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OBJECTIVE: To evaluate the accuracy of the galactomannan serum test in diagnosing oral invasive aspergillosis. METHODS: This prospective observational study included oncohematological neutropenic patients with suspected invasive aspergillosis, but without signs of pulmonary involvement. These patients underwent nasofibroscopy, biopsy, galactomannan serum testing, and maxillofacial high-resolution computed tomography to diagnose invasive aspergillosis. Patients were divided into two groups: Group 1 consisted of those with proven invasive aspergillosis, while Group 2 included patients without proven invasive aspergillosis. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Thirteen patients were included in Group 1 and four in Group 2. The sensitivity, specificity, positive predictive and negative predictive values were 0.69, 1.0, 1.0 and 0.5, respectively. Sensitivity was higher in cases with Aspergillus sinusitis than in cases with exclusive oral lesions (0.77 versus 0.5, respectively). The galactomannan serum test optical density index was higher in Group 1 (2.4; range 0.2-3.5) than in Group 2 (0.2; range: 0.1-0.3; P-value = 0.007. CONCLUSIONS: The galactomannan serum test is a valuable tool for screening invasive aspergillosis, especially in cases with nasal or sinus involvement, but biopsy is still the gold standard for diagnosis.
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BACKGROUND: Telomeropathies are a group of inherited disorders caused by germline pathogenic variants in genes involved in telomere maintenance, resulting in excessive telomere attrition that affects several tissues, including hematopoiesis. RecQ and RTEL1 helicases contribute to telomere maintenance by unwinding telomeric structures such as G-quadruplexes (G4), preventing replication defects. Germline RTEL1 variants also are etiologic in telomeropathies. METHODS AND RESULTS: Here we investigated the expression of RecQ (RECQL1, BLM, WRN, RECQL4, and RECQL5) and RTEL1 helicase genes in peripheral blood mononuclear cells (PBMCs) from human telomeropathy patients. The mRNA expression levels of all RecQ helicases, but not RTEL1, were significantly downregulated in patients' primary cells. Reduced RecQ expression was not attributable to cell proliferative exhaustion, as RecQ helicases were not attenuated in T cells exhausted in vitro. An additional fifteen genes involved in DNA damage repair and RecQ functional partners also were downregulated in the telomeropathy cells. CONCLUSION: These findings indicate that the expression of RecQ helicases and functional partners involved in DNA repair is downregulated in PBMCs of telomeropathy patients.
Subject(s)
Leukocytes, Mononuclear , RecQ Helicases , Adult , Female , Humans , Male , DNA Helicases/genetics , DNA Helicases/metabolism , DNA Repair/genetics , Leukocytes, Mononuclear/metabolism , RecQ Helicases/genetics , RecQ Helicases/metabolism , Telomere/metabolism , Telomere/genetics , Telomere Homeostasis/geneticsSubject(s)
Antigens, CD19 , Immunotherapy, Adoptive , Lymphoma, Non-Hodgkin , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Lymphoma, Non-Hodgkin/therapy , Brazil , Antigens, CD19/immunology , Antigens, CD19/therapeutic use , Male , Immunotherapy, Adoptive/methods , Female , Adult , Middle Aged , Receptors, Chimeric Antigen/therapeutic use , AdolescentABSTRACT
Gastric cancer (GC) remains a formidable global health challenge, ranking among the top-five causes of cancer-related deaths worldwide. The majority of patients face advanced stages at diagnosis, with a mere 6% five-year survival rate. First-line treatment for metastatic GC typically involves a fluoropyrimidine and platinum agent combination; yet, predictive molecular markers have proven elusive. This review navigates the evolving landscape of GC biomarkers, with a specific focus on Claudin 18.2 (CLDN18.2) as an emerging and promising target. Recent phase III trials have unveiled the efficacy of Zolbetuximab, a CLDN18.2-targeting antibody, in combination with oxaliplatin-based chemotherapy for CLDN18.2-positive metastatic GC. As this novel therapeutic avenue unfolds, understanding the nuanced decision making regarding the selection of anti-CLDN18.2 therapies over other targeted agents in metastatic GC becomes crucial. This manuscript reviews the evolving role of CLDN18.2 as a biomarker in GC and explores the current status of CLDN18.2-targeting agents in clinical development. The aim is to provide concise insights into the potential of CLDN18.2 as a therapeutic target and guide future clinical decisions in the management of metastatic GC.
ABSTRACT
Applying surfactants to reduce the interfacial tension (IFT) on water/oil interfaces is a proven technique. The search for new surfactants and delivery strategies is an ongoing research area with applications in many fields such as drug delivery through nanoemulsions and enhanced oil recovery. Experimentally, the combination of hyperbranched polyglycerol (HPG) with cetyltrimethylammonium bromide (CTAB) substantially reduced the observed IFT of oil/water interface, 0.9 mN/m, while HPG alone was 5.80 mN/m and CTAB alone IFT was 8.08 mN/m. Previous simulations in an aqueous solution showed that HPG is a surfactant carrier. Complementarily, in this work, we performed classical molecular dynamics simulations on combinations of CTAB and HPG with one aliphatic chain to investigate further the interaction of this pair in oil interfaces and propose the mechanism of IFT decrease. Basically, from our results, one can observe that the IFT reduction comes from a combination of effects that have not been observed for other dual systems: (i) Due to the CTAB-HPG strong interaction, a weakening of their specific and isolated interactions with the water and oil phases occurs. (ii) Aggregates enlarge the interfacial area, turning it into a less ordered interface. (iii) The spread of individual molecules charge profiles leads to the much lower interfacial tension observed with the CTAB+HPG systems.
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Objective To evaluate the postoperative functional and radiographic outcomes of the shoulder of patients submitted to transosseous suturing of a greater tuberosity fracture (GTF) through an anterolateral route and the influence of the glenohumeral dislocation on these outcomes. Methods We conducted a retrospective study and functional assessment using the Constant-Murley score. The distance between the greater tuberosity and the joint surface of the proximal humerus (in true anteroposterior radiographs) after the union was calculated. We used the Fisher exact test for the categorical independent variables, and the Student t or Mann-Whitney test for the non-categorical variables. Results In total, 26 patients met the inclusion criteria, and 38% of the sample presented an association between glenohumeral dislocation and GTF. The mean Constant-Murley score was of 82.5 + 8.02 points. The presence of an associated dislocation did not alter the functional outcome. The mean distance between the greater tuberosity of the humerus and the joint surface of the humeral head after the union was of 9 ± 4.3 mm below the articular line of the humeral head. The dislocation led to a lower level of reduction, but this did not influence the Constant-Murley score. Conclusion The cases of GTF submitted to surgical treatment with transosseous sutures had good functional outcomes. The presence of dislocation made the anatomical reduction of the greater tuberosity difficult. However, it did not influence the Constant-Murley score.
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BACKGROUND: Steroid-refractory acute graft-vs.-host disease (SR-aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation with a dismal prognosis and for which there is no consensus-based second-line therapy. Ruxolitinib is not easily accessible in many countries. A possible therapy is the administration of mesenchymal stromal cells (MSCs). METHODS: In this retrospective study, 52 patients with severe SR-aGVHD were treated with MSCs from umbilical cord (UC-MSCs) in nine institutions. RESULTS: The median (range) age was 12.5 (0.3-65) years and the mean ± SD dose (×106/kg) was 4.73 ± 1.3 per infusion (median of four infusions). Overall (OR) and complete response (CR) rates on day 28 were 63.5% and 36.6%, respectively. Children (n = 35) had better OR (71.5% vs. 47.1%, p = 0.12), CR (48.6% vs. 11.8%, p = 0.03), overall survival (p = 0.0006), and relapse-free survival (p = 0.0014) than adults (n = 17). Acute adverse events (all of them mild or moderate) were detected in 32.7% of patients, with no significant difference in children and adult groups (p = 1.0). CONCLUSIONS: UC-MSCs are a feasible alternative therapy for SR-aGVHD, especially in children. The safety profile is favorable.
ABSTRACT
Abstract Objective To evaluate the postoperative functional and radiographic outcomes of the shoulder of patients submitted to transosseous suturing of a greater tuberosity fracture (GTF) through an anterolateral route and the influence of the glenohumeral dislocation on these outcomes. Methods We conducted a retrospective study and functional assessment using the Constant-Murley score. The distance between the greater tuberosity and the joint surface of the proximal humerus (in true anteroposterior radiographs) after the union was calculated. We used the Fisher exact test for the categorical independent variables, and the Student t or Mann-Whitney test for the non-categorical variables. Results In total, 26 patients met the inclusion criteria, and 38% of the sample presented an association between glenohumeral dislocation and GTF. The mean Constant-Murley score was of 82.5 + 8.02 points. The presence of an associated dislocation did not alter the functional outcome. The mean distance between the greater tuberosity of the humerus and the joint surface of the humeral head after the union was of 9 + 4.3 mm below the articular line of the humeral head. The dislocation led to a lower level of reduction, but this did not influence the Constant-Murley score. Conclusion The cases of GTF submitted to surgical treatment with transosseous sutures had good functional outcomes. The presence of dislocation made the anatomical reduction of the greater tuberosity difficult. However, it did not influence the Constant-Murley score.
Resumo Objetivo Avaliar os resultados funcional e radiográfico pós-operatórios do ombro, em pacientes submetidos a sutura transóssea de fratura da tuberosidade maior (FTM) por acesso anterolateral, e a influência da luxação glenoumeral nesses resultados. Métodos Realizou-se estudo retrospectivo e avaliação funcional (pela escala de Constant-Murley). Calculou-se a distância entre a tuberosidade maior e a superfície articular do úmero proximal (por meio de radiografia em incidência anteroposterior verdadeira) após a consolidação. Usou-se o teste Exato de Fisher para as variáveis independentes categóricas, e os testes tde Student ou de Mann-Whitney para as não categóricas. Resultados Ao todo, 26 pacientes preencheram os critérios de inclusão. A associação de luxação glenoumeral com FTM foi observada em 38% da amostra. A média da pontuação na escala de Constant-Murley foi de 82,5 + 8,02. A presença de luxação associada não alterou o resultado funcional. A distância média da consolidação da tuberosidade maior do úmero em relação à superfície articular da cabeça umeral foi de 9 + 4,3 mm abaixo da linha articular da cabeça umeral. Pacientes com luxação associada evoluíram com redução menor, mas isso não influenciou na pontuação na escala de Constant-Murley. Conclusão As FTMs submetidas ao tratamento cirúrgico com sutura transóssea evoluíram com bom resultado funcional. A presença de luxação dificultou a redução anatômica da tuberosidade maior. Entretanto, isso não influenciou na pontuação na escala de Constant-Murley.
Subject(s)
Humans , Shoulder Dislocation/surgery , Suture Techniques , Suture Anchors , Humeral Fractures/surgeryABSTRACT
INTRODUCTION: Allogeneic Hematopoietic Stem Cells Transplantation (allo-HSCT) is capable of curing patients with neoplastic or non-neoplastic hematologic disorders or of prolonging their survival. This study assessed if the insertion of the clinical pharmacist in the allo-HSCT team modified the outcomes: transplantation-related mortality, grafting failure, incidence of Graft versus Host Disease, hospitalization time, time for grafting, number of readmissions, number of drug-related problems (DRPs), adherence and knowledge about pharmacotherapy. METHODS: Interventional study with historical control carried out in an allo-HSCT unit, in which the intervention group (IG) included 33 individuals who received pharmacotherapy follow-up. Control Group (CG) consisted of 28 individuals. RESULTS: A total of 250 DRPs were identified, 59 team's doubts were clarified, and 309 interventions were conducted in the IG. The DRPs mainly arose from safety (51.60%) and effectiveness (38.40%) problems. A mean of 9.36 (SD = 6.97) interventions per patient was obtained, mainly including dose reductions (19.09%), adjustments in administration time (18.12%), educational activities (15.21%) and drug removal (10.68%). Clinical significance of the interventions was considered high (75.7% extremely significant, very significant or significant), as well as their acceptability (89.7% accepted). Each patient attended a mean of 4.68 pharmaceutical consultations (SD = 1.91) after hospital discharge, presenting increase in knowledge (p = 0.0001) and in adherence (p = 0.0115). There was no evidence of differences between the groups in the other outcomes analyzed. CONCLUSIONS: The pharmacotherapy follow-up allowed detecting several DRPs and performing interventions of high clinical relevance and acceptability, in addition to improving adherence and individualizing the pharmacotherapy.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Pharmacists , Hematopoietic Stem Cell Transplantation/adverse effects , Hospitalization , Graft vs Host Disease/prevention & control , Graft vs Host Disease/etiology , Hematopoietic Stem Cells , Retrospective StudiesABSTRACT
BACKGROUND: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) is currently one of the most effective therapies in onco-hematology. For the treatment of the disease and prevention of such complications, a complex pharmacotherapeutic regimen is employed. Non-compliance is prevalent among adolescents and young adults with chronic hematological diseases, being reported by up to 50% of the patients. OBJECTIVE: To evaluate the results of pharmacotherapeutic follow-up on medication compliance and on the knowledge about pharmacotherapy of patients who underwent allo-HSCT. METHODS: A single-arm, open-label and non-randomized intervention study developed in an allo-HSCT outpatient clinic. The participants attended pharmaceutical consultations and had their knowledge about pharmacotherapy and medication compliance measured by MedTake and Brief Medication Questionnaire (BMQ), respectively. RESULTS: A total of 27 patients attended pharmaceutical consultations (4.81 consultations/patient; SD = 1.80). There was an improvement in medication compliance and in knowledge between the first and last consultations (p < 0.05). In the final consultation, 70.37% of the patients showed compliance, with a knowledge rate of 98.35% (SD = 3.63). Non-compliant individuals presented a greater tendency to hospital readmissions. There was no relationship between medication compliance and sociodemographic variables, graft-versus-host disease, and knowledge about pharmacotherapy. CONCLUSIONS: Pharmacotherapeutic follow-up contributed to improving medication compliance. Knowledge about pharmacotherapy alone does not translate into behaviors, which corroborates the complexity of the biopsychosocial factors associated with medication compliance.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Adolescent , Young Adult , Humans , Follow-Up Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/drug therapy , Graft vs Host Disease/prevention & control , Graft vs Host Disease/etiology , Medication Adherence , Pharmaceutical Preparations , Retrospective StudiesABSTRACT
ABSTRACT Objective: The objective of this study was to evaluate the oral health condition and dental treatments performed in patients in pre-allogeneic HCT. Method: The records of patients treated during 2018 at a Brazilian HCT service were reviewed. The following oral health data were obtained: 1. Decayed, missing and filled teeth / correlated index for primary dentition (DMFT/dmft); 2. Quality of oral hygiene and 3. Dental pathologies: 3.1 Periodontal infectious focus, 3.2 Endodontic infectious focus and 3.3 Carie incidence. All dental procedures performed were surveyed. Results: Thirty-three patients were included, with a mean age of 28.42 (±16.37), 20 male (60%) and 13 female. The average DMFT/dmft found in this study was 10.24 (± 8.37), similar to the index found in the population in southeastern Brazil. The younger study population presented a DMFT/dmft considered high, when compared to the general population. A total of 27.2% of the patients had active caries lesions, 33.3%, foci of periodontal infection, 15.1%, endodontic infectious focus and 40%, poor oral hygiene. Almost half of the patients (48.4%) had to undergo dental intervention, 24.2% needing periodontal scaling, 21.2%, fillings and 12.1%, tooth extractions. Conclusion: We conclude that the studied population had an important incidence of dental pathologies and infectious conditions that could complicate throughout HCT, especially in younger patients, therefore presenting a high demand for dental treatment in the pre-HCT. Studies that assess the impact of dental conditioning on the outcomes of HCT with an emphasis on dental infectious complications, days of hospitalization and survival are necessary."
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Young Adult , Oral Health , Hematopoietic Stem Cell Transplantation , Transplantation, Homologous , Bone Marrow Transplantation , Focal InfectionABSTRACT
CAR-T cell therapies have been recognized as one of the most advanced and efficient strategies to treat patients with hematologic malignancies. However, similar results have not been observed for the treatment of solid tumors. One of the explanations is the fact that tumors have extremely hostile microenvironments for the infiltration and effector activity of T-cells, mainly due to the presence of highly suppressive cytokines, hypoxia, and reactive oxygen species. Taking advantage of cytokines functionally, new fourth-generation CAR constructs have been developed to target tumor cells and additionally release cytokines that can contribute to the cytotoxicity of T-cells. The manufacturing process, including the use of cytokines in the expansion and differentiation of T cells, is also discussed. Finally, the clinical aspects and the influence of cytokines on the clinical condition of patients, such as cytokine release syndrome, who receive treatment with CAR-T cells are addressed. Therefore, this review aims to highlight how important cytokines are as one of the major players of cell therapy.
Subject(s)
Neoplasms , Receptors, Chimeric Antigen , Cell- and Tissue-Based Therapy , Cytokines , Cytotoxicity, Immunologic , Humans , Immunomodulation , Neoplasms/therapy , Reactive Oxygen Species , Receptors, Chimeric Antigen/genetics , Tumor MicroenvironmentSubject(s)
Humans , Female , Middle Aged , Mycoplasma salivarium , Graft vs Host Disease/diagnosis , Mouth Mucosa , Transplantation, Homologous , InfectionsABSTRACT
INTRODUCTION: The optimization of oral health before allogeneic hematopoietic cell transplantation (HCT) is important for preventing infectious complications during treatment. OBJECTIVE: The objective of this study was to evaluate the oral health condition and dental treatments performed in patients in pre-allogeneic HCT. METHOD: The records of patients treated during 2018 at a Brazilian HCT service were reviewed. The following oral health data were obtained: 1. Decayed, missing and filled teeth / correlated index for primary dentition (DMFT/dmft); 2. Quality of oral hygiene and 3. Dental pathologies: 3.1 Periodontal infectious focus, 3.2 Endodontic infectious focus and 3.3 Carie incidence. All dental procedures performed were surveyed. RESULTS: Thirty-three patients were included, with a mean age of 28.42 (±16.37), 20 male (60%) and 13 female. The average DMFT/dmft found in this study was 10.24 (± 8.37), similar to the index found in the population in southeastern Brazil. The younger study population presented a DMFT/dmft considered high, when compared to the general population. A total of 27.2% of the patients had active caries lesions, 33.3%, foci of periodontal infection, 15.1%, endodontic infectious focus and 40%, poor oral hygiene. Almost half of the patients (48.4%) had to undergo dental intervention, 24.2% needing periodontal scaling, 21.2%, fillings and 12.1%, tooth extractions. CONCLUSION: We conclude that the studied population had an important incidence of dental pathologies and infectious conditions that could complicate throughout HCT, especially in younger patients, therefore presenting a high demand for dental treatment in the pre-HCT. Studies that assess the impact of dental conditioning on the outcomes of HCT with an emphasis on dental infectious complications, days of hospitalization and survival are necessary."
ABSTRACT
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only currently available curative treatment for sickle cell disease (SCD). However, the effects of HSCT on SCD pathophysiology are poorly elucidated. Here, we assessed red blood cell (RBC) adhesiveness, intensity of hemolysis, vascular tone markers and systemic inflammation, in SCD patients treated with allogeneic HSCT. Thirty-two SCD patients were evaluated before and on long-term follow-up after HSCT. Overall survival was 94% with no severe (grade III-IV) graft-vs-host disease and a 22% rejection rate (graft failure). Hematological parameters, reticulocyte counts, and levels of lactate dehydrogenase (LDH), endothelin-1 and VCAM-1 normalized in SCD patients post-HSCT. Expression of adhesion molecules on reticulocytes and RBC was lower in patients with sustained engraftment. Levels of IL-18, IL-15 and LDH were higher in patients that developed graft failure. Increased levels of plasma pro-inflammatory cytokines, mainly TNF-α, were found in SCD patients long-term after transplantation. SCD patients with sustained engraftment after allo-HSCT showed decreased reticulocyte counts and adhesiveness, diminished hemolysis, and lower levels of vascular tonus markers. Nevertheless, systemic inflammation persists for at least five years after transplantation, indicating that allo-HSCT does not equally affect all aspects of SCD pathophysiology.
Subject(s)
Anemia, Sickle Cell/complications , Disease Susceptibility , Inflammation/etiology , Adolescent , Adult , Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/therapy , Biomarkers , Blood Cell Count , Child , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Hemolysis , Humans , Inflammation/diagnosis , Inflammation Mediators , Male , Nitric Oxide/metabolism , Time Factors , Transplantation, Homologous , Young AdultABSTRACT
Chimeric antigen receptor T (CAR-T) cell therapy is a novel therapeutic modality for acute lymphoblastic leukemia (ALL) with robust outcomes in patients with refractory or relapsed disease. At the same time, CAR-T cell therapy is associated with unique and potentially fatal toxicities, such as cytokine release syndrome (CRS) and neurological toxicities (ICANS). This manuscript aims to provide a consensus of specialists in the fields of Hematology Oncology and Cellular Therapy to make recommendations on the current scenario of the use of CAR-T cells in patients with ALL.
ABSTRACT
The treatment and evolution of B-cell non-Hodgkin lymphoma (B-NHL) has undergone important changes in the last years with the emergence of targeted therapies, such as monoclonal antibodies, small molecules, antibody-drug conjugates, and bispecific antibodies. Nevertheless, a significant portion of patients remains refractory or relapsed (R/R) to the new therapeutic modalities, representing thus an unmet medical need. The use of CAR-T cells for the treatment of B-NHL patients has shown to be a promising therapy with impressive results in patients with R/R disease. The expectations are as high as the imminent approval of CAR-T cell therapy in Brazil, which it is expected to impact the prognosis of R/R B-NHL. The aim of this manuscript is to offer a consensus of specialists in the field of onco-hematology and cellular therapy, working in Brazil and United States, in order to discuss and offer recommendations in the present setting of the use of CAR-T cells for patients with B-NHL.