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Background and Aims: Patients with type 2 diabetes (T2D) constitute a risk group for presence and severity of metabolic dysfunction–associated steatotic liver disease (MASLD). Yet, there are few published examples of collaborations between endocrinologists and hepatologists in caring for patients with T2D and MASLD. Here, we describe a pathway for screening of liver fibrosis in routine specialist diabetes care at a tertiary care hospital. Methods: Patients with T2D seen at the Endocrinology department at Karolinska University Hospital, Stockholm, Sweden, during a structured intervention for T2D between October 2016 and September 2023 were eligible for inclusion. Liver stiffness measurements (LSM) and controlled attenuation parameter (CAP) as proxies for liver fibrosis and steatosis, respectively, were obtained utilizing vibration-controlled transient elastography (VCTE). An LSM cut-off to exclude advanced fibrosis was set to

Background: Optimal protocols for efficient and reproducible protein extraction from formalin-fixed paraffin-embedded (FFPE) tissues are not yet standardised and new techniques are continually developed and improved. The effect of polyethylene glycol (PEG) 20 000 on protein extraction efficiency has not been evaluated using human FFPE colorectal cancer tissues and there is no consensus on the protein extraction solution required for efficient, reproducible extraction. Objective: The impact of PEG 20 000 on protein extraction efficiency, reproducibility and protein selection bias was evaluated using FFPE colonic tissue via liquid chromatography tandem mass spectrometry analysis. Methods: This study was conducted from August 2017 to July 2019 using human FFPE colorectal carcinoma tissues from the Anatomical Pathology department at Tygerberg Hospital in South Africa. Samples were analysed via label-free liquid chromatography tandem mass spectrometry to determine the impact of using PEG 20 000 in the protein extraction solution. Data were assessed regarding peptide and protein identifications, method efficiency, reproducibility, protein characteristics and organisation relating to gene ontology categories. Results: Polyethylene glycol 20 000 exclusion increased peptides and proteins identifications and the method was more reproducible compared to the samples processed with PEG 20 000. However, no differences were observed with regard to protein selection bias. We found that higher protein concentrations ( 10 µg) compromised the function of PEG. Conclusion: This study indicates that protocols generating high protein yields from human FFPE tissues would benefit from the exclusion of PEG 20 000 in the protein extraction solution.

Abstract Aims Diabetic foot complications, a serious consequence of diabetes mellitus, are associated with a tremendous burden on both individual patients and health care systems. Since prevention strategies may reduce the incidence of this complication, identification of risk factors in large longitudinal studies is essential to optimize early detection and personalized screening of patients at increased risk. Materials and methods We conducted a registry‐based retrospective cohort study using data from 10,688 patients with type 2 diabetes mellitus aged ≥18 years. Cox regression models were used to identify risk factors for foot complications while adjusting for potential confounders. Results We observed 140 diabetic foot complications in our patient cohort. The multivariate Cox regression model revealed neuropathy, peripheral arterial disease and male gender as being positively associated with foot complications. The same effect was detected for nephropathy in the time >10 years after T2DM diagnosis. For higher age at diagnosis and use of insulin, however, a negative association was retrieved. Conclusion Male gender and several diabetes‐related comorbidities were identified as risk factors for subsequent initial foot complications in patients with type 2 diabetes mellitus. These findings suggest that personalized early detection of patients at increased risk might be feasible by using information on demographics, medical history and comorbidities.

Abstract Aims With increasing numbers of patients with type 2 diabetes mellitus (T2DM) worldwide, the number of associated diabetic foot complications might also increase. This systematic review was performed to summarize published data about risk factors for the diabetic foot (DF) syndrome in order to improve the identification of high‐risk patients. Materials and methods Six electronic databases were searched for publications up to August 2019 using predefined stringent inclusion and exclusion criteria. Results Of 9,476 identified articles, 31 articles from 28 different study populations fulfilled the criteria for our evaluation. The overall quality of the studies was good, and the risk of bias was low. There was large heterogeneity among the studies concerning study protocols and patient populations analysed. A total of 79 risk factors were analysed within this review. The majority of studies described a consistently positive association with different outcomes of interest related to DF for gender, peripheral neuropathy, retinopathy, nephropathy, poor glycaemic control, insulin use, duration of diabetes, smoking and height. For age, hypertension, dyslipidaemia and body mass index, the results remain inconsistent. Conclusion A most up‐to‐date literature review resulted in glycaemic control and smoking as the only amenable risk factors with a consistently positive association for DF. Due to the high personal and financial burden associated with DF and the large heterogeneity among included studies, additional longitudinal studies in large patient populations are necessary to identify more modifiable risk factors that can be used in the prediction and prevention of DF complications.

Background: Native cluster of differentiation (CD) 19 targeting antibodies are poorly effective in triggering antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which are crucial effector functions of therapeutic antibodies in cancer immunotherapy. Both functions can be enhanced by engineering the antibody’s Fc region by altering the amino acid sequence (Fc protein-engineering) or the Fc-linked glycan (Fc glyco-engineering). We hypothesized that combining Fc glyco-engineering with Fc protein-engineering will rescue ADCC and CDC in CD19 antibodies. Results: Four versions of a CD19 antibody based on tafasitamab’s V-regions were generated: a native IgG1, an Fc protein-engineered version with amino acid exchanges S267E/H268F/S324T/G236A/I332E (EFTAE modification) to enhance CDC, and afucosylated, Fc glyco-engineered versions of both to promote ADCC. Irrespective of fucosylation, antibodies carrying the EFTAE modification had enhanced C1q binding and were superior in inducing CDC. In contrast, afucosylated versions exerted an enhanced affinity to Fcγ receptor IIIA and had increased ADCC activity. Of note, the double-engineered antibody harboring the EFTAE modification and lacking fucose triggered both CDC and ADCC more efficiently. Conclusions: Fc glyco-engineering and protein-engineering could be combined to enhance ADCC and CDC in CD19 antibodies and may allow the generation of antibodies with higher therapeutic efficacy by promoting two key functions simultaneously.