Ulcer Research Articles

Continuous Diffused Oxygen Therapy for Wound Healing

What Is the Issue? Wounds are prevalent across health care settings, costing Canada an estimated $12 billion per year in wound care. Chronic wounds (wounds that do not heal in the typical amount of time, which can depend on the size and type of wound) can have a significant impact on a patient’s quality of life and health. Healing tissue has a high need for oxygen. Oxygen can be delivered in several ways, including topical oxygen therapy, which delivers oxygen directly to the wound. One type of topical oxygen therapy is continuously diffused oxygen (CDO) therapy, which uses a device that takes oxygen from the air and then delivers pure, humidified oxygen to the wound. We previously completed a Rapid Review on CDO therapy for wounds in 2020. This review aimed to determine if new evidence has since been published on this topic. What Did We Do? To inform decisions about CDO therapy for wound healing, we sought to identify and summarize literature comparing the clinical effectiveness and cost-effectiveness of CDO therapy versus conventional wound care. We also attempted to identify evidence-based recommendations for the use of CDO therapy. We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2019. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings. What Did We Find? CDO therapy appears to be clinically effective for treating patients with diabetic foot ulcers, particularly chronic or hard-to-heal ulcers that have not responded to standard care. Rates of adverse events were comparable between patients receiving CDO and patients receiving standard care. Two cost-effectiveness studies reported that CDO is likely to be cost-effective compared to standard care for patients with chronic, hard-to-heal diabetic foot ulcers. We identified fewer studies for other types of wounds. Preliminary evidence suggests that CDO therapy may be helpful for patients with other types of wounds that are chronic or have not responded to standard care. Reporting on adverse events was limited. Limited evidence suggests that patients receiving CDO therapy had better outcomes if their wound was debrided more frequently as well as if they received CDO therapy for a longer time. The evidence-based guidelines recommend the use of topical oxygen therapy (of which CDO is a subtype) for treating diabetic foot ulcers that have failed to heal with standard care. One guideline suggested that topical oxygen therapy may be considered for other types of non-neoplastic, hard-to-heal wounds. We did not find cost-effectiveness evidence for wounds other than diabetic foot ulcers that met the inclusion criteria for our report. We also did not identify any clinical effectiveness or cost-effectiveness evidence, or any guidelines regarding the use of CDO to treat First Nations, Inuit, and Métis patients, that met the inclusion criteria for our report. What Does This Mean? CDO therapy may be beneficial and more cost-effective than standard care for patients with hard-to-heal, chronic diabetic foot ulcers that have not responded to standard care. Evidence-based guidelines also recommend the use of CDO therapy for this patient population. The clinical effectiveness and cost-effectiveness of CDO therapy for other types of wounds is still unclear. It is also unclear if there is an optimal way to provide CDO (e.g., oxygen flow rate, debridement, length of treatment). We identified limited evidence that reported on patient ethnicity. Considering that some groups, including First Nations, Inuit, and Métis Peoples, have higher rates of diabetes than the overall population in Canada — which may lead to higher rates of diabetic foot ulcers — decision-makers involved in implementing CDO therapy should consider ways to ensure equitable access for all patients who may need this treatment.

Histological analysis of debrided tissue from chronic ulcers in people with diabetes mellitus

Histological analysis of debrided tissue from chronic ulcers in people with diabetes mellitus

Dysregulated S100A9 Expression Impairs Matrix Deposition in Chronic Wounds.

Chronic non-healing wounds are characterized by persistent inflammation, excessive matrix-degrading proteolytic activity and compromised extracellular matrix (ECM) synthesis. Previous studies showed that S100A8/A9 are strongly dysregulated in delayed wound healing and impair the proper function of immune cells. Here, we demonstrate an unrecognized pathological function of S100A9 overexpression in wounds with impaired healing that directly affects ECM functions in fibroblasts. S100A9 was analyzed in two different mouse models mimicking the features of the two most prominent types of non-healing wounds in humans. Db/db mice were used as a model for diabetes-associated impaired wound healing. Iron-overloaded mice were used to mimic the conditions of impaired wound healing in chronic venous leg ulcers. The skin wounds of both mouse models are characterized by delayed wound closure, high and sustained expression of pro-inflammatory mediators and a substantially decreased ECM deposition, all together the hallmarks of non-healing wounds in humans. The wounds of both mouse models also present a solid and prolonged expression of S100A8 and S100A9 that coincides with a compromised ECM deposition and that was confirmed in chronic wounds in humans. Mechanistically, we reveal that S100A9 directly affects ECM deposition by shifting the balance of expression of ECM proteins and ECM degrading enzymes in fibroblasts via toll-like-receptor 4-dependent signaling. Consequently, blocking S100A9 during delayed wound healing in db/db mice restores fibroblast ECM functions eliciting increased matrix deposition. Our data indicate that the dysregulation of S100A9 directly contributes to a compromised ECM deposition in chronic wounds and further suggests S100A9 as a promising therapeutic target to improve tissue repair in chronic wounds.

Natural Bacterial Co-Infection in Farmed European Sea Bass Intended for Experimental Research in Sicily, Southern Italy: Pathological Findings

In mariculture facilities, bacterial infections pose significant production challenges, with potentially catastrophic impacts on fish species. Bacterial co-infections are a widespread phenomenon in the natural marine environment, although their impact on aquatic organisms remains poorly investigated. This study aimed to detail the pathological findings associated with a natural bacterial co-infection caused by three different pathogens, namely Photobacterium damselae subsp. piscicida, Tenacibaculum maritimum and Vibrio sp., as the cause of mass mortality in European sea bass. The fish had been reared in open-net cages in Sicily and later transferred for experimental research purposes to a user establishment after immunization with an inactivated vaccine. Macroscopic, cytological and histopathological examinations were performed on 109 animals, and bacterial species were identified by the 16S rRNA gene. Overall, ulcerative skin lesions, necrotizing myositis and tail rot with occasional tail loss were associated with tenacibaculosis and vibriosis, while P. damselae subsp. piscicida mainly caused granulomatous inflammation in the spleen and head kidney. Finally, an injection site reaction due to the oil-adjuvanted vaccine administered intraperitoneally was observed in the abdominal fat. Understanding the impact of bacterial pathogens is essential to manage the health and welfare of farmed fish, and the importance of a good health monitoring program cannot be overstated to avoid outbreaks and the possible emergence of new pathogens due to the intensification of the production systems, antibiotic resistance and climate changes. The study would also highlight the importance of the quarantine period when animals supplied for research come from aquaculture farms and how the main goal in the near future should be to better define the procedures to provide completely pathogen-free animals.

Punch Grafting Technique for the Treatment of Chronic Venous Leg Ulcers

Punch Grafting Technique for the Treatment of Chronic Venous Leg Ulcers

Tibial transverse transport promotes wound healing in diabetic foot ulcers by stimulating endothelial progenitor cell mobilization and homing mediated neovascularization

Background Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes, often leading to amputation and decreased quality of life. Current treatment methods have limited success rates, highlighting the need for new approaches. This study investigates the potential of tibial transverse transport (TTT) to promote wound healing in DFUs. Methods To test this hypothesis, the study used New Zealand White rabbits to establish a diabetic model and simulate foot ulcers, followed by the treatment of unilateral TTT or bilateral TTT. The study employed histological analysis, flow cytometry, ELISA, and qPCR to assess the impact of TTT on tissue repair and endothelial progenitor cell (EPC) mobilization and homing, aiming to understand the underlying biological processes in wound healing. Results TTT significantly enhanced wound healing in diabetic rabbit foot ulcers. Specifically, bilateral TTT led to complete wound healing by day 19, faster than the unilateral TTT group, which healed by day 26, and the sham operation group, which nearly healed by day 37. Histological analysis showed improved tissue architecture, collagen deposition, and neovascularization in TTT-treated groups. Furthermore, TTT treatment resulted in a significant increase in VEGFR2 expression and VEGFR2/Tie-2 positive cells, particularly in the bilateral group. These findings were corroborated by qPCR results, which showed increased expression of VEGFA and CXCL12 by TTT. Conclusions: TTT may be a promising treatment for DFUs, significantly enhancing wound healing by stimulating EPC mobilization and homing mediated angiogenesis. This novel approach could substantially improve treatment outcomes for diabetic patients with chronic foot ulcers.

Anti-inflammatory Effect of Symplocos prunifolia Extract in an In Vitro Model of Acute Pneumonia.

Acute pneumonia is a respiratory disease characterized by inflammation within the lung tissue, exhibiting higher morbidity rates and mortality rates among immunocompromised children and older adults. Symplocos species have been traditionally used as herbal remedies for conditions like dysentery, skin ulcers, diarrhea, and dyspepsia. Contemporary research has employed various Symplocos species in the study of diverse diseases. However, the exact efficacy and mechanisms of action of Symplocos Prunifolia remain unknown. Therefore, this study investigated the anti-inflammatory mechanism of S. prunifolia extract (SPE) in A549 and RAW264.7 cells stimulated by lipopolysaccharide (LPS). SPE significantly reduced nitric oxide (NO) production and the protein expression levels of like inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 cells. Furthermore, it reduced the protein expression levels of iNOS, COX-2 and the levels of pro-inflammatory cytokines in LPS-stimulated A549 cells. The mechanism underlying the anti-inflammatory effect of SPE was associated with the inhibition of LPS stimulated the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) and Mitogen-activated protein kinase (MAPK) phosphorylation. Moreover, we confirmed that SPE decreased the nuclear translocation of nuclear factor-κB (NF-κB)/p65 stimulated by LPS. In conclusion, these results demonstrate that SPE alleviates inflammatory responses by deactivating the PI3K/Akt, MAPK, and NF-κB signaling pathways. Our findings suggest that SPE is a potential candidate for acute pneumonia prevention.

Oral Live-Carrier Vaccine of Recombinant Lactococcus lactis Inducing Prophylactic Protective Immunity Against Helicobacter pylori Infection.

Helicobacter pylori infects the gastric mucosa and induces chronic gastritis, peptic ulcers, and gastric cancer. Research has demonstrated that vaccination can induce a protective immune response and prevent H. pylori infection. Oral administration of the Lactococcus lactis live-carrier vaccine is safe and easily complied with by the public. In this study, two recombinant L. lactis strains were constructed that expressed antigens of H. pylori urease subunit alpha (UreA) and UreA fused with Escherichia coli heat-labile toxin B subunit (LTB-UreA), named LL-UreA and LL-LTB-UreA, respectively. The expression of antigen proteins was confirmed by Western blotting analysis. Survival assessment indicated that the engineered L. lactis could colonize in the digestive tract of BALB/c mice up to 10 days after the last oral administration with our immunization protocol. The ability to induce immune response and immune protective efficacy of the L. lactis were confirmed. These results indicated that oral administration with LL-UreA or LL-LTB-UreA could induce UreA-specific mucosal secretory IgA (sIgA) and cellular immune response, significantly increasing the cytokines levels of interferon-gamma (IFN-γ), interleukin (IL)-17A, and IL-10, together with the proportion of CD4+IFN-γ+ T cells and CD4+IL17A+ T cells. More importantly, oral administration of LL-UreA and LL-LTB-UreA brought about effective protection in mice to prevent H. pylori infection, especially LL-UreA, resulting in 70% of mice showing no H. pylori colonization and the remaining 30% showing only low levels of colonization. These findings underscore the potential of using orally administered engineered L. lactis vaccines to prevent H. pylori infection.

Application of Physically Crosslinked Hyaluronic Acid Hydrogel in the Treatment of Radiation‐Induced Skin Injury

AbstractWounds caused by radiation exposure are often hard to heal. The functional hydrogel can be used as a wound treatment material of multiple dimensions according to patients' needs. Hyaluronic acid hydrogel can be used to create a moist environment conducive to wound healing. In this study, new complex hydrogels based on physically crosslinked hyaluronic acid are investigated, which adopt the freeze‐thaw technique, loaded with small molecule drugs deferoxamine and retinoic acid, and effectively promote the healing of radiation‐induced skin ulcers. The combined application of deferoxamine and retinoic acid can improve skin injury after radiation, promoting angiogenesis, reducing inflammation, and protecting skin appendages. In vitro and in vivo results show enhanced cell viability and biological function, significantly accelerate healing of the irradiated wounds, and improve collagen deposition in the skin of the irradiated rats. Also, the skin appendages, such as hair follicles, are protected to a certain extent, implying functionally repairing the skin. Considering the ease of use of the hydrogel system in clinical applications, complex hydrogels can be considered a suitable candidate for treating radiation‐induced skin injury.

On the issue of the syndromic forms of pyoderma gangrenosum

Gangrenous pyoderma (PG) is an autoinflammatory polygenic neutrophilic dermatosis characterized by the formation of painful ulcerative skin defects with boldly raised undercut edges of purplish-cyanotic coloration and an erythema zone around the focus. Gangrenous pyoderma can manifest as an isolated dermatosis, and be associated with various autoinflammatory syndromes: PASH (gangrenous pyoderma, conglobate acne and purulent hydradenitis), PAPA (gangrenous pyoderma, pyogenic arthritis and conglobate acne), PAPASH (gangrenous pyoderma, pyogenic arthritis, conglobate acne and purulent hydradenitis), PAPASC (gangrenous pyoderma, pyogenic arthritis, conglobate acne, purulent hydradenitis and ulcerative colitis), etc. A number of genetic mutations have been found in the syndromic forms of gangrenous pyoderma (MEFV, NOD2, LPIN2, NLRP3, NLRP12, PSMB8, MVK, IL1RN, PSTPIP1) affecting inflammatory regulatory proteins, which contributes to the development of an autoaggressive process. Neutrophilic autoinflammatory syndromes have a common pathogenesis mechanism, which is an excessive activation of the innate link of the immune system, with hyperproduction of proinflammatory IL-1, IL-17 and chemokines, leading to aseptic neutrophilic inflammation of the skin. At the moment, the treatment of syndromic conditions remains a difficult task. Systemic glucocorticosteroids, immunosuppressants, antimetabolites, and sulfone preparations are used in complex therapy, however, more and more studies indicate the possibility of therapy with genetically engineered biological drugs with TNF inhibitors, IL-1 and IL-17. We present two clinical observations of rare forms of autoinflammatory neutrophilic syndromic conditions PASH and PAPASC in patients aged 20 and 21 years

Investigation of vibriosis caused by Vibrio anguillarum in rainbow trout (Oncorhynchus mykiss).

Identifying pathogenic microorganisms causing disease is important for epidemiological research, antimicrobial therapy, and control. The current study was carried out to use different methods for the identification of Vibrio anguillarum from diseased rainbow trout (Oncorhynchus mykiss) obtained from Türkiye (Muğla-Fethiye), the damage caused by the pathogenic microorganism in the tissues and organs, and the determination of the antibiotic effective against the pathogen. Hemorrhagic and ulcerative skin lesions and diffuse petechial hemorrhage in the internal organs were clinically detected in diseased fish obtained from the rainbow trout farm. Bacteria isolated from diseased fish were subjected to analysis using conventional bacteriological methods, a commercial bacterial identification test kit (API), an automated bacteria identification system known as Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS), BD Phoenix™, and 16S rRNA sequence analysis. All isolated bacteria were identified as V. anguillarum by API 20E and conventional bacteriological method. These results have been confirmed with 16S rRNA sequence analysis. However, the isolated bacteria were identified as Grimontia hollisae (syn. Vibrio holisae) with the BD Phoenix system. Histologically, tissue damage such as melano-macrophage centers and necrosis in the kidney and spleen, hyperemia and mononuclear cell infiltration in the liver, as well as mononuclear cell infiltration on muscles, talengectiasis in the gill tissue was observed. In addition, it has been determined that the most effective antibiotic against the pathogen was enrofloxacin. When comparing all identification methods used for this pathogen causing tissue damage, it was demonstrated that the MALDI-TOF MS provides better results than other methods in terms of cost and identification time, and it could be used as an alternative to the conventional method to the identification of V. anguillarum.

A Patient With Exposed Costal Cartilage After Microtia Surgery Successfully Treated With Perifascial Areolar Tissue Grafting

Postoperative costal cartilage exposure is a troublesome complication following costal cartilage grafting for microtia. The authors report a case of attempted recovery using perifascial areolar tissue (PAT) transplantation that achieved favorable results. The patient was a 13-year-old boy, who developed a 27 × 11 mm2 skin ulcer with a 6 × 3.5 mm2 area of exposed cartilage at the helix 1 month after ear ablation surgery. PAT harvested from above the trapezius muscle was grafted onto the ulcer. The wound was closed 14 days later using a split-thickness skin graft from the head. PAT transplants can be harvested from anywhere in the body, are minimally invasive, and are highly flexible. This case demonstrates that, although factors such as the extent and location of cartilage exposure must be considered, PAT transplants are an option for microtia salvage surgery.

Idiopathic Inflammatory Myopathies-associated Interstitial Lung Disease in Adults.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune diseases characterized by muscle involvement and various extramuscular manifestations. Interstitial lung disease (ILD) is one of the most common extramuscular manifestations of IIM and is associated with significant mortality and morbidity. The clinical phenotypes, treatment responses, and prognosis of IIM-ILD are significantly related to myositis-specific antibody (MSA) profiles, with some racial differences. The features associated with MSA in IIM-ILD could also be relevant to cases of ILD where MSA is present but does not meet the criteria for IIM. The anti-melanoma differentiation-associated gene 5 antibody is highly associated with rapidly progressive ILD (RP-ILD), especially in Asian populations, and with characteristic cutaneous manifestations, such as skin ulcers. Radiologically, ground-glass opacities, consolidations, and nonsegmental linear opacities were more predominant than reticular opacities and honeycombing. While the mortality rate is still around 30%, the prognosis can be improved with early intensive therapy with corticosteroids and multiple immunosuppressants. In contrast, anti-aminoacyl-tRNA synthetase (ARS) antibodies are associated with chronic ILD, although RP-ILD is also common. Patients with anti-ARS antibodies often show lung-predominant presentations, with subtle muscle and skin involvement. Radiologically, reticular opacities, with or without consolidation, are predominant and may progress to honeycombing over time. Combination therapy with corticosteroids and a single immunosuppressant is recommended to prevent relapses, which often lead to a decline in lung function and fatal long-term outcomes. Significant advances in immunology and genetics holds promise for fostering more personalized approaches to managing IIM-ILD.

A mouldable fibreglass backslab device as a novel approach to offload chronic plantar foot ulcers: A retrospective observational audit.

Pressure offloading is a critical component of plantar foot ulcer management, including diabetes-related foot ulcers (DFU). Conventional offloading options such as total contact casting and removable knee-high walkers may be unsuitable or unsuccessful in patients with morbid obesity, intermittent lower limb oedema, high exudative wounds or poor mobility. A mouldable fibreglass backslab device (BSD) may be a practical alternative to be considered in these situations. Data were retrospectively collected on 28 patients (29 foot ulcers) with non-healing ulcers who received a BSD to offload their foot ulcer as an extension to standard offloading care. Baseline data included: patient demographics, type of offloading prior to BSD application, date of ulcer onset, days ulcer present prior to BSD application and ulcer size at BSD initiation. Measures of success included ulcer size reduction 12weeks post-BSD application, time to complete ulcer healing in BSD, time to 50% reduction in ulcer size post-BSD application and total number of days ulcer present. The median (IQR) ulcer area and ulcer duration at baseline for 19 patients (20 ulcers) who used the BSD was 1.65 (0.4-3.8) cm2 and 531 (101-635) days. At 12weeks, the median (IQR) ulcer area was 0.3 (0-0.55) cm2 with a median (IQR) reduction of 97 (80-100) %. Nine (45%) ulcers achieved complete wound healing (100% reduction in wound size) at 12weeks post-BSD application, and the remaining 11 (55%) ulcers achieved at least 50% reduction in wound size. The median (IQR) time to complete wound healing and 50% reduction in wound size was 71 (35-134) days and 24 (15-44) days, respectively. Nine patients ceased use of the BSD and reverted to conventional offloading before their wounds had healed. Of these, four patients achieved a 50% reduction in wound size at the 12-week mark with conventional offloading. Our preliminary data suggests that a mouldable fibreglass BSD may be a practical offloading option in the management of DFUs, especially when conventional offloading methods are unsuccessful, unsuitable or unacceptable to patients. Higher level evidence is required to demonstrate suitability or efficacy of the BSD compared to current evidence-based recommended offloading methods.

Cytokine stability in chronic wound fluid and its association to fibroblast proliferation.

Cytokines are commonly deregulated in venous leg ulcers. We have investigated cytokine stability by incubating sterile-filtered wound fluids from chronic venous leg ulcers in vitro. Incubation of wound fluids for 24 h at 37°C decreased IL-1β levels by 88% and TNF-α levels by 64%. IL-1β was degraded by serine proteinases and metalloproteinases while the mechanism for reduced TNF-α remains elusive. The levels of the other peptides did not change significantly (p > 0.05). Normal human dermal fibroblasts exposed to five of the six wound fluids showed increased proliferation with the length of prior incubation using an assay optimised for evaluation of wound fluid bioactivity. Exogenous IL-1β and TNF-α unexpectedly increased (p < 0.001) cell proliferation at concentrations that were measured in the wound fluids. In conclusion, the stability of the eight investigated cytokines in wound fluids differed and presumably the loss of detrimental factors, unlikely IL-1β or TNF-α, resulted in increased fibroblast proliferation.

Early Identification, Intervention, and Prevention of Hospital-Acquired Pressure Injuries Using a Nurse-Driven Pressure Injury Prevention Program.

The purpose of this quality improvement project was to reduce the hospital-acquired pressure injury (HAPI) rate to less than 1.177 per 1000 patient-days, increase staff competency and care in pressure injury prevention best practices through implementation of a nurse-driven pressure injury prevention program, to engage patients in pressure injury prevention through implementation of skin rounds, and improve staff adherence to documentation requirements for pressure injury interventions on an amputee/stroke unit. HAPIs can lead to negative patient outcomes including pain, infection, extended hospitalization, and morbidity. Using an evidence-based education strategy, the Agency for Healthcare Research and Quality pressure ulcer prevention clinical pathway and skin rounds were implemented. Focused education for nursing, staff competency, daily audits, HAPI rates, and documentation compliance were evaluated pre and post intervention. The HAPI rate reduced from 1.177 to 0.272 per 1000 patient-days. After completion, the unit maintained zero pressure injuries, daily patient care for pressure injuries improved, documentation compliance increased, and staffs' knowledge and skill set in early identification, intervention, and prevention of pressure injuries heightened. A nurse-driven pressure injury prevention program was successful in the reduction of the HAPI rate.

Ultra Structural and Immunohistochemical Study on the Healing Effect of Nano Silver versus Nanozinc on Induced Traumatic Ulcer in the Buccal Mucosa of Albino Rats

Ultra Structural and Immunohistochemical Study on the Healing Effect of Nano Silver versus Nanozinc on Induced Traumatic Ulcer in the Buccal Mucosa of Albino Rats

Development of Postsurgical Pyoderma Gangrenosum with New Keloid after Keloid Resection.

Keloids are a dermal fibroproliferative disorder and can arise from trauma, acne, vaccination, and herpes zoster. Pyoderma gangrenosum (PG) is a painful ulcerative skin disorder that is associated with neutrophilic dysfunction. However, the pathophysiologies of keloids and PG are not fully understood. The authors encountered an unusual case of a 24-year-old woman who presented with an anterior chest keloid that bore an ulcer. The keloid was resected along with the ulcer, and histology revealed the ulcer to be a neutrophilic PG ulcer. A year after surgery, another ulcer developed in the scar. The ulcer met the PARACELSUS criteria of a postsurgical PG ulcer. After treatment with systemic prednisone and adalimumab for 250 days, the ulcer re-epithelialized. However, relapsed keloids were then observed at the PG site. Corticosteroid taping may be the safest therapy for patients with a history of PG. Conversely, if there is suspicion that a patient is prone to keloid development, diagnostic biopsies and surgical management of PG ulcers should be avoided or conducted with care.

Isolation, identification and histopathological observation of Francisella noatunensis subsp. orientalis from Nile tilapia (Oreochromis niloticus)

In April 2023, a substantial mortality event struck the primary Nile tilapia (Oreochromis niloticus) breeding areas in Maoming City, Guangdong Province, resulting in considerable economic losses. To unravel the etiology of this disease outbreak, thorough farm field necropsies were conducted, encompassing detailed descriptions of gross clinical signs and diagnostic sample collection. Clinically, affected tilapia primarily manifested multifocal superficial skin ulcers, mild focal congestion, and hemorrhage in the jaws, eyes' irises, and other integumentary regions. Tissue specimens from diseased fish were screened for Francisella spp., using a polymerase chain reaction (PCR) assay. The PCR product targeting polymerase gene showed 99.64 % nucleotide sequence identity to the published sequence of Francisella noatunensis subsp. orientalis (F. noatunensis subsp. orientalis). Histopathological examination of selected tissues revealed acute to subacute, severe necrotizing bacterial splenitis accompanied by diffuse vasculitis, marked necrotizing nephritis, mild necrotizing hepatitis, and prominent proliferative vasculitis. Transmission electron microscopy (TEM) further demonstrated that F. noatunensis subsp. orientalis was predominantly found in macrophage cytoplasm, appearing as round, spheroidal bacteria. Koch's postulates were successfully confirmed through challenge testing. Moreover, F. noatunensis subsp. orientalis exhibited high sensitivity to Gentamicin, Vancomycin, Minocycline, Imipenem, and Ceftazidime. In conclusion, F. noatunensis subsp. orientalis has emerged as a significant pathogen affecting Nile tilapia in China, characterized by systemic multi-organ necrotizing vasculitis with the spleen and head kidney being the primary targets.

Limb salvage using radical combined hyperthermia and radiotherapy for myxofibrosarcoma of the lower leg in an elderly patient.

Soft tissue sarcomas account for only 1.5% of malignant tumors in adults and are therefore challenging to treat. We present a case of myxofibrosarcoma of the lower leg in an 88-year-old woman who successfully responded to combined hyperthermia and radiotherapy. We proposed a below-knee amputation because of the spread of the lesion, but the patient opted for hyperthermia with radiotherapy. One and a half years later, the tumor partially regrew, and the regrown mass was resected with an R0 margin. Unfortunately, the patient developed a surgical site infection immediately after the resection, and a skin ulcer formed. It took about 2years for conservative treatment to result in complete ulcer epithelization. The patient has been ambulant, and has not experienced any symptoms of local recurrence or metastasis in the two and a half years since the surgery. Although adverse events related to combined hyperthermia and radiotherapy, such as delayed wound healing, should be considered, it could be an option for the treatment of localized soft-tissue sarcoma, especially in elderly patients.