ESMO expert consensus statements on the screening and management of financial toxicity in patients with cancer.

BACKGROUND: Financial toxicity, defined as both the objective financial burden and subjective financial distress from a cancer diagnosis and its treatment, is a topic of interest in the assessment of the quality of life of patients with cancer and their families. Current evidence implicates financial toxicity in psychosocial, economic and other harms, leading to suboptimal cancer outcomes along the entire trajectory of diagnosis, treatment, supportive care, survivorship and palliation. This paper presents the results of a virtual consensus, based on the evidence base to date, on the screening and management of financial toxicity in patients with and beyond cancer organized by the European Society for Medical Oncology (ESMO) in 2022. METHODS: A Delphi panel of 19 experts from 11 countries was convened taking into account multidisciplinarity, diversity in health system contexts and research relevance. The international panel of experts was divided into four working groups (WGs) to address questions relating to distinct thematic areas: patients with cancer at risk of financial toxicity; management of financial toxicity during the initial phase of treatment at the hospital/ambulatory settings; financial toxicity during the continuing phase and at end of life; and financial risk protection for survivors of cancer, and in cancer recurrence. After comprehensively reviewing the literature, statements were developed by the WGs and then presented to the entire panel for further discussion and amendment, and voting. RESULTS AND DISCUSSION: A total of 25 evidence-informed consensus statements were developed, which answer 13 questions on financial toxicity. They cover evidence summaries, practice recommendations/guiding statements and policy recommendations relevant across health systems. These consensus statements aim to provide a more comprehensive understanding of financial toxicity and guide clinicians globally in mitigating its impact, emphasizing the importance of further research, best practices and guidelines.

Knowledge of cancer risk factors and risk-reduction in high-income countries.

According to the International Public Opinion Survey on Cancer 2020, on average, nearly 1 in 3 individuals in high-income countries (HIC) did not engage in risk reduction. Meanwhile, only 1 in 4 individuals reported being aware that eating red and processed meat was a cancer risk factor. We explored relations between risk-reduction behavior and self-perceived knowledge of cancer risk factors in HIC using data from the survey. The average effect of knowledge, and interaction effects with country and risk factor were estimated using a linear model fit. The model included main and two-way interaction terms between the proportion of respondents who knew about a specific risk factor, and risk factor and country. The overall significance of knowledge impact and interaction terms was tested using type III tests in ANCOVA. Based on our analysis, we found that knowledge of cancer risk factors was positively associated with risk reduction in HIC. Every unit increase in the proportion of the population knowledgeable about a cancer risk factor, on average across risk factors and HIC, significantly increases the proportion of people engaging in risk reduction by approximately 16.91%. A significant interaction effect was found between knowledge and country, but not between knowledge and risk factor. Using respondents' non-response options to represent lack of risk factor knowledge Japan had the largest percentage of individuals lacking knowledge about risk factors as well as the largest percentage of individuals not engaging in risk reduction.

Features of aerobic granular sludge formation treating fluctuating industrial saline wastewater at pilot scale.

A pilot-scale sequencing batch reactor, with a working volume of 3 m3, was installed in a fish cannery to develop aerobic granular sludge treating the produced effluents. Depending on the nitrogen (N) and organic matter (COD) concentration, the effluents were named in this study as medium-low-strength (Stage I) and high-strength (Stage II) wastewater. The composition of the wastewater was found to be a crucial factor to select granule-forming organisms. With medium-low-strength wastewater as feeding, the first granules were observed after 30 days, but the extremely high COD/N ratios of the wastewater provoked the overgrowth of filamentous bacteria after 4 months of operation (Stage I). When treating high-strength wastewater, stable aggregates with good settleability appeared, but well-shaped granules were not observed since the granulation process was not completed. The system was able to remove both COD (70-95%) and N (30-90%) treating both types of effluents. Biomass growth was the main N removal pathway. The reactor was found to be robust against factory production stops and, thus, a suitable alternative to treat wastewater from industries with discontinuous operation.

Germinal BRCA1-2 pathogenic variants (gBRCA1-2pv) and pancreatic cancer: epidemiology of an Italian patient cohort.

OBJECTIVE: Germline BRCA1-2 pathogenic variants (gBRCApv) increase the risk of pancreatic cancer and predict for response to platinating agents and poly(ADP-ribose) polymerase inhibitors. Data on worldwide gBRCApv incidence among pancreatic ductal adenocarcinoma (PDAC) patients are sparse and describe a remarkable geographic heterogeneity. The aim of this study is to analyze the epidemiology of gBRCApv in Italian patients. MATERIALS AND METHODS: Patients of any age with pancreatic adenocarcinoma, screened within 3 months from diagnosis for gBRCApv in Italian oncologic centers systematically performing tests without any selection. For the purposes of our analysis, breast, ovarian, pancreas, and prostate cancer in a patient's family history was considered as potentially BRCA-associated. Patients or disease characteristics were examined using the χ2 test or Fisher's exact test for qualitative variables and the Student's t-test or Mann-Whitney test for continuous variables, as appropriate. RESULTS: Between June 2015 and May 2020, 939 patients were tested by 14 Italian centers; 492 (52%) males, median age 62 years (range 28-87), 569 (61%) metastatic, 273 (29%) with a family history of potentially BRCA-associated cancers. gBRCA1-2pv were found in 76 patients (8.1%; 9.1% in metastatic; 6.4% in non-metastatic). The gBRCA2/gBRCA1 ratio was 5.4 : 1. Patients with gBRCApv were younger compared with wild-type (59 versus 62 years, P = 0.01). The gBRCApv rate was 17.1% among patients <40 years old, 10.4% among patients 41-50 years old, 9.2% among patients 51-60 years old, 6.7% among patients aged 61-70 years, and 6.2% among patients >70 years old (none out of 94 patients >73 years old). gBRCApv frequency in 845 patients <74 years old was 9%. Patients with/without a family history of potentially BRCA-associated tumors had 14%/6% mutations. CONCLUSION: Based on our findings of a gBRCApv incidence higher than expected in a real-life series of Italian patients with incident PDAC, we recommend screening all PDAC patients <74 years old, regardless of family history and stage, due to the therapeutic implications and cancer risk prevention in patients' relatives.

Quantitative analysis of p16 methylation in Barrett's carcinogenesis.

p16 hypermethylation in Barrett's carcinogenesis has been evaluated in studies which did not take into account sample heterogeneity and yielded qualitative (methylated/unmethylated) instead of accurate quantitative (percentage of CpG methylation) data. We aimed to measure the degree of p16 methylation in pure samples representing all the steps of Barrett's tumorogenesis and to evaluate the influence of sample heterogeneity in methylation analysis. METHODS: 77 paraffin-embedded human esophageal samples were analyzed. Histological grading was established by two pathologists in: negative for dysplasia, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia and adenocarcinoma. Areas of interest were selected by laser-capture microdissection. p16 methylation was quantified by pyrosequencing. An adjacent section of the whole sample was also analyzed to compare methylation data. RESULTS: After microdissection, we obtained 15 samples of squamous epithelium, 36 non-dysplastic Barrett's esophagus, 3 indefinite for dysplasia, 24 low-grade dysplasia, 4 high-grade dysplasia and 12 adenocarcinoma. Squamous epithelium showed the lowest methylation rates: 6% (IQR 5-11) vs. 11%(7-39.50) in negative/indefinite for dysplasia, p<0.01; 10.60%(6-24) in low-grade dysplasia, p<0.05; and 44.50%(9-66.75) in high-grade dysplasia/adenocarcinoma, p<0.01. This latter group also exhibited higher methylation rates than Barrett's epithelium with and without low-grade dysplasia (p<0.05). p16 methylation rates of microdissected and non-microdissected samples did not correlate unless the considered histological alteration comprised >71% of the sample. CONCLUSIONS: p16 methylation is an early event in Barrett's carcinogenesis which increases with the severity of histological alteration. p16 methylation rates are profoundly influenced by sample heterogeneity, so selection of samples is crucial in order to detect differences.

Target Strength and swimbladder morphology of Mueller's pearlside (Maurolicus muelleri).

In the last few years, there has been increasing interest in the commercial exploitation of mesopelagic fish and a trawl-acoustic methodology has been recommended to make estimates of abundance of these resources. This study provides relevant information on the scattering properties of a key mesopelagic fish species in the Bay of Biscay, Mueller's pearlside (Maurolicus muelleri), necessary to convert the acoustic density into numerical abundance. The target strength (TS) of pearlside was estimated for the first time at five frequencies commonly used in acoustic surveys. A high-density filter was applied to reduce the bias derived from overlapping echoes erroneously assigned to single targets. Its relationship with fish length (b20) was also determined (-65.9 ± 2, -69.2 ± 3, -69.2 ± 2, -69.5 ± 2.5 and -71.5 ± 2.5 dB at 18, 38, 70, 120 and 200 kHz, respectively). Biomass estimates of pearlside in the Bay of Biscay during the four years of study (2014-2017) are given using the 38 kHz frequency. Morphological measurements of the swimbladder were obtained from soft X-ray images and used in the backscattering simulation of a gas-filled ellipsoid. Pearlside is a physoclist species, which means that they can compensate the swimbadder volume against pressure changes. However, the best fit between the model and the experimental data showed that they lose that capacity during the trawling process, when the swimbladder volume is affected by Boyle's law.

Does the feeding strategy enhance the aerobic granular sludge stability treating saline effluents?

The development and stability of aerobic granular sludge (AGS) was studied in two Sequencing Batch Reactors (SBRs) treating fish canning wastewater. R1 cycle comprised a fully aerobic reaction phase, while R2 cycle included a plug-flow anaerobic feeding/reaction followed by an aerobic reaction phase. The performance of the AGS reactors was compared treating the same effluents with variable salt concentrations (4.97-13.45 g NaCl/L) and organic loading rates (OLR, 1.80-6.65 kg CODs/(m3·d)). Granulation process was faster in R2 (day 34) than in R1 (day 90), however the granular biomass formed in the fully aerobic configuration was more stable to the variable feeding composition. Thus, in R1 solid retention times (SRT), up to 15.2 days, longer than in R2, up to 5.8 days, were achieved. These long SRTs values helped the retention of nitrifying organisms and provoked the increase of the nitrogen removal efficiency to 80% in R1 while it was approximately of 40% in R2. However, the presence of an anaerobic feeding/reaction phase increased the organic matter removal efficiency in R2 (80-90%) which was higher than in R1 with a fully aerobic phase (75-85%). Furthermore, in R2 glycogen-accumulating organisms (GAOs) dominated inside the granules instead of phosphorous-accumulating organisms (PAOs), suggesting that GAOs resist better the stressful conditions of a variable and high-saline influent. In terms of AGS properties an anaerobic feeding/reaction phase is not beneficial, however it enables the production of a better quality effluent.

Survival prediction models in motor neuron disease.

BACKGROUND AND PURPOSE: This study aimed to assess the predictive value of multimodal brain magnetic resonance imaging (MRI) on survival in a large cohort of patients with motor neuron disease (MND), in combination with clinical and cognitive features. METHODS: Two hundred MND patients were followed up prospectively for a median of 4.13 years. At baseline, subjects underwent neurological examination, cognitive assessment and brain MRI. Grey matter volumes of cortical and subcortical structures and diffusion tensor MRI metrics of white matter tracts were obtained. A multivariable Royston-Parmar survival model was created using clinical and cognitive variables. The increase of survival prediction accuracy provided by MRI variables was assessed. RESULTS: The multivariable clinical model included predominant upper or lower motor neuron presentations and diagnostic delay as significant prognostic predictors, reaching an area under the receiver operating characteristic curve (AUC) of a 4-year survival prediction of 0.79. The combined clinical and MRI model including selected grey matter fronto-temporal volumes and diffusion tensor MRI metrics of the corticospinal and extra-motor tracts reached an AUC of 0.89. Considering amyotrophic lateral sclerosis patients only, the clinical model including diagnostic delay and semantic fluency scores provided an AUC of 0.62, whereas the combined clinical and MRI model reached an AUC of 0.77. CONCLUSION: Our study demonstrated that brain MRI measures of motor and extra-motor structural damage, when combined with clinical and cognitive features, are useful predictors of survival in patients with MND, particularly when a diagnosis of amyotrophic lateral sclerosis is made.

Novel system configuration with activated sludge like-geometry to develop aerobic granular biomass under continuous flow.

A novel continuous flow system with "flat geometry" composed by two completely mixed aerobic tanks in series and a settler was used to promote the formation of aerobic granular sludge. Making similarities of this system with a typical sequencing batch reactor (SBR), for aerobic granules cultivation, the value of the tank 1/tank 2 vol ratio and the biomass recirculation rate would correspond with the feast/famine length ratio and the length of the operational cycle, respectively, while the settler upflow liquid velocity imposed would be related to the settling time. From the three experiments performed the best results were obtained when the tank 1/tank 2 vol ratio was of 0.28, the sludge recycling ratio of 0.25 and the settler upflow velocity of 2.5 m/h. At these conditions the aggregates had settling velocities between 29 and 113 m/h, sludge volume index at 10 min (SVI10) of 70 mL/g TSS and diameters between 1.0 and 5.0 mm.

A cross-species approach to identify transcriptional regulators exemplified for Dnajc22 and Hnf4a.

There is an enormous need to make better use of the ever increasing wealth of publicly available genomic information and to utilize the tremendous progress in computational approaches in the life sciences. Transcriptional regulation of protein-coding genes is a major mechanism of controlling cellular functions. However, the myriad of transcription factors potentially controlling transcription of any given gene makes it often difficult to quickly identify the biological relevant transcription factors. Here, we report on the identification of Hnf4a as a major transcription factor of the so far unstudied DnaJ heat shock protein family (Hsp40) member C22 (Dnajc22). We propose an approach utilizing recent advances in computational biology and the wealth of publicly available genomic information guiding the identification of potential transcription factor candidates together with wet-lab experiments validating computational models. More specifically, the combined use of co-expression analyses based on self-organizing maps with sequence-based transcription factor binding prediction led to the identification of Hnf4a as the potential transcriptional regulator for Dnajc22 which was further corroborated using publicly available datasets on Hnf4a. Following this procedure, we determined its functional binding site in the murine Dnajc22 locus using ChIP-qPCR and luciferase assays and verified this regulatory loop in fruitfly, zebrafish, and humans.

Genetic divergence between Mexican Opuntia accessions inferred by polymerase chain reaction-restriction fragment length polymorphism analysis.

Molecular methods are powerful tools in characterizing and determining relationships between plants. The aim of this study was to study genetic divergence between 103 accessions of Mexican Opuntia. To accomplish this, polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis of three chloroplast intergenic spacers (atpB-rbcL, trnL-trnF, and psbA-trnH), one chloroplast gene (ycf1), two nuclear genes (ppc and PhyC), and one mitochondrial gene (cox3) was conducted. The amplified products from all the samples had very similar molecular sizes, and there were only very small differences between the undigested PCR amplicons for all regions, with the exception of ppc. We obtained 5850 bp from the seven regions, and 136 fragments were detected with eight enzymes, 37 of which (27.2%) were polymorphic. We found that 40% of the fragments from the chloroplast regions were polymorphic, 9.8% of the bands detected in the nuclear genes were polymorphic, and 20% of the bands in the mitochondrial locus were polymorphic. trnL-trnF and psbA-trnH were the most variable regions. The Nei and Li/Dice distance was very short, and ranged from 0 to 0.12; indeed, 77 of the 103 genotypes had the same genetic profile. All the xoconostle accessions (acidic fruits) were grouped together without being separated from three genotypes of prickly pear (sweet fruits). We assume that the genetic divergence between prickly pears and xoconostles is very low, and question the number of Opuntia species currently considered in Mexico.

Efecto de edulcorantes no calóricos en la calidad sensorial de jugo de naranja / Effect of non caloric sweeteners in sensory quality of orange juice

The consumption of non-caloric sweeteners is increasing in Chile being present in a wide variety of foods. The objective of this study was to evaluate the effect of distinct non-caloric sweeteners in the sensory qualities of orange juice as compared to sugar. The sweeteners selected were stevia, sucralose, saccharin and aspartame. These were added to natural juices in amounts equivalent to sugar in sweetness. Sensory analysis was performed with a group of youths of both sexes. An acceptability test was applied with an hedonic scale of 5 points evaluating aroma and flavor. The results indicate that the juice aroma is not affected by the use of sugar or sweeteners rated 3.5 to 3.7 (corresponding to "I like"). However, in the evaluation of flavor, significant differences were found, the best results corresponding to juice sweetened with sugar and sucralose (3,5 y 3,6 respectively).

El consumo de edulcorantes no calóricos es cada vez más masivo en nuestro país y están presentes en una gran variedad de alimentos. El objetivo de este estudio fue evaluar el efecto de edulcorantes no calóricos en la calidad sensorial de jugo de naranja, en comparación con el azúcar. Los edulcorantes seleccionados fueron estevia, sucralosa, sacarina y aspartamo. Se adicionaron a jugos naturales en cantidades equivalentes de dulzor respecto al azúcar. El análisis sensorial se realizó con un grupo de jóvenes de ambos sexos. Se aplicó una prueba de aceptabilidad con escala hedónica de 5 puntos, evaluando los parámetros de aroma y sabor. Los resultados indican que el aroma de los jugos no se ve afectado por la utilización de azúcar o edulcorantes, con calificación entre 3,5 a 3,7 (que corresponde a "me gusta"). Sin embargo, en la evaluación de sabor las muestras significativamente mejor evaluadas corresponden a jugos endulzados con azúcar y sucralosa (3,5 y 3,6 respectivamente).

New trend in non-invasive prenatal diagnosis.

The presence of fetal DNA in maternal plasma represents a source of genetic material which can be obtained non-invasively. To date, the translation of noninvasive prenatal diagnosis from research into clinical practice has been rather fragmented, and despite the advances in improving the analytical sensitivity of methods, distinguishing between fetal and maternal sequences remains very challenging. Thus, the field of noninvasive prenatal diagnosis of genetic diseases has yet to attain a routine application in clinical diagnostics. On the contrary, fetal sex determination in pregnancies at high risk of sex-linked disorders, tests for fetal RHD genotyping and non-invasive assessment of chromosomal aneuploidies are now available worldwide.

Why do patients engage in medical tourism?

Medical tourism is commonly perceived and popularly depicted as an economic issue, both at the system and individual levels. The decision to engage in medical tourism, however, is more complex, driven by patients' unmet need, the nature of services sought and the manner by which treatment is accessed. In order to beneficially employ the opportunities medical tourism offers, and address and contain possible threats and harms, an informed decision is crucial. This paper aims to enhance the current knowledge on medical tourism by isolating the focal content of the decisions that patients make. Based on the existing literature, it proposes a sequential decision-making process in opting for or against medical care abroad, and engaging in medical tourism, including considerations of the required treatments, location of treatment, and quality and safety issues attendant to seeking care. Accordingly, it comments on the imperative of access to health information and the current regulatory environment which impact on this increasingly popular and complex form of accessing and providing medical care.

Learning chronobiology by improving Wikipedia.

Although chronobiology is of growing interest to scientists, physicians, and the general public, access to recent discoveries and historical perspectives is limited. Wikipedia is an online, user-written encyclopedia that could enhance public access to current understanding in chronobiology. However, Wikipedia is lacking important information and is not universally trusted. Here, 46 students in a university course edited Wikipedia to enhance public access to important discoveries in chronobiology. Students worked for an average of 9 h each to evaluate the primary literature and available Wikipedia information, nominated sites for editing, and, after voting, edited the 15 Wikipedia pages they determined to be highest priorities. This assignment (http://www.nslc.wustl.edu/courses/Bio4030/wikipedia_project.html) was easy to implement, required relatively short time commitments from the professor and students, and had measurable impacts on Wikipedia and the students. Students created 3 new Wikipedia sites, edited 12 additional sites, and cited 347 peer-reviewed articles. The targeted sites all became top hits in online search engines. Because their writing was and will be read by a worldwide audience, students found the experience rewarding. Students reported significantly increased comfort with reading, critiquing, and summarizing primary literature and benefited from seeing their work edited by other scientists and editors of Wikipedia. We conclude that, in a short project, students can assist in making chronobiology widely accessible and learn from the editorial process.

Impacto de la diabetes en la carga hospitalaria / Impact of diabetes on hospital consumption

Objetivo: Analizar el impacto de la diabetes en el consumo de recursos hospitalarios. Método: Se analizaron todos los ingresos de un hospital terciario en 2006, registrados en el conjunto mínimo básico de datos (CMBD). Se estudiaron las características demográficas, de complejidad y de uso de servicios de pacientes con y sin diabetes. Resultados: En el 14,11 % constaba el diagnóstico de diabetes. El 66,4 % fueron ingresos urgentes y un 6,2 % fallecieron en el hospital. El 24 % tuvo más de un ingreso durante el año de estudio. La estancia media fue de 10,26 días frente a los 7,72 de los no diabéticos (p < 0,001). Complejidad, número de diagnósticos secundarios, sexo, tipo de ingreso y tipo de GRD influyeron en la duración de la estancia. Conclusiones: El diagnóstico de diabetes es frecuente en los pacientes hospitalizados (14 %) y estos pacientes presentan estancias más elevadas (AU)

Objective: To analyze the impact of diabetes on hospital resources utilization by inpatients. Method: We analyzed all the episodes of hospitalisation in the year 2006 of a tertiary hospital by means of the Basic Minimun data Set (CMBD).We studied demographic characteristics, case-mix, and use of hospital services for patients with and without diabetes. Results: A total of 28.383 episodes of hospitalisation wereregistered and out of these: 14.11 % were diabetic patients. Out of the total episodes, 66.4 % were emergency admissions with a hospital mortality rate of 6.2 %. Of these patients 24 % had more than one episode of hospitalisation during the study time period. The mean stay in the hospital was 10.26 days. Variables such as the complexity, the number of secondary diagnosis, sex, type of admission and the type of GRD’S affects the mean hospital stay in these patients. Conclusions: Diabetic patients account for more than 14 % of hospital admissions, and have a higher average stay than non-diabetics (AU)

Fatal respiratory failure in a full-term newborn with two ABCA3 gene mutations: a case report.

Genetic mutations associated with pulmonary surfactant protein deficiency are associated with diverse clinical phenotypes. Mutations of the surfactant protein B and C genes were the first to be described. In 2004, fatal surfactant deficiency in newborns due to mutations of the gene encoding the adenosine triphosphate-binding cassette transporter A3 (ABCA3) was first reported. Few cases of lethal adenosine triphosphate-binding cassette transporter A3 mutations have been described to date. In our report, we describe a full-term newborn that died because of respiratory failure secondary to an uncommon ABCA3 genetic configuration.