Hospital Central Militar

New therapies are improving outcomes even in advanced stages of multiple myeloma. To describe the experience of bispecific antibodies (BsAbs) in Mexico. The study included 41 patients with triple-class refractory (88%) and penta-drug refractory (61%) myeloma. The median number of prior treatment lines was 3, and the median time to response was 2 months. Step-up dosages were administered on an outpatient basis in 34 patients (83%). BsAbs were administered every 2 weeks to 19 patients (46%) and monthly to 17 patients (41.5%). Thirteen of these (31.5%) switched to monthly doses early in treatment and maintained their response. Twenty-five of 38 evaluated patients (66%) achieved a complete response or better, and 84% were negative for minimal residual disease. The median response duration was 10 months, while median progression-free survival and overall survival were 12 and 13 months, respectively. Extramedullary disease, no complete response, positivity for minimal residual disease, and penta-refractoriness were associated with poor outcomes. The adverse events were lower than those reported in clinical trials. In conclusion, using outpatient step-up dosing followed by planned de-escalation to monthly doses of BsAbs in responding patients with MM is feasible, safe, and effective, and may improve access to this novel therapy.

• Median age at CML diagnosis in Mexico is 43 years, almost two decades earlier than in high-income countries. • In a military system with universal TKI access, 10-year OS reached 90%. Chronic myeloid leukemia (CML) is the most frequent chronic leukemia in Mexico, with patients diagnosed nearly two decades younger than in high-income countries. While tyrosine kinase inhibitors (TKIs) have transformed outcomes, disparities in access persist in civilian hospitals. The military health system, in contrast, guarantees universal TKI access. We conducted a retrospective cohort study of patients with CML treated at the Hospital Central Militar (HCM) between January 2000 and July 2024. Clinical characteristics, treatment patterns, and survival outcomes were analyzed. Kaplan–Meier estimates were used for overall survival (OS). Sixty-six patients were included. The median age at diagnosis was 43.3 years (IQR, 36.3–52.1); 33.3% (n=22) were <40 years and 10.6% (n=7) were ≥60 years. First-line treatment consisted of imatinib in 92.4% (n=61), dasatinib in 3.0% (n=2), and nilotinib in 4.5% (n=3). Sixty-two percent of patients (n = 41) required second-line therapy, predominantly due to inadequate response. The median follow-up was 5 years (range, 0–24.5). Overall survival (OS) probabilities were 98.1% at 5 years, 90.3% at 10 years, and 72.4% at 15 years; the median OS was not reached. Outcomes were preserved even among patients requiring ≥2 lines. In this military cohort, where TKI access was universally guaranteed, survival was comparable to international benchmarks despite the younger age at diagnosis. These results indicate that favorable long-term survival can be observed in settings with uninterrupted access to therapy. The next step is to strengthen molecular monitoring and implement structured treatment-free remission programs to consolidate these gains.

In the original publication [...].

This article analyzes the work Recreações e Material Didático de Matemática (1962), by Manoel Jairo Bezerra, seeking to understand its contribution to the constitution of Mathematics Didactics in Brazil and to the consolidation of an Active Didactics in primary education. The research, of a historical-documentary nature, is grounded in an interpretative analysis of Bezerra’s text, taken as a pedagogical source representative of the circulation of didactic knowledge in the twentieth century. The results show that the author establishes didactic materials as a central device of learning, legitimizing the concrete as a mediator between action and abstraction and formalizing playfulness as a prescriptive teaching procedure. The study also observes the standardization of the use of these resources as an expression of a broader movement of teacher professionalization, by assigning to the teacher the role of mediator of the child’s reflective action. It concludes that the work contributes to redefining pedagogical practices, discourses, and modes of organizing the teaching of mathematics, consolidating epistemological and methodological foundations aligned with the psychological theories of its time.

The glymphatic system (GS) consists of a paravascular fluid-exchange network that regulates cerebrospinal and interstitial fluid dynamics, clears metabolic waste, and modulates neuroinflammation. Aquaporin-4 (AQP-4), expressed in astrocytic end-feet, is central to GS function and blood-brain barrier integrity, but in cerebral ischemia (CI), GS disruption and AQP-4 mislocalization drive cytotoxic edema, inflammation, and vascular dysfunction, worsening outcomes. This review aimed to examine the role of the GS in CI, focusing on pathophysiology and potential therapeutic targets. A PubMed-based literature review was conducted, selecting 51 studies from 115 screened that addressed GS, AQP-4, and ischemic stroke. Evidence suggests that modulating GS flow, through strategies such as enhancing arterial pulsations or regulating AQP-4, may reduce edema and neuroinflammation, although selectively targeting AQP-4 without impairing waste clearance remains a key challenge. The GS represents a promising therapeutic target in ischemic stroke, and a deeper understanding of its physiology may guide the development of neuroprotective interventions; future research should refine pharmacological strategies to optimize glymphatic function and improve recovery in CI patients.

BackgroundPulse pressure depends mostly on arterial wall stiffness. Several studies have focused on the fact that many factors, including the metabolic syndrome or its components, interact to impact on great vessels elastic properties, increasing arterial wall stiffness. ObjectiveTo evaluate the influence of the metabolic syndrome and its components on pulse pressure in persons without any apparent disease. Material and MethodsA total of 1.155 subjects without demonstrable disease were randomly selected. The metabolic variables defining metabolic syndrome (ATP III) were recorded: fasting HDL-cholesterol ≤40/50 mg/dl (men/women), fasting triglycerides ≥150 mg/dl, fasting glycemia ≥100 mg/dl, waist circumference ≥102/88 cm (men/women) and systolic/diastolic blood pressure ≥130/85 mm Hg. Patients’ pulse pressure values were compared among different groups according to gender and age. The frequency of the metabolic syndrome components was determined and pulse pressure was adjusted by gender, age and all the components using multiple linear regression analysis. The adjusted value of pulse pressure corresponding to each metabolic syndrome component was determined and compared to that of normal subjects. Finally, adjusted pulse pressure was calculated according to the possible combinations of three factors or greater (diagnostic criteria of metabolic syndrome) and was compared with that of individuals without any component of the metabolic syndrome. ResultsGeneral characteristics of the 1.155 individuals: men 62%, age 38±9 years (range 20-66), waist circumference 89±13 cm, triglycerides 107±74 mg/dl, glycemia 82±16 mg/dl, HDL-cholesterol 48±13 mg/dl, systolic blood pressure 124±14 mm Hg, diastolic blood pressure 78±9 mm Hg, pulse pressure 46±9 mm Hg. Age: 38±9 years in men (n=712) and 37±9 years in women (n=443); p=ns. Pulse pressure was 48±8 mm Hg in men versus 43±9 mm Hg in women; p&lt;0.001. Influence of age on pulse pressure: 45±8 in individuals &lt;35 years versus 47±9 in ≥35 years; p&lt;0.001. Frequency of metabolic syndrome components: waist circumference ≥102/88 cm: 18%, glycemia ≥100 mg/dl: 7%, triglycerides ≥150 mg/dl: 17%, HDL-cholesterol ≤40/50 mg/dl: 45%, systolic blood pressure ≥130 mm Hg: 40%, diastolic blood pressure ≥85 mm Hg: 16%. When pulse pressure adjusted by each component of the metabolic syndrome was compared to that of controls, the following values were obtained: waist circumference ≥102/88 cm: 48±4 versus 46±3, glycemia ≥100 mg/dl: 52±5 versus 46±3, triglycerides ≥150 mg/dl: 48±3 versus 46±4, HDL-cholesterol ≤40/50 mg/dl: 44±3 versus 47±3; systolic blood pressure ≥130 mm Hg: 48±4 versus 45±3; diastolic blood pressure ≥85 mm Hg: 48±5 versus 46±3, all p&lt;0.001. Finally, adjusted pulse pressure according to the possible combinations of three factors or greater was calculated and compared with that of individuals without any component of the metabolic syndrome: 49±5 versus 46±3, p&lt;0,001. ConclusionsThe metabolic syndrome and/or its components induce pulse pressure elevation, except for HDL-cholesterol. This effect seems to be independent of age, gender and the eventual interaction of the variables analyzed.

Abstract Background and Aims Aminoglycosides, such as Amikacin, are the cornerstone to treat severe infections in pediatric patients. Amikacin dosing requires achieving high peak concentrations to ensure efficacy against bacterial strains (up to &amp;gt; 60 mg/L depending on the strain) while maintaining trough levels &amp;lt; 2.5 mg/L to minimize nephrotoxic risks [1]. The minimum effective dose and frequency has been a debate due to the challenges of predicting ontogeny physiological changes. Current dosing schemes often miss peak and trough target levels in pediatric populations [1]. We present an age-stratified in-silico study to evaluate Amikacin dosing strategies in pediatric patients aged 2 to 24 months, focusing on optimizing peak and trough levels within a 24-hour dosing interval. Method An in-silico pharmacokinetic (PK) model based on [2] was validated against the clinical study results in [1]. Age-stratified virtual pediatric populations (2–24 months) were generated to account for maturational changes in GFR, weight, and height age-dependence based on growth charts and GFR data derived from (51)Cr-EDTA clearance measurements using a single blood sample method [3, 4]. Virtual populations were created for 2-, 6-, 12-, and 24-month-old cohorts (Table 1). The body surface area was computed using Mosteller's formula. Simulations in Python were conducted to evaluate Amikacin dosing strategies with 24-hour dosing intervals over 5 days of treatment. Results Using the standard maximal dosing scheme of 30 mg/kg once daily [1], the simulation shows that the fraction of patients with trough levels &amp;gt; 2.5 mg/L after 24 hours was 61.3%, 19.7%, 4.7% and 1.1% for the 2-, 6-, 12-, and 24-month age cohorts, respectively. Simulations using an optimized 24-hours dosing scheme, designed to maximize peak levels while maintaining trough levels below 2.5 mg/L, revealed a marked age-dependent difference in peak concentrations (Fig. 1). Median peak concentrations after initial administration were 42.5 mg/L, 48.9 mg/L, 50.9 mg/L, and 52.0 mg/L for the 2-, 6-, 12-, and 24-month age cohorts, respectively. A fraction of 6.2% of 2-month-olds and 18.8% of 24-month-olds reached peak levels &amp;gt;60 mg/L after the initial administration. Peak concentrations declined progressively across all age groups over the treatment days. The median peak concentration decreased by 56.4% for the 2-month-olds and 13.8% for the 24-month-olds by day 5 of treatment. Moreover, by day 5, none of the 2-month-olds and 11.4% of the 24-month-olds reached peak concentrations &amp;gt;60 mg/L. Conclusion Further dosage stratification of Amikacin by age is necessary in infants due to physiological kidney maturation and other developmental changes. High inter-patient variability emphasizes the need for therapeutic drug monitoring and dose adjustments during the treatment to optimize efficacy while minimizing the risk of nephrotoxicity.

Objetivo: Evaluar la eficacia y seguridad de la lipotransferencia autóloga (AFG), sola o en combinación con bioestimuladores, en el rejuvenecimiento facial y la reconstrucción oncológica. Métodos: Se realizó una revisión sistemática siguiendo la declaración PRISMA 2020. Se consultaron PubMed, Embase y Cochrane Library entre enero de 2014 y julio de 2024. Se incluyeron ensayos clínicos, estudios observacionales y revisiones sistemáticas que evaluaran AFG aislada, bioestimuladores (ácido poli-L-láctico [PLLA], hidroxiapatita cálcica [CaHA]) o la combinación de ambas en rejuvenecimiento y oncología reconstructiva. Resultados: De 642 artículos identificados, 26 cumplieron los criterios de inclusión. La AFG aislada mostró mejoras en volumen y calidad tisular, aunque con variabilidad en la supervivencia del injerto (reabsorción 20–40%). Los bioestimuladores demostraron eficacia en elasticidad y densidad dérmica, con resultados sostenidos 18–24 meses. La combinación de AFG y bioestimuladores ofreció beneficios superiores en retención volumétrica, textura cutánea y satisfacción del paciente (&gt;90%), con complicaciones leves (&lt;5%). En pacientes irradiados, la AFG mejoró elasticidad y vascularización sin evidencia de aumento en la recurrencia tumoral, aunque se recomienda precaución y seguimiento estrecho. Conclusión: La lipotransferencia autóloga, sola o combinada con bioestimuladores, es una técnica segura y efectiva para rejuvenecimiento facial y reconstrucción en pacientes seleccionados. Se requieren estudios multicéntricos con mayor tamaño muestral, seguimiento prolongado y estandarización de protocolos, así como investigación en biomarcadores predictivos para avanzar hacia una medicina personalizada.

Existen varios factores predisponentes para el desarrollo de endocarditis infecciosa; entre ellos se destacan el antecedente de haber padecido endocarditis infecciosa y el recambio valvular con válvula protésica. La endocarditis infecciosa de válvula protésica producida por Salmonella es una entidad de muy baja incidencia. En esta presentación se describe el caso de una paciente con antecedente de doble recambio valvular, mitral y aórtico, que ingresó con un cuadro de sepsis grave. Se llegó al diagnóstico etiológico de endocarditis infecciosa por Salmonella enteritidis a través de hemocultivos. La paciente tuvo una evolución fulminante y falleció antes de las 24 horas.