Polygenic risk scores (PRSs) aggregate the many small effects of alleles across the human genome to estimate the risk of a disease or disease-related trait for an individual. The potential benefits ...of PRSs include cost-effective enhancement of primary disease prevention, more refined diagnoses and improved precision when prescribing medicines. However, these must be weighed against the potential risks, such as uncertainties and biases in PRS performance, as well as potential misunderstanding and misuse of these within medical practice and in wider society. By addressing key issues including gaps in best practices, risk communication and regulatory frameworks, PRSs can be used responsibly to improve human health. Here, the International Common Disease Alliance's PRS Task Force, a multidisciplinary group comprising expertise in genetics, law, ethics, behavioral science and more, highlights recent research to provide a comprehensive summary of the state of polygenic score research, as well as the needs and challenges as PRSs move closer to widespread use in the clinic.
•Intensity modulated proton therapy (IMPT) is a sophisticated mode of proton therapy.•Dosimetric studies have demonstrated the superiority of IMPT over IMRT to improve dose sparing of organs in ...located in the head and neck.•There is clinical evidence that IMPT can translate to toxicity reductions for patients with HNCs.•This review will discuss existing literature and future directions of IMPT use for HNCs.
Radiation therapy plays an integral role in the management of head and neck cancers (HNCs). While most HNC patients have historically been treated with photon-based radiation techniques such as intensity modulated radiation therapy (IMRT), there is a growing awareness of the potential clinical benefits of proton therapy over IMRT in the definitive, postoperative and reirradiation settings given the unique physical properties of protons. Intensity modulated proton therapy (IMPT), also known as “pencil beam proton therapy,” is a sophisticated mode of proton therapy that is analogous to IMRT and an active area of investigation in cancer care. Multifield optimization IMPT allows for high quality plans that can target superficially located HNCs as well as large neck volumes while significantly reducing integral doses. Several dosimetric studies have demonstrated the superiority of IMPT over IMRT to improve dose sparing of nearby organs such as the larynx, salivary glands, and esophagus. Evidence of the clinical translation of these dosimetric advantages has been demonstrated with documented toxicity reductions (such as decreased feeding tube dependency) after IMPT for patients with HNCs. While there are relative challenges to IMPT planning that exist today such as particle range uncertainties and high sensitivity to anatomical changes, ongoing investigations in image-guidance techniques and robust optimization methods are promising. A systematic approach towards utilizing IMPT and additional prospective studies are necessary in order to more accurately estimate the clinical benefit of IMPT over IMRT and passive proton therapy on a case-by-case basis for patients with sub-site specific HNCs.
Clinical efficiency is a key component of the value-based care model and a driver of patient satisfaction. The purpose of this study was to identify and address inefficiencies at a high-volume ...radiation oncology clinic.
Patient flow analysis (PFA) was used to create process maps and optimize the workflow of consultation visits in a gastrointestinal radiation oncology clinic at a large academic cancer center. Metrics such as cycle times, waiting times, and rooming times were assessed by using a real-time patient status function in the electronic medical record for 556 consults and compared between before vs after implementation of the PFA recommendations.
The initial PFA revealed four inefficiencies: (1) protracted rooming time, (2) inefficient communications, (3) duplicated tasks, and (4) ambiguous clinical roles. We analyzed 485 consult-visits before the PFA and 71 after the PFA. The PFA recommendations led to reductions in overall median cycle time by 21% (91 min vs 72 min, p < 0.001), in cumulative waiting times by 64% (45 min vs 16 min; p < 0.001), which included waiting room time (14 min vs 5 min; p < 0.001) and wait for physician (20 min vs. 6 min; p < 0.001). Slightly less than one-quarter (22%) of consult visits before the PFA lasted > 2 h vs. 0% after implementation of the recommendations (p < 0.001). Similarly, the proportion of visits requiring < 1 h was 16% before PFA vs 34% afterward (p < 0.001).
PFA can be used to identify clinical inefficiencies and optimize workflows in radiation oncology consultation clinics, and implementing their findings can significantly improve cycle times and waiting times. Potential downstream effects of these interventions include improved patient experience, decreased staff burnout, financial savings, and opportunities for expanding clinical capacity.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Camera traps (CTs) are used for wildlife monitoring globally. How CTs are used in wildlife studies across Africa, however, remains unknown. We provide the first literature review of CT studies ...conducted across Africa, to describe where, to what end, and by whom CTs are used, and to identify apparent gaps in the use of CTs. We found 172 CT studies published across 60 scientific journals, conducted in 30 of 55 African countries from 2005 to 2017. Most studies were conducted over a single year/season (74%) and primarily addressed habitat use/species distribution (43%), species presence/richness (38.4%), behaviour (35.5%) or demographics (29.7%). Most studies took place in forest (52%), woodland (33%) and grassland (33%) habitat types, and focused on a single species (45.3%). Carnivores were the most commonly studied species group (86%), followed by large herbivores (58%) and primates (38%). Our results suggest that camera trapping is rapidly increasing in use across Africa and potentially driven by country‐based economic factors; however, there is room for improvement. CTs could be expanded in use for studies on underrepresented taxa (i.e. small mammals, reptiles and birds), investigations of human–wildlife conflict and understudied ecoregions (i.e. Sahara Desert).
Résumé
Les pièges photographiques (CT) sont utilisés dans le monde entier pour le suivi de la faune sauvage. Mais on ne sait pas comment les CT sont utilisés dans les études de la faune en Afrique. Nous proposons ici la première analyse de la littérature portant sur les études menées par CT en Afrique, pour décrire où et qui s'en sert, et pour identifier les lacunes apparentes de leur utilisation. Nous avons trouvé 172 publications sur des études réalisées avec CT dans 60 revues scientifiques, dans 30 des 55 pays Africains entre 2005 et 2017. La plupart des études avaient été menées en une seule année/saison (74%) et concernaient principalement l'utilisation des habitats/la distribution des espèces (43%), la présence/richesse en espèces (38.4%), le comportement (35.5%) ou la démographie (29.7%). La plupart des études s’étaient déroulées en forêt (52%), zone boisée (33%) et prairie (33%) et se focalisaient sur une seule espèce (45.3%). Les carnivores étaient le groupe le plus fréquemment étudié (86%), suivis par les grands herbivores (58%) et les primates (38%). Nos résultats laissent penser que l'utilisation du piégeage photographique est en croissance rapide dans toute l'Afrique, peut‐être encouragée par des facteurs économiques nationaux. Mais il y a moyen de faire mieux. On pourrait étendre l'utilisation des CT à des études de taxons sous‐représentés (e.x. petits mammifères, reptiles, oiseaux), à des recherches sur des conflits hommes‐faune sauvage, et à des écorégions trop peu étudiées (e.x. Désert du Sahara).
This study analyzes practice patterns, treatment-related mortality, survival, and predictors thereof in elderly patients with early-stage esophageal cancer (EC).
The National Cancer Data Base was ...queried for cT1-2 N0 EC in patients 80 years of age and older. Patients were divided into four treatment groups: observation (Obs), chemoradiotherapy (CRT), local excision (LE), and esophagectomy (Eso). Patient, tumor, and treatment parameters were extracted and compared. Analyses were performed on overall survival (OS) and postoperative 30- and 90-day mortality.
A total of 923 patients from 2004 to 2012 were analyzed. Of these, 43% underwent clinical Obs, 22% underwent CRT, 25% underwent LE, and 10% underwent Eso. Patients undergoing Obs were older, had more comorbidities, were treated at nonacademic centers, and lived 25 miles or less from the facility. Patients receiving an operation (Eso or LE) were more often younger, male, white, and in the top income quartile. The postoperative 30-day mortality rates in the LE and Eso groups were 1.3% and 9.6%, respectively (p < 0.001) and increased to 2.6% and 20.2% at 90 days, respectively (p < 0.001). The 5-year OS rate was 7% for Obs, 20% for CRT, 33% for LE, and 45% for Eso (p < 0.001). Multivariate analyses showed improved OS with any local definitive therapy: CRT (hazard ratio HR = 0.42, 95% confidence interval CI: 0.34–0.52, p < 0.001), LE (HR = 0.3, 95% CI: 0.24–0.38, p < 0.001), and Eso (HR = 0.32, 95% CI: 0.23–0.44, p < 0.001).
There are noteworthy demographic, socioeconomic, and regional disparities influencing management of elderly patients with stage I EC. Despite high rates of Obs, careful consideration of all local therapy options is warranted, given the improved outcomes with treatment.
•Non-discriminant derivatization of biological samples using DmPABr reagent.•Single RPLC-MS/MS analysis in positive ionisation mode provides full coverage.•Absolute quantification utilising internal ...standards labelled by stable isotopes.•Proof of concept for amines, carboxylic acids and thiol-containing metabolites.•Application to a variety of biological matrices including urine and cell extracts.
Recent advances in metabolomics have enabled larger proportions of the human metabolome to be analyzed quantitatively. However, this usually requires the use of several chromatographic methods coupled to mass spectrometry to cover the wide range of polarity, acidity/basicity and concentration of metabolites. Chemical derivatization allows in principle a wide coverage in a single method, as it affects both the separation and the detection of metabolites: it increases retention, stabilizes the analytes and improves the sensitivity of the analytes. The majority of quantitative derivatization techniques for LC–MS in metabolomics react with amines, phenols and thiols; however, there are unfortunately very few methods that can target carboxylic acids at the same time, which contribute to a large proportion of the human metabolome. Here, we describe a derivatization technique which simultaneously labels carboxylic acids, thiols and amines using the reagent dimethylaminophenacyl bromide (DmPABr). We further improve the quantitation by employing isotope-coded derivatization (ICD), which uses internal standards derivatized with an isotopically-labelled reagent (DmPABr-D6). We demonstrate the ability to measure and quantify 64 central carbon and energy-related metabolites including amino acids, N-acetylated amino acids, metabolites from the TCA cycle and pyruvate metabolism, acylcarnitines and medium-/long-chain fatty acids. To demonstrate the applicability of the analytical approach, we analyzed urine and SUIT-2 cells utilizing a 15-minute single UPLC-MS/MS method in positive ionization mode. SUIT-2 cells exposed to rotenone showed definitive changes in 28 out of the 64 metabolites, including metabolites from all 7 classes mentioned. By realizing the full potential of DmPABr to derivatize and quantify amines and thiols in addition to carboxylic acids, we extended the coverage of the metabolome, producing a strong platform that can be further applied to a variety of biological studies.
Background
Following complete resection of pN2 non-small cell lung cancer (NSCLC), national guidelines recommend either sequential (sCRT) or concurrent chemoradiotherapy (cCRT). This is the largest ...study to date evaluating survival between both approaches. In sCRT patients, sequencing ‘chemotherapy first’ versus ‘radiotherapy first’ was also addressed.
Methods
The National Cancer Data Base (NCDB) was queried for patients with primary NSCLC undergoing surgery (without neoadjuvant radiotherapy or chemotherapy), pN2 disease with negative surgical margins, and receiving postoperative CRT. Multivariable logistic regression ascertained factors associated with cCRT administration. Kaplan–Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS. Propensity matching was performed to address group imbalances and indication biases.
Results
Of 1924 total patients, 1115 (58%) received sCRT and 809 (42%) underwent cCRT. Median OS in the sCRT and cCRT cohorts was 53 months versus 37 months (
p
< 0.001); differences persisted following propensity matching (
p
= 0.002). In the sCRT population, there was a trend for higher OS in the ‘chemotherapy first’ group, relative to ‘radiotherapy first’ (55 vs. 44 months,
p
= 0.079), but there were no statistically apparent differences following propensity matching (
p
= 0.302).
Conclusions
For completely resected pN2 NSCLC, delivering adjuvant sCRT was associated with improved survival over cCRT. Toxicity-related factors may help to explain these results but need to be better addressed in further investigations. Differential sequencing of sCRT did not appear to affect survival.
: Metaplastic breast cancer (BC) is an uncommon yet aggressive histologic subtype of BC. We sought to identify factors associated with its diagnosis and compare the management and outcomes of ...metaplastic BC with those of other BCs and triple negative invasive ductal carcinoma in particular given how often it has a triple negative phenotype.
: We identified women diagnosed with invasive BC in 2010-2014 in the National Cancer Data Base, and used univariate analysis to compare baseline patient and tumor characteristics by BC subtype. Overall survival (OS) was estimated with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to identify independent predictors of OS.
: Of 247,355 cases, 2,084 (0.8%) were metaplastic BC, 55,998 (23%) triple negative BC, and 77% other BC. Relative to non-metaplastic BC, women with metaplastic BC were more likely to be older at diagnosis (median age, 62 vs. 59 years), have ≥1 comorbid conditions (22% vs. 18%), and be on Medicare (41% vs. 33%;
<0.001). Metaplastic BCs tended to be basal-like (77%), and relative to triple-negative or other BC, metaplastic BC was associated with higher clinical T status (cT3-4, 18% vs. 11%, 8%), no clinical nodal involvement (cN0, 86%, 77%, 80%), no lymphovascular invasion (72%, 65%, 62%), and high-grade tumors (71%, 77%, 35%) (
<0.001). Most metaplastic BCs were treated with mastectomy (58%), sentinel lymph node dissection (65%), chest wall or breast irradiation (74%), and chemotherapy (75%) as adjuvant therapy (60%). At a median follow-up time of 44.5 months, OS rates were lower for metaplastic BC than for triple-negative or other BC across all clinical stages at 5 years (stage I, 85%, 87%, 91%; II, 73%, 77%, 87%; III, 43%, 53%, 75%) and at 3 years (Stage IV, 15%, 22%, 64%;
<0
001). On multivariate analysis, increasing age, advanced clinical stage, lymphovascular invasion, axillary (vs. sentinel) node dissection, and no radiation or chemotherapy were associated with worse outcomes in metaplastic BC. Extent of surgery affected survival for triple-negative and other BC but not for metaplastic BC.
: Outcomes for metaplastic BC continue to be worse than those for other BC subtypes despite modern treatments. Optimizing systemic therapy options, which was a significant predictor of survival, should be a priority in managing metaplastic BC.
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