Hospital Luis Calvo Mackenna

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Pediatric hematopoietic stem cell transplantation (HSCT) is a life-saving therapy for malignant and non-malignant hematologic diseases. However, access to this high-complexity treatment remains limited and uneven across the Andean subregion. This study aimed to evaluate the current status, capacity, and equity of pediatric HSCT programs in six Andean countries (Bolivia, Chile, Colombia, Ecuador, Peru, and Venezuela) within the framework of WHO Global Initiative of Childhood Cancer. A mixed-methods, cross-sectional situational assessment was conducted between November 2024 and January 2025 under the coordination of the Andean Health Organization (ORAS-CONHU) and the Pan American Health Organization (PAHO). Standardized national and center-level surveys (34 and 150 items, respectively) were applied to Ministries of Health and HSCT centers to collect data on infrastructure, workforce, financing, quality management, and barriers to access. Quantitative data were analyzed descriptively and validated by national committees, complemented by qualitative interviews with key stakeholders. Twenty-seven HSCT centers were identified across the subregion, revealing major disparities in access and capacity. Chile reached 100% coverage of estimated transplant needs, whereas Colombia, Peru, and Venezuela achieved 80%, 29%, and 42.5%, respectively. Bolivia and Ecuador had the lowest coverage (1.6% and 24%). Only 28% of units were pediatric-exclusive, and less than two-thirds met full quality and training standards. High-cost medicines, limited infrastructure, and shortages of specialized personnel were identified as critical barriers, whereas regional collaboration and national policies emerged as key facilitators. The study highlights significant inequities in pediatric HSCT access and capacity across the Andean subregion. Strengthening infrastructure, workforce training, financing mechanisms, and data systems, supported by sustained regional cooperation, is essential to achieve equitable, high-quality transplant care for all children.

Introduction CD40 ligand (CD40L) deficiency is a rare X-linked primary immunodeficiency. Hematopoietic stem cell transplant (HSCT) is currently the only curative treatment. To date, regional studies have focused on reporting the clinical characteristics of this disease rather than transplant outcomes. This study aims to characterize pediatric patients with CD40L deficiency who have undergone HSCT in centers from Chile, Colombia, Brazil, Mexico, and Argentina. Objectives include describing clinical features, evaluating survival, identifying mortality-associated factors, and reporting major posttransplant complications. Methods We retrospectively reviewed pediatric patients with CD40L deficiency who underwent HSCT between January 2002 and December 2024. We analyzed clinical characteristics, survival outcomes, and complications. Descriptive statistics were used, and overall survival was estimated using Kaplan–Meier analysis. During this period, 27 patients with CD40L deficiency were included in the study. For one patient, data from a second HSCT were also collected. Results Twenty-seven pediatric patients with CD40L deficiency underwent HSCT, with a median age at transplant of 6 years (range 1–18). A confirmed genetic diagnosis was present in 96% of cases, and 12 patients (44%) had a positive family history. Pretransplant complications included pneumonia in 14 patients (52%), gastrointestinal symptoms in 15 patients (56%), neutropenia (26%), and cholangitis (11%). Infectious history included Pneumocystis jirovecii (22%), CMV (7%), Cryptosporidium (15%), and Candida (26%). Intravenous immunoglobulin (IVIG) supplementation was administered before transplant in 96% of patients, and 67% continued IVIG posttransplant. Cotrimoxazole prophylaxis was given prior to HSCT in 93% of cases. Unrelated donors were used in 70% of patients, and most received conditioning with treosulfan/busulfan plus fludarabine. Graft versus host disease (GVHD) prophylaxis included antithymocyte globulin (ATG) in 59% of patients and calcineurin inhibitors in 96%. Engraftment was achieved in 93% of patients, and 3 required a second transplant. Acute GVHD grade III–IV occurred in 30%, and chronic GVHD in 26%. CMV occurred in 10 patients, with one fatal case. A total of four deaths were reported—three were HSCT-related. Overall survival was 83.6% at 1 year, 78.7% at 3 years, and 78.7% at 5 years. Conclusions This multicenter retrospective study analyzed pediatric patients with CD40L deficiency who underwent HSCT. The cohort showed favorable 5-year overall survival. A genetic diagnosis was confirmed in 96% of patients, while one-third had a positive family history. Most patients experienced significant complications prior to transplant, and HSCT was delayed by a median of 5.5 years. Prophylaxis included IVIG in 96% of cases and cotrimoxazole in 93%. Most transplants used matched unrelated donors (MUD), with busulfan/fludarabine-based conditioning regimens. Conditioning approaches varied by center. Serotherapy (mainly ATG) was used in 70% of patients. Engraftment was successful in 93% of cases. Posttransplant complications were frequent. Acute GVHD occurred in 30% of patients, mostly in severe forms (grade III–IV), while 26% developed chronic GVHD. CMV reactivation was reported in 44%, and graft-related complications (“graft problems”), including secondary graft failure and mixed chimerism, were observed in 26% of cases.

<title>Abstract</title> <italic>Trials</italic> guidance: The Abstract should not exceed 350 words. Please minimize the use of abbreviations and do not cite references in the abstract. The abstract must include the following separate sections: <bold>Background</bold> <italic>: Mycobacterium tuberculosis</italic> acquisition after exposure is common but difficult to diagnose and frequently requires serial testing given that immunological evidence of infection can take several weeks to develop. Even though tuberculosis infection (TBI) is asymptomatic, its long-term effects remain unclear due to poorly understood host-pathogen interactions and delayed disease development, and research has shown that active mycobacterial replication and inflammation occur during TBI. Although the main purpose of antituberculosis prophylaxis has been to prevent people with established TBI from progressing to active tuberculosis disease, a few studies have suggested that this prophylaxis, when administered during the window period after exposure, can prevent the acquisition of TBI in very young children. Considering that newer preventive regimens are shorter and safer, this study aims to assess whether tuberculosis prophylaxis —when given in the window period after exposure— can prevent new infections in older children and adolescents who have been recently exposed. <bold>Methods</bold> : A multicentre cluster-randomized controlled clinical trial will be performed in Chile. A total of 360 households (clusters) with children aged ≥5 to &lt;18 years, who have been recently exposed to a new case of pulmonary tuberculosis will be randomized to intervention or control arm. In the intervention arm, contacts will receive immediate tuberculosis prophylaxis, regardless of the interferon-gamma release assay (IGRA) result. In the control arm, participants will receive tuberculosis prophylaxis only if the IGRA test results positive, as per standard of care. In both arms, the prophylaxis scheme will be the usual weekly isoniazid plus rifapentine for 12 weeks regimen. The primary outcome will be assessed at the individual level by IGRA conversions from negative at baseline to positive at the 12-week follow-up. <bold>Discussion</bold> : This trial will establish the effectiveness of a window prophylaxis strategy in reducing the risk of TBI acquisition after exposure in a community setting, a strategy that can potentially contribute to global tuberculosis elimination by reducing <italic>M. tuberculosis</italic> reservoirs. <bold>Trial registration</bold> : ClinicalTrials.gov, NCT07086820. Registered 17 July 2025, https://clinicaltrials.gov/study/NCT07086820.

Febrile neutropenia (FN) is one of the most frequent complications of antineoplastic treatment in patients with cancer. Invasive bacterial infections and invasive fungal infections are a major cause of morbidity and mortality in this population, along with respiratory viral infections, which are increasingly recognized in children with FN episodes. This study aimed to compare the clinical outcome of children with persistent high-risk FN (HRFN) that have an abnormal chest computed tomography (CT) versus those with normal chest CT or in which chest CT was not indicated, and to evaluate the microbiologic etiology and pulmonary tomographic findings in this population. Patients with persistent HRFN were prospectively enrolled between 2016 and 2021 and classified into 2 groups: children with persistent HRFN that had an abnormal chest CT and children that had a normal chest CT or in which chest CT was not clinically indicated. We compared the clinical outcome of the patients of the 2 groups. Children with abnormal chest CT underwent a microbiologic and molecular study to evaluate the etiology of the pulmonary compromise. After discharge, all children with persistent HRFN that had an abnormal chest CT were evaluated by 2 groups of independent, blind investigators: 1 pediatric infectious disease specialist that classified the etiology of the pulmonary infiltrate as bacterial, fungal, viral or unknown etiology and 2 pediatric radiologists that classified each chest CT, as defined by the Fleischner Society. We enrolled 176 children with persistent HRFN, of which 36 had abnormal chest CT. In 27/36 episodes (75%), the etiology was determined (12 bacterial, 8 viral and 7 fungal). Subjects with an abnormal chest CT had more days of fever, longer length of hospital stay, higher PICU admission, more use of mechanical ventilation, more oxygen requirement, longer periods of antibacterial and antifungal therapy. Chest CT showed no statistically significant differences when findings were compared by etiology of the episodes. Our results strongly support that abnormal findings on chest CT in children with persistent HRFN should be interpreted as a predictor of poor clinical outcome, as not as a marker of etiology.

The present literature review tries to investigate the possible influence of P. gingivalis and HCMV co-infection in fostering the development of oral cancer and chronic periodontitis. A comprehensive search was conducted in PubMed and Google Scholar, focusing on the relevance and significance of articles that examine the role of P. gingivalis and HCMV in periodontal disease and oral cancer. The evidence suggests that P. gingivalis and HCMV may act synergistically to modulate host immunity, disrupt epithelial integrity, and interfere with key cellular pathways. These interactions may enhance tissue destruction and foster a microenvironment conducive to malignant transformation. However, most of these findings stem from in vitro models and small-scale clinical studies, limiting the generalizability and clinical relevance of current conclusions. Although the proposed interaction between P. gingivalis and HCMV provides a compelling framework for understanding how microbial co-infections may influence oral cancer, the evidence remains preliminary and largely associative. To support these mechanistic hypotheses, future studies should give top priority to in vivo models, bigger patient cohorts, and longitudinal clinical studies.

Abstract We explore the meromorphic structure of the ζ-function associated with the boundary eigenvalue problem of a modified Sturm–Liouville operator subject to spectral-dependent boundary conditions at one end of a segment of length l. We find that it presents isolated simple poles that follow the general rule valid for second-order differential operator subject to standard local boundary conditions. We employ our results to evaluate the determinant of the operator and the Casimir energy of the system it describes, and study its dependence on l for both the massive and the massless cases.