Autologous Hematopoietic Stem Cell Transplantation (AHSCT): Standard of Care for Relapsing–Remitting Multiple Sclerosis Patients

Abstract Autologous hematopoietic stem cell transplantation (AHSCT) has been used in the treatment of highly active multiple sclerosis (MS) for over two decades. It has been demonstrated to be highly efficacious in relapsing–remitting (RR) MS patients failing to respond to disease-modifying drugs (DMDs). AHSCT guarantees higher rates of no evidence of disease activity (NEDA) than those achieved with any other DMDs, but it is also associated with greater short-term risks which have limited its use. In the 2019 updated EBMT and ASBMT guidelines, which review the clinical evidence of AHSCT in MS, AHSCT indication for highly active RRMS has changed from “clinical option” to “standard of care”. On this basis, AHSCT must be proposed on equal footing with second-line DMDs to patients with highly active RRMS, instead of being considered as a last resort after failure of all available treatments. The decision-making process requires a close collaboration between transplant hematologists and neurologists and a full discussion of risk–benefit of AHSCT and alternative treatments. In this context, we propose a standardized protocol for decision-making and informed consent process

Nitrogen fertilization and arbuscular mycorrhizal fungi do not mitigate the adverse effects of soil contamination with polypropylene microfibers on maize growth

Soil contamination with microplastics may adversely affect soil properties and functions and consequently crop productivity. In this study, we wanted to verify whether the adverse effects of microplastics in the soil on maize plants (Zea mays L.) are due to a reduction in nitrogen (N) availability and a reduced capacity to establish symbiotic relationships with arbuscular mycorrhizal (AM) fungi. To do this, we performed a pot experiment in which a clayey soil was exposed to two environmentally relevant concentrations of polypropylene (PP; one of the most used plastic materials) microfibers (0.4% and 0.8% w/w) with or without the addition of N fertilizer and with or without inoculation with AM fungi. The experiment began after the soil had been incubated at 23 °C for 5 months. Soil contamination with PP considerably reduced maize root and shoot biomass, leaf area, N uptake, and N content in tissue. The adverse effects increased with the concentration of PP in the soil. Adding N to the soil did not alleviate the detrimental effects of PP on plant growth, which suggests that other factors besides N availability played a major role. Similarly, although the presence of PP did not inhibit root colonization by AM fungi (no differences were observed for this trait between the uncontaminated and PP-contaminated soils), the addition of the fungal inoculum to the soil failed to mitigate the negative impact of PP on maize growth. Quite the opposite: mycorrhization further reduced maize root biomass accumulation. Undoubtedly, much research remains to be done to shed light on the mechanisms involved in determining plant behavior in microplastic-contaminated soils, which are most likely complex. This research is a priority given the magnitude of this contamination and its potential implications for human and environmental health

Acute kidney injury and acute kidney disease in high-dose cisplatin-treated head and neck cancer

Background: In locally advanced head and neck squamous cell carcinoma (LA-SCCHN) at least 200mg/m2 (standard dose 300 mg/m2) of cisplatin concomitant with radiotherapy represents the standard of care, both in postoperative and conservative settings. Nevertheless, high dose administration every 3 weeks is often replaced with low dose weekly cisplatin to avoid toxicities like kidney injury, though often failing to reach the therapeutic dose. Our aim was to investigate the incidence of renal impairment in the real-life setting, integrating high dose cisplatin with adequate supportive therapy, and to explore both Acute Kidney Injury (AKI) and Acute Kidney Disease (AKD), a recently described clinical renal syndrome that encompasses functional alterations of the kidney lasting fewer than 3 months. Methods: One hundred and nine consecutive patients affected by LA-SCCHN and treated with at least a cumulative dosage of 200 mg/m2 of cisplatin concomitant with radiotherapy were enrolled in this prospective observational study. Results: AKI was reported in 12.8% of patients, 50% of whom were stage 1 (KDIGO criteria), while 25.7% of the cohort developed AKD. Patients with baseline estimated Glomerular Filtration Rate (eGFR) < 90 ml/min showed a higher incidence of AKD (36.2% vs 17.7%). Hypertension, baseline eGFR, and therapy with Renin-angiotensin-aldosterone system inhibitors proved to be significant factors associated with both AKI and AKD. Conclusion: AKI and AKD are not rare complications of high-dose cisplatin, but an appropriate prevention strategy and accurate monitoring of patients during treatment could lead to a reduction of the burden of these conditions

Somatostatin receptor PET/CT imaging for the detection and staging of pancreatic NET. A systematic review and meta-analysis

We investigated the diagnostic performance of Somatostatin Receptor Positron Emission Tomography/Computed Tomography (SSR-PET/CT) for the detection of primary lesion and initial staging of pancreatic neuroendocrine tumors (pNETs). A comprehensive literature search up to January 2020 was performed selecting studies in presence of: sample size ≥10 patients; index test (i.e., 68Ga-DOTATOC or 68Ga-DOTANOC or 68Ga-DOTATATE PET/CT); and outcomes (i.e., detection rate (DR), true positive, true negative, false positive, and false-negative). The methodological quality was evaluated with QUADAS-2. Pooled DR and pooled sensitivity and specificity for the identification of the primary tumor were assessed by a patient-based and a lesion-based analysis. Thirty-eight studies were selected for the qualitative analysis, while 18 papers were included in the meta-analysis. The number of pNET patients ranged from 10 to 142, for a total of 1143 subjects. At patient-based analysis, the pooled sensitivity and specificity for the assessment of primary pNET were 79.6% (95% confidence interval (95%CI): 71–87%) and 95% (95%CI: 75–100%) with a heterogeneity of 59.6% and 51.5%, respectively. Pooled DR for the primary lesion was 81% (95%CI: 65–90%) and 92% (95%CI: 80–97%), respectively, at patient-based and lesion-based analysis. In conclusion, SSR-PET/CT has high DR and diagnostic performances for primary lesion and initial staging of pNETs

Predictors of Patient-Reported Dysphagia Following IMRT Plus Chemotherapy in Oropharyngeal Cancer

The aim of this cross-sectional study is to evaluate the factors associated with patient-reported dysphagia in patients affected by locally advanced oropharyngeal cancer (OPC) treated with definitive intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy (CHT), with or without induction CHT. We evaluated 148 OPC patients treated with IMRT and concurrent CHT, without evidence of disease and who had completed their treatment since at least 6 months. At their planned follow-up visit, patients underwent clinical evaluation and completed the M.D. Anderson dysphagia inventory (MDADI) questionnaire. The association between questionnaire composite score (MDADI-CS) and different patients\u2019 and tumor\u2019s characteristics and treatments (covariates) was investigated by univariable and multivariable analyses, the latter including only covariates significant at univariable analysis. With a median time from treatment end of 30 months [range 6\u201374 months, interquartile range (IQR) 16\u201350 months], the median (IQR) MDADI-CS was 72 (63\u201384). The majority of patients (82.4%) had a MDADI-CS 65 60. At multivariable analysis, female gender, human papilloma virus (HPV)-negative status, and moderate and severe clinician-rated xerostomia were significantly associated with lower MDADI-CS. Patient-perceived dysphagia was satisfactory or acceptable in the majority of patients. HPV status and xerostomia were confirmed as important predictive factors for swallowing dysfunction after radiochemotherapy. Data regarding female gender are new and deserve further investigation

MICROALGAE BIOPOLYMERS: A REVIEW

Algae are ubiquitous organisms whose capabilities have drawn much attention as of late in the bioengineering field due to their potential to enable a wide range of bioproducts. Microalgae are ideal organisms for the application of the biorefinery concept since they can be grown in wastewater and, at the same time, produce many products of commercial interest. These microorganisms are also known for their resilience to extreme environmental conditions and suitable cell growth rates. Beyond the known potential for biofuel production, these microorganisms can still produce other compounds, being lipids, pigments, vitamins, proteins, and polysaccharides, whose applications go from pharmaceutical to agricultural industries. Recently, the research focus has been directed to the biopolymer-producing ability of both micro- and macroalgae, as they can be rather varied and useful to many applications. However, this is still an ongoing research field, and new data are frequently added in the literature, notably on biomass processing, which can be done with the intent of use into dyes, bioplastics, paints, and even as biochar in solid fuel cells. Microalgae-based biopolymers can be used in a wide range of products, nevertheless, the resulting process efficiency and yields depend on the extraction process utilized, as well as on the microalgae species used and the culture conditions. Furthermore, the polymer extraction can be done directly with common solvents at atmospheric pressure or with other fluids, such as supercritical CO2 or subcritical solvents, and assisted by specific treatments, e.g., ultrasound and microwave. The residual biomass can still be used to produce other less valuable products, such as feedstock, and energy via combustion. In this sense, the present work aims to provide a state-of-the-art review on microalgae biopolymers. Issues related to the efficiency of current treatment methods, industrial applications, and environmental performance are presented and discussed. Besides, the perspectives in this area of knowledge are also a contribution of the present work, the extent to which scientific research is still under development

Development and Validation of the Career Competencies Indicators (CCI)

This paper describes the development and validation of the Career Competencies Indicator (CCI); a 43-item measure to assess career competencies. Following an extensive literature review, a comprehensive item generation process involving consultation with subject matter experts, a pilot study and a factor analytic study on a large sample yielded a seven factor structure; goal setting and career planning, self-knowledge, job-performance, career-related skills, knowledge of (office) politics, career guidance and networking, and feedback seeking and self-presentation. Coefficient alpha reliabilities of the seven dimensions ranged from .93 to .81. Convergent validity was established by showing below chance similarity between CCI sub-scales, and discrminant validity between the CCI sub-scales and the big five personality scales. The results also suggested criterion-related validity of the CCI, since career competencies were found to jointly predict objective and subjective career success

Galaxy populations in the Hydra i cluster from the VEGAS survey:I. Optical properties of a large sample of dwarf galaxies

At ~50 Mpc, the Hydra I cluster of galaxies is among the closest cluster in the z=0 Universe, and an ideal environment to study dwarf galaxy properties in a cluster environment. We exploit deep imaging data of the Hydra I cluster to construct a new photometric catalog of dwarf galaxies in the cluster core, which is then used to derive properties of the Hydra I cluster dwarf galaxies population as well as to compare with other clusters. Moreover, we investigate the dependency of dwarf galaxy properties on their surrounding environment. The new Hydra I dwarf catalog contains 317 galaxies with luminosity between -18.5<$M_r$<-11.5 mag, a semi-major axis larger than ~200 pc (a=0.84 arcsec), of which 202 are new detections, previously unknown dwarf galaxies in the Hydra I central region. We estimate that our detection efficiency reaches 50% at the limiting magnitude $M_r$=-11.5 mag, and at the mean effective surface brightness $\overline{\mu}_{e,r}$=26.5 mag/$arcsec^2$. We present the standard scaling relations for dwarf galaxies and compare them with other nearby clusters. We find that there are no observational differences for dwarfs scaling relations in clusters of different sizes. We study the spatial distribution of galaxies, finding evidence for the presence of substructures within half the virial radius. We also find that mid- and high-luminosity dwarfs ($M_r$<-14.5 mag) become on average redder toward the cluster center, and that they have a mild increase in $R_e$ with increasing clustercentric distance, similar to what is observed for the Fornax cluster. No clear clustercentric trends are reported with surface brightness and S\'ersic index. Considering galaxies in the same magnitude-bins, we find that for high and mid-luminosity dwarfs ($M_r$<-13.5 mag) the g-r color is redder for the brighter surface brightness and higher S\'ersic n index objects.Comment: Accepted for publication in A&A. 25 pages, 21 figure

The observational clinical registry (cohort design) of the European Reference Network on Rare Adult Solid Cancers: The protocol for the rare head and neck cancers

Care for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers. In the EU, a unique opportunity is provided by the European Reference Networks (ERN). The ERN EURACAN is dedicated to rare adults solid cancers, here we present the protocol of the EURACAN registry on rare head and neck cancers (ClinicalTrials.gov Identifier: NCT05483374). Study design Registry-based cohort study including only people with rare head and neck cancers. Objectives 1.To help describe the natural history of rare head and neck cancers; 2.To evaluate factors that influence prognosis; 3.To assess treatment effectiveness; 4.To measure indicators of quality of care. Methods Settings and participants It is an hospital based registry established in hospitals with expertise in head and neck cancers. Only adult patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses; salivary gland cancer in large and small salivary glands; and middle ear will be included in the registry. This registry won t select a sample of patients. Each patient in the facility who meets the above mentioned inclusion criteria will be followed prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for the patient follow-up. Variables Data will be collected on patient characteristics (eg. patient demographics, lifestyle, medical history, health status); exposure data (eg. disease, procedures, treatments of interest) and outcomes (e.g. survival, progression, progression-free survival, etc.). In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will be also collected. Statistical methods The data analyses will include descriptive statistics showing patterns of patients and cancers variables and indicators describing the quality of care. Multivariable Cox s proportional hazards model and Hazard ratios (HR) for all-cause or cause specific mortality will be used to determine independent predictors of overall survival, recurrence etc. Variables to include in the multivariable regression model will be selected based on the results of univariable analysis. The role of confounding or effect modifiers will be evaluated using stratified analysis or sensitivity analysis. To assess treatment effectiveness, multivariable models with propensity score adjustment and progression-free survival will be performed. Adequate statistical (eg. marginal structural model) methods will be used if time-varying treatments/ confounders and confounding by indication (selective prescribing) will be present. Results The registry initiated recruiting in May 2022. The estimated completion date is December 2030 upon agreement on the achievement of all the registry objectives. As of October 2022, the registry is recruiting. There will be a risk of limited representativeness due to the hospital-based nature of the registry and to the fact that hospital contributing to the registry are expert centres for these rare cancers. Clinical Follow-up could also be an issue but active search of the life status of the patients will be guaranteed

α-thalassaemia

Alpha-thalassaemia is inherited as an autosomal recessive disorder characterised by a microcytic hypochromic anaemia, and a clinical phenotype varying from almost asymptomatic to a lethal haemolytic anaemia