Clinical performance and risk factors of all-ceramic screw-retained implant crowns in the posterior region based on a retrospective investigation.

OBJECTIVES: Clinical data on all-ceramic screw-retained implant crowns (SICs) luted on titanium base abutments (TBAs) over more than 3 years are sparse. This study aimed to evaluate the clinical performance and potential risk factors for these restorations. MATERIALS AND METHODS: Analysis took place based on the medical patient-records of three dental offices. Implant survival and prosthetic complications over time were evaluated. The study included SICs in premolar and molar regions made from monolithic lithium disilicate ceramic (M_LiDi) or veneered zirconia (V_ZiO) luted on a TBA documented over an observation time of at least 3 years. Survival and complication rates were calculated and compared by a log-rank test. Cox-Regressions were used to check potential predictors for the survival (p < .05). RESULTS: Six hundred and one crowns out of 371 patients met the inclusion criteria and follow-up period was between 3.0 and 12.9 (mean: 6.4 (SD: 2.1)) years. Over time, six implants had to be removed and 16 restorations had to be refabricated. The estimated survival rates over 10 years were 93.5% for M_LiDi and 95.9% for V_ZiO and did not differ significantly among each other (p = .80). However, V_ZiO showed significantly higher complication rates (p = .003). Material selection, sex, age, and implant diameter did not affect the survival of investigated SICs but crown height influences significantly the survival rate (hazard ratio, HR = 1.26 (95%CI: 1.08, 1.49); p = .043). CONCLUSIONS: Screw-retained SICs luted on TBAs that were fabricated from monolithic lithium disilicate ceramic or veneered zirconia showed reliable and similar survival rates. Increasing crown heights reduced survival over the years.

Ubiquitin: Characterization of a Host Cell Protein Covalently Attached to a Monoclonal Antibody Product by LC-MS/MS.

Host cell protein (HCP) characterization is a crucial quality parameter for biotherapeutic drug safety and stability. With a liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach, we identified ubiquitin in ultrafiltration/diafiltration (UF/DF) pools of one of our monoclonal antibody (mAb) products. Since ubiquitin occurs physiologically as a post-translational modification (PTM) involved in many cellular functions, we suspected the possibility that if identified as an HCP, it may occur as a covalent modification on the mAb. In fact, in this study we characterized and quantified the ubiquitin modification on the Fc domain of mAbX by data dependent acquisition (DDA) and data independent acquisition (DIA) - MS workflows. Covalent binding and site localization were confirmed by identifying a characteristic diglycine motif on the modified peptide. Initially observed reduced detectability of ubiquitin in samples prepared with native digestion was attributed to impaired digestion and subsequent removal along with the mAb in the precipitation step. Our work has contributed to a better understanding of ubiquitin as an HCP considering its specific features such as occurrence in different topologies and provided insight into how covalent binding to a drug product can affect its identification by MS when native digestion conditions are used.

Dimensional reliability in CAD/CAM production of complete denture bases: A comparative study of milling and various 3D printing technologies.

This study aims to assess the dimensional accuracy of complete denture bases fabricated from different CAD/CAM technologies and a conventional method, including milling (CNC), PolyJet (PJ), laser sintering (SLS), digital light processing (DLP), and injection molding (IM). It also examines the influence of the removal of technology-specific connectors or support structures when present. Denture base surfaces were digitized using a laboratory scanner, and virtual measurement points were calculated with tetrahedral reference geometries. Defined distances were measured in all spatial directions and compared to design data (p<0.05), revealing significant differences in sagittal (p=0.004), transversal (p<0.001), and vertical (p<0.001) dimensions. Connector removal had no significant impact for CNC but significantly affected DLP. All technologies yielded clinically acceptable results, with CNC milling demonstrating the best overall outcome.

Monolithic hybrid abutment crowns: Influence of crown height, crown morphology and material on the implant-abutment complex.

PURPOSE: This in vitro study investigated the influence of material selection, crown morphology, and vertical crown height on the biomechanical behavior of monolithic hybrid abutment crowns (HACs). METHODS: Ninety implants were embedded in accordance with ISO standard 14801; ninety HACs were mounted (N=90). Monolithic crowns with varying group-specific designs were luted using titanium bases. HACs were fabricated from monolithic lithium disilicate ceramic (LD) or zirconia-reinforced lithium silicate ceramic (ZLS). The crown morphology was either maxillary premolar (LD_PM, ZLS_PM) or molar (LD_MO). The three groups were further divided into three subgroups of ten specimens, each designed with a small (7.5 mm), middle (10.5 mm), and high (13.5 mm) configuration of crown heights (N=10). A load-to-failure test at 30° off-axis was conducted using a universal testing machine until failure. For statistical analysis, Kolmogorov-Smirnov and Mann-Whitney U tests were conducted (P < 0.05). RESULTS: All LD_MO groups presented the highest failure values (808.7 to 947.9 N), followed by the LD_PM (525.8 to 722.8 N) and ZLS_PM groups (312.6 to 478.8N). A comparison between LD and ZLS materials (P < 0.001) as well as the crown morphology (P < 0.001) showed significant differences in failure values. The values in the subgroups of ZLS_PM (low, middle, high) decreased as the crown height increased. The fracture modes showed no consistent patterns across the test groups. CONCLUSIONS: Material selection, crown morphology, and vertical crown height appear to be important factors that may influence the clinical failure values and patterns of HACs.

Expediting online liquid chromatography for real-time monitoring of product attributes to advance process analytical technology in downstream processing of biopharmaceuticals.

The application of Process Analytical Technology (PAT) principles for manufacturing of biotherapeutics proffers the prospect of ensuring consistent product quality along with increased productivity as well as substantial cost and time savings. Although this paradigm shift from a traditional, rather rigid manufacturing model to a more scientific, risk-based approach has been advocated by health authorities for almost two decades, the practical implementation of PAT in the biopharmaceutical industry is still limited by the lack of fit-for-purpose analytical methods. In this regard, most of the proposed spectroscopic techniques are sufficiently fast but exhibit deficiencies in terms of selectivity and sensitivity, while well-established offline methods, such as (ultra-)high-performance liquid chromatography, are generally considered as too slow for this task. To address these reservations, we introduce here a novel online Liquid Chromatography (LC) setup that was specifically designed to enable real-time monitoring of critical product quality attributes during time-sensitive purification operations in downstream processing. Using this online LC solution in combination with fast, purpose-built analytical methods, sampling cycle times between 1.30 and 2.35 min were achieved, without compromising on the ability to resolve and quantify the product variants of interest. The capabilities of our approach are ultimately assessed in three case studies, involving various biotherapeutic modalities, downstream processes and analytical chromatographic separation modes. Altogether, our results highlight the expansive opportunities of online LC based applications to serve as a PAT tool for biopharmaceutical manufacturing.

A contemporary training concept in critical care cardiology.

Critical care cardiology (CCC) in the modern era is shaped by a multitude of innovative treatment options and an increasingly complex, ageing patient population. Generating high-quality evidence for novel interventions and devices in an intensive care setting is exceptionally challenging. As a result, formulating the best possible therapeutic approach continues to rely predominantly on expert opinion and local standard operating procedures. Fostering the full potential of CCC and the maturation of the next generation of decision-makers in this field calls for an updated training concept, that encompasses the extensive knowledge and skills required to care for critically ill cardiac patients while remaining adaptable to the trainee's individual career planning and existing educational programs. In the present manuscript, we suggest a standardized training phase in preparation of the first ICU rotation, propose a modular CCC core curriculum, and outline how training components could be conceptualized within three sub-specialization tracks for aspiring cardiac intensivists.

Sex-related differences in patients presenting with heart failure-related cardiogenic shock.

BACKGROUND: Heart failure-related cardiogenic shock (HF-CS) accounts for a significant proportion of all CS cases. Nevertheless, there is a lack of evidence on sex-related differences in HF-CS, especially regarding use of treatment and mortality risk in women vs. men. This study aimed to investigate potential differences in clinical presentation, use of treatments, and mortality between women and men with HF-CS. METHODS: In this international observational study, patients with HF-CS (without acute myocardial infarction) from 16 tertiary-care centers in five countries were enrolled between 2010 and 2021. Logistic and Cox regression models were used to assess differences in clinical presentation, use of treatments, and 30-day mortality in women vs. men with HF-CS. RESULTS: N = 1030 patients with HF-CS were analyzed, of whom 290 (28.2%) were women. Compared to men, women were more likely to be older, less likely to have a known history of heart failure or cardiovascular risk factors, and lower rates of highly depressed left ventricular ejection fraction and renal dysfunction. Nevertheless, CS severity as well as use of treatments were comparable, and female sex was not independently associated with 30-day mortality (53.0% vs. 50.8%; adjusted HR 0.94, 95% CI 0.75-1.19). CONCLUSIONS: In this large HF-CS registry, sex disparities in risk factors and clinical presentation were observed. Despite these differences, the use of treatments was comparable, and both sexes exhibited similarly high mortality rates. Further research is necessary to evaluate if sex-tailored treatment, accounting for the differences in cardiovascular risk factors and clinical presentation, might improve outcomes in HF-CS.