Necrosis Research Articles

First Report of Rosa roxburghii Rot Disease Caused by Fusarium annulatum in China.

Rosa roxburghii Tratt is a rosaceous shrub originating from southwest China (Fu et al. 2020). From September to October 2022, R. roxburghii rot occurred in Guizhou Province, China, within a major R. roxburghii production area covering from 5 ha to 50 ha, with an incidence rate of 10 to 15%. Symptoms manifested as black and brown lesions on the fruit surface, which were concave, soft, foul-smelling, and surrounded by grayish-brown tissue. Three infected R. roxburghii shrubs were randomly collected from each household, placed in transparent plastic bags, and pathogen isolation was conducted in a laboratory. Infected R. roxburghii fruits were surface-sterilized with 0.5% NaOCl for 2 min, rinsed five times with sterile water, and dried. Symptomatic tissues from the margin between necrotic and healthy tissues were cut into 5 × 5 mm pieces, placed onto potato dextrose agar (PDA), and incubated at 28ºC in the dark for 5 days. Hyphal tips of fungi growing from the samples were transferred onto new PDA plates and incubated until they produced conidia. A total of five fungal isolates with similar morphological characteristics were obtained. The colony obtained by single-spore purification was light purple to dark purple with abundant aerial mycelium. Macroconidia were relatively slender with a curve and zero to three septate. Microconidia appeared obovoid to pyriform, with sizes of 5.2 to 17.2 × 2.1 to 3.3 μm (n = 50). The morphological characteristics were consistent with Fusarium annulatum (Yilmaz et al. 2021). Genomic DNA of two representative isolates (Zhaochanglin 1621 and 1622) was extracted using the DN14 cetyltrimethylammonium bromide rapid plant genome extraction kit (Aidlab Biotechnologies Co., Ltd, Beijing). The TEF1 and RPB2 gene were amplified by Polymerase Chain Reaction using primers EF1-983F/EF1-2218R (Rehner et al, 2005), bRPB2-6F/bRPB2-7.1R (Matheny et al, 2002), respectively. All sequences were deposited in GenBank (TEF1, PP236860, PP236861; RPB2, PP767864, PP767865). BLAST searches of the TEF1, and RPB2 sequences revealed the TEF1 sequences had 99.89% (937/938 bp) identity with F. annulatum isolate CBS 258.54; and the RPB2 sequences had 99.86% (737/738 bp) identity to isolate CBS 267.93. In the phylogenetic tree, the isolates (Zhaochanglin 1621 and 1622) clustered with the representative strains of F. annulatum. The morphology and multi-gene phylogenetic analysis indicated that is the isolates were F. annulatum. To complete Koch's postulates, five mature, healthy R. roxburghii fruits were surface disinfected with 1% NaClO solution for 1 min, rinsed with sterile water, and dried at 25℃ for 30 min. A conidial suspension (106 spores/ml) collected from two isolates (Zhaochanglin 1621 and 1622) was sprayed onto R. roxburghii fruits, and the control treatments were sprayed with sterile distilled water. All R. roxburghii fruits were incubated at 25 ºC with 80% relative humidity. The experiment had five replicates. After 7 days of incubation, all the inoculated fruits showed similar symptoms to those initially observed on the originally infected plants. The same pathogen was reisolated and identified by morphological character ization and molecular analysis, fulfilling Koch's postulates. Thus, the pathogen causing rot of R. roxburghii was determined to be F. annulatum (H. Zhang et al, 2024). To our knowledge, this is the first report of F. annulatum causing R. roxburghii rot disease in China. F.annulatum has a wide range of hosts and has been reported to infect a wide range of crops, fruits, and vegetables (Bacon and Nelson 1994). This study lays a foundation for further study and developing disease control methods and the improvement of the economic benefits of R. roxburghii.

Importance and implementation of radiological modalities in the diagnostics of soft tissue tumors

Malignant soft tissue tumors, in particular, require amultimodal treatment concept involving interdisciplinary cooperation between radiologists, pathologists, surgeons and oncologists at special tumor centers. The foundations of the treatment decision are the imaging diagnostics and the diagnosis confirmation based on tissue samples. The (local) extent and growth behavior of atumor are among the most important findings of imaging as they have adirect influence on the surgical procedure. The most important diagnostic procedure here is magnetic resonance imaging (MRI). The T1-weighted and fat-suppressed sequences after i.v. contrast administration are used to visualize the extent of the tumor. In synopsis with diffusion-weighted and T2-weighted sequences, adifferentiation between vital tumor tissue and tumor necrosis is additionally possible. This also enables targeted sampling from vital tumor parts so that the patient can be assigned to the appropriate treatment concept as quickly as possible.

Use of Melaleuca Essential Oil in Healing Pressure Injuries (LP): Case Series

To monitor and describe the healing process of pressure injuries (PI) grades I, II, III, and IV using tea tree essential oil (TTEO). A descriptive-exploratory study, using a multiple case study approach, was developed by monitoring patients with PI at different stages in a teaching hospital in the interior of Rio Grande do Sul, Brazil, from July to October 2021. The Bates-Jensen Wound Assessment Tool (BWAT) was used to assess wound characteristics. The study included 11 male patients hospitalized in the Intensive Care Unit (ICU) and the COVID-19 and clinical-surgical inpatient unit, with eleven PIs predominantly grade III in the sacral region. Regarding the characteristics evaluated by BWAT, a favorable progression in the lesions was observed in the following items when comparing the first and third days of TTEO use: peripheral skin color, exudate type, granulation tissue, wound edges, exudate amount, and epithelialization. However, an increase in scores was noted for necrotic tissue amount, undermining, necrotic tissue type, size, and depth, indicating regression in these aspects. The pharmaceutical formulations used in this study not only highlighted the benefits of TTEO in the healing process but also reinforced its advantages for being natural and more cost-effective compared to existing commercial formulations on the market.

Predictive model for laser-induced tissue necrosis with immunohistochemistry validation

Predictive model for laser-induced tissue necrosis with immunohistochemistry validation

CLINICAL COMPLICATIONS OF MALIGNANT OTITIS EXTERNA AND SURGICAL TREATMENT

For clinical complications of malignant otitis externa and its surgical treatment, the introduction addresses a rare and serious condition, characterized by necrotizing infection of the external auditory canal, often associated with comorbidities such as decompensated diabetes mellitus. This condition requires rapid intervention due to the potential for spread to adjacent structures such as the skull and skull base, resulting in serious complications such as facial paralysis, osteomyelitis, and meningitis. Management includes broad-spectrum intravenous antibiotic therapy and, in many cases, surgical intervention to debride necrotic tissue and control infection. Objective: to synthesize recent evidence on the effectiveness of surgical treatments in malignant otitis externa, highlighting clinical outcomes and associated mortality. Methodology: it was structured according to the PRISMA checklist, using PubMed, Scielo and Web of Science databases to search for articles published in the last 10 years. Descriptors included "malignant otitis externa", "surgical treatment", "complications", "mortality" and "intervention". Inclusion criteria were clinical studies and systematic reviews that addressed surgical treatment and clinical outcomes. Exclusion criteria were studies focusing exclusively on non-surgical treatments, isolated case reports and studies with fewer than 10 participants. Results: highlighted the effectiveness of early surgical debridement in reducing mortality and serious neurological complications. The analysis revealed that adjuvant antibiotic therapy and intensive surveillance are crucial for successful management. Conclusion: the importance of a multidisciplinary approach and timely surgical intervention is emphasized to improve outcomes in patients with malignant otitis externa, highlighting the need for further studies to elucidate ideal therapeutic protocols and prevention strategies

Copper-MOF and tannic acid-empowered composite cryogel as a skin substitute for accelerated deep wound healing

The effective management of deep skin wounds remains a significant healthcare challenge that often deteriorates with bacterial infection, oxidative stress, tissue necrosis, and excessive production of wound exudate. Current medical approaches, including traditional wound dressing materials, cannot effectively address these issues. There is a great need to engineer advanced and multifunctional wound dressings to address this multifaceted problem effectively. Herein, a rationally designed composite cryogel composed of a Copper Metal-Organic Framework (Cu-MOF), tannic acid (TA), polyvinyl alcohol (PVA), and zein protein has been developed by freeze-thaw technique. Cryogels display a remarkable swelling capacity attributed to their interconnected microporous morphology. Moreover, dynamic mechanical behaviour with the characteristics of potent antimicrobial, antioxidant, and biodegradation makes it a desirable wound dressing material. It was further confirmed that the material is highly biocompatible and can release TA and copper ions in a controlled manner. In-vivo skin irritation in a rat model demonstrated that composite cryogel did not provoke any irritation/inflammation when applied to the skin of a healthy recipient. In a deep wound model, the composite cryogel significantly accelerates the wound healing rate. These findings highlight the multifunctional nature of composite cryogels and their promising potential for clinical applications as advanced wound dressings.

Neutrophil extracellular traps induce intrahepatic thrombotic tendency and liver damage in cholestatic liver disease.

Cholestatic liver diseases induce local and systemic hypercoagulation, with neutrophil extracellular traps (NETs) serving as major drivers. These NETs have been linked to decreased liver function in patients with obstructive jaundice. However, the impact of NETs on liver hypercoagulation in cholestatic liver disease remains unknown. We utilized bile duct ligation to create experimental mice and analyzed NETs formation in the liver. Fibrin deposition, tissue factor expression, and inflammation in the liver were visualized through western blot and immunohistochemical techniques. LSECs were incubated with isolated NETs, and we detected endothelial procoagulant activity using coagulation protein production assays and measuring endothelial permeability. In both in vivo and in vitro settings, DNase I was applied to clarify the effect of NETs on intrahepatic hypercoagulability, hepatotoxicity, LSEC, and macrophage activation or injury. Bile duct ligation mice exhibited significantly increased levels of NETs in liver tissue, accompanied by neutrophil infiltration, tissue necrosis, fibrin deposition, and thrombophilia compared to sham mice. Notably, NETs resulted in phosphatidylserine and tissue factor exposure on LSEC, enhancing coagulation Factor Xa and thrombin production. The enhanced procoagulant activity could be reversed by degrading NETs with DNase I. Additionally, NETs-induced permeability changes in LSECs, characterized by increased VE-cadherin expression and F-actin retraction, which could be rescued by DNase I. Meanwhile, NET formation is associated with KC activation and the formation of inflammatory factors. NETs promote intrahepatic activation of coagulation and inflammation, leading to liver tissue injury. Strategies targeting NET formation may offer a potential therapeutic approach for treating cholestatic liver disease.

RBBP4: A novel diagnostic and prognostic biomarker for non-small-cell lung cancer correlated with autophagic cell death.

Non-small-cell lung cancer (NSCLC) often presents at later stages, typically associated with poor prognosis. Autophagy genes play a role in the progression of tumors. This study investigated the clinical relevance, prognostic value, and biological significance of RBBP4 in NSCLC. We assessed RBBP4 expression using the GSE30219 and TCGA NSCLC datasets and NSCLC cells, exploring its links with clinical outcomes, tumor immunity, and autophagy genes through bioinformatics analysis after transcriptome sequencing of RBBP4-knockdown and control PC9 cells. We identified differentially expressed genes (DEGs) and conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction network analyses. The significance of autophagy-related DEGs was evaluated for diagnosis and prognosis using the GSE30219 dataset. Experiments both invivo and invitro explored the biological mechanisms behind RBBP4-mediated autophagic cell death in NSCLC. RBBP4 overexpression in NSCLC correlates with a poorer prognosis. Eighteen types of immune cell were significantly enriched in cultures that had low RBBP4 expression compared high expression. DEGs associated with RBBP4 are enriched in autophagy pathways. Transcriptomic profiling of the PC9 cell line identified autophagy-related DEGs associated with RBBP4 that exhibited differential expression in NSCLC, suggesting prognostic applications. Invitro experiments demonstrated that RBBP4 knockdown induced autophagy and apoptosis in PC9 cells, promoting cell death, which was inhibited by 3-MA. Invivo, targeted siRNA against RBBP4 significantly reduced tumor development in PC9 cell-injected nude mice, elevating autophagy-related protein levels and inducing apoptosis and necrosis in tumor tissues. In NSCLC, RBBP4 upregulation correlates with poor prognosis and altered immunity. Its knockdown induces autophagic cell death in NSCLC cells. These results indicate RBBP4 as a potential NSCLC diagnostic marker and its autophagy modulation as a prospective therapeutic target.

Toxicological effects of Honokiol on zebrafish and its underlying mechanism.

The compound Honokiol, derived from the bark of Magnolia officinalis, possesses the ability to induce apoptosis and inhibit cellular damage caused by reactive oxygen species. The objective of this study was to investigate the toxicological and histopathological effects of Honokiol on zebrafish (Danio rerio) through conducting a semistatic acute toxicity test involving immersion in an Honokiol-containing solution. The results showed that the toxic effects of Honokiol on zebrafish were primarily manifested in the liver and gills. When exposed to 0.6 mg/L of Honokiol, it could lead to liver hemorrhage as well as swelling and necrosis of gill tissues, and high concentrations of Honokiol could trigger inflammatory responses. Additionally, research found that Honokiol could induce apoptosis in liver and gill tissues through the P53 pathway and possessed the ability to enhance antioxidation. The present findings significantly contribute to a more profound understanding of the toxic impact of Honokiol and its underlying mechanism, thereby providing a valuable reference for the future safe utilization of Honokiol and related pharmaceutical advancements.

The impact of subdermal adipose derived stem cell injections and early excision on systemic oxidative stress and wound healing in rats with severe scald burns

AimThis study aims to develop an experimental treatment model effective against oxidative stress in the acute period of severe burns and to analyze the mechanisms of healing large wound defects. MethodsFive rats, including 2 females and 3 males, were used as donors to obtain adipose-derived stem cells (ADSC) from the inguinal fat pad. The stem cells were labeled with green fluorescent protein. The study included four groups of 17 rats, each with grade 3 scalding burns on 30 % of their body surface, and a control group of 10 rats with an equal number of males and females. After early excision, 106 ADSC-derived stem cells were administered subdermally to the burned wound and autografted to the stem cell group (n = 17). The early excision group (n = 17) received early excision and autograft, with 2 ml of normal saline injected subdermally into the burn wound edge. The PLM group (n = 17) was treated with a polylactic membrane (PLM) dressing after the burn. No treatment was given to the burn group (n = 17). Ten rats from all groups were sacrificed on the 4th day post-burn for oxidative stress evaluation. The control group (n = 10) was sacrificed on day 4. Blood and tissue samples were collected post-sacrifice. Oxidative stress and inflammation in the blood, as well as cell damage in the skin, liver, kidneys, and lungs, were investigated histopathologically and biochemically on the 4th day post-burn. On the 70th day post-burn, wound healing was examined macroscopically and histopathologically. ResultsOn the 4th day, oxidative stress results showed that the levels of Total Oxidative Capacity (TOC) in the blood were lowest in the stem cell (7.4 [6–8.8]), control (6.7 [5.9–7.6]), and early excision (7.5 [6.6–8.5]) groups, with no significant difference between them. The burn group (14.7 [12.5–16.9]) had the highest TOC levels. The PLM group (9.7 [8.6–10.7]) had lower TOC levels than the burn group but higher levels than the other groups.Histopathological examination on the 4th day revealed low liver caspase-3 immunoreactivity in the stem cell and early excision groups among the burn groups. Caspase-3 immunoreactivity levels were as follows: stem cell group (20 [10–30]), early excision group (25 [15–50]), PLM group (70 [50–100]), control group (0), and burn group (80 [60–120]). Other oxidative stress and end-organ damage outcomes were consistent with these results.All rats in the stem cell group had burn wounds that healed completely by the 70th day. Examination of the skin and its appendages from the stem cell group with an immunofluorescence microscope demonstrated green coloration, indicating incorporation of stem cells. ConclusionStem cells may have the potential to form new skin and its appendages, providing better healing for large skin defects. Early excision treatment, by removing local necrotic tissues after extensive and deep burns, can prevent end-organ damage due to systemic oxidative stress and inflammation. We also believe that when these two treatments are used together, they can achieve the best results.

Postextraction infections, prevention, and treatment.

Postoperative infection is one of the most common complications of tooth extraction. It may manifest as localized infection or develop to systemic infection. Clinically, oral surgeons can prevent postoperative infections by urging patients to strengthen oral hygiene, applying antibiotics in a rational and compliant manner, and choosing appropriate surgical methods for tooth extraction. For the treatment of infection, the oral surgeon should formulate a response strategy on the basis of different diagnoses. For local infections such as dry socket, delayed alveolar osteitis, gap infection, and marginal osteomyelitis of the jaws, the infection can be controlled by local debridement, therapeutic use of antibiotics, and incise and drain if necessary. For patients suspected of necrotizing fasciitis, timely extensive debridement should be made to reduce the area of tissue necrosis. For those who have received radiotherapy or anti-resorptive drugs, tooth extraction should follow the recommendations of the relevant clinical guidelines or expert consensus to minimize the risk of osteonecrosis of the jaws. For patients with poor systemic health or dysfunction of the immune system, attention should be paid to identifying infective endocarditis and intracranial infection to ensure the life safety of patients. In this study, the author intends to combine literature review and clinical experience to tackle postextraction infection and its prevention to provide a reference for colleagues on oral and maxillofacial surgery.

The effects of using hydrolyzed feather meal, amino acids, and probiotics in the diet of juvenile rainbow trout on growth, digestibility, and expression of growth-related genes

AbstractThe study investigated the effect of replacing fishmeal by varying levels of hydrolyzed feather meal (HFM) as well as dietary probiotic supplementation on growth performance, digestibility, histology, and gene expression of juvenile rainbow trout (Oncorhynchus mykiss). Five iso-nitrogenous (average of 50.60% crude protein), iso-energetic (average of 21.79 kJ/g), and iso-lipidic (average of 21.86% crude lipid) diets were formulated and fed to triplicate groups of juvenile rainbow trout weighing 29.65 ± 0.39 g (mean ± SD) for 75 days. Dietary treatments included one control (50% fishmeal) and four experimental diets, each containing 2 g/kg probiotics (Lactobacillus plantarum and Bacillus subtilis). The experimental diets included HFM30 (150 g/kg HFM, 9 g/kg lysine, and 4 g/kg methionine), HFM35 (175 g/kg HFM, 11 g/kg lysine, and 5 g/kg methionine), HFM40 (200 g/kg HFM, 13 g/kg lysine, and 6 g/kg methionine), and HFM45 (225 g/kg HFM, 15 g/kg lysine, and 7 g/kg methionine). Up to 40% replacement of fishmeal with HFM showed no significant difference compared to control group in growth performance (P > 0.05). Feed utilization of HFM45 was slightly lower than control and all the other experimental groups. There was no statistically significant difference in FCR value between HFM40 and control groups (P > 0.05). The apparent digestibility coefficients (ADCs) for protein and amino acids were very high in all groups (P < 0.05). Intestinal mucosa and sub‐mucosa layers of experimental fish showed general tissue integrity with no signs of tissue necrosis. For intestinal morphology, where 45% HFM replacement was applied, villus length to crypt depth (VL to CD) and villus surface area (SA) decreased by 46.01% and 44.44%, respectively, compared to the control group (P < 0.05). This situation shows that intestinal morphology can be damaged when the highest level (HFM45) of feather meal is used. Dietary HFM upregulated growth-related genes such as IGF-II, IGFBP-1b, IGFr1a, GDF9, and FGF2 and downregulated GHR-I and IGF-I. Overall, inclusion of HFM at 40% showed similar results to control group in juvenile rainbow trout feeding.

Outcomes of cooled radiofrequency ablation of cervical nerves for the treatment of chronic pain.

Chronic pain, defined as pain persisting for more than 3-6 months, has a mean one-year prevalence in the United States of 25.8% and is one of the most frequent reasons adults seek medical care. Treatment options include physical therapy, analgesics, anticonvulsants, exercise, and muscle relaxants. Even with conventional treatment modalities, in a subset of patients, pain may persist. Cooled radiofrequency ablation (c-RFA), a minimally invasive therapy, employs thermal energy generated by electrical currents to disrupt the transmission of pain stimuli along nociceptive pathways. This leads to an attenuation of pain impulses, primarily through nerve tissue necrosis. The potential of c-RFA to alleviate chronic pain for patients who struggle to find relief elsewhere accentuates the importance of rigorously investigating its outcomes. This study investigates whether patients receiving c-RFA for relief of chronic neck pain caused by cervical facet joint arthropathy experience a reduction in pain scores, the length of this reduction in pain scores, and the magnitude of this reduction in pain. This study was a retrospective analysis of data extracted from UW-Health Electronic Medical Health records (EMR), encompassing cervical c-RFA procedures performed from 2015 through 2022. Patient data were obtained, including diagnosis, pre-operative pain score, post-operative pain score, duration of relief, patient age, sex, and BMI. A two-tailed paired t-test was used to statistically analyze the pre-operative and post-operative pain scores, in which a p-value ≤0.05 was considered significant. A total of 450 cervical c-RFA procedures were reviewed, 152 were excluded due to absent pre- or post-op pain scores. 298 were included in the analysis, comprising 203 unique patients: 129 females and 74 males with an average age of 56.03 ± 12.76 and a BMI of 28.76 ± 6.05. Improvement of pain symptoms was reported in 85.23% (n = 263), 6% (n = 19) reported complete pain remission, 8.72% (n = 26) reported no change, and 3.02% (n = 9) reported worsening symptoms. Patients reported an average pre-operative pain score of 6.15 (M = 6.15, SD = 1.55) and an average post-operative pain score of 3.64 (M = 3.64, SD = 2.09) this achieved significance (p < 0.0001). Of the 85.23% (n = 263) charts that noted improvement, there is an average of 48.04% ± 26.53 reduction from their pre-operative pain scores. The average duration of relief lasted 6.67 ± 4.84 months. This study supports the potential efficacy of c-RFA as a minimally invasive treatment for chronic neck pain secondary to cervical facet joint arthropathy refractory to conventional treatment measures, demonstrating significant relief for a substantial length of time. Due to chronic pain's detrimental effect on one's quality of life, finding effective treatment options is essential, especially for those refractory to conventional treatments.

Review of the Adverse Effects Associated with Dermal Filler Treatments: Part I Nodules, Granuloma, and Migration

The increase in the use of filler treatments within minimally invasive cosmetic surgery has correspondingly escalated the variety and frequency of associated side effects. Initially, unregulated procedures led to primary side effects such as infections, foreign body reactions, and granuloma formation. However, severe vascular complications like skin and tissue necrosis and blindness have emerged as recognized risks. Side effects from filler treatments can range from mild to life-threatening, including edema, pain, tenderness, numbness, bleeding, bruising, hematoma, redness, erythema, pigmentation, allergic reactions, itching, pruritus, the Tyndall effect, asymmetry, irregularity, migration, skin and soft tissue infections, nodules, granulomas, and vascular compromise. These side effects are categorized into early and delayed types. Many complications, particularly those related to vascular abnormalities, are frequently linked to procedural issues, emphasizing the importance of understanding filler properties, injection techniques, and facial anatomy. Preventing side effects is ideal, but early detection and treatment are crucial. Recognizing potential side effects based on their timing and understanding appropriate preemptive treatment methods is essential. This discussion addresses non-vascular side effects, highlighting their onset, symptoms, and management strategies. The comprehensive understanding and careful management of these side effects are vital for minimizing complications and ensuring patient safety in filler treatments.

Electrochemotherapy with intravenous, intratumoral, or combined administration of bleomycin in the treatment of colorectal hepatic metastases in a rat model

Electrochemotherapy (ECT) combines the reversible electroporation (rEP) with intravenous (i.v.) or intratumoral (i.t.) administration of chemotherapeutic drugs. We conducted this study to compare the efficacy of i.v., i.t., and i.v. + i.t. injection of bleomycin (BLM) in ECT treatment of colorectal hepatic metastases in a rat model. WAG/Rij rats were randomized into three groups and underwent ECT with i.v., i.t., or i.v. + i.t. injection of BLM. Tumor volumes and oxygenation were measured by means of ultrasound and photoacoustic imaging. Moreover, liver and tumor tissue were analyzed by histology and immunohistochemistry. The i.v. and i.v. + i.t. groups exhibited a 44.0% and 46.6% reduction in oxygen saturation of the tumor tissue when compared to pretreatment values, whereas the i.t. group only showed a reduction of 35.2%. The extent of tumor tissue necrosis did not statistically differ between the groups. However, the i.t. group showed a tendency towards a lower necrosis rate. Cell proliferation, apoptotic cell death, vascularization, and immune cell infiltration were comparable in the treated tumors of the three groups. ECT with i.v. administration of BLM should be preferred in clinical practice, as the combined i.v. + i.t. therapy did not show superior oncological outcomes in the present study.

Infections following rattlesnake envenomation and use of antibiotics.

There are 7000-8000 venomous snake bites annually in the USA. Antibiotics are commonly administered to bite victims because infection is difficult to differentiate from local tissue injury following envenomation. The Arizona Poison and Drug Information Center (APDIC) in Tucson oversees antivenom administration for 14 Arizona counties. Records (1999-2021) were searched for antibiotic use and confirmed infections after a rattlesnake bite. There were 4160 calls to APDIC regarding rattlesnakes. After excluding bites to animals, 'dry bites', prisoners and records with missing data, 2059 records were evaluated. Systemic antibiotics were administered to 206 patients (10% of bite victims). Twenty patients (0.97%) had confirmed infections, including cellulitis (n=10), fasciitis (n=4), abscess (n=3) and osteomyelitis (n=3). Five of the victims had positive blood cultures. The presence of tissue necrosis, leukocytosis, fever and elevated fibrinogen levels did not discriminate between toxic effects of venom and infection. Confirmed infections following a rattlesnake bite are uncommon (0.97% of bites). Physicians should refrain from prescribing antibiotics, as they are not justified for most rattlesnake bite victims and the variety of pathogens encountered precludes use of any single effective antibiotic.

SILDENAFIL DECREASED TNF-α AND IL-6 LEVELS IN CD‐INDUCED ACUTE TOXICITY

Objective: This study aimed to evaluate the effects of sildenafil (SIL) on inflammation and histopathological changes in cadmium (Cd)-induced toxicity in female rats. Material and Method: Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF- α) levels were measured to assess the degree of inflammation. Histopathological changes in the liver, lungs and kidneys were also assessed. Result and Discussion: SIL significantly reduced the cellular release of TNF-α and IL-6, which have been implicated in the pathogenesis of Cd-induced tissue damage. When SIL was administered alone, it showed histopathological effects similar to the control group. However, it was found that co-administration of SIL with Cd prevented portal vein dilation and central vein enlargement in the liver, prevented necrosis in kidney tissue, but did not affect the lung. Although SIL has variable protective effects on tissues, our results are in support of the idea that the use of SIL in tissue damage management can be investigated for its efficacy in modulating oxidative stress-induced proinflammatory cytokine activation in vivo and ultimately help prevent Cd-induced tissue damage. Our study has shown that SIL can reduce Cd-induced acute toxicity in rats. SIL may be use as a protective agent against toxicity of heavy metals.

Regeneration following tissue necrosis is mediated by non-apoptotic caspase activity.

Tissue necrosis is a devastating complication for many human diseases and injuries. Unfortunately, our understanding of necrosis and how it impacts surrounding healthy tissue - an essential consideration when developing methods to treat such injuries - has been limited by a lack of robust genetically tractable models. Our lab previously established a method to study necrosis-induced regeneration in the Drosophila wing imaginal disc, which revealed a unique phenomenon whereby cells at a distance from the injury upregulate caspase activity in a process called Necrosis-induced Apoptosis (NiA) that is vital for regeneration. Here we have further investigated this phenomenon, showing that NiA is predominantly associated with the highly regenerative pouch region of the disc, shaped by genetic factors present in the presumptive hinge. Furthermore, we find that a proportion of NiA fail to undergo apoptosis, instead surviving effector caspase activation to persist within the tissue and stimulate reparative proliferation late in regeneration. This proliferation relies on the initiator caspase Dronc, and occurs independent of JNK, ROS or mitogens associated with the previously characterized Apoptosis-induced Proliferation (AiP) mechanism. These data reveal a new means by which non-apoptotic Dronc signaling promotes regenerative proliferation in response to necrotic damage.

Development of Fournier's gangrene after chemotherapy for the recurrence of testicular cancer despite the absence of anorectal lesions: A case report.

Fournier's gangrene usually occurs when a specific bacterium intrudes into soft tissue, causing a wound or tumor. We encountered a patient with Fournier's gangrene due to severe myelosuppression after chemotherapy, despite the absence of an initial lesion on the anus and rectum. A 54-year-old man with a left testicular cancer recurrence had undergone chemotherapy. He had asymptomatic hepatitis and high hepatitis B virus DNA levels, which were normalized by administering tenofovir alafenamide fumarate. Twelve days after the start of chemotherapy, he complained of severe pain around the anus. The following day, he went into septic shock. Visual inspection showed dark purple skin discoloration on the left side of the anus. Laboratory data revealed severe neutropenia. Computed tomography showed a high density of soft tissue on the left side of the anus and gas bubbles in the left femoral ring. We diagnosed the patient with Fournier's gangrene due to a severe immunosuppressive state resulting from chemotherapy. We emergently removed necrotic tissue to the fullest extent possible. However, because the patient was in severe sepsis status, careful management in the intensive care unit was required for 32 days. After the first emergency operation, we performed several additional excisions. Finally, 391 days after the initial surgery, the patient was discharged from our hospital. The tumor has not recurred, and he is under outpatient observation in the urology department. Fournier's gangrene should be considered in patients who are in a severe myelosuppressive state due to chemotherapy, have normal hepatitis B virus DNA levels but high hepatitis B surface antigen after tenofovir administration, complain of severe pain in the perianal area, and have a dark purple skin discoloration around the anus, despite having no initial anorectal lesions.

Treatment of Fournier's gangrene with "firebreak" drainage based on skin preservation

Objective: To observe the clinical efficacy of a new type of "firebreak" drainage with skin preservation in the treatment of Fournier's gangrene. Methods: This technique is suitable for patients with perianal necrotizing fasciitis who can tolerate surgery without large area of skin blackness and necrosis. Procedure and key points: (1) The dividing line between inflammatory tissue and normal tissue was determined according to imaging examination and intraoperative exploration; (2) The abscess cavity was cut along the most obvious part of the abscess fluctuation, with a long diameter of 3~4 cm and a short diameter of 1~2 cm; (3) Necrotic tissue was discreetly separated and removed from the main incision to the outer edge of the infection. A fusiform incision was made every 3 to 5 cm, with a long diameter of 2 to 3 cm and a short diameter of 1 cm, and discreetly separated until the normal tissue, and a hose was hung between the adjacent incisions for drainage. (4) Each adjacent edge cut between the stealth separation and hanging hose drainage, forming a "firebreak"; (5) Rinse the wound repeatedly; (6) If the infection invades the rectum, colostomy is performed as required. The case data of 11 patients with perianal necrotizing fasciitis admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from July 2019 to February 2023 were retrospectively analyzed. All patients were treated with emergency surgical debridement by "firebreak" drainage with skin preservation. Results: All 11 cases were cured with 100%. One case underwent multiple operations. The hospitalization time was 11-46 days, with an average of 22 days. The wound healing time was 28-75 days, with an average of 43 days. Except for 1 patient with trauma, all the other patients had no significant anal function injury after surgery. All the 11 patients recovered and were discharged from hospital with a median follow-up of 136 (115-413) days. Conclusions: The "firebreak" drainage based on skin preservation has the advantages of less trauma and faster recovery, and do not cause obvious anal function damage.