Empagliflozin protects mice against diet-induced obesity, insulin resistance and hepatic steatosis

Bernhard Radlinger1,2 & Claudia Ress1,2 & Sabrina Folie1,2 & Karin Salzmann1,2 & Ana Lechuga1,2 & Bernhard Weiss 1,2,3 & Willi Salvenmoser4 & Michael Graber5 & Jakob Hirsch5 & Johannes Holfeld5 & Christian Kremser6 & Patrizia Moser3 & Gabriele Staudacher1,2 & Tomas Jelenik7 & Michael Roden7,8,9 & Herbert Tilg2 & Susanne Kaser1,2

Susanne Kaser

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1 Christian Doppler Laboratory for Metabolic Crosstalk, Medical University Innsbruck, Innsbruck, Austria

2 Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria

3 Innpath GmbH, Innsbruck, Austria

4 Institute of Zoology and Center of Molecular Biosciences Innsbruck (CBMI), Leopold Franzens University Innsbruck, Innsbruck, Austria

5 Department of Cardiac Surgery, Medical University Innsbruck, Innsbruck, Austria

6 Department of Radiology, Medical University Innsbruck, Innsbruck, Austria

7 Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

8 Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

9 German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany

Received: 5 September 2022 /Accepted: 31 October 2022 / Published online: 16 December 2022 © The Author(s) 2022

Abstract Aims/hypothesis Sodium–glucose cotransporter 2 (SGLT2) inhibitors are widely used in the treatment of type 2 diabetes, heart failure and chronic kidney disease. Their role in the prevention of diet-induced metabolic deteriorations, such as obesity, insulin resistance and fatty liver disease, has not been defined yet. In this study we set out to test whether empagliflozin prevents weight gain and metabolic dysfunction in a mouse model of diet-induced obesity and insulin resistance.

Methods C57Bl/6 mice were fed a western-type diet supplemented with empagliflozin (WDE) or without empagliflozin (WD) for 10 weeks. A standard control diet (CD) without or with empagliflozin (CDE) was used to control for diet-specific effects.

Metabolic phenotyping included assessment of body weight, food and water intake, body composition, hepatic energy metabolism, skeletal muscle mitochondria and measurement of insulin sensitivity using hyperinsulinaemic–euglycaemic clamps.

Results Mice fed the WD were overweight, hyperglycaemic, hyperinsulinaemic and insulin resistant after 10 weeks. Supplementation of the WD with empagliflozin prevented these metabolic alterations. While water intake was significantly increased by empagliflozin supplementation, food intake was similar in WDE- and WD-fed mice. Adipose tissue depots measured by MRI were significantly smaller in WDE-fed mice than in WD-fed mice. Additionally, empagliflozin supplementation prevented significant steatosis found in WD-fed mice. Accordingly, hepatic insulin signalling was deteriorated in WD-fed mice but not in WDE-fed mice. Empagliflozin supplementation positively affected size and morphology of mitochondria in skeletal muscle in both CD- and WD-fed mice.

Conclusions/interpretation Empagliflozin protects mice from diet-induced weight gain, insulin resistance and hepatic steatosis in a preventative setting and improves muscle mitochondrial morphology independent of the type of diet.

Keywords Empagliflozin . Insulin resistance . Obesity . SGLT2 inhibition . Skeletal muscle mitochondria . Steatosis . Western-type diet

Do sex differences in paediatric type 1 diabetes care exist? A systematic review

Silvia A. G. de Vries1 iD Carianne L. Verheugt1 iD Dick Mul2 iD Max Nieuwdorp1 iD Theo C. J. Sas2,3

Received: 26 April 2022 /Accepted: 25 November 2022

© The Author(s) 2023

Abstract

      Aims/hypothesis Sex differences are present in cardiovascular care and in outcomes among adults with type 1 diabetes mellitus, which typically commences in childhood. Whether sex influences care and outcomes in childhood is not known. This systematic review provides an overview of sex differences in children with type 1 diabetes, focusing on patient and disease characteristics, treatment, comorbidities and complications.

      Methods Literature in MEDLINE up to 15 June 2021 was searched, using the terms diabetes mellitus, sex characteristics, sex distribution, children and/or adolescents. All primary outcome studies on children with type 1 diabetes that mentioned a sex difference in outcome were included, with the exception of qualitative studies, case reports or case series. Studies not pertaining to the regular clinical care process and on incidence or prevalence only were excluded. Articles reporting sex differences were identified and assessed on quality and risk of bias using Joanna Briggs Institute critical appraisal tools. Narrative synthesis and an adapted Harvest plot were used to summarise evidence by category.

      Results A total of 8640 articles were identified, rendering 90 studies for review (n=643,217 individuals). Studies were of observational design and comprised cohort, cross-sectional and case–control studies. Most of the included studies showed a higher HbA1c in young female children both at diagnosis (seven studies, n=22,089) and during treatment (20 out of 21 studies, n=144,613), as well as a steeper HbA1c increase over time. Many studies observed a higher BMI (all ages, ten studies, n=89,700; adolescence, seven studies, n=33,153), a higher prevalence of being overweight or obese, and a higher prevalence of dyslipidaemia among the female sex. Hypoglycaemia and partial remission occurred more often in male participants, and ketoacidosis (at diagnosis, eight studies, n=3561) and hospitalisation was more often seen in female participants. Most of the findings showed that female participants used pump therapy more frequently (six studies, n=211,324) and needed higher insulin doses than male participants. Several comorbidities, such as thyroid disease and coeliac disease, appeared to be more common in female participants. All studies reported lower quality of life in female participants (15 studies, n=8722). Because the aim of this study was to identify sex differences, studies with neutral outcomes or minor differences may have been under-targeted. The observational designs of the included studies also limit conclusions on the causality between sex and clinical outcomes.

Conclusions/interpretation Sex disparities were observed throughout diabetes care in children with type 1 diabetes. Several outcomes appear worse in young female children, especially during adolescence. Focus on the cause and treatment of these differences may provide opportunities for better outcomes.

Registration This systematic review is registered in PROSPERO (CRD42020213640)

Keywords Child . Diabetes mellitus . Narrative synthesis . Sex differences . Systematic review . Type 1 diabetes

* Silvia A. G. de Vries

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1 Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands

2 Diabeter, Center for Paediatric and Adult Diabetes Care and Research, Rotterdam, the Netherlands

3 Department of Paediatrics, Division of Paediatric Endocrinology, Erasmus University Medical Center, Sophia Children’s Hospital, Rotterdam, the Netherlands

https://doi.org/10.1007/s00125-022-05866-4

/ Published online: 26 January 2023

Comparison of the effect of Triticum Vulgare and Hyperici Oleum on healing in traumatic membrane perforation: an animal study

Adem Bora1* , Kasım Durmuş1 , Zeynep D.Şahin İnan2 , Berat Baturay Demirkıran1 and Emine E. Altuntas1

Abstract

Background Traumatic tympanic membrane (TM) perforations usually heal spontaneously. The aim of this study was to investigate whether the topical application of Triticum Vulgare (TV) in experimentally induced traumatic TM perforations in the rats has a positive effect on wound healing process.

Methods The rats were randomly assigned to four experimental groups. Drugs were introduced twice a day for 7 days. On the 7th day, specimens were sent for histological examination.

Results Mean values found in group NC in terms of epithelial regeneration mean scores are as follows: fibroblast and collagen density, neovascularization, and density of inflammation cells were lower than all groups (p<0.05). It was found that reepithelization on the post-perforation 7th day was better in the HO group than the TV group. In terms of the subepithelial fibroblast cells, density of collagen fibers, formation of new veins, and inflammatory cell

accumulation, it was observed that the group TV was better than the group HO.

Conclusion This is the first study investigating the potential curative role of TV in an experimental rat model of tympanic membrane perforation. Considering these findings, it is concluded that TV can be more effective than HO on

wound healing in TM perforation.

Keywords Hyperici oleum, Triticum vulgare, Traumatic tympanic membrane perforation

*Correspondence:

Adem Bora

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1 Department of Otolaryngology, Faculty of Medicine Sivas Cumhuriyet University, 58140 Sivas, Turkey

2 Department of Histology and Embriology, Faculty of Medicine Sivas Cumhuriyet University, 58140 Sivas, Turkey © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Negative Pressure Wound Therapy for the Prevention of Surgical Site Infections Using Fascia Closure After EVAR—A Randomized Trial

Robert Svensson-Bjo ¨rk1 • Julien Hasselmann1,2 • Giuseppe Asciutto1,3 • Moncef Zarrouk1,2 • Jonas Bjo ¨rk4,5 • Linda Bilos6 • Artai Pirouzram6 • Stefan Acosta1,2 ID

Accepted: 29 August 2022 / Published online: 14 October 2022© The Author(s) 2022

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1 Vascular Diseases Research Unit, Department of Clinical Sciences, Lund University, Ruth Lundskogs gata 10, 205 02 Malmo ¨, Sweden

2 Vascular Center, Skane University Hospital, Malmo ¨, Sweden

3 Department of Vascular Surgery, Uppsala University Hospital, Uppsala, Sweden

4 Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden

5 Clinical Studies Sweden, Lund University, Forum South, Lund, Sweden

6 Vascular Surgery Unit, Department of Cardiothoracic and Vascular Surgery, Linko ¨ping University Hospital, Linko ¨ping, Sweden

Abstract

      Background Surgical site infections (SSI) in the groin after vascular surgery are common. The aim of the study was to evaluate the effect of negative pressure wound therapy (NPWT) on SSI incidence when applied on closed inguinal incisions after endovascular aneurysm repair (EVAR).

      Methods A multicenter randomized controlled trial (RCT). Between November 2013 and December 2020, 377 incisions (336 bilateral and 41 unilateral) from elective EVAR procedures with the primary intent of fascia closure were randomized and included, receiving either NPWT or a standard dressing. In bilateral incisions, each incision randomly received the opposite dressing of the other side, thereby becoming each other’s control. The primary endpoint was SSI incidence at 90 days postoperatively, analyzed on an intention-to-treat basis. Uni and bilaterally operated incisions were analyzed separately, and their respective p-values combined using Fisher’s method for combining P-values. Study protocol (NCT01913132).

      Results The SSI incidence at 90 days postoperatively in bilateral incisions was 1.8% (n = 3/168) in the NPWT and 4.8% (n = 8/168) in the standard dressing group, and in unilateral incisions 13.3% (n = 2/15) and 11.5% (n = 3/26), respectively (combined p = 0.49). In all SSIs, bacteria were isolated from incisional wound cultures. No additional SSIs were diagnosed between 90 days and 1 year follow-up. Conclusions No evidence of difference in SSI incidence was seen in these low-risk inguinal incisions when comparing NPWT with standard dressings after EVAR with the primary intent of fascia closure.

Clinical Trials: NCT01913132.

Predictors of sternal wound infection post cardiac surgery in a Saudi Centre: a case control study

Adil A. Isaac*

*Correspondence:

Adil A. Isaac

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Department of Infectious Diseases, Saud Al-Babtain Cardiac Centre

(SBCC), 5443 King Khalid Street, Dammam, Eastern Province, Kingdom

of Saudi Arabia

Abstract

Background Sternal wound infection (SWI) post cardiac surgery remains an important cause of extra morbidity, mortality and cost. The objective was to identify risk factors for SWI in a cardiac centre in Eastern Saudi Arabia as part of the investigation into Surveillance variance in the local rates of SWI.

Methods We included cases and controls from a cross section of patients who underwent major cardiac surgery between 2017 and 2020 matched for age, sex and time of surgery. An explanatory logistic regression model was fitted to estimate the risk factors.

Results N=204 (51 cases and 153 controls matching ratio 1:3, from a source population of 985 patients). factors significantly associated with SWI in the final multivariate model: hospital stay OR (1.05, Cl 1.01–1.10), Graft Conduit BIMA versus No Graft OR (10.94, Cl 1.60–74.63), transfusion of both packed cells plus other blood products versus

no transfusion OR (3.53, Cl 93–13.44), HbA1c OR (1.09 Cl 0.84–1.41), BMI OR (1.25, Cl 1.04–1.50), perioperative blood

glucose OR (1.02, Cl 1.004–1.03), surgery time OR (1.19, Cl 1.00–1.58).

Conclusions The diverse aetiology, cross-disciplinary nature of SWI prevention, and despite improved prevention

and control practices, including related care bundles with their proven value, SWI remain a serious challenge in cardiac surgery. Multidisciplinary consensus guidelines are well overdue.

Keywords Sternal wound infection, Mediastinitis, Sternotomy, Cardiac surgery, Case control, Saudi Arabia

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Wound infection in colorectal cancer resections through a laparoscopic approach: a single‑center prospective observational study of over 3000 cases

Atsushi Ikeda1,2 · Yosuke Fukunaga1  · Takashi Akiyoshi1  · Satoshi Nagayama1  · Toshiya Nagasaki1  · Tomohiro Yamaguchi1  · Toshiki Mukai1  · Yukiharu Hiyoshi1  · Tsuyoshi Konishi1,3

Received: 7 January 2021 / Accepted: 27 January 2021 © The Author(s) 2021 

Abstract

Objectives This prospective observational study aimed to clarify the incidence and independent risk factors of wound infection after laparoscopic surgery for primary colonic and rectal cancer.

Methods A prospective surveillance of surgical site infection (SSI) was conducted in consecutive patients with primary colorectal cancer, who underwent elective laparoscopic surgery in a single comprehensive cancer center between 2005 and 2014. The outcomes of interest were the incidence and risk factors of wound infection.

Results In total, 3170 patients were enrolled in the study. The overall incidence of wound infection was 3.0%. The incidence of wound infection was significantly higher in rectal surgery than in colonic surgery (4.7 vs. 2.1%, p<0.001). In rectal surgery, independent risk factors for developing wound infection included abdominoperineal resection (p<0.001, odds ratio [OR]=11.4, 95% confidence interval [CI]: 5.04–24.8), body mass index (BMI)≥25 kg/m2 (p=0.041, OR=1.97, 95% CI, 1.03–3.76), and chemoradiotherapy (p=0.032, OR=2.18, 95% CI, 1.07–4.45). In laparoscopic colonic surgery, no significant risk factors were identified.

Conclusions Laparoscopic rectal surgery has a higher risk of wound infection than colonic surgery. Laparoscopic rectal surgery involving abdominoperineal resection, patients with higher BMI, and chemoradiotherapy requires careful observation in wound care and countermeasures against wound infection.

Tsuyoshi Konishi, 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 | 1 Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese

Foundation for Cancer Research, Tokyo, Japan. 2 Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 3 Department of Surgical Oncology, The University of Texas, M.D. Anderson Cancer Center, 1400 Pressler Street Unit 1484, Houston, TX 77030, USA.