Josef Fritz - Academia.edu (original) (raw)
Papers by Josef Fritz
Clinical Nuclear Medicine
Sleep
Short and long sleep duration are associated with adverse metabolic outcomes, such as obesity and... more Short and long sleep duration are associated with adverse metabolic outcomes, such as obesity and diabetes. We evaluated cross-sectional differences in metabolite levels between women with self-reported habitual short (<7 h), medium (7–8 h), and long (≥9 h) sleep duration to delineate potential underlying biological mechanisms. In total, 210 metabolites were measured via liquid chromatography-mass spectrometry in 9207 women from the Nurses’ Health Study (NHS; N = 5027), the NHSII (N = 2368), and the Women’s Health Initiative (WHI; N = 2287). Twenty metabolites were consistently (i.e. praw < .05 in ≥2 cohorts) and/or strongly (pFDR < .05 in at least one cohort) associated with short sleep duration after multi-variable adjustment. Specifically, levels of two lysophosphatidylethanolamines, four lysophosphatidylcholines, hydroxyproline and phenylacetylglutamine were higher compared to medium sleep duration, while levels of one diacylglycerol and eleven triacylglycerols (TAGs; a...
Cancers, 2021
Coronavirus-19 (COVID-19)-induced effects on deferred diagnosis and treatment of bladder cancer (... more Coronavirus-19 (COVID-19)-induced effects on deferred diagnosis and treatment of bladder cancer (BC) patients are currently not clarified. The aim of this study was to evaluate outcomes of the COVID-19 pandemic by considering its effects on tumor stage and grade, and to create feasible clinical triage decisions. A retrospective single-center analysis of all patients who underwent diagnostic and surgical procedures due to BC, during January 2019 and December 2020, was performed. Due to COVID-19 lockdowns, significantly fewer (diagnostic and therapeutic) endoscopic procedures were performed in the first 6 months of 2020 compared to 2019 (p = 0.002). In patients with a primary diagnosis of BC, a significant increase of high-grade tumors (p < 0.001), as well as advanced tumor stages (p = 0.014), were noticed during 2020 in comparison to 2019. On the contrary, patients with recurrent BC undergoing risk-adapted surveillance, depending on previous tumor histology, showed no adverse outc...
Cancers, 2021
We conducted a retrospective National Cancer Registry study in Austria to assess a possible seaso... more We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend (p < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr–Sep) and an increase during the winter months (Oct–Mar) were observed (p < 0.001). Focusing on seasonality, the incidence during the months of Oct–Dec (p = 0.008) and Jan–Mar (p < 0.001) was significantly higher compared to the months of Jul–Sep, respectively. Regarding histopathological features, there is a predomin...
Acta Anaesthesiologica Scandinavica, 2021
BackgroundBleeding is a common problem in children with congenital heart disease undergoing major... more BackgroundBleeding is a common problem in children with congenital heart disease undergoing major cardiac surgery requiring cardiopulmonary bypass (CPB). Little is known about optimal management with blood products.ObjectiveTo investigate clinical outcome and hemostatic effects of fibrinogen concentrate (FC) in combination with prothrombin complex concentrate (PCC) versus standard treatment with fresh frozen plasma (FFP) in children undergoing cardiac surgery.MethodsFor this single‐institution cohort study, data on 525 children were analyzed. Propensity score matching in 210 children was applied to reduce the impact of various baseline characteristics.ResultsThree children treated with FC/PCC developed surgical site bleeding requiring surgical revision. One child developed central venous line‐related thrombosis. Blood loss through chest tube drainage was independent of FC/PCC. Coagulation abnormalities were not present in any of these children. Time to extubation and ICU stay did no...
Revista Española de Medicina Nuclear e Imagen Molecular, 2021
INTRODUCTION Nephro- and hematotoxicity after peptide receptor radionuclide therapy (PRRT) have b... more INTRODUCTION Nephro- and hematotoxicity after peptide receptor radionuclide therapy (PRRT) have been described in multiple studies with heterogeneous cumulative activities, number of cycles or radiolabelled peptides. Though highly differentiated metastasized neuroendocrine tumours (NET) have long progression free survival, they may progress. We analysed long-term side effects in a homogenous treatment schedule in PRRT-patients and their impact on future oncologic treatment in case of progression. METHODS From our database 89/384 patients receiving the same PRRT (Lu-177-DOTATATE or Y-90-DOTATOC) 4 times every 10 to 12 weeks and a follow-up at 12 months were analysed. One patient had three and 11 patients had two times four PRRT-cycles resulting in 102 cases. eGFR, Hb, WBC and platelets before the first and one year after the fourth therapy cycle were compared. eGFR-Grading was done according to chronic kidney disease classification (CKD) and grading of hematotoxicity according to Common Terminology Criteria for Adverse Events (CTCAE). Impact of age, gender, cumulative activity, type of PRRT on long-term-toxicity was also assessed. RESULTS eGFR grade 1-2 dropped from 87/102 at the baseline to 71 cases at follow-up (p<0.001). Before treatment grade 3a was found in 13, grade 3b in 2 cases, and at follow-up grade 3a in 25, grade 3b in 5, and grade 4 in 1 case. Anaemia prior to PRRT and at follow-up was grade 0 in 63 versus 48 (p<0.001), grade 1 in 36 versus 48, and grade 2 in three versus six cases. In white blood cell count and platelets, there were no significant changes in grading occurring. Subgroup analysis revealed that only in the age group 65 and older was there a higher incidence for anaemia (p=0.006). CONCLUSIóN: In roughly 20% of cases an increase in grading of nephro- or hematotoxicity is observed. In those patients, except in one, toxicity findings were mild or moderate one year after completion of four cycles of PRRT with either Y-90- or Lu-177-SST-analogues. In terms of safety, PRRT has no critical impact on further oncologic treatment options in the case of disease progression.
![Research paper thumbnail of Impact of forced diuresis with furosemide and hydration on the halo artefact and intensity of tracer accumulation in the urinary bladder and kidneys on [68Ga]Ga-PSMA-11-PET/CT in the evaluation of prostate cancer patients](https://attachments.academia-assets.com/119080156/thumbnails/1.jpg)
](European Journal of Nuclear Medicine and Molecular Imaging, 2020
Purpose to assess the influence of intravenous hydration and forced diuresis with furosemide in t... more Purpose to assess the influence of intravenous hydration and forced diuresis with furosemide in two different dosages (20 vs 40 mg) on the intensity of tracer accumulation in the urinary collection system and on the occurrence of halo artefact surrounding the urinary bladder and kidneys in [ 68 Ga]Ga-PSMA-11-PET/CT scans. Materials and methods Comparison of four groups with 50 patients each, receiving different preparation prior to [ 68 Ga]Ga-PSMA-11-PET/CT. Group one, no preparation. Group two, 500 ml sodium chloride administered immediately after tracer injection. Group three, 500 ml sodium chloride and injection of 20 mg furosemide immediately after tracer administration. Group four, 500 ml sodium chloride and injection of 40 mg furosemide immediately after tracer injection. Images were judged visually whether halo artefact was present; semiquantitative measurements were performed with standardised uptake value (SUV). Results Halo artefact of the urinary bladder was present in twelve patients without preparation, in eight patients receiving only sodium chloride, in one patient injected with 20 mg furosemide/sodium chloride and in two patients receiving 40 mg furosemide/sodium chloride, showing a median SUV mean in the bladder of 45.8, 14.4, 4.6 and 5.8, respectively. Differences between patient group without preparation and the two groups with furosemide/sodium chloride were statistically significant. Patient groups receiving 20 mg furosemide and 40 mg furosemide did not differ significantly. Renal halo artefacts were observed in 15 patients of group one, in ten patients of group two, in 14 patients of group three and in 14 patients of group four, with corresponding median SUV mean values of 33.9, 32.0, 37.8 and 30.4 (no statistically significant differences). Conclusion Performing [ 68 Ga]Ga-PSMA-11-PET/CT, intravenous injection of 20-mg furosemide and 500-ml sodium chloride significantly reduces the number of bladder halo artefacts and intensity of tracer accumulation in the urinary bladder. A total of 40 mg furosemide does not further improve results.
British Journal of Haematology, 2020
SummaryFluconazole is one of the most commonly used drugs for antifungal prophylaxis in childhood... more SummaryFluconazole is one of the most commonly used drugs for antifungal prophylaxis in childhood leukaemia. However, its interaction with vincristine may induce neuropathy and the emergence of antifungal drug resistance contributes to substantial mortality caused by invasive fungal infections (IFIs). In a retrospective single‐centre study, we compared tolerability and outcome of different antifungal prophylaxis strategies in 198 children with acute leukaemia (median age 5·3 years). Until 2010, antifungal prophylaxis with fluconazole was offered to most of the patients and thereafter was replaced by liposomal amphotericin‐B (L‐AMB) and restricted to high‐risk patients only. Vincristine‐induced neurotoxicity was significantly reduced under L‐AMB, as the percentage of patients with severe constipation decreased (15·4% vs. 3·7%, before vs. after 31 December·2010, P = 0·01) and stool frequency increased by up to 38% in polyene‐treated patients (P = 0·005). Before 2011, 10 patients devel...
Blood, 2018
BACKGROUND: Prophylaxis of invasive fungal infections in children treated for malignant hematolog... more BACKGROUND: Prophylaxis of invasive fungal infections in children treated for malignant hematologic disease has traditionally been based on the widespread use of fluconazole. With the awareness of increasing rates of invasive mould infections, new agents have been developed and offered to patients at highest risk. METHODS: We compared the tolerance and outcome of different antifungal prophylaxis in 198 childhood patients treated for acute myeloid and lymphoblastic leukemia in a pediatric cancer center. Until 2011 antifungal prophylaxis with fluconazole was offered to all patients, resulting in 15.2-19.4% of invasive mould infections. As the burden of fungal infections was restricted to high risk patients only (i.e. acute myeloid leukemia, leukemia relapse, high risk acute lymphoblastic leukemia and patients after stem cell transplant) and no infection with candida was registered, antifungal prophylaxis was replaced with liposomal amphotericin and offered to this particular patient g...
Cancer Science, 2018
Nivolumab belongs to the standard therapy in the second‐line setting of metastatic renal cell car... more Nivolumab belongs to the standard therapy in the second‐line setting of metastatic renal cell carcinoma (mRCC). Although deep and long‐lasting responses are seen in some patients, the majority of patients will further progress. PD‐L1 is still under critical evaluation as a predictive biomarker. Thus, more accurate biomarkers are clearly warranted. Here, we investigated for the first time the predictive role of IDO‐1, a negative immune‐regulatory molecule, on clear cell RCC tissues of 15 patients undergoing nivolumab therapy. IDO‐1 and other immune inhibitory molecules (PD‐L1, PD‐L2, FOXP3) as well as immune cell subsets (CD3, CD4 and CD8) were measured on formalin‐fixed, paraffin‐embedded sections of RCC specimens by immunohistochemistry. IDO‐1 was predominantly expressed in tumor endothelial cells, and was totally absent from tumor cells itself. IDO‐1 overexpression (>10%) could be detected more frequently in responders (100%, n = 6/6) compared to non‐responders (33.3%, n = 3/9;...
European Urology Supplements, 2019
Bladder-sparing radiotherapy with vinorelbine in localized muscle-invasive bladder cancer: A vali... more Bladder-sparing radiotherapy with vinorelbine in localized muscle-invasive bladder cancer: A valid option for cisplatin-unfit patients?
![Research paper thumbnail of Comparison of [68Ga]Ga-PSMA-11 PET/CT with [18F]NaF PET/CT in the evaluation of bone metastases in metastatic prostate cancer patients prior to radionuclide therapy](https://attachments.academia-assets.com/119080157/thumbnails/1.jpg)
](European Journal of Nuclear Medicine and Molecular Imaging, 2018
Aim The purpose of this study was to investigate the diagnostic performance of 68 Ga-PSMA-11 PET/... more Aim The purpose of this study was to investigate the diagnostic performance of 68 Ga-PSMA-11 PET/CT in the evaluation of bone metastases in metastatic prostate cancer (PC) patients scheduled for radionuclide therapy in comparison to [ 18 F]sodium fluoride (18 F-NaF) PET/CT. Methods Sixteen metastatic PC patients with known skeletal metastases, who underwent both 68 Ga-PSMA-11 PET/CT and 18 F-NaF PET/CT for assessment of metastatic burden prior to radionuclide therapy, were analysed retrospectively. The performance of both tracers was calculated on a lesion-based comparison. Intensity of tracer accumulation of pathologic bone lesions on 18 F-NaF PET and 68 Ga-PSMA-11 PET was measured with maximum standardized uptake values (SUV max) and compared to background activity of normal bone. In addition, SUV max values of PET-positive bone lesions were analysed with respect to morphologic characteristics on CT. Bone metastases were either confirmed by CT or follow-up PET scan. Results In contrast to 468 PET-positive lesions suggestive of bone metastases on 18 F-NaF PET, only 351 of the lesions were also judged positive on 68 Ga-PSMA-11 PET (75.0%). Intensity of tracer accumulation of pathologic skeletal lesions was significantly higher on 18 F-NaF PET compared to 68 Ga-PSMA-11 PET, showing a median SUV max of 27.0 and 6.0, respectively (p < 0.001). Background activity of normal bone was lower on 68 Ga-PSMA-11 PET, with a median SUV max of 1.0 in comparison to 2.7 on 18 F-NaF PET; however, tumour to background ratio was significantly higher on 18 F-NaF PET (9.8 versus 5.9 on 68 Ga-PSMA-11 PET; p = 0.042). Based on morphologic lesion characterisation on CT, 18 F-NaF PET revealed median SUV max values of 23.6 for osteosclerotic, 35.0 for osteolytic, and 19.0 for lesions not visible on CT, whereas on 68 Ga-PSMA-11 PET median SUV max values of 5.0 in osteosclerotic, 29.5 in osteolytic, and 7.5 in lesions not seen on CT were measured. Intensity of tracer accumulation between 18 F-NaF PET and 68 Ga-PSMA-11 PET was significantly higher in osteosclerotic (p < 0.001) and lesions not visible on CT (p = 0.012). Conclusion In comparison to 68 Ga-PSMA-11 PET/CT, 18 F-NaF PET/CT detects a higher number of pathologic bone lesions in advanced stage PC patients scheduled for radionuclide therapy. Our data suggest that 68 Ga-PSMA-11 PET should be combined with 18 F-NaF PET in PC patients with skeletal metastases for restaging prior to initiation or modification of therapy.
Archives of Orthopaedic and Trauma Surgery, 2018
Introduction For the treatment of scaphoid non-unions (SNU), different surgical techniques, inclu... more Introduction For the treatment of scaphoid non-unions (SNU), different surgical techniques, including vascularized and non-vascularized bone grafts, are applied. Besides stability, vascularity, and the biological situation at the non-union site are important for healing and the appropriate choice of treatment. We assessed the healing potential of SNUs by histological parameters and compared it to CT parameters of bone structure and fracture location. Based on the results, we developed a CT classification and a treatment algorithm to impact graft selection in SNU surgery. Patients and methods Preoperative 2D-CT reformations of 29 patients were analyzed for trabecular structure, sclerosis, and fragmentation of the proximal fragment. The fracture location was assessed on 3D-CT reconstructions and grouped in three zones depending on the potential blood supply. Samples were taken during surgery for histological evaluation. Histological parameters of bone healing were defined and a bone healing capacity score (BHC), reflecting histological bone viability, was calculated. CT findings were compared to BHC, age of SNU, and time to union. Results Cases with trabecular structure and without fragmentation showed a statistically significant higher BHC. Time to union was significantly faster if trabecular structure was present and sclerosis was absent. In intraarticular proximal pole non-unions, where no blood supply is assumed, the BHC was statistically significantly lower and time to union was longer compared to SNUs of the other locations. A statistically significant correlation between BHC and time to union was found in the proximal and distal fragment with higher BHC associated with faster healing. Conclusions CT parameters of bone structure and fracture location can reflect histological healing capacity of SNUs. This can guide bone graft selection in SNU surgery.
Archives of Physical Medicine and Rehabilitation, 2018
To report our experience using continuous intrathecal baclofen (ITB) administration prior to a po... more To report our experience using continuous intrathecal baclofen (ITB) administration prior to a possible ITB device implantation. Design: Retrospective open label study. Mean duration of follow-up 64 months. Setting: Primary-care and referral center, ambulatory and hospitalized care. Participants: Patients (NZ116) undergoing continuous ITB trials between 2006 and 2017. Interventions: Continuous application of baclofen via a temporary intrathecal catheter connected to an external pump. Main Outcome Measures: Assessment of the modified Ashworth Scale and range of movement prior versus end of ITB trial. According to the Barthel Index, definition of high-level patients (60-100 scoring points) and low-level patients (0-55 scoring points). Calculation of the Rivermead Mobility Index in high-level patients prior versus end of ITB trial. Evaluation of occurring adverse events. Results: A total of 119 ITB trials were performed in 116 patients (78 men, mean age 41AE16), 113 patients completed the trials (31 of 113 high level, 82 of 113 low level). The median modified Ashworth scale improved from 4 (interquartile range [IQR] 3-4) to 2 (IQR 1-2; P .001), the range of movement from 2 (IQR 1-3) to 3 (IQR 3-3; P .001). The Rivermead Mobility Index increased from 9 (IQR 6-12) to 10 (IQR 7-12.5; PZ.004) in high-level patients. Eighty-eight out of 113 patients (78%) were appropriate candidates for ITB device surgery, 75 of 88 (85%) proceeded to an implantation. A total of 69 adverse events occurred in 57 of 119 trials (48%), 37 of 69 (54%) were drug related, 32 of 69 (46%) were procedure related, and 42 of 69 (61%) were minor. The ITB device was implanted in 69 of 75 patients (92%) at last follow-up. Conclusions: Continuous administration of ITB is an effective and useful alternative to ITB bolus application during ITB screening period. Half of the patients experienced adverse events; the majority were minor events.
European Journal of Gastroenterology & Hepatology, 2018
Background and aims Nonalcoholic steatohepatitis (NASH) is an increasingly prevalent indication f... more Background and aims Nonalcoholic steatohepatitis (NASH) is an increasingly prevalent indication for liver transplantation (LT) across the world. The relative outcomes following transplantation are poorly described in this cohort. We aimed to analyze the incidence and outcome of LT for NASH as compared with other indications. Patients and methods This is a retrospective analysis of 513 patients who underwent deceased-donor, adult LT between 2002 and 2012 as recorded at the Medical University of Innsbruck, Austria. Results The prevalence of NASH cirrhosis as indication for liver transplantation was 12.7% (65/513). Patient survival in patients with NASH was comparable to other indications, including alcohol-induced liver steatosis (ALD) and hepatitis C virus (HCV) (P=0.208). Patients with NASH were older, had a higher model of end-stage liver disease score and a higher BMI, but patient survival and graft survival were equivalent to other indications. Patients with hepatocellular carcin...
International Journal of Medical Sciences, 2017
Background: Non-muscle invasive bladder cancer (NMIBC) is associated with high rates of recurrenc... more Background: Non-muscle invasive bladder cancer (NMIBC) is associated with high rates of recurrence, resulting in frequent follow-up cystoscopies. We evaluated the use of two point-of-care tests-the nuclear matrix protein 22 (NMP22) and urinary bladder cancer antigen (UBC) Rapid-compared to routine follow-up in patients with a previous history of NMIBC. Methods: 31 patients with cystoscopy-verified active bladder cancer, and 44 follow-up patients without disease as confirmed by cystoscopy were prospectively enrolled. All urine samples were analyzed by voided urine and bladder washing cytology, NMP22 and UBC rapid test (qualitatively and quantitatively). The best cutoff (highest Youden index; ≥6.7 ng/ml) for the quantitative UBC was determined by receiver operating characteristic curves. Results: Voided urine and barbotage cytology resulted in a sensitivity of 25.8% and 32.3%, and a specificity of 100% and 100%, while the NMP22 showed a sensitivity and specificity of 12.9% and 100%, respectively. The qualitative and quantitative UBC Rapid revealed a sensitivity of 61.3% and 64.5%, with a specificity of 77.3% and 81.8%. Barbotage cytology and qualitative UBC test proved to be the best dual combination with the highest overall sensitivity (77.4%). In contrast to barbotage cytology alone, sensitivity increased from 21.4% to 50% for detecting low-grade tumors, and from 43.8% to 100% for high-grade cancers, but reducing specificity from 100% to 77.3%. Conclusion: Compared to urinary cytology, UBC tests alone as well as UBC tests in combination with bladder washing cytology revealed higher sensitivities in detecting low-and high-grade tumors, but at the expense of a lower specificity. Thus, currently cystoscopy cannot be replaced by any of the evaluated methods.
![Research paper thumbnail of Early PET imaging with [68]Ga-PSMA-11 increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence](https://attachments.academia-assets.com/119080154/thumbnails/1.jpg)
](European Journal of Nuclear Medicine and Molecular Imaging, 2017
High-intensity focused ultrasound (HIFU) is a promising new modality for the treatment of localiz... more High-intensity focused ultrasound (HIFU) is a promising new modality for the treatment of localized prostate cancer (PCa). Follow up of patients is recommended with biopsies and multiparametric MRI (mpMRI). However, mpMRI in the postinterventional setting is often false negative. It was our aim to investigate if the new tracer targeting the prostate specific membrane antigen (68 Ga-PSMA-11) could be used to localize recurrent disease with PET/MR in patients with discrepant findings between mpMRI and template biopsies. Methods: Interim analysis of the first ten patients scanned between 09/2016-05/2018 with positive template biopsy and negative mpMRI after HIFU from an ongoing clinical trial (NCT02265159). All patients underwent a 68 Ga-PSMA-11 PET/MRI within 3 months. Four prostatic quadrants were defined and for every quadrant suspicion for recurrence was rated on a 5 point Likert scale from definitely no recurrence (1) to highly suspicious for recurrence (5), with (4) used as cut off for suspected disease based on PET/MRI by one blinded reader. 68 Ga-PSMA-11 uptake of suspicious lesions and background areas was measured with the maximum standardized uptake value (SUV max). The apparent diffusion coefficient (ADC) values of lesions and background was given for each segment. PET/MRI scans were compared with the template biopsy results including corresponding Gleason Scores (GS), number of positive cores and tumor length. Results: The quadrant-based sensitivity, specificity, positive and negative predictive value for PET/MRI was 55%, 100%, 100% and 85%, respectively. Patient based, PET/MRI was negative in four cases with GS3+4 and a tumor length between 0.1-3mm. All tumor lesions with GS4+3 or higher were detected on PET/MRI. Conclusion: Our preliminary results indicate that 68 Ga-PSMA-11-PET/MR has the potential to localize PCa recurrence after HIFU occult on mpMRI.
Journal of the American Heart Association, Jan 20, 2017
Family history of coronary heart disease (CHD) as well as genetic predisposition to CHD assessed ... more Family history of coronary heart disease (CHD) as well as genetic predisposition to CHD assessed by a genetic risk score (GRS) are predictors of CHD risk. It is, however, uncertain to what extent these risk predictors are mediated by major metabolic pathways. Total effects of self-reported family history and a 50-variant GRS (GRS50), as well as effects mediated by apolipoprotein B and A-I (apoB, apoA-I), blood pressure, and diabetes mellitus, on incidence of CHD were estimated in 23 595 participants of the Malmö Diet and Cancer study (a prospective, population-based study). During a median follow-up of 14.4 years, 2213 participants experienced a first CHD event. Family history of CHD and GRS50 (highest versus other quintiles) were associated with incident CHD, with hazard ratios of 1.52 (95% CI: 1.39-1.65) and 1.53 (95% CI: 1.39-1.68), respectively, after adjusting for age, sex, and smoking status. Small proportions of the family history effect were mediated by metabolic risk factor...
European journal of nuclear medicine and molecular imaging, Jan 31, 2017
Prostate cancer (PC) cells typically show increased expression of prostate-specific membrane anti... more Prostate cancer (PC) cells typically show increased expression of prostate-specific membrane antigen (PSMA), which can be visualized by (68)Ga-PSMA-11 PET/CT. The aim of this study was to assess the intensity of (68)Ga-PSMA-11 uptake in the primary tumour and metastases in patients with biopsy-proven PC prior to therapy, and to determine whether a correlation exists between the primary tumour-related (68)Ga-PSMA-11 accumulation and the Gleason score (GS) or prostate-specific antigen (PSA) level. Ninety patients with transrectal ultrasound biopsy-proven PC (GS 6-10; median PSA: 9.7 ng/ml) referred for (68)Ga-PSMA-11 PET/CT were retrospectively analysed. PET images were analysed visually and semiquantitatively by measuring the maximum standardized uptake value (SUVmax). The SUVmax of the primary tumour and pathologic lesions suspicious for lymphatic or distant metastases were then compared to the physiologic background activity of normal prostate tissue and gluteal muscle. The SUVmax ...
Oncotarget, 2016
Although Bacillus Calmette-Guérin (BCG) is the most successful immunotherapy for high-risk non-mu... more Although Bacillus Calmette-Guérin (BCG) is the most successful immunotherapy for high-risk non-muscle-invasive bladder cancer, approximately 30% of patients are unresponsive to treatment. New biomarkers are important to identify patients who will benefit most from BCG during a worldwide BCG shortage. Local immune cell subsets were measured on formalin-fixed, paraffin-embedded tissue sections of bladder cancer by immunohistochemistry, using monoclonal antibodies to tumor-associated macrophages (TAMs; CD68, CD163), B-lymphocytes (CD20) and T-lymphocyte subsets (CD3, CD4, CD8, GATA3, T-bet, FOXP3 and CD25). Cell densities in the lamina propria without invasion, at the invasive front if present, in the papillary tumor stroma, and in the neoplastic urothelium were calculated. Twenty-nine (72.5%) of 40 patients were classified as BCG responders after a mean follow-up of 35.3 months. A statistically significant association was observed for BCG failure with low density of CD4+ and GATA3+ T-cells, and increased expression of FOXP3+ and CD25+ regulatory T-cells (Tregs) as well as CD68+ and CD163+ TAMs. Survival analysis demonstrated prolonged recurrence-free survival (RFS) in patients with an increased count of CD4+ and GATA3+ T-cells. TAMs, Tregs and T-bet+ T-cells were inversely correlated with RFS. Thus, the tumor microenvironment seems to influence the therapeutic response to BCG, permitting an individualized treatment.
Clinical Nuclear Medicine
Sleep
Short and long sleep duration are associated with adverse metabolic outcomes, such as obesity and... more Short and long sleep duration are associated with adverse metabolic outcomes, such as obesity and diabetes. We evaluated cross-sectional differences in metabolite levels between women with self-reported habitual short (<7 h), medium (7–8 h), and long (≥9 h) sleep duration to delineate potential underlying biological mechanisms. In total, 210 metabolites were measured via liquid chromatography-mass spectrometry in 9207 women from the Nurses’ Health Study (NHS; N = 5027), the NHSII (N = 2368), and the Women’s Health Initiative (WHI; N = 2287). Twenty metabolites were consistently (i.e. praw < .05 in ≥2 cohorts) and/or strongly (pFDR < .05 in at least one cohort) associated with short sleep duration after multi-variable adjustment. Specifically, levels of two lysophosphatidylethanolamines, four lysophosphatidylcholines, hydroxyproline and phenylacetylglutamine were higher compared to medium sleep duration, while levels of one diacylglycerol and eleven triacylglycerols (TAGs; a...
Cancers, 2021
Coronavirus-19 (COVID-19)-induced effects on deferred diagnosis and treatment of bladder cancer (... more Coronavirus-19 (COVID-19)-induced effects on deferred diagnosis and treatment of bladder cancer (BC) patients are currently not clarified. The aim of this study was to evaluate outcomes of the COVID-19 pandemic by considering its effects on tumor stage and grade, and to create feasible clinical triage decisions. A retrospective single-center analysis of all patients who underwent diagnostic and surgical procedures due to BC, during January 2019 and December 2020, was performed. Due to COVID-19 lockdowns, significantly fewer (diagnostic and therapeutic) endoscopic procedures were performed in the first 6 months of 2020 compared to 2019 (p = 0.002). In patients with a primary diagnosis of BC, a significant increase of high-grade tumors (p < 0.001), as well as advanced tumor stages (p = 0.014), were noticed during 2020 in comparison to 2019. On the contrary, patients with recurrent BC undergoing risk-adapted surveillance, depending on previous tumor histology, showed no adverse outc...
Cancers, 2021
We conducted a retrospective National Cancer Registry study in Austria to assess a possible seaso... more We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend (p < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr–Sep) and an increase during the winter months (Oct–Mar) were observed (p < 0.001). Focusing on seasonality, the incidence during the months of Oct–Dec (p = 0.008) and Jan–Mar (p < 0.001) was significantly higher compared to the months of Jul–Sep, respectively. Regarding histopathological features, there is a predomin...
Acta Anaesthesiologica Scandinavica, 2021
BackgroundBleeding is a common problem in children with congenital heart disease undergoing major... more BackgroundBleeding is a common problem in children with congenital heart disease undergoing major cardiac surgery requiring cardiopulmonary bypass (CPB). Little is known about optimal management with blood products.ObjectiveTo investigate clinical outcome and hemostatic effects of fibrinogen concentrate (FC) in combination with prothrombin complex concentrate (PCC) versus standard treatment with fresh frozen plasma (FFP) in children undergoing cardiac surgery.MethodsFor this single‐institution cohort study, data on 525 children were analyzed. Propensity score matching in 210 children was applied to reduce the impact of various baseline characteristics.ResultsThree children treated with FC/PCC developed surgical site bleeding requiring surgical revision. One child developed central venous line‐related thrombosis. Blood loss through chest tube drainage was independent of FC/PCC. Coagulation abnormalities were not present in any of these children. Time to extubation and ICU stay did no...
Revista Española de Medicina Nuclear e Imagen Molecular, 2021
INTRODUCTION Nephro- and hematotoxicity after peptide receptor radionuclide therapy (PRRT) have b... more INTRODUCTION Nephro- and hematotoxicity after peptide receptor radionuclide therapy (PRRT) have been described in multiple studies with heterogeneous cumulative activities, number of cycles or radiolabelled peptides. Though highly differentiated metastasized neuroendocrine tumours (NET) have long progression free survival, they may progress. We analysed long-term side effects in a homogenous treatment schedule in PRRT-patients and their impact on future oncologic treatment in case of progression. METHODS From our database 89/384 patients receiving the same PRRT (Lu-177-DOTATATE or Y-90-DOTATOC) 4 times every 10 to 12 weeks and a follow-up at 12 months were analysed. One patient had three and 11 patients had two times four PRRT-cycles resulting in 102 cases. eGFR, Hb, WBC and platelets before the first and one year after the fourth therapy cycle were compared. eGFR-Grading was done according to chronic kidney disease classification (CKD) and grading of hematotoxicity according to Common Terminology Criteria for Adverse Events (CTCAE). Impact of age, gender, cumulative activity, type of PRRT on long-term-toxicity was also assessed. RESULTS eGFR grade 1-2 dropped from 87/102 at the baseline to 71 cases at follow-up (p<0.001). Before treatment grade 3a was found in 13, grade 3b in 2 cases, and at follow-up grade 3a in 25, grade 3b in 5, and grade 4 in 1 case. Anaemia prior to PRRT and at follow-up was grade 0 in 63 versus 48 (p<0.001), grade 1 in 36 versus 48, and grade 2 in three versus six cases. In white blood cell count and platelets, there were no significant changes in grading occurring. Subgroup analysis revealed that only in the age group 65 and older was there a higher incidence for anaemia (p=0.006). CONCLUSIóN: In roughly 20% of cases an increase in grading of nephro- or hematotoxicity is observed. In those patients, except in one, toxicity findings were mild or moderate one year after completion of four cycles of PRRT with either Y-90- or Lu-177-SST-analogues. In terms of safety, PRRT has no critical impact on further oncologic treatment options in the case of disease progression.
European Journal of Nuclear Medicine and Molecular Imaging, 2020
Purpose to assess the influence of intravenous hydration and forced diuresis with furosemide in t... more Purpose to assess the influence of intravenous hydration and forced diuresis with furosemide in two different dosages (20 vs 40 mg) on the intensity of tracer accumulation in the urinary collection system and on the occurrence of halo artefact surrounding the urinary bladder and kidneys in [ 68 Ga]Ga-PSMA-11-PET/CT scans. Materials and methods Comparison of four groups with 50 patients each, receiving different preparation prior to [ 68 Ga]Ga-PSMA-11-PET/CT. Group one, no preparation. Group two, 500 ml sodium chloride administered immediately after tracer injection. Group three, 500 ml sodium chloride and injection of 20 mg furosemide immediately after tracer administration. Group four, 500 ml sodium chloride and injection of 40 mg furosemide immediately after tracer injection. Images were judged visually whether halo artefact was present; semiquantitative measurements were performed with standardised uptake value (SUV). Results Halo artefact of the urinary bladder was present in twelve patients without preparation, in eight patients receiving only sodium chloride, in one patient injected with 20 mg furosemide/sodium chloride and in two patients receiving 40 mg furosemide/sodium chloride, showing a median SUV mean in the bladder of 45.8, 14.4, 4.6 and 5.8, respectively. Differences between patient group without preparation and the two groups with furosemide/sodium chloride were statistically significant. Patient groups receiving 20 mg furosemide and 40 mg furosemide did not differ significantly. Renal halo artefacts were observed in 15 patients of group one, in ten patients of group two, in 14 patients of group three and in 14 patients of group four, with corresponding median SUV mean values of 33.9, 32.0, 37.8 and 30.4 (no statistically significant differences). Conclusion Performing [ 68 Ga]Ga-PSMA-11-PET/CT, intravenous injection of 20-mg furosemide and 500-ml sodium chloride significantly reduces the number of bladder halo artefacts and intensity of tracer accumulation in the urinary bladder. A total of 40 mg furosemide does not further improve results.
British Journal of Haematology, 2020
SummaryFluconazole is one of the most commonly used drugs for antifungal prophylaxis in childhood... more SummaryFluconazole is one of the most commonly used drugs for antifungal prophylaxis in childhood leukaemia. However, its interaction with vincristine may induce neuropathy and the emergence of antifungal drug resistance contributes to substantial mortality caused by invasive fungal infections (IFIs). In a retrospective single‐centre study, we compared tolerability and outcome of different antifungal prophylaxis strategies in 198 children with acute leukaemia (median age 5·3 years). Until 2010, antifungal prophylaxis with fluconazole was offered to most of the patients and thereafter was replaced by liposomal amphotericin‐B (L‐AMB) and restricted to high‐risk patients only. Vincristine‐induced neurotoxicity was significantly reduced under L‐AMB, as the percentage of patients with severe constipation decreased (15·4% vs. 3·7%, before vs. after 31 December·2010, P = 0·01) and stool frequency increased by up to 38% in polyene‐treated patients (P = 0·005). Before 2011, 10 patients devel...
Blood, 2018
BACKGROUND: Prophylaxis of invasive fungal infections in children treated for malignant hematolog... more BACKGROUND: Prophylaxis of invasive fungal infections in children treated for malignant hematologic disease has traditionally been based on the widespread use of fluconazole. With the awareness of increasing rates of invasive mould infections, new agents have been developed and offered to patients at highest risk. METHODS: We compared the tolerance and outcome of different antifungal prophylaxis in 198 childhood patients treated for acute myeloid and lymphoblastic leukemia in a pediatric cancer center. Until 2011 antifungal prophylaxis with fluconazole was offered to all patients, resulting in 15.2-19.4% of invasive mould infections. As the burden of fungal infections was restricted to high risk patients only (i.e. acute myeloid leukemia, leukemia relapse, high risk acute lymphoblastic leukemia and patients after stem cell transplant) and no infection with candida was registered, antifungal prophylaxis was replaced with liposomal amphotericin and offered to this particular patient g...
Cancer Science, 2018
Nivolumab belongs to the standard therapy in the second‐line setting of metastatic renal cell car... more Nivolumab belongs to the standard therapy in the second‐line setting of metastatic renal cell carcinoma (mRCC). Although deep and long‐lasting responses are seen in some patients, the majority of patients will further progress. PD‐L1 is still under critical evaluation as a predictive biomarker. Thus, more accurate biomarkers are clearly warranted. Here, we investigated for the first time the predictive role of IDO‐1, a negative immune‐regulatory molecule, on clear cell RCC tissues of 15 patients undergoing nivolumab therapy. IDO‐1 and other immune inhibitory molecules (PD‐L1, PD‐L2, FOXP3) as well as immune cell subsets (CD3, CD4 and CD8) were measured on formalin‐fixed, paraffin‐embedded sections of RCC specimens by immunohistochemistry. IDO‐1 was predominantly expressed in tumor endothelial cells, and was totally absent from tumor cells itself. IDO‐1 overexpression (>10%) could be detected more frequently in responders (100%, n = 6/6) compared to non‐responders (33.3%, n = 3/9;...
European Urology Supplements, 2019
Bladder-sparing radiotherapy with vinorelbine in localized muscle-invasive bladder cancer: A vali... more Bladder-sparing radiotherapy with vinorelbine in localized muscle-invasive bladder cancer: A valid option for cisplatin-unfit patients?
European Journal of Nuclear Medicine and Molecular Imaging, 2018
Aim The purpose of this study was to investigate the diagnostic performance of 68 Ga-PSMA-11 PET/... more Aim The purpose of this study was to investigate the diagnostic performance of 68 Ga-PSMA-11 PET/CT in the evaluation of bone metastases in metastatic prostate cancer (PC) patients scheduled for radionuclide therapy in comparison to [ 18 F]sodium fluoride (18 F-NaF) PET/CT. Methods Sixteen metastatic PC patients with known skeletal metastases, who underwent both 68 Ga-PSMA-11 PET/CT and 18 F-NaF PET/CT for assessment of metastatic burden prior to radionuclide therapy, were analysed retrospectively. The performance of both tracers was calculated on a lesion-based comparison. Intensity of tracer accumulation of pathologic bone lesions on 18 F-NaF PET and 68 Ga-PSMA-11 PET was measured with maximum standardized uptake values (SUV max) and compared to background activity of normal bone. In addition, SUV max values of PET-positive bone lesions were analysed with respect to morphologic characteristics on CT. Bone metastases were either confirmed by CT or follow-up PET scan. Results In contrast to 468 PET-positive lesions suggestive of bone metastases on 18 F-NaF PET, only 351 of the lesions were also judged positive on 68 Ga-PSMA-11 PET (75.0%). Intensity of tracer accumulation of pathologic skeletal lesions was significantly higher on 18 F-NaF PET compared to 68 Ga-PSMA-11 PET, showing a median SUV max of 27.0 and 6.0, respectively (p < 0.001). Background activity of normal bone was lower on 68 Ga-PSMA-11 PET, with a median SUV max of 1.0 in comparison to 2.7 on 18 F-NaF PET; however, tumour to background ratio was significantly higher on 18 F-NaF PET (9.8 versus 5.9 on 68 Ga-PSMA-11 PET; p = 0.042). Based on morphologic lesion characterisation on CT, 18 F-NaF PET revealed median SUV max values of 23.6 for osteosclerotic, 35.0 for osteolytic, and 19.0 for lesions not visible on CT, whereas on 68 Ga-PSMA-11 PET median SUV max values of 5.0 in osteosclerotic, 29.5 in osteolytic, and 7.5 in lesions not seen on CT were measured. Intensity of tracer accumulation between 18 F-NaF PET and 68 Ga-PSMA-11 PET was significantly higher in osteosclerotic (p < 0.001) and lesions not visible on CT (p = 0.012). Conclusion In comparison to 68 Ga-PSMA-11 PET/CT, 18 F-NaF PET/CT detects a higher number of pathologic bone lesions in advanced stage PC patients scheduled for radionuclide therapy. Our data suggest that 68 Ga-PSMA-11 PET should be combined with 18 F-NaF PET in PC patients with skeletal metastases for restaging prior to initiation or modification of therapy.
Archives of Orthopaedic and Trauma Surgery, 2018
Introduction For the treatment of scaphoid non-unions (SNU), different surgical techniques, inclu... more Introduction For the treatment of scaphoid non-unions (SNU), different surgical techniques, including vascularized and non-vascularized bone grafts, are applied. Besides stability, vascularity, and the biological situation at the non-union site are important for healing and the appropriate choice of treatment. We assessed the healing potential of SNUs by histological parameters and compared it to CT parameters of bone structure and fracture location. Based on the results, we developed a CT classification and a treatment algorithm to impact graft selection in SNU surgery. Patients and methods Preoperative 2D-CT reformations of 29 patients were analyzed for trabecular structure, sclerosis, and fragmentation of the proximal fragment. The fracture location was assessed on 3D-CT reconstructions and grouped in three zones depending on the potential blood supply. Samples were taken during surgery for histological evaluation. Histological parameters of bone healing were defined and a bone healing capacity score (BHC), reflecting histological bone viability, was calculated. CT findings were compared to BHC, age of SNU, and time to union. Results Cases with trabecular structure and without fragmentation showed a statistically significant higher BHC. Time to union was significantly faster if trabecular structure was present and sclerosis was absent. In intraarticular proximal pole non-unions, where no blood supply is assumed, the BHC was statistically significantly lower and time to union was longer compared to SNUs of the other locations. A statistically significant correlation between BHC and time to union was found in the proximal and distal fragment with higher BHC associated with faster healing. Conclusions CT parameters of bone structure and fracture location can reflect histological healing capacity of SNUs. This can guide bone graft selection in SNU surgery.
Archives of Physical Medicine and Rehabilitation, 2018
To report our experience using continuous intrathecal baclofen (ITB) administration prior to a po... more To report our experience using continuous intrathecal baclofen (ITB) administration prior to a possible ITB device implantation. Design: Retrospective open label study. Mean duration of follow-up 64 months. Setting: Primary-care and referral center, ambulatory and hospitalized care. Participants: Patients (NZ116) undergoing continuous ITB trials between 2006 and 2017. Interventions: Continuous application of baclofen via a temporary intrathecal catheter connected to an external pump. Main Outcome Measures: Assessment of the modified Ashworth Scale and range of movement prior versus end of ITB trial. According to the Barthel Index, definition of high-level patients (60-100 scoring points) and low-level patients (0-55 scoring points). Calculation of the Rivermead Mobility Index in high-level patients prior versus end of ITB trial. Evaluation of occurring adverse events. Results: A total of 119 ITB trials were performed in 116 patients (78 men, mean age 41AE16), 113 patients completed the trials (31 of 113 high level, 82 of 113 low level). The median modified Ashworth scale improved from 4 (interquartile range [IQR] 3-4) to 2 (IQR 1-2; P .001), the range of movement from 2 (IQR 1-3) to 3 (IQR 3-3; P .001). The Rivermead Mobility Index increased from 9 (IQR 6-12) to 10 (IQR 7-12.5; PZ.004) in high-level patients. Eighty-eight out of 113 patients (78%) were appropriate candidates for ITB device surgery, 75 of 88 (85%) proceeded to an implantation. A total of 69 adverse events occurred in 57 of 119 trials (48%), 37 of 69 (54%) were drug related, 32 of 69 (46%) were procedure related, and 42 of 69 (61%) were minor. The ITB device was implanted in 69 of 75 patients (92%) at last follow-up. Conclusions: Continuous administration of ITB is an effective and useful alternative to ITB bolus application during ITB screening period. Half of the patients experienced adverse events; the majority were minor events.
European Journal of Gastroenterology & Hepatology, 2018
Background and aims Nonalcoholic steatohepatitis (NASH) is an increasingly prevalent indication f... more Background and aims Nonalcoholic steatohepatitis (NASH) is an increasingly prevalent indication for liver transplantation (LT) across the world. The relative outcomes following transplantation are poorly described in this cohort. We aimed to analyze the incidence and outcome of LT for NASH as compared with other indications. Patients and methods This is a retrospective analysis of 513 patients who underwent deceased-donor, adult LT between 2002 and 2012 as recorded at the Medical University of Innsbruck, Austria. Results The prevalence of NASH cirrhosis as indication for liver transplantation was 12.7% (65/513). Patient survival in patients with NASH was comparable to other indications, including alcohol-induced liver steatosis (ALD) and hepatitis C virus (HCV) (P=0.208). Patients with NASH were older, had a higher model of end-stage liver disease score and a higher BMI, but patient survival and graft survival were equivalent to other indications. Patients with hepatocellular carcin...
International Journal of Medical Sciences, 2017
Background: Non-muscle invasive bladder cancer (NMIBC) is associated with high rates of recurrenc... more Background: Non-muscle invasive bladder cancer (NMIBC) is associated with high rates of recurrence, resulting in frequent follow-up cystoscopies. We evaluated the use of two point-of-care tests-the nuclear matrix protein 22 (NMP22) and urinary bladder cancer antigen (UBC) Rapid-compared to routine follow-up in patients with a previous history of NMIBC. Methods: 31 patients with cystoscopy-verified active bladder cancer, and 44 follow-up patients without disease as confirmed by cystoscopy were prospectively enrolled. All urine samples were analyzed by voided urine and bladder washing cytology, NMP22 and UBC rapid test (qualitatively and quantitatively). The best cutoff (highest Youden index; ≥6.7 ng/ml) for the quantitative UBC was determined by receiver operating characteristic curves. Results: Voided urine and barbotage cytology resulted in a sensitivity of 25.8% and 32.3%, and a specificity of 100% and 100%, while the NMP22 showed a sensitivity and specificity of 12.9% and 100%, respectively. The qualitative and quantitative UBC Rapid revealed a sensitivity of 61.3% and 64.5%, with a specificity of 77.3% and 81.8%. Barbotage cytology and qualitative UBC test proved to be the best dual combination with the highest overall sensitivity (77.4%). In contrast to barbotage cytology alone, sensitivity increased from 21.4% to 50% for detecting low-grade tumors, and from 43.8% to 100% for high-grade cancers, but reducing specificity from 100% to 77.3%. Conclusion: Compared to urinary cytology, UBC tests alone as well as UBC tests in combination with bladder washing cytology revealed higher sensitivities in detecting low-and high-grade tumors, but at the expense of a lower specificity. Thus, currently cystoscopy cannot be replaced by any of the evaluated methods.
European Journal of Nuclear Medicine and Molecular Imaging, 2017
High-intensity focused ultrasound (HIFU) is a promising new modality for the treatment of localiz... more High-intensity focused ultrasound (HIFU) is a promising new modality for the treatment of localized prostate cancer (PCa). Follow up of patients is recommended with biopsies and multiparametric MRI (mpMRI). However, mpMRI in the postinterventional setting is often false negative. It was our aim to investigate if the new tracer targeting the prostate specific membrane antigen (68 Ga-PSMA-11) could be used to localize recurrent disease with PET/MR in patients with discrepant findings between mpMRI and template biopsies. Methods: Interim analysis of the first ten patients scanned between 09/2016-05/2018 with positive template biopsy and negative mpMRI after HIFU from an ongoing clinical trial (NCT02265159). All patients underwent a 68 Ga-PSMA-11 PET/MRI within 3 months. Four prostatic quadrants were defined and for every quadrant suspicion for recurrence was rated on a 5 point Likert scale from definitely no recurrence (1) to highly suspicious for recurrence (5), with (4) used as cut off for suspected disease based on PET/MRI by one blinded reader. 68 Ga-PSMA-11 uptake of suspicious lesions and background areas was measured with the maximum standardized uptake value (SUV max). The apparent diffusion coefficient (ADC) values of lesions and background was given for each segment. PET/MRI scans were compared with the template biopsy results including corresponding Gleason Scores (GS), number of positive cores and tumor length. Results: The quadrant-based sensitivity, specificity, positive and negative predictive value for PET/MRI was 55%, 100%, 100% and 85%, respectively. Patient based, PET/MRI was negative in four cases with GS3+4 and a tumor length between 0.1-3mm. All tumor lesions with GS4+3 or higher were detected on PET/MRI. Conclusion: Our preliminary results indicate that 68 Ga-PSMA-11-PET/MR has the potential to localize PCa recurrence after HIFU occult on mpMRI.
Journal of the American Heart Association, Jan 20, 2017
Family history of coronary heart disease (CHD) as well as genetic predisposition to CHD assessed ... more Family history of coronary heart disease (CHD) as well as genetic predisposition to CHD assessed by a genetic risk score (GRS) are predictors of CHD risk. It is, however, uncertain to what extent these risk predictors are mediated by major metabolic pathways. Total effects of self-reported family history and a 50-variant GRS (GRS50), as well as effects mediated by apolipoprotein B and A-I (apoB, apoA-I), blood pressure, and diabetes mellitus, on incidence of CHD were estimated in 23 595 participants of the Malmö Diet and Cancer study (a prospective, population-based study). During a median follow-up of 14.4 years, 2213 participants experienced a first CHD event. Family history of CHD and GRS50 (highest versus other quintiles) were associated with incident CHD, with hazard ratios of 1.52 (95% CI: 1.39-1.65) and 1.53 (95% CI: 1.39-1.68), respectively, after adjusting for age, sex, and smoking status. Small proportions of the family history effect were mediated by metabolic risk factor...
European journal of nuclear medicine and molecular imaging, Jan 31, 2017
Prostate cancer (PC) cells typically show increased expression of prostate-specific membrane anti... more Prostate cancer (PC) cells typically show increased expression of prostate-specific membrane antigen (PSMA), which can be visualized by (68)Ga-PSMA-11 PET/CT. The aim of this study was to assess the intensity of (68)Ga-PSMA-11 uptake in the primary tumour and metastases in patients with biopsy-proven PC prior to therapy, and to determine whether a correlation exists between the primary tumour-related (68)Ga-PSMA-11 accumulation and the Gleason score (GS) or prostate-specific antigen (PSA) level. Ninety patients with transrectal ultrasound biopsy-proven PC (GS 6-10; median PSA: 9.7 ng/ml) referred for (68)Ga-PSMA-11 PET/CT were retrospectively analysed. PET images were analysed visually and semiquantitatively by measuring the maximum standardized uptake value (SUVmax). The SUVmax of the primary tumour and pathologic lesions suspicious for lymphatic or distant metastases were then compared to the physiologic background activity of normal prostate tissue and gluteal muscle. The SUVmax ...
Oncotarget, 2016
Although Bacillus Calmette-Guérin (BCG) is the most successful immunotherapy for high-risk non-mu... more Although Bacillus Calmette-Guérin (BCG) is the most successful immunotherapy for high-risk non-muscle-invasive bladder cancer, approximately 30% of patients are unresponsive to treatment. New biomarkers are important to identify patients who will benefit most from BCG during a worldwide BCG shortage. Local immune cell subsets were measured on formalin-fixed, paraffin-embedded tissue sections of bladder cancer by immunohistochemistry, using monoclonal antibodies to tumor-associated macrophages (TAMs; CD68, CD163), B-lymphocytes (CD20) and T-lymphocyte subsets (CD3, CD4, CD8, GATA3, T-bet, FOXP3 and CD25). Cell densities in the lamina propria without invasion, at the invasive front if present, in the papillary tumor stroma, and in the neoplastic urothelium were calculated. Twenty-nine (72.5%) of 40 patients were classified as BCG responders after a mean follow-up of 35.3 months. A statistically significant association was observed for BCG failure with low density of CD4+ and GATA3+ T-cells, and increased expression of FOXP3+ and CD25+ regulatory T-cells (Tregs) as well as CD68+ and CD163+ TAMs. Survival analysis demonstrated prolonged recurrence-free survival (RFS) in patients with an increased count of CD4+ and GATA3+ T-cells. TAMs, Tregs and T-bet+ T-cells were inversely correlated with RFS. Thus, the tumor microenvironment seems to influence the therapeutic response to BCG, permitting an individualized treatment.