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1.
Article in English | MEDLINE | ID: mdl-38995337

ABSTRACT

Microorganisms can play a key role in selenium (Se) bioremediation and the fabrication of Se-based nanomaterials by reducing toxic forms (Se(VI) and Se(IV)) into Se(0). In recent years, omics have become a useful tool in understanding the metabolic pathways involved in the reduction process. This paper aims to elucidate the specific molecular mechanisms involved in Se(VI) reduction by the bacterium Stenotrophomonas bentonitica. Both cytoplasmic and membrane fractions were able to reduce Se(VI) to Se(0) nanoparticles (NPs) with different morphologies (nanospheres and nanorods) and allotropes (amorphous, monoclinic, and trigonal). Proteomic analyses indicated an adaptive response against Se(VI) through the alteration of several metabolic pathways including those related to energy acquisition, synthesis of proteins and nucleic acids, and transport systems. Whilst the thioredoxin system and the Painter reactions were identified to play a crucial role in Se reduction, flagellin may also be involved in the allotropic transformation of Se. These findings suggest a multi-modal reduction mechanism is involved, providing new insights for developing novel strategies in bioremediation and nanoparticle synthesis for the recovery of critical materials within the concept of circular economy.

2.
Materials (Basel) ; 17(11)2024 May 28.
Article in English | MEDLINE | ID: mdl-38893853

ABSTRACT

The development of bio-insultation materials has attracted increasing attention in building energy-saving fields. In tropical and hot-humid climates, building envelope insulation is important for an energy efficient and comfortable indoor environment. In this study, several experiments were carried out on a bio-insulation material, which was prepared by using rice husk as a raw material. Square rice husk-based insultation panels were developed, considering the ASTM C-177 dimensions, to perform thermal conductivity coefficient tests. The thermal conductivity coefficient obtained was 0.073 W/(m K), which is in the range of conventional thermal insulators. In a second phase of this study, two experimental enclosures (chambers) were constructed, one with rice husk-based insulation panels and the second one without this insulation. The measures of the temperatures and thermal flows through the chambers were obtained with an electronic module based on the ARDUINO platform. This module consisted of three DS18B20 temperature sensors and four Peltier plates. Daily temperature and heat flux data were collected for the two chambers during the dry season in Panama, specifically between April and May. In the experimental chamber that did not have rice husk panel insulation on the roof, a flow of up to 28.18 W/m2 was observed, while in the chamber that did have rice husk panels, the presence of a flow toward the interior was rarely observed. The rice husk-based insulation panels showed comparable performance with conventional insulators, as a sustainable solution that takes advantage of a local resource to improve thermal comfort and the reduction of the environmental impact.

3.
ACS Appl Mater Interfaces ; 16(25): 32118-32127, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38862123

ABSTRACT

The SARS-CoV-2 (COVID-19) pandemic outbreak led to enormous social and economic repercussions worldwide, felt even to this date, making the design of new therapies to combat fast-spreading viruses an imperative task. In the face of this, diverse cutting-edge nanotechnologies have risen as promising tools to treat infectious diseases such as COVID-19, as well as challenging illnesses such as cancer and diabetes. Aside from these applications, nanoscale metal-organic frameworks (nanoMOFs) have attracted much attention as novel efficient drug delivery systems for diverse pathologies. However, their potential as anti-COVID-19 therapeutic agents has not been investigated. Herein, we propose a pioneering anti-COVID MOF approach by studying their potential as safe and intrinsically antiviral agents through screening various nanoMOF. The iron(III)-trimesate MIL-100 showed a noteworthy antiviral effect against SARS-CoV-2 at the micromolar range, ensuring a high biocompatibility profile (90% of viability) in a real infected human cellular scenario. This research effectively paves the way toward novel antiviral therapies based on nanoMOFs, not only against SARS-CoV-2 but also against other challenging infectious and/or pulmonary diseases.


Subject(s)
Antiviral Agents , COVID-19 Drug Treatment , COVID-19 , Metal-Organic Frameworks , SARS-CoV-2 , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Humans , SARS-CoV-2/drug effects , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/virology , Chlorocebus aethiops , Vero Cells , Cell Survival/drug effects
4.
Clin Cancer Res ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38900037

ABSTRACT

PURPOSE: This phase II clinical trial evaluated the combination of Ibrutinib with rituximab, gemcitabine and oxaliplatin (R-GemOx) in patients with non-germinal centre B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: The IBDCL trial (NCT02692248) included patients with histological diagnosis of non-GCB DLBCL with relapsed or refractory disease and non-candidates for stem cell transplantation. Patients received an induction treatment consisting of 6 or 8 cycles of R-GemOx at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. The primary objective was to evaluate the overall response rate (ORR) after 4 cycles. RESULTS: Sixty-four patients were included, 72% of them refractory to the last regimen. The ORR and CR rate after the 4th cycle were 53% (95% confidence interval [CI], 41-65) and 34% (95% CI, 24-46), respectively. Twenty-four (37%) patients started maintenance and 7 (11%) completed the planned 2 years. After a median follow-up of 29.7 months (range: 0.4-48.6), the estimated 2-year PFS and OS were 18% (95% CI, 8 - 28) and 26% (95% CI, 14 - 37), respectively. The most common grade ≥3 treatment-related adverse events (TRAEs) were thrombocytopenia (44%), neutropenia (30%) and anemia (14%). Grade ≥3 infectious and cardiovascular TRAEs were reported in 6 (9%) and 1 (2%) patient, respectively. CONCLUSIONS: Ibrutinib in combination with R-GemOx, followed by ibrutinib maintenance, demonstrated encouraging antitumor activity with durable responses and a manageable toxicity in patients with non-GCB DLBCL.

5.
Blood Cancer J ; 14(1): 75, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38697976

ABSTRACT

Follicular lymphoma (FL), the most common indolent non-Hodgkin lymphoma, constitutes a paradigm of immune tumor microenvironment (TME) contribution to disease onset, progression, and heterogenous clinical outcome. Here we present the first FL-Patient Derived Lymphoma Spheroid (FL-PDLS), including fundamental immune actors and features of TME in FL lymph nodes (LNs). FL-PDLS is organized in disc-shaped 3D structures composed of proliferating B and T cells, together with macrophages with an intermediate M1/M2 phenotype. FL-PDLS recapitulates the most relevant B-cell transcriptional pathways present in FL-LN (proliferation, epigenetic regulation, mTOR, adaptive immune system, among others). The T cell compartment in the FL-PDLS preserves CD4 subsets (follicular helper, regulatory, and follicular regulatory), also encompassing the spectrum of activation/exhaustion phenotypes in CD4 and CD8 populations. Moreover, this system is suitable for chemo and immunotherapy testing, recapitulating results obtained in the clinic. FL-PDLS allowed uncovering that soluble galectin-9 limits rituximab, rituximab, plus nivolumab/TIM-3 antitumoral activities. Blocking galectin-9 improves rituximab efficacy, highlighting galectin-9 as a novel immunotherapeutic target in FL. In conclusion, FL-PDLS maintains the crosstalk between malignant B cells and the immune LN-TME and constitutes a robust and multiplexed pre-clinical tool to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.


Subject(s)
Galectins , Lymph Nodes , Lymphoma, Follicular , Tumor Microenvironment , Humans , Lymphoma, Follicular/immunology , Lymphoma, Follicular/pathology , Lymphoma, Follicular/therapy , Lymph Nodes/pathology , Lymph Nodes/immunology , Tumor Microenvironment/immunology , Spheroids, Cellular , Immunotherapy/methods , Signal Transduction , Tumor Cells, Cultured
6.
Rev Esp Enferm Dig ; 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38591625

ABSTRACT

Sclerosing angiomatoid nodular transformation (SANT) is a rare benign lesion of the spleen. SANT cannot be distinguished from other benign or malignant splenic tumors based on imaging findings. So, diagnosis relies on histopathologic examination. Although splenectomy is frequently considered as an option, core needle biopsy tissue analysis is safe and accurate to avoid surgery.

7.
Leuk Lymphoma ; 65(7): 911-921, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38598516

ABSTRACT

Parsaclisib, a potent and highly selective phosphoinositide 3-kinase δ inhibitor, has shown clinical activity in relapsed/refractory (R/R) B-cell lymphoma. The phase 1 CITADEL-112 (NCT03424122) study assessed safety and efficacy of parsaclisib in combination with investigator choice standard of care (SOC; rituximab [Treatment A], rituximab plus bendamustine [Treatment B], or ibrutinib [Treatment C]) in 50 patients with R/R B-cell lymphoma. The most common treatment-emergent adverse events included neutropenia (62.5%, 50.0%, and 50.0% of patients in Treatments A, B, and C, respectively); diarrhea (37.5%) and anemia (31.3%) in Treatment A; abdominal pain, asthenia, diarrhea, and nausea (each 33.3%) in Treatment B; and increased alanine and aspartate aminotransferase (each 37.5%) in Treatment C. Objective responses were observed in 13 patients (81.3%) in Treatment A, 10 (55.6%) in Treatment B, and 8 (50.0%) in Treatment C. Parsaclisib combined with SOC therapies had an expected safety profile and promising efficacy in patients with R/R B-cell lymphomas.


Subject(s)
Adenine , Antineoplastic Combined Chemotherapy Protocols , Bendamustine Hydrochloride , Lymphoma, B-Cell , Piperidines , Rituximab , Humans , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Piperidines/administration & dosage , Piperidines/therapeutic use , Piperidines/adverse effects , Rituximab/administration & dosage , Rituximab/adverse effects , Rituximab/therapeutic use , Male , Female , Bendamustine Hydrochloride/administration & dosage , Bendamustine Hydrochloride/adverse effects , Middle Aged , Aged , Adenine/analogs & derivatives , Adenine/administration & dosage , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/pathology , Adult , Treatment Outcome , Aged, 80 and over , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyrazoles/therapeutic use , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Pyrimidines/therapeutic use
8.
Front Endocrinol (Lausanne) ; 15: 1227196, 2024.
Article in English | MEDLINE | ID: mdl-38449853

ABSTRACT

Introduction: Axial spondyloarthritis (axSpA) is a heterogeneous disease that can be represented by radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA). This study aimed to evaluate the relationship between the markers of inflammation and bone turnover in r-axSpA patients and nr-axSpA patients. Methods: A cross-sectional study included 29 r-axSpA patients, 10 nr-axSpA patients, and 20 controls matched for age and sex. Plasma markers related to bone remodeling such as human procollagen type 1 N-terminal propeptide (P1NP), sclerostin, tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) were measured by an ELISA kit. A panel of 92 inflammatory molecules was analyzed by proximity extension assay. Results: R-axSpA patients had decreased plasma levels of P1NP, a marker of bone formation, compared to controls. In addition, r-axSpA patients exhibited decreased plasma levels of sclerostin, an anti-anabolic bone hormone, which would not explain the co-existence of decreased plasma P1NP concentration; however, sclerostin levels could also be influenced by inflammatory processes. Plasma markers of osteoclast activity were similar in all groups. Regarding inflammation-related molecules, nr-axSpA patients showed increased levels of serum interleukin 13 (IL13) as compared with both r-axSpA patients and controls, which may participate in the prevention of inflammation. On the other hand, r-axSpA patients had higher levels of pro-inflammatory molecules compared to controls (i.e., IL6, Oncostatin M, and TNF receptor superfamily member 9). Correlation analysis showed that sclerostin was inversely associated with IL6 and Oncostatin M among others. Conclusion: Altogether, different inflammatory profiles may play a role in the development of the skeletal features in axSpA patients particularly related to decreased bone formation. The relationship between sclerostin and inflammation and the protective actions of IL13 could be of relevance in the axSpA pathology, which is a topic for further investigation.


Subject(s)
Non-Radiographic Axial Spondyloarthritis , Humans , Oncostatin M , Cross-Sectional Studies , Interleukin-13 , Interleukin-6 , Inflammation/diagnostic imaging , Biomarkers
10.
Sci Rep ; 14(1): 5462, 2024 03 05.
Article in English | MEDLINE | ID: mdl-38443503

ABSTRACT

Feline leukemia virus (FeLV) infection is considered one of the most serious disease threats for the endangered Iberian lynx (Lynx pardinus) Over 14 years (2008-2021), we investigated FeLV infection using point-of-care antigen test and quantitative real-time TaqMan qPCR for provirus detection in blood and tissues in lynxes from Andalusia (Southern Spain). A total of 776 samples from 586 individuals were included in this study. The overall prevalence for FeLV antigen in blood/serum samples was 1.4% (5/360) (95% CI: 0.2-2.6), FeLV proviral DNA prevalence in blood samples was 6.2% (31/503) (95% CI: 4.1-8.6), and FeLV proviral DNA in tissues samples was 10.2% (34/333) (95% CI: 7-13.5). From a subset of 129 longitudinally sampled individuals, 9.3% (12/129) PCR-converted during the study period. Our results suggest that FeLV infection in the Andalusian population is enzootic, with circulation of the virus at low levels in almost all the sampling years. Moreover, since only one viremic individual succumbed to the infection, this study suggests that lynxes may therefore control the infection decreasing the possibility of developing a more aggressive outcome. Although our results indicate that the FeLV infection in the Iberian lynx from Andalusia tends to stay within the regressive stage, continuous FeLV surveillance is paramount to predict potential outbreaks and ensure the survival of this population.


Subject(s)
Leukemia, Feline , Lynx , Animals , Cats , Humans , Leukemia Virus, Feline/genetics , Spain/epidemiology , DNA
11.
Pain Manag ; 14(3): 139-151, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38379521

ABSTRACT

Aims: Pain diagnoses in the 10th version of the International Classification of Diseases (ICD-10) did not adequately support the current management of pain. Therefore, we aimed to review the new 11th revision (ICD-11) in order to analyze its usefulness for the management, coding, research and education of chronic pain from a Latin American perspective. Methods: The Latin American Federation of Associations for the Study of Pain convened a meeting of pain experts in Lima, Peru. Pain specialists from 14 Latin American countries attended the consensus meeting. Results: In ICD-11, chronic pain is defined as pain that persists or recurs longer than 3 months and is subdivided into seven categories: chronic primary pain and six types of chronic secondary pain. Chronic primary pain is now considered a disease in itself, and not a mere symptom of an underlying disease. Conclusion: The novel definition and classification of chronic pain in ICD-11 is helpful for better medical care, research and health statistics. ICD-11 will improve chronic pain management in Latin American countries, for both the pain specialist and the primary care physician.


Chronic pain is one of the most frequent reasons for medical consultation in Latin America. In the tenth revision of the International Classification of Diseases and Related Health Problems (ICD-10), chronic pain was not adequately defined and individual pain diagnoses were poorly defined. For the first time in Latin America, a meeting of pain experts analyzed and reviewed the 11th version of the International Classification of Diseases (ICD-11), when the Latin America Federation of Associations for the Study of Pain organized a meeting of experts from 14 Latin American countries. In ICD-11, chronic pain is recognized as a biopsychosocial phenomenon and defined as pain that continues or returns for more than 3 months. It is split into seven types: chronic primary pain and six types of chronic secondary pain. In ICD-11, chronic primary pain is now considered a disease in itself, not a mere manifestation of other disease. Our article is the first to address the problems, challenges and benefits of using ICD-11 from a Latin American perspective. It will help to facilitate and disseminate the use of this new classification of chronic pain. This will improve chronic pain treatment, statistics, research and development of better health strategies for pain management in Latin America.


Subject(s)
Chronic Pain , Humans , Chronic Pain/diagnosis , Consensus , International Classification of Diseases , Latin America
12.
Children (Basel) ; 11(2)2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38397312

ABSTRACT

Diagnostic reference levels (DRLs) are a pivotal strategy to be implemented since pediatric interventional cardiology procedures are increasing. This work aimed to propose an initial set of Brazilian DRLs for pediatric interventional diagnostic and therapeutic (D&T) procedures. A retrospective study was carried out in four Brazilian states, distributed across the three regions of the country. Data were collected from pediatric patients undergoing cardiac interventional procedures (CIPs), including their age and anthropometric characteristics, and at least four parameters (number of images, exposure time, air kerma-area product-PKA, and cumulative air kerma). Data from 279 patients undergoing CIPs were gathered (147 diagnostic and 132 therapeutic procedures). There were no significant differences in exposure time and the number of images between the D&T procedures. A wide range of PKA was observed when the therapeutic procedures were compared to diagnostics for all age groups. There were significant differences between the D&T procedures, whether grouping data by patient weight or age. In terms of cumulative air kerma, it was noted that no value exceeded the level to trigger a monitoring process for patients. This study shows that it is possible to adopt them as the first proposal to establish national DRLs considering pediatric patient groups.

13.
Nat Med ; 30(2): 507-518, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38233586

ABSTRACT

The phase 3 ZUMA-7 trial in second-line large B cell lymphoma demonstrated superiority of anti-CD19 CAR T cell therapy (axicabtagene ciloleucel (axi-cel)) over standard of care (SOC; salvage chemotherapy followed by hematopoietic transplantation) ( NCT03391466 ). Here, we present a prespecified exploratory analysis examining the association between pretreatment tumor characteristics and the efficacy of axi-cel versus SOC. B cell gene expression signature (GES) and CD19 expression associated significantly with improved event-free survival for axi-cel (P = 0.0002 for B cell GES; P = 0.0165 for CD19 expression) but not SOC (P = 0.9374 for B cell GES; P = 0.5526 for CD19 expression). Axi-cel showed superior event-free survival over SOC irrespective of B cell GES and CD19 expression (P = 8.56 × 10-9 for B cell GES high; P = 0.0019 for B cell GES low; P = 3.85 × 10-9 for CD19 gene high; P = 0.0017 for CD19 gene low). Low CD19 expression in malignant cells correlated with a tumor GES consisting of immune-suppressive stromal and myeloid genes, highlighting the inter-relation between malignant cell features and immune contexture substantially impacting axi-cel outcomes. Tumor burden, lactate dehydrogenase and cell-of-origin impacted SOC more than axi-cel outcomes. T cell activation and B cell GES, which are associated with improved axi-cel outcome, decreased with increasing lines of therapy. These data highlight differences in resistance mechanisms to axi-cel and SOC and support earlier intervention with axi-cel.


Subject(s)
Biological Products , Lymphoma, Large B-Cell, Diffuse , Humans , Immunotherapy, Adoptive , Tumor Microenvironment , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/therapy , B-Lymphocytes , Adaptor Proteins, Signal Transducing , Antigens, CD19
14.
Rev Esp Enferm Dig ; 2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38235692

ABSTRACT

Inflammatory bowel disease is a known risk factor for enteric infections such as Salmonella. This infection can affect almost all major organs. Acute Salmonella pancreatitis is a rare complication. This is the case of a 61-year-old man with ulcerative colitis who developed acute pancreatitis complicating Salmonella infection.

15.
Endocrine ; 83(2): 405-413, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37581746

ABSTRACT

BACKGROUND: The cardiovascular (CV) system is profoundly affected by thyroid hormones. Both hypo- and hyperthyroidism can increase the risk of severe CV complications. OBJECTIVE: To assess the association of hyperthyroidism with major CV risk factors (CVRFs) and CV diseases (CVDs) using a big data methodology with the Savana Manager platform. MATERIAL AND METHODS: This was an observational and retrospective study. The data were obtained from the electronic medical records of the University Hospital Puerta de Hierro Majadahonda (Spain). Artificial intelligence techniques were used to extract the information from the electronic health records and Savana Manager 3.0 software was used for analysis. RESULTS: Of a total of 540,939 patients studied (53.62% females; mean age 42.2 ± 8.7 years), 5504 patients (1.02%; 69.9% women) had a diagnosis of hyperthyroidism. Patients with this diagnosis had a significantly (p < 0.0001) higher frequency of CVRFs than that found in non-hyperthyroid subjects. The higher frequency of CVRFs in patients with hyperthyroidism was observed in both women and men and in patients younger and older than 65 years of age. The total frequency of CVDs was also significantly (p < 0.0001) higher in patients diagnosed with hyperthyroidism than that found in patients without this diagnosis. The highest odds ratio values obtained were 6.40 (4.27-9.61) for embolic stroke followed by 5.99 (5.62-6.38) for atrial fibrillation. The frequency of all CVDs evaluated in patients with a diagnosis of hyperthyroidism was significantly higher in both women and men, as well as in those younger and older than 65 years, compared to subjects without this diagnosis. A multivariate regression analysis showed that hyperthyroidism was significantly and independently associated with all the CVDs evaluated except for embolic stroke. CONCLUSION: The data from this hospital cohort suggest that there is a significant association between the diagnosis of hyperthyroidism and the main CVRFs and CVDs in our population, regardless of the age and gender of the patients. Our study, in addition to confirming this association, provides useful information for understanding the applicability of artificial intelligence techniques to "real-world data and information".


Subject(s)
Cardiovascular Diseases , Embolic Stroke , Hyperthyroidism , Male , Humans , Female , Adult , Middle Aged , Cardiovascular Diseases/etiology , Retrospective Studies , Data Science , Artificial Intelligence , Embolic Stroke/complications , Hyperthyroidism/complications , Risk Factors
16.
Am J Dermatopathol ; 46(2): 104-106, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38055983

ABSTRACT

ABSTRACT: A 38-year-old man presented with fever, cough, and jaundice. Four days before, he had started taking amoxicillin/clavulanic acid. He subsequently developed a morbilliform rash, and, according to clinical features and blood analyses, a diagnosis of mononucleosis with Epstein-Barr virus-associated antibiotic-induced exanthema and secondary hemophagocytic lymphohistiocytosis was made. A skin biopsy revealed a superficial perivascular lymphohistiocytic infiltrate with interface dermatitis and many foamy macrophages in the papillary dermis and around the vessels of the superficial dermal plexus. A blood lipid test uncovered marked hypercholesterolemia and hypertriglyceridemia. After treatment with dexamethasone and immunoglobulin, the skin rash, liver function, and lipid profile progressively improved. Xanthomatous cells have been observed in skin biopsies of acute graft-versus-host disease with liver involvement, and these cells have been suggested to represent a clue to the presence of hepatic disease. In our case, underlying cholestatic hepatopathy with hyperlipidemia was present. We believe that the incidental finding of foamy cells in graft-versus-host disease cases and in our case are likely related to the presence of severe liver disease with cholestatic hepatopathy and secondary hyperlipidemia in different background conditions.


Subject(s)
Epstein-Barr Virus Infections , Exanthema , Graft vs Host Disease , Hyperlipidemias , Lymphohistiocytosis, Hemophagocytic , Male , Humans , Adult , Lymphohistiocytosis, Hemophagocytic/pathology , Epstein-Barr Virus Infections/complications , Hyperlipidemias/chemically induced , Hyperlipidemias/complications , Herpesvirus 4, Human , Amoxicillin , Exanthema/chemically induced , Exanthema/complications , Lipids , Macrophages/pathology
17.
Hematol Oncol ; 42(1): e3235, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37942762

ABSTRACT

Watchful waiting is an acceptable management strategy for advanced-stage, low tumor burden (LTB) patients with follicular lymphoma (FL). However, the prediction of how long this treatment-free observation period will last remains imperfect. We explored whether total metabolic tumor volume (TMTV) and other positron emission tomography parameters were predictive of time to first treatment (TTFT). We analyzed 97 grade 1-3A advanced-stage LTB FL patients and found that a high TMTV was associated with other tumor burden features at diagnosis. Patients with a TMTV above our established cutoff of 50 mL had a significantly shorter median duration of observation (2.6 vs. 8.8 years; p = 0.001). At 5 years, 77% of patients with a high TMTV and 46% of patients with a low TMTV required treatment. In the multivariable analysis, a high TMTV was the only independent factor predicting TTFT (hazard ratio = 2.09; p = 0.017). Overall, TMTV is a strong predictor of the duration of observation in LTB FL patients. Upon validation of our cutoff in external series and standardization of the methodology, the TMTV could become an additional factor to consider deferring or initiating treatment in otherwise LTB patients.


Subject(s)
Lymphoma, Follicular , Humans , Lymphoma, Follicular/therapy , Tumor Burden , Prognosis , Fluorodeoxyglucose F18 , Proportional Hazards Models , Positron Emission Tomography Computed Tomography/methods , Retrospective Studies
18.
Br J Haematol ; 204(2): 525-533, 2024 02.
Article in English | MEDLINE | ID: mdl-37905734

ABSTRACT

Varnimcabtagene autoleucel (var-cel) is an academic anti-CD19 chimeric antigen receptor (CAR) product used for the treatment of non-Hodgkin lymphoma (NHL) in the CART19-BE-01 trial. Here we report updated outcomes of patients with NHL treated with var-cel. B-cell recovery was compared with patients with acute lymphoblastic leukaemia (ALL). Forty-five patients with NHL were treated. Cytokine release syndrome (any grade) occurred in 84% of patients (4% grade ≥3) and neurotoxicity in 7% (2% grade ≥3). The objective response rate was 73% at Day +100, and the 3-year duration of response was 56%. The 3-year progression-free and overall survival were 40% and 52% respectively. High lactate dehydrogenase was the only covariate with an impact on progression-free survival. The 3-year incidence of B-cell recovery was lower in patients with NHL compared to ALL (25% vs. 60%). In conclusion, in patients with NHL, the toxicity of var-cel was manageable, while B-cell recovery was significantly prolonged compared to ALL. This trial was registered as NCT03144583.


Subject(s)
Lymphoma, B-Cell , Lymphoma, Non-Hodgkin , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Receptors, Chimeric Antigen , Humans , Point-of-Care Systems , Lymphoma, B-Cell/therapy , Lymphoma, Non-Hodgkin/therapy , Immunotherapy, Adoptive/adverse effects , Antibodies , Antigens, CD19 , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , T-Lymphocytes
19.
Pediatr Dermatol ; 41(2): 307-310, 2024.
Article in English | MEDLINE | ID: mdl-37817291

ABSTRACT

Barber-Say syndrome (BSS) is a rare congenital ectodermal dysplasia with few cases reported in the literature. We describe a 9-year-old boy with congenital generalized hypertrichosis and multiple rhabdomyomatous mesenchymal hamartomas (RMHs) on his nose and periocular region. Next-generation sequencing, performed in DNA from a blood sample, and RMH tissue, revealed a pathogenic variant in the TWIST2 gene, which was not detected in a salivary sample of the patient, nor in his parents. Therefore, we consider this variant as de novo mosaicism. To our knowledge, this is the first case of multiple RMHs associated with BSS.


Subject(s)
Abnormalities, Multiple , Eyelid Diseases , Hamartoma , Hypertelorism , Hypertrichosis , Macrostomia , Skin Abnormalities , Male , Humans , Child , Hypertrichosis/genetics , Hypertrichosis/congenital , Abnormalities, Multiple/genetics , Hirsutism/genetics , Hamartoma/complications , Hamartoma/diagnosis , Hamartoma/genetics
20.
J Clin Med ; 12(21)2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37959184

ABSTRACT

Primary hyperparathyroidism (PHPT) seems to be associated with different cardiovascular diseases (CVDs). We evaluated the association of PHPT with major CV risk factors (CVRFs) and CVDs by using artificial intelligence (AI) tools. An observational and retrospective study was conducted using data from the electronic health records (EHRs) of the Hospital Universitario Puerta de Hierro Majadahonda (Spain). Of a total of 699,157 patients over 18 years of age studied (54.7% females), 6515 patients (0.9%; 65.4% women; mean age 67.6 ± 15.9 years) had a diagnosis of PHPT. The overall frequencies of hypertension, dyslipidemia, diabetes mellitus, and smoking habit in the cohort of patients with PTHP were all significantly (p < 0.001) higher than those found in patients without a diagnosis of PTHP. The total frequency of stroke, ischemic heart disease, atrial fibrillation, deep vein thrombosis, and pulmonary embolism in the cohort of PHPT patients were significantly (p < 0.001) higher than that found in patients without the diagnosis of PHPT. A multivariate regression analysis showed that PHPT was significantly (p < 0.001) and independently associated with all the CVDs evaluated. Our data show that there is a significant association between the diagnosis of PHPT and the main CVRFs and CVDs in our hospital population.

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