Surgical treatment of early breast cancer in day surgery

Quadrantectomy and associated sentinel lymph node biopsy (SLNB) is currently employed in most breast surgery centres as the gold standard in the treatment of early breast cancer. This approach has a modest morbidity and can usually be performed in a day-surgery regimen, leading to best acceptance by the patients. This reports outlines the experience of our Breast Unit with quadrantectomy and SLNB in day surgery for early breast cancer. One hundred patients presenting to our institution with primary invasive breast cancer measuring less than 3 cm and clinically negative axillary nodes underwent quadrantectomy and SLNB in day surgery. For 60 women with breast cancer the sentinel node was negative, so the only definitive surgical treatment was performed in the day-surgery regimen; 40 patients with positive sentinel nodes were hospitalised a second time for axillary dissection. In these patients that needed clearance of the axilla, SLNB was performed on the only positive node in 22 cases (55%). None of the patients admitted for quadrantectomy and SLNB in day surgery required re-hospitalisation after discharge. All patients proved to be fully satisfied with early discharge from hospital when questioned on the occasion of subsequent monitoring. Short-stay surgical programs in early invasive breast cancer treatment are feasible today owing to the availability of less invasive approaches such as quadrantectomy and SLNB. There are two main pointers to a distinct advantage for this kind of approach, i.e. recovery and psychological adjustment. Recovery from surgery is faster and the patient tends to play down the seriousness of the operation and to have a better mental attitude to neoplastic disease. Moreover, when performing quadrantectomy with SLNB in day surgery fewer than 50% of breast cancer patients (40% in our experience) require another surgical treatment, concluding the surgery in a single sessio

A two-step learning approach for solving full and almost full cold start problems in dyadic prediction

Dyadic prediction methods operate on pairs of objects (dyads), aiming to infer labels for out-of-sample dyads. We consider the full and almost full cold start problem in dyadic prediction, a setting that occurs when both objects in an out-of-sample dyad have not been observed during training, or if one of them has been observed, but very few times. A popular approach for addressing this problem is to train a model that makes predictions based on a pairwise feature representation of the dyads, or, in case of kernel methods, based on a tensor product pairwise kernel. As an alternative to such a kernel approach, we introduce a novel two-step learning algorithm that borrows ideas from the fields of pairwise learning and spectral filtering. We show theoretically that the two-step method is very closely related to the tensor product kernel approach, and experimentally that it yields a slightly better predictive performance. Moreover, unlike existing tensor product kernel methods, the two-step method allows closed-form solutions for training and parameter selection via cross-validation estimates both in the full and almost full cold start settings, making the approach much more efficient and straightforward to implement

α-Synuclein Aggregated with Tau and β-Amyloid in Human Platelets from Healthy Subjects: Correlation with Physical Exercise

The loss of protein homeostasis that has been associated with aging leads to altered levels and conformational instability of proteins, which tend to form toxic aggregates. In particular, brain aging presents characteristic patterns of misfolded oligomers, primarily constituted of β-amyloid (Aβ), tau, and α-synuclein (α-syn), which can accumulate in neuronal membranes or extracellular compartments. Such aging-related proteins can also reach peripheral compartments, thus suggesting the possibility to monitor their accumulation in more accessible fluids. In this respect, we have demonstrated that α-syn forms detectable hetero-aggregates with Aβ or tau in red blood cells (RBCs) of healthy subjects. In particular, α-syn levels and its heteromeric interactions are modulated by plasma antioxidant capability (AOC), which increases in turn with physical activity. In order to understand if a specific distribution of misfolded proteins can occur in other blood cells, a cohort of human subjects was enrolled to establish a correlation among AOC, the level of physical exercise and the concentrations of aging-related proteins in platelets. The healthy subjects were divided depending on their level of physical exercise (i.e., athletes and sedentary subjects) and their age (young and older subjects). Herein, aging-related proteins (i.e., α-syn, tau and Aβ) were confirmed to be present in human platelets. Among such proteins, platelet tau concentration was demonstrated to decrease in athletes, while α-syn and Aβ did not correlate with physical exercise. For the first time, α-syn was shown to directly interact with Aβ and tau in platelets, forming detectable hetero-complexes. Interestingly, α-syn interaction with tau was inversely related to plasma AOC and to the level of physical activity. These results suggested that α-syn heterocomplexes, particularly with tau, could represent novel indicators to monitor aging-related proteins in platelets

A Sensitive Tg Assay or rhTSH Stimulated Tg: What's the Best in the Long-Term Follow-Up of Patients with Differentiated Thyroid Carcinoma?

Sensitivity of thyroglobulin (Tg) measurement in the follow-up of differentiated thyroid carcinoma (DTC) can be optimized by using a sensitive Tg assay and rhTSH stimulation. We evaluated the diagnostic yield of a sensitive Tg assay and rhTSH stimulated Tg in the detection of recurrences in the follow-up of DTC. Additionally the value of imaging techniques for the localization of recurrences was evaluated. We included 121 disease free patients in long-term follow-up for DTC (median 10 years, range 1–34). Tg during thyroid hormone suppression therapy (Tg-on) and rhTSH stimulated Tg were measured with a sensitive Tg assay. Patients with rhTSH stimulated Tg ≥1.0 ng/ml underwent imaging with neck ultrasound, FDG-PET and post therapy 131I WBS. Sensitive Tg measurement resulted in 3 patients with Tg-on ≥1.0 ng/ml, recurrence could be localized in 2 of them. RhTSH stimulation resulted in Tg ≥1.0 ng/ml in another 17 of 118 patients. Recurrence could be localized in only 1 additional patient (1 out of 118 patients). Recurrence was localized by neck ultrasound in 1 of 3, by FDG-PET in 2 of 3 and by post therapy 131I WBS in 2 of 3 patients. In the detection of recurrences in DTC, rhTSH stimulation had very limited additional value in comparison to Tg-on measurement with a sensitive Tg assay. We consider this too low to justify rhTSH stimulation in all patients during long-term follow up. Neck ultrasound, FDG-PET and post therapy 131I WBS showed complementary value in localization of disease, but were only positive in a small fracture of all procedures

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons