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Background: Superparamagnetic iron nanoparticles perform comparably to radioisotope +/- blue dye for sentinel lymph node detection in breast cancer, even when injected up to 8 weeks before surgery. Using superparamagnetic iron nanoparticles for sentinel lymph node detection after primary systemic therapy, and the maximum time frame of superparamagnetic iron nanoparticle administration have not been investigated. Methods: This cohort study included cN0/1-to-ycN0 patients undergoing sentinel lymph node detection or targeted axillary dissection. All patients received superparamagnetic iron nanoparticles either before primary systemic therapy or before surgery, and radioisotope on the day of surgery. Results: For 113 patients analysed, superparamagnetic iron nanoparticles were injected a median of 3 (range 0-248) days before surgery, with a 97.4% detection rate compared with 91.2% for radioisotope (P = 0.057). Concordance for radioisotope was 97.1% and this was not affected by timing of superparamagnetic iron nanoparticle injection (Kendall's tau 0.027; P = 0.746). The median sentinel lymph node yield was 3 (interquartile range (i.q.r.) 2-3) for superparamagnetic iron nanoparticles and 2 (i.q.r. 2-3) for radioisotope (P < 0.001). In targeted axillary dissection, detection was 100% for superparamagnetic iron nanoparticles and 81.8% for radioisotope (P = 0.124). The index node was magnetic in 93.9% and radioactive in 66.7% (P = 0.007), an outcome that was not affected by any factors. For patients with metastases, superparamagnetic iron nanoparticle detection was 100% and radioisotope-based detection was 84.2% (P = 0.083), with superparamagnetic iron nanoparticles detecting more metastatic sentinel lymph nodes (median of 1 (i.q.r. 1-2) for superparamagnetic iron nanoparticles compared with a median of 1 (i.q.r. 0-1) for radioisotope; P = 0.005). Conclusion: Injection before primary systemic therapy is feasible and does not affect concordance with radioisotope. Superpara

Objectives: This study aimed to identify factors related to changes in walking performance in individuals 3 months after a stroke or TIA. Design: Cross-sectional study with post hoc analysis of a randomised controlled study. Setting: University Hospital, Sweden. Participants 79 individuals, 64 (10) years, 37% women, who were acutely hospitalised because of stroke or TIA between November 2016 and December 2018. Inclusion criteria were patients aged 18 or above and the major eligibility criterion was the ability to perform the 6 min walking test. Intervention: The intervention group received standard care plus daily mobile phone text messages (short message service) with instructions to perform regular outdoor walking and functional leg exercises in combination with step counting and training diaries. The control group received standard care. Outcome measures Multivariate analysis was performed and age, sex, group allocation, comorbidity, baseline 6 min walk test, body mass index (BMI), cognition and chair-stand tests were entered as possible determinants for changes in the 6 min walk test. Results: Multiple regression analyses showed that age (standardised beta -0.33, 95% CI -3.8 to -1.05, p<0.001), sex (-0.24, 95% CI -66.9 to -8.0, p=0.014), no comorbidity (-0.16, 95% CI -55.5 to 5.4, p=0.11), baseline BMI (-0.29, 95% CI -8.1 to -1.6, p=0.004), baseline 6 min walk test (-0.55, 95% CI -0.5 to -0.3, p<0.001) were associated with changes in 6 min walk test 3 months after the stroke event. The regression model described 36% of the variance in changes in the 6 min walk test. Conclusions: Post hoc regression analyses indicated that younger age, male sex, lower BMI and shorter 6 min walk test at baseline and possible no comorbidity contributed to improvement in walking performance at 3 months in patients with a recent stroke or TIA. These factors may be important when planning secondary prevention actions.

Introduction: Dogs play an important role in society, which increased during the covid epidemics. This has led to a much higher workload for the veterinarians. Therefore, there is a need for efficient diagnostic tools to identify risk of malignant diseases. Here the development of a new test that can solve some of these problems is presented. It is based on serum Thymidine Kinase 1 (TK1), which is a biomarker for cell proliferation and cell lysis. Methods: Anti-TK1 monoclonal antibodies were produced against two different epitopes, the active site of the TK1 protein and the C-terminal region of canine TK1. The antibodies were developed with hybridoma technology and validated using dot blot, Quartz Crystal Microbalance (QCM) technology, western blots, immunoprecipitation (IP), and enzyme-linked immunosorbent assay (ELISA). Clinical evaluation of Canine TK1 ELISA was done by using sera from 131 healthy dogs and 93 dogs with lymphoma. The two selected Anti-TK1 monoclonal antibodies have Kd values in the range of 10(-9) M and further analysis with dot and western blots confirmed the high affinity binding of these antibodies. A sandwich Canine TK1 ELISA was developed using the anti-TK1 antibodies, and TK1 concentrations in serum samples were determined using dog recombinant TK1 as a standard. Results: Serum TK1 protein levels were significantly higher in dogs with lymphoma compared to those in healthy dogs (p < 0.0001). Receiver operating curve analysis showed that the canine TK1-ELISA obtain a sensitivity of 0.80, at a specificity of 0.95. Moreover, the Canine TK1 ELISA has a positive predictive value (PPV) of 97%, and the negative predictive value (NPV) of 83%, reflecting the proportion of test results that are truly positive and negative. Furthermore, Canine TK1 ELISA had significantly higher capacity to differentiate dogs with T-cell lymphoma from those with B-cell lymphoma compared to earlier used TK1 activity assays. Discussion: These results demonstrate that th

Background: Superparamagnetic iron oxide nanoparticles (SPIO) have been used as a tracer for sentinel lymph node (SLN) localization in breast cancer, demonstrating comparable performance to the combination of radioisotope (RI) and blue dye (BD). Methods: A systematic literature search and meta-analysis with subgroup and meta-regression analysis were undertaken to update the available evidence, assess technique evolution, and define knowledge gaps. Recommendations were made using the GRADE approach. Results: In 20 comparative studies, the detection rate was 97.5 per cent for SPIO and 96.5 per cent for RI +/- BD (risk ratio 1.006, 95 per cent c.i. 0.992 to 1.019; P = 0.376, high-certainty evidence). Neoadjuvant therapy, injection site, injection volume or nodal metastasis burden did not affect the detection rate, but injection over 24 h before surgery increased the detection rate on meta-regression. Concordance was 99.0 per cent and reverse concordance 97.1 per cent (rate difference 0.003, 95 per cent c.i. -0.009 to 0.015; P = 0.656, high-certainty evidence). Use of SPIO led to retrieval of slightly more SLNs (pooled mean 1.96 versus 1.89) with a higher nodal detection rate (94.1 versus 83.5 per cent; RR 1.098, 1.058 to 1.140; P < 0.001; low-certainty evidence). In meta-regression, injection over 24 h before surgery increased the SPIO nodal yield over that of RI +/- BD. The skin-staining rate was 30.8 per cent (very low-certainty evidence), and possibly prevented with use of smaller doses and peritumoral injection. Conclusion: The performance of SPIO is comparable to that of RI +/- BD. Preoperative injection increases the detection rate and nodal yield, without affecting concordance. Whether skin staining and MRI artefacts are reduced by lower dose and peritumoral injection needs to be investigated.

Importance Guidewires have been the standard for breast lesion localization but pose operative and logistic challenges. Paramagnetic seeds have shown promising results, but to the authors’ knowledge, no randomized comparison has been performed. Objective To determine whether the combination of a paramagnetic seed and superparamagnetic iron oxide (SPIO) is equivalent to guidewire and SPIO for breast cancer localization and sentinel lymph node detection (SLND). Design, Setting, and Participants This was a phase 3, pragmatic, equivalence, 2-arm, open-label, randomized clinical trial conducted at 3 university and/or community hospitals in Sweden from May 2018 to May 2022. Included in the study were patients with early breast cancer planned for breast conservation and SLND. Study data were analyzed July to November 2022. Interventions Participants were randomly assigned 1:1 to a paramagnetic seed or a guidewire. All patients underwent SLND with SPIO. Main Outcomes and Measures Re-excision rate and resection ratio (defined as actual resection volume / optimal resection volume). Results A total of 426 women (median [IQR] age, 65 [56-71] years; median [IQR] tumor size, 11 [8-15] mm) were included in the study. The re-excision rate was 2.90% (95% CI, 1.60%-4.80%), and the median (IQR) resection ratio was 1.96 (1.15-3.44). No differences were found between the guidewire and the seed in re-excisions (6 of 211 [2.84%] vs 6 of 209 [2.87%]; difference, −0.03%; 95% CI, −3.20% to 3.20%; P = .99) or resection ratio (median, 1.93; IQR, 1.18-3.43 vs median, 2.01; IQR, 1.11-3.47; P = .70). Overall SLN detection was 98.6% (95% CI, 97.1%-99.4%) with no differences between arms (203 of 207 [98.1%] vs 204 of 206 [99.0%]; difference, −0.9%; 95% CI, −3.6% to 1.8%; P = .72). More failed localizations occurred with the guidewire (21 of 208 [10.1%] vs 4 of 215 [1.9%]; difference, 8.2%; 95% CI, 3.3%-13.2%; P < .001). Median (IQR) time to specimen excision was shorter for the seed (15 [1

Thymidylate kinase (TMPK) phosphorylates deoxythymidine monophosphate (dTMP) and plays an important role in genome stability. Deficiency in TMPK activity due to genetic alterations of DTYMK, i.e., the gene coding for TMPK, causes severe microcephaly in humans. However, no defects were observed in other tissues, suggesting the existence of a compensatory enzyme for dTTP synthesis. In search for this compensatory enzyme we analyzed 6 isoforms of TMPK mRNA deposited in the GenBank. Of these, only isoform 1 has been characterized and represents the known human TMPK. Our results reveal that isoform 2, 3, 4 and 5 lack essential structural elements for substrate binding and, thus, they are considered as nonfunctional isoforms. Isoform 6, however, has intact catalytic centers, i.e., dTMP-binding, DRX motif, ATP-binding p-loop and lid region, which are the key structural elements of an active TMPK, suggesting that isoform 6 may function as TMPK. When isoform 6 was expressed and purified, it showed only minimal activity (<0.1%) as compared with isoform 1. A putative isoform 6 was detected in a cancer cell line, in addition to the dominant isoform 1. However, because of its low activity, isoform 6 is unlikely be able to compensate for the loss of TMPK activity caused by deletions and/or point mutations of the DTYMK gene. Thereby, future studies to identify and characterize the compensatory TMPK enzyme found in patients with DTYMK mutations may contribute to the understanding of dTTP synthesis and of the pathophysiological role of DTYMK mutations in neurodegenerative disorders.

Simple Summary Both superparamagnetic iron oxide nanoparticles (SPIO) and blue dye (BD) have been reported to cause skin staining after breast-conserving surgery. SPIO is a novel tracer that has been shown to identify sentinel lymph nodes (SLNs) in patients with breast cancer. Our study was the first to compare the incidence and size of skin staining between the two tracers. We reported on these outcomes in a preplanned secondary analysis of a prospective clinical trial in which women received both SPIO and BD. This study investigated whether there was a difference in the incidence and size of skin staining between SPIO and BD after SLN-dissection. In all, 270 women were operated on with breast-conserving surgery and received SPIO, and 204 of these women also received BD. After 24 months of follow up, there was no statistically significant difference between the two tracers with regard to the size and incidence of skin staining. Superparamagnetic iron oxide nanoparticles (SPIO) are a tracer for sentinel lymph node (SLN) detection. In a preplanned secondary analysis of a prospective clinical trial (SentiDose) we reported on skin staining after SPIO and blue dye (BD) injections. For SPIO, either a 1.5 mL retroareolar injection on the day of surgery or a 1.0 mL peritumoral/retroareolar injection 1-7 days before surgery was given. A 1.0 mL sub-/intradermal periareolar injection of BD was also administered to all these women. Staining was then assessed at 6, 12 and 24 months after surgery. A total of 270 women received SPIO and were operated on with breast-conserving surgery. Of these, 204 women also received BD. A total of 58 (21.5%) women had an SPIO stain 6 months postoperatively with a median size of 6.8 cm(2) (p = 0.56), while 51 (25.0%) had a BD stain with a median size of 8.5 cm(2) (p = 0.93). The incidence and size of SPIO and BD staining decreased over time reciprocally. At 24 months, the incidence and median size of SPIO was 23 (8.6%) and 4 cm(2), respectively.