction. CONCLUSIONS: Surgical correction of the coronal plane in AIS patients preserves sagittal and spino-pelvic alignment as compared to age-matched asymptomatic adolescents.

Intracardiac tumor causing left-ventricular outflow-tract obstruction in a newborn

The following report describes the case of newborn girl with an asymptomatic systolic murmur, which on imaging revealed a nearly obstructive mass in the left-ventricular outflow tract. The mass was resected and found to be consistent with a rhabdomyoma. Here, we describe the pathologic and clinical characteristics of this tumor

Multimodality Imaging Approach in Alzheimer disease. Part I: Structural MRI, Functional MRI, Diffusion Tensor Imaging and Magnetization Transfer Imaging / Abordagem e multimodalidade de imagem em doença de Alzheimer. Parte I: RM estrutural, RMI funcional, tensor de difusão e transferência de magnetização de imagens

ABSTRACT The authors make a complete review of the potential clinical applications of traditional and novel magnetic resonance imaging (MRI) techniques in the evaluation of patients with Alzheimer's disease, including structural MRI, functional MRI, diffusion tension imaging and magnetization transfer imaging.

RESUMO Os autores fazem uma revisão complete das potenciais aplicações clínicas de técnicas tradicional e inovadoras de ressonância magnética na avaliação de pacientes com doença de Alzheimer, incluindo ressonância magnética estrutural, técnicas funcionais de ressonância magnética, técnica de "diffusion tensor imaging" e imagem de transferência magnética.

Multimodality Imaging Approaches in Alzheimer's disease. Part II: 1H MR spectroscopy, FDG PET and Amyloid PET / Abordagem e multimodalidade de imagem em doença de Alzheimer. Parte II: espectroscopia, FDG-PET, e imagem Amilóide

ABSTRACT. In this Part II review, as a complement to the Part I published in this supplement, the authors cover the imaging techniques that evaluates the Alzheimer's disease according to the different metabolic and molecular profiles. In this section MR spectroscopy, FDG-PET and amyloid PET are deeply discussed.

RESUMO Nesta revisão Parte II, como complemento da revisão Parte I publicada nesta edição, os autores descrevem as técnicas de imagem que avaliam a doença de Alzheimer de acordo com os diferentes perfis metabólicos e moleculares que caracterizam esta doença. Nesta seção são discutidos em profundidade a espectroscopia por ressonância magnética, FDG-PET and imagem com marcadores de peptide beta amilóide.

Qinghuachang Decoction Inhibited NF-kappaB Activation in LPS-induced Human Enterocytes / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore anti-inflammation and mechanism of Qinghuachang Decoction (QD) by using LPS stimulated differentiated colon cancer Caco-2 cells (as an inflammation model of human enterocytes).</p><p><b>METHODS</b>QD was prepared. Human colonic epithelial Caco-2 cells were cultured. Expressions of TNF-alpha and IL-8 were determined using ELISA. Expressions of inhibitory Kaba protein (IkappaB-alpha), phosphorylated inhibitory Kaba protein (p-lkappaB-alpha), nuclear transcription factor p50 (p50), and nuclear transcription factor ReIA (ReIA) protein were determined by Western blot.</p><p><b>RESULTS</b>Compared with the negative control group (without LPS stimulation), LPS stimulated the release of IL-8 and TNF-alpha in Caco-2 cells (P < 0.05). QD treatment could reduce the secretion of TNF-alpha and IL-8 induced by LPS in a dose dependent manner (P < 0.05). QD at 0, 5, 10, and 50 microg/mL had no significant effect on Caco-2 cell survival rates (P > 0.05), with no statistical difference among various concentrations (P > 0.05). QD could significantly suppress nuclear factor-kappa B (NF-kappaB) phosphorylation stimulated by LPS. The expression of p-IKappaB-alpha was decreased with increasing concentrations of QD (P < 0.05). There was no obvious change in IKB-alphaB expressions (P > 0.05). Expressions of p50 and ReIA decreased with increasing concentrations of QD (P < 0.05). Both of them were in a dose dependent manner.</p><p><b>CONCLUSION</b>QD inhibited LPS mediated NF-kappaB activation, which might be one of its mechanisms for treating inflammatory bowel disease (IBD).</p>

Resident Participation in International Surgical Missions is Predictive of Future Volunteerism in Practice

BACKGROUND: Interest in global health and international mission trips among medical student and resident trainees is growing rapidly. How these electives and international mission experiences affect future practice is still being elucidated. No study has identified if participation in international surgical missions during residency is a predictor of participation in international surgical missions in practice after training completion. METHODS: All trainees of our plastic surgery residency program from 1990 to 2011, during the implementation of optional annual international surgical missions, were surveyed to determine if the graduate had gone on a mission as a resident and as a plastic surgeon. Data were compared between graduates who participated in missions as residents and graduates who did not, from 1990 to 2011 and 1990 to 2007. RESULTS: Of Plastic Surgery graduates from 1990 to 2011 who participated in international missions as residents, 60% participated in missions when in practice, versus 5.9% of graduates participating in missions in practice but not residency (P<0.0001). When excluding last 5 years, graduates participating in international missions in practice after doing so as residents increases to 85.7%, versus 7.41% who participate in practice but not residency P<0.002. CONCLUSIONS: Results reveal plastic surgeons who participate in international surgical missions as residents participate in international surgical missions in practice at higher rates than graduates who did not participate in missions during residency. International missions have significant intrinsic value both to trainee and international communities served, and this opportunity should be readily and easily accessible to all plastic surgery residents nationwide.