Causal factors underlying diabetes risk informed by Mendelian randomisation analysis: evidence, opportunities and challenges

Shuai Yuan1 & Jordi Merino2,3,4,5 & Susanna C. Larsson1,6

Received: 5 October 2022 /Accepted: 4 January 2023 / Published online: 14 February 2023

© The Author(s) 2023

Abstract

      Diabetes and its complications cause a heavy disease burden globally. Identifying exposures, risk factors and molecular processes causally associated with the development of diabetes can provide important evidence bases for disease prevention and spur novel therapeutic strategies. Mendelian randomisation (MR), an epidemiological approach that uses genetic instruments to infer causal associations between an exposure and an outcome, can be leveraged to complement evidence from observational and clinical studies. This narrative review aims to summarise the evidence on potential causal risk factors for diabetes by integrating published MR studies on type 1 and 2 diabetes, and to reflect on future perspectives of MR studies on diabetes. Despite the genetic influence on type 1 diabetes, few MR studies have been conducted to identify causal exposures or molecular processes leading to increased disease risk. In type 2 diabetes, MR analyses support causal associations of somatic, mental and lifestyle factors with development of the disease. These studies have also identified biomarkers, some of them derived from the gut microbiota, and molecular processes leading to increased disease risk. These studies provide valuable data to better understand disease pathophysiology and explore potential therapeutic targets. Because genetic association studies have mostly been restricted to participants of European descent, multi-ancestry cohorts are needed to examine the role of different types of physical

Susanna C. Larsson

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 Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

2 Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA

3 Programs in Metabolism and Medical and Population Genetics, Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA, USA

4 Department of Medicine, Harvard Medical School, Boston, MA, USA

5 Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

6 Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden activity, dietary components, metabolites, protein biomarkers and gut microbiome in diabetes development.

Keywords Causality . Diabetes . Mendelian randomisation . Review . Risk factor

Vacuum-assisted closure versus conventional dressing in necrotizing fasciitis: a systematic review and meta-analysis

Rongli Zhang, Yahui Zhang, Liyuan Hou and Chengyong Yan*

Abstract

Background Necrotizing fasciitis is a rapid and severe soft tissue infection that targets subcutaneous fat tissue, muscle, and fascia. This study compares the clinical outcomes of vacuum-assisted closure (VAC) versus conventional dressing on necrotizing fasciitis.

Methods We systematically searched Embase, Cochrane, and PubMed for clinical trials (published between January 1, 1995 and September 30, 2021), which compared VAC with conventional dressing for necrotizing fasciitis. The mortality rate of necrotizing fasciitis was the primary outcome of this study. The number of debridements, the total length of hospital stay, and the complication rate were secondary outcomes. A random effects model assessed all pooled

Results A total of 230 identified studies and seven controlled clinical trials met the inclusion criteria and were included in this analysis (n =249 participants). Compared to the conventional dressing, patients treated with VAC had a significantly lower mortality rate [OR =0.27, 95% CI (0.09, 0.87)] (P=0.03). Total length of hospital stays [MD=8.46, 95% CI (− 0.53, 17.45)] (P=0.07), number of debridements [MD =0.86, 95% CI (− 0.58, 2.30)] (P=0.24), and complication rate [OR=0.64, 95% CI (0.07, 5.94)] (P=0.69) were not significant. These results did not show significant diferences between both groups treated with VAC or conventional treatment.

Conclusion VAC could significantly decrease the death rate compared to conventional dressing. No significant impacts were found on the number of debridements, the total length of hospital stay, and the complication rate in this study. Level of evidence Level-III. Registration Research Registry (reviewregistry1246).

Keywords Necrotizing fasciitis, Vacuum-assisted closure, Conventional dressing, Meta-analysis

*Correspondence:

Chengyong Yan

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。

Department of Orthopaedic Surgery, Third Hospital of Hebei Medical

University, Shijiazhuang, China

© 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.

Serum neurofilament light chain: a novel biomarker for early diabetic sensorimotor polyneuropathy

Haifa Maalmi1,2  iD  Alexander Strom1,2  iD Agnese Petrera2,3  iD Stefanie M. Hauck2,3  iD Klaus Strassburger2,4  iD Oliver Kuss2,4,5  iD Oana-Patricia Zaharia1,2,6  iD Gidon J. Bönhof1,2,6  iD Wolfgang Rathmann2,4  iD Sandra Trenkamp1,2  iD Volker Burkart1,2  iD Julia Szendroedi1,2,7,8  iD Dan Ziegler1,2,6  iD Michael Roden1,2,6  iD Christian Herder 1,2,6  iD the GDS Group

Received: 31 May 2022 / Accepted: 19 October 2022 /Published online: 6 December 2022  ©The Author(s) 2022

Abstract

Aims/hypothesis No established blood-based biomarker exists to monitor diabetic sensorimotor polyneuropathy (DSPN) and evaluate treatment response. The neurofilament light chain (NFL), a blood biomarker of neuroaxonal damage in several neurodegenerative diseases, represents a potential biomarker for DSPN. We hypothesised that higher serum NFL levels are associated with prevalent DSPN and nerve dysfunction in individuals recently diagnosed with diabetes.

Methods This cross-sectional study included 423 adults with type 1 and type 2 diabetes and known diabetes duration of less than 1 year from the prospective observational German Diabetes Study cohort. NFL was measured in serum samples of fasting participants in a multiplex approach using proximity extension assay technology. DSPN was assessed by neurological examination, nerve conduction studies and quantitative sensory testing. Associations of serum NFL with DSPN (defined according to the Toronto Consensus criteria) were estimated using Poisson regression, while multivariable linear and quantile regression models were used to assess associations with nerve function measures. In exploratory analyses, other biomarkers in the multiplex panel were also analysed similarly to NFL.

Results DSPN was found in 16% of the study sample. Serum NFL levels increased with age. After adjustment for age, sex, waist circumference, height, HbA1c, known diabetes duration, diabetes type, cholesterol, eGFR, hypertension, CVD, use of lipidlowering drugs and use of non-steroidal anti-inflammatory drugs, higher serum NFL levels were associated with DSPN (RR [95% CI] per 1-normalised protein expression increase, 1.92 [1.50, 2.45], p<0.0001), slower motor (all p<0.0001) and sensory (all p≤0.03) nerve conduction velocities, lower sural sensory nerve action potential (p=0.0004) and higher thermal detection threshold to warm stimuli (p=0.023 and p=0.004 for hand and foot, respectively). There was no evidence for associations between other neurological biomarkers and DSPN or nerve function measures.

Dan Ziegler, Michael Roden and Christian Herder contributed equally to this study.

Christian Herder

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 Institute for Clinical Diabetology, German Diabetes Center (Deutsches Diabetes-Zentrum/DDZ), Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany

2 German Center for Diabetes Research (DZD), München-Neuherberg, Germany

3 Metabolomics and Proteomics Core, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany

4 Institute for Biometrics and Epidemiology, German Diabetes Center (Deutsches Diabetes-Zentrum/DDZ), Düsseldorf, Germany

5 Centre for Health and Society, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany

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

7 Department of Endocrinology, Diabetology, Metabolism and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany

8 Institute for Diabetes and Cancer (IDC) & Joint Heidelberg–IDC Translational Diabetes Program, Helmholtz Center Munich, München-Neuherberg, Germany

Conclusions/interpretation Our findings in individuals recently diagnosed with diabetes provide new evidence associating higher serum NFL levels with DSPN and peripheral nerve dysfunction. The present study advocates NFL as a potential

Keywords Axonal damage . Biomarker . Demyelination . Diabetes . Diabetic neuropathy . Diabetic sensorimotor polyneuropathy . Distal sensorimotor polyneuropathy . Electrophysiological tests . Large fibre . Nerve conduction study . Nerve dysfunction . Nerve injury . Neurofilament light chain . Neurofilaments . Neurological biomarkers . Peripheral nervous system . Peripheral neuropathy . Quantitative sensory tests . Small fibre biomarker for DSPN.

Abbreviations

ADAM15 Disintegrin and metalloproteinase domain

containing protein 15

CDH Cadherin

DSPN Diabetic sensorimotor polyneuropathy

GDS German Diabetes Study

MNCV Motor nerve conduction velocity

NCS Nerve conduction study

NCV Nerve conduction velocity

NFL Neurofilament light chain

NPX Normalised protein expression

NSAID Non-steroidal anti-inflammatory drug

QST Quantitative sensory testing

SFRP1 Secreted frizzled-related protein 1

SNAP Sensory nerve action potential

SNCV Sensory nerve conduction velocity

TDT Thermal detection threshold

A prospective, randomized assessment of a novel, local antibiotic releasing platform for the prevention of superfcial and deep surgical site infections

O.Zmora1 · Y. Stark2  · O. Belotserkovsky2  · M. Reichert2  · G. A. Kozloski2  · N. Wasserberg3  · H. Tulchinsky4  · L. Segev5  · A.J. Senagore2 · N. Emanuel2

Received: 11 May 2022 / Accepted: 16 August 2022 / Published online: 1 September 2022

© The Author(s) 2022

A. J. Senagore

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 Shamir Medical Center, Be’er Ya’akov, Israel

2 PolyPid Ltd, Petach Tikvah, Israel

3 Rabin Medical Center, Beilinson Campus, Petach Tikva,

Israel

4 Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel

5 Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel

Abstract

Background Despite significant advances in infection control guidelines and practices, surgical site infections (SSIs) remain a substantial cause of morbidity, prolonged hospitalization, and mortality among patients having both elective and emergent surgeries. D-PLEX100 is a novel, antibiotic-eluting polymer–lipid matrix that supplies a high, local concentration of doxycycline for the prevention of superficial and deep SSIs. The aim of our study was to evaluate the safety and efficacy of D-PLEX in addition to standard of care (SOC) in preventing superficial and deep surgical site infections for patients undergoing elective colorectal surgery.

Methods From October 10, 2018 to October 6, 2019, as part of a Phase 2 clinical trial, we randomly assigned 202 patients who had scheduled elective colorectal surgery to receive either standard of care SSI prophylaxis or D-PLEX100 in addition to standard of care. The primary objective was to assess the efficacy of D-PLEX100 in superficial and deep SSI reduction, as measured by the incidence of SSIs within 30 days, as adjudicated by both an individual assessor and a three-person endpoint adjudication committee, all of whom were blinded to study-group assignments. Safety was assessed by the stratification and incidence of treatment-emergent adverse events.

Results One hundred and seventy-nine patients were evaluated in the per protocol population, 88 in the intervention arm [51 males, 37 females, median age (64.0 range: 19–92) years] and 91 in the control arm [57 males, 34 females, median age 64.5 (range: 21–88) years]. The SSI rate within 30 day post-index surgery revealed a 64% relative risk reduction in SSI rate in the D-PLEX100 plus standard of care (SOC) group [n=7/88 (8%)] vs SOC alone [n=20/91 (22%)]; p=0.0115. There was no significant difference in treatment-emergent adverse events.

Conclusions D-PLEX100 application leads to a statistically significant reduction in superficial and deep surgical site infections in this colorectal clinical model without any associated increase in adverse events.

Keywords Surgical site infection · Localized antibiotic therapy · Doxycycline

Optimisation of perioperative procedural factors to reduce the risk of surgical site infection in patients undergoing surgery: a systematic review

P.Calò1 · F. Catena2  · D. Corsaro3  · L. Costantini4  · F. Falez5  · B. Moretti6  · V. Parrinello7  · E. Romanini8,9 · A. Spinarelli10 · G. Vaccaro11,12· F. Venneri13

Received: 27 December 2022 / Accepted: 26 January 2023 

Published online:13 February 2023

© The Author(s) 2023 OPEN

G. Vaccaro, 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 University Teaching Hospital of Cagliari and Surgical Department at University of Cagliari, Cagliari, Italy. 2 Department General and Emergency Surgery at Bufalini Hospital, Cesena, Italy. 3 International Research at BHAVE, Via GiambattistaVico 1, 00196 Rome, Italy. 4 Department of Medical and Surgical Sciences, School of Community Medicine and Primary Care, University of Modena and Reggio Emilia, Modena, Italy. 5 Department of Orthopaedics ASL Roma 1 and Director UOC Orthopaedics Hospital San Filippo Neri, Rome, Italy. 6 Orthopedics and Traumatology Complex Operative Unit, University Teaching Hospital of Bari Polyclinic, Bari, Italy. 7 Operative Unit of Quality and Clinical Risk Manager at “G.Rodolico-San Marco” University Teaching Hospital in Catania, Catania, Italy. 8 SIOT Guidelines Commission, Rome, Italy. 9 Complex Operative Unit of Orthopedics and Traumatology at University Teaching Hospital of Bari Polyclinic, Bari, Italy. 10Operative Unit of Orthopedics and Traumatology at University Teaching Hospital of Bari Polyclinic, Bari, Italy. 11Social, Epidemiological and Outcome Research at BHAVE, Via Giambattista Vico 1, 00196 Rome, Italy. 12Sociologist UO Education and Health Promotion, Asp Catania, Via Santa Maria la Grande 5, 95124 Catania, Italy. 13Simple Structure Clinical Risk and Surgical Emergency in Florence, Florence, Italy.

Abstract

      Surgical site infections (SSI) are the leading cause of hospital readmission after surgical procedures with significant impact on post-operative morbidity and mortality. Modifiable risk factors for SSI include procedural aspects, which include the possibility of instrument contamination, the duration of the operation, the number of people present and the traffic in the room and the ventilation system of the operating theatre.The aim of this systematic review was to provide literature evidence on the relationship between features of surgical procedure sets and the frequency of SSI in patients undergoing surgical treatment, and to analyse how time frames of perioperative processes and operating theatre traffic vary in relation to the features of the procedure sets use, in order tooptimise infection control in OT. The results of the systematic review brought to light observational studies that can be divided into two categories: evidence of purely clinical significance and evidence of mainly organisational, managerial and financial significance. These two systems are largely interconnected, and reciprocally influence each other. The decision to use disposable devices and instruments has been accompanied by a lower incidence in surgical site infections and surgical revisions for remediation. A concomitant reduction in post-operative functional recovery time has also been observed. Also, the rationalisation of traditional surgical sets has also been observed in conjunction with outcomes of clinical significance.

Global variation in skin injures and skincare practices in extremely preterm infants

Pranav Jani1,2  · Umesh Mishra1,2 · Julia Buchmayer3  · Rajesh Maheshwari1,2 · Daphne D’Çruz2  · Karen Walker1,4,5,6,7 · Duygu Gözen8  · Krista Lowe2  · Audrey Wright2  · James Marceau2  · Mihaela Culcer1,2 · Archana Priyadarshi1,2 · Adrienne Kirby9  · James E. Moore10,11 · Ju Lee Oei12,13 · Vibhuti Shah14 · Umesh Vaidya15 · Abdelmoneim Khashana16 · Sunit Godambe17 · Fook Choe Cheah18,19 · Wen‑Hao Zhou20 · Xiao‑Jing Hu21 · Muneerah Satardien22,23

Received: 28 July 2022 / Accepted: 19 September 2022 / Published online: 13 November 2022 © The Author(s) 2022

Abstract

Background Globally, are skincare practices and skin injuries in extremely preterm infants comparable? This study describes skin injuries, variation in skincare practices and investigates any association between them.

Methods A web-based survey was conducted between February 2019 and August 2021. Quantifying skin injuries and describing skincare practices in extremely preterm infants were the main outcomes. The association between skin injuries and skincare practices was established using binary multivariable logistic regression adjusted for regions.

Results Responses from 848 neonatal intensive care units, representing all geographic regions and income status groups were received. Diaper dermatitis (331/840, 39%) and medical adhesive-related skin injuries (319/838, 38%) were the most common injuries. Following a local skincare guideline reduced skin injuries [medical adhesive-related injuries: adjusted odds ratios (aOR)=0.63, 95% confidence interval (CI)=0.45–0.88; perineal injuries: aOR=0.66, 95% CI=0.45–0.96; local skin infections: OR=0.41, 95% CI=0.26–0.65; chemical burns: OR=0.46, 95% CI=0.26–0.83; thermal burns: OR=0.51, 95% CI=0.27–0.96]. Performing skin assessments at least every four hours reduced skin injuries (abrasion: aOR=0.48, 95% CI=0.33–0.67; pressure: aOR=0.51, 95% CI=0.34–0.78; diaper dermatitis: aOR=0.71, 95% CI=0.51–0.99; perineal: aOR=0.52, 95% CI=0.36–0.75). Regional and resource settings-based variations in skin injuries and skincare practices were observed.

Conclusions Skin injuries were common in extremely preterm infants. Consistency in practice and improved surveillance appears to reduce the occurrence of these injuries. Better evidence regarding optimal practices is needed to reduce skin injuries and minimize practice variations.

Keywords Extremely premature infants · Injuries · Neonatal intensive care unit · Skin care · Wounds

Pranav Jani

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。

Extended author information available on the last page of the article