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- ischemic stroke (4)
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Introduction: The calipered kinematically-aligned (KA) total knee arthroplasty (TKA) strives to restore the patient's individual pre-arthritic (i.e., native) posterior tibial slope when retaining the posterior cruciate ligament (PCL). Deviations from the patient's individual pre-arthritic posterior slope tighten and slacken the PCL in flexion that drives tibial rotation, and such a change might compromise passive internal tibial rotation and coupled patellofemoral kinematics. Methods: Twenty-one patients were treated with a calipered KA TKA and a PCL retaining implant with a medial ball-in-socket and a lateral flat articular insert conformity that mimics the native (i.e., healthy) knee. The slope of the tibial resection was set parallel to the medial joint line by adjusting the plane of an angel wing inserted in the tibial guide. Three trial inserts that matched and deviated 2°> and 2°< from the patient's pre-arthritic slope were 3D printed with goniometric markings. The goniometer measured the orientation of the tibia (i.e., trial insert) relative to the femoral component. Results: There was no difference between the radiographic preoperative and postoperative tibial slope (0.7 ± 3.2°, NS). From extension to 90° flexion, the mean passive internal tibial rotation with the pre-arthritic slope insert of 19° was greater than the 15° for the 2°> slope (p < 0.000), and 15° for the 2°< slope (p < 0.000). Discussion: When performing a calipered KA TKA with PCL retention, the correct target for setting the tibial component is the patient's individual pre-arthritic slope within a tolerance of ±2°, as this target resulted in a 15–19° range of internal tibial rotation that is comparable to the 15–18° range reported for the native knee from extension to 90° flexion.
Isolated 2‐phenylallyl radicals (2‐PA), generated by pyrolysis from a nitrite precursor, have been investigated by IR/UV ion dip spectroscopy using free electron laser radiation. 2‐PA is a resonance‐stabilized radical that is considered to be involved in the formation of polycyclic aromatic hydrocarbons (PAH) in combustion, but also in interstellar space. The radical is identified based on its gas‐phase IR spectrum. Furthermore, a number of bimolecular reaction products are identified, showing that the self‐reaction as well as reactions with unimolecular decomposition products of 2‐PA form several PAH efficiently. Possible mechanisms are discussed and the chemistry of 2‐PA is compared with the one of the related 2‐methylallyl and phenylpropargyl radicals.
Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with \(^{68}\)Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world. However, recent years have witnessed the start of a shift from \(^{68}\)Ga- to \(^{18}\)F-labeled PSMA-targeted compounds. The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic. First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite \(^{68}\)Ge/\(^{68}\)Ga generator. Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production. Moreover, \(^{18}\)F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions. In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy. Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron. In light of these advantageous characteristics, \(^{18}\)F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available. We have aimed to provide a concise overview of emerging \(^{18}\)F-labeled PSMA-targeted radiotracers undergoing active clinical development. Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available \(^{18}\)F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios.
Ischemic stroke caused by thromboembolic occlusion of large cerebral arteries, such as the internal carotid (ICA) and/or the middle cerebral artery (MCA), is treated by mechanical thrombectomy (MT). MT allows salvage of the vessel-occluding thrombemboli, which most frequently originate from the left atrium or the left ventricle of the heart or from sites of plaque rupture within large arteries above the heart. Clot composition may influence the efficacy of (intravenous) thrombolysis and MT, respectively. We analyzed 37 human thrombemboli obtained from acute ischemic stroke patients during MT with special emphasis on histological staining of neutrophils and neutrophil extracellular traps (NETs). We found neutrophils as the main cellular component of cerebral thrombemboli but encountered considerable morphological heterogeneity. Neutrophils accumulated in the border region of fibrin-rich structures indicating possible interaction of neutrophils with distinct structural thrombembolus components. Web-like NETs were found in 35 of 37 thrombemboli in varying amounts. NETs were almost exclusively found within fibrin-rich areas. Importantly, stroke etiology, age and present oral anticoagulation was associated with morphological patterns and the amount of neutrophils. Correlation of histological data and imaging data revealed that relative Hounsfield units of cerebral thrombemboli positively correlated with the amount of red blood cells. In summary, our results demonstrate that neutrophils and NETs are substantial constituents of cerebral thrombemboli and contribute to their structural complexity.
(1) Background: The aim of this study is to assess perioperative therapy in stage IA-III pancreatic cancer cross-validating the German Cancer Registry Group of the Society of German Tumor Centers — Network for Care, Quality, and Research in Oncology, Berlin (GCRG/ADT) and the National Cancer Database (NCDB). (2) Methods: Patients with clinical stage IA-III PDAC undergoing surgery alone (OP), neoadjuvant therapy (TX) + surgery (neo + OP), surgery+adjuvantTX (OP + adj) and neoadjuvantTX + surgery + adjuvantTX (neo + OP + adj) were identified. Baseline characteristics, histopathological parameters, and overall survival (OS) were evaluated. (3) Results: 1392 patients from the GCRG/ADT and 29,081 patients from the NCDB were included. Patient selection and strategies of perioperative therapy remained consistent across the registries for stage IA-III pancreatic cancer. Combined neo + OP + adj was associated with prolonged OS as compared to neo + OP alone (17.8 m vs. 21.3 m, p = 0.012) across all stages in the GCRG/ADT registry. Similarly, OS with neo + OP + adj was improved as compared to neo + OP in the NCDB registry (26.4 m vs. 35.4 m, p < 0.001). (4) Conclusion: The cross-validation study demonstrated similar concepts and patient selection criteria of perioperative therapy across clinical stages of PDAC. Neoadjuvant therapy combined with adjuvant therapy is associated with improved overall survival as compared to either therapy alone.
Platelet collagen interactions at sites of vascular injuries predominantly involve glycoprotein VI (GPVI) and the integrin α2β1. Both proteins are primarily expressed on platelets and megakaryocytes whereas GPVI expression is also shown on endothelial and integrin α2β1 expression on epithelial cells. We recently showed that depletion of GPVI improves stroke outcome without increasing the risk of cerebral hemorrhage. Genetic variants associated with higher platelet surface integrin α2 (ITGA2) receptor levels have frequently been found to correlate with an increased risk of ischemic stroke in patients. However until now, no preclinical stroke study has addressed whether platelet integrin α2β1 contributes to the pathophysiology of ischemia/reperfusion (I/R) injury. Focal cerebral ischemia was induced in C57BL/6 and Itga2\(^{−/−}\) mice by a 60 min transient middle cerebral artery occlusion (tMCAO). Additionally, wild-type animals were pretreated with anti-GPVI antibody (JAQ1) or Fab fragments of a function blocking antibody against integrin α2β1 (LEN/B). In anti-GPVI treated animals, intravenous (IV) recombinant tissue plasminogen activator (rt-PA) treatment was applied immediately prior to reperfusion. Stroke outcome, including infarct size and neurological scoring was determined on day 1 after tMCAO. We demonstrate that targeting the integrin α2β1 (pharmacologic; genetic) did neither reduce stroke size nor improve functional outcome on day 1 after tMCAO. In contrast, depletion of platelet GPVI prior to stroke was safe and effective, even when combined with rt-PA treatment. Our results underscore that GPVI, but not ITGA2, is a promising and safe target in the setting of ischemic stroke.
Previous research suggested that people prefer to administer unpleasant electric shocks to themselves rather than being left alone with their thoughts because engagement in thinking is an unpleasant activity. The present research examined this negative reinforcement hypothesis by giving participants a choice of distracting themselves with the generation of electric shock causing no to intense pain. Four experiments (N = 254) replicated the result that a large proportion of participants opted to administer painful shocks to themselves during the thinking period. However, they administered strong electric shocks to themselves even when an innocuous response option generating no or a mild shock was available. Furthermore, participants inflicted pain to themselves when they were assisted in the generation of pleasant thoughts during the waiting period, with no difference between pleasant versus unpleasant thought conditions. Overall, these results question that the primary motivation for the self-administration of painful shocks is avoidance of thinking. Instead, it seems that the self-infliction of pain was attractive for many participants, because they were curious about the shocks, their intensities, and the effects they would have on them.
Objective
Bridging the gap between experimental stroke and patients by ischemic blood probing during the hyperacute stage of vascular occlusion is crucial to assess the role of inflammation in human stroke and for the development of adjunct treatments beyond recanalization.
Methods
We prospectively observed 151 consecutive ischemic stroke patients with embolic large vessel occlusion of the anterior circulation who underwent mechanical thrombectomy. In all these patients, we attempted microcatheter aspiration of 3 different arterial blood samples: (1) within the core of the occluded vascular compartment and controlled by (2) carotid and (3) femoral samples obtained under physiological flow conditions. Subsequent laboratory analyses comprised leukocyte counting and differentiation, platelet counting, and the quantification of 13 proinflammatory human chemokines/cytokines.
Results
Forty patients meeting all clinical, imaging, interventional, and laboratory inclusion criteria could be analyzed, showing that the total number of leukocytes significantly increased under the occlusion condition. This increase was predominantly driven by neutrophils. Significant increases were also apparent for lymphocytes and monocytes, accompanied by locally elevated plasma levels of the T‐cell chemoattractant CXCL‐11. Finally, we found evidence that short‐term clinical outcome (National Institute of Health Stroke Scale at 72 hours) was negatively associated with neutrophil accumulation.
Interpretation
We provide the first direct human evidence that neutrophils, lymphocytes, and monocytes, accompanied by specific chemokine upregulation, accumulate in the ischemic vasculature during hyperacute stroke and may affect outcome. These findings strongly support experimental evidence that immune cells contribute to acute ischemic brain damage and indicate that ischemic inflammation initiates already during vascular occlusion. Ann Neurol 2020;87:466–479
Background
In acute ischemic stroke, cessation of blood flow causes immediate tissue necrosis within the center of the ischemic brain region accompanied by functional failure in the surrounding brain tissue designated the penumbra. The penumbra can be salvaged by timely thrombolysis/thrombectomy, the only available acute stroke treatment to date, but is progressively destroyed by the expansion of infarction. The underlying mechanisms of progressive infarction are not fully understood.
Methods
To address mechanisms, mice underwent filament occlusion of the middle cerebral artery (MCAO) for up to 4 h. Infarct development was compared between mice treated with antigen-binding fragments (Fab) against the platelet surface molecules GPIb (p0p/B Fab) or rat immunoglobulin G (IgG) Fab as control treatment. Moreover, Rag1\(^{−/−}\) mice lacking T-cells underwent the same procedures. Infarct volumes as well as the local inflammatory response were determined during vessel occlusion.
Results
We show that blocking of the platelet adhesion receptor, glycoprotein (GP) Ibα in mice, delays cerebral infarct progression already during occlusion and thus before recanalization/reperfusion. This therapeutic effect was accompanied by decreased T-cell infiltration, particularly at the infarct border zone, which during occlusion is supplied by collateral blood flow. Accordingly, mice lacking T-cells were likewise protected from infarct progression under occlusion.
Conclusions
Progressive brain infarction can be delayed by blocking detrimental lymphocyte/platelet responses already during occlusion paving the way for ultra-early treatment strategies in hyper-acute stroke before recanalization.
Objectives: Deep brain stimulation (DBS) programming is based on clinical response testing. Our clinical pilot trial assessed the feasibility of image-guided programing using software depicting the lead location in a patient-specific anatomical model.
Methods: Parkinson's disease patients with subthalamic nucleus-DBS were randomly assigned to standard clinical-based programming (CBP) or anatomical-based (imaging-guided) programming (ABP) in an 8-week crossover trial. Programming characteristics and clinical outcomes were evaluated.
Results: In 10 patients, both programs led to similar motor symptom control (MDS-UPDRS III) after 4 weeks (medicationOFF/stimulationON; CPB: 18.27 ± 9.23; ABP: 18.37 ± 6.66). Stimulation settings were not significantly different, apart from higher frequency in the baseline program than CBP (p = 0.01) or ABP (p = 0.003). Time spent in a program was not significantly different (CBP: 86.1 ± 29.82%, ABP: 88.6 ± 29.0%). Programing time was significantly shorter (p = 0.039) with ABP (19.78 ± 5.86 min) than CBP (45.22 ± 18.32).
Conclusion: Image-guided DBS programming in PD patients drastically reduces programming time without compromising symptom control and patient satisfaction in this small feasibility trial.
Lymphoid aggregates in the CNS of progressive multiple sclerosis patients lack regulatory T cells
(2020)
In gray matter pathology of multiple sclerosis, neurodegeneration associates with a high degree of meningeal inflammatory activity. Importantly, ectopic lymphoid follicles (eLFs) were identified at the inflamed meninges of patients with progressive multiple sclerosis. Besides T lymphocytes, they comprise B cells and might elicit germinal center (GC)-like reactions. GC reactions are controlled by FOXP3+ T-follicular regulatory cells (TFR), but it is unknown if they participate in autoantibody production in eLFs. Receiving human post-mortem material, gathered from autopsies of progressive multiple sclerosis patients, indeed, distinct inflammatory infiltrates enriched with B cells could be detected in perivascular areas and deep sulci. CD35+ cells, parafollicular CD138+ plasma cells, and abundant expression of the homing receptor for GCs, CXCR5, on lymphocytes defined some of them as eLFs. However, they resembled GCs only in varying extent, as T cells did not express PD-1, only few cells were positive for the key transcriptional regulator BCL-6 and ongoing proliferation, whereas a substantial number of T cells expressed high NFATc1 like GC-follicular T cells. Then again, predominant cytoplasmic NFATc1 and an enrichment with CD3+CD27+ memory and CD4+CD69+ tissue-resident cells implied a chronic state, very much in line with PD-1 and BCL-6 downregulation. Intriguingly, FOXP3+ cells were almost absent in the whole brain sections and CD3+FOXP3+ TFRs were never found in the lymphoid aggregates. This also points to less controlled humoral immune responses in those lymphoid aggregates possibly enabling the occurrence of CNS-specific autoantibodies in multiple sclerosis patients.
Polymer micelles are an attractive means to solubilize water insoluble compounds such as drugs. Drug loading, formulations stability and control over drug release are crucial factors for drug‐loaded polymer micelles. The interactions between the polymeric host and the guest molecules are considered critical to control these factors but typically barely understood. Here, we compare two isomeric polymer micelles, one of which enables ultra‐high curcumin loading exceeding 50 wt.%, while the other allows a drug loading of only 25 wt.%. In the low capacity micelles, steady‐state fluorescence revealed a very unusual feature of curcumin fluorescence, a high energy emission at 510 nm. Time‐resolved fluorescence upconversion showed that the fluorescence life time of the corresponding species is too short in the high‐capacity micelles, preventing an observable emission in steady‐state. Therefore, contrary to common perception, stronger interactions between host and guest can be detrimental to the drug loading in polymer micelles.
After starting an orthopedic practice, a surgeon with a fellowship in mechanically aligned (MA) TKA initiated this study to characterize their learning curve after they switched to unrestricted kinematic alignment (KA) TKA using manual instruments. Accordingly, the present study determined for the inexperienced (IE) surgeon the number of cases required to achieve consistent femoral resections and operating times, and whether the femoral resection accuracy, patient-reported outcome measures (PROMs), and component alignment were different from an experienced (E) surgeon. This prospective cohort study analyzed the IE surgeon's first 30 TKAs, all performed with KA, and 30 consecutive KA TKAs performed by an E surgeon. The resection accuracy or deviation was the calipered thickness of the distal and posterior medial and lateral femoral resections minus the planned resection thickness, which was the thickness of the corresponding condyle of the femoral component, minus 2 mm for cartilage wear, and 1 mm for the kerf of the blade. Independent observers recorded the femoral resection thickness, operative times, PROMs, and alignment. For each femoral resection, the deviation between three groups of patients containing ten consecutive KA TKAs, was either insignificant (p = 0.695 to 1.000) or within the 0.5 mm resolution of the caliper, which indicated no learning curve. More than three groups were needed to determine the learning curve for the operative time; however, the IE surgeon's procedure dropped to 77 min for the last 10 patients, which was 20 min longer than the E surgeon. The resection deviations of the IE and E surgeon were comparable, except for the posterolateral femoral resection, which the IE surgeon under-resected by a mean of −0.8 mm (p < 0.0001). At a mean follow-up of 9 and 17 months, the Forgotten Joint Score, Oxford Knee Score, KOOS, and the alignment of the components and limbs were not different between the IE and E surgeon (p ≥ 0.6994). A surgeon that switches to unrestricted KA with manual instruments can determine their learning curve by computing the deviation of the distal and posterior femoral resections from the planned resection. Based on the present study, an IE surgeon could have resection accuracy, post-operative patient outcomes, and component alignment comparable to an E surgeon.
Serotonin (5-hydroxytryptamine, 5-HT) as well as noradrenaline (NA) are key modulators of various fundamental brain functions including the control of appetite. While manipulations that alter brain serotoninergic signaling clearly affect body weight, studies implicating 5-HT transporters and NA transporters (5-HTT and NAT, respectively) as a main drug treatment target for human obesity have not been conclusive. The aim of this positron emission tomography (PET) study was to investigate how these central transporters are associated with changes of body weight after 6 months of dietary intervention or Roux-en-Y gastric bypass (RYGB) surgery in order to assess whether 5-HTT as well as NAT availability can predict weight loss and consequently treatment success. The study population consisted of two study cohorts using either the 5-HTT-selective radiotracer [\(^{11}\)C]DASB to measure 5-HTT availability or the NAT-selective radiotracer [\(^{11}\)C]MRB to assess NAT availability. Each group included non-obesity healthy participants, patients with severe obesity (body mass index, BMI, >35 kg/m\(^2\)) following a conservative dietary program (diet) and patients undergoing RYGB surgery within a 6-month follow-up. Overall, changes in BMI were not associated with changes of both 5-HTT and NAT availability, while 5-HTT availability in the dorsal raphe nucleus (DRN) prior to intervention was associated with substantial BMI reduction after RYGB surgery and inversely related with modest BMI reduction after diet. Taken together, the data of our study indicate that 5-HTT and NAT are involved in the pathomechanism of obesity and have the potential to serve as predictors of treatment outcomes.
(1) Background: Metabolically healthy obesity (MHO) is a concept that applies to obese patients without any elements of metabolic syndrome (metS). In turn, metabolically unhealthy obesity (MUO) defines the presence of elements of metS in obese patients. The components of MUO can be divided into subgroups regarding the elements of inflammation, lipid and glucose metabolism and cardiovascular disease. MUO patients appear to be at greater risk of developing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) compared to MHO patients. The aim of this study was to evaluate the influence of different MUO components on NAFLD and NASH in patients with morbid obesity undergoing bariatric surgery. (2) Methods: 141 patients undergoing bariatric surgery from September 2015 and October 2021 at RWTH Aachen university hospital (Germany) were included. Patients were evaluated pre-operatively for characteristics of metS and MUO (HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension). Intraoperatively, a liver biopsy was taken from the left liver lobe and evaluated for the presence of NAFLD or NASH. In ordinal regression analyses, different factors were evaluated for their influence on NAFLD and NASH. (3) Results: Mean BMI of the patients was 52.3 kg/m\(^2\) (36–74.8, SD 8.4). Together, the parameters HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension accounted for a significant amount of variance in the outcome, with a likelihood ratio of χ\(^2\) (9) = 41.547, p < 0.001, for predicting the presence of NASH. Only HOMA was an independent predictor of NASH (B = 0.102, SE = 0.0373, p = 0.007). Evaluation of steatosis showed a similar trend (likelihood ratio χ\(^2\) (9) = 40.272, p < 0.001). Independent predictors of steatosis were HbA1c (B = 0.833, SE = 0.343, p = 0.015) and HOMA (B = 0.136, SE = 0.039, p < 0.001). (4) Conclusions: The above-mentioned model, including components of MUO, was significant for diagnosing NASH in patients with morbid obesity undergoing bariatric surgery. Out of the different subitems, HOMA independently predicted the presence of NASH and steatosis, while HbA1c independently predicted steatosis and fibrosis. Taken together, the parameter of glucose metabolism appears to be more accurate for the prediction of NASH than the parameters of lipid metabolism, inflammation or the presence of cardiovascular disease.
Background: In total knee arthroplasty (TKA), inserts can have different levels of medial and lateral congruency determined by the acuteness of the upslopes of the anterior and posterior articular surfaces. The present study evaluated an insert with different levels of lateral congruency and a medial ball-in-socket congruency to test the hypothesis that a lateral flat (F) insert maximizes external tibial orientation at extension and internal orientation at 90° flexion and lowers the incidence of anterior lift-off relative to low-congruent (LC) and ultracongruent (UC) lateral inserts. Methods: Two surgeons treated 23 patients with unrestricted caliper-verified kinematic alignment (KA) and posterior cruciate ligament (PCL) retention. They randomly trialed inserts with a medial radial dial that functioned as a built-in goniometer by measuring the tibial orientation relative to a sagittal line on the femoral trial component. Anterior lift-off of the insert from the baseplate indicated PCL tightness. Results: The F insert’s mean of 9° of external tibial orientation was higher than that of the LC (5°, p < 0.0001) and UC inserts (2°, p < 0.0001). The −13° of internal tibial orientation at 90° flexion was higher than that of the LC (−9°, p < 0.0001) and UC inserts (−7°, p < 0.0001). The 0% incidence of anterior lift-off was less than that of the LC (26%) and UC inserts (57%) (p < 0.0001). Conclusions: Surgeons and implant manufacturers should know that adding congruency to the lateral articular surface limits external tibial orientation in extension and internal tibial orientation at 90° flexion and overtightens the PCL. These rotational limitations and flexion space tightness can adversely affect patellofemoral tracking and knee flexion.
As the conformity of a medial ball-in-socket total knee arthroplasty (TKA) provides intrinsic anterior-posterior (A-P) stability, surgeons cannot rely on the manual examination of sagittal laxity to identify the optimal insert thickness. Instead, the present study determined whether measuring tibial axial orientation in extension and 90° flexion with an insert goniometer could identify the optimal thickness that, when implanted, provides high postoperative function. In twenty-two patients that underwent unrestricted caliper-verified kinematic alignment (KA) with a PCL retaining implant, two surgeons measured tibial orientation in extension and 90° flexion with 10, 11, 12, and 13 mm thick insert goniometers. Each TKA had one insert thickness that restored either the maximum external tibial orientation in extension, the maximum internal tibial orientation at 90° flexion, or both relative to 1 mm thinner and thicker inserts. In addition, the 6-month median [interquartile range] Forgotten Joint Score of 73 (54–87) and Oxford Knee Score of 42 (38–45) indicated high satisfaction and function. In conclusion, surgeons using a medial ball-in-socket TKA design can measure external tibial orientation in extension and internal tibial orientation at 90° flexion with an insert goniometer. Furthermore, implanting an insert with the thickness that provided the maximum orientation values resulted in high postoperative function, thereby personalizing PCL tension.
Background: Unrestricted caliper-verified kinematically aligned (KA) TKA restores patient’s prearthritic coronal and sagittal alignments, which have a wide range containing outliers that concern the surgeon practicing mechanical alignment (MA). Therefore, knowing which radiographic parameters are associated with dissatisfaction could help a surgeon decide whether to rely on them as criteria for revising an unhappy patient with a primary KA TKA using MA principles. Hence, we determined whether the femoral mechanical angle (FMA), hip–knee–ankle angle (HKAA), tibial mechanical angle (TMA), tibial slope angle (TSA), and the indicators of patellofemoral tracking, including patella tilt angle (PTA) and the lateral undercoverage of the trochlear resection (LUCTR), are associated with clinical outcome scores. Methods: Forty-three patients with a CT scan and skyline radiograph after a KA TKA with PCL retention and medial stabilized design were analyzed. Linear regression determined the strength of the association between the FMA, HKA angle, PTS, PTA, and LUCTR and the forgotten joint score (FJS), Oxford knee score (OKS), and KOOS Jr score obtained at a mean of 23 months. Results: There was no correlation between the FMA (range 2° varus to −10° valgus), HKAA (range 10° varus to −9° valgus), TMA (range 10° varus to −0° valgus), TSA (range 14° posterior to −4° anterior), PTA (range, −10° medial to 14° lateral), and the LUCTR resection (range 2 to 9 mm) and the FJS (median 83), the OKS (median 44), and the KOOS Jr (median 85) (r = 0.000 to 0.079). Conclusions: Surgeons should be cautious about using postoperative FMA, HKAA, TMA, TSA, PTA, and LUCTR values within the present study’s reported ranges to explain success and dissatisfaction after KA TKA.
(1) Background: Global incidence of type 1 diabetes (T1D) is rising and nearly half occurred in adults. However, it is unclear if certain early-life childhood T1D risk factors were also associated with adult-onset T1D. This study aimed to assess associations between birth order, delivery mode or daycare attendance and type 1 diabetes (T1D) risk in a population-based cohort and whether these were similar for childhood- and adult-onset T1D (cut-off age 15); (2) Methods: Data were obtained from the German National Cohort (NAKO Gesundheitsstudie) baseline assessment. Self-reported diabetes was classified as T1D if: diagnosis age ≤ 40 years and has been receiving insulin treatment since less than one year after diagnosis. Cox regression was applied for T1D risk analysis; (3) Results: Analyses included 101,411 participants (100 childhood- and 271 adult-onset T1D cases). Compared to “only-children”, HRs for second- or later-born individuals were 0.70 (95% CI = 0.50–0.96) and 0.65 (95% CI = 0.45–0.94), respectively, regardless of parental diabetes, migration background, birth year and perinatal factors. In further analyses, higher birth order reduced T1D risk in children and adults born in recent decades. Caesarean section and daycare attendance showed no clear associations with T1D risk; (4) Conclusions: Birth order should be considered in both children and adults’ T1D risk assessment for early detection.
Medication-related osteonecrosis of the jaw (MRONJ) represents an adverse side effect of antiresorptive and antiangiogenic medications. It is associated with impaired quality of life, oral health, and oral function and can be classified into various stages. The purpose of this prospective clinical study is to evaluate the impact of stages I and II MRONJ on oral-health-related quality of life (OHRQoL) and related parameters. Patients’ OHRQoL, satisfaction with life, oral discomfort, and oral health were assessed using the German version of the Oral Health Impact Profile (OHIP-G49), visual analog scales (VAS), and Satisfaction with Life Scale (SWLS) at baseline (T0), 10 days (T1), and 3 months after treatment (T2) in 36 patients. Data were analyzed using Kolmogorov–Smirnov test, two-way mixed ANOVAs, and follow-up Mann–Whitney U tests. The impact of treatment effects on the original seven OHIP domain structures and the recently introduced four-dimensional OHIP structure were evaluated using linear regression analysis. Thirty-six patients received surgical MRONJ treatment. Before treatment, patients’ perceived OHRQoL, oral discomfort, oral health, and satisfaction with life were negatively affected by MRONJ. Surgical treatment significantly improved OHRQoL and related parameters (all p ≤ 0.012). This improvement was greater in patients with higher impairment at T0. OHRQoL and oral restrictions were still impaired after treatment in patients who needed prosthetic treatment. The four-dimensional structure revealed valuable information beyond the standard seven OHIP domains. Increased awareness of MRONJ risks and an interdisciplinary treatment approach for MRONJ patients are needed.