Progression of Skin Ulcer Secondary to Calciphylaxis in a Patient With End-Stage Renal Disease (ESRD) on Hemodialysis and the Therapeutic Approach.

Calciphylaxis is a rare and severe medical condition characterized by the calcification of small blood vessels and soft tissues, leading to tissue damage, skin ulcers, and intense pain. It most commonly affects individuals with underlying health conditions such as kidney disease, particularly end-stage renal disease (ESRD), and is associated with high mortality rates. Understanding the diagnosis and management of calciphylaxis is crucial for improving patient outcomes. Diagnosing calciphylaxis can be challenging due to its rarity and overlapping symptoms with other skin conditions. Healthcare professionals typically use a combination of clinical evaluation and diagnostic tests to reach a conclusive diagnosis. The management of calciphylaxis is multifaceted and typically involves a collaborative effort between various healthcare specialists, including nephrologists, dermatologists, and wound care experts. The primary goals of treatment are to alleviate pain, promote wound healing, address underlying causes, and prevent further complications.

Acute Gastric Ischemia in a Case of Small Bowel Obstruction.

Gastric ischemia is a relatively rare condition that can lead to severe or life-threatening outcomes. It can be caused by various etiological factors, including vascular occlusion, atherosclerosis, vasculitis, hypovolemic shock, cardiac failure, mesenteric ischemia, splanchnic vasoconstriction, and abdominal compartment syndrome. Furthermore, gastric dilation can be caused by volvulus and acute necrotizing gastritis. This condition may go unnoticed in the setting of intestinal obstruction. In this case report, we describe a 43-year-old female who presented with signs, symptoms, and radiological findings indicative of small bowel obstruction accompanied by a severely dilated stomach. Our aim is to highlight the importance of considering gastric ischemia in patients with small bowel obstruction and to demonstrate the outcomes of a surgical approach in such presentations.

Real-world effectiveness of a single conventional disease-modifying anti-rheumatic drug (cDMARD) plus an anti-TNF agent versus multiple cDMARDs in rheumatoid arthritis: a prospective observational study.

Objective: The objective of this prospective, observational multicenter study (NCT03264703) was to compare the effectiveness of single conventional disease-modifying anti-rheumatic drug (cDMARD) plus anti-tumor necrosis factor (TNF) therapy versus multiple cDMARD treatments in patients with moderate-to-severe rheumatoid arthritis (RA) following cDMARD failure in the real-world setting in South Korea. Methods: At the treating physicians' discretion, patients received single cDMARD plus anti-TNF therapy or multiple cDMARDs. Changes from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), corticosteroid use, and Korean Health Assessment Questionnaire (KHAQ-20) scores were evaluated at 3, 6, and 12 months. Results: Of 207 enrollees, the final analysis included 45 of 73 cDMARD plus anti-TNF and 91 of 134 multiple-cDMARD recipients. There were no significant between-group differences (BGDs) in ANCOVA-adjusted changes from baseline in DAS28-ESR at 3, 6 (primary endpoint), and 12 months (BGDs -0.18, -0.38, and -0.03, respectively). More cDMARD plus anti-TNF than multiple-cDMARD recipients achieved a >50% reduction from baseline in corticosteroid dosage at 12 months (35.7% vs 14.6%; p=0.007). Changes from baseline in KHAQ-20 scores at 3, 6, and 12 months were significantly better with cDMARD plus anti-TNF therapy than with multiple cDMARDs (BGD -0.18, -0.19, and -0.19 points, respectively; all p≤0.024). Conclusion: In the real-world setting, relative to multiple cDMARDs, single cDMARD plus anti-TNF therapy significantly improved quality-of-life scores and reduced corticosteroid use, with no significant BGD in disease activity, in RA patients in whom previous cDMARD therapy had failed.

Mitochondrial P-JNK target, SAB (SH3BP5), in regulation of cell death.

Cell death occurs in various circumstances, such as homeostasis, stress response, and defense, via specific pathways and mechanisms that are regulated by specific activator-induced signal transductions. Among them, Jun N-terminal kinases (JNKs) participate in various aspects, and the recent discovery of JNKs and mitochondrial protein SAB interaction in signal regulation of cell death completes our understanding of the mechanism of sustained activation of JNK (P-JNK), which leads to triggering of the machinery of cell death. This understanding will lead the investigators to discover the modulators facilitating or preventing cell death for therapeutic application in acute or chronic diseases and cancer. We discuss here the mechanism and modulators of the JNK-SAB-ROS activation loop, which is the core component of mitochondria-dependent cell death, specifically apoptosis and mitochondrial permeability transition (MPT)-driven necrosis, and which may also contribute to cell death mechanisms of ferroptosis and pyroptosis. The discussion here is based on the results and evidence discovered from liver disease models, but the JNK-SAB-ROS activation loop to sustain JNK activation is universally applicable to various disease models where mitochondria and reactive oxygen species contribute to the mechanism of disease.

Tissue Necrosis: A Burden of Pentazocine Abuse in South East Nigeria.

Background: Tissue necrosis from pentazocine abuse is becoming a burden in our environment. Pentazocine is an opioid of the benzomorphan class. It is commonly used for post-traumatic and postoperative pain and vaso-occlusive pain of sickle cell disease (SCD). Its prolonged use can lead to addiction and may result in severe injection site necrosis, often worsened by infection due to a lack of aseptic principles during administration. Although pentazocine is a controlled drug in our environment, it is readily available. Objectives: To review patients with tissue necrosis from pentazocine injection, share the challenges in their management, and proffer solutions. Materials and Methods: Clinical summaries of patients with tissue necrosis and ulcers due to pentazocine addiction were reviewed. Results: Twenty-five patients, comprising nine females and 16 males aged 22-61 years, were recorded. Twenty had SCD, while five had other underlying conditions. The duration of abuse was 1-16 years, while the average maximum daily dose was 348.75 ± 346.04 mg. Most patients used multiple sites for injection. Lesions included abscesses, tissue necrosis with ulcers, lymphoedema, exposed necrotic bones, and osteomyelitis. Most had multidisciplinary care. The outcome of wound care was good in two. Three had major limb amputations, four died, three signed against medical advice, six were still receiving care while seven were lost to follow-up. None was completely weaned from the drug at the time of this report. Conclusion: Rising cases of tissue necrosis from pentazocine abuse are disturbing. Treatment is frustrating. Concerted efforts at prevention should be made to stem the tide.

Genetic analysis of cassava brown streak disease root necrosis using image analysis and genome-wide association studies.

Cassava brown streak disease (CBSD) poses a substantial threat to food security. To address this challenge, we used PlantCV to extract CBSD root necrosis image traits from 320 clones, with an aim of identifying genomic regions through genome-wide association studies (GWAS) and candidate genes. Results revealed strong correlations among certain root necrosis image traits, such as necrotic area fraction and necrotic width fraction, as well as between the convex hull area of root necrosis and the percentage of necrosis. Low correlations were observed between CBSD scores obtained from the 1-5 scoring method and all root necrosis traits. Broad-sense heritability estimates of root necrosis image traits ranged from low to moderate, with the highest estimate of 0.42 observed for the percentage of necrosis, while narrow-sense heritability consistently remained low, ranging from 0.03 to 0.22. Leveraging data from 30,750 SNPs obtained through DArT genotyping, eight SNPs on chromosomes 1, 7, and 11 were identified and associated with both the ellipse eccentricity of root necrosis and the percentage of necrosis through GWAS. Candidate gene analysis in the 172.2kb region on the chromosome 1 revealed 24 potential genes with diverse functions, including ubiquitin-protein ligase, DNA-binding transcription factors, and RNA metabolism protein, among others. Despite our initial expectation that image analysis objectivity would yield better heritability estimates and stronger genomic associations than the 1-5 scoring method, the results were unexpectedly lower. Further research is needed to comprehensively understand the genetic basis of these traits and their relevance to cassava breeding and disease management.

Incidence of avascular necrosis of native femur following hip transposition surgery for periacetabular malignancies: a single-centre experience.

BACKGROUND: Hip transposition surgery after surgical resection of large pelvic tumours is a well-established alternate to endoprosthetic reconstruction. The major goals of surgery are to ensure adequate resection margins with limb salvation, albeit with acceptable levels of morbidity. While surveillance is aimed at diagnosing local recurrence or distant metastasis primarily, other complications may occasionally be seen.The aim of this study was to assess incidence of avascular necrosis (AVN) in the preserved native femoral heads after hip transposition surgery for periacetabular malignancies, also known as hanging hip surgery. PATIENTS AND METHODS: Patient records and follow-up imaging of 22 patients who had undergone hanging hip surgery from 1999 to 2020 were retrospectively analysed to assess for any probable causes of AVN. RESULTS: Of the 22 patients, 5 (22.7%) had developed AVN on follow-up with a mean time of onset of about 10.5 months from surgery (5 months-2 years). A review of the patient demographics, surgical notes, preoperative management did not offer any clues as to the cause of AVN in these patients. Osteopenia was the most common radiological finding (59%) in most patients, but this also did not herald AVN onset. CONCLUSIONS: The theory that loss of major vascular supply to the femoral head from capsular disruption during hip transposition surgery would lead to AVN in most patients did not hold true as AVN occurred in a small number of patients.

TACE inhibition: a promising therapeutic intervention against AATF-mediated steatohepatitis to hepatocarcinogenesis.

Metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma (MASH-HCC) is a global clinical challenge for which there is a limited understanding of disease pathogenesis and a subsequent lack of therapeutic interventions. We previously identified that tumor necrosis factor-alpha (TNF-α) upregulated apoptosis antagonizing transcription factor (AATF) in MASH. Here, we investigated the effect of TNF-α converting enzyme (TACE) inhibition as a promising targeted therapy against AATF-mediated steatohepatitis to hepatocarcinogenesis. A preclinical murine model that recapitulates human MASH-HCC was used in the study. C57Bl/6 mice were fed with chow diet normal water (CD) or western diet sugar water (WD) along with a low dose of carbon tetrachloride (CCl4; 0.2 µL·g-1, weekly) for 24 weeks. TACE activity, TNF-α levels, and AATF expression were measured. The mice were treated with the TACE inhibitor Marimastat for 12 weeks, followed by analyses of liver injury, fibrosis, inflammation, and oncogenic signaling. In vitro experiments using stable clones of AATF control and AATF knockdown were also conducted. We found that AATF expression was upregulated in WD/CCl4 mice, which developed severe MASH at 12 weeks and advanced fibrosis with HCC at 24 weeks. WD/CCl4 mice showed increased TACE activity with reduced hepatic expression of sirtuin 1 (Sirt1) and tissue inhibitor of metalloproteinase 3 (Timp3). The involvement of the SIRT1/TIMP3/TACE axis was confirmed by the release of TNF-α, which upregulated AATF, a key molecular driver of MASH-HCC. Interestingly, TACE inhibition by Marimastat reduced liver injury, dyslipidemia, AATF expression, and oncogenic signaling, effectively preventing hepatocarcinogenesis. Furthermore, Marimastat inhibited the activation of JNK, ERK1/2, and AKT, which are key regulators of tumorigenesis in WD/CCl4 mice and in AATF control cells, but had no effect on AATF knockdown cells. This study shows that TACE inhibition prevents AATF-mediated inflammation, fibrosis, and oncogenesis in MASH-HCC, offering a potential target for therapeutic intervention.

External border zone may be correlated with radiation necrosis after radiosurgery in metastatic brain tumor.

BACKGROUND: Radiation necrosis (RN) after stereotactic radiosurgery (SRS) in brain metastases has been extensively evaluated, and RN is correlated with various risk factors. However, no study comprehensively analyzed the correlation between RN and the border zones of the brain that are vulnerable to ischemia. We hypothesized that patients with tumors in the border zone are at high risk of RN. Hence, the current study aimed to assess the correlation between border zone lesions and RN, with consideration of other predetermined factors. METHODS: This retrospective study included 117 patients with 290 lesions who underwent Gamma Knife® stereotactic radiosurgery (SRS). Radiological and clinical analyses were performed to identify factors possibly correlated with RN. Notably, the lesion location was classified into two groups (border zone and non-border zone) based on the blood supply. RESULTS: In total, 22 (18.8%) patients with 22 (7.5%) lesions developed RN. Univariate analysis revealed a significant correlation between RN and external border zone lesions, second course of SRS administered at the same site of the previous SRS, prescribed dose, and tumor volume. Multivariate analysis showed that border zone lesions, second course of SRS at the same site of the previous SRS, and tumor volume were significantly correlated with RN. CONCLUSIONS: Patients with tumors in the border zone are at high risk of RN. The potential risks of RN can be attributed hypothetically to hypoperfusion. Hence, the association between RN and border zone lesions seems reasonable.

Prognosis of subsequent pregnancy in uterine necrosis after uterine artery embolization.

In an 8-year period at two medical center, 138 patients underwent uterine artery embolization, and 11 of them were diagnosed with uterine necrosis. Among them, three were successfully conceived. However, one of them developed an arteriovenous malformation after an artificial abortion, and another experienced complications, including placenta previa and placenta accreta spectrum, which resulted in early preterm delivery and recurrent postpartum hemorrhage, necessitating subtotal hysterectomy. Therefore, it is crucial to prepare for potential adverse pregnancy outcomes in subsequent pregnancies for patients with a history of uterine necrosis.

Reliable differentiation of necrosis and active metabolically contours of glioblastoma multiforme using susceptibility-based imaging.

Purpose: Gadolinium-enhancing necrosis in glioblastoma multiforme (GBM), as an occasionally occurring false positive in contrast enhancement (CE) imaging, leads to trouble for segmentation of GBM and treatment. Therefore, the investigation of complementary detection way to identify the metabolically active volume of the tumor with high reliability is very worth to be addressed. Here, we reported on a case of GBM with gadolinium-enhancing necrosis in an experimental CE imaging study in mice and evaluated the discrimination of the necrosis and metabolically active parts of the GBM using conventional and state-of-the-art susceptibility-based MRI. Methods: In this study, following 5-aminolevulinic acid (ALA) and iron supplements (FAC, 6 h after ALA, intra-tumoral injection) to animal, T2*-W imaging and quantitative susceptibility mapping (QSM) were performed, and compared with CE imaging. Results: The signal intensity (SI) of the active and necrosis areas of the case in the CE image demonstrated no significant difference while the SI on the T2*-W images and susceptibility value in QSM changed 24 and 150%, respectively. Conclusion: The preclinical case report provides valuable insights into the potential of susceptibility-based MRI using ALA + FAC to apply as a robust discriminator between necrotic and viable tumors.

The effect of anti-TNF drugs on the intestinal microbiota in patients with spondyloarthritis, rheumatoid arthritis, and inflammatory bowel diseases.

Spondyloarthritis (SpA), rheumatoid arthritis (RA), and inflammatory bowel diseases (IBD) are chronic inflammatory autoimmune diseases that are associated with alterations in the composition of the intestinal microbiota (i.e., dysbiosis). For SpA and RA, a gut-joint-enthesis axis is hypothesized and recent data suggests that dysbiosis may contribute directly to initiating and perpetuating joint and spine inflammation. Biologic drugs targeting tumor necrosis factor (TNF) are effective in treating these diseases and have been shown to partially restore the disrupted microbiome. Hence, drugs that affect both the intestinal and joint components of these diseases, such as anti-TNF drugs, may act on the intestinal microbiome. However, despite the remarkable efficacy of anti-TNF-α treatments, non-responders are frequent, and predictors of patient outcomes have not been identified. In this narrative review, we summarize recent research on the downstream effects of anti-TNF drugs on the intestinal microbiota in SpA, RA, and IBD. We also discuss whether these changes could have a role as predictive biomarkers of anti-TNF response.

Risk of pulp necrosis and related complications in the permanent anterior teeth with lateral luxation: A systematic review and meta-analysis.

This systematic review aimed to evaluate the evidence related to the occurrence of pulp necrosis and related complications in permanent anterior teeth with lateral luxation. It was envisaged to address the ambiguity related to the recommendation for pulp extirpation in teeth with mature root apex. An a priori protocol was formulated as per the best practices of evidence-based medicine and registered in PROSPERO. A comprehensive search was performed electronically in PubMed, LILACS, Web of Science, EMBASE, Scopus, and Cochrane on July 10,2023 without any restriction of language or year of publication. The screening of titles and abstracts and later the full-text articles were performed. Later, the data extraction was performed by using a self-designed sheet, risk of bias (ROB) assessment was done, meta-analysis was performed, and the GRADE approach was used to assess the quality of evidence. The qualitative synthesis was performed on 13 studies done from 1985 to 2020 in hospital settings. There was variability in the minimum and total observation periods, sample sizes, and characteristics of the sample population. The overall pooled prevalence of pulp necrosis was found to be 57% (95% CI: 42, 72%). It was 12% (95% CI: 8%, 18%, I2 = 0%) in immature teeth, and 58% (95% CI: 42, 73%, I2 = 86%) in mature teeth. The pooled prevalence of EIRR was found to be 11% (95% CI: 4, 27%, I2 = 95%) with greater risk in teeth with mature root apex (RR: 1.26, 95% CI: 1.12, 1.42, I2 = 0%). The ROB was moderate or high in nine studies and the GRADE of evidence was very low in 14 of 15 outcomes. There are greater chances of pulp necrosis in teeth with lateral luxation, especially with mature apex. However, it can still be less than 60% in most cases with the prevalence of EIRR less than 20%. Hence, an absolute recommendation for endodontic intervention in mature teeth with lateral luxation must be interpreted with slight caution.

Use of Endodontic Procedures in Young Permanent Teeth.

Background: Regenerative endodontic procedures (REPs) have emerged as a promising treatment option for young permanent teeth with pulp necrosis, offering the potential for tissue repair and preservation. Materials and Methods: A retrospective analysis was conducted on a cohort of 30 patients aged 8 to 16 years with pulp necrosis in young permanent teeth. The patients underwent REPs, including disinfection, triple antibiotic paste application, and a coronal barrier. Clinical and radiographic data were collected at baseline and follow-up appointments at 6, 12, and 24 months. Radiographs were analyzed for root lengthening, apical closure, and resolution of periapical lesions. Results: The mean increase in root length after 24 months was 3.42 mm (SD ± 1.12 mm), and 90% of cases demonstrated complete apical closure. The overall success rate, defined as the absence of clinical symptoms and radiographic evidence of pathology, was 80. Conclusion: REPs show promising outcomes in young permanent teeth with pulp necrosis, promoting root development, and apical closure.

A missense mutation in human INSC causes peripheral neuropathy.

PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.

A Panoramic Review on the Management of Rheumatoid Arthritis through Herbalism.

Arthritis is a chronic inflammatory condition that affects millions of individuals worldwide. The conventional treatment options for arthritis often come with limitations and potential side effects, leading to increased interest in herbal plants as alternative therapies. This article provides a comprehensive overview of the use of herbal plants in arthritis treatment, focusing on their traditional remedies, active components, mechanisms of action, and pharmaceutical approaches for enhancing their delivery. Various herbal plants, including turmeric, ginger, Boswellia, and willow bark, have shown anti-inflammatory and analgesic properties, making them valuable options for managing arthritis symptoms. The active components of these herbal plants, such as curcumin, gingerols, and boswellic acids, contribute to their therapeutic effects. To enhance the delivery of herbal medicines, pharmaceutical approaches like nanoparticle-based drug delivery systems, liposomes, polymeric nanoparticles, nanoemulsions, microneedles, and inhalation systems have been explored. These approaches aim to improve bioavailability, targeted delivery, and controlled release of herbal compounds. Safety considerations, including potential interactions with medications and the risk of allergic reactions, are also discussed. Future perspectives for this field involve conducting well-designed clinical studies, enhancing standardization and quality control measures, exploring novel drug delivery systems, and fostering collaborations between traditional medicine practitioners and healthcare professionals. Continued research and development in these areas will help unlock the full potential of herbal plants in arthritis treatment, offering personalized and effective care for affected individuals.

Interactions between Age-Related Type 2 Diabetes and the Small Intestine.

The number of patients with type 2 diabetes is increasing worldwide. The mechanisms leading to type 2 diabetes and its complications is being researched; however, the pathological mechanisms of diabetes in the small intestine remain unclear. Therefore, we examined these pathological mechanisms in the small intestine using a mouse model of type 2 diabetes (KK-Ay/TaJcl) aged 10 and 50 weeks. The results showed that diabetes worsened with age in the mice with type 2 diabetes. In these mice, advanced glycation end products (AGEs) in the small intestine and mast cell expression increased, whereas diamine oxidase (DAO) decreased; increased tumor necrosis factor (TNF)-α and histamine levels in the plasma and small intestine were also detected. Additionally, the expression of zonula occludens (ZO)-1 and Claudin1 and cell adhesion molecules in the small intestine reduced. These results exacerbated with age. These findings indicate that type 2 diabetes causes AGE/mast cell/histamine and TNF-α signal transmission in the small intestine and decreases small intestinal wall cell adhesion molecules cause TNF-α and histamine to flow into the body, worsening the diabetic condition. In addition, this sequence of events is suggested to be strengthened in aged mice with type 2 diabetes, thus exacerbating the disease. These findings of this study may facilitate the elucidation of the pathological mechanisms of type 2 diabetes and its associated complications.

NF-κB affected the serum levels of TNF-α and IL-1ß via activation of the MAPK/NF-κB signaling pathway in rat model of acute pulmonary microthromboembolism.

Pulmonary thromboembolism caused by thrombi blocking major pulmonary artery and its branches, is a frequently encountered phenomenon and an important cause of high morbidity and mortality in lung diseases and may develop into persistent pulmonary hypertension (PH). Nuclear factor-κB (NF-κB) signaling pathway had been reported participated in the formation and development of PH by promoting inflammatory response. The aim of this study was to investigate the effects of NF-κB activation on the serum levels of tumor necrosis factor α (TNF-α) and interleukin-1ß (IL-1ß) in acute pulmonary microthromboembolism (APMTE) rats. Rats were randomized into five groups. APMTE group received jugular vein injection of autologous thrombus, while control group rats received normal saline injection. Pulmonary hemodynamic parameters were measured through ECHO-guided transthoracic puncture. Pulmonary vascular morphological changes were analyzed by HE. The expression changes of NF-κB and serum TNF-α、IL-1ß levels were detected by enzyme-linked immunosorbent assay. Protein expression of the MAPK/NF-κB signaling pathway including p-IκBα, p-p38 MAPK, p-NF-κB p65, IκBα, p38 MAPK, and NF-κB p65 was determined using western blot analysis. Compared with control group, the expression of NF-κB in lung tissue and the levels of serum TNF-α and IL-1ß rats were higher, a significant reduction in IκBα and elevation in the phosphorylation of IκBα, p38 MAPK, and NF-κB p65 were found in APMTE group rats. And UK administration reversed the APMTE-induced increase in TNF-α, IL-1ß, p-IκBα, p-MAPK, and p-NF-κB protein. Furthermore, the levels of NF-κB, TNF-α, and IL-1ß were positively correlated with mean pulmonary artery. And the levels of TNF-α and IL-1ß were positively correlated with NF-κB. These findings suggest that the activation of MAPK/NF-κB pathway as a critical driver of increasing TNF-α and IL-1ß level in APMTE rats and UK exerted protective effects against APMTE-induced PH may be related to the downregulation of the MAPK/NF-κB signaling pathway.

Case report: Envafolimab causes local skin necrosis.

Envafolimab is a Chinese domestic innovative fusion of a humanized single-domain programmed death-ligand 1 (PD-L1) antibody (dAb) and human immunoglobulin IgG1 crystalline fragment (Fc) developed for subcutaneous injections. It was granted conditional market authorization by the China National Medical Product Administration (NMPA) in December 2021. Envafolimab is used to treat adult patients with previously treated microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) advanced solid tumors, including patients with advanced colorectal cancer disease progression who were previously administered fluorouracil, oxaliplatin, and irinotecan, as well as other patients with advanced solid tumors who experienced disease progression after receiving standard treatment and had no other alternative treatment options. However, the lack of post-marketing clinical trial data requires conducting more clinical studies on the safety and efficacy of envafolimab in order to provide scientific basis and a reference for future therapeutic applications. In this paper, we report a case of severe skin necrosis and bleeding in the area of injection after subcutaneous administration of envafolimab in a patient diagnosed with hepatocellular carcinoma. We discuss issues that must be considered before administration of a PD-L1 inhibitor subcutaneously, which could induce immune mechanisms leading to skin necrosis in the area of injection.