Refine
Document Type
- Article (11)
Language
- English (11)
Has Fulltext
- yes (11)
Is part of the Bibliography
- no (11)
Keywords
- 177Lu-PSMA-617 (3)
- PSMA (3)
- metastatic castration-resistant prostate cancer (2)
- 99mTc-MIBI (1)
- 99mTc-pertechnetate (1)
- COVID-19 (1)
- Effective half-life (1)
- FOXO3a (1)
- Graves’ disease (1)
- Hashimoto’s thyroiditis (1)
Institute
- Medizin (11)
Aim: Radioiodine therapy (RIT) may trigger the development of Graves’ ophthalmopathy (GO) or exacerbate pre-existing subclinical GO. Therefore, glucocorticoid administration is recommended for patients with pre-existing GO. Aim of this study was to analyze the influence of glucocorticoid therapy with methylprednisolone on intratherapeutic effective half-life (EHL) of radioiodine-131 in patients with Graves’ disease (GD) as recent studies showed an effect for prednisolone.
Methods: In a retrospective study, 264 patients with GD who underwent RIT without any additional antithyroid medication were evaluated. Intrathyroidal EHL was determined pre- and intratherapeutically. Patients with co-existing GO (n = 43) received methylprednisolone according to a fixed scheme starting 1 day prior to RIT, patients without GO (n = 221) did not receive any protective glucocorticoid medication. The ratios of EHL during RIT and during radioiodine uptake test (RIUT) were compared.
Results: Patients receiving methylprednisolone showed a slight decrease of the mean EHL from 5.63 d (RIUT) to 5.39 d (RIT) (p > 0.05). A comparable result was obtained in patients without glucocorticoids (5.71 d (RIUT) to 5.47 d (RIT); p > 0.05). The ratios of the EHL between RIT and RIUT failed to show a significant difference between the two groups. EHL is therefore not significantly influenced by an additional protective treatment with methylprednisolone.
Conclusions: In the present study a decreased intrathyroidal EHL under glucocorticoid medication with methylprednisolone could not be detected. Therefore, co-medication with methylprednisolone in patients with GO may be preferred to avoid an intratherapeutic decrease of EHL by accompanying protective glucocorticoides.
TRIANNI mice carry an entire set of human immunoglobulin V region gene segments and are a powerful tool to rapidly isolate human monoclonal antibodies. After immunizing these mice with DNA encoding the spike protein of SARS-CoV-2 and boosting with spike protein, we identified 29 hybridoma antibodies that reacted with the SARS-CoV-2 spike protein. Nine antibodies neutralize SARS-CoV-2 infection at IC50 values in the subnanomolar range. ELISA-binding studies and DNA sequence analyses revealed one cluster of three clonally related neutralizing antibodies that target the receptor-binding domain and compete with the cellular receptor hACE2. A second cluster of six clonally related neutralizing antibodies bind to the N-terminal domain of the spike protein without competing with the binding of hACE2 or cluster 1 antibodies. SARS-CoV-2 mutants selected for resistance to an antibody from one cluster are still neutralized by an antibody from the other cluster. Antibodies from both clusters markedly reduced viral spread in mice transgenic for human ACE2 and protected the animals from SARS-CoV-2-induced weight loss. The two clusters of potent noncompeting SARS-CoV-2 neutralizing antibodies provide potential candidates for therapy and prophylaxis of COVID-19. The study further supports transgenic animals with a human immunoglobulin gene repertoire as a powerful platform in pandemic preparedness initiatives.
Background The arterial in line application of the leukocyte inhibition module (LIM) in the cardiopulmonary bypass (CPB) limits overshooting leukocyte activity during cardiac surgery. We now studied in a porcine model whether LIM may have beneficial effects on cardiac function after CPB. Methods German landrace pigs underwent CPB (60 min myocardial ischemia; 30 min reperfusion)without (group I; n=6) or with LIM (group II; n=6). The cardiac indices (CI) and cardiac function were analyzed pre and post CPB with a Swan-Ganz catheter and the cardiac function analyzer. Neutrophil labeling with technetium, scintigraphy, and histological analyses were done to track activated neutrophils within the organs. Results LIM prevented CPB-associated increase of neutrophil counts in peripheral blood. In group I, the CI significantly declined post CPB (post: 3.26 +/- 0.31; pre: 4.05 +/- 0.45 l/min/m2; p<0.01). In group II, the CI was only slightly reduced (post: 3.86 +/- 0.49; pre 4.21 +/- 1.32 l/min/m2; p=0.23). Post CPB, the intergroup difference showed significantly higher CI values in the LIM group (p<0.05) which was in conjunction with higher pre-load independent endsystolic pressure volume relationship (ESPVR) values (group I: 1.57 +/- 0.18; group II: 1.93 +/- 0.16; p<0.001). Moreover, the systemic vascular resistance and pulmonary vascular resistance were lower in the LIM group. LIM appeared to accelerate the sequestration of hyperactivated neutrophils in the spleen and to reduce neutrophil infiltration of heart and lung. Conclusions Our data provide strong evidence that LIM improves perioperative hemodynamics and cardiac function after CPB by limiting neutrophil activity and inducing accelerated sequestration of neutrophils in the spleen.
Background: Protective effects of vitamin D have been reported in autoimmune and malignant thyroid diseases, though little is known about the underlying mechanism. Sirtuin 1 histon deacethylase (SIRT1) links the vitamin D pathway with regulation of transcription factor FOXO3a, a key player in cell cycle regulation and apoptosis. Aim of the present study was to investigate common single nucleotide polymorphisms (SNP's) in FOXO3a gene in respect to thyroid diseases, as well as to evaluate the hypothesis of Sirtuin1-FOXO3a interaction being a mediator of anti-proliferative vitamin D effects.
Methods: The SNP's FOXO3a rs4946936/rs4945816/rs9400239 were genotyped in 257 patients with differentiated thyroid carcinoma (DTC), 139 patients with Hashimoto thyroiditis (HT) and 463 healthy controls (HC). Moreover, T-helper cells of HC and papillary thyroid cancer cell line BCPAP were incubated with 1,25(OH)2D3 and/or SIRT1 inhibitor Ex-527 in order to elucidate SIRT1- dependent vitamin D effects on cell proliferation and FOXO3a gene expression in vitro.
Results: Patients with DTC tended to carry more often allele C in FOXO3a rs4946936 in comparison to HC (pcorrected = pc = 0.08). FOXO3a rs9400239T and rs4945816C was more frequent in HT in comparison to HC (pc = 0.02 and pc = 0.01, respectively). In both DTC and HT, we could not find a correlation of FOXO3a SNP's with vitamin D status. However, on in vitro level, 1,25(OH)2D3 showed an anti-proliferative effect in both T-helper cells and BCPAP, that was blocked by SIRT1 inhibition (T-helper cells: p = 0.0059, BCPAP: p = 0.04) and accompanied by elevated FOXO3a gene expression in T-helper cells (p = 0.05).
Conclusions: FOXO3a rs9400239T and rs4945816C may constitute risk factors for HT, independent of the vitamin D status.This indicates the implication of FOXO3a in pathogenesis of autoimmune thyroid diseases. The dependency of anti-proliferative vitamin D effects on SIRT1 activity further suggests a key role of vitamin D-SIRT1-FOXO3a axis for protective vitamin D effects.
Peptide receptor radionuclide therapy (PRRT) of metastatic neuroendocrine tumors (NET) can be successfully repeated but may eventually be dose-limited. Since 177Lu-DOTATATE dose limitation may come from hematological rather than renal function, hematological peripheral blood stem cell backup might be desirable. Here, we report our initial experience of peripheral blood stem-cell collection (PBSC) in patients with treatment-related cytopenia and therefore high risk of bone-marrow failure. Five patients with diffuse bone-marrow infiltration of NET and relevant myelosuppression (≥grade 2) received PBSC before one PRRT cycle with 177Lu-DOTATATE (7.6 ± 0.8 GBq/cycle). Standard stem-cell mobilization with Granulocyte-colony stimulating factor (G-CSF) was applied, and successful PBSC was defined as a collection of >2 × 106/kg CD34+ cells. In case of initial failure, Plerixafor was administered in addition to G-CSF prior to apheresis. PBSC was successfully performed in all patients with no adverse events. Median cumulative activity was 44.8 GBq (range, 21.3–62.4). Three patients had been previously treated with PRRT, two of which needed the addition of Plerixafor for stem-cell mobilization. Only one of five patients required autologous peripheral blood stem-cell transplantation during the median follow up time of 28 months. PBSC collection seems to be feasible in NET with bone-marrow involvement and might be worth considering as a backup strategy prior to PRRT, in order to overcome dose-limiting bone-marrow toxicity.
Background and Aims. Biliary complications are the most frequent complications after common liver surgeries. In this study, accuracy of hepatobiliary scintigraphy (HBS) and impact of hyperbilirubinemia were evaluated. Methods. Between November 2007 and February 2016, 131 patients underwent hepatobiliary scintigraphy after having liver surgery. 39 patients with 42 scans after LTX (n=13) or hepatic resection (n=26) were evaluated in the study; 27 were male, with mean age 60 years. The subjects underwent hepatobiliary scintigraphy with Tc-99m labeled Mebrofenin. The results were compared to ERCP as gold standard performed within one month after HBS. We calculated sensitivity, specificity, PPV, and NPV. We compared LTX patients to patients with other liver surgeries. Furthermore the influence of hyperbilirubinemia on HBS scans was evaluated. Results. HBS always provided the correct diagnosis in cases of bile leak in the liver-resected group (14/14). Overall diagnostic accuracy was 76% (19/25) in this group and 54% (7/13) in the LTX group. False negative (FN) diagnoses occurred more often among LTX patients (p=0.011). Hyperbilirubinemia (>5 mg/dL) significantly influenced the excretion function of the liver, prolonging HBS’s time-activity-curve (p=0.001). Conclusions. Hepatobiliary scintigraphy is a reliable tool to detect biliary complications, but reduced accuracy must be considered after LTX.
Background: High-intensity focused ultrasound (HIFU) allows to inflict intracorporal thermal lesions without penetrating the skin or damaging the surrounding tissue. This analysis intends to assess the magnitude of HIFU-induced ablations within benign thyroid nodules using scintigraphic imaging with 99mTc.
Methods: Ten cold, hot, or indifferent nodules were treated using multiple pulses of HIFU to induce temperatures of around 85°C within the ablation zone. Pre- and posttreatment, uptake values of 99mTc pertechnetate or 99mTc-MIBI were recorded. The pre-post reduction of nodular uptake was evaluated to assess ablation magnitude.
Results: Relative nodular uptake in relation to total thyroidal uptake decreased after one session of HIFU in all cases. Median 99mTc-MIBI uptake reduction was 35.5% (ranging from 11% to 57%; p < 0.1), while 99mTc-pertechnetate scintigraphy showed a median uptake reduction of 27% (range 10% to 44%; p < 0.1). No major complications were observed.
Conclusions: HIFU appears to be safe and is an easy to perform means of thermal ablation. This study shows that HIFU treatment in thyroidal nodules can be evaluated by scintigraphic means shortly after the intervention. Due to small sample size, the exact magnitude of HIFU ablation efficiency in thyroidal nodules remains a value to beassessed in a larger study.
Objective: The aim of this study was to evaluate and compare the efficacy of single-treatment cooled and uncooled microwave ablation in thyroid nodules.
Methods: Eighteen patients (11 women) with an average age of 62 years (range: 41–80) with 18 cold, mainly solid or solid thyroid nodules were treated with cooled or uncooled microwave ablation. Pain during the treatment was measured on a 10-point score. Side effects revealed by ultrasound or patients’ complaints were documented. Laboratory data was evaluated before, 24 h and three months after MWA. Nodule volumes were measured before and three months after MWA.
Results: Cooled MWA was better tolerated than uncooled MWA. A significant reduction of thyroid nodule volume was observed in all cases. The reduction after cMWA was higher (40%) than after uMWA (29%). Pain intensity during cMWA was significantly lower than after uMWA. CMWA and uMWA led to a significant decrease of nodule blood circulation and echogenicity and to a significant increase of nodule elasticity. Thyroid function remained intact in all cases. The energy (kJ/s) administered into the nodules in relation to the ablation time during cMWA was higher than during uMWA.
Conclusions: CMWA leads to a slightly higher but statistically not significant nodule volume reduction than uMWA. Patient comfort during cMWA is higher than during uMWA. The risk of unintended side effects is less in cMWA. A Single-treatment provides sufficient results.
Advanced stage metastatic prostate cancer with extensive bone marrow involvement is associated with a high risk of therapy-induced myelotoxicity and unfavorable outcomes. The role of salvage radioligand therapy (RLT) with 177Lu-PSMA-617 in this subset of patients remains to be further elucidated. Forty-five patients with progressive metastatic castration-resistant prostate cancer (mCRPC) and diffuse bone marrow involvement were treated with repeated cycles of RLT after having exhausted standard treatment options. A mean treatment activity of 7.4 ± 1.4 GBq 177Lu-PSMA-617 was administered in a median of four treatment cycles (IQR 2-6) and the mean cumulative activity was 32.6 ± 20.1 GBq. After two RLT cycles, ≥50% PSA decline was observed in 25/45 (56%) patients and imaging-based partial remission (PR) was observed in 18/45 (40%) patients. Median imaging-based progression-free survival (PFS) was 6.4 mo (95% CI, 3.0–9.8) and the median overall survival (OS) was 10.2 months (95% CI, 7.2–12.8). The biochemical response translated into a significantly prolonged PFS (12.9 vs. 2.8 mo, p < 0.001) and OS (13.5 vs. 6.7 mo, p < 0.001). Patients with PR on interim imaging after two cycles had a longer median OS compared to patients with stable or progressive disease (15.5 vs. 7.1 mo, p < 0.001). Previous taxane-based chemotherapy (HR 3.21, 95%CI 1.18–8.70, p = 0.02) and baseline LDH levels (HR 1.001, 95%CI 1.000–1.001, p = 0.04) were inversely associated with OS on a Cox-regression analysis. Grade ≥ 3 hematological decline was observed after 22/201 (11%) cycles with anemia, leukopenia and thrombocytopenia in 15/45 (33%), 6/45 (13%) and 8/45 (18%) patients, respectively. Cumulative treatment activity and absorbed whole-body dose were not correlated with new onset grade ≥ 3 hematotoxicity (p = 0.91, p = 0.69). No event of grade ≥ 3 chronic kidney disease was observed during RLT or the follow-up. Last line RLT with 177Lu-PSMA-617 in mCRPC patients with diffuse bone marrow involvement may thus contribute to prolonged disease control at an acceptable safety profile.
The aim of this retrospective study was to assess the outcome of patients with metastasized castration-resistant early-onset prostate cancer refractory to chemotherapy receiving radioligand therapy with 177Lutetium-PSMA-617 (LuPSMA-RLT). Twenty-five patients of ≤55 years of age at prostate cancer diagnosis, treated with a median of four (IQR 2–6) cycles (mean of 7.7 ± 1.4 GBq per cycle) every 6–8 weeks, were analyzed. Survival outcome was calculated based on the Kaplan–Meier method. The median progression-free survival (PFS) was 3.8 months (95% CI 2.3–5.3), and overall survival (OS) was 8.5 months (95% CI 6.2–10.8). An initial PSA reduction (≥ 50%) was observed in 9/25 (36%) of patients without being significantly associated with OS (p = 0.601). PSA response (PSA decline ≥50% at 12 weeks) was observed in 12/25 (48%) of patients and significantly associated with longer OS (16.0 months, 95% CI 7.4–24.6 vs. 4.0 months, 95% CI 1.1–6.9, p = 0.002). Imaging-based response using 68Ga-PSMA-11-PET/CT after two to three cycles was seen in 11/25 (44%). Additionally, responders had a significantly longer median PFS (8.7 months, 95% CI 1.3–16.1 vs. 1.9 months, 95% CI 1.7–2.2, p < 0.001) and OS (16.0 months, 95% CI 7.6–24.4 vs. 4.0 months, 95% CI 0.9–7.1; p = 0.002). Intra- or post-therapeutic toxicity was graded according to the CTCAE v5.0 criteria. Newly developing grade ≥ 3 anemia, leukopenia, and thrombocytopenia occurred in three (12%), one (4%), and three (12%) patients, respectively. One patient showed renal toxicity (grade ≥ 3) during follow-up. Pain palliation (>2 level VAS decline) was achieved in 9/14 (64%) and performance status improvement (ECOG level decline ≥ 1) in 8/17 (47%) of patients. Compared to previous reports, radioligand therapy with 177Lu-PSMA-617 in metastasized castration-resistant early-onset prostate cancer patients refractory to chemotherapy yields similar response rates with a comparable safety profile, but is associated with shorter survival.
