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Meaning in Life in Palliative Cancer Care: Psychosocial and Existential Outcomes-A Systematic Review.

BackgroundExistential distress, marked by hopelessness, loss of meaning, and spiritual suffering, is prevalent among patients with advanced illness, and is associated with psychological burden and a wish to hasten death (WTHD).PurposeThis systematic review aimed to synthesize current evidence on meaning in life (MIL) in adult palliative care (PC) populations, focusing on its associations with quality of life (QOL), mental health, existential and spiritual well-being (SWB), and WTHD.MethodsMEDLINE, Web of Science, Scopus, and the Cochrane Library were searched for eligible studies (English, 2016-2024) involving adult cancer patients receiving PC. MIL was examined as a central intervention component or outcome. Risk of bias was assessed: findings were synthesized narratively. The review was registered in PROSPERO.ResultsEight studies (n = 1733 participants) were included: four cross-sectional, two randomized controlled trials, one longitudinal observational study, and one qualitative study. Several studies had small samples and substantial attrition. Risk of bias was high (n = 7), and moderate in one cross-sectional study. MIL was inversely associated with depression, anxiety, demoralization, and WTHD; and positively associated with QOL and SWB. MIL may also mediate psychological outcomes (eg, purpose, coherence, and personal values). However, heterogeneity in MIL conceptualization and measurement, combined with low methodological quality, limited comparability and certainty of findings.ConclusionMIL may be relevant to psychosocial/existential outcomes in PC. Conclusions are constrained by a small and methodologically weak evidence base. Further high-quality, longitudinal research is needed before MIL-centered interventions can be recommended for routine clinical practice.

Humans

Parent-Child Communication after Parental Exposure to Potentially Traumatic Events: A Systematic Review.

Intergenerational traumatization poses a risk for the well-being of children whose parents have been exposed to potentially traumatic events (PTEs). Previous research has implied that parent-child communication may significantly contribute to the transmission of trauma across generations, but findings remain limited and inconclusive, particularly regarding the mechanisms and factors that could underlie this process. Therefore, the present paper performed a mixed methods systematic literature review to methodically map how PTE-exposed parents communicate with their children-both in general and about parental PTEs-and how such communication may contribute to trauma transmission. Five electronic databases were accessed to conduct keyword-led searches, yielding a final inclusion of 31 peer-reviewed, empirical studies that investigated parent-child communication among PTE-exposed parents and/or their nonexposed children. Parental PTE exposure was found to have a negative impact on general parent-child communication, often due to the presence of parental anger, irritability, and withdrawal. Conversations about parental PTEs showed substantial diversity in their frequency, content and style, with strategies of partial/modulated disclosure appearing most common. How parents approached PTE communication frequently stemmed from a desire to keep their children safe and unburdened by their previous experiences. Finally, both general communication and PTE communication were implied to contribute to trauma transmission, revealing a significant impact of parent-child communication on child functioning, identity, and well-being. Based on these key findings, the authors discuss meaningful implications for future research (i.e., prospective directions, addressing methodological concerns) and formulate suggestions for clinicians and policymakers surrounding the treatment of PTE-exposed parents and their offspring.

Humans

Complement component C4 and neuroimaging in psychiatry: A systematic review.

INTRODUCTION: Genomic, transcriptomic, and proteomic studies suggest that the complement system contributes to the pathophysiology of various psychiatric disorders partly through neurodevelopmental effects linked to C4A protein levels variations. We conducted a systematic review to characterize how brain micro- and macrostructure and connectivity vary with proxies of in vivo brain C4A protein levels in both psychiatric and general-population cohorts. METHODS: We used Medline, Web of Science, and Embase, and included all studies published before April 14, 2025. Inclusion criteria were: (1) inclusion of healthy controls and/or individuals with psychiatric disorders assessed according to recognized diagnostic manuals (DSM or ICD); (2) use of MRI-based neuroimaging; and (3) use of genomic, transcriptomic and/or proteomic approaches as proxies of in vivo brain C4A proteins levels. RESULTS: From 317 identified articles, 11 were included. Associations between C4A levels and brain structure were heterogeneous across regions. Only the mOFC, dlPFC, and entorhinal cortex were implicated in more than one study. Findings for the mOFC and dlPFC varied by the type of metrics and clinical status, whereas higher C4A levels were more consistently associated with smaller entorhinal cortex surface area and cortical thickness in pediatric, middle-aged, and older general-population cohorts. In addition, one study found higher genetically predicted C4A expression to be associated with higher TSPO levels. CONCLUSION: The limited number of available studies and their methodological heterogeneity make synthesis challenging. However, biological hypotheses such as excessive synaptic pruning or broader inflammatory effects on the brain may provide plausible explanatory frameworks for the reported associations.

Humans

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

Systems Factors Contributing to Racial/Ethnic Disparities in Maternal Health: A Systematic Review.

INTRODUCTION: Despite ongoing efforts to reduce adverse maternal outcomes, including maternal mortality and severe maternal morbidity, racial/ethnic disparities in outcomes persist in high-income countries, including the United States (US) and Canada. Limited research has examined hospital-level factors that may drive disparities and contribute to adverse outcomes. This systematic review summarizes factors within the health system contributing to adverse outcomes and racial/ethnic disparities in the US and Canada to inform future policies and practices. METHOD: We searched SCOPUS, PubMed, EBSCOhost, and ProQuest Healthcare Administration for studies that reported hospital-level factors contributing to adverse maternal outcomes and racial/ethnic disparities. The review followed a two-stage screening process. The risk of bias of the included studies was evaluated using the Mixed Methods Appraisal Tool. The System Engineering Initiative for Patient Safety (SEIPS) 2.0 framework guided the identification and categorization of factors. RESULTS: Of 2441 studies retrieved, 30 met the inclusion criteria. Twenty-eight studies were conducted in the US, and 2 were conducted in Canada. The review included 16 qualitative, 11 quantitative, and 3 mixed-methods studies. We identified 60 factors associated with different system components, including person(s) (12%), tasks (28%), tools and technology (7%), internal environment (10%), organization (28%), and external environment (15%). Shortage of resources, including staffing, poor care coordination, and discriminatory organizational practices, were key factors described in the studies. CONCLUSION: Addressing health system factors in addition to broader societal factors is important to reduce adverse outcomes and promote equity for all women and birthing persons.

Humans

Metabolic and endocrine modulation of the gut-adipose tissue axis via pro-, pre-, and postbiotics in overweight dogs: A systematic review.

Canine obesity is a complex metabolic disorder driven by luminal dysbiosis, impaired gut barrier function, and metaflammation. Following PRISMA 2020 guidelines, this systematic review evaluated the efficacy of pro-, pre-, and postbiotics in modulating the gut-adipose tissue axis in overweight dogs (BCS ≥ 6/9) or diet-induced obesity models. Searches across PubMed and Dimensions (April 2026) identified seven eligible experimental trials. Results suggest that postbiotic Bifidobacterium animalis subsp. lactis CECT 8145 reduced postprandial glucose AUC by 6 % strictly during energy restriction. Pasteurized Akkermansia muciniphila postbiotics limited diet-induced weight gain, though glucoregulatory impacts were highly strain-specific (AKK2 reduced fasting glucose and insulin resistance indexes, whereas EB-AMDK19 exerted no significant effect). Specific probiotics (including Enterococcus faecium, Bifidobacterium lactis, Lactiplantibacillus plantarum and Bifidobacterium breve) attenuated fasting hyperinsulinemia and preserved circulating adiponectin, but lipid profile improvements (triglycerides and total cholesterol) were inconsistent across trials. In dogs, increased luminal short-chain fatty acids are not consistently mirrored by endocrine responses, so the coupling between microbial metabolites and incretin signaling remains incomplete. A critical lack of standardized reporting for species-validated insulin sensitivity metrics was identified. In conclusion, microbiome-targeted therapies, particularly inanimate postbiotics, may represent useful adjunctive strategies to mitigate metabolic dysregulation in obesogenic environments. However, clinical efficacy remains strictly strain-specific and dependent on host energy balance. Given the scarcity of high-certainty evidence, future trials must integrate dynamic physiological assessments with species-validated surrogate indexes alongside standardized dietary controls.

Animals

How is goal setting used in interventions for chronic disease prevention and management in sub-Saharan Africa? A systematic review and narrative synthesis.

Non-communicable diseases are increasingly prevalent in sub-Saharan Africa, and goal setting is often used to promote healthy self-management behaviours. In this review, we aimed to synthesise literature around how goal setting is used, for application in future interventions in the region. A systematic search was conducted in six databases and results screened for eligibility. Study characteristics, intervention details, goal setting components, feedback from participants and facilitators were extracted. Data were analysed using narrative synthesis and thematic analysis. The Mixed Methods Appraisal Tool was used to assess study quality. We included 24 publications describing 18 unique interventions. Included studies were of high to moderate methodological quality. Goal setting intervention components were informed by a variety of frameworks and involved a range of tasks. Interventions were often facilitator-led; many were conducted in group settings. Participants reported goal setting as useful for putting self-management into practice but encountered challenges related to language and literacy levels. Adequate detail on goal setting intervention components was not always present. Through this review, we provide a comprehensive picture of the variability of goal setting approaches in chronic disease prevention and management in sub-Saharan Africa and recommend more standardised use and reporting of goal setting intervention components.

Humans

Brain network alterations underlying cue reactivity and craving in abstinent methamphetamine users: a systematic review of functional MRI findings.

BACKGROUND: Methamphetamine use disorder (MUD) is marked by intense craving and high relapse risk, often triggered by drug-related cues. Functional magnetic resonance imaging (fMRI) provides key insight into the neural basis of this cue reactivity, implicating large-scale brain networks for reward, motivation, and control. Yet, findings remain inconsistent across studies due to differences in task design, abstinence duration, and participant characteristics. OBJECTIVE: This systematic review synthesises evidence on how abstinence influences brain network alterations underlying cue reactivity and craving in methamphetamine users, integrating task-based and resting-state fMRI findings within leading neurobiological models of addiction. METHODS: A systematic search of PubMed, Scopus, Web of Science, and Ovid was conducted up to August 10, 2025, following PRISMA 2020 guidelines. Eligible fMRI studies examined cue reactivity or craving in abstinent methamphetamine users. Data were extracted on activation, connectivity, and brain-behaviour associations, and synthesised narratively. RESULTS: Task-based studies revealed heightened activation across reward, salience, and control networks during cue exposure, which diminished as parietal and executive control systems re-engaged with longer abstinence. Resting-state findings showed disrupted intrinsic connectivity among default mode, salience, and frontoparietal networks, reflecting persistent imbalances linked to craving and use severity. CONCLUSION: fMRI evidence shows that MUD is marked by network-level disruption linking reward, salience, and control systems. Task-based findings reveal strong cue reactivity in reward circuits, while resting-state data show persistent imbalance among default mode and control networks. With abstinence, partial restoration of network integrity emerges, highlighting both vulnerability and opportunities for targeted, recovery-based interventions.

Humans

Longitudinal associations between family factors and the neurodevelopmental and psychosocial outcomes of children with congenital heart disease: A systematic review.

Family factors have been gaining increased attention in understanding adverse neurodevelopmental and psychosocial outcomes for children with congenital heart disease (CHD). To clarify relevance, we undertook a systematic review of only longitudinal studies which assessed such associations. Comparisons with the contribution of disease/surgical factors were also made where included studies considered such. We included longitudinal studies which assessed dynamic family factors (e.g. parent mental health, attachment, family functioning) and later child outcomes. Searches were conducted across CINAHL, Medline-Pubmed, PsychInfo and SCOPUS Web of Science. The NIH Quality Assessment Tool was used to evaluate study quality and risk of bias. Eighteen studies, utilizing data from 11 study samples and 2109 participants, met inclusion criteria. These studies included samples from infancy, with follow-up periods stretching into young adulthood, and with various degrees of CHD severity. The quality of studies was "good" to "fair", with key limitations of attrition and limited sociocultural diversity in samples. Findings suggested that family factors predicted later child psychosocial outcomes and more consistently than severity of disease indicators. This contrasted with a much smaller number of studies examining family factors and child neurodevelopmental outcomes, where no reliable conclusions could be reached. Findings highlight the importance of screening and family focused interventions for this population.

Child

Cisplatin-Induced Hearing Loss Prevention With Intratympanic Therapy Systematic Review and Meta-Analysis.

INTRODUCTION: Cisplatin-induced hearing loss (CIHL) is a well-described, long-term consequence of cisplatin treatment for malignancy. Intratympanic (IT) injections have been trialed to prevent CIHL in humans. To provide clarity on which agents have been studied through IT injection and to review their efficacy for hearing loss prevention, we performed a systematic review and meta-analysis. DATA SOURCES: OVID Medline, Embase, Web of Science, and Cochrane Library were queried. METHODS: Databases were searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Prospective randomized trials were included, and a systematic review was performed for all studies. Demographic, audiometric, and therapeutic data were collected. Random-effects models were used to compare across studies, and subgroup analyses were performed for each IT agent. RESULTS: The initial database search yielded 1017 articles, which were screened according to inclusion and exclusion criteria. Ten studies were identified, involving a total of 284 patients. Studies included data on IT dexamethasone, IT N-acetylcysteine (NAC), and IT sodium thiosulfate (STS). Pooled analysis across all agents and frequencies did not reveal a significant difference in hearing thresholds between treatment and control ears [prediction interval [-3.77, 3.20], negative favors treatment). Subgroup analysis of IT dexamethasone [-1.74, 3.80] and IT NAC [-1.02, 4.64] also did not demonstrate significant differences. STS data were not amenable to pooled analysis; however, one study demonstrated a significant decrease in ASHA-defined ototoxicity (40% vs. 85%, P =0.0027). CONCLUSIONS: To date, no IT agent has consistently prevented CIHL, although limited data suggest that IT STS may decrease ototoxicity. More trials are necessary to fully elucidate these effects.

Humans

Measuring economic efficiency in adult intensive care units: A systematic review of methods, metrics, and evidence.

OBJECTIVES: Intensive care units (ICUs) consume substantial hospital resources, yet "efficiency" is inconsistently defined and measured. This study systematically reviewed how economic efficiency has been conceptualised and quantified in adult ICUs and appraised the quality of evidence. METHODS: Following PRISMA 2020 and a PROSPERO-registered protocol (CRD420251107866), we searched MEDLINE, Embase, CINAHL, Cochrane Library and Web of Science (2000-August 2025), plus global grey sources. Eligible studies explicitly defined efficiency and reported an efficiency metric/model linking ICU inputs (e.g., staff, beds/capacity, time, consumables, or costs) to outputs/outcomes (e.g., throughput/discharges, length of stay/resource use, risk-adjusted mortality). Dual independent screening and extraction were performed. Study quality was appraised using MMAT, and findings were synthesised narratively (SWiM), given heterogeneity. RESULTS: 39 studies (2001-2025) from 17 countries were included, all from high-income or upper-middle-income settings. Four methodological families were identified: (1) frontier modelling (predominantly DEA; occasional SFA/RFDH), (2) benchmarking indicators (risk-adjusted mortality and LOS/resource-use ratios; "efficiency matrix" quadrant classification), (3) cost-outcome evaluations, and (4) operational/process metrics. Across families, variation in decision-making units, input/output selection, and risk adjustment limited comparability; long-term and patient-reported outcomes were absent, and equity considerations were uncommon. CONCLUSIONS: ICU efficiency research is feasible but fragmented and often methodologically limited. Standardised definitions, validated risk adjustment, uncertainty quantification, and inclusion of patient-centred and equity-relevant outcomes are needed before efficiency metrics can reliably inform value-based decision making.

Intensive Care Units

Robot-assisted versus freehand cannulated-screw fixation for femoral neck fractures: a systematic review of technical, clinical and adoption outcomes.

Robot-assisted guidance may improve the technical precision of percutaneous cannulated-screw fixation for femoral neck fractures. Whether these procedural advantages translate into better clinical outcomes remains uncertain. We compared robot-assisted and conventional freehand fixation in adults with femoral neck fractures. MEDLINE, Embase and CINAHL were searched from inception to 15 July 2026 without language restrictions. Google Scholar was used only as a supplementary search source, together with forward and backward citation searching. Comparative studies of robot-assisted versus freehand fluoroscopy-guided cannulated-screw fixation were included. Risk of bias was assessed using RoB 2 and ROBINS-I, with the Newcastle-Ottawa Scale used as a complementary appraisal of non-randomised studies. Random-effects meta-analyses included prediction intervals and prespecified sensitivity analyses. The protocol was registered prospectively (PROSPERO CRD420261465038). Sixteen comparative studies involving 1,293 participants were included. Of these, 597 underwent robot-assisted fixation and 696 underwent freehand fixation. Two studies reporting random allocation and 14 non-randomised studies were included in the study. Robot-assisted fixation was associated with fewer guide-wire manipulations, greater screw-placement accuracy and 13.9 fewer fluoroscopic acquisitions per procedure (95% confidence interval [CI] -20.3 to -7.5). Earlier radiographic healing and modestly higher final Harris Hip Scores were also observed. Pooled estimates suggested lower risks of union failure, avascular necrosis and composite complications. Fluoroscopy duration, overall operative time and reoperation did not differ significantly. Heterogeneity was substantial for several continuous outcomes, with prediction intervals crossing the null for several estimates, indicating that the magnitude of benefit varied considerably between studies. Some clinical associations were also sensitive to eligibility-restricted analyses. Robot-assisted cannulated-screw fixation improves technical execution compared with freehand fixation. Patient-important clinical superiority and economic value have not been established, and evidence concerning learning curves, operator acceptability and system reliability remains insufficient. Current evidence does not support routine widespread adoption; adequately powered multicentre randomised trials incorporating economic and implementation evaluation are required.

Humans

Glucocorticoids and placental 11βHSD2 - A systematic review of human studies and animal models.

CONTEXT: Elevated prenatal glucocorticoid (GC) exposure is linked to adverse offspring outcomes. The placental enzyme 11β-hydroxysteroid-dehydrogenase-type-2 (11βHSD2) protects the fetus by converting maternal derived cortisol to inactive cortisone. Although in vitro studies suggest GC mediated upregulation of 11βHSD2, in vivo evidence remains inconclusive. METHODS: PubMed, Embase, and PsycInfo were searched in October 2024 for human and mammalian animal studies on endogenous or exogenous GCs during pregnancy and associations with placental 11βHSD2 (mRNA, protein, activity, gene methylation). Narrative synthesis was conducted due to heterogeneity precluding meta-analysis. RESULTS: Eighteen studies (eight human, ten animal populations) met inclusion criteria. Exogenous GC exposure was associated with modifications in placental 11βHSD2 expression in animal models, with effects varying by substance, timing, and species. Dexamethasone trended towards increased expression in rodents, whereas betamethasone increased expression in non-human primates but not rodents. Human studies on endogenous GCs showed inconsistent associations with 11βHSD2 changes. In asthmatic pregnancies, moderate inhaled GC-use maintained enzyme activity compared to untreated patients. No convincing sex-specific trend emerged. CONCLUSIONS: GC exposure alters placental 11βHSD2 in a substance- and species-specific way; translational relevance remains limited based on current literature. Future studies should employ technological advances and include GC-sensitive biomarkers to clarify mechanisms of maternal-fetal stress transmission.

Female

Comparative safety and operative efficiency of surgical approaches for open reduction and internal fixation of mandibular condylar fractures: a systematic review and network meta-analysis.

BACKGROUND: The optimal surgical approach for mandibular condyle fractures remains controversial, particularly regarding the trade-off between facial nerve safety and surgical efficiency. METHODS: Our systematic review and frequentist NMA analyzed studies evaluating open reduction and internal fixation (ORIF) for mandibular condyle fractures. The primary safety outcome was transient or persistent (≥6 months) facial nerve weakness. The efficiency outcome was operative exposure time. Surgical approaches were categorized, and random-effects NMAs estimated odds ratios (ORs) and mean differences (MDs). Treatments were ranked using P-scores, and clustered rankings explored safety-efficiency relationships. RESULTS: Overall, 121 studies (n = 6659 patients) were included. For facial nerve safety, endoscope-assisted (EA), preauricular transmasseteric anteroparotid (PATMA), and high submandibular (HSMA) approaches ranked highest, while the retromandibular transparotid (RMTA) approach carried a higher risk. Analyses restricted to persistent weakness yielded consistent results. For exposure time, submandibular (SM), HSMA, and retromandibular transmasseteric anteroparotid (RMTMA) approaches were most efficient. Clustered ranking analysis identified HSMA and RMTMA as achieving the best overall balance between safety and efficiency. Subgroup analyses confirmed the overall hierarchy, though evidence for high-level and intracapsular fractures remains limited. CONCLUSIONS: HSMA and RMTMA offer an optimal compromise between safety and efficiency for extracapsular condylar fractures, while EA may minimize nerve injury risk where technical expertise allows. High-quality comparative trials - particularly for intracapsular fractures - are warranted.

Humans

Epidemiological status of bovine viral diarrhea virus in water buffalo (Bubalus bubalis): A global systematic review and meta-analysis.

Bovine viral diarrhea virus (BVDV) remains a neglected viral disease in water buffalo despite its significant economic impact in production systems. Although limited epidemiological studies have been reported worldwide, the serostatus and active infection in buffalo have not been systematically reviewed. A systematic review and meta-analysis were conducted to estimate BVDV prevalence in water buffalo and identify associated epidemiological factors. Relevant studies published up to January 31, 2026, were retrieved from five electronic databases. A total of 49 studies were identified from 15 different countries were found for inclusion. A random-effects model was used to estimate pooled-prevalence and assess heterogeneity among studies. A meta-analysis of 37 studies (9270 buffalo) estimated a pooled BVDV seroprevalence of 30.5%, while analysis of 16 studies (7189 animals) indicated an antigen prevalence of 16.5%. Continent-wise analysis revealed the highest BVDV seroprevalence in South-America (44.0%), while antigen prevalence was highest in Africa (21.2%) followed by Asia at 12.2%, and no BVDV data reported from North-America. Among the different countries, the highest BVDV seroprevalence was detected in Turkey (61.6%) and Argentina (59.0%), while antigen prevalence was highest in Egypt (21.2%), with lower estimates in Brazil (11.8%) and Iraq (11.3%). Notably, high heterogeneity (I2 > 90%) was observed in the all-pooled estimates, indicating variations in sampling period, age, sex, sample source and types, diagnostic methods, production-system, and study quality. These findings demonstrate the widespread presence of BVDV in water buffalo populations and indicate the need for targeted control strategies to mitigate its impact on health and productivity.

Animals

A systematic literature review on low-grade myofibroblastic sarcoma of the trunk.

BACKGROUND: Low-grade myofibroblastic sarcoma (LGMS) is a rare malignant mesenchymal tumor, with primary trunk involvement being particularly uncommon. Due to its rarity, associated diagnostic challenges, and variability in management, a comprehensive evaluation of the available evidence is required. This study aims to systematically review the clinical characteristics, treatment strategies, and outcomes of truncal LGMS. METHODS: A systematic literature search was conducted using PubMed, Web of Science, and Embase for articles published from January 1998 to January 2026. The review included full-text articles involving patients with a pathologically confirmed diagnosis of truncal LGMS. The collected data included patient demographics, tumor features, treatment modalities, recurrence, and follow-up status. RESULTS: Of the 404 studies initially identified, 30 studies involving 59 patients with pathologically confirmed truncal LGMS met the inclusion criteria. Outcome analyses of therapeutic management and clinical course included 45 patients with complete follow-up data, including 42 surgically treated patients and 3 non-surgically managed patients. The final evidence base consisted solely of retrospective studies and case reports. No prospective studies or randomized controlled trials were identified. Consequently, a descriptive statistical analysis was conducted instead of a meta-analysis. CONCLUSION: Current evidence indicates that wide excision with negative margins may be a reasonable primary treatment option for truncal LGMS, with case-based reports showing numerically lower recurrence after wide excision, although the evidence is limited and potentially confounded by multiple factors. Radiotherapy or chemotherapy may be considered only on a highly individualized basis for selected unresectable, recurrent, metastatic, anatomically constrained, or margin-positive cases. Given the very limited sample size and heterogeneous treatment indications across published cases, treatment efficacy cannot be reliably estimated from the available data. Prolonged long-term regular follow-up is recommended for all patients, considering the risk of late recurrence.

Humans

Predictive Models for Hypoglycemia Risk in Haemodialysis Patients With Diabetic Kidney Disease: Systematic Review and Meta-Analysis.

AIM: To provide evidence for selecting and developing reliable clinical assessment tools for hypoglycemia in diabetic kidney disease patients during haemodialysis. DESIGN: Review. METHODS: Systematic searches were performed in 9 Chinese and English databases to collect literature regarding the development of hypoglycemia risk prediction models in haemodialysis patients with diabetic kidney disease. Two reviewers independently performed literature screening, data extraction, risk-of-bias assessment, and applicability evaluation. The Prediction Model Risk of Bias Assessment Tool was used to assess the risk of bias and applicability of the included studies. Meta-analysis was conducted using R software. DATA SOURCES: CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, EMbase, Web of Science, and CINAHL. The search period covered from the establishment date of each database to December 2025. RESULTS: Six studies, comprising six prediction models, were included. Two studies performed internal validation, and three conducted external validation. All models reported the area under the curve, ranging from 0.813 to 0.866, and calibration measures. Four studies were rated as having a high risk of bias, while all six demonstrated good overall applicability. The meta-analysis showed that the pooled AUC value of the six studies was 0.846 (95% CI: 0.823-0.867). CONCLUSION: Research on hypoglycemia risk prediction models in haemodialysis patients with diabetic kidney disease remains in the developmental stage. Although the included prediction models exhibited satisfactory apparent discriminatory ability and clinical applicability, most of the original studies suffered from a high risk of bias and lacked adequate validation. The true predictive performance and clinical application value of these models remain to be further verified. Accordingly, routine and unconditional clinical application is not recommended at this stage. Future studies should include more high-quality, multicenter external validation and develop models with high generalizability, favourable clinical applicability, and robust predictive performance to facilitate early identification of hypoglycemia risk in this population. IMPACT: This study systematically evaluated the hypoglycemia risk prediction models for diabetic kidney disease patients during haemodialysis, and the research on hypoglycemia risk prediction models for maintenance haemodialysis patients during dialysis is still in the development stage. This study provides a reference for clinical medical staff to select or develop hypoglycemia risk prediction and assessment tools for diabetic kidney disease patients during haemodialysis. REPORTING METHOD: This study was conducted in accordance with the relevant guidelines of the EQUATOR Network and followed the TRIPOD-SRMA Checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. TRIAL REGISTRATION: PROSPERO: CRD420251243352.

Humans

Fluoride as a Modifier of Metallome Homeostasis: A Systematic Review of Animal Studies.

Fluoride is widely used for caries prevention due to its effects on mineralized tissues, yet its potential role as a modifier of systemic metal homeostasis remains insufficiently explored. This systematic review synthesizes preclinical evidence on the association between fluoride exposure and changes in metal and semi-metal concentrations across biological matrices. A comprehensive search strategy was conducted across major databases without language or date restrictions, following SyRF, CAMARADES and PRISMA 2020 guidelines. Thirty-one animal studies were included, encompassing multiple species, exposure conditions and analytical approaches. Despite substantial methodological heterogeneity, consistent patterns emerged. Fluoride exposure was associated with element-specific redistribution of the metallome rather than uniform change. Essential elements were predominantly depleted, most consistently zinc, copper and manganese, whereas the toxic metals lead and cadmium tended to be retained. This contrast between homeostatically regulated essential elements that are lost and non-regulated toxic metals that accumulate supports the hypothesis that fluoride differentially modifies the distribution and retention of co-existing elements. The novelty of this review lies in integrating metallomic outcomes across experimental models, highlighting fluoride as a potential systemic modulator rather than a tissue-specific agent. Although variability in study design and risk of bias limits causal inference, the consistent directionality of findings across models reinforces their biological plausibility and translational relevance.

Animals