University Medical Center Freiburg
  • Freiburg, Baden-Württemberg, Germany
Recent publications
Purpose To evaluate the outcome of phacoemulsification in patients with chronic ocular Graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplantation (aHSCT). Methods Retrospective, observational multicenter study from 1507 oGVHD patients. From the patient files, data were collected including best-corrected visual acuity (BCVA), intraocular pressure (IOP), Schirmer’s test I , tear film break-up time (TFBUT), corneal fluorescein staining score, postoperative complications, and pre- and post-operative topical therapy. Results Seventy-three patients underwent cataract surgery in 104 eyes. In n = 84 eyes, the oGVHD NIH grade was documented; 12% ( n = 12) of analyzed eyes were staged oGVHD NIH grade 1, 31% ( n = 32) NIH 2 and 39% ( n = 41) NIH 3. The mean BCVA improved in 82% of the eyes ( n = 86 eyes). BCVA significantly increased from 0.7 ± 0.5 to 0.4 ± 0.4 LogMAR after surgery independent from oGVHD severity. The mean IOP decreased from 14 ± 4 to 13 ± 4 mmHg after surgery. Visual acuity was moderately correlated to the pre-operative degree of corneal staining (Pearson p = 0.26, p = 0.002, Cohen’s effect size f = 0.29). The visual acuity decreased by 0.078 LogMar units (95% CI = 0.027–0.141) with each increase of corneal staining by one grade ( p = 0.05). After surgery, corneal epitheliopathy increased significantly in 42% ( n = 44) of the eyes. Postoperative complications included corneal perforation ( n = 6, 6%), cystoid macular edema ( n = 4, 4%), and endophthalmitis ( n = 1, 1%). Conclusion Phacoemulsification in patients with chronic oGVHD significantly improves visual acuity, but is associated with an increased risk of complications in particular corneal epitheliopathy and corneal perforations.
Purpose This study aimed at investigating five dimensions of the psychological impact (post-traumatic stress symptoms (PTSS), anxiety, depression, sleep disturbance or profession-related burnout) of COVID-19 on healthcare workers (HCW) in China. Methods Studies that evaluated at least one of the five target dimensions of the psychological impact of COVID-19 on HCW in China were included. Studies with no data of our interest were excluded. Relevant Databases were searched from inception up to June 10, 2020. Preprint articles were also included. The methodological quality was assessed using the checklist recommended by AHRQ. Both the rate of prevalence and the severity of symptoms were pooled. The protocol was registered in PROSPERO (CRD42020197126) on July 09, 2020. Results We included 44 studies with a total of 65,706 HCW participants. Pooled prevalence rates of moderate to severe PTSS, anxiety, depression, and sleep disturbances were 27% (95% CI 16%-38%), 17% (13–21%), 15% (13–16%), and 15% (7–23%), respectively; while the prevalence of mild to severe level of PTSS, anxiety, and depression was estimated as 31% (25–37%), 37% (32–42%) and 39% (25–52%). Due to the lack of data, no analysis of profession-related burnout was pooled. Subgroup analyses indicated higher prevalence of moderate to severe psychological impact in frontline HCW, female HCW, nurses, and HCW in Wuhan. Conclusion About a third of HCW in China showed at least one dimension of psychological symptoms during the COVID-19 pandemic, whereas the prevalence of moderate and severe syndromes was relatively low. Studies on profession-related burnout, long-term impact, and the post-stress growth are still needed.
In recent years considerable variations in conditioning protocols for allogeneic hematopoietic cell transplantation (allo-HCT) protocols have been introduced for higher efficacy, lower toxicity, and better outcomes. To overcome the limitations of the classical definition of reduced intensity and myeloablative conditioning, a transplantation conditioning intensity (TCI) score had been developed. In this study, we compared outcome after two frequently used single alkylator-based conditioning protocols from the intermediate TCI score category, fludarabine/melphalan 140 mg/m2 (FluMel) and fludarabine/treosulfan 42 g/m2 (FluTreo) for patients with acute myeloid leukemia (AML) in complete remission (CR). This retrospective analysis from the registry of the Acute Leukemia Working Party (ALWP) of the European Society of Bone Marrow Transplantation (EBMT) database included 1427 adult patients (median age 58.2 years) receiving either Flu/Mel (n = 1005) or Flu/Treo (n = 422). Both groups showed similar 3-year overall survival (OS) (54% vs 51.2%, p value 0.49) for patients conditioned with FluMel and FluTreo, respectively. However, patients treated with FluMel showed a reduced 3-year relapse incidence (32.4% vs. 40.4%, p value < 0.001) and slightly increased non-relapse mortality (NRM) (25.7% vs. 20.2%, p value = 0.06) compared to patients treated with FluTreo. Our data may serve as a basis for further studies examining the role of additional agents/ intensifications in conditioning prior to allo-HCT.
Purpose We aimed at exploring the quality of life (QOL) of lung cancer survivors with proven tyrosine-kinase receptor (RTK) genetic alterations and targeted tyrosine-kinase inhibitors (TKI) therapy, compared to lung cancer survivors with no-RTK alterations and no-TKI therapy. Methods Data were collected in a cross-sectional multi-centre study. Primary lung cancer survivors were asked about their socio-demographic and clinical information, QOL, symptom burden, and distress. QOL and symptom burden were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), and distress with the Patient Health Questionnaire-4 (PHQ-4). Demographic and clinical characteristics were reported in absolute and relative frequencies, QOL, and symptom burden using mean scores. Differences in mean scores with relative 95% confidence intervals were used for comparison. Results Three groups of survivors were defined: group A with proven RTK alterations, TKI therapy at any time during therapy, and stage IV lung cancer at diagnosis (n = 49); group B: non-TKI therapy and stage IV lung cancer (n = 121); group C: non-TKI therapy and stage I–III lung cancer (n = 495). Survivors in group A reported lower QOL (mean score difference = -11.7 vs. group B) and symptom burden for dyspnoea (difference = -11.5 vs. group C), and higher symptom burden for appetite loss (difference = + 11.4 vs. group C), diarrhoea and rash (differences = + 25.6, + 19.6 and + 13.2, + 13.0, respectively, vs. both groups). Conclusions Our results suggest that the specific side effects of TKI therapy can impair QOL among lung cancer survivors. Therefore, specific focus towards the optimal management of these side effects should be considered.
Purpose The DEGRO Expert Commission on Prostate Cancer has revised the indication for radiation therapy of the primary prostate tumor in patients with synchronous distant metastases with low metastatic burden. Methods The current literature in the PubMed database was reviewed regarding randomized evidence on radiotherapy of the primary prostate tumor with synchronous low metastatic burden. Results In total, two randomized trials were identified. The larger study, the STAMPEDE trial, demonstrated an absolute survival benefit of 8% after 3 years for patients with low metastatic burden treated with standard of care (SOC) and additional radiotherapy (RT) (EQD2 ≤ 72 Gy) of the primary tumor. Differences in the smaller Horrad trial were not statistically significant, although risk reduction in the subgroup (< 5 bone metastases) was equal to STAMPEDE. The STOPCAP meta-analysis of both trials demonstrated the benefit of local radiotherapy for up to 4 bone lesions and an additional subanalysis of STAMPEDE also substantiated this finding in cases with M1a-only metastases. Conclusion Therefore, due to the survival benefit after 3 years, current practice is changing. New palliative SOC is radiotherapy of the primary tumor in synchronously metastasized prostate cancer with low metastatic burden (defined as ≤ 4 bone metastases, with or without distant nodes) or in case of distant nodes only detected by conventional imaging.
Structure and integrity of the mitochondrial network play important roles in many cellular processes. Loss of integrity can lead to the activation of a variety of signalling pathways and affect the cell’s response to infections. The activation of such mitochondria-mediated cellular responses has implications for infection recognition, signal transduction and pathogen control. Although we have a basic understanding of mitochondrial factors such as mitochondrial DNA or RNA that may be involved in processes like pro-inflammatory signalling, the diverse roles of mitochondria in host defence remain unclear. Here we will first summarise the functions of mitochondria in the host cell and provide an overview of the major known mitochondrial stress responses. We will then present recent studies that have contributed to the understanding of the role of mitochondria in infectious diseases and highlight a number of recently investigated models of bacterial and viral infections.
Bmp‐Encoding Adenoviral Vector Tethered to Dental Implants Enhances Bone Regeneration In article number 2200531, Shogo Maekawa, Young‐Dan Cho, William Giannobile, and co‐workers demonstrate that immobilizing bone morphogenetic protein (BMP) genes onto the surfaces of dental implants by chemical vapor deposition technology enhances bone regeneration.
One of the great challenges in psychiatry is finding reliable biomarkers that may allow for more accurate diagnosis and treatment of patients. Neural variability received increasing attention in recent years as a potential biomarker. In the present explorative study we investigated temporal variability in visually evoked EEG activity in a cohort of 16 adult participants with Asperger Syndrome (AS) and 19 neurotypical (NT) controls. Participants performed a visual oddball task using fine and coarse checkerboard stimuli. We investigated various measures of neural variability and found effects on multiple time scales. (1) As opposed to the previous studies, we found reduced inter-trial variability in the AS group compared to NT. (2) This effect builds up over the entire course of a 5-min experiment and (3) seems to be based on smaller variability of neural background activity in AS compared to NTs. The here reported variability effects come with considerably large effect sizes, making them promising candidates for potentially reliable biomarkers in psychiatric diagnostics. The observed pattern of universality across different time scales and stimulation conditions indicates trait-like effects. Further research with a new and larger set of participants are thus needed to verify or falsify our findings.
Infection with the pandemic human coronavirus SARS-CoV-2 elicits a respiratory tract disease, termed Coronavirus disease 2019 (COVID-19). While a variable degree of disease-associated symptoms may emerge, severe COVID-19 is commonly associated with respiratory complications such as acute respiratory distress syndrome (ARDS), the necessity for mechanical ventilation or even extracorporeal membrane oxygenation (ECMO). Amongst others, disease outcome depends on age and pre-existing conditions like cardiovascular diseases, metabolic disorders but also age and biological sex. Intriguingly, increasing experimental and clinical evidence suggests that an exacerbated inflammatory response and in particular IgG immune complexes (ICs), significantly contribute to severe and prolonged COVID-19 disease progression. Vast amounts of deposited, unresolved ICs in tissue are capable to initiate an exaggerated Fc gamma receptor (FcγR) mediated signalling cascade which eventually results in common IC-associated organ diseases such as vasculitis, glomerulonephritis and arthritis, comorbidities that have been frequently reported for COVID-19. Moreover and independent of deposited ICs, very recent work identified soluble ICs (sIC) to be also present in the circulation of a majority of severely ill patients, where their systemic abundance correlated with disease severity. Thus, detection of circulating sICs in patients represents a potential marker for critical COVID-19 disease progression. Their detection early after clinical deterioration might become an indicator for the requirement of prompt anti-inflammatory treatment. Here, we review the role of ICs in COVID-19 progression, their possible origins and potential intervention strategies. Graphical abstract
Purpose Radiotherapy (RT) constitutes a mainstay in the treatment of elderly patients with head and neck cancer (HNC), but use of simultaneous chemoradiotherapy (CRT) remains controversial. We have conducted a prospective analysis based on real-world patient data to examine the health-related quality of life (HRQoL) and cost effectiveness (CE) of CRT vs. RT in elderly HNC patients. Methods Eligible participants ≥ 65 years treated in a large tertiary cancer center between July 2019 and February 2020 who completed the validated EQ-5D-5L questionnaire (health state index [HI] and visual analog scale [VAS]) before and after RT were included. CE referred to direct medical costs, including diagnosis-related group (DRG)-based billings for inpatients and uniform assessment standard (EBM)-based costs for outpatients. The primary endpoint was cost (euros [€]) per quality-adjusted life year (QALY). The incremental cost-effectiveness ratios (ICERs) were calculated. Costs and QALYs were not discounted for short overall survival (OS). Results Baseline HRQoL was 0.878 (±0.11) in the CRT group and 0.857 (±0.17) in the RT group. Upon completion of therapy, HRQoL amounted to 0.849 (±0.14) in the CRT and 0.850 (±0.13) in the RT group. The mean treatment-related cost in the CRT cohort was €22,180.17 (±8325.26) vs. €18,027.87 (±26,022.48) in the RT group. The corresponding QALYs amounted to 2.62 in the CRT and 1.91 in the RT groups. The ICER was €5848.31. Conclusion This is the first analysis from the German health care system demonstrating that the addition of chemotherapy to RT for selected elderly HNC patients is cost effective and not associated with a significant HRQoL decline.
Hardware prominence remains a clinical challenge in focus for implant design in subcutaneous plate applications. Existing evaluation of hardware prominence relies on plate-to-bone distance at a single point or on average. A reproducible measure for plate prominence remains undefined. This study mathematically defines the plate prominence linked to the cross-sectional area change due to the plate presence on the bone. Two anatomical plate designs were fitted to 100 clavicles, and afterwards plate prominence parameters were evaluated and compared. This methodology enables the quantification of hardware prominence for different plate designs to inform the development of implants targeting low prominence.
Androgen insufficiency under treatment with opioids, antidepressants and anticonvulsants in chronic pain diseases is a side effect with a high prevalence. It can lead to clinical metabolic alterations, adynamia, stress intolerance, anemia or osteoporosis and has a significant impact on the quality of life. Opioids, antidepressants and anticonvulsants affect the hypothalamic-pituitary-gonadal axis of sex hormones. A urologist, andrologist or endocrinologist should be involved in the treatment at an early stage. The recommendation of a differential therapeutic selection of certain substances is only indicative and does not meet evidential criteria. The indications for androgen substitution must be individualized and in consideration of the risk-benefit profile. Awareness of this side effect of an otherwise lege artis medicinal pain therapy must be sharpened and compulsory included in the differential diagnostic considerations.
Objective: This study evaluated the preventive effect of a chitosan gel containing CaneCPI-5 against enamel erosion and erosion + abrasion in situ. Methods: Sixteen volunteers participated in a crossover, double-blind protocol, comprising 4 phases: (1) no treatment (Nt); (2) chitosan gel (Cg); (3) chitosan gel + 12,300 ppm NaF (Cg + NaF); and (4) chitosan gel + 0.1 mg/mL CaneCPI-5 (Cg + Cane). Volunteers wore an appliance containing 4 specimens. Once/day, they applied the gel (except for Nt) (4 min/specimen). Erosive challenges were performed extra-orally (0.1% citric acid, 90 s, 4 × /day; ERO). Specimens were also abraded (toothbrush, 15 s/specimen, 2 × /day; ERO + ABR). Enamel wear was assessed by profilometry and relative surface reflection intensity (%SRI). Two-way RM-ANOVA/Sidak's tests and Spearman's correlation were used (p < 0.05). Results: For profilometry, ERO + ABR promoted significantly greater wear when compared with ERO. There was a significant difference among all treatments. The lowest enamel loss occurred for Cg + Cane, followed by Cg + NaF, Cg, and Nt (p < 0.05). The %SRI was significantly lower for ERO + ABR when compared to ERO, only for the Nt group. The greatest %SRI was found for the Cg + NaF and Cg + Cane groups, which did not differ significantly, regardless of the conditions. The lowest %SRI was found for the Nt and Cg groups, which did not differ from each other, regardless of the conditions. The Nt group did not differ significantly from the Cg + NaF (ERO). There was a significant correlation between both analyses. Conclusion: The incorporation of CaneCPI-5 in the chitosan gel prevented erosive wear in situ. Clinical relevance: These results open a new perspective for the use of CaneCPI-5 in other application vehicles, such as chitosan gel.
Insomnia and circadian dysregulation during adolescence represent important risk factors for emotional and psychological problems. Recent studies have shown that the coronavirus disease 2019 (COVID‐19) pandemic has been linked to a high prevalence of behavioural sleep problems in the general population. This study aimed to provide two pictures of two different time points of the pandemic regarding the prevalence of sleep problems in adolescents and their association with psychological health variables. Two different independent large samples of Italian adolescents aged 13–17 years were recruited at two pandemic time points. A total of 1,146 adolescents at Time 1 (T1; April 2020) and 1,406 at Time 2 (T2; April 2021) took part in the study. Measures of insomnia symptoms, sleep hygiene, chronotype, psychological distress and emotion regulation were collected. Prevalence of insomnia was 12.13% at T1 and 23.19% at T2. Furthermore, high levels of poor sleep habits (late bedtime, poor sleep hygiene, use of electronic devices at bedtime) were also detected at both time points. Insomnia symptoms strongly correlated with poor sleep hygiene, higher psychological distress, and emotional suppression at both time points. Results highlighted an alarming picture for two large samples at two different time points of the pandemic that showed a potential negative impact of the COVID‐19 pandemic, in both the first outbreak and in the later phase of the pandemic, on sleep habits, psychological distress and insomnia symptoms in adolescents. This strongly suggests the need for monitoring these variables and their interaction in the post‐pandemic period and to develop and promote interventions for insomnia and circadian disturbances during adolescence.
The treatment of patients with advanced heart failure requires interdisciplinary care in a qualified heart failure team, especially prior to and in the follow-up of mechanical circulatory support (MCS) implantation and heart transplantation (HTx). The basic prerequisite is the early specialized evaluation of symptomatic patients even under optimized heart failure treatment. Diagnostics and treatment are initially aimed at improving the prognosis. If the prerequisites for MCS or HTx treatment are present, possible contraindications and problems have to be evaluated in order to achieve an optimal risk-benefit ratio for the abovementioned complex treatments with limited resources. The optimal treatment is still HTx if the conditions are right, so this should be sought in all potential patients. At the same time, the optimal individual transplantation window should not be missed. The provision of a MCS system is a treatment performed with very good results for patients with exclusion criteria for HTx or with hemodynamic instability that prevents a longer waiting time for a donor organ. Short-term and medium-term survival is now comparable to HTx when carefully indicated. Timely implantation before the onset of manifest end-organ damage is crucial. Optimized implementation of advanced treatment requires professional structures that enable effective interdisciplinary cooperation between different sectors of health care.
The treatment of patients with advanced heart failure requires interdisciplinary care in a qualified heart failure team, especially prior to and in the follow-up of mechanical circulatory support (MCS) implantation and heart transplantation (HTx). The basic prerequisite is the early specialized evaluation of symptomatic patients even under optimized heart failure treatment. Diagnostics and treatment are initially aimed at improving the prognosis. If the prerequisites for MCS or HTx treatment are present, possible contraindications and problems have to be evaluated in order to achieve an optimal risk-benefit ratio for the abovementioned complex treatments with limited resources. The optimal treatment is still HTx if the conditions are right, so this should be sought in all potential patients. At the same time, the optimal individual transplantation window should not be missed. The provision of a MCS system is a treatment performed with very good results for patients with exclusion criteria for HTx or with hemodynamic instability that prevents a longer waiting time for a donor organ. Short-term and medium-term survival is now comparable to HTx when carefully indicated. Timely implantation before the onset of manifest end-organ damage is crucial. Optimized implementation of advanced treatment requires professional structures that enable effective interdisciplinary cooperation between different sectors of health care.
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1,797 members
Toni Cathomen
  • Institute for Transfusion Medicine and Gene Therapy
Anne Halenius
  • Institute of Virology
Lars Maruschke
  • Department of Radiology and Radiotherapy
Information
Address
Hugstetter Str. 55, 79106, Freiburg, Baden-Württemberg, Germany
Head of institution
Prof. Dr. Frederik Wenz
Website
www.uniklinik-freiburg.de