Neutrophil extracellular traps promote immune escape in hepatocellular carcinoma by up-regulating CD73 through Notch2.

Immune escape is the main reason that immunotherapy is ineffective in hepatocellular carcinoma (HCC). Here, this study illustrates a pathway mediated by neutrophil extracellular traps (NETs) that can promote immune escape of HCC. Mechanistically, we demonstrated that NETs up-regulated CD73 expression through activating Notch2 mediated nuclear factor kappa B (NF-κB) pathway, promoting regulatory T cells (Tregs) infiltration to mediate immune escape of HCC. In addition, we found the similar results in mouse HCC models by hydrodynamic plasmid transfection. The treatment of deoxyribonuclease I (DNase I) could inhibit the action of NETs and improve the therapeutic effect of anti-programmed cell death protein 1 (PD-1). In summary, our results revealed that targeting of NETs was a promising treatment to improve the therapeutic effect of anti-PD-1.

Construction of m7G RNA modification-related prognostic model and prediction of immune therapy response in hepatocellular carcinoma.

Background: RNA plays an important role in tumorigenesis. Changes in RNA may cause changes in the biological function. The N7-methylguanosine (m7G) methylation modification performs an integral function in tumor progression as the most widely existed RNA modification. Hepatocellular carcinoma (HCC) is among the greatest threats to human health worldwide. Low detection rates remain the main cause of advanced disease progression. Therefore, finding significant biomarkers for prognosis prediction and immune therapy response in HCC is valuable and urgently needed. Methods: RNA expression and clinical data were acquired from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. Different subtypes screening was finished by consensus cluster. Different expression was performed by R software. The results were validated by western blot (WB) methods. Genes with HCC prognostic potential were identified utilizing least absolute shrinkage and selection operator (LASSO) analyses. A prognosis model was established with the help of the risk score that we calculated. Related genes screening and protein-protein interactions (PPI) network construction were performed using the GeneMANIA database. Functional annotation was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) databases. In addition, gene set enrichment analysis (GSEA) of key genes and immune infiltration status were both done by R software. Finally, the immune infiltration was performed by cibersort method and single sample GSEA (ssGSEA) method. The response of immune therapy was validated by Tumor Immune Dysfunction and Exclusion database (TIDE) and the immune therapy cohort in GEO database. Results: We found that two different subtypes related with m7G RNA modification and four genes associated with m7G RNA modification were differentially expressed in the TCGA-Liver Hepatocellular Carcinoma (TCGA-LIHC) database. Additionally, to examine the value of these four genes in the HCC patients' prognoses according to the LASSO, we selected three genes, including WDR4, AGO2, and NCBP2, as prognostic related genes. Premised on the expression of these three genes, a risk score model and nomogram were constructed to provide a prediction of the HCC patients' prognoses. We performed functional annotation and created a PPI network based on the three genes (WDR4, NCBP2, and AGO2). Using R software, we performed the GSEA and immune regulation analyses. Finally, we predicted the relationship between the gene expression and the response of immune therapy. Conclusions: Our study suggests that high expression of m7G RNA modification subtype is related with poor prognosis and immune response. WDR4, AGO2, and NCBP2 are key regulators of m7G RNA modification which can be clinically promising biomarkers that can be used to treat HCC. In addition, our risk score model was shown to have a strong link to OS in patients with HCC.

Reoperation for ipsilateral local recurrence following prior nephron-sparing surgery: innovative surgical insights from a high-volume urological center with cross-sectional study.

BACKGROUND: The main aim of this study was to examine the perioperative results of reoperations and suggest novel surgical approaches. Based on a substantial number of robotic and laparoscopic nephron-sparing surgery (NSS), we aim to propose novel surgical strategies that offer practical recommendations to surgeons. METHODS: Renal cell carcinoma patients with ipsilateral recurrent tumors, without evidence of metastasis, and who underwent primary NSS at our center between 2013 and 2023 were enrolled in this study, and all received the second time surgery. We conducted an analysis to evaluate perioperative outcomes and observed trends over a decade. Additionally, based on the findings from this study, we developed our surgical strategies. RESULTS: In the past decade, our center has successfully conducted a total of 2546 surgeries for renal cell carcinoma, out of which this study includes 15 patients who met the specified criteria. For reoperation, robotic-assisted surgery was applied in 5 cases (33.3%), laparoscopic surgery in 6 cases (40%), and open surgeries in 4 cases (26.7%). While 4 (26.7%) patients underwent NSS while radical nephrectomy was performed on 11 patients (73.3%). The median operative time was 215 minutes (IQR: 135-300), and the median estimated blood loss was 50 ml (IQR: 50-100). The median length of postoperative hospitalization was 6 days (IQR: 5-9). Furthermore, there has been a yearly increase in the application of robotic-assisted NSS at our institution. CONCLUSION: Reoperation following the pNSS is a secure and effective surgical approach. We introduce novel surgical strategies for primary surgery and reoperation, which offer valuable insights to surgeons in current study.

Chemo-photothermal therapy of chitosan/gold nanorod clusters for antibacterial treatment against the infection of planktonic and biofilm MRSA.

Bacterial infections trigger inflammation and impede the closure of skin wounds. The misuse of antibiotics exacerbates skin infections by generating multidrug-resistant bacteria. In this study, we developed chemo-photothermal therapy (chemo-PTT) based on near-infrared (NIR)-irradiated chitosan/gold nanorod (GNR) clusters as anti-methicillin-resistant Staphylococcus aureus (MRSA) agents. The nanocomposites exhibited an average size of 223 nm with a surface charge of 36 mV. These plasmonic nanocomposites demonstrated on-demand and rapid hyperthermal action under NIR. The combined effect of positive charge and PTT by NIR-irradiated nanocomposites resulted in a remarkable inhibition rate of 96 % against planktonic MRSA, indicating a synergistic activity compared to chitosan nanoparticles or GNR alone. The nanocomposites easily penetrated the biofilm matrix. The combination of chemical and photothermal treatments by NIR-stimulated clusters significantly damaged the biofilm structure, eradicating MRSA inside the biomass. NIR-irradiated chitosan/GNR clusters increased the skin temperature of mice by 13 °C. The plasmonic nanocomposites induced negligible skin irritation in vivo. In summary, this novel nanosystem demonstrated potent antibacterial effects against planktonic and biofilm MRSA, showcasing the possible efficacy in treating skin infections.

Serum alpha-fetoprotein response as a preoperative prognostic indicator in unresectable hepatocellular carcinoma with salvage hepatectomy following conversion therapy: a multicenter retrospective study.

Background: This study evaluates the efficacy of alpha-fetoprotein (AFP) response as a surrogate marker for determining recurrence-free survival (RFS) in patients with unresectable hepatocellular carcinoma (uHCC) who undergo salvage hepatectomy following conversion therapy with tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody-based regimen. Methods: This multicenter retrospective study included 74 patients with uHCC and positive AFP (>20 ng/mL) at diagnosis, who underwent salvage hepatectomy after treatment with TKIs and anti-PD-1 antibody-based regimens. The association between AFP response-defined as a ≥ 80% decrease in final AFP levels before salvage hepatectomy from diagnosis-and RFS post-hepatectomy was investigated. Results: AFP responders demonstrated significantly better postoperative RFS compared to non-responders (P<0.001). The median RFS was not reached for AFP responders, with 1-year and 2-year RFS rates of 81.3% and 70.8%, respectively. In contrast, AFP non-responders had a median RFS of 7.43 months, with 1-year and 2-year RFS rates at 37.1% and 37.1%, respectively. Multivariate Cox regression analysis identified AFP response as an independent predictor of RFS. Integrating AFP response with radiologic tumor response facilitated further stratification of patients into distinct risk categories: those with radiologic remission experienced the most favorable RFS, followed by patients with partial response/stable disease and AFP response, and the least favorable RFS among patients with partial response/stable disease but without AFP response. Sensitivity analyses further confirmed the association between AFP response and improved RFS across various cutoff values and in patients with AFP ≥ 200 ng/mL at diagnosis (all P<0.05). Conclusion: The "20-80" rule based on AFP response could be helpful for clinicians to preoperatively stratify the risk of patients undergoing salvage hepatectomy, enabling identification and management of those unlikely to benefit from this procedure.

Antibiotic exposure during pregnancy increases risk for childhood atopic diseases: a nationwide cohort study.

PURPOSE: The prevalence of atopic diseases has increased in recent decades. A possible link between antibiotic use during pregnancy and childhood atopic disease has been proposed. The aim of this study is to explore the association of antibiotic exposure during pregnancy with childhood atopic diseases from a nationwide, population-based perspective. METHODS: This was a nationwide population-based cohort study. Taiwan's National Health Insurance Research Database was the main source of data. The pairing of mothers and children was achieved by linking the NHIRD with the Taiwan Maternal and Child Health Database. This study enrolled the first-time pregnancies from 2004 to 2010. Infants of multiple delivery, preterm delivery, and death before 5 years old were excluded. All participants were followed up at least for 5 years. Antenatal antibiotics prescribed to mothers during the pregnancy period were reviewed. Children with more than two outpatient visits, or one admission, with a main diagnosis of asthma, allergic rhinitis, or atopic dermatitis were regarded as having an atopic disease. RESULTS: A total of 900,584 children were enrolled in this study. The adjusted hazard ratios of antibiotic exposure during pregnancy to childhood atopic diseases were 1.12 for atopic dermatitis, 1.06 for asthma, and 1.08 for allergic rhinitis, all of which reached statistical significance. The trimester effect was not significant. There was a trend showing the higher the number of times a child was prenatally exposed to antibiotics, the higher the hazard ratio was for childhood atopic diseases. CONCLUSIONS: Prenatal antibiotic exposure might increase the risk of childhood atopic diseases in a dose-dependent manner.

Dual deficiency of melatonin and dihydrotestosterone promotes stromal cell damage and mediates prostatitis via the cGAS-STING pathway in sleep-deprived mice.

PURPOSE: Prostatitis is a highly prevalent condition that seriously affects men's physical and mental health. Although epidemiological investigations have provided evidence of a correlation between insufficient sleep and prostatitis, the pathogenesis of prostatitis remains unclear. We sought to identify the underlying mechanism involved and identify a promising therapeutic target. METHODS: Sleep deprivation (SD) was utilized to establish a mouse model of insufficient sleep in a special device. Prostatitis was observed at different time points post-SD. The degree of prostatitis was evaluated by pathological section and behavioural tests. Using immunofluorescence, western blot, and proteomic analyses, the underlying mechanism of SD-related prostatitis was investigated, and the development and therapeutic target of prostatitis were elucidated. RESULTS: SD, as an initial pathological trigger, resulted in a reduction in dihydrotestosterone and melatonin levels. Proteomic analysis revealed that the cGAS-STING pathway may play a significant role in inducing prostatitis. The subsequent results illustrated that the dual reduction in dihydrotestosterone and melatonin led to an accumulation of reactive oxygen species and the release of mitochondrial DNA (mt-DNA). The accumulation of mt-DNA activated the cGAS-STING pathway, which recruited inflammatory cells into the prostatic stroma through the secretion of interferon-ß. Consequently, an inflammatory microenvironment was formed, ultimately promoting the development of prostatitis. Notably, mice with SD-induced prostatitis gradually recovered to a normal state within 7 days of recovery sleep. However, after being subjected to SD again, these mice tended to have a more pronounced manifestation of prostatitis within a shorter timeframe, which suggested that prostatitis is prone to relapse. CONCLUSIONS: The cGAS-STING pathway activated by dual deficiency of dihydrotestosterone and melatonin plays a comprehensive inflammatory role in SD-related prostatitis. This research provides valuable insights into the pathogenesis, therapeutic targets, and prevention strategies of prostatitis.

Modulations of ocean-atmosphere interactions on squid abundance over Southwest Atlantic.

Anthropogenic shifts in seas are reshaping fishing trends, with significant implications for aquatic food sources throughout this century. Examining a 21-year abundance dataset of Argentine shortfin squids Illex argentinus paired with a regional oceanic analysis, we noted strong correlations between squid annual abundance and sea surface temperature (SST) in January and February and eddy kinetic energy (EKE) from March to May in the Southwest Atlantic. A deeper analysis revealed combined ocean-atmosphere interactions, pinpointed as the primary mode in a rotated empirical orthogonal function analysis of SST. This pattern produced colder SST and amplified EKE in the surrounding seas, factors crucial for the unique life stages of squids. Future projections from the CMIP6 archive indicated that this ocean-atmosphere pattern, referred to as the Atlantic symmetric pattern, would persist in its cold SST phase, promoting increased squid abundance. However, rising SSTs due to global warming might counteract the abundance gains. Our findings uncover a previously unrecognized link between squids and specific environmental conditions governed by broader ocean-atmosphere interactions in the Southwest Atlantic. Integrating these insights with seasonal and decadal projections can offer invaluable information to stakeholders in squid fisheries and marine conservation under a changing climate.

The scaffold of neutrophil extracellular traps promotes CCA progression and modulates angiogenesis via ITGAV/NFκB.

Neutrophil extracellular traps (NETs) have garnered attention for their dual role in host defense and tumor promotion. With their involvement documented across a spectrum of tumors, their influence on the progression of cholangiocarcinoma (CCA) is of paramount interest. We employed immunohistochemistry and immunofluorescence to detect NET deposition in CCA tissues. Through in vitro and in vivo investigation, including CCA organoid and transposon-based models in PAD4 KO mice, we explored the effects of NETs on cell proliferation and metastasis. Molecular insights were gained through RNA sequencing, enzyme linked immunosorbent assay, and chromatin immunoprecipitation. Elevated intratumoral NET deposition within CCA tissues was associated with poor survival. The influence of NETs on CCA proliferation, migration and invasion was primarily mediated by NET-DNA. RNA sequencing unveiled the activation of the NFκB signaling pathway due to NET-DNA stimulation. NET-DNA pull-down assay coupled with mass spectrometry revealed the interaction between NET-DNA and αV integrin (ITGAV), culmination in the activation of the NFκB pathway. Furthermore, NET-DNA directly upregulated the expression of VEGF-A in cancer cells. The study unequivocally establishes NETs as facilitators of CCA progression, orchestrating proliferation, metastasis, and angiogenesis through ITGAV/NFκB pathway activation. This novel insight positions NETs as prospective therapeutic targets for managing CCA patients. By implementing a variety of methodologies and drawing intricate connections between NETs, DNA interactions, and signaling pathways, this research expands our comprehension of the complex interplay between the immune system and cancer progression, offering promising avenues for intervention.

PD-L1 inhibitor plus gemcitabine and cisplatin therapy followed by conversion surgery for initially unresectable advanced gallbladder cancer.

Advanced gallbladder cancer (GBC) is not amenable to surgical resection. There are limited treatment options and the prognosis is dismal. The role of immune checkpoint inhibitors in conversion therapy remains unclear for initially unresectable advanced GBC. We present a case of a woman in her late 60s diagnosed with stage IV GBC with liver and para-aortic and retroperitoneal lymph node metastases, who achieved a pathological complete response after three cycles of programmed cell death-ligand 1 inhibitor durvalumab combined with gemcitabine and cisplatin regimen and underwent conversion surgery without complication. The patient went on to develop disease progression without adjuvant therapy 6 months after surgery.

A Novel Allogeneic Rituximab-Conjugated Gamma Delta T Cell Therapy for the Treatment of Relapsed/Refractory B-Cell Lymphoma.

Chimeric antigen receptor T cell (CAR-T) therapy has been applied in the treatment of B-cell lymphoma; however, CAR-T manufacturing requires virus- or non-virus-based genetic modification, which causes high manufacturing costs and potential safety concerns. Antibody-cell conjugation (ACC) technology, which originated from bio-orthogonal click chemistry, provides an efficient approach for arming immune cells with cancer-targeting antibodies without genetic modification. Here, we applied ACC technology in Vγ9Vδ2 T (γδ2 T) cells to generate a novel off-the-shelf CD20-targeting cell therapy ACE1831 (rituximab-conjugated γδ2 T cells) against relapsed/refractory B-cell lymphoma. ACE1831 exhibited superior cytotoxicity against B-cell lymphoma cells and rituximab-resistant cells compared to γδ2 T cells without rituximab conjugation. The in vivo xenograft study demonstrated that ACE1831 treatment strongly suppressed the aggressive proliferation of B-cell lymphoma and prolonged the survival of tumor-bearing mice with no observed toxicity. Mass spectrometry analysis indicated that cell activation receptors including the TCR complex, integrins and cytokine receptors were conjugated with rituximab. Intriguingly, the antigen recognition of the ACC-linked antibody/receptor complex stimulated NFAT activation and contributed to ACE1831-mediated cytotoxicity against CD20-expressing cancer cells. This study elucidates the role of the ACC-linked antibody/receptor complex in cytotoxicity and supports the potential of ACE1831 as an off-the-shelf γδ2 cell therapy against relapsed/refractory B-cell lymphoma.

Bioaerosols are the dominant source of warm-temperature immersion-mode INPs and drive uncertainties in INP predictability.

Ice-nucleating particles (INPs) are rare atmospheric aerosols that initiate primary ice formation, but accurately simulating their concentrations and variability in large-scale climate models remains a challenge. Doing so requires both simulating major particle sources and parameterizing their ice nucleation (IN) efficiency. Validating and improving model predictions of INP concentrations requires measuring their concentrations delineated by particle type. We present a method to speciate INP concentrations into contributions from dust, sea spray aerosol (SSA), and bioaerosol. Field campaign data from Bodega Bay, California, showed that bioaerosols were the primary source of INPs between -12° and -20°C, while dust was a minor source and SSA had little impact. We found that recent parameterizations for dust and SSA accurately predicted ambient INP concentrations. However, the model did not skillfully simulate bioaerosol INPs, suggesting a need for further research to identify major factors controlling their emissions and INP efficiency for improved representation in models.

Deep Learning-Based Automatic Duckweed Counting Using StarDist and Its Application on Measuring Growth Inhibition Potential of Rare Earth Elements as Contaminants of Emerging Concerns.

In recent years, there have been efforts to utilize surface water as a power source, material, and food. However, these efforts are impeded due to the vast amounts of contaminants and emerging contaminants introduced by anthropogenic activities. Herbicides such as Glyphosate and Glufosinate are commonly known to contaminate surface water through agricultural industries. In contrast, some emerging contaminants, such as rare earth elements, have started to enter the surface water from the production and waste of electronic products. Duckweeds are angiosperms from the Lemnaceae family and have been used for toxicity tests in aquatic environments, mainly those from the genus Lemna, and have been approved by OECD. In this study, we used duckweed from the genus Wolffia, which is smaller and considered a good indicator of metal pollutants in the aquatic environment. The growth rate of duckweed is the most common endpoint in observing pollutant toxicity. In order to observe and mark the fronds automatically, we used StarDist, a machine learning-based tool. StarDist is available as a plugin in ImageJ, simplifying and assisting the counting process. Python also helps arrange, manage, and calculate the inhibition percentage after duckweeds are exposed to contaminants. The toxicity test results showed Dysprosium to be the most toxic, with an IC50 value of 14.6 ppm, and Samarium as the least toxic, with an IC50 value of 279.4 ppm. In summary, we can provide a workflow for automatic frond counting using StarDist integrated with ImageJ and Python to simplify the detection, counting, data management, and calculation process.

Digestive system deep infiltrating endometriosis: What do we know.

Digestive system infiltrating endometriosis (DSIE) is an uncommon form of endometriosis in the digestive system. DSIE often occurs in the intestines (especially the sigmoid rectum), liver, gallbladder and pancreas. Clinically, DSIE presents with the same symptoms as endometriosis, including cyclic pain, bleeding and infertility, in addition to specific biliary/intestinal obstruction and gastrointestinal bleeding. Compared to general endometriosis, DSIE has unique biological behaviour and pathophysiological mechanisms. Most DSIEs are deep invasive endometrioses, characterized by metastasis to the lymph nodes and lymphatic vessels, angiogenesis, peripheral nerve recruitment, fibrosis and invasion of surrounding tissues. DSIE-related peripheral angiogenesis is divided into three patterns: angiogenesis, vasculogenesis and inosculation. These patterns are regulated by interactions between multiple hypoxia-hormone cytokines. The nerve growth factors regulate the extensive neurofibril recruitment in DSIE lesions, which accounts for severe symptoms of deep pain. They are also associated with fibrosis and the aggressiveness of DSIE. Cyclic changes in DSIE lesions, recurrent inflammation and oxidative stress promote repeated tissue injury and repair (ReTIAR) mechanisms in the lesions, accelerating fibril formation and cancer-related mutations. Similar to malignant tumours, DSIE can also exhibit aggressiveness derived from collective cell migration mediated by E-cadherin and N-cadherin. This often makes DSIE misdiagnosed as a malignant tumour of the digestive system in clinical practice. In addition to surgery, novel treatments are urgently required to effectively eradicate this lesion.

Genomic profiles of renal cell carcinoma in a small Chinese cohort.

Objectives: Our aim was to describe the molecular characteristics of Renal Cell Carcinoma (RCC) and develop a small panel of RCC-associated genes from a large panel of cancer-related genes. Materials and methods: Clinical data of 55 patients with RCC diagnosed in four hospitals from September 2021 to August 2022 were collected. Among the 55 patients, 38 were diagnosed with clear cell RCC (ccRCC), and the other 17 were diagnosed with non-clear cell RCC (nccRCC), including 10 cases of papillary renal cell carcinoma, 2 cases of hereditary leiomyomatosis and RCC syndrome (HLRCC), 1 eosinophilic papillary RCC, 1 tubular cystic carcinoma, 1 TFE3 gene fusion RCC, and 2 RCC with sarcomatoid differentiation. For each patient, 1123 cancer-related genes and 79 RCC-associated genes were analyzed. Results: The most frequent mutations in a large panel of 1123 cancer-related genes in the overall population of RCC patients were VHL (51%), PBRM1 (35%), BAP1 (16%), KMT2D (15%), PTPRD (15%), and SETD2 (15%). For ccRCC patients, mutations in VHL, PBRM1, BAP1, and SERD2 can reach 74%, 50%, 24%, and 18%, respectively, while for nccRCC patients, the most frequent mutation was FH (29%), MLH3 (24%), ARID1A (18%), KMT2D (18%), and CREBBP (18%). The germline mutation rate in all 55 patients reached 12.7% (five with FH, one with ATM, and one with RAD50). The small panel containing only 79 RCC-associated genes demonstrated that mutations of VHL, PBRM1, BAP1, and SETD2 in ccRCC patients were 74%, 50%, 24%, and 18% respectively, while for the nccRCC cohort, the most frequent mutations were FH (29%), ARID1A (18%), ATM (12%), MSH6 (12%), BRAF (12%), and KRAS (12%). For ccRCC patients, the spectrum of mutations by large and small panels was almost the same, while for nccRCC patients, the mutation spectrum showed some differences. Even though the most frequent mutations (FH and ARID1A) in nccRCC were both demonstrated by large panels and small panels, other less frequent mutations such as MLH3, KMT2D, and CREBBP were not shown by the small panel. Conclusion: Our study revealed that nccRCC is more heterogeneous than ccRCC. For nccRCC patients, the small panel shows a more clear profile of genetic characteristics by replacing MLH3, KMT2D, and CREBBP with ATM, MSH6, BRAF, and KRAS, which may help predict prognosis and make clinical decisions.

Development and validation of a prognostic model incorporating tumor thrombus grading for nonmetastatic clear cell renal cell carcinoma with tumor thrombus: A multicohort study.

There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole-exome sequencing on normal-tumor-thrombus-metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C-index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501-0.610, 0.667 versus 0.544-0.651, and 0.719 versus 0.511-0.700 for Training, China-Validation, and Poland-Validation cohorts, respectively). We constructed a risk predicting model, TT-GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT-GPS score displayed better discriminatory ability (OS, c-index: 0.706-0.840, AUC: 0.788-0.874; DFS, c-index: 0.691-0.717, AUC: 0.771-0.789) than previously reported models in risk assessment. In conclusion, we identified for the first-time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT-GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.

Perioperative safety, oncologic outcome, and risk factors of salvage liver resection for initially unresectable hepatocellular carcinoma converted by transarterial chemoembolization plus tyrosine kinase inhibitor and anti-PD-1 antibody: a retrospective multicenter study of 83 patients.

BACKGROUND: To assess the perioperative safety, oncological outcomes, and determinants influencing the oncological outcomes of salvage liver resection for initially unresectable hepatocellular carcinoma (HCC) rendered resectable through transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies (α-PD-1). METHODS: We retrospectively reviewed data from 83 consecutive patients across six tertiary hospitals who underwent salvage liver resection for initially unresectable HCC following conversion by TACE combined with TKIs and α-PD-1, emphasizing perioperative and oncological outcomes. Multivariate Cox regression analysis was employed to discern independent risk factors for postoperative recurrence-free survival (RFS). RESULTS: The median operative duration was 200 min, with a median blood loss of 400 ml. Intraoperative blood transfusions were necessitated for 27 patients. The overall perioperative complication rate was 48.2%, with a major complication rate of 16.9%. One patient died during the perioperative period due to postoperative liver failure. During the median follow-up period of 15.1 months, 24 patients experienced recurrence, with early and intrahepatic recurrence being the most common. Seven patients died during follow-up. Median RFS was 25.4 months, with 1- and 2-year RFS rates of 68.2% and 61.8%, respectively. Median overall survival was not reached, with 1- and 2-year overall survival rates of 92.2% and 87.3%, respectively. Multivariate Cox regression analysis revealed that pathological complete response (pCR) and intraoperative blood transfusion served as independent prognostic determinants for postoperative RFS. CONCLUSIONS: Our study provides preliminary evidence suggesting that salvage liver resection may be an effective and feasible treatment option for patients with unresectable HCC who achieve resectability after conversion therapy with TACE, TKIs, and α-PD-1. The perioperative safety of salvage liver resection for these patients was manageable and acceptable. However, further research, particularly prospective comparative studies, is needed to better evaluate the potential benefits of salvage liver resection in this patient population.

[Platelet Transfusion Strategies for MASPAT-Matched Platelet Transfusion Failed Patient with Allogeneic Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the causes of ineffectiveness of platelet transfusion with monoclonal antibody solid phase platelet antibody test (MASPAT) matching in patients with allogeneic hematopoietic stem cell transplantation and explore the strategies of platelet transfusion. METHODS: A case of donor-specific HLA antibodies (DSA) induced by transfusion which ultimately resulted in transplantation failure and ineffective platelet transfusion with MASPAT matching was selected, and the causes of ineffective platelet transfusion and platelet transfusion strategy were retrospectively analyzed. RESULTS: The 32-year-old female patient was diagnosed as acute myeloid leukemia (high risk) in another hospital with the main symptoms of fever and leukopenia, who should be admitted for hematopoietic stem cell transplantation after remission by chemotherapy. In the course of chemotherapy, DSA was generated due to platelet transfusion, and had HLA gene loci incompatible with the donor of the first transplant, leading to the failure of the first transplant. The patient received platelet transfusion for several times before and after transplantation, and the results showed that the effective rate of MASPAT matched platelet transfusion was only 35.3%. Further analysis showed that the reason for the ineffective platelet transfusion was due to the missed detection of antibodies by MASPAT method. During the second hematopoietic stem cell transplantation, the DSA-negative donor was selected, and the matching platelets but ineffective transfusion during the primary transplantation were avoided. Finally, the patient was successfully transplanted and discharged from hospital. CONCLUSIONS: DSA can cause graft failure or render the graft ineffective. For the platelet transfusion of patients with DSA, the platelet transfusion strategy with matching type only using MASPAT method will miss the detection of antibodies, resulting in invalid platelet transfusion.