Nano-Oxy: Diabetic ulcer treatment using oxygen nanoparticles concept as innovation in reducing amputation rates and antibiotics usage

Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia caused by defects in insulin secretion, insulin reactions, or both. More than one third of diabetic patients have complications in the form of diabetic ulcers, and half are infected, and 15% of these infections require limb amputation. High cost expenditure and risks of microbial resistance to antibiotics also adds the complexity of the problem. The purpose of this literature review is to offer Nano-Oxy, using oxygen in nanoparticle size, as an alternative diabetic ulcer treatment. Literature searching was conducted through online search method. Oxygen therapy has been widely used to treat diabetic ulcers, including hyperbaric oxygen therapy (HOT) and topical oxygen therapy (TOT). Both of them have good results on diabetic ulcer therapy. Oxygen can act as an antimicrobial agent through the activation mechanism of neutrophils and macrophages which play a role in phagocytosis process and ROS regeneration. Nano-Oxy has advantages than the previous therapy, such as it does not cause barotrauma, oxygen poisoning, and low risk of burning. The mechanism of how Nano-Oxy works is similar with the Micro-nanobubbles (MNBs) concept. The negatively charged surface of MNBs can prevent them from aggregating, attracts particles, and help remove debris. MNBs also generate free radicals while shrinking in water, which contribute to its antibacterial effect. In addition, Nano-oxygen technology can be applied externally, but still have effect on the intended target cells. Therefore, Nano-oxygen can be used as a diabetic ulcer therapy to replace the role of antibiotics.

Modified poly(L-lysine)-based structures as novel antimicrobials for diabetic foot infections, an in-vitro study

Background: Wound infections occur as sequelae to skin trauma and cause significant hospitalizations, morbidity and mortality. Skin traumas arise more frequently in those with diabetes or cardiovascular disease and in these settings, may be chronic with poorer outcomes including lower limb amputation. Treatment of chronic wound infection is challenging due to antibiotic resistance and biofilm formation by bacteria including S. aureus and P. aeruginosa, which are among the most frequent causative pathogens. Managing these challenging infections requires new molecules and modalities. Methods: We evaluated antimicrobial and anti-biofilm activity of star-shaped poly(L-lysine) (PLL) polymers against S. aureus and P. aeruginosa strains and clinical isolates recovered from wounds including diabetic foot wounds (DFW) in a Dublin Hospital in 2019. A star-shaped PLL polypeptide series, specifically G2(8)PLL20, G3(16)PLL10, G4(32)PLL5 with variation in polypeptide chain length and arm-multiplicity, were compared to a linear peptide, PLL160 with equivalent number of lysine residues. Results: All PLLs, including the linear polypeptide, were bactericidal at 1mM against S. aureus 25923 and P. aeruginosa PAO1, with log reduction in colony forming units/ml between 2.7-3.6. PLL160 demonstrated similar killing potency against 20 S. aureus and five P. aeruginosa clinical isolates from DFW, mean log reductions: 3.04 ± 0.16 and 3.96 ± 0.82 respectively after 1 hour incubation. Potent anti-biofilm activity was demonstrated against S. aureus 25923 but for clinical isolates, low to moderate loss of biofilm viability was shown using PLL160 and G3(16)PLL10 at 50 mM (S. aureus) and 200 mM (P. aeruginosa) with high inter-isolate variability. In the star-shaped architecture, antimicrobial activity was retained with incorporation of 5-mer hydrophobic amino-acid modifications to the arms of the polypeptides (series G3(16)PLL20-coPLT5, G3(16)PLL20-coPLI5, G3(16)PLL20-coPLP5). Conclusion: These polypeptides offer structural flexibility for clinical applications and have potential for further development, particularly in the setting of diabetic foot and other chronic wound infections.

3D bioprinted scaffolds for diabetic wound-healing applications

The treatment strategy required for the effective healing of diabetic foot ulcer (DFU) is a complex process that is requiring several combined therapeutic approaches. As a result, there is a significant clinical and economic burden associated in treating DFU. Furthermore, these treatments are often unsuccessful, commonly resulting in lower-limb amputation. The use of drug-loaded scaffolds to treat DFU has previously been investigated using electrospinning and fused deposition modelling (FDM) 3D printing techniques; however, the rapidly evolving field of bioprinting is creating new opportunities for innovation within this research area. In this study, 3D-bioprinted scaffolds with different designs have been fabricated for the delivery of an antibiotic (levoflocixin) to DFU. The scaffolds were fully characterised by a variety of techniques (e.g. SEM, DSC/TGA, FTIR, and mechanical characterisation), demonstrating excellent mechanical properties and providing sustained drug release for 4 weeks. This proof of concept study demonstrates the innovative potential of bioprinting technologies in fabrication of antibiotic scaffolds for the treatment of DFU. Graphical abstract

Issues Faced by Prosthetists and Physiotherapists During Lower-Limb Prosthetic Rehabilitation: A Thematic Analysis

Successful prosthetic rehabilitation is essential to improve the physical and mental outcomes of people with lower-limb amputation. Evaluation of prosthetic services from a prosthesis user perspective have been published and commissioned by the national bodies, however, the perspectives of clinicians working with service users during rehabilitation have not to date been sought. We sought to determine factors impacting lower-limb prosthetic rehabilitation from a clinician's perspective to inform studies focusing on prosthetic and socket design and fitting. Six clinician (2 prosthetists, 4 physiotherapists) interviewees were self-selected from a survey exploring issues and frustrations during lower-limb prosthetic rehabilitation. Semi-structured interviews explored the impactors on and frustrations with rehabilitation and the prosthetic socket. A thematic analysis was subsequently conducted to identify themes in the responses. Five themes were identified: Service Disparity, Body Impactors, Consequences of Ill-Fit, Prosthesis Irritants, and Limitations of Practice. Each theme, though distinct, relates to the others either as a cause or consequence and should be viewed as such. Addressing the themes will have benefits beyond the issues addressed but also expand into the other themes. This study provides an insight into the clinician perspectives on lower-limb prosthetic rehabilitation, which has not been formally documented to date.

Lower Limb Amputation Rates in Germany

Background and Objectives: The current epidemiology of lower limb amputations is unknown. Therefore, the purpose of this study was to determine (1) lower extremity amputation rates as a function of age, gender, and amputation level between 2015 and 2019, (2) main diagnoses indicating amputation, (3) revision rates after lower extremity amputation. Materials and Methods: Lower extremity amputation rates were quantified based on annual Operation and Procedure Classification System (OPS) and International Classifications of Disease (ICD)-10 codes from all German medical institutions between 2015 through 2019, provided by the Federal Statistical Office of Germany (Destatis). Results: In 2019, 62,016 performed amputations were registered in Germany. Out of these 16,452 procedures (26.5%) were major amputations and 45,564 patients (73.5%) underwent minor amputations. Compared to 2015, the incidence of major amputations decreased by 7.3% to 24.2/100,000 inhabitants, whereas the incidence of minor amputation increased by 11.8% to 67.1/100,000 inhabitants. Highest incidence was found for male patients aged 80–89 years. Patients were mainly diagnosed with peripheral arterial disease (50.7% for major and 35.7% for minor amputations) and diabetes mellitus (18.5% for major and 44.2% for minor amputations). Conclusions: Lower limb amputations remain a serious problem. Further efforts in terms of multidisciplinary team approaches and patient optimization strategies are required to reduce lower limb amputation rates.

Embolism to the main limb arteries in patients with atrial fibrillation

Introduction. Acute limb ischemia due to embolism in patients with atrial fibrillation remains poorly studied. Objective – to study the clinical significance and role of atrial fibrillation (AF) in the development of embolism to the bifurcation of the aorta and the main arteries of the limbs. Materials and methods. Treatment results of 1816 patients with acute ischemia of the extremities due to embolism treated at a specialized vascular surgical department for the past 30 years were analyzed. 1611 (88.7 %) of them had AF. The distribution into studied groups was according to the period time factor. Group 1 (n = 744) consisted of patients admitted in the period from 1991 to 2000; in group 2 (n = 568) – admitted in the period from 2001 to 2010, in group 3 (n = 299) – from 2011 to 2020. Methods included clinical examination, electrocardiography, Doppler-ultrasound, echocardiography. Results. The role of rheumatic heart disease as a cause of AF has decreased over the past decades by almost 10 times (from 19.5 % in group 1 to 2.0 % in group 3). Currently, the main background diseases for the development of AF are arterial hypertension and various forms of coronary artery disease. Embolism in patients with AF may develop in the arteries of all vascular areas of the systemic circulation, but in the practice of a vascular surgeon more often in the main arteries of minor caliber – the brachial (24.5 %) and popliteal (13.0 %). Multiple embolisms to various vascular areas were found in 2.8 % of patients. Urgent surgical revascularization of the limb by open embolectomy was performed in 1481 (91.9 %) patients that allowed 1348 (83.7 %) to be discharged with limb-sparing. Conclusion. In patients with acute limb ischemia of embologenic ethiology, comorbid AF has 88.7 % of them. Urgent embolectomy allows 83.7 % of patients to be discharged without limb amputation. Hospital mortality in the period 1991–2000 was 15.6 %, the last decade has been reduced to 7.4 %.

Reconstruction of infrarenal abdominal aortic occlusion using the Culotte stenting technique: a case report

Patients with clinically significant infrarenal abdominal aortic atherosclerosis are often encountered in the clinical practice of vascular and endovascular surgeons. In the absence of timely treatment, the ability to work and life quality of patients are sharply reduced, and in some cases, patients require limb amputation. Until recently, the only treatment option for such a lesion was an open surgery. However, a good skill level of endovascular surgeons and the device availability allow today to perform minimally invasive operations with comparable effectiveness and greater safety in comparison with open surgery. We present a case report of successful endovascular treatment of aortic occlusion involving the right and left common and external iliac arteries using Culotte stenting technique with further 12-month follow-up.

Trends of limb amputation considering type, level, sex and age in Saskatchewan, Canada 2006–2019: an in-depth assessment

Background Most epidemiologic reports focus on lower extremity amputation (LEA) caused specifically by diabetes mellitus. However, narrowing scope disregards the impact of other causes and types of limb amputation (LA) diminishing the true incidence and societal burden. We explored the rates of LEA and upper extremity amputation (UEA) by level of amputation, sex and age over 14 years in Saskatchewan, Canada. Methods We calculated the differential impact of amputation type (LEA or UEA) and level (major or minor) of LA using retrospective linked hospital discharge data and demographic characteristics of all LA performed in Saskatchewan and resident population between 2006 and 2019. Rates were calculated from total yearly cases per yearly Saskatchewan resident population. Joinpoint regression was employed to quantify annual percentage change (APC) and average annual percent change (AAPC). Negative binomial regression was performed to determine if LA rates differed over time based on sex and age. Results Incidence of LEA (31.86 ± 2.85 per 100,000) predominated over UEA (5.84 ± 0.49 per 100,000) over the 14-year study period. The overall LEA rate did not change over the study period (AAPC -0.5 [95% CI − 3.8 to 3.0]) but fluctuations were identified. From 2008 to 2017 LEA rates increased (APC 3.15 [95% CI 1.1 to 5.2]) countered by two statistically insignificant periods of decline (2006–2008 and 2017–2019). From 2006 to 2019 the rate of minor LEA steadily increased (AAPC 3.9 [95% CI 2.4 to 5.4]) while major LEA decreased (AAPC -0.6 [95% CI − 2.1 to 5.4]). Fluctuations in the overall LEA rate nearly corresponded with fluctuations in major LEA with one period of rising rates from 2010 to 2017 (APC 4.2 [95% CI 0.9 to 7.6]) countered by two periods of decline 2006–2010 (APC -11.14 [95% CI − 16.4 to − 5.6]) and 2017–2019 (APC -19.49 [95% CI − 33.5 to − 2.5]). Overall UEA and minor UEA rates remained stable from 2006 to 2019 with too few major UEA performed for in-depth analysis. Males were twice as likely to undergo LA than females (RR = 2.2 [95% CI 1.99–2.51]) with no change in rate over the study period. Persons aged 50–74 years and 75+ years were respectively 5.9 (RR = 5.92 [95% Cl 5.39–6.51]) and 10.6 (RR = 10.58 [95% Cl 9.26–12.08]) times more likely to undergo LA than those aged 0–49 years. LA rate increased with increasing age over the study period. Conclusion The rise in the rate of minor LEA with simultaneous decline in the rate of major LEA concomitant with the rise in age of patients experiencing LA may reflect a paradigm shift in the management of diseases that lead to LEA. Further, this shift may alter demand for orthotic versus prosthetic intervention. A more granular look into the data is warranted to determine if performing minor LA diminishes the need for major LA.