Logic programming-based Minimal Cut Sets reveal consortium-level therapeutic targets for chronic wound infections.

Minimal Cut Sets (MCSs) identify sets of reactions which, when removed from a metabolic network, disable certain cellular functions. The traditional search for MCSs within genome-scale metabolic models (GSMMs) targets cellular growth, identifies reaction sets resulting in a lethal phenotype if disrupted, and retrieves a list of corresponding gene, mRNA, or enzyme targets. Using the dual link between MCSs and Elementary Flux Modes (EFMs), our logic programming-based tool aspefm was able to compute MCSs of any size from GSMMs in acceptable run times. The tool demonstrated better performance when computing large-sized MCSs than the mixed-integer linear programming methods. We applied the new MCSs methodology to a medically-relevant consortium model of two cross-feeding bacteria, Staphylococcus aureus and Pseudomonas aeruginosa. aspefm constraints were used to bias the computation of MCSs toward exchanged metabolites that could complement lethal phenotypes in individual species. We found that interspecies metabolite exchanges could play an essential role in rescuing single-species growth, for instance inosine could complement lethal reaction knock-outs in the purine synthesis, glycolysis, and pentose phosphate pathways of both bacteria. Finally, MCSs were used to derive a list of promising enzyme targets for consortium-level therapeutic applications that cannot be circumvented via interspecies metabolite exchange.

Metal-based nanoparticles: an alternative treatment for biofilm infection in hard-to-heal wounds.

Metal-based nanoparticles (MNPs) are promoted as effective compounds in the treatment of bacterial infections and as possible alternatives to antibiotics. These MNPs are known to affect a broad spectrum of microorganisms using a multitude of strategies, including the induction of reactive oxygen species and interaction with the inner structures of the bacterial cells. The aim of this review was to summarise the latest studies about the effect of metal-based nanoparticles on pathogenic bacterial biofilm formed in wounds, using the examples of Gram-positive bacterium Staphylococcus aureus and Gram-negative bacterium Pseudomonas aeruginosa, as well as provide an overview of possible clinical applications.

Multifunctional fucoidan-loaded Zn-MOF-encapsulated microneedles for MRSA-infected wound healing.

Infected wound healing remains a challenging task in clinical practice due to several factors: (I) drug-resistant infections caused by various pathogens, (II) persistent inflammation that hinders tissue regeneration and (III) the ability of pathogens to persist intracellularly and evade antibiotic treatment. Microneedle patches (MNs), recognized for their effecacious and painless subcutaneous drug delivery, could greatly enhance wound healing if integrated with antibacterial functionality and tissue regenerative potential. A multifunctional agent with subcellular targeting capability and contained novel antibacterial components, upon loading onto MNs, could yield excellent therapeutic effects on wound infections. In this study, we sythesised a zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) loaded with low molecular weight fucoidan (Fu) and further coating by hyaluronic acid (HA), obtained a multifunctional HAZ@Fu NPs, which could hinders Methicillin-resistant Staphylococcus aureus (MRSA) growth and promotes M2 polarization in macrophages. We mixed HAZ@Fu NPs with photocrosslinked gelatin methacryloyl (GelMA) and loaded it into the tips of the MNs (HAZ@Fu MNs), administered to mice model with MRSA-infected full-thickness cutaneous wounds. MNs are able to penetrate the skin barrier, delivering HAZ@Fu NPs into the dermal layer. Since cells within infected tissues extensively express the HA receptor CD44, we also confirmed the HA endows the nanoparticles with the ability to target MRSA in subcellular level. In vitro and in vivo murine studies have demonstrated that MNs are capable of delivering HAZ@Fu NPs deep into the dermal layers. And facilitated by the HA coating, HAZ@Fu NPs could target MRSA surviving at the subcellular level. The effective components, such as zinc ions, Fu, and hyaluronic acid could sustainably released, which contributes to antibacterial activity, mitigates inflammation, promotes epithelial regeneration and fosters neovascularization. Through the RNA sequencing of macrophages post co-culture with HAZ@Fu, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis reveals that the biological functionalities associated with wound healing could potentially be facilitated through the PI3K-Akt pathway. The results indicate that the synergistic application of HAZ@Fu NPs with biodegradable MNs may serve as a significant adjunct in the treatment of infected wounds. The intricate mechanisms driving its biological effects merit further investigation.

The efficacy and safety of perioperative glucocorticoid for total knee arthroplasty: a systematic review and meta-analysis.

BACKGROUND: An increasing number of individuals undergo total knee arthroplasty (TKA), which can result in pain, limited motor function and adverse complications such as infection, nausea and vomiting. Glucocorticoids have been shown anti-inflammatory and antiemetic effects, but can also elevate blood glucose levels and increase the risk of wound infection. Thus, it is essential to investigate the efficacy and safety of glucocorticoid usage in TKA. METHOD: A comprehensive systematic search of PubMed, Medline, EMBASE, Cochrane databases, to identify relevant randomized controlled trials (RCTs) of glucocorticoid application in TKA. The primary outcomes assessed were the postoperative pain assessment. Secondary outcomes included the range of motion in knee joint, levels of inflammatory cytokines, adverse complications, and the length of hospital stay. RESULTS: Thirty-six randomized controlled trials were included in the final analysis. The glucocorticoid group exhibited significant reduction in the resting VAS scores on postoperative days 1, 2 (POD1, 2)and postoperative 3 months (POM3), as well as decreased morphine consumption on POD1 and increased range of motion (ROM) in knee joint on POD1, 3. Additionally, the glucocorticoid group exhibited decreased levels of postoperative inflammatory cytokines and the incidence of PONV along with a shorter length of hospital stay. The blood glucose concentration was significantly increased in the glucocorticoid group on POD1 compared with the control group. While the blood glucose on POD2 and occurrence of postoperative adverse complications were similar between two groups including wound infection and venous thrombosis. The periarticular injection analgesia (PIA) group demonstrated lower VAS scores on POD2 comparing to the systemic administration (SA) group according to two studies. However, there was no significant difference of the resting VAS on POD1 and POD2 between PIA and SA group across all studies. CONCLUSION: Perioperative glucocorticoids treatment in TKA significantly reduced short-term pain score and opioid-use which was probably not patient relevant. The application of glucocorticoids in TKA implied a beneficial trend in analgesic, anti-inflammatory, and antiemetic effects, as well as improved range of motion and shortened hospital stay. While it will not increase the risk of continued high glucose, postoperative wound infection and venous thrombosis.

pH-Responsive Co-Assembled Peptide Hydrogel to Inhibit Drug-Resistant Bacterial Infection and Promote Wound Healing.

Drug-resistant bacterial infection and biofilm formation are the key inhibitors of wound healing, and new strategies are urgently needed to address these issues. In this study, we designed a pH-responsive co-assembled peptide hydrogel to inhibit Methicillin-resistant Staphylococcus aureus (MRSA) infection and promote wound healing. We synthesized a cationic short peptide (Nap-FFKKK) and a co-assembled hydrogel with curcumin at pH ∼ 7.8. The loaded curcumin was continuously released in a weak acid environment (pH ∼ 5.5). The lysine-rich cationic peptide inhibited biofilm formation in MRSA via electrostatic interaction with the negatively charged bacterial cell surface and, thus, provided a reinforcing antibacterial effect with curcumin. In vitro antibacterial experiments showed that the co-assembled system considerably reduced the minimum inhibitory concentration of curcumin against MRSA by 10-fold and promoted wound healing in a mouse model of MRSA-infected wounds. This study provides a simple and promising strategy to treat drug-resistant bacterial infections in wounds.

Analysis of risk factors affecting wound healing and wound infection after meningioma resection.

To analyse the risk factors affecting wound healing and infection after spinal meningioma resection surgery. The surgical incision healing of 137 patients who underwent spinal meningioma resection at our hospital from January 2021 to January 2024 was analysed. The data collected included physical examination findings, haematological and biochemical measurements, and various scales assessed upon admission and after surgery. These data were then analysed. The surgical wound healing, infection and postoperative complications were statistically analysed. Multiple logistic regression analysis method was used to conduct risk factor analysis on corresponding indicators; the odds ratio and p value of 95% confidence interval were calculated. Factors such as age and smoking history were significantly negatively correlated with wound healing after meningioma resection (odds ratio < 1.000, p < 0.05), while preoperative albumin and platelet count were significantly positively correlated with wound healing (odds ratio > 1.000, p < 0.05). Age, WHO Meningioma Grading, preoperative albumin and preoperative platelet were significantly negatively correlated with wound infection after meningioma resection (odds ratio < 1.000, p < 0.05). The history of virus infection and history of neurological disorders were significantly positively correlated with wound infection (odds ratio > 1.000, p < 0.05). The influence of each factor is different. Age, smoking history, WHO Meningioma Grading, preoperative albumin, preoperative platelets, history of virus infection and history of neurological disorders had the greatest influence on wound healing and infection after meningioma resection.

Impacts of enhanced recovery after surgery nursing interventions on wound infection and complications following bladder cancer surgery: A meta-analysis.

A meta-analysis was executed to comprehensively examine the impacts of enhanced recovery after surgery (ERAS) care interventions on complications and wound infections following bladder cancer (BCa) surgery. Computer searches were carried out in Embase, Google Scholar, Cochrane Library, PubMed, Wanfang and CNKI, from their inception to November 2023, for RCTs regarding perioperative ERAS nursing interventions in patients with BCa. Two independent researchers performed literature screening, extracted data and carried out quality evaluations. Stata 17.0 software was utilized for the analysis of the data. Ultimately, 16 RCTs, involving 1190 patients, were included. The analysis showed that, in comparison with conventional nursing methods, perioperative ERAS nursing application in patients with BCa remarkably decreased the occurrence of wound infections (OR: 0.31, 95% CI: 0.16-0.59) and complications (OR: 0.19, 95% CI: 0.13-0.28). Our study indicates that perioperative care based on the ERAS concept remarkably decreased the occurrence of wound infections and complications following BCa surgery, demonstrating notable nursing efficacy and meriting widespread clinical promotion.

Effect of platelet-rich plasma on healing of lower extremity diabetic skin ulcers: A meta-analysis.

The aim of this research is to explore the therapeutic efficacy of platelet-rich plasma (PRP) on the cutaneous ulceration of diabetes mellitus (DM). From the beginning of the database until January 2024, we looked through several databases to obtain randomised, controlled PRP studies to treat the wound healing of DM in adult patients. The Cochrane Collaboration's Risk-Of-Bias Instrument was used to evaluate the risk of bias in randomised, controlled studies. Funnel plots, sensitivity analyses and Egger regression tests were employed to determine the reliability and effectiveness of the meta-analyses. Depending on the degree of heterogeneity, a fixed or random effect model has been used. The statistical significance was determined to be below 0.05. Altogether 281 trials were collected from the database and entered into Endnote Software for screening, and 15 trials were analysed. It was found that PRP was associated with a higher rate of wound healing (OR, 3.23; 95% CI, 2.42, 4.31 p < 0.0001). PRP was associated with a reduction in the risk of post-operative wound infection (OR, 0.46; 95% CI, 0.21, 0.99 p = 0.05). PRP was associated with a reduction in the risk of amputations amongst those with DM (OR, 0.50; 95% CI, 0.30, 0.84 p = 0.009). Overall, PRP treatment for DM is expected to improve the rate of wound healing, decrease the risk of wound infection and decrease the risk of amputations.

Bactericidal Efficacy of the Combination of Maresin-like Proresolving Mediators and Carbenicillin Action on Biofilm-Forming Burn Trauma Infection-Related Bacteria.

Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage, and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), by macrophages and other leukocytes. SPMs exhibit strong inflammation-resolving activities, especially inflammation provoked by bacterial infection. In this study, we explored the potential direct inhibitory activities of three MarLs on Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria in their biofilms that are leading bacteria in burn trauma-related infections. We also examined the effects of MarLs on the bactericidal activities of a typical broad-spectrum antibiotic, carbenicillin (carb), on these bacteria in their preformed biofilms. The results revealed that MarLs combined with carbenicillin can inhibit the survival of Gram-positive and Gram-negative bacteria in their biofilms although MarLs alone did not exhibit bactericidal activity. Thus, our findings suggest that the combination of MarLs and carbenicillin can lower the antibiotic requirements to kill the bacteria in preformed biofilms.

A Multi-Institutional Study Comparing Stoma Location in Neonates With Intestinal Perforation.

INTRODUCTION: Neonates with intestinal perforation often require laparotomy and intestinal stoma creation, with the stoma placed in either the laparotomy incision or a separate site. We aimed to investigate if stoma location is associated with risk of postoperative wound complications. METHODS: A multi-institutional retrospective review was performed for neonates ≤3 mo who underwent emergent laparotomy and intestinal stoma creation for intestinal perforation between January 1, 2009 and April 1, 2021. Patients were stratified by stoma location (laparotomy incision versus separate site). Outcomes included wound infection/dehiscence, stoma irritation, retraction, stricture, and prolapse. Multivariable regression identified factors associated with postoperative wound complications, controlling for gestational age, age and weight at surgery, and diagnosis. RESULTS: Overall, 79 neonates of median gestational age 28.8 wk (interquartile range [IQR]: 26.0-34.2 wk), median age 5 d (IQR: 2-11 d) and median weight 1.4 kg (IQR: 0.9-2.42 kg) had perforated bowel from necrotizing enterocolitis (40.5%), focal intestinal perforation (31.6%), or other etiologies (27.8%). Stomas were placed in the laparotomy incision for 41 (51.9%) patients and separate sites in 38 (48.1%) patients. Wound infection/dehiscence occurred in 7 (17.1%) neonates with laparotomy stomas and 5 (13.2%) neonates with separate site stomas (P = 0.63). There were no significant differences in peristomal irritation, stoma retraction, or stoma stricture between the two groups. On multivariable regression, separate site stomas were associated with increased likelihood of prolapse (odds ratio 6.54; 95% confidence interval: 1.14-37.5). CONCLUSIONS: Stoma incorporation within the laparotomy incision is not associated with wound complications. Separate site stomas may be associated with prolapse. Patient factors should be considered when planning stoma location in neonates undergoing surgery for intestinal perforation.

Supramolecular coordination platinum metallacycle-based multilevel wound dressing for bacteria sensing and wound healing.

The exploitation of novel wound healing methods with real-time infection sensing and high spatiotemporal precision is highly important for human health. Pt-based metal-organic cycles/cages (MOCs) have been employed as multifunctional antibacterial agents due to their superior Pt-related therapeutic efficiency, various functional subunits and specific geometries. However, how to rationally apply these nanoscale MOCs on the macroscale with controllable therapeutic output is still challenging. Here, a centimeter-scale Pt MOC film was constructed via multistage assembly and subsequently coated on a N,N'-dimethylated dipyridinium thiazolo[5,4-d]thiazole (MPT)-stained silk fabric to form a smart wound dressing for bacterial sensing and wound healing. The MPT on silk fabric could be used to monitor wound infection in real-time through the bacteria-mediated reduction of MPT to its radical form via a color change. The MPT radical also exhibited an excellent photothermal effect under 660 nm light irradiation, which could not only be applied for photothermal therapy but also induce the disassembly of the Pt MOC film suprastructure. The highly ordered Pt MOC film suprastructure exhibited high biosafety, while it also showed improved antibacterial efficiency after thermally induced disassembly. In vitro and in vivo studies revealed that the combination of the Pt MOC film and MPT-stained silk can provide real-time information on wound infection for timely treatment through noninvasive techniques. This study paves the way for bacterial sensing and wound healing with centimeter-scale metal-organic materials.

Telodendrimer functionalized hydrogel platform for sustained antibiotics release in infection control.

Wound infection commonly causes delayed healing, especially in the setting of chronic wounds. Local release of antibiotics is considered a viable approach to treat chronic wounds. We have developed a versatile telodendrimer (TD) platform for efficient loading of charged antibiotic molecules via a combination of multivalent and synergistic charge and hydrophobic interactions. The conjugation of TD in biocompatible hydrogel allows for topical application to provide sustained antibiotic release. Notably, a drug loading capacity as high as 20 % of the drug-to-resin dry weight ratio can be achieved. The payload content (PC) and release profile of the various antibiotics can be optimized by fine-tuning TD density and valency in hydrogel based on the charge and hydrophobic features of the drug, e.g., polymyxin B (PMB), gentamycin (GM), and daptomycin (Dap), for effective infection control. We have shown that hydrogel with moderately reduced TD density demonstrates a more favorable release profile than hydrogel with higher TD density. Antibiotics loaded in TD hydrogel have comparable antimicrobial potency and reduced cytotoxicity compared to the free antibiotics due to a prolonged, controlled drug release profile. In a mouse model of skin and soft tissue infection, the subcutaneous administration of PMB-loaded TD hydrogel effectively eliminated the bacterial burden. Overall, these results suggest that engineerable TD hydrogels have great potential as a topical treatment to control infection for wound healing. STATEMENT OF SIGNIFICANCE: Wound infection causes a significant delay in the wound healing process, which results in a significant financial and resource burden to the healthcare system. PEGA-telodendrimer (TD) resin hydrogel is an innovative and versatile platform that can be fine-tuned to efficiently encapsulate different antibiotics by altering charged and hydrophobic structural moieties. Additionally, this platform is advantageous as the TD density in the resin can also be fine-tuned to provide the desired antibiotic payload release profile. Sustained antibiotics release through optimization of TD density provides a prolonged therapeutic window and reduces burst release-induced cytotoxicity compared to conventional antibiotics application. Studies in a preclinical mouse model of bacteria-induced skin and soft tissue infection demonstrated promising therapeutic efficacy as evidenced by effective infection control and prolonged antibacterial efficacy of antibiotics-loaded PEGA-TD resin. In conclusion, the PEGA-TD resin platform provides a highly customizable approach for effective antibiotics release with significant potential for topical application to treat various bacterial wound infections to promote wound healing.

Modified in-vitro AATCC-100 procedure to measure viable bacteria from wound dressings.

Chronic wounds are reoccurring healthcare problems in the United States and cost up to $50 billion annually. Improper wound care results in complications such as wound debridement, surgical amputation, and increased morbidity/ mortality due to opportunistic infections. To eliminate wound infections, many antimicrobial dressings are developed and submitted to FDA for evaluation. AATCC-100 is a standard method widely used to evaluate cloth wound dressings. This method, requires enrichment, followed by culturing to measure the concentration of culturable organisms; a caveat to this method could result in neglected viable but nonculturable (VBNC) bacteria and overestimate the antimicrobial properties of wound dressings. Therefore, the objectives of this study were to assess this accepted protocol with quantitative real-time polymerase chain reaction (qRT-PCR), to measure time dependent antimicrobial efficacy of wound dressing, and to examine for potential viable bacteria but non-culturable as compared with traditional plating methods. The test organisms included opportunistic pathogens: Pseudomonas aeruginosa (ATCC 15692) and Staphylococcus aureus (ATCC 43300). To mimic a wound dressing environment, samples of commercially available wound dressings (McKesson Inc.) with silver ion (positive control) and dressings without silver ion (positive control) were assessed under sterile conditions. All samples were examined by the original protocol (the extended AATCC-100 method) and qRT-PCR. The expression of specific housekeeping genes was measured (proC for P. aeruginosa and 16s rRNA for S. aureus). Based on these tests, log reduction of experimental conditions was compared to identify time dependent and precise antimicrobial properties from wound dressing samples. These results showed antimicrobial properties of wound dressings diminished as incubation days are increased for both methods from day 1 PCR result of 4.31 ± 0.54 and day 1 plating result of 6.31 ± 3.04 to day 3 PCR result of 1.22 ± 0.97 and day 3 plating result of 5.89 ± 2.41. These results show that data from qRT-PCR generally produced lower standard deviation than that of culture methods, hence shown to be more precise. Complementary parallel analysis of samples using both methods better characterized antimicrobial properties of the tested samples.

Retrospective Study to Compare the Effectiveness of Minimally Invasive Microscopic Unilateral Laminotomy with Microscopic Bilateral Laminotomy for Bilateral Decompression in the Early Postoperative Period in 142 Patients with Single-Level Lumbar Spinal Stenosis.

BACKGROUND We aimed to compare the effectiveness of microscopic unilateral laminotomy for bilateral decompression (ULBD) and microscopic bilateral laminotomy for bilateral decompression (BLBD) in the early postoperative period among patients with single-level lumbar spinal stenosis (LSS). MATERIAL AND METHODS A retrospective cohort study was conducted on patients with LSS who underwent ULBD or BLBD between January 2020 and December 2023, including 94 patients who underwent ULBD and 58 who underwent BLBD. Patient demographics, comorbidities, smoking status, and data related to LSS were reviewed. Preoperative and postoperative assessments on day 10 included back pain visual analog scale (VAS), walking distance, and Odom criteria. Disability was evaluated using the self-assessment Oswestry Disability Index (ODI) preoperatively and on day 30. Additionally, wound infection, postoperative modified MacNab criteria, and pain (back, leg, and hip) were recorded. RESULTS Age and sex were similar in the 2 groups. Both surgeries significantly reduced low back pain, increased walking distance, and improved Odom category on day 10, compared with baseline (P<0.001 for all). A significant decrease in 30-day ODI, compared with baseline, was observed in both groups (P<0.001 for both). The ULBD group had a significantly higher percentage of patients with wound infection (P=0.014); however, the ODI score among ULBD recipients was significantly lower (better) on day 30 (P=0.047). CONCLUSIONS ULBD may represent a less invasive, more effective, and safer surgical alternative than BLBD and classical laminectomy in patients with single-level LSS, but precautions are essential concerning wound infection.

Effects of photodynamic therapy in patients with infected skin ulcers: A meta-analysis.

The purpose of the meta-analysis was to evaluate and compare the photodynamic therapy's effectiveness in treating infected skin wounds. The results of this meta-analysis were analysed, and the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated using dichotomous or contentious random- or fixed-effect models. For the current meta-analysis, 6 examinations spanning from 2013 to 2021 were included, encompassing 154 patients with infected skin wounds were the used studies' starting point. Photodynamic therapy had a significantly lower wound ulcer size (MD, -4.42; 95% CI, -7.56--1.28, p = 0.006), better tissue repair (MD, -8.62; 95% CI, -16.76--0.48, p = 0.04) and lower microbial cell viability (OR, 0.13; 95% CI, 0.04-0.42, p < 0.001) compared with red light exposure in subjects with infected skin wounds. The examined data revealed that photodynamic therapy had a significantly lower wound ulcer size, better tissue repair and lower microbial cell viability compared with red light exposure in subjects with infected skin wounds. However, given that all examinations had a small sample size, consideration should be given to their values.

An antibacterial membrane based on Janus bacterial cellulose with nano-sized copper oxide through polydopamine conjugation for infectious wound healing.

Bacterial cellulose (BC) produced by Acetobacter xylinum has great advantages in wound dressing. However, the structural limitation under static culture, and lack of antibacterial properties restrict its application, especially for infectious wound healing. The present study reported an original wound dressing, which was composed of a Janus BC membrane with antibacterial nano-sized copper oxide (CuO) through polydopamine (PDA) conjugation to promote wound healing under infectious condition. The finished product (CuO/PDA/BC membrane) exhibited favorable air permeability, high hydrophilicity and good mechanical properties, as well as strong antibacterial effects by the sustained release of CuO and photothermal effect of CuO/PDA. Furthermore, CuO/PDA/BC membrane inhibited inflammatory response and promoted wound healing in an infectious wound model in vivo. These results suggested that our CuO/PDA/BC membrane had great potential as wound dressing for infectious wound healing.

Staphopain mediated virulence and antibiotic resistance alteration in co-infection of Staphylococcus aureus and Pseudomonas aeruginosa: an animal model.

Polymicrobial communities lead to worsen the wound infections, due to mixed biofilms, increased antibiotic resistance, and altered virulence production. Promising approaches, including enzymes, may overcome the complicated condition of polymicrobial infections. Therefore, this study aimed to investigate Staphopain A-mediated virulence and resistance alteration in an animal model of Staphylococcus aureus and Pseudomonas aeruginosa co-infection. S. aureus and P. aeruginosa were co-cultured on the L-929 cell line and wound infection in an animal model. Then, recombinant staphopain A was purified and used to treat mono- and co-infections. Following the treatment, changes in virulence factors and resistance were investigated through phenotypic methods and RT-PCR. Staphopain A resulted in a notable reduction in the viability of S. aureus and P. aeruginosa. The biofilm formed in the wound infection in both animal model and cell culture was disrupted remarkably. Moreover, the biofilm-encoding genes, quorum sensing regulating genes, and virulence factors (hemolysin and pyocyanin) controlled by QS were down-regulated in both microorganisms. Furthermore, the resistance to vancomycin and doripenem decreased following treatment with staphopain A. According to this study, staphopain A might promote wound healing and cure co-infection. It seems to be a promising agent to combine with antibiotics to overcome hard-to-cure infections.

Cytotoxicity and concentration of silver ions released from dressings in the treatment of infected wounds: a systematic review.

Introduction: Silver-releasing dressings are used in the treatment of infected wounds. Despite their widespread use, neither the amount of silver released nor the potential in vivo toxicity is known. The aim of this study was to evaluate the cytotoxic effects and the amount of silver released from commercially available dressings with infected wounds. Methods: The review was conducted according to the PRISMA statement. The Web of Science, PubMed, Embase, Scopus, and CINAHL databases were searched for studies from 2002 through December 2022. The criteria were as follows: population (human patients with infected wounds); intervention (commercial dressings with clinical silver authorized for use in humans); and outcomes (concentrations of silver ions released into tissues and plasma). Any study based on silver-free dressings, experimental dressings, or dressings not for clinical use in humans should be excluded. According to the type of study, systematic reviews, experimental, quasi-experimental, and observational studies in English, Spanish, or Portuguese were considered. The quality of the selected studies was assessed using the JBI critical appraisal tools. Studies that assessed at least 65% of the included items were included. Data were extracted independently by two reviewers. Results: 740 articles were found and five were finally selected (all of them quasi-experimental). Heterogeneity was found in terms of study design, application of silver dressings, and methods of assessment, which limited the comparability between studies. Conclusion: In vivo comparative studies of clinical dressings for control of infection lack a standardized methodology that allows observation of all the variables of silver performance at local and systemic levels, as well as evaluation of its cytotoxicity. It cannot be concluded whether the assessed concentrations of released silver in commercial dressings for the topical treatment of infected wounds are cytotoxic to skin cells. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351041, PROSPERO [CRD42022351041].

Comparison of scrotal and inguinal orchiopexy for palpable undescended testis: a meta-analysis of randomized controlled trials.

INTRODUCTION: Scrotal and inguinal orchiopexy are two commonly used surgical approaches for palpable undescended testis (UDT), each with distinct advantages. However, the optimal approach remains a matter of debate, warranting a comprehensive meta-analysis of randomized controlled trials (RCTs) to guide clinical decision-making. MATERIALS AND METHODS: A comprehensive literature search was conducted, adhering to PRISMA guidelines, to select RCTs comparing scrotal and inguinal orchiopexy for palpable UDT. Eight RCTs were selected for meta-analysis. Outcome measures included operative time, hospitalization duration, total complications, wound infection or dehiscence, testicular atrophy or hypotrophy, and testicular re-ascent rate. The evaluation of the study's quality was conducted by utilizing the revised Cochrane risk-of-bias tool. RESULTS: Scrotal orchiopexy showed significantly shorter operative time compared to the inguinal approach (WMD: - 15.06 min; 95% CI: - 21.04 to - 9.08). However, there was no significant difference in hospitalization duration (WMD: - 0.72 days; 95% CI: - 1.89-0.45), total complications (OR: 1.08; 95% CI: 0.70-1.66), wound infection or dehiscence (OR: 0.73; 95% CI: 0.27-1.99), testicular atrophy or hypotrophy (OR: 1.03; 95% CI: 0.38-2.78), and testicular re-ascent (OR: 1.43; 95% CI: 0.67-3.06) between the two approaches. A small proportion of cases (7.3%) required conversion from scrotal to inguinal orchiopexy due to specific anatomical challenges. CONCLUSION: Both scrotal and inguinal orchiopexy are safe and effective for palpable UDT, with comparable outcomes in terms of hospitalization and complications. Scrotal orchiopexy offers the advantage of shorter operative time. Clinicians can use this evidence to make informed decisions on the surgical approach for palpable UDT.