Search

In this case report, we present the treatment outcomes of the first patient enrolled in the LuDO-N trial. The patient is a 21-month-old girl diagnosed with high-risk neuroblastoma (NB) and widespread skeletal metastasis. The patient initially underwent first-line therapy according to SIOPEN HRNBL-1 but was switched to second-line treatments due to disease progression, and she was finally screened for enrollment in the LuDO-N trial due to refractory disease. Upon enrollment, the patient received two rounds of the radiolabeled somatostatin analogue lutetium-177 octreotate (177Lu-DOTATATE), which was well tolerated. A dosimetry analysis revealed a heterogeneous uptake across tumor lesions, resulting in a significant absorbed dose of 54 Gy in the primary tumor, but only 2 Gy at one of the metastatic sites in the distal femur. While the initial treatment response showed disease stabilization, the distal femoral metastasis continued to progress, leading to the eventual death of the patient. A tissue analysis of the biopsies collected throughout the course of the disease revealed heterogeneous drug target expression of somatostatin receptor 2 (SSTR2) across and within tumor lesions. Furthermore, genomic profiling revealed a novel KIAA1549::BRAF fusion oncogene amplification in the distal femoral metastasis at recurrence that might be related with resistance to radiation, possibly through the downregulation of SSTR2. This case report demonstrates a mixed response to molecular radiotherapy (MRT) with 177Lu-DOTATATE. The observed variation in SSTR2 expression between tumor lesions suggests that heterogeneous target expression may have been the reason for treatment failure in this patient’s case. Further investigation within the LuDO-N trial will give a more comprehensive understanding of the correlation between SSTR2 expression levels and treatment outcomes, which will be important to advance treatment strategies based on MRT for children with high-risk NB.

Career building can be challenging for young surgeons, especially when topics such as lifestyle, work–life balance and subspecialization arise. Suggestions and advice from senior colleagues is very valuable but many young surgeons do not have such opportunities or are limited to a few senior surgeons. The International Microsurgery Club (IMC), in collaboration with the World Society of Reconstructive Microsurgery, organized a combined webinar for this topic and invited world renowned microsurgery masters polled by the IMC members to join, including Prof. Peter Neligan (Emeritus from University of Washington, United States), Prof. Raja Sabapathy (Ganga Hospital, India), Dr. Gregory Buncke (The Buncke Clinic, United States), Prof. Isao Koshima (Hiroshima University Hospital, Japan), Prof. David Chwei-Chin Chuang (Chang Gung Memorial Hospital, Taiwan), and Prof. Eric Santamaria (Hospital General Dr. Manuel Gea Gonzalez, Mexico) on May 1, 2022. Prof. Joon-Pio Hong (Asan Medical Center, South Korea) and Prof. Fu-Chan Wei (Chang Gung Memorial Hospital, Taiwan) were also selected but unfortunately could not make it and were therefore invited to another event in April 2023, summarized in a recently published paper.

Abstract Background Peptide receptor radionuclide therapy is effective in treating neuroendocrine tumours, but treatment may be limited by kidney and bone marrow toxicity. In this work, the absorbed dose burden to the bone marrow was estimated using image-based dosimetry and its potential use for predicting treatment-altering toxicity was studied. Peripheral blood samples taken before and after 229 treatments with 177Lu-DOTATATE in 59 patients were studied. In connection to the treatments, a total of 940 blood sample occasions provided data on white blood cell, neutrophil granulocyte, platelet, erythrocyte and haemoglobin concentrations. SPECT/CT image data were collected at two or three time points after each treatment. Absorbed doses to bone marrow were calculated from the activity concentration in a metastasis-free lumbar vertebra. The rate of delayed and aborted treatments was analysed based on medical records. Results The average absorbed dose to the bone marrow was 0.42 Gy (median 0.33 Gy, SD 0.27 Gy) per treatment. Dose–response relationships between white blood cells, neutrophil granulocytes and haemoglobin concentrations were observed, most prominently at 31–45 days after each treatment. The correlations were stronger in patients with skeletal metastases. The rates of haematological toxicity-related delays and aborted treatments were 6% and 12%, respectively. None of the studied bone marrow dosimetric parameters could clearly predict treatment-related toxicity. However, patients with skeletal metastases had higher risk of treatment-altering toxicity (odds ratio = 6.0). Conclusions Treatment-altering haematological toxicity in peptide receptor radionuclide therapy is relatively rare and appears difficult to fully predict from post-therapeutic image-based dosimetry. However, for patients with skeletal metastases, the haematological dose–response relationships are stronger. Future studies may focus on this patient group, to further investigate the usefulness of dosimetry in predicting decreases in blood values.

Abstract Flexible low‐voltage organic thin‐film transistors (TFTs) with Ag source/drain contacts are fabricated, and the contact resistance is measured using the transfer length method. The TFTs are fabricated in the inverted coplanar (bottom‐gate, bottom‐contact) device architecture, using the vacuum‐deposited small‐molecule semiconductor dinaphtho[2,3′b:2′,3′‐f]thieno[3,2‐b]thiophene (DNTT). Prior to the semiconductor deposition, the contact surface is functionalized with a chemisorbed monolayer of pentafluorobenzenethiol (PFBT). For comparison, TFTs with PFBT‐functionalized Au source/drain contacts are fabricated on the same substrate. Overall, the performance of the TFTs with the Ag contacts is very similar to that of the TFTs with the Au contacts, and the contact resistance of the TFTs with the Ag contacts (377 Ωcm) is the smallest reported to date for p‐channel organic TFTs with a contact material other than Au or Pt.

Abstract Background In vivo monitoring of cell biodistribution using positron emission tomography (PET) provides a quantitative non-invasive method to further optimize cell therapies and related new developments in the field. Our group has earlier optimized and evaluated the in vitro properties of two radiotracers,[89Zr]Zr-(oxinate)4 and [89Zr]Zr-DFO-NCS, for the radiolabelling of different cell types. Here, we performed a microPET study to assess the in vivo biodistribution of cells in rats using these two radiotracers. Human decidual stromal cells (hDSC) and rat macrophages (rMac) were radiolabelled with [89Zr]Zr-(oxinate)4 or [89Zr]Zr-DFO-NCS. Rats were intravenously injected with radiolabelled cells, and the in vivo biodistribution was monitored with microPET/CT imaging for up to day 7. Organ uptake was evaluated and presented as a percentage of injected activity per gram tissue (%IA/g) and total absorbed organ doses (mSv/MBq). Results The biodistribution in vivo showed an immediate uptake in the lungs. Thereafter, [89Zr]Zr-(oxinate)4 labelled cells migrated to the liver, while the signal from [89Zr]Zr-DFO-NCS labelled cells lingered in the lungs. The differences in the in vivo behaviour for the same cell type appeared related to the radiotracer labelling. After 24 h, [89Zr]Zr-(oxinate)4 labelled cells had over 70% higher liver uptake for both hDSC and rMac compared to [89Zr]Zr-DFO-NCS labelled cells, whereas [89Zr]Zr-DFO-NCS labelled cells showed over 60% higher uptake in the lungs compared to [89Zr]Zr-(oxinate)4 labelled cells. This difference in both lung and liver uptake continued until day 7. Dosimetry calculations showed a higher effective dose (mSv/MBq) for [89Zr]Zr-DFO-NCS compared to [89Zr]Zr-(oxinate)4, for both cell types. Although the bone uptake was higher for [89Zr]Zr-(oxinate)4 labelled cells, the prolonged uptake in the lungs contributed to a significant crossfire to bone marrow resulting in a higher bone dose. Conclusion The [89Zr]Zr-DFO-NCS labelled cells suggest a prolonged accumulation in the lungs, while [89Zr]Zr-(oxinate)4 suggests quicker clearance of the lungs followed by accumulation in the liver. Accumulation of radiolabelled cells in the liver corresponds to other cell-tracking methods. Further studies are required to determine the actual location of the [89Zr]Zr-DFO-NCS labelled cell.

Background: Successful radioiodine treatment of differentiated thyroid canc er requires iodine avidity: that is, the concentration and retention of iodine in cancer tissue. Several parameters have previously been linked with lower iodine avidity. However, a comprehensive analysis of which factors best predict iodine avidity status, and the magnitude of their impact, is lacking. Methods: Quantitative measurements of iodine avidity in surgical specimens (primary tumour and lymph node metastases) of 28 patients were compared to immunohistochemical expression of the thyroid-stimulating hormone receptor, thyroid peroxidase (TPO), pendrin, sodium–iodide symporter (NIS) and mutational status of BRAF and the TERT promoter. Regression analysis was used to identify independent predictors of poor iodine avidity. Results: Mutations in BRAF and the TERT promoter were significantly associated with lower iodine avidity for lymph node metastases (18-fold and 10-fold, respectively). Membranous NIS localisation was found only in two cases but was significantly associated with high iodine avidity. TPO expression was signific antly correlated with iodine avidity (r = 0.44). The multivariable modelling showed that tumour tissue localisation (primary tumour or lymph node metastasis), histological subtype, TPO and NIS expression and TERT promoter mutation were each independent predictors of iodine avidity that could explain 68% of the observed variation of iodine avidity. Conclusions: A model based on histological subtype, TPO and NIS expression and TERT promoter mutation, all evaluated on initial surgical material, can predict iodine avidity in thyroid cancer tissue ahead of treatment. This could inform early adaptation with respect to expected treatment effect.

Abstract Purpose To evaluate if satisfactory post-therapeutic image-based dosimetry can be achieved for Lu-177-DOTATATE treatments using a reduced number of image acquisitions to improve patient comfort and reduce economical costs. Methods 39 patients who underwent 147 treatment cycles of Lu-177-DOTATATE for neuroendocrine tumors were included in the study. A total of 291 and 284 absorbed doses were calculated to kidneys and tumors, respectively. Single-point dosimetry was performed using one SPECT/CT image acquired at 1 d or 7 d post-treatment using a fixed effective half-life (T eff) or using a patient-specific T eff determined for the initial cycle. Also, dose-per-activity values, (D/A)1, were determined from the first cycle and used to calculate doses for subsequent cycles. All absorbed doses were evaluated against “true” doses calculated using both the 1 d and 7 d images. The relation between tumor grade and absorbed doses was also investigated. All dosimetry was performed on SPECT images. Results Absorbed doses to kidneys were most accurate when single-point dosimetry was performed using 1 d images with median ratios in relation to “true” doses in total dose of 1.00 (IQR: 0.97–1.03) when using fixed T eff and 1.01 (IQR: 0.98–1.04) when using T eff from the initial cycle. Calculations based on the 7 d image were most accurate for tumors with corresponding ratios in total absorbed dose of 0.98 (IQR: 0.96–1.00) and 1.00 (IQR: 0.99–1.01) when using a fixed T eff or T eff from the first cycle, respectively. The (D/A)1 approach performed worse, as 2 of 77 total absorbed doses to the kidneys deviated with > 30%, and tumor-absorbed doses were increasingly overestimated with every cycle. Absorbed doses, T eff and 1 d uptake were higher for G1 tumors than G2 tumors. Conclusion Dosimetry can be performed with satisfactory accuracy when using single SPECT/CT images acquired at 1 d for kidneys or at 7 d for tumors.

Abstract Background Hyperthyroidism has been treated with radioiodine therapy for eight decades, with known benefits and side-effects. No consensus exists on which activity dosage and pre-therapeutic measurements are required for optimal treatment, balancing risk of incomplete response, therapy-induced hypothyroidism and radiation exposure. A retrospective analysis was performed to assess these questions. Methods Data was collected on radioiodine treatment outcomes for 904 patients treated for Graves' disease or toxic nodular goitres at our institution during 2016–2020. The prescribed absorbed doses were 120 Gy (Graves’ disease), 200 Gy (toxic multinodular goitre) and 300 Gy (solitary toxic adenoma). Univariate analysis and multivariate regression modelling were used to find factors linked to treatment outcome. Results The cure rate of hyperthyroidism after one administration of radioiodine was 79% for Graves' disease, 94% for toxic multinodular goitre and 98% for solitary toxic adenoma. Thyroid mass, uptake and effective half-life were all significantly associated with cure in Graves’ disease, but not in toxic multinodular goitre. The rates of therapy-induced hypothyroidism were 20% and 29% for toxic multinodular goitre and solitary toxic adenoma. Neither the cure rate nor the hypothyroidism rate was found to be superior among patients with individualised effective half-life measurements in toxic nodular goitres. Poor renal function was associated with dubious iodine uptake measurements but was not found to correlate with worse outcome. Conclusions Multiple measurements of individual iodine uptake for kinetics estimation may be unnecessary, and a population-based value can be used instead. Patients with renal impairment had similar outcome as other patients, but with a higher risk of dubious uptake measurements.

In this work, multi-layer PECVD SiNx/SiNx and SiNx/SiOy passivations are developed featuring very high soft breakdown strength and tunable stress properties, which would allow for stress engineering and wafer bow minimization. AlGaN/GaN-on-Si wafers (150 mm) with very low initial bow (

Bladder exstrophy requires staged reconstruction to achieve control over bladder function. In case of failure, bladder neck closure with augmentation enterocystoplasty and appendicovesicostomy is a good surgical option. We report the case of a girl born with bladder exstrophy who, despite multiple surgical reconstructions in childhood, developed severe stress incontinence with contracted bladder and recurrent urinary tract infections during adolescence. The patient had a large abdominal pannus and in order to realize the appendicovesicostomy, we combined this intervention with a body contouring abdominoplasty to achieve tension free closure.

In this case report, we present the treatment outcomes of the first patient enrolled in the LuDO-N trial. The patient is a 21-month-old girl diagnosed with high-risk neuroblastoma (NB) and widespread skeletal metastasis. The patient initially underwent first-line therapy according to SIOPEN HRNBL-1 but was switched to second-line treatments due to disease progression, and she was finally screened for enrollment in the LuDO-N trial due to refractory disease. Upon enrollment, the patient received two rounds of the radiolabeled somatostatin analogue lutetium-177 octreotate (177Lu-DOTATATE), which was well tolerated. A dosimetry analysis revealed a heterogeneous uptake across tumor lesions, resulting in a significant absorbed dose of 54 Gy in the primary tumor, but only 2 Gy at one of the metastatic sites in the distal femur. While the initial treatment response showed disease stabilization, the distal femoral metastasis continued to progress, leading to the eventual death of the patient. A tissue analysis of the biopsies collected throughout the course of the disease revealed heterogeneous drug target expression of somatostatin receptor 2 (SSTR2) across and within tumor lesions. Furthermore, genomic profiling revealed a novel KIAA1549::BRAF fusion oncogene amplification in the distal femoral metastasis at recurrence that might be related with resistance to radiation, possibly through the downregulation of SSTR2. This case report demonstrates a mixed response to molecular radiotherapy (MRT) with 177Lu- DOTATATE. The observed variation in SSTR2 expression between tumor lesions suggests that heterogeneous target expression may have been the reason for treatment failure in this patient's case. Further investigation within the LuDO-N trial will give a more comprehensive understanding of the correlation between SSTR2 expression levels and treatment outcomes, which will be important to advance treatment strategies based on MRT for children with high-risk NB. [ABSTRACT FROM AUTHOR]

In this work, the dynamic behavior of gallium nitride on silicon high electron mobility transistors (GaN/Si HEMT) with carbon doped buffer is modeled using a finite state machine embedded into the core Advanced SPICE Model for High Electron Mobility Transistor (ASM-HEMT). The model is based on the physics of trapping and detrapping of electrons in carbon at nitrogen-site acceptor trap (denoted here as $\text{C}_{N}$ ) and does not require an equivalent Resistance-Capacitance circuit. The model is validated against three off-state stress drain voltages of 50 V, 100 V, and 150 V using only $\text{C}_{N}$ as trap species.

The widespread adoption of organic thin-film transistors (TFTs) in low-voltage high-frequency device applications is impeded by the contact resistance in the TFTs. Here, the authors report record-low contact resistance in bottom-gate, bottom-contact organic TFTs with an ultrathin gate dielectric.

This paper reports on the status of a comprehensive ten-year research and development effort toward hybrid system-in-foil (HySiF). In HySiF, the merits of high-performance integrated circuits on ultra-thin chips and of large-area and discrete electronic component implementation are combined in a complementary fashion in and on a flexible carrier substrate. HySiF paves the way to entirely new applications of electronic products where form factor, form adaptivity and form flexibility are key enablers. In this review paper the various aspects of thin-chip fabrication and embedding, device and circuit design under impact of unknown or variable mechanical stress, and the on- and off-chip implementation of sensor, actuator, microwave, and energy supply components are addressed.

Recently, a new approach to extension and climate information services, namely Participatory Integrated Climate Services for Agriculture (PICSA) has been developed. PICSA makes use of historical climate records, participatory decision-making tools and forecasts to help farmers identify and better plan livelihood options that are suited to local climate features and farmers’ own circumstances. This approach was implemented in 2016 in two sites in Senegal and Mali, with 57 and 47 farmers, respectively. At the end of the growing season, these farmers were surveyed to explore their perceptions on the use of the approach. In Senegal and Mali, respectively 97% and 76% of the respondents found the approach ‘very useful’. The approach enabled farmers to make strategic plans long before the season, based on their improved knowledge of local climate features. Moreover, evidence demonstrates that PICSA stimulated farmers to consider and then implement a range of innovations which included: (i) changes in timing of activities such as sowing dates, (ii) implementing soil and water management practices, (iii) selection of crop varieties, (iv) fertiliser management and (v) adaptation of plans for the season (farm size, etc.) to the actual resources available to them. The study also demonstrated the potential of farmer-to-farmer extension in scaling up the approach, which is of great interest especially in the current context of limited extension services in the West African region. Keywords: Climate change, Climate information services, Climate variability, Food security, Livelihood options, West Africa

Career building can be challenging for young surgeons, especially when topics such as lifestyle, work–life balance and subspecialization arise. Suggestions and advice from senior colleagues is very valuable but many young surgeons do not have such opportunities or are limited to a few senior surgeons. The International Microsurgery Club (IMC), in collaboration with the World Society of Reconstructive Microsurgery, organized a combined webinar for this topic and invited world renowned microsurgery masters polled by the IMC members to join, including Prof. Peter Neligan (Emeritus from University of Washington, United States), Prof. Raja Sabapathy (Ganga Hospital, India), Dr. Gregory Buncke (The Buncke Clinic, United States), Prof. Isao Koshima (Hiroshima University Hospital, Japan), Prof. David Chwei-Chin Chuang (Chang Gung Memorial Hospital, Taiwan), and Prof. Eric Santamaria (Hospital General Dr. Manuel Gea Gonzalez, Mexico) on May 1, 2022. Prof. Joon-Pio Hong (Asan Medical Center, South Korea) and Prof. Fu-Chan Wei (Chang Gung Memorial Hospital, Taiwan) were also selected but unfortunately could not make it and were therefore invited to another event in April 2023, summarized in a recently published paper. There is ample literature reporting on different aspects of developing a microsurgical career but the goal of this session was to offer an opportunity for direct exchange with experienced mentors. Moreover, insights from experienced microsurgeons from different part of the world were more likely to offer different perspectives on aspects such as career building, failure management, and team culture. This webinar event was moderated by Dr. Jung-Ju Huang (Taiwan), Dr. Susana Heredero (Spain), and Dr. Wei F. Chen (United States). [ABSTRACT FROM AUTHOR]