Spanish Preanalytical Quality Monitoring Program (SEQC), an overview of 12 years' experience

Preanalytical variables, such as sample collection, handling and transport, may affect patient results. Preanalytical phase quality monitoring should be established in order to minimize laboratory errors and improve patient safety. A retrospective study (2001-2013) of the results obtained through the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC) External quality assessment (preanalytical phase) was performed to summarize data regarding the main factors affecting preanalytical phase quality. Our aim was to compare data from 2006 to 2013 with a previously published manuscript assessing the 2001-2005 period. A significant decrease in rejection rates was observed both for blood and urine samples. For serum samples, the most frequent rejection causes in the first period were non-received samples (37.5%), hemolysis (29.3%) and clotted samples (14.4%). Conversely, in the second period, hemolysis was the main rejection cause (36.2%), followed by non-received samples (34.5%) and clotted samples (11.1%). For urine samples, the main rejection cause overall was a non-received sample (up to 86.1% of cases in the second period, and 81.6% in the first). For blood samples with anticoagulant, the number of rejections also decreased. While plasma-citrate-ESR still showed the highest percentages of rejections (0.980% vs. 1.473%, p<0.001), the lowest corresponded to whole-blood EDTA (0.296% vs. 0.381%, p<0.001). For the majority of sample types, a decrease in preanalytical errors was confirmed. Improvements in organization, implementation of standardized procedures in the preanalytical phase, and participation in a Spanish external quality assessment scheme may have notably contributed to error reduction in this phase

Detection of active hepatitis C in a single visit and linkage to care among marginalized people using a mobile unit in Madrid, Spain

Background: The burden of hepatitis C virus (HCV) infection among marginalized people in Spain is high, despite the fact that HCV prevalence has decreased in recent years. We aimed to assess the effectiveness of a simplified point-of-care (PoC) model for screening for active HCV infection via a mobile unit and subsequent linkage to care with the assistance of navigators. Methods: We carried out a prospective study on 2001 participants from Madrid, Spain. A nurse and a navigator/educator screened for hepatitis C in a mobile unit, using the OraQuick HCV Rapid Antibody Test and Xpert HCV VL Fingerstick assay. Participants with active HCV were referred to the hospital the same day with a navigator for evaluation and treatment of HCV. Results: Overall, 1621 (81%) participants had not been exposed to HCV, 380 (18.9%) were positive for HCV antibodies, and 136 (6.8%) had active hepatitis C. Among the latter, 134 (98.5%) received the HCV screening results, 133 (97.8%) had an appointment at the hospital, 126 (92.8%) were seen by a physician once they were at the hospital, and 105 (77.2%) started HCV treatment. Being over 50 years old and a person who uses drugs, particularly people who inject drugs (PWID), was directly associated with active hepatitis C (p<0.05). PWID were the only patients with HCV reinfection (4.3% in people without recent injecting drug use and 5.9% in people with recent injecting drug use). Among PWID, no income and daily alcohol intake were also directly associated with active hepatitis C. People with recent injecting drug use showed the lowest rates of attendance at the hospital (91.8%) and starting HCV treatment (70.4%). Conclusion: HCV screening using a two-step PoC-based strategy and its linkage to care was extremely efficient for identifying and treating marginalized people with active hepatitis C, thanks to the use of a mobile unit with personnel and technical equipment, an interdisciplinary team, and collaboration between institutions.This work was funded by a research grant from Gilead Science (IN-ES-987-5391 and GLD20_0144) and Instituto de Salud Carlos III (ISCII; grant numbers PI20CIII/00004 and RD16CIII/0002/0002 to SR). It also received funding from AbbVie, Asociación Española para Estudio del Higado (AEEH), and Madrid Positivo Association.S

Dose volume histogram constraints in patients with soft tissue sarcomas of the extremities and the superficial trunk treated with surgery and perioperative HDR brachytherapy

Background: Wound healing complications (WHC), osteoradionecrosis (ORN), and nerve damage (ND) are common adverse effects in adult patients with soft tissue sarcomas of the extremities and the superficial trunk treated with surgery and perioperative high dose rate brachytherapy (PHDRB) alone or combined with external beam radiotherapy (EBRT). Rationale: Analysis of the treatment factors contributing to these complications can potentially minimize their occurrence and severity. Patients: A total of 169 patients enrolled in two parallel prospective studies were included in this analysis. Previously Unirradiated cases (Group 1; n = 139) were treated with surgical resection, 16–24 Gy of PHDRB and 45 Gy of EBRT. Adjuvant chemotherapy was given to selected patients with high-grade tumors. Previously irradiated cases (Group 2; n = 30) were treated with surgical resection and 32– 40 Gy of PHDRB without further EBRT. Methods: Patient factors, tumor factors, surgical factors, PHDRB factors and EBRT factors were analyzed using Cox univariate and multivariate analysis. Results: In Previously Unirradiated cases, WHC, ORN and ND occurred in 38.8%, 5.0% and 19.4%. Multivariate analysis indicated that WHC increased with CTV size (p = 0.02) and CTV2cm3 Physical dose (p = 0.02). ORN increased with Bone2cm3 EQD2 67 Gy (p = 0.01) and ND was more frequent in patients with TV100 DVH-based dose (tissue volume encompassed by the 100% isodose) 84 Gy (p < 0.01). In Previously Irradiated cases, WHC, ORN and ND occurred in 63.3%, 3.3% and 23.3%. Multivariate analysis showed that WHC was more frequent in patients with Skin2cm3 Lifetime EQD2 84 Gy (p = 0.01) and ND was more frequent after CTVD90 Physical Doses 40 Gy (p < 0.01). Conclusions: WHC in Previously Unirradiated patients can be minimized by using a more conservative CTV definition together with a meticulous implant technique and planning aimed to minimize hyperdose CTV2cm3 areas. In Previously Irradiated patients WHC may be mimimized considering Lifetime EQD2 Skin2cm3 doses. ORN can be reduced by using the Bone2cm3 EQD2 constraint. ND occurs more frequently in patients with large tumors receiving high treated volume doses, but no specific constraints can be recommended due to the lack of peripheral nerve definition during brachytherapy planning

Dynamical Patterns of Cattle Trade Movements

Despite their importance for the spread of zoonotic diseases, our understanding of the dynamical aspects characterizing the movements of farmed animal populations remains limited as these systems are traditionally studied as static objects and through simplified approximations. By leveraging on the network science approach, here we are able for the first time to fully analyze the longitudinal dataset of Italian cattle movements that reports the mobility of individual animals among farms on a daily basis. The complexity and inter-relations between topology, function and dynamical nature of the system are characterized at different spatial and time resolutions, in order to uncover patterns and vulnerabilities fundamental for the definition of targeted prevention and control measures for zoonotic diseases. Results show how the stationarity of statistical distributions coexists with a strong and non-trivial evolutionary dynamics at the node and link levels, on all timescales. Traditional static views of the displacement network hide important patterns of structural changes affecting nodes' centrality and farms' spreading potential, thus limiting the efficiency of interventions based on partial longitudinal information. By fully taking into account the longitudinal dimension, we propose a novel definition of dynamical motifs that is able to uncover the presence of a temporal arrow describing the evolution of the system and the causality patterns of its displacements, shedding light on mechanisms that may play a crucial role in the definition of preventive actions

Dynamical Patterns of Cattle Trade Movements

Despite their importance for the spread of zoonotic diseases, our understanding of the dynamical aspects characterizing the movements of farmed animal populations remains limited as these systems are traditionally studied as static objects and through simplified approximations. By leveraging on the network science approach, here we are able for the first time to fully analyze the longitudinal dataset of Italian cattle movements that reports the mobility of individual animals among farms on a daily basis. The complexity and inter-relations between topology, function and dynamical nature of the system are characterized at different spatial and time resolutions, in order to uncover patterns and vulnerabilities fundamental for the definition of targeted prevention and control measures for zoonotic diseases. Results show how the stationarity of statistical distributions coexists with a strong and non-trivial evolutionary dynamics at the node and link levels, on all timescales. Traditional static views of the displacement network hide important patterns of structural changes affecting nodes' centrality and farms' spreading potential, thus limiting the efficiency of interventions based on partial longitudinal information. By fully taking into account the longitudinal dimension, we propose a novel definition of dynamical motifs that is able to uncover the presence of a temporal arrow describing the evolution of the system and the causality patterns of its displacements, shedding light on mechanisms that may play a crucial role in the definition of preventive actions

Male breast cancer

Male breast cancer (MBC) is a rare disease representing less than 1% of all breast cancers (BC) and less than 1% of cancers in men. Age at presentation is mostly in the late 60s. MBC is recognized as an estrogen-driven disease, specifically related to hyperestrogenism. About 20% of MBC patients have family history for BC. Mutations in BRCA1 and, predominantly, BRCA2, account for approximately 10% of MBC cases. Because of its rarity, MBC is often compared with female BC (FBC). Based on age-frequency distribution, age-specific incidence rate patterns and prognostic factors profiles, MBC is considered similar to late-onset, postmenopausal estrogen/progesterone receptor positive (ER+/PR+) FBC. However, clinical and pathological characteristics of MBC do not exactly overlap FBC. Compared with FBC, MBC has been reported to occur later in life, present at a higher stage, and display lower histologic grade, with a higher proportion of ER+ and PR+ tumors. Although rare, MBC remains a substantial cause for morbidity and mortality in men, probably because of its occurrence in advanced age and delayed diagnosis. Diagnosis and treatment of MBC generally is similar to that of FBC. Men tend to be treated with mastectomy rather than breast-conserving surgery. The backbone of adjuvant therapy or palliative treatment for advanced disease is endocrine, mostly tamoxifen. Use of FBC-based therapy led to the observation that treatment outcomes for MBC are worse and that survival rates for MBC do not improve like FBC. These different outcomes may suggest a non-appropriate utilization of treatments and that different underlying pathogenetic mechanisms may exist between male and female BC

Ni-62(n,gamma) and Ni-63(n,gamma) cross sections measured at the n_TOF facility at CERN

The cross section of the Ni-62(n,gamma) reaction was measured with the time-of-flight technique at the neutron time-of-flight facility n_TOF at CERN. Capture kernels of 42 resonances were analyzed up to 200 keV neutron energy and Maxwellian averaged cross sections (MACS) from kT = 5-100 keV were calculated. With a total uncertainty of 4.5%, the stellar cross section is in excellent agreement with the the KADoNiS compilation at kT = 30 keV, while being systematically lower up to a factor of 1.6 at higher stellar temperatures. The cross section of the Ni-63(n,gamma) reaction was measured for the first time at n_TOF. We determined unresolved cross sections from 10 to 270 keV with a systematic uncertainty of 17%. These results provide fundamental constraints on s-process production of heavier species, especially the production of Cu in massive stars, which serve as the dominant source of Cu in the solar system.Peer reviewedFinal Accepted Versio

Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A

Precision oncology research is challenging outside the contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conduct a phosphoproteomic screening of samples from HER2-negative female breast cancer receiving neoadjuvant paclitaxel (N = 130), aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 11 candidate biomarkers through 2 independent patient sets (N= 218) allowed the identification of a subgroup of patients characterized by high levels of CDK4 and filamin-A who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulates filamin-A transcription, which in turn forms a complex with tubulin and CLIP-170, which elicits increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allows the identification of explainable factors for predicting response to paclitaxel