RepoMed (Medizinische Hochschule Hannover)
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Effects of sandblasting and acid etching on the surface properties of additively manufactured and machined titanium and their consequences for osteoblast adhesion under different storage conditions
Full text linkAdditive manufacturing (AM) enables the production of complex, patient-specific titanium implants. However, the as-built surfaces of AM parts often require postprocessing to enhance surface properties for optimal osseointegration. This study investigates the effects of varying sandblasting pressures (2 bar vs. 6 bar) and subsequent acid etching (SAE) on the surface properties of additively manufactured and machined titanium (Ti-6Al-4V and commercially pure titanium (cp-Ti), respectively). While changes in surface roughness and morphology were assessed at different process stages using optical profilometry and scanning electron microscopy, the analyses of surface wettability (contact angle measurement) were focused on effects after SAE and during different storage conditions (ambient air vs. NaCl). The resulting differences in material properties were then evaluated for their biological impact on osteoblast compatibility. For this purpose, the parameters cell adhesion, morphology, and membrane integrity were investigated using confocal laser microscopy and LDH assay. Initial high roughness of AM titanium surfaces was decreased by sandblasting, while initial smooth machined surfaces (MM) increased in roughness. Acid etching introduced characteristic irregular patterns on the surface with only marginal consequences for the resulting overall roughness. While all surfaces demonstrated high hydrophilicity directly after etching, storage under ambient air increased hydrophobicity over time, while NaCl storage preserved hydrophilicity and improved biocompatibility marginally. Osteoblast adhesion and morphology were optimal only under no storage condition, with uncompromised membrane integrity. Notably, the biological consequences observed for MM and AM titanium were rather similar, considering the differences in used materials, production techniques, and subsequent surface morphologies. Carefully applied SAE can also optimize the surface characteristics of additive manufactured titanium for an improved implant performance, with storage conditions critically influencing surface wettability and bioactivity
PET imaging of tissue reactions in the implanted cochlea: results of a pilot study
Full text linkPurpose After cochlear implantation, molecular processes at the electrode-nerve interface significantly influence the variability in clinical outcomes. The present study investigates molecular processes in a guinea pig model of cochlear implant (CI) using positron emission tomography/computed tomography (PET/CT) and correlates the imaging findings with histological analyses. Methods Animals were examined with PET in the 3 weeks and 9-12 months post-implantation using the inflammation marker [18F]FDG and, at the later time points, [68Ga]FAPI-46 as a marker for fibrosis. Tracer accumulation in the cochlea was determined from PET imaging based on the co-registered CT. Nine animals (seven with unilateral CI) were included. Uptake in non-implanted cochleae served as reference. Tissue growth around the implant was evaluated histologically. Results Post-implantation, [18F]FDG uptake was significantly increased when pooling early and late in investigation time points, while after 1 year, [68Ga]FAPI-46 uptake was increased inside the cochlear. Cochlear volumes measured by CT did not show significant differences between compared groups. Tissue growth around the implant was observed in all animals, with a trend toward increased growth associated with insertion depth. However, no clear correlation was observed between the extent of tissue growth and the uptake intensities of FDG and FAPI. Discussion The data indicate that increased accumulation of PET biomarkers in the cochlea after implantation can be detected in guinea pigs using a dedicated PET/CT. Given the high resolution of current clinical PET/CT devices, this method is expected to be suitable for use in patients, particularly for assessing the effect of anti-inflammatory or anti-fibrotic therapies
Lung adenocarcinoma cell sensitivity to chemotherapies: a spotlight on lipid droplets and SREBF1 Gene
Full text linkLungentransplantation trotz präformierter donorspezifischer HLA-Antikörper: 9 Jahre Erfahrungen eines Zentrums
Full text linkOutpatient interface challenges for drug safety in Parkinson’s disease patients: a questionnaire based cross-sectional study
Full text linkBackground: Parkinson’s disease (PD) is a chronic and multifaceted disease with a variety of motor and non-motor symptoms. The safe symptomatic drug therapy of often multimorbid patients places enormous demands on the competence, communication and coordination of the treating physicians, particularly in the outpatient sector. Objectives: This study aimed to explore aspects of drug safety and interdisciplinary communication in the outpatient sector of PD patients. Methods: A semistructured questionnaire was designed addressing various aspects of drug safety in the outpatient setting. The questionnaire was sent to a total of 1,002 general practitioners (GP) and 1,005 neurologists (NEU). Results: One hundred and forty-seven NEU and eighty-four GP answered the questionnaire. Overall, NEU treated more PD patients, while GP cared for more geriatric PD patients, especially outside of the outpatient clinic (home visits, nursing homes). Regarding the execution of recommended laboratory or technical check-ups, as well as the prescription of new medications, neither a formal agreement nor structured communication existed. Merely the identification of potential drug–drug interactions (DDI) was regularly carried out by both professions. Conclusion: The inadequate interdisciplinary communication hampers therapy safety and consequently the safety of the vulnerable PD patient group. For this reason, standardized and comprehensive communication mechanisms are urgently needed. Solution approaches may include an individual protected digital health record or integrated treatment networks comprising all professionals participating in the management of PD patients
Distinct Inflammatory Imprint in Non-Cirrhotic and Cirrhotic Patients Before and After Direct-Acting Antiviral Therapy
Full text linkBackground/aims Hepatitis C virus (HCV) infection remains a global health challenge, leading to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). Despite the high efficacy of direct-acting antiviral (DAA) therapy in achieving sustained virologic response (SVR), concerns persist regarding long-term immune alterations and residual risks, particularly in cirrhotic patients. Methods This study investigates 75 soluble immune mediator (SIM) profiles in 102 chronic HCV patients, stratified by cirrhosis status, at therapy initiation, end of treatment, and long-term follow-up (median 96 weeks). Findings were compared with 51 matched healthy controls and validated in an independent cohort of 47 cirrhotic patients, 17 of whom developed HCC. Results We observed significant SIM alterations at baseline, with cirrhotic patients displaying a more profoundly dysregulated inflammatory milieu. Despite an overall decline in inflammatory markers following SVR, persistent alterations were evident, particularly in cirrhotic patients. Notably, those with liver stiffness exceeding 14 kPa exhibited sustained inflammatory dysregulation, correlating with liver elastography values. Key SIM such as IL-6, IL-8, urokinase plasminogen activator (uPA), and hepatocellular growth factor (HGF) remained elevated and were associated with HCC development. Network analysis highlighted their roles in liver fibrosis, regeneration, and carcinogenesis. Conclusions These findings underscore the importance of early antiviral intervention to prevent cirrhosis-related sequelae. Future studies should explore the mechanistic pathways linking chronic inflammation, fibrosis, and oncogenesis to identify predictive biomarkers and novel therapeutic targets. Addressing persistent immune alterations post-HCV clearance may improve long-term outcomes, particularly in patients with advanced liver disease
Sex disparities in non-small cell lung cancer: mechanistic insights from a cRaf transgenic disease model
Full text linkDrug utilization in geriatric psychiatric patients in the emergency department: a cohort study under real-world conditions
Full text linkBackground Psychiatric emergencies include agitation, substance-related (e.g., withdrawal) symptoms, and suicidal as well as self-harming behavior and require interdisciplinary management. Drug treatment of geriatric patients in emergency situations may be complicated by adverse drug reactions (ADRs). Objectives This study aimed to investigate prescriptions of potentially inappropriate medications (PIMs) and potential drug-drug interactions (DDIs) in the context of geriatric psychiatric emergencies in the emergency department (ED). Design Retrospective single-center study. Methods The medication lists of 87 consecutively acquired geriatric patient cases receiving pharmacological treatment between January 2018 and December 2022 in a psychiatric emergency department were analyzed. Herein, utilizing the PRISCUS 2.0 list and the Fit fOR The Aged (FORTA) classification, prescriptions of PIMs were assessed, and DDIs were classified with the aid of the drug interaction program AiDKlinik® (Arzneimittel-Informations-Dienste, Dosing GmbH, Heidelberg, Germany). Results A total of 94 drugs were administered during treatment in the ED. The total number of drugs per patient was on average 5.9 1 (median: 5; interquartile range: 4) hereafter. 77.7% of the newly prescribed drugs were PIMs according to the PRISCUS 2.0 list, while 18.1% were designated as therapeutic alternatives to PIMs. 70.2% and 22.3% of the newly recommended drugs were FORTA category C and D drugs, respectively. An average of 0.8 (median: 0; interquartile range: 1) potential DDIs existed before psychiatric ED treatment, and 0.9 (median: 0; interquartile range: 2) potential DDIs thereafter (p = 0.002). Coercive measures-such as administration of medication against the patient's will-were rarely required in the study population. Conclusion The majority of all drug prescriptions for the treatment of geriatric psychiatric emergencies were categorized as PIMs according to the PRISCUS 2.0 list and the FORTA classification. However, it should be noted that these PIM classification systems were not specifically designed for geriatric psychiatric settings. The number of potential DDIs was significantly higher after drug administration in the ED than before, which should prompt the monitoring of certain clinical parameters in the further course of treatment
Age- and sex-specific differences in propofol consumption and extubation time: an analysis of a data set from an observational multicenter trial
Full text linkThe objective of the present analysis was to investigate the effect of age and sex on propofol doses and emergence times in a dataset of propofol/remifentanil anesthetics. A total of 876 patients (339 men, 537 women; age: 18-87 years) with target electroencephalogram (EEG) stage D/E during maintenance of anesthesia and EEG stage D2/E0 at the end of propofol infusion were included (EEG monitor: Narcotrend; EEG in D/E range is characterized by delta activity [0.5-3.5 Hz]). Multiple linear regression analysis showed that total propofol dose (mean [standard deviation (SD)]: 6.81 (2.16) mg/kg/h) was significantly predicted by age (unstandardized regression coefficient b = -0.033, 95% confidence interval [CI]: -0.048 to -0.019, P < .001), sex (b = 1.542 [w (for women)], 95% CI: 0.573-2.512, P = .002), and interaction of age and sex (b = -0.022 [w], 95% CI: -0.041 to -0.004, P = .016). Propofol steady state dose (mean [SD]: 4.77 [1.74] mg/kg/h) was significantly predicted by age (b = -0.021, 95% CI: -0.036 to -0.006, P = .005), sex (b = 1.811 [w], 95% CI: 0.795-2.828, P < .001), and interaction of age and sex (b = -0.028 [w], 95% CI: -0.048 to -0.009, P = .004). For time to extubation (mean [SD]: 9.67 [4.51] mg/kg/h), age (b = 0.042, 95% CI: 0.010-0.073, P = .009) was a significant predictor, while sex (b = -0.655 [w], 95% CI: -2.785 to 1.475, P =.546) and interaction of age and sex (b = -0.011 [w], 95% CI: -0.051 to 0.029, P = .585) were not significant predictors. The administered remifentanil steady state dose (mean [SD]: 0.26 [0.12] µg/kg/min) did not differ significantly between men and women (P = .156) and decreased significantly with increasing age in men (P < .001) and women (P < .001). Age- and sex-associated differences in propofol requirements and a wide variation in propofol doses were observed. On average, women aged ≤40 years required comparatively high doses of propofol. The observations underline the importance of individually adapted anesthesia management, including monitoring of cerebral effects of propofol