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Highlights
• Early reconstruction of injured cruciate ligaments improves functional outcomes.
• Modern CT imaging can be used to rapidly identify patients with injury to the cruciate ligaments and streamline therapeutic pathways.
• Dual-energy CT demonstrates superior diagnostic accuracy compared to single-energy CT.
Abstract
Background: This study aimed to evaluate the clinical utility of modern single and dual-energy computed tomography (CT) for assessing the integrity of the cruciate ligaments in patients that sustained acute trauma.
Methods: Patients who underwent single- or dual-energy CT followed by 3 Tesla magnetic resonance imaging (MRI) or knee joint arthroscopy between 01/2016 and 12/2022 were included in this retrospective, monocentric study. Three radiologists specialized in musculoskeletal imaging independently evaluated all CT images for the presence of injury to the cruciate ligaments. An MRI consensus reading of two experienced readers and arthroscopy provided the reference standard. Diagnostic accuracy parameters and area under the receiver operator characteristic curve (AUC) were the primary metrics for diagnostic performance.
Results: CT images of 204 patients (median age, 49 years; IQR 36 – 64; 113 males) were evaluated. Dual-energy CT yielded significantly higher diagnostic accuracy and AUC for the detection of injury to the anterior (94% [240/255] vs 75% [266/357] and 0.89 vs 0.66) and posterior cruciate ligaments (95% [243/255] vs 87% [311/357] and 0.90 vs 0.61) compared to single-energy CT (all parameters, p <.005). Diagnostic confidence and image quality were significantly higher in dual-energy CT compared to single-energy CT (all parameters, p <.005).
Conclusions: Modern dual-energy CT is readily available and can serve as a screening tool for detecting or excluding cruciate ligament injuries in patients with acute trauma. Accurate diagnosis of cruciate ligament injuries is crucial to prevent adverse outcomes, including delayed treatment, chronic instability, or long-term functional limitations.
Highlights
• Assessment of coronary artery plaque burden according to the CAC-DRS Score correlated well with pulmonary involvement of SARS-CoV-2 pneumonia (min. r=0.81, 95% CI 0.76 to 0.86).
• Visual and quantitative CAC-DRS Score of coronary artery plaque burden provided independent prognostic information on all-cause mortality in patients with SARS-CoV-2 pneumonia (p=0.0016 and p<0.0001, respectively).
• Incorporating CAC-DRS Score and pulmonary involvement into clinical decision making revealed great potential to discriminate patients with fatal outcomes from a mild course of disease (AUC 0.938, 95% CI 0.89 to 0.97) and the need for intensive care treatment (AUC 0.801, 95% CI 0.77 to 0.83).
Purpose: To assess and correlate pulmonary involvement and outcome of SARS-CoV-2 pneumonia with the degree of coronary plaque burden based on the CAC-DRS classification (Coronary Artery Calcium Data and Reporting System).
Methods: This retrospective study included 142 patients with confirmed SARS-CoV-2 pneumonia (58 ± 16 years; 57 women) who underwent non-contrast CT between January 2020 and August 2021 and were followed up for 129 ± 72 days. One experienced blinded radiologist analyzed CT series for the presence and extent of calcified plaque burden according to the visual and quantitative HU-based CAC-DRS Score. Pulmonary involvement was automatically evaluated with a dedicated software prototype by another two experienced radiologists and expressed as Opacity Score.
Results: CAC-DRS Scores derived from visual and quantitative image evaluation correlated well with the Opacity Score (r=0.81, 95% CI 0.76-0.86, and r=0.83, 95% CI 0.77-0.89, respectively; p<0.0001) with higher correlation in severe than in mild stage SARS-CoV-2 pneumonia (p<0.0001). Combined, CAC-DRS and Opacity Scores revealed great potential to discriminate fatal outcomes from a mild course of disease (AUC 0.938, 95% CI 0.89-0.97), and the need for intensive care treatment (AUC 0.801, 95% CI 0.77-0.83). Visual and quantitative CAC-DRS Scores provided independent prognostic information on all-cause mortality (p=0.0016 and p<0.0001, respectively), both in univariate and multivariate analysis.
Conclusions: Coronary plaque burden is strongly correlated to pulmonary involvement, adverse outcome, and death due to respiratory failure in patients with SARS-CoV-2 pneumonia, offering great potential to identify individuals at high risk.
Background: Dual-energy CT (DECT)-derived bone mineral density (BMD) of the distal radius and other CT-derived metrics related to bone health have been suggested for opportunistic osteoporosis screening and risk evaluation for sustaining distal radius fractures (DRFs).
Methods: The distal radius of patients who underwent DECT between 01/2016 and 08/2021 was retrospectively analyzed. Cortical Hounsfield Unit (HU), trabecular HU, cortical thickness, and DECT-based BMD were acquired from a non-fractured, metaphyseal area in all examinations. Receiver-operating characteristic (ROC) analysis was conducted to determine the area under the curve (AUC) values for predicting DRFs based on DECT-derived BMD, HU values, and cortical thickness. Logistic regression models were then employed to assess the associations of these parameters with the occurrence of DRFs.
Results: In this study, 263 patients (median age: 52 years; interquartile range: 36–64; 132 women; 192 fractures) were included. ROC curve analysis revealed a higher area under the curve (AUC) value for DECT-derived BMD compared to cortical HU, trabecular HU, and cortical thickness (0.91 vs. 0.61, 0.64, and 0.69, respectively; p <.001). Logistic regression models confirmed the association between lower DECT-derived BMD and the occurrence of DRFs (Odds Ratio, 0.83; p <.001); however, no influence was observed for cortical HU, trabecular HU, or cortical thickness.
Conclusions: DECT can be used to assess the BMD of the distal radius without dedicated equipment such as calibration phantoms to increase the detection rates of osteoporosis and stratify the individual risk to sustain DRFs. In contrast, assessing HU-based values and cortical thickness does not provide clinical benefit.
Rationale and Objectives: Bone non-union is a serious complication of distal radius fractures (DRF) that can result in functional limitations and persistent pain. However, no accepted method has been established to identify patients at risk of developing bone non-union yet. This study aimed to compare various CT-derived metrics for bone mineral density (BMD) assessment to identify predictive values for the development of bone non-union.
Materials and Methods: CT images of 192 patients with DRFs who underwent unenhanced dual-energy CT (DECT) of the distal radius between 03/2016 and 12/2020 were retrospectively identified. Available follow-up imaging and medical health records were evaluated to determine the occurrence of bone non-union. DECT-based BMD, trabecular Hounsfield unit (HU), cortical HU and cortical thickness ratio were measured in normalized non-fractured segments of the distal radius.
Results: Patients who developed bone non-union were significantly older (median age 72 years vs. 54 years) and had a significantly lower DECT-based BMD (median 68.1 mg/cm3 vs. 94.6 mg/cm3, p < 0.001). Other metrics (cortical thickness ratio, cortical HU, trabecular HU) showed no significant differences. ROC and PR curve analyses confirmed the highest diagnostic accuracy for DECT-based BMD with an area under the curve (AUC) of 0.83 for the ROC curve and an AUC of 0.46 for the PR curve. In logistic regression models, DECT-based BMD was the sole metric significantly associated with bone non-union.
Conclusion: DECT-derived metrics can accurately predict bone non-union in patients who sustained DRF. The diagnostic performance of DECT-based BMD is superior to that of HU-based metrics and cortical thickness ratio.
Highlights
• Piriform cortex and amgydala can be separated based on their distinct structural connectivity.
• Similar to histological findings, the connectivity of the piriform cortex suggests posterior frontal and temporal subregions.
• Subregions of the piriform cortex have distinct connectivity profiles.
• Anterior PC extended into ventrotemporal PC posteriorly, which has not been described before, requiring further investigation.
• All parcellations were made publicly available.
Abstract
The anatomy of the human piriform cortex (PC) is poorly understood. We used a bimodal connectivity-based-parcellation approach to investigate subregions of the PC and its connectional differentiation from the amygdala.
One hundred (55 % female) genetically unrelated subjects from the Human Connectome Project were included. A region of interest (ROI) was delineated bilaterally covering PC and amygdala, and functional and structural connectivity of this ROI with the whole gray matter was computed. Spectral clustering was performed to obtain bilateral parcellations at granularities of k = 2–10 clusters and combined bimodal parcellations were computed. Validity of parcellations was assessed via their mean individual-to-group similarity per adjusted rand index (ARI).
Individual-to-group similarity was higher than chance in both modalities and in all clustering solutions. The amygdala was clearly distinguished from PC in structural parcellations, and olfactory amygdala was connectionally more similar to amygdala than to PC. At higher granularities, an anterior and ventrotemporal and a posterior frontal cluster emerged within PC, as well as an additional temporal cluster at their boundary. Functional parcellations also showed a frontal piriform cluster, and similar temporal clusters were observed with less consistency. Results from bimodal parcellations were similar to the structural parcellations. Consistent results were obtained in a validation cohort.
Distinction of the human PC from the amygdala, including its olfactory subregions, is possible based on its structural connectivity alone. The canonical fronto-temporal boundary within PC was reproduced in both modalities and with consistency. All obtained parcellations are freely available.
Purpose: To describe a novel surgical technique of a combined implantation of an artificial iris and a scleral fixated intraocular lens (IOL) using flanged IOL haptics (“Yamane” technique).
Observations: The suturelessly implanted artificial iris-IOL-sandwich was stable with good functional as well as aesthetic results. However, our case showed a postoperative intraocular pressure rise.
Conclusions: The presented case demonstrates that a visual as well as cosmetical rehabilitation seems to be possible even after severe, penetrating ocular trauma with profound iris defects.
Importance: The sutureless IOL scleral fixation technique can also be used in combination with a sutureless artificial iris implantation. Further studies are needed to evaluate the long-term safety profile and rates of postoperative complications.
Purpose: The IC-8® Apthera™ (AcuFocus Inc.™, Irvine, California, USA) is the first small aperture intraocular lens (IOL) to receive FDA approval for presbyopia correction in the summer of 2022. It is a single-piece hydrophobic acrylic monofocal lens, which is placed in the capsular bag. In its center it carries a black circular mask (FilterRing™) with a diameter of 3.23 mm consisting of polyvinylidene fluoride and carbon black nanoparticles. In the center of this mask sits a 1.36 mm wide aperture. Thanks to this pinhole effect the IC-8® serves as an extended-depth-of-focus (EDOF) IOL and can be used in presbyopia correction.
This report describes the case of a patient with an IC-8® implant who underwent Nd:YAG laser capsulotomy for posterior capsule opacification (PCO). The post laser checkup showed a dark central optical change within the IOL and the patient described optical phenomena as well as blurred central vision, which is why he received IOL exchange. The explanted IC-8® was sent to the Intermountain Ocular Research Center at the University of Utah for further analysis.
Observations: A 56-year-old male underwent cataract surgery with implantation of a non-diffractive EDOF-IOL on the right and the IC-8® small aperture IOL on the left eye. On the left eye, the patient had received penetrating keratoplasty seven years prior to the cataract operation due to posttraumatic corneal scarring. The early checkups after cataract surgery showed a corrected distance visual acuity (CDVA) in the left eye of +0.1 logMAR in the first month. About 5 months after the operation, PCO was first described on the left eye leading to a decrease in visual acuity to +0.4 logMAR (CDVA). Due to PCO, Nd:YAG laser capsulotomy was conducted 5 months after the cataract operation on the left eye. 12 shots were applied at 2.7 mJ. The following appointments showed a continuously reduced visual acuity of +1.3 logMAR (uncorrected) on the left eye and the patient described blurry and ‘swirled’ central vision. By slightly tilting his head and thus not using the center of his optic axis, he would be able to see sharper. Slit lamp examination showed a small optical change inside the IC-8® IOL not resembling a pit but believed to be a small pocket of air. Due to the ongoing symptoms as well as the reduced VA, the seemingly damaged small aperture IOL was exchanged for a three-piece hydrophobic acrylic monofocal lens, which was also placed in the posterior chamber. The explanted IC-8® was sent to the Intermountain Ocular Research Center at the University of Utah for further analysis. Results from gross and light microscopic analysis showed that the change caused by the Nd:YAG laser application consisted of a localized optical area containing carbon black nanoparticles used for the circular mask within the IOL.
Conclusions and importance: When dealing with PCO and performing Nd:YAG laser capsulotomy in eyes with an IC-8® IOL implant, the laser shots should be applied either inside the aperture or outside of the black circular mask of the IOL. Otherwise, the Nd:YAG laser can lead to bursts of carbon nanoparticles within the IOL which may cause optical phenomena as well as decreased visual acuity possibly resulting in an IOL exchange.
Ferroptosis is a regulated form of cell death which is considered an oxidative iron-dependent process. The lipid hydroperoxidase glutathione peroxidase 4 prevents the iron (Fe2+)-dependent formation of toxic lipid reactive oxygen species. While emerging evidence indicates that inhibition of glutathione peroxidase 4 as a hallmark of ferroptosis in many cancer cell lines, the involvement of this biochemical pathway in neuronal death remains largely unclear. Here, we investigate, first whether the ferroptosis key players are involved in the neuronal cell death induced by erastin. The second objective was to examine whether there is a cross talk between ferroptosis and autophagy. The third main was to address neuron response to erastin, with a special focus on ferritin and nuclear receptor coactivator 4-mediated ferritinophagy. To test this in neurons, erastin (0.5–8 µM) was applied to hippocampal HT22 neurons for 16 hours. In addition, cells were cultured with the autophagy inhibitor, 3-methyladenin (10 mM) and/or ferroptosis inhibitors, ferrostatin 1 (10–20 µM) or deferoxamine (10–200 µM) before exposure to erastin. In this study, we demonstrated by immunofluorescence and western blot analysis, that erastin downregulates dramatically the expression of glutathione peroxidase 4, the sodium-independent cystine-glutamate antiporter and nuclear receptor coactivator 4. The protein levels of ferritin and mitochondrial ferritin in HT22 hippocampal neurons did not remarkably change following erastin treatment. In addition, we demonstrated that not only the ferroptosis inhibitor, ferrostatin1/deferoxamine abrogated the ferroptotic cell death induced by erastin in hippocampal HT22 neurons, but also the potent autophagy inhibitor, 3-methyladenin. We conclude that (1) erastin-induced ferroptosis in hippocampal HT22 neurons, despite reduced nuclear receptor coactivator 4 levels, (2) that either nuclear receptor coactivator 4-mediated ferritinophagy does not occur or is of secondary importance in this model, (3) that ferroptosis seems to share some features of the autophagic cell death process.
In the basal, proliferative layer of healthy skin, the mTOR complex 1 (mTORC1) is activated, thus regulating proliferation while preventing differentiation. When cells leave the proliferative, basal compartment, mTORC1 signaling is turned off, which allows differentiation. Under inflammatory conditions, this switch is hijacked by cytokines and prevents proper differentiation. It is currently unknown how mTORC1 is regulated to mediate these effects on keratinocyte differentiation. In other tissues, mTORC1 activity is controlled through various pathways via the tuberous sclerosis complex (TSC). Thus, we investigated whether the TS complex is regulated by proinflammatory cytokines and contributes to the pathogenesis of psoriasis. TNF-α as well as IL-1β induced the phosphorylation of TSC2, especially on S939 via the PI3-K/AKT and MAPK pathway. Surprisingly, increased TSC2 phosphorylation could not be detected in psoriasis patients. Instead, TSC2 was strongly downregulated in lesional psoriatic skin compared to non-lesional skin of the same patients or healthy skin. In vitro inflammatory cytokines induced dissociation of TSC2 from the lysosome, followed by destabilization of the TS complex and degradation. Thus, we assume that in psoriasis, inflammatory cytokines induce strong TSC2 phosphorylation, which in turn leads to its degradation. Consequently, chronic mTORC1 activity impairs ordered keratinocyte differentiation and contributes to the phenotypical changes seen in the psoriatic epidermis.
The culture of primary intestinal epithelia cells is not possible in a normal culture system. In 2009 a three-dimensional culture system of intestinal stem cells was established that shows many of the physiological features of the small intestine, such as crypt-villus structure, stem cell niche and all types of differentiated intestinal epithelial cells. These enteroids can be used to analyze biology of intestinal stem cells, gut homeostasis and the development of diseases. They also give the possibility to reduce animal numbers, as enteroids can be cryo-conserved and cultivated for many passages. To investigate the influence of genes such as NADPH oxidases on the gut homeostasis, transgenic approached are the method of choice. The generation of enteroids from knockout mice allows real-time observations of knockout effects. Often conditional knockout or overexpression strategies using inducible Cre recombinase are applied to avoid effects of adaption to the knockout. However, the Cre recombinase has many known caveats from unspecific binding and its endonuclease activity. In this study, we show that although NADPH oxidases are important for in vivo differentiation and proliferation of the intestine, their expression is drastically reduced in the organoid system. Activation of Cre recombinase by 4-hydroxy tamoxifen in freshly isolated enteroids, independently of floxed genes, leads to decreased diameter of organoids. This effect is concentration-dependent and is caused by reduced cell proliferation and induction of apoptosis and DNA damage. In contrast, constitutive expression of Cre has no impact on the enteroids. Therefore, reduction of tamoxifen concentration and treatment duration should be carefully titrated, and appropriate controls are necessary.