Use of current automatic smoke evacuation system in flexible gastrointestinal endoscopy: Its feasibility and potential usefulness.

Objectives: Flexible endoscopy does not have a system that can automatically evacuate surgical smoke generated in the gastrointestinal lumen. We aimed to investigate the feasibility and potential usefulness of automatic smoke evacuation systems in flexible endoscopy. Methods: [Bench] After surgical smoke generated in the stomach was evacuated by the evacuator, the degree of residual smoke and gastric luminal collapse were evaluated to optimize the evacuator settings. [Animal] Insufflation, suction, and total operation time to complete the protocol of 10 cauterizations of the gastric mucosa were measured in three groups: "manual suction only," "manual suction with automatic evacuation (50% force)," and "manual suction with automatic evacuation (70% force)." The stability of endoscopic visualization and operability was evaluated by 10 endoscopists blinded to those suction settings, and the number of manual suctions, insufflations, and total operation time were measured. Results: [Bench] The degree of residual smoke and gastric luminal collapse were inversely correlated. [Animal] When the automatic evacuator was partially used, there was no difference in the insufflation time, but the suction time (vs 50%; p = 0.011, vs. 70%; p = 0.011) and total operation time (vs. 50%; p = 0.012, vs. 70%; p = 0.036) were significantly reduced compared to manual operation only. Furthermore, manual suction with automatic evacuation (50% force) significantly improved the stability of endoscopic visualization and operability compared to manual operation only (p = 0.041, p = 0.0085). Conclusions: The automatic smoke evacuation in flexible gastrointestinal endoscopy was potentially feasible and useful by improving the device setting.

Spatial and single-cell colocalisation analysis reveals MDK-mediated immunosuppressive environment with regulatory T cells in colorectal carcinogenesis.

BACKGROUND: Cell-cell interaction factors that facilitate the progression of adenoma to sporadic colorectal cancer (CRC) remain unclear, thereby hindering patient survival. METHODS: We performed spatial transcriptomics on five early CRC cases, which included adenoma and carcinoma, and one advanced CRC. To elucidate cell-cell interactions within the tumour microenvironment (TME), we investigated the colocalisation network at single-cell resolution using a deep generative model for colocalisation analysis, combined with a single-cell transcriptome, and assessed the clinical significance in CRC patients. FINDINGS: CRC cells colocalised with regulatory T cells (Tregs) at the adenoma-carcinoma interface. At early-stage carcinogenesis, cell-cell interaction inference between colocalised adenoma and cancer epithelial cells and Tregs based on the spatial distribution of single cells highlighted midkine (MDK) as a prominent signalling molecule sent from tumour epithelial cells to Tregs. Interaction between MDK-high CRC cells and SPP1+ macrophages and stromal cells proved to be the mechanism underlying immunosuppression in the TME. Additionally, we identified syndecan4 (SDC4) as a receptor for MDK associated with Treg colocalisation. Finally, clinical analysis using CRC datasets indicated that increased MDK/SDC4 levels correlated with poor overall survival in CRC patients. INTERPRETATION: MDK is involved in the immune tolerance shown by Tregs to tumour growth. MDK-mediated formation of the TME could be a potential target for early diagnosis and treatment of CRC. FUNDING: Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Science Research; OITA Cancer Research Foundation; AMED under Grant Number; Japan Science and Technology Agency (JST); Takeda Science Foundation; The Princess Takamatsu Cancer Research Fund.

Japanese Classification of Esophageal Cancer, 12th Edition: Part I.

This is the first half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

Application of a laparoscopic device for cell-derived sheet transplantation on the liver in a porcine model.

BACKGROUND: Cell-derived sheets are of global interest for regenerative therapy. Transplanting a sheet for abdominal organs requires a device for laparoscopic delivery to minimize invasiveness. Here, using a porcine model, we aimed to confirm the feasibility of a device developed to deliver sheets to the thoracic cavity in a laparoscopic transplantation procedure. MATERIAL AND METHODS: We used the device to transplant human skeletal myoblast cell sheets onto the liver and measured extra-corporeal, intra-abdominal, and total procedure times for sheet transplantation. Tissues, including the liver and the sheet, were collected two days after transplantation and analyzed histologically. RESULTS: In all experiments (n = 27), all sheets were successfully placed at target locations. The mean (± standard deviation) extra-corporeal, intra-abdominal, and total procedure times were 44 ± 29, 33 ± 12, and 77 ± 36 s, respectively. We found no difference between the two surgeons in procedure times. Histological analyses showed no liver damage with the transplantation and that sheets were transplanted closely onto the liver tissue without gaps. CONCLUSION: We confirmed the feasibility of a simple universal device to transplant cell-derived sheets via laparoscopic surgery. This device could support a minimally invasive procedure for sheet transplantation.

Results of a Randomized Clinical Study of Gemcitabine Plus Nab-Paclitaxel Versus Gemcitabine Plus S-1 as Neoadjuvant Chemotherapy for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma (RCT, CSGO-HBP-015).

BACKGROUND: The optimal neoadjuvant chemotherapy (NAC) regimen for patients with localized pancreatic ductal adenocarcinoma (PDAC) remains uncertain. This trial aimed to evaluate the efficacy and safety of two neoadjuvant chemotherapy (NAC) regimens, gemcitabine plus nab-paclitaxel (GA) and gemcitabine plus S-1 (GS), in patients with resectable/borderline-resectable (R/BR) PDAC. PATIENTS AND METHODS: Treatment-naïve patients with R/BR-PDAC were enrolled and randomly allocated. They received two cycles (2 months) of each standard protocol, followed by radical surgery for those without tumor progression in general hospitals belonging to our intergroup. The primary endpoint was to determine the superior regimen on the basis of achieving a 10% increase in the rate of patients with progression-free survival (PFS) at 2 years from allocation. RESULTS: A total of 100 patients were enrolled, with 94 patients randomly assigned to the GS arm (N = 46) or GA arm (N = 48). The 2-year PFS rates did not show the stipulated difference [GA, 31% (24-38%)/GS, 26% (18-33%)], but the Kaplan-Myer analysis showed significance (median PFS, GA/GS 14 months/9 months, P = 0.048; HR 0.71). Secondary endpoint comparisons yielded the following results (GA/GS arm, P-value): rates of severe adverse events during NAC, 73%/78%, P = 0.55; completion rates of the stipulated NAC, 92%/83%, P = 0.71; resection rates, 85%/72%, P = 0.10; average tumor marker (CA19-9) reduction rates, -50%/-21%, P = 0.01; average numbers of lymph node metastasis, 1.7/3.2, P = 0.04; and median overall survival times, 42/22 months, P = 0.26. CONCLUSIONS: This study found that GA and GS are viable neoadjuvant treatment regimens in R/BR-PDAC. Although the GA group exhibited a favorable PFS outcome, the primary endpoint was not achieved.

KLK10 derived from tumor endothelial cells accelerates colon cancer cell proliferation and hematogenous liver metastasis formation.

Tumor endothelial cells (TECs), which are thought to be structurally and functionally different from normal endothelial cells (NECs), are increasingly attracting attention as a therapeutic target in hypervascular malignancies. Although colorectal liver metastasis (CRLM) tumors are hypovascular, inhibitors of angiogenesis are a key drug in multidisciplinary therapy, and TECs might be involved in the development and progression of cancer. Here, we analyzed the function of TEC in the CRLM tumor microenvironment. We used a murine colon cancer cell line (CT26) and isolated TECs from CRLM tumors. TECs showed higher proliferation and migration than NECs. Coinjection of CT26 and TECs yielded rapid tumor formation in vivo. Immunofluorescence analysis showed that coinjection of CT26 and TECs increased vessel formation and Ki-67+ cells. Transcriptome analysis identified kallikrein-related peptide 10 (KLK10) as a candidate target. Coinjection of CT26 and TECs after KLK10 downregulation with siRNA suppressed tumor formation in vivo. TEC secretion of KLK10 decreased after KLK10 downregulation, and conditioned medium after KLK10 knockdown in TECs suppressed CT26 proliferative activity. Double immunofluorescence staining of KLK10 and CD31 in CRLM tissues revealed a significant correlation between poor prognosis and positive KLK10 expression in TECs and tumor cells. On multivariate analysis, KLK10 expression was an independent prognostic factor in disease-free survival. In conclusion, KLK10 derived from TECs accelerates colon cancer cell proliferation and hematogenous liver metastasis formation. KLK10 in TECs might offer a promising therapeutic target in CRLM.

Tumor suppressive role of the epigenetic master regulator BRD3 in colorectal cancer.

Bromodomain and extraterminal domain (BET) family proteins are epigenetic master regulators of gene expression via recognition of acetylated histones and recruitment of transcription factors and co-activators to chromatin. Hence, BET family proteins have emerged as promising therapeutic targets in cancer. In this study, we examined the functional role of bromodomain containing 3 (BRD3), a BET family protein, in colorectal cancer (CRC). In vitro and vivo analyses using BRD3-knockdown or BRD3-overexpressing CRC cells showed that BRD3 suppressed tumor growth and cell cycle G1/S transition and induced p21 expression. Clinical analysis of CRC datasets from our hospital or The Cancer Genome Atlas revealed that BET family genes, including BRD3, were overexpressed in tumor tissues. In immunohistochemical analyses, BRD3 was observed mainly in the nucleus of CRC cells. According to single-cell RNA sequencing in untreated CRC tissues, BRD3 was highly expressed in malignant epithelial cells, and cell cycle checkpoint-related pathways were enriched in the epithelial cells with high BRD3 expression. Spatial transcriptomic and single-cell RNA sequencing analyses of CRC tissues showed that BRD3 expression was positively associated with high p21 expression. Furthermore, overexpression of BRD3 combined with knockdown of, a driver gene in the BRD family, showed strong inhibition of CRC cells in vitro. In conclusion, we demonstrated a novel tumor suppressive role of BRD3 that inhibits tumor growth by cell cycle inhibition in part via induction of p21 expression. BRD3 activation might be a novel therapeutic approach for CRC.

Skeletal Muscle-Derived Irisin Enhances Gemcitabine Sensitivity and Suppresses Migration Ability in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: High skeletal muscle mass might be a prognostic factor for patients with pancreatic ductal adenocarcinoma (PDAC); however, the underlying reason is unclear. We hypothesized that myokines, which are cytokines secreted by the skeletal muscle, function as suppressors of PDAC. We specifically examined irisin, a myokine, which plays a critical role in the modulation of metabolism, to clarify the anticancer mechanisms. METHODS: First, the effect of the conditioned medium (CM) from skeletal muscle cells and from irisin-knockdown skeletal muscle cells on PDAC cell lines was evaluated. We then investigated the effects and anticancer mechanism of irisin in PDAC cells, and evaluated the anticancer effect of recombinant irisin in a PDAC xenograft mouse model. Finally, patients undergoing pancreatic resection for PDAC were divided into two groups based on their serum irisin level, and the long-term outcomes were evaluated. RESULTS: The CM enhanced gemcitabine sensitivity by inducing apoptosis and decreasing cell migration by inhibiting epithelial-mesenchymal transition (EMT) in PDAC cell lines. The CM derived from irisin-knockdown skeletal muscle cells did not affect the PDAC cell lines. The addition of recombinant irisin to PDAC cell lines facilitated sensitivity to gemcitabine by inhibiting the mitogen-activated protein kinase (MAPK) pathway, and decreased migration by inhibiting EMT via the transforming growth factor-ß/SMAD pathway. Xenografts injected with gemcitabine and recombinant irisin grew slower than the xenografts injected with gemcitabine alone. The overall survival was prolonged in the high-irisin group compared with that in the low-irisin group. CONCLUSIONS: Skeletal muscle-derived irisin may affect PDAC by enhancing its sensitivity to gemcitabine and suppressing EMT.

Long-term impact of replaced right hepatic artery resection in pancreaticoduodenectomy.

The clinical impact of replaced right hepatic artery (rRHA) resection during pancreaticoduodenectomy (PD) has not been thoroughly investigated. We therefore assessed the short- and long-term effects of rRHA resection during PD, with special reference to alterations in the volumetric profile of the liver. Patients with rRHA were divided into two groups based on the presence (R group) or absence (nR group) of resection. The nR group included cases of rRHA resection and reconstruction. We compared the postoperative short-term complications and detailed liver volume profile by CT volumetry in the long term between the R and nR groups. Forty-seven patients were eligible for the analyses of short-term outcomes (R: n = 7, nR: n = 40), and no marked difference was observed in the incidence of short-term postoperative complications. The patient cohort for the long-term investigations included 34 cases (R: n = 6, nR: n = 28), excluding patients with early recurrence. There was no significant difference in the preoperative liver volume profiles between the two groups. At 12 postoperative months, although the whole liver (WL) volume did not significantly change in either group, the ratio of the volume of the anterior/posterior sections significantly increased in the R group (R: pre- vs. 12 months, 1.01 vs. 1.28, p < 0.05; nR: pre- vs. 12 months, 1.40 vs. 1.33, p = 0.99). Long-term rRHA resection did not significantly affect the WL volume with alteration of the liver volumetric profile of each section.

Serum NY-ESO-1 and p53 antibodies as useful tumor markers in gastric cancer.

Purpose: The NY-ESO-1 antigen is highly immunogenic and often spontaneously induces an immune response in patients with cancer. We conducted a large-scale multicenter cohort study to investigate the utility of serum NY-ESO-1 and p53 antibodies as predictive markers for the postoperative recurrence of gastric cancer. Here, we examined the usefulness of pre-treatment NY-ESO-1 and p53 antibodies as tumor markers for the diagnosis of gastric cancer in combination with carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). Methods: A total of 1031 patients with cT3-4 gastric cancer were enrolled in the study. NY-ESO-1 and p53 antibodies were assessed prior to treatment. The positivity of NY-ESO-1 and p53 antibodies, CEA, and CA19-9 was evaluated before treatment. Results: Serum NY-ESO-1 and p53 antibodies were positive in 12.6% and 18.1% of the patients, respectively. Positive NY-ESO-1 antibody response was correlated with male gender, higher cStage, and upper tumor location. However, a positive p53 antibody response was not associated with tumor factors. The combination of NY-ESO-1 or p53 antibody response with CEA and CA19-9, or the 4-factors, was positive in 45.1%, 49.6%, and 53.8% of patients, respectively. Moreover, the 4-factor combination was able to detect >60% of cStage III-IV diseases, which was 14% higher than that with the combination of CEA and CA19-9. Conclusion: The combination of NY-ESO-1 and p53 antibody responses to CEA and CA19-9 increases the diagnostic accuracy of gastric cancer. Serum NY-ESO-1 and p53 antibodies may be useful tumor markers for gastric cancer.

Japanese Classification of Esophageal Cancer, 12th Edition: Part II.

This is the second half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

The role of anterior gastropexy in elderly Japanese hiatal hernia patients.

PURPOSE: As Japanese society ages, the number of surgeries performed in elderly patients with hiatal hernia (HH) is increasing. In this study, we examined the feasibility, safety, and potential effectiveness of the addition of anterior gastropexy to hiatoplasty with or without mesh repair and/or fundoplication in elderly Japanese HH patients. METHODS: We retrospectively evaluated 39 patients who underwent laparoscopic HH repair between 2010 and 2021. We divided them into 2 groups according to age: the "younger" group (< 75 years old, n = 21), and the "older" group (≥ 75 years old, n = 18). The patient characteristics, intraoperative data, and postoperative results were collected. RESULTS: The median ages were 68 and 82 years old in the younger and older groups, respectively, and the female ratio was similar between the groups (younger vs. older: 67% vs. 78%, p = 0.44). The older group had more type III/IV HH cases than the younger group (19% vs. 83%, p < 0.001). The operation time was longer in the older group than in the younger group, but there was no significant difference in blood loss, perioperative complications, or postoperative length of stay between the groups. The older group had significantly more cases of anterior gastropexy (0% vs. 78%, p < 0.001) and less fundoplication (100% vs. 67%, p = 0.004) than the younger group. There was no significant difference in HH recurrence between the groups (5% vs. 11%, p = 0.46). CONCLUSIONS: The addition of anterior gastropexy to other procedures is feasible, safe, and potentially effective in elderly Japanese patients with HH.

Circulating tumor-associated antigen-specific IFNγ+4-1BB+ CD8+ T cells as peripheral biomarkers of treatment outcomes in patients with pancreatic cancer.

CD8+ T cells affect the outcomes of pancreatic ductal adenocarcinoma (PDAC). Using tissue samples at pre-treatment to monitor the immune response is challenging, while blood samples are beneficial in overcoming this limitation. In this study, we measured peripheral antigen-specific CD8+ T cell responses against four different tumor-associated antigens (TAAs) in PDAC using flow cytometry and investigated their relationships with clinical features. We analyzed the optimal timing within the treatment course for effective immune checkpoint inhibition in vitro. We demonstrated that the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells was correlated with a fold reduction in CA19-9 before and after neoadjuvant therapy. Moreover, patients with TAA-specific IFNγ+4-1BB+ CD8+ T cells after surgery exhibited a significantly improved disease-free survival. Anti-PD-1 treatment in vitro increased the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells before neoadjuvant therapy in patients, suggesting the importance of the timing of anti-PD-1 inhibition during the treatment regimen. Our results indicate that peripheral immunophenotyping, combined with highly sensitive identification of TAA-specific responses in vitro as well as detailed CD8+ T cell subset profiling via ex vivo analysis, may serve as peripheral biomarkers to predict treatment outcomes and therapeutic efficacy of immunotherapy plus neoadjuvant chemotherapy.

Venous Thromboembolism Following Lateral Lymph Node Dissection for Rectal Cancer.

BACKGROUND/AIM: Postoperative venous thromboembolism (VTE) is a well-recognized complication that leads to morbidity and mortality. Lateral lymph node dissection (LLND) for rectal cancer is thought to potentially increase the risk of VTE due to its technical complexity. However, the relationship between LLND and VTE remains inadequately understood. The aim of this study was to elucidate the impact of LLND on the incidence of postoperative VTE. PATIENTS AND METHODS: This is a retrospective analysis of patients who underwent rectal cancer resection between 2010 and 2018 to identify the risk factors associated with postoperative VTE. Patients were divided into two groups: those who underwent surgery with LLND (LLND+ group) and those who underwent surgery without LLND (LLND- group). RESULTS: A total of 543 patients were enrolled in this study, and 113 patients underwent surgery for rectal cancer with LLND. VTE developed in 8 patients (1.47%), with the incidence rates being 4.42% in the LLND+ group and 0.69% in the LLND- group, respectively (p=0.012). Three of 8 patients had developed severe postoperative complications, and the other two patients needed intraoperative repair of the iliac vein during LLND procedure. Multivariate analysis identified the incidence of postoperative complications and LLND as the independent risk factors of VTE. CONCLUSION: Patients undergoing rectal cancer surgery with LLND should be closely monitored for signs of VTE.

Remarkable response as a new indicator for endoscopic evaluation of local efficacy of non-surgical treatments for esophageal cancer.

In Japan, standard of care of the patients with resectable esophageal cancer is neoadjuvant chemotherapy (NAC) followed by esophagectomy. Patients unfitted for surgery or with unresectable locally advanced esophageal cancer are generally indicated with definitive chemoradiotherapy (CRT). Local disease control is undoubtful important for the management of patients with esophageal cancer, therefore endoscopic evaluation of local efficacy after non-surgical treatments must be essential. The significant shrink of primary site after NAC has been reported as a good indicator of pathological good response as well as favorable survival outcome after esophagectomy. And patients who could achieve remarkable shrink to T1 level after CRT had favorable outcomes with salvage surgery and could be good candidates for salvage endoscopic treatments. Based on these data, "Japanese Classification of Esophageal Cancer, 12th edition" defined the new endoscopic criteria "remarkable response (RR)", that means significant volume reduction after treatment, with the subjective endoscopic evaluation are proposed. In addition, the finding of local recurrence (LR) at primary site after achieving a CR was also proposed in the latest edition of Japanese Classification of Esophageal Cancer. The findings of LR are also important for detecting candidates for salvage endoscopic treatments at an early timing during surveillance after CRT. The endoscopic evaluation would encourage us to make concrete decisions for further treatment indications, therefore physicians treating patients with esophageal cancer should be well-acquainted with each finding.

Investigation of Expanded Human Adipose-derived Stem Cell Dosage and Timing for Improved Defecation Function.

BACKGROUND/AIM: Although certain treatment options exist for intestinal incontinence, none are curative. Adipose-derived stem cells (ADSCs) have emerged as promising therapeutic agents, but most preclinical studies of their effectiveness for anal function have used autologous or allogeneic ADSCs. In this study, the effectiveness, timing of administration, and required dosage of human ADSCs were investigated for clinical application. MATERIALS AND METHODS: A 10-mm balloon catheter was used to induce anal sphincter injury in immunodeficient mice in the following experimental groups (n=4 per group): ADSC (injected ADSCs after injury), PBS (injected phosphate-buffered saline after injury), and control (uninjured). The effects of different timing (immediately after injection and 30 days following injury) and number of human ADSCs administered was compared among groups based on defecation status and pathological evaluation. RESULTS: In terms of defecation status, groups receiving ≥1×104 human ADSCs after injection showed improvement. Pathological images showed that compared to the PBS group, the thinnest part of the sphincter was thicker for animals that received ≥1×104 human ADSCs, and fibrosis of the sphincter was notable in those treated with 1×103 human ADSCs or PBS. Furthermore, defecation status was improved by administration of human ADSCs, not only immediately after injury, but also at 30 days following injury. CONCLUSION: Human ADSC administration in a mouse model of anal sphincter injury was effective. Injection of ≥1×104 human ADSCs was the amount necessary to improve defecation status, an effect detected in both the acute and chronic phases.

Recurrence-free survival as a surrogate endpoint for overall survival after neoadjuvant chemotherapy and surgery for oesophageal squamous cell carcinoma.

BACKGROUND: Overall survival is considered as one of the most important endpoints of treatment efficacy but often requires long follow-up. This study aimed to determine the validity of recurrence-free survival as a surrogate endpoint for overall survival in patients with surgically resectable advanced oesophageal squamous cell carcinoma (OSCC). METHODS: Patients with OSCC who received neoadjuvant cisplatin and 5-fluorouracil, or docetaxel, cisplatin and 5-fluorouracil, at 58 Japanese oesophageal centres certified by the Japan Esophageal Society were reviewed retrospectively. The correlation between recurrence-free and overall survival was assessed using Kendall's τ. RESULTS: The study included 3154 patients. The 5-year overall and recurrence-free survival rates were 56.6 and 47.7% respectively. The primary analysis revealed a strong correlation between recurrence-free and overall survival (Kendall's τ 0.797, 95% c.i. 0.782 to 0.812) at the individual level. Subgroup analysis showed a positive relationship between a more favourable pathological response to neoadjuvant chemotherapy and a higher τ value. In the meta-regression model, the adjusted R2 value at the institutional level was 100 (95% c.i. 40.2 to 100)%. The surrogate threshold effect was 0.703. CONCLUSION: There was a strong correlation between recurrence-free and overall survival in patients with surgically resectable OSCC who underwent neoadjuvant chemotherapy, and this was more pronounced in patients with a better response to neoadjuvant chemotherapy.

Innovative device for surgical wound irrigation: a preclinical testing and pilot clinical validation study.

INTRODUCTION: Surgical site infection (SSI) poses a substantial postoperative challenge, affecting patient recovery and healthcare costs. While surgical wound irrigation is pivotal in SSI reduction, consensus on the optimal method remains elusive. We developed a novel device for surgical wound irrigation and conducted preclinical and clinical evaluations to evaluate its efficacy and safety. METHODS: Two preclinical experiments using swine were performed. In the washability test, two contaminated wound model were established, and the cleansing rate between the device and the conventional method were compared. In the contamination test, the irrigation procedure with a fluorescent solution assessed the surrounding contamination of drapes. Subsequently, a clinical trial involving patients undergoing abdominal surgery was conducted. RESULTS: The washability test demonstrated significantly higher cleansing rates with the device method (86.4% and 82.5%) compared to the conventional method (65.2% and 65.1%) in two contamination models. The contamination test revealed a smaller contaminated region with the device method than the conventional method. In the clinical trial involving 17 abdominal surgery cases, no superficial SSIs or adverse events related to device use were observed. CONCLUSIONS: Our newly developed device exhibits potential for achieving more effective and safe SSI control compared to conventional wound irrigation.

Humoral and cellular immune responses to COVID-19 mRNA vaccines in immunosuppressed liver transplant recipients.

BACKGROUND: Liver transplant recipients (LTRs) are at a high risk of severe COVID-19 owing to immunosuppression and comorbidities. LTRs are less responsive to mRNA vaccines than healthy donors (HDs) or other immunosuppressed patients. However, the disruption mechanism in humoral and cellular immune memory responses is unclear. METHODS: We longitudinally collected peripheral blood mononuclear cells and plasma samples from HDs (n = 44) and LTRs (n = 54) who received BNT162b2 or mRNA-1273 vaccines. We measured the levels of anti-receptor-binding domain (RBD) antibodies and spike-specific CD4+ and CD8+ T-cell responses. RESULTS: Here, we show that the induction of anti-RBD IgG was weaker in LTRs than in HDs. The use of multiple immunosuppressive drugs is associated with lower antibody titers than only calcineurin inhibitor, and limits the induction of CD4+ T-cell responses. However, spike-specific CD4+ T-cell and antibody responses improved with a third vaccination. Furthermore, mRNA vaccine-induced spike-specific CD8+ T cells are quantitatively, but not qualitatively, limited to LTRs. Both CD4+ and CD8+ T cells react to omicron sublineages, regardless of the presence in HDs or LTRs. However, there is no boosting effect of spike-specific memory CD8+ T-cell responses after a third vaccination in HDs or LTRs. CONCLUSIONS: The third mRNA vaccination improves both humoral responses and spike-specific CD4+ T-cell responses in LTRs but provides no booster effect for spike-specific memory CD8+ T-cell responses. A third mRNA vaccination could be helpful in LTRs to prevent severe COVID-19, although further investigation is required to elicit CD8+ T-cell responses in LTRs and HDs.

People with a liver transplant don't have as strong an immune response to COVID-19 vaccines as healthy people. This study investigates how these individuals produce protective proteins, called antibodies, and CD4 and CD8 T cell immune responses. CD4 T cells are responsible for commanding the immune response and CD8 T cells for remembering and fighting the virus in future. We found that liver transplant recipients have a weaker ability to produce antibodies after vaccination, which is even more noticeable in those taking drugs to prevent transplant rejection. While a third vaccine dose improves their ability to produce antibodies, and to have a CD4 T cell response, it doesn't boost the CD8 T cell response. In summary, an extra vaccine dose can strengthen the immune response in liver transplant recipients but doesn't improve some aspects of their immune memory.