The Latin-American Experience in POEMS Syndrome: A Study of the GELAMM (Grupo de Estudio Latinoamericano de Mieloma Múltiple).

INTRODUCTION: POEMS syndrome is a rare paraneoplastic syndrome caused by an underlying plasma cell disorder. The acronym refers to the following features: polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal paraproteinemia, and skin changes. METHODS: The study was conducted at 24 hematological centers across 8 Latin-American countries. The study included a total of 46 patients {median age was 52 years (interquartile range [IQR]: 42-61.5), 30 males and 16 females} fulfilling the POEMS syndrome criteria diagnosed over a period of 12 years (January 1, 2011, through July 31, 2023). Epidemiological and clinical data were collected in an ad hoc database sent to the members of GELAMM, as well as the Kolmogorov-Smirnov test and Kaplan-Meier estimates. RESULTS: All patients had polyneuropathy and monoclonal gammopathy; 89% had bone marrow plasma cell infiltration, 33% had sclerotic bone lesions. Only 10 patients underwent vascular endothelial growth factor (VEGF) testing in plasma samples. The paraproteinemia was IgG λ in 32% and IgA λ in 30%. 59% patients presented with cutaneous changes, mainly hyperpigmentation, 54% had organomegaly, and 74% endocrinopathy. The median interval from symptom onset to diagnosis was 7.7 months (IQR: 4.0-12.6). 69% of patients received a single line of treatment. The median follow-up period was 25 months (IQR: 9.37-52.0) and the 2-year overall survival rate was 100%. All patients who underwent transplantation (43%) are alive, with a median follow-up of 45.62 months (IQR: 15.46-70). CONCLUSION: This study investigates POEMS syndrome in Latin America and presents an initial overview of the disease in the region. VEGF usage is recommended for accurate diagnosis, but only 7 hematology centers in the region used it. Survival rate in Latin America is comparable with those observed internationally.

Suicide Risk Factors in High School Students.

In Mexico, suicide has become an important public health problem, representing the third leading cause of death in the adolescent population. Suicidal behavior in adolescents is associated with the interaction of complex relationships between personal, interpersonal, and sociocultural factors. Through a quantitative, descriptive, and correlational cross-sectional study, the present study aimed to analyze the prevalence and risk factors associated with suicidal ideation among adolescents from different high schools of the high school system (SEMS) of the University of Guadalajara, in response to the psychosocial impact of the COVID-19 pandemic. A descriptive statistical analysis was carried out on the data obtained from the 3583 students surveyed, followed by a principal component analysis (PCA) to identify closely related social, emotional, and behavioral variables. The PCA yielded eight principal components, which together represent 75.42% of the variance across psychometric tests. A multiple linear regression analysis was used, with a regression value (R2) of 0.4811, indicating that the explanatory model can predict 48.1% of the variability in suicidal ideation, with a statistical significance level of 0.05. According to the studies conducted, 19% (688 students) showed indicators of high suicide risk and 26.8% (960 students) showed moderate risk. Depression, mental health, health-related quality of life, physical and psychological well-being, and mood and emotions are the most influential factors in suicidal ideation.

Mexican Registry of Cardiomyopathies: baseline data, diagnostic strategies, and treatment approaches in Mexico.

Objectives: The study aimed to know the clinical, demographic, diagnostic, and treatments characteristics in patients with cardiomyopathies in Mexico. Methods: The Mexican Registry of Cardiomyopathies (REMEMI) is an observational, prospective and national study of patients with cardiomyopathies, which includes: Dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM) and arrhythmogenic cardiomyopathy of the right ventricle (ARVC). Results: A total of 1026 patients from most states of the Mexican Republic (19) were included, with 494 corresponding to DCM, 490 to HCM, 35 to RCM, and seven to ARVC. We found significant differences between the various cardiomyopathy phenotypes (p < 0.05) in the coexistence with diabetes, use of implantable defibrillator, presence of ventricular tachycardia, and NYHA functional class ≥ 1. There were no significant differences in age and predominant gender between each one. When analyzing by phenotype, we found that patients with HCM have limited use of diagnostic methods considered indispensable, such as cardiac magnetic resonance, Holter monitoring, and genetic testing in patients and their relatives. Conclusion: Seeking contemporary information through observational registries in Mexico is a valuable opportunity to understand the characteristics of the methods used in the study and treatment of diseases such as cardiomyopathies by Mexican physicians. It can provide information for the implementation of management guidelines and strategies to disseminate findings to improve healthcare in our country.

Objetivo: Conocer las características clínicas y demográficas, así como las herramientas diagnósticas y tratamientos utilizados en pacientes con miocardiopatías en México. Métodos: El Registro Mexicano de Miocardiopatías (REMEMI) es un estudio observacional, prospectivo y nacional de pacientes con diagnóstico de miocardiopatía, que incluye: miocardiopatía dilatada (MCD), miocardiopatía hipertrófica (MCH), miocardiopatía restrictiva (MCR) y miocardiopatía arritmogénica del ventrículo derecho (MAVD). Resultados: Se incluyó un total de 1026 pacientes provenientes de la mayoría de los estados de la República Mexicana (19), de los cuales 494 corresponden a MCD, 490 a MCH, 35 a MCR y 7 a MAVD. Encontramos diferencias significativas entre los diversos fenotipos de miocardiopatías (p < 0.05) en la coexistencia con diabetes, empleo de desfibrilador implantable, presencia de taquicardia ventricular y la clase funcional de la NYHA ≥ 1. No hubo diferencias significativas en la edad y sexo predominante entre cada uno. Al analizar por fenotipo encontramos que la MCH tienen poco empleo de métodos diagnósticos considerados como indispensables como la resonancia magnética cardiaca, el monitoreo Holter y el estudio genético en los pacientes y sus familiares. Conclusión: La búsqueda de información contemporánea a través de registros observacionales en México es una buena oportunidad para conocer las características de los métodos empleados en el estudio y tratamiento de enfermedades como las miocardiopatías por médicos mexicanos, y puede ofrecernos información para la implementación de guías de manejo y estrategias de difusión de los hallazgos para así mejorar el cuidado de la salud en nuestro país.

Therapeutic Choices in Patients with Ph-Positive Chronic Myelogenous Leukemia In Mexico in the Era of Tyrosine Kinase Inhibitors: Stem Cell Transplantation or Tyrosine Kinase Inhibitors? Fifteen Years Later.

Background: Chronic myelogenous leukemia is a neoplastic proliferation of the granulocytic series. In Mexico, chronic myelogenous leukemia accounts for approximately 10% of all leukemias. Tyrosine-kinase inhibitors are considered front-line therapy in high-income countries, whereas allogeneic hematopoietic stem cell transplantation is a recognized therapeutic approach, mainly in low- and middle-income countries. Objective: To analyze the overall survival of persons with chronic myelogenous leukemia who have received tyrosine-kinase inhibitors or allogeneic hematopoietic stem cell transplantation in a medical center, since 1994, and briefly discuss the current indications of these treatments in the tyrosine-kinase inhibitors era. Methods: We retrospectively analyzed all patients with a diagnosis of chronic myelogenous leukemia treated in a medical center between 1994 and 2023; subsets of individuals who received an allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors therapy as first-line treatment were analyzed. Results: 60 persons with chronic myelogenous leukemia were treated with allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors: 35 received an allogeneic hematopoietic stem cell transplantation, whereas 25 were given tyrosine-kinase inhibitors. All patients who underwent an allogeneic hematopoietic stem cell transplantation engrafted successfully, and the procedure was completed on an outpatient basis in most cases (29/35). The median survival in allogeneic hematopoietic stem cell transplantation was 78.3 months (CI 95%: 0-205.6) and in persons given tyrosine-kinase inhibitors the median was not reached. Conclusion: Tyrosine-kinase inhibitors were significantly superior to allogeneic hematopoietic stem cell transplantation in prolonging the overall survival of persons with chronic myelogenous leukemia in our single institution experience.

Energy Expenditure in Humans: Principles, Methods, and Changes Throughout the Life Course.

Humans require energy to sustain their daily activities throughout their lives. This narrative review aims to (a) summarize principles and methods for studying human energy expenditure, (b) discuss the main determinants of energy expenditure, and (c) discuss the changes in energy expenditure throughout the human life course. Total daily energy expenditure is mainly composed of resting energy expenditure, physical activity energy expenditure, and the thermic effect of food. Total daily energy expenditure and its components are estimated using variations of the indirect calorimetry method. The relative contributions of organs and tissues determine the energy expenditure under different physiological conditions. Evidence shows that energy expenditure varies along the human life course, at least in part due to changes in body composition, the mass and specific metabolic rates of organs and tissues, and levels of physical activity. This information is crucial to estimate human energy requirements for maintaining health throughout the life course.

Unveiling the role of hydroxyapatite and hydroxyapatite/silver composite in osteoblast-like cell mineralization: An exploration through their viscoelastic properties.

Mechanical properties are becoming fundamental for advancing the comprehension of cellular processes. This study addresses the relationship between viscoelastic properties and the cellular mineralization process. Osteoblast-like cells treated with an osteogenic medium were employed for this purpose. Additionally, the study explores the impact of hydroxyapatite (HA) and hydroxyapatite/silver (HA/Ag) composite on this process. AFM relaxation experiments were conducted to extract viscoelastic parameters using the Fractional Zener (FZ) and Fractional Kelvin (FK) models. Our findings revealed that the main phases of mineralization are associated with alterations in the viscoelastic properties of osteoblast-like cells. Furthermore, HA and HA/Ag treatments significantly influenced changes in the viscoelastic properties of these cells. In particular, the HA/Ag treatment demonstrated a marked enhancement in cell fluidity, suggesting a possible role of silver in accelerating the mineralization process. Moreover, the study underscores the independence observed between fluidity and stiffness, indicating that modifications in one parameter may not necessarily correspond to changes in the other. These findings shed light on the factors involved in the cellular mineralization process and emphasize the importance of using viscoelastic properties to discern the impact of treatments on cells.

Therapeutic Choices in Patients with Ph-Positive Chronic Myelogenous Leukemia In Mexico in the Era of Tyrosine Kinase Inhibitors: Stem Cell Transplantation or Tyrosine Kinase Inhibitors? Fifteen Years Later

ABSTRACT Background: Chronic myelogenous leukemia is a neoplastic proliferation of the granulocytic series. In Mexico, chronic myelogenous leukemia accounts for approximately 10% of all leukemias. Tyrosine-kinase inhibitors are considered front-line therapy in high-income countries, whereas allogeneic hematopoietic stem cell transplantation is a recognized therapeutic approach, mainly in low- and middle-income countries. Objective: To analyze the overall survival of persons with chronic myelogenous leukemia who have received tyrosine-kinase inhibitors or allogeneic hematopoietic stem cell transplantation in a medical center, since 1994, and briefly discuss the current indications of these treatments in the tyrosine-kinase inhibitors era. Methods: We retrospectively analyzed all patients with a diagnosis of chronic myelogenous leukemia treated in a medical center between 1994 and 2023; subsets of individuals who received an allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors therapy as first-line treatment were analyzed. Results: 60 persons with chronic myelogenous leukemia were treated with allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors: 35 received an allogeneic hematopoietic stem cell transplantation, whereas 25 were given tyrosine-kinase inhibitors. All patients who underwent an allogeneic hematopoietic stem cell transplantation engrafted successfully, and the procedure was completed on an outpatient basis in most cases (29/35). The median survival in allogeneic hematopoietic stem cell transplantation was 78.3 months (CI 95%: 0-205.6) and in persons given tyrosine-kinase inhibitors the median was not reached. Conclusion: Tyrosine-kinase inhibitors were significantly superior to allogeneic hematopoietic stem cell transplantation in prolonging the overall survival of persons with chronic myelogenous leukemia in our single institution experience. (Rev Invest Clin. 2024;76(2):91-6)

Prevalence and Consequences of a Delayed Diagnosis in Multiple Myeloma: A Single Institution Experience.

BACKGROUND: Multiple myeloma (MM) is a disease with unspecific initial symptoms which may lead into a delay in the diagnosis, seemingly increasing the risk of complications and in turn reducing the overall survival (OS). OBJECTIVE: To analyze the consequences of a delayed diagnosis of MM in both the OS and the progression-free survival (PFS) of the patients in a single center in México. METHODS: The study included patients with MM who were diagnosed at Clínica Ruiz, Puebla, México, between 1983 and 2022. According to the time elapsed between the onset of symptoms to the establishment of the definite diagnosis of MM, 4 groups were constructed: 1) Less than 3 months, 2) 3-6 months, 3) 6-12 months, and 4) More than 12 months. RESULTS: About 136 patients had a complete clinical record and at least a 3-month follow up period. A delay in the diagnosis of MM (more than 3 months from the onset of symptoms) was recorded in 92/136 persons (68%). The median follow-up for the whole group was 24.7 months, median OS was 131.4 months, whereas median PFS was 85.4 months. There was a significant trend for being in earlier stages of the disease and being diagnosed within 3 months from the onset of symptoms (P = .049). Both OS and PFS were similar in the patients diagnosed before or after 3 months from the symptoms onset (P = .772). The 6-12 months group was the group with the better median both OS (197.4 months) and DFS (197.4) from the diagnosis. The median OS for the other groups were similar among them. CONCLUSION: A delay in the diagnosis of MM is very frequent in México (68% of cases); despite the fact that there was a significant trend for being in earlier stages of the disease and being diagnosed within 3 months from the onset of symptoms, we did not find a relationship between a delay on the diagnosis of the disease and a higher risk of complications and/or poor prognosis. Possible explanations to these findings are discussed.

Neutrophil to lymphocyte ratio and systemic immune-inflammatory index as markers of response to autologous hematopoietic stem cell transplantation in persons with multiple sclerosis.

INTRODUCTION: Biomarkers that help to evaluate the immune system and could be useful in multiple sclerosis (MS) are the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII). The objective of this work is to evaluate the significance of the SII index, PLR, and NLR before and after transplantation in individuals with MS who underwent autologous hematopoietic stem cell transplant (aHSCT) at a single institution. METHODS: Patients with MS who received an aHSCT between 2017 and 2022 were included in the study. NLR, PLR, and SII index were calculated prior to the transplant and 100 days after, and evaluation of the expanded disability status scale (EDSS) was done before the transplant and 12 months after. The cohort was divided into two groups: aHSCT responders (R) and nonresponders (NR). RESULTS: Fifty-eight individuals were examined: 37 patients in the responders group R group and 21 in NR group. There was no statistically significant difference in the SII, NLR, and PLR prior to the transplant, however at 100 days post-HSCT, NLR in the R group was 1.8 versus 3.1 in the NR group (p = 0.003), PLR was 194 versus 295, respectively (p = 0.024), meanwhile SII index was 489.5 versus 729.3 (p < 0.001). CONCLUSION: High NLR and SII index values after the aHSCT were associated with a worsening in the EDSS score. However, since this is the first ever study that compared NLR and SII index with the aHSCT response in persons with MS, further studies must be performed to corroborate this information.

Larvicidal Activity against Spodoptera frugiperda of some Constituents from two Diospyros Species. In silico Pesticide-likeness Properties, Acetylcholinesterase Activity and Molecular Docking.

This report informs for the first time the chemical constituents of Diospyros xolocotzii and Diospyros digyna, the pesticidal and the acetylcholinesterase (AChE) inhibition potential of some compounds calculated by in silico approaches, the larvicidal activity against Spodoptera frugiperda of available compounds, the AChE inhibition of selected compounds, and the results of the molecular docking of the most active ones with this receptor. From the aerial parts of D. xolocotzii were isolated pentacyclic triterpenes (1-4, 6, 10, 11-13), phytosterols (15-17), and isodiospyrin (18), whereas the analysis of aerial parts of D. digyna conducted to the isolation of pentacyclic triterpenes (4, 5, 7-9, 11-14), (4S)-shinanolone (19), and scopoletin (20). For comparison purposes, origanal (21) was chemically prepared from 11. The in silico analysis showed that the tested compounds have pesticide potential. The larvicidal activities of 11>13>12 indicated that the increase of the oxidation degree at C-28 increases their bioactivity. Compounds 11 and 21 presented the higher inhibition in the acetylcholinesterase assay, and the higher binding energies, and for the interactionswith AChE by molecular docking. Both Diospyros species are sources of triterpenes with pesticidal potential and the molecular changes in lupane triterpenes correlate with the observed bioactivity and molecular docking.

Cold exposure modulates potential brown adipokines in humans, but only FGF21 is associated with brown adipose tissue volume.

OBJECTIVE: The study objective was to investigate the effect of cold exposure on the plasma levels of five potential human brown adipokines (chemokine ligand 14 [CXCL14], growth differentiation factor 15 [GDF15], fibroblast growth factor 21 [FGF21], interleukin 6 [IL6], and bone morphogenic protein 8b [BMP8b]) and to study whether such cold-induced effects are related to brown adipose tissue (BAT) volume, activity, or radiodensity in young humans. METHODS: Plasma levels of brown adipokines were measured before and 1 h and 2 h after starting an individualized cold exposure in 30 young adults (60% women, 21.9 ± 2.3 y; 24.9 ± 5.1 kg/m2 ). BAT volume, 18 F-fluorodeoxyglucose uptake, and radiodensity were assessed by a static positron emission tomography-computerized tomography scan after cold exposure. RESULTS: Cold exposure increased the concentration of CXCL14 (Δ2h = 0.58 ± 0.98 ng/mL; p = 0.007), GDF15 (Δ2h = 19.63 ± 46.2 pg/mL; p = 0.013), FGF21 (Δ2h = 33.72 ± 55.13 pg/mL; p = 0.003), and IL6 (Δ1h = 1.98 ± 3.56 pg/mL; p = 0.048) and reduced BMP8b (Δ2h = -37.12 ± 83.53 pg/mL; p = 0.022). The cold-induced increase in plasma FGF21 was positively associated with BAT volume (Δ2h: ß = 0.456; R2 = 0.307; p = 0.001), but not with 18 F-fluorodeoxyglucose uptake or radiodensity. None of the changes in the other studied brown adipokines was related to BAT volume, activity, or radiodensity. CONCLUSIONS: Cold exposure modulates plasma levels of several potential brown adipokines in humans, whereas only cold-induced changes in FGF21 levels are associated with BAT volume. These findings suggest that human BAT might contribute to the circulatory pool of FGF21.

Second Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis: A Single-Center Prospective Experience.

Immunosuppressive therapy is useful in persons with multiple sclerosis (MS), and autologous hematopoietic stem cell transplantation (aHSCT) is the most effective immunosuppressive treatment in this setting. Information on the usefulness of a second aHSCT in patients with MS is scarce. In a group of 1225 individuals with MS prospectively managed with aHSCT, we analyzed the salient features of 4 patients who received 2 consecutive transplants. After a moderate initial response to the first aHSCT, the patients were transplanted again after deterioration of their neurologic status; the second transplant was well tolerated and, in all instances, was completed on an outpatient basis and with no associated undesired toxicity. The autograft protocol is registered in ClinicalTrials.gov, identifier NCT02674217. After the second graft, the expanded disability status scale score stabilized in 2 patients; in 1, the post-transplant period was too short to assess the response, and in another, the development of associated Parkinson's disease precluded the assessment of the outcome. In conclusion, a second aHSCT in persons with MS is feasible, safe, and may lead to a positive response in some cases.

Adults with metabolically healthy overweight or obesity present more brown adipose tissue and higher thermogenesis than their metabolically unhealthy counterparts.

BACKGROUND: There is a subset of individuals with overweight/obesity characterized by a lower risk of cardiometabolic complications, the so-called metabolically healthy overweight/obesity (MHOO) phenotype. Despite the relatively higher levels of subcutaneous adipose tissue and lower visceral adipose tissue observed in individuals with MHOO than individuals with metabolically unhealthy overweight/obesity (MUOO), little is known about the differences in brown adipose tissue (BAT). METHODS: This study included 53 young adults (28 women) with a body mass index (BMI) ≥25 kg/m2 which were classified as MHOO (n = 34) or MUOO (n = 19). BAT was assessed through a static 18F-FDG positron emission tomography/computed tomography scan after a 2-h personalized cooling protocol. Energy expenditure, skin temperature, and thermal perception were assessed during a standardized mixed meal test (3.5 h) and a 1-h personalized cold exposure. Body composition was assessed by dual-energy x-ray absorptiometry, energy intake was determined during an ad libitum meal test and dietary recalls, and physical activity levels were determined by a wrist-worn accelerometer. FINDINGS: Participants with MHOO presented higher BAT volume (+124%, P = 0.008), SUVmean (+63%, P = 0.001), and SUVpeak (+133%, P = 0.003) than MUOO, despite having similar BAT mean radiodensity (P = 0.354). In addition, individuals with MHOO exhibited marginally higher meal-induced thermogenesis (P = 0.096) and cold-induced thermogenesis (+158%, P = 0.050). Moreover, MHOO participants showed higher supraclavicular skin temperature than MUOO during the first hour of the postprandial period and during the cold exposure, while no statistically significant differences were observed in other skin temperature parameters. We observed no statistically significant differences between MHOO and MUOO in thermal perception, body composition, outdoor ambient temperature exposure, resting metabolic rate, energy intake, or physical activity levels. INTERPRETATION: Adults with MHOO present higher BAT volume and activity than MUOO. The higher meal- and cold-induced thermogenesis and cold-induced supraclavicular skin temperature are compatible with a higher BAT activity. Overall, these results suggest that BAT presence and activity might be linked to a healthier phenotype in young adults with overweight or obesity. FUNDING: See acknowledgments section.

Cold-induced changes in plasma signaling lipids are associated with a healthier cardiometabolic profile independently of brown adipose tissue.

Cold exposure activates brown adipose tissue (BAT) and potentially improves cardiometabolic health through the secretion of signaling lipids by BAT. Here, we show that 2 h of cold exposure in young adults increases the levels of omega-6 and omega-3 oxylipins, the endocannabinoids (eCBs) anandamide and docosahexaenoylethanolamine, and lysophospholipids containing polyunsaturated fatty acids. Contrarily, it decreases the levels of the eCBs 1-LG and 2-LG and 1-OG and 2-OG, lysophosphatidic acids, and lysophosphatidylethanolamines. Participants overweight or obese show smaller increases in omega-6 and omega-3 oxylipins levels compared to normal weight. We observe that only a small proportion (∼4% on average) of the cold-induced changes in the plasma signaling lipids are slightly correlated with BAT volume. However, cold-induced changes in omega-6 and omega-3 oxylipins are negatively correlated with adiposity, glucose homeostasis, lipid profile, and liver parameters. Lastly, a 24-week exercise-based randomized controlled trial does not modify plasma signaling lipid response to cold exposure.

The consequences of delayed diagnosis and treatment in persons with multiple sclerosis given autologous hematopoietic stem cell transplantation.

OBJECTIVES: We have analyzed the association of delayed both diagnosis and treatment of persons with MS with the long-term results of patients given autologous hematopoietic stem cell transplantation (aHSCT). METHODS: Patients with MS referred to the HSCT-Mexico program were included in the study; in 103, detailed pre- and post-transplant evolution could be recorded. Two groups of patients were analyzed according to the time of evolution between the onset of symptoms and the definite diagnosis of MS: more than 8 months (delayed diagnosis, DD), or less than 8 months (non-delayed diagnosis, NDD). The progression of MS was assessed by changes in the expanded disability status scale (EDSS). RESULTS: The time elapsed between the onset of symptoms and the correct diagnosis was lower for the NDD group (1.55 vs. 35.87 months, p<0.05). Both groups of patients showed a similar EDSS score at diagnosis (1.5 vs. 1.5); however, the EDSS at the time of the transplant was higher in the DD group (4.5 vs. 3.0, p=0.3) and the response of the EDSS score to the transplant was significantly better for the NDD group, the last EDSS scores being 2.5 vs. 4.25 (p=0.03). Both groups of patients responded to aHSCT by diminishing the EDSS, but the response was significantly better in the NDD group. CONCLUSIONS: These data indicate that both the pre-transplant progression of the disease and the response to aHSCT were significantly worse in the DD group. An early diagnosis and an early aHSCT intervention are critical for a good prognosis, in terms of lowering and stabilizing the motor disability in MS patients given autografts.

Evaluation of selected natural sesquiterpenes as sensitizing agents of ß-lactam-resistant bacterial strains.

AIMS: To evaluate the capacity of fourteen sesquiterpenes to enhance the action of known antibiotics against two ß-lactam resistant strains, and to determine a possible mechanism of antibiotic sensitization by assessing their ability to inhibit a ß-lactamase enzyme. METHODS AND RESULTS: The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of ß-lactams cefuroxime (CEFM) and cefepime (CPM) against Staphylococcus aureus 23MR and Escherichia coli 82MR strains in the absence and presence of subinhibitory concentrations of fourteen natural sesquiterpenes. (1R,4R)-4H-1,2,3,4-tetrahydro-1-hydroxycadalen-15-oic acid (5), xerantolide (8), estafiatin (11), and ambrosin (12) exhibited the best sensitizing effects in both strains. These compounds were able to reduce the MIC of CEFM by 2-fold (from 15.0 to 7.5 µg/mL) and CPM by 15-fold (from 0.9 to 0.06 µg/mL) in S. aureus 23MR. For E. coli 82MR, the MIC of CEFM was reduced up to 8-fold (from 120.0 to 15.0 µg/mL). In this strain, the activity of 8 and 11 surpassed that of clavulanic acid (positive reference), which reduced the MIC of CEFM from 120.0 to 60.0 µg/mL. To elucidate a possible mechanism of antibiotic sensitization, molecular docking studies were conducted with ß-lactamases. These studies revealed an affinity with the enzymes (energies > -4.93 kcal/mol) by the formation of hydrogen bonds with certain conserved amino acid residues within the active sites. However, the in vitro results indicated only marginal inhibition, with percentages <50%. CONCLUSIONS: The bioevaluations indicate that nine of fourteen sesquiterpenes enhance the action of CEFM and CPM against the ß-lactam resistant strains, and these compounds displayed moderate activity as inhibitors of ß-lactamase.

In persons with CIDP, auto-HSCT can be conducted fully on an outpatient basis and induces significant clinical responses: A prospective study in a single center.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is one of the world's most common treatable neuropathy which usually responds to immunosuppressive treatment. Autologous hematopoietic stem cell transplantation (aHSCT) is an intense way of inducing immunosuppression. OBJECTIVE: We analyze the evolution of CIDP patients treated with aHSCT in our center. METHODS: Between 2018 and 2023, persons with CIDP were prospectively autografted employing the "Mexican method" to conduct grafts on an outpatient basis, employing cyclophosphamide 200 mg/Kg and rituximab 1000 mg. The protocol is registered in ClinicalTrials.gov identifier NCT02674217. RESULTS: In our center 21 autologous transplant cases were completed in 2018-2023. Seven patients provided data to assess the efficacy of the procedure. Positive responses (stabilization and/or improvement) were observed in all seven patients: Five reported improvements in the Inflammatory Neuropathy Cause and Treatment (INCAT) score and one reported stabilization. In the Inflammatory Rasch-Built Overall Disability Scale (I-RODS) score. Median INCAT score was 5 (range 1-9), whereas median I-RODS score was 24 (range 11-29). Five patients (71%) reported improvement in the INCAT score, one reported stabilization and one informed worsening; concerning the I-RODS score 5 (71%) informed improvement, whereas two reported stabilization. CONCLUSION: aHSCT conducted fully in an outpatient basis, employing the conditioning regimen of the "Mexican method" appears to be a feasible therapeutic option for persons with CIDP. Additional studies are needed to confirm these observations.

Effect of Moderate Versus Vigorous Exercise Intensity on Body Composition in Young Untrained Adults: The Activating Brown Adipose Tissue Through Exercise (ACTIBATE) Randomized Controlled Trial.

The present study aimed to investigate the effect of a 24-week aerobic + resistance training programs at moderate versus vigorous intensity on body composition, and the persistence of the changes after a 10-month free-living period, in young untrained adults. This report is based on a secondary analysis from the activating brown adipose tissue through exercise (ACTIBATE) single-center unblinded randomized controlled trial. A total of 144 young adults (65.6% women) aged 18-25 years were randomly allocated to three different groups: (a) aerobic + resistance exercise training program based on the international physical activity recommendations at vigorous intensity (Ex-Vigorous group), (b) at moderate intensity (Ex-Moderate group), and (c) control group (no exercise). Body composition outcomes were determined by a dual-energy X-ray absorptiometry scanner. Both Ex-Vigorous and Ex-Moderate decreased body weight, fat mass, and visceral adipose tissue mass in a similar manner (all p < .04). After a 10-month free-living period, these parameters returned to baseline levels in both exercise groups (all ps < .03). No differences between the exercise groups and the control group were noted in lean mass changes (all ps > .1). A 24-week aerobic + resistance training intervention based on the international physical activity recommendations was enough to improve body weight, fat mass, and visceral adipose tissue mass in untrained young adults, independently of the exercise intensity (moderate vs. vigorous).

Can doses of post-transplantation cyclophosphamide in haploidentical stem cell allografts be reduced?

Objectives: Allogeneic hematopoietic stem cell transplantation (HSCT) remains the most important curative modality for several hematologic malignancies, but an HLA-matched sibling or unrelated donor is not always available, particularly for ethnic minorities and multiethnic families. We have shown that Haplo-HSCT can be conducted safely on an outpatient basis, using peripheral blood stem cells; this leading into substantial decreases in the costs. Methods: In this study twenty-one patients prospectively received the conventional dose of post-transplantation cyclophosphamide (PTCy): (50 mg/Kg on days 3 and 4), whereas 10 were given reduced doses of the drug (25 mg/Kg on days 3 and 4). Results: According to the statistical analysis, the two comparative groups (PTCy 50 mg/kg vs PTCy 25 mg/kg) had no significant difference in terms of age, sex, hematological recovery, and type of conditioning regimen. The median OS for the group PTCy 50 mg/kg is 5.7 months meanwhile for the group PTCy 25 mg/kg the median is 6.4 months. The median follow up for entire group is 4.5 months (IQR: 1.1-18.9 mo). Conclusion: These results could indicate that the Cy-dependent hematological toxicity can be reduced without compromising its effectivity. This preliminary observation may be considered as an idea to conduct prospective randomized studies to explore the possibility of significantly reducing the doses of PT-Cy in the setting of Haplo-HSCT.Trial registration: ClinicalTrials.gov identifier: NCT05780554.

Therapy of childhood acute lymphoblastic leukemia in resource-poor geospaces.

The therapy of children with acute lymphoblastic leukemia (ALL) in limited resource geospaces is challenging and must balance safety, efficacy, availability, and affordability. We modified the control arm of the St. Jude Total XI protocol for outpatient delivery including once-weekly daunorubicin and vincristine in initial therapy, postponing intrathecal chemotherapy until day 22, prophylactic oral antibiotics/antimycotics, use of generic drugs, and no central nervous system (CNS) radiation. Data were interrogated from 104 consecutive children ≤12 years (median, 6 years [interquartile range (IQR), 3, 9 years]. All therapies were given in an outpatient setting in 72 children. Median follow-up is 56 months (IQR 20, 126 months). A total of 88 children achieved a hematological complete remission. Median event-free survival (EFS) is 87 months [95% confidence interval (CI), 39, 60], 7.6 years in low-risk children (3.4, 8 years) whereas 2.5 years (1, 10 years) in high-risk children. The 5-year cumulative incidence of relapse (CIR) is 28% (18, 35%), 26% (14, 37%) in low-risk children and 35% (14, 52%) in high-risk children. Median survival for all subjects is not reached but must exceed 5 years. A total of 36 children relapsed at a median of 12 months (5, 23 months). Outcomes were comparable to those reported in the control arm of the Total Therapy XI study, but inferior to current treatment protocols in high-income countries. The average cost of the first 2 years of therapy was $28,500 USD compared with an average cost of approximately $150,000 USD in the US, an 80% saving. In conclusion, using an outpatient-based modification of the St. Jude Total XI protocol, we obtained good results with relatively few hospitalizations or adverse events and at a substantial saving. This model can be applied in other resource-poor geospaces.