Ex-vivo expanded CD34+ cell transplantation alleviates fibrotic liver injury via innate immune modulation in metabolic dysfunction-associated steatohepatitis mice.

BACKGROUND: In drug-induced liver injury, vascular endothelial progenitor cells, specifically the CD34+ cell fractions, have been found to decrease liver fibrosis and promote regeneration. However, it is unclear whether CD34+ cell transplantation has anti-fibrogenic effects on MASH, which has previously been treated effectively with anti-angiogenic therapy. We investigated the efficacy of ex vivo-expanded CD34+ cells in treating MASH livers. MATERIALS AND METHODS: Diet-induced MASH mice were fed a choline-deficient, L-amino acid-defined, high-fat diet for 12 or 20 weeks, and were designated as a mild and a severe fibrosis model, respectively. Mouse bone marrow CD34+ cells were expanded for 7 days, transplanted into each mouse once or twice 2 weeks later, and sacrificed at 4 weeks after the first transplantation. RESULTS: Expanded CD34+ cell transplantation ameliorated liver fibrosis, regardless of fibrosis degree, as indicated by the decrease in α-smooth muscle actin-positive cells, hydroxyproline concentration, and fibrogenic gene expression of Col1a1 and Timp1. Furthermore, engrafted CD34+ cells reduced alanine transaminase levels, the number of TUNEL+ hepatocytes, and 8-OHdG concentration. RNA-sequencing data showed that "defense response to virus" was the most down-regulated category in the Gene Ontology analysis and subsequent analysis revealed the suppression of RIG-I-like receptors/Irf7/Stat1/Cxcl10 axis in expanded CD34+ cell-transplanted livers. Finally, the downregulation of CXCL10 expression inhibits the mobilization of inflammatory immune cells, macrophages, T cells, and natural killer cells to the MASH liver. CONCLUSIONS: These findings suggest that transplanted expanded CD34+ cells alleviate fibrotic liver injury in MASH mouse models through possible modulation of the innate immune response, which is abnormally activated by hepatocyte lipotoxicity.

Comparison of guidelines for biological ancillary materials used for the manufacture of gene and cellular therapy products in Asia.

BACKGROUND AIMS: Although biologiocal ancillay materials (AMs) have specific risk associated with their derivations, it plays key role to manufature cell and gene therapy (CGT) products. It is important to understand the regulation relevant to AMs for developers. METHODS: The authors investigated the guidelines and pharmacopeia (hereinafter referred to as "guidelines") for biological AMs used for the manufacture of CGT products in Asia (China, India, Japan, Korea and Taiwan). In addition, the authors benchmarked the relevant guidelines in the United States (US) and European Union (EU). RESULTS AND DISCUSSIONS: The guidelines could be classified into two types based on whether specific AMs are scoped: (i) general guidelines for risk assessment of AMs and (ii) guidelines for specific AMs. The authors compared the risk categories for each type of AM provided in the general guidelines between the US and China and the specific requirements for bovine serum and trypsin in the guidelines of China, Japan, Taiwan, US and EU. The authors further compiled in-depth descriptions of the respective regulations in China, India, Japan, Korea and Taiwan. There is limited availability of some guidelines for specific AMs. Moreover, there are no common requirements established across the surveyed countries and regions. Therefore, the authors suggest a risk assessment approach for AMs with consideration of their biological origin and traceability, production steps applied and ability to control or remove AMs from the final medicinal product over the CGT manufacturing process.

Non-clinical, quality and environmental impact assessments of cell and gene therapy products: Report on the 5th Asia Partnership Conference of Regenerative Medicine - April 7, 2022.

The 5th Asia Partnership Conference of Regenerative Medicine (APACRM) was held online on April 7, 2022 to promote regulatory harmonization of regenerative medicine products throughout Asia. The recognition of domestic regulatory guidelines within each country and region and the underpinning rationales are important initial steps toward the harmonization of regulations. The 5th APACRM featured open dialog regarding non-clinical, quality and environmental impact assessment settings for cell and gene therapy products through presentations from the industry and panel discussions with regulatory agencies. The latest updates on regenerative medicine fields in each country and region were also introduced. This paper summarizes the proceedings of the 5th APACRM for public dissemination to foster future discussion.

High intramuscular adipose tissue content was a favorable prognostic factor in patients with advanced gastric cancer treated with nivolumab monotherapy.

BACKGROUND: Nivolumab extends the overall survival (OS) of patients with advanced gastric cancer (AGC). Intramuscular adipose tissue (IMAT) is associated with the prognosis of patients with various cancers. We investigated the effect of IMAT on OS in patients with AGC treated with nivolumab. METHODS: We enrolled patients with AGC treated with nivolumab (n = 58, 67 years old, men/women 40/18). The subjects were classified into long-term or short-term survival groups according to the median value. The IMAT was evaluated using computed tomography scans at the umbilical level. The decision tree algorithm was employed to reveal the profile associated with prognosis. RESULTS: In decision tree analysis, immune-related adverse events (irAEs) were the first divergence variable, and prolonged survival was observed in 100% of patients with irAEs (profile 1). However, long survival was observed in 38% of patients with no irAEs. Among these patients, IMAT was identified as the second divergence variable, and long survival was observed in 63% of patients with high IMAT (profile 2). In patients with low IMAT, only 21% showed prolonged survival (profile 3). Median OS was 717 days (95% confidence interval [CI], 223 to not reached) in profile 1, 245 days (95% CI, 126 to 252) in profile 2, and 132 days (95% CI, 69 to 163) in profile 3. CONCLUSION: Immune-related adverse events and high IMAT were favorable factors for OS in patients with AGC treated with nivolumab. Thus, along with irAEs, skeletal muscle quality is important in managing patients with AGC treated with nivolumab.

Nonclinical and quality assessment of cell therapy products: Report on the 4th Asia Partnership Conference of Regenerative Medicine, April 15, 2021.

The 4th Asia Partnership Conference of Regenerative Medicine (APACRM) was held online on April 15, 2021, to promote regulatory harmonization of regenerative medicine products throughout Asia. Recognizing domestic regulatory guidelines within each country and region, and their underpinning rationales, is an important initial step toward a convergence of regulations. The 4th APACRM consisted of an open dialog with regulatory agencies regarding nonclinical and quality settings for cell therapy products (CTPs) through industry presentations and panel discussions with regulatory agencies. The latest updates on regenerative medicine fields in each country and region, and specific regulatory schematics in Japan, were also introduced. The objective of this paper is to summarize the proceedings of the 4th APACRM for public dissemination and to foster further discussion in the future.

Glycosylation of ascites-derived exosomal CD133: a potential prognostic biomarker in patients with advanced pancreatic cancer.

Cancer cells surviving in ascites exhibit cancer stem cell (CSC)-like features. This study analyzed the expression of the CSC marker CD133 in the ascites-derived exosomes obtained from patients with unresectable pancreatic cancer. In addition, inverse correlation of CD133 expression with prognosis was examined. Of the 133 consecutive patients, 19 patients were enrolled in the study. Exosomes derived from the malignant ascites demonstrated higher density and wider variation in size than those from non-malignant ascites. Western blot revealed enhanced expression of CD133 in exosomes obtained from patients with pancreatic cancer compared to those obtained from patients with gastric cancer or liver cirrhosis. A xenograft mouse model with malignant ascites was established by intraperitoneal inoculation of human pancreatic cancer cells in nude mice. Results obtained from the human study were reproduced in the mouse model. Statistically significant equilateral correlation was identified between the band intensity of CD133 in western blot and overall survival of patients. Lectin microarray analyses revealed glycosylation of CD133 by sialic acids as the major glycosylation among diverse others responsible for the glycosylation of exosomal CD133. These findings suggest that highly glycosylated CD133 in ascites-derived exosomes as a potential biomarker for better prognosis of patients with advanced pancreatic cancer.

[A Case of Chemotherapy-Induced Hyperammonemic Encephalopathy in a Patient with Metastatic Colon Cancer].

A 70-year-old man was diagnosed with colon cancer with multiple liver metastases.He was administered modified FOLFOX6 plus panitumumab as first-line chemotherapy.He showed consciousness disturbance on the 3rd day during the 8 cycle and was hospitalized urgently.We diagnosed him with 5-FU-induced hyperammonemia.Administration of branchedchain amino acid preparation improved his consciousness disturbance.After changing the regimen of chemotherapy to another one containing oral fluoropyrimidine, the recurrence of hyperammonemic encephalopathy was not found.

High expression of CD44v9 and xCT in chemoresistant hepatocellular carcinoma: Potential targets by sulfasalazine.

CD44v9 is expressed in cancer stem cells (CSC) and stabilizes the glutamate-cystine transporter xCT on the cytoplasmic membrane, thereby decreasing intracellular levels of reactive oxygen species (ROS). This mechanism confers ROS resistance to CSC and CD44v9-expressing cancer cells. The aims of the present study were to assess: (i) expression status of CD44v9 and xCT in hepatocellular carcinoma (HCC) tissues, including those derived from patients treated with hepatic arterial infusion chemoembolization (HAIC) therapy with cisplatin (CDDP); and (ii) whether combination of CDDP with sulfasalazine (SASP), an inhibitor of xCT, was more effective on tumor cells than CDDP alone by inducing ROS-mediated apoptosis. Twenty non-pretreated HCC tissues and 7 HCC tissues administered HAIC therapy with CDDP before surgical resection were subjected to immunohistochemistry analysis of CD44v9 and xCT expression. Human HCC cell lines HAK-1A and HAK-1B were used in this study; the latter was also used for xenograft experiments in nude mice to assess in vivo efficacy of combination treatment. CD44v9 positivity was significantly higher in HAIC-treated tissues (5/7) than in non-pretreated tissues (2/30), suggesting the involvement of CD44v9 in the resistance to HAIC. xCT was significantly expressed in poorly differentiated HCC tissues. Combination treatment effectively killed the CD44v9-harboring HAK-1B cells through ROS-mediated apoptosis and significantly decreased xenografted tumor growth. In conclusion, the xCT inhibitor SASP augmented ROS-mediated apoptosis in CDDP-treated HCC cells, in which the CD44v9-xCT system functioned. As CD44v9 is typically expressed in HAIC-resistant HCC cells, combination treatment with SASP with CDDP may overcome such drug resistance.

Decreased serum levels of immunoglobulin A, immunoglobulin M and immunoglobulin G in a patient with primary biliary cirrhosis: A case report.

Primary biliary cirrhosis (PBC) is a cholestatic liver disease with an elevated serum immunoglobulin (Ig)M level. Patients with PBC may develop extrahepatic manifestations, including hypogammaglobulinemia. However, hypogammaglobulinemia seldom occurs, and the associated changes of lymphocytes remain unknown. Furthermore, the impact of Ig on the progression of PBC is still unclear. Here, we describe a case of hypogammaglobulinemia developed in a female patient with PBC. The patient was diagnosed with PBC at the age of 46 years and treated with ursodeoxycholic acid and bezafibrate. At the age of 50 years, the patient developed bronchitis, and laboratory test results indicated a marked decrease in serum levels of IgA, IgM and IgG. Then, the patient was diagnosed as having idiopathic hypogammaglobulinemia and treated with Ig replacement therapy; however, respiratory infections recurred frequently, leading to the patient's death at the age of 53 years. An autopsy revealed hyperplastic bone marrow with CD3, CD20 and IgG positive lymphocytes. However, no CD79a, CD138, IgA and IgM positive lymphocytes were observed. Moreover, the severity of PBC progressed even after the onset of hypogammaglobulinemia. In addition, CD3 positive cells were seen around chronic non-suppurative destructive cholangitis in the autopsy specimen of the liver. Thus, the present case demonstrated changes of lymphocytes in hypogammaglobulinemia developed in patients with PBC. Furthermore, the clinical course of the present case of PBC may indicate that the Ig-mediated mechanisms may be non-essential for the progression of PBC.

Fibroblast growth factor inhibition by molecular-targeted agents mitigates immunosuppressive tissue microenvironment in hepatocellular carcinoma.

BACKGROUND & AIMS: Combination immunotherapy refers to the use of immune checkpoint inhibitors (ICI) and molecular-targeted agents (MTA), which have recently been approved for the treatment of advanced hepatocellular carcinoma (HCC). Owing to its relatively low antitumor effect (up to 30%), sequential therapy following ICIs treatment is required in patients with HCC. This study aimed to determine the impact of MTAs on the tumor immune microenvironment (TIME). METHODS: We established immune syngeneic orthotopic HCC mouse models using Hep-55.1C and Hep-53.4, and treated them with MTAs (lenvatinib, sorafenib, regorafenib, cabozantinib, and DC101 as anti-vascular endothelial growth factor receptor-2 antibodies, and AZD4547 as a fibroblast growth factor receptor (FGFR)-1/2/3/4 inhibitor) for 2 weeks. Subsequently, alterations in the TIME caused by MTAs were evaluated using immunohistochemistry (antibodies for CD3, CD8, Foxp3, Granzyme B, Arginase-1, NK1.1, F4/80, CD11c, PD-1, and PD-L1). We conducted RNA-seq analysis using lenvatinib- and AZD4547-treated tumors. To confirm the clinical relevance of these findings, we analyzed the transcriptome data of human HCC cells (MHCC-97H) treated with various concentrations of lenvatinib for 24 h using RNA-seq data from the Gene Expression Omnibus database. RESULTS: The number of Foxp3- and F4/80-positive cells in the TIME was decreased in many MTAs. Cabozantinib increased the numbers in NK1.1-, Granzyme B, and CD11c-positive cells. Lenvatinib and AZD4547 increased the number of CD8, Granzyme B, and PD-L1-positive cells. Gene ontology enrichment analysis revealed that lipid metabolism-related genes were downregulated by lenvatinib and AZD4547. In total, 161 genes downregulated by FGFR inhibition in rodent models overlapped with those downregulated by lenvatinib in human HCC cells. CONCLUSIONS: In this study, we showed that cabozantinib activated the innate immune system, and lenvatinib and AZD4547, which commonly inhibit FGFR signaling, altered TIME to a hot immune state by downregulating lipid metabolism-related genes. These findings support the therapeutic use of combination immunotherapies.

Patient Satisfaction Survey on Portable Infusion Pumps for Colorectal Cancer Chemotherapy: Hard-Shelled or Soft-Shelled?

Purpose: Elastomeric infusion pumps are widely used in colorectal cancer chemotherapy. However, no studies to date have investigated patient preferences regarding different infusion pump types. Patients and Methods: Twenty patients with unresectable colorectal cancer undergoing chemotherapy were initially treated with a portable hard-shelled continuous infusion pump, followed by a soft-shelled continuous infusion pump. The respondents used a numerical rating scale (0-10) to rate their comfort when using each pump, their ease of carrying it, the pump size and shape, its weight, their ease of reading its memory, and their overall satisfaction with it. They were then asked to determine which pump they would ultimately prefer. Results: In terms of comfort, significantly higher user satisfaction was reported for the soft-shelled pump during the daytime and when going out (P < 0.001, P < 0.001, respectively). For pump portability, size, shape, and weight, the soft-shelled type also outperformed the hard-shelled one (P < 0.001, P=0.0011, P < 0.001, respectively). However, the hard-shelled pump scored significantly better in terms of ease of viewing memory (P < 0.001). Overall satisfaction was significantly higher for the soft-shelled pump than the hard-shelled type (P=0.0095). Finally, 13 patients (65%) indicated that they would prefer a soft-shelled pump for their next treatment, while only one patient (5%) preferred a hard-shelled alternative. A preference for soft-shelled pump was observed, particularly in female patients and those with a body mass index of < 22 kg/m2. Conclusion: The selection of portable elastomeric infusion pumps should consider the preferences of patients with colorectal cancer, as these devices have the potential to enhance their quality of life.

A tumor endothelial cell-specific microRNA replacement therapy for hepatocellular carcinoma.

Current approved anti-angiogenic drugs (AAD) for hepatocellular carcinoma (HCC) inhibit tumor angiogenesis, but affect the hepatic vasculature resulting in adverse effects. Tumor endothelial cells (TECs) differ from normal endothelial cells. In this study, we aimed to detect TEC-specific miRNAs and develop an anti-angiogenic treatment specific for TECs. We established HCC orthotopic mouse models. TEC-specific miRNAs were detected using a microRNA array. Finally, we evaluated the therapeutic effects of the TEC-specific miRNA agonist cocktail. In total, 260 TEC-specific genes were detected. Among the top ten downregulated TEC-specific miRNAs, miR-139-3p and 214-3p were important for the TEC phenotype. The TEC-specific microRNA agonist cocktail showed significant anti-tumor effects by inhibiting tumor angiogenesis without affecting hepatic vasculatures in HCC orthotopic mouse models. Moreover, it significantly downregulated tip-cell sprouting-related genes. We identified two downregulated TEC-specific miRNAs; microRNA replacement therapy, which targets the downregulated TEC-specific miRNAs, is an effective and promising treatment for HCC.

Simple method for differentiating measles vaccine from wild-type strains using loop-mediated isothermal amplification.

Because of increasing measles vaccine coverage, the proportion of patients with modified measles has been increasing. Such patients have low-grade fever with very mild eruptions similar to vaccine-related adverse events. Differentiation between these two pathogenic conditions is required to improve the quality of laboratory-based measles surveillance. In this study, vaccine-specific and wild-type specific primer sets were designed for loop-mediated isothermal amplification in the N gene, and vaccine strains, C1, D3, D4, D5, D8, D9, G3 and H1 wild strains were examined. Three vaccine strains were efficiently amplified using a vaccine-specific primer set with an approximately 10-times higher sensitivity than wild-type primer. Modified measles was differentiated from vaccine-associated cases by this system, but limitations were encountered with the other genotypes.

Unilateral renal agenesis and ipsilateral absence of the vas deferens in a cryptorchid infant with Klippel-Feil syndrome.

We report an exceedingly rare case of Klippel-Feil syndrome (KFS), compounded by ipsilateral absence of the vas deferens, renal agenesis, and diaphragmatic hernia. Unilateral absence of the vas deferens was found incidentally during orchidopexy. To the best of our knowledge, no case of unilateral absence of the kidney and vas deferens has been reported in children with KFS.

Fat Necrosis Mimicking Local Recurrence With Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Positivity After Partial Nephrectomy for Renal Cell Carcinoma.

We report a case of fat necrosis with positive results on fluorodeoxyglucose positron emission tomography (FDG-PET)-CT imaging after partial nephrectomy. A 77-year-old man underwent a partial nephrectomy for a right renal mass. The histopathological results showed clear cell renal cell carcinoma, G1>G2, pT1a. Four and a half years after surgery, a nodule appeared in the retroperitoneal space on CT. FDG-PET CT showed increased uptake in the nodule, indicating local recurrence of carcinoma. A right nephrectomy was performed. The histopathological diagnosis was fat necrosis.

Case Report: A case of complete response to entrectinib in NTRK fusion gene-positive parotid gland cancer.

Introduction: Expression of the NTRK gene is rare in solid tumors but is highly prevalent in salivary gland secretory carcinomas. Here, we report a case of a complete response to entrectinib in a patient with NTRK fusion gene-positive parotid carcinoma. Case description: The patient was a 44-year-old man who underwent total left parotidectomy and left cervical lymph node dissection for a left parotid tumor at 24 years of age. The histopathological diagnosis was mammary analog secretory carcinoma. Postoperatively, the patient received only radiation therapy. Sixteen years after the surgery, the patient became aware of a mass in the left parotid region. A close examination revealed local recurrence and multiple cervical lymph node metastases. S-1 monotherapy was started as chemotherapy but was discontinued 3 years later because of disease progression. As there was no standard treatment, a comprehensive genomic profiling test using a next-generation sequencer was performed, and the ETV6-NTRK3 fusion gene was identified. Entrectinib, an NTRK inhibitor, was immediately administered at a dose of 600 mg/day. The local recurrence rapidly shrank grossly from the beginning of treatment, and a complete response was observed 6 months later. However, creatinine levels exhibited an increase at week 68 of treatment; consequently, entrectinib dosage was lowered to 400 mg/day, leading to an immediate improvement in creatinine levels. Entrectinib was associated with additional side effects, including dysgeusia, fatigue, dizziness, and weight gain, all of which were also alleviated by the reduction in entrectinib dose. Thirty months after treatment initiation, the patient maintained a complete response and continued to receive entrectinib. Conclusion: The NTRK fusion gene should always be checked in the presence of salivary gland secretory carcinoma.

Anti-PD-L1 antibodies promote cellular proliferation by activating the PD-L1-AXL signal relay in liver cancer cells.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are emerging treatments for advanced hepatocellular carcinoma (HCC); however, evidence has shown they may induce hyperprogressive disease via unexplained mechanisms. METHODS: In this study, we investigated the possible stimulative effect of ICIs on programmed cell death-ligand 1 (PD-L1)-harboring liver cancer cells under immunocompetent cell-free conditions. RESULTS: The sarcomatous HAK-5 cell line displayed the highest expression of PD-L1 among 11 human liver cancer cell lines used in this study. HLF showed moderate expression, while HepG2, Hep3B, and HuH-7 did not show any. Moreover, sarcomatous HCC tissues expressed high levels of PD-L1. We observed approximately 20% increase in cell proliferation in HAK-5 cells treated with anti-PD-L1 antibodies, such as durvalumab and atezolizumab, for 48 h compared with that of those treated with the control IgG and the anti-PD-1 antibody pembrolizumab. No response to durvalumab or atezolizumab was shown in PD-L1-nonexpressing cells. Loss-of-function and gain-of-function experiments for PD-L1 in HAK-5 and HepG2 cells resulted in a significant decrease and increase in cell proliferation, respectively. Phosphorylated receptor tyrosine kinase array and immunoprecipitation revealed direct interactions between PD-L1 and AXL in tumor cells. This was stabilized by extrinsic anti-PD-L1 antibodies in a glycosylated PD-L1-dependent manner. Activation of AXL, triggering signal relay to the Akt and Erk pathways, boosted tumor cell proliferation both in vitro and in xenografted tumors in NOD/SCID mice. CONCLUSION: Collectively, this suggests that anti-PD-L1 antibodies stimulate cell proliferation via stabilization of the PD-L1-AXL complex in specific types of liver cancer, including in HCC with mesenchymal components. SIGNIFICANCE: Therapeutic anti-PD-L1 antibodies promote cell proliferation by stabilizing the PD-L1-AXL complex in PD-L1-abundant neoplasms, including in HCC with mesenchymal components. Such a mechanism may contribute to the development of hyperprogressive disease.

Safety of Early Bevacizumab Administration after Central Venous Port Placement for Patients with Colorectal Cancer.

Bevacizumab (BEV) requires an adequate withdrawal period to avoid BEV-related complications during major surgery. However, the safety of BEV administration immediately after surgical placement of the central venous (CV) port, a minor surgery, is still unclear. This study aimed to investigate whether BEV is safe when administered early after CV port placement. We retrospectively evaluated 184 patients with advanced colorectal cancer (CRC) treated with a BEV-containing regimen and divided them into two groups according to the interval between CV port implantation and chemotherapy initiation, with the early administration group being ≤7 days and late administration group being >7 days. Complications were then compared between the two groups. The early-administration group was significantly older and had a higher rate of colon cancer than the late-administration group. Overall, 24 (13%) patients developed CV port-related complications. Male sex was a risk factor for complications (odds ratio [OR], 3.154; 95% CI, 1.19-8.36). The two groups showed no significant difference in the frequency of complications (p = 0.84) or patient characteristics (after the inverse probability of treatment weighting, p = 0.537). In conclusion, the frequency of complications is not affected by the timing of BEV initiation after CV port implantation. Thus, early BEV administration after CV port placement is safe.

Case report: A case of fulminant type 1 diabetes mellitus after COVID-19 vaccination during treatment of advanced gastric cancer: pitfall in managing immune-related adverse events.

The occurrence of fulminant type 1 diabetes mellitus as an adverse event during cancer immunotherapy has been previously reported. However, little is known about the causal relationship between the coronavirus disease 2019 (COVID-19) vaccination and fulminant type 1 diabetes mellitus. A 60-year-old man with advanced gastric cancer, receiving S-1 + oxaliplatin and nivolumab therapy, followed by nab-paclitaxel + ramucirumab as a second-line treatment, with steroid supplementation for complications of hypopituitarism-induced hypoadrenocorticism, was administered a COVID-19 vaccine after three cycles of nab-paclitaxel + ramucirumab. Two days later, he developed severe malaise and anorexia, which required emergency admission to our hospital for suspected adrenal insufficiency. Despite increasing steroids, his general condition changed suddenly after 12 hours leading to his death. Histopathological analysis of autopsy samples revealed loss of the islets of Langerhans, indicating fulminant type 1 diabetes mellitus. We failed to recognize the onset of fulminant type 1 diabetes mellitus because its symptoms were similar to those of adrenal insufficiency. The number of reports on the onset of fulminant type 1 diabetes mellitus after COVID-19 vaccination has been increasing, and in this case, the onset occurred on the second day after COVID-19 vaccination, suggesting an association between vaccination and fulminant type 1 diabetes mellitus. Clinicians should be aware of the risk of fulminant type 1 diabetes mellitus, although rare, after COVID-19 vaccination.