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Background: Primary eosinophilic gastrointestinal diseases (EGID) are chronic inflammatory disorders of the gastrointestinal tract with unknown etiology. Features, utility, and evolution are still unknown in screening for EGID in adult patients with eosinophilic esophagitis (EoE)., Objectives: To evaluate the prevalence, characteristics, comorbidities, and evolution of EGID in adults diagnosed with EoE and investigate differences between both groups., Methods: Prospective unicenter observational and analytical study. Gastric and duodenal biopsies were obtained during upper baseline endoscopy in all consecutive EoE adult patients evaluated. A colonoscopy with colon biopsies was performed upon persistent diarrhea and normal duodenal biopsies., Results: 212 EoE patients were included. Nine patients (4.3%) also showed significant eosinophilic infiltration in at least one organ within the digestive tract. The most common site affected was the small bowel (78%). Gastrointestinal symptoms (43% vs. 100%, p<0.002) and, more specifically, either abdominal pain or diarrhea (17% vs. 78%, p<0.001), some food sensitizations, and digestive comorbidities (p<0.05) were significantly more common in patients with EGID. Gastrointestinal symptoms were present in 94/212 (44%) patients, of whom 9 (10%) had EGID. Considering only abdominal pain or diarrhea, 20% suffered from it., Conclusions: EGID rarely coexist with EoE, even when gastrointestinal symptoms are present. These findings advise against routine gastric, duodenal, or colon biopsies in adult EoE patients with gastrointestinal symptoms. Most of the characteristics of EoE do not change due to having EGID except gastrointestinal symptoms, digestive comorbidities, and sensitizations to some foods. The evolution was generally favorable despite intermittent adherence to treatment, especially maintenance., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

Aim: To evaluate the effect of the historic Spanish heatwave (9th-26th July 2022) over glycemic control in adults with type 1 diabetes (T1D)., Methods: Cross-sectional retrospective analysis of adult patients with T1D in Castilla-La Mancha (south-central Spanish region) using intermittently scanned continuous glucose monitoring (isCGM) during and after the heatwave. Primary outcome was change in time in range (TIR) 3.0-10 mmol/L (70-180 mg/dL) of interstitial glucose in the two weeks following the heatwave., Results: A total of 2701 T1D patients were analyzed. We detected a TIR reduction of 4.0 % (95 % CI -3.4, -4.6; P < 0.001) in the two weeks following the heatwave. Patients in the highest daily scan frequency quartile (>13 scans/day) during the heatwave showed the greatest deterioration in TIR after it concluded (-5.4 % [95 % CI -6.5, -4.3; P < 0.001]). The percentage of patients meeting all the recommendations of the International Consensus of Time in Range was greater during the heatwave than after it ended (10.6 % vs. 8.4 %, P < 0.001)., Conclusions: Adults with T1D had better glycemic control during the historic Spanish heatwave compared to the following period., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: To evaluate the effect of faster aspart over glycaemic variability in type 1 diabetes (T1D) patients treated with sensor-augmented pump (SAP) in a real-world scenario., Methods: Observational study with SAP-treated adult T1D patients treated with faster aspart for three months. The primary endpoint was the mean amplitude of glucose excursions (MAGE)., Results: Fifty patients were treated with faster aspart. Eleven patients (23%) withdrew during the follow-up mainly due to worsening of diabetes control (9 patients). Mean age was 41.2 yrs. (range 21-59) and T1D duration 22.4±10.0 yrs. Mean SAP treatment duration was 3.6±3.1 yrs. We detected a reduction of -7.0 (95% CI -1.1, -12.9; p=0.021) in MAGE at the end of the study. Other glycemic variability indices were also improved: standard deviation of mean interstitial glucose (-3mg/dl; 95% CI, -1, -5; p=0.01), CONGA4 (-2.2; 95% CI -0.3, -4.2; p=0.029), CONGA6 (-2.6; 95% CI -0.6, -4.6; p=0.011), GRADE (-0.5; 95% CI -0.1, -0.9; p=0.022), HBGI (-0.7; 95% CI -0.2, -1.3; p=0.013), J-index (-2.9; 95% CI -0.7, -5.0; p=0.011) and MODD (-5.7; 95% CI -1.7, -9.7; p=0.006). A slight reduction in mean glucose management indicator was also detected (-0.14%; 95% CI, -0.02, -0.27; -1.4mmol/mol; 95% CI -0.1, -3.3; p=0.03)., Conclusions: In SAP-treated T1D patients, faster aspart insulin was associated with reduced glycaemic variability, but also a high percentage of dropouts due to worsened glycaemic control. NCT04233203., (Copyright © 2022 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Aim: To evaluate the use and clinical effect of intermittently scanned continuous glucose monitoring (isCGM) in adults with type 1 diabetes (T1D) in a public health service scenario., Method: Cross-sectional retrospective analysis of all patients with T1D and medical indication for isCGM use from a cohort followed since 2010 at Castilla-La Mancha Public Health Service (Spain). Primary outcome was HbA1c change during the first year of follow-up after isCGM initiation. Secondary outcomes included evaluation of self-monitoring of blood glucose (SMBG), isCGM and insulin use, along with glycometric indexes., Results: A total of 945 T1D patients were analyzed. Median age was 49.5 years (IQ range 19.0 years) and T1D duration of 28.9 years (IQ range 14.0 years). The most frequent insulin therapy alternatives were multiple daily injections (85%) followed by insulin pump (11%). Eighty percent of the patients were active isCGM users with a 90% of adherence to the device. Patients showed a mean daily scan frequency of 10.1±6.4scans/day. Daily SMBG reduced by -3.5 test/day [95% CI -3.7, -3.2; P<0.001]. We detected an HbA1c reduction of -0.3% (-4mmol/mol) [95% CI -0.2, -0.4 (-3, -5); P<0.001] at the end of the follow-up. An inverse correlation between HbA1c levels at the end of the follow-up and daily frequency of isCGM scanning (R=-0.34, P<0.001) was observed. Dropout rate was 4%, and 4% of patients were not willing to use isCGM., Conclusions: Adult patients with T1D improved glycaemic control after isCGM initiation in a public health service scenario. Despite described clinical benefits, a higher than expected percentage of patients were not using isCGM technology. NCT05095610., (Copyright © 2022 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Eosinophilic esophagitis (EoE) is a disease characterized by symptoms of esophageal dysfunction and at least 15 eosinophils/hpf in the esophagus. Other systemic and local causes of esophageal eosinophilia should be excluded., Objectives: The study objectives were to examine the annual epidemiology of EoE for 14 consecutive years, investigate whether there is a relationship between the count of aeroallergens and the incidence of EoE for 12 years, evaluate whether there are family ties between the patients with EoE, and determine whether there are cases of EoE that are triggered or exacerbated by pollens., Methods: We conducted a prospective, descriptive, and analytic study in patients with EoE for 14 years (2007-2020). The study variables were age, sex, relatives with EoE, time of evolution of the symptoms until diagnosis of the disease, and symptoms. We examined incidence and prevalence, annual counts of aeroallergens for 12 years, and number of diagnoses per year (in 2007-2020). We studied patients with active EoE (in April-July) and EoE in remission (in August-March) for 2 consecutive years. Exacerbations were investigated by measuring symptoms using a visual analog scale of 1 to 10., Results: Of the 366 patients with EoE (studied from 2007 to 2020), 83.5% were atopic, with respiratory allergy and 28% had a food allergy. Their mean age was 35 years. The time of evolution of the symptoms was more than 6 years. Only 11% of the patients had a degree of kinship. Of the 366 patients, 87% had dysphagia, 27% had had impactions, and 12.5% had other symptoms of esophageal dysfunction. We found a positive correlation between the incidence of EoE and Platanaceae pollens. We did not detect any case of EoE triggered or exacerbated by pollens., Conclusions: The epidemiology of EoE in southwestern Europe continues to grow. We have corroborated the relevant impact of the environment on genetics. Future studies will clarify the possible relevance of Platanaceae pollens in the increased epidemiology of EoE. The role of grass and Oleaceae pollens in triggering EoE is limited by having a short pollination in time., (© 2023 The Authors.)

Aim: To evaluate clinical status and mortality in older adults with long-standing type 1 diabetes mellitus (T1D)., Methods: Cross-sectional analysis of all patients with T1D for 50 years or more from a cohort followed since 2010 at Castilla-La Mancha Public Health Service (Spain). Primary outcome was HbA1c change during the follow-up (2010-2020 period). Secondary outcomes included evaluation of insulin and continuous glucose monitoring (CGM) use, cardiovascular risk factors (CVRF), diabetes chronic complications and mortality., Results: A total of fifty-five T1D patients were analysed. Mean age was 69.5 ± 8.3 yrs. and T1D duration of 54.7 ± 4.7 yrs. We detected a HbA1c reduction of -0.5% (-6 mmol/mol) [95% CI -0.1, -0.9 (-2, -10); P = 0.016]. CGM was used by 26% of the patients. More patients suffered from hypertension and obesity in 2020 (66% vs. 78%, P = 0.016; and 26% vs. 31%, P = 0.016; respectively). An increase of diabetic polyneuropathy was detected (45% vs. 67%, P = 0.008). Rate of mortality was higher among patients with long-standing T1D (26% vs. 3.5%, P < 0.001), due to cardiovascular disease (57%)., Conclusions: Older adults with long-standing T1D patients improved glycemic control although a worsening of CVRF and higher mortality rateweredetected., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aim: To analyse the real-life outcomes of two sensor-augmented pumps (SAP) with predictive low glucose suspend (PLGS) function, Medtronic Minimed 640G™ with SmartGuard (MM640G) and Tandem T Slim X2™ with Basal-IQ™ (TTSX2), in Type 1 Diabetes Mellitus (T1DM) patients., Methods: Observational cross-sectional study using data obtained from computerized clinical records. All T1DM patients on TTSX2 therapy were compared (1:1) with MM640G treated patients selected through stratified sampling. Primary efficacy outcome was to describe time in rage (TIR, 70-180 mg/dL, 3.9-10 mmol/L) interstitial glucose differences according to a non-inferiority hypothesis with TTSX2 compared to MM640G., Results: Forty-four patients were analyzed (female 66%). Mean age was 38.9 yrs. (range 23-59 yrs.) and mean diabetes duration was 23.4 ± 9.2 yrs. Patients treated with TTSX2 showed a numerically slightly lower, but non-statistically significantly different, TIR from the MM640G pump group (64.9 ± 16.4% vs. 72.4 ± 17.0%, P = 0.108). Similarly, we did no find differences in HbA1c between T1D patients treated with TTSX2 and MM640G (6.8 ± 1.0% vs. 7.0 ± 0.9%, 51 ± 11 mmol/mol vs. 53 ± 10 mmol/mol, P = 0.312). Moreover, rest of evaluated glycemic outcomes were similar between both treatment groups., Conclusions: Patients using two different SAP with PLGS automatic function showed similar glycaemic control in a real-world scenario. NCT04741685., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare that they have not received research support or compensation from Medtronic or Tandem. JMF reports consultant fees and speaker honoraria from Medtronic, Tandem, Dexcom, Abbott, Roche and Ypsomed. PB has received speaking/consulting honoraria from Medtronic Diabetes, Roche Diabetes, Abbott, Novalab and Lilly. Rest of authors declare that they have no conflicts of interest concerning this article., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Chronic ultraviolet B (UV-B) irradiation is known to be one of the most important hazards acting on the skin and poses a risk of developing photoaging, skin with cutaneous field cancerization (CFC), actinic keratosis (AKs), and squamous cell carcinomas (SCCs). Most of the UV-B light is absorbed in the epidermis, affecting the outermost cell layers, the stratum corneum, and the stratum granulosum, which protects against this radiation and tries to maintain the permeability barrier. In the present work, we show an impairment in the transepidermal water loss, stratum corneum hydration, and surface pH after chronic UV-B light exposure in an immunologically intact mouse model (SKH1 aged mice) of skin with CFC. Macroscopic lesions of AKs and SCCs may develop synchronically or over time on the same cutaneous surface due to both the presence of subclinical AKs and in situ SCC, but also the accumulation of different mutations in keratinocytes. Focusing on skin with CFC, yet without the pathological criteria of AKs or SCC, the presence of p53 immunopositive patches (PIPs) within the epidermis is associated with these UV-B-induced mutations. Reactive epidermis to chronic UV-B exposure correlated with a marked hyperkeratotic hyperplasia, hypergranulosis, and induction of keratinocyte hyperproliferation, while expressing an upregulation of filaggrin, loricrin, and involucrin immunostaining. However, incidental AKs and in situ SCC might show neither hypergranulosis nor upregulation of differentiation markers in the upper epidermis. Despite the overexpression of filaggrin, loricrin, involucrin, lipid enzymes, and ATP-binding cassette subfamily A member 12 (ABCA12) after chronic UV-B irradiation, the permeability barrier, stratum corneum hydration, and surface pH were severely compromised in the skin with CFC. We interpret these results as an attempt to restore the permeability barrier homeostasis by the reactive epidermis, which fails due to ultrastructural losses in stratum corneum integrity, higher pH on skin surface, abundant mast cells in the dermis, and the common presence of incidental AKs and in situ SCC. As far as we know, this is the first time that the permeability barrier has been studied in the skin with CFC in a murine model of SCC induced after chronic UV-B irradiation at high doses. The impairment in the permeability barrier and the consequent keratinocyte hyperproliferation in the skin of CFC might play a role in the physiopathology of AKs and SCCs.

Objective: To determine whether topical applications of thiosulfinate-enriched Allium sativum extract (TASE) can accelerate acute cutaneous wound healing (WH) in a murine model., Methods: Keratinocyte viability and in vitro wound closure were assessed in keratinocyte cultures. Effects of topical TASE (0.5 μg/mL of allicin in 97% ethanol) on acute cutaneous WH were determined in a murine model of acute cutaneous wound. Twelve mice were alternately assigned to the vehicle- and TASE-treated groups (n=6 per group). Expression levels of mRNA for keratinocyte differentiation marker-related proteins (filaggrin, loricrin and involucrin) and lipid synthetic enzymes (elongation of very long chain fatty acids protein 4 (ELOVL4), fatty acid synthase (FA2H), 3-hydroxy- 3-methyl-glutaryl-coenzyme A reductase (HMGCoA), and serine palmitoyltransferase (SPT)) were assessed using real-time quantitative polymerase chain reaction on day 3 and 8 after wounding, while transepidermal water loss (TEWL) rates were measured in wounded areas., Results: TASE accelerated WH both in vivo (40% vs. 22% reduction in wound area, P<0.01) and in vitro (90% vs. 65% reduction in wound area, P<0.01). Moreover, topical applications of TASE upregulated the expression levels of epidermal mRNA for ELOVL4, HMGCoA, SPT, filaggrin, loricrin and involucrin (P<0.05 vs. vehicle-treated controls) on day 3 after wounding. Likewise, TASE significantly lowered TEWL rates in comparison with vehicle alone on day 8 (33.06±2.09 g/(m 2 ·h) vs. 24.60±2.04 g/(m 2 ·h), P<0.01)., Conclusions: Topical applications of TASE stimulated keratinocyte proliferation and formation of epidermal permeability barrier function, leading to acceleration of acute cutaneous WH. Topical products containing TASE could be used to manage acute cutaneous WH.