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Savigny, Clara von ; Juratli, Mazen A. ; Koch, Christine ; Gruber-Rouh, Tatjana ; Bechstein, Wolf Otto ; Schreckenbach, Teresa
Aim: The reversal of diverting loop ileostomy (DLI) is one of surgical trainees’ first procedures. Complications of DLI reversal can cause life-threatening complications and increase patient morbidity. This study compared DLI reversals performed by surgical trainees with those by attending surgeons.
Method: This retrospective cohort study was performed at a single primary care center on 300 patients undergoing DLI reversal. The primary outcome was morbidity, according to the Clavien-Dindo classification (CDC), with special attention paid to the surgeon’s level of training. The secondary endpoint was postoperative intestinal motility dysfunction.
Results: Surgical trainees had significantly longer operation times (p < 0.001) than attending surgeons. Univariate analyses revealed no influence on the level of training for postoperative morbidity. First bowel movement later than 3 days after surgery was a significant risk factor for CDC 3 (OR, 4.348; 96% CI, 1670–11.321; p = 0.003). Independent risk factors for surgical site infections (SSIs) were an elevated BMI (OR, 1.162; 95% CI, 1.043–1.1294; p = 0.007) and a delayed bowel movement (OR, 3.973; 95% CI, 1.300–12.138; p = 0.015). For postoperative intestinal motility dysfunction, an independent risk factor was a primary malignant disease (OR, 1.980; 95% CI, 1.120–3.500; p = 0.019), and side-to-side stapled anastomosis was a protective factor (OR, 0.337; 95% CI 0.155–0.733; p = 0.006).
Conclusion: Even though surgical trainees needed significantly more time to perform the surgery, the level of surgical training was not a risk factor for increased postoperative morbidity. Instead, delayed first bowel movement was predictive of SSI.
Koschade, Sebastian E. ; Stratmann, Jan Alexander ; Steffen, Björn ; Shaid, Shabnam ; Finkelmeier, Fabian ; Serve, Hubert ; Miesbach, Wolfgang ; Brandts, Christian Hubertus ; Ballo, Olivier
Objectives and methods: Venous thromboembolic (VTE) events are emerging as frequent complications in acute myeloid leukemia (AML); however, there is insufficient data regarding epidemiology, risk factors, and impact on outcomes. The optimal approach to balance risks of thrombosis and hemorrhage remains unclear. This retrospective single-center study in AML patients undergoing induction chemotherapy between 2007 and 2018 assessed incidence, risk factors, features, and outcomes of early-onset VTE.
Results: 423 patients (median age 59 years) were enrolled. VTE was diagnosed in 31 patients (7.3%) within 3 months of admission. The median time to VTE was 3 days. Non-central venous catheter (CVC)-related VTE occurred in 19 patients (61%). Main risk factor for VTE was leukocytosis at admission, independent of platelet counts/INR. Four patients (13%) exhibited VTE recurrence. No deaths directly related to VTE or major bleeding events associated with platelet-adjusted anticoagulation in patients with VTE were recorded. There was no clear impact of VTE on 1-year overall survival; however, non-CVC-related VTE may be associated with adverse outcomes.
Conclusions: Early-onset VTE is a common complication in newly diagnosed AML patients admitted for induction chemotherapy. Leukocytosis is an independent VTE risk factor. The potentially adverse impact of non-CVC-related VTE merits further study.
Mende, Hannah ; Khatri, Anshu ; Lange, Carolin ; Poveda-Cuevas, Sergio Alejandro ; Tascher, Georg ; Covarrubias-Pinto, Adriana ; Löhr, Frank ; Koschade, Sebastian E. ; Đikić, Ivan ; Münch, Christian ; Bremm, Anja ; Brunetti, Lorenzo ; Brandts, Christian Hubertus ; Uckelmann, Hannah Julia ; Dötsch, Volker ; Rogov, Vladimir V. ; Bhaskara, Ramachandra M. ; Müller, Stefan
Highlights
• NPM1/NPM1c induce the autophagy-lysosome pathway by activating the master regulator TFEB
• NPM1/NPM1c bind to GABARAP proteins via an atypical module in their N-terminal regions
• The pro-autophagic activity of NPM1c depends on this GABARAP binding module
Summary
The nucleolar scaffold protein NPM1 is a multifunctional regulator of cellular homeostasis, genome integrity, and stress response. NPM1 mutations, known as NPM1c variants promoting its aberrant cytoplasmic localization, are the most frequent genetic alterations in acute myeloid leukemia (AML). A hallmark of AML cells is their dependency on elevated autophagic flux. Here, we show that NPM1 and NPM1c induce the autophagy-lysosome pathway by activating the master transcription factor TFEB, thereby coordinating the expression of lysosomal proteins and autophagy regulators. Importantly, both NPM1 and NPM1c bind to autophagy modifiers of the GABARAP subfamily through an atypical binding module preserved within its N terminus. The propensity of NPM1c to induce autophagy depends on this module, likely indicating that NPM1c exerts its pro-autophagic activity by direct engagement with GABARAPL1. Our data report a non-canonical binding mode of GABARAP family members that drives the pro-autophagic potential of NPM1c, potentially enabling therapeutic options.
Drosos, Ioannis ; De Rosa, Roberta ; Cremer, Sebastian ; Seppelt, Philipp ; Hemmann, Katrin ; Oppermann, Jana ; Blessing, Recha Ruth Liselotte ; Mas-Peiro, Silvia ; Vasa-Nicotera, Mariuca ; Zeiher, Andreas M. ; Dimitriadis, Zisis
Background: Percutaneous left atrial appendage occlusion (LAAO) represents an alternative stroke prevention method in patients with atrial fibrillation and an increased bleeding risk, chronic kidney disease or contraindications to oral anticoagulants. Aim of our study was to evaluate the feasibility and safety of percutaneous LAAO in high-risk, frail patients having undergone transcatheter aortic valve implantation (TAVI).
Methods: Thirty-one patients having undergone TAVI and scheduled for LAAO were prospectively included in our study.
Results:Implantation was successful in 29 of 31 cases (93.5%).There were no patients that developed a major acute cardiovascular event, stroke, or device dislocation/embolization. There was a single case of major bleeding (3.2%) and 3 cases of acute kidney injury (9.7%). At 3 months, no patients experienced a stroke, one patient had a device-related thrombus (3.4%), one patient showed a significant peri-device leak, and one patient had a persistent iatrogenic atrial septal defect.
Conclusions: Our study shows that percutaneous LAAO may represent a feasible alternative strategy for stroke prevention, that can be safely performed in high-risk, multimorbid patients with high bleeding risk or contraindications to oral anticoagulation.
Müller, Angelina ; Gruhn, Sebastian ; Sawicki, Olga Anastasia ; Glushan, Anastasiya ; Witte, Claudia ; Klaaßen-Mielke, Renate ; Lembeck, Burkhard ; Gerlach, Ferdinand M. ; Greiner, Wolfgang ; Karimova, Kateryna
Objective: To evaluate a novel healthcare programme for the treatment of patients with hip and knee osteoarthritis in southern Germany in terms of clinical and health economic outcomes. The study is based on claims data from 2014 to 2017.
Methods: We conducted a retrospective comparative cohort study of 9768 patients with hip and knee osteoarthritis, of whom 9231 were enrolled in a collaborative ambulatory orthopaedic care programme (intervention group), and 537 patients received usual orthopaedic care (control group). Key features of the programme are coordinated care, morbidity-adapted reimbursement and extended consultation times. Multivariable analysis was performed to determine effects on health utilisation outcomes. The economic analysis considered annual costs per patient from a healthcare payer perspective, stratified by healthcare service sector. Besides multivariable regression analyses, bootstrapping was used to estimate confidence intervals for predicted mean costs by group.
Results: Musculoskeletal-disease-related hospitalisation was much less likely among intervention group patients than control group patients [odds ratio (OR): 0.079; 95% CI: 0.062–0.099]. The number of physiotherapy prescriptions per patient was significantly lower in the intervention group (RR: 0.814; 95% CI: 0.721–0.919), while the likelihood of participation in exercise programmes over one year was significantly higher (OR: 3.126; 95% CI: 1.604–6.094). Enrolment in the programme was associated with significantly higher ambulatory costs (€1048 vs. €925), but costs for inpatient care, including hospital stays, were significantly lower (€1003 vs. €1497 and €928 vs. €1300 respectively). Overall annual cost-savings were €195 per patient.
Conclusions: Collaborative ambulatory orthopaedic care was associated with reduced hospitalisation in patients with hip and knee osteoarthritis. Health costs for programme participants were lower overall, despite higher costs for ambulatory care.
Schweiger, Josef ; Erdelt, Kurt-Jürgen ; Graf, Tobias ; Sciuk, Thomas ; Edelhoff, Daniel ; Güth, Jan-Frederik
The thickness of a material has a significant impact on its fracture load. The aim of the study was to find and describe a mathematical relationship between the material thickness and the fracture load for dental all-ceramics. In total, 180 specimens were prepared from a leucite silicate ceramic (ESS), a lithium disilicate ceramic (EMX), and a 3Y-TZP zirconia ceramic (LP) in five thicknesses (0.4, 0.7, 1.0, 1.3, and 1.6 mm; n = 12). The fracture load of all specimens was determined using the biaxial bending test according to the DIN EN ISO 6872. The regression analyses for the linear, quadratic, and cubic curve characteristics of the materials were conducted, and the cubic regression curves showed the best correlation (coefficients of determination (R2): ESS R2 = 0.974, EMX R2 = 0.947, LP R2 = 0.969) for the fracture load values as a function of the material thickness. A cubic relationship could be described for the materials investigated. Applying the cubic function and material-specific fracture-load coefficients, the respective fracture load values can be calculated for the individual material thicknesses. These results help to improve and objectify the estimation of the fracture loads of restorations, to enable a more patient- and indication-centered situation-dependent material choice.
The mechanisms underlying the altered postural control and risk of falling in patients with osteoporosis are not yet fully understood. The aim of the present study was to investigate postural sway in women with osteoporosis and a control group. The postural sway of 41 women with osteoporosis (17 fallers and 24 non-fallers) and 19 healthy controls was measured in a static standing task with a force plate. The amount of sway was characterized by traditional (linear) center-of-pressure (COP) parameters. Structural (nonlinear) COP methods include spectral analysis by means of a 12-level wavelet transform and a regularity analysis via multiscale entropy (MSE) with determination of the complexity index. Patients showed increased body sway in the medial–lateral (ML) direction (standard deviation in mm: 2.63 ± 1.00 vs. 2.00 ± 0.58, p = 0.021; range of motion in mm: 15.33 ± 5.58 vs. 10.86 ± 3.14, p = 0.002) and more irregular sway in the anterior–posterior (AP) direction (complexity index: 13.75 ± 2.19 vs. 11.18 ± 4.44, p = 0.027) relative to controls. Fallers showed higher-frequency responses than non-fallers in the AP direction. Thus, postural sway is differently affected by osteoporosis in the ML and AP directions. Clinically, effective assessment and rehabilitation of balance disorders can benefit from an extended analysis of postural control with nonlinear methods, which may also contribute to the improvement of risk profiles or a screening tool for the identification of high-risk fallers, thereby prevent fractures in women with osteoporosis.
A 23-year observational follow-up clinical evaluation of direct posterior composite restorations
(2023)
Gehren, Marie O. von ; Rüttermann, Stefan ; Romanos, Georgios ; Herrmann, Eva ; Gerhardt-Szép, Susanne
The purpose of this observational follow-up clinical study was to observe the quality of posterior composite restorations more than 23 years after application. A total of 22 patients, 13 male and 9 female (mean age 66.1 years, range 50–84), with a total of 42 restorations attended the first and second follow-up examinations. The restorations were examined by one operator using modified FDI criteria. Statistical analysis was performed with the Wilcoxon Mann–Whitney U test and Wilcoxon exact matched-pairs test with a significance level of p = 0.05. Bonferroni–Holm with an adjusted significance level of alpha = 0.05 was applied. With the exception of approximal anatomical form, significantly worse scores were seen for six out of seven criteria at the second follow-up evaluation. There was no significant difference in the first and second follow-up evaluations in the grades of the restorations with regard to having been placed in the maxilla or mandible, as well as for one-surface or multiple-surface restorations. The approximal anatomical form showed significantly worse grades at the second follow-up when having been placed in molars. In conclusion, the study results show that significant differences regarding FDI criteria in posterior composite restorations occur after more than 23 years of service. Further studies with extended follow-up time and at regular and short time intervals are recommended.
Dissecting the diversity of midbrain dopamine (DA) neurons by optotagging is a promising addition to better identify their functional properties and contribution to motivated behavior. Retrograde molecular targeting of DA neurons with specific axonal projection allows further refinement of this approach. Here, we focus on adult mouse DA neurons in the substantia nigra pars compacta (SNc) projecting to dorsal striatum (DS) by demonstrating the selectivity of a floxed AAV9-based retrograde channelrhodopsin-eYFP (ChR-eYFP) labeling approach in DAT-cre mice. Furthermore, we show the utility of a sparse labeling version for anatomical single-cell reconstruction and demonstrate that ChR-eYFR expressing DA neurons retain intrinsic functional properties indistinguishable from conventionally retrogradely red-beads-labeled neurons. We systematically explore the properties of optogenetically evoked action potentials (oAPs) and their interaction with intrinsic pacemaking in this defined subpopulation of DA neurons. We found that the shape of the oAP and its first derivative, as a proxy for extracellularly recorded APs, is highly distinct from spontaneous APs (sAPs) of the same neurons and systematically varies across the pacemaker duty cycle. The timing of the oAP also affects the backbone oscillator of the intrinsic pacemaker by introducing transient “compensatory pauses”. Characterizing this systematic interplay between oAPs and sAPs in defined DA neurons will also facilitate a refinement of DA neuron optotagging in vivo.
Federspiel, Jan M. ; Lux, Constantin Peter ; Burkhard, Katrin ; Kettner, Mattias ; Verhoff, Marcel A. ; Tschernig, Thomas ; Ramsthaler, Frank
Highlights
• Retrograde dye perfusion facilitates functional analysis of aortic valve competency.
• Retrograde dye perfusion visualizes vasa vasorum of the aorta and pulmonary artery.
• Vasa vasorum of the pulmonary artery derive from conal coronary branches in humans.
Abstract
Introduction: Multiple cardiovascular conditions can lead to unexpected fatality, which is defined as sudden cardiac death. One of these potentially underlying conditions is aortic regurgitation, which can be caused by discrete changes of the geometry of the proximal aorta. To analyze aortic valve competency and furthermore to elucidate underlying pathological alterations of the coronary arteries and the vasa vasorum a perfusion method to simulate a diastolic state was designed.
Material and methods: A postmortem approach with retrograde perfusion of the ascending aorta with methylene blue was applied to three bodies. The procedure comprised cannulation of the brachiocephalic trunk, clamping of the aortic arch between brachiocephalic trunk and left carotid artery, infusion of 250 ml of methylene blue, and optical clearing of the superficial tissue layers after perfusion. Organs were examined directly following perfusion and after optical clearing.
Results: Assessment and visualization of aortic valve competency and the vasa vasorum were possible in all three instances. Visualization of the coronary perfusion was impaired by postmortem thrombus formation. Optical clearing did not provide additional information.
Discussion: The method presented here is a time- and cost-efficient way of visualizing aortic valve competency and the vasa vasorum. The visualization of the vasa vasorum highlights the potential of this method in basic research on diseases of the great arteries and coronaries. However, for a time-efficient functional analysis of the coronaries, other methods must be applied.