Infected Ulcers Research Articles

Increased risk of major adverse cardiovascular events in patients with deep and infected diabetes-related foot ulcers.

Diabetes-related foot ulceration (DFU) is associated with increased cardiovascular risk, but the mechanisms remain unclear. Inflammation and infection are mediators of CVD, which may be important in DFU. Prospectively collected data from patients attending a multidisciplinary DFU service were analysed. A deep ulcer was defined as one that reached muscle, tendon or deeper structures. Patients were categorised into four DFU groups: not deep and no infection (D-/I-), not deep but infected (D-/I+), deep with no infection (D+/I-) or deep with infection (D+/I+). Incident major adverse cardiovascular events (MACE) were defined as hospitalisation for myocardial infarction, stroke or transient ischaemic attack, or heart failure. Survival analyses were performed using the logrank test and multivariate Cox regression. Of 513 patients, 241 (47.0%) were in the D-/I- group, 110 (21.4%) were in the D-/I+ group, 35 (6.8%) were in the D+/I- group and 127 (24.8%) were in the D+/I+ group. MACE or all-cause mortality occurred in 75 patients (14.6%), and MACE alone occurred in 46 patients (9.0%) after median follow-up of 381 days (IQR 220-551) and 404 days (IQR 228-576), respectively. Infection was associated with significantly higher MACE or all-cause mortality (21.5% vs 8.7%; p<0.001) and MACE alone (13.5% vs 5.1%; p=0.003). MACE or all-cause mortality was significantly higher in the D+/I+ group (D-/I- 7.9%; D-/I+ 15.5%; D+/I- 14.3%; D+/I+ 26.8%; p<0.001), as was MACE alone (D-/I- 5.0%; D-/I+ 10.9%; D+/I- 5.7%; D+/I+ 15.7%; p=0.017). Infection and a deep ulcer were independent predictors of adverse outcomes. Deep and/or infected DFUs are associated with increased cardiovascular risk compared with DFUs that are not deep or infected. These findings provide a potential mechanistic explanation that requires investigation.

Evaluation of Fungitell (1,3)-β-D-glucan assay in tear samples for rapid diagnosis of fungal keratitis.

Fungal keratitis (FK) is a serious suppurative and ulcerative corneal infection leading to blindness and vision loss. Rapid diagnosis of FK can contribute to prompt clinical management with early recovery. The study aimed to standardize the detection of (1,3)-β-D-glucan (BDG) and establish the diagnostic cut-off concentration in tears of suspected FK patients along with non-infected controls. This prospective multicentric study was conducted between the period of August 2022 and April 2024. Samples were collected from three tertiary eye-care facilities across India. All suspected FK patients were enrolled in the study. Prior to tear collection, the eye and eyelid were gently cleansed using sterile normal saline (NS) and lint-free tissue paper. Subsequently, 50 µL of sterile NS was instilled into the eye, followed by tear sample collection after 60 s using sterile fine microtips. Tear samples were collected from the contralateral eyes of the FK patients, and those from healthy volunteers served as controls. The concentration of BDG in tears in varying dilutions was quantitatively measured using the Fungitell Assay Kit (Associates of Cape Cod, East Falmouth, Massachusetts). A total of 53 tear samples were analyzed at 1:10 and 1:20 dilutions. The receiver operating curve revealed an area under the curve (AUC) of 0.919 for the 1:10 dilution, with a cut-off value of 123 pg/mL, yielding a sensitivity of 100% and specificity of 84.85%. The corresponding Youden Index was 0.798. At the 1:20 dilution, the AUC was 0.898 with a cut-off of 84 pg/mL, achieving a sensitivity of 70% and specificity of 96.88% with a Youden Index of 0.670. Given the higher specificity at the 1:20 dilution, it was further validated in 145 tear samples. The validation cohort demonstrated a sensitivity of 95.56%, specificity of 83%, positive predictive value (PPV) of 71.67%, negative predictive value (NPV) of 97.65%, and diagnostic odds ratio of 112.4. Notably, a significantly higher BDG concentration (P < 0.0001) was observed in infected tear samples compared to controls (270.6 ± 128.5 vs 37.31 ± 31.32). Detection of BDG in tear samples is a new, non-invasive, and rapid technique showing excellent performance and can be effectively implemented for diagnosing FK in laboratories.

Efficacy of Bismuth Quadruple Therapy in the Treatment of Helicobacter pylori-Infected Peptic Ulcer Children in Vietnam.

The continuous increase in drug-resistant strains, the lack of novel antibiotics, and the fewer options available to combat antibiotic-resistant infections in pediatrics pose significant challenges to the eradication of Helicobacter pylori (H. pylori) in children. This study evaluated the efficacy of first-line therapy with bismuth quadruple therapy in H. pylori-positive pediatric patients with peptic ulcers. 136 patients (aged between 8 and 17 years) diagnosed with active peptic ulcers with H. pylori infection were enrolled in this study. Patients with H. pylori strain sensitive to tetracycline and metronidazole were assigned to bismuth quadruple therapy, including a proton pump inhibitor (PPI), bismuth, tetracycline, and metronidazole. Antibiotic resistance of H. pylori was analyzed by the Epsilometer test. Treatment efficacy was evaluated at 12 weeks based on H. pylori eradication and peptic ulcer healing rates. H. pylori infection status was evaluated by a 13C-urea breath test. Most isolates showed extremely high rates of resistance to commonly prescribed antibiotics used for children, including clarithromycin (97.0%) and amoxicillin (84.6%), while the low rate of resistance to levofloxacin (16.2%). The overall success rate of eradication therapy in the intention-to-treat and the per-protocol group were 86.0% and 89.3%, respectively. Peptic ulcer healing rates for total patients at 6 weeks and 12 weeks were 75.0% and 97.7%, respectively. There were no entail unpleasant adverse events, and peptic ulcer symptoms decreased steadily over time in all cases. The bismuth quadruple therapy with a 2-week PPI pretreatment and followed by prolonged PPI was highly successful in eradicating H. pylori infection and healing ulcers in pediatric patients with active peptic ulcer. This might be preferable as a first-line empiric treatment regimen for H. pylori-positive pediatric patients with peptic ulcers, especially in populations with high rates of resistance to amoxicillin and clarithromycin.

COVID-19 and COVID-19 Vaccine-Related Skin Ulcerations in the Lower Extremities: A Case Report and Literature Review

Several associations have been made between COVID-19 and vasculitis. Recent data also shows the prevalence and association of de novo vasculitis with either COVID-19 infection or COVID-19 post vaccination. In this article, we present the case of new-onset leukocytoclastic vasculitis, secondary to COVID-19 vaccination, that was complicated by severe infected and nonhealing ulcers in the lower extremities. Case A 53-year-old male patient presented to the dermatology clinics with a three-week history of painful necrotic patches coalescent of the lateral malleolus of the right and left ankles. History goes back to when the patient reported developing pruritic papules two weeks after receiving his second shot of the Pfizer BioNTech COVID-19 vaccine (BNT162b2). Punch biopsy was consistent with leukocytoclastic vasculitis. He was prescribed a four-week course of systemic corticosteroids and antibiotics as per cultures. Vascular assessment confirmed normal peripheral arterial and venous system. Two months later, the patient re-presented with fever and worsening of his lower extremity ulcers. He underwent debridement of his wounds. Intra-operative cultures revealed multidrug resistant bacteria. He required an additional debridement session a few days later and a 14-day course of Piperacillin-Tazobactam. The patient was subsequently discharged on corticosteroids and Azathioprine and followed up in the vascular surgery and rheumatology clinics. At four months follow-up, the patient's wounds were almost completely healed. Conclusion This article highlights a case of severe new-onset COVID-19 vaccine-associated leukocytoclastic vasculitis complicated with infected ulcers that required debridement twice in addition to a prolonged course of antibiotics and immunosuppression therapy. To our knowledge, none of the cases reported in the literature were this severe in nature. In this post-pandemic era, it must remain high on the differential list, and healthcare specialists should maintain a high index of suspicion when evaluating sudden new-onset skin lesions that do not have an immediately apparent etiology.

Streptococcus dysgalactiae subsp.-equisimilis as an emerging secondary pathogen in leprosy foot ulcers.

Leprosy foot ulcers (LFU) tend to become chronic due to secondary bacterial infections, leading to subsequent disfigurement and disability. Treatment modality for infected plantar ulcers thus so far is majorly based on conventional approach of empirical antibacterial therapy. However, this approach tends to overlook unconventional pathogens which are likely to be present in the LFU. Twenty-six leprosy patients (17 males and 9 females) who had completed multidrug therapy (MDT) and those are suffering from foot ulcer were included. Using sterile cotton swabs, two wound swabs were collected, of these; one for bacterial culture and another for NGS (Next Generation Sequencing). Out of 26 samples tested on conventional bacterial culture, Streptococcus spp. (50%) was predominant organism. On NGS, 09/26 (34.61%) showed Streptococcus-dysgalactiae-subsp.-equisimilis-GGS 12 as the most abundant single organism, along with some unknown and unclassified organisms; 03/26 (11.5%) were Arcanobacterium-haemolyticum-DSM-20595 alone and 02/26 (7.69%) were Streptococcus-pyogenes alone.Acombination of Arcanobacterium-haemolyticum-DSM-20595 and Streptococcus-dysgalactiae-subsp.-equisimilis-GGS 124 was found in nine (34.61%) specimens. Polymicrobial infection with conventional and unconventional pathogenic bacteria is another notable finding suggesting appropriate interventions. The study findings also reiterate the need for understanding the polymicrobial infections and their role in the clinical progression of the LFU.

POSSIBILITIES OF NON-STANDARD METHODS FOR TREATING INFECTED WOUNDS

Summary. Introduction. Some representatives of the microcosm can secrete a variety of biologically active substances that have a detrimental effect on other groups of microorganisms. The geniuses of humanity noticed this, and today medicine has about 1600 antibacterial drugs. However, the struggle for survival at all levels continues. Many bacteria have become resistant to existing antibiotics. Taking this into account, the treatment of purulent-inflammatory diseases faces insurmountable difficulties. Contaminated ulcerative processes and various wounds of the legs are accompanied by suppuration, the treatment of which is extended by weeks and months. The above justifies the relevance of the problem. Aim: to study the possibilities of using non-standard methods for treating purulent and infected wounds and ulcers. Materials and methods. In experimental conditions (patent), we studied and tested the treatment of purulent ulcers (S=2.0–42.0 cm2) and wounds (S=22.0–48.0 cm2) in 21 patients without the use of antibiotics. Apatite polymer drainage bandages (APDB) were applied under compression conditions. Results and discussion. The dressing was changed after 12–24–48 hours, depending on the exudation level. The clinical effect was observed from the 4th day. Epithelization of wound surfaces was observed on days 14–21, of ulcerative defects – on days 18–32. Conclusions. APDB based on zinc oxide may be an alternative to existing standard treatment methods for purulent diseases. Funding. This study was carried out with grant support from the National Research Foundation of Ukraine (project No. 2023.04/0109).

Double Enzyme Active Hydrogel Program Regulates the Microenvironment of Staphylococcus aureus-Infected Pressure Ulcers.

The treatment of infected pressure ulcers (IUPs) requires addressing diverse microenvironments. A pressing challenge is to effectively enhance the regenerative microenvironment at different stages of the healing process, tailoring interventions as needed. Here, a dual enzyme mimetic and bacterial responsive self-activating antimicrobial hydrogel designed to enhance IPUs healing is introduced. This hydrogel incorporates pH-responsive dual enzyme-active nanoplatforms (HNTs-Fe-Ag) encapsulated within a methacrylate-modified silk fibroin (SFMA) and dopamine methacrylamide (DMA) matrix. This composite hydrogel exhibits adaptive microenvironment regulation capabilities. Under the low pH microenvironment of bacterial infection, it has excellent antimicrobial activity by self-activating the •OH generation in conjunction with photothermal effects. Under the neutral and alkaline microenvironment of chronic inflammation, it catalyzes the decomposition of hydrogen peroxide (H2O2) to produce oxygen (O2), thereby alleviating hypoxia and scavenging reactive oxygen species (ROS), which in turn remodulates the phenotype of macrophages. The composite hydrogel demonstrates on-demand therapeutic effects in the microenvironment of infected wounds, significantly enhancing the regenerative microenvironment of IUPs by promoting wound closure, inflammation regulation, and collagen deposition through self-activated antimicrobial action during infection and adaptive hypoxia relief during recovery. This approach offers a novel strategy for developing smart wound dressings.

An integrated active case detection and management of skin NTDs in yaws endemic health districts in Cameroon, Côte d'Ivoire and Ghana.

Integrated approaches to mapping skin Neglected Tropical Diseases (NTDs) may be cost-effective way to guide decisions on resource mobilization. Pilot studies have been carried out, but large-scale data covering multiple countries endemic for skin NTDs are lacking. Within the LAMP4YAWS project, we collected integrated data on the burden of multiple skin NTDs. From March 2021 to March 2023, integrated case searches for yaws alongside other skin conditions were performed in endemic health districts of yaws in Cameroon, Côte d'Ivoire, and Ghana. Integrated activities included training, social mobilization and active case detection. Initial screening involved a brief clinical examination of participants to determine if any skin conditions were suspected. Cases of skin NTDs were then referred to a health facility for appropriate management. Overall 61,080 individuals screened, 11,387 (18.6%) had skin lesions. The majority of individuals (>90%) examined were children aged 15 years old and under. The proportion of serologically confirmed yaws cases was 8.6% (18/210) in Cameroon, 6.8% (84/1232) in Côte d'Ivoire, and 26.8% (440/1643) in Ghana. Other skin conditions based on clinical examination included: scabies, Buruli ulcer, leprosy, lymphatic filariasis (lymphoedema and hydrocele), tungiasis, and fungal infections. The most common conditions were scabies and superficial fungal infections. In Cameroon, scabies and superficial fungal infections accounted for 5.1% (214/4204) and 88.7% (3730/4204) respectively, 25.2% (1285/5095) and 50.4% (2567/5095) in Côte d'Ivoire. In Ghana, 20% (419/2090) of individuals had scabies but superficial fungal infections were not routinely recorded and were reported in only 1.3% (28/2090). Other skin NTDs were less common across all three countries. This study confirms that integrated screening allows simultaneous detection of multiple skin NTDs, maximising use of scarce resources.

Is it really descemetocele? Morphology of extremely thin membrane that remained after severe corneal melting: a case report.

The aim of this study was to report transmission electron microscopic findings of a case with whole corneal descemetocele following infective corneal ulcer for the first time in literature. A 72-year-old male patient presented with infective corneal ulcer. After resolution of the infection, corneoscleral transplantation was performed. The excised very thin corneal membrane was processed for transmission electron microscopic examination. Transmission electron microscopic examination of the specimen revealed many layered structures that consisted of two different types of cells. The first type consisted of lighter staining polygonal cells, while the second consisted of elongated cells with relatively dense staining. All cells were connected with a large number of gap or adherens junctions with intercalation of the cell membranes of adjacent cells. A haphazard distribution of cytoplasmic microfilaments were also observed in all of the cell types. There was no evidence of the presence of endothelial cells throughout the specimen. There was also no evidence of Descemet membrane presence except for a small part adjacent to iris tissue that contained some melanosomes. Although we clinically diagnosed descemetocele, Descemet membrane was not present at the electron microscopic level, and thus, the expression "descemetocele" is inappropriate.

Prospective Observational Study of Microbiology of Infected Diabetic Foot Ulcers in a Tertiary-Care Hospital.

Diabetic foot ulcers (DFUs) are a major cause of morbidity and mortality in people with diabetes mellitus. DFUs are the leading cause of hospitalisation for diabetic patients worldwide, especially in developing countries such as India. This study presents the microbiology profile of DFUs in a tertiary care hospital in the eastern part of India. We conducted a prospective observational study for 150 DFU patients over a period of two years. We took samples from the DFUs of these patients, cultured them, and tested their antimicrobial susceptibility. Most diabetic foot infections (DFIs) in our study patients were caused by Gram-negative bacteria, mainly Escherchia coli(E. coli) (19.3%), Pseudomonas (14%), and Staphylococcus aureus(S. aureus) (12%). The majority of Gram-positive bacteria were susceptible to linezolid, followed by vancomycin and amoxycillin, while the majority of Gram-negative bacteria were susceptible to imipenem and meropenem, followed by ampicillin with sulbactam, amikacin, gentamicin, and ciprofloxacin. Our study revealed that 88.3% of the isolates were monomicrobial. These findings demonstrated the importance of a local antibiogram, a microbiological exam, and antimicrobial susceptibility testing before starting antibiotic treatment for infections caused by DFUs. This protocol is different from the recommended guidelines for using empirical antibiotics.

Glucose and pH dual-responsive hydrogels with antibacterial, reactive oxygen species scavenging, and angiogenesis properties for promoting the healing of infected diabetic foot ulcers

The healing process of diabetic foot ulcers is challenging due to the presence of a complex and severe inflammatory microenvironment, characterized by hyperglycemia, low pH, susceptibility to infection, vascular dysfunction, and over-expression of reactive oxygen species (ROS), which can potentially lead to amputation or even mortality. Herein, a glucose and pH dual-responsive hydrogel was designed and prepared by crosslinking phenylboronic acid-grafted quaternary chitosan (QF, 4 wt%) with dopamine-grafted oxidized hyaluronic acid (OD, 5 wt%) through phenylboronation, schiff-base reaction, and other techniques. The multifunctional QO/@PV@AB7 hydrogel was prepared by incorporating pravastatin-loaded chitosan nanoparticles (CSNPs@PV, 2 mg/mL) and antimicrobial peptide AMP-AB7 loaded silica nanoparticles (SiO2NPs@AB7, 0.5 mg/mL). The results demonstrate that the QO/@PV@AB7 hydrogel exhibits good responsiveness to acidic conditions and high glucose levels, while effectively scavenging various types of ROS. Moreover, it exerted protective effects against oxidative stress on cells, enhanced HUVECs viability, and promoted angiogenesis. Notably, the QO/@PV@AB7 hydrogel displayed potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. Additionally, in an MRSA-infected rat model of diabetic foot wounds, administration of the QO/@PV@AB7 hydrogel led to increased secretion of pro-angiogenic factors such as vascular endothelial nitric oxide synthase (eNOS), vascular endothelial-generating factor (VEGF), and endothelial cell adhesion molecule (CD31). Furthermore, the hydrogel significantly reduced the levels of inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), while simultaneously increasing the levels of anti-inflammatory cytokines such as interleukin-10 (IL-10). The findings suggest that multifunctional hydrogels incorporating PV@CSNPs and SiO2NPs@AB7 demonstrate promising potential as a therapeutic approach for the treatment of diabetic foot. Statement of SignificanceHere, a glucose and pH dual-responsive QO/@PV@AB7 hydrogel with antimicrobial and angiogenesis-promoting properties was developed for the treatment of infected wounds in diabetic feet. Our findings demonstrate that the proposed hydrogel exhibits good responsiveness, effectively scavenges various types of reactive oxygen species (DPPH, O2-, -OH, and ABTS+), provides protection against oxidative stress, enhances HUVECs cell viability, and promotes angiogenesis. Notably, it also demonstrates potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. Additionally, in vivo experiments demonstrated that the hydrogel exhibited accelerated wound healing in MRSA-infected diabetic foot ulcers, with a reduction of four days compared to the control group.

Occurrence of Entamoeba Histolytica infection in patients with Ulcerative colitis attending to the Al-Diwaniyah gastroenterology center/ Iraq

One Hundred Eighteen (118) Stool testers were composed from ulcerative colitis patients distress from intestinal sicknesses, abdominal discomfort, and cases of diarrhea which presence to gastroenterology center in Al-Diwaniyah Teaching Hospital and outpatient clinics from different age groups. for the period from August 2023 - March 2024. The samples were examined with a light microscope using The direct wet smear method from Human stool samples. Microscopic study revealed a important variance at (P ≤ 0.05) among ulcerative colitis patients and infection with E. histolytica was 81.35% (96 positive samples from 118). The results of showed that non-significant alterations at (p ≤ 0.05) between infection with the E. histolytica and age groups, Gender and Residency.

Computer-aided drug design to generate a unique antibiotic family.

The World Health Organization has identified antibiotic resistance as one of the three greatest threats to human health. The need for antibiotics is a pressing matter that requires immediate attention. Here, computer-aided drug design is used to develop a structurally unique antibiotic family targeting holo-acyl carrier protein synthase (AcpS). AcpS is a highly conserved enzyme essential for bacterial survival that catalyzes the first step in lipid synthesis. To the best of our knowledge, there are no current antibiotics targeting AcpS making this drug development program of high interest. We synthesize a library of > 700 novel compounds targeting AcpS, from which 33 inhibit bacterial growth in vitro at ≤ 2 μg/mL. We demonstrate that compounds from this class have stand-alone activity against a broad spectrum of Gram-positive organisms and synergize with colistin to enable coverage of Gram-negative species. We demonstrate efficacy against clinically relevant multi-drug resistant strains in vitro and in animal models of infection in vivo including a difficult-to-treat ischemic infection exemplified by diabetic foot ulcer infections in humans. This antibiotic family could form the basis for several multi-drug-resistant antimicrobial programs.

Clinical outcomes in patients with critical limb-threatening ischemia and infected ulcers following endovascular therapy are pathogen dependent: A single-center experience from 2012 to 2021

Clinical outcomes in patients with critical limb-threatening ischemia and infected ulcers following endovascular therapy are pathogen dependent: A single-center experience from 2012 to 2021

Amniotic membrane graft (AMG) for persistent epithelial defects following infective corneal ulcers and keratitis - A systematic review.

Management of nonhealing corneal ulcers is challenging as it can lead to complications such as melting, descemetocele, and perforation, which can be prevented by amniotic membrane graft (AMG). The absence of any review (English language) on AMG for corneal ulcers prompted us to conduct this review. We looked for clinical trials (randomized and controlled) on the effect of AMG combined with other treatments, through various search engines utilizing the terms amniotic membrane and corneal ulcer. All patients who received AMG and/or conventional medication were included. Risk of bias tools derived from Cochrane collaboration were used to ascertain the standard and quality of the trials. Visual acuity and epithelial healing time were the main outcome measures studied. Three trials were finally selected for analysis. AMG was noted to be associated with better uncorrected visual acuity and reduction in neovascularization. There was no difference in best corrected visual acuity, epithelial healing time, and corneal opacity. There is evidence that the use of AMG is associated with improved uncorrected visual acuity as well as reduction in neovascularization of the cornea among patients with corneal ulcers, but there was no improvement in epithelial healing time or corneal opacity. Further multicenter randomized controlled trials are needed to elicit the beneficial effects of the intervention and augment the validity of this review.

Novel Supramolecular Hydrogel for Infected Diabetic Foot Ulcer Treatment.

Multifunctional responsive hydrogels hold significant promise for diabetic foot ulcer (DFU) treatment, though their complex design and manufacturing present challenges. This study introduces a novel supramolecular guanosine-phenylboronic-chlorogenic acid (GBC) hydrogel developed using a dynamic covalent strategy. The hydrogel forms through guanosine quadruplex assembly in the presence of potassium ions and chlorogenic acid (CA) linkage via dynamic borate bonds. GBC hydrogels exhibit pH and glucose responsiveness, releasing more chlorogenic acid under acidic and high glucose conditions due to borate bond dissociation and G-quadruplex (G4)hydrogel disintegration. Experimental results indicate that GBC hydrogels exhibit good self-healing, shear-thinning, injectability, and swelling properties. Both in vitro and in vivo studies demonstrate the GBC hydrogel's good biocompatibility, ability to eliminate bacteria and reactive oxygen species (ROS), facilitate macrophage polarization from the M1 phenotype to the M2 phenotype (decreasing CD86 expression and increasing CD206 expression), exhibit anti-inflammatory effects (reducing TNF-α expression and increasing IL-10 expression), and promote angiogenesis (increasing VEGF, CD31, and α-SMA expression). Thus, GBC hydrogels accelerate DFU healing and enhance tissue remodeling and collagen deposition. This work provides a new approach to developing responsive hydrogels to expedite DFU healing.

Systematic review and meta-analysis of the diagnostic accuracy of inflammatory markers for infected diabetic foot ulcer

The aim was to evaluate the diagnostic value of ESR, CPR, PCT, and WBC in patients with infected diabetic foot ulcer (DFU). The MEDLINE, Embase, BIOSIS, Cochrane databases, and Web of Knowledge databases were searched, without language restriction, to July 2023. Original studies were selected that reported the performance of ESR, CPR, PCT, and WBC in diagnosing infected DFU. To assess the diagnostic value of biomarkers for infected DFU, pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (ROC-AUC) were calculated. Ten studies with 765 patients were identified in our meta-analysis. The pooled sensitivity and specificity of ESR was 0.82 (95% CI: 0.68-0.91) and 0.83 (95% CI: 0.69-0.91) respectively. The pooled sensitivity and specificity of CRP was 0.81 (95% CI: 0.65-0.91) and 0.91 (95% CI: 0.79-0.96) respectively. The pooled sensitivity and specificity of PCT was 0.76 (95% CI: 0.65-0.85) and 0.89 (95% CI: 0.78-0.95) respectively. The pooled sensitivity and specificity of WBC was 0.75 (95% CI: 0.64-0.83) and 0.79 (95% CI: 0.67-0.88) respectively. CRP showed the best diagnostic accuracy at distinguishing infected DFU from noninfected DFU with an AUC of 0.93, followed by PCT (AUC of 0.89), ESR (AUC of 0.89), and WBC (AUC of 0.84). CPR levels had high efficiency in distinguishing infected DFU from noninfected DFU, followed by PCT, ESR and WBC. All of these biomarkers could be helpful for early diagnosis of infected DFU. New biomarkers for improving medical decision in diagnosis of infected DFU are highly desirable.

Metatarsal Osteotomy versus Metatarsal Head Resection for Distal Diabetic Foot Ulcers.

We compared the effectiveness of metatarsal osteotomy, specifically using the osteoclasis (OC) technique, with that of metatarsal head resection (MHR) in healing distal metatarsal plantar ulcers. This retrospective study reviewed patients who underwent OC or MHR for the treatment of submetatarsal ulcers between January 1, 2014, and December 31, 2017. Patients with infected ulcers or osteomyelitis were excluded. A 1-year follow-up was used to evaluate the results. Of the 31 study patients (seven women and 24 men; mean ± SD age, 55.3 ± 11.7 years), 17 underwent MHR and 14 underwent OC. All of the patients had diabetic neuropathy and distal submetatarsal ulcer. Four of 17 patients in the MHR group and three of 14 patients in the OC group had moderate peripheral vascular disease. All of the patients in the MHR group healed their ulcers in a mean ± SD of 5.8 ± 2.3 weeks. During 12-month follow-up of the MHR group, one patient needed revision, one developed a transfer ulcer, and two developed toe ulcers. In the OC group, all of the patients healed after surgery in a mean ± SD of 4.2 ± 1.8 weeks. During the 12-month follow-up of the OC group, one patient developed Charcot's neuropathy and two developed transfer ulcers. For metatarsal head neuropathic ulcers, both OC and MHR achieved healing in a relatively short time, with few complications. A prospective study with a larger patient population is needed to better compare the two procedures.

Mosquitoes as Vectors of Mycobacterium ulcerans Based on Analysis of Notifications of Alphavirus Infection and Buruli Ulcer, Victoria, Australia.

Alphavirus infections are transmitted by mosquitoes, but the mode of transmission for Mycobacterium ulcerans, which causes Buruli ulcer, is contested. Using notification data for Victoria, Australia, during 2017-2022, adjusted for incubation period, we show close alignment between alphavirus and Buruli ulcer seasons, supporting the hypothesis of mosquito transmission of M. ulcerans.

Dysregulated NOX1-NOS2 activity as hallmark of ileitis in mice

Inflammation of the ileum, or ileitis, is commonly caused by Crohn’s disease (CD) but can also accompany ulcerative colitis (backwash ileitis), infections or drug-related damage. Oxidative tissue injury triggered by reactive oxygen species (ROS) is considered part of the ileitis etiology. However, not only elevated ROS but also permanently decreased ROS are associated with inflammatory bowel disease (IBD). While very early onset IBD (VEO-IBD) is associated with a spectrum of NOX1 variants, how NOX1 inactivation contributes to disease development remains ill-defined. Besides propagating signaling responses, NOX1 provides superoxide for peroxynitrite formation in the epithelial barrier. Here we report that NOX4, an H2O2-generating NADPH oxidase with documented tissue protective effects in the intestine and other tissues, limits the generation of ileal peroxynitrite by NOX1/NOS2. Deletion of NOX4 leads to persistent peroxynitrite excess, hyperpermeability, villus blunting, muscular hypertrophy, chemokine/cytokine upregulation and dysbiosis. Conversely, SAMP1/YitFc mice, a CD-like ileitis model, showed age-dependent NOX1/NOS2 downregulation preventing ileal peroxynitrite formation in homeostasis and LPS-induced acute inflammation. Deficiency in NOX1 correlated with the upregulation of antimicrobial peptides, suggesting that ileal peroxynitrite acts as chemical barrier and microbiota modifier in the ileum.