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Like other odontocetes, Risso's dolphins actively emit clicks and passively listen to the echoes during echolocation. However, the head anatomy of Risso's dolphins differs from that of other odontocetes by a unique vertical cleft along the anterior surface of the forehead and a differently-shaped lower jaw. In this study, 3D finite-element sound reception and production models were constructed based on CT data of a deceased Risso's dolphin. Our results were verified by finding good agreement with experimental measurements of hearing sensitivity. Moreover, the acoustic pathway for sounds to travel from the seawater into the dolphin's tympanoperiotic complexes (TPCs) was computed. The gular reception mechanism, previously discovered in Delphinus delphis and Ziphius cavirostris, was also found in this species. The received sound pressure levels and relative displacement at TPC surfaces were compared between the cases with and without the mandibular fats or mandible. The results demonstrate a pronounced wave-guiding role of the mandibular fats and a limited bone-conductor role of the mandible. For sound production modelling, we digitally filled the cleft with neighbouring soft tissues, creating a hypothetical "cleftless" head. Comparison between sound travelling through a "cleftless" head vs. an original head indicates that the distinctive cleft plays a limited role in biosonar sound propagation.
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Therapeutic drug monitoring (TDM) of imatinib (IM) in cancer therapy offers the potential to improve treatment efficacy while minimizing toxicity. There was a significant correlation between unbound concentration and clinical response and toxicity, compared with total plasma concentrations, and the quantification of unbound IM and its metabolite, N-desmethyl imatinib (NDI) are of interest for TDM. However, traditional unbound drug separation methods have shortcomings, especially are susceptible to non-specific binding (NSB) of drugs to the polymer-constructed components of filter membranes, which are difficult to avoid at present. Hence it is necessary to developed a reliable separation method for the analysis of the unbound fraction of IM and NDI in TDM. We developed and validated an hollow fiber solid phase microextraction (HF-SPME) method coupled with high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) that to measure unbound IM and NDI concentration in human plasma. It used the NSB phenomenon and solve the NSB problem. The preparation procedure only involves a common vortex and ultrasonication without dilution of samples and modification of membrane. A total of 50 chronic myeloid leukemia (CML) patients were enrolled in our study. The relationship between the unbound and total concentrations for IM and NDI, as well as the concentration ratios of NDI to IM in 50 clinical plasma samples were investigated. The extraction recovery is high to 95.5-106â¯% with validation parameters for the methodological results were all excellent. There were both a poor linear relationship between the unbound and total concentrations for IM (r2=0.504) and NDI (r2=0.201) in 50 clinical plasma samples. The unbound concentration ratios of NDI to IM varied widely in CML patients. The determination of unbound IM and NDI concentration is meaningful and necessary. The developed HF-SPME method is simple, accurate and precise that could be used to measure unbound IM and NDI concentration in clinical TDM.
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Monitoreo de Drogas , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva , Microextracción en Fase Sólida , Espectrometría de Masas en Tándem , Humanos , Mesilato de Imatinib/sangre , Mesilato de Imatinib/farmacocinética , Microextracción en Fase Sólida/métodos , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Monitoreo de Drogas/métodos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Femenino , Masculino , Persona de Mediana Edad , Adulto , Reproducibilidad de los ResultadosRESUMEN
Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.
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Diagnosis of intravascular large B-cell lymphoma (IVLBCL) is a challenge due to its heterogeneous clinical presentation and lack of specific markers. This retrospective study investigated the utility of circulating tumour DNA (ctDNA) sequencing for diagnosing IVLBCL and analysing its mutation landscape. A cohort of 34 IVLBCL patients enrolled and underwent plasma ctDNA targeted sequencing. The median plasma ctDNA concentration was 135.0 ng/mL, significantly higher than that in diffuse large B-cell lymphoma (DLBCL) controls. Correlations were found between ctDNA concentration and disease severity indicators, LDH and SF. Mutation analysis revealed frequent mutations in B-cell receptor and NF-κB signalling pathways, including MYD88 (56%), CD79B (44%), TNFAIP3 (38%) and IRF4 (29%). CNS involvement was significantly related with BCL6 and CD58 mutation. Patients with complicated hemophagocytic lymphohistiocytosis had significantly higher mutation rates in B2M. Comparison with DLBCL subtypes showed distinctive mutation profiles in IVLBCL. Moreover, plasma ctDNA detected more mutations with higher variant allele fraction than tissue DNA, suggesting its superiority in sensitivity and accessibility. Dynamic monitoring of ctDNA during treatment correlated with therapeutic responses. This study revealed the role of ctDNA in IVLBCL diagnosis, mutation analysis, and treatment monitoring, offering a promising avenue for improving patient diagnosis in this rare lymphoma subtype.
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Biomarcadores de Tumor , ADN Tumoral Circulante , Linfoma de Células B Grandes Difuso , Mutación , Humanos , ADN Tumoral Circulante/genética , ADN Tumoral Circulante/sangre , Femenino , Masculino , Persona de Mediana Edad , Anciano , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/sangre , Análisis Mutacional de ADN/métodos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Adulto , Estudios Retrospectivos , Anciano de 80 o más AñosRESUMEN
OBJECTIVES: First-line pemetrexed-platinum chemotherapy + osimertinib(Pem-Plat-Osi) improves progression-free survival as compared to osimertinib alone in advanced epidermal growth factor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, many patients are hesitant to commence chemotherapy upfront. We describe outcomes to Pem-Plat-Osi after first-line osimertinib failure. MATERIALS AND METHODS: Patients with advanced EGFR-mutated (ex19del/L858R) NSCLC who had Pem-Plat-Osi between 1/7/2018-30/9/2023 after progression on first-line osimertinib at National Cancer Centre Singapore, Prince of Wales Hospital and Chinese University of Hong Kong were identified. Key endpoints were time to treatment failure (TTF) and overall survival (OS). RESULTS: A total of 60 patients were included. Median age at diagnosis was 62, 53.3 % (32/60) were male and 76.7 % (46/60) were never smokers. Ex19del comprised 56.7 % (34/60) and L858R 43.3 % (26/60). Baseline central nervous system (CNS) metastases were present in 66.7 % (40/60). Median TTF on osimertinib (TTF1) was 14.4 months(m) and median time to initiation of Pem-Plat-Osi was 41 days(d) (range 0-652) after progression on osimertinib. Partial response (PR) or stable disease to Pem-Plat-Osi was achieved in 81.7 %(49/60). Intracranial disease control was achieved in 90.6 % (29/32) of patients with measurable CNS metastases, including those who did not undergo brain radiotherapy. At median follow up of 31.2 m, median TTF on Pem-Plat-Osi (TTF2) was 6.6 m. Median TTF1 + TTF2 was 23.4 m and median OS was 34.2 m. Survival outcomes were similar comparing ex19del and L858R (median TTF1 + TTF2 21.8 m vs 23.5 m, p = 0.90; median OS 34.2 m vs 36.8 m, p = 0.37) and in patients without/with baseline CNS metastases (median TTF1 + TTF2 21.8 m vs 23.4 m, p = 0.44; median OS 36.2 m vs 31.9 m, p = 0.65). TTF1 duration was not significantly associated with TTF2 (p = 0.76). Patients who started Pem-Plat-Osi within 20d of progression on osimertinib had significantly longer TTF2 as compared to patients who started after 20d (median 8.4 m versus 6.0 months, p = 0.03), which remained statistically significant on multivariable analysis. CONCLUSIONS: Our real-world data supports the efficacy of Pem-Plat-Osi after progression on first-line osimertinib, including L858R and baseline CNS metastases. Chemotherapy initiation within 20d of Osi progression was predictive of superior TTF2.
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Acrilamidas , Compuestos de Anilina , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Mutación , Pemetrexed , Femenino , Humanos , Masculino , Persona de Mediana Edad , Acrilamidas/uso terapéutico , Compuestos de Anilina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Progresión de la Enfermedad , Receptores ErbB/genética , Indoles , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Pemetrexed/uso terapéutico , Pemetrexed/administración & dosificación , Platino (Metal)/uso terapéutico , Platino (Metal)/administración & dosificación , Pirimidinas , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Dual channel photo-driven H2O2 production in pure water on small-scale on-site setups is a promising strategy to provide low-concentrated H2O2 whenever needed. This process suffers, however, strongly from the fast recombination of photo-generated charge carriers and the sluggish oxidation process. Here, insoluble Keggin-type cesium phosphomolybdate Cs3PMo12O40 (abbreviated to Cs3PMo12) is introduced to carbonized cellulose (CC) to construct S-scheme heterojunction Cs3PMo12/CC. Dual channel H2O2 photosynthesis from both H2O oxidation and O2 reduction in pure water has been thus achieved with the production rate of 20.1 mmol L-1 gcat. -1 h-1, apparent quantum yield (AQY) of 2.1% and solar-to-chemical conversion (SCC) efficiency of 0.050%. H2O2 accumulative concentration reaches 4.9 mmol L-1. This high photocatalytic activity is guaranteed by unique features of Cs3PMo12/CC, namely, S-scheme heterojunction, electron reservoir, and proton reservoir. The former two enhance the separation of photo-generated charge carriers, while the latter speeds up the torpid oxidation process. In situ experiments reveal that H2O2 is formed via successive single-electron transfer in both channels. In real practice, exposing the reaction system under natural sunlight outdoors successfully results in 0.24 mmol L-1 H2O2. This work provides a key practical strategy for designing photocatalysts in modulating redox half-reactions in photosynthesis.
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BACKGROUND: Acute ischemic stroke (AIS) is one of the most common cerebrovascular diseases which accompanied by a disruption of aminothiols homeostasis. To explore the relationship of aminothiols with neurologic impairment severity, we investigated four aminothiols, homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CG) and glutathione (GSH) in plasma and its influence on ischemic stroke severity in AIS patients. METHODS: A total of 150 clinical samples from AIS patients were selected for our study. The concentrations of free reduced Hcy (Hcy), own oxidized Hcy (HHcy), free reduced Cys (Cys), own oxidized Cys (cysteine, Cyss), free reduced CG (CG) and free reduced GSH (GSH) were measured by our previously developed hollow fiber centrifugal ultrafiltration (HFCF-UF) method coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The concentration ratio of Hcy to HHcy (Hcy/HHcy), Cys to Cyss (Cys/Cyss) were also calculated. The neurologic impairment severity of AIS was evaluated using National Institutes of Health Stroke Scale (NIHSS). The Spearman correlation coefficient and logistic regression analysis was used to estimate and perform the correlation between Hcy, HHcy, Cys, Cyss, CG, GSH, Hcy/HHcy, Cys/Cyss and total Hcy with NIHSS score. RESULTS: The reduced Hcy and Hcy/HHcy was both negatively correlated with NIHSS score in AIS patients with P = 0.008, r=-0.215 and P = 0.002, r=-0.249, respectively. There was no significant correlation of Cys, CG, GSH, HHcy, Cyss, Cys/Cyss and total Hcy with NIHSS score in AIS patients with P value > 0.05. CONCLUSIONS: The reduced Hcy and Hcy/HHcy, not total Hcy concentration should be used to evaluate neurologic impairment severity of AIS patient.
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Cisteína , Glutatión , Homocisteína , Accidente Cerebrovascular Isquémico , Oxidación-Reducción , Índice de Severidad de la Enfermedad , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/diagnóstico , Homocisteína/sangre , Anciano , Persona de Mediana Edad , Cisteína/sangre , Glutatión/sangre , Dipéptidos/sangre , Anciano de 80 o más AñosRESUMEN
An integrated path differential absorption (IPDA) lidar can accurately measure regional C O 2 weighted column average concentrations (X C O 2), which are crucial for understanding the carbon cycle in climate change studies. To verify the performance and data inversion methods of space-borne IPDA lidar, in July 2021, we conducted an airborne lidar validation experiment in Dunhuang, Gansu Province, China. An aircraft was equipped with a lidar system developed to measure X C O 2 and an in situ greenhouse gas analyzer (GGA). To minimize measurement errors, energy monitoring was optimized. The system bias error of the DAOD was determined by changing the laser output mode from the off/on to the on/on mode. The X C O 2 inversion results obtained through comparing the schemes of averaging signals before "log (logarithm)" and averaging after "log" indicate that the former performs better. The IPDA lidar measured X C O 2 over the validation site at 405.57 ppm, and both the IPDA lidar and GGA measured sudden changes in the C O 2 concentration. The assimilation data showed a similar trend according to the altitude to the data measured by the in situ instrument. A comparison of the mean X C O 2 derived from the GGA results and assimilation data with the IPDA lidar measurements showed biases of 0.80 and 1.12 ppm, respectively.
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Autophagy is a cellular catabolic process characterized by the formation of double-membrane autophagosomes. Transmission electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation. A large number of studies have shown that autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal (GI) cells. However, the role of autophagy in GI diseases remains controversial. This article focuses on the morphological and biochemical characteristics of autophagy in GI diseases, in order to provide new ideas for their diagnosis and treatment.
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Enfermedades Gastrointestinales , Humanos , Autofagia , Microscopía Electrónica de TransmisiónRESUMEN
The pathogenesis and progression of follicular lymphoma (FL) depends on immune evasion mechanisms. The gut microbiota has been reported to be associated with the development and outcome of several human diseases by modulating host immunity. Thus, the present study investigated the characteristics and prognostic value of the gut microbiota in FL. Fecal samples from treatment-naïve patients with FL (n=28) and healthy controls (n=18) were prospectively collected. The gut microbiota diversity and composition were examined by 16S ribosomal RNA sequencing. The results demonstrated that patients with FL had distinct microbiota compositions. The relative abundance of the Ruminococcaceae family was significantly increased in patients with FL (P=0.01). Furthermore, a high level of Ruminococcus was identified as a strong indicator of tumor burden (P=0.001), and was related to the FL International Prognostic Index score and serum lactate dehydrogenase levels. The present results indicated an association between the gut microbiota and FL prognosis. Findings from the present study may provide a rational foundation for further investigation of the role of gut microbiota in lymphoma management.
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Despite great advances in treatment, 30-40% of patients with DLBCL undergo relapses. Patients with a relapse within 1 year or beyond have a distinct outcome. Few clinical characteristics and survival data in the Chinese population have been published. We aimed to define the incidence and clinical features of DLBCL patients with very early relapse after front-line immunochemotherapy who may benefit greatly from the emerging chimeric antigen receptor T-cell therapy. Data of 564 DLBCL patients were analyzed. Among the 413 patients achieving a first complete remission, 59 underwent relapses: 32 patients (54.2%) relapsed within 1 year, and 27 patients (46.8%) relapsed 1 year or more. Patients relapsing within 1 year, in comparison with the other group, showed an inferior risk profile at diagnosis: elevated lactate dehydrogenase level (P = 0.002), high Eastern Cooperative Oncology Group performance score (P = 0.02), and high international prognosis index (P = 0.004). As expected, a worse overall survival was observed in the early relapse group. Multivariate analysis for OS showed that relapse within 1 year was an independent parameter for reduced overall survival (HR 0.241, P = 0.002).
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Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Recurrencia Local de Neoplasia , Recurrencia , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , PronósticoRESUMEN
The goal of this paper is to fabricate innovative diaphragm headphones using graphene oxide paper (GOP) and GOP/epoxy nanocomposites (GOPC). Initially, graphene oxide suspension is fabricated, and the vacuum filtration method is adopted to make GOP. Then, vacuum bag molding is used to fabricate GOPC from GOP. Hot pressing and associated molds are adopted to fabricate line-indented (GOPC-L) or curve-indented patterns (GOPC-C) on the GOPC. The performances of one kind of GOP and three kinds of GOPC diaphragm headphones are analyzed based on their sound pressure level (SPL) curves achieved by the Soundcheck measurement system. There are four important processing parameters that will influence the performance of the diaphragm, including material type GOP versus GOPC, indented pattern type, sonication time on suspension, and graphene weight fraction in suspension. Compliances of various diaphragms are measured by the Klippel LPM laser measurement system. The results indicate that effects of sonication time and graphene weight fraction on SPL of GOP and GOPC headphones are in reverse, and this is associated with their difference on compliance (modulus), mass, damping ratio, and microstructure uniformity. Either GOPC-L or GOPC-C seems to improve the microstructure of the GOPC, and leads to better SPL performance. The correlation between the previous four factors and SPLs of four kinds of diaphragm headphones is proposed by using scanning electron microscope (SEM) to examine the microstructure of these diaphragms.
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Germline mutations in genes involved in perforin-granzyme-mediated cytotoxicity such as PRF1, UNC13D, STX11, and STXBP2 were known to cause familial hemophagocytic lymphohistiocytosis (FHL). In this study, we reported a unique group of 3 patients with germline mutations of UNC13D and STX11 genes and presented as adult-onset peripheral T-cell lymphoma (PTCL) with cytotoxic T-cell phenotype and atypical lymphoma presentations. CD107a degranulation assay and NK-cell activity analysis demonstrated impaired cytotoxic function of the NK/T-cells of the patients with FHL-related mutations. Gene expression profile study revealed that up-regulated genes of the cytotoxic T-cells were enriched in autoimmune-related pathways. It was possible that impaired cytotoxic lymphocyte-mediated immune surveillance and autoantigen stimulation may both participate in PTCL oncogenesis. Germline defects of FLH-related genes may represent a novel predisposing factor for PTCLs.
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Linfohistiocitosis Hemofagocítica , Linfoma de Células T Periférico , Adulto , Humanos , Proteínas Citotóxicas Formadoras de Poros/genética , Células Asesinas Naturales , Células Germinativas/metabolismo , Proteínas de la MembranaRESUMEN
The gut microbiome (GMB) has been extensively reported to be associated with the development and prognosis of human diseases. This study aims to investigate the relationship between GMB composition and chemotherapy efficacy in diffuse large B-cell lymphoma (DLBCL). We demonstrated that DLBCL patients at diagnosis have altered GMB compositions. Significant enrichment of the Proteobacteria phylum in DLBCL patients was observed. Gene analysis showed a high abundance of virulence factors genes. We found baseline GMB to be associated with clinical outcomes. The emergence of Lactobacillus fermentum was correlated with better treatment outcome. Our pilot results suggested a correlation between GMB composition and DLBCL development and prognosis. Clues from our study, together with previous research, provided a rational foundation for further investigation on the pathogenesis, prognosis value, and targeted therapy of GMB in DLBCL.
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Anciano , Humanos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/diagnóstico , Síndrome , Neoplasias Vasculares/complicaciones , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/tratamiento farmacológico , Vasoconstricción/efectos de los fármacosRESUMEN
The supracondylar humeral fracture (SCHF) is the most common fracture seen in children, forming up to 70% of all pediatric elbow fractures. The decision to surgically explore the brachial artery in a well-perfused, pulseless arm remains a controversial one among vascular and orthopedic surgeons and is something we seek to explore in this article. We reviewed the literature from electronic databases such as PubMed and Embase for studies focusing on the management of the pink pulseless hand (PPH) following SCHF. We gathered a total of 23 articles to be analyzed in this review. We found 336 PPH postreduction and evaluated the management as well as the follow-up and complications of the PPH involved. Most recent articles have cited the close observation strategy as the most reliable strategy. It is clear that the management of a SCHF requires immediate reduction and fixation. In the management of a postoperatively pulseless pink humerus, we do agree with the latest conclusion of Delionitis et al . who advocate the traditional dogma of watchful waiting in the case of a PPH postreduction and fixation as long as no signs of vascular deterioration appear. However, the outcome of this study also advocates for the monitoring of up to 24-48â h postreduction and the use of noninvasive tools such as ultrasound Doppler, Color flow duplex Ultrasound and pulse oximetry to monitor perfusion as they all have had good outcomes in the articles cited in this review. Still, in the event of vascular deterioration or development of complications of the hand, immediate vascular exploration is still indicated.
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Arteria Braquial , Fracturas del Húmero , Humanos , Fracturas del Húmero/cirugía , Niño , Arteria Braquial/cirugíaRESUMEN
Intravascular large B-cell lymphoma (IVLBCL) is a rare type of aggressive B-cell non-Hodgkin lymphoma that poses a great diagnostic challenge due to its highly heterogenous clinical manifestations. Although 18F-fluorodeoxyglucose (FDG) is widely used as a diagnostic tool for patients suspected of having lymphoma, as it reveals FDG-avid lesions, the FDG avidity of IVLBCL has not been extensively characterized. Here, we present a comprehensive report of FDG avidity in IVLBCL and its association with clinicopathological features and survival. This descriptive observational study included consecutive patients aged at least 18 years diagnosed with IVLBCL in Peking Union Medical Hospital across 9 years. Among 50 screened IVLBCL patients, 42 had undergone 18F-FDG PET/CT to detect possible lesions for biopsy before pathological diagnosis; their FDG PET/CT (positron emission computed tomography, PET/CT) reports were retrospectively reviewed. The primary endpoint was the clinical description of FDG avidity of newly diagnosed intravascular large B-cell lymphoma and frequency. A total of 73.8% patients showed FDG-avid lesions, with a median SUVmax of 7.4 (range 1-27.7), which was lower than that for other aggressive lymphomas. Clinicopathological features were the same between the FDG-avid group and the non-FDG-avid group, except that the latter had a higher Ki-67 index (median 90% in the nonavid group vs. 80% in the avid group, P = 0.043). The overall survival rate was not different between the PET/CT groups. Our findings demonstrate that FDG PET/CT is a useful diagnostic tool for detecting FDG-avid lesions in IVLBCL patients. A random skin biopsy is essential for assisting in the diagnosis of IVLBCL, even for those with negative PET/CT.
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Linfoma de Células B Grandes Difuso , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Adolescente , Adulto , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Estudios Retrospectivos , Tomografía de Emisión de Positrones/métodos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , RadiofármacosRESUMEN
CAR-T cell therapy did not achieve the desired efficacy in some patients with diffuse large B-cell lymphoma (DLBCL). We conducted single-cell RNA and TCR sequencing as well as methylation chip profiling of peripheral blood samples in DLBCL patients. Patients who achieved complete remission (CR) showed an upward trend in T-cell levels, especially CD8-effector T cells. The responders exhibited T-cell clone expansion, more active T-cell transformation, and frequent cell communication. Highly expressed genes in the CR group were enriched in functions like leukocyte-mediated cytotoxicity and activation of immune response, while the non-CR group was enriched in pathways related to DNA damage and P53-mediated intrinsic apoptotic. More differentially methylated probes (DMPs) were identified in the baseline of the non-CR group (779 vs 350). GSEA analysis revealed that the genes annotated by DMPs were associated with cellular immune functions in T cells, including the generation of chemokines, leukocyte-mediated cytotoxicity, and cell-killing functions. The genes with low expression in the non-CR group exhibited a high methylation status. There is heterogeneity in the cellular, molecular, and epigenetic characteristics of host T cells in patients with different clinical outcomes. Intrinsic defects in T cells are important factors leading to poor efficacy of CAR-T therapy.
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Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Humanos , Linfocitos T , Receptores Quiméricos de Antígenos/genética , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/terapia , Inmunoterapia Adoptiva/efectos adversosRESUMEN
Purpose: To evaluate progression-free survival (PFS) as early surrogate endpoints for overall survival (OS) in primary CNS lymphoma (PCNSL). Methods: PubMed, Embase and Cochrane Central Library were searched up to 7 June 2022. Trial-level analyses were performed by weighted linear regression of logarithmic hazard ratios for PFS and OS. Treatment arm-level analyses were performed between PFS rates and 3- or 5-year OS rates. Results: 1471 PCNSL patients in nine randomized control trials were included. PFS was associated with OS (r = 0.750; 95% CI: 0.228-0.937). Strong linear correlations existed between 1-, 2- and 3-year PFS and 3-year OS (r = 0.896-0.928), moderate or weak correlations existed between 3- to 6-month PFS and 3-year OS, 3-month to 5-year PFS and 5-year OS. Conclusion: Short-term PFS can validly substitute for long-term OS in PCNSL.