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A Respiratory Therapist-Driven High-Flow Nasal Cannula Liberation Protocol at High Altitude.
(SAGE Publications, 2026-08-26) Vásquez Hoyos, Pablo; Villa Rosero, Yinna M.; Jaramillo-Bustamante, Juan C.; Gómez Lund, Oscar; Carvajal, Cristóbal; Díaz, Franco; González-Dambrauskas, Sebastián; Caporal, Paula; Jabornisky, Roberto; Serra, Alberto; Monteverde-Fernandez, Nicolás
Background: High-flow nasal cannula (HFNC) liberation strategies in pediatric intensive care often transition patients directly from HFNC to room air. At high altitude, oxygen requirements may persist after flow-dependent respiratory support is no longer needed. We evaluated the association between a protocolized, respiratory therapist-driven HFNC liberation strategy and time to successful liberation from high-flow support in children with acute respiratory failure. Methods: We conducted a retrospective cohort study using prospectively collected LARed Network registry data from a tertiary PICU in Bogotá, Colombia (2,600 m altitude). In September 2022, the unit implemented an HFNC liberation strategy designed to separate persistent oxygen requirement from ongoing need for high-flow support. The primary analysis included the first HFNC episode per PICU admission from March 2018 to March 2025. The primary outcome was time to successful HFNC liberation. Kaplan-Meier curves and multivariable Cox regression were used; gamma log-link models were used for sensitivity analyses, including a prespecified bronchiolitis subgroup. Results: We included 1,086 PICU admissions, 627 before and 459 after implementation. Median HFNC duration decreased from 59.8 h (interquartile ranges [IQR] 34.7-91.4) to 53.1 h (IQR 32.3-80.5, P = .01). Kaplan-Meier analysis showed earlier HFNC liberation after implementation (log-rank P < .01). Implementation was associated with earlier liberation in adjusted Cox regression (hazard ratio 1.17, 95% CI 1.03-1.34, P = .02). PICU stay decreased from 4.7 days (IQR 3.2-6.9) to 4.0 days (IQR 2.9-5.8, P < .01). In bronchiolitis, implementation was associated with an 18.2% relative reduction in HFNC duration (95% CI 7.7-27.5%, P < .01). Conclusions: In a high-altitude PICU, a respiratory therapist-driven HFNC liberation strategy was associated with earlier liberation from high-flow support. A strategy that preserves oxygen delivery while testing tolerance of minimal flow may be useful in high-altitude settings
Adenovirus Versus Respiratory Syncytial Virus in Children With Severe Viral Acute Respiratory Failure: A Multicenter Latin American Cohort.
(Wolters Kluwer Health, 2026-08-26) Barajas-Romero, Juan Sebastián; Reyes-Téllez, Mario Andrés; Jaramillo-Bustamante, Juan Camilo; Gómez-Lund, Oscar; Decía, Mónica; Monteverde-Fernández, Nicolás; Serra, Jesús Alberto; Caporal, Paula; Lasso-Palomino, Rubén; Zemanate Zuñiga, Eliana; Martínez, Javier; Menta, Soledad; Martínez-Arroyo, Luis; Herrera-Salazar, Hernán; Castro-Zamorano, Francisca; Carvajal, Cristóbal; Jabornisky, Roberto; Cruces, Pablo; Díaz, Franco; González-Dambrauskas, Sebastián; Vásquez-Hoyos, Pablo
Background: Respiratory syncytial virus (RSV) commonly causes severe lower respiratory tract disease. Adenovirus is detected less often, but severe pneumonia may occur. The pediatric intensive care unit (PICU) course associated with adenovirus detection compared with RSV-only detection is not well defined. Methods: We studied clinician-tested, virus-positive PICU admissions of children aged 1 month to 18 years from 37 PICUs in 7 Latin American countries (2017-2025). Children with RSV and/or adenovirus detection who used respiratory support were grouped as RSV-only, adenovirus-only or RSV-adenovirus codetection. The primary outcome was PICU death or worse functional status at discharge. Adjusted associations were estimated with logistic regression; Firth penalization was used for mortality. Results: Among 3196 PICU admissions, 2859 had RSV-only, 257 adenovirus-only and 80 codetection. PICU mortality was 12/257 (4.7%) in adenovirus-only, 13/2859 (0.5%) in RSV-only and 2/80 (2.5%) in codetection. Compared with RSV-only detection, adenovirus-only detection was associated with mortality [adjusted odds ratio (OR): 10.56; 95% confidence interval (CI): 4.57-24.43] and with PICU death or worse functional status at discharge [21/222 (9.5%) vs 45/2308 (1.9%); adjusted OR: 6.57; 95% CI: 3.59-12.03]. Among nonsurvivors, the median PICU day of death was 3 (IQR: 2-6) with adenovirus-only detection and 8 (IQR: 3-9) with RSV-only detection. Conclusions: In this multicenter Latin American PICU cohort, adenovirus-only detection was associated with a higher-risk acute course than RSV-only detection, including higher mortality and worse functional status at PICU discharge.
Automated segmentation of postsurgical resection cavities on magnetic resonance imaging in focal epilepsy: A Multicentre Epilepsy Lesion Detection study
(John Wiley & Sons, 2026-08-19) Seo, Jieun; Ripart, Mathilde; Kaas, Helene; Kronlage, Cornelius; Sinclair, Ben; Vivash, Lucy; Courtney, Merran R.; O'Brien, Terence J.; Gopinath, Siby; Parasuram, Harilal; Kandemirli, Sedat; Alarab, Natally; Lai, Lillian; Likeman, Marcus; Zhang, Kai; Mo, Jiajie; Ciobotaru, Georgian; Galea, James; Sequeiros-Peggs, Philip; Hamandi, Khalid; Xie, Hua; Illapani, Venkata Sita Priyanka.; Gaillard, William D.; Cohen, Nathan T.; Weil, Alexander G.; Henrichon-Goulet, Florence; Lahlou, Kenza S.; Hadjinicolaou, Aristides; Ibáñez, Agustín; Rojas-Costa, Gonzalo M.; Urbach, Horst; Bücheler, Lara; Heers, Marcel; Valls Carbó, Adrián; Toledano, Rafael; Nobile, Giulia; Parodi, Costanza; Tortora, Domenico; Consales, Alessandro; Riva, Antonella; Severino, Mariasavina; Tisdall, Martin; D'Arco, Felice; Mankad, Kshitij; Chari, Aswin; Eriksson, Maria H.; Piper, Rory J.; Cross, J. Helen; Baldeweg, Torsten; González-Ortiz, Sofia; Pariente, Jose; Bargalló, Nuria; Liu, Yawu; Kälviäinen, Reetta; Barba, Carmen; Lenge, Matteo; Guerrini, Renzo; Iwasaki, Masaki; Sone, Daichi; Maki, Hiroyuki; Imokawa, Tomoki; Sato, Noriko; Jung, Julien; Sepulveda, Francisco; Mansilla, Daniel; Goycoolea, Andres; Lopez, Ingeborg; Napolitano, Antonio; De Benedictis, Alessandro; De Palma, Luca; Rossi-Espagnet, Maria Camilla; Kondylidis, Nikolaos; Gkiatis, Kostakis; Garganis, Kyriakos; Pepper, Joshua; Seri, Stefano; Duncan, John S.; Yasuda, Clarissa L.; Scárdua-Silva, Lucas; Alvim, Marina K. M.; Cendes, Fernando; Gennari, Antonio G.; O'Gorman Tuura, Ruth; Ramantani, Georgia; Josyula, Mariam; Stein, Joel; Sinha, Nishant; Davis, Kate; Hogan, R. Edward.; Maccotta, Luigi; Adler, Sophie; Wagstyl, Konrad
Objective Quantitative assessment of extent of tissue resection following epilepsy surgery requires accurate delineation of the resection cavity on postoperative magnetic resonance imaging (MRI). Current methods for resection cavity masking are time-consuming and labor-intensive, and existing automated approaches exhibit variable segmentation accuracy, particularly on extratemporal resections. We developed MELD-PostOp, a deep learning tool trained and evaluated on a large, heterogeneous cohort to automatically segment resection cavities. Methods The study included 1.5- and 3T postoperative three-dimensional T1-weighted MRI images from the Multicentre Epilepsy Lesion Detection (MELD) project (nsubjects = 969, 27 centers) and from the EPISURG dataset (n = 133). The cohort included children and adults, alongside a range of resection locations, pathologies, and MRI characteristics. Resection cavities were individually segmented in 285 subjects and used to train an nnU-Net prototype model. The prototype model was used to generate an additional 680 resection masks, which were subsequently quality-controlled, edited, and combined with the original 285 to train the final MELD-PostOp model (n = 965). A Stratified Test Cohort (n = 50) and Independent Test Cohort (n = 87) were withheld for model evaluation. Performance was evaluated using Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95), number of predicted clusters, and inference runtime, and compared against established tools (Epic-CHOP, ResectVol, and RESSEG). Results MELD-PostOp achieved a median DSC of .85 and HD95 of 3.61 on the combined test cohort, outperforming Epic-CHOP (DSC .69, HD95 9.67), ResectVol (DSC .66, HD95 15.05), and RESSEG (DSC .43, HD95 32.67), with significant improvements seen in both temporal and especially extratemporal resections. The model detected 98.5% (135/137) of resection cavities. MELD-PostOp runtime was 17 s per MRI, compared to 612 s (ResectVol), 3205 s (Epic-CHOP), and 4 s (RESSEG). MELD-PostOp performance remained high across clinical and imaging subgroups (median DSC > .8). Significance MELD-PostOp is an open-source research tool that provides an accurate, efficient, and generalizable solution for postoperative resection cavity segmentation using only postoperative MRI scans.
Mapping intensive care across Ibero-America: The FEPIMCTI multinational survey of bed capacity, workforce, and pandemic response
(Elsevier, 0022-07-26) Matos, Alfredo; Giglio, Andrés; Pérez-Fernandez, Javier; Nates, Joseph; Cárdenas, Yenny; Raimondi, Nestor; Sánchez, Jorge; Hidalgo, Jorge; Rezende, Ederlon; Borges-Sa, Marcio
Background: Intensive care resources are unequally distributed across Ibero-America, and reliable comparable data are scarce, hindering cross-national comparison and health-system planning. Methods: We conducted a cross-sectional survey of the 25 national critical care societies affiliated with FEPIMCTI. Presidents or designated representatives reported country-level data on ICU beds, intensivist and nursing workforce, organizational models, training pathways, and surge capacity before and during the COVID-19 pandemic. Resource density was summarized as the country-level median with IQR and as the population-weighted regional rate. Results: Twenty-one countries, including Spain and Portugal, participated, representing 693.6 million inhabitants. A total of 78,723 ICU beds were reported (country-level median 6.1 per 100,000, IQR 3.3–12.4; population-weighted rate 11.3), with public ICUs accounting for 51.6%. A total of 23,803 intensivists were identified (median 2.6 per 100,000, IQR 1.0–5.0), with five countries below 1 per 100,000. Nurse-to-patient ratios ranged from 1:1 to 1:7, and universal 24/7 intensivist coverage was reported in only a subset of countries. During the pandemic, ICU bed capacity rose 69%; among the 20 countries with data for both periods, physician involvement rose 32%, largely through redeployment of non-intensivists rather than growth of the certified workforce. Conclusions: Critical care capacity, workforce, and organization vary widely across Ibero-America, with many countries below high-income benchmarks and pandemic surges met largely through temporary redeployment. These findings provide the first coordinated regional benchmark to guide workforce development, standardized training, and organizational strengthening.
Service-Specific Heterogeneity in Sepsis Variable Significance and Machine Learning Model Performance: A Stratified Analysis of the BIAlert Cohort
(MDPI, 2026-06-24) Borges-Sa, Marcio; Macias-Fassio, Eric; Delgado, Alejandro; Santiago Salas Sosa; Aranda, María; Socias, Antonia; del Castillo, Alberto; Giglio, Andrés
Background/Objectives: Sepsis detection relies on clinical variables and scoring systems assumed to perform uniformly across hospital settings. However, sepsis phenotype distributions shift between clinical environments, suggesting that variable importance may be setting dependent. This study aimed to quantify service-specific variability in the discriminatory capacity of clinical variables for sepsis detection and to evaluate whether this heterogeneity translates into differential performance of machine learning models compared to traditional clinical scoring systems. Methods: This stratified sub-analysis of the BIAlert Sepsis cohort (203,755 patients; 11,864 sepsis episodes, 2014–2018) evaluated 61 structured quantitative variables across nine hospital services (≥90 sepsis episodes each). Within each service, the Mann–Whitney–Wilcoxon test (p < 0.01, Holm-corrected) assessed differences between septic and non-septic episodes. Five machine learning models (Random Forest/BIAlert, XGBoost, CatBoost, SVM, Neural Network) and three clinical rules (NEWS, SIRS, qSOFA) were evaluated globally and stratified across four clinical environments. Results: The proportion of significant variables ranged from 95.1% in the Emergency Department (58/61) to 37.7% in the Intensive Care Unit (23/61). Lactate was the only universally significant variable (9/9 services). Clinical scoring systems collapsed in Critical Care (qSOFA and NEWS AUC 0.459). BIAlert maintained the highest AUC across all environments (0.975–0.857). The Friedman test confirmed significant differences (χ2 = 28.00, p < 0.001), with BIAlert achieving a mean rank of 1.0. Conclusions: The discriminatory capacity of clinical variables for sepsis detection is not uniform across hospital services. ML models, particularly BIAlert, maintained robust performance where fixed-rule scoring systems failed.
From development to clinical practice: deployment of an interoperable and secure ML-based CDSS to aid in the early detection of sepsis
(Elsevier, 2026-06-17) Serrano García, Ana; López, David; Macias-Fassio, Eric; Salas-Sosa, Santiago; Pascual, Iván; Pruenza, Cristina; Borges-Sa, Marcio; Giglio, Andrés; Cruz-Rojo, Jaime; Pacheco-Puig, Rodrigo
Recent research has increasingly focused on machine learning (ML) models for early disease prediction, yet practical frameworks for integrating these models into clinical workflows remain limited. BIAlert is a microservices-based framework designed to operate as a real-time early-warning system for ML-driven disease prediction in hospitalised patients. It can be deployed remotely on physical or virtual servers and is composed of coupled microservices that communicate through Apache Kafka queues, using HL7 FHIR resources as the message format. The system comprises four core components: (1) the Connector, which ingests raw hospital data and converts it into standardised healthcare formats; (2) the Writer, which stores FHIR-formatted data in an internal database and triggers the prediction pipeline; (3) the Predictor, which hosts ML models and generates patient-specific alerts; and (4) the Model Evaluator, which supports prospective monitoring of model performance. Alerts are displayed through the BIAlert user interface and can also be integrated directly into the electronic health record (EHR). BIAlert is currently deployed and operating in real-time clinical settings in two hospitals, demonstrating its feasibility as a scalable and interoperable solution for ML-based clinical decision support.
The ICU pharmacist’s contribution to antimicrobial optimization through routine pharmacist interventions
(Revista Española de Quimioterapia, 2026-07-08) Sánchez-Ocaña, Natalia; Pérez-de-Amezaga-Tomás, Luis; Giglio, Andres; Borges, Marcio
Background: Antimicrobials are among the medication groups most frequently involved in medication errors and adverse drug events in the Intensive Care Unit (ICU). Despite growing evidence supporting the role of Critical Care Pharmacists (CCPs) in antimicrobial stewardship, their integration into ICU teams remains inconsistent across European healthcare systems. Methods: A prospective observational study was conducted over five months in an 18-bed medical-surgical ICU at a tertiary-level hospital in Spain. All admitted patients were included. A specialist pharmacist reviewed daily antimicrobial prescriptions through the electronic prescribing system. Pharmaceutical interventions (PIs) were classified as proactive or reactive and categorised by intervention type according to a predefined taxonomy. A descriptive analysis was performed. Results: A total of 331 PIs were recorded, of which 150 (45.31%) corresponded to antimicrobial therapy, representing the most frequently involved medication group. This figure corresponds to a mean of 1.50 antimicrobial-related PIs per working day. Of these, 115 (76.67%) were proactive. The most frequent intervention type was dose adjustment for overdosing or excessive duration (47.33%), followed by dose adjustment for underdosing or insufficient duration (18.00%), therapeutic drug monitoring recommendations (10.67%), and drug information to clinical staff (6.66%). Conclusions: CCPs identify a substantial number of antimicrobial-related drug problems in the ICU through routine prospective review. The coexistence of overdosing and underdosing interventions reflects the pharmacokinetic complexity of this population. These findings support the formal integration of CCPs into ICU antimicrobial stewardship activities.
Activity and Outcomes of a Multidisciplinary Sepsis Unit: Fifty Thousand Consultations over Thirteen Years
(MDPI, 0030-07-26) Borges-Sa, Marcio; Martin-Martinez, Elena; Aranda, Maria; Socias, Antonia; Tejada, Sofia; del Castillo, Alberto; Garau, Margarita; Pérez de Amezaga, Luis; Mena, Joana; Giglio, Andres
Background. Sepsis is a leading, time-dependent cause of in-hospital death, and guidelines now prioritize organized care such as code-sepsis protocols. Yet little is known about the long-term activity, organization and outcomes of permanent, hospital-scale programs. We characterized the activity of a hospital-wide multidisciplinary sepsis unit (MSU) over thirteen years and evaluated mortality trends. Methods. Retrospective cohort study using the registry of a hospital-wide MSU (2011–2023). The analysis unit was the sepsis event. Activity, referral pathways, interventions, follow-up and mortality were analyzed; temporal trends used multivariable logistic regression and standardized mortality ratios (SMR). Results. The unit attended 10,874 patients across 15,723 events and 50,925 consultations (median age 67; 59.3% men), referred mainly through the sepsis code (45.0%) and, increasingly, proactive early-warning detection (15.2%). An antibiotic change was recommended in 57.2% of events, and 89.8% of all suggested changes were implemented. Follow-up was sustained (median 3 visits; 61.8%). In-hospital mortality was 7.6%, and 11.8% in protocol-confirmed sepsis. Crude mortality did not fall, but severity rose (organ dysfunctions 1.67 to 2.72; septic shock 8 to 13%; both p < 0.001) with stable age; after adjustment the calendar-year effect disappeared (adjusted OR 1.00/year, p = 0.70) and the SMR stayed near 1.0, including pandemic years. Age, ICU admission (OR 2.65) and organ-dysfunction count (OR 1.37) independently predicted death. Conclusions. Over thirteen years, this hospital-wide MSU delivered large-scale, multi-channel, longitudinal care to an increasingly severe population while maintaining stable risk-adjusted mortality, supporting the long-term feasibility of a model integrating early detection, multidisciplinary decision-making, antimicrobial stewardship and follow-up.
International multidisciplinary consensus statement on sepsis code guidelines: A Delphi approach
(John Wiley & Sons Ltd, 0004-08-26) Borges-Sa, Marcio; Giglio, Andrés; Martin-Loeches, Ignacio; Nates, Joseph; González del Castillo, Josemaría; Cárdenas, Yenny; Mergulhao, P.; Candel, F. J.; Zaragoza, R.; Larrosa-Escartin, M. N.; Vidal-Cortés, P.; Maseda, E.; Reina, R.; Paiva, J. A.; del Pozo, J. L.; Villegas, M. V.; Salavert, M.; Soriano, C.; Hidalgo, J.; Machuca, I.; Gonçalves-Pereira, J.; Manuel-Vázquez, A.; Lisboa, T.; Pichardo-Viñas, M.; Barberán, J.; Esparza, G.; Castillo-Abrego, G.; Estella, A.; Ortega, K.; Matos, A.; Raimondi, N.; Ferrer, R.; Sanchez, J. R.; Huelmo, I.; Gorordo-Delsol, L. A.; Campozano, V.; Soriano, A.; Perez, J.; Rodriguez, A.
Background. Sepsis remains a major global health challenge. International guidelines exist, but their implementation is inconsistent, and supporting evidence largely comes from high-income settings. The objective of this study was to generate international, multidisciplinary expert consensus on controversial aspects of sepsis management within the framework of sepsis code programs. Methods. A multinational modified Delphi study was conducted with 164 experts from 22 countries, 12 specialties, and 105 scientific societies. Seven domains were evaluated: early diagnosis, biomarkers, diagnostic microbiology, hemodynamic monitoring, source control, antimicrobial therapy, and hemodynamic management. Consensus was defined as ≥70% agreement across three iterative rounds using Likert scales (Rounds 1–2) and binary format (Round 3). Results. Consensus was achieved for 40 statements. Strong endorsement (82%–95%) was reached for structured hospital sepsis programs, NEWS-2 as the preferred early recognition tool, biomarker use (notably procalcitonin) to complement clinical assessment, urgent source control within 6 h independent of hemodynamic status, rapid molecular diagnostics integrated with antimicrobial stewardship, and norepinephrine as first-line vasopressor therapy. Experts also supported pharmacokinetic- and pharmacodynamic-guided antibiotic dosing, prolonged infusion of time-dependent agents, and dynamic rather than fixed fluid strategies. No consensus was reached on routine reliance on Sepsis-2, Sepsis-3, or qSOFA; high mean arterial pressure targets; or universal combination antimicrobial therapy. Conclusions. These results provide multidisciplinary guidance for sepsis management, with emphasis on rapid recognition, targeted antimicrobial therapy, timely source control, and hemodynamic management guided by patient physiology. The recommendations are applicable to high- and middle-income healthcare systems.
Preoperative dynamic anterior tibial translation is not predictive of graft rupture after anterior cruciate ligament reconstruction
(John Wiley & Sons Inc., 2026) Pineda, Tomás; Mazy, David; Cance, Nicolas; Angelelli, Lucia; Dan, Michael James; Dejour, David Henri
Purpose: This study aimed to determine whether higher preoperative dynamic anterior tibial translation (DATT) using laximetry is a risk factor for graft rupture after anterior cruciate ligament reconstruction (ACLR). Methods: This retrospective study included all patients who underwent primary ACLR with hamstring autograft between January 2014 and December 2017. Demographic data, absolute DATT on the injured side and ΔDATT (side‐to‐side difference), posterior tibial slope (PTS), static anterior tibial translation (SATT), concomitant lateral extra‐articular tenodesis (LET) and meniscal tears were collected. Subgroup analysis was performed using a ΔDATT threshold of 6 mm. Univariate and multivariable logistic regression analyses were conducted to identify independent risk factors for ACL graft rupture. Results: Among the 680 patients included with a minimum follow‐up of 6 years, 41 (6%) experienced graft rupture at a mean of 45 ± 30 months postoperatively. The median DATT on the injured side was 9 mm [inter- quartile range, IQR, 5], and the median ΔDATT was 6 mm [IQR, 4]. Graft rupture occurred in 5.8% for patients with ΔDATT < 6 mm and in 6.3% for patients with ΔDATT ≥ 6 mm (p = 0.787). Patients with ΔDATT ≥ 6 mm demonstrated a higher prevalence of medial meniscal tears (31% vs. 24%, p = 0.026). Independent risk factors for graft rupture included PTS ≥ 12° (odds ratio [OR] 3.1; 95% confidence interval [CI], 1.6–6.3; p < 0.001) and SATT ≥ 5 mm (OR 2.6; 95% CI, 1.2–5.5; p = 0.027), whereas neither ΔDATT nor absolute DATT was significantly associated with graft rupture. Conclusion: Preoperative DATT is not predictive of graft rupture following ACLR using hamstring autograft. PTS and SATT remain stronger predictors and should be prioritised for preoperative risk stratification.
Anterior tibial translation versus rotational instability in ACL reconstruction: Defining the problem before choosing the procedure
(John Wiley & Sons Inc., 2026) Pineda, Tomás; David H; Musahl, Volker; Seil, Romain; Zaffagnini, Stefano; Ollivier, Matthieu
The expanding use of lateral extra‐articular procedures (LEAPs) and tibial deflexion osteotomy (TDO)—also referred to as slope‐reducing anterior closing wedge high tibial osteotomy—in anterior cruciate ligament (ACL) reconstruction reflects meaningful progress in our understanding of mechanisms of graft failure. However, as their use expands, an important distinction must be maintained: they do not address the same problem.
Confirmation bias in orthopaedic surgery: the challenge of the information overload era
(Elsevier, 2026) Pineda, Tomás; Saffarini, Mo; Karlsson, Jon; Musahl, Volker; Ayeni, Olufemi R.
Modern orthopaedic practice takes place in a context of information abundance. Clinical trials, national registries, systematic reviews, and meta-analyses are published constantly, producing more evidence than any clinician can follow. Over the past decade, the number of publications in high-impact orthopaedic journals has grown steadily, with post-pandemic years showing a particularly steep increase. One might expect that more evidence leads to better and more objective decisions. However, having access to information does not always guarantee that new studies are interpreted without bias
Pilgrimage to sacrifice: Mechanisms, causes, and time of death of the Western Andean Capacocha of the Southern Tawantinsuyu
(American Association for the Advancement of Science (AAAS), 2026-07-15) Silva-Pinto, Verónica; Sepúlveda, Marcela; Gayo, Eugenia M; Mendez-Quiros, Pablo; Castro, Mario; Menéndez, Lumila Paula; Rojas-Costa, Gonzalo M; Cerón, María L; Wilson, Andrew S; Catalán, Verónica; Silva, Claudio; Stecher, Ximena; Soffia, Pablo; Salazar-García, Domingo C
Capacocha was a key Inca state rite that intertwined pilgrimage, sacrifice, and imperial incorporation across the Andes. We present a multianalytical investigation into two Capacocha cases from the western slope of the Andes: Cerro Esmeralda, located in the coastal Atacama Desert of northern Chile, and Cerro El Plomo, in the high mountains of central Chile. Stable isotope analysis reveals commensality practices during the pilgrimage, integrating local communities into the imperial order. Furthermore, computed tomography, dermatoscopy, and skin histology provide new evidence regarding the causes and mechanisms of death, identifying violent acts associated with sacrifice. Last, we present a pair of radiocarbon dates to discuss the chronology of both Capacocha contexts. In sum, these practices specify the materialization of Inca statecraft and contribute to characterizing the complexity and diversity of Capacocha ritual as an extension of the Inca biopolitical conquest.
Automated and Interpretable Detection of Hippocampal Sclerosis in Temporal Lobe Epilepsy: AID-HS
(Wiley Periodicals LLC, 2024-11-14) Ripart, Mathilde; DeKraker, Jordan; Eriksson, Maria H; Piper, Rory J; Gopinath, Siby; Parasuram, Harilal; Mo, Jiajie; Likeman, Marcus; Ciobotaru, Georgian; Sequeiros-Peggs, Philip; Hamandi, Khalid; Xie, Hua; Cohen, Nathan T; Su, Ting-Yu; Kochi, Ryuzaburo; Wang, Irene; Rojas-Costa, Gonzalo M; Gálvez, Marcelo; Parodi, Constanza; Riva, Antonella; D'Arco, Felipe; Mankad, Kshitij; Clark, Chris A; Carbó, Adrián Valls; Toledano, Rafael; Taylor, Peter; Napolitano, Antonio; Rossi-Espagnet, Maria Camilla; Willard, Anna; Sinclair, Benjamin; Pepper, Joshua; Seri, Stefano; Devinsky, Orrin; Pardoe, Heath R; Winston, Gavin P; Duncan, John S; Yasuda, Clarissa L; Scárdua-Silva, Lucas; Walger, Lennart; Rüber, Theodor; Khan, Aali R; Baldeweg, Torsten; Adler, Sophie; Wagstyl, Konrad; MELD HS study group
Objective: Hippocampal sclerosis (HS), the most common pathology associated with temporal lobe epilepsy (TLE), is not always visible on magnetic resonance imaging (MRI), causing surgical delays and reduced postsurgical seizure-freedom. We developed an open-source software to characterize and localize HS to aid the presurgical evaluation of children and adults with suspected TLE. Methods: We included a multicenter cohort of 365 participants (154 HS; 90 disease controls; 121 healthy controls). HippUnfold was used to extract morphological surface-based features and volumes of the hippocampus from T1-weighted MRI scans. We characterized pathological hippocampi in patients by comparing them to normative growth charts and analyzing within-subject feature asymmetries. Feature asymmetry scores were used to train a logistic regression classifier to detect and lateralize HS. The classifier was validated on an independent multicenter cohort of 275 patients with HS and 161 healthy and disease controls. Results: HS was characterized by decreased volume, thickness, and gyrification alongside increased mean and intrinsic curvature. The classifier detected 90.1% of unilateral HS patients and lateralized lesions in 97.4%. In patients with MRI-negative histopathologically-confirmed HS, the classifier detected 79.2% (19/24) and lateralized 91.7% (22/24). The model achieved similar performances on the independent cohort, demonstrating its ability to generalize to new data. Individual patient reports contextualize a patient's hippocampal features in relation to normative growth trajectories, visualise feature asymmetries, and report classifier predictions. Interpretation: Automated and Interpretable Detection of Hippocampal Sclerosis (AID-HS) is an open-source pipeline for detecting and lateralizing HS and outputting clinically-relevant reports.
Neurocognitive correlates of semantic memory navigation in Parkinson’s disease
(Nature Portfolio, 2024-01-09) Toro-Hernández, Felipe Diego; Migeot, Joaquín; Marchant, Nicolás; Olivares, Daniela; Ferrante, Franco; González-Gómez, Raúl; González Campo, Cecilia; Fittipaldi, Sol; Rojas-Costa, Gonzalo M; Moguilner, Sebastian; Slachevsky, Andrea; Chaná Cuevas, Pedro; Ibáñez, Agustín; Chaigneau, Sergio; García, Adolfo M
Cognitive studies on Parkinson’s disease (PD) reveal abnormal semantic processing. Most research, however, fails to indicate which conceptual properties are most affected and capture patients’ neurocognitive profiles. Here, we asked persons with PD, healthy controls, and individuals with behavioral variant frontotemporal dementia (bvFTD, as a disease control group) to read concepts (e.g., ‘sun’) and list their features (e.g., hot). Responses were analyzed in terms of ten word properties (including concreteness, imageability, and semantic variability), used for group-level comparisons, subject-level classification, and brain-behavior correlations. PD (but not bvFTD) patients produced more concrete and imageable words than controls, both patterns being associated with overall cognitive status. PD and bvFTD patients showed reduced semantic variability, an anomaly which predicted semantic inhibition outcomes. Word-property patterns robustly classified PD (but not bvFTD) patients and correlated with disease-specific hypoconnectivity along the sensorimotor and salience networks. Fine-grained semantic assessments, then, can reveal distinct neurocognitive signatures of PD.
Intracranial volume variation in Chinchorro mummies: a comparative study with prehispanic farmers and contemporary Chilean populations
(Nature, 0002-11-25) Rojas-Costa, Gonzalo M; Silva-Pinto, Verónica; Valenzuela, Yanis; de la Iglesia-Vayá, María; Molina-Mateo, José; Salazar-García, Domingo C; Valdes-Sosa, Pedro A; Gálvez, Marcelo
The Chinchorro culture inhabited the coastal Atacama Desert between 7,500 and 3,500 years BP, maintaining a hunter-gatherer-fisher lifestyle and practicing complex mortuary rituals. With the later adoption of agriculture, shifts in subsistence strategies and burial customs emerged. This study investigated long-term biological variation across three diachronic populations from northern Chile: Archaic-period Chinchorro individuals, pre-Hispanic agriculturalists, and contemporary Chileans. Using computed tomography (CT) and 3D reconstruction techniques, we analyzed intracranial volume (ICV) and estimated stature to assess morphological differences. The results show that both ICV and stature are significantly greater in the present-day Chilean population than in the pre-Hispanic groups. The average ICV was 1,321.26 cc in Chinchorro individuals, 1,336.57 cc in pre-Hispanic agriculturalists, and 1,481.22 cc in modern Chileans—representing a 12.05% increase between the earliest and most recent groups. Males and females exhibited 14.62% and 10.81% increases, respectively. Sexual dimorphism in the ICV was lower among agriculturalists (8.97%) than among Chinchorro (10.84%) and modern individuals (13.68%). Notably, the transition to agriculture did not result in significant changes in either ICV or stature. Instead, the marked increases observed in modern individuals have been associated primarily with improved nutrition, healthcare, and overall living conditions since the 20th century.
Vitamin D Supplementation, Total Testosterone, and Androgen Bioavailability Markers in Adult Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
(MPDI, 2026) Paez-Allendes, Loreto
Background: Vitamin D has traditionally been recognized for its role in calcium homeostasis and skeletal health, but vitamin D receptor expression and vitamin D-metabolizing enzymes have also been identified in extra-skeletal tissues, including components of the male reproductive tract. Observational evidence has suggested associations between vitamin D status and androgen-related markers; however, whether vitamin D supplementation has a measurable effect on androgen bioavailability remains uncertain. Objective: This systematic review and meta-analysis evaluated the effects of vitamin D supplementation on total testosterone (TT) and androgen bioavailability markers in adult men, including sex hormone-binding globulin (SHBG), free androgen index (FAI), calculated free testosterone (calculated FT), and bioactive testosterone (BAT) where methodologically compatible. Methods: The review was registered in PROSPERO (CRD420261365005) and conducted according to PRISMA 2020 and Cochrane methodological guidance. Searches were conducted from database inception to April 2026 in PubMed, Web of Science, Scopus, ClinicalTrials.gov, and the WHO ICTRP. Embase was initially planned but was not searched because institutional access was unavailable; this amendment was made before screening, extraction, risk-of-bias assessment, and synthesis. Records were deduplicated in Zotero, screened in a structured matrix, and converted from report-level records into independent comparison-level datasets where appropriate. Meta-analyses used random-effects REML models with Hartung–Knapp adjustment. Results: The official search set comprised 2854 records, of which 703 duplicates were removed, leaving 2151 records for title and abstract screening. The full-text screening file was reconciled to 162 PRISMA-countable reports/records: 135 reports were assessed, 27 reports could not be assessed because the full text was unavailable or had not been obtained for review, and 27 reports/studies were retained for qualitative synthesis. Eighteen reports were considered candidate sources for quantitative synthesis and were operationalized into 21 comparison-level records. The primary TT model included 11 comparisons and showed no clear effect of vitamin D supplementation on final TT (MD 0.47 nmol/L, 95% CI −0.50 to 1.44; $I^2$ = 24.1%). No clear effects were observed for SHBG (MD 0.27 nmol/L, 95% CI −2.14 to 2.68), FAI (MD −0.37, 95% CI −4.28 to 3.55), calculated FT sensitivity evidence (MD −0.0096 nmol/L, 95% CI −0.0525 to 0.0332), or BAT exploratory evidence (MD −0.47 nmol/L, 95% CI −1.77 to 0.83). GRADE certainty was low for TT, SHBG, and FAI, and very low for calculated FT and BAT. Conclusions: Current randomized evidence does not demonstrate a statistically clear or reproducible effect of vitamin D supplementation on total testosterone or androgen bioavailability markers in adult men. GRADE certainty was low for total testosterone, SHBG, and FAI, and very low for calculated free testosterone and bioactive testosterone. Because directly measured and calculated free testosterone are not analytically equivalent, free testosterone was not pooled as a primary outcome; method-compatible calculated FT was handled as sensitivity evidence and BAT as exploratory evidence.
Occipitalization of the atlas: prevalence, functional and anatomical considerations. A systematic review and meta-analysis
(Elsevier, 2026) Bruna-Mejias, Alejandro
Background: Occipitalization of the atlas, defined as a congenital fusion between the first cervical vertebra (C1) and the occipital bone, is an uncommon anatomical variant of the craniovertebral junction. Reported prevalence in the general population varies widely, and the condition is often identified incidentally during imaging or anatomical assessment. Objective: To synthesize available evidence on the prevalence of atlas occipitalization and to describe its anatomical characteristics across different populations and study designs. Methods: A comprehensive literature search was conducted in MEDLINE, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS from inception to January 2025. Study selection and data extraction were performed independently by four reviewers. Methodological quality was assessed using the Anatomical Quality Assessment (AQUA) tool. A random-effects meta-analysis was applied to estimate pooled prevalence values and explore predefined subgroups. Results: Twenty-five studies met the inclusion criteria for qualitative synthesis, of which eleven were included in the meta-analysis, encompassing a total of 4219 subjects. The pooled prevalence of atlas occipitalization was 0.64% (95% confidence interval: 0.00–1.00%). Variability in prevalence estimates was observed across populations and assessment methods. Conclusion: Atlas occipitalization is a rare congenital anatomical variant of the craniovertebral junction. Although often asymptomatic, its identification is anatomically relevant due to potential associations with other craniovertebral anomalies. Awareness of this variant is important for accurate anatomical interpretation and for planning procedures involving the craniovertebral junction.
GLP-1RA- and Incretin-Based Therapies Within Lifestyle Interventions for Adults with Overweight or Obesity: A Systematic Review and Meta-Analysis
(MPDI, 2026) Bruna-Mejias, Alejandro
Background/Objectives: Glucagon-like peptide-1 receptor agonist (GLP-1RA)- and incretin-based therapies are now central to obesity management. Their clinical value, however, should be interpreted beyond total weight loss, because changes in fat mass, lean mass, physical function, and cardiometabolic risk may depend on the accompanying dietary, behavioral, and exercise co-interventions. This systematic review and meta-analysis evaluated GLP-1RA- and incretin-based therapies delivered within lifestyle interventions in adults with overweight or obesity. Methods: The protocol was registered in PROSPERO (CRD420261360837). PubMed/MEDLINE, Web of Science, Scopus, CINAHL, SPORTDiscus, and CENTRAL were searched from inception to the final search dates. Records were deduplicated in Zotero. Risk of bias was assessed using the Cochrane RoB 2 tool. Random-effects meta-analyses were estimated using restricted maximum likelihood with Hartung–Knapp adjustment when pooling was appropriate. Results: Across all database sources, 1651 records were identified. After removing 113 duplicate records and 212 records with an ineligible publication type before screening, 1326 records were screened. Seventy-seven reports were sought for retrieval, five were not retrieved, 72 were assessed at full text, and 48 reports corresponding to 35 independent parent trials or trial clusters were retained for qualitative synthesis. The primary kilogram-scale meta-analysis included eight independent comparisons and showed greater body-weight reduction with GLP-1RA/incretin-based therapy delivered within a lifestyle background than with placebo/control (mean difference [MD] −10.08 kg, 95% confidence interval [CI] −12.76 to −7.39; 95% prediction interval [PI] −17.86 to −2.29; $I^2 = 95.6\%$). Percentage body-weight change was analyzed separately across 11 independent comparisons and also favored GLP-1RA/incretin-based therapy (MD −9.53 percentage points, 95% CI −11.92 to −7.14; 95% PI −17.58 to −1.48; $I^2 = 95.4\%$). Conclusions: GLP-1RA- and incretin-based therapies delivered within lifestyle interventions are associated with clinically meaningful reductions in body weight in adults with overweight or obesity. Absolute and relative body-weight change metrics should remain analytically separate. The magnitude of benefit varies across trial contexts, and certainty remains limited by risk-of-bias concerns and considerable heterogeneity. Future trials should standardize the reporting of lifestyle co-interventions, body composition, adherence, physical-function outcomes, and safety monitoring.
Effectiveness of arthrocentesis versus other therapeutic modalities in patients with temporomandibular disorders. Systematic review and meta-analysis
(Elsevier, 2026-12) Valenzuela-Fuenzalida, Juan José
Background: Temporomandibular disorders (TMD) are a heterogeneous group of conditions frequently associated with pain and functional impairment. Arthrocentesis has been proposed as a minimally invasive therapeutic option; however, its comparative effectiveness versus other treatments remains uncertain. Objective: To evaluate the effectiveness of arthrocentesis compared with other therapeutic modalities in patients with TMD, focusing on pain relief and mandibular functional outcomes. Methods: A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines. Randomized controlled trials comparing arthrocentesis with other therapeutic interventions for TMD were included. Primary outcomes were pain intensity assessed by visual analogue scale (VAS) and mandibular functional outcomes, including maximum mouth opening, maximum incisal opening, masticatory efficiency, mandibular movements, and overall joint mobility. Results: Thirty-two randomized controlled trials were included in the quantitative synthesis. No statistically significant difference in pain reduction was observed between arthrocentesis and comparator interventions, with very high heterogeneity. Masticatory efficiency showed a small statistically significant improvement favoring arthrocentesis, based on very low-certainty evidence. Overall, the certainty of evidence ranged from low to very low across outcomes. Conclusions: Arthrocentesis may provide modest symptomatic improvement in selected patients with TMD; however, it does not demonstrate superiority over alternative therapeutic modalities for most functional outcomes. Further well-designed randomized controlled trials with standardized diagnostic criteria, clearly defined comparators, and longer follow-up are required to better define the role of arthrocentesis in the management of temporomandibular disorders.

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