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PubMed2026

Parallel evolutionary trajectories rewire enteropathogenic Escherichia coli adhesion to restore host attachment.

Enteropathogenic Escherichia coli (EPEC) causes disease in children, presenting as chronic diarrhea that can impair physical and cognitive development. The attachment of typical EPEC (tEPEC) to the gut epithelium via bundle-forming pili (BFP) is a key factor in its virulence. Yet, infections by atypical EPEC (aEPEC), which lack BFP, have become increasingly common. To investigate how aEPEC recover host-attachment in the absence of BFP, we performed experimental evolution using a non-adherent E. coli, constructed to mimic the ancestor of aEPEC, and selected adherent progeny. Highly adherent variants evolved through phase-variable activation of type I fimbriae (T1F), followed by two alternative trajectories: bacterial filamentation, which increases T1F avidity, or point mutations in the T1F adhesin FimH that enhance ligand affinity. Extending our analysis to the genomes of 327 aEPEC strains isolated from infected patients revealed that similar FimH mutations are common. We further demonstrated experimentally that these naturally occurring variants often increase epithelial-attachment. Our findings implicate T1F in aEPEC pathogenesis and suggest it may be clinically relevant for anti-adhesion therapy. More broadly, these results indicate that impaired host-attachment can be rapidly compensated by upregulating and optimizing an alternative adhesin, and that combining experimental evolution with comparative genomics can reveal evolutionary trajectories occurring in nature.

Bacterial Adhesion↗

PubMed2026

"Orphaned bereavement": Toward a public health model for bereavement.

Bereavement is increasingly recognized as a public health concern, yet support systems in many welfare states continue to allocate support according to the circumstances of death rather than the functional needs of bereaved families. Existing bereavement frameworks have substantially advanced understanding of social recognition and public legitimacy but provide more limited guidance for understanding how institutional responsibility for bereaved families is organized. using Israel as a bereavement-saturated case, this study introduces the concept of orphaned bereavement to describe bereavement in which no institution holds clearly defined and continuing responsibility for identifying needs, coordinating support, and ensuring continuity of care. Drawing on 25 semi-structured interviews with five bereaved family members and 20 professionals, analyzed using reflexive thematic analysis, the analysis generated three interrelated themes: institutionalized invisibility and unequal recognition; reorganizing life in the absence of institutional support; and pathways toward a needs-based model of bereavement support. The findings extend existing theories of disenfranchized grief and grievability by introducing institutional responsibility as a complementary lens for understanding bereavement inequality and support a needs-based public health approach in which support is organized according to families' evolving functional needs rather than the circumstances of death.

Journal Article↗

PubMed2026

Final-year nursing students' clinical practice experiences: a reflection study.

OBJECTIVES: This study aimed to explore the most impactful clinical practice experiences of final-year nursing students and the future-oriented actions developed in response to these experiences. METHODS: A retrospective descriptive qualitative design was used. Following reflection training in the internship practice course, 134 final-year nursing students were asked to describe the experience that affected them most during clinical practice. A total of 123 written reflections were analyzed using content analysis. RESULTS: Three themes emerged: near-miss events, incivility behaviors, and positive preceptoring roles. Negative experiences were mainly related to patients, relatives, and nurses and often led students to feel fear and inadequacy. Students reported action plans focused on effective communication, safe patient care, and becoming positive role models. CONCLUSIONS: These findings highlight the importance of supportive clinical learning environments and positive professional socialization during the transition from student to nurse. IMPLICATIONS FOR INTERNATIONAL AUDIENCE: Nursing students worldwide may encounter incivility and near-miss events during clinical practice, potentially adversely affecting their learning experiences and professional development.

Humans↗

PubMed2026

The combination of morphogenic regulators BABY BOOM and GRF-GIF improves maize transformation efficiency and promotes leaf regeneration.

Transformation is an indispensable tool for plant genetics and functional genomics. Although stable transformation in maize is no longer a major obstacle, there remains a need for accessible and efficient methods for academic laboratories. Here, we present the GGB system, a rapid and efficient approach optimized for immature embryo transformation in B104 and other maize lines. This system combines two distinct morphogenetic regulators, the wheat GRF4-GIF1 chimera and the maize BABY BOOM (BBM) transcription factor (hence the name "GGB") with a modified QuickCorn protocol, enabling regeneration of transformed maize plantlets in c. 2 months with an efficiency 7-fold higher than when compared to either morphogenic factor used in isolation. Expression of both regulators did not significantly affect development, eliminating the need to excise them after regeneration. However, transmission of the transgenic GGB construct through pollen was significantly reduced, potentially aiding transgenic line containment. We show that the GGB system is adaptable for CRISPR-Cas9 editing and reporter line generation. Furthermore, stable GGB transformants exhibited high leaf regeneration capacity via somatic embryogenesis. RNA-seq time-course profiling of GGB leaf cultures identified additional factors that could promote regeneration and led to the discovery of asparagine and trehalose as additional media components that significantly enhanced leaf regeneration.

Zea mays↗

PubMed2026

Olive leaf protein hydrolysates yield gastro-resistant peptides with antioxidant and anti-inflammatory potential: peptidomics, in vitro validation and molecular docking analyses.

Olive (Olea europaea L.) leaves are an abundant olive-oil by-product and a promising feedstock for sustainable valorisation. An olive leaf protein isolate (OLPI) from olive-leaf powder (OLP) was enzymatically hydrolysed to yield seven hydrolysates (OLPHs). All showed notable antioxidant activity as whole hydrolysate matrices (EC₅₀ = 0.11-0.28 mg mL-1); likely reflecting the combined contribution of released peptides and co-extracted phenolic compounds; the 15-min Alcalase product (OLPH15A) showed high activity with the shortest processing time. Its INFOGEST digest (dOLPH15A) attenuated LPS-induced inflammation in Caco-2 cells, down-regulating pro-inflammatory and up-regulating anti-inflammatory genes. Peptidomics identified 7037 peptides in OLPH15A and 534 in dOLPH15A, from which twenty gastro-resistant sequences were prioritised for in silico analysis. Multi-tool prediction and docking highlighted four peptides, GAAGGIGQPL, QSAYPGTGPL, GGGAGGGDGGIL and LDAQFPGVN, with favourable predicted affinity for the TLR4/MD2 complex, suggesting that they may contribute to the observed immunomodulatory response. These findings position olive leaves as a viable source of protein hydrolysate-based ingredients with antioxidant and anti-inflammatory potential, advancing the valorisation of olive-oil by-products.

Olea↗

PubMed2026

Beyond risk factors: A capacity framework for cancer survivorship research.

Cancer survivorship research has identified numerous biological, behavioral, psychosocial, health care, and structural factors that influence recovery. However, these factors are typically studied as separate determinants rather than interacting influences. This commentary proposes available survivorship capacity as a unifying framework that explains how these diverse determinants collectively shape recovery and survivorship outcomes. Concepts from geroscience, health care delivery, rehabilitation, occupational therapy, and human factors science were synthesized to develop a conceptual framework of available survivorship capacity. The framework conceptualizes recovery as a function of the capacity remaining after competing health care and life demands draw upon survivors' finite physical, cognitive, emotional, social, financial, temporal, and health care resources. It generates testable propositions for measurement, intervention research, health care delivery, and implementation science while positioning available survivorship capacity as a common mechanism linking diverse determinants of recovery and identifying actionable targets for intervention. Available capacity offers a unifying conceptual framework for understanding heterogeneity in survivorship outcomes and intervention effectiveness while generating a research agenda for future survivorship science. Measuring and strengthening survivors' available capacity, while reducing unnecessary demands, may improve engagement in care, health behaviors, and long-term recovery.

Humans↗

PubMed2026

Walking Together: A Cross-Cultural Study of the Relationship Between Religiosity and Substance Use Disorder.

The literature suggests that religiosity is a protective factor for substance use. However, individuals with substance use disorder (SUD) may actively cultivate their religiosity during substance use. This qualitative study analyzed the perceptions and meanings homeless people attribute to their substance use trajectories and religiosity, as well as the potential connections between these two themes. The analysis was conducted based on the content analysis technique proposed by Bardin. A total of 40 semi-structured interviews were conducted with 20 Brazilian and 20 Portuguese participants. The present study found that religiosity can play a role in the substance use trajectory and the development of SUD by offering a subjective sense of protection, serving as a marker for the need for change, or providing relief from the suffering associated with SUD. We discuss how homeless people with SUD experience religiosity and how religious aspects traditionally seen as protective in the literature, such as church attendance, may paradoxically become risk factors for these socially vulnerable populations.

Humans↗

PubMed2026

Azithromycin-resistant Salmonella enterica Typhi with AcrB R717L/Q mutations in the United States.

BACKGROUND AND OBJECTIVES: Azithromycin is a critical oral treatment for typhoid fever caused by Salmonella enterica serovar Typhi (Salmonella Typhi), since XDR has rendered other first-line treatment options ineffective. Azithromycin resistance conferred by amino acid changes in AcrB, an AcrAB-TolC efflux pump component, represents an emerging public health concern. Leveraging phenotypic and genotypic data from U.S. Salmonella Typhi surveillance systems, this study describes the prevalence, phenotype and genomic epidemiology of Salmonella Typhi with AcrB mutations in U.S. patients since the first detection in 2015. METHODS: AST and WGS data of >3000 Salmonella Typhi isolates were used to identify all cases with an AcrB mutation in the United States (2015-2025). We calculated annual prevalence and MIC ranges. Phylogenetic analysis was used to contextualize U.S. cases of Salmonella Typhi with an AcrB mutation within all globally reported cases. RESULTS: While the prevalence of AcrB mutations in the United States is low (1.5%), it has risen significantly in recent years, from 0.2% in 2016-2022 to 2.2% in 2023-2025. This increase is predominantly driven by clonal expansion of existing strains circulating in South Asia. AcrB mutations do not reliably confer resistance to azithromycin (MIC ≥ 32 mg/L), complicating clinical interpretation. CONCLUSIONS: The prevalence of AcrB mutations in Salmonella Typhi is increasing in the United States, and likely globally, given that U.S. data function as an informal proxy for regions without routine surveillance infrastructure. Clinical outcomes data are needed to inform Salmonella Typhi treatment guidelines and potentially amend clinical breakpoints for azithromycin.

Journal Article↗

PubMed2026

Lower androgen sulfate metabolites in women with hypermobile Ehlers-Danlos syndrome may be associated with changed metabolism and disposition.

Hypermobile Ehlers-Danlos Syndrome (hEDS), characterized by joint hypermobility and multisystem involvement, is the most common type of EDS. Its comorbidities are wide-ranging, reflecting the involvement of connective tissue and its role in a multitude of processes. hEDS has been hypothesized to have hormonal aspects since the disorder is diagnosed more often in women and symptom changes closely correlate with hormonal shifts. To better understand the etiology and biochemical changes in hEDS and its comorbidities, a multiple-omics study was performed in women, controls (n = 45) and those with hEDS (n = 45), alongside the collection of questionnaires related to symptom severity. Metabolomic evaluation was performed on serum samples and RNA isolated from fibroblasts cultured from skin punches was analyzed for transcriptomics. Samples from hEDS patients had statistically significantly lower levels of multiple androgen sulfate metabolites, compared with controls, driven largely by participants aged 30-49. Changes to other classes of steroid hormones (corticosteroids, progestogens, and estrogens) were largely not significant between hEDS and control groups. Transcriptomics of skin fibroblasts from hEDS patients revealed downregulation of multiple enzymes involved in biosynthesis, metabolism, and disposition of androgens, compared with controls. Multiple steroid hormones correlated with symptoms surveyed in 18-29 year old participants with hEDS. Shifts in steroid hormone metabolites in hEDS compared with controls may be due to changes to metabolism and disposition, but more validation is necessary to be conclusive. This data provides insights into the unclear links between steroid hormones and hEDS and its comorbidities.

Humans↗

PubMed2026

A host-encoded prophage targets a Candidate Phyla Radiation bacterium and shapes episymbiotic interactions.

The Patescibacteriota, also known as the Candidate Phyla Radiation (CPR), represent a large lineage of ultrasmall bacteria with highly reduced genomes and obligate dependence on bacterial hosts. Although genomic analyses have revealed CRISPR-Cas and restriction-modification systems in many CPR genomes, no cognate bacteriophages (phages) have been isolated, leaving CPR-phage interactions unexplored. Nanosynbacter lyticus TM7x, the first cultivated CPR bacterium, grows episymbiotically on its host, Schaalia odontolytica XH001, in the human oral microbiome. Here, we identify Xhp1, an inducible prophage of XH001 that is preferentially activated during episymbiosis with TM7x. Released Xhp1 particles infect prophage-free XH001 via distinct strategies determined by host growth mode, establishing lysogeny under planktonic conditions but driving lytic infection during surface-associated growth. Xhp1 also binds efficiently to TM7x and exhibits limited infection under the conditions tested, indicating direct phage-CPR interactions. Importantly, TM7x modulates Xhp1 availability in a spatially dependent manner. In planktonic culture, free-floating TM7x reduces lysogenic conversion of XH001ΔXhp1, consistent with TM7x acting as a phage sink that lowers effective phage concentration. In contrast, during surface-associated growth, TM7x increases XH001ΔXhp1 susceptibility to lytic infection, likely by locally concentrating phage particles within a constrained niche. These results demonstrate that CPR bacteria can regulate viral encounter rates through spatial organization. In spatially structured environments such as oral biofilms, such modulation may shape infection dynamics and community structure. Together, this work characterizes the first CPR-targeting phage and reveals a an important role for phages in CPR-host bacteria interactions.

Prophages↗

PubMed2026

Emerging techniques of CRISPR/Cas system in antiviral therapy and diagnostics: Applications, limitations, and translational perspectives.

The CRISPR/Cas (clustered regularly interspaced short palindromic repeats) system is a versatile technology for developing antiviral medicines and editing viral genomes in both diagnostics and vaccine synthesis. Emerging insights into class 2 effectors, such as Cas9, Cas12, and Cas13, which target viral DNA and RNA, have revolutionized vaccines against viruses such as HIV, HPV, HBV, and EBV. Innovative diagnostic techniques such as SHERLOCK, DETECTR, and FELUDA have demonstrated system's diversity and accuracy in detecting the virus markers, supporting clinical decision-making, indicating adaptability and precision of CRISPR. This review critically evaluates CRISPR's role in RNA editing, emphasizing its importance for functional genomics and development of recombinant vaccines. Translational challenges are critically discussed, including off-target effects, delivery limitations, and ethical issues, for which unique approaches such as high-fidelity Cas variants, non-viral delivery systems, and bioethical frameworks are evaluated to address these limitations. This review also covers other social implications, such as accessibility and biosecurity risks, associated with CRISPR technologies Collectively, these advances underscore the transformative potential of CRISPR technologies in shaping next-generation antiviral diagnostics and therapeutics.

CRISPR-Cas Systems↗

PubMed2026

Analyzing the impact of subcutaneous injection needle, device, and administration characteristics on patient pain, anxiety, and safety: a systematic literature review.

The subcutaneous (SC) injection route is a commonly used and important method for therapeutic delivery of a wide range of compounds, and needle characteristics have a significant influence on patient pain, anxiety, safety, and other outcomes. This systematic review evaluates the evidence on how needle-specific characteristics (e.g. gauge, length, tip design, wall thickness, concealment) and administration- or device-related factors can affect patient-reported outcomes and clinical safety indicators during and following SC injections. A comprehensive search was conducted in MEDLINE, PubMed, Embase, and ClinicalTrials.gov in June 2024. Studies were included if they assessed the relationship between needle characteristics and pain, anxiety, safety, or related outcomes in individuals receiving SC injections. A dual-reviewer process was used for study selection, data extraction, and quality assessment. Sixty-two studies met inclusion criteria. Evidence consistently indicated that thinner and shorter needles reduced patient-reported pain and adverse events such as bruising and bleeding. Tapered and lubricated needles, hidden or retractable needle designs, and use of autoinjectors or prefilled syringes also contributed to reduced anxiety and improved user satisfaction. However, results were heterogeneous, and many studies lacked sufficient power or single-variable evaluation of individual needle parameters, limiting definitive conclusions. Needle characteristics significantly influence patient experience and safety with SC delivery. While both clinical evidence and practical experience clearly favor thinner, shorter, and concealed needles, further standardized, high-quality research is needed to isolate and quantify the specific contributions of individual needle characteristics to optimize injection practices and support patient-centered device design.

Humans↗

PubMed2026

Leveraging environmental applications and risks of coal gangue: A critical review on authigenic inorganic heavy metals, organic contaminants, and the removal of exogenetic contaminants.

Coal gangue (CG) as bulk solid waste has seriously threatened the ecosystem. Therefore, identifying the key risk drivers and exploring feasible disposal methods for CG are essential for developing a sustainable strategy. However, there is currently a lack of comprehensive information that balances the contamination risks with the valuable constituents present in CG, which hinders its full potential for sustainable use without negative environmental impacts. Given the complex composition and associated risks, we propose that addressing the critical properties related to contamination is crucial for the efficient utilization of CG. On this premise, we summarized several practical resource pathways (ecological multifunctional materials, extraction of rare elements, and soil additives) that are more favorable for sustainable development relative to conventional disposals. Meanwhile, we also propose that coupling disposals could intensely reduce CG's environmental footprints and capital costs. Consequently, regardless of the number of challenges to be solved, we believe the CG has broad application prospects, and we hope this review will promote the conversion of CG into an asset with lower ecological and social impacts.

Metals, Heavy↗

PubMed2026

The knee-ankle link: impact of knee varus severity on distal joint malalignment and concomitant pathologies.

BACKGROUND: Knee varus deformity is traditionally managed as an isolated joint pathology; however, persistent distal symptoms following proximal realignment suggest a more extensive kinetic chain dysfunction. The degree to which knee varus severity dictates distal malalignment and secondary pathologies remains poorly quantified in the current literature. METHODS: This systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines (PROSPERO: CRD420261363327). A comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library was performed from inception to April 2026. Studies examining the relationship between knee varus (HKA angle) and radiographic distal alignment or pathologies were included. Data synthesis utilized random-effects models, with prevalence analyzed via generalized linear mixed models (GLMM). RESULTS: Fourteen studies were included in the final synthesis. While pooling of continuous radiographic parameters was limited by high statistical heterogeneity in Talar Tilt (I2 = 96.5%), individual large-cohort data (Huang et al.) indicated that severe knee varus (HKA > 10°) was associated with increased odds of concomitant ankle osteoarthritis (OR 2.29; 95% CI 1.28-4.11) and a specific cohort prevalence of 37.1%. Furthermore, single-arm prevalence data revealed divergent trends across different study populations, with compensatory hindfoot valgus reaching 69.9% in some cohorts and rigid varus up to 63.9% in others. CONCLUSIONS: Severe genu varum is associated with distal kinetic chain alterations and concomitant ankle pathologies. However, due to the extreme heterogeneity and divergent distal adaptations observed across different cohorts, standardized knee-centric protocols may be insufficient. Further longitudinal and interventional studies are required to establish phenotype-specific rehabilitation guidelines.

Humans↗

PubMed2026

Comparative profiling of microbial community structure, enzyme potential, metabolic features, and volatile composition in craft and Jiafan Huangjiu processes.

Craft Huangjiu and Jiafan Huangjiu represent two distinct industrial Huangjiu product outcomes with contrasting volatile profiles. This study compared craft Huangjiu (L70) and Jiafan Huangjiu (L79) to characterize their physicochemical, microbial, gene-level functional, metabolic, and volatile features. Because L70 involved mid-fermentation addition of finished Huangjiu, this comparison was not intended to isolate the sole effect of fermentation interruption versus continued fermentation. L79 showed more extensive carbon and nitrogen utilization, with lower residual substrates and higher ethanol and acetic acid contents than L70, whereas L70 retained a less complete fermentation state. At the volatile level, GC-MS and volatile metabolomics consistently showed an ester-enriched profile in L79 and a more alcohol-dominant profile in L70. FlavorDB-based putative annotation and threshold-based OAV analysis further indicated distinct database-assigned descriptor distributions and potential odor-active compounds, with more OAV > 1 ester-related compounds in L79. Metagenomic analysis showed that L70 was dominated by Lactobacillus acetotolerans, whereas L79 contained higher relative abundances of Saccharomyces cerevisiae, Aspergillus oryzae, Aspergillus flavus, and Fructilactobacillus fructivorans. Metagenomic functional annotation showed higher representation of hydrolysis-related CAZy genes and ester-related enzyme annotations in L79. KEGG-based pathway mapping further indicated greater gene-level potential for ethanol-, acetate-, and acetyl-CoA-related metabolism in L79. Accordingly, the L70 profile should be interpreted as the integrated final-product outcome of process intervention, exogenous input, and subsequent fermentation. The findings provide a comparative basis for future flavor regulation and process optimization in Huangjiu and other fermented alcoholic beverages.

Volatile Organic Compounds↗

PubMed2025

Tracking microplastic contamination across seasons in a freshwater reservoir: Evidence from surface water, sediments, and fishes.

Microplastics (MPs) are prevalent contaminants in aquatic environments, posing substantial ecological and health risks. These particles migrate within the different layers of aquatic bodies with time and affect the respective biota. Thus, to get an in-depth understanding of the particles, this current study investigated the seasonal distribution, morphological and chemical characteristics, along with potential ecological and human health impacts in the samples including surface water, sediment, and fish from a drinking water supplying reservoir in eastern India. Across three different seasons, pre-monsoon, monsoon, and post-monsoon samples were collected using optimized methods. Results revealed distinct seasonal trends: MP abundance in surface water peaked during the monsoon (mean: 1.15 MPs/L), while sediment showed the highest concentrations in the pre-monsoon (mean: 596 MPs/kg), indicating temporal accumulation dynamics influenced by runoff, hydrodynamics, and sedimentation. Fish gut analysis confirmed ingestion of MPs across five species, with concentrations ranging from 26 to 100 MPs/kg, depending on feeding habits. The most dominant MP type were fragments, followed by fibers, films, and beads. Polymer analysis via µFTIR identified polyethylene, polypropylene, and polyvinyl chloride as prevalent, with hazard assessments (i.e., Polymer Hazard Index (PHI)) indicating medium to very high ecological risks. Heavy metal association was more dominant in the MPs isolated from sediments than the waterborne MPs. Pollution Load Index (PLI) values were > 1 in most seasons, confirming contamination. Health risk analysis suggested potential exposure through both drinking water and fish consumption. This study emphasizes the need for seasonal monitoring, improved waste management, and mitigation strategies to address MP pollution in freshwater ecosystems.

Microplastics↗

PubMed2026

Fungal drivers of mycotoxin contamination in wheat: Early warning and plasma-based control.

Mycotoxin contamination in wheat is a major food safety concern; however, quantitative evidence linking fungal community signals, mycotoxin exceedance risk, and wheat quality traits in naturally contaminated wheat remains limited. In this study, wheat samples were collected from mycotoxin-prone monitoring sites under unusually rainy conditions in 2022 to explore early-warning indicators and post-harvest mitigation strategies. According to the National Food Safety Standard of China GB 2761-2017, aflatoxin B1 (AFB1), deoxynivalenol (DON), and zearalenone (ZEN) exceeded the maximum limits in 52.24, 47.76, and 23.88% of samples, respectively; 38.81% exceeded the reference EU threshold for T-2 toxin, and 46.27% showed co-contamination with at least two mycotoxins above their respective thresholds. Although Alternaria, Cladosporium, and Epicoccum dominated the fungal community, Fusarium abundance was significantly associated with DON contamination and Fusarium-damaged kernels (FDKs). Mediation analysis identified DON as a significant mediator linking Fusarium abundance to FDKs, accounting for 68.41% of the total effect. In addition, Fusarium abundance above 3.70% showed strong predictive performance for DON exceedance, with an area under the curve of 0.906, indicating its potential as an early-warning indicator. Culture-based assays confirmed the toxigenic potential of Aspergillus and Fusarium isolates under simulated temperature and moisture conditions. After optimization using a toxin-spiked wheat flour model, dielectric barrier discharge cold plasma degraded AFB1, DON, and ZEN by 29.30-35.68%, disrupted the morphology of toxigenic fungi, and did not significantly affect wheat quality. This study provides practical insights into mycotoxin risk warning and post-harvest mitigation in wheat.

Triticum↗

PubMed2026

Hypothalamic-Pituitary Axis Involvement in Primary Central Nervous System Lymphoma.

CONTEXT: Primary central nervous system lymphoma (PCNSL) is a rare malignancy that may involve the hypothalamic-pituitary axis (HPA), leading to underrecognized but clinically significant endocrine dysfunction. OBJECTIVE: This work aims to characterize the spectrum and patterns of HPA-related endocrine disturbances in patients with PCNSL. DATA SOURCES: A systematic search was conducted in PubMed, EMBASE, Scopus, and Web of Science, supplemented by gray literature. The search concluded in February 2025. STUDY SELECTION: We included studies reporting adult PCNSL cases with documented dysfunction of at least one hormonal axis. Exclusion criteria were preexisting hypopituitarism or lack of endocrine data. DATA EXTRACTION: Data on demographics, tumor localization, hormonal axes affected, radiological findings, treatment, and outcomes were extracted. Risk of bias was assessed using JBI tools. RESULTS: Ninety-nine cases met the inclusion criteria. Diffuse large B-cell lymphoma accounted for 84% of cases. Endocrine dysfunction included isolated adenohypophyseal involvement (46%), neurohypophyseal (8%), and combined (45%). The most affected pituitary axes were the gonadal and thyroid axes, with 89.7% and 89.2% involvement, respectively. Hypothalamic tumors were strongly associated with combined dysfunction (odds ratio = 9.47; 95% CI, 3.76-23.86; P < .001). Persistent endocrinopathy was more frequent in progressive disease. No direct association was found between endocrine dysfunction and mortality. CONCLUSION: HPA dysfunction in PCNSL is frequent and often underdiagnosed. Hypothalamic involvement is associated broader hormonal impairment. Routine hormonal screening and multidisciplinary management should be standard in PCNSL care to minimize complications and improve outcomes.

Humans↗