POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery patients (POSITiVE) II-study protocol of a randomized clinical trial.

BACKGROUND: One single-center randomized clinical trial showed that INTELLiVENT-adaptive support ventilation (ASV) is superior to conventional ventilation with respect to the quality of ventilation in post-cardiac surgery patients. Other studies showed that this automated ventilation mode reduces the number of manual interventions at the ventilator in various types of critically ill patients. In this multicenter study in patients post-cardiac surgery, we test the hypothesis that INTELLiVENT-ASV is superior to conventional ventilation with respect to the quality of ventilation. METHODS: "POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery patients II (POSITiVE II)" is an international, multicenter, two-group randomized clinical superiority trial. In total, 328 cardiac surgery patients will be randomized. Investigators screen patients aged > 18 years of age, scheduled for elective cardiac surgery, and expected to receive postoperative ventilation in the ICU for longer than 2 h. Patients either receive automated ventilation by means of INTELLiVENT-ASV or ventilation that is not automated by means of a conventional ventilation mode. The primary endpoint is quality of ventilation, defined as the proportion of postoperative ventilation time characterized by exposure to predefined optimal, acceptable, and critical (injurious) ventilatory parameters in the first two postoperative hours. One major secondary endpoint is ICU team staff workload, captured by the ventilator software collecting manual settings on alarms. Patient-centered endpoints include duration of postoperative ventilation and length of stay in ICU. DISCUSSION: POSITiVE II is the first international, multicenter, randomized clinical trial designed to confirm that POStoperative INTELLiVENT-ASV is superior to non-automated conventional ventilation and secondary to determine if this closed-loop ventilation mode reduces ICU team staff workload. The results of POSITiVE II will support intensive care teams in their choices regarding the use of automated ventilation in postoperative care of uncomplicated cardiac surgery patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT06178510 . Registered on December 4, 2023.

Assessing the Fractional Curve for Proper Management of Adult Degenerative Scoliosis.

Adult degenerative scoliosis (ADS) is a coronal plane deformity often accompanied by sagittal plane malalignment. Surgical correction may involve the major and/or distally-located fractional curves (FCs). Correction of the FC has been increasingly recognized as key to ameliorating radicular pain localized to the FC levels. The present study aims to summarize the literature on the rationale for FC correction in ADS. Three databases were systematically reviewed to identify all primary studies reporting the rationale for correcting the FC in ADS. Articles were included if they were English full-text studies with primary data from ADS ( ≥ 18 years old) patients. Seventy-four articles were identified, of which 12 were included after full-text review. Findings suggest FC correction with long-segment fusion terminating at L5 increases the risk of distal junctional degeneration as compared to constructs instrumenting the sacrum. Additionally, circumferential fusion offers greater FC correction, lower reoperation risk, and shorter construct length. Minimally invasive surgery (MIS) techniques may offer effective radiographic correction and improve leg pain associated with foraminal stenosis on the FC concavity, though experiences are limited. Open surgery may be necessary to achieve adequate correction of severe, highly rigid deformities. Current data support major curve correction in ASD where the FC concavity and truncal shift are concordant, suggesting that the FC contributes to the patient's overall deformity. Circumferential fusion and the use of kickstand rods can improve correction and enhance the stability and durability of long constructs. Last, MIS techniques show promise for milder deformities but require further investigation.

Lymphotoxin ß receptor and tertiary lymphoid organs shape acute and chronic allograft rejection.

Solid organ transplantation remains the life-saving treatment for end-stage organ failure, but chronic rejection remains a major obstacle to long-term allograft outcomes and has not improved substantially. Tertiary lymphoid organs (TLO) are ectopic lymphoid structures that form under conditions of chronic inflammation, and evidence from human transplantation suggests that TLO regularly form in allografts undergoing chronic rejection. In this study, we utilized a mouse renal transplantation model and manipulation of the lymphotoxin alpha (LTα) - lymphotoxin beta receptor (LTßR) pathway, which is essential for TLO formation, to define the role of TLO in transplantation. We showed that intragraft TLO are sufficient to activate the alloimmune response and mediate graft rejection in a model where the only lymphoid organs are TLO in the allograft. When transplanted to recipients with a normal set of secondary lymphoid organs, the presence of graft TLO or LTα overexpression accelerated rejection. If the LTßR pathway was disrupted in the donor graft, TLO formation was abrogated, and graft survival prolonged. Intravital microscopy of renal TLO demonstrated that local T and B cell activation in TLOs is similar to that observed in secondary lymphoid organs. In summary, we demonstrated that immune activation in TLO contributes to local immune responses, leading to earlier allograft failure. TLO and the LTαß-LTßR pathway are therefore prime targets to limit local immune responses and prevent allograft rejection. These findings are applicable to other diseases such as autoimmunity or tumors, where either limiting or boosting local immune responses is beneficial and improves disease outcomes.

Anti-Leptospira Seroprevalence and Associated Risk Factors among Forestry Workers in Lower Saxony, North-West Germany.

As leptospirosis is re-emerging, a seroprevalence study was conducted, assessing the prevalence of anti-Leptospira IgG antibodies and infection-associated risk factors among forestry workers (FWs) in Lower Saxony, Germany, to develop targeted public health measures. Sera of 877 FWs, sampled in 2016, were tested for anti-Leptospira seropositivity by commercial IgG-ELISA. Data on demographics and Leptospira-specific exposures, knowledge, sources of information, and preventive measures were collected by standardized, self-administered questionnaire. A subset of 244 sera was retested via in-house IgG-ELISA. Risk factors were assessed from the subset using multivariable logistic regression analysis. The commercial IgG-ELISA revealed a seroprevalence of 4.8% (95% confidence interval CI95 = 3.5-6.4). Of the 601 FWs who completed the questionnaire, 67.9% had been informed about leptospirosis and Leptospira spp., mainly by employers (55.2%) and peers (38.9%). Positive associations with seropositivity were observed for canoeing (adjusted odds ratio (aOR) = 2.35, p = 0.044), touching rodents (aOR = 2.4, p = 0.021), and living close to beech trees (aOR = 2.18, p = 0.075). Frequently cleaning animal stables was negatively associated (aOR = 0.20, p = 0.002). The unexpected positive association with wearing gloves when handling plants and soil (aOR = 2.16, p = 0.011) needs further discussion. Overall, seroprevalence was in the range of other studies in Germany. The identified factors will be used to develop targeted information reaching out to at-risk groups tapping various communication channels.

Treatment-free survival and partitioned survival analysis of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib: 5-year update of CheckMate 214.

BACKGROUND: Immunotherapy can be associated with prolonged disease control even after cessation of treatment without the need for further cancer-directed therapy. Treatment-related adverse events (TRAEs) can also persist after discontinuation of therapy. Treatment-free survival (TFS) with and without toxicity as a component of a partitioned survival model can characterize patient survival time, which is not captured by standard outcome measures. METHODS: Data from 1096 patients with advanced renal cell carcinoma treated with first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in the CheckMate 214 trial were analyzed. TFS was defined as the area between two Kaplan-Meier curves for time from randomization to protocol therapy discontinuation and time from randomization to subsequent systemic therapy initiation or death, estimated as the difference in 60-month restricted mean times with confidence intervals (CIs) obtained using bootstrap sampling. Time on protocol therapy and TFS were further characterized as time with and without grade 2+ and 3+TRAEs. Survival functions were estimated in subgroups including International Metastatic Renal Cell Carcinoma Database Consortium risk groups using the Kaplan-Meier method. RESULTS: At 5 years from randomization, 48% of patients treated with NIVO+IPI and 37% of patients treated with SUN were alive. In the intent-to-treat population, 18% of the NIVO+IPI-treated and 5% of SUN-treated patients are surviving treatment-free. For favorable-risk patients, the 60-month mean TFS was 14.4 months for NIVO+IPI versus 5.5 months for SUN (difference 8.9 months (95% CI 4.9 to 12.8)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 5.0 and 2.1 months, respectively, and with grade 3+TRAEs was 1.2 and 0.3 months, respectively. For intermediate/poor-risk patients, the 60-month mean TFS was 10.1 months for NIVO+IPI versus 4.1 months for SUN (difference 6.1 months (95% CI 4.2 to 7.9)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 4.0 versus 2.0 months, respectively, and 0.6 versus 0.3 months with grade 3+TRAEs. CONCLUSIONS: Although overall survival was similar, favorable-risk patients treated with NIVO+IPI spent more time surviving treatment-free with and without toxicity versus SUN after 60 months of follow-up. Intermediate/poor-risk patients treated with NIVO+IPI had longer survival and longer TFS without toxicity versus SUN. TRIAL REGISTRATION NUMBER: NCT02231749.

Immunisation of pigs with recombinant HEV vaccines does not protect from infection with HEV genotype 3.

Hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide. Up to now, no approved treatment nor a globally licensed vaccine is available. Several recombinant HEV vaccines have been developed to protect against HEV infection in humans, including the commercially available Hecolin vaccine, which are mainly based on HEV genotype 1. However, the efficacy of these vaccines against other HEV genotypes, especially genotype 3 is unknown. In this study, we evaluated the protective efficacy of Hecolin® and a novel genotype 3-based vaccine p239(gt3) against HEV-3 in a pig infection model. Pigs were divided into three groups: one group was vaccinated with Hecolin®, the second group was vaccinated with p239(gt3), and the control group received no vaccine. All pigs were subsequently challenged with HEV genotype 3 to assess the effectiveness of the vaccines. Although all immunised animals developed a high titer of neutralizing antibodies, the results showed that both vaccine applications could not provide complete protection against HEV (gt3) infection: Two out of four animals of the Hecolin® group displayed even virus shedding, and viral RNA could be detected in bile and/or liver of three out of four animals in both vaccination groups. Only one out of four animals in each group was fully protected. Neither Hecolin® nor the novel p239(gt3) vaccine provided sufficient protection against genotype 3 infection. While Hecolin® only partial protected pigs from HEV shedding, the novel p239(gt3) vaccine was at least able to prevent infected pigs from virus shedding. The results highlight the need for further development of HEV vaccines that exhibit broad protection against multiple HEV genotypes and the use of appropriate animal infection models.

Physiological and clinical effects of trunk inclination adjustment in patients with respiratory failure: a scoping review and narrative synthesis.

BACKGROUND: Adjusting trunk inclination from a semi-recumbent position to a supine-flat position or vice versa in patients with respiratory failure significantly affects numerous aspects of respiratory physiology including respiratory mechanics, oxygenation, end-expiratory lung volume, and ventilatory efficiency. Despite these observed effects, the current clinical evidence regarding this positioning manoeuvre is limited. This study undertakes a scoping review of patients with respiratory failure undergoing mechanical ventilation to assess the effect of trunk inclination on physiological lung parameters. METHODS: The PubMed, Cochrane, and Scopus databases were systematically searched from 2003 to 2023. INTERVENTIONS: Changes in trunk inclination. MEASUREMENTS: Four domains were evaluated in this study: 1) respiratory mechanics, 2) ventilation distribution, 3) oxygenation, and 4) ventilatory efficiency. RESULTS: After searching the three databases and removing duplicates, 220 studies were screened. Of these, 37 were assessed in detail, and 13 were included in the final analysis, comprising 274 patients. All selected studies were experimental, and assessed respiratory mechanics, ventilation distribution, oxygenation, and ventilatory efficiency, primarily within 60 min post postural change. CONCLUSION: In patients with acute respiratory failure, transitioning from a supine to a semi-recumbent position leads to decreased respiratory system compliance and increased airway driving pressure. Additionally, C-ARDS patients experienced an improvement in ventilatory efficiency, which resulted in lower PaCO2 levels. Improvements in oxygenation were observed in a few patients and only in those who exhibited an increase in EELV upon moving to a semi-recumbent position. Therefore, the trunk inclination angle must be accurately reported in patients with respiratory failure under mechanical ventilation.

Trophic effects of Bti-based mosquito control on two top predators in floodplain pond mesocosms.

Chironomid (Diptera: Chironomidae) larvae play a key role in aquatic food webs as prey for predators like amphibian and dragonfly larvae. This trophic link may be disrupted by anthropogenic stressors such as Bacillus thuringiensis var. israelensis (Bti), a biocide widely used in mosquito control. In a companion study, we recorded a 41% reduction of non-target larval chironomids abundance in outdoor floodplain pond mesocosms (FPMs) treated with Bti. Therefore, we examined the diet of two top predators in the FPMs, larvae of the palmate newt (Salamandridae: Lissotriton helveticus) and dragonfly (Aeshnidae: predominantly Anax imperator), using bulk stable isotope analyses of carbon and nitrogen. Additionally, we determined neutral lipid fatty acids in newt larvae to assess diet-related effects on their physiological condition. We did not find any effects of Bti on the diet proportions of newt larvae and no significant effects on the fatty acid content. We observed a trend in Aeshnidae larvae from Bti-FPMs consuming a higher proportion of large prey (Aeshnidae, newt, damselfly larvae; ~42%), and similar parts of smaller prey (chironomid, mayfly, Libellulidae, and zooplankton), compared to controls. Our findings may suggest bottom-up effects of Bti on aquatic predators but should be further evaluated, for instance, by using compound-specific stable isotope analyses of fatty acids or metabarcoding approaches.

A method to efficiently and rapidly approximate the vectorial fields generated by large area metasurfaces.

In order to calculate the electromagnetic fields that are produced after light passes through a metasurface, simulation methods such as the Finite-Difference Time-Domain method are often employed. While these provide a good approximation to the fields, the level of detail at which the volume of space that the light is propagating in needs to be modelled and the time for which simulations need to run, mean that as the area of the metasurface is increased these simulations rapidly become unwieldy. In this paper we show how the result of a FDTD simulation of a unit cell can be used to generate a good approximation of the vectorial field that large area metasurfaces will generate, but using a fraction of the computational resources. This approach can provide an intermediate design step, allowing potentially interesting designs to be rapidly identified or discarded.

Outcomes of Tube Thoracostomies in COVID-19 Patients: A Retrospective Cohort Study in the University of the Philippines - Philippine General Hospital COVID-19 Referral Center.

Objective: To describe the treatment outcomes of patients who underwent tube thoracostomy for pleural complications in patients with COVID-19 and determine the association between patient profile and treatment outcomes. Methods: A single-institution retrospective review of patients who underwent tube thoracostomy for complications of COVID-19 infection in the University of the Philippines - Philippine General Hospital (UP-PGH) from March 30, 2020, to March 31, 2021, was performed. These patients' demographic and clinical profiles were evaluated using median, frequencies, and percentages. The association between patient profile, and mortality and reintervention rates was assessed using univariable Cox proportional hazards regression analysis. Results: Thirty-four (34) of 3,397 patients (1.00%) admitted for COVID-19 pneumonia underwent tube thoracostomy. Of these, 34, 47.06% were male, 52.94% were female, the median age was 51.5 years old, 85.29% had comorbid conditions, and 29.41% had a previous or ongoing tuberculous infection. The most common indication for tube thoracostomy was pleural effusion (61.76%), followed by pneumothorax (29.41%), and pneumo-hydrothorax (8.82%). The mortality rate was 38.24%, and the reintervention rate was 14.71%. Intubated patients had 14.84 times higher mortality hazards than those on room air. For every unit increase in procalcitonin levels, the mortality hazards were increased by 1.06 times. Conclusion: An increasing level of oxygen support on admission and a level of procalcitonin were directly related to mortality risk in COVID-19 patients who underwent tube thoracostomy for pleural complications. There is insufficient evidence to conclude that patient-related, COVID-19 pneumonia-related, and procedure-related factors included in this study were significantly associated with reintervention risk.

Clinical and Economic Implications of Hydroxyurea Intolerance in Polycythemia Vera in Routine Clinical Practice.

Background/Objectives: Polycythemia vera (PV) is a chronic hematologic neoplasm commonly treated with hydroxyurea (HU). We utilized the advanced digitalized database of Maccabi Healthcare Services to retrospectively investigate the clinical and economic implications of HU intolerance in the routine clinical care of PV patients in Israel. Methods: We collected data on demographics, physician visits, hospitalizations, laboratory results, medication purchases, cardiovascular and thrombotic events, mental health, economic outcomes, and mortality. Outcomes included cardiovascular and other thrombotic events, disease progression, mental health events, economic outcomes, and overall mortality. Results: Of the 830 patients studied, 3 (0.4%) were resistant to HU treatment, 318 (38.3%) were intolerant to HU treatment, and 509 (61.3%) were stable on HU treatment. The venous thrombosis rate was significantly higher among HU-intolerant compared to HU-stable patients (1.58 vs. 0.47 per 100 person-years [PY], respectively; p < 0.001). The rate of progression to myelofibrosis was 6 vs. 0.9 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively (p < 0.001), and the rate of progression to acute myeloid leukemia (AML) was 1.16 vs. 0.2 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively (p < 0.001). The phlebotomy requirement, mortality rate, and total hospitalization days among HU-intolerant patients were significantly higher than in HU-stable patients (p = 0.049, p < 0.001, p < 0.001, respectively). More mental health-related events were noted in HU-intolerant patients vs. HU-stable patients (p = 0.007), and the total healthcare cost ratio was 2.65 for the HU-intolerant patients compared with HU-stable patients. Conclusions: This study suggests that HU-intolerant patients are more likely to have worse outcomes than HU-stable patients, highlighting the need for the close monitoring of these patients for disease-related complications or progression.

The undetected murder? Evaluation and validation of a practicable and rapid inductively coupled plasma-mass spectrometry method for the detection of arsenic, lead, and thallium intoxications in postmortem blood.

Homicide, suicide, or accident - elemental intoxication may be a cause in each of these types of deaths. Inductively coupled plasma mass spectrometry (ICP-MS) has emerged as the gold standard analytical method for toxic metal analysis in both clinical and forensic settings. An ICP-MS method was developed using a modified acidic workup for the quantitative determination of arsenic, lead, and thallium. Method validation focused on the assessment of linearity, between- and within-day precisions, limits of detection (LoD) and lower limits of quantification (LLoQ), and carryover. The method was applied to analysis of postmortem peripheral blood samples from 279 forensic cases for which orders for chemical-toxicological examination had been received from the public prosecutor's office. Using six-point and one-point calibrations (latter for rapid screening purposes), precisions and accuracies ranged from -4.8 to 5.8% and -6.4 to 7.5%. Analytical sensitivities for As, Pb, and Tl were 0.08, 0.18, and 0.01 µg/l (LoD) and 0.23, 0.66, and 0.03 µg/l (LLoQ), respectively. Observed postmortem peripheral blood concentrations were As, 1.31 ± 3.42 µg/L; Pb, 17.4 ± 13.1 µg/L; and Tl, 0.11 ± 0.07 µg/L (mean ± standard deviation [SD]). Elemental concentrations, determined in additional quality control samples, were in good agreement to those obtained with an external ICP-MS method based on alkaline sample processing. The current method is practicable and compatible with an ICP-MS system used for trace element analysis in an accredited medical laboratory. It allows for implementation of low-threshold investigations when metal intoxications are suspected in forensic routine.

The role of functional vitamin D deficiency and low vitamin D reservoirs in relation to cardiovascular health and mortality.

OBJECTIVES: The role of vitamin D deficiency in cardiovascular disease (CVD) is controversial. Inherent biological and analytical limitations compromise the specificity of widely used 25-hydroxyvitamin D [25(OH)D] cut-offs. Simultaneous determination of 25(OH)D and 24,25-dihydroxyvitamin D [24,25(OH)2D] permits a functional assessment of vitamin D metabolism. The present study compared the associations of functional vitamin D deficiency and low vitamin D reservoirs with CVD mortality and CVD burden. METHODS: 25(OH)D, 24,25(OH)2D, the degree of coronary obstruction on angiography, high-sensitive cardiac troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP), and 10-year CVD mortality were obtained from 2,456 participants of the LURIC (Ludwigshafen Risk and Cardiovascular Health) study. RESULTS: Neither low 25(OH)D concentrations nor functional vitamin D deficiency were associated with the number of atherosclerotic coronary arteries or the degree of coronary obstruction. Over a median follow-up of 9.9 years, 454 participants died (23.6 %) due to CVD. CVD mortality was doubled in individuals with 25(OH)D concentrations below the widely used cut-off for deficiency of <50 nmol/L [20 ng/mL] (21.6 vs. 11.5 %). In individuals with and without functional vitamin D deficiency, CVD mortality was 25.0 and 16.7 %, respectively. NT-proBNP and heart failure prevalence were also higher in vitamin D deficient individuals. CONCLUSIONS: Vitamin D deficient individuals have markedly higher CVD mortality, but only marginally higher hs-cTnT concentrations. A higher prevalence of heart failure and higher NT-proBNP concentrations suggest a link between vitamin D deficiency and cardiac function. The traditional and metabolic assessment of vitamin D status showed comparable associations for the different parameters of cardiac health.

Differences in the molecular organisation of tumours along the colon are linked to interactions within the tumour ecosystem.

Tumours exhibit significant heterogeneity in their molecular profiles across patients, largely influenced by the tissue of origin, where certain driver gene mutations are predominantly associated with specific cancer types. Here, we unveil an additional layer of complexity: some cancer types display anatomic location-specific mutation profiles akin to tissue-specificity. To better understand this phenomenon, we concentrate on colon cancer. While prior studies have noted changes of the frequency of molecular alterations along the colon, the underlying reasons and whether those changes occur rather gradual or are distinct between the left and right colon, remain unclear. Developing and leveraging stringent statistical models on molecular data from 522 colorectal tumours from The Cancer Genome Atlas, we reveal disparities in molecular properties between the left and right colon affecting many genes. Interestingly, alterations in genes responsive to environmental cues and properties of the tumour ecosystem, including metabolites which we quantify in a cohort of 27 colorectal cancer patients, exhibit continuous trends along the colon. Employing network methodologies, we uncover close interactions between metabolites and genes, including drivers of colon cancer, showing continuous abundance or alteration profiles. This underscores how anatomic biases in the composition and interactions within the tumour ecosystem help explaining gradients of carcinogenesis along the colon.

Tangent space functional reconfigurations in individuals at risk for alcohol use disorder.

Human brain function dynamically adjusts to ever-changing stimuli from the external environment. Studies characterizing brain functional reconfiguration are nevertheless scarce. Here we present a principled mathematical framework to quantify brain functional reconfiguration when engaging and disengaging from a stop signal task (SST). We apply tangent space projection (a Riemannian geometry mapping technique) to transform functional connectomes (FCs) and quantify functional reconfiguration using the correlation distance of the resulting tangent-FCs. Our goal was to compare functional reconfigurations in individuals at risk for alcohol use disorder (AUD). We hypothesized that functional reconfigurations when transitioning in/from a task would be influenced by family history of alcohol use disorder (FHA) and other AUD risk factors. Multilinear regression model results showed that engaging and disengaging functional reconfiguration were driven by different AUD risk factors. Functional reconfiguration when engaging in the SST was negatively associated with recent drinking. When disengaging from the SST, however, functional reconfiguration was negatively associated with FHA. In both models, several other factors contributed to the explanation of functional reconfiguration. This study demonstrates that tangent-FCs can characterize task-induced functional reconfiguration, and that it is related to AUD risk.

Potential Mediating Role of Iron Biomarkers in the Association of Sex With Glucose, Insulin, and Type 2 Diabetes.

Context: Sex-specific prevalence and incidence of type 2 diabetes (T2D) have been reported, but the underlying mechanisms are uncertain. Objective: In this study, we aimed to investigate whether iron biomarkers mediate the association between biological sex and glucose metabolism and the incidence of T2D. Methods: We used data from the general population enrolled in the prospective Prevention of REnal and Vascular ENd-stage Disease study in Groningen, The Netherlands. We measured ferritin, transferrin saturation (TSAT), hepcidin, soluble transferrin receptor (sTfR), fasting plasma glucose (FPG), fasting plasma insulin (FPI) levels, and incidence of T2D. We used multivariable regression and mediation analyses to investigate our hypothesis. All iron biomarkers, FPG, and FPI were log-transformed. Results: The mean (SD) age of the 5312 (51.3% female) individuals was 52.2 (11.6) years. Compared with males, females had lower FPG (ß = -.01; 95% CI -0.02, -0.01) and FPI (ß = -.03; 95% CI -0.05, -0.02) levels. Ferritin, hepcidin, and sTfR showed potential mediating effects on the association between sex and FPG, 21%, 5%, and 7.1%, respectively. Furthermore, these variables mediated 48.6%, 5.7%, and 3.1% of the association between sex and FPI, respectively. Alternatively, TSAT had a suppressive mediating role in the association of sex with FPG and FPI. The incidence of T2D was lower in females than in males (hazard ratio 0.58; 95% CI 0.44, 0.77), with 19.2% of this difference being mediated by ferritin. Conclusion: Iron biomarkers may partially mediate the association between sex and glucose homeostasis. Future studies addressing the causality of our findings are needed.