Naturally selected CD7 CAR-T therapy without genetic manipulations for T-ALL/LBL: first-in-human phase 1 clinical trial.

Derivation of CD7-targeted chimeric antigen receptor (7CAR) T cells often requires genetic manipulations to ablate the CD7 gene or block CD7 cell surface expression. Our novel approach deriving naturally selected 7CAR (NS7CAR) T cells from bulk T cells was able to overcome major fratricide by minimizing accessible CD7 epitopes. The CD7 molecules of NS7CAR T cells were masked or sequestered by the CD7-targeting CAR. Compared with sorted CD7-negative 7CAR T cells and CD7 knocked-out 7CAR T cells, NS7CAR exhibited similar or superior therapeutic properties, including a greater percentage of CAR+ cells and a higher proportion of CD8+ central memory T cells. In our first-in-human phase 1 trial (NCT04572308), 20 patients with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) (n = 14) and T-cell lymphoblastic lymphoma (T-LBL) (n = 6) were treated with NS7CAR. Nineteen patients achieved minimal residual disease negative complete remission (CR) in the bone marrow (BM) by day 28, and 5 of 9 patients achieved extramedullary CR. With a median follow-up of 142.5 (32-311) days after infusion, 14 patients subsequently received allogeneic hematopoietic stem cell transplant (10 consolidative, 4 salvage) following NS7CAR infusion with no relapses to date. Of the 6 patients who did not receive a transplant, 4 remained in CR at a median time of 54 (32-180) days. Eighteen patients experienced mild cytokine release syndrome (CRS) (grade ≤2), 1 developed grade 3 CRS, and 2 had grade 1 neurotoxicity. These results indicate that NS7CAR-T therapy is a safe and highly effective treatment for T-ALL/LBL. More patients and longer follow-up are needed for validation.

Advances towards genome-based acute myeloid leukemia classification: A comparative analysis of WHO-HAEM4R, WHO-HAEM5, and International Consensus Classification.

Two recent guidelines, the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) and the International Consensus Classification (ICC), were published to refine the diagnostic criteria of acute myeloid leukemia (AML). They both consider genomic features more extensively and expand molecularly defined AML subtypes. In this study, we compared the classifications of 1135 AML cases under both criteria. According to WHO-HAEM5 and ICC, the integration of whole transcriptome sequencing, targeted gene mutation screening, and conventional cytogenetic analysis identified defining genetic abnormalities in 89% and 90% of AML patients, respectively. The classifications displayed discrepancies in 16% of AML cases after being classified using the two guidelines, respectively. Both new criteria significantly reduce the number of cases defined by morphology and differentiation. However, their clinical implementation heavily relies on comprehensive and sophisticated genomic analysis, including genome and transcriptome levels, alongside the assessment of pathogenetic somatic and germline variations. Discrepancies between WHO-HAEM5 and ICC, such as the assignment of RUNX1 mutations, the rationality of designating AML with mutated TP53 as a unique entity, and the scope of rare genetic fusions, along with the priority of concurrent AML-defining genetic abnormalities, are still pending questions requiring further research for more elucidated insights.

Protein Design: From the Aspect of Water Solubility and Stability.

Water solubility and structural stability are key merits for proteins defined by the primary sequence and 3D-conformation. Their manipulation represents important aspects of the protein design field that relies on the accurate placement of amino acids and molecular interactions, guided by underlying physiochemical principles. Emulated designer proteins with well-defined properties both fuel the knowledge-base for more precise computational design models and are used in various biomedical and nanotechnological applications. The continuous developments in protein science, increasing computing power, new algorithms, and characterization techniques provide sophisticated toolkits for solubility design beyond guess work. In this review, we summarize recent advances in the protein design field with respect to water solubility and structural stability. After introducing fundamental design rules, we discuss the transmembrane protein solubilization and de novo transmembrane protein design. Traditional strategies to enhance protein solubility and structural stability are introduced. The designs of stable protein complexes and high-order assemblies are covered. Computational methodologies behind these endeavors, including structure prediction programs, machine learning algorithms, and specialty software dedicated to the evaluation of protein solubility and aggregation, are discussed. The findings and opportunities for Cryo-EM are presented. This review provides an overview of significant progress and prospects in accurate protein design for solubility and stability.

Analysis of 60 patients with relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma treated with CD7-targeted chimeric antigen receptor-T cell therapy.

While the use of chimeric antigen receptor-T (CAR-T) therapy for T-cell malignancies is in the early stage of clinical trials, it exhibits substantial potential to offer long-term remission for patients with refractory/relapsed (R/R) T-cell malignancies. In our phase I/II clinical trials, 65 pediatric and adult patients with R/R T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma (T-ALL/LBL) were enrolled (NCT04572308 and NCT04916860). Of these, 60 participants (T-ALL 35, T-LBL 25) received a single dose of naturally selected anti-CD7 CAR (NS7CAR) T cells at three levels: a low dose (5 × 105 /kg), a medium dose (1 to 1.5 × 106 /kg), and a high dose (2 × 106 /kg). On day 28, 94.4% of patients achieved deep complete remission (CR) in bone marrow. Among the 32 patients with extramedullary disease, 78.1% showed response, with 56.3% in CR and 21.9% in partial remission. The 2-year overall survival and progression-free survival (PFS) were 63.5% (95% CI 47.7-79.4) and 53.7% (95% CI, 38.9-68.6), with no difference between pediatric and adult patients. PFS was significantly higher among the 37 CR patients who proceeded with consolidation transplant than the 10 patients who did not with 1-year PFS 67.2% (95% CI 51.9-82.4) versus 15.0% (95% CI 0-40.2), p < .0001. Of the 10 CR patients without transplants, eight relapsed, while two sustained CR on day 128, and day 180, respectively. Cytokine release syndrome occurred in 91.7% of patients (grade 1/2 in 80.0%, grade 3/4 in 11.7%) and 5% of patients had neurotoxicity. NS7CAR-T therapy is effective in treating R/R T-ALL/LBL patients with promising PFS while maintaining a manageable safety profile.

Hospital Frailty Risk Score (HFRS) Predicts Adverse Outcomes Among Hospitalized Patients with Chronic Pancreatitis.

INTRODUCTION: The prevalence of frailty among patients with chronic pancreatitis (CP) and its impact on clinical outcomes is unclear. We report the impact of frailty on mortality, readmission rates, and healthcare utilization among patients with chronic pancreatitis in the United States. METHODS: We extracted data on patients hospitalized with a primary or secondary diagnosis of CP from the Nationwide Readmissions Database 2019. We applied a previously validated hospital frailty risk scoring system to classify CP patients into frail and non-frail on index hospitalization and compared the characteristics of frail and non-frail patients. We studied the impact of frailty on mortality, readmission, and healthcare utilization. RESULTS: Of 56,072 patients with CP, 40.78% of patients were classified as frail. Frail patients experienced a higher rate of unplanned and preventable hospitalizations. Almost two-thirds of frail patients were younger than 65, and one-third had no or only single comorbidity. On multivariate analysis, frailty was independently associated with two times higher mortality risk (adjusted hazard ratio [aHR], 2.05; 95% CI 1.7-2.5). Frailty was also associated with a higher risk of all-cause readmission with an aHR of 1.07; (95% CI 1.03-1.1). Frail patients experienced a longer length of stay, higher hospitalization costs, and hospitalization charges. Infectious causes were the most common cause of readmission among frail patients compared to acute pancreatitis among non-frail patients. CONCLUSIONS: Frailty is independently associated with higher mortality, readmission rates, and healthcare utilization among patients with chronic pancreatitis in the US.

Dedicated Next Day Discharge Post Minimalist TAVI: The Tasmanian Experience.

OBJECTIVES: To assess the safety, feasibility and independent predictors of next day discharge (NDD) in patients undergoing minimalist transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) in a real-world Australian population. METHODS: This single centre study reviewed 135 consecutive patients who underwent minimalist transfemoral TAVI from June 2020 to February 2022. Baseline demographics, procedural characteristic and outcomes were obtained. All patients were assessed by the local protocol for NDD. Patients were then divided into two groups: those who achieved next day discharge (NDD) and those requiring >1 overnight hospital stay. Univariate, bivariate and stepwise multivariate logistic regression modelling was used to identify the predictors of successful next day discharge. RESULTS: The mean age of the cohort was 82.9±5.7 years with 62.3% patients male, the average STS score was 4.1±2.4. All 135 patients underwent a successful transfemoral TAVI procedure, with 131 (97%) receiving a balloon-expandable valve. Ninety-seven (97) (71.9%) patients achieved NDD. Thirty (30)-day outcomes were excellent with a 30-day mortality of 0.7%, transient ischaemic attack/cardiovascular accident (TIA/CVA) 1.5%, major vascular complication 1.5% and 11.4% need for permanent pacemaker (PPM). In patients not achieving NDD, the average length of stay (LOS) was 3.0 days. Baseline characteristics demonstrated pre-existing first degree atrioventricular (AV) block and right bundle branch block (RBBB) as statistically significant negative predictors of NDD on univariate analysis. Next day discharge was achievable in only 50% of patients who suffered any minor or major procedural complication (15/30). Stepwise multivariate logistic regression modelling demonstrated female gender (OR 3.094, 95% CI 1.141-8.391, p=0.026), smaller aortic valve area (AVA) (OR 48.265, 95% CI 2.269-102.6, p=0.013), the presence of diabetes mellitus (OR 0.594, 95% CI 0.356-0.991, p=0.046) and a longer procedure time (OR 0.960, 95% CI 0.935-0.986, p=0.002) as statistically significant negative predictors of NDD. In addition, there was no difference in 30-day readmission rates between the NDD and non-NDD cohort (7.2% vs 10.5%, p=0.386). CONCLUSION: Next day discharge is safe and feasible in almost three quarters of patients undergoing minimalist TAVI for severe AS in a predominantly balloon expandable valve cohort, with a very low rate of 30-day readmission. NDD provides advantages for hospital efficiency and improved cost-effectiveness. Female gender, smaller AVA, the presence of diabetes mellitus and a longer procedure time were independent negative predictors of successful NDD.

Early infection is an independent risk factor for increased mortality in patients with culture-confirmed infected pancreatic necrosis.

BACKGROUND: Mortality in infected pancreatic necrosis (IPN) is dynamic over the course of the disease, with type and timing of interventions as well as persistent organ failure being key determinants. The timing of infection onset and how it pertains to mortality is not well defined. OBJECTIVES: To determine the association between mortality and the development of early IPN. METHODS: International multicenter retrospective cohort study of patients with IPN, confirmed by a positive microbial culture from (peri) pancreatic collections. The association between timing of infection onset, timing of interventions and mortality were assessed using Cox regression analyses. RESULTS: A total of 743 patients from 19 centers across 3 continents with culture-confirmed IPN from 2000 to 2016 were evaluated, mortality rate was 20.9% (155/734). Early infection was associated with a higher mortality, when early infection occurred within the first 4 weeks from presentation with acute pancreatitis. After adjusting for comorbidity, advanced age, organ failure, enteral nutrition and parenteral nutrition, early infection (≤4 weeks) and early open surgery (≤4 weeks) were associated with increased mortality [HR: 2.45 (95% CI: 1.63-3.67), p < 0.001 and HR: 4.88 (95% CI: 1.70-13.98), p = 0.003, respectively]. There was no association between late open surgery, early or late minimally invasive surgery, early or late percutaneous drainage with mortality (p > 0.05). CONCLUSION: Early infection was associated with increased mortality, independent of interventions. Early surgery remains a strong predictor of excess mortality.

Characteristics of 30-Day All-Cause Hospital Readmissions Among Patients with Acute Pancreatitis and Substance Use.

BACKGROUND/OBJECTIVES: Previous studies on healthcare resource utilization and 30-day readmission risks among patients with acute pancreatitis (AP) have focused upon opioid and alcohol use. The data on other substance types are lacking. In this study we aim to estimate the 30-day readmission rates, predictors of readmission, impact of readmission on patient outcomes and resulting economic burden among patients with AP and substance use in the USA. METHODS: This was a retrospective cohort study, based upon data from 2017 National Readmission Database of adult patients with AP and substance use (alcohol in combination, opioid, cannabis, cocaine, sedatives, other stimulants, other hallucinogens, other psychoactive, inhalant and miscellaneous). We estimated the 30-day readmission rates and predictors of 30-day readmission. RESULTS: Among 25,795 eligible patients, most were male, belonged to the lower income quartile, resided in the urban facility and had a Charlson comorbidity score of 0 or 1. The use of a combination of substances was the most common in 17,265 (66.9%) patients followed by only opioids in 4691 (18.2%) patients and only marijuana in 3839 (14.9%) patients. A total of 14.6% patients were readmitted within 30 days after discharge for non-elective causes with the highest risk of readmission within the 1st week after discharge with 5.2% readmissions. Among top ten causes of readmission, most of the principal diagnosis were related to AP in 53.1%. Compared to index admission, readmitted patients had significantly higher rates of acute cardiac failure, shock, and higher in-hospital mortality rate. Overall, readmission attributed to an additional 17,801 days of hospitalization resulting in a total of $150 million in hospitalization charges and $36 million in hospitalization costs in 2017. On multivariate analysis, chronic pancreatitis, self-discharge against medical advice, treatment at the highest volume centers, higher Charlson comorbidity index, increasing length of stay and severe disease were associated with higher odds of readmission while female gender and private insurance were associated with lower odds. CONCLUSION: Readmission was associated with higher morbidity and in-hospital mortality among patients with AP and substance use and resulted in a significant monetary burden on the US healthcare system. Several factors identified in this study may be useful for categorizing patients at higher risk of readmission warranting special attention during discharge planning.

Provider type influences adherence to lifestyle changes in chronic pancreatitis.

BACKGROUND: /Objectives: Alcohol and smoking cessation are recommended in chronic pancreatitis. The aim of this study is to measure the rates of alcohol and smoking cessation counselling among providers and adherence to recommendations. METHODS: Retrospective cohort study of chronic pancreatitis patients at a tertiary hospital. Provider types were defined as primary care (PCP), gastroenterologist, or pancreas specialist. Pairwise comparisons and multivariable analysis were conducted to assess the relation between provider type and smoking/alcohol cessation. RESULTS: Of 256 patients with chronic pancreatitis, 142 (55.5%) consumed alcohol and 130 (91.5%) were advised to stop. Alcohol cessation was advised to 88.9, 96.0 and 92.5% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively. Sixty-one patients (46.9%) were compliant with the recommendation: 31.3, 44.0 and 54.1% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively (Pairwise comparisons PCP vs Pancreas: p = 0.03, others nonsignificant). In multivariable analysis, patients followed by pancreas specialists were more likely to adhere to alcohol cessation recommendation compared to those followed by PCP (OR = 4.31, CI 1.52-12.20, p = 0.006). Smoking cessation was advised to all the 127 current smokers (100%). Fifty-six (44.1%) were compliant with the recommendation: 24.1, 58.3 and 47.3% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively (Pairwise comparisons PCP vs Pancreas: p = 0.03, PCP vs. Gastroenterologist: p = 0.01, others nonsignificant). Multivariable analysis did not confirm this finding. CONCLUSIONS: The majority of providers counsel for alcohol/smoking cessation. Less than half the patients follow the recommendations. Patients followed by pancreas specialists were more likely to adhere to alcohol cessation recommendation.

Does Provider Type Affect Bone Health Surveillance in Chronic Pancreatitis?

BACKGROUND: Bone density screening (DEXA) and vitamin D serum assay (Vit-D) are recommended in chronic pancreatitis, but adherence by providers is unknown. AIMS: Assess DEXA/Vit-D testing according to provider type. METHODS: A retrospective cohort study of chronic pancreatitis patients followed in a tertiary hospital (August 2017-2018) was conducted. Provider type was primary care (PCP), gastroenterologist, and pancreas specialist. Chi-square test and multivariable analysis were conducted to assess the relation between provider type and DEXA/Vit-D testing. Subset analyses were performed among patients with fecal elastase < 200 mcg/g. RESULTS: A total of 478 charts were reviewed, and 256 (53.6%) met diagnosis of chronic pancreatitis; 184 (71.9%) definite, 45 (17.6%) probable, and 27 (10.6%) borderline chronic pancreatitis. DEXA was tested in 112/256 (43%) patients; 16/57(28%) patients followed by PCP, 11/38 (28.9%) by gastroenterologists, and 85/161(52.2%) by pancreas specialists (p = 0.001). Vit-D was tested in 210/256 (82.0%) patients; 42/57(73.7%) followed by PCP, 29/38 (76.3%) by gastroenterologists, and 139/161(86.3%) by pancreas specialists (p = 0.06). Multivariate analysis assessing DEXA/Vit-D testing showed pancreas specialists were more likely to test compared to PCP (DEXA: OR 3.70, CI 1.77-7.74, p = 0.001. Vit-D: OR 3.24, CI 1.43-7.38, p = 0.005), but gastroenterologists were not. In patients with low fecal elastase, pancreas specialists were more likely to test DEXA (pancreas specialists: 62.1%, PCP: 40.0%, Gastroenterologists: 11.1%, p = 0.01) and all patients received Vit-D testing. CONCLUSIONS: Chronic pancreatitis patients often do not receive optimal preventive care. Pancreas specialists were more likely to perform DEXA and Vit-D testing compared to PCP and gastroenterologists. More physician education is needed.

Prevalence of imaging findings of acute pancreatitis in emergency department patients with elevated serum lipase.

PURPOSE: To assess the association of imaging features of acute pancreatitis (AP) with the magnitude of lipase elevation in Emergency Department (ED) patients. METHODS: This Institutional Review Board-approved retrospective study included 509 consecutive patients presenting from 9/1/13-8/31/15 to a large academic ED with serum lipase levels ≥3× the upper limit of normal (ULN) (≥180 U/L). Patients were excluded if they did not have imaging (n = 131) or had a history of trauma, abdominal metastases, altered mental status, or transfer from an outside hospital (n = 190); the final study population was 188 patients. Imaging exams were retrospectively evaluated, and a consensus opinion of two subspecialty-trained abdominal radiologists was used to diagnose AP. Primary outcome was presence of imaging features of AP stratified by lipase level (≥3×-10× ULN and > 10× ULN). Secondary outcome was rate of discordant consensus evaluation compared to original radiologist's report. RESULTS: 25.0% of patients (47/188) had imaging features of AP. When lipase was >10× ULN (n = 94), patients were more likely to have imaging features of AP (34%) vs. those with mild elevation (16%) (p = 0.0042). There was moderately strong correlation between lipase level and presence of imaging features of AP (r = 0.48, p < 0.0001). Consensus review of CT and MRI images was discordant with the original report in 14.9% (28/188) of cases. CONCLUSION: Prevalence of imaging signs of AP in an ED population with lipase ≥3× ULN undergoing imaging is low. However, the probability of imaging features of AP increases as lipase value increases.

Lipase Elevation in Patients With COVID-19.

INTRODUCTION: Although coronavirus disease (COVID-19) has been associated with gastrointestinal manifestations, its effect on the pancreas remains unclear. We aimed to assess the frequency and characteristics of hyperlipasemia in patients with COVID-19. METHODS: A retrospective cohort study of hospitalized patients across 6 US centers with COVID-19. RESULTS: Of 71 patients, 9 (12.1%) developed hyperlipasemia, with 2 (2.8%) greater than 3 times upper limit of normal. No patient developed acute pancreatitis. Hyperlipasemia was not associated with poor outcomes or symptoms. DISCUSSION: Although a mild elevation in serum lipase was observed in some patients with COVID-19, clinical acute pancreatitis was not seen.

Opiate Prescriptions at Discharge Are Not Associated with Early Readmissions in Acute Pancreatitis.

BACKGROUND: Early readmissions in acute pancreatitis (AP) are common. The impact of opiate prescriptions on readmissions is unknown. AIMS: To determine whether the prescription of opiates at hospital discharge and the dose prescribed are associated with early readmissions in AP. METHODS: Direct admissions from the Emergency Department (ED) for AP from September 1, 2013, to August 31, 2016 were identified. Opiate prescription was defined as a new prescription at discharge in an opiate-naïve patient. Early readmission was ED visit or hospitalization within 30 days for an AP-related reason. Multivariable logistic regression was performed, adjusted for age, Charlson Comorbidity Index, pancreatic necrosis, baseline opiate use, non-opiate analgesics, and pain score at discharge. RESULTS: A total of 318 AP patients were identified; the overall early readmission rate was 18%. One hundred and twenty-one (38%) were prescribed opiates at discharge, and 22% had an early readmission. One hundred and ninety-seven (62%) were not prescribed opiates, and 16% had an early readmission. Median opiate dose was 48 mg (24-h morphine equivalents). On multivariable analysis, neither the prescription of opiates (OR 1.2, 95% CI 0.6-2.4, p = 0.55) nor the dose of opiates (OR 0.99, 95% CI 0.99-1.00, p = 0.39) was associated with early readmission. In subset analysis of patients discharged with an opiate prescription, those on opiates at baseline were significantly more likely to have an early readmission (OR 4.19, 95% CI 1.04-16.94, p = 0.04). CONCLUSIONS: In AP patients, neither prescription of opiates at discharge nor prescribed dose was associated with early readmission. Patients on opiates at baseline discharged with an opiate prescription were more likely to have an early readmission.

Transcatheter aortic valve implantation for severe aortic stenosis in the Australian regional population.

OBJECTIVE: To compare clinical and functional outcomes of regional and urban patients after transcatheter aortic valve implantation for severe aortic stenosis. METHODS: Data were collected at patient follow-up post-transcatheter aortic valve implantation at 30 days and 12 months. Patients were stratified by residential postcodes into remoteness areas using the Australian Statistical Geography Standard. DESIGN: Retrospective cohort study. SETTING: Single-centre tertiary referral hospital. PARTICIPANTS: Patients undergoing transcatheter aortic valve implantation (n = 142) from 2009 to 2018 were analysed, with 77 patients (54.2%) residing in regional Victoria and New South Wales. MAIN OUTCOME MEASURES: Procedural success, adverse event rates, readmission rates, mortality rates, loss to follow-up and functional improvement. RESULTS: Patients residing in regional areas had a lower mean age (81.8 vs 83.7 years) and proportion of Stage 4 or 5 chronic kidney disease (1.3% vs 9.2%), compared with urban patients. Procedural characteristics and immediate post-procedural outcomes were similar between both groups. There was no statistically significant difference in mortality, readmission rates or loss to follow-up between the two cohorts. Regional patients demonstrated poorer rates of functional improvement at 30 days (50.7% vs 67.7%); however, this difference was not sustained at 12 months (79.2% vs 71.0%). Frailty was demonstrated to be an independent predictor of poor 30-day functional improvement. CONCLUSION: Regional patients treated with transcatheter aortic valve implantation for severe aortic stenosis have non-inferior 30-day and 12-month outcomes, when compared with urban patients. Frailty is a predictor of poor functional improvement post-transcatheter aortic valve implantation.

A novel anti-inflammatory mechanism of high density lipoprotein through up-regulating annexin A1 in vascular endothelial cells.

High density lipoprotein (HDL) as well as annexin A1 have been reported to be associated with cardiovascular protection. However, the correlation between HDL and annexin A1 was still unknown. In this study, HDL increased endothelial annexin A1 and prevented the decrease of annexin A1 in TNF-α-activated endothelial cells in vitro and in vivo, and above effects were attenuated after knockdown of annexin A1. Annexin A1 modulation affected HDL-mediated inhibition of monocyte adhesion to TNF-α-activated endothelium (45.2±13.7% decrease for annexin A1 RNA interference; 78.7±16.3% decrease for anti-Annexin A1 antibody blocking; 11.2±6.9% increase for Ad-ANXA1 transfection). Additionally, HDL up-regulated annexin A1 through scavenger receptor class B type I, involving ERK, p38MAPK, Akt and PKC signaling pathways, and respective inhibitors of these pathways attenuated HDL-induced annexin A1 expression as well as impaired HDL-mediated inhibition of monocyte-endothelial cell adhesion. Apolipoprotein AI also increased annexin A1 and activated similar signaling pathways. Endothelial annexin A1 from apolipoprotein AI knockout mice was decreased in comparison to that from wild type mice. Finally, HDL-induced annexin A1 inhibited cell surface VCAM-1, ICAM-1 and E-selectin, and secretion of MCP-1, IL-8, VCAM-1 and E-selectin, thereby inhibiting monocyte adhesion.

Early Abdominal Imaging Remains Over-Utilized in Acute Pancreatitis.

BACKGROUND: Early abdominal computed tomography (CT) or magnetic resonance (MR) imaging is common in acute pancreatitis (AP). Guidelines (2007-2013) indicate routine use is unwarranted. AIMS: To compare the frequency and evaluate the predictors of early CT/MR utilization for AP between September 2006-2007 (period A) and September 2014-2015 (period B). METHODS: AP patients presenting directly to a large academic emergency department were prospectively enrolled during each period. Cases requiring imaging to fulfill diagnostic criteria were excluded. Early CT/MR (within 24 h of presentation) utilization rates were compared using Fisher's exact test. Predictors of early imaging usage were assessed with multivariate logistic regression. RESULTS: The cohort included 96 AP cases in period A and 97 in period B. There were no significant differences in patient demographics, comorbidity scores, or AP severity. Period B cases manifested decreased rates of the systemic inflammatory response syndrome (SIRS) during the first 24 h of hospitalization (67% period A vs. 43% period B, p = 0.001). Independent predictors of early imaging included age >60 and SIRS or organ failure on day 1. No significant decrease in early CT/MR usage was observed from period A to B on both univariate (49% period A vs. 40% period B, p = 0.25) and multivariate (OR 1.0 for period B vs. A, 95% CI 0.5-1.9) analysis. CONCLUSIONS: In a comparison of imaging practices for AP, there was no significant decrease in early abdominal CT/MR utilization from 2007 to 2015. Quality improvement initiatives specifically targeting early imaging overuse are needed.

Plant-Based Alternatives Need Not Be Inferior: Findings from a Sensory and Consumer Research Case Study with Cream Cheese.

Reliance on animal foods must be reduced to improve planetary and human well-being. This research studied plant-based cheese alternatives (PBCA) relative to dairy cheese in a consumer taste test with 157 consumers in New Zealand. A case study approach used cream cheese (commercially available) as the focal product category (2 PBCA, 2 dairy) and implemented a multi-response paradigm (hedonic, sensory, emotional, conceptual, situational). "Beyond liking" insights were established, including drivers of liking (sensory, non-sensory) and sensory drivers of non-sensory product associations. Two consumer segments were identified, of which the largest (n = 111) liked PBCA and dairy samples equally (6.5-6.7 of 9). In this PBCA Likers cluster, the key sensory drivers of liking were 'creamy/smooth mouthfeel', 'dissolves quickly in mouth', and 'sweet', while a significant penalty was associated with 'mild/bland flavour'. The non-sensory data contributed additional consumer insights, including the four samples being perceived as differently appropriate for 9 of 12 use situations, with PBCA being regarded as less appropriate. In the limited confines of this case on cream cheese, the findings show that PBCA need not be inferior to their dairy counterparts despite a general narrative to the contrary. Of note, the results were obtained among participants who were open to eating a more PB diet but were not vegetarian or vegan.

A Shift Toward Early Oral Feeding in Acute Pancreatitis.

OBJECTIVES: The 2018 American Gastroenterological Association (AGA) guidelines strongly recommended early oral feeding as tolerated in patients with acute pancreatitis (AP). We compare early oral feeding rates in AP patients hospitalized in the periods before (2013-2016, Period A) and after (2019-2020, Period B) publication of the AGA guidelines, hypothesizing increased adherence in Period B. METHODS: We performed a retrospective cohort study of AP patients presenting to the emergency department during each period. Early oral feeding was defined as diet initiation within the first 48 hours of presentation. RESULTS: The cohort included 276 AP cases in period A and 104 in period B. A higher percentage of patients were offered early oral feeding during period B as compared to period A (70.2% vs. 43.5%). Similarly, more patients in period B were started on solid diet as compared to period A (34.6% vs. 20.3%). On multivariable regression analysis, the independent predictors of delayed oral feeding included early opioid analgesics use (OR 0.37), presence of pancreatic necrosis (OR 0.14), and organ failure (OR 0.33). CONCLUSIONS: More AP patients were initiated on early oral feeding in the period following the publication of the AGA guidelines. Opioid analgesics use, pancreatic necrosis, and organ failure were associated with delayed oral feeding.

A simple and precise alignment calibration method for cone-beam computed tomography with the verifications.

Cone-beam Computed Tomography (CBCT) is widely used in dental imaging, small animal imaging, radiotherapy, and non-destructive industrial inspection. The quality of CBCT images depends on the precise knowledge of the CBCT system's alignment. We introduce a distinct procedure, "precision alignment loop (PAL)", to calibrate any CBCT system with a circular trajectory. We describe the calibration procedure by using a line-beads phantom, and how PAL determines the misalignments from a CBCT system. PAL also yields the uncertainties in the simulated calibration to give an estimate of the errors in the misalignments. From the analytical simulations, PAL can precisely obtain the source-to-rotation axis distance (SRD), and the geometric center G, "the point in z-axis meets the detector", where the z-axis is coincident with the line from the X-ray source that intersects the axis of the rotation (AOR) orthogonally. The uncertainties of three misalignment angles of the detector are within ±0.05°, which is close to ±0.04° for the results of Yang et al. [18], but our method is easy and simple to implement. Our distinct procedure, on the other hand, yields the calibration of a micro-CT system and an example of reconstructed images, showing our calibration method for the CBCT system to be simple, precise, and accurate.