Clinical studies have demonstrated the safety and effectiveness of drug-coated balloon (DCB) angioplasty for femoropopliteal revascularization. Long-term studies in routine practice are limited.

The aim of this study was to assess long-term outcomes after DCB angioplasty for femoropopliteal peripheral artery disease in a real-word-French population.

Patients with lower-limb PAD treated with at least one IN.PACT Admiral DCB in the year 2018 were identified from the French National Health Data System, representing > 99% of the French population. Primary outcomes were all-cause mortality, major amputation (including target and nontarget limbs and vessels), and reintervention (any infrainguinal reintervention or new intervention of the target lesions, nontarget lesions, target limbs, or contralateral limbs) within 1 year from the date of angioplasty. Patients were followed for 3 years from the date of angioplasty.

A total of 3595 patients (average age 71.2 years) were enrolled, including 35.7% females, 35.3% with chronic limb-threatening ischemia (CLTI), 38.2% with diabetes, and 35.9% with a history of revascularization. All-cause mortality was 7.5% at 1 year and 19.7% at 3 years. The major amputation rate was 2.7% at 1 year and 4.6% at 3 years. The total reintervention rate was 25.9% at 1 year and 43.4% at 3 years. Three-year rates were significantly higher in patients with CLTI (vs. patients with intermittent claudication), diabetes (vs. no diabetes), and prior revascularization (vs. no prior revascularization).

This real-world analysis with long-term follow-up showed satisfactory limb salvage and low mortality following angioplasty with DCBs for the treatment of femoropopliteal artery disease.

Major lower limb amputation is associated with high morbidity and mortality, particularly among patients with diabetes. Previous studies suggest variable mortality rates, but none have investigated the impact of diabetes in Wales.

A population-based cohort study was conducted using anonymised data from the Secure Anonymised Information Linkage Databank. Survival from all incident major amputations in persons ≥ 18 years from 2006 to 2013 in Wales was assessed over 5-year follow-up. Kaplan-Meier survival curves and Cox regression models, stratified by amputation level, were used to examine the time-dependent effect of diabetes on mortality while adjusting for confounding factors.

2542 individuals underwent major amputation, 48.4 % had diabetes. Mortality at 30 days was 9.2 % and 61.9 % within 5 years. Patients with diabetes had higher 5-year mortality (67.0 %) compared to those without diabetes (57.1 %). Diabetes was associated with an increased risk of long-term mortality (hazard ratio 1.62, p < 0.001), but a reduced risk of death in the first 30 days post-amputation. A history of peripheral vascular disease and above-knee amputation were strong predictors of mortality.

Time-stratified analysis demonstrates lower short-term but higher long-term mortality risk for persons with diabetes following major amputation. Further research is required to explore interventions aimed at improving survival.

Background: Percutaneous superficial femoral interventions remain the preferred method of treatment for superficial femoral artery (SFA) disease. Nevertheless, long term restenosis continues to be a major limitation of percutaneous interventions. In this context, the objective of this study is to compare the efficacies of CHA2DS2-VASc, CHA2DS2-VASc-HS, ATRIA, ATRIA-HSV, and HATCH risk scoring systems in predicting long-term (5 years) restenosis due to percutaneous interventions to the superficial femoral artery. Patients and methods: The sample of this retrospective study consisted of 545 peripheral artery disease (PAD) patients with a percutaneous intervention to the SFA. Of these patients, 362 and 183 were included in the group of PAD patients without long-term (5 years) SFA restenosis (Group 1) and in the group of PAD patients with long-term SFA restenosis (Group 2). The efficacies of CHA2DS2-VASc, CHA2DS2-VASc-HS, ATRIA, ATRIA-HSV, and HATCH risk scoring systems in predicting the development of long-term SFA restenosis were comparatively analyzed. Results: CHA2DS2-VASc, CHA2DS2-VASc-HS, ATRIA, ATRIA-HSV, and HATCH risk scores all increased with long-term SFA restenosis. The receiver operating characteristic (ROC) curve analysis revealed that all five risk scoring systems successfully predicted long-term SFA restenosis, whereas the paired ROC curve analysis revealed that CHA2DS2-VASc-HS scores of >4 had the best prognostic power in predicting long term SFA restenosis. Conclusions: The study findings indicated that the CHA2DS2-VASc-HS score was an independent predictor of the development of SFA restenosis. The CHA2DS2-VASc-HS risk scoring system, which is the modified version of CHA2DS2-VASc, outperformed the CHA2DS2-VASc, HATCH, ATRIA, and ATRIA-HSV, the modified version of ATRIA, risk scoring systems in predicting long-term (5 years) SFA restenosis.

Diabetic foot ulcers (DFUs) are a prevalent and severe complication of diabetes, leading to significant morbidity, impaired health-related quality of life (HRQoL) and economic burden on healthcare systems. The complexity of DFUs often results in prolonged healing and high recurrence rates. Effective management strategies are crucial for improving outcomes and reducing complications.

This study aimed to review the efficacy of antiseptic solutions in the treatment and care of DFUs.

A literature analysis was conducted to review clinical studies and guidelines on the use and efficacy of antiseptic solutions, particularly Octenisept® (0.1% octenidine dihydrochloride and 2% 2-phenoxyethanol). The review focused on the antimicrobial properties, biofilm-disruption capabilities and wound healing outcomes associated with the use of antiseptic solutions in DFU management.

Antiseptic solutions have potential to reduce bioburden, disrupt biofilm and modulate healing. There is a need to balance antimicrobial clinical efficacy with tolerability and cytotoxicity. The use and choice of adjunctive antiseptic solutions must be tailored to the patient, as antimicrobial efficacy can vary for antiseptic solutions, particularly for hypochlorous solutions. It is important to use products according to their instructions, with consideration of minimum contact time to maximise clinical efficacy. Low-pressure irrigation is adjunctive, and concurrent wound-bed preparation, including debridement, frequent inspection, infection and moisture control, remain important.

The therapeutic application of antiseptic solutions in DFU care presents a promising approach to enhancing wound healing and reducing infection risks. Integrating these solutions into standard wound care protocols could lower the incidence of complications, improve HRQoL and decrease the economic burden associated with diabetic foot disease. Further large-scale studies are recommended to validate these findings and refine guidelines for antiseptic use in DFU management.

Free tissue transfer is a well-described tool for complex lower extremity reconstruction in areas of local tissue paucity. Successful coverage of orthopedic hardware or exposed vital structures create opportunities for limb salvage.

A retrospective chart review was performed of a patient sustaining a gunshot wound to the lower extremity with bony and soft tissue loss who underwent orthopedic fixation and free tissue transfer at the authors' institution with resultant distal extremity necrosis consistent with vascular steal phenomenon. A systematic literature review using preferred reporting items for systematic reviews and meta-analyses guidelines was performed using the keywords "free tissue transfer," OR "free flap," AND "vascular steal" on PubMed, Ovid/Medline, and Scopus.

After orthopedic fixation, a free anterolateral thigh flap anastomosed end-to-end with an already transected posterior tibial artery for soft tissue coverage. Despite a technically uncomplicated and successful reconstruction, the patient's postoperative course was complicated by steal syndrome, which ultimately led to distal forefoot necrosis and need for transmetatarsal amputation and secondary intention wound healing. Literature review of cases with similar vascular steal phenomenon after free tissue transfer yielded 6 studies totaling 10 patients. All patients with vascular steal phenomenon were previously diagnosed with diabetes and peripheral vascular disease. Despite a majority of single-vessel extremities receiving free tissue transfer with end-to-side techniques, outcomes after vascular steal universally resulted in amputation.

Although vascular steal after free flap reconstruction is a documented phenomenon, this is the first recorded description of vascular steal syndrome from a ballistic-type mechanism in the trauma setting. Overall, this case and review of literature serves as a reminder of the tenuous nature of distal perfusion to the diseased extremity and prompts careful consideration during reconstruction to prevent high morbidity distal ischemia.

To compare ankle brachial pressure index (ABPI) in normal weight and obese/overweight type 2 diabetes mellitus patients (T2DM) to see the impact of obesity on the occurrence of peripheral artery disease (PAD) in T2DM patients. Secondly to investigate the relationship between ABPI, insulin resistance, and beta cell function and between adipocytokines and obesity parameters.

A total of 120 BMI-categorized Normal weight (NW) T2DM (n = 53) patients and obese/overweight T2DM (n = 67) patients were recruited in this study. ABPI measurements were performed for the assessment of PAD. The anthropometry and body composition of the patients were measured. Plasma fasting insulin, adiponectin, and IL-6 levels were measured by ELISA kits.

ABPI scores were found to be comparable between both groups of patients (p = 0.787). A significant positive correlation was observed between ABPI and beta cell function. Insulin resistance was found to correlate positively while adiponectin negatively with obesity parameters.

The ABPI score was comparable between both groups of patients, suggesting that vascular complications may occur at the same rate in NW as well as in obese/overweight diabetic patients. The positive association of insulin resistance as well as the negative association of adiponectin with obesity parameters, are suggestive of the importance of body fat distribution in predicting insulin resistance and the inflammatory status of the cells.

Charcot Neuro-Osteoarthropathy (CNO) is a debilitating complication predominantly affecting individuals with diabetes and peripheral neuropathy. Radiological assessment plays a central role in the diagnosis, staging, and management of CNO. While plain radiographs remain the cornerstone of initial imaging, advanced modalities such as Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) have significantly enhanced diagnostic accuracy. Nuclear imaging, including bone scintigraphy, radiolabeled leukocyte scans, and FDG-PET/CT, offers additional diagnostic precision in complex cases, especially when differentiating CNO from infections or evaluating patients with metal implants. This review underscores the importance of a multimodal imaging approach suited to the clinical stage and specific diagnostic challenges of CNO. It highlights the critical need for standardized imaging protocols and integrated diagnostic algorithms that combine radiological, clinical, and laboratory findings. Advances in imaging biomarkers and novel techniques such as diffusion-weighted MRI hold promise for improving early detection and monitoring treatment efficacy. In conclusion, the effective management of CNO in diabetic foot patients requires a multidisciplinary approach that integrates advanced imaging technologies with clinical expertise. Timely and accurate diagnosis not only prevents debilitating complications but also facilitates the development of personalized therapeutic strategies, ultimately improving patient outcomes.

Continuous glucose monitoring (CGM) metrics, such as time in range (TIR) and glycemic risk index (GRI), have been linked to various diabetes-related complications, including diabetic foot (DF).

To investigate the association between CGM-derived indicators and the risk of DF in individuals with type 2 diabetes mellitus (T2DM).

A total of 591 individuals with T2DM (297 with DF and 294 without DF) were enrolled. Relevant clinical data, complications, comorbidities, hematological parameters, and 72-hour CGM data were collected. Logistic regression analysis was employed to examine the relationship between these measurements and the risk of DF.

Individuals with DF exhibited higher mean blood glucose (MBG) levels and increased proportions of time above range (TAR), TAR level 1, and TAR level 2, but lower TIR (all P < 0.001). Patients with DF had significantly lower rates of achieving target ranges for TIR, TAR, and TAR level 2 than those without DF (all P < 0.05). Logistic regression analysis revealed that GRI, MBG, and TAR level 1 were positively associated with DF risk, while TIR was inversely correlated (all P < 0.05). Achieving TIR and TAR was inversely correlated with white blood cell count and glycated hemoglobin A1c levels (P < 0.05). Additionally, achieving TAR was influenced by fasting plasma glucose, body mass index, diabetes duration, and antidiabetic medication use.

CGM metrics, particularly TIR and GRI, are significantly associated with the risk of DF in T2DM, emphasizing the importance of improved glucose control.

Diabetic foot (DF) is a major public health concern. As evident from numerous previous studies, supervision of DF ulcer (DFU) is crucial, and a specific quality check-up is needed. Patients should be educated about glycaemic management, DFUs, foot lesions, proper care for injuries, diet, and surgery. Certain reasonably priced treatments, such as hyperbaric oxygen and vacuum-assisted closure therapy, are also available for DFUs, along with modern wound care products and techniques. Nonetheless, DF care (cleaning, applying antimicrobial cream when wounded, and foot reflexology), blood glucose monitoring to control diabetes, and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs. Between 50% and 80% of DF infections are preventable. Regardless of the intensity of the lesion, it needs to be treated carefully and checked daily during infection. Tissue regeneration can be aided by cleaning, dressing, and application of topical medicines. The choice of shoes is also important because it affects blood circulation and nerve impulses. In general, regular check-ups, monitoring of the patient's condition, measuring blood glucose levels, and providing frequent guidance regarding DFU care are crucial. Finally, this important clinical problem requires involvement of multiple professionals to properly manage it.

The formation of lower limb arterial plaques, exacerbated by type 2 diabetes (T2D), represents an early stage of lower limb peripheral artery disease (PAD). Second near-infrared region (NIR-II) imaging is an emerging technique with high sensitivity for detecting perfusion levels. This study explores the value of NIR-II imaging in identifying perfusion changes due to lower extremity arterial plaques in T2D patients without PAD.

NIR-II imaging with indocyanine green (ICG) was conducted on 120 T2D patients, who were categorized into two groups: plaque and non-plaque. NIR-II parameters and clinical characteristics were analyzed between the two groups to identify significant predictors of lower extremity arterial plaques.

Six NIR-II imaging parameters (T start, T 1/2, Tmax, Ingress rate, Egress, and Egress rate) showed significant differences and diagnostic efficacy between the two groups. Three NIR-II parameters (T start, Egress, and Egress rate) and two clinical characteristics (age and sex) were identified as independent predictors of lower limb artery plaques. The nomogram showed that a combined model with NIR-II parameters and clinical characteristics exhibited higher diagnostic efficacy.

NIR-II imaging can effectively detect early perfusion changes in T2D patients, showing great potential for pre-diagnosis of individuals at high risk for PAD.

This review examines the challenges posed by Diabetic Foot Infections (DFIs), focusing on the impact of neuropathy, peripheral arterial disease, immunopathy, and the polymicrobial nature of these infections. The aim is to explore the factors contributing to antimicrobial resistance and assess the potential of novel antimicrobial treatments and drug delivery systems in improving patient outcomes.

A comprehensive analysis of existing literature on DFIs was conducted, highlighting the multifactorial pathogenesis and polymicrobial composition of these infections. The review delves into the rise of antimicrobial resistance due to the overuse of antimicrobials, biofilm formation, and microbial genetic adaptability. Additionally, it considers glycemic control, patient adherence, and recurrence rates as contributing factors to treatment failure. Emerging therapies, including new antimicrobial classes and innovative drug delivery systems, were evaluated for their potential efficacy.

DFIs present unique treatment challenges, with high rates of antimicrobial resistance and poor response to standard therapies. Biofilm formation and the genetic adaptability of pathogens worsen resistance, complicating treatment. Current antimicrobial therapies are further hindered by poor glycemic control and patient adherence, leading to recurrent infections. Novel antimicrobial classes and innovative delivery systems show promise in addressing these challenges by offering more targeted, effective treatments. These new approaches aim to reduce resistance and improve treatment outcomes.

DFIs remain a clinical challenge due to their multifactorial nature and antimicrobial resistance. The development of novel antimicrobials and drug delivery systems is crucial to improving patient outcomes and combating resistance. Future research should focus on enhancing treatment efficacy, reducing resistance, and addressing patient adherence to reduce the burden of DFIs.

Peripheral artery disease (PAD) is a significant complication of type 2 diabetes (T2D), yet the association between plasma proteomics and PAD in people with T2D remains unclear. We aimed to explore the relationship between plasma proteomics and PAD in individuals with T2D, and assess whether proteomics could refine PAD risk prediction.

This cohort study included 1,859 individuals with T2D from the UK Biobank. Multivariable-adjusted Cox regression models were used to explore associations between 2,920 plasma proteins and incident PAD. Proteins were further selected as predictors using least absolute shrinkage and selection operator (LASSO) penalty. Predictive performance was assessed using Harrell's C-index, time-dependent area under the receiver operating characteristic curve, continuous/categorical net reclassification improvement, and integrated discrimination improvement.

Over a median follow-up of 13.2 years, 157 incident PAD cases occurred. We observed 463 proteins associated with PAD risk, primarily involved in pathways related to signal transduction, inflammatory response, plasma membrane, protein binding, and cytokine-cytokine receptor interactions. Ranking by P values, the top five proteins associated with increased PAD risk included EDA2R, ADM, NPPB, CD302, and NPC2, while BCAN, UMOD, PLB1, CA6, and KLK3 were the top five proteins inversely associated with PAD risk. Incorporating 45 LASSO-selected proteins or a weighted protein risk score significantly enhanced PAD prediction beyond clinical variables alone, reaching a maximum C-index of 0.835.

This study identified plasma proteins associated with PAD risk in individuals with T2D. Adding proteomic data into the clinical model significantly improved PAD prediction.

Aim: To describe the demographic and clinical characteristics of patients with Charcot neuro-osteoarthropathy (CNO) and to examine for differences between participants with Type 1 diabetes mellitus (DM) (T1DM) and Type 2 diabetes mellitus (T2DM). Materials and Methods: Multicenter observational study in eight diabetic foot clinics in six countries between January 1, 1996, and December 31, 2022. Demographic, clinical, and laboratory parameters were obtained from the medical records. Analyses were performed using parametric or nonparametric statistical tests for variables with normally or nonnormally distributed values, respectively. Comparisons of the qualitative data were performed using the chi-square test. Results: Seven hundred seventy-four patients with DM and CNO were included. The mean age at diagnosis of CNO was 54.5 ± 11.7 years, and the median (interquartile range (IQR)) diabetes duration at diagnosis of CNO was 15 (10-22) years. Among participants, 71.8% (n = 546) were male and 83.2% (n = 634) had T2DM. Neuropathy was present in 91.7% (n = 688), retinopathy in 60.2% (n = 452), and nephropathy in 45.2% (n = 337). Subjects with T1DM, compared to T2DM, were diagnosed with CNO at a younger age (46.9 ± 11.0 vs. 57.9 ± 10.2 years, p < 0.001), had longer diabetes duration (median value (IQR): 29.0 (21.0-38.0) vs. 14.0 (8.0-20.0) years, p < 0.001), and had more often microvascular complications (neuropathy, 95.2% in T1DM vs. 87.4% in T2DM, p = 0.006; retinopathy, 83.3% vs. 55.4%, p < 0.001; and nephropathy 67.5% vs. 40.5%, p < 0.001). Conclusions: CNO is predominant in males, occurs in long-standing DM, and is often accompanied by microvascular complications. People with T1DM, compared to those with T2DM, are affected at a younger age, have longer diabetes duration, and have more often microvascular complications.

 Multidisciplinary care with vascular surgery and plastic surgery is essential for lower extremity free flap (LEFF) success in the chronic wound population with diabetes and peripheral vascular disease. There is a lack of understanding on performing targeted direct endovascular reperfusion on a vessel that will be used as the flap recipient. Our study compares outcomes of patients who received targeted revascularization (TR) to the recipient vessel for LEFF anastomosis versus nontargeted revascularization (NR) of arterial recipients prior to LEFF.

 LEFF patients who underwent preoperative endovascular revascularization (ER) from July 2011 to January 2023 were reviewed. Location of ER, demographics, perioperative details, and outcomes were collected. TR was performed on the same vessel as the flap recipient and NR was located on a different vessel than the flap recipient.

 A total of 55 LEFF patients were identified. Overall, 50.91% (n = 28) received TR and 49.1% (n = 27) received NR. Average age was 60.3 ± 10.9 years and average Charlson Comorbidity Index was 5.3 ± 1.9. On preoperative angiogram, the TR group had significantly lower rates of ER above the knee (3.6 vs. 33.3%, p < 0.001). Immediate flap success rate was 98.2%, with no differences between groups (p = 1.000). No significant differences were found in rates of any postoperative flap complications (p = 0.898), takeback (p = 0.352), partial flap necrosis (p = 0.648), or dehiscence (p = 0.729). Both TR and NR groups had similar rates of a postoperative angiogram (42.9 vs. 48.2%, p = 0.694) and reintervention (35.7 vs. 40.7% p = 0.701). Amputation rates were similar between TR and NR (17.9 vs. 14.8%, p = 1.000).

 Close follow-up with vascular and plastic surgery is required for patients who undergo ER prior to LEFF, as nearly half of our cohort required additional endovascular procedures. Overall, we observed no significant differences in complication rates for the TR and NR groups, informing revascularization strategies for free tissue transfer in a highly comorbid chronic wound population.

The aging global population presents challenges in medication management, particularly among diabetic elderly patients vulnerable to potentially inappropriate medications (PIM). PIM can lead to adverse outcomes like hypoglycemia, falls, cognitive decline, and hospitalizations, affecting quality of life and survival. This study aimed to assess PIM prevalence among diabetic elderly patients in a tertiary care hospital in Saudi Arabia, using the American Geriatrics Society 2023 Updated Beers Criteria.

A cross-sectional retrospective study was conducted among 480 diabetic adults aged 60 years or older at a tertiary care hospital over 3 months. Data, including demographics, comorbidities, and medication use, were extracted from Electronic Health Records. 2023 AGS Updated Beers Criteria® was followed.

The median age was 66 years with a male predominance (62.7%). Peripheral vascular disease (42.7%) and prior myocardial infarction (22.7%) were prevalent comorbidities. Inappropriate insulin use was observed in 17.7% of insulin users, mainly short-acting insulin without basal/long-acting insulin. Approximately 39.2% of patients were prescribed antidiabetic drugs deemed inappropriate by Beers Criteria, with Gliclazide being the most common (35.6%). Despite potential drug-disease interactions, such as urogenital infections, half of the patients received cautioned drugs, while only 4.2% experienced such infections.

The study highlights the prevalence of PIMs among diabetic elderly patients in Madinah, Saudi Arabia. Adherence to Beers Criteria guidelines is crucial to optimize therapy for this population. Age and congestive heart failure were significant predictors of PIM use.

Cerebrovascular accidents (CVA) represent a major complication in diabetes (DM). Real-life evidence as to whether modern management of CVA and DM have softened this relationship is limited. Therefore, we estimated prevalence and impact of DM on in-hospital survival and complications in a contemporary cohort of subjects with CVA.

We retrospectively evaluated the records of 937 patients admitted for CVA at the Stroke Unit of Verona University Hospital during a 3-year period. Pre-existing or de novo DM was ascertained by prior diagnosis, glucose-lowering therapy at admission/discharge or admittance plasma glucose ≥ 200 mg/dL. Multiple regressions were applied to test DM as predictor of in-hospital mortality, complications (composite of infections, cardio- and cerebrovascular complications, major bleeding and pulmonary complications), duration and costs of hospitalization.

Diabetes prevalence was 21%, of which 22% de novo diagnoses. Compared to non-DM, diabetic individuals were older and carried an increased burden of cardiovascular risk factors. Compared to known DM, de novo DM individuals were younger, had higher admittance plasma glucose and poorer cardiovascular comorbidities. Overall, DM versus non-DM individuals did not show significantly increased risk of death (14.0 vs. 9.3%; crude-OR 1.59 95% CI 0.99-2.56). Controlling for confounders did not improve significance. DM resulted independent predictor for in-hospital complications (36.2% vs. 26.9%; adj-OR 1.49, 1.04-2.13), but not for duration and costs of hospitalization.

DM frequently occurs in patients admitted for stroke and carries an excess burden of adverse in-hospital complications, urgently calling for strategies to anticipate DM diagnosis and tailored treatment in high-risk individuals.

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in regulating blood pressure (BP), with dysregulation of RAAS resulting in hypertension and potentially heart failure (HF), myocardial infarction (MI), cardio-renal syndrome, and stroke. RAAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs), have advantages beyond BP control. However, differences between these two drug classes need to be considered when choosing a therapy for preventing cardiovascular events.

A panel of 36 Egyptian cardiologists developed consensus statements on RAAS inhibitors for primary and secondary prevention of cardiovascular outcomes and stroke, using a modified three-step Delphi process.

The consensus statements highlight the importance of effective BP control and the role of RAAS blockade for prevention and management of various cardiovascular diseases. ACEis and ARBs differ in their mode of action and, thus, clinical effects. On the basis of available evidence, the consensus group recommended the following: ACEis should be considered as first choice (in preference to ARBs) to reduce the risk of MI, for primary prevention of HF, and for secondary prevention of stroke. ACEis and ARBs show equivalent efficacy for the primary prevention of stroke. Evidence also favors the preferential use of ACEis in patients with type 2 diabetes, for BP control, for the primary prevention of diabetic kidney disease, and to reduce the risk of major cardiovascular and renal outcomes. Treatment with an ACEi should be started within 24 h of ST segment elevation MI (and continued long term) in patients with HF, left ventricular systolic dysfunction, and/or diabetes. Angiotensin receptor/neprilysin inhibitors (ARNIs) are the first choice for patients with HF and reduced ejection fraction, with ACEis being the second choice in this group. ARBs are indicated as alternatives in patients who cannot tolerate ACEis. ACEis may be associated with cough development, but the incidence tends to be overestimated, and the risk can be reduced by use of a lipophilic ACEi or combining the ACEi with a calcium channel blocker.

RAAS blockade is an essential component of hypertension therapy; however, the protective effects provided by ACEis are superior to those of ARBs. Therefore, an ACEi is indicated in almost all cases, unless not tolerated.

Endothelial cells (ECs) use glycolysis to produce energy. In preclinical models of peripheral arterial disease, further activation of EC glycolysis was ineffective or deleterious in promoting hypoxia-dependent angiogenesis, whereas pentose phosphate pathway activation was effective. Hexosamine biosynthesis pathway, pentose phosphate pathway, and glycolysis are closely linked. Glucosamine directly activates hexosamine biosynthesis pathway.

Hind-limb ischemia in endothelial nitric oxide synthase knockout (eNOS-/-) and BALB/c mice was used. Glucosamine (600 μg/g per day) was injected intraperitoneally. Blood flow recovery was assessed using laser Doppler perfusion imaging and angiogenesis was studied by CD31 immunostaining. In vitro, human umbilical vein ECs and mouse microvascular ECs with glucosamine, L-glucose, or vascular endothelial growth factor (VEGF165a) were tested under hypoxia and serum starvation. Cell Counting Kit-8, tube formation, intracellular reactive oxygen species, electric cell-substrate impedance sensing, and fluorescein isothiocyanate dextran permeability were assessed. Glycolysis and oxidative phosphorylation were assessed by seahorse assay. Gene expression was assessed using RNA sequencing, real-time quantitative polymerase chain reaction, and Western blot. Human muscle biopsies from patients with peripheral arterial disease were assessed for EC O-GlcNAcylation before and after supervised exercise versus standard medical care.

On day 3 after hind-limb ischemia, glucosamine-treated versus control eNOS-/- mice had less necrosis (n=4 or 5 per group). Beginning on day 7 after hind-limb ischemia, glucosamine-treated versus control BALB/c mice had higher blood flow, which persisted to day 21, when ischemic muscles showed greater CD31 staining per muscle fiber (n=8 per group). In vitro, glucosamine versus L-glucose ECs showed improved survival (n=6 per group) and tube formation (n=6 per group). RNA sequencing of glucosamine versus L-glucose ECs showed increased amino acid metabolism (n=3 per group). That resulted in increased oxidative phosphorylation (n=8-12 per group) and serine biosynthesis pathway without an increase in glycolysis or pentose phosphate pathway genes (n=6 per group). This was associated with better barrier function (n=6-8 per group) and less reactive oxygen species (n=7 or 8 per group) compared with activating glycolysis by VEGF165a. These effects were mediated by activating transcription factor 4, a driver of exercise-induced angiogenesis. In muscle biopsies from humans with peripheral arterial disease, EC/O-GlcNAcylation was increased by 12 weeks of supervised exercise versus standard medical care (n=6 per group).

In cells, mice, and humans, activation of hexosamine biosynthesis pathway by glucosamine in peripheral arterial disease induces an "exercise-like" angiogenesis and offers a promising novel therapeutic pathway to treat this challenging disorder.

Prior studies have described risk factors associated with amputation in patients with concomitant diabetes and peripheral arterial disease (DM/PAD). However, the association between the severity and extent of tissue loss type and amputation risk remains less well-described. We aimed to quantify the role of different tissue loss types in amputation risk among patients with DM/PAD, in the context of demographic, preventive, and socioeconomic factors.

Applying International Classification of Diseases (ICD)-9 and ICD-10 codes to Medicare claims data (2007-2019), we identified all patients with continuous fee-for-service Medicare coverage diagnosed with DM/PAD. Eight tissue loss categories were established using ICD-9 and ICD-10 diagnosis codes, ranging from lymphadenitis (least severe) to gangrene (most severe). We created a Cox proportional hazards model to quantify associations between tissue loss type and 1- and 5-year amputation risk, adjusting for age, race/ethnicity, sex, rurality, income, comorbidities, and preventive factors. Regional variation in DM/PAD rates and risk-adjusted amputation rates was examined at the hospital referral region level.

We identified 12,257,174 patients with DM/PAD (48% male, 76% White, 10% prior myocardial infarction, 30% chronic kidney disease). Although 2.2 million patients (18%) had some form of tissue loss, 10.0 million patients (82%) did not. The 1-year crude amputation rate (major and minor) was 6.4% in patients with tissue loss, and 0.4% in patients without tissue loss. Among patients with tissue loss, the 1-year any amputation rate varied from 0.89% for patients with lymphadenitis to 26% for patients with gangrene. The 1-year amputation risk varied from two-fold for patients with lymphadenitis (adjusted hazard ratio, 1.96; 95% confidence interval, 1.43-2.69) to 29-fold for patients with gangrene (adjusted hazard ratio, 28.7; 95% confidence interval, 28.1-29.3), compared with patients without tissue loss. No other demographic variable including age, sex, race, or region incurred a hazard ratio for 1- or 5-year amputation risk higher than the least severe tissue loss category. Results were similar across minor and major amputation, and 1- and 5-year amputation outcomes. At a regional level, higher DM/PAD rates were inversely correlated with risk-adjusted 5-year amputation rates (R2 = 0.43).

Among 12 million patients with DM/PAD, the most significant predictor of amputation was the presence and extent of tissue loss, with an association greater in effect size than any other factor studied. Tissue loss could be used in awareness campaigns as a simple marker of high-risk patients. Patients with any type of tissue loss require expedited wound care, revascularization as appropriate, and infection management to avoid amputation. Establishing systems of care to provide these interventions in regions with high amputation rates may prove beneficial for these populations.

Symmetrical peripheral gangrene (SPG) is a serious and rare complication in patients with urosepsis, characterized by distal limb symmetry impairment.

In this study, 3 cases of SPG caused by urosepsis were reported, and the Chinese and English literature on SPG caused by urosepsis was reviewed. The demographic, clinicopathological, treatment, and follow-up data of the patients were summarized and analyzed.

SPG was diagnosed with clinical symptoms.

We conducted urological invasive surgery, administered anti-infective therapy, implemented fluid resuscitation and blood product transfusion, provided mechanical ventilation support, optimized myocardial contractility, administered heparin and B vitamins, utilized papaverine for vasodilation, performed hemodialysis and plasma exchange, peripheral skin warming along with other treatment modalities.

Two patients died and 1 patient underwent autoamputation.

Our cases and literature review demonstrate that timely and accurate diagnosis, effective infection control, correction of hypoperfusion, organ function support, early management of disseminated intravascular coagulation, avoidance of premature amputation, and multidisciplinary comprehensive treatment are crucial for the successful treatment of SPG caused by urosepsis.

The estimation of vessels' centerlines is a critical step in assessing the geometry of the vessel, the topological representation of the vessel tree, and vascular network visualization. In this research, we present a novel method for obtaining geometric parameters from peripheral arteries in 3D medical binary volumes. Our approach focuses on centerline extraction, which yields smooth and robust results. The procedure starts with a segmented 3D binary volume, from which a distance map is generated using the Euclidean distance transform. Subsequently, a skeleton is extracted, and seed points and endpoints are identified. A search methodology is used to derive the best path on the skeletonized 3D binary array while tracking from the goal points to the seed point. We use the distance transform to calculate the distance between voxels and the nearest vessel surface, while also addressing bifurcations when vessels divide into multiple branches. The proposed method was evaluated on 22 real cases and 10 synthetically generated vessels. We compared our method to different state-of-the-art approaches and demonstrated its better performance. The proposed method achieved an average error of 1.382 mm with real patient data and 0.571 mm with synthetic data, both of which are lower than the errors obtained by other state-of-the-art methodologies. This extraction of the centerline facilitates the estimation of multiple geometric parameters of vessels, including radius, curvature, and length.

Peripheral artery disease (PAD) is an atherosclerotic occlusive disease of the lower extremities and is associated with an increased risk of amputation and cardiovascular events. The interplay between diabetes and PAD is complex, influenced by shared risk factors such as hypertension, dyslipidemia, and smoking. High rates of undiagnosed diabetes, coupled with barriers to accessing care, contribute to the complexity of managing PAD. Unique to the Sub-Sahara region is associations with communicable diseases such as human immunodeficiency virus and tuberculosis which further complicates the epidemiological landscape. Comprehensive management strategies, including lifestyle modifications, pharmacological interventions, and revascularization procedures, are essential. However, the region faces challenges such as inadequate healthcare infrastructure and high costs of treatment. This narrative review highlights the epidemiology of PAD in people with diabetes, the risk factors associated with PAD, the impact of PAD on the morbidity and mortality of individuals with diabetes, as well as the management of PAD in individuals with diabetes, with attention geared toward Sub-Saharan Africa These insights are critical for developing effective strategies to mitigate the burden of PAD in diabetes, especially in Sub-Saharan Africa. Further research is essential to understand the associations between diabetes and other diseases in the region.

Diabetic foot is one of the complications in type 2 diabetes mellitus. Adequate knowledge and practice are an important aspect to control further deteriorating conditions such as ulcers and amputations. Thus, the objective of this cross-sectional study was to investigate the impact of the education levels of diabetic patients on diabetic foot care knowledge and practice. This cross-sectional study with a convenient sampling technique was conducted on 534 patients with diabetes mellitus from public and private care hospitals. The data was collected using a validated, pretested and structured bilingual (Arabic, English) questionnaire. There were 534 patients interviewed, 39.1% of whom were males and 60.9% of whom were females and 61.4% of the patients had had T2DM for over 10 years. There was a significant difference in education levels between the male and female patients (53.8% and 46.2%, P = .001). Furthermore, 83.9% patients were married. The difference in education between the married and the single, divorced, and widowed patients was significant (P = .007). Patients with uncontrolled HbA1c were 2.43 times more likely to have hypertension (RR = 2.43, P = .03), while patients with highly uncontrolled diabetes had 3.1 times more chances of hypertension (RR = 3.1, P = .009). Heart disease prevalence was 3.27 times higher in diabetes patients with uncontrolled HbA1c and 3.37 times higher in patients with highly uncontrolled HbA1c. Patients with diabetes who have been diabetic for more than 10 years have a greater risk of heart disease (RR = 2.1; P = .03). Patients with lower education levels exhibited more diabetic complications compared to patients with higher education levels (P < .05). The present study highlights the importance of education and awareness campaigns targeting diabetic patients, especially those with lower education levels, to improve diabetes control and prevent, or manage, comorbidities. Healthcare providers should also prioritize patient education and medication adherence to improve diabetes management and reduce the risk of complications.

Evidence on the prevalence of foot problems among people with diabetes in India at a national level is lacking. Hence, this study was aimed to assess the burden of high-risk (HR) feet in people with diabetes across India.

A cross-sectional national-level project 'Save the Feet and Keep Walking' campaign was conducted by the Research Society for the Study of Diabetes in India (RSSDI) from July 10, 2022 to August 10, 2022. A modified version of 3 min foot examination was used to assess the foot problems. Around 10 000 doctors with RSSDI membership were trained online to conduct foot screening and provided a standardised monofilament for detection of loss of protective sensation. People with diabetes aged >18 years who visited the clinics during the study period were examined for foot problems. Data were collected online using the semi-structured questionnaire. A total of 33 259 participants with complete information were included for the final analysis. The foot at risk was categorised based on International Working Group on the Diabetic Foot guidelines 2023.

Nearly 75% of the participants were aged above 45 years. Around 49% had diabetes duration >5 years and uncontrolled diabetes (hemoglobin A1c >8%). Presence of history of foot ulcer (20%), lower limb amputation (15.3%), foot deformities (24.5%) and absence of diminished dorsal pedis and posterior tibial pulses (26.4%) was noted in the study participants. Around 25.2% of them had HR feet and highly prevalent among males. Diabetic kidney and retinal complications were present in 70% and 75.5% of people with HR feet. Presence of heel fissures (OR (95% CI) 4.6 (4.2 to 5.1)) and callus or corns (OR (95% CI) 3.6 (3.3 to 4.0)) were significantly associated with HR feet.

One-fourth of people with diabetes were found to have HR feet in India. The findings are suggestive of regular screening of people with diabetes for foot problems and strengthening of primary healthcare.

The development of natural substances derived from nature poses a significant challenge as technologies for the extraction and characterization of active principles advance. Hispolon has received a lot of attention in recent years, ascribable to its wide range of biological activities. It is a phenolic molecule that was extracted from several mushroom species such as Phellinus igniarius, Phellinus linteus, Phellinus lonicerinus, Phellinus merrillii, and Inonotus hispidus. To provide a comprehensive overview of the pharmacological activities of hispolon, this review highlights its anticancer, anti-inflammatory, antioxidant, antibacterial, and anti-diabetic activities. Several scientific research databases, including Google Scholar, Web of Science, PubMed, SciFinder, SpringerLink, Science Direct, Scopus, and, Wiley Online were used to gather the data on hispolon until May 2024. The in vitro and in vivo studies have revealed that hispolon exhibited significant anticancer properties through modifying several signaling pathways including cell apoptosis, cycle arrest, autophagy, and inhibition of angiogenesis and metastasis. Hispolon's antimicrobial activity was proven against many bacterial, fungal, and viral pathogens, highlighting its potential use as a novel antimicrobial agent. Additionally, hispolon displayed potent anti-inflammatory activity through the suppression of key inflammatory mediators, such as inducible NO synthase (iNOS), tumor necrosis factor-α (TNF-α), and cyclooxygenases-2 (COX-2), and the modulation of mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. The antioxidant potential of hispolon was attributed to its capacity to neutralize reactive oxygen species (ROS) and to increase the activity of antioxidant enzymes, indicating a possible involvement in the prevention of oxidative stress-related illnesses. Hispolon's antidiabetic activity was associated with the inhibition of aldose reductase and α-glucosidase. Studies on hispolon emphasized its potential use as a promising scaffold for the development of novel therapeutic agents targeting various diseases, including cancer, infectious diseases, inflammatory disorders, and diabetes.

Chronic inflammation has long been considered the characteristic feature of type II diabetes mellitus (T2DM) Immunopathogenesis. Pro-inflammatory cytokines are considered the central drivers of the inflammatory cascade leading to β-cell dysfunction and insulin resistance (IR), two major pathologic events contributing to T2DM. Analyzing the cytokine profile of T2DM patients has also introduced interleukin-17 (IL-17) as an upstream regulator of inflammation, regarding its role in inducing the nuclear factor-kappa B (NF-κB) pathway. In diabetic tissues, IL-17 induces the expression of inflammatory cytokines and chemokines. Hence, IL-17 can deteriorate insulin signaling and β-cell function by activating the JNK pathway and inducing infiltration of neutrophils into pancreatic islets, respectively. Additionally, higher levels of IL-17 expression in patients with diabetic complications compared to non-complicated individuals have also proposed a role for IL-17 in T2DM complications. Here, we highlight the role of IL-17 in the Immunopathogenesis of T2DM and corresponding pathways, recent advances in preclinical and clinical studies targeting IL-17 in T2DM, and corresponding challenges and possible solutions.

Localized delivery of angiogenesis-promoting factors such as small molecules, nucleic acids, peptides, and proteins to promote the repair and regeneration of damaged tissues remains a challenge in vascular tissue engineering. Current delivery methods such as direct administration of therapeutics can fail to maintain the necessary sustained release profile and often rely on supraphysiologic doses to achieve the desired therapeutic effect. By implementing a microparticle delivery system, localized delivery can be coupled with sustained and controlled release to mitigate the risks involved with the high dosages currently required from direct therapeutic administration.

For this purpose, poly(lactic-co-glycolic acid) (PLGA) microparticles were fabricated via anti-solvent microencapsulation and the loading, release, and delivery of model angiogenic molecules, specifically a small molecule, nucleic acid, and protein, were assessed in vitro using microvascular fragments (MVFs).

The microencapsulation approach utilized enabled rapid spherical particle formation and encapsulation of model drugs of different sizes, all in one method. The addition of a fibrin scaffold, required for the culture of the MVFs, reduced the initial burst of model drugs observed in release profiles from PLGA alone. Lastly, in vitro studies using MVFs demonstrated that higher concentrations of microparticles led to greater co-localization of the model therapeutic (miRNA) with MVFs, which is vital for targeted delivery methods. It was also found that the biodistribution of miRNA using the delivered microparticle system was enhanced compared to direct administration.

Overall, PLGA microparticles, formulated and loaded with model therapeutic compounds in one step, resulted in improved biodistribution in a model of the vasculature leading to a future in translational revascularization.

Trimethyl-N-oxide (TMAO) has been linked to peripheral artery disease (PAD). TaurisoloⓇ is a natural, balanced phytocomplex containing resveratrol, quercetin, catechins, procianidins, gallic acid, and caffeic acid. Numerous studies have shown that TaurisoloⓇ reduces the damage of TMAO and exerts a protective effect on endothelial cells (ECs). The aim of this randomized, double-blind, single-center study was to evaluate the effects of TaurisoloⓇ on claudication in patients with PAD (Rutheford grade I, category II, Fontaine Classification: Stage IIA, American Medical Association Whole Person Impairment Classification: Class 0-WPI 0%) in two parallel groups of 31 patients. The primary outcomes were an increase in the pain-free walking distance and the ankle/brachial pressure index at the beginning and at the end of the treatment with Taurisolo. The secondary endpoint was the serum TMAO changes. The claudication distance improved by 14.1% in the Taurisolo group and by 2.0% in the placebo group, while the maximal distance increased by 15.8% and 0.6% only, respectively (both p < 0.05). The TMAO plasma levels decreased from 3.97 ± 2.13 micromole/L to 0.87 ± 0.48 (p < 0.0001) in the treated group. All these changes were highly significant both in univariate mixed models as well as in the adjusted model. Ultimately, TaurisoloⓇ might be an effective intervention to ameliorate intermittent claudication.

Type 2 diabetes mellitus (T2DM) is linked to impaired mitochondrial function. Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a gadolinium-contrast-free 1H method to assess mitochondrial function by measuring low-concentration metabolites. A CEST MRI-based technique may serve as a non-invasive proxy for assessing mitochondrial health.

A 1H CEST MRI technique may detect significant differences in in vivo skeletal muscle phosphocreatine (SMPCr) kinetics between healthy volunteers and T2DM patients undergoing standardized isometric exercise.

Cross-sectional study.

Seven subjects without T2DM (T2DM-) and seven age, sex, and BMI-matched subjects with T2DM (T2DM+).

Single-shot rapid acquisition with refocusing echoes (RARE) and single-shot gradient-echo sequences, 3 T.

Subjects underwent a rest-exercise-recovery imaging protocol to dynamically acquire SMPCr maps in calf musculature. Medial gastrocnemius (MG) and soleus SMPCr concentrations were plotted over time, and SMPCr recovery time, τ , was determined. Mitochondrial function index was calculated as the ratio of resting SMPCr to τ . Participants underwent a second exercise protocol for imaging of skeletal muscle blood flow (SMBF), and its association with SMPCr was assessed.

Unpaired t-tests and Pearson correlation coefficient. A P value <0.05 was considered statistically significant.

SMPCr concentrations in MG and soleus displayed expected declines during exercise and returns to baseline during recovery. τ was significantly longer in the T2DM+ cohort (MG 83.5 ± 25.8 vs. 54.0 ± 21.1, soleus 90.5 ± 18.9 vs. 51.2 ± 14.5). The mitochondrial function index in the soleus was significantly lower in the T2DM+ cohort (0.33 ± 0.08 vs. 0.66 ± 0.19). SMBF was moderately correlated with the SMPCr in T2DM-; this correlation was not significant in T2DM+ (r = -0.23, P = 0.269).

The CEST MRI method is feasible for quantifying SMPCr in peripheral muscle tissue. T2DM+ individuals had significantly lower oxidative capacities than T2DM- individuals. In T2DM, skeletal muscle metabolism appeared to be decoupled from perfusion.

1 TECHNICAL EFFICACY: Stage 1.

Peripheral artery disease (PAD) affects millions of people worldwide, presenting with varying symptom severity, including chronic total occlusion of arteries, and occasionally, limb amputation. There are various interventions, such as atherectomy and the use of drug-coated balloons and stents, which have been developed to revascularize affected ischemic regions. However, each interventional approach must be individualized due to a patient's unique underlying conditions. Comorbid conditions, especially diabetes, play a significant role in PAD, as poorly controlled diabetes can accelerate PAD progression. For this reason, an early and accurate diagnosis of PAD is crucial, especially when symptoms may present dissimilar to classic PAD symptoms, often leading to misdiagnosis. The presented cases highlight the tailored interventions to revascularize arteries in patients with diabetic foot wounds utilizing catheters, stents, guidewires, and balloons, made possible after early angiogram. These interventions have been promising in treating PAD patients, and highlight the need for early diagnosis and timely and customized interventions to prevent limb amputation and mitigate potential complications.

Diabetes mellitus (DM) is a major risk factor for lower extremity arterial disease (LEAD) and about 20% of symptomatic patients with LEAD have DM. In subjects with DM, LEAD is a cause of morbidity and mortality. DM typically causes complications in the form of macro- and microangiopathy. In these patients, macroangiopathy manifests as atherosclerosis like in non-diabetic patients. However, its course is accelerated due to accompanying risk factors like hyperlipidemia and hypertension, with cumulative effects. Other factors are also relevant such as inflammation, endothelial dysfunction, platelet activation, blood rheological properties, hypercoagulability, and factors stimulating vascular smooth muscle cell proliferation. Additionally, DM is a risk factor for restenosis and amputation. DM is strongly associated with femoral-popliteal and tibial LEAD, which manifests earlier in patients with DM and may progress more rapidly to critical limb ischemia. Diabetic microangiopathy is characterized by arteriolosclerosis and interstitial fibrosis which additionally affects progression and outcomes of angiopathy of lower limbs. Glycemic control particularly decreases microangiopathic complications, while prevention of macrovascular complications requires treatment of accompanying risk factors like hypertension and dyslipidemia.

Diabetes mellitus (DM) is a major risk factor for peripheral artery disease. The association of DM with major adverse limb events (MALE) after lower extremity revascularization remains controversial, as patients with diabetes are typically analyzed as a single, homogenous group. Using a large national database, this study examines the impact of insulin use and glycemic control on the outcomes following infrainguinal bypass. The hypothesis is that prevalent insulin therapy and elevated hemoglobin A1c (HbA1c) are associated with an increased risk of MALEs after infrainguinal bypass in patients with DM and could therefore be used for risk stratification.

The Vascular Quality Initiative database files for infrainguinal bypass (2007-2021) were retrospectively reviewed. Patients with DM undergoing bypass for peripheral artery disease were included. Patients on dialysis or with prior kidney transplantation were excluded. The characteristics and outcomes of patients with insulin-requiring diabetes mellitus (IRDM) were compared to those of patients not requiring insulin (noninsulin-requiring diabetes mellitus [NIRDM]) prior to the bypass procedure.

A total of 9,686 patients with DM (56% IRDM) underwent bypass. Patients with IRDM were significantly younger than patients with NIRDM, more likely to be female (P < 0.01), African American (P < 0.01), and Hispanic (P = 0.031), and more likely to have comorbidities and be categorized into American Society of Anesthesiologist classes IV-V. They were more likely to be treated for chronic limb-threatening ischemia (P < 0.001). Patients with IRDM had significantly higher perioperative complications with no difference in perioperative mortality between the 2 groups. Beyond the perioperative period, with a mean follow-up of 427 days, patients with IRDM had significantly lower crude rates of primary patency and higher crude rates of major amputation, MALE, and mortality compared to patients with NIRDM. Regression analyses demonstrated that insulin requirement, but not HbA1c, was independently associated with a higher risk of MALE (hazard ratio = 1.17 [1.06-1.29]) and mortality (hazard ratio = 1.28 [1.16-1.43]).

Insulin requirement, but not HbA1c, is significantly associated with MALEs and survival after infrainguinal bypass in the Vascular Quality Initiative. Stratification of patients with DM based on their prevalent insulin use prior to infrainguinal bypass surgery could improve the prediction of outcomes of peripheral arterial bypass surgery in patients with diabetes.

Metformin is a synthetic biguanide used as an antidiabetic drug in type 2 diabetes mellitus, achieved by studying the bioactive metabolites of Galega officinalis L. It is also used off-label for various other diseases, such as subclinical diabetes, obesity, polycystic ovary syndrome, etc. In addition, metformin is proposed as an add-on therapy for several conditions, including autoimmune diseases, neurodegenerative diseases, and cancer. Although metformin has been used for many decades, it is still the subject of many pharmacodynamic and pharmacokinetic studies in light of its extensive use. Metformin acts at the mitochondrial level by inhibiting the respiratory chain, thus increasing the AMP/ATP ratio and, subsequently, activating the AMP-activated protein kinase. However, several other mechanisms have been proposed, including binding to presenilin enhancer 2, increasing GLP1 release, and modification of microRNA expression. Regarding its pharmacokinetics, after oral administration, metformin is absorbed, distributed, and eliminated, mainly through the renal route, using transporters for cationic solutes, since it exists as an ionic molecule at physiological pH. In this review, particular consideration has been paid to literature data from the last 10 years, deepening the study of clinical trials inherent to new uses of metformin, the differences in effectiveness and safety observed between the sexes, and the unwanted side effects. For this last objective, metformin safety was also evaluated using both VigiBase and EudraVigilance, respectively, the WHO and European databases of the reported adverse drug reactions, to assess the extent of metformin side effects in real-life use.

Diabetes foot syndrome is one of the common complications of diabetes. Detailed information on the clinical and vascular characteristics of patients with diabetic foot disease in relation to the outcome of the care provided to these patients will be useful to policymakers and clinicians in early detection and timely interventions for the prevention of disabling complications.

This is a review of patients with diabetic foot managed in Aminu Kano Teaching Hospital over 5 years (January 2017-May 2022). The sociodemographic characteristics, Wagner classification of the foot, Doppler sonographic characteristics and clinical outcomes, etc., were reviewed.

A total of 51 patients were reviewed. Males and females accounted for 56.8% and 43.1%, respectively. Twenty-five patients had Wagner grade 4 ulcers, and fewer patients had Wagner grade 1 and 5-foot ulcers. The mean ± standard deviation Doppler arterial intimal media thickness was 1.53 ± 0.33 (range 0.90-2.40 mm). The majority of DFS patients had Doppler sonographic lesions on the right lower limb 28 (54.9%) only, and 11 (21.6%) of the lesions were bilateral. The posterior tibial artery 11 (21.6%) was the most involved arterial segment with plaques, followed by a combination of popliteal and tibial arterial 10 (19.6%) segments. At 6 months, 45.2% had limb amputation, 17.6% healed ulcers, 17.6% delayed wound healing, and 9.8% died.

There is an unacceptably high prevalence of poor treatment outcomes, thus, contributing to a huge burden of care to patients living with diabetes. There is a strong association between severe arterial stenosis detected by Doppler ultrasound and higher rates of amputations.

Racial, ethnic, and socioeconomic disparities in the major risk factors for vascular disease and access to vascular specialist care are well-documented.1-3 The higher incidence of diabetes, peripheral artery disease (PAD), and related nontraumatic lower extremity amputation among racial and ethnic minority groups, those of low socioeconomic status, and those with poor access to care based on geography (together, referred to below as disadvantaged groups) are particularly pervasive.1,4-9 Practitioners of vascular surgery and endovascular therapy are uniquely positioned to address health inequities in lower extremity screening, medical management, intervention, and limb preservation among the population of adults at the highest risk for limb loss.

Multimorbidity is common in patients who experience stroke. Less is known about the effect of specific multimorbidity patterns on long-term disability in patients with stroke. Furthermore, given the increased poststroke disability frequently seen in female vs male patients, it is unknown whether multimorbidity has a similar association with disability in both sexes. We assessed whether specific multimorbidity clusters were associated with greater long-term poststroke disability burden overall and by sex.

In the Taiwan Stroke Registry, an ongoing nationwide prospective registry, patients with first-ever ischemic stroke were enrolled; this analysis is restricted to those individuals surviving to at least 6 months poststroke. Using a hierarchical clustering approach, clusters of prestroke multimorbidity were generated based on 16 risk factors; the algorithm identified 5 distinct clusters. The association between clusters and 12-month poststroke disability, defined using the modified Rankin Scale (mRS), was determined using logistic regression models, with additional models stratified by sex. The longitudinal association between multimorbidity and functional status change was assessed using mixed-effects models.

Nine-thousand eight hundred eighteen patients with first-ever ischemic stroke were included. The cluster with no risk factors was the reference, "healthier" risk group (N = 1,373). Patients with a cluster profile of diabetes, peripheral artery disease (PAD), and chronic kidney disease (CKD) (N = 1882) had significantly greater disability (mRS ≥ 3) at 1 month (OR [95% CI] = 1.36 [1.13-1.63]), 3 months (OR [95% CI] = 1.27 [1.04-1.55]), and 6 months (OR [95% CI] = 1.30 [1.06-1.59]) but not at 12 months (OR [95% CI] = 1.16 [0.95-1.42]) than patients with a healthier risk factor profile. In the sex-stratified analysis, the associations with this risk cluster remained consistent in male patients (OR [95% CI] = 1.42 [1.06-1.89]) at 12 months, who also had a higher comorbidity burden, but not in female patients (OR [95% CI] = 0.95 [0.71-1.26]), who had higher proportions of severe strokes and severe disability (p-interaction = 0.04).

Taiwanese patients with multimorbidity, specifically the concurrent presence of diabetes, PAD, and CKD, had higher odds of a worse functional outcome in the first 6 months poststroke. Clusters of multimorbidity may be less informative for long-term disability in female patients. Further studies should evaluate other mechanisms for worse disability in female patients poststroke.

Arterial catheters (ACs) are critical for haemodynamic monitoring and blood sampling but are prone to complications. We investigated the incidence and risk factors of AC failure.

Secondary analysis of a multi-centre randomised controlled trial (ACTRN 12610000505000). Analysis included a subset of adult intensive care unit patients with an AC. The primary outcome was all-cause device failure. Secondary outcomes were catheter associated bloodstream infection (CABSI), suspected CABSI, occlusion, thrombosis, accidental removal, pain, and line fracture. Risk factors associated with AC failure were investigated using Cox proportional hazards and competing-risk models.

Of 664 patients, 173 (26%) experienced AC failure (incidence rate [IR] 37/1000 catheter days). Suspected CABSI was the most common failure type (11%; IR 15.3/1000 catheter days), followed by occlusion (8%; IR 11.9/1,000 catheter days), and accidental removal (4%; IR 5.5/1000 catheter days). CABSI occurred in 16 (2%) patients. All-cause failure and occlusion were reduced with ultrasound-assisted insertion (failure: adjusted hazard ratio [HR] 0.43, 95% CI 0.25, 0.76; occlusion: sub-HR 0.11, 95% CI 0.03, 0.43). Increased age was associated with less AC failure (60-74 years HR 0.63, 95% CI 0.44 to 0.89; 75 + years HR 0.36, 95% CI 0.20, 0.64; referent 15-59 years). Females experienced more occlusion (adjusted sub-HR 2.53, 95% CI 1.49, 4.29), while patients with diabetes had less (SHR 0.15, 95% CI 0.04, 0.63). Suspected CABSI was associated with an abnormal insertion site appearance (SHR 2.71, 95% CI 1.48, 4.99).

AC failure is common with ultrasound-guided insertion associated with lower failure rates. Trial registration Australian New Zealand Clinical Trial Registry (ACTRN 12610000505000); date registered: 18 June 2010.