Sensory profiles in women with neuropathic pain after breast cancer surgery

Purpose We performed a detailed analysis of sensory function in patients with chronic post-surgical neuropathic pain (NP) after breast cancer treatments by quantitative sensory testing (QST) with DFNS (German Research Network on Neuropathic Pain) protocol and bed side examination (BE). The nature of sensory changes in peripheral NP may reflect distinct pathophysiological backgrounds that can guide the treatment choices. NP with sensory gain (i.e., hyperesthesia, hyperalgesia, allodynia) has been shown to respond to Na+-channel blockers (e.g., oxcarbazepine). Methods 104 patients with at least "probable" NP in the surgical area were included. All patients had been treated for breast cancer 4-9 years ago and the handling of the intercostobrachial nerve (ICBN) was verified by the surgeon. QST was conducted at the site of NP in the surgical or nearby area and the corresponding contralateral area. BE covered the upper body and sensory abnormalities were marked on body maps and digitalized for area calculation. The outcomes of BE and QST were compared to assess the value of QST in the sensory examination of this patient group. Results Loss of function in both small and large fibers was a prominent feature in QST in the area of post-surgical NP. QST profiles did not differ between spared and resected ICBN. In BE, hypoesthesia on multiple modalities was highly prevalent. The presence of sensory gain in BE was associated with more intense pain. Conclusions Extensive sensory loss is characteristic for chronic post-surgical NP several years after treatment for breast cancer. These patients are unlikely to respond to Na+-channel blockers.Peer reviewe

Influences of Orally Taken Carotenoid-Rich Curly Kale Extract on Collagen I/Elastin Index of the Skin

Two differently designed, spatially resolved reflectance spectroscopy-based scanners and two-photon tomography were used for noninvasive in vivo determination of cutaneous carotenoids, and collagen I/elastin aging index of dermis, respectively, in the skin of 29 healthy female volunteers between 40 and 56 years of age. The volunteers received a supplement in the form of a carotenoid-rich natural curly kale extract containing 1650 µg of carotenoids in total (three capsules of 550 µg), once a day. Measurements were taken before, after 5 months and after 10 months of daily supplementation. The results showed significantly increased values for the cutaneous carotenoids and the collagen I/elastin aging index of dermis 5 and 10 months after the beginning of the study. The obtained results show that a natural carotenoid- rich extract could prevent the aging-related collagen I degradation in the dermis and improve the extracellular matrix

Designing a Locally Manufacturable Wheelchair for Nepal

Persons with disabilities in developing countries often lack the basic equipment needed to assist them in their daily lives. International Nepal Fellowship (INF) is a Christian medical organization located in Nepal that provides medical care and assistance to people with disabilities and other conditions. Currently, INF imports expensive wheelchairs that undergo a prolonged border process before being received by INF. INF has reached out to the Collaboratory to design a wheelchair that can withstand the challenges of Nepal’s terrain and can be manufactured from local materials. The Nepal Wheelchair team accepted this challenge and set out to design a wheelchair that can fulfill the needs of INF. The team began by researching wheelchair models for inspiration and eventually settled on two preliminary designs. In January 2020, the team traveled to Pokhara, Nepal to gain feedback from the staff at INF and select a final design based on their comments. During this trip, the team acquired and brought back locally available materials and parts in order to be able to construct a prototype using materials which are actually available in Nepal. After returning, the team began performing Finite Element Analysis on the frame design and tested the steel from the trip to determine its physical properties. With prototyping progress stalled by recent events, the team is focusing on perfecting the design and preparing an instruction manual for INF.https://mosaic.messiah.edu/engr2020/1005/thumbnail.jp

Respuesta del cultivo de maíz a la fertilización nitrogenada en la pampa ondulada, campañas 1980-81 - 1983-84 : I- análisis de los resultados

p.45-64Se presentan los resultados correspondientes a los experimentos de campo realizados a lo largo de las cuatro últimas campañas agrícolas dentro del marco del Programa de Investigación Experimental sobre Fertilización en el cultivo de maíz. La dosis de nutrientes estudiadas fueron de 0,60 y 120 kg N-ha (Campaña 1980-81) y 0,40 y 80 kg N-ha (restantes campañas), mientras que predominaron los materiales genéticos Dekalb, Cargill y Morgan. La red de ensayos, ubicada en la Pampa Ondulada, cubrió 31 situaciones sometidas a diversas combinaciones de factores culturales, edáficos y climáticos los que sufrieron una marcada variación a lo largo de los distintos años. Variaciones concomitantes fueron registradas tanto en el promedio de los rendimientos del tratamiento testigo (70, 61, 59 y 54 qq-ha, en cada uno de los respectivos años), como en la eficiencia de la primera dosis (7,8; 15,1; 10,9 y 15,3;respectivamente). Se determinó, a través del análisis de regresión del rendimiento en función de la dosis de N que el modelo parabólico presentó, en relación a otros modelos, el mejor ajuste a los datos individuales. Sin embargo, al efectuar un análisis de la población total de ensayos no fue posible obtener un buen ajuste a través de los modelos estudiados. Se demuestra finalmente la necesidad de elaborar modelos multivariados para explicar el hecho de que al pasar de la población de ensayos con respuesta significativa a los restantes, tanto los promedios de la eficiencia como del rendimiento del testigo presentan una marcada discontinuidad (de más de 20 a menos de 6 y de 51 a 69 qq-ha, respectivamente)

Mechanical detection and pain thresholds: comparability of devices using stepped and ramped stimuli

Quantitative sensory testing is used to assess somatosensory function in humans. The protocol of the German Research Network on Neuropathic Pain (DFNS) provides comprehensive normative values using defined tools; however, some of these may not be feasible in low-resource settings. Objectives: To compare the standard DFNS devices for assessment of mechanosensory function to a low resource tool, the Sorri-Bauru-monofilaments. Methods: Mechanical detection thresholds (MDT), pain thresholds (MPT), and suprathreshold pinprick ratings (pain sensitivity: MPS) were measured over cheek, hand dorsum, and fingertip in 13 healthy subjects (7 female, aged 21-44 years). Mechanical detection threshold was assessed with DFNS standard glass monofilaments (0.25-512 mN, 0.5 mm tip) and nylon monofilaments (Sorri-Bauru; 0.5-3000 mN). MPT was assessed with DFNS standard cylindrical probes (8-512 mN, 0.25 mm tip), Sorri-Bauru monofilaments, and with ramped stimuli using an electronic von Frey aesthesiometer (10 mN/s or 100 mN/s, 0.20 mm tip). MPS was measured in response to stepped and ramped pinpricks (128 and 256 mN). Results: Mechanical detection thresholds were the same for DFNS and Sorri-Bauru monofilaments. For MPT, Sorri-Bauru filaments yielded lower values than PinPricks over face but not hand. Pain thresholds were higher at all test sites for ramped than stepped pinpricks (P < 0.01). Suprathreshold ratings were lower for ramped than stepped pinpricks (P < 0.05). Conclusion: Sorri-Bauru filaments are acceptable substitutes for DFNS standards in estimating tactile sensitivity, but are not consistent with standard probes for pinprick sensitivity because of their nonstandardized tips. Ramped stimuli overestimated MPT and underestimated MPS due to reaction time artefacts and therefore need their own normative values

The need for tumor surveillance of children and adolescents with cancer predisposition syndromes: a retrospective cohort study in a tertiary-care children’s hospital

Expert recommendations for the management of tumor surveillance in children with a variety of cancer predisposition syndromes (CPS) are available. We aimed (1) at identifying and characterizing children who are affected by a CPS and (2) at comparing current practice and consensus recommendations of the American Association for Cancer Research workshop in 2016. We performed a database search in the hospital information system of the University Children’s Hospital for CPS in children, adolescents, and young adults and complemented this by review of electronic patients’ charts. Between January 1, 2017, and December 3, 2019, 272 patients with 41 different CPS entities were identified in 20 departments (144 [52.9%] male, 128 [47.1%] female, median age 9.1 years, range, 0.4–27.8). Three (1.1%) patients died of non-malignancy-associated complications of the CPS; 49 (18.0%) patients were diagnosed with malignancy and received regular follow-up. For 209 (95.0%) of the remaining 220 patients, surveillance recommendations were available: 30/220 (13.6%) patients received CPS consultations according to existing consensus recommendations, 22/220 (10.0%) institutional surveillance approaches were not complying with recommendations, 84/220 (38.2%) patients were seen for other reasons, and 84/220 (38.2%) were not routinely cared for. Adherence to recommendations differed extensively among CPS entities. Conclusion: The spectrum of CPS patients at our tertiary-care children’s hospital is manifold. For most patients, awareness of cancer risk has to be enhanced and current practice needs to be adapted to consensus recommendations. Offering specialized CPS consultations and establishing education programs for patients, relatives, and physicians may increase adherence to recommendations

Protocol for a systematic review of guidelines for rigour in the design, conduct and analysis of biomedical experiments involving laboratory animals

Objective: Within the last years, there has been growing awareness of the negative repercussions of unstandardized planning, conduct and reporting of preclinical and biomedical research. Several initiatives have set the aim of increasing validity and reliability in reporting of studies and publications, and publishers have formed similar groups. Additionally, several groups of experts across the biomedical spectrum have published experience and opinion-based guidelines and guidance on potential standardized reporting. While all these guidelines cover reporting of experiments, an important step prior to this should be rigours planning and conduction of studies. The aim of this systematic review is to identify and harmonize existing experimental design, conduct and analysis guidelines relating to internal validity and reproducibility of preclinical animal research. The review will also identify literature describing risks of bias pertaining to the design, conduct and analysis of preclinical biomedical research. Search strategy: PubMed, Embase and Web of Science will be searched systematically to identify guidelines published in English language in peer-reviewed journals before January 2018 (box 1). All articles or systematic reviews in English language that describe or review guidelines on the internal validity and reproducibility of animal studies will be included. Google search for guidelines published on the websites of major funders and professional organisations can be found in (Box 2). Screening and annotation: Unique references will be screened in two phases: screening for eligibility based on title and abstract, followed by screening for definitive inclusion based on full text. Screening will be performed in SyRF (http://syrf.org.uk). Each reference will be randomly presented to two independent reviewers. Disagreements between reviewers will be resolved by additional screening of the reference by a third, senior researcher. Data management and reporting: All data, including extracted text and guidelines, will be stored in the SyRF platform. Elements of the included guidelines will be identified using a standardized extraction form. Reporting will follow the PRISMA guidelines as far as applicable

Clinical relevance assessment of animal preclinical research (RAA) tool: development and explanation.

Only a small proportion of preclinical research (research performed in animal models prior to clinical trials in humans) translates into clinical benefit in humans. Possible reasons for the lack of translation of the results observed in preclinical research into human clinical benefit include the design, conduct, and reporting of preclinical studies. There is currently no formal domain-based assessment of the clinical relevance of preclinical research. To address this issue, we have developed a tool for the assessment of the clinical relevance of preclinical studies, with the intention of assessing the likelihood that therapeutic preclinical findings can be translated into improvement in the management of human diseases. We searched the EQUATOR network for guidelines that describe the design, conduct, and reporting of preclinical research. We searched the references of these guidelines to identify further relevant publications and developed a set of domains and signalling questions. We then conducted a modified Delphi-consensus to refine and develop the tool. The Delphi panel members included specialists in evidence-based (preclinical) medicine specialists, methodologists, preclinical animal researchers, a veterinarian, and clinical researchers. A total of 20 Delphi-panel members completed the first round and 17 members from five countries completed all three rounds. This tool has eight domains (construct validity, external validity, risk of bias, experimental design and data analysis plan, reproducibility and replicability of methods and results in the same model, research integrity, and research transparency) and a total of 28 signalling questions and provides a framework for researchers, journal editors, grant funders, and regulatory authorities to assess the potential clinical relevance of preclinical animal research. We have developed a tool to assess the clinical relevance of preclinical studies. This tool is currently being piloted

Improve Management of acute heart failure with ProcAlCiTonin in EUrope:results of the randomized clinical trial IMPACT EU Biomarkers in Cardiology (BIC) 18

Aim: To determine whether initiation of antibiotic therapy (ABX) by procalcitonin (PCT) within 8 h of admission in patients presenting to the emergency department with symptoms and signs of acute heart failure (AHF) and elevated natriuretic peptides would improve clinical outcomes. Methods and results: The study was a randomized multicentre clinical trial conducted at 16 sites in Europe. Patients were randomized to either a PCT-guided strategy or standard care. Patients with PCT-guided strategy (n = 370) had ABX initiated if PCT was > 0.2 μg/L. Patients with standard care (n = 372) had AHF care in accordance with published guidelines without PCT. The primary endpoint was 90-day all-cause mortality. Pre-specified secondary endpoints included 30-day all-cause mortality and readmission and rate of pneumonia. The Data Safety and Review Committee recommended stopping the study for futility when 762 of the planned 792 patients had been enrolled. A total of 742 patients could be analysed. Patients were elderly (median age: 77 years), 38% were women, and had typical signs and symptoms of AHF. All-cause mortality at 90 days was 10.3% in the PCT-guided group vs. 8.2% in standard care (P = 0.316). Thirty-day readmission was significantly higher in the PCT-guided group vs. standard care but the difference vanished until day 90. The rate of pneumonia was overall low (7.5%) and not different between groups. Conclusions: In patients with AHF, a strategy of PCT-guided initiation of ABX was not more effective than a standard care strategy in improving clinical outcomes

Multicentre cross-sectional observational registry to monitor the safety of early discharge after rule-out of acute myocardial infarction by copeptin and troponin: the Pro-Core registry

Objectives: There is sparse information on the safety of early primary discharge from the emergency department (ED) after rule-out of myocardial infarction in suspected acute coronary syndrome (ACS). This prospective registry aimed to confirm randomised study results in patients at low-to-intermediate risk, with a broader spectrum of symptoms, across different institutional standards and with a range of local troponin assays including high-sensitivity cTn (hs-cTn), cardiac troponin (cTn) and point-of-care troponin (POC Tn). Design Prospective, multicentre European registry. Setting 18 emergency departments in nine European countries (Germany, Austria, Switzerland, France, Spain, UK, Turkey, Lithuania and Hungary) Participants: The final study cohort consisted of 2294 patients (57.2% males, median age 57 years) with suspected ACS. Interventions: Using the new dual markers strategy, 1477 patients were eligible for direct discharge, which was realised in 974 (42.5%) of patients. Main outcome measures: The primary endpoint was allcause mortality at 30 days. Results: Compared with conventional workup after dual marker measurement, the median length of ED stay was 60 min shorter (228 min, 95% CI: 219 to 239 min vs 288 min, 95% CI: 279 to 300 min) in the primary dual marker strategy (DMS) discharge group. All-cause mortality was 0.1% (95% CI: 0% to 0.6%) in the primary DMS discharge group versus 1.1% (95% CI: 0.6% to 1.8%) in the conventional workup group after dual marker measurement. Conventional workup instead of discharge despite negative DMS biomarkers was observed in 503 patients (21.9%) and associated with higher prevalence of ACS (17.1% vs 0.9%, p<0.001), cardiac diagnoses (55.2% vs 23.5%, p<0.001) and risk factors (p<0.01), but with a similar all-cause mortality of 0.2% (95% CI: 0% to 1.1%) versus primary DMS discharge (p=0.64). Conclusions Copeptin on top of cardiac troponin supports safe discharge in patients with chest pain or other symptoms suggestive of ACS under routine conditions with the use of a broad spectrum of local standard POC, conventional and high-sensitivity troponin assays. Trial registration number NCT02490969