Use of Eltrombopag to Improve Thrombocytopenia and Tranfusion Requirement in Anti-CD19 CAR-T Cell-Treated Patients.

Background/Objectives: Immune effector cell-associated hematotoxicity (ICAHT) is a frequent adverse event after chimeric antigen receptor (CAR)-T cell therapy. Grade ≥ 3 thrombocytopenia occurs in around one-third of patients, and many of them become platelet transfusion-dependent. Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) able to accelerate megakaryopoiesis, which has been used successfully in patients with bone marrow failure and immune thrombocytopenia (ITP). Its role in managing thrombocytopenia and other cytopenias in CAR-T cell-treated patients has been scarcely addressed. Our aim was to report the safety and efficacy of this approach in patients included in the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC) registry. Methods: This is a retrospective, multicenter, observational study. Patients who developed platelet transfusion dependence subsequently to CAR-T cells and received eltrombopag to improve platelet counts were recruited in 10 Spanish hospitals. Results: Thirty-eight patients were enrolled and followed up for a median (interquartile range [IQR]) of 175 (99, 489) days since CAR-T cell infusion. At the moment eltrombopag was indicated, 18 patients had thrombocytopenia and another severe cytopenia, while 8 patients had severe pancytopenia. After 32 (14, 38) days on eltrombopag, 29 (76.3%) patients recovered platelet transfusion independence. The number of platelet units transfused correlated with the time needed to restore platelet counts higher than 20 × 109/L (Rho = 0.639, p < 0.001). Non-responders to eltrombopag required more platelet units (58 [29, 69] vs. 12 [6, 26] in responders, p = 0.002). Nineteen out of twenty-three (82.6%) patients recovered from severe neutropenia after 22 (11, 31) days on eltrombopag. Twenty-nine out of thirty-five (82.9%) patients recovered red blood cell (RBC) transfusion independence after 29 (17, 44) days. Seven patients recovered all cell lineages while on treatment. No thromboembolic events were reported. Only two transient toxicities (cholestasis, hyperbilirubinemia) were reported during eltrombopag treatment, none of which compelled permanent drug withdrawal. Conclusions: Eltrombopag could be safely used to manage thrombocytopenia and accelerate transfusion independence in CAR-T cell-treated patients.

Mother-child bond and its relationship with maternal postpartum depression.

BACKGROUND: The mother-child bond may be related to maternal health, especially postpartum depression (PPD). Existing studies show the need for further in-depth research on the subject. AIM: To determine the relationship between bonding and the probability of the development and presence of PPD in women with a biological child between 6 weeks and 18 months of age. METHODS: A cross-sectional study was conducted. A questionnaire containing sociodemographic, psychosocial, and health variables referring to the mother and the newborn, a questionnaire measuring the mother-child bond (VAMF-bond), and the Edinburgh Postpartum Depression Scale (EDPS) were administered. RESULTS: 1114 women participated. The association between the items of the VAMF-bond subscale and the risk of PPD was statistically significant for all items (p < 0.05), except items 4 and 10. The multivariate analysis showed that the risk of PPD (EPDS scale) was lower in women with higher scores on bond (Adjusted Odds Ratio: aOR = 0.85; 95%CI: 0.81, 0.88), whose birth experience was good or very good (aOR = 0.57; 95%CI: 0.36, 0.89), who received high or very high support from their partner (aOR = 0.34; 95%CI: 0.18, 0.66), and family (aOR = 0.53; 95%CI: 0.32, 0.86). The presence of PPD was less frequent in women who presented higher scores for bond (aOR = 0.90; 95%CI: 0.84, 0.97), who had skin-to-skin contact (aOR = 0.39; 95%CI: 0.17, 0.93) and who received high or very high support from the family (aOR = 0.36; 95%CI: 0.12, 1.04). CONCLUSIONS: High scores on the subscale VAMF-bond were associated with a lower risk of PPD.

Clinical features and prognosis of prosthetic valve endocarditis due to Staphylococcus aureus.

PURPOSE: Staphylococcus aureus prosthetic valve endocarditis (SAPVE) is a serious infection with high mortality. The main objective of this study was to identify factors associated with in-hospital mortality. METHODS: From January 2008 to December 2021, consecutive patients from a Spanish cohort of infective endocarditis with a definitive diagnosis of SAPVE were analyzed. RESULTS: During the study period, 219 cases of definitive SAPVE were diagnosed, which accounted for 16.7% of a total of 1309 cases of definitive prosthetic valve endocarditis (PVE). Patients presented advanced age and marked comorbidity. There was a higher incidence of persistent bacteremia, septic shock, stroke, and acute kidney injury than in cases of PVE caused by other microorganisms. Methicillin resistance was not associated with differences in clinical presentation, echocardiographic findings, or mortality. Only 50.6% of the patients with surgical indications (88 patients) underwent surgery. Overall, in-hospital mortality was 47.9%. The variables associated with in-hospital mortality were age (OR:1.03, 95% CI: 1.00-1.05; p = 0.016), heart failure (OR:2.86, 95% CI: 1.53-5.32; p = 0.001), acute kidney injury (OR:2.42, 95%CI:1.28-4.58; p = 0.006), stroke (OR:3.53, 95%CI:1.79-6.96; p < 0.001) and surgery indicated but not performed (OR:2.01, 95%CI:1.06-3.8; p = 0.030). On the other hand, the performance of surgery per se in patients with SAPVE, regardless of whether there was a surgical indication according to the guidelines, was not associated with a reduction in in-hospital mortality. CONCLUSIONS: SAPVE is characterized by high mortality, which is more marked in patients who present a surgical indication but do not undergo surgery.

Phytoene and Phytoene-Rich Microalgae Extracts Extend Lifespan in C. elegans and Protect against Amyloid-ß Toxicity in an Alzheimer's Disease Model.

Phytoene is a colourless carotenoid widely available from dietary sources and a precursor for the synthesis of other carotenoids. Although present at high concentrations across different tissues, phytoene is largely viewed as not having physiological activity. Here, we utilize the model organism C. elegans to show that phytoene is bioactive and has anti-ageing properties. Supplementation with phytoene protects against oxidative damage and amyloid-ß42 proteotoxicity (a major pathology of Alzheimer's disease), and extends lifespan. We also examine extracts from two microalgae, Chlorella sorokiniana and Dunaliella bardawil. We show that the extracts contain high levels of phytoene, and find that these phytoene-rich extracts have protective effects similar to pure phytoene. Our findings show that phytoene is a bioactive molecule with positive effects on ageing and longevity. Our work also suggests that phytoene-rich microalgae extracts can utilized to produce foods or supplements that promote healthy ageing and prevent the development of chronic age-related diseases.

Analysis of HLA Alleles in Different Cohorts of Patients Infected by L. infantum from Southern Spain.

Leishmaniasis is an infectious disease caused by protozoa of the genus Leishmania, which is endemic in certain areas of Europe, such as southern Spain. The disease manifests in various clinical phenotypes, including visceral, cutaneous, mucosal, or asymptomatic leishmaniasis. This diversity in clinical outcomes may be influenced by the host immune response, with human leukocyte antigen (HLA) molecules playing a crucial role in determining susceptibility and progression of the infection. This study explores the association between specific HLA variants and Leishmania infantum infection. We recruited four cohorts: a control group, asymptomatic individuals, patients with symptomatic disease, and cohabitants of infected individuals. HLA typing was performed for all participants, followed by an association analysis with infection status and disease progression. Our findings indicate that the HLA-B*38 and HLA-C*03 alleles are associated with protection against L. infantum infection. These results contribute to a better understanding of the disease's progression, offer potential for new therapeutic approaches such as vaccines, and expand the existing knowledge in the literature.

Towards more sustainable cooking practices to increase the bioaccessibility of colourless and provitamin A carotenoids in cooked carrots.

The effect of different cooking methods (boiling, baking, steaming and microwaving) on the colour and texture of carrots, as well as on the bioaccessibility of carotenoids, was investigated in order to identify the more "sustainable cooking" methods. Cooking resulted in statistically significant increases in total carotenoid bioaccessibility, both with intensity and duration of treatments. In particular, significant increases in carotenoid bioaccessible content (CBC) were observed, ranging from 6.03-fold (microwave) to 8.90-fold (baking) for the most intense cooking conditions tested. Although the relative concentration of the colourless carotenoids (phytoene and phytofluene) in raw carrots is lower than that of provitamins A α- and ß-carotene, the bioaccessible content of the colourless ones is much higher. From an energy consumption standpoint and considering samples with the same tenderness, the highest CBC values per kWh decreased in the order microwaving > baking > water cooking > steaming. Our findings are important to help combat vitamin A deficiency since increases of up to ∼40-fold and ∼70-fold in the CBCs of the vitamin A precursors α- and ß-carotene, respectively, were observed. These results provide a basis for defining "sustainable cooking" as "cooking practices that optimize intensity, duration and other parameters leading to a more efficient use of energy to maximize the bioavailability of nutrients and other beneficial food components (such as bioactives) while ensuring food appeal and safety".

The value of the reflective discussion in decision-making using multi-criteria decision analysis (MCDA): an example of determining the value contribution of tabelecleucel for the treatment of the Epstein Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD).

BACKGROUND: The aim of this study was to assess the contribution of the reflective multidisciplinary discussion in determining the value contribution of innovative drugs through the multi-criteria decision analysis (MCDA). This methodology considers all relevant criteria for healthcare decision-making in a global, transparent, and systematic manner and from the perspective of relevant stakeholders. The determination of value contribution of tabelecleucel for the treatment of Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD) compared to salvage therapy was used as an example. RESULTS: Tabelecleucel obtained a value contribution score of 0.63 and increased to 0.75 after the reflective discussion. EBV+ PTLD was considered a life-threatening disease (5.0 ± 0.0), with a significant unmet need for an approved treatment (5.0 ± 0.0). Tabelecleucel was perceived as bringing improvements in terms of efficacy (4.2 ± 0.8) and safety (3.8 ± 0.8) compared to the salvage therapy. Most experts considered that the high efficacy and safety results could represent an improvement in the quality of life of patients (2.3 ± 1.2) along with savings in medical costs (2.3 ± 2.0) and non-medical costs (2.7 ± 1.6) compared to the salvage therapy. However, others emphasized the need of more evidence to confirm these improvements and savings over time. Tabelecleucel was regarded as potentially modifying the clinical course of the disease (4.3 ± 0.8) and supported by high-quality evidence (3.2 ± 0.4). All contextual criteria were valued highly positively for tabelecleucel. "Safety/Tolerability" and "Other medical costs" were the criteria that experienced the highest change in the re-test conducted after the reflective discussion. The reflective discussion allowed resolving doubts or misinterpretations of the experts, so the re-test obtained more accurate and consistent results of the value contribution of tabelecleucel. CONCLUSIONS: The study shows that the MCDA methodology is a useful tool for decision-making on innovative treatments for the management of rare diseases. It also highlights the importance of reflective multidisciplinary discussion for its ability to resolve doubts or misinterpretations of experts, subsequently allowing to obtain more consistent and reliable results on the value contribution of the drug, being potentially more positive.

Oxygen and air cold plasma for the inactivation of Bacillus cereus in low-water activity soy powder.

Cold plasma (CP) technology is a promising alternative to thermal treatments for the microbial decontamination of foods with low-water activity. The aim of this work is study the application of low-pressure CP (0.35 mbar) for the inactivation of Bacillus cereus in a soybean powder matrix using O2 and synthetic air as ionizing gases. The parameters tested were an input power of 100, 200 and 300 W and an exposure time of 10 to 30 min. The excited reactive species formed were monitored by optical emission spectroscopy, and survival data were analyzed using the Weibull mathematical model. Treatments with both gases were effective in inactivating B. cereus. Air plasma resulted in a maximum 3.71-log reduction in bacterial counts at 300 W and 30 min, while O2 plasma showed the strongest inactivation ability, achieving levels higher than 5 log cycles at 300 W and > 25 min. This is likely due to the strong antimicrobial activity of oxygen-derived radicals together with carbon monoxide as an oxidation by-product. In addition, the Weibull distribution function accurately modeled the inactivation of B. cereus. Cold plasma technology is a promising approach for the decontamination of bacteria in low-water activity foods.

Instrument to evaluate the perception of abuse and/or disrespectful treatment during childbirth: A validation study.

AIM: To design and validate a tool to assess a woman's perception of whether she has experienced a situation of abuse or disrespect during childbirth attendance: "Childbirth Abuse and Respect Evaluation-Maternal Questionnaire" (CARE-MQ). METHODS: Multidisciplinary panel of experts (gynecologists, midwives, mothers) participated in creating CARE-MQ. A cross-sectional study was carried out on 901 Spanish women who had given birth between 1 and 3 months before to determine psychometric characteristics. Finally, an exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and a convergent validity study were carried out with the Quality Questionnaire from the Patient's Perspective-Intrapartum (QPP-I), and a reliability study using internal consistency (Cronbach's α) and coefficient of intraclass correlation (CCI). FINDINGS: The KMO test gave a value of 0.935, and Bartlett's sphericity test was <0.001. The EFA identified four components ("Emotional Abuse", "Inadequate Professionalism", "Physical Abuse" y "Lost contact") that explained 55.16 % of variance. In the CFA, a good fit was observed for most of the evaluated indicators. CARE-MQ correlated negatively with QPP-I (Spearman's rho = -0.641, 95 % CI: -0.679, -0.600; p < 0.001) and was statistically associated with variables related to childbirth experience (p < 0.005) such as the use of a birth plan, use of regional analgesia, type of birth, episiotomy, presence of severe tears, skin-to-skin contact, length of hospital stay and postpartum surgical intervention. Cronbach's α value was 0.903. The ICC of absolute agreement after administering the questionnaire one week after was 0.927 (95 % CI: 0.85-0.97). CONCLUSIONS: CARE-MQ is a valid and reliable instrument to evaluate the perception of a woman regarding the situation of abuse and/or disrespect that she may have experienced during birth in a population of Spanish postpartum women.

Safety and Efficacy of High-Dose Memory CD45RO+ Donor Lymphocyte Infusion in Pediatric Recipients after Hematopoietic Stem Cell Transplantation.

Memory T selected cells (CD45RA-/RO+) as donor lymphocyte infusion are less capable of producing alloreactivity and graft versus host disease (GvHD) compared with naïve T cells. The objective of this study was to evaluate the safety and efficacy of high-dose memory (CD45RA-/RO+) donor lymphocyte infusion (mDLI) after allogeneic hematopoietic cell transplantation (HCT). Indications for mDLI were "as needed" and "as prophylactic regimen." Sixty-one children diagnosed with malignant (82%) and non-malignant diseases (18%) received 241 mDLIs. Patients received a median of three infusions (range 1‒13) of mDLI with a median infused dose of 1.35 × 107/kg CD45RO+ containing 8.96 × 106/kg CD3+CD45RO+ and 3.81 × 103/kg CD3+CD45RA+. De novo GvHD developed in 7 patients following 4% of the mDLI infusions. Among patients with GvHD before mDLI, this condition worsened following 6 infusions (11%) in the 3 patients with grade II-IV acute GvHD. A decrease in cytomegalovirus viral load followed 65% of mDLI infusions. Two-year overall survival (OS) for the total cohort was 64% (95% CI 57%‒72%). For patients receiving prophylactic mDLI, the two-year non-relapse mortality was 10% (95% CI 9%‒11%). In summary, high-dose mDLI is feasible and safe, with a relatively low risk of severe GvHD even in patients with active GvHD. Importantly, mDLI was associated with positive effects, including enhanced control of CMV viremia.

Clinical and serological characteristics of patients allergic to LTP.

BACKGROUND: Allergy to lipid transfer proteins (LPT) is common in Mediterranean Europe, and it causes severe reactions in patients and affects multiple foods, impairing the quality of life. OBJECTIVE: This study aimed to describe the clinical and sensitization profile of patients with LTP syndrome and to determine a clinical pattern of severity. Molecular diagnosis is shown in a broad population through microarrays. MATERIAL AND METHODS: This study was performed at the LTP Allergy Consultation of the Reina Sofia Hospital in Murcia, Spain. We analyzed the patients' characteristics, reactions, cofactors, food implicated, quality of life, skin prick test to food and aeroallergens, and serologic parameters, such as total immunoglobulin E, peach LTP (Pru p 3 IgE) and immunoglobulin G4, and microarray Immuno Solid-phase Allergen Chip (ISAC). We related the severity of the reactions with other variables. RESULTS: We presented a series of 236 patients diagnosed with LTP allergy, 54.66% suffering from anaphylaxis, 36.02% from urticaria angioedema, and 9.32% from oral allergy syndrome. The most frequently implicated food was peach, producing symptoms in 70% of patients, followed by walnut in 55%, peanut in 45%, hazelnut in 44%, and apple in 38% patients. Regarding the food that provoked anaphylaxis, walnut was the most frequent instigator, along with peach, peanut, hazelnut, almond, sunflower seed, and apple. According to the severity of LPT reaction, we did not discover significant differences in gender, age, food group involved, and serologic parameters. We found differences in the presence of cofactors, with 48.84% of cofactors in patients with anaphylaxis, compared to 27.1% in patients without anaphylaxis and in family allergy background (P < 0.0001). CONCLUSION: In our series of patients, 54% presented anaphylaxis, and the foods that most frequently produced symptoms were peaches, apples, and nuts. Cofactors and family allergy backgrounds were associated with the severity of LPT reaction.

Inactivation of Bacillus cereus Spores and Vegetative Cells in Inert Matrix and Rice Grains Using Low-Pressure Cold Plasma.

This study investigated the effects of low-pressure cold plasma on the inactivation of Bacillus cereus vegetative cells and spores in an inert matrix (borosilicate glass slide) and in rice grains, using oxygen as ionization gas. Greater reductions in B. cereus counts were observed in vegetative cells rather than spores. The experimental data obtained show that both the power of the plasma treatment and the matrix proved to be determining factors in the inactivation of both the spores and vegetative cells of B. cereus. To characterize the inactivation of B. cereus, experimental data were accurately fitted to the Weibull model. A significant decrease in parameter "a", representing resistance to treatment, was confirmed with treatment intensification. Furthermore, significant differences in the "a" value were observed between spores in inert and food matrices, suggesting the additional protective role of the food matrix for B. cereus spores. These results demonstrate the importance of considering matrix effects in plasma treatment to ensure the effective inactivation of pathogenic microorganisms, particularly in foods with low water activity, such as rice. This approach contributes to mitigating the impact of foodborne illnesses caused by pathogenic microorganisms.

The green seaweed Ulva: tomorrow's "wheat of the sea" in foods, feeds, nutrition, and biomaterials.

Ulva, a genus of green macroalgae commonly known as sea lettuce, has long been recognized for its nutritional benefits for food and feed. As the demand for sustainable food and feed sources continues to grow, so does the interest in alternative, plant-based protein sources. With its abundance along coastal waters and high protein content, Ulva spp. have emerged as promising candidates. While the use of Ulva in food and feed has its challenges, the utilization of Ulva in other industries, including in biomaterials, biostimulants, and biorefineries, has been growing. This review aims to provide a comprehensive overview of the current status, challenges and opportunities associated with using Ulva in food, feed, and beyond. Drawing on the expertise of leading researchers and industry professionals, it explores the latest knowledge on Ulva's nutritional value, processing methods, and potential benefits for human nutrition, aquaculture feeds, terrestrial feeds, biomaterials, biostimulants and biorefineries. In addition, it examines the economic feasibility of incorporating Ulva into aquafeed. Through its comprehensive and insightful analysis, including a critical review of the challenges and future research needs, this review will be a valuable resource for anyone interested in sustainable aquaculture and Ulva's role in food, feed, biomaterials, biostimulants and beyond.

Haploidentical versus Cord Blood Transplantation in Pediatric AML. A Retrospective Outcome Analysis on Behalf of the Pediatric Subcommittee of GETH (Grupo Español de Trasplante Hematopoyético).

Haploidentical stem cell transplantation (Haplo-SCT) and cord blood transplantation (CBT) are both effective alternative treatments in patients suffering from acute myeloid leukemia (AML) and lacking a matched HLA donor. In the last years, many centers have abandoned CBT procedures mostly due to concern about poorer immune recovery compared with Haplo-SCT. We conducted a retrospective multicenter study comparing the outcomes using both alternative approaches in AML. A total of 122 transplants (86 Haplo-SCTs and 36 CBTs) from 12 Spanish centers were collected from 2007 to 2021. Median age at hematopoietic stem cell transplantation (HSCT) was 7 years (0.4-20). Thirty-nine patients (31.9%) showed positive minimal residual disease (MRD) at HSCT and a previous HSCT was performed in 37 patients (30.3%). The median infused cellularity was 14.4 × 106/kg CD34+ cells (6.0-22.07) for Haplo-SCT and 4.74 × 105/kg CD34+ cells (0.8-9.4) for CBT. Median time to neutrophil engraftment was 14 days (7-44) for Haplo-SCT and 17 days (8-29) for CBT (P = .03). The median time to platelet engraftment was 14 days (6-70) for Haplo-SCT and 43 days (10-151) for CBT (P < .001). Graft rejection was observed in 13 Haplo-SCTs (15%) and in 6 CBTs (16%). The cumulative incidence of acute graft versus host disease (GvHD) grades II-IV was 54% and 51% for Haplo-SCT and CBT, respectively (P = .50). The cumulative incidence of severe acute GvHD (grades III-IV) was 22% for Haplo-SCT and 25% for CBT (P = .90). There was a tendency to a higher risk of chronic GvHD in the Haplo-SCT group being the cumulative incidence of 30% for Haplo-SCT and 12% for CBT (P = .09). The cumulative incidence of relapse was 28% and 20% for Haplo-SCT and CBT, respectively (P = .60). We did not observe statistically significant differences in outcome measures between Haplo-SCT and CBT procedures: 5-year overall survival (OS) was 64% versus 57% (P = .50), 5-year disease-free survival (DFS) 58% versus 57% (P = .80), GvHD-free and relapse-free survival (GFRFS) 41% versus 54% (P = .30), and cumulative incidence of transplant-related mortality (TRM) 14% versus 15% (P = .80), respectively. In the multivariate analysis, MRD positivity and a disease status >CR1 at the time of HSCT were significantly associated with poorer outcomes (P < .05). In conclusion, our study supports that both haploidentical and cord blood transplantation show comparable outcomes in pediatric AML patients. We obtained comparable survival rates, although CBT showed a trend to lower rates of chronic GvHD and higher GFRFS, demonstrating that it should still be considered a valuable option, particularly for pediatric patients.

Fecal microbiota transplantation as a preventive treatment for recurrent acute cholangitis.

Background: Recurrent acute cholangitis (RAC) is a relatively uncommon entity that presents significant management difficulties. We present the case of a patient with RAC in whom the number of episodes was reduced after a novel therapeutic procedure. Case report: A 93-year-old male who in June 2019 was admitted for chills without fever, shivering, epigastric abdominal pain and moderate jaundice. Both abdominal ultrasound and CT scan showed intrahepatic and extrahepatic duct dilatation up to the papilla with no evidence of mass at that level. Endoscopic retrograde cholangiopancreatography (ERCP) was performed and abundant biliary sludge was removed. E. coli was identified as the cause of several of the episodes. Some isolates were shown to produce extended spectrum beta-lactamase (ESBL). Papillotomy was performed and plastic prosthesis and later a metallic prosthesis were implanted. Several months later a surgical bypass of the biliary tract was performed due to persistent episodes of cholangitis. When the chronic suppressive antibiotic treatment subsequently instituted to prevent new episodes of cholangitis failed, it was decided to perform a fecal microbiota transplant from a healthy donor and to suspend the chronic suppressive treatment. Since then, she has not presented new episodes of RAC for more than 10 months of clinical follow-up. BLEE-producing E. coli in the gastrointestinal tract could not be eradicated. Comment: Chronic colonization of the biliary tract by certain enterobacteria such as E. coli has been identified as a relevant pathogenic factor in cases of RAC. FMT may be a promising tool to improve the clinical course of patients with RAC.

Anti-CD19 CAR-T Cell Therapy in Elderly Patients: Multicentric Real-World Experience from GETH-TC/GELTAMO.

Chimeric antigen receptor (CAR)-T cell therapy is approved for the treatment of relapsed/refractory (R/R) large B cell lymphoma (LBCL). However, elderly patients might not be candidates for this therapy due to its toxicity, and criteria for candidate selection are lacking. Our aim was to analyze efficacy and toxicity results of CAR-T cell therapy in the population of patients 70 years and older as compared to those obtained in younger patients in the real-world setting. A multicentric retrospective study was performed including patients with R/R aggressive LBCL who received commercial CAR-T cell therapy with either tisagenlecleucel or axicabtagene ciloleucel within the Spanish Group of Hematopoietic Transplant and Cell Therapy/Spanish Group of Lymphomas and Autologous Transplant (GETH-TC/GELTAMO) centers between 2019 and 2023. As of August 2023, 442 adult patients with aggressive LBCL underwent apheresis for CAR-T cell therapy as third or subsequent line and follow-up data was collected. Of 412 infused patients, 71 (17%) were 70 years or older. Baseline characteristics, product selection, and characteristics at apheresis (including disease status, Ann Arbor stage, revised international prognosis index (R-IPI), bulky disease, lactate dehydrogenase [LDH] and ECOG [Eastern Cooperative Group performance status]) were comparable between groups. Median time from both approval to infusion and apheresis to infusion did not differ. No differences were found between groups in overall and complete response rates at 1 and 3 months. With a median follow-up of 12.2 months (range 1-44), 12-month progression-free survival (PFS) and overall survival (OS) were comparable between groups (35.2% in <70 years vs. 35.9% in ≥70 years (P = .938) and 51.1% and 52.1% (P = .885), respectively). Age ≥70 years did not affect PFS (hazard ratio (HR) 0.98, P = .941) and OS (HR 0.97, P = .890) in the univariate and multivariate analysis. Cytokine release syndrome (CRS) was observed in 82% of patients <70 years old and 84.5% in ≥ 70 years old (P = .408). Grade ≥3 CRS was more frequent in the older group (5% vs. 15%, P = .002). In the multivariate analysis, age ≥70 years was associated with an increased risk of grade ≥3 CRS (OR 3.7, P = .013). No differences were observed in terms of overall neurotoxicity (35% vs. 42%, P = .281) or grade ≥3 (12% vs. 17%, P = .33). The proportion of patients with infections, admission to the intensive care unit within the first month, and non-relapse mortality were similar between both groups. CAR-T cell therapy in patients older than 70 years showed similar efficacy to that observed in younger patients in the real-world setting. However, age ≥70 years was an independent risk factor for grades 3-4 CRS. The need for additional strategies to reduce toxicity in this population should be addressed in future studies.

Outcomes of Cardiac Resynchronization Therapy by New York Heart Association Class: A Patient-Level Meta-Analysis.

BACKGROUND: Data on the benefits of cardiac resynchronization therapy (CRT) in patients with severe heart failure symptoms are limited. We investigated the relative effects of CRT in patients with ambulatory New York Heart Association (NYHA) IV versus III functional class at the time of device implantation. METHODS AND RESULTS: In this meta-analysis, we pooled patient-level data from the MIRACLE (Multicenter InSync Randomized Clinical Evaluation), MIRACLE-ICD (Multicenter InSync Implantable Cardioversion Defibrillation Randomized Clinical Evaluation), and COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trials. Outcomes evaluated were time to the composite end point of the first heart failure hospitalization or all-cause mortality, and time to all-cause mortality alone. The association between CRT and outcomes was evaluated using a Bayesian hierarchical Weibull survival regression model. We assessed if this association differed between NYHA III and IV groups by adding an interaction term between CRT and NYHA class as a random effect. A sensitivity analysis was performed by including data from RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure). Our pooled analysis included 2309 patients. Overall, CRT was associated with a longer time to heart failure hospitalization or all-cause mortality (adjusted hazard ratio [aHR], 0.79 [95% credible interval [CI], 0.64-0.99]; posterior probability or P=0.044), with a similar association with time to all-cause mortality (aHR, 0.78 [95% CI, 0.59-1.03]; P=0.083). Associations of CRT with outcomes were not significantly different for those in NYHA III and IV classes (ratio of aHR, 0.72 [95% CI, 0.30-1.27]; P=0.23 for heart failure hospitalization/mortality; ratio of aHR, 0.70 [95% CI, 0.35-1.34]; P=0.27 for all-cause mortality alone). The sensitivity analysis, including RAFT data, did not show a significant relative CRT benefit between NYHA III and IV classes. CONCLUSIONS: Overall, there was no significant difference in the association of CRT with either outcome for patients in NYHA functional class III compared with functional class IV.

Clinical Management and Outcomes of Nontuberculous Mycobacterial Infections in Solid Organ Transplant Recipients: A Multinational Case-control Study.

BACKGROUND: The management and outcomes of nontuberculous mycobacterial (NTM) infections in solid organ transplant (SOT) recipients are poorly characterized. We aimed to describe the management and 1-y mortality of these patients. METHODS: Retrospective, multinational, 1:2 matched case-control study included SOT recipients aged 12 y old or older diagnosed with NTM infection between January 1, 2008, and December 31, 2018. Controls were matched on transplanted organs, NTM treatment center, and posttransplant survival at least equal to the time to NTM diagnosis. The primary aim was 1-y mortality after NTM diagnosis. Differences between cases and controls were compared using the log-rank test, and Cox regression models were used to identify factors associated with mortality at 12 mo among cases. RESULTS: In 85 patients and 169 controls, the median age at the time of SOT was 54 y (interquartile range, 40-62 y), 59% were men, and the lungs were the most common site of infection after SOT (57.6%). One-year mortality was significantly higher in cases than in controls (20% versus 3%; P < 0.001), and higher mortality was associated with lung transplantation (hazard ratio 3.27; 95% confidence interval [1.1-9.77]; P = 0.034). Median time (interquartile range) from diagnosis to treatment initiation (20 [4-42] versus 11 [3-21] d) or the reduction of net immunosuppression (36% versus 45%, hazard ratio 1.35 [95% CI, 0.41-4.43], P = 0.618) did not differ between survivors and those who died. CONCLUSIONS: NTM disease in SOT recipients is associated with a higher mortality risk, especially among lung transplant recipients. Time to NTM treatment and reduction in net immunosuppression were not associated with mortality.

Frailty as a Risk Factor for Depression after COVID-19 Hospital Admission.

BACKGROUND: This work aims to establish the relationship between depression and epidemiological or imaging variables, frailty, and cognitive status in patients who suffered hospital admission for COVID-19. METHODS: A longitudinal observational study investigated 72 patients admitted for COVID-19 to a hospital in Spain. Patients were evaluated at discharge and six months later. Clinical, analytical, and imaging variables were collected. A neurocognitive, nutritional, and frailty (FRAIL scale) assessment of the included patients was carried out. The risk of depression was considered for a result above 5 points on the PHQ-9 scale. RESULTS: The variables that were significantly related to the risk of depression 6 months after admission for COVID-19 were frailty (p = 0.006 for pre-frail and p = 0.001 for frail), small-vessel vascular disease in imaging tests (p = 0.033), vitamin D level (p = 0.006), and taking antidepressants (p = 0.011). Factors that were negatively associated with the presence of depression 6 months after discharge were a higher score on the CAMCOG cognitive scale (p = 0.041) and older age (p = 0.006). CONCLUSIONS: Frailty worsened the score on the PHQ-9 depression scale in patients who required hospital admission for SARS-CoV-2 infection. It is important to implement prevention measures both for frailty and depression in these patients.