Catch bond kinetics are instrumental to cohesion of fire ant rafts under load.

Dynamic networks composed of constituents that break and reform bonds reversibly are ubiquitous in nature owing to their modular architectures that enable functions like energy dissipation, self-healing, and even activity. While bond breaking depends only on the current configuration of attachment in these networks, reattachment depends also on the proximity of constituents. Therefore, dynamic networks composed of macroscale constituents (not benefited by the secondary interactions cohering analogous networks composed of molecular-scale constituents) must rely on primary bonds for cohesion and self-repair. Toward understanding how such macroscale networks might adaptively achieve this, we explore the uniaxial tensile response of 2D rafts composed of interlinked fire ants (S. invicta). Through experiments and discrete numerical modeling, we find that ant rafts adaptively stabilize their bonded ant-to-ant interactions in response to tensile strains, indicating catch bond dynamics. Consequently, low-strain rates that should theoretically induce creep mechanics of these rafts instead induce elastic-like response. Our results suggest that this force-stabilization delays dissolution of the rafts and improves toughness. Nevertheless, above 35[Formula: see text] strain low cohesion and stress localization cause nucleation and growth of voids whose coalescence patterns result from force-stabilization. These voids mitigate structural repair until initial raft densities are restored and ants can reconnect across defects. However mechanical recovery of ant rafts during cyclic loading suggests that-even upon reinstatement of initial densities-ants exhibit slower repair kinetics if they were recently loaded at faster strain rates. These results exemplify fire ants' status as active agents capable of memory-driven, stimuli-response for potential inspiration of adaptive structural materials.

Material assembly from collective action of shape-changing polymers.

Some animals form transient, responsive and solid-like ensembles through dynamic structural interactions. These ensembles demonstrate emergent responses such as spontaneous self-assembly, which are difficult to achieve in synthetic soft matter. Here we use shape-morphing units comprising responsive polymers to create solids that self-assemble, modulate their volume and disassemble on demand. The ensemble is composed of a responsive hydrogel, liquid crystal elastomer or semicrystalline polymer ribbons that reversibly bend or twist. The dispersions of these ribbons mechanically interlock, inducing reversible aggregation. The aggregated liquid crystal elastomer ribbons have a 12-fold increase in the yield stress compared with cooled dispersion and contract by 34% on heating. Ribbon type, concentration and shape dictate the aggregation and govern the global mechanical properties of the solid that forms. Coating liquid crystal elastomer ribbons with a liquid metal begets photoresponsive and electrically conductive aggregates, whereas seeding cells on hydrogel ribbons enables self-assembling three-dimensional scaffolds, providing a versatile platform for the design of dynamic materials.

The Causal Effect of Intra-Pancreatic Fat Deposition on Acute and Chronic Pancreatitis: A Mendelian Randomization Study.

INTRODUCTION: Recent associative studies have linked intra-pancreatic fat deposition (IPFD) with risk of pancreatitis, but the causal relationship remains unclear. METHODS: Utilizing Mendelian randomization, we evaluated the causal association between genetically predicted IPFD and pancreatitis. This approach utilized genetic variants from genome-wide association studies of IPFD (n=25,617), acute pancreatitis (n=6,787 cases/361,641 controls), and chronic pancreatitis (n=3,875 cases/361,641 controls). RESULTS: Genetically predicted IPFD was significantly associated with acute pancreatitis (OR per 1-SD increase: 1.40[95%CI:1.12-1.76], p=0.0032) and chronic pancreatitis (OR:1.64[95%CI:1.13-2.39], p=0.0097). DISCUSSION: Our findings support a causal role of IPFD in pancreatitis, suggesting that reducing IPFD could lower the risk of pancreatitis.

Blood coagulation in Prediabetes clusters-impact on all-cause mortality in individuals undergoing coronary angiography.

BACKGROUND: Metabolic clusters can stratify subgroups of individuals at risk for type 2 diabetes mellitus and related complications. Since obesity and insulin resistance are closely linked to alterations in hemostasis, we investigated the association between plasmatic coagulation and metabolic clusters including the impact on survival. METHODS: Utilizing data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, we assigned 917 participants without diabetes to prediabetes clusters, using oGTT-derived glucose and insulin, high-density lipoprotein cholesterol, triglycerides, and anthropometric data. We performed a comprehensive analysis of plasmatic coagulation parameters and analyzed their associations with mortality using proportional hazards models. Mediation analysis was performed to assess the effect of coagulation factors on all-cause mortality in prediabetes clusters. RESULTS: Prediabetes clusters were assigned using published tools, and grouped into low-risk (clusters 1,2,4; n = 643) and high-risk (clusters 3,5,6; n = 274) clusters. Individuals in the high-risk clusters had a significantly increased risk of death (HR = 1.30; CI: 1.01 to 1.67) and showed significantly elevated levels of procoagulant factors (fibrinogen, FVII/VIII/IX), D-dimers, von-Willebrand factor, and PAI-1, compared to individuals in the low-risk clusters. In proportional hazards models adjusted for relevant confounders, elevated levels of fibrinogen, D-dimers, FVIII, and vWF were found to be associated with an increased risk of death. Multiple mediation analysis indicated that vWF significantly mediates the cluster-specific risk of death. CONCLUSIONS: High-risk prediabetes clusters are associated with prothrombotic changes in the coagulation system that likely contribute to the increased mortality in those individuals at cardiometabolic risk. The hypercoagulable state observed in the high-risk clusters indicates an increased risk for cardiovascular and thrombotic diseases that should be considered in future risk stratification and therapeutic strategies.

Impact of physical fitness and exercise training on subcutaneous adipose tissue beiging markers in humans with and without diabetes and a high-fat diet-fed mouse model.

AIMS: Exercise training induces white adipose tissue (WAT) beiging and improves glucose homeostasis and mitochondrial function in rodents. This could be relevant for type 2 diabetes in humans, but the effect of physical fitness on beiging of subcutaneous WAT (scWAT) remains unclear. This translational study investigates if beiging of scWAT associates with physical fitness in healthy humans and recent-onset type 2 diabetes and if a voluntary running wheel intervention is sufficient to induce beiging in mice. MATERIALS AND METHODS: Gene expression levels of established beiging markers were measured in scWAT biopsies of humans with (n = 28) or without type 2 diabetes (n = 28), stratified by spiroergometry into low (L-FIT; n = 14 each) and high physical fitness (H-FIT; n = 14 each). High-fat diet-fed FVB/N mice underwent voluntary wheel running, treadmill training or no training (n = 8 each group). Following the training intervention, mitochondrial respiration and content of scWAT were assessed by high-resolution respirometry and citrate synthase activity, respectively. RESULTS: Secreted CD137 antigen (Tnfrsf9/Cd137) expression was three-fold higher in glucose-tolerant H-FIT than in L-FIT, but not different between H-FIT and L-FIT with type 2 diabetes. In mice, both training modalities increased Cd137 expression and enhanced mitochondrial content without changing respiration in scWAT. Treadmill but not voluntary wheel running led to improved whole-body insulin sensitivity. CONCLUSIONS: Higher physical fitness and different exercise interventions associated with higher gene expression levels of the beiging marker CD137 in healthy humans and mice on a high-fat diet. Humans with recent-onset type 2 diabetes show an impaired adipose tissue-specific response to physical activity.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with lower visceral and hepatic lipid content in recent-onset type 1 diabetes and type 2 diabetes.

AIM: To investigate the associations of the Dietary Approaches to Stop Hypertension (DASH) score with subcutaneous (SAT) and visceral (VAT) adipose tissue volume and hepatic lipid content (HLC) in people with diabetes and to examine whether changes in the DASH diet were associated with changes in these outcomes. METHODS: In total, 335 participants with recent-onset type 1 diabetes (T1D) and type 2 diabetes (T2D) from the German Diabetes Study were included in the cross-sectional analysis, and 111 participants in the analysis of changes during the 5-year follow-up. Associations between the DASH score and VAT, SAT and HLC and their changes were investigated using multivariable linear regression models by diabetes type. The proportion mediated by changes in potential mediators was determined using mediation analysis. RESULTS: A higher baseline DASH score was associated with lower HLC, especially in people with T2D (per 5 points: -1.5% [-2.7%; -0.3%]). Over 5 years, a 5-point increase in the DASH score was associated with decreased VAT in people with T2D (-514 [-800; -228] cm3). Similar, but imprecise, associations were observed for VAT changes in people with T1D (-403 [-861; 55] cm3) and for HLC in people with T2D (-1.3% [-2.8%; 0.3%]). Body mass index and waist circumference changes explained 8%-48% of the associations between DASH and VAT changes in both groups. In people with T2D, adipose tissue insulin resistance index (Adipo-IR) changes explained 47% of the association between DASH and HLC changes. CONCLUSIONS: A shift to a DASH-like diet was associated with favourable VAT and HLC changes, which were partly explained by changes in anthropometric measures and Adipo-IR.

Association of dietary patterns with diabetes-related comorbidities varies among diabetes endotypes.

BACKGROUND AND AIMS: Differences of dietary pattern adherence across the novel diabetes endotypes are unknown. This study assessed adherence to pre-specified dietary patterns and their associations with cardiovascular risk factors, kidney function, and neuropathy among diabetes endotypes. METHODS AND RESULTS: The cross-sectional analysis included 765 individuals with recent-onset (67 %) and prevalent diabetes (33 %) from the German Diabetes Study (GDS) allocated into severe autoimmune diabetes (SAID, 35 %), severe insulin-deficient diabetes (SIDD, 3 %), severe insulin-resistant diabetes (SIRD, 5 %), mild obesity-related diabetes (MOD, 28 %), and mild age-related diabetes (MARD, 29 %). Adherence to a Mediterranean diet score (MDS), Dietary Approaches to Stop Hypertension (DASH) score, overall plant-based diet (PDI), healthful (hPDI) and unhealthful plant-based diet index (uPDI) was derived from a food frequency questionnaire and associated with cardiovascular risk factors, kidney function, and neuropathy using multivariable linear regression analysis. Differences in dietary pattern adherence between endotypes were assessed using generalized mixed models. People with MARD showed the highest, those with SIDD and MOD the lowest adherence to the hPDI. Adherence to the MDS, DASH, overall PDI, and hPDI was inversely associated with high-sensitivity C-reactive protein (hsCRP) among people with MARD (ß (95%CI): -9.18 % (-15.61; -2.26); -13.61 % (-24.17; -1.58); -19.15 % (-34.28; -0.53); -16.10 % (-28.81; -1.12), respectively). Adherence to the PDIs was associated with LDL cholesterol among people with SAID, SIRD, and MOD. CONCLUSIONS: Minor differences in dietary pattern adherence (in particular for hPDI) and associations with markers of diabetes-related complications (e.g. hsCRP) were observed between endotypes. So far, evidence is insufficient to derive endotype-specific dietary recommendations. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01055093.

"Quality of life" analysis in the long-term follow-up after "Fontan" palliation for CHDs-a single-centre experience.

BACKGROUND: Complex CHDs are life threatening, and surgical treatment is needed for survival. Fontan palliation led to a significant increase in survival rates during the last decades. Consequently, quality of life became more essential. While a reduced quality of life compared to healthy children has been reported, detailed knowledge about individual quality of life and particular areas is lacking. Furthermore, the effect of different risk factors on quality of life is only rarely evaluated. METHOD AND RESULTS: Database of the department for pediatric cardiology, Heart Center Leipzig, was screened for children after total cavopulmonary connection palliation. n = 39 patients were included in the study, the outcome after total cavopulmonary connection was analysed in detail and quality of life data were collected and analysed using the standardised questionnaire "Pediatric quality of life inventory", version 4.0. We compared the total health score of our patients to the mean score of healthy children in the literature. The mean follow-up time was 6.4 ± 3.2 years, the overall survival was 100% after maximal follow-up time of 11.1 years. We could not find any age or gender dependence, nor an influence of age at total cavopulmonary connection on the later quality of life. Yet, patients with three-staged surgery exhibited a worse quality of life than patients with two-staged palliation. Late complications might influence quality of life, but patient number is too small, to find universal results. CONCLUSION: The total cavopulmonary connection palliation affects physical and psychological quality of life as well as cardiac health independently from age and gender. More patients and longer observation should be examined to confirm the results.

Orthogonal plating for complex olecranon fractures: retrospective case series with patient-reported outcomes.

INTRODUCTION: Treatment for complex olecranon fractures with metaphyseal comminution can be challenging. To improve reduction maneuvers and augment stability, we apply a small medial and/or lateral locking compression plate (LCP) prior to placing a posterior contoured 3.5 mm-2.7 mm LCP. The aim is to describe our technique and outcomes of this "orthogonal" plating technique. MATERIAL AND METHODS: 26 patients were treated with orthogonal plating. Clinical outcome variables were available for all patients at a median of 27 months (IQR 6-54), and patient-reported outcomes (Q-DASH and MEPS) for 23 patients at 38 months (IQR 18-71). RESULTS: All fractures healed at a median of 2.0 months (IQR 1.5-3.8). The median elbow flexion was 120°, extension-deficit 15°, pronation 88°, and supination 85°. The median Q-DASH was 9 (IQR 0-22) and the median MEPS was 90 (IQR 80-100). Hardware was electively removed in seven patients. One patient had a late superficial infection that resolved with hardware removal and antibiotics, and one patient had two consecutive re-fractures after two hardware removals; and healed after the second revision surgery. CONCLUSION: Orthogonal plating with a posterior LCP and a small medial and/or lateral LCP is a safe technique that leads to excellent healing rates, and good clinical and patient-reported outcomes.

Deep Impact: Shifts of Native Cultivable Microbial Communities on Fresh Lettuce after Treatment with Plasma-Treated Water.

Foods consumed raw, such as lettuce, can host food-borne human-pathogenic bacteria. In the worst-case, these diseases cause to death. To limit illness and industrial losses, one innovative sanitation method is non-thermal plasma, which offers an extremely efficient reduction of living microbial biomass. Unfortunately, the total viable count (TVC), one of the most common methods for quantifying antimicrobial effects, provides no detailed insights into the composition of the surviving microbial community after treatment. To address this information gap, different special agars were used to investigate the reduction efficiency of plasma-treated water (PTW) on different native cultivable microorganisms. All tested cultivable microbial groups were reduced using PTW. Gram-negative bacteria showed a reduction of 3.81 log10, and Gram-positive bacteria showed a reduction of 3.49 log10. Fungi were reduced by 3.89 log10. These results were further validated using a live/dead assay. MALDI-ToF (matrix-assisted laser-desorption-ionization time-of-flight)-based determination was used for a diversified overview. The results demonstrated that Gram-negative bacteria were strongly reduced. Interestingly, Gram-positive bacteria and fungi were reduced by nearly equal amounts, but could still recover from PTW treatment. MALDI-ToF mainly identified Pseudomonas spp. and groups of Bacillus on the tested lettuce. These results indicate that the PTW treatment could efficiently achieve a ubiquitous, spectrum-wide reduction of microbial life.

Implications of lung shunt fraction calculation discrepancy in Yttrium-90 radioembolization treatment from 2D planar vs 3D single photon emission CT imaging.

The safety and efficacy of Yttrium-90 (Y-90) radio-embolization therapy is partly dependent on the lung shunt fraction (LSF). There may be a notable disparity between LSF when calculated using 2D planar imaging vs 3D single photon emission CT (SPECT); this can affect the total allowable Y-90 dose delivered and therefore change the effectiveness of the procedure. The case presented demonstrates an 81% decrease in LSF when calculated by SPECT as compared to 2D planar imaging. This case highlights the importance of considering the imaging technique and the potential discrepancies that can arise between planar and SPECT imaging in LSF assessment.

Long-term patient reported outcomes after revision surgery for lower extremity nonunion: A retrospective cohort study.

INTRODUCTION: Ongoing lower extremity long-bone nonunion is a devastating condition and associated with substantial patient morbidity. There is limited evidence regarding physical and mental function after surgical management of lower extremity nonunions. The purpose of this study was to assess general physical and mental health and lower extremity specific physical function of patients that underwent surgery for a lower extremity long-bone nonunion. METHODS: One-hundred and twenty-four adult patients who underwent successful surgical management for a lower extremity long-bone nonunion between June 2002 and December 2021 were evaluated at an average follow-up of 8.6 years (interquartile range [IQR]: 4 - 12). General physical and mental health was assessed with the Short-Form 12 (SF-12) physical (PCS) and mental (MCS) component summaries, and lower extremity specific physical function with the Lower Extremity Functional Scale (LEFS). Multivariable linear regression was performed to identify variables that were independently associated with outcomes. RESULTS: The median LEFS was 50 (IQR: 37 - 63) and the median SF-12 PCS was 43 (IQR: 33 - 52), which are both lower than normative population scores (LEFS: 77 and PCS: 51, p < 0.0001). The median SF-12 MCS was 50, which was comparable to the normative population score of 51 (p < 0.0001). The number of previous surgeries before the index nonunion treatment (p = 0.018 and p = 0.041) and the number of revision surgeries after the index nonunion treatment (p = 0.022 and p = 0.041) were associated with lower LEFS and SF-12 PCS scores. CONCLUSION: At an average of 8.6 years after lower extremity nonunion surgery that led to bone healing, patients continue to report lower general and lower extremity specific physical functioning compared to the normative population. The number of surgical attempts to obtain definitive healing was associated with compromised physical function scores. Mental health scores may return close to normative population scores. These results can be used to inform patients and guide treatment strategies and healthcare policies.

Surrogate measures of first-phase insulin secretion versus reference methods intravenous glucose tolerance test and hyperglycemic clamp: a systematic review and meta-analyses.

INTRODUCTION: In this systematic review, we investigated the diagnostic accuracy of surrogate measures of insulin secretion based on fasting samples and the oral glucose tolerance test (OGTT). The first phase of insulin secretion was calculated using two gold standard methods; the hyperglycemic clamp (HGC) test and intravenous glucose tolerance test (IVGTT). RESEARCH DESIGN AND METHODS: We conducted searches in the PubMed, Cochrane Central, and Web of Science databases, the last of which was conducted at the end of June 2021. Studies were included that measured first-phase insulin secretion in adults using both a gold-standard reference method (either HGC or IVGTT) and one or more surrogate measures from either fasting samples, OGTT or a meal-tolerance test. QUADAS-2, a revised tool for the quality assessment of diagnostic accuracy studies, was used for quality assessment. Random-effects meta-analyses were performed to examine the correlation between first-phase measured with gold standard and surrogate methods. RESULTS: A total of 33 articles, encompassing 5362 individuals with normal glucose tolerance, pre-diabetes or type 2 diabetes, were included in our systematic review. Homeostatic model assessment (HOMA)-beta and Insulinogenic Index 30 (IGI(30)) were the surrogate measures validated in the largest number of studies (17 and 13, respectively). HOMA-beta's pooled correlation to the reference methods was 0.48 (95% CI 0.40 to 0.56) The pooled correlation of IGI to the reference methods was 0.61 (95% CI 0.54 to 0.68). The surrogate measures with the highest correlation to the reference methods were Kadowaki (0.67 (95% CI 0.61 to 0.73)) and Stumvoll's first-phase secretion (0.65 (95% CI 0.58 to 0.71)), both calculated from an OGTT. CONCLUSIONS: Surrogate measures from the first 30 min of an OGTT capture the first phase of insulin secretion and are a good choice for epidemiological studies. HOMA-beta has a moderate correlation to the reference methods but is not a measure of the first phase specifically. PROSPERO REGISTRATION NUMBER: The meta-analysis was registered at PROSPERO (Id: CRD42020169064) before inclusion started.

Characteristics and Outcomes of Occult Infections in Presumed Aseptic Nonunions: A Retrospective Cohort Study.

OBJECTIVES: To determine (1) the rate of positive cultures in presumed aseptic nonunions, (2) the rate and microbial spectrum of positive cultures that represented occult infection, and (3) rates of nonunion healing. DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS SELECTION CRITERIA: Adult patients with a presumed aseptic nonunion treated with single-stage revision between 2002 and 2022. OUTCOME MEASURES AND COMPARISONS: The rate of positive cultures compared for 2 protocols: old: 1-2 samples cultured 7 days versus new: 5 samples cultured 14 days. The rate of positive cultures meeting occult infection criteria with the new protocol (≥2 samples with phenotypically indistinguishable microorganisms, or ≥1 sample with a high virulent microorganism). Nonunion healing rates between protocols and between groups based on culture results with the new protocol. RESULTS: One hundred seventy-nine patients were included. The rate of positive cultures was 14% (n = 15/105) with the old protocol and 51% (n = 38/74) with the new protocol (P < 0.001). With the new protocol, the rate of positive cultures meeting occult infection criteria was 19% (n = 14/74), and coagulase-negative staphylococci (48%) and Cutibacterium acnes (38%) were the most common microorganisms. Nonunion healing rates after the primary revision did not differ between protocols (old: 82% vs. new: 86%, P = 0.41) and groups based on culture result (sterile: 86% vs. occultly infected: 93%, P = 0.66). The final overall nonunion healing rate was 97%. CONCLUSIONS: Occult infections were identified in 1 in 5 presumed aseptic nonunions using a standardized protocol with 5 intraoperative samples cultured 14 days and were predominantly caused by slow growing, gram-positive microorganisms. The local spectrum and antimicrobial sensitivity of occult infections should be considered when developing empiric antimicrobial protocols. Patients with presumed aseptic nonunions can expect high healing rates, regardless of the culture result. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Genetic Evidence for a Causal Link between Intra-Pancreatic Fat Deposition and Pancreatitis: a Mendelian Randomization Study.

Introduction: Recent associative studies have linked intra-pancreatic fat deposition (IPFD) with risk of pancreatitis, but the causal relationship remains unclear. Methods: Utilizing Mendelian randomization, we evaluated the causal association between genetically predicted IPFD and pancreatitis. This approach utilized genetic variants from genome-wide association studies of IPFD (n=25,617), acute pancreatitis (n=6,787 cases/361,641 controls), and chronic pancreatitis (n=3,875 cases/361,641 controls). Results: Genetically predicted IPFD was significantly associated with acute pancreatitis (OR per 1-SD increase: 1.40[95%CI:1.12-1.76], p=0.0032) and chronic pancreatitis (OR:1.64[95%CI:1.13-2.39], p=0.0097). Discussion: Our findings support a causal role of IPFD in pancreatitis, suggesting that reducing IPFD could lower the risk of pancreatitis.

Safety of Magnetic Resonance Imaging in Orthopaedic Trauma Patients With External Fixation: A Two-Center Case Series.

OBJECTIVES: To report on adverse events during magnetic resonance imaging (MRI) in patients with external fixators. METHODS: . DESIGN: Retrospective case series. SETTING: Two Level 1 trauma centers. PATIENT SELECTION CRITERIA: Patients with external fixators on the appendicular skeleton or pelvis undergoing MRI between January 2005 and September 2023. OUTCOME MEASURES AND COMPARISONS: Adverse events, defined as any undesirable event associated with the external fixator being inside or outside the MRI bore during imaging, including (subjective) heating, displacement or pullout of the external fixator, or early MRI termination for any reason. RESULTS: A total of 97 patients with 110 external fixators underwent at least one MRI scan with an external fixator inside or outside of the MRI bore. The median age was 51 years (interquartile range: 39-63) and 56 (58%) were male. The most common external fixator locations were the ankle (24%), knee (21%), femur (21%), and pelvis (19%). The median duration of the MRI was 40 minutes (interquartile range: 26-58), 86% was performed using 1.5-Tesla MRI, and 14% was performed using 3.0-Tesla MRI. Ninety-five percent of MRI was performed for the cervical spine/head. Two MRI scans (1.6%), one of the shoulder and one of the head and cervical spine, with the external fixator outside of the bore were terminated early because of patient discomfort. There were no documented events of displacement or pullout of the external fixator. CONCLUSIONS: These findings suggest that MRI scans of the (cervical) spine and head can be safely obtained in patients with external fixators on the appendicular skeleton or pelvis. Given the low numbers of MRI scans performed with the external fixator inside the bore, additional studies are necessitated to determine the safety of this procedure. The results from this study can aid orthopaedic surgeons, radiologists, and other stakeholders in developing local institutional guidelines on MRI scanning with external fixators in situ. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Evidence for a causal link between intra-pancreatic fat deposition and pancreatic cancer: A prospective cohort and Mendelian randomization study.

Prior observational studies suggest an association between intra-pancreatic fat deposition (IPFD) and pancreatic ductal adenocarcinoma (PDAC); however, the causal relationship is unclear. To elucidate causality, we conduct a prospective observational study using magnetic resonance imaging (MRI)-measured IPFD data and also perform a Mendelian randomization study using genetic instruments for IPFD. In the observational study, we use UK Biobank data (N = 29,463, median follow-up: 4.5 years) and find that high IPFD (>10%) is associated with PDAC risk (adjusted hazard ratio [HR]: 3.35, 95% confidence interval [95% CI]: 1.60-7.00). In the Mendelian randomization study, we leverage eight out of nine IPFD-associated genetic variants (p < 5 × 10-8) from a genome-wide association study in the UK Biobank (N = 25,617) and find that genetically determined IPFD is associated with PDAC (odds ratio [OR] per 1-standard deviation [SD] increase in IPFD: 2.46, 95% CI: 1.38-4.40) in the Pancreatic Cancer Cohort Consortium I, II, III (PanScan I-III)/Pancreatic Cancer Case-Control Consortium (PanC4) dataset (8,275 PDAC cases and 6,723 non-cases). This study provides evidence for a potential causal role of IPFD in the pathogenesis of PDAC. Thus, reducing IPFD may lower PDAC risk.

A Cadaveric Study: Does Ankle Positioning Affect the Quality of Anatomic Syndesmosis Reduction?

OBJECTIVE: The objective of this study was to compare the quality of syndesmotic reduction with the ankle in maximal dorsiflexion versus neutral plantarflexion (normal resting position). METHODS: Baseline computed tomography (CT) imaging of 10 cadaveric ankle specimens from 5 donors was obtained with the ankles placed in normal resting position. Two fellowship-trained orthopaedic surgeons disrupted the syndesmosis of each ankle specimen. All ankles were then placed in neutral plantarflexion and were subsequently reduced with thumb pressure under direct visualization through an anterolateral approach and stabilized with one 0.062-inch K-wire placed from lateral to medial in a quadricortical fashion across the syndesmosis. Postreduction CT scans were then obtained with the ankle in normal resting position. This process was repeated with the ankles placed in maximal dorsiflexion during reduction and stabilization. Postreduction CT scans were then obtained with the ankles placed in normal resting position. All postreduction CT scans were compared with baseline CT imaging using mixed-effects linear regression with significance set at P < 0.05. RESULTS: Syndesmotic reduction and stabilization in maximal dorsiflexion led to increased external rotation of the fibula compared with baseline scans [13.0 ± 5.4 degrees (mean ± SD) vs. 7.5 ± 2.4 degrees, P = 0.002]. There was a tendency toward lateral translation of the fibula with the ankle reduced in maximal dorsiflexion (3.3 ± 1.0 vs. 2.7 ± 0.7 mm, P = 0.096). No other statistically significant differences between measurements of reduction with the ankle placed in neutral plantarflexion or maximal dorsiflexion compared with baseline were present (P > 0.05). CONCLUSIONS: Reducing the syndesmosis with the ankle in maximal dorsiflexion may lead to malreduction with external rotation of the fibula. There was no statistically significant difference in reduction quality with the ankle placed in neutral plantarflexion compared with baseline. Future studies should assess the clinical implications of ankle positioning during syndesmotic fixation.

Two big bones, one big decision: When to fix bilateral femur fractures.

PURPOSE: For polytrauma patients with bilateral femoral shaft fractures (BFSF), there is currently no consensus on the optimal timing of surgery. This study assesses the impact of early (≤ 24 h) versus delayed (>24 h) definitive fixation on clinical outcomes, especially focusing on concomitant versus staged repair. We hypothesized that early definitive fixation leads to lower mortality and morbidity rates. METHODS: The 2017-2020 Trauma Quality Improvement Program was used to identify patients aged ≥16 years with BFSF who underwent definitive fixation. Early definitive fixation (EDF) was defined as fixation of both femoral shaft fractures within 24 h, delayed definitive fixation (DDF) as fixation of both fractures after 24 h, and early staged fixation (ESF) as fixation of one femur within 24 h and the other femur after 24 h. Propensity score matching and multilevel mixed effects regression models were used to compare groups. RESULTS: 1,118 patients were included, of which 62.8% underwent EDF. Following propensity score matching, 279 balanced pairs were formed. EDF was associated with decreased overall morbidity (12.9% vs 22.6%, p = 0.003), lower rate of deep venous thrombosis (2.2% vs 6.5%, p = 0.012), a shorter ICU LOS (5 vs 7 days, p < 0.001) and a shorter hospital LOS (10 vs 15 days, p < 0.001). When compared to DDF, early staged fixation (ESF) was associated with lower rates of ventilator acquired pneumonia (0.0% vs 4.9%, p = 0.007), but a longer ICU LOS (8 vs 6 days, p = 0.004). Using regression analysis, every 24-hour delay to definitive fixation increased the odds of developing complications by 1.05, postoperative LOS by 10 h and total hospital LOS by 27 h. CONCLUSION: Early definitive fixation (≤ 24 h) is preferred over delayed definitive fixation (>24 h) for patients with bilateral femur shaft fractures when accounting for age, sex, injury characteristics, additional fractures and interventions, and hospital level. Although mortality does not differ, overall morbidity and deep venous thrombosis rates, and length of hospital and intensive care unit stay are significantly lower. When early definitive fixation is not possible, early staged repair seems preferable over delayed definitive fixation.

BCG Vaccination-Associated Lower HbA1c and Increased CD25 Expression on CD8+ T Cells in Patients with Type 1 Diabetes in Ghana.

BCG vaccination affects other diseases beyond tuberculosis by unknown-potentially immunomodulatory-mechanisms. Recent studies have shown that BCG vaccination administered during overt type 1 diabetes (T1D) improved glycemic control and affected immune and metabolic parameters. Here, we comprehensively characterized Ghanaian T1D patients with or without routine neonatal BCG vaccination to identify vaccine-associated alterations. Ghanaian long-term T1D patients (n = 108) and matched healthy controls (n = 214) were evaluated for disease-related clinical, metabolic, and immunophenotypic parameters and compared based on their neonatal BCG vaccination status. The majority of study participants were BCG-vaccinated at birth and no differences in vaccination rates were detected between the study groups. Notably, glycemic control metrics, i.e., HbA1c and IDAA1c, showed significantly lower levels in BCG-vaccinated as compared to unvaccinated patients. Immunophenotype comparisons identified higher expression of the T cell activation marker CD25 on CD8+ T cells from BCG-vaccinated T1D patients. Correlation analysis identified a negative correlation between HbA1c levels and CD25 expression on CD8+ T cells. In addition, we observed fractional increases in glycolysis metabolites (phosphoenolpyruvate and 2/3-phosphoglycerate) in BCG-vaccinated T1D patients. These results suggest that neonatal BCG vaccination is associated with better glycemic control and increased activation of CD8+ T cells in T1D patients.