Hospital Pablo Tobon Uribe

Penetrating traumatic brain injury (pTBI) is a severe subset of cranial trauma associated with high mortality and a substantial burden of intracranial infections. The pTBI infection rates have decreased from approximately 60% in the pre-war era to about 10% today, due to improvements in operative debridement, critical care, and widespread antibiotic availability; however, the independent effect of prophylactic antibiotics remains uncertain, and clinical practice is highly variable. This systematic review and meta-analysis aims to determine whether prophylactic antibiotics truly reduce intracranial infections in pTBI patients. A systematic review and meta-analysis were conducted following PRISMA guidelines. The PubMed, Scopus, and LILACS were rigorously searched. The primary effectiveness outcome analyzed was the risk of central nervous system infection. Secondary outcomes included antibiotic regimens and duration, mortality, and functional outcomes were assessed. Data were analyzed using a random-effects meta-analysis, and statistical heterogeneity was assessed. The study was registered with PROSPERO (CRD420251033854). Eight studies comprising 1372 patients (891 received antibiotic prophylaxis and 481 did not) were included. We found that the administration of prophylactic antibiotics did not significantly reduce the risk of suffering an intracranial infection OR 1.10 (95% CI 0.29-4.22 I2 = 48.8%). Furthermore, there was no statistically significant difference between monotherapy and multiple antibiotics, or shorter versus longer courses. Moreover, only one study employed a standardized antibiotic regimen. Prophylactic antibiotic administration in patients with penetrating traumatic brain injury was not associated with a statistically significant reduction in the risk of intracranial infections, as evidenced by substantial heterogeneity in the available literature. However, if prophylaxis is administered, it should be a short-course, monotherapy regimen. These findings highlight the urgent need for high-quality, standardized clinical trials to establish evidence-based guidelines for the use of prophylactic antibiotics in this high-risk population.

Moderate-to-severe thyroid eye disease (TED) is a potentially vision-threatening inflammatory condition that requires timely, evidence-based medical management. Although intravenous glucocorticoids remain the mainstay of therapy, several biologic and immunosuppressive agents have emerged as potential alternatives, particularly in steroid-refractory disease. To evaluate and compare the efficacy, safety, and therapeutic positioning of medical treatments for active moderate-to-severe thyroid eye disease. A comprehensive search of PubMed, Embase, and the Cochrane Library was conducted through February 2025. Eligible studies included randomized controlled trials, meta-analyses, systematic reviews, observational cohorts, and selected case series evaluating pharmacological interventions for moderate-to-severe TED. Outcomes of interest were proptosis reduction, Clinical Activity Score (CAS) improvement, diplopia response, and safety/tolerability. A semi-quantitative synthesis approach was used to integrate evidence across heterogeneous study designs. Fifty-eight studies met the inclusion criteria. Intravenous glucocorticoids (IVGCs) demonstrated the most consistent efficacy in controlling inflammatory activity, with modest effects on proptosis and favorable tolerability at cumulative doses below 8 g. Among biologic therapies, teprotumumab showed the greatest magnitude of benefit across all efficacy domains but was limited by safety considerations and access constraints. Rituximab and tocilizumab demonstrated moderate efficacy, particularly in glucocorticoid-resistant cases. Mycophenolate mofetil emerged as the most reliable non-biologic immunosuppressive option. Oral glucocorticoids and several adjunctive therapies showed limited or inconsistent benefit. This systematic review provides an integrated framework to support therapeutic decision-making in moderate-to-severe TED. Intravenous glucocorticoids remain the most consistently supported first-line therapy, while IGF-1R-targeted biologic therapy offers the most comprehensive efficacy across key clinical domains in selected patients. Not registered.

Abstract Background Defaecatory urgency is a cardinal and distressing symptom in ulcerative colitis (UC), strongly associated with disease activity and reduced quality of life. Its resolution represents a key therapeutic goal, often paralleling mucosal healing and remission. Upadacitinib (UPA), a selective JAK1 inhibitor, has demonstrated robust efficacy for induction and maintenance of remission in UC; however, its specific impact on urgency in real-world Latin American settings remains poorly characterised. Methods We conducted a multicentre observational study including adults with moderate-to-severe UC treated with UPA 45 mg/day for induction and 30 mg/day for maintenance. Changes in defaecatory urgency (present/absent), clinical response (≥3-point decrease in Mayo score), and clinical remission (Mayo < 2) were evaluated at weeks 8–16 (induction) and 24 (maintenance). Biochemical remission was defined as faecal calprotectin < 150 µg/g and/or C-reactive protein < 5 mg/L. Absolute differences were calculated with 95 % confidence intervals (CI), and Fisher’s exact test was applied for categorical variables (p < 0.05). Results A total of 47 patients with UC were included; mean age 39.8 ± 14.6 years; 59.6 % female; 83 % previously exposed to at least one anti-TNF agent. At baseline, 66 % of patients reported defaecatory urgency, which decreased to 31.9 % after induction (Δ − 34.1 %; 95 % CI − 49.5 to − 18.7; p = 0.001) and 25.5 % at six months (p = 0.003). Clinical response was achieved in 81.2 % (95 % CI 66.1–91.4), and clinical remission in 61.7 % (95 % CI 46.4–75.1). Improvement in urgency strongly correlated with clinical remission (r = 0.72; p < 0.001). Biochemical remission (faecal calprotectin < 150 µg/g or CRP < 5 mg/L) occurred in 57.4 % of patients. No serious adverse events were observed; mild transaminase elevations occurred in 8.5 %. Conclusion Upadacitinib rapidly and sustainably reduced defaecatory urgency in Colombian patients with moderate-to-severe UC, with improvement in over two-thirds of cases and a strong association with clinical remission and biomarker normalisation. These findings provide the first real-world Latin American evidence highlighting upadacitinib’s impact on patient-centred symptomatic control in ulcerative colitis, supporting its role as an effective induction and maintenance therapy.

Abstract Background Epidemiological and phenotypic variability across regions for IBD is well recognised; however, data from Latin America (LATAM) remain limited. Furthermore, specific data Crohn’s Disease (CD) related perianal fistula (PF-CD), a severe phenotype of CD is not available from across LATAM countries. This study aimed to compare the demographic, clinical, and phenotypic characteristics of PF-CD across four LATAM cohorts. Methods A retrospective study was conducted including patients with an established diagnosis of PF-CD from Argentina (N = 75), Chile (N = 49), Colombia (N = 145), and Peru (N = 22). Variables assessed included age at fistula diagnosis, CD duration prior to fistula onset, and prior exposure to immunomodulators and corticosteroids. Inter-country comparisons were performed using the chi-square test for categorical variables and the Kruskal–Wallis test for continuous variables. Results Based on the demographic profile described in Table 1, the cohort included 291 patients with a median age of 30 years at Crohn’s disease diagnosis and 31 years at PF-CD diagnosis, with a predominance of non-stricturing, non-penetrating disease (55%) and colonic or ileocolonic involvement (79%). As shown in Table 2, the median delay from CD diagnosis to PF-CD onset was 21 months [6–48], with substantial variation across countries. Overall, 54% of fistulas were classified as simple and 46% as complex. Active proctitis was present in 44% of patients, with the highest proportions observed in Argentina and Peru. Proctectomy was required in 3% of the cohort, though with notable inter-country variation. These findings highlight the clinical heterogeneity of PF-CD across Latin American settings. Conclusion This multicentre LATAM analysis demonstrates substantial inter-country variability in PF-CD presentation, including differences in disease behaviour, fistula complexity, and time to fistula development. Nearly half of patients presented with complex fistulas, and active proctitis was frequent across cohorts. These results underscore the importance of improving early detection and optimising multidisciplinary management. Overall, the findings highlight the phenotypic heterogeneity of PF-CD in Latin America and support the need for region-specific clinical strategies. Conflict of interest: Dr. Pavez, Carolina: No conflict of interest Juliao Baños, Fabián: No conflict of interest Balderramo, Domingo Cesar: No conflict of interest Cedron Cheng, Hugo Guillermo: No conflict of interest Hernandez-Rocha, Cristian: No conflict of interest Parra Izquierdo, Leidy Viviana: None Osorio, Laura: No conflict of interest Gil Parada, Fabio Leonel: No conflict of interest Puentes-Manosalva, Fabian: No conflict of interest Pizarro, Paula A.: No conflict of interest Etchevers, Maria Josefina: No conflict of interest Sobrero, Maria Josefina: No conflict of interest Montero, Joaquin: No conflict of interest Gil, Anibal Hector: No conflict of interest Sanchez, Maria Belen: No conflict of interest Sambuelli, Alicia: no Balaban, Ezequiel: No conflict of interest Rohwain, María José: No conflict of interest Alvarez-lobos, Manuel: No Conflicts Bellolio, Felipe: No conflict of interest Sepúlveda, Ignacia: No conflict of interest Hernandez, Elisa: No conflict of interest Pérez, Tamara: No conflict of interest Estay, Camila: No conflict of interest Rojas, René: No conflict of interest Sepulveda, Rolando: No conflict of interest Perez Alfaro, Ignacio: No conflict of interest Paredes Mendez, Juan: No conflict of interest Cervera Caballero, Luis: No conflict of interest Sebastian, Shaji: No conflict of interest Catalàn-Serra, Ignacio: No conflict of interest

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.

BackgroundWe previously estimated the age of amyloid plaque onset at 28.2 years using florbetapir PET measurements of cerebral amyloid deposition in a cross‐sectional study of a convenience sample of PSEN1 E280A carriers and non‐carriers, ages 20‐56, recruited from the world's largest autosomal dominant Alzheimer’s disease (ADAD) cohort. Here we capitalized on longitudinal data from a different sample than used previously, to estimate the age of amyloid onset (EOA) in carriers who were cognitively unimpaired at baseline and examine differences associated with apolipoprotein ε4 (APOE4) status and between men and women.MethodWe analyzed baseline, 2‐year, and 5‐year florbetapir PET scans from 161 initially cognitively unimpairedPSEN1 E280A carriers (ages 30–56) enrolled in the Alzheimer’s Prevention Initiative (API) ADAD Colombia Trial of crenezumab vs placebo, in which crenezumab did not lower brain amyloid (NCT01998841). We included PSEN1 E280A carriers with at least 1 amyloid‐positive (A+) PET scan, using cortical‐to‐pontine standard‐uptake value ratios converted to centiloids (CL). Out of the 169 PSEN1 E280A carriers in the trial, 12 were A‐ and 149 were A+ at baseline, we excluded 1 PSEN1 E280A carrier who did not have A+ longitudinal data and 7 who did not have A+ scans at baseline or follow‐up. The Sample Iterative Local Approximation (SILA) model was applied to estimate EOA using a 20 CL threshold for positivity. We estimated amyloid chronicity and compared EOAs, adjusted for baseline age, between A+ male (n =68) and female (n =98) PSEN1 E280A carriers and between A+ PSEN1 E280A APOE4‐carriers (n =35) and non‐carriers (n =126).ResultMedian EOA was 26.1 years (SD ±7.89, range 1‐54) and estimates were normally distributed. PSEN1 E280A females had a mean EOA of 25.8 years which was not significantly different than the estimates in males (M=27.8 years). PSEN1 E280A APOE4 carriers had an EOA about 3 years younger (M=24.1) than APOE4 non‐carriers (M=27.3, p =0.03).ConclusionThis study illustrates the ability to use longitudinal biomarker data to characterize the onset of biomarker changes and impact of putative disease modifiers like APOE4 in ADAD mutation carriers.