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Tem tomado seus cuidados com a pele? Neste artigo vamos ensinar a fazer limpeza de pele caseira. Conhecer  os benefícios para limpeza de pele. Conheça o passo a passo a…

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Guillermo E. Umpierrez
Jan 1, 2002; 15:
Articles

(Kudos Innovations Ltd) Kudos helps researchers maximize reach and visibility of research by opening up Kudos Pro. The platform helps showcase work to a range of target audiences, supporting researchers in fields where conferences have been cancelled -- and those with COVID-19-relevant work that needs rapid communication. Over 2,000 researchers have already signed up.

(Oregon State University) Clinical trial data behind drug dose recommendations for elevated cholesterol and chronic obstructive pulmonary disease illustrate how larger doses may not be worth the extra costs for many types of patients.

Guillermo E. Umpierrez
Jan 1, 2002; 15:
Articles

¹⁸F-PI-2620 is a next generation tau positron emission tomography (PET)-tracer that has demonstrated ability to image the spatial distribution of suspected tau pathology. The objective of this study was to assess the tracer biodistribution, dosimetry and quantitative methods of ¹⁸F-PI-2620 in the human brain. Full kinetic modelling approaches to quantify tau load were investigated. Non-invasive kinetic modeling approaches and semi-quantitative methods were evaluated against the full tracer kinetics. Finally, the reproducibility of PET measurements from test and retest scans was assessed. Methods: Three healthy controls (HC) and 4 Alzheimer disease (AD) subjects underwent two dynamic PET scans including arterial sampling. Distribution volume ratio (DVR) was estimated using full tracer kinetics (2 Tissue Compartment (2TC) models, Logan Graphical Analysis (LGA)) and non-invasive kinetic models (Non-Invasive Logan Graphical Analysis (NI-LGA) and the multilinear reference tissue model (MRTM2)). Standardized uptake value ratio (SUVR) was determined at different imaging windows after injection. Correlation between DVR and SUVR, effect size (Cohen’s d) and test-retest variability (TRV) were evaluated. Additionally, 6 HC subjects received one tracer administration and underwent whole-body PET for dosimetry calculation. Organ doses and the whole-body effective dose were calculated using OLINDA 2.0. Results: Strong correlation was found across different kinetic models (R2 >0.97) and between DVR(2TC) and SUVRs between 30 to 90 min with R2>0.95. Secular equilibrium was reached around 40 min post injection (p.i.) in most regions and subjects. The TRV and effect size for the SUVR across different regions was similar at 30-60 min (TRV=3.8%, d=3.80), 45-75 min (TRV=4.3%, d=3.77) and 60-90 min (TRV=4.9%, d=3.73) and increased at later time points. Elimination was via the hepatobiliary and urinary system. The whole-body effective dose was determined to be 33.3±2.1 μSv/MBq for an adult female and 33.1±1.4 μSv/MBq for an adult male with a 1.5 hour urinary bladder voiding interval. Conclusion: ¹⁸F-PI-2620 exhibits fast kinetics, suitable dosimetry and low TRV. DVR measured using the 2TC model with arterial sampling correlated strongly with DVR measured by NI-LGA, MRTM2 and SUVR. SUVR can be used for ¹⁸F-PI-2620 PET quantification of tau deposits avoiding arterial blood sampling. Static ¹⁸F-PI-2620 PET scans between 45-75min p.i. provide excellent quantification accuracy, large effect size and low TRV.

Calculation of radiation dosimetry in targeted nuclear medicine therapies is traditionally resource-intensive requiring multiple post-therapy SPECT acquisitions. An alternative approach is to take advantage of existing pharmacokinetic data from these smaller cohorts to enable dose computation from a single post-treatment scan in a manner that may be applied to a much broader patient population. Methods: In this work, a technical description for simplified dose estimation is presented and applied to assessment of ¹⁷⁷Lu-PSMA-617 therapy (Prostate-Specific Membrane Antigen) for metastatic prostate cancer. By normalizing existing time-activity curves to a single measurement time, it is possible to calculate a mean and range of time-integrated activity values which relate to radiation absorbed dose. To assist with accurate pharmacokinetic modelling of the training cohort, a method for contour-guided image registration was developed. Results: Tissue-specific dose conversion factors for common post-treatment imaging times are reported along with a characterization of added uncertainty in comparison to a traditional serial imaging protocol. Single time point dose factors for tumor were determined to be 11.0, 12.1, 13.6, and 15.2 Gy per MBq/mL at image times of 24, 48, 72, and 96 hours, respectively. For normal tissues, parotid gland factors were 6.7, 9.4, 13.3, and 19.3 Gy per MBq/mL and kidneys were 7.1, 10.3, 15.0, and 22.0 Gy per MBq/mL at those times. Tumor dose estimates were most accurate using delayed scanning at times beyond 72 hours. Dose to healthy tissues is best characterized by scanning patients in the first two days of treatment owing to the larger degree of tracer clearance in this early phase. Conclusion: The work demonstrates a means for efficient dose estimation in ¹⁷⁷Lu-PSMA-617 therapy. By providing methods to simplify and potentially automate radiation dosimetry we hope to accelerate the understanding of radiobiology and development of dose-response models in this unique therapeutic context.

P-glycoprotein (ABCB1) plays an important role at the blood-brain barrier (BBB) in promoting the clearance of neurotoxic beta-amyloid (Aß) peptides from the brain into the blood. ABCB1 expression and activity were found to be decreased in the brains of Alzheimer disease (AD) patients. Treatment with drugs which induce cerebral ABCB1 activity may be a promising approach to delay the build-up of Aß deposits in the brain by enhancing the clearance of Aß peptides from the brain. The aim of this study was to investigate whether PET with the weak ABCB1 substrate radiotracer ¹¹C-metoclopramide can measure ABCB1 induction at the BBB in a beta-amyloidosis mouse model (APP/PS1-21 mice) and in wild-type mice. Methods: Groups of wild-type and APP/PS1-21 mice aged 50 or 170 days underwent ¹¹C-metoclopramide baseline PET scans or scans after intraperitoneal treatment with the rodent pregnane X receptor (PXR) activator 5-pregnen-3β-ol-20-one-16α-carbonitrile (PCN, 25 mg/kg) or its vehicle over 7 days. At the end of the PET scans, brains were harvested for immunohistochemical analysis of ABCB1 and Aß levels. In separate groups of mice, radiolabeled metabolites of ¹¹C-metoclopramide were determined in plasma and brain at 15 min after radiotracer injection. As an outcome parameter of cerebral ABCB1 activity, the elimination slope of radioactivity washout from the brain (kE,brain) was calculated. Results: PCN treatment resulted in an increased clearance of radioactivity from the brain as reflected by significant increases in kE,brain (from +26% to +54% relative to baseline). Immunohistochemical analysis confirmed ABCB1 induction in the brains of PCN-treated APP/PS1-21 mice with a concomitant decrease in Aß levels. There was a significant positive correlation between kE,brain values and ABCB1 levels in the brain. In wild-type mice, a significant age-related decrease in kE,brain values was found. Metabolite analysis showed that the majority of radioactivity in the brain was composed of unmetabolized ¹¹C-metoclopramide in all animal groups. Conclusion: ¹¹C-metoclopramide can measure ABCB1 induction in the mouse brain without the need to consider an arterial input function and may find potential application in AD patients to non-invasively evaluate strategies to enhance the clearance properties of the BBB.

Background: Targeting cancer-associated fibroblasts (CAFs) has become an attractive goal for diagnostic imaging and therapy as they can constitute as much as 90% of tumor mass. The serine protease fibroblast activation protein (FAP) is overexpressed selectively in CAFs, drawing interest in FAP as a stromal target. The quinoline-based FAP-inhibitor PET tracer, ⁶⁸Ga-FAPI-04, has been previously shown to yield high tumor-to-background ratios (TBR) in patients with various cancers. Recent developments towards an improved compound for therapeutic application have identified FAPI-46 as a promising agent due to a longer tumor retention time in comparison with FAPI-04. Here we present a PET biodistribution and radiation dosimetry study of ⁶⁸Ga-FAPI-46 in cancer patients. Methods: Six patients with different cancers underwent serial ⁶⁸Ga-FAPI-46 PET/CT scans at three time points following radiotracer injection: 10 minutes, 1 hour, and 3 hours. The source organs consisted of the kidneys, bladder, liver, heart, spleen, bone marrow, uterus, and body remainder. OLINDA/EXM v.1.1 software was used to fit and integrate the kinetic organ activity data to yield total body and organ time-integrated activity coefficients/residence times and finally organ absorbed doses. Standardized uptake values (SUV) and TBR were generated from the contoured tumor and source organ volumes. Spherical volumes in muscle and blood pool were also obtained for TBR (Tumor SUV_max / Organ SUVmean). Results: At all timepoints, the highest organ SUV_max was observed in the liver. Tumor and organ mean SUVs decreased whereas TBRs in all organs but the uterus increased with time. The highest TBRs at 3 hours were observed with the bone marrow (31.1), muscle (22.8), heart (19.1), and spleen (19.0). Organs with the highest effective doses were the bladder wall (2.41E-03 mSv/MBq), followed by ovaries (1.15E-03 mSv/MBq) and red marrow (8.49E-04mSv/MBq). The average effective total body dose was 7.80E-03 mSv/MBq. Thus for administration of 200 MBq ⁶⁸Ga-FAPI-46 the effective total body dose is 1.56 mSv ± 0.26 mSv, in addition to approximately 3.7 mSv from one low-dose CT scan done for attenuation correction. Conclusion: ⁶⁸Ga-FAPI-46 PET/CT has a favorable dosimetry profile with an estimated whole body dose of 5.3 mSv for an administration of 200 MBq (5.4 mCi) of ⁶⁸Ga-FAPI-46 (1.56± 0.26 mSv from the PET tracer and 3.7 mSv from one low-dose CT scan). The biodistribution study showed high TBRs increasing over time, suggesting high diagnostic performance and favorable tracer kinetics for potential therapeutic applications.

Due to improvements in quantitative SPECT/CT, voxel-based dosimetry for radionuclide therapies has aroused growing interest as it promises the visualization of absorbed doses at a voxel level. In this work, SPECT/CT-based voxel-based dosimetry of a 3D printed 2-compartment kidney phantom was performed, and the resulting absorbed dose distributions were examined. Additionally, the potential of the PETPVC partial-volume correction tool was investigated. Methods: Both kidney compartments (70% cortex, 30% medulla) were filled with different activity concentrations and SPECT/CT imaging was performed. The images were reconstructed using varying reconstruction settings (iterations, subsets, and post-filtering). Based on these activity concentration maps, absorbed dose distributions were calculated with pre-calculated ¹⁷⁷Lu voxel S values and an empirical kidney half-life. An additional set of absorbed doses was calculated after applying PETPVC for partial-volume correction of the SPECT reconstructions. Results: SPECT/CT imaging blurs the two discrete sub-organ absorbed dose values into a continuous distribution. While this effect is slightly improved by applying more iterations, it is enhanced by additional post-filtering. By applying PETPVC, the absorbed dose values are separated into 2 peaks. Although this leads to a better agreement between SPECT/CT-based and nominal values, considerable discrepancies remain. In contrast to the calculated nominal absorbed doses of 7.8/1.6 Gy (cortex/medulla), SPECT/CT-based voxel-level dosimetry resulted in mean absorbed doses ranging from 3.0-6.6 Gy (cortex) and 2.7-5.1 Gy (medulla). PETPVC led to improved ranges of 6.1-8.9 Gy (cortex) and 2.1-5.4 Gy (medulla). Conclusion: Our study shows that ¹⁷⁷Lu quantitative SPECT/CT imaging leads to voxel-based dose distributions largely differing from the real organ distribution. SPECT/CT imaging and reconstruction deficiencies might directly translate into unrealistic absorbed dose distributions, thus questioning the reliability of SPECT-based voxel-level dosimetry. Therefore, SPECT/CT reconstructions should be adapted to ensure an accurate quantification of the underlying activity and, therefore, absorbed dose in a volume-of-interest of the expected object size (e.g. organs, organ sub-structures, lesions or voxels). As an example, PETPVC largely improves the match between SPECT/CT-based and nominal dose distributions. In conclusion, the concept of voxel-based dosimetry should be treated with caution. Specifically, it should be kept in mind that the absorbed dose distribution is mainly a convolved version of the underlying SPECT reconstruction.

Purpose: To assess the performance of full dose (FD) positron emission tomography (PET) image synthesis in both image and projection space from low-dose (LD) PET images/sinograms without sacrificing diagnostic quality using deep learning techniques. Methods: Clinical brain PET/CT studies of 140 patients were retrospectively employed for LD to FD PET conversion. 5% of the events were randomly selected from the FD list-mode PET data to simulate a realistic LD acquisition. A modified 3D U-Net model was implemented to predict FD sinograms in the projection-space (PSS) and FD images in image-space (PIS) from their corresponding LD sinograms/images, respectively. The quality of the predicted PET images was assessed by two nuclear medicine specialists using a five-point grading scheme. Quantitative analysis using established metrics including the peak signal-to-noise ratio (PSNR), structural similarity index metric (SSIM), region-wise standardized uptake value (SUV) bias, as well as first-, second- and high-order texture radiomic features in 83 brain regions for the test and evaluation dataset was also performed. Results: All PSS images were scored 4 or higher (good to excellent) by the nuclear medicine specialists. PSNR and SSIM values of 0.96 ± 0.03, 0.97 ± 0.02 and 31.70 ± 0.75, 37.30 ± 0.71 were obtained for PIS and PSS, respectively. The average SUV bias calculated over all brain regions was 0.24 ± 0.96% and 1.05 ± 1.44% for PSS and PIS, respectively. The Bland-Altman plots reported the lowest SUV bias (0.02) and variance (95% CI: -0.92, +0.84) for PSS compared with the reference FD images. The relative error of the homogeneity radiomic feature belonging to the Grey Level Co-occurrence Matrix category was -1.07 ± 1.77 and 0.28 ± 1.4 for PIS and PSS, respectively Conclusion: The qualitative assessment and quantitative analysis demonstrated that the FD PET prediction in projection space led to superior performance, resulting in higher image quality and lower SUV bias and variance compared to FD PET prediction in the image domain.

Acidosis is a key driver for many diseases, including cancer, sepsis, and stroke. The spatiotemporal dynamics of dysregulated pH across disease remains elusive and current diagnostic strategies do not provide localization of pH alterations. We sought to explore if PET imaging using hydrophobic cyclic peptides that partition into the cellular membrane at low extracellular pH (denoted as "pHLIC") can permit accurate in vivo visualization of acidosis. Methods: Acid-sensitive cyclic peptide c[E4W5C] pHLIC was conjugated to bifunctional maleimide-NO2A and radiolabeled with copper-64 (t1/2 = 12.7 h). C57BL/6J mice were administered LPS (15 mg/kg) or saline (vehicle) and serially imaged with [⁶⁴Cu]Cu-c[E4W5C] over 24 h. Ex vivo autoradiography was performed on resected brain slices and subsequently stained with cresyl violet to enable high-resolution spatial analysis of tracer accumulation. A non- pH-sensitive cell-penetrating control peptide (c[R4W5C]) was used to confirm specificity of [⁶⁴Cu]Cu-c[E4W5C]. CD11b (macrophage/microglia) and TMEM119 (microglia) immunostaining was performed to correlate extent of neuroinflammation with [⁶⁴Cu]Cu-c[E4W5C] PET signal. Results: [⁶⁴Cu]Cu-c[E4W5C] radiochemical yield and purity was >95% and >99% respectively, with molar activity >0.925 MBq/nmol. Significantly increased [⁶⁴Cu]Cu-c[E4W5C] uptake was observed in LPS-treated mice (vs. vehicle) within peripheral tissues including blood, lungs, liver, and small intestines (P < 0.001-0.05). Additionally, there was significantly increased [⁶⁴Cu]Cu-c[E4W5C] uptake in the brains of LPS-treated animals. Autoradiography confirmed increased uptake in the cerebellum, cortex, hippocampus, striatum, and hypothalamus of LPS-treated mice (vs. vehicle). Immunohistochemical (IHC) analysis revealed microglial/macrophage infiltrate, suggesting activation in brain regions containing increased tracer uptake. [⁶⁴Cu]Cu-c[R4W5C] demonstrated significantly reduced uptake in the brain and periphery of LPS mice compared to the acid-mediated [⁶⁴Cu]Cu-c[E4W5C] tracer. Conclusion: Here, we demonstrate that a pH-sensitive PET tracer specifically detects acidosis in regions associated with sepsis-driven pro-inflammatory responses. This study suggests that [⁶⁴Cu]Cu-pHLIC is a valuable tool to noninvasively assess acidosis associated with both central and peripheral innate immune activation.

We reviewed ¹¹¹In-DOTA-anti-CD45 antibody (BC8) imaging and bone marrow biopsy measurements to ascertain biodistribution and biokinetics of the radiolabeled antibody and to investigate differences based on type of hematologic malignancy. Methods: Serial whole-body scintigraphic images (4 time-points) were obtained after infusion of the ¹¹¹In-DOTA-BC8 (176-406 MBq) in 52 adult patients with hematologic malignancies (lymphoma, multiple myeloma, acute myeloid leukemia and myelodysplastic syndrome). Counts were obtained for the regions of interest for spleen, liver, kidneys, testicles (in males), and two marrow sites (acetabulum and sacrum) and correction for attenuation and background was made. Bone marrow biopsies were obtained 14-24 hours post-infusion and percent of administered activity was determined. Radiation absorbed doses were calculated. Results: Initial uptake in liver averaged 32% ± 8.4% (S.D.) of administered activity (52 patients), which cleared monoexponentially with biological half-time of 293 ± 157 hours (33 patients) or did not clear (19 patients). Initial uptake in spleen averaged 22% ± 12% and cleared with a biological half-time 271 ± 185 hours (36 patients) or longer (6 patients). Initial uptake in kidney averaged 2.4% ± 2.0% and cleared with a biological half-time of 243 ± 144 hours (27 patients) or longer (9 patients). Initial uptake in red marrow averaged 23% ± 11% and cleared with half-times of 215 ± 107 hours (43 patients) or longer (5 patients). Whole-body retention half-times averaged 198 ± 75 hours. Splenic uptake was higher in the AML/MDS group when compared to the lymphoma group (p ≤ 0.05) and to the multiple myeloma group (p ≤ 0.10). Liver represented the dose-limiting organ. For liver uptake, no significant differences were observed between the three malignancy groups. Average calculated radiation absorbed doses per unit administered activity for a therapy infusions of ⁹⁰Y-DOTA-BC8 were for red marrow: 470 ± 260 cGy/MBq, liver 1100 ± 330 cGy/MBq, spleen 4120 ± 1950 cGy/MBq, total body 7520 ± 20 cGy/MBq, osteogenic cells 290 ± 200 cGy/MBq, and kidneys 240 ± 200 cGy/MBqR. Conclusion: ¹¹¹In-DOTA-BC8 had long retention time in liver, spleen, kidneys, and red marrow, and the highest absorbed doses were calculated for spleen and liver. Few differences were observed by malignancy type. The exception was greater splenic uptake among leukemia/MDS group when compared to lymphoma and multiple myeloma groups.

Background: Radiopharmaceutical dosimetry depends on the localization in space and time of radioactive sources and requires the estimation of the amount of energy emitted by the sources deposited within targets. In particular, when computing resources are not accessible, this task can be carried out using precomputed tables of Specific Absorbed Fractions (SAFs) or S values based on dosimetric models. The OpenDose collaboration aims to generate and make freely available a range of dosimetric data and tools. Methods: OpenDose brings together resources and expertise from 18 international teams to produce and compare traceable dosimetric data using 6 of the most popular Monte Carlo codes in radiation transport (EGSnrc/EGS++, FLUKA, GATE, Geant4, MCNP/MCNPX and PENELOPE). SAFs are uploaded, together with their associated statistical uncertainties, in a relational database. S values are then calculated from mono-energetic SAFs, based on the radioisotope decay data presented in the International Commission on Radiological Protection (ICRP) publication 107. Results: The OpenDose collaboration produced SAFs for all source regions and targets combinations of the two ICRP 110 adult reference models. SAFs computed from the different Monte Carlo codes were in good agreement at all energies, with standard deviations below individual statistical uncertainties. Calculated S values were in good agreement with OLINDA 2 (commercial) and IDAC 2.1 (free) software. A dedicated website (www.opendose.org) has been developed to provide easy and open access to all data. Conclusion: The OpenDose website allows the display and download of SAFs and the corresponding S values for 1252 radionuclides. The OpenDose collaboration, open to new research teams, will extend data production to other dosimetric models and implement new free features, such as online dosimetric tools and patient-specific absorbed dose calculation software, together with educational resources.

Rationale: Fluorescence molecular endoscopy (FME) is an emerging technique that has the potential to improve the 22% colorectal polyp detection miss-rate. We determined the optimal dose-to-imaging interval and safety of FME using EMI-137, a c-Met targeted fluorescent peptide, in a population at high-risk for colorectal cancer. Methods: We performed in vivo FME and quantification of fluorescence by multi-diameter single-fiber reflectance, single-fiber fluorescence spectroscopy in 15 patients with a dysplastic colorectal adenoma. EMI-137 was intravenously administered (0.13mg/kg) at a one-, two- or three-hour dose-to-imaging interval (N = 3 patients per cohort). Two cohorts were expanded to six patients based on target-to-background ratios (TBR). Fluorescence was correlated to histopathology and c-Met expression. EMI-137 binding specificity was assessed by fluorescence microscopy and in vitro experiments. Results: FME using EMI-137 appeared to be safe and well tolerated. All dose-to-imaging intervals showed significantly increased fluorescence in the colorectal lesions compared to surrounding tissue, with a TBR of 1.53, 1.66 and 1.74 respectively (mean intrinsic fluorescence (Q·μ^f_a,x) = 0.035 vs. 0.023mm^-1, P<0.0003; 0.034 vs. 0.021mm^-1, P<0.0001; 0.033 vs. 0.019mm^-1, P<0.0001). Fluorescence correlated to histopathology on a macroscopic and microscopic level, with significant c-Met overexpression in dysplastic mucosa. In vitro, a dose-dependent specific binding was confirmed. Conclusion: FME using EMI-137 appeared to be safe and feasible within a one-to-three hour dose-to-imaging interval. No clinically significant differences were observed between the cohorts, although a one-hour dose-to-imaging interval was preferred from a clinical perspective. Future studies will investigate EMI-137 for improved colorectal polyp detection during screening colonoscopies.

The purpose of this study was to establish the dose-response relationship of selective internal radiation therapy (SIRT) in patients with metastatic colorectal cancer (mCRC), when informed by radiobiological sensitivity parameters derived from mCRC cell lines exposed to yttrium-90 (⁹⁰Y). Methods: 23 mCRC patients with liver metastases refractory to chemotherapy were included. ⁹⁰Y bremsstrahlung SPECT images were transformed into dose maps assuming the local dose deposition method. Baseline and follow-up CT scans were segmented to derive liver and tumor volumes. Mean, median, and D₇₀ (minimum dose to 70% of tumor volume) values determined from dose maps were correlated with change in tumor volume and vRECIST response using linear and logistic regression, respectively. Radiosensitivity parameters determined by clonogenic assays of mCRC cell lines HT-29 and DLD-1 after exposure to ⁹⁰Y or external beam radiotherapy (EBRT; 6MV photons) were used in biological effective dose (BED) calculations. Results: Mean administered radioactivity was 1469±428 MBq (847-2185 MBq), achieving a mean radiation absorbed tumor dose of 35.5±9.4 Gy and mean normal liver dose of 26.4±6.8 Gy. A 1.0 Gy increase in mean, median, and D₇₀ absorbed dose was associated with reduction in tumor volume of 1.8%, 1.8%, and 1.5%, respectively, and increased probability of vRECIST response (odds ratio: 1.09, 1.09, and 1.10 respectively). Threshold mean, median and D₇₀ doses for response were 48.3, 48.8, and 41.8 Gy respectively. EBRT-equivalent BEDs for ⁹⁰Y are up to 50% smaller than those calculated by applying protraction-corrected radiobiological parameters derived from EBRT alone. Conclusion: Dosimetric studies have assumed equivalence between ⁹⁰Y SIRT and EBRT, leading to inflation of BED for SIRT and possible under-treatment. Radiobiological parameters for ⁹⁰Y were applied to a BED model, providing a calculation method that has the potential to improve assessment of tumor control.

Purpose: This study is designed to assess the safety and therapeutic response to ¹⁷⁷Lu-EB-PSMA treatment with escalating doses in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: With institutional review board approval and informed consent, patients were randomly divided into three groups: Group A (n = 10) were treated with 1.18 ± 0.09 GBq/dose of ¹⁷⁷Lu-EB-PSMA. Group B (n = 10) were treated with 2.12 ± 0.19 GBq/dose of ¹⁷⁷Lu-EB-PSMA. Group C (n = 8) were treated with 3.52 ± 0.58 GBq/dose of ¹⁷⁷Lu-EB-PSMA. Eligible patients received up to three cycles of ¹⁷⁷Lu-EB-PSMA therapy, at eight-week intervals. Results: Due to disease progression or bone marrow suppression, 4 out of 10, 5 out of 10, and 5 out of 10 patients completed three cycles therapy as planned in Groups A, B, and C, respectively. The prostate-specific antigen (PSA) response was correlated with treatment dose, with PSA disease control rates in Group B (70%) and C (75%) being higher than that in Group A (10%) (P = 0.007), but no correlation between Group B and Group C was found. ⁶⁸Ga-PSMA PET/CT showed response in all the treatment groups, however, there was no significant difference between the three groups. Hematologic toxicity study found that platelets in Group B and Group C decreased more than those in Group A, and that Grade 4 thrombocytopenia occurred in 2 (25.0%) patients in Group C. No serious nephritic or hepatic side effects were observed. Conclusion: This study demonstrates that 2.12 GBq/dose of ¹⁷⁷Lu-EB-PSMA seems to be safe and adequate in tumor treatment. Further investigations with increased number of patients are warranted.

This week our host Scott Carey catches up with Sean Bradley and Dominic Preston fresh off the back of the International Consumer Electronics Show (CES) in Las Vegas.

Dom explains why he was surprised, both in a good and bad way, by the latest foldable screen technology and Sean talks about what is going on in the gaming laptop space, as Alienware looks to soften its image.

Then Dom talks about a piece of connected wood and the gang break down the big controversy from the show floor regarding a certain innovative dildo.

We are also announcing the sad news that the UK Tech Weekly Podcast will be going on an indefinite hiatus while we reassess our podcasting output. We would like to thank anyone that has taken the time to listen to us for these one hundred and twelve (112!) episodes and rest assured we will be back in some guise soon.

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Islet transplantation is an emerging therapy for type 1 diabetes (T1D) and hypoglycaemic unawareness. However, a key challenge for islet transplantation is cellular rejection and the requirement for long-term immunosuppression. In this study we established a diabetic-humanized NOD-scidIL2R^null(NSG) mouse model of T cell mediated human islet-allograft rejection and developed a therapeutic regimen of low-dose recombinant human interleukin2(IL-2) combined with low-dose rapamycin to prolong graft survival. NSG-mice that had received renal-subcapsular human islet-allografts and were transfused with 1x10⁷ of human-spleen-mononuclear-cells (hSPMCs), reconstituted human CD45⁺ cells that were predominantly CD3⁺ T cells and rejected their grafts with a median survival time of 27 days. IL-2 alone (0.3x10⁶ IU/m² or 1x10⁶ IU/m²), or rapamycin alone (0.5-1mg/kg) for 3 weeks did not prolong survival. However, the combination of rapamycin with IL-2 for 3 weeks significantly prolonged human islet-allograft survival. Graft survival was associated with expansion of CD4⁺CD25⁺FOXP3⁺ Tregs and enhanced TGF-β production by CD4⁺ T cells. CD8⁺ T cells showed reduced IFN- production and reduced expression of perforin-1. The combination of IL-2 and rapamycin has the potential to inhibit human islet-allograft rejection by expanding CD4⁺FOXP3⁺ Tregs in vivo and supressing effector cell function, and could be the basis of effective tolerance-based regimens.

Ray Moynihan is a senior research assistant at Bond University, a journalist, champion of rolling back too much medicine, and host of a new series “The Recommended Dose” from Cochrane Australia. In the series, Ray has talked to some of the people who shape the medical evidence that underpin healthcare around the world - the series aim is to...

PORT OF SPAIN, Trinidad, CMC – Thirty three Trinidad and Tobago nationals who have been stranded in Barbados since March 23 are scheduled to return home on Tuesday. It’s reported that early Tuesday, National Security Minister...

Barbados Prime Minister Mia Mottley has announced a phased reopening of government and business operations, ending a mandatory 24-hour lockdown imposed on April 3 amid the global coronavirus pandemic. The phased reopening will begin on...

THE EDITOR, Madam: As the COVID-19 pandemic sweeps through across the world, causing stress, and pain for everyone; I would like to commend Andrew Holness, prime minister of Jamaica; Dr Christopher Tufton, minister of health and wellness; and Dr...

Intravenous access is difficult in some patients referred for ¹⁸F-FDG PET imaging. Extravasation at the injection site and accumulation in central catheters can lead to limited tumor ¹⁸F-FDG uptake, erroneous quantitation, and significant image artifacts. In this study, we compared the human biodistribution and dosimetry for ¹⁸F-FDG after oral and intravenous administrations sequentially in the same subjects to ascertain the dosimetry and potential suitability of orally administered ¹⁸F-FDG as an alternative to intravenous administration. We also compared our detailed intravenous ¹⁸F-FDG dosimetry with older dosimetry data. Methods: Nine healthy volunteers (6 male and 3 female; aged 19–32 y) underwent PET/CT imaging after oral and intravenous administration of ¹⁸F-FDG. Identical preparation and imaging protocols (except administration route) were used for oral and intravenous studies. During each imaging session, 9 whole-body PET scans were obtained at 5, 10, 20, 30, 40, 50, 60, 120, and 240 min after ¹⁸F-FDG administration (370 ± 16 MBq). Source organ contours drawn using CT were overlaid onto registered PET images to extract time–activity curves. Time-integrated activity coefficients derived from time–activity curves were given as input to OLINDA/EXM for dose calculations. Results: Blood uptake after orally administered ¹⁸F-FDG peaked at 45–50 min after ingestion. The oral-to-intravenous ratios of ¹⁸F-FDG uptake for major organs at 45 min were 1.07 ± 0.24 for blood, 0.94 ± 0.39 for heart wall, 0.47 ± 0.12 for brain, 1.25 ± 0.18 for liver, and 0.84 ± 0.24 for kidneys. The highest organ-absorbed doses (μGy/MBq) after oral ¹⁸F-FDG administration were observed for urinary bladder (75.9 ± 17.2), stomach (48.4 ± 14.3), and brain (29.4 ± 5.1), and the effective dose was significantly higher (20%) than after intravenous administration (P = 0.002). Conclusion: ¹⁸F-FDG has excellent bioavailability after oral administration, but peak organ activities occur later than after intravenous injection. These data suggest PET at 2 h after oral ¹⁸F-FDG administration should yield images that are comparable in biodistribution to conventional clinical images acquired 1 h after injection. Oral ¹⁸F-FDG is a palatable alternative to intravenous ¹⁸F-FDG when venous access is problematic.

¹⁶⁶Ho-microspheres have recently been approved for clinical use for hepatic radioembolization in the European Union. The aim of this study was to investigate the absorbed dose–response relationship and its association with overall survival for ¹⁶⁶Ho radioembolization in patients with liver metastases. Methods: Patients treated in the HEPAR I and II studies who underwent an ¹⁸F-FDG PET/CT scan at baseline, a posttreatment ¹⁶⁶Ho SPECT/CT scan, and another ¹⁸F-FDG PET/CT scan at the 3-mo follow-up were included for analysis. The posttreatment ¹⁶⁶Ho-microsphere activity distributions were estimated with quantitative SPECT/CT reconstructions using a quantitative Monte Carlo–based method. The response of each tumor was based on the change in total lesion glycolysis (TLG) between baseline and follow-up and was placed into 1 of 4 categories, according to the PERCIST criteria, ranging from complete response to progressive disease. Patient-level response was grouped according to the average change in TLG per patient. The absorbed dose–response relationship was assessed using a linear mixed model to account for correlation of tumors within patients. Median overall survival was compared between patients with and without a metabolic liver response, using a log-rank test. Results: Thirty-six patients with a total of 98 tumors were included. The relation between tumor-absorbed dose and both tumor-level and patient-level response was explored. At a tumor level, a significant difference in geometric mean absorbed dose was found between complete response (232 Gy; 95% confidence interval [CI], 178–303 Gy; n = 32) and stable disease (147 Gy; 95% CI, 113–191 Gy; n = 28) (P = 0.01) and between complete response and progressive disease (117 Gy; 95% CI, 87–159 Gy; n = 21) (P = 0.0008). This constitutes a robust absorbed dose–response relationship. At a patient level, a significant difference was found between patients with complete or partial response (210 Gy; 95% CI, 161–274 Gy; n = 13) and patients with progressive disease (116 Gy; 95% CI, 81–165 Gy; n = 9) (P = 0.01). Patients were subsequently grouped according to their average change in TLG. Patients with an objective response (complete or partial) exhibited a significantly higher overall survival than nonresponding patients (stable or progressive disease) (median, 19 mo vs. 7.5 mo; log-rank, P = 0.01). Conclusion: These results confirm a significant absorbed dose–response relationship in ¹⁶⁶Ho radioembolization. Treatment response is associated with a higher overall survival.

La migración centroamericana a los Estados Unidos comenzó en gran números en los años ochenta, impulsada por la inestabilidad política, los desastres naturales y las dificultades económicas. Aproximadamente 3,4 millones de centroamericanos vivieron en los Estados Unidos en 2015, principalmente de El Salvador, Guatemala y Honduras. Dónde viven en los Estados Unidos, su competencia en inglés, su estado legal, las vías de inmigración, y más, están cubiertos en este artículo.

Una llamada en español que analiza las dinámicas cambiantes y las cuestiones políticas relacionadas con la migración a través de México a los Estados Unidos.

Durante este seminario, ponentes presentaron hallazgos de un reciente informe que utiliza datos de agencias gubernamentales mexicanas, entrevistas con funcionarios clave y relatos de la sociedad civil para examinar el marco legal para la protección de menores no acompañados y su aplicación, al igual que las brechas entre este marco y su aplicación durante los procesos de detención, interrogación y alojamiento. El presidente de MPI, Andrew Selee, también expuso cómo el cambio en la dinámica política en Estados Unidos puede afectar las cuestiones migratorias con México, así como los efectos en la relación bilateral en medio de tensiones sobre el muro fronterizo, la renegociación del acuerdo del TLCAN y una cifra significativa de repatriaciones de migrantes mexicanos.

OBJECTIVE

To assess the impact of a telemedicine visit using the platform Diabetic compared with a face-to-face visit on clinical outcomes, patients’ health-related quality of life (HRQoL), and physicians’ satisfaction in patients with type 1 diabetes.

OBJECTIVE

To evaluate and compare the efficacy of long-term use of low-dose aspirin for the prevention of dementia in men and women.

Brian J. Welch
Oct 1, 2004; 22:198-200
Case Studies

OBJECTIVE

Many patients with hyperglycemic crises present with combined features of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). The implications of concomitant acidosis and hyperosmolality are not well known. We investigated hospital outcomes in patients with isolated or combined hyperglycemic crises.

Si bien se ha prestado mucha atención a los centroamericanos recién llegados a la frontera entre los Estados Unidos y México, casi la mitad de los aproximadamente 3.5 millones que vivían en los Estados Unidos en 2017 llegaron antes de 2000. Aproximadamente un tercio son ciudadanos estadounidenses y tienden a participar en la fuerza laboral con más frecuencia que otros extranjeros y estadounidenses. Descubra más en este artículo lleno de datos.

Presentación del reporte que refleja el contenido de encuentros del grupo de estudio sobre la migración México-Estados Unidos convocado por El Colegio de México y el Migration Policy Institute (MPI).

Dado el incremento de los flujos migratorios provenientes de Centroamérica, el pasado mes de junio de 2019, los Estados Unidos y México acordaron tomar una serie de medidas para reducir los flujos irregulares. Sin embargo, será muy difícil mantener estos esfuerzos de corto plazo, debido a una debilidad institucional crónica y a estructuras de política pública poco planificadas en ambos países. Este comentario ofrece cinco recomendaciones a ambos países considerando soluciones de mediano y largo plazo para disuadir la migración irregular y, al mismo tiempo, garantizar que aquellos que busquen protección tengan un proceso justo.

Cancer survivors have a lower risk for a fatal opioid overdose -- from prescription pain medications or illegal drugs -- than those without the disease, an analysis published Thursday by JAMA Oncology shows.

OBJECTIVE

To compare the risk of lactic acidosis hospitalization between patients treated with metformin versus sulfonylureas following development of reduced kidney function.

About 25 years ago, Cass Sunstein opened a retirement account that had two portfolios. One was mostly bonds, the other mostly stocks. Like many academics who use the TIAA-CREF investment program, Sunstein divided his money equally between stocks and bonds.

La migración entre México y Estados Unidos ha cambiado dramáticamente en los últimos años, pero las políticas y la retórica política en ambos países no se han actualizado a este contexto a la misma velocidad. Este reporte explora esta nueva realidad migratoria y cómo los dos gobiernos podrían trabajar juntos para abordar los desafíos de políticas públicas que tienen en común.

By Scott T. Allison Devs is the ideal TV mini-series for people to sink their teeth into, for many reasons: (1) It’s both science and science-fiction; (2) it’s brilliant mix of psychology, philosophy, religion, and technology; (3) it tantalizes us with the mysteries of love, life, death, time, and space; and (4) it features a … Continue reading The Miniseries ‘Devs’ Delivers a Delicious Dose of Heroism and Villainy →

Leipzig : F. Deuticke, 1898.

Valencia : M. Alufre, 1886.

London : J. Churchill, 1864.

Tubingen : H. Laupp, 1889.

Gábor Lugosi, Shahar Mendelson, Nikita Zhivotovskiy.

Source: Bernoulli, Volume 26, Number 3, 2253--2274.

Abstract:
We present results on the concentration properties of the spectral norm $|A_{p}|$ of the adjacency matrix $A_{p}$ of an Erdős–Rényi random graph $G(n,p)$. First, we consider the Erdős–Rényi random graph process and prove that $|A_{p}|$ is uniformly concentrated over the range $pin[Clog n/n,1]$. The analysis is based on delocalization arguments, uniform laws of large numbers, together with the entropy method to prove concentration inequalities. As an application of our techniques, we prove sharp sub-Gaussian moment inequalities for $|A_{p}|$ for all $pin[clog^{3}n/n,1]$ that improve the general bounds of Alon, Krivelevich, and Vu ( Israel J. Math. 131 (2002) 259–267) and some of the more recent results of Erdős et al. ( Ann. Probab. 41 (2013) 2279–2375). Both results are consistent with the asymptotic result of Füredi and Komlós ( Combinatorica 1 (1981) 233–241) that holds for fixed $p$ as $n oinfty$.