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BACKGROUND: The effect of preprandial or postprandial administration of amoxicillin on the efficacy of vonoprazan-amoxicillin dual therapy (VA-dual therapy) for Helicobacter pylori treatment has not been studied. It is also unclear whether amoxicillin dosing four times daily is more effective than three times daily. We aimed to investigate the effect of different amoxicillin administration regimens on the efficacy of VA-dual therapy. MATERIALS AND METHODS: H. pylori-infected subjects were randomly assigned to three groups in a 1:1:1 ratio to receive a 14-day dual therapy consisting of vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily before meals (BM-TID) or 1000 mg three times daily after meals (AM-TID) or 750 mg four times daily after meals (AM-QID). H. pylori eradication rates, adverse events rates, compliance, and antibiotic resistance were compared. RESULTS: Between May 2021 to April 2023, 327 subjects were enrolled. The eradication rates of BM-TID, AM-TID, and AM-QID dual therapy were 88.1%, 89.9%, and 93.6% in intention-to-treat (ITT) analysis, 90.6%, 94.2%, and 99.0% in modified ITT (MITT) analysis, and 90.4%, 94.1%, and 99.0% in per-protocol (PP) analysis. Although there was non-inferiority between BM-TID and AM-TID, as well as between AM-TID and AM-QID, AM-QID was significantly more effective than BM-TID. There were no significant differences in adverse event rates, compliance, and antibiotic resistance among the three groups. CONCLUSIONS: Postprandial administration and the increased frequency of administration of amoxicillin may contribute to a better efficacy of VA-dual therapy, especially for rescue therapy. All VA-dual therapy in our study could achieve good efficacy for first-line treatment. TRIAL REGISTRATION: clinicaltrials.gov: NCT05901051.
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Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Pirroles , Sulfonamidas , Humanos , Amoxicilina/administración & dosificación , Amoxicilina/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Masculino , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Femenino , Persona de Mediana Edad , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Helicobacter pylori/efectos de los fármacos , Pirroles/administración & dosificación , Pirroles/uso terapéutico , Resultado del Tratamiento , Anciano , Adulto , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéutico , Esquema de MedicaciónRESUMEN
Objectives: MDS and AML characterized by TP53 variations have a poor prognosis in general. However, specifically, differences in prognosis have also been observed in patients with different TP53 variants and VAFs.Methods: Here, we retrospectively analyzed datasets of patients with MDS, MPN, and AML who underwent targeted DNA sequencing from February 2018 to December 2023, and patients with reportable TP53 variations were screened. Demographic data and clinical data were collected, and the relationship between TP53 alterations and patient prognosis (AML/MDS) was analyzed using the cBioPortal and Kaplan-Meier Plotter databases. The relationship between the VAFs of TP53 variations and prognoses was analyzed using data from the present study.Results: Sixty-two variants of TP53 were identified in 58 patients. We mainly identified single mutations (79.31%, 46/58), followed by double (17.24%, 10/58) and triple (3.45%, 2/58) mutations. The variations were mainly enriched in exon4-exon8 of TP53. Missense (72.58%, 45/62) mutations were the main type of variations, followed by splice-site (9.68%, 6/62), nonsense (9.68%, 6/62), frameshift (6.45%, 4/62), and indel (1.61%, 1/62) mutations. In this study, p.Arg175His and p.Arg273His were high-frequency TP53 mutations, and DNMT3A and TET2 were commonly co-mutated genes in the three types of myeloid neoplasms; However, we reported some new TP53 variants in MPN that have not been found in the public database. Moreover, MDS or AML characterized by altered TP53 had a shorter OS than patients in the unaltered group (P<0.01), low TP53 mRNA levels were associated with shorter OS in patients with AML (P<0.01). Data from our center further found higher VAF (≥10%) associated with shorter OS in patients with MDS (median 2.75 vs. 24 months) (P<0.01).Conclusion: TP53 mutations are mainly enriched in exon4-exon8, are missense and single mutations in myeloid neoplasms, and are associated with poor prognosis of MDS/AML, and higher VAF (≥10%) of TP53 mutations associated with a shorter OS in patients with MDS.
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Mutación , Síndromes Mielodisplásicos , Proteína p53 Supresora de Tumor , Humanos , Proteína p53 Supresora de Tumor/genética , Masculino , Femenino , Persona de Mediana Edad , Anciano , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/mortalidad , Estudios Retrospectivos , Pronóstico , Adulto , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Anciano de 80 o más Años , Relevancia ClínicaRESUMEN
Objectives: Regulatory T (Treg) cells regulate immunity in autoimmune diseases and cancers. However, immunotherapies that target tumor-infiltrating Treg cells often induce unwanted immune responses and tissue inflammation. Our research focussed on exploring the expression pattern of CD177 in tumor-infiltrating Treg cells with the aim of identifying a potential target that can enhance immunotherapy effectiveness. Methods: Single-cell RNA sequencing (scRNA-seq) data and survival data were obtained from public databases. Twenty-one colorectal cancer patient samples, including fresh tumor tissues, peritumoral tissues and peripheral blood mononuclear cells (PBMCs), were analysed using flow cytometry. The transendothelial activity of CD177+ Treg cells was substantiated using in vitro experiments. Results: ScRNA-seq and flow cytometry results indicated that CD177 was exclusively expressed in intratumoral Treg cells. CD177+ Treg cells exhibited greater activation status and expressed elevated Treg cell canonical markers and immune checkpoint molecules than CD177- Treg cells. We further discovered that both intratumoral CD177+ Treg cells and CD177-overexpressing induced Treg (iTreg) cells had lower levels of PD-1 than their CD177- counterparts. Moreover, CD177 overexpression significantly enhanced the transendothelial migration of Treg cells in vitro. Conclusions: These results demonstrated that Treg cells with higher CD177 levels exhibited an enhanced activation status and transendothelial migration capacity. Our findings suggest that CD177 may serve as an immunotherapeutic target and that overexpression of CD177 may improve the efficacy of chimeric antigen receptor T (CAR-T) cell therapy.
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BACKGROUND: The ubiquitin-proteasome pathway (UPP) has been proven to play important roles in cancer. AIM: To investigate the prognostic significance of genes involved in the UPP and develop a predictive model for liver cancer based on the expression of these genes. METHODS: In this study, UPP-related E1, E2, E3, deubiquitylating enzyme, and proteasome gene sets were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, aiming to screen the prognostic genes using univariate and multivariate regression analysis and develop a prognosis predictive model based on the Cancer Genome Atlas liver cancer cases. RESULTS: Five genes (including autophagy related 10, proteasome 20S subunit alpha 8, proteasome 20S subunit beta 2, ubiquitin specific peptidase 17 like family member 2, and ubiquitin specific peptidase 8) were proven significantly correlated with prognosis and used to develop a prognosis predictive model for liver cancer. Among training, validation, and Gene Expression Omnibus sets, the overall survival differed significantly between the high-risk and low-risk groups. The expression of the five genes was significantly associated with immunocyte infiltration, tumor stage, and postoperative recurrence. A total of 111 differentially expressed genes (DEGs) were identified between the high-risk and low-risk groups and they were enriched in 20 and 5 gene ontology and KEGG pathways. Cell division cycle 20, Kelch repeat and BTB domain containing 11, and DDB1 and CUL4 associated factor 4 like 2 were the DEGs in the E3 gene set that correlated with survival. CONCLUSION: We have constructed a prognosis predictive model in patients with liver cancer, which contains five genes that associate with immunocyte infiltration, tumor stage, and postoperative recurrence.
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Background: Bariatric surgeries, including the sleeve gastrectomy, have been recognized as the most effectively treatment strategy for severe obesity. Magnetic devices have been successfully used in bariatric surgeries. Here, we intended to evaluate the safety and efficiency of magnetic anchoring device assisted-laparoscopic sleeve gastrectomy (MLSG), and to make a comparison of the short-term results between conventional laparoscopic sleeve gastrectomy (CLSG) and MLSG. Methods: The retrospective cohort study was carried out by analyzing and summarizing the data from a database of routinely collected data. The cohort included the patients who underwent either CLSG (n = 120) or MLSG (n = 115) at a single center between January 2018 and December 2020 with a two-year follow-up. The effects of these two surgeries on the weight loss, resolution of comorbidities and quality of life (QOL) were analyzed. Results: The two groups were similar in gender, age, body mass index, abdominal girth, as well as the type and proportion of comorbidities. And the cases in MLSG group had a markedly shorter time of operation (MLSG, 72.59 min vs. CLSG, 76.67 min; P = 0.003). Length of stay in hospital was significantly shorter in the MLSG group than that in the CLSG group (MLSG, 5.59 days vs. CLSG, 5.96 days; P = 0.016). Neither fatal event nor conversion to open surgery happened among all cases. There were no differences in terms of the postoperative complications between the two groups. Magnetic device-related mild hepatic lacerations occurred and were handled by hemostatic treatments in 3 cases. The QOL of patients in MLSG was better at 6-month after surgery, but there was no significant difference between the two groups at 1-year or 2-year after surgery. Conclusion: Both MLSG and CLSG prove safe and effective, and the patients underwent MLSG have a shorter length of stay in hospital, and a better QOL during 6 months after surgery.
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Helicobacter pylori is one of the main predisposing factors for gastric cancer, causing chronic inflammation and proper glands atrophy in the gastric mucosa. Although H. pylori-induced inflammation is a key inducer of precancerous lesions in the gastric mucosa, it remains unclear which precise immune cell subsets are responsible for the progression of H. pylori-induced gastritis. Here, we observed an abundance of CD4+ IL-17A+ FOXP3+ T cells exhibiting a Th17-like phenotype within the microenvironment of H. pylori-induced gastritis. Mechanistically, H. pylori upregulated the expression of IL-6 in Dendritic cells and macrophages, by activating NF-κB signaling through the virulence factor CagA and thus, induced IL-17A expression in FOXP3+ T cells. Moreover, CD4+ IL-17A+ FOXP3+ T cells were positively associated with advanced precancerous lesions. Therefore, these findings offer essential insights into how FOXP3+ T cells sense inflammatory signals from the environment, such as IL-6, during H. pylori infections, thereby guiding the effector immune response and aggravating the gastritis.
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Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Lesiones Precancerosas , Humanos , Interleucina-17/metabolismo , Interleucina-6 , Gastritis/metabolismo , Gastritis/patología , Inflamación , Linfocitos T Reguladores , Factores de Transcripción Forkhead/metabolismo , Microambiente TumoralRESUMEN
Background: Due to the rarity of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, the best first-line treatment has not been established, although there are several options in guidelines. The preferred treatments vary according to the preference of the physician and anecdote. Objectives: First, to analyze the efficacy of a new treatment mode in POEMS syndrome that uses the four-cycle treatment as the induction regimen, followed by sequential transplantation as the consolidation regimen for transplantation-eligible patients, or received another two-cycle treatment for transplantation-ineligible patients. Second, to compare the efficacy and safety of regimens with a proteasome inhibitor (bortezomib-cyclophosphamide-dexamethasone, BCD) or without a proteasome inhibitor (cyclophosphamide-dexamethasone ± thalidomide, CD ± T). Design: We conducted a retrospective study using real-world data from Capital Medical University, Xuanwu Hospital. Methods: A total of 34 newly diagnosed POEMS syndrome patients met Dispenzieri's diagnostic criteria, and those who completed at least four cycles of treatment from July 2013 to March 2021 were included. Results: The overall vascular endothelial growth factor (VEGF) response rate of this new treatment mode was 100%. The cumulative VEGF complete remission (CRV) rate was 67.9%, and the cumulative complete hematological response (CRH) rate was 55.6%. During the median 49-month follow-up, the 5-year-overall survival (OS) rate was 90.7%, the 3-year-progression-free survival (PFS) rate was 78.4%, and the 5-year-PFS rate was 73.8%. The BCD regimen achieved a 75% CRV rate (median time from diagnosis to CRV = 130 days) and 66.7% CRH rate (median time from diagnosis to CRH = 218 days). In addition, the VEGF response was less than the partial remission (PRV) after four-cycle induction treatment, which, together with a decrease on the Overall Neurological Limitation Scale of less than three points 1 year after consolidation treatment, was an independent poor prognostic factor. Conclusion: Bortezomib was well-tolerated by patients with POEMS syndrome. Compared with CD ± T regimen, BCD as the induction regimen achieved better VEGF response and earlier hematological remission. Autologous stem cell transplantation used as consolidation therapy further improved the neurological and hematological remission rates, resulting in better OS and PFS.
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Enrichment of regulatory T cells (Tregs) in the tumour microenvironment (TME) has been recognized as one of the major factors in the initiation and development of resistance to immune checkpoint inhibitors. C-C motif chemokine receptor 8 (CCR8), a marker of activated suppressive Tregs, has a significant impact on the functions of Tregs in the TME. However, the regulatory mechanism of CCR8 in Tregs remains unclear. Here, we reveal that a high level of TNF-α in the colorectal cancer (CRC) microenvironment upregulates CCR8 expression in Tregs via the TNFR2/NF-κB signalling pathway and the FOXP3 transcription factor. Furthermore, in both anti-PD1-responsive and anti-PD1-unresponsive tumour models, PD1 blockade induced CCR8+ Treg infiltration. In both models, Tnfr2 depletion or TNFR2 blockade suppressed tumour progression by reducing CCR8+ Treg infiltration and thus augmented the efficacy of anti-PD1 therapy. Finally, we identified that TNFR2+CCR8+ Tregs but not total Tregs are positively correlated with adverse prognosis in CRC and gastric cancer. Our work reveals the regulatory mechanisms of CCR8 in Tregs and identifies TNFR2 as a promising target for immunotherapy.
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AIMS: Operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia assessment (OLGIM) systems are histological staging systems of gastritis for gastric cancer (GC) risk estimation. Intermediate OLGA/OLGIM stages are of concern in a region with high incidence of GC. This study aimed to validate OLGA and OLGIM staging systems for early GC (EGC) in Chinese population. METHODS: This single-centre, case-control study included 196 patients with EGC and 196 age-matched and sex-matched health screening control subjects. OLGA and OLGIM systems, and other clinical parameters were evaluated using logistic regression analysis. RESULTS: OLGA and OLGIM stages II/III/IV were more prevalent in patients with EGC than in the control subjects. Multivariable analysis revealed family history of GC, previous Helicobacter pylori (H. pylori) infection, OLGA stages II and III-IV, OLGIM stages II and III-IV as independent risk factors for EGC (ORs, 4.04, 1.87, 2.52, 6.79, 4.11 and 10.78, respectively). Area under the receiver operating characteristic curve on EGC risk estimation was improved for OLGIM compared with OLGA (0.78 vs 0.71, p<0.001). Autoantibody seropositivity of gastric mucosa was not associated with EGC risk stratified by H. pylori status. CONCLUSIONS: Surveillance of intermediate-risk patients (OLGA/OLGIM II) should be emphasised in our region. The OLGIM may be preferred over the OLGA for EGC risk estimation.
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The Membrane Attack Complex and Perforin (MACPF) proteins play a crucial role in plant development and adaptation to environmental stresses. Heretofore, few MACPF genes have been functionally identified, leaving gaps in our understanding of MACPF genes in other plants, particularly in the Solanaceae family, which includes economically and culturally significant species, such as tomato, potato, and pepper. In this study, we have identified 26 MACPF genes in three Solanaceae species and in the water lily, which serves as the base group for angiosperms. Phylogenetic analysis indicates that angiosperm MACPF genes could be categorized into three distinct groups, with another moss and spikemoss lineage-specific group, which is further supported by the examination of gene structures and domain or motif organizations. Through inter-genome collinearity analysis, it is determined that there are 12 orthologous SolMACPF gene pairs. The expansion of SolMACPF genes is primarily attributed to dispersed duplications, with purifying selection identified as the principal driving force in their evolutionary process, as indicated by the ω values. Furthermore, the analysis of expression patterns revealed that Solanaceae genes are preferentially expressed in reproductive tissues and regulated by various environmental stimuli, particularly induced by submergence. Taken together, these findings offer valuable insights into and a fresh perspective on the evolution and function of SolMACPF genes, thereby establishing a foundation for further investigations into their phenotypic and functional characteristics.
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Magnoliopsida , Solanum tuberosum , Perforina/genética , Complejo de Ataque a Membrana del Sistema Complemento , Filogenia , VerdurasRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and challenging cancers in the world. N6-methyladenosine (m6A) modification and long non-coding RNAs (lncRNAs) play critical roles in the progression of HCC. However, there are few reports on genome-wide screening and functional annotations of m6A-methylated lncRNAs in HCC. METHODS: The expression levels of m6A methyltransferase METTL3 and the association with the prognosis in HCC were determined by RT-qPCR, public dataset platforms. Then, RNA-seq, Pearson correlation analysis, MeRIP-qPCR, RNA half-life assay, gene site-directed mutation, RIP assay and RT-qPCR analysis were employed to determine the downstream target of METTL3 in HCC. Subsequently, the expression levels and roles of lncRNA glucosylceramidase beta pseudogene 1 (GBAP1) in HCC were determined by Kaplan-meier curves, RT-qPCR, in vitro functional experiments and in vivo tumorigenesis and lung metastasis models. Then, the downstream target and pathway of GBAP1 were explored by GO biological process, KEGG pathway enrichment, luciferase reporter assay, RIP assay and rescue experiments and so on. RESULTS: METTL3 was upregulated in HCC and closely related to HCC prognosis. And METTL3 induced GBAP1 expression by acting as the m6A writer of GBAP1 and IGF2BP2 worked as its m6A reader. Clinically, GBAP1 expression was significantly associated with tumor size, venous infiltration, TNM stage and prognosis of HCC, Functionally, GBAP1 promoted HCC metastasis and growth both in vitro and in vivo. Furthermore, GBAP1 acted as the molecular sponge for miR-22-3p to increase the expression of bone morphogenetic protein receptor type 1A (BMPR1A), which then activated BMP/SMAD pathway in HCC cells. CONCLUSIONS: Our findings demonstrated that METTL3-induced GBAP1 promoted migration, invasion and proliferation of HCC cells via GBAP1/miR-22-3p/BMPR1A/SMAD axis. GBAP1 could be a potential prognosis indicator and therapeutic target for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante , Humanos , Carcinogénesis , Metiltransferasas , Proteínas de Unión al ARNRESUMEN
Existing immune checkpoint inhibitors focus on activating T cells and show limited effectiveness in gastric cancer (GC). SIGLEC10 is identified as a novel tumor-associated macrophage-related immune checkpoint in other cancer types. However, its immunosuppressive role and clinical significance in GC remain unclear. In this study, we find a dominant expression of SIGLEC10 on CD68+ macrophages in GC. SIGLEC10 can suppress the proliferation and function of tumor-infiltrating CD8+ T cells in vitro via the Akt/P38/Erk signaling pathway. Furthermore, in ex vivo and in vivo models, SIGLEC10 blockade promotes CD8+ T cell effector function. Finally, SIGLEC10+ macrophages are positively correlated with the adverse prognosis of GC. Our study highlights that SIGLEC10 directly suppresses T cell function and serves as a promising target for immunotherapy and suggests SIGLEC10+ macrophages as a novel potential predictor of the clinical prognosis of GC.
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Neoplasias Gástricas , Humanos , Linfocitos T CD8-positivos , Macrófagos , Pronóstico , Inmunoterapia , Microambiente Tumoral , Receptores de Superficie Celular/metabolismo , Lectinas/metabolismoRESUMEN
BACKGROUND: Gastric cancer is associated with significant morbidity and mortality in the world. Blocking programmed cell death protein 1 pathway have been approved for the treatment of a variety of tumors and have achieved remarkable clinical therapeutic effects. However, immune checkpoint inhibitors failed to achieve satisfactory results in gastric cancer. There is a need to identify novel immunotherapy targets in gastric cancer. METHODS: We analysed the correlation between Treg cells and CD8 + T cells in gastric cancer samples. We studied the relationship between chemokines and Treg cells or CD8 + T cells in gastric cancer. We compared CCL19/CCR7 expression in gastric cancer patients in TCGA database. We performed transwell experiments to determine the influence of CCL19 on Treg cells and CD8 + T cells migratory capacity. We conducted survival analysis of CCL19 and CCR7 in gastric cancer database. RESULTS: Treg cells show positive correlation with CD8 + T cells in gastric cancer. Treg cell expression was significantly upregulated in tumor tissues. Patients with high FOXP3 expression had worse overall survival than those with low FOXP3 expression. CCL19 had strong correlation with FOXP3 and weak correlation with CD8A. CCL19 had strong impact on the migratory capacity of Treg cells but weak impact on the migratory capacity of CD8 + T cells. Both CCL19 and CCR7 expression were significantly upregulated in gastric cancer tissues. Survival analysis demonstrated that both CCL19 and CCR7 indicate poor prognosis in gastric cancer. CONCLUSIONS: CCL19/CCR7 may be a potential novel therapeutic target in gastric cancer.
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Neoplasias Gástricas , Linfocitos T Reguladores , Humanos , Receptores CCR7/genética , Receptores CCR7/metabolismo , Neoplasias Gástricas/patología , Pronóstico , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Quimiocina CCL19RESUMEN
Meprin and TRAF homology (MATH)-domain-containing proteins are pivotal in modulating plant development and environmental stress responses. To date, members of the MATH gene family have been identified only in a few plant species, including Arabidopsis thaliana, Brassica rapa, maize, and rice, and the functions of this gene family in other economically important crops, especially the Solanaceae family, remain unclear. The present study identified and analyzed 58 MATH genes from three Solanaceae species, including tomato (Solanum lycopersicum), potato (Solanum tuberosum), and pepper (Capsicum annuum). Phylogenetic analysis and domain organization classified these MATH genes into four groups, consistent with those based on motif organization and gene structure. Synteny analysis found that segmental and tandem duplication might have contributed to MATH gene expansion in the tomato and the potato, respectively. Collinearity analysis revealed high conservation among Solanaceae MATH genes. Further cis-regulatory element prediction and gene expression analysis showed that Solanaceae MATH genes play essential roles during development and stress response. These findings provide a theoretical basis for other functional studies on Solanaceae MATH genes.
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Capsicum , Solanaceae , Solanum lycopersicum , Solanum tuberosum , Solanaceae/genética , Solanaceae/metabolismo , Tiopronina/metabolismo , Filogenia , Solanum lycopersicum/genética , Capsicum/genética , Solanum tuberosum/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
BACKGROUND: We compared the efficacy and safety of rifabutin-containing triple therapy with bismuth quadruple therapy for rescue treatment of Helicobacter pylori. METHODS: This was a noninferiority study trial of H. pylori treatment for subjects who had failed at least 2 prior treatments. Subjects were randomly assigned to receive rifabutin triple therapy with 14-day esomeprazole (20 mg), amoxicillin (1.0 g), and rifabutin (150 mg) twice a day; or bismuth quadruple therapy with esomeprazole (20 mg) and bismuth (220 mg) twice a day, plus metronidazole (400 mg) and tetracycline (500 mg) 4 times a day. Antimicrobial susceptibility was assessed by agar dilution and E-test. RESULTS: From May 2021 to October 2022, a total of 364 subjects were randomized. The eradication rates by intention-to-treat, per-protocol, and modified intention-to-treat were 89.0% (162/182; 95% confidence interval [CI], 83.6%-92.8%), 94.0% (157/167; 95% CI, 89.3%-96.7%), and 93.6% (162/173; 95% CI, 89.0%-96.4%) for rifabutin triple group. For bismuth quadruple group, they were 89.6% (163/182; 95% CI, 84.3%-93.2%), 95.3% (143/150; 95% CI, 90.7%-97.7%), and 93.7% (163/174; 95% CI, 89.0%-96.4%). CONCLUSIONS: The rifabutin triple therapy is an alternative to classical bismuth quadruple therapy for the rescue treatment of H. pylori with fewer side effects and higher compliance. CLINICAL TRIALS REGISTRATION: NCT04879992.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Bismuto/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Esomeprazol/uso terapéutico , Rifabutina/uso terapéutico , Quimioterapia Combinada , Antibacterianos/uso terapéutico , Amoxicilina/uso terapéutico , Metronidazol/uso terapéutico , Resultado del Tratamiento , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
This study aimed to examine the effect of venetoclax coupled with azacytidine in treating older adults with relapsed and refractory (R/R) acute myeloid leukemia (AML). The clinical data of 10 senior patients with AML over 65 years old who were treated with venetoclax and azacytidine, including six patients with R/R AML, were retrospectively evaluated. This study comprised seven males and three females with a median age of 71 years. Five patients had at least one relapse, and one patient did not achieve remission after four cycles of azacytidine monotherapy, considering it resistant. AML with myelodysplasia-related changes was found in four cases. One of the 10 patients died early after 1-13 cycles of venetoclax plus azacytidine treatment due to a protracted period of neutropenia and severe lung infection induced by medications. Six of the remaining nine patients, including six R/R patients, achieved a complete remission (CR) or a CR with incomplete hematologic recovery (CRi). After two cycles of therapy, one patient did not react. Neutropenia lasted an average of 10.5 (6-15) days in all patients, with the most severe cases occurring in the second and third weeks of therapy. Three patients who tested positive for the TP53 gene mutation had the following outcomes: One relapsed patient has been in progression-free remission (PFS) for the past 24 months, whereas another has been in full remission but relapsed 2 months later. Another patient experienced complete remission in myelology for 4 months, but the variable allele fraction (VAF) value steadily rose, suggesting that the illness was on the verge of progressing. IDH2 gene alterations were found in three of four patients who obtained maintained CR for more than 18 months following recurrence. Venetoclax in combination with azacytidine is a successful and well-tolerated therapy for R/R AML in the elderly. Venetoclax and azacytidine may help patients with TP53 mutations and reduce VAF. The IDH2 mutation might be a good predictor of veneclax sensitivity. A notable adverse response in the treatment phase of the regimen is severe infection induced by neutropenia.
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Leucemia Mieloide Aguda , Neutropenia , Masculino , Femenino , Humanos , Anciano , Azacitidina/efectos adversos , Estudios Retrospectivos , Leucemia Mieloide Aguda/tratamiento farmacológico , Compuestos Bicíclicos Heterocíclicos con Puentes , Neutropenia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
PURPOSE: To explore the potential value of diffusion kurtosis imaging (DKI) for identification of cytokeratin 19 (CK19) status of HCCs. METHODS: This study was approved by the local institute review board and written informed consent was obtained. 73 patients with pathologically confirmed HCCs were included in this prospective study. All the diffusion-weighted (DW) images were acquired using a 3.0-T MR scanner with 4 b-values (0, 800, 1500 and 2000 s/mm2). The mean diffusion value (MD) and mean kurtosis coefficient (MK) from DKI, apparent diffusion coefficient (ADC) from DW imaging (b = 0, 500 s/mm2), and tumor-to-liver signal intensity ratios on ADC map (SIRADC) and DW images with b-value of 500 s/mm2 (SIRb500) were calculated and compared between CK19-positive (n = 23) and CK19-negative (n = 50) HCC groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for the positive expression of CK19. RESULTS: Increased a-fetoprotein level (p = 0.021) and SIRb500 (p = 0.006) and decreased ADC (p = 0.021) and MD (p < 0.001) were significantly correlated with CK19-positive HCCs at univariate analysis. Decreased MD value (odds ratio: 0.042, p = 0.002) and a-fetoprotein level (odds ratio: 5.139, p = 0.015) were the independent risk factors for CK19-positive HCCs at multivariate analysis. The area under the curve of MD value by receiver operating characteristic analysis was 0.823 with a sensitivity of 86.96% and a specificity of 76% for the prediction of CK19-positive HCCs. CONCLUSION: The decreased MD value derived from DKI is potential quantitative biomarker for predicting CK19-positive HCCs.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Estudios Prospectivos , Queratina-19 , alfa-Fetoproteínas , Imagen de Difusión por Resonancia Magnética/métodos , Sensibilidad y EspecificidadRESUMEN
PURPOSE: To assess the clinical potential of a set of new diffusion parameters (D, ß, and µ) derived from fractional order calculus (FROC) diffusion model in predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Between January 2019 to November 2020, a total of 63 patients with HCC were enrolled in this study. Diffusion-weighted images were acquired by using ten b-values (0-2000 s/mm2). The FROC model parameters including diffusion coefficient (D), fractional order parameter (ß), a microstructural quantity (µ) together with a conventional apparent diffusion coefficient (ADC) were calculated. Intraclass coefficients were calculated for assessing the agreement of parameters quantified by two radiologists. The differences of these values between the MVI-positive and MVI-negative HCC groups were compared by using independent sample t-test or the Mann-Whitney U test. Then the parameters showing significant differences between subgroups, including the ß and D, were integrated to develop a comprehensive predictive model via binary logistic regression. The diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: Among all the studied diffusion parameters, significant differences were found in D, ß, and ADC between the MVI-positive and MVI-negative groups. MVI-positive HCCs showed significantly higher ß values (0.65 ± 0.17 vs. 0.51 ± 0.13, P = 0.001), along with lower D values (0.84 ± 0.11 µm2/ms vs. 1.03 ± 0.13 µm2/ms, P < 0.001) and lower ADC values (1.38 ± 0.46 µm2/ms vs. 2.09 ± 0.70 µm2/ms, P < 0.001) than those of MVI-negative HCCs. According to the ROC analysis, the combination of D and ß demonstrated the largest area under the ROC curve (0.920) compared with individual parameters (D: 0.912; ß: 0.733; and ADC: 0.831) for differentiating MVI-positive from MVI-negative HCCs. CONCLUSIONS: The FROC parameters can be used as noninvasive quantitative imaging markers for preoperatively predicting the MVI status of HCCs.
Asunto(s)
Cálculos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Proyectos Piloto , Imagen de Difusión por Resonancia Magnética/métodos , Estudios RetrospectivosRESUMEN
POEMS syndrome is a plasma cell disease. Clinical manifestations and clinical onset are variable. In recent years, more and more cases of POEMS syndrome with cerebrovascular disease and ischemic stroke have been reported. However, it is rare for patients with POEMS syndrome to present with a cerebrovascular accident as the first clinical manifestation. We presented three cases of POEMS syndrome with cerebral infarction in different phases of the disease. We then searched the literature for studies involving POEMS syndrome complicated with cerebral infarction. There were 81 cases in total. In nine patients, cerebral infarctions occurred before polyneuropathy. Patients with cerebral infarction before polyneuropathy have better prognosis of POEMS than those with cerebral infarction after polyneuropathy.
RESUMEN
Immunotherapy targeting glucocorticoid-induced TNFR-related protein (GITR) exhibited strong anti-tumor capacity in mouse model but poor efficacy in clinical trials. This may be attributed to the different GITR expression mode between human and mouse. In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data of human gastric cancer (GC) and used flow to explore the GITR expression across T cell subsets and tissue types in GC patients. We revealed that GITR+ CD4 T cells, including regulatory CD4 T (Treg) cells and conventional CD4 T (Tconv) cells, might contribute to the immunosuppressive microenvironment in GC. The enrichment of these cells was associated with a worse prognosis. Moreover, we found the cellular distribution of GITR protein in Treg cells was microenvironment dependent. In conclusion, GITR is still an important immune checkpoint need to be studied.