Innsbruck Medical University
Recent publications
Objective Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting 2.9 million people worldwide, often leading to permanent disability. MS patients frequently use eHealth tools due to their relatively young age. The Floodlight® MS app is a scientifically designed smartphone application that helps patients monitor hand motor skills, walking ability and cognition between medical appointments. This study assesses the cost-effectiveness of using the Floodlight® MS app alongside standard-of-care (SoC) versus SoC alone in patients with relapsing-remitting MS (RRMS) from the perspective of the healthcare system. Methods A 10-year decision-analytic model was developed to assess the cost-effectiveness of incorporating the Floodlight® MS app alongside SoC. The analysis included treatment-naive individuals and those already on drug therapy, modelling the app's role in early detection of disease progression and relapses to improve quality-of-life. Results For treatment-naive patients, using the Floodlight® MS app resulted in a 2,660 € increase in total costs but yielded potential medical-cost savings of 786 € through health improvements. These patients experienced fewer relapses and slower disability progression, translating to a quality-of-life improvement of 4.5 months in perfect health and an incremental-cost-effectiveness-ratio (ICER) of 7,071 €. Pre-treated patients showed similar trends, with medical-cost savings of 718 €, an ICER of 7,864 €, and a quality-of-life improvement of 4.2 months. Higher effectiveness (+5%) led to an additional 8.3 months in perfect health and a reduction in overall costs. Conclusion The analysis demonstrates that the Floodlight® MS app is a cost-effective digital health application, encouraging broader discussions on maximizing the potential of software-as-medical-devices within the care pathway.
The prediction of survival rate probability for hip implants, based on clinical data acquired before and after surgery, incorporating patient-specific parameters, represents a pivotal advancement in enabling more precise risk assessment for potential complications, such as aseptic loosening and implant wear-related inflammation, on an individualized basis. This critical step marks a substantial progression toward the realization of digitized and personalized medicine. The objective of this study was to establish prediction aiding correlations between implant wear and migration data, derived from X-ray imaging of 149 patients diagnosed with hip arthritis, and the performance of hip implants. The patients underwent cementless hip replacement surgery, receiving implants consisting of ultra-high-molecular-weight polyethylene (UHMWPE) paired with titanium-aluminum-vanadium (Ti6Al4V) wedges. Over the course of a median follow-up period of 4 years, X-ray assessments were conducted to monitor the migration of the femoral head and acetabular components using Ein Bild Röntgen Analyse (EBRA). Clinical findings revealed a linear relationship between average migration and wear. Notably, it was observed that increased cup migration corresponded proportionally to greater wear values. Furthermore, in-depth analysis revealed significant distinctions based on gender and age. Specifically, the established relationship can confidently serve as a reliable predictive model for the behavior of hip implants in female subjects and individuals aged 50–60 years.
Ultrasound is a highly effective imaging tool for assessing abnormalities within the breast. However, especially the identification of malignant tumors of the breast mimicking fibroadenomas (MTMF) by means of breast ultrasound can be challenging. This study aimed to identify reliable imaging characteristics of MTMF. This retrospective study was approved by the local ethics review board. After screening 623 patients, 421 cases with histologically verified fibroadenomas and MTMF between 2011 and 2021 were included. Sonographic features were compared to histopathological results and an algorithm-based quantitative ranking of predictors contributing most to the correct classification of malignant tumors was conducted. A total of 363 benign, 18 intermediate, and 40 malignant lesions were analyzed. Algorithm-based quantitative ranking showed that the most predictive features indicating malignancy were a hyperechoic rim (gain ratio merit 0.135 ± 0.004), an irregular border (0.057 ± 0.002), perilesional stiffening (0.054 ± 0.002), pectoral contact (0.051 ± 0.003), an irregular shape (0.029 ± 0.001), and irregular vasculature (0.027 ± 0.002). Ultrasound findings for fibroadenomas vary, making identification of MTMF challenging. Features such as indistinct margins and increased perilesional echogenicity are predictors for malignancy and should be considered during sonographic evaluation of fibroadenomas and MTMF.
Introduction Neurogenic bladder dysfunction is a prevalent condition characterized by impaired bladder control resulting from neurological conditions, for example, spinal cord injury or traumatic brain injury (TBI). Detrusor overactivity is a typical symptom of central nervous system damage. A lesion affecting the pontine neural network typically results in loss of tonic inhibition exerted by the pontine micturition center and causes involuntary detrusor contractions. Intrathecal baclofen (ITB), primarily indicated for spasticity management, holds potential in addressing the underlying mechanisms of neurogenic bladder dysfunction. Methods Urodynamic data were extracted from clinical charts of patients with severe supraspinal spasticity who received ITB treatment. Urodynamic studies were performed before pump implantation (PRE), after surgery (POST), and when achieving an effective steady state ITB dosage (ss‐ITB), as reflected by a reduction in Modified Ashworth Scale (MAS) score. To determine potential risk factors for a poor response to ITB with respect to bladder function, patients were post hoc categorized into good and poor responders based on post void residual volume at ss‐ITB. Results Apart from significantly reducing MAS scores, ITB caused significant increases in reflex volume, bladder capacity, and residual volume, and significant decreases in maximal detrusor and vesical pressures. Significant differences between good and poor responders (with respect to bladder function) were noted for reflex volume, bladder capacity, and residual volume at ss‐ITB, whereas no urodynamic parameter served to differentiate the two groups at PRE. Discussion This study confirms a beneficial effect of ITB on bladder function in patients with severe supraspinal spasticity. However, concurring with the literature, a small subgroup of patients experienced serious deterioration in terms of increased reflex volume and residual volume, posing the risk of subsequent renal damage. Unfortunately, no urodynamic parameter predicted such a poor response to ITB before treatment initiation.
Purpose Pyogenic liver abscesses are challenging due to their diverse etiology and the risk of severe complications. In many cases, surgical interventions are initiated. However, these are only applicable in selected scenarios. We report the case of a 63-year-old woman with multiple large liver abscesses of up to 6.7 cm spread across both liver lobes, which could not be managed surgically. Methods & Results Streptococcus intermedius was isolated in blood culture and PCR positivity for this pathogen was obtained in liver puncture specimen. Following a two-weeks course of intravenous therapy with cefuroxime, metronidazole and fosfomycin, the patients received a consecutive, combined oral antibiotic treatment with clindamycin and cephalexin for four months. This resulted in complete resolution of the abscesses, with no evidence of relapse at follow-up. Conclusion This case illustrates the complex therapeutic challenges in the management of multiple, large hepatic abscesses, highlighting the potential of antibiotic therapy to cure even inoperable patients.
Proprotein convertase 1/3 (PC1/3), encoded by PCSK1, is expressed in neuronal and endocrine cell types, where it activates a number of protein precursors that play roles in energy homeostasis. Biallelic PCSK1 loss‐of‐function mutations cause a polyendocrinopathy; a total of 34 patients were reported. An infant with congenital malabsorptive diarrhea of all carbohydrates underwent exome sequencing (ES), with particular consideration of PC1/3 deficiency, but no mutations were found. The onset of obesity in the second year of life increased suspicion of PC1/3 deficiency in the proband, as well as in his equally affected cousin. Transcript analysis revealed minor amounts of an aberrant PCSK1 transcript containing intron 9 sequence and encoding a premature stop codon (p.Pro400Valfs*35). A deep intronic PCSK1 variant, NG_021161.1(NM_000439.5):c.1196+2681T>A, was found to segregate in the proband's family with the disease. A minigene approach demonstrated that the identified deep‐intronic variant underlies pseudo‐exon inclusion of the intron 9 sequence in the transcript. The characteristic phenotype of PC1/3 deficiency might require extended genetic testing to make a timely diagnosis.
Traumatic lumbosacral instability (TLSI) refers to a traumatic disruption of the axial skeleton at the level of the lumbosacral motion segment and/or sacrum, resulting in mechanical separation of the caudal spinal column from the posterior pelvic ring. Managing TLSI and its four underlying conditions poses unique challenges among spinal and pelvic injuries. This second part of a two-part series focuses on treatment strategies and decision making in TLSI, with an emphasis on surgical stabilization techniques. The primary objectives of this article are to: (1) elucidate factors influencing clinical decision-making, (2) synthesize current treatment options for the injury patterns underlying TLSI, and (3) briefly outline expected outcomes and complications.
Recent phase 3 randomized controlled trials (RCTs) demonstrate the promising impact of immune checkpoint inhibitor (ICI)-based combination therapies on locally advanced or metastatic urothelial carcinoma (UC). However, comparative data on the efficacy and toxicity of different ICI-based combinations are lacking. This study aims to compare the efficacy of first-line ICI-based combination therapies for locally advanced or metastatic UC using phase 3 RCT data. In November 2023, three databases were searched for RCTs evaluating oncological outcomes in patients with locally advanced or metastatic UC who were treated with first-line ICI-based combination therapies. Network meta-analysis (NMA) was conducted to compare outcomes, including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), and treatment-related adverse events (TRAEs). Subgroup analyses were based on PD-L1 status and cisplatin eligibility. The NMA included five RCTs. Enfortumab vedotin (EV) + pembrolizumab ranked the highest for improving OS (100%), PFS (100%), ORR (96%), and CRR (96%), followed by nivolumab + chemotherapy. EV + pembrolizumab combination superiority held across PD-L1 status and cisplatin eligibility. In patients who are cisplatin-eligible, EV + pembrolizumab significantly improved OS (HR: 0.68, 95%CI 0.47–0.99) and PFS (HR: 0.67, 95%CI 0.49–0.92) compared to nivolumab + chemotherapy. Durvalumab + tremelimumab was the safest combination for severe TRAEs, and EV + pembrolizumab ranked second. Our analyses support EV + pembrolizumab combination as a first-line treatment for locally advanced or metastatic UC. Thus, EV + pembrolizumab may become a guideline-changing standard treatment.
Background Huntington’s disease (HD) is caused by CAG trinucleotide expansion on chromosome 4, leading to mutant Huntingtin production. Premanifest carriers show no obvious clinical signs, and early symptoms progress slowly. Fluid biomarkers like neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), measurable in cerebrospinal fluid and serum (sNfL, sGFAP), offer potential predicting HD progression. Objective To assess the role of sGFAP and sNfL and clinical biomarkers in different disease stages and correlate with disease progression. Methods HD mutation carriers were categorized into clinical stages according to their motor symptoms and functional capacities. The Unified HD Rating Scale, cognitive assessments and olfactory tests were used to characterize the patients clinically. Furthermore, sNfL and sGFAP levels were assessed. Results We consecutively included 44 HD mutation carriers (13 premanifest HD (preHD), 18 in early (early HD) and 13 in advanced (advanced HD) disease stages) and 19 healthy controls (HC). Advanced HD patients performed worse on all clinical tasks and had higher sGFAP and sNfL levels compared to other groups (all p values < 0.05). We did not find difference in sGFAP levels between the preHD, early HD and HC group (all p values > 0.05). In contrast, sNfL levels differed significantly between preHD and early HD, and HC (all p values < 0.05). ROC curve analysis revealed that the AUC of sGFAP (0.970) exhibited superior discriminatory accuracy compared to sNfL (0.791) levels in separating advanced from early HD patients. By contrast, ROC curve analysis revealed that the AUC of sNFL (0.988) exhibited superior discriminatory accuracy compared to sGFAP (0.609) levels in separating all HD mutation carriers from HC. Conclusions Our study indicates that sNfL can detect changes in very early and premanifest HD stages, whereas sGFAP showed differences in more advanced stages only.
Transmission of Zika virus (ZIKV) has been reported in 92 countries and the geographical spread of invasive virus-borne vectors has increased in recent years. Arboviruses naturally survive between vertebrate hosts and arthropod vectors. Transmission success requires the mosquito to feed on viraemic hosts. There is little specific understanding of factors that may promote ZIKV transmission-success. Here we show that mosquito host-seeking behaviour is impacted by viral infection of the vertebrae host and may be essential for the effective transmission of arboviruses like ZIKV. Human skin fibroblasts produce a variety of metabolites, and we show that ZIKV immediately alters gene/protein expression patterns in infected-dermal fibroblasts, altering their metabolism to increase the release of mosquito-attractive volatile organic compounds (VOCs), which improves its transmission success. We demonstrate that at the invasion stage, ZIKV differentially altered the emission of VOCs by significantly increasing or decreasing their amounts, while at the transmission stage of the virus, all VOCs are significantly increased. The findings are complemented by an extensive meta-proteome analysis. Overall, we demonstrate a multifaceted role of virus-host interaction and shed light on how arboviruses may influence the behaviour of their vectors as an evolved means of improving transmission-success.
OBJECTIVES This fourth report aimed to provide insights into patient characteristics, outcomes, and standardized outcome ratios of patients implanted with durable Mechanical Circulatory Support across participating centers in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) registry. METHODS All registered patients receiving durable mechanical circulatory support up to August 2024 were included. Expected number of events were predicted using penalized logistic regression. Standardized outcome ratios (Observed/Expected events) were presented in plots to assess 30-day and 1-year mortality, ischaemic stroke, and major bleeding outcomes. Expected events were estimated using penalized logistic regression using demographics and comorbidities as predictors. Centers with <90% follow-up completeness were excluded from standardized outcome ratio assessment. RESULTS Analysis included 6962 implants in 6408 patients (457 patients underwent repeated implants) registered in EUROMACS from 17 countries (32 centres) (median age: 58 years, 83% males, 17% INTERMACS class 1). Thirty-day mortality, major bleeding and ischaemic stroke probabilities were 9.6, 12.6%, and 2.1%, respectively. Standardized mortality ratios showed variability between centres, ranging from 0 (95% CI : 0–0) to 1.4 (95% CI : 1.2–1.7). Higher standardized bleeding outcome ratios correlated with higher standardized ischaemic stroke ratio’s (Spearman r: 0.56, P = 0.008). CONCLUSIONS Most included centers perform as expected given the demographics and comorbidities of patients. A positive correlation was found between standardized bleeding and ischaemic stroke ratios, reflecting the need of continuously monitoring of adverse events by quality improvement programs.
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2,105 members
Erich Brenner
  • Institute for Clinical and Functional Anatomy
Beatrice Frajo-Apor
  • Department of Psychiatry and Psychotherapy
Stefan Höfer
  • Department of Medical Psychology
Thomas J Luger
  • Department of Anaesthesiology and Critical Care Medicine
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Innsbruck, Austria
Head of institution
Univ.-Prof. Dr. Wolfgang Fleischhacker