Aquacel Ag Advantage/Ag+ Extra and Cutimed Sorbact in the management of hard-to-heal wounds: a cohort study.

OBJECTIVE: To compare Aquacel Ag Advantage/Ag+ Extra (Aquacel Ag+) (Convatec, UK) and Cutimed Sorbact (Sorbact) (Essity, US) dressings indicated for the treatment of patients with venous leg ulcers (VLUs), diabetes foot ulcers (DFUs) and pressure injuries (PIs) for clinical performance and outcomes using real-world evidence in Germany and the US. METHOD: This study was a chart audit review of patients who used either Aquacel Ag+ or Sorbact dressings in the 24 months prior to October 2022. Healthcare providers with access to electronic medical records and charts were asked to capture data via patient record forms. The quantitative data were analysed. RESULTS: Findings in Germany were comparable between Aquacel Ag+ and Sorbact with regards to wound description, management and treatment outcomes, including percent area reduction and wound closure. A difference was that a greater proportion of Sorbact patients required surgery (0% versus 11%; p=0.039). In the US, a greater proportion of wounds were worsening before dressing in the Aquacel Ag+ cohort (49% versus 34%; p=0.010). A multinomial logistic regression yielded the result that patients who received Aquacel Ag+ were 3.53 times more likely to have the wound completely healed (p=0.033). CONCLUSION: Both Aquacel Ag+ and Sorbact dressings are widely used in Germany and the US for patients with VLUs, DFUs and PIs. Our study found two important differences: patients who used Aquacel Ag+ were less likely to need further surgery in Germany; and in the US, there were significantly higher odds that wounds would completely heal with Aquacel Ag+ dressings compared to Sorbact.

Impact of Infusion Set Materials and Designs on the Subcutaneous Response in People With Diabetes: A Rapid Review of the Literature.

Insulin infusion sets (IISs) are an integral and intricate part of continuous subcutaneous insulin infusion for subjects with type 1 diabetes, infusing insulin from pump to the subcutaneous space. Insulin infusion sets interface with the skin surface, the dermis, and the subcutaneous space and may be the cause of infusion failure due to biological events or mechanical problems. Novel IISs with extended wear time and anti-inflammatory properties to mitigate these issues are described in the literature although material-tissue interactions are poorly understood. This rapid review focuses on the impact of IIS materials and designs on the subcutaneous response in people with diabetes and includes literature identified in PubMed, Embase, and Cochrane databases. Twenty-one studies were identified for qualitative synthesis that encompassed a limited and heterogenic body of evidence including 10 clinical reports, six reviews, one case report, two abstracts, and two communications. Two clinical reports were randomized crossover studies. Reports on materials mostly compared steel versus polytetrafluoroethylene (Teflon) cannulas and suggested no substantial difference in tissue response to these materials. Reports on designs focused mostly on the angle of cannula insertion. To drive and improve research on extended wear and nonimmunogenic IISs, future studies should focus on material-tissue interaction as dedicated outcome measures, quantified with punch biopsy and imaging techniques such as ultrasound, optical coherence tomography, and confocal reflectance microscopy. Original studies are required to further a field too young for a systematic meta-analysis.

Flash glucose monitoring in type 2 diabetes managed with basal insulin in the USA: a retrospective real-world chart review study and meta-analysis.

INTRODUCTION: Evidence supporting use of continuous glucose monitoring in type 2 diabetes treated with basal insulin is unclear. This real-world study aimed to assess the impact on glycated hemoglobin (HbA1c) of flash glucose monitoring use in adults with type 2 diabetes managed with basal insulin. RESEARCH DESIGN AND METHODS: Medical records were reviewed for adult individuals with type 2 diabetes using basal insulin for ≥1 year with or without additional antihyperglycemic medication, HbA1c 8.0%-12.0% prior to FreeStyle Libre Flash Glucose Monitoring use for ≥90 days and an HbA1c measurement recorded between 90 and 194 days after device use. Exclusion criteria included utilization of bolus insulin. Meta-analysis data are from the current study (USA) and a similar Canadian cohort. RESULTS: Medical record analysis (n=100) from 8 USA study sites showed significant HbA1c decrease of 1.4%±1.3%, from 9.4%±1.0% at baseline to 8.0%±1.2% after device use, p<0.0001 (mean±SD).Meta-analysis of medical records from USA and Canada sites (n=191) showed HbA1c significantly decreased by 1.1%±0.14% (mean±SE), from baseline 9.2%±1.0% to 8.1%±1.1%, p≤0.0001, with moderate to high heterogeneity between sites (Q=43.9, I2=74.9, p<0.0001) explained by differences in baseline HbA1c between sites.The HbA1c improvement in both groups was observed by age group, body mass index, duration of insulin use and sex at birth. CONCLUSIONS: In a real-world retrospective USA study and a meta-analysis of a larger USA and Canada cohort, HbA1c significantly reduced in basal insulin-treated type 2 diabetes, without bolus insulin initiation and following the commencement of flash glucose monitoring technology.

Fast Acting Insulin Aspart Compared with Insulin Aspart in the Medtronic 670G Hybrid Closed Loop System in Type 1 Diabetes: An Open Label Crossover Study.

This is a single-center randomized open label active-controlled crossover trial comparing efficacy and safety of fast acting insulin aspart (FA) (FIASP®) versus insulin aspart (IAsp) (NovoLog®) when used in the Medtronic 670G system in auto mode in patients with type 1 diabetes. Forty patients were randomized to either IAsp or FA. Each treatment period was 7 weeks and a standardized meal test was administered 6 weeks after the start of each treatment period. The primary endpoint was postprandial glucose (PPG) increment after the meal test at 1 h. Treatment with FA using the MiniMed 670G hybrid closed loop (HCL) led to a greater reduction in 1-h postprandial glucose increase compared with treatment with IAsp during the standardized mixed meal test. Change in glucose: [estimated treatment difference (ETD ± standard deviation [SD]); 95% confidence interval]: 70.27 (±17.36) mg/dL (3.9 ± 1.0 mmol/L) with FA versus 98.42 (±17.36) mg/dL (5.5 ± 1.0 mmol/L) with IAsp (P = 0.008). Patients spent 1.81% (P = 0.016) more time (equivalent to 26 min per day) in the 70-180 mg/dL (3.89-9.99 mmol/L) range with FA than with IAsp. The entire sample spent only 0.5% of time <54 mg/dL (<3.0 mmol/L) range. The increment in the 1 h postmeal test glucose was significantly lower with FA versus IAsp. FA in a HCL setting is safe and effective with patients spending more time in the 70-180 mg/dL (3.89-9.99 mmol/L) target range than with IAsp. Trial registration: Clinicaltrials.gov identifier: NCT03977727.

Telemedicine During the COVID-19 Crisis and Beyond.

On March 18, as the COVID 19 crisis accelerated, we converted overnight to "seeing" our patients by video. Our journey into telemedicine was abrupt, and there was a steep learning curve.

Anatabine supplementation decreases thyroglobulin antibodies in patients with chronic lymphocytic autoimmune (Hashimoto's) thyroiditis: a randomized controlled clinical trial.

CONTEXT: Hashimoto's thyroiditis is less prevalent in tobacco smokers. Anatabine, an alkaloid found in Solanaceae plants including tobacco, has been reported to ameliorate a mouse model of Hashimoto's thyroiditis. OBJECTIVE: The effects of anatabine in patients with Hashimoto's thyroiditis were studied. DESIGN, SETTING, PATIENTS, AND INTERVENTION: This was a double-blind, randomized, placebo-controlled multisite study. A total of 146 patients (70 treated with anatabine and 76 with placebo) completed the study. Approximately 50% of patients in each group were taking levothyroxine. Anatabine lozenges (9-24 mg/d) or placebo, each containing vitamins A and D3, were administered orally 3 times a day for 3 months. MAIN OUTCOME MEASURES: Serum thyroperoxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels were assessed. Safety was assessed through adverse events, clinical laboratory evaluations, and vital sign measurements. RESULTS: Anatabine-treated patients had a significant reduction in absolute serum TgAb levels from baseline by study end relative to those receiving placebo (P=.027); however, there were no significant changes or differences in treatment group means for TPOAb or TgAb levels. Mean±SD TgAb values decreased by 46.2±101.1 and 3.9±83.9 World Health Organization units for the anatabine and placebo groups, respectively. Significantly more patients had a >20% drop in TgAb levels in the anatabine than placebo group (P=.023). Overall, the anatabine supplement was safe and well tolerated, although significantly (P<.05) more patients in the anatabine group reported adverse events. CONCLUSIONS: These results demonstrate an immunological effect of anatabine on TgAb levels. Further studies are warranted to determine the longer-term effects and possible actions of anatabine on the course of Hashimoto's thyroiditis.

Islet-specific T-cell responses and proinflammatory monocytes define subtypes of autoantibody-negative ketosis-prone diabetes.

OBJECTIVE: Ketosis-prone diabetes (KPD) is characterized by diabetic ketoacidosis (DKA) in patients lacking typical features of type 1 diabetes. A validated classification scheme for KPD includes two autoantibody-negative ("A-") phenotypic forms: "A-ß-" (lean, early onset, lacking ß-cell functional reserve) and "A-ß+" (obese, late onset, with substantial ß-cell functional reserve after the index episode of DKA). Recent longitudinal analysis of a large KPD cohort revealed that the A-ß+ phenotype includes two distinct subtypes distinguished by the index DKA episode having a defined precipitant ("provoked," with progressive ß-cell function loss over time) or no precipitant ("unprovoked," with sustained ß-cell functional reserve). These three A- KPD subtypes are characterized by absence of humoral islet autoimmune markers, but a role for cellular islet autoimmunity is unknown. RESEARCH DESIGN AND METHODS: Islet-specific T-cell responses and the percentage of proinflammatory (CD14+CD16+) blood monocytes were measured in A-ß- (n = 7), provoked A-ß+ (n = 15), and unprovoked A-ß+ (n = 13) KPD patients. Genotyping was performed for type 1 diabetes-associated HLA class II alleles. RESULTS: Provoked A-ß+ and A-ß- KPD patients manifested stronger islet-specific T-cell responses (P < 0.03) and higher percentages of proinflammatory CD14+CD16+ monocytes (P < 0.01) than unprovoked A-ß+ KPD patients. A significant relationship between type 1 diabetes HLA class II protective alleles and negative T-cell responses was observed. CONCLUSIONS: Provoked A-ß+ KPD and A-ß- KPD are associated with a high frequency of cellular islet autoimmunity and proinflammatory monocyte populations. In contrast, unprovoked A-ß+ KPD lacks both humoral and cellular islet autoimmunity.

Characteristics of patients with ketosis-prone diabetes (KPD) presenting with acute pancreatitis: implications for the natural history and etiology of a KPD subgroup.

OBJECTIVE: Reports of concomitant diabetic ketoacidosis (DKA) and acute pancreatitis (AP) are lacking among emerging forms of diabetes. This longitudinal study characterized ketosis-prone diabetes (KPD) in patients presenting with concomitant AP and DKA. METHODS: Multi-ethnic KPD patients (N = 755) were followed prospectively for 1 year from the time of index DKA using repeated metabolic and beta cell functional reserve measures. Baseline and longitudinal characteristics were compared between KPD patients whose index DKA was associated with (n = 54) or without (n = 701) AP. RESULTS: The AP group had significantly higher baseline serum amylase, lipase, and triglyceride levels and significantly lower bicarbonate levels than the non-AP group. AP patients had significantly greater C-peptide area-under-the-curve with glucagon stimulation shortly after the index DKA, and higher fasting C-peptide (FCP) levels 6 to 12 months later. Using the validated "Aß" KPD classification, 85% of AP patients had ß+ status (preserved beta cell functional reserve), compared to 60% of non-AP patients (P = .04). Multivariate analysis revealed that among the ß+ KPD subgroup with an identifiable precipitating factor for DKA ("provoked" DKA), patients with AP had worse long-term glycemic outcomes than patients whose DKA was associated with other factors. CONCLUSION: Despite greater clinical severity at presentation, KPD patients with AP have better preserved beta cell function than those without AP. ß+ KPD patients presenting with AP have worse long-term glycemic control than those with other causes of provoked DKA. Factors other than beta cell function negatively impact glycemic control in KPD patients presenting with AP.

Pathogenesis of A⁻ß⁺ ketosis-prone diabetes.

A⁻ß⁺ ketosis-prone diabetes (KPD) is an emerging syndrome of obesity, unprovoked ketoacidosis, reversible ß-cell dysfunction, and near-normoglycemic remission. We combined metabolomics with targeted kinetic measurements to investigate its pathophysiology. Fasting plasma fatty acids, acylcarnitines, and amino acids were quantified in 20 KPD patients compared with 19 nondiabetic control subjects. Unique signatures in KPD--higher glutamate but lower glutamine and citrulline concentrations, increased ß-hydroxybutyryl-carnitine, decreased isovaleryl-carnitine (a leucine catabolite), and decreased tricarboxylic acid (TCA) cycle intermediates--generated hypotheses that were tested through stable isotope/mass spectrometry protocols in nine new-onset, stable KPD patients compared with seven nondiabetic control subjects. Free fatty acid flux and acetyl CoA flux and oxidation were similar, but KPD had slower acetyl CoA conversion to ß-hydroxybutyrate; higher fasting ß-hydroxybutyrate concentration; slower ß-hydroxybutyrate oxidation; faster leucine oxidative decarboxylation; accelerated glutamine conversion to glutamate without increase in glutamate carbon oxidation; and slower citrulline flux, with diminished glutamine amide-nitrogen transfer to citrulline. The confluence of metabolomic and kinetic data indicate a distinctive pathogenic sequence: impaired ketone oxidation and fatty acid utilization for energy, leading to accelerated leucine catabolism and transamination of α-ketoglutarate to glutamate, with impaired TCA anaplerosis of glutamate carbon. They highlight a novel process of defective energy production and ketosis in A⁻ß⁺ KPD.

Presence or absence of a known diabetic ketoacidosis precipitant defines distinct syndromes of "A-ß+" ketosis-prone diabetes based on long-term ß-cell function, human leukocyte antigen class II alleles, and sex predilection.

Ketosis-prone diabetes (KPD) is heterogeneous. Longitudinal follow-up revealed that patients with "A-ß+" KPD (absent autoantibodies and preserved ß-cell function) segregated into 2 subgroups with distinct evolution of ß-cell function and glycemic control. Generalized linear analysis demonstrated that the variable that most significantly differentiated them was presence of a clinically evident precipitating event for the index diabetic ketoacidosis (DKA). Hence, we performed a comprehensive analysis of A-ß+ KPD patients presenting with "provoked" compared with "unprovoked" DKA. Clinical, biochemical, and ß-cell functional characteristics were compared between provoked and unprovoked A-ß+ KPD patients followed prospectively for 1 to 8 years. Human leukocyte antigen class II allele frequencies were compared between these 2 groups and population controls. Unprovoked A-ß+ KPD patients (n = 83) had greater body mass index, male preponderance, higher frequency of women with oligo-/anovulation, more frequent African American ethnicity, and less frequent family history of diabetes than provoked A-ß+ KPD patients (n = 64). The provoked group had higher frequencies of the human leukocyte antigen class II type 1 diabetes mellitus susceptibility alleles DQB1*0302 (than the unprovoked group or population controls) and DRB1*04 (than the unprovoked group), whereas the unprovoked group had a higher frequency of the protective allele DQB1*0602. ß-Cell secretory reserve and glycemic control improved progressively in the unprovoked group but declined in the provoked group. The differences persisted in comparisons restricted to patients with new-onset diabetes. "Unprovoked" A-ß+ KPD is a distinct syndrome characterized by reversible ß-cell dysfunction with male predominance and increased frequency of DQB1*0602, whereas "provoked" A-ß+ KPD is characterized by progressive loss of ß-cell reserve and increased frequency of DQB1*0302 and DRB1*04. Unprovoked DKA predicts long-term ß-cell functional reserve, insulin independence, and glycemic control in KPD.

Gene therapy with neurogenin 3 and betacellulin reverses major metabolic problems in insulin-deficient diabetic mice.

Insulin deficiency in type 1 diabetes leads to disruptions in glucose, lipid, and ketone metabolism with resultant hyperglycemia, hyperlipidemia, and ketonemia. Exogenous insulin and hepatic insulin gene therapy cannot mimic the robust glucose-stimulated insulin secretion (GSIS) from native pancreatic islets. Gene therapy of streptozotocin-diabetic mice with neurogenin 3 (Ngn3) and betacellulin (Btc) leads to the induction of periportal oval cell-derived neo-islets that exhibit GSIS. We hence hypothesized that this gene therapy regimen may lead to a complete correction of the glucose and lipid metabolic abnormalities associated with insulin deficiency; we further hypothesized that the neo-islets formed in response to Ngn3-Btc gene delivery may display an ultrastructure and transcription profile similar to that of pancreatic islets. We injected streptozotocin-diabetic mice with helper-dependent adenoviral vectors carrying Ngn3 and Btc, which restored GSIS and reversed hyperglycemia in these animals. The treatment also normalized hepatic glucose secretion and reversed ketonemia. Furthermore, it restored hepatic glycogen content and reinstated hepatic lipogenesis-related gene transcripts back to nondiabetic levels. By transmission electron microscopy, the neo-islets displayed electron-dense granules that were similar in appearance to those in pancreatic islets. Finally, using RNA obtained by laser capture microdissection of the periportal neo-islets and normal pancreatic islets, we found that the neo-islets and pancreatic islets exhibited a very similar transcription profile on microarray-based transcriptome analysis. Taken together, this indicates that Ngn3-Btc gene therapy corrects the underlying dysregulated glucose and lipid metabolism in insulin-deficient diabetic mice by inducing neo-islets in the liver that are similar to pancreatic islets in structure and gene expression profile.

Optical coherence tomography and its use in detection of vulnerable plaque.

Acute coronary syndromes and their associated complications related to coronary ischemia continue to be the leading cause of morbidity and mortality in the world. The most commonly encountered pathophysiologic cascade of events resulting in this picture is initiated by formation of a vulnerable plaque. Despite the widespread use of a variety of imaging technologies, high-resolution detection of the vulnerable plaque and designing a method to correlate the results of the imaging modality with disease severity and prognosis have proven to be an arduous task. The recent introduction of optical coherence tomography has proven to be an innovative contribution to the diagnostic armamentarium for the cardiologist. This article presents an overview of vulnerable plaque and methods for its imaging. It focuses on how optical coherence tomography comes into play and how it compares with other modalities in regard to plaque characterization.

The lectin-like oxidized low-density lipoprotein receptor and its role in atherosclerosis.

The lectin-like oxidized low-density lipoprotein receptor (LOX-1), a recently identified receptor that plays a role in the uptake of oxidized low-density lipoproteins into endothelial cells, has a pivotal role in the pathogenesis of atherosclerosis. The ways this receptor takes part in atherosclerosis is through uptake of oxidized low-density lipoproteins into endothelial cells, smooth muscle cells, and macrophages; decreasing nitric oxide production; increasing inflammatory cell recruitment; and increasing smooth muscle cell proliferation. LOX-1 is inducible and regulated by multiple factors known to underlie atherogenesis. Further understanding of this receptor may lead to potential molecular targets for prevention and treatment of atherosclerosis.

Vulnerable plaque: definition, detection, treatment, and future implications.

Atherosclerosis continues to account for significant morbidity and mortality in most of the world. The major proportion of atherosclerosis mortality is related to atherosclerotic coronary artery disease, yet there still is not an optimal method for making the diagnosis of vulnerable plaque in vivo. The search for such an undefined method, along with studies on amelioration of currently available technology, gains special significance when the association between the qualitative definition of lesions in an individual and cardiovascular risks are considered. We, therefore, start by defining the critical lesion of coronary atherosclerosis and review the advantages and potential for clinical use of various methods to detect the vulnerable plaque and comment on possible future implications in this field.