The Role of Pancreatitis Risk Genes in Endocrine Insufficiency Development After Acute Pancreatitis in Children.

BACKGROUND & AIMS: Acute pancreatitis (AP) is increasingly recognized as a risk factor for diabetes mellitus (DM). We aimed to study the association of pancreatitis genes with pancreatic endocrine insufficiency (pre-DM and DM) development post-AP in children. METHODS: This was an observational cohort study that enrolled subjects ≤21 years with their first episode of AP and followed them for 12 months for the development of pancreatic endocrine insufficiency. Pancreatitis risk genes (CASR, CEL, CFTR, CLDN2, CPA1, CTRC, PRSS1, SBDS, SPINK1, and UBR1) were sequenced. A genetic risk score was derived from all genes with univariable P < .15. RESULTS: A total 120 subjects with AP were genotyped. Sixty-three subjects (52.5%) had at least 1 reportable variant identified. For modeling the development of pancreatic endocrine insufficiency at 1 year, 6 were excluded (2 with DM at baseline, 3 with total pancreatectomy, and 1 death). From this group of 114, 95 remained normoglycemic and 19 (17%) developed endocrine insufficiency (4 DM, 15 pre-DM). Severe AP (58% vs 20%; P = .001) and at least 1 gene affected (79% vs 47%; P = .01) were enriched among the endocrine-insufficient group. Those with versus without endocrine insufficiency were similar in age, sex, race, ethnicity, body mass index, and AP recurrence. A model for pre-DM/DM development included AP severity (odds ratio, 5.17 [1.66-16.15]; P = .005) and genetic risk score (odds ratio, 4.89 [1.83-13.08]; P = .002) and had an area under the curve of 0.74. CONCLUSIONS: In this cohort of children with AP, pancreatitis risk genes and AP disease severity were associated with pre-DM or DM development post-AP.

Pancreas volumes in pediatric patients following index acute pancreatitis and acute recurrent pancreatitis.

BACKGROUND/OBJECTIVES: Pancreas volume derived from imaging may objectively reveal volume loss relevant to identifying sequelae of acute pancreatitis (AP) and ultimately diagnosing chronic pancreatitis (CP). The purposes of this study were to: (1) quantify pancreas volume by imaging in children with either (a) a single episode of AP or (b) acute recurrent pancreatitis (ARP), and (2) compare these volumes to normative volumes. METHODS: This retrospective study was institutional review board approved. A single observer segmented the pancreas (3D Slicer; slicer.org) on n = 30 CT and MRI exams for 23 children selected from a prospective registry of patients with either an index attack of AP or with ARP after a known index attack date. Patients with CP were excluded. Segmented pancreas volumes were compared to published normal values. RESULTS: Mean pancreas volumes normalized to body surface area (BSA) in the index AP and ARP groups were 38.2 mL/m2 (range: 11.8-73.5 mL/m2) and 27.9 mL/m2 (range: 8.0-69.2 mL/m2) respectively. 43 % (6/14) of patients post-AP had volumes below the 25th percentile, 1 (17 %) of which was below the 5th percentile (p = 0.3027 vs. a normal distribution). Post-ARP, 44 % (7/16) of patients had volumes below the 5th percentile (p < 0.001). CONCLUSIONS: A significant fraction (40 %) of children with ARP have pancreas volumes <5th percentile for BSA even in the absence of CP. A similar, but not statistically significant, fraction have pancreas volumes <25th percentile after an index attack of AP. Pancreatic parenchymal volume deserves additional investigation as an objective marker of parenchymal damage from acute pancreatitis and of progressive pancreatitis in children.

Faster discharge with lactated ringers than normal saline in first 72 h of acute pancreatitis: A multicenter randomized trial.

OBJECTIVES: Data driven strategies for acute pancreatitis (AP) in pediatrics are limited; adult data suggests lactated ringers (LR) compared to normal saline (NS) resulted in favorable outcomes, but has not been studied in pediatrics. Our objective was to evaluate the efficacy of LR during the first 48 h of an AP episode compared with NS. STUDY DESIGN: A multisite randomized controlled clinical trial, from 2015 to 2020 (Clinical Trials.gov NCT03242473). Patients were randomized to exclusively LR or NS for the first 48 h. Primary outcomes were serial C-reactive protein (CRP) values. Secondary outcomes included other lab values, time to feeds, length of stay (LOS), systemic inflammatory response syndrome (SIRS) development, and progression to severe AP (SAP). RESULTS: We studied 76 patients (38 LR, 38 NS). CRP at 24 and 48 h were not significantly different between LR or NS group. Additionally, there were no differences in trends of BUN, amylase, lipase, SIRS status, or SAP development between the LR and NS group at 24 and 48 h. A higher proportion of LR patients (32%, 12/38) were discharged before 48 h compared to NS (13%, 5/38). The LR group had a significantly higher rate of discharge within the first 72 h compared to the NS group (p = 0.02). CONCLUSION: The use of LR was associated with a faster rate of discharge during the intervention period and in the first 72 h, but no other differences compared to NS. This reduction in length of hospitalization has significant implications for patients and healthcare costs.

Screening and Referral for Behavioral Health Symptoms in Collegiate Athletes.

OBJECTIVE: We aim to investigate the prevalence of behavioral health symptoms in collegiate athletes and the frequency of referrals prompted by a preparticipation behavioral health screener. DESIGN: Athletes completed a screening battery to detect behavioral health symptoms and sports psychology clinicians designed criteria for intervention based on the severity of symptoms reported. Data from the screener was retrospectively de-identified and analyzed. SETTING: National Collegiate Athletic Association Division-I university. PARTICIPANTS: All athletes on active rosters were required to complete the screener as a component of the preparticipation examination. INTERVENTIONS: Sports psychology clinicians created a protocol for intervention based on the number and severity of symptoms reported on the screener. MAIN OUTCOME MEASURES: Communication with athletes and referrals made to behavioral health services. RESULTS: Of the 1126 surveys completed, 39% had behavioral health symptoms necessitating behavioral health referral. Twelve percent required a safety check-in, given the severity of their symptoms. Seven percent of the respondents were newly established with behavioral health services. CONCLUSIONS: Symptoms of behavioral health disorders are common among athletes and yet, for a myriad of reasons, many choose to forgo treatment. By implementing a behavioral health screening battery, the prevalence of behavioral health symptoms among athletes at our institution was elucidated and many athletes were newly established with behavioral health services. The tiered intervention protocol in this study allowed for appropriate assessment and triage of high-risk individuals, while simultaneously providing lower-risk individuals with appropriate resources. Surveillance for behavioral health symptoms among college athletes using a screening battery with a tiered intervention protocol can ensure at-risk athletes are identified, contacted, and referred to behavioral health services, potentially improving their athletic performance and overall well-being, while averting poor outcomes.

Prevalence of Gastrointestinal Symptoms and Impact on Quality of Life at 1-Year Follow-Up of Initial Attack of Acute Pancreatitis.

OBJECTIVES: This study aims to describe the prevalence of gastrointestinal (GI) symptoms following the first time occurrence of acute pancreatitis (AP) and to measure the impact of the episode on patient health-related quality of life (HRQOL) from the perspectives of patients and parents. METHODS: Questionnaires regarding GI symptoms 1 year following the initial occurrence of AP were obtained from 74 pediatric patients. Thirty of these patients completed both the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and the PedsQL Gastrointestinal Symptoms and Worry Scales. These data were compared to legacy-matched healthy controls. RESULTS: Children with a standalone occurrence of AP experienced a similar rate of GI symptoms compared to those who progressed to acute recurrent pancreatitis (ARP) within 1 year. PedsQL 4.0 Generic Core Scales scores were significantly lower for children self-report and parent proxy-report for patients that experienced AP compared to healthy controls. AP patients also demonstrated significantly more symptoms than healthy controls in the Gastrointestinal Symptoms and Worry Scales across multiple domains. CONCLUSIONS: Gastrointestinal symptoms affect many children who experience a single AP event even without recurrent attacks. The burden of symptoms is not significantly different from those who develop ARP. This is a novel study that evaluates patient-reported outcomes in children following an AP attack and demonstrates there is a significant impact on HRQOL in children and family experiences post AP. More data are needed to study the progression of disease and the extended impact of AP following an initial AP attack in pediatric patients.

Digestible indispensable amino acid score (DIAAS) is greater in animal-based burgers than in plant-based burgers if determined in pigs.

PURPOSE: Determine digestible indispensable amino acid score (DIAAS) for animal- and plant-based burgers and test the hypothesis that DIAAS calculated for a burger and a burger bun is additive in a combined meal. METHODS: Ten ileal cannulated gilts were fed experimental diets for six 9-d periods with ileal digesta being collected on d 8 and 9 of each period. Six diets contained a burger (i.e., 80% lean beef, 93% lean beef, 80% lean pork, Impossible Burger, or Beyond Burger) or a burger bun as the sole source of crude protein and amino acids. Three additional diets were based on a combination of the bun and 80% beef, pork, or Impossible Burger. A nitrogen-free diet was also used. The DIAAS for all ingredients and mixed meals was calculated for children from 6 months to 3 years and for individuals older than 3 years, and DIAAS for combined meals was predicted from individual ingredient DIAAS. RESULTS: The 93% lean beef and the pork burgers had greater (P < 0.05) DIAAS than the plant-based burgers for both age groups. The 80% lean beef burger had greater (P < 0.05) DIAAS than the plant burgers for children from 6 months to 3 years, and greater (P < 0.05) DIAAS than the Beyond Burger for individuals older than 3 years. There were no differences between the measured and predicted DIAAS. CONCLUSIONS: The protein quality of animal-based burgers is greater than that of plant-based burgers. However, for individuals older than 3 years, the Impossible Burger has comparable protein quality to the 80% lean beef burger. The DIAAS obtained from individual foods is additive in mixed meals.

Cytokine Profile Elevations on Admission Can Determine Risks of Severe Acute Pancreatitis in Children.

OBJECTIVES: To utilize a Luminex platform to examine multiple cytokines simultaneously as well as clinical laboratory testing to identify markers that predict acute pancreatitis severity in the pediatric population on admission. STUDY DESIGN: Patients (<19 years of age) prospectively enrolled over a 4-year period in a single institution acute pancreatitis database were included in separate derivation and validation cohorts. Plasma samples were obtained within 48 hours of admission and stored for analysis. Samples from mild acute pancreatitis and severe acute pancreatitis (moderately severe and severe combined) were analyzed using Luminex panels and C-reactive protein (CRP) testing. RESULTS: The derivation cohort examined 62 cytokines in 66 subject samples (20 control, 36 mild acute pancreatitis, 10 severe acute pancreatitis) and identified interleukin 6 (IL-6) (P = .02) and monocyte chemotactic protein-1 (MCP-1) (P = .02) as cytokines that were differentially expressed between mild and severe acute pancreatitis. Our validation cohort analyzed 76 cytokines between 10 controls, 19 mild acute pancreatitis, and 6 severe acute pancreatitis subjects. IL-6 (P = .02) and MCP-1 (P = .007) were again found to differentiate mild acute pancreatitis from severe acute pancreatitis. CRP values were obtained from 53 of the subjects, revealing a strong association between elevated CRP values and progression to severe disease (P < .0001). CONCLUSIONS: This study identified and validated IL-6 and MCP-1 as predictors of severe acute pancreatitis using 2 distinct cohorts and showed that CRP elevation is a marker of progression to severe acute pancreatitis. These biomarkers have not been extensively studied in the pediatric acute pancreatitis population. Our data allows for risk-stratification of patients with acute pancreatitis, and represent novel insight into the immunologic response in severe acute pancreatitis.

Carotid Stent Explant Indications and Outcomes.

BACKGROUND: Carotid artery stenting is an alternative to carotid endarterectomy, especially in patients deemed to have significant anatomic or medical risk for the latter. There is scant literature, however, on indications for and outcomes of carotid stent (CAS) explant. We sought to determine indications and outcomes of CAS explant at our institution. METHODS: We queried a prospectively maintained institutional vascular surgery database as well as hospital records to identify patients undergoing carotid stent explant from 2010-2020. Ten patients were identified. Their charts were reviewed to obtain demographic, comorbidity, procedural, and outcomes data. Data of particular interest were preoperative atherosclerotic factors, indications for CAS explant, carotid repair strategy, and 30-day post-procedural complications. Data were analyzed for ranges and means. RESULTS: Ten patients were identified. Comorbidity was common: all patients had at least 1 atherosclerotic risk factor, with hypertension and hypercholesterolemia being the most common. Seven (70.0%) patients had recurrent stenosis as the indication for explant. Seven (70.0%) presented symptomatically. Five (50.0%) cases of restenosis had been refractory to angioplasty. There were 3 (30.0%) instances of CAS explant due to infection. Only 1 (12.5%) index CAS was performed at our institution. There was a mean hospital length of stay of 4.5 days. One patient had vocal cord paralysis requiring no intervention. There was no (0%) 30-day mortality, stroke, or postoperative wound infections. CONCLUSIONS: Our series had 0% 30-day mortality, stroke, and postoperative wound infection suggesting that CAS explant may be performed safely. Our series is small but represents the largest single institution series to date. This procedure may become increasingly common in the coming years with the more frequent use of CAS; additional data is needed to rigorously understand outcomes.

Drug induced pancreatitis is the leading known cause of first attack acute pancreatitis in children.

BACKGROUND/OBJECTIVES: Drug induced acute pancreatitis (DIAP) as one of the acute pancreatitis (AP) risks factors is a poorly understood entity. The aim of the current study was to compare the characteristics and course of DIAP cases in children presenting with a first attack of AP. METHODS: Patients presenting with AP were included in a prospective database. We enrolled 165 AP patients that met criteria for inclusion. DIAP patients were included in that group if they were exposed to a drug known to be associated with AP and the rest were included in the non-drug induced-acute pancreatitis (non-DIAP) group. RESULTS: DIAP was observed in 40/165 (24%) of cases, 24 cases had drug-induced as the sole risk factor, and 16 had DIAP with another risk factor(s). The two groups were similar in intravenous fluid and feeding managements, but ERCP was more commonly performed in the non- DIAP group, 14 (11%), vs 0% in the DIAP group, p = 0.02. Moderately severe [9 (23%) vs 11 (9%)] and severe AP [7 (18%) vs 6 (5%)] were more commonly associated with DIAP than non- DIAP, p = 0.001. DIAP was more commonly associated with ICU stay, 10 (25%), vs 12 (10%), p = 0.01, hospital stay was longer in DIAP median (IQR) of 6 (3.9-11) days vs 3.3 (2-5.7) days in non- DIAP, p = 0.001. The DIAP group had a significantly higher proportion of comorbidities (p < 0.0001). CONCLUSIONS: DIAP is a leading risk factor for a first attack of AP in children and is associated with increased morbidity and severity of the pancreatitis course. DIAP warrants further investigation in future studies.

Collective motion of driven semiflexible filaments tuned by soft repulsion and stiffness.

In active matter systems, self-propelled particles can self-organize to undergo collective motion, leading to persistent dynamical behavior out of equilibrium. In cells, cytoskeletal filaments and motor proteins form complex structures important for cell mechanics, motility, and division. Collective dynamics of cytoskeletal systems can be reconstituted using filament gliding experiments, in which cytoskeletal filaments are propelled by surface-bound motor proteins. These experiments have observed diverse dynamical states, including flocks, polar streams, swirling vortices, and single-filament spirals. Recent experiments with microtubules and kinesin motor proteins found that the collective behavior of gliding filaments can be tuned by altering the concentration of the crowding macromolecule methylcellulose in solution. Increasing the methylcellulose concentration reduced filament crossing, promoted alignment, and led to a transition from active, isotropically oriented filaments to locally aligned polar streams. This emergence of collective motion is typically explained as an increase in alignment interactions by Vicsek-type models of active polar particles. However, it is not yet understood how steric interactions and bending stiffness modify the collective behavior of active semiflexible filaments. Here we use simulations of driven filaments with tunable soft repulsion and rigidity in order to better understand how the interplay between filament flexibility and steric effects can lead to different active dynamic states. We find that increasing filament stiffness decreases the probability of filament alignment, yet increases collective motion and long-range order, in contrast to the assumptions of a Vicsek-type model. We identify swirling flocks, polar streams, buckling bands, and spirals, and describe the physics that govern transitions between these states. In addition to repulsion and driving, tuning filament stiffness can promote collective behavior, and controls the transition between active isotropic filaments, locally aligned flocks, and polar streams.

Sensitivity of Biochemical and Imaging Findings for the Diagnosis of Acute Pancreatitis in Children.

OBJECTIVE: To determine the diagnostic sensitivity of serum biomarkers and imaging in the diagnosis of acute pancreatitis in children. STUDY DESIGN: This was a cross-sectional analysis of prospective registry data for children (age <21 years) whose first documented attack of acute pancreatitis occurred between March 2013 and October 2016 at a single-institution, tertiary care center. Main outcome was sensitivity of serum biomarkers and of imaging modalities, measured via descriptive statistics. RESULTS: In total, 112 children met the criteria for acute pancreatitis; 57 (51%) were male with a median age of 13.4 years (IQR 9.3-15.8 years). Serum amylase and lipase levels were obtained in 85 (76%) and 112 (100%) patients, respectively. Imaging was performed in 98 (88%) patients, with abdominal ultrasound (US) performed in 84 (75%) and computed tomography and/or magnetic resonance imaging performed in 46 (41%) patients. Fifty-three (47%) patients met all 3 diagnostic criteria (clinical, biochemical, and imaging) for acute pancreatitis. Laboratory testing had a 5.4% false-negative rate for acute pancreatitis. Serum lipase alone and amylase alone were 95% (95% CI 89%-98%) and 39% (95% CI 28%-50%) sensitive for acute pancreatitis, respectively. Imaging (any modality) was 61% sensitive (95% CI 51%-71%) for acute pancreatitis with a 34% false-negative rate. US alone was 52% (95% CI 41%-63%) sensitive for acute pancreatitis and computed tomography/magnetic resonance imaging was 78% (95% CI 63%-89%) sensitive. Combinations of diagnostic criteria performed no better than laboratory testing alone. CONCLUSIONS: The majority of children coming to medical attention with their first documented occurrence of acute pancreatitis have characteristic symptoms. Serum lipase is highly sensitive for the diagnosis of acute pancreatitis, and serum amylase is moderately sensitive. Imaging, particularly US, is only moderately sensitive, and cross-sectional imaging provides greater sensitivity for diagnosing acute pancreatitis.

Genetic variants in acute, acute recurrent and chronic pancreatitis affect the progression of disease in children.

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) is emerging in pediatrics. A subset of children with AP progresses to acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). The role of extensive gene testing in the progression has not been investigated previously. We have followed children enrolled in the registry and at our center for progression to ARP and CP after the first attack. METHODS: This study utilizes an extensive gene sequencing panel as a platform to evaluate the role of genetics in first attack AP, and the progression over time, from first attack to ARP and CP in children. RESULTS: Genes, with corresponding variants were involved in the 3 groups studied: AP, ARP and CP. We have shown that the presence of gene variants from the eight tested genes is enriched in the CP group compared to the AP and ARP groups. The presence of more than one gene was associated with CP (p = 0.01). SPINK1 mutation(s) was significantly associated with faster progression to ARP, (p = 0.04). Having a variant from CFTR, SPINK1 or PRSS1, was associated with the faster progression from AP to CP over time (p < 0.05). CONCLUSIONS: This study shows that genetics have a significant role in progression to ARP and CP from the first attack of pancreatitis.

Rapid Progression of Acute Pancreatitis to Acute Recurrent Pancreatitis in Children.

OBJECTIVE: Research is lacking on the natural history of acute pancreatitis (AP) progression to acute recurrent pancreatitis (ARP). The aim of this project was to study the progression from AP to ARP among pediatric patients with pancreatitis to better understand the presentation and natural history of pancreatitis. METHODS: Patients presenting with AP were included in a prospective database in Research Electronic Data Capture. We enrolled 115 patients with AP from March 2013 to November 2016. Physicians completed surveys regarding clinical data for patients with first attack of AP. Patients were followed prospectively, with data on progression entered when patients presented with ARP. RESULTS: The most common etiologies for the first attack of AP were idiopathic (31%), toxic/drug-related (23%), and biliary/gallstone (18%). Twenty of the 115 patients (17%) developed ARP during the follow-up period. Seventy percent (14/20) of patients with ARP progressed from AP to ARP within 5 months from first diagnosis. A comparison of patients who rapidly progressed to ARP within 3 months (n = 12) to those followed for >3 months without progression in 3 months (n = 97) revealed associations with a higher weight percentile for age (P = 0.045), male sex (P = 0.03), and presence of pancreatic necrosis during first AP attack (P = 0.004). Progression to ARP significantly differed by etiology group with genetics having the highest risk for ARP progression over time and patients with gallstone/biliary, viral/systemic, and obstructive (nongallstone) having the lowest risk for ARP progression over time (P = 0.02). CONCLUSIONS: Most patients who progressed from AP to ARP progressed within 5 months. The presence of a higher weight percentile for age, male sex, and pancreatic necrosis during the first AP attack are associated with rapid progression to ARP.

Human Neural Stem Cell Extracellular Vesicles Improve Recovery in a Porcine Model of Ischemic Stroke.

BACKGROUND AND PURPOSE: Recent work from our group suggests that human neural stem cell-derived extracellular vesicle (NSC EV) treatment improves both tissue and sensorimotor function in a preclinical thromboembolic mouse model of stroke. In this study, NSC EVs were evaluated in a pig ischemic stroke model, where clinically relevant end points were used to assess recovery in a more translational large animal model. METHODS: Ischemic stroke was induced by permanent middle cerebral artery occlusion (MCAO), and either NSC EV or PBS treatment was administered intravenously at 2, 14, and 24 hours post-MCAO. NSC EV effects on tissue level recovery were evaluated via magnetic resonance imaging at 1 and 84 days post-MCAO. Effects on functional recovery were also assessed through longitudinal behavior and gait analysis testing. RESULTS: NSC EV treatment was neuroprotective and led to significant improvements at the tissue and functional levels in stroked pigs. NSC EV treatment eliminated intracranial hemorrhage in ischemic lesions in NSC EV pigs (0 of 7) versus control pigs (7 of 8). NSC EV-treated pigs exhibited a significant decrease in cerebral lesion volume and decreased brain swelling relative to control pigs 1-day post-MCAO. NSC EVs significantly reduced edema in treated pigs relative to control pigs, as assessed by improved diffusivity through apparent diffusion coefficient maps. NSC EVs preserved white matter integrity with increased corpus callosum fractional anisotropy values 84 days post-MCAO. Behavior and mobility improvements paralleled structural changes as NSC EV-treated pigs exhibited improved outcomes, including increased exploratory behavior and faster restoration of spatiotemporal gait parameters. CONCLUSIONS: This study demonstrated for the first time that in a large animal model novel NSC EVs significantly improved neural tissue preservation and functional levels post-MCAO, suggesting NSC EVs may be a paradigm changing stroke therapeutic.

Predictive biomarkers for acute gallstone pancreatitis in the pediatric population.

BACKGROUND: Early biomarkers for diagnosis of gallstone pancreatitis (GP) in pediatrics have not been well studied. Reliably differentiating GP from other causes of acute pancreatitis (AP) would allow for early diagnosis and prompt management. We sought to assess biomarkers and clinical variables for early GP diagnosis from a prospectively-enrolled registry of pediatric patients presenting with first AP episode. METHODS: Cross-sectional analysis of a prospective acute pancreatitis registry of children enrolled from March 2013 through October 2016 was performed. Fisher's exact test and Wilcoxon rank sum test were used to compare demographic and clinical variables between GP and non-GP groups. A multivariable logistic regression model was derived, and receiver operating characteristic (ROC) curve was built using stepwise selection. RESULTS: 114 subjects were enrolled (21 with GP, 93 as non-GP). Median was statistically higher for GP patients in lipase values X upper limit of normal (ULN) on admission, weight percentile for age, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase. By multivariable analysis, significant predictors were ALT and Lipase xULN. A model built using these two variables for prediction of GP identified an AUROC of 0.85. At a predictive probability of 0.35, the model had an 80% sensitivity, 93% specificity, 76% positive predictive value and 95% negative predictive value. CONCLUSIONS: We have developed a model for predicting GP in children that could help guide clinical management of AP patients. Future studies are needed to validate use of laboratory findings and clinical variables in evaluation of gallstone etiology in pediatric AP patients.

Immediate but Temporal Response: The Role of Distal Epithelial Cells in Wound Healing.

Efficient oral mucosal wound healing requires coordinated responses from epithelial progenitor cells, yet their spatiotemporal recruitment and activation remain unclear. Using a mouse model of palatal mucosal wound healing, we investigated the dynamics of epithelial cells during this process. Proliferation analysis revealed that, in addition to the expected proliferation center near the wound edge, distal cell populations rapidly activated post-injury by elevating their mitotic activity. These distal cells displayed predominant lateral expansion in the basal layer, suggesting roles beyond just tissue renewal. However, while proximal proliferation center cells sustained heightened proliferation until re-epithelialization was completed, distal cells restored basal turnover rates before wound closure, indicating temporally confined contributions. Lineage tracing of Wnt-responsive epithelial cells showed remarkable clone expansion in basal layers both proximally and distally after wounding, contrasting with gradual clone expansion in homeostasis. Although prioritizing tissue repair, epithelial progenitor cells maintained differentiation programs and barrier functions, with the exception of the leading edge. At the leading edge, we found accelerated cell turnover, but the differentiation program was suspended. In summary, our findings uncovered that oral wound re-epithelialization involves two phases: an initial widespread response with proliferation of proximal and distal cells, followed by proliferation confined to the wound proximal region. Uncovering these stage-specific healing mechanisms provides insights for developing targeted therapeutic strategies to improve wound care.

Nutritional parameters following first episode of pediatric acute pancreatitis.

BACKGROUND AND OBJECTIVES: Acute pancreatitis (AP) carries the risk of subsequent nutritional deficiencies. The prevalence of these deficiencies following a single episode of AP in children is unknown. We aimed to determine prevalence of anthropometric and laboratory-based measures of nutritional status in children following their first (index) admission for AP. METHODS: Prospective observational cohort study of patients ≤21 years of age with first episode of confirmed AP. Anthropometric and laboratory values were obtained at time of AP onset and at follow up time points of 3 and 12 months (m) post AP. AP attack was classified as either: mild, moderately severe or severe (which were combined in one group (SAP)). RESULTS: 181 patients met criteria and were followed prospectively with 52% male, a median age of 13.7 years (IQR 9.4-16.0) and median Body Mass Index (BMI) Z-score of 0.6 (IQR -0.5, 1.6). Most patients had mild AP (140, 77%), with 23% meeting criteria for moderate or severe (41/181). 6 (3%) had diabetes mellitus (DM) predating AP and were excluded from further analysis. BMI Z-score remained stable during the follow up period. 13% of patients developed pre-DM or DM at 3m or 12m. Nearly one third of patients had low ferritin at 3m (29%) or 12m (29%). At 12m, 8% of patients had Vitamin A deficiency. 6% of patients had low Vitamin E levels at 3m and 5% at 12m. Over half of patients at both 3m and 12m had 25 OH Vitamin D insufficiency or deficiency (56% and 56%). Prolonged International Normalized Ratio (INR) (>1.3) was seen in 9% of patients at 12m. Very low albumin (<3.5 g/dL) was found in 24% of patients at 3m and 18% at 12m (Table 1). Patients with very low albumin at 3m were younger (median 10.7 vs. 14.2 years, p = 0.04), however sex, BMI Z-score and AP severity were not associated with albumin level. Although BMI Z-score did not differ between the groups, those with SAP had a significant decrease in BMI Z-score from first attack compared to mild AP at 3m (-0.4 vs. 0.0, p = 0.0002, Figure 2). At 3m, Vitamin E deficiency in SAP versus mild AP was found in 20% vs 2% (p = 0.04) and SAP had a lower median hematocrit (35.8 vs. 37.6, p = 0.046). There were no other laboratory significant differences at 3m in mild versus SAP groups. At 12m, those with SAP were more likely to have pre-DM or DM compared to mild AP (31% vs. 7%, p = 0.002). No other significant laboratory differences occurred at 12m. CONCLUSIONS: After the first AP attack patients experience nutritional deficiencies, including ferritin, all fat-soluble vitamins, and low albumin. SAP is associated with a decrease in BMI Z-score, increased prevalence of vitamin E deficiency at 3m, and an increase in pre-diabetes and diabetes at 12m. Serial monitoring of vitamin and mineral values post AP is warranted and further prospective studies are needed.

Comparison of the In Vitro Iron Bioavailability of Tempeh Made with Tenebrio molitor to Beef and Plant-Based Meat Alternatives.

Iron is an essential mineral that supports biological functions like growth, oxygen transport, cellular function, and hormone synthesis. Insufficient dietary iron can lead to anemia and cause fatigue, cognitive impairment, and poor immune function. Animal-based foods provide heme iron, which is more bioavailable to humans, while plant-based foods typically contain less bioavailable non-heme iron. Edible insects vary in their iron content and may have heme or non-heme forms, depending on their diet. Edible insects have been proposed as a protein source that could address issues of food insecurity and malnutrition in low resource contexts; therefore, it is important to understand the bioavailability of iron from insect-based foods. In this study, we used Inductively Coupled Plasma and Mass Spectrometry (IPC-MS) and Caco-2 cell culture models to compare the soluble and bioavailable iron among five different lab-produced tempeh formulations featuring Tenebrio molitor (mealworm) with their non-fermented raw ingredient combinations. Finally, we compared the iron bioavailability of a mealworm tempeh with two sources of conventional beef (ground beef and sirloin steaks) and two commercially available plant-based meat alternatives. The results show that while plant-based meat alternatives had higher amounts of soluble iron, particularly in the Beyond Burger samples, the fermented mealworm-based tempeh had greater amounts of bioavailable iron than the other samples within the set. While all the samples presented varying degrees of iron bioavailability, all products within the sample set would be considered good sources of dietary iron.

Acute pancreatitis is associated with gut dysbiosis in children.

BACKGROUND: Pediatric acute pancreatitis (AP) is associated with significant morbidity. Therefore, improved understanding of children who will develop severe AP is critical. Adult studies have reported AP associated gut dysbiosis, but pediatric studies are lacking. AIMS: Assess stool microbial taxonomic and functional profiles of children with first attack of AP compared to those of healthy controls (HC), and between mild and severe AP METHODS: Children under 21 years hospitalized at a tertiary center (n = 30) with first AP attack were recruited including HC (n = 34) from same region. Shotgun metagenomic sequencing was performed on extracted DNA. RESULTS: Demographics were similar between AP and HC. Alpha diversity (-0.68 ± 0.13, p-value < 0.001), and beta-diversity (R2=0.13, p-value < 0.001) differed, in children with AP compared to HC. Species including R.gnavus, V.parvula, E.faecalis, C.innocuum were enriched in AP. MetaCyc pathways involved in amino acid metabolism and fatty acid beta-oxidation were enriched in AP. Beta-diversity (R2=0.06, p-value = 0.02) differed for severe AP compared to mild AP with enrichment in E.faecalis and C.citroniae. CONCLUSIONS: Gut dysbiosis occurs in pediatric AP and is associated with AP severity. A multicenter study confirming these findings could pave way for interventional trials manipulating the gut microbiome to mitigate AP severity.