Highly dynamic gamma-ray emissions are common in tropical thunderclouds.

Thunderstorms emit fluxes of gamma rays known as gamma-ray glows1,2, sporadically observed by aircraft1,3-7, balloons8-11 and from the ground12-18. Observations report increased gamma-ray emissions by tens of percent up to two orders of magnitude above the background, sometimes abruptly terminated by lightning discharges1,3-5. Glows are produced by the acceleration of energetic electrons in high-electric-field regions within thunderclouds8 and contribute to charge dissipation3. Glows had been considered as quasi-stationary phenomena3,5,12, with durations up to a few tens of seconds and spatial scales up to 10-20 km. However, no measurements of the full extension in space and time of a gamma-ray-glow region and their occurring frequency have been reported so far. Here we show that tropical thunderclouds over ocean and coastal regions commonly emit gamma rays for hours over areas up to a few thousand square kilometres. Emission is associated with deep convective cores; it is not uniform and continuous but shows characteristic timescales of 1-10 s and even subsecond for individual glows. The dynamics of gamma-glowing thunderclouds strongly contradicts the quasi-stationary picture of glows and instead resembles that of a huge gamma-glowing 'boiling pot' in both pattern and behaviour.

Flickering gamma-ray flashes, the missing link between gamma glows and TGFs.

Two different hard-radiation phenomena are known to originate from thunderclouds: terrestrial gamma-ray flashes (TGFs)1 and gamma-ray glows2. Both involve an avalanche of electrons accelerated to relativistic energies but are otherwise different. Glows are known to last for one to hundreds of seconds, have moderate intensities and originate from quasi-stationary thundercloud fields2-5. TGFs exhibit high intensities and have characteristic durations of tens to hundreds of microseconds6-9. TGFs often show a close association with an emission of strong radio signals10-17 and optical pulses18-21, which indicates the involvement of lightning leaders in their generation. Here we report unique observations of a different phenomenon, which we call flickering gamma-ray flashes (FGFs). FGFs resemble the usual multi-pulse TGFs22-24 but have more pulses and each pulse has a longer duration than ordinary TGFs. FGF durations span from 20 to 250 ms, which reaches the lower boundary of the gamma-ray glow duration. FGFs are radio and optically silent, which makes them distinct from normal TGFs. An FGF starts as an ordinary gamma-ray glow, then suddenly increases exponentially in intensity and turns into an unstable, 'flickering' mode with a sequence of pulses. FGFs could be the missing link between the gamma-ray glows and conventional TGFs, whose absence has been puzzling the atmospheric electricity community for two decades.

Follow-Up Colonoscopy for Detection of Missed Colorectal Cancer After Diverticulitis.

BACKGROUND & AIMS: Colonoscopy often is recommended after an episode of diverticulitis to exclude missed colorectal cancer (CRC). This is a controversial recommendation based on limited evidence. We estimated the prevalence and odds of CRC and advanced colorectal neoplasia on colonoscopy in patients with diverticulitis compared with CRC screening. METHODS: Using data from the Gastrointestinal Quality Improvement Consortium registry, we performed a cross-sectional study with patients ≥40 years old undergoing outpatient colonoscopy for an indication of diverticulitis follow-up evaluation or CRC screening. The primary outcome was CRC. The secondary outcome was advanced colorectal neoplasia. Odds ratios (ORs) and 95% CIs were calculated. RESULTS: We identified 4,591,921 outpatient colonoscopies performed for screening and 91,993 colonoscopies for diverticulitis follow-up evaluation. CRC prevalence was 0.33% in colonoscopies for screening and 0.31% in colonoscopies for diverticulitis. Compared with screening, patients with diverticulitis were less likely to have CRC (adjusted OR, 0.84; 95% CI, 0.74-0.94). CRC prevalence decreased to 0.17% in colonoscopies performed for diverticulitis only. Compared with screening, patients with diverticulitis as the only indication were less likely to have CRC (adjusted OR, 0.49; 95% CI, 0.36-0.68). CRC prevalence increased to 1.43% in patients with complicated diverticulitis. Compared with screening, patients with complicated diverticulitis were more likely to have CRC (adjusted OR, 3.57; 95% CI, 1.59-8.01). CONCLUSIONS: The risk of CRC cancer is low in most patients with diverticulitis. Patients with complicated diverticulitis are the exception. Our results suggest that colonoscopy to detect missed CRC should include diverticulitis patients with a complication and those not current with CRC screening.

Clinical Features and Treatment Response to Topical Steroids in Ethnic and Racial Minority Patients With Eosinophilic Esophagitis.

INTRODUCTION: Differences in eosinophilic esophagitis (EoE) presentation and outcomes by ethnicity or race remain understudied. We aimed to determine whether EoE patients of Hispanic/Latinx ethnicity or non-White race have differences in presentation at diagnosis or response to topical corticosteroid (tCS) treatment. METHODS: This retrospective cohort study included subjects of any age with a new diagnosis of EoE and documentation of ethnicity or race. For those who had treatment with tCS and follow-up endoscopy/biopsy, we assessed histologic response (<15 eosinophils/hpf), global symptom response, and endoscopic response. Hispanic EoE patients were compared with non-Hispanics at baseline and before and after treatment. The same analyses were repeated for White vs non-Whites. RESULTS: Of 1,026 EoE patients with ethnicity data, just 23 (2%) were Hispanic. Most clinical features at presentation were similar to non-Hispanic EoE patients but histologic response to tCS was numerically lower (38% vs 57%). Non-White EoE patients (13%) were younger at diagnosis and had less insurance, lower zip code-level income, shorter symptom duration, more vomiting, less dysphagia and food impaction, fewer typical endoscopic features, and less dilation. Of 475 patients with race data treated with tCS, non-Whites had a significantly lower histologic response rate (41% vs 59%; P = 0.01), and odds of histologic response remained lower after controlling for potential confounders (adjusted odds ratio 0.40, 95% confidence intervals: 0.19-0.87). DISCUSSION: Few EoE patients at our center were Hispanic, and they had similar clinical presentations as non-Hispanics. The non-White EoE group was larger, and presentation was less dysphagia-specific. Non-White patients were also less than half as likely to respond to tCS.

The diabetes management experiences questionnaire: Psychometric validation among adults with type 1 diabetes.

AIMS: To examine the psychometric properties of the Diabetes Management Experiences Questionnaire (DME-Q). Adapted from the validated Glucose Monitoring Experiences Questionnaire, the DME-Q captures satisfaction with diabetes management irrespective of treatment modalities. METHODS: The DME-Q was completed by adults with type 1 diabetes as part of a randomized controlled trial comparing hybrid closed loop (HCL) to standard therapy. Most psychometric properties were examined with pre-randomization data (n = 149); responsiveness was examined using baseline and 26-week follow-up data (n = 120). RESULTS: Pre-randomization, participants' mean age was 44 ± 12 years, 52% were women. HbA1c was 61 ± 11 mmol/mol (7.8 ± 1.0%), diabetes duration was 24 ± 12 years and 47% used an insulin pump prior to the trial. A forced three-factor analysis revealed three expected domains, that is, 'Convenience', 'Effectiveness' and 'Intrusiveness', and a forced one-factor solution was also satisfactory. Internal consistency reliability was strong for the three subscales ( α range = 0.74-0.84) and 'Total satisfaction' ( α = 0.85). Convergent validity was demonstrated with moderate correlations between DME-Q 'Total satisfaction' and diabetes distress (PAID: rs = -0.57) and treatment satisfaction (DTSQ; rs = 0.58). Divergent validity was demonstrated with a weak correlation with prospective/retrospective memory (PRMQ: rs = -0.16 and - 0.13 respectively). Responsiveness was demonstrated, as participants randomized to HCL had higher 'Effectiveness' and 'Total satisfaction' scores than those randomized to standard therapy. CONCLUSIONS: The 22-item DME-Q is a brief, acceptable, reliable measure with satisfactory structural and construct validity, which is responsive to intervention. The DME-Q is likely to be useful for evaluation of new pharmaceutical agents and technologies in research and clinical settings.

Association between time from esophageal food impaction to endoscopy and adverse events.

BACKGROUND AND AIMS: Guidelines recommend emergent or urgent EGD for esophageal food impaction (EFI), but data on how time to EGD impacts the risk of adverse events remain limited. We determined whether EFI-to-EGD time was associated with adverse events. METHODS: In this retrospective cohort study of patients with endoscopically confirmed EFI, adverse events were classified as esophageal (mucosal tear, bleeding, perforation) or extraesophageal (aspiration, respiratory compromise, hypotension, arrhythmia). Esophageal perforation and extraesophageal adverse events requiring intensive care unit admission were classified as serious adverse events. Baseline characteristics, event details, and procedural details were compared between patients with and without adverse events. Multivariable logistic regression was performed to assess for an association between EFI-to-EGD time and adverse events. RESULTS: Of 188 patients with EFI, 22 (12%) had any adverse event and 2 (1%) had a serious adverse event. Patients with adverse events were older and more likely to have an esophageal motility disorder, to tolerate secretions at presentation, and to have a higher American Society of Anesthesiologists score. EFI-to-EGD time was similar in those with and without adverse events. On multivariable analysis, EFI-to-EGD time was not associated with adverse events (odds ratio, 1.00 [95% confidence interval, .97-1.04] for 1-hour increments; odds ratio, 1.03 [95% confidence interval, .86-1.24] for 6-hour increments). Results were similar after stratifying by eosinophilic esophagitis status and after adjusting for possible confounders. CONCLUSIONS: Because the time from EFI to EGD is not associated with adverse events, emergent EGD for EFI may be unnecessary, and other considerations may determine EGD timing.

Perceptions of neighborhood disorder and gun carrying during adolescence: The indirect effect of exposure to violence.

OBJECTIVE: As society strives to curb gun violence among adolescents, understanding the risk factors associated with gun carrying is of critical importance. The current study seeks to examine the relationship between perceived neighborhood disorder and adolescents' susceptibility to carrying a gun to school. More specifically, the aim of the current study was threefold: (1) to examine the direct relationship between perceived neighborhood disorder and exposure to violence, (2) to investigate the association between perceived neighborhood disorder and gun carrying, and (3) to test the mediating effect of exposure to violence on the relationship between perceived neighborhood disorder and gun carrying. METHODS: Data from waves I and II (1994-1996) of the National Longitudinal Study of Adolescent to Adult Health was analyzed (N = 11,887). Due to the binary nature of the mediating and dependent variables (i.e., exposure to violence and gun carrying) a series of logistic regression models were estimated. RESULTS: Our analyses revealed that perceived neighborhood disorder is positive and significantly associated with, both, exposure to violence and gun carrying. The relationship between perceived neighborhood disorder and gun carrying was fully mediated by exposure to violence. CONCLUSIONS: While neighborhood disorder is a risk factor for gun carrying among youth, exposure to violence explains the relationship between perceived neighborhood disorder and carrying a gun to school. To reduce the prevalence of gun carrying and gun violence among the adolescent population, mental health resources should be provided to those who reside in communities with high levels of disorder and violence.

Baseline Peripheral Eosinophil Count Independently Predicts Proton Pump Inhibitor Response in Eosinophilic Esophagitis.

GOALS: To assess the predictive value of baseline peripheral absolute eosinophil counts (AECs) for proton pump inhibitor (PPI) response in eosinophilic esophagitis (EoE). BACKGROUND: PPI leads to histologic remission in ~50% of EoE patients, although there are few distinguishing clinical features between PPI-responsive (PPI-r-EoE) and nonresponsive (PPI-nr-EoE) diseases. Peripheral eosinophilia is present in ~50% of EoE cases and is associated with eosinophil density on esophageal biopsy and worse clinical outcomes. The association between peripheral eosinophilia and PPI-responsiveness in EoE remains unclear. STUDY: This is a retrospective cohort study of adult EoE patients at a tertiary center between 2012 and 2016. All patients underwent twice daily PPI trials for ≥8 weeks followed by repeat esophageal biopsies and were classified as PPI-r-EoE or PPI-nr-EoE based on histologic response (<15 eosinophils/high power field). Baseline peripheral AEC was obtained within 1 month before index endoscopy. Analyses were performed using Fisher exact/Student t test (univariate) and logistic regression (multivariable). RESULTS: One hundred eighty-three patients (91 PPI-nr-EoE and 92 PPI-r-EoE) were included. Mean peripheral AEC was higher among PPI-nr-EoE patients (0.41 vs 0.24 K/µL, P = 0.013). Baseline peripheral eosinophilia (>0.5 K/µL) was more prevalent among patients with PPI-nr-EoE (70.4% vs 45.5%, P = 0.023) and a history of food impaction (51.9% vs 23.7%, P = 0.0082). On multivariable analyses, peripheral eosinophilia remained an independent predictor for PPI response (adjacent odds ratio = 2.86, CI: 1.07-7.62, P = 0.036) and food impaction (adjacent odds ratio = 2.80, CI: 1.07-7.35, P = 0.037). CONCLUSIONS: Baseline peripheral eosinophilia independently predicts PPI nonresponse and food impaction in EoE patients. Peripheral AEC may help therapy selection in EoE and prevent delays in achieving histologic remission.

Topical Steroids Are Effective and Safe in Patients With Eosinophilic Esophagitis Over a Median of 6.5 Years of Chronic Use.

GOALS: To determine long-term efficacy and safety of tCS for treatment of EoE. BACKGROUND: Maintenance therapy with topical corticosteroids (tCS) is recommended for eosinophilic esophagitis (EoE), but data for long-term use are still needed. STUDY: This retrospective cohort study assessed newly diagnosed patients with EoE who were treated with a tCS and had a follow-up endoscopy with biopsy after at least 5 years. Histologic symptomatic and endoscopic responses were extracted from medical records. Patients who did and did not have long-term tCS treatment were compared at baseline, and outcomes for patients were assessed at their last endoscopy while on tCS. RESULTS: Of 431 patients with EoE treated with tCS, 104 met inclusion criteria for long-term use. For patients with long-term tCS use, the median time (IQR) on tCS was 6.5 years (5.4 to 8.8 y). At the last endoscopy, 54% had histologic response (<15 eos/hpf), but those with excellent adherence had a histologic response of 64%. Endoscopic severity also decreased with improved adherence which was strongly associated with EREFS (1.7 vs. 2.8 vs. 4.0 for excellent, good, and poor adherence; P<0.001). Symptomatic response was 68% overall, but only 40% in those with poor adherence (P=0.07). Complications of taking tCS were uncommon (adrenal insufficiency: 1%; osteopenia: 1%; and esophageal candidiasis: 4% at final endoscopy). CONCLUSIONS: Long-term tCS (median 6.5 y) were generally effective, especially with better adherence, and also safe, with only rare serious complications. These data can be used to help patients make clinical decisions about chronic tCS use in EoE.

Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis.

BACKGROUND AND AIM: Food/environmental allergens have been associated with eosinophilic esophagitis (EoE); however, the correlation between allergy profiles and disease responsiveness to proton pump inhibitor (PPI) therapy remains unclear. We aimed to assess the association between food/environmental allergies identified on allergen testing and histologic response to PPI in patients with treatment-naive EoE. METHODS: Adults with newly diagnosed EoE who underwent formal testing for food/environmental allergies at a tertiary center were included. All patients underwent twice-daily PPI for 8 weeks with subsequent repeat endoscopy and biopsy to assess histologic response. Patients with <15 eosinophils/hpf on post-PPI mucosal biopsies were classified as responders (PPI-r-EoE), while those with ≥15 eosinophils/hpf were nonresponders (PPI-nr-EoE). RESULTS: Sixty-one patients met inclusion criteria (21 PPI-r-EoE vs 40 PPI-nr-EoE). Demographic, clinical, and endoscopic finding variables were similar between groups. Positive food allergen test was more prevalent among PPI-nr-EoE patients (82.5% vs 42.9%, P = 0.003). On multivariable analysis, positive food allergen testing remained an independent predictor for PPI nonresponse (aOR 0.15, CI: 0.04-0.58, P = 0.0006). Positive environmental allergen testing was highly prevalent, with no significant differences between groups (77.5% vs 95.2%, P = 0.14). However, higher number of positive environmental allergens (23.3% [≥5 allergens] vs 73.3% [<5 allergens], P = 0.003) and specific aeroallergens correlated with PPI-nr-EoE. CONCLUSION: Positive food allergy testing and increased environmental allergens predicted lower likelihood of histologic response to PPI in EoE. Our findings support an allergic phenotype of EoE that may less likely respond to PPI therapy. Formal allergen testing may play a role in therapy selection and tailored management in EoE.

Performing Esophageal Biopsies Is Safe During Upper Endoscopy for Food Impaction but Are Underperformed in Certain Populations.

BACKGROUND: Despite recommendations to perform esophageal biopsies during esophagogastroduodenoscopy (EGD) for esophageal food impaction to evaluate for eosinophilic esophagitis (EoE), endoscopists often forgo biopsies. There are minimal data on the risks of biopsies in this setting. AIMS: To determine the safety of performing biopsies during EGD for food impaction. METHODS: We conducted a retrospective cohort study of patients who presented to University of North Carolina Hospitals from 2014 to 2021 with endoscopically confirmed food impaction. Data were abstracted from the medical records. Baseline clinical characteristics, procedural details, and adverse events were compared between patients who did and did not undergo biopsy. Adverse events were classified as esophageal (mucosal tear, bleeding, perforation) or extra-esophageal (aspiration, respiratory compromise, hypotension, arrhythmia). RESULTS: Of 188 patients who underwent EGD for food impaction, 73 (39%) had biopsies taken. Older and non-White patients were less likely to be biopsied. None of the Black patients had biopsies taken. Only 2 (2.7%) of the 73 biopsied patients had an adverse event, and neither was related to the biopsies. Patients who were biopsied were less likely to experience adverse events. There were no differences in re-admission, ICU admission, or 30-day mortality between patients who were and were not biopsied. CONCLUSIONS: Esophageal biopsies remain underperformed during EGD for food impaction, especially in certain patient populations. Esophageal biopsies at the time of food impaction are unlikely to cause adverse events. Safety concerns should not preclude biopsies, and biopsies should be performed in the absence of extenuating circumstances.

Increasing Age at the Time of Diagnosis and Evolving Phenotypes of Eosinophilic Esophagitis Over 20 Years.

BACKGROUND: The presentation of eosinophilic esophagitis (EoE) is heterogeneous, but trends over time are not known. AIM: To determine whether clinical and endoscopic phenotypes at EoE diagnosis have changed over the past 2 decades. METHODS: In this retrospective cohort study, adults and children with newly diagnosed EoE were phenotyped as follows: (1) inflammatory vs fibrostenotic vs mixed on endoscopy; (2) atopic vs non-atopic; (3) age at symptom onset; (4) age at diagnosis; (5) presence of autoimmune or connective tissue disease; and (6) responsive to steroids. The prevalence of different phenotypes was categorized by 5-year intervals. Multivariate analysis was performed to assess for changes in patient features over time. RESULTS: Of 1187 EoE patients, age at diagnosis increased over time (from 22.0 years in 2002-2006 to 31.8 years in 2017-2021; p < 0.001) as did the frequency of dysphagia (67% to 92%; p < 0.001). Endoscopic phenotypes were increasingly mixed (26% vs 68%; p < 0.001) and an increasing proportion of patients had later onset of EoE. However, there were no significant trends for concomitant autoimmune/connective tissue disease or steroid responder phenotypes. On multivariate analysis, after accounting for age, dysphagia, and food impaction, the increase in the mixed endoscopic phenotype persisted (aOR 1.51 per each 5-year interval, 95% CI 1.31-1.73). CONCLUSION: EoE phenotypes have changed over the past two decades, with increasing age at diagnosis and age at symptom onset. The mixed endoscopic phenotype also increased, even after controlling for age and symptomatology. Whether this reflects changes in provider recognition or disease pathophysiology is yet to be elucidated.

Impact of cannabis use on presentation and treatment response in eosinophilic esophagitis.

Cannabis use is becoming increasingly common, both for recreational and medical purposes. However, there is a paucity of data regarding cannabis use in the context of eosinophilic esophagitis (EoE). We aimed to determine the impact of cannabis use on presentation and treatment response in EoE. To this end, we conducted a retrospective cohort study at a large academic medical center of newly diagnosed EoE patients age ≥ 12 years. Self-reported cannabis use status, baseline characteristics, and treatment response to topical corticosteroids and dietary therapy data were extracted. Bivariate and multivariable analyses were used to compare cannabis users and non-users at time of EoE diagnosis and to assess treatment response. Of 983 EoE patients, 80 reported using cannabis, with the majority reporting daily use and administration by inhalation. Baseline symptoms and peak eosinophil count were similar between cannabis users and non-users; cannabis users were less likely to have baseline endoscopic findings of exudates, edema, and stricture, and lower total Endoscopic Reference Score. On multivariable analysis, younger age, male sex, non-White race, and psychiatric diagnosis were independently associated with history of cannabis use at EoE presentation and stricture was independently associated with cannabis non-use. Post-treatment symptom and histologic responses were similar between cannabis users and non-users though there was a higher odds of post-treatment endoscopic inflammatory features with cannabis use. In conclusion, despite presenting with milder initial endoscopic findings, cannabis users exhibited greater inflammatory findings after treatment, highlighting a potential negative influence of cannabis use on EoE management.

Higher Body Mass Index Is Associated With Decreased Treatment Response to Topical Steroids in Eosinophilic Esophagitis.

BACKGROUND & AIMS: Understanding which eosinophilic esophagitis (EoE) patients will respond to treatment with topical corticosteroids (tCS) remains challenging, and it is unknown whether obesity impacts treatment response. This study aimed to determine whether treatment outcomes to tCS in EoE patients vary by body mass index (BMI). METHODS: This retrospective cohort study of the University of North Carolina EoE Clinicopathologic database assessed subjects age 14 years or older with a new diagnosis of EoE. Their BMI was calculated and histologic, symptom, and endoscopic responses were recorded after tCS treatment. The treatment response of obese (BMI, ≥30 kg/m2) and nonobese EoE status was compared using bivariate and multivariate analyses. RESULTS: We identified 296 EoE patients treated with tCS. Baseline characteristics were similar, although obese EoE patients had more heartburn and hiatal hernias. Histologic response was higher for those who were nonobese compared with obese at fewer than 15 (61% vs 47%; P = .049) and 6 or fewer (54% vs 38%; P = .02) eosinophils per high-power field, respectively. In addition, nonobese patients had significantly greater endoscopic and symptomatic responses. On multivariate analysis, increasing BMI was associated independently with decreased histologic response after accounting for age, heartburn, dilation, and hiatal hernia whether BMI was assessed as a continuous variable (adjusted odds ratio [aOR], 0.93; 95% CI, 0.89-0.98), as nonobese vs obese (aOR, 0.38; 95% CI, 0.21-0.68), or in 4 categories (overweight vs normal [aOR, 0.46; 95% CI, 0.26-0.84] or obese vs normal [aOR, 0.26; 95% CI, 0.13-0.51]). CONCLUSIONS: As BMI increases in EoE patients, the odds of histologic, symptomatic, and endoscopic responses to tCS decreases, with obese patients having an approximately 40% decrease in odds of response.

IL-10 promotes endothelial progenitor cell infiltration and wound healing via STAT3.

Endothelial progenitor cells (EPCs) contribute to de novo angiogenesis, tissue regeneration, and remodeling. Interleukin 10 (IL-10), an anti-inflammatory cytokine that primarily signals via STAT3, has been shown to drive EPC recruitment to injured tissues. Our previous work demonstrated that overexpression of IL-10 in dermal wounds promotes regenerative tissue repair via STAT3-dependent regulation of fibroblast-specific hyaluronan synthesis. However, IL-10's role and specific mode of action on EPC recruitment, particularly in dermal wound healing and neovascularization in both normal and diabetic wounds, remain to be defined. Therefore, inducible skin-specific STAT3 knockdown mice were studied to determine IL-10's impact on EPCs, dermal wound neovascularization and healing, and whether it is STAT3-dependent. We show that IL-10 overexpression significantly elevated EPC counts in the granulating wound bed, which was associated with robust capillary lumen density and enhanced re-epithelialization of both control and diabetic (db/db) wounds at day 7. We noted increased VEGF and high C-X-C motif chemokine 12 (CXCL12) levels in wounds and a favorable CXCL12 gradient at day 3 that may support EPC mobilization and infiltration from bone marrow to wounds, an effect that was abrogated in STAT3 knockdown wounds. These findings were supported in vitro. IL-10 promoted VEGF and CXCL12 synthesis in primary murine dermal fibroblasts, with blunted VEGF expression upon blocking CXCL12 in the media by antibody binding. IL-10-conditioned fibroblast media also significantly promoted endothelial sprouting and network formation. In conclusion, these studies demonstrate that overexpression of IL-10 in dermal wounds recruits EPCs and leads to increased vascular structures and faster re-epithelialization.

Endogenous Interleukin-10 Contributes to Wound Healing and Regulates Tissue Repair.

INTRODUCTION: Interleukin-10 (IL-10) is essential in fetal regenerative wound healing and likewise promotes a regenerative phenotype in adult dermal wounds. However, the role of endogenous IL-10 in postnatal dermal wound healing is not well-established. We sought to determine the function of endogenous IL-10 in murine full thickness excisional wounds that are splinted to prevent contracture and mimic human patterns of wound closure. METHODS: Full-thickness excisional wounds were made in wildtype (WT) and IL-10-/- mice on a C57BL/6J background (F/M, 8 wk old). In a subset of wounds, contraction was prevented by splinting with silicone stents (stenting) and maintaining a moist wound microenvironment using a semiocclusive dressing. Wounds were examined for re-epithelialization, granulation tissue deposition, and inflammatory cell infiltrate at day 7 and fibrosis and scarring at day 30 postwounding. RESULTS: We observed no difference in wound healing rate between WT and IL-10-/- mice in either the stented or unstented group. At day 7, unstented IL-10-/- wounds had a larger granulation tissue area and more inflammatory infiltrate than their WT counterparts. However, we did observe more F4/80+ cell infiltrate in stented IL-10-/- wounds at day 7. At day 30, stented wounds had increased scar area and epithelial thickness compared to unstented wounds. CONCLUSIONS: These data suggest that endogenous IL-10 expression does not alter closure of full thickness excisional wounds when wound hydration and excessive contraction of murine skin are controlled. However, the loss of IL-10 leads to increased inflammatory cell infiltration and scarring. These new findings suggest that IL-10 contributes to the regulation of inflammation without compromising the healing response. These data combined with previous reports of increased rates of healing in IL-10-/- mice wounds not controlled for hydration and contraction suggest an important role for murine wound healing models used in research studies of molecular mechanisms that regulate healing.

Eosinophilic esophagitis patients with multiple atopic conditions: Clinical characteristics and treatment response to topical steroids.

BACKGROUND: Patients with eosinophilic esophagitis (EoE) typically have concomitant atopic conditions, but whether there are differences in presentation or treatment response by the number of atopic diseases is unknown. OBJECTIVE: To determine whether patients with EoE having multiple atopic conditions have differences in presentation or response to topical corticosteroid (TCS) treatment. METHODS: We performed a retrospective cohort study of adults and children with newly diagnosed EoE. The total number of atopic comorbidities (allergic rhinitis, asthma, eczema, food allergy) was calculated. Patients with at least 2 atopic conditions other than allergic rhinitis were defined as having multiple atopic conditions and their baseline characteristics were compared with those with less than 2 atopic conditions. Histologic, symptom, and endoscopic responses to TCS treatment were also compared with bivariable and multivariable analyses. RESULTS: Of the 1020 patients with EoE having atopic disease information, 235 (23%) had 1 atopic comorbidity, 211 (21%) had 2, 113 (11%) had 3, and 34 (3%) had 4. At baseline, the 180 (18%) patients with 2 or more atopic diseases were younger and had more vomiting, less abdominal pain, more exudates and edema on endoscopy, and higher peak eosinophil counts. Among those treated with TCS, there was a trend toward better global symptom response in patients with less than 2 atopic conditions, but there was no difference in histologic or endoscopic response compared with those with 2 or more atopic conditions. CONCLUSION: There were differences in the initial presentation of EoE between those with and without multiple atopic conditions, but there were no major differences in histologic treatment response to corticosteroids by atopic status.

Feeding Tube Placement, Complications, and Treatment Responses in a Large Eosinophilic Esophagitis Patient Population.

OBJECTIVES: Feeding tubes can provide a temporary or long-term solution for nutritional therapy. Little is known regarding the use of feeding tubes in patients with eosinophilic esophagitis (EoE). We sought to describe the characteristics and outcomes in EoE patients requiring tube feeding. METHODS: This was a retrospective cohort study of EoE patients at a large tertiary care health system. Demographics, clinical characteristics, and endoscopic findings were extracted from medical records, and patients who had a feeding tube were identified. Patients with and without a feeding tube were compared. Details about the tube, complications, and treatment were extracted. Growth, global symptomatic, endoscopic, and histopathologic (<15 eos/hpf) responses were compared before and after the initiation of feeding tube therapy. RESULTS: We identified 39 of 1216 EoE patients who had a feeding tube (3%). Feeding tube patients were younger (mean age 6.3 years), reported more vomiting, and had a lower total endoscopic reference score than non-feeding tube patients ( P < 0.01 for all). Tubes were used for therapy for an average of 6.8 years, with most patients (95%) receiving both pharmacologic and formula treatment for EoE. An emergency department visit for a tube complication was required in 26%. Tube feeding improved body mass index z score ( P < 0.01), symptomatic response (42%), endoscopic response (53%), and histologic response (71%). CONCLUSIONS: Among EoE patients, only a small subset required a feeding tube and predominantly were young children with failure to thrive. Feeding tubes significantly improved growth and, when used in combination with other treatments, led to reduced esophageal eosinophilic inflammation.

Glycaemic outcomes in Australasian children and adults with type 1 diabetes: failure to meet targets across the age spectrum.

BACKGROUND: The goal of therapy in type 1 diabetes (T1D) is to achieve optimal glycaemic targets and reduce complications. Robust data representing glycaemic outcomes across the lifespan are lacking in Australasia. AIMS: To examine contemporary glycaemic outcomes and rate of use of diabetes technologies in Australasian people with T1D. METHODS: Cross-sectional analysis of de-identified data from 18 diabetes centres maintained in the Australasian Diabetes Data Network registry during 2019. Glycaemia was measured using glycated haemoglobin (HbA1c). The proportion of people with T1D achieving the international HbA1c target of <53 mmol/mol (7%) was calculated. Rates of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) use were determined. RESULTS: A total of 7988 individuals with T1D with 30 575 visits were recorded in the registry. The median (interquartile range) age was 15.3 (10.0) years and diabetes duration was 5.7 (9.4) years with 49% on multiple daily injections (MDI) and 36% on CSII. The mean HbA1c for the whole cohort was 66 mmol/mol (8.2%). HbA1c increased with age, from 60 mmol/mol (7.6%) in children <10 years, increasing during adolescence and peaking at 73 mmol/mol (8.8%) in the 20-25 years age group. The HbA1c target of <53 mmol/mol (7%) was met in 18% of children and 13% of adults. HbA1c was lower on CSII as compared with those on MDI (P < 0.0001). CONCLUSIONS: Only a minority of children and adults achieve the recommended glycaemic goals despite access to specialist care in major diabetes centres. There is a need to identify factors that improve glycaemic outcomes.

Malignant spinal cord compression in the paediatric population-a systematic review, meta-analysis.

BACKGROUND: Malignant spinal cord compression (MSCC) has been noted in 3-5% of children with primary tumours. MSCC can be associated with permanent neurological deficits and prompt treatment is necessary. Our aim was to perform a systematic review on MSCC in children < 18 years to help formulate national guidelines. METHODS: A systematic review of the English language was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search criteria included 'MSCC in children, paediatric and metastases' for papers published between January1999 and December 2022. Isolated case reports/case series with < 10 patients were excluded. RESULTS: From a total of 17 articles identified, a final 7 were analysed (Level III/IV). Neuroblastoma constituted the most common cause for MSCC in children (62.7%) followed by sarcoma (14.2%). Soft tissue sarcomas were the most frequent cause of MSCC in children > 5 years old, while for neuroblastomas, the mean age of presentation was 20 months. The median age at time of diagnosis for the entire cohort of patients was 50.9 months (14.8-139). The median follow-up duration was 50.7 months (0.5-204). Motor deficits were the presenting symptom in 95.6% of children followed by pain in 65.4% and sphincter disturbance in 24%. There was a delay of about 26.05 days (7-600) between the onset of symptoms and diagnosis. A multimodality approach to treatment was utilised depending on the primary tumour. The prognosis for neurological recovery was found to be inversely proportional to the degree of neurological deficits and duration of symptoms in four studies. CONCLUSION: Neuroblastoma is the most common cause for MSCC in children (62.7%) followed by sarcoma (14.2%), whilst soft tissue sarcomas constituted the most frequent cause of MSCC in children > 5 years old. The majority of patients presented with motor deficit, followed by pain. In children with neuroblastoma /lymphoma, chemotherapy was the primary treatment. Early surgery should be a consideration with rapid deterioration of neurology despite chemotherapy. A multimodality approach including chemo-radiotherapy and surgery should be the treatment of choice in metastatic sarcomas. It is worth noting that multi-level laminectomy/decompression and asymmetrical radiation to the spine can lead to spinal column deformity in the future.