• antibiotic resistance
• coagulase-negative staphylococci
• diabetes
• gram-negative bacilli
• gram-positive cocci
• pathogen
• periprosthetic joint infection
• staphylococcus aureus

• NHANES
• albumin/neutrophil to lymphocyte ratio
• diabetic foot ulcers
• inflammation
• nutrition

• Adaptive immunity
• Clinical presentation
• Innate immunity
• Pathogenesis
• Skin diseases

• Humans
• Skin Diseases, Bacterial/drug therapy
• Skin Diseases, Bacterial/microbiology
• Skin Diseases, Bacterial/immunology
• Anti-Bacterial Agents/therapeutic use
• Diabetes Complications/drug therapy
• Diabetic Foot/microbiology
• Diabetic Foot/drug therapy
• Diabetic Foot/immunology

• diabetes mellitus
• feature extraction
• machine learning
• metabolic syndrome
• peripheral neuropathy
• sensor-equipped insoles
• video games

• Humans
• Video Games
• Peripheral Nervous System Diseases/diagnosis
• Male
• Female
• Proof of Concept Study
• Middle Aged
• Adult
• Wearable Electronic Devices
• Artificial Intelligence
• Cohort Studies
• Aged

• Diabetes
• Global Leadership Initiative on Malnutrition
• Nutritional assessment
• Subjective Global Assessment
• Wound healing

• Humans
• Malnutrition/diagnosis
• Diabetic Foot/diagnosis
• Male
• Female
• Aged
• Retrospective Studies
• Wound Healing
• Middle Aged
• Nutrition Assessment
• Nutritional Status
• Predictive Value of Tests

• antibiotic resistance
• cultures
• diabetic foot
• diabetic foot infection

• Humans
• Cross-Sectional Studies
• Male
• Female
• Middle Aged
• Anti-Bacterial Agents/pharmacology
• Anti-Bacterial Agents/therapeutic use
• Aged
• Microbial Sensitivity Tests/methods
• Wound Infection/microbiology
• Wound Infection/epidemiology
• Wound Infection/drug therapy
• Adult
• Drug Resistance, Bacterial
• Lower Extremity/microbiology

• diabetic foot
• osteomyelitis
• ultrasonography
• wound healing

• Humans
• Diabetic Foot/diagnostic imaging
• Prospective Studies
• Osteomyelitis/diagnostic imaging
• Ultrasonography
• Bone and Bones
• Diabetes Mellitus

Diabetic foot ulceration is a devastating complication of diabetes that is associated with infection, amputation, and death, and is affecting increasing numbers of patients with diabetes mellitus. The pathogenesis of foot ulcers is complex, and different factors play major roles in different stages. The refractory nature of foot ulcer is reflected in that even after healing there is still a high recurrence rate and amputation rate, which means that management and nursing plans need to be considered carefully. The importance of establishment of measures for prevention and management of DFU has been emphasized. Therefore, a validated and appropriate DFU classification matching the progression is necessary for clinical diagnosis and management. In the first part of this review, we list several commonly used classification systems and describe their application conditions, scope, strengths, and limitations; in the second part, we briefly introduce the common risk factors for DFU, such as neuropathy, peripheral artery disease, foot deformities, diabetes complications, and obesity. Focusing on the relationship between the risk factors and DFU progression may facilitate prevention and timely management; in the last part, we emphasize the importance of preventive education, characterize several of the most frequently used management approaches, including glycemic control, exercise, offloading, and infection control, and call for taking into account and weighing the quality of life during the formulation of treatment plans. Multidisciplinary intervention and management of diabetic foot ulcers (DFUs) based on the effective and systematic combination of these three components will contribute to the prevention and treatment of DFUs, and improve their prognosis.

• Diabetes
• Diabetes foot ulceration
• Classification
• Diabetes complications
• Clinical management
• Lower limb complications

Transmetatarsal amputation (TMA) involves the surgical removal of the distal portion of metatarsals in the foot. It aims to maintain weight-bearing and independent ambulation while eliminating the risk of spreading soft tissue infection or gangrene. This study aimed to explore the risk factors and surgical outcomes of TMA in patients with diabetes at an academic tertiary referral center in Jordan. Medical records of all patients with diabetes mellitus who underwent TMA at King Abdullah University Hospital, Jordan, between January 2017 and January 2019 were retrieved. Patient characteristics along with clinical and laboratory findings were analyzed retrospectively. Pearson’s chi-square test of association, Student’s t-test, and multivariate regression analysis were used to identify and assess the relationships between patient findings and TMA outcome. The study cohort comprised 81 patients with diabetes who underwent TMA. Of these, 41 (50.6%) patients achieved complete healing. Most of the patients were insulin-dependent (85.2%). Approximately half of the patients (45.7%) had severe ankle-brachial index (ABI). Thirty patients (37.1%) had previous revascularization attempts. The presence of peripheral arterial disease (P<0.05) exclusively predicted poor outcomes among the associated comorbidities. Indications for TMA included infection, ischemia, or both. The presence of severe ABI (≤0.4, P<0.01) and a previous revascularization attempt (P<0.05) were associated with unfavorable outcomes of TMA. Multivariate analysis that included all demographic, clinical, and laboratory variables in the model revealed that insulin-dependent diabetes, low albumin level (< 33 g/L), high C-reactive protein level (> 150 mg/L), and low score of Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC, <6) were the main factors associated with poor TMA outcomes. TMA is an effective technique for the management of diabetic foot infection or ischemic necrosis. However, attention should be paid to certain important factors such as insulin dependence, serum albumin level, and LRINEC score, which may influence the patient’s outcome.

• Diabetic ulcer
• Fibroblast
• Ruyi Jinhuang powder
• Wnt/β-catenin
• Wound healing

• Animals
• Cell Proliferation
• Diabetes Complications
• Diabetes Mellitus, Experimental/drug therapy
• Diabetes Mellitus, Experimental/metabolism
• Fibroblasts
• Inflammation/metabolism
• Mice
• Powders/metabolism
• Ulcer/metabolism
• Wnt Signaling Pathway
• Wound Healing

• Amputation
• Foot ulcer
• Limb salvage
• Veteran

• Antibiotic stewardship program
• antimicrobial resistance
• rational antibiotic use

• antimicrobial resistance
• diabetic foot infection
• major amputation
• multidrug-resistant organisms
• reinfection

About 422 million people worldwide have diabetes and approximately one-third of them have a major risk factor for diabetic foot ulcers, including poor sensation in their feet from peripheral neuropathy and/or poor perfusion to their feet from peripheral artery disease. The current healthcare ecosystem, which is centered on the treatment of established foot disease, often fails to adequately control key reversible risk factors to prevent diabetic foot ulcers leading to unacceptable high foot disease amputation rate, 40% recurrence of ulcers rate in the first year, and high hospital admissions. Thus, the latest diabetic foot ulcer guidelines emphasize that a paradigm shift in research priority from siloed hospital treatments to innovative integrated community prevention is now critical to address the high diabetic foot ulcer burden. The widespread uptake and acceptance of wearable and digital health technologies provide a means to timely monitor major risk factors associated with diabetic foot ulcer, empower patients in self-care, and effectively deliver the remote monitoring and multi-disciplinary prevention needed for those at-risk people and address the health care access disadvantage that people living in remote areas. This narrative review paper summarizes some of the latest innovations in three specific areas, including technologies supporting triaging high-risk patients, technologies supporting care in place, and technologies empowering self-care. While many of these technologies are still in infancy, we anticipate that in response to the Coronavirus Disease 2019 pandemic and current unmet needs to decentralize care for people with foot disease, we will see a new wave of innovations in the area of digital health, smart wearables, telehealth technologies, and “hospital-at-home” care delivery model. These technologies will be quickly adopted at scale to improve remote management of diabetic foot ulcers, smartly triaging those who need to be seen in outpatient or inpatient clinics, and supporting acute or subacute care at home.

• amputation
• care in place
• diabetic foot
• diabetic peripheral neuropathy
• digital health
• foot disease
• remote patient monitoring
• telehealth
• ulcer
• wearable

• Amputation, Surgical
• COVID-19
• Diabetes Mellitus
• Diabetic Foot/prevention & control
• Ecosystem
• Humans
• SARS-CoV-2

• R01DK124789 NIDDK NIH HHS

• academic medical centers
• acute kidney Injury
• bacterial infections
• diabetic foot
• evidence-based medicine

• Corynebacterium
• biofilm
• bone and joint infection
• intracellular
• osteoblasts

• Clostridium
• Gas gangrene
• Group A streptococcus
• Myonecrosis
• Necrotizing fasciitis
• Necrotizing soft tissue infection
• Polymicrobial infection

• TCpO2
• critical limb ischemia
• diabetic foot ulcer
• non-invasive diagnosis
• perfusion
• peripheral arterial occlusive disease

Diabetes mellitus is a major global health issue with a growing prevalence. In this context, the number of diabetic complications is also on the rise, such as diabetic foot ulcers (DFU), which are closely linked to the risk of lower extremity amputation (LEA). Statistical prediction tools may support clinicians to initiate early tertiary LEA prevention for DFU patients. Thus, we designed Bayesian prediction models, as they produce transparent decision rules, quantify uncertainty intuitively and acknowledge prior available scientific knowledge.

A logistic regression using observational collected according to the standardised PEDIS classification was utilised to compute the six-month amputation risk of DFU patients for two types of LEA: 1.) any-amputation and 2.) major-amputation. Being able to incorporate information which is available before the analysis, the Bayesian models were fitted following a twofold strategy. First, the designed prediction models waive the available information and, second, we incorporated the a priori available scientific knowledge into our models. Then, we evaluated each model with respect to the effect of the predictors and validity of the models. Next, we compared the performance of both models with respect to the incorporation of prior knowledge.

This study included 237 patients. The mean age was 65.9 (SD 12.3), and 83.5% were male. Concerning the outcome, 31.6% underwent any- and 12.2% underwent a major-amputation procedure. The risk factors of perfusion, ulcer extent and depth revealed an impact on the outcomes, whereas the infection status and sensation did not. The major-amputation model using prior information outperformed the uninformed counterpart (AUC 0.765 vs AUC 0.790, Cohen’s d 2.21). In contrast, the models predicting any-amputation performed similarly (0.793 vs 0.790, Cohen’s d 0.22).

Both of the Bayesian amputation risk models showed acceptable prognostic values, and the major-amputation model benefitted from incorporating a priori information from a previous study. Thus, PEDIS serves as a valid foundation for a clinical decision support tool for the prediction of the amputation risk in DFU patients. Furthermore, we demonstrated the use of the available prior scientific information within a Bayesian framework to establish chains of knowledge.

• bacterial infection
• diabetic foot
• drug resistance

• antibacterial agents
• bacteremia
• diabetic foot
• hospitalization
• osteomyelitis
• sensitivity and specificity

Bacterial biofilms do serious harm to the diabetic foot ulcer (DFU) because they play a crucial role in infection invasion and spread. Staphylococcus aureus, the predominant Gram-positive bacteria in diabetic foot infection (DFI), is often associated with colonization and biofilm formation. Through biofilm formation tests in vitro, we observed that S. aureus bacteria isolated from DFU wounds were more prone to form biofilms than those from non-diabetic patients, while there was no difference in blood sugar between the biofilm (+) diabetics (DB+) and biofilm (-) diabetics (DB-). Furthermore, we found that advanced glycation end products (AGEs) promoted the biofilm formation of S. aureus in clinical isolates and laboratory strains in vitro, including a methicillin-resistant strain. Analysis of biofilm components demonstrated that the biofilms formed mainly by increasing extracellular DNA (eDNA) release; remarkably, the S. aureus global regulator sigB was upregulated, and its downstream factor lrgA was downregulated after AGE treatments. Mechanism studies using a sigB-deleted mutant (Newman-ΔsigB) confirmed that AGEs decreased expression of lrgA via induction of sigB, which is responsible for eDNA release and is a required component for S. aureus biofilm development. In conclusion, the present study suggests that AGEs promote S. aureus biofilm formation via an eDNA-dependent pathway by regulating sigB. The data generated by this study will provide experimental proof and theoretical support to improve DFU infection healing.

• Staphylococcus aureus
• advanced glycation end products
• biofilm formation
• diabetic foot infection
• eDNA
• sigB

In recent years, as living standards have continued to improve, the number of diabetes patients in China, along with the incidence of complications associated with the disease, has been increasing. Among these complications, diabetic foot disease is one of the main causes of disability and death in diabetic patients. Due to the differences in economy, culture, religion and level of medical care available across different regions, preventive and treatment methods and curative results for diabetic foot vary greatly. In multidisciplinary models built around diabetic foot, the timely assessment and diagnosis of wounds and appropriate methods of prevention and treatment with internal and external surgery are key to clinical practice for this pathology. In 2019, under the leadership of the Jiangsu Medical Association and Chinese Diabetes Society, the writing group for the Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition) was established with the participation of scholars from the specialist areas of endocrinology, burn injury, vascular surgery, orthopedics, foot and ankle surgery and cardiology. Drawing lessons from diabetic foot guidelines from other countries, this guide analyses clinical practices for diabetic foot, queries the theoretical basis and grades and gives recommendations based on the characteristics of the pathology in China. This paper begins with assessments and diagnoses of diabetic foot, then describes treatments for diabetic foot in detail, and ends with protections for high-risk feet and the prevention of ulcers. This manuscript covers the disciplines of internal medicine, surgical, nursing and rehabilitation and describes a total of 50 recommendations that we hope will provide procedures and protocols for clinicians dealing with diabetic foot.

Registry number: IPGRP-2020cn124

• Ankle-brachial index
• Diabetic complication
• Diabetic foot disease
• Diabetic foot infection
• Diabetic foot osteomyelitis
• Diabetic peripheral neuropathy
• Peripheral arterial disease
• Randomized controlled trials
• Recommendation
• Transcutaneous oxygen pressure

The aim of this study was to develop a population pharmacokinetic model for piperacillin (PIPC)/tazobactam (TAZ) in late elderly patients with pneumonia and to optimize the administration planning by applying pharmacokinetic/pharmacodynamic (PK/PD) criteria. PIPC/TAZ (total dose of 2.25 or 4.5 g) was infused intravenously three times daily to Japanese patients over 75 years old. The plasma concentrations of PIPC and TAZ were determined using high-performance liquid chromatography and modeled using the NONMEM program. PK/PD analysis with a random simulation was conducted using the final population PK model to estimate the probability of target attainment (PTA) profiles for various PIPC/TAZ-regimen–minimum-inhibitory-concentration (MIC) combinations. The PTAs for PIPC and TAZ were determined as the fraction that achieved at least 50% free time > MIC and area under the free-plasma-concentration–time curve over 24 h ≥ 96 μg h/mL, respectively. A total of 18 cases, the mean age of which was 86.5 ± 6.0 (75–101) years, were investigated. The plasma-concentration–time profiles of PIPC and TAZ were characterized by a two-compartment model. The parameter estimates for the final model, namely the total clearance, central distribution volume, peripheral distribution volume, and intercompartmental clearance, were 4.58 + 0.061 × (CL_cr − 37.4) L/h, 5.39 L, 6.96 L, and 20.7 L/h for PIPC, and 5.00 + 0.059 × (CL_cr − 37.4) L/h, 6.29 L, 7.73 L, and 24.0 L/h for TAZ, respectively, where CL_cr is the creatinine clearance. PK/PD analysis using the final model showed that in drug-resistant strains with a MIC > 8 μg/mL, 4.5 g of PIPC/TAZ every 6 h was required, even for the patients with a CL_cr of 50–60 mL/min. The population PK model developed in this study, together with MIC value, can be useful for optimizing the PIPC/TAZ dosage in the over-75-year-old patients, when they are administered PIPC/TAZ. Therefore, the findings of present study may contribute to improving the efficacy and safety of the administration of PIPC/TAZ therapy in late elderly patients with pneumonia.

• late elderly patients
• piperacillin
• pneumonia
• population pharmacokinetic/pharmacodynamic analysis
• tazobactam

• diabetes mellitus
• diabetic foot
• haemodialysis
• infection
• mortality

• hyaluronic acid
• nano-hydrogel
• oleic acid
• quercetin
• wound healing

• amniotic membrane
• cryopreservation
• diabetic foot ulcer
• wound healing

• biopsy
• diabetes
• diagnosis
• foot ulcer
• infection
• osteomyelitis

• Ankle
• Biopsy
• Bone Diseases, Infectious/diagnosis
• Bone Diseases, Infectious/microbiology
• Foot
• Humans
• Soft Tissue Infections/diagnosis
• Soft Tissue Infections/microbiology

• AKIN
• KDIGO
• KIM-1
• MRSA
• RIFLE
• acute kidney injury
• creatinine
• nephrotoxicity
• piperacillin-tazobactam
• vancomycin

• Diabetic foot ulcers
• HbA1c
• Mortality
• Wound healing

• bone infection
• diabetic foot
• diabetic foot infection
• diabetic foot ulcers

• C-reactive protein
• Diabetic foot
• Dynamic contrast-enhanced imaging
• Erythrocyte sedimentation rate
• Neuropathic arthropathy
• Osteomyelitis

• Aged
• Arthropathy, Neurogenic/diagnostic imaging
• Contrast Media
• Diabetes Mellitus, Type 2/complications
• Diabetic Foot/complications
• Diabetic Foot/diagnostic imaging
• Diagnosis, Differential
• Female
• Humans
• Magnetic Resonance Imaging/methods
• Male
• Middle Aged
• Osteomyelitis/diagnostic imaging
• Prospective Studies
• ROC Curve

• Classification and treatment
• Combat injuries
• Expert consensus
• Pelvic fractures