Chronic inflammation driven by microbial translocation is implicated in the increased risk of skeletal-related events (SREs) among people with HIV (PWH) on antiretroviral therapy (ART). We aimed to assess the association between plasma biomarkers of gut barrier dysfunction and incident SREs in PWH on suppressive ART, and whether the host's baseline immune status modifies this association. We employed a nested case-cohort design within the Spanish CoRIS cohort. We quantified baseline plasma markers (zonulin-1, LPS, LBP, flagellin) in 65 incident SRE cases and a randomly selected subcohort of 263 PWH. Borgan II-weighted Cox regression models were used to test for associations and interactions between log2-transformed biomarkers and baseline CD4+ T-cell counts (<500 vs. ≥500 cells/mm³). In the overall population, zonulin-1 was not significantly associated with SRE risk (aHR 1.54; 95% CI 0.90-2.62). However, we detected a significant interaction between zonulin-1 and immune status (interaction p < 0.001). In participants with suboptimal immune recovery (CD4 + <500 cells/mm³), higher zonulin-1 levels were associated with incident SREs (aHR 5.14; 95% CI 2.25-11.77; interaction q < 0.001). Conversely, this association was absent in participants with preserved immune status (CD4 + ≥500 cells/mm³; aHR 0.98; 95% CI 0.58-1.67). LPS, LBP, and flagellin showed no association with SREs regardless of immune status. Gut barrier dysfunction, measured by plasma zonulin-1, is associated with a higher risk of SREs; however, this association is restricted to PWH with incomplete immune reconstitution. These findings support a "two-hit" model in which immune competence and aging modulate the skeletal consequences of gut leakage.
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Clinically silent MRI lesions occur frequently in people with relapsing-remitting multiple sclerosis (RRMS) despite disease modifying therapy (DMT). Guidelines only routinely recommend DMT escalation after multiple silent lesions, and adherence is variable. We explored outcomes and the effect of treatment escalation following single and multiple on-treatment silent lesions. This cohort study and emulated target trial used MSBase registry data from 99 clinics in 26 countries between 2007 and 2025. Clinically stable participants receiving any DMT for RRMS with silent lesions versus without silent lesions were compared. Among participants with silent lesions while taking platform or moderate-efficacy DMTs, outcomes following treatment escalation within 6 months versus no treatment escalation (unless a post-MRI clinical event occurred) were compared. The primary outcome was an MS relapse, and the secondary outcome was 6-month confirmed disability worsening. A total of 10,232 participants met inclusion criteria (71.7% female, mean age 41 [SD 11]). The 2-year cumulative incidence of relapse was 27.8% (95% CI: 25.7%-29.9%) in participants with silent lesions versus 14.3% (95% CI: 13.5%-15.2%) without (adjusted hazard ratio [aHR] 1.76 [95% CI: 1.57-1.97]). The 2-year cumulative incidence of disability worsening was 13.8% (95% CI: 12.2%-15.5%) in participants with silent lesions versus 11.4% (95% CI: 10.7%-12.2%) without (aHR 1.38 [95% CI: 1.18-1.62]). Rates of relapse and disability worsening were higher following single and multiple silent lesions versus no silent lesions. The emulated trial included 2,264 participants with ≥1 silent lesion on platform or moderate efficacy DMTs, 286 of whom escalated DMT within 6 months following silent lesions. The 4-year cumulative incidence of relapse was lower following treatment escalation (16.8% [95% CI: 12.4%-23.4%]) versus continuation (38.9% [95% CI: 35.8%-42.1%]), aHR 0.34 (95% CI: 0.23-0.47), with similar aHRs following single and multiple silent lesions. The 4-year cumulative incidence of disability worsening was similar following treatment escalation (16.0% [95% CI: 10.8%-22.2%]) versus continuation (17.7% [95% CI: 15.3%-20.1%]), aHR 0.89 (95% CI: 0.56-1.33). People with RRMS with single or multiple on-treatment silent MRI lesions have higher subsequent risks of relapse and disability worsening than people without silent lesions. DMT escalation mitigates the relapse risk, though disability worsening continues at a similar rate over 4 years. Contrary to guidelines, DMT escalation should be considered after single or multiple silent lesions.
Endoscopic sleeve gastroplasty (ESG) is increasingly combined with anti-obesity medications (AOMs), but the incremental benefit of combination therapy over ESG alone remains uncertain METHODS: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251179747). Comparative studies evaluating ESG plus AOMs versus ESG alone in adults with overweight or obesity were included. Random-effects models were used for pooled analyses RESULTS: Ten studies comprising 578 participants met inclusion criteria. At approximately seven months, combination therapy showed a modest, non-significant advantage in total weight loss (mean difference +1.9% TWL; 95% CI - 1.22 to 4.99), with substantial heterogeneity (I2 ≈ 80-90%). For metabolic outcomes, the pooled mean difference in HbA1c change was minimal (- 0.04%; 95% CI - 0.37 to 0.28; p = 0.79), and individual studies reported inconsistent effects CONCLUSIONS: ESG combined with AOMs may enhance early weight loss in selected settings; however, current evidence does not support consistent long-term superiority over ESG alone for weight or glycemic outcomes. Although the available data remain limited and heterogeneous, concomitant therapy may be considered in selected patients rather than as a universally superior strategy. Multicenter randomized trials with standardized pharmacotherapy protocols, longer follow-up, and improved patient stratification are needed to clarify durability, cost-effectiveness, and the subgroups most likely to benefit.
Acromegalic heart disease (AHD) is a common complication of acromegaly; however, evidence specifically focused on women in Latin America remains limited. To characterize cardiomyopathy in women with acromegaly and identify clinical factors associated with its presence. We conducted a secondary analysis of the multicenter RAPACO-Heart registry in Colombia. Women aged ≥18 years with confirmed acromegaly and available echocardiographic evaluation were included. Clinical, anthropometric, biochemical, and echocardiographic data were analyzed. Cardiomyopathy was defined by echocardiographic abnormalities consistent with AHD. Multivariable logistic regression was used to identify factors independently associated with cardiomyopathy. A total of 116 women were included, of whom 34 (29.3%) had cardiomyopathy. Women with cardiomyopathy were older and had longer disease duration. Hypertension, arrhythmias, and carpal tunnel syndrome were more frequent in this group. In multivariable analysis, age (adjusted OR 1.07 per year; 95% CI 1.03-1.12; p = 0.001), hypertension (adjusted OR 3.9; 95% CI 1.4-11.1; p = 0.009), arrhythmias (adjusted OR 2.8; 95% CI 1.1-7.4; p = 0.03), and carpal tunnel syndrome (adjusted OR 2.6; 95% CI 1.1-6.5; p = 0.04) were independently associated with cardiomyopathy. Cardiomyopathy was present in nearly one-third of women with acromegaly and was associated with older age and a higher burden of cardiovascular comorbidities. These findings highlight an underrecognized cardiovascular burden and support targeted cardiovascular assessment in this population.
BackgroundQuality feedback is essential to surgical learning. Simulation training accelerates skill acquisition, and video-based assessment (VBA) offers proven educational benefits. However, evidence of their combined effect in real surgical cases is limited. We conducted a multi-center intervention integrating VBA and remote-asynchronous feedback for real laparoscopic cholecystectomies (LC) and the completion of an Advanced Laparoscopy Course (ALC). Users experience, and an analysis of objective performance outcomes was performed.MethodsSeven general-surgery residency programs in Chile participated (2022-2025). Residents uploaded LC videos to the LAPPCLINIC platform and were randomized to receive either assessment-only or assessment + asynchronous expert feedback. Perceptions were evaluated through an online survey and focus group. Videos were assessed using OSATS and OPRS. ALC status was registered. The primary outcome was achievement of OSATS ≥20. Mixed-effects logistic regression adjusted for ALC status, feedback arm, cumulative case number, and surgical difficulty.ResultsOf 142 invited residents, 51 (35.9%) participated, uploading 455 videos (436 eligible). Twenty-eight residents completed the survey: 96% desired additional feedback beyond the OR. Platform feedback was rated higher than OR feedback (6.2 vs 5.25/7, P = .0065). ALC completion was independently associated with higher odds of OSATS ≥20 (OR 4.69; 95% CI 1.53-14.4; P = .0069). Feedback allocation was not significant (OR 0.40; 95% CI 0.15-1.08; P = .070).ConclusionsResidents rated asynchronous feedback higher than conventional OR feedback. Completion of the ALC correlated with objectively higher surgical performance, supporting the integration of structured simulation and video-based coaching within residency curricula.
Timely transfer of patients with suspected LVO remains critical in acute stroke systems. Artificial intelligence (AI)-based imaging tools are increasingly implemented to support triage in non-thrombectomy centres. We assessed whether integrating an AI algorithm within established tele-stroke centres reduces time to transfer decision. We conducted a prospective, multicentre, quasi-experimental study comparing consecutive cohorts in 2 tele-stroke centres referring to a single comprehensive stroke centre, before and after implementation of the Methinks Stroke Suite, an AI algorithm for LVO detection on non-contrast CT (NCCT) and CTA. Consecutive transferred patients with suspected acute ischaemic stroke were included. Remote vascular neurologists retained responsibility for final transfer decisions. Each phase spanned approximately 15 months. The primary outcome was time from arrival at the local centre to emergency medical services activation. Secondary outcomes included workflow intervals, imaging utilisation and algorithm performance. We included 265 patients (136 in the post-implementation cohort; 129 in the pre-implementation cohort). Adjusted median time from arrival to transfer request did not differ (median difference - 2.40 min; 95% CI, -6.16 to 4.48). Post-implementation, time from imaging to transfer request (-7.16 min; 95% CI, -13.02 to -1.85) and arrival to groin puncture (-31.28 min; 95% CI, -60.89 to -13.74) decreased. Computed tomography angiography acquisition at referring centres increased (28%-81%), reducing repeat imaging at the comprehensive centre (79%-42%). Non-contrast CT-based AI prediction yielded a positive predictive value of 66% for endovascular treatment. Artificial intelligence implementation was not associated with a shorter time to transfer decision. Fewer redundant imaging examinations were associated with a shorter time to reperfusion.
Prematurity remains a major global health challenge and is a leading cause of neonatal morbidity and mortality worldwide. The risk of adverse outcomes is inversely associated with gestational age and birth weight. Although advances in neonatal intensive care have improved survival rates over recent decades, very-low-birth-weight (VLBW) preterm neonates continue to experience substantial morbidity and remain vulnerable to long-term complications. This study aimed to evaluate the morbidity and mortality of very-low-birth-weight preterm neonates (<1500 g) admitted to the Neonatal Intensive Care Unit (NICU) of the Hospital Regional de Alta Especialidad de Ciudad Victoria (HRAEV), Mexico. A retrospective observational cohort study was conducted through a review of medical records of VLBW preterm neonates admitted to the NICU between January 2019 and December 2023. Demographic, perinatal, clinical, and outcome-related data were collected and analyzed. A total of 58 VLBW preterm neonates were included. Mean gestational age was 29.8 ± 2.7 weeks, and mean birth weight was 1109 ± 238 g. The most common morbidities were respiratory distress syndrome (81.0%), apnea of prematurity (72.4%), hyperbilirubinemia (68.9%), pneumonia (34.5%), sepsis (32.7%), patent ductus arteriosus (25.8%), bronchopulmonary dysplasia (26.9% among infants who survived to 36 weeks' PMA), necrotizing enterocolitis (15.5%), and intraventricular hemorrhage (12.0%) and retinopathy of prematurity (8.6%). Overall mortality was 10.3%. VLBW preterm neonates remain at high risk for significant morbidity despite relatively favorable survival rates. Respiratory distress syndrome, apnea of prematurity, hyperbilirubinemia, and sepsis were the most frequent complications, whereas deaths occurred mainly in the context of severe respiratory and systemic complications, including neonatal asphyxia, pulmonary hypertension, sepsis, shock, and multiple organ failure. Survival outcomes should be interpreted cautiously because of differences in study populations, referral patterns, local viability practices, and study design across neonatal settings.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition that results from a severe inflammation caused by an exaggerated immune response. HLH may have a genetic cause affecting the proper function of cytotoxic immune cells or it canbe linked to other pathological settings including inborn errors of immunity, malignancies, autoinflammatory and autoimmune syndromes, metabolic diseases, or acquired immunodeficiencies. HLH due to a genetic error remains difficult to diagnose because anormal Natural Killer (NK) or cytotoxic T lymphocyte (CTL) function does not necessarily exclude a familial form of HLH affecting immune cells other than cytotoxic lymphocytes, or because patients with autoimmune or autoinflammatory syndromes can also fulfill the HLH criteria. In consequence, sensitive functional assays and assessment of the expression of proteins involved in lytic-granules exocytosis may be useful approaches for discriminating between familial forms of HLH from those where a genetic cause is not affecting cytotoxic cell function, or from acquired forms of HLH. By different approaches, including functional assays and biochemical studies, we were able to obtain molecular diagnostics for patients, while next-generation sequencing identified the disease-associated gene variants. Here we presented a multi-center experience in approaching and diagnosing patients with familial HLH. Our study included a cohort of 31 patients that fulfill the criteria of HLH. Genetic testing, led to identified variants in PRF1, UNC13D, STX11, STXBP2, RAB27A, LYST, AP3B1 and SH2D1A, confirming most of the initial molecular diagnoses. From allfound variants, 15 were novel and not previously reported in patients with HLH nor found in homozygous condition. Our results highlight the importance of taking into consideration molecular studies to increase the proportion of patients that obtain a molecular diagnosis, especially in countries where high-throughput genetic analyses are difficult to access or time-consuming.
Background and Aims: Pancreatic hyperenzymemia in inflammatory bowel disease (IBD) is an under-recognized and challenging condition, as elevated pancreatic enzymes may arise from heterogeneous mechanisms and do not necessarily reflect true pancreatic disorder. This multicenter study aimed to characterize the clinical spectrum, diagnostic work-up, and outcomes of hyperenzymemia in IBD. Methods: This retrospective multicenter study was conducted within the PANDORA network, including 34 international IBD centers. For the present analysis, only centers providing patient-level data on pancreatic hyperenzymemia were considered. Collected variables included demographic, clinical, biochemical, imaging, and therapeutic data. Cases were categorized into three predefined phenotypes: chronic asymptomatic pancreatic hyperenzymemia (CAPH), reclassified acute pancreatitis not meeting Atlanta criteria (recAP), and autoimmune pancreatitis (AIP). Results: A total of 148 IBD patients with elevated pancreatic enzymes were included (CAPH 54.7%, RecAP 35.1%, AIP 10.1%). Ulcerative colitis (UC) accounted for 56.8% of cases and Crohn's disease (CD) for 43.2%. Overall, 73.6% of patients were asymptomatic at the time of enzyme elevation. Marked hyperenzymemia (≥3× ULN) occurred in 22.3% of patients and was more frequent in RecAP than in CAPH or AIP (50.0%, 6.2%, and 13.3%, respectively). IBD was clinically active in 48.6% of patients, with higher rates in CD. Notably, the clinical meaning of hyperenzymemia differed across IBD phenotypes: in CD it was more often associated with active inflammation, whereas in UC it more frequently prompted advanced imaging and led to the identification of AIP. Imaging strategies differed significantly across phenotypes, and drug withdrawal was common in CAPH and RecAP but unnecessary in AIP. Only two rechallenges confirmed a drug-related mechanism. Conclusions: Pancreatic hyperenzymemia in IBD encompasses a spectrum of conditions with different implications. A phenotype-oriented diagnostic approach is essential to avoid misclassification and unnecessary treatment changes.
Prediabetic neuropathy refers to early dysfunction of peripheral and autonomic nerves and may be present in individuals with impaired glucose regulation before the diagnosis of type 2 diabetes. Epidemiological evidence suggests that a substantial proportion of individuals with prediabetes may show signs of neuropathic involvement, mainly affecting small sensory fibers and autonomic function. These changes are thought to arise from multiple interacting metabolic and vascular mechanisms, including oxidative stress, microvascular dysfunction, low-grade inflammation, and impaired insulin signaling. Despite this burden, pharmacological management remains limited and is mainly focused on preventing progression to type 2 diabetes rather than directly targeting early nerve dysfunction. Emerging approaches such as modulation of the renin angiotensin system, SGLT2 inhibition, mitochondrial-targeted antioxidants, and gene-based therapies are being investigated, although most evidence remains preclinical or early clinical. Their translation into routine practice is still limited by the lack of large randomized trials and ongoing underdiagnosis. Overall, current evidence suggests a potential role for earlier mechanism informed approaches that combine pharmacological and lifestyle strategies, although stronger clinical evidence is still needed.
Maternal mortality is a serious public health problem and reflects social, ethnic, racial, and regional inequalities in access to and quality of obstetric care. Despite advances in the surveillance and investigation of maternal deaths in Brazil, late maternal deaths (occurring between 43 days and 1 year after birth) are still underestimated and underexplored. Therefore, the objective of this study was to analyze the distribution and factors associated with maternal deaths and late maternal deaths in Brazil between 2010 and 2023. This was a population-based, retrospective cohort study with a quantitative approach, using secondary data from the Mortality Information System. All maternal deaths (Chapter XV of ICD-10) and late deaths recorded during the period were included. Sociodemographic, clinical, and administrative variables were analyzed. Statistical tests of association (chi-square, test of proportions, and 95% CI) were used, with a significance level of 5%. A total of 26,953 deaths were identified, of which 24,387 were maternal and 2566 were late deaths. Most deaths occurred among single, mixed-race women with 8 to 11 years of schooling, and residing in the Southeast region. Late deaths were more frequent in the South and among women aged 40 to 49. The main causes were direct obstetric conditions. A statistically significant association was observed between the type of death and sociodemographic variables. The results highlight structural inequalities in maternal mortality in Brazil and reinforce the importance of expanding postpartum surveillance beyond 42 days, with a focus on equity and continuity of care.
Cystic Echinococcosis (CE), caused by the larval stage of Echinococcus granulosus sensu lato, elicits a complex host immune response characterized by the formation of a fibrotic capsule known as the adventitial layer. While the cellular composition of this layer has been previously studied, the spatial distribution of T lymphocytes remains poorly defined, particularly in relation to cyst fertility, host species, organ localization, and co-infection with Fasciola hepatica. In this study, we evaluated the distribution of CD3⁺ T cells in the adventitial layer of hepatic and pulmonary CE cysts collected from naturally infected cattle and sheep. Using immunohistochemistry and image analysis, we quantified CD3 expression across the adventitial layer and within three defined sub-regions (proximal, intermediate, and distal to the laminated layer). Our results show that while total CD3⁺ T-cell abundance did not vary significantly according to cyst fertility or co-infection status, their distribution patterns within the adventitial layer did. In cattle, CD3⁺ T cells were uniformly distributed throughout the adventitial layer, whereas in sheep, T cells were predominantly localized to the distal third, near the organ parenchyma. This pattern was more pronounced in non-fertile cysts. Additionally, no significant alteration in CD3 distribution or abundance was observed in the presence of F. hepatica co-infection. These findings reveal a species-specific pattern of T-cell localization within the adventitial layer and suggest that immune cell positioning, rather than quantity, may play a role in local immune modulation and cyst outcome.
Antimicrobial resistance (AMR) is a rising public health issue that compromises human, animal and environmental health. This study assessed AMR in the swine production chain in Costa Rica using commensal Escherichia coli as an indicator microorganism. Sampling of feces, carcass and lymphoid tissue at exporting swine abattoirs yielded 269 presumed E. coli isolates identified by lactose-positive growth on MacConkey agar and indole production. A subset of isolates (n=40) was confirmed as E. coli by VITEK® 2 GN testing. Antimicrobial susceptibility testing against 18 antibiotics was performed using the antibiotic disk agar diffusion method in 242 recovered isolates, and resistance to all antimicrobial classes evaluated was detected. The highest resistance levels were observed for ampicillin, cefazolin and chloramphenicol, and notable resistance to quinolones, trimethoprim-sulfamethoxazole and β-lactam combination agents. Resistance to clinically-important drugs including ceftazidime, cefepime, aztreonam and imipenem was observed, as well as selected β-lactamase genes. Overall, 50 distinct AMR profiles were identified, and more than half of the isolates displayed multidrug-resistance. A subset of isolates (n=30) underwent uidA PCR and ERIC-PCR analysis, revealing evidence of fecal and cross-contamination as plausible routes for dissemination of resistant bacteria during slaughter. Antimicrobial susceptibility testing by VITEK®2 automated system and whole genome sequencing (WGS) of 27 isolates further characterized phenotype-genotype concordance, AMR determinants, virulence factors, serotypes and sequence types of public health relevance. These findings provide insight into current AMR trends in the Costa Rican swine production system and highlight the role of abattoir-level contamination in AMR transmission, supporting targeted interventions to mitigate the emergence and dissemination of AMR along the pork production chain.
Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and were long regarded as inert remnants of ancestral retroviral infections. Increasing evidence indicates that HERVs are active genomic elements capable of influencing transcriptional programs, modulating immune responses, and contributing to disease pathogenesis. Under physiological conditions, HERV expression is tightly controlled by epigenetic mechanisms; however, infections, chronic inflammation, aging, and diverse environmental stimuli can promote HERV reactivation. HERV-derived RNAs and proteins engage innate immune sensors and trigger antiviral-like responses through mechanisms of viral mimicry, leading to activation of type I interferon and other inflammatory pathways. HERV dysregulation has been associated with disease-relevant immune pathways. This review summarizes recent advances linking HERVs to autoimmune disease pathogenesis and discusses their potential translational relevance as biomarkers and therapeutic targets.
Ambient artificial intelligence scribes (AI scribes) are emerging as tools to optimize clinical documentation, although the need persists to evaluate their comprehensive impact on quality of care beyond operational efficiency. The aim of this study is to explore the perception of medical professionals in a tertiary pediatric hospital regarding the expected impact of AI scribes on effectiveness, efficiency, patient safety, and patient experience, and to identify facilitators and barriers to their adoption. Cross-sectional observational study using an anonymous survey of 120 physicians in October 2025. Rogers' framework (technology adoption), CFIR (implementation), and WHO/AHRQ quality dimensions were applied. Descriptive analysis, comparison by specialty (Fisher's exact test), and multivariate analysis (PCA and K-Means) were performed. 82% had prior knowledge of this technology and 89% expressed willingness to use it. Perceived improvement was higher for efficiency (80.8%; 95%CI: 72.9%-86.9%) and effectiveness (73.3%; 95%CI: 64.8%-80.4%), while patient safety (35.0%; 95%CI: 27.1%-43.9%) and patient experience (43.3%; 95%CI: 34.8%-52.3%) generated greater uncertainty. Professionals were concentrated in intermediate adoption phases (decision: 32%; implementation: 30%). Multivariate analysis identified three profiles: pragmatic (35.8%), humanistic (43.3%), and resistant (20.8%). Resources considered essential were technical support (87%), training (86%), and time (74%). Despite high willingness to adopt AI scribes, perceived impact focuses on efficiency and effectiveness, with uncertainty regarding safety and patient experience. Implementation strategies should include specific training that highlights these connections and contextualized pilot evaluations.
Shwachman-Diamond syndrome (SDS1) is an autosomal recessive disorder principally characterized by exocrine pancreatic insufficiency, a mild to severe bone marrow failure, peripheral blood cytopenias and an increased risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Since 1995 several cytogenetic studies were performed mainly in relation to the myelodysplastic/myeloproliferative risk, and recurrent chromosome changes in bone marrow (BM) were discovered. In this paper we extensively reviewed the cytogenetic studies in SDS patients, and the related significance highlighted over the years. The conclusions were drawn from analyses of our large Italian cohort by long-term monitoring (up to 27 years), together with a comprehensive review of the literature.
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Aminoacyl-tRNA synthetases (ARSs) assemble with ARS-interacting multifunctional proteins (AIMPs) to form the multi-tRNA synthetase complex (MSC), a supramolecular complex proposed to enhance efficiency of tRNA aminoacylation. Here, we show that disassembly of MSC via siRNA-mediated depletion of the scaffold protein AIMP2 promotes a transient activation of the eIF2α kinase GCN2 in mouse embryonic fibroblasts (MEFs). Activation of GCN2 was accompanied by increased eIF2α phosphorylation, induction of ATF4, and attenuation of global protein synthesis. Importantly, these effects were abolished in Gcn2-/- MEFs, indicating that translational repression following MSC disassembly is largely dependent on GCN2. Notably, GCN2 activation and eIF2α phosphorylation were induced at early time points and resolved by 24h following AIMP2 depletion and progressively resolved despite sustained suppression of AIMP2 expression, suggesting adaptive restoration of translational homeostasis. Together, our findings link disruption of MSC integrity to the GCN2-dependent integrated stress response and support a functional link between higher-order organization of the translational machinery and cellular stress sensing.