Acute appendicitis is one of the most common surgical emergencies (8.6 % in men and 6.4 % in women), with varying presentations, including complications such as appendicular abscess. While the typical clinical course involves right lower quadrant pain and fever, rare complications can present with atypical symptoms, particularly in high-risk patients such as those with diabetes.

A 55-year-old diabetic female presented with a 10-day history of worsening abdominal pain, foul-smelling discharge at the anterior abdominal wall below the umbilicus, and fever. Imaging revealed an appendicular abscess extending into the anterior abdominal wall. Emergency exploratory laparotomy showed a perforated appendix with a purulent collection in the peritoneal cavity extending to the anterior abdominal wall, requiring drainage and right hemicolectomy.

Perforated appendicitis (incidence of 20-30 %), particularly in diabetic patients, can lead to localized abscesses or soft tissue infections in atypical locations such as the abdominal wall. These rare complications are more likely in immunocompromised individuals, including those with diabetes, where the incidence of perforated appendicitis is notably higher. Early imaging with ultrasonography or Contrast Enhanced Computed Tomography is critical for identifying complicated appendicitis and guiding surgical intervention.

Anterior abdominal wall abscesses as a complication of perforated appendicitis are rare but significant. This case underscores the importance of early and accurate diagnosis, supported by imaging, to guide appropriate surgical management. Timely intervention can help prevent life-threatening conditions such as necrotizing fasciitis, improve patient outcomes, and reduce the risk of postoperative complications, particularly in high-risk populations.

Negatively charged polystyrene microspheres (NCMs) have been demonstrated as a novel and effective therapy for managing hard-to-heal diabetic foot ulcers (DFUs). However, one limitation of this therapy is that the protocol is based on daily application, which sometimes does not fit local protocols of wound care. Thus, we aimed to analyze the safety and efficacy of a new dose regimen. We conducted a randomized blinded controlled trial in a specialized diabetic foot unit between May 2019 and February 2021 with a total of 30 patients who had neuropathic or neuroischemic DFUs that had not responded after four weeks of standard treatment. Patients were randomized consecutively into a group that received daily application (control) or one that received applications three times per week (experimental). The clinical outcomes were evaluated using the Wollina score and wound-area reduction (WAR) weekly during a treatment period of 28 days. The histological outcomes were assessed using a soft-tissue punch biopsy (3 mm) at 0, 14, and 28 days to evaluate cellular proliferation. The Wollina scores were higher at the end of treatment by week 4 in both groups, but the differences were not significant between groups. The averages were 6 (5, 7) points in Experimental group (EG) and 6 (6,7) points in Control group (CG) (p = 0.848). Wound area reduction at day 28 was 53.57 [37.43, 79.16] % in the CG and 79.37 [42.74, 93.57] % in the EG, without differences among groups (p = 0.305). Cellular proliferation was similar in both groups at day 28. Application three times per week showed similar clinical and histological outcomes to those of daily application, both dose regimens demonstrated significant improvement of granulation tissue formation and WAR during the treatment.

Few studies have addressed the interaction of specific pathogens with clinical outcomes in patients with diabetic foot infection (DFI). Our study aim was to compare the clinical outcomes among patients with DFI caused by methicillin-resistant Staphylococcus aureus (MRSA) with cases caused by methicillin-sensitive Staphylococcus aureus (MSSA). We gathered the data of 75 consecutive patients admitted at specialized outpatients diabetic with mild or moderate DFI in which S. aureus was isolated from bone or soft tissue specimens in pure or as a part of the polymicrobial culture. Patients were divided into two groups: those with MRSA infection and those with MSSA infection. Patients with MRSA diabetic foot infections were significantly associated with male gender (86% vs. 64%, P = .029), higher SINBAD Classification Score (3.6 ± 0.99 points vs. 2.8 ± 1.06 points, P = .001), longer mean wound evolution [17.8 (3;29.5) weeks versus 9.1 (1;12) weeks, P = .008], bone involvement [18 (50%) versus 9 (23.1%), P = .015] and longer mean healing time [18.2(8;28) weeks versus 9.1 (1;12) weeks, P = .008]. In addition, male gender (OR 8.81, 95% CI 2.00-38.84) and SINBAD Classification Score (OR 2.70, 1.46-5.00) were identified as independent risk factors for MRSA DFI. Significant differences in the number of surgical procedures to resolve infection [15 (41.7%) versus 13 (33.3%), P = .456] or in the mean healing time after surgical treatment [10.5 weeks (6.7;16.5) versus 6.1 weeks (3;8.7), P = .068] were not observed among groups, suggesting that when treatment is based on early and surgical debridement, MRSA infections are not associated with worse prognosis. In conclusion MRSA DFI has importance in clinical outcomes such as time to healing. We propose that recent lines of research regarding the genetic virulence of strains of S. aureus could provide new insights into our results.

Diabetic foot infections (DFIs) are associated with major morbidity, reduced quality of life and increased mortality. Osteomyelitis is a leading cause of lower-extremity amputation in diabetic patients. We aimed to examine whether a multifaceted strategy for treating hospitalized patients with a DFI effectively influenced microbiological culture results and outcomes. A retrospective cohort-study in a 1100-bed, tertiary-care university hospital was conducted. Adult patients with a DFI admitted to the orthopedics department between 2015 and 2019 were included. During the pre-intervention period (2015-2016), one general orthopedic department was in operation. In the post-intervention period (2017-2019), a second department was created with a designated "complicated wound unit". The multifaceted strategy included revising local guidelines for DFI culturing emphasizing bone cultures, correct sample handling, and adjusting antibiotic treatment to culture results. Additionally, a weekly multidisciplinary-team grand round was instigated and post-discharge outpatient follow-up was scheduled. 652 patients with DFIs were included; 101 during the pre-intervention period and 551 during the post-intervention period. Compared to the pre-intervention, during the post-intervention period mainly bone or deep-tissue cultures were performed (9.7% vs. 98.2%, P < 0.001). Bacteriology cultures in the pre-intervention versus post-intervention period revealed: among staphylococcus isolates, fewer methicillin-resistant Staphylococcus aureus detected (20.4% vs. 9.8%, P = 0.010); within Enterobacteriaceae isolates, fewer extended-spectrum β-lactamase producing bacteria detected (51.6% vs. 23.6%, P < 0.001); a decrease in Pseudomonas aeruginosa isolates (28% vs. 10.6%, P < 0.001) and an increase in anaerobic bacterial isolates (0 vs. 11.1%, P < 0.001). On multivariate regression, the post-intervention period (ie multifaceted strategy) was a protective measure against readmissions (P = 0.007 OR 0.50 95% CI 0.30-0.82). We conclude that our interventive multifaceted strategy led to accurate bacterial diagnosis, de-escalation of antibiotic treatment and readmission reduction.

The Japanese Dermatological Association aimed to prepare a second edition of guidelines for the management of diabetic ulcer/gangrene with emphasis on the diagnosis and treatment of skin symptoms. This new edition serves as a tool to improve the quality of the diagnosis and treatment in each patient and, further, to improve the level of care for such skin conditions. All sections have been updated by collecting documents published since the publication of the first edition. In the antibacterial drug treatment for bacterial infection of ulcers, oral administration was added after consideration. In the treatment of antibacterial drugs for bacterial infection of ulcers, not only infusion but also oral administration was mentioned. In addition, clinical questions (CQs) for imaging tests for diagnosing ischemia of the limbs were newly created. The titles of some CQs were changed to conform to the actual clinical setting. (i) The content has been updated by adding and collecting documents for all sections; (ii) we have additionally included oral antibiotic treatment for bacterial infection of ulcers; (iii) we have added CQs pertaining to imaging tests for diagnosing ischemia of the limbs; and (iv) we have revised the titles of some CQs to conform to the actual clinical setting. In particular, the recommendation levels of dressing materials newly covered by Japanese national health insurance are mentioned. In addition, CQs regarding the initial treatment of electrical (CQ15) and chemical burns (CQ16), and the use of escharotomy (CQ22) have been created.

Diabetic foot infections (DFIs) contribute to the global disability burden. Beta-lactams are the most commonly used antibiotics for treating DFIs. However, the use of antibiotics may lead to disruption of the healthy balance of the gut microbiota, causing dysbiosis.

Patients with infected diabetic foot ulcers (iDFUs) were treated with two kinds of beta-lactams (amoxicillin/clavulanic acid or ceftazidime) according to microbial sensitivity of causative agents via bolus or continuous administration modes. Changes in the gut microbiome of patients were analyzed. Diabetic patients without iDFUs were used as a control group. 16 S ribosomal RNA gene amplicon sequencing was performed on stool samples collected from participants.

Alpha diversity and beta diversity of gut microbiota of treated patients did not show significant differences between bolus and continuous modes. However, significant differences were observed between gut microbiota diversity of treated patients and control group. PCoA plots showed individualized responses of the patient's gut microbiota to antibiotics at different times using both administration forms associated with the pre-treatment state of microbiota composition. Enterococcus, Sellimonas, and Lachnoclostridium were the common bacterial markers differentially abundant in the gut microbiota of antibiotic-treated patients with iDFUs while Roseburia, Dorea, and Monoglobus were mainly abundant in the gut microbiota of patients without iDFUs. Predicted pathways like "Transporters", "ABC transporters" and "Phosphotranspherase system (PTS)" were upregulated in the gut microbiome of patients treated with bolus regime which may lead to increased intestinal barrier permeability.

The present study reported alterations in gut microbiota composition and functionality and provided the bacterial markers as well as potential metabolic signatures associated with each administration mode in patients with iDFUs, which may be used as a reference set for future studies of the effect of antibiotics administration on the gut microbiome of patients with iDFUs. This study shed light on the importance of understanding the effect of antibiotic administration form on gut microbiome in patients with iDFUs.

The DFIATIM Clinical Trial (Full title: "Rationalisation of ATB therapy in diabetic foot infection and its impact on the intestinal microbiota") is submitted to the European Union Clinical Trials Database under the EudraCT Number: 2019-001997-27. The date of registration is July 17th, 2020.

This prospective cohort study systematically analyzed the demographic profile, clinical characteristics, spectrum of microorganisms, and antimicrobial resistance pattern in 248 patients with diabetic foot ulcer (DFU) over 2.7 years. Most patients were male (75.4%) and had a mean age of 56.1 years, and high comorbidity rates (81% neuropathy, 77% retinopathy, and 67.7% hypertension). A combined 439 bacterial isolates were obtained, with the dominance of Gram-negative pathogens, including Escherichia coli (16.6%) and Pseudomonas aeruginosa (15.3%). Staphylococcus aureus was also the dominant Gram-positive pathogen (12.8%). Polymicrobial infections were found in 43.1% of cases, and 71% of strains were biofilm-producing. The prevalence of multidrug-resistant (MDR) was alarmingly high (67%), particularly among Escherichia coli (97.3%), Staphylococcus aureus (83.9%), and Proteus mirabilis (90.5%). MDR infections were associated with tobacco use, biofilm formation, polymicrobial infection, and clinical complications. In specific, seven bacterial types, Pseudomonas aeruginosa, Staphylococcus aureus, Providencia rettgeri, Enterococcus faecalis, Enterobacter cloacae, Pseudomonas flourescens, and Staphylococcus epidermidis, as described, were statistically associated with amputation. Beta-lactams (ampicillin, piperacillin) showed 100% resistance. Cephalosporins (ceftazidime, ceftriaxone, cefotaxime, cefepime) had resistance rates ranging from 25 to 96%. Amoxicillin-clavulanic acid showed 30 to 92.3% resistance, while piperacillin-tazobactam ranged from 7.7 to 71.4% resistance. Out of 338 Gram-negative isolates, 105 (31.1%) were ESBL producers, and molecular characterization shows blaCTX-M as the most predominant, 40 (38.1%), followed by blaSHV 20 (19.0%), and blaTEM 7 (6.7%) isolates. Methicillin and vancomycin resistance were common among Gram-positive isolates, particularly Methicillin-resistant Staphylococcus aureus (MRSA) (51.8%) and Vancomycin-resistant Enterococci (VRE) (33.3%). Despite widespread resistance, antibacterial drugs such as colistin (100%), polymyxin B (100%), linezolid (100%), and vancomycin (100%) retained efficacy. These data emphasize the significant burden of MDR infections in DFUs and emphasize the urgent actions needed for aggressive antimicrobial stewardship, early infection control, and personalized treatment approaches to prevent amputation and enhance patient outcomes.

Diabetic foot ulcer (DFU) is a prevalent and challenging clinical condition characterized by impaired microcirculation, chronic wound infections, and a hyperglycemic, high-reactive oxygen species (ROS) environment. These factors make treatment particularly complex, often requiring a multidisciplinary approach that yields suboptimal results. In this study, a novel therapeutic strategy was developed using metal-polyphenol nanoparticles synthesized from (-)-Epigallocatechin-3-gallate (EGCG) and ferric ions (Fe3+). These nanoparticles were further loaded with salvianolic acid B (SAB) and glucose oxidase (GOx) to enhance their multifunctional biological properties. Complementing these nanoparticles, a polysaccharide hydrogel was engineered using quaternized chitosan (QCS) and oxidized fucoidan (OFu), forming a robust and stable network through Schiff base linkages. This innovative platform demonstrated strong antibacterial activity against DFU-associated pathogens. Within the ulcer's hostile microenvironment, the hydrogel degraded via dynamic bond cleavage, releasing nanoparticles that boosted mitochondrial metabolism, induced M2 macrophage polarization, promoted angiogenesis and reduced ROS levels. These combined effects accelerated tissue regeneration and wound healing. The results suggest that this advanced hydrogel system holds significant promise as a therapeutic option for improving DFU management and addressing its multifaceted challenges.

Osteomyelitis (OM) associated with diabetic foot ulceration (DFU) is a growing public health challenge worldwide. Since 2012 the number of patients presenting with DFU per year to our centre has doubled.

This study aims to evaluate outcomes from outpatient antibiotic therapy (OPAT) in the management of OM in DFU patients.

A retrospective analysis was performed of medical notes, radiology, and vascular laboratory reports for all DFU patients with OM treated from April 2016 to April 2020. Variables analyzed included age, gender, site of OM, WIfI Score (Wound Ischaemia and foot Infection Score), probe-to-bone test (PTB), imaging (X-ray/magnetic resonance imaging (MRI), co-morbidities (peripheral arterial disease (PAD), chronic kidney disease (CKD), hypertension (HTN), smoking, ischemic heart disease (IHD), and dyslipidaemia. Outcomes evaluated were healing, recurrent DFU, and freedom from amputation at 12 months.

185 patients were admitted with 264 infected digits (Male 223; Female 41). The mean age was 66 years. Only 168 (63.6%) were fully healed at 12 months. Of the 96 patients who failed to heal, 43 underwent a repeat course of prolonged antibiotics without improvement. Factors associated with treatment failure were PAD, poorly controlled HbA1c and Deep or Extensive Ulcer or Gangrene.

Extended outpatient antibiotic therapy (with an inpatient multidisciplinary approach) is an effective treatment for digital OM in DFU with a success rate of 63%. In recurrence, repeating prolonged antibiotics is unlikely to achieve healing. PAD, poorly controlled HbA1c and Deep or Extensive Ulcer or Gangrene are predictors of treatment failure.

Diabetic foot ulcers (DFUs) are a severe complication of diabetes, often leading to amputation. Hyperglycemia induced nerve and vascular damage significantly increases DFU risk. The advent of 3D printing technology presents a revolutionary concurrently address glycemic control and wound management, potentially improving patient adherence and offering a more holistic treatment strategy.

This article reviews current oral antidiabetic medications and explores the potential of innovative 3D printing technology to develop extended release tablets in two distinct release profiles. Additionally, it investigates the application of this technology in creating novel wound dressing solutions aimed at facilitating DFU healing. .

The integration of 3D printing technology enables the production of customized, extended-release oral medications that optimize glycemic control while minimizing fluctuations in blood sugar levels. Furthermore, 3D-printed wound dressings demonstrate promising potentialfor enhancing wound healing by providing personalized structural support and controlled drug delivery.

A multidisciplinary approach that integrates advanced wound care and diabetes management is crucial to address the escalating challenges posed by DFUs. Leveraging3D printing technology to develop sustained-release medications and innovative wound dressingsmay significantly improve DFU outcomes and improve the quality of life for individuals with diabetes.

To investigate the microbiological trends of community-acquired diabetic foot osteomyelitis (DFO) over the past two decades in specialized academic centres in Switzerland, Spain, and Turkey.

A retrospective analysis of DFO cohorts (2000-2019) from five centres (Geneva, Zurich, Las Palmas, Barcelona, Istanbul) stratified into four periods (P1-P4) to assess microbiological changes.

Among 1379 DFO episodes (76% male, median age 67 years; 90% type 2 diabetes, median duration 17 years), gram-positive bacteria were identified in 82%, including Staphylococcus aureus (47%). Methicillin-resistant S. aureus (MRSA) was more prevalent in Barcelona (36%), Las Palmas (24%), and Geneva (29%) than in Zurich (7%). Over time, gram-positive bacteria remained stable or decreased, particularly in Las Palmas (83% to 65%, P = 0.03). The proportion of MRSA decreased in Geneva (39% to 16%) and Las Palmas (37% to 9%), but remained stable in Barcelona. Enterobacteriaceae prevalence increased, notably in Geneva (16% to 39%, P < 0.01) and Las Palmas (27% to 41%, P < 0.01). Among gram-negative pathogens quinolone resistance was 12.5%. Enterobacteriaceae-DFO was associated with ischemic necrosis (OR 1.65), Las Palmas cohort (OR 3.14), and 2016-2019 period (OR 2.68).

A significant increase in Enterobacteriaceae-related DFOs was observed from 2016 to 2019, particularly in Mediterranean Europe.

CODIFI2 compared wound swabbing and tissue sampling in people with infected diabetic foot ulcers (DFU) to determine the effects on clinical outcomes.

Multicentre, Phase III, prospective, non-blind, 2-arm parallel group, randomised controlled trial comparing time to ulcer healing (primary outcome), proportions healed, antimicrobial regimen, ulcer area reduction, hospitalisation duration, and time to death for swab compared to tissue sampling. Allocation was via a central and independent randomisation system, with minimisation by DFU site, number, type, size, location, and duration. Follow-up was 52-104 weeks, with healing confirmed by a blinded assessor. Samplesize target was 730 participants for 90% power to detect a 12.5% difference in healing at 52 weeks.

Between May 2019 and May 2022, 149 participants were recruited (75 Swab, 74 Tissue) from 21 UK sites. The 52-week cumulative incidence of confirmed healing as the first event was 45.3% (33.5%-56.4%) and 44.6% (33.0-55.6%) for swab vs. tissue. The hazard ratio (HR) for healing for tissue vs. swab was 1.01 (95% CI 0.65-1.55). The median (IQR) days in hospital was 17 (12-39) for swab and 16 (10-32) for tissue. Seventeen swab and 7 tissue participants died during follow-up, and 18.7% and 24.3% of participants in the swab and tissue groups, respectively, had an amputation.

This trial was underpowered to determine whether swab or tissue sampling impacted the rate of healing or time to healing. Clinical prescribing and patient outcomes differed slightly between groups; hence, the clinical benefit of tissue sampling is not established.

Diabetic foot infections constitute 20% of hospital admissions and are the underlying cause of 80% of amputations annually. Staging magnetic resonance imaging (MRI) may decrease reamputation rates in diabetic foot osteomyelitis.

A retrospective chart review was conducted to analyze the risk of reamputation in patients with diabetic foot osteomyelitis hospitalized between 2005 and 2022. MRI-guided therapy and proximal surgical margin pathologic evidence of osteomyelitis were compared. The primary outcome was the rate of reamputation up to 365 days.

Enrollment consisted of 386 veterans with a diabetic foot infection complicated by osteomyelitis that required initial amputation, of which 110 patients required reamputation. MRI-guided therapy occurred in 89 of these patients. Preoperative MRI and subsequent MRI-guided therapy were associated with a significant decrease in the chance of reamputation for up to a year after the initial amputation as compared with non-MRI-guided therapy (14/89 [15.7%] vs 96/297 [32.3%], respectively; P = .0024, χ2 test). A Cox proportional hazard model demonstrated that MRI-guided therapy had a significant association with decreasing the relative risk of reamputation (hazard ratio, 0.47; 95% CI, .26-.83; P = .0098). Initial proximal margin pathologic findings consistent with osteomyelitis were not associated with the risk of reamputation (hazard ratio, 1.25; 95% CI, .81-1.93; P = .31).

These findings support that incorporating preamputation MRI and MRI-guided therapy into the diagnostic and treatment approach for diabetic foot osteomyelitis may reduce the risk for subsequent amputations over 1 year.

Diabetic foot infections (DFIs) are commonly associated with frequent hospitalizations, limb amputations, and premature death due to the profile of the bacteria infecting foot ulcers. DFIs are generally colonized by a polymicrobial net of bacteria that grows in biofilms, developing an increased antimicrobial resistance to multiple antibiotics. DFI treatment is a hurdle, and the need to develop new therapies that do not promote resistance is urgent. Therefore, the antibacterial efficacy of Nisin Z (antimicrobial peptide), a core-shell polycationic polyurea pharmadendrimer (PUREG4OEI48) (antimicrobial polymer), and amlodipine (antihypertensive drug) was evaluated against S. aureus and P. aeruginosa isolated from a DFI and previously characterized.

The antibacterial activity was analyzed in vitro by determining the minimal inhibitory concentration (MIC) and in vivo in a Galleria mellonella model by assessing the larvae survival and health index.

The results indicate that Nisin Z exhibited antibacterial activity against S. aureus in vivo, allowing larvae full survival, and no antibacterial activity against P. aeruginosa. Nisin Z may have reduced the antibacterial effectiveness of both PUREG4OEI48 and amlodipine. PUREG4OEI48 significantly increased the survival of the larvae infected with P. aeruginosa, while amlodipine showed no activity against both bacteria in vivo.

These findings suggest that both Nisin Z and PUREG4OEI48 could potentially be used individually as adjunct treatments for mild DFIs. However, further studies are needed to confirm these findings and assess the potential toxicity and efficacy of PUREG4OEI48 in more complex models.

Background/Objectives: Current international guidelines recommend choosing an empirical antibiotic regimen for treating diabetic foot infections (DFI) based largely on clinical severity of the infection and local microbiological epidemiology. This may lead to selecting unnecessarily broad-spectrum initial empiric antibiotic therapy. Methods: Using data from our hospital in a large Swiss city, we retrospectively analyzed the performance of the Gram-stained smears of predominantly deep surgical DFI specimens processed by our microbiology laboratory in predicting the microorganism grown on standard cultures. We excluded episodes with paucibacillary stain results, which we interpret as contamination. Results: Among 1235 operated moderates or severe DFIs, Gram-stained smear was reported in 321 (26%) of cases, and showed bacteria in 172 episodes (54%) of these. Overall, among Gram stain results with organism seen, the sensitivity, specificity, accuracy, positive and negative predictive values of the Gram stain smear when compared with the cultures was 56%, 93%, 97%, and 38%, respectively. The accuracy was 73%. The corresponding statistical values specifically for Gram-negative bacteria were 61%, 97%, 50%, and 82%. Conclusions: The results of routine Gram stain smears of deep intraoperative DFI specimens generally lack sufficient sensitivity, and was only useful to reasonably exclude a DFI caused predominantly by Gram-negative bacteria. For Gram-stained smears results to be useful for guiding antibiotic stewardship, we need prospective trials to assess their value in different types of DFIs.

Hand infections in diabetic patients are a serious concern, as they can lead to significant functional impairment and, if not promptly treated, may result in extensive tissue destruction or even sepsis. Unlike diabetic foot infections, hand infections are less understood and often present unique challenges in management. Diabetic patients are at an increased risk due to factors such as neuropathy, impaired immune function, and poor wound healing. These infections, if neglected, can result in permanent disability. This report presents a rare case of a diabetic hand infection that was complicated by compartment syndrome, a condition that further exacerbates the risk of tissue damage. Due to the nature of the infection and the rapid progression of compartment syndrome, immediate surgical intervention was necessary. Early tendon transfer, a technique not commonly used in such infections, was employed to restore function and prevent further damage. The case highlights the importance of early recognition and aggressive management of diabetic hand infections. Prompt surgical intervention, including tendon transfer, can play a critical role in preventing long-term disability. This case contributes to the limited body of literature on diabetic hand infections, emphasizing the need for tailored treatment approaches to address the specific complications that arise in such cases.

Peripheral arterial disease (PAD) is characterized by atherosclerotic arterial occlusive disease of the lower extremities and is associated with an increased risk of major adverse cardiovascular events (MACE) in addition to disabling clinical sequelae, including intermittent claudication and chronic limb-threatening ischemia (CLTI). Given the growing burden of disease, knowledge of modern practices to prevent MACE and major adverse limb events (MALE) is essential. This review article examines evidence for medical management of PAD and its associated risk factors, as well as wound prevention and care.

A thorough review of the literature was performed, with attention to evidence for the management of modifiable atherosclerotic risk factors, claudication symptoms, wound prevention, and wound care.

Contemporary management of PAD requires a multi-faceted approach to care, with medical optimization of smoking, hypertension, hyperlipidemia, and diabetes mellitus. The use of supervised exercise therapy for intermittent claudication is highlighted. The anatomic disease patterns of smoking and diabetes mellitus are discussed further, and best practices for diabetic foot ulcer prevention, including offloading footwear, are described. Quality wound care is essential in this patient population and involves strategic use of debridement, wound-healing adjuncts, and skin substitutes, when appropriate.

The objective of medical management of PAD is to reduce the risk of MACE and MALE. Atherosclerotic risk factor optimization, appropriate wound care, and management of diabetic foot ulcers, foot infections, gangrene, and chronic, non-healing wounds are critical components of PAD care. Interdisciplinary care is essential to coordinate care, leverage expertise, and improve outcomes.

To present standards and recent technical innovations in the surgical management of skin and soft tissue infections (SSTI).

SSTI are a frequent cause of presentation in the acute care setting. They can range from simple and uncomplicated to severe and necrotizing infections. Surgical management plays an important role in the treatment of uncomplicated SSTI. Recent evidence indicates that a subgroup of patients (e.g. immunocompromised patients) profits from a postoperative course of antibiotic treatment of 5-7 days. In diabetic foot infections (DFI), repeated debridement to remove necrotic tissue and control infection can prevent minor and major amputation. In necrotizing soft tissue infections (NSTI), early and aggressive surgical debridement is paramount. Recent advancements have explored skin-sparing techniques in selective cases.

The management of SSTIs requires a combination of surgical and antimicrobial strategies tailored to the type and severity of the infection. Further clinical research is necessary in order to define more accurately those collectives in severe SSTI who profit from a less aggressive surgical approach.

Background/Objectives: The treatment of diabetic foot ulcers (DFU) is a challenging medical problem of extreme clinical and social importance, as a consequence of the emerging antibiotic resistance and decreased quality of life of diabetic patients due to impaired wound healing. One of the current trends in world science is the search for biologically active substances derived from living organisms. Biologically active peptides from snail mucus attract considerable scientific interest because of their pleiotropic pharmacological properties. The aim of our study was to evaluate the activity of a combination between a snail mucus protein fraction (MW > 20 kDa) obtained from the garden snail Cornu aspersum and the clinically applied antibacterial chemotherapeutic ciprofloxacin on pathogenic bacterial strains isolated from DFU. Results: The test bacterial strains were characterized as multidrug resistant. The combination between ciprofloxacin and the snail mucus fraction of interest led to additive or synergistic effects depending on the test strain. The mucus fraction exerted a well-pronounced wound-healing effect and no cytotoxicity on normal human fibroblasts and keratinocytes. Methods: The snail mucus was obtained by a patented technology (BG Utility model 2097/2015) and its electrophoretic profile was presented by SDS-PAGE. The bacterial strains were identified and tested for antimicrobial susceptibility (BD Phoenix M50 and Kirby-Bauer assay). The in vitro cytotoxicity of the mucus was evaluated by ISO 10995-5. The antimicrobial activity and combination effects were tested through ISO 20776/1 and the Checkerboard assay. Conclusions: The obtained results are promising and open new horizons for the development of novel combination treatment schemas for healing of infected DFU.

Diabetic foot ulcers (DFUs) are one of the most serious chronic diabetes-related complications. Since medial arterial calcification (MAC) can be present in patients with a DFU, toe pressure (TP) measurements are advised to grade potential ischemia. However, the value of TP to predict clinical outcomes in this group of patients is poorly understood. Therefore, the primary aim of this study was to investigate the relationship between TP values and ulcer healing in patients with DFU and concomitant MAC.

A single-center retrospective cohort study was conducted. Patients were included if they were 18 years or older, presented with a DFU, had a TP measurement and concomitant MAC in the same limb. MAC was defined as an ankle-brachial index (ABI) above 1.30, or incompressible arteries during ABI measurement. Multistate models were fitted to analyze the outcomes of interest (ulcer healing, revascularization, amputation, and mortality).

In total, 148 patients were included. During the 180 days follow-up, the cumulative incidence of a healed ulcer was 34% (95% confidence interval [CI]: 27-42%), whereas 32% (95% CI: 26-41%) of patients had a persisting open wound. An approximately positive linear correlation was observed between TP values and the probability of ulcer healing, regardless of whether patients had undergone a revascularization procedure. However, the absolute healing rate was low, and no clear distinction could be made for intermediate TP values (between 30 and 80 mm Hg).

Lower TP values are correlated with nonhealing of a DFU in patients with MAC, but clear absolute differences in healing are only seen between very low (below 30 mm Hg) and high (above 80 mm Hg) measurements. For intermediate TP values, the predictive strength of ulcer healing is weak. This should be of particular importance when grading ischemia in this subgroup of patients in wound classification systems.

Arterial ulcers are a clinical symptom of a complex array of underlying comorbid factors, namely peripheral artery disease (PAD). Chronic limb-threatening ischemia is representative of end-stage PAD. Ulcers of other etiologies can carry an arterial component, mandating recognition of risk factors, a comprehensive history and physical examination, and appropriate diagnostic testing in lower extremity ulcers. The primary therapy for arterial ulcers is re-establishment of in-line arterial flow, achieved by endovascular therapy or open revascularization. Medical management is essential to slow disease progression, and topical therapies are crucial to promote rapid ulcer closure and reduce infection risk.

To assess the yield and clinical impact of image-guided bone biopsy for osteomyelitis of the appendicular skeleton.

A literature search of several databases was conducted from inception to August 2023. Eligible studies reported patients who underwent image-guided bone biopsy for investigation of osteomyelitis of the appendicular skeleton. The pooled proportions were analyzed using a random-effects model. This review was registered in PROSPERO (CRD42023466419).

From 370 initial studies screened, eight met the eligibility criteria, with a total of 700 patients. The pooled technical success rate was 99.6% (95% CI: 0.992, 1.001; I2 = 0%). Positive bone cultures were pooled at 31.9% (95% CI: 0.222, 0.416; I2 = 87.83%) and negative cultures at 68.1% (95% CI: 0.584, 0.778; I2 = 87.83%). Methicillin-Sensitive Staphylococcus Aureus and Methicillin-Resistant Staphylococcus Aureus yield was 24.5% (95% CI: 0.096, 0.394; I2 = 90.98%) and 7.6% (95% CI: 0.031, 0.121; I2 = 34.42%) respectively. Group A Streptococcus yield was 7.0% (95% CI: 0.014, 0.127; I2 = 70.94%). Polymicrobial culture yield was 15.7% (95% CI: 0.018, 0.297; I2 = 88.90%). Post-procedural management change rate was 36.5% (95% CI: 0.225, 0.504; I2 = 92.39%). No complications were reported across studies.

For patients under investigation of osteomyelitis of the appendicular skeleton, image-guided bone biopsy demonstrates a good rate of technical success. Additional studies may provide further support for the use of image-guided bone biopsy in this population. Image-guided bone biopsy results lead to change in antibiotics therapy in a portion of patients with suspected osteomyelitis suggesting its potential utility in select patients.

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.

Diabetes foot disease (DFD) contributes to poor quality of life, clinical and economic burden. Multidisciplinary diabetes foot teams provide prompt access to specialist teams thereby improving limb salvage. We present a 17-year review of an inpatient multidisciplinary clinical care path (MCCP) for DFD in Singapore.

This was a retrospective cohort study of patients admitted for DFD and enrolled in our MCCP to a 1700-bed university hospital from 2005 to 2021.

There were 9279 patients admitted with DFD with a mean of 545 (±119) admissions per year. The mean age was 64 (±13.3) years, 61% were Chinese, 18% Malay and 17% Indian. There was a higher proportion of Malay (18%) and Indian (17%) patients compared to the country's ethnic composition. A third of the patients had end stage renal disease and prior contralateral minor amputation. There was a reduction in inpatient major lower extremity amputation (LEA) from 18.2% in 2005 to 5.4% in 2021 (odds ratio 0.26, 95% confidence interval 0.16-0.40, P < .001) which was the lowest since pathway inception. Mean time from admission to first surgical intervention was 2.8 days and mean time from decision for revascularization to procedure was 4.8 days. The major-to-minor amputation rate reduced from 1.09 in 2005 to 0.18 in 2021, reflecting diabetic limb salvage efforts. Mean and median length of stay (LOS) for patients in the pathway was 8.2 (±14.9) and 5 (IQR = 3) days, respectively. There was a gradual trend of increase in the mean LOS from 2005 to 2021. Inpatient mortality and readmission rate was stable at 1% and 11%.

Since the institution of a MCCP, there was a significant improvement in major LEA rate. An inpatient multidisciplinary diabetic foot care path helped to improve care for patients with DFD.

There are few data comparing outcomes after hallux amputation or partial first ray resection after diabetic foot ulcer (DFU). In a similar context, the choice to perform one of these two surgeries is attributable to clinician preference based on experience and characteristics of the patient and the DFU. Therefore, the purpose of this study was to determine the more definitive surgery between hallux amputation and partial first ray resection. We abstracted data from a cohort of 70 patients followed for a 1-year postoperative period to support clinical practice. We also attempted to identify patient characteristics leading to these outcomes. Our results suggested no statistical difference between the type of surgery and outcomes such as recurrence of DFU and amputation at 3, 6, and 12 months or death. However, there was a statistically significantly increased likelihood of re-ulceration for patients with CAD who underwent hallux amputation (p = 0.02). There was also a significantly increased likelihood of re-ulceration for people with depression or a history when the partial ray resection was performed (p = 0.02). Patients with prior amputation showed a higher probability of undergoing another re-amputation with partial ray resection (p = 0.01). Although the trends that emerge from this project are limited to what is observed in this statistical context, where the number of patients included and the number of total observations per outcome were limited, it highlights interesting data for future research to inform clinical decisions to support best practices for the benefit of patients.

Diabetic foot infection can lead to limb amputation in approximately 17% of affected patients. Given the complex pathophysiology associated with diabetic foot infection, the goal of limb preservation is best achieved with a multidisciplinary approach and a team of providers including infectious disease consultants. However, these infections often affect populations living in nonmetropolitan areas, where access to an infectious disease physician may be limited. It may fall on the surgeons and primary care providers to not only diagnose infections early, including osteomyelitis, but also facilitate prompt, appropriate antibiotic management. The decision to treat with antibiotics alone versus surgery, choice of antibiotic, route of administration, and duration of treatment are complicated concepts that require a patient-specific approach. In addition, use of oral antibiotics and long-acting lipoglycopeptides has gained prominence and offers an alternate solution to the tedious, resource-intense process of outpatient intravenous antibiotic treatment. The goal of this article is to outline and address diagnostic and management questions that would be posed to an infectious disease consultant. The responses would include a literature review of current management concepts and highlights from the 2023 Infectious Disease Society of America and International Working Group on the Diabetic Foot guidelines.

Extracellular matrix (ECM) and angiogenesis are critical controls of wound regeneration, and their dysfunction delays diabetes recovery. CXXC5 belongs to the CXXC protein family that can regulate the function of human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs); However, awareness of its functional role remains limited.

Mice were divided into control (CON), diabetic (DM), diabetic + KY19382 (DM + KY19382), and diabetic + vehicle (DM + Vehicle) groups. HDFs and HUVECs were stimulated under different CXXC5 conditions and mice were treated with KY19382, followed by the application of assays including Western blotting (WB), immunofluorescence (IF) and quantitative reverse transcription-PCR (qRT-PCR) to assess wound healing and molecular signaling.

Mice in DM had fewer blood vessels, a slower wound healing rate, and more disrupted collagen than CON. Application of KY19382 improved these conditions, which promoted fibroblast activation and vascularization in high glucose environments and DM. Mechanistically, blocking CXXC5 promotes Wnt/β-catenin-mediated stabilization by reducing the binding of the deterrent factor CTBP1 to β-catenin, which induces dermal fibroblast activation and facilitates HUVECs tube formation and migration via VEGFA/VEGFR2 and NFκB signaling pathways. KY19382 promotes HUVECs activation by blocking CTBP1 transcription to activate the NFκB signaling pathway, thus wound re-vascularization.

CXXC5 is an essential regulatory factor of wound healing and a prospective therapeutic target for treating chronic wound damage in diabetes.

To compare the clinical outcomes of patients with lower limb osteomyelitis (LLOM) and negative methicillin-resistant Staphylococcus aureus (MRSA) cultures treated with anti-MRSA therapy (AMT) versus those treated with no-anti-MRSA therapy (NAMT).

Retrospective cohort study.

Hospitalized adult (≥18 yr of age) patients admitted to multiple tertiary referral centers in a single healthcare system between April 1, 2017 and April 1, 2023, with LLOM and planned intravenous antibiotics for at least four weeks.

Electronic medical records were queried for demographic information, admission dates, treatment strategies, imaging and culture results, and discharge diagnoses. Descriptive statistics measured baseline characteristics, imaging, and culture results.

Out of 473 patients, 64 met the inclusion criteria and 409 were excluded. Of the 64 patients, 26 (40%) had AMT and 38 (59%) had NAMT. A larger but statistically insignificant portion of patients in the NAMT cohort failed therapy (23% AMT vs 32% NAMT, P = 0.325). However, hospital readmission for LLOM within 180 days of antibiotic completion (46.2% vs 47%, P = 0.92), hospital length of stay (median (IQR): 6 (5-9) d vs 7 (5-12.5) d, P = 0.285), incidence of new renal replacement therapy initiation (0% vs 2.6%, P = 0.594), creatinine kinase levels (0 vs 2.6%, P = 0.594), and drug-induced immune thrombocytopenia (0% vs 5.3% P = 0.349) were comparable between the two cohorts.

Treatment failure rates and adverse events did not differ significantly among patients with LLOM treated with AMT or NAMT. Further investigation of determinants of clinical failures in LLOM may help optimize overall treatment.

Diabetic foot ulcer (DFU) inpatients admitted with non-ulcer complaints constitute a neglected group that might suffer from more non-standard treatments. This study intends to describe their clinical characteristics, and clarify the problems existing in the DFU management process.

In this retrospective study, admission complaints were determined by combining the final diagnosis and clinical documentation, and were categorized as: ulcer-related or non-ulcer complaints.

A total of 264 DFU inpatients were included in the final analysis, of which, 80 (30.3%) were admitted with non-ulcer complaints. A total of 82.5% of the DFU inpatients with non-ulcer complaints were admitted to departments without DF specialists. IWGDF/IDSA grade, cerebrovascular diseases, chronic kidney disease, infection in other parts, glycosylated hemoglobin A1c and the source of hospitalization expenses were the independent influencing factors for admission with non-ulcer complaints (all P < 0.05). Before admission, only 11.3% of the patients with non-ulcer complaints had ever been treated by a DF specialist and/or in a clinical setting with DF specialists. After admission, 25.0% of the DFU inpatients with non-ulcer complaints did not receive any local wound care, and only 7.6% of the patients admitted to the departments without DF specialists obtained a referral.

Approximately one-third of inpatients with DFU are admitted with non-ulcer complaints and most of them are admitted to departments without DF specialists. Inpatients with non-ulcer complaints have milder wounds but more severe and greater comorbidities and worse organ function. These patients do not receive standardized management for DFU either before or after admission. Targeted measures are needed to improve this situation.

Diabetic wounds (DWs) are the most devastating complication, resulting in significant mortality and morbidity in diabetic patients. Although the pathophysiology of DWs is multifaceted, evidence has revealed that prolonged inflammation with infections, extracellular matrix (ECM) degradation, and unnecessary NETosis impair DW healing. This theoretical problem highlights the necessity of developing a novel strategy focused on targeting the "specific" molecular modalities of DWs. The primary culprits, matrix metalloproteinase (MMP)-9 and protein kinase C (PKC)-βII, are responsible for impaired angiogenesis, NETosis, and ECM degradation. Thus, interest in identifying selective inhibitors for the effective management of DW has increased. The current study exemplified human β-defensin-2 (HBD-2), a biological macromolecule that functions as a dual inhibitor of MMP-9 and PKC-βII, via protein-protein docking and molecular dynamics simulation studies. Overall, the data analysis revealed that HBD-2 possesses strong binding affinity and stability against MMP-9 and PKC-βII, suggesting that HBD-2 may be an ideal therapeutic for the accelerated healing of DW. Our findings suggest HBD-2's potential as an innovative therapeutic for accelerated DW healing, offering valuable insights into its molecular mechanisms. However, in vitro and in vivo studies are required to bridge the gap between computational modeling and clinical application.

Foot ulcers are a common and feared complication for people with diabetes because 20% of foot ulcers become infected and lead to a lower extremity amputation.

To evaluate the effect of daily foot care using chlorhexidine wipes vs soap-and-water wipes for 1 year on the risk of developing new foot complications in veterans with diabetes.

This double-blind, placebo-controlled, phase 2b randomized clinical trial was conducted at the Baltimore Veterans Affairs (VA) Medical Center between January 2019 to January 2023. Veterans were eligible if they had a diabetes diagnosis, were at high risk for diabetic foot complications, were ambulatory, had both feet, and did not have a current foot infection. Participants were randomly assigned 1:1 to receive either soap-and-water wipes (control group) or 2% chlorhexidine wipes (chlorhexidine group). Intention-to-treat data analysis was conducted from October 5, 2023, to April 24, 2024.

Daily use of a 2% chlorhexidine wipe or a soap-and-water wipe on the feet for 1 year. Wipes were nearly identical in color, size, shape, thickness, feel, and scent. Both chlorhexidine and control groups received the same lotion for application on the feet after wipe use and education on foot self-care.

The primary outcome was time in days from randomization to new foot complication, including chronic foot ulcer, foot infection, or foot amputation.

A total of 175 participants (170 males [97%]; mean [SD] age at enrollment, 68 [9] years; 1 Asian [1%], 117 Black or African American [67%], 53 White [30%] individuals) were randomly assigned to the chlorhexidine group (n = 88) or the control group (n = 87). Twelve participants (14%) in the chlorhexidine group and 14 participants (16%) in the control group developed a new foot complication within 1 year. Median (IQR) time from randomization to development of a new foot complication was 232 (115-315) days. The reduction in hazard of new foot complications in the chlorhexidine group compared with the control group was not significant (hazard ratio, 0.83; 95% CI, 0.39-1.80). The intervention was well tolerated, with 145 participants (83%) continuing it over the study period. Sixty adverse events occurred, but none was related to the study products or procedures.

This randomized clinical trial found that daily use of chlorhexidine wipes for foot washing for 1 year did not lead to a significant reduction in the risk of new foot complications compared with daily use of soap-and-water wipes. The intervention was well tolerated, and the trial provides important lessons for future studies on diabetic foot ulcer prevention.

ClinicalTrials.gov Identifier: NCT03503370.

Chronic wounds are prone to infections with multidrug-resistant bacteria, forming polymicrobial biofilms that limit treatment options and increase the risk of severe complications. Current cleansing options are insufficient to disrupt and remove tenacious biofilms; antibiotic treatments, on the other hand, often fall short against these biofilm-embedded bacteria. This study explores an non-antibiotic approach that extends beyond conventional porphyrin-based phototherapy by using blue light (BL) in conjunction with ferric ions (Fe(III)) to disrupt and eradicate biofilms. The dual not only degraded biofilm extracellular polymeric substances (EPS) in mono-species and polymicrobial biofilms by specifically targeting carboxyl-containing polysaccharides within the matrix but also exhibited broad-spectrum antimicrobial activity by affecting key components of the outer membrane and cell wall. Bacteria, such as K. pneumoniae, with compromised EPS after photolysis, demonstrated increased susceptibility to macrophage phagocytosis. Disruption of the polymicrobial biofilm structure also enhanced the bacterial susceptibility to bactericidal drugs. Treating wounds infected by mixed-species biofilm in diabetic mice demonstrated a substantial reduction in bacterial colonization and improved tissue repair. The BL-Fe(III) modality offers a safe, efficient alternative for managing chronic wound infections, making it ideal for repeated, non-invasive use at home, especially in resource-limited areas.

Diabetic foot ulcers (DFUs) are characterized by dynamic wound microbiome, the timely and accurate identification of pathogens in the clinic is required to initiate precise and individualized treatment. Metagenomic next-generation sequencing (mNGS) has been a useful supplement to routine culture method for the etiological diagnosis of DFUs. In this study, we utilized a routine culture method and mNGS to analyze the same DFU wound samples and the results were compared.

Forty samples from patients with DFUs at a tertiary medical center in South China were collected, the microorganisms were identified with mNGS and routine culture method simultaneously.

The results showed that the positive detection rate of microorganisms in DFUs with mNGS was much higher (95% vs. 60%). Thirteen strains of microorganisms were detected with routine culture method, and seventy-seven strains were detected with mNGS. Staphylococcus aureus was the most common microorganism detected with culture method, while Enterococcus faecalis was the most common microorganism detected with mNGS. The false negative rate of the culture method was 35%, that was, 14 samples with negative results with culture method were found to be positive with mNGS.

The mNGS method had a higher positive detection rate and identified a broader spectrum of microorganisms in DFUs, thus, mNGS provided a more comprehensive understanding of the microbiome of DFUs to facilitate the development of timely and optimal treatment.

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethical Review Committee of the Fujian Medical University Union Hospital (approval number 2021KY054).

To compare the clinical outcomes and healthcare utilization of patients enrolled in the multidisciplinary Diabetic Foot in Primary and Tertiary (DEFINITE) Care program with a matched historical cohort and estimate the program's long-term cost-effectiveness using simulation.

This study consisted of two components: a 1-year observational outcome evaluation and a long-term simulation-based cost-effectiveness analysis (CEA). We conducted an observational study to analyze 2798 patients with diabetic foot ulcers (DFUs) enrolled in the program between June 2020 and June 2021 (DEFINITE Care group) and 5462 patients with DFUs from June 2016 to December 2017 as historical controls. One-to-one propensity score matching (PSM) with replacement was conducted to estimate the treatment effect of the program on clinical outcomes and healthcare utilization over 1 year. For the simulation component, a long-term CEA was performed using a Markov state transition model on a simulated cohort of 10 000 patients with DFUs over a 20-year period, assessing transitions between health states, including minor and major amputations and death. The incremental cost-effectiveness ratio (ICER) was calculated for the DEFINITE Care program relative to routine care.

The estimation of average treatment effects based on propensity scores showed that the DEFINITE Care group exhibited a 9% lower mortality, 5% higher lower extremity amputation (LEA)-free survival, yet a 5% higher minor LEA rate compared with the matched historical controls. Additionally, they experienced fewer inpatient admissions (0.98 fewer episodes) and shorter hospital stays (5.5 fewer days) within 1 year (p-value <0.001). The ICER was US$22 707 (SE: 430) per quality-adjusted life year gained, indicating long-term cost-effectiveness. Probabilistic sensitivity analysis supported these findings.

The integrated multidisciplinary DEFINITE Care program improved LEA-free survival, reduced inpatient admissions and length of stay within 1 year and demonstrated long-term cost-effectiveness managing DFUs.