Aceruloplasminemia (ACP) is a rare neurodegenerative disorder characterized by extreme cerebral iron overload and a shift towards larger iron aggregates, providing a unique possibility to study how iron aggregation shapes MRI contrast in vivo . We introduce a clinically feasible, multi-parametric quantitative MRI (qMRI) framework that combines quantitative susceptibility mapping (QSM), , and R 2 to disentangle changes in total iron concentration from alterations in iron aggregation and its spatial organization at the cellular scale. Our biophysical model links the microstructure sensitive ratio and the slope of the susceptibility–relaxation relationship ( α iron ) to iron aggregation size and distribution. In a 3T qMRI study of three patients with ACP and three matched controls, we observe a marked increase in and a pronounced increase of the –QSM slope ( α iron : controls 154.09 ± 52.89 s −1 ppm −1 ; patients 296.68 ± 57.18 s −1 ppm −1 ; p = 0.016), consistent with enhanced iron aggregation and altered spatial organization. Model-based decomposition of transverse relaxation indicates that up to approximately 40% of the observed R 2 ∗ elevation in ACP is attributable to changes in iron distribution beyond increased iron concentration alone. These findings establish a robust, translational qMRI approach for quantitative in vivo assessment of iron aggregation, revealing microstructural drivers of iron-related neurodegeneration that extend beyond bulk iron load.

Objectives: We aimed to determine quantitative photon-counting CT (PCCT)-derived iodine map (IM) attenuation associated with visual detectability of parenchymal hyperattenuation on conventional brain window (BW) images after mechanical thrombectomy (MT) and to assess corresponding relative BW attenuation changes. Methods: In this retrospective single-center study, 12 patients with anterior circulation large vessel occlusion underwent MT followed by post-interventional PCCT. BW, IM, and virtual non-contrast reconstructions were generated. Follow-up non-contrast CT served as reference for final infarction extent. Of 54 ASPECTS regions with final infarction, 40 showed IM hyperattenuation and were included in the detectability analysis. Two blinded readers assessed visual detectability. IM attenuation and relative BW attenuation increase (%ΔHU) were evaluated using ROC analysis with clustered bootstrap resampling. Thresholds were determined using the Youden index. Results: Across all 54 regions with final infarction, median IM attenuation was significantly higher in infarcted than contralateral regions (6.39 vs. 2.18 HU, p < 0.001), while absolute BW attenuation did not differ significantly. Among the 40 regions with IM hyperattenuation, 15 were visually detectable on BW images. ROC analysis showed excellent performance for IM (AUC = 0.997) and %ΔHU (AUC = 0.984). The optimal IM threshold in the original cohort was 8.33 HU (sensitivity 100%, specificity 96.0%), and the optimal %ΔHU threshold was 3.06% (sensitivity 100%, specificity 92.0%). Bootstrap-derived median thresholds were 11.69 HU (95% interval 8.33–12.67) for IM and 3.06% (3.06–20.16%) for %ΔHU. Inter-reader agreement was excellent (κ = 0.81–0.86). Conclusions: PCCT-derived iodine quantification enables objective assessment of visual detectability of post-interventional parenchymal hyperattenuation. In this cohort, an internally derived IM cutoff of 8.33 HU was associated with BW visibility. These preliminary findings require validation in larger, independent multicenter cohorts.

ABSTRACT:Modern IV iron formulations allow treatment of iron deficiency anemia (IDA) with 1 or 2 infusions. Ferric carboxymaltose (FCM) is a widely used IV iron, which causes hypophosphatemia in most of the patients. Osteomalacia and fractures are increasingly recognized after repeated infusions of FCM. It is unknown why ferric derisomaltose (FDI) rarely causes hypophosphatemia. In this study, we compare the effects of FCM and FDI on fracture risk and investigate potential underlying mechanisms explaining the different effects on bone and mineral metabolism. For this aim, fracture rate and osteomalacia were assessed in a cohort of 357 patients treated with either drug, who reported a significantly higher rate of incident osteomalacia or fracture after FCM. These findings were validated in >20 000 patients from the TriNetX database, where FCM treatment was independently associated with a higher fracture risk compared with FDI. The underlying mechanisms were investigated in a mouse model of IDA treated with FCM or FDI, an osteocyte model, and biochemically. FCM caused lower expression of collagen and ossification genes, associated with significantly higher bone iron concentrations than FDI. Electron microscopy showed iron-loaded vesicles in osteoblasts and early osteocytes. FCM but not FDI inhibited the binding of dentin matrix protein 1 to αVβ3-integrin on osteocytes. This is a potential mechanism for reduced bone formation and higher levels of intact fibroblast growth factor 23 after FCM. Our data report that IDA and FCM treatment can directly impair bone formation and increase fracture risk.

OBJECTIVE:The aim of this study was to display and quantify signal loss artifacts in 1.5T and 3T brain MRI on a volunteer with different orthodontic appliances. MATERIALS AND METHODS:In this experimental study, three different orthodontic appliances were examined on a 1.5T and a 3T MRI scanner in a healthy adult with normal dental occlusion: stainless-steel brackets paired with a nickel-titanium archwire; brackets, archwire, and stainless-steel molar bands; brackets, archwire, molar bands, and a stainless-steel trans-palatal archwire. Assessment of diverse anatomical structures, including different cerebral structures and blood vessels, was conducted using a six-point Likert scale. RESULTS:Utilizing conventional stainless-steel brackets and a nickel-titanium archwire, with or without the inclusion of stainless-steel molar bands, all cerebral structures demonstrated satisfactory assessability with high diagnostic quality under both 1.5T and 3T MRI. For example, with an average rating of 85/85 for T2 and 77/85 for susceptibility-weighted imaging (SWI). Upon introduction of the stainless-steel trans-palatal archwire, additional artifacts were observed, predominantly manifesting in SWI (20/85), diffusion-weighted imaging (DWI) sequences (31/85), and phase contrast angiography (PCA) (17/20). Differences in artifact severity were mainly observed in the SWI and DWI sequences. CONCLUSION:Based on the findings of this study, it is not imperative to entirely remove orthodontic appliances to achieve sufficient diagnostic quality in brain MRI. In instances where SWI or DWI sequences are necessitated, the removal of solely the trans-palatal stainless-steel archwire should be contemplated, given its straightforward execution. CLINICAL RELEVANCE:These results highlight the potential to reduce injury risk during orthodontic appliance removal, expedite imaging procedures, and consequently accelerate diagnostic processes, particularly crucial in emergencies.

To evaluate the diagnostic impact of fixed orthodontic appliances on brain MRI under clinically realistic conditions, and to clarify the scope and focus of our Technical Note in response to commentary Common orthodontic appliances, including brackets, archwires, molar bands, and transpalatal arches, were assessed in vivo during brain MRI. The analysis was designed as a Technical Note, with emphasis on empirical diagnostic imaging rather than detailed metallurgical characterization For most orthodontic configurations, brain MRI images remained interpretable across standard sequences. Severe artifacts were observed primarily in the presence of a transpalatal arch, especially in SWI and DWI sequences. These findings provide actionable insights for radiologists and orthodontists While theoretical alloy-based compatibility assessments remain valuable, empirical MRI data are indispensable in clinical practice, where detailed material information is often unavailable. Our study confirms that standard orthodontic appliances usually allow interpretable brain MRI, with specific exceptions The study offers practical guidance for imaging patients with fixed orthodontic appliances. It highlights the need for interdisciplinary collaboration to establish standardized classifications of MRI-compatible products, building on both clinical imaging data and metallurgical analyses.

BACKGROUND: Flow-controlled ventilation (FCV) ensures a constant gas flow whereby precise determination of dynamic compliance is feasible. Accordingly, ventilator pressure settings can be adjusted to achieve the highest compliance. This setting will automatically adapt tidal volume to the functionally available lung volume as a personalized approach. This is in contrast to current ventilation settings, where fixed tidal volumes according to predicted body weight (PBW) are recommended. Aim of this subgroup-analysis was to determine whether applied tidal volume differs in male and female patients after compliance guided individualization of ventilation parameters. METHODS: A sub-group analysis of 24 patients randomized to receive flow-controlled ventilation in cardiac surgery was performed. Linear mixed-effects model was used in order to investigate sex related differences in respiratory parameters. RESULTS: Compliance guided pressure titration led to comparable pressure settings in male (N.=18) and female (N.=6) patients. In contrast, the applied tidal volume was significantly lower in female patients (8.6 vs. 9.9, 95% CI:-2.3 to-0.2 mL/kg PBW; P=0.029) compared to male individuals, due to a significantly lower compliance (49.3 vs. 70.3, 95% CI:-33.1 to-8.8 mL/cmH2O; P=0.003). Gas exchange parameters were comparable in either sex. CONCLUSIONS: Female patients were found to receive lower tidal volumes after compliance guided individualization compared to men during cardiac surgery. This finding may indicate that the functionally available lung volume in women is lower and thus using PBW may not adequately comply with sex related differences, which supports the use of a personalized ventilation strategy.

Patients with Crohn's disease are at increased risk for symptomatic nephrolithiasis. Stones in these patients are most commonly composed of calcium oxalate monohydrate or mixed calcium-oxalate and calcium-phosphate. Precipitation of both minerals depends on urinary pH, calcium, phosphate and oxalate excretion. The present manuscript reports on two patients with Crohn's disease and bowel resection, in whom the onset of symptomatic urolithiasis occurred after repeated infusions of ferric carboxymaltose – a drug, which is known to cause hyperphosphaturia. The present study shows that ferric carboxymaltose-induced hyperphosphaturia can be associated with kidney stone formation and symptomatic urolithiasis, especially in patients treated with calcitriol. Calcitriol has been shown to mitigate ferric carboxymaltose-induced secondary hyperparathyroidism and hyperphosphaturia, but is known to increase urinary calcium excretion. Chemical analysis of recovered stones revealed that they were mixed calcium oxalate and phosphate stones. Ring-like deposition of iron detected by spatially resolved elemental analysis using laser ablation-inductively coupled plasma mass spectrometry, showed that the stones also contained iron. Based on our findings, we propose that patients with inflammatory bowel disease requiring intravenous iron therapy should be carefully monitored for the development of hypophosphatemia and urolithiasis. If hypophosphatemia occurs in such patients, calcitriol should be used with caution.

Background Bolus administration of adrenaline during cardiopulmonary resuscitation (CPR) results in only short-term increases in systemic and cerebral perfusion pressure (CePP) with unclear effects on cerebral oxygenation. The aim of this study was to investigate the effects of bolus compared to continuous adrenaline administration on cerebral oxygenation in a porcine CPR model. Methods After five minutes of cardiac arrest, mechanical CPR was performed for 15 min. Adrenaline (45 μg/kg) was administered either as a bolus every five minutes or continuously over the same period via an infusion pump. Main outcome parameter was brain tissue oxygen tension (PbtO2), secondary outcome parameters included mean arterial pressure (MAP), intracranial pressure (ICP), CePP and cerebral regional oxygen saturation (rSO2) as well as arterial and cerebral venous blood gases. Results During CPR, mean MAP (45 ± 8 mmHg vs. 38 ± 8 mmHg; p = 0.0827), mean ICP (27 ± 7 mmHg vs. 20 ± 7 mmHg; p = 0.0653) and mean CePP (18 ± 8 mmHg vs. 18 ± 8 mmHg; p = 0.9008) were similar in the bolus and the continuous adrenaline group. Also, rSO2 (both 24 ± 6 mmHg; p = 0.9903) and cerebral venous oxygen saturation (18 ± 12% versus 27.5 ± 12%; p = 0.1596) did not differ. In contrast, relative PbtO2 reached higher values in the continuous group after five minutes of CPR and remained significantly higher than in the bolus group until the end of resuscitation. Conclusion Continuous administration of adrenaline improved brain tissue oxygen tension compared with bolus administration during prolonged CPR.

BACKGROUND:Endoleaks are the most common complication after endovascular aneurysm repair (EVAR). Computed tomography angiography (CTA) is presently the golden standard for lifelong surveillance after EVAR. Several studies and meta-analyses have shown contrast-enhanced ultrasound (CEUS) to be a good alternative. The main goal of our study was to further validate the inclusion of CEUS in follow-up examination protocols for the systematic surveillance after EVAR.METHODS:A retrospective analysis of patients who had received CEUS as part of their routine surveillance after EVAR at our center was conducted. Detection rate and classification of endoleak types were compared between available postinterventional CTA/magnetic resonance angiography and follow-up CEUS examinations. Last preinterventional CTAs before EVAR served as baselines with focus on potential cofactors such as age, body mass index, maximum aortic aneurysm diameters, endoleak orientation, and distance-to-surface influencing detection rates and classification.RESULTS:In total, 101 patients were included in the analysis. Forty-four endoleaks (43.5% of cases) were detected by either initial CEUS or CTA, mostly type II (37.6% of the included patients). Initial CEUS showed an endoleak sensitivity of 91.2%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 84.6%. No covariate with an influence on the correct classification could be identified either for CEUS or CT.CONCLUSIONS:CEUS should be considered a valid complementary method to CTA in the lifelong surveillance after EVAR. As type II endoleaks seem to be a common early-term, sometimes spontaneously resolving complication that can potentially be missed by CTA, we suggest combined follow-up protocols including CEUS in the early on postinterventional assessment.

Background Aim of this study was to evaluate feasibility and effects of individualised flow-controlled ventilation (FCV), based on compliance guided pressure settings, compared to standard of pressure-controlled ventilation (PCV) in a porcine intra-abdominal hypertension (IAH) model. The primary aim of this study was to investigate oxygenation. Secondary aims were to assess respiratory and metabolic variables and lung tissue aeration. Methods Pigs were randomly assigned to FCV ( n = 9) and PCV ( n = 9). IAH was induced by insufflation of air into the abdomen to induce IAH grades ranging from 0 to 3. At each IAH grade FCV was undertaken using compliance guided pressure settings, or PCV ( n = 9) was undertaken with the positive end-expiratory pressure titrated for maximum compliance and the peak pressure set to achieve a tidal volume of 7 ml/kg. Gas exchange, ventilator settings and derived formulas were recorded at two timepoints for each grade of IAH. Lung aeration was assessed by a computed tomography scan at IAH grade 3. Results All 18 pigs (median weight 54 kg [IQR 51–67]) completed the observation period of 4 h. Oxygenation was comparable at each IAH grade, but a significantly lower minute volume was required to secure normocapnia in FCV at all IAH grades (7.6 vs. 14.4, MD − 6.8 (95% CI − 8.5 to − 5.2) l/min; p < 0.001). There was also a significant reduction of applied mechanical power being most evident at IAH grade 3 (25.9 vs. 57.6, MD − 31.7 (95% CI − 39.7 to − 23.7) J/min; p < 0.001). Analysis of Hounsfield unit distribution of the computed tomography scans revealed a significant reduction in non- (5 vs. 8, MD − 3 (95% CI − 6 to 0) %; p = 0.032) and poorly-aerated lung tissue (7 vs. 15, MD − 6 (95% CI − 13 to − 3) %, p = 0.002) for FCV. Concomitantly, normally-aerated lung tissue was significantly increased (84 vs. 76, MD 8 (95% CI 2 to 15) %; p = 0.011). Conclusions Individualised FCV showed similar oxygenation but required a significantly lower minute volume for CO 2 -removal, which led to a remarkable reduction of applied mechanical power. Additionally, there was a shift from non- and poorly-aerated lung tissue to normally-aerated lung tissue in FCV compared to PCV.

Intensive care unit (ICU) acquired weakness is a major contributor to poor functional outcome of ICU patients. Quantification of temporal muscle volume assessed on routine computed tomography (CT) scans may serve as a biomarker for muscle wasting in patients suffering from acute brain injury. This is a retrospective analysis of prospectively collected data. Temporal muscle volume was assessed on head CT scans of consecutive patients with spontaneous subarachnoid hemorrhage within prespecified time frames (on admission, then weekly ± 2 days). Whenever possible, temporal muscle volume was assessed bilaterally and averaged for the analysis. Poor functional outcome was defined as a 3-month modified Rankin Scale Score ≥ 3. Statistical analysis was performed using generalized estimating equations to handle repeated measurements within individuals. The analysis comprised 110 patients with a median Hunt Hess score of 4 (interquartile range 3–5). Median age was 61 (50–70) years, 73 patients (66 Temporal muscle volume, which is easily assessable on routine head CT scans, progressively decreases during the ICU stay after spontaneous subarachnoid hemorrhage. Because of its association with disease severity and functional outcome, it may serve as a biomarker for muscle wasting and outcome prognostication.

In pressure-controlled ventilation (PCV), a decelerating gas flow pattern occurs during inspiration and expiration. In contrast, flow-controlled ventilation (FCV) guarantees a continuous gas flow throughout the entire ventilation cycle where the inspiration and expiration phases are simply performed by a change of gas flow direction. The aim of this trial was to highlight the effects of different flow patterns on respiratory variables and gas exchange. Anesthetized pigs were ventilated with either FCV or PCV for 1 h and thereafter for 30 min each in a crossover comparison. Both ventilation modes were set with a peak pressure of 15 cmH2O, positive end-expiratory pressure of 5 cmH2O, a respiratory rate of 20/min, and a fraction of inspired oxygen at 0.3. All respiratory variables were collected every 15 min. Tidal volume and respiratory minute volume were significantly lower in FCV (n = 5) compared with PCV (n = 5) animals [4.6 vs. 6.6, MD -2.0 (95% CI -2.6 to -1.4) mL/kg; P < 0.001 and 7.3 vs. 9.5, MD -2.2 (95% CI -3.3 to -1.0) L/min; P = 0.006]. Notwithstanding these differences, CO2-removal as well as oxygenation was not inferior in FCV compared with PCV. Mechanical ventilation with identical ventilator settings resulted in lower tidal volumes and consecutive minute volume in FCV compared with PCV. This finding can be explained physically by the continuous gas flow pat-tern in FCV that necessitates a lower alveolar pressure amplitude. Interestingly, gas exchange was comparable in both groups, which is suggestive of improved ventilation efficiency at a continuous gas flow pattern.NEW & NOTEWORTHY This study examined the effects of a continuous (flow-controlled ventilation, FCV) vs. decelerating (pres-sure-controlled ventilation, PCV) gas flow pattern during mechanical ventilation. It was shown that FCV necessitates a lower alve-olar pressure amplitude leading to reduced applied tidal volumes and consequently minute volume. Notwithstanding these differences, CO2-removal as well as oxygenation was not inferior in FCV compared with PCV, which is suggestive of improved gas exchange efficiency at a continuous gas flow pattern.

Purpose:To directly measure lateral extra-articular tenodesis (LET) forces supporting anterior cruciate ligament reconstruction (ACLR) during dynamic flexion-extension cycles induced by simulated active muscle forces, to investigate the influence of random surgical variation in the femoral LET insertion point around the target insertion position, and to determine potential changes to the extension behavior of the knee joint in a cadaveric model. Methods:After iatrogenic anterior cruciate ligament deficiency and simulated anterolateral rotatory instability, 7 fresh-frozen cadaveric knee joints were treated with isolated ACLR followed by combined ACLR-LET. The specimens were tested on a knee joint test bench during active dynamic flexion-extension with simulated muscle forces. LET forces and the degree of knee joint extension were measured. Random variation in the LET insertion point around the target insertion position was postoperatively quantified by computed tomography. Results:In extension, the median LET force increased to 39 ± 2 N (95% confidence interval [CI], 36 to 40 N). In flexion over 70°, the LET was offloaded (2 ± 1 N; 95% CI, 0 to 2 N). In this study, small-scale surgical variation in the femoral LET insertion point around the target position had a negligible effect on the graft forces measured. We detected no difference in the degree of knee joint extension after combined ACLR-LET (median, 1.0° ± 3.0°; 95% CI, -6.2° to 5.2°) in comparison with isolated ACLR (median, 1.1° ± 3.3°; 95% CI, -6.7° to 6.1°; P = .62). Conclusions:LET forces in combined ACLR-LET increased to a limited extent during active knee joint flexion-extension independent of small-scale variation around 1 specific target insertion point. Combined ACLR-LET did not change knee joint extension in comparison with isolated ACLR under the testing conditions used in this biomechanical study. Clinical Relevance:Low LET forces can be expected during flexion-extension of the knee joint. Small-scale deviations in the femoral LET insertion point around the target insertion position in the modified Lemaire technique might have a minor effect on graft forces during active flexion-extension.

BACKGROUND A continuous gas flow provided by flow-controlled ventilation (FCV) facilitates accurate dynamic compliance measurement and allows the clinician to individually optimise positive end-expiratory and peak pressure settings accordingly. OBJECTIVE The aim of this study was to compare the efficiency of gas exchange and impact on haemodynamics between individualised FCV and pressure-controlled ventilation (PCV) in a porcine model of oleic acid-induced acute respiratory distress syndrome (ARDS). DESIGN Randomised controlled interventional trial conducted on 16 pigs. SETTING Animal operating facility at the Medical University Innsbruck. INTERVENTIONS ARDS was induced in lung healthy pigs by intravenous infusion of oleic acid until moderate-to-severe ARDS at a stable Horowitz quotient (PaO2 FiO2 −1) of 80 to 120 over a period of 30 min was obtained. Ventilation was then either performed with individualised FCV (n = 8) established by compliance-guided pressure titration or PCV (n = 8) with compliance-guided titration of the positive end-expiratory pressure and peak pressure set to achieve a tidal volume of 6 ml kg−1 over a period of 2 h. MAIN OUTCOME MEASURES Gas exchange parameters were assessed by the PaO2 FiO2 −1 quotient and CO2 removal by the PaCO2 value in relation to required respiratory minute volume. Required catecholamine support for haemodynamic stabilisation was measured. RESULTS The FCV group showed significantly improved oxygenation [149.2 vs. 110.4, median difference (MD) 38.7 (8.0 to 69.5) PaO2 FiO2 −1; P = 0.027] and CO2 removal [PaCO2 7.25 vs. 9.05, MD −1.8 (−2.87 to −0.72) kPa; P = 0.006] at a significantly lower respiratory minute volume [8.4 vs. 11.9, MD −3.6 (−5.6 to −1.5) l min−1; P = 0.005] compared with PCV. In addition, in FCV-pigs, haemodynamic stabilisation occurred with a significant reduction of required catecholamine support [norepinephrine 0.26 vs. 0.86, MD −0.61 (−1.12 to −0.09) μg kg−1 min−1; P = 0.037] during 2 ventilation hours. CONCLUSION In this oleic acid-induced porcine ARDS model, individualised FCV significantly improved gas exchange and haemodynamic stability compared with PCV. TRIAL REGISTRATION Protocol no.: BMBWF-66.011/0105-V/3b/2019)