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Blanka Halamoda Kenzaoui1, Maya R Vilà2, Josep M Miquel2, Feride Cengelli1, Lucienne Juillerat-Jeanneret11Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland; 2Leitat Technological Center, Barcelona, SpainAbstract: Nanoparticles (NPs) are in clinical use or under development for therapeutic imaging and drug delivery. However, relatively little information exists concerning the uptake and transport of NPs across human colon cell layers, or their potential to invade three-dimensional models of human colon cells that better mimic the tissue structures of normal and tumoral colon. In order to gain such information, the interactions of biocompatible ultrasmall superparamagnetic iron oxide nanoparticles (USPIO NPs) (iron oxide core 9–10 nm) coated with either cationic polyvinylamine (aminoPVA) or anionic oleic acid with human HT-29 and Caco-2 colon cells was determined. The uptake of the cationic USPIO NPs was much higher than the uptake of the anionic USPIO NPs. The intracellular localization of aminoPVA USPIO NPs was confirmed in HT-29 cells by transmission electron microscopy that detected the iron oxide core. AminoPVA USPIO NPs invaded three-dimensional spheroids of both HT-29 and Caco-2 cells, whereas oleic acid-coated USPIO NPs could only invade Caco-2 spheroids. Neither cationic aminoPVA USPIO NPs nor anionic oleic acid-coated USPIO NPs were transported at detectable levels across the tight CacoReady™ intestinal barrier model or the more permeable mucus-secreting CacoGoblet™ model.Keywords: iron oxide nanoparticles, human colon cells, spheroids, transport, gastrointestinal barrier

Background: as chromium (Cr) is known to contaminate components of parenteral nutrition (PN), Cr-free PN is recommended for preterm infants. Exposure to Cr by PN in preterm infants is scarcely investigated., Objective: to describe Cr levels in plasma (Crp) and urine (Cru) during the first month of life in premature newborns ≤ 1500 g of birthweight (BW) receiving PN, and to evaluate the impact on postnatal clinical parameters., Methods: a prospective observational study. Cr-free PN was administered at day 1 of life and continued until full enteral feeding with fortified breastmilk began. Crp levels at day 15 and 30 and Cru at day 30 of life were assessed according to demographic factors, biochemical markers and postnatal morbidity., Results: 97 infants had a median gestational age (GA) of 29.9 weeks, and a median BW of 1205 g. Median Crp remained at 1.0 µg/L at 15 and 30 days (IQR 0.7-1.4 and 0.7-1.3, respectively). Premature babies < 26 weeks had a significantly higher Crp at one month than the remainder (p = 0.043) and higher Cr elimination in the urine (p = 0.026). Crp increased with prolonged PN (p < 0.001), even after adjusting for gestational age (p = 0.001). Laboratory parameters were not influenced by Crp or Cru, nor was morbidity., Conclusion: Crp increases with days of PN even when a trace mineral supplement without Cr is used, and the level reached persists during the first month of life with the introduction of Cr-supplemented breastmilk feeding. No relation to morbidity was observed.

Objective: To investigate differences in arterial involvement patterns on 18 F-FDG PET-CT between predominant cranial and isolated extracranial phenotypes of giant cell arteritis (GCA)., Methods: A retrospective review of 18 F-FDG PET-CT findings was conducted on 140 patients with confirmed GCA. The patients were divided into two groups: the cranial group, which presented craniofacial ischemic symptoms either at diagnosis or during follow-up, and the isolated extracranial group which never exhibited such manifestations., Results: Of the 140 patients (90 women), 99 (71%) were considered to have a predominantly cranial phenotype, while 41 (29%) had isolated extracranial GCA. Patients with the extracranial phenotype were younger (p = 0.001), had lower TAB positivity (25%), and experienced longer diagnostic delays (p = 0.004). Polymyalgia rheumatica was more common in the extracranial group (p = 0.029), which also showed fewer constitutional symptoms, milder increases in acute phase reactants, and more frequent limb claudication and aortic complications, although these differences were not statistically significant. When comparing arterial involvement on 18 F-FDG PET-CT, we observed statistically significant differences. The extracranial phenotype showed greater involvement across all segments of the thoracic aorta (p = 0.001), as well as in the abdominal aorta (p = 0.005), subclavian (p = 0.021), iliac (p = 0.004), and femoral arteries (p = 0.025). In contrast, the cranial phenotype exhibited a higher frequency of vertebral artery involvement (p < 0.001)., Conclusion: Significant differences in arterial involvement patterns on 18 F-FDG PET-CT were observed between phenotypes. These findings may explain atypical symptoms such as inflammatory lower back pain or limb claudication and the increased risk of aortic complications in extracranial GCA., Competing Interests: Declarations. Ethics approval: The study has bee approved by of our institutional ethics committee (Clinical Research Ethics Committee of Bellvitge University Hospital-IDIBELL). The local ethics committee confirm that the findings in this report were based on normal clinical practice and were therefore suitable for dissemination. Since our study was performed retrospectively, we were relieved by the ethics committee of our hospital from obtaining informed consent. Informed consent was not obtained from the patients, but their clinical records and information were anonymized prior to analysis. This study was conducted inaccordance with the principles of the Declaration of Helsinki and the International Conference for Harmonization. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Use of AI and AI-assisted technologies in the writing process: No., (© 2024. The Author(s).)

Background: The growing diffusion of artificial intelligence, data science and digital health has highlighted the role of collection of data and biological samples, thus raising legal and ethical concerns regarding its use and dissemination. Further, the expansion of biobanking, from the basic collection of frozen specimens to the virtual biobanks of specimens and associated data that exist today, has given a revolutionary potential on healthcare systems, particularly in the field of neurological diseases, due to the inaccessibility of central nervous system and the need of non-invasive investigation approaches. Informed Consent (IC) is considered mandatory in all research studies and specimen collections, and must specifically take into account the ethical respect to the individuals to whom the used biological material and data belong., Methods: We evaluated the attitudes of patients with neurological diseases (NP) and healthy volunteers (HV) towards the donation of biological samples to a biobank for future research studies on neurological diseases, and limitations on the use of data, related to the requirements set by the General Data Protection Regulation (GDPR). The study involved a total of 1454 subjects, including 502 HVs and 952 NPs, recruited at Santa Lucia Foundation IRCCS, Rome, from 2020 to 2024., Results: We found that (i) almost all subjects agreed with the participation in biobanking (ii) and authorization to genetic studies (HV = 99.1%; NP = 98.3%); Regarding the return of results, (iii) we found a statistically significant difference between NP and HV, the latter preferring not to be informed of potential results (HV = 43%; NP = 11.3%; p < 0.0001); (iv) a small number limited the sharing inside European Union (EU) (HV = 4.6%; NP = 6.6%), whereas patients were more likely to refuse transfer outside EU (HV = 7.4%; NP = 10.7% p = 0.05); (v) nearly all patients agreed with the use of additional health data from EMR for research purposes (98.9%)., Conclusions: Consent for the donation of material for research purposes is crucial for biobanking and biomedical research studies that use biological material of human origin. Here, we have shown that choices regarding participation in a neurological biobank can be different between HVs and NPs, even if the benefit for research and scientific progress is recognized. NP have a strong interest in being informed of possible results but limit sharing of samples, highlighting a perception of greater individual or relative benefit, while HV prefer a wide dissemination and sharing of data but not to have the return of the results, favoring a possible benefit for society and knowledge. The results underline the need to carefully manage biological material and data collected in biobanks, in compliance with the GDPR and the specific requests of donors., (© 2024. The Author(s).)

Competing Interests: Conflicto de intereses: Los autores declaran no tener ningún conflicto de intereses.

Background : Lower respiratory tract infections (LRTIs) are a significant cause of primary care consultations. Differentiating between viral and bacterial infections is critical for effective treatment and to minimize unnecessary antibiotic use. This study investigates the impact of combining lung ultrasound (LUS) with capillary blood C-reactive protein (CRP) rapid testing on clinical decision-making for patients with LRTIs. Objectives : The primary objective is to assess how the integration of CRP testing and LUS influences antibiotic prescription decisions. The study aims to quantify the percentage change in antibiotic prescriptions before and after performing LUS, following history taking, clinical examination, and CRP testing. Methods : This analytical observational study will be conducted in six primary care centers within the Health Region of Lleida, Catalonia, serving a mixed urban and rural population of approximately 105,000 residents. The study will recruit 196 patients aged 18 and over, presenting with LRTI symptoms and not treated with antibiotics in the preceding 14 days. Participants will undergo CRP testing followed by LUS during their consultation. Statistical analyses, including linear regression, bivariate analysis, Pearson or Spearman correlation, and logistic regression, will be used to evaluate the impact of LUS on clinical decisions and its predictive value in diagnosing bacterial infections. Results and Conclusions : This study will provide insights into the role of LUS combined with CRP testing in improving diagnostic accuracy and guiding antibiotic prescription decisions in primary care. The findings aim to enhance treatment protocols for LRTIs, reducing unnecessary antibiotic use and improving patient outcomes.

Background: In response to the rising population of nursing home residents with frailty and multimorbidity, optimizing medication safety through drug utilization review and addressing medication-related problems (MRPs) is imperative. Clinical decision support systems help reduce medication errors and detect potential MRPs, as well as medication reviews performed by a multidisciplinary team, but these combined assessments are not commonly performed. The objective of this study was to evaluate the impact on medication plans of a multidisciplinary team intervention in nursing homes, by analyzing the medication plan before and after the intervention and assessing whether the recommendations given had been implemented., Methods: A multicenter before-after study, involving five nursing homes, assessed the impact of a multidisciplinary team intervention, to estimate effectiveness related to the review of the prescribed medications. The follow-up period for each patient was 12 months or until death if prior, from July 2020 to February 2022, and involved 483 patients. The clinical pharmacologist coordinated the intervention and reviewed all the prescribed medications to make recommendations, focused on the completion of absent data, withdrawal of a drug, verification of whether a drug was adequate, the substitution of a drug, and the addition of drugs. Since the intervention was performed during the COVID-19 pandemic, optimization of psychotropic drugs and absorbent pads were limited., Results: The intervention had an impact with recommendations given for 398 (82.4%) of the patients and which were followed by 58.5% of them. At least one drug was withdrawn in 293 (60.7%) of the patients, with a mean of 2.3 (SD 1.7). As for the total of 1,097 recommendations given, 355 (32.4%) were followed. From the intervention, antipsychotics, antidepressants, benzodiazepines, statins, and diuretics were the most frequently withdrawn., Conclusion: The findings underscore the impact of targeted interventions to reduce inappropriate medications and enhance medication safety in nursing homes. The proposed recommendations given and followed show the importance of a multidisciplinary team, coordinated by a clinical pharmacologist, for a patient-centered approach to make medication reviews regularly, with the help of clinical decision support systems, to help reduce potential MRPs and polypharmacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Anderssen-Nordahl, Fernández-Liz, Sabaté Gallego, Bosch Ferrer, Sánchez-Arcilla Rosanas, Cervera León, Magrinyà and Barceló-Colomer.)

Colorectal cancer (CRC) is a significant global health issue where early detection is crucial for improving treatment outcomes and survival rates. This comprehensive review assesses the utility of stool-based tests in CRC screening, including traditional fecal occult blood tests (FOBT), both chemical (gFOBT) and immunochemical techniques (FIT), as well as multitarget stool DNA (mt-sDNA) as a novel and promising biomarker. The advancements, limitations and the impact of false positives and negatives of these methods are examined. The review analyzed various studies on current screening methods, focusing on laboratory tests and biomarkers. Findings indicate that while FIT and mt-sDNA tests offer enhanced sensitivity and specificity over traditional guaiac-based FOBT, they also come with higher costs and potential for increased false positives. FIT shows better patient adherence due to its ease to use, but incorrect usage and interpretation of FOBT can lead to significant diagnostic errors. In conclusion, despite the improvements in FOBT methods like FIT in CRC detection, careful consideration of each method's benefits and drawbacks is essential. Effective CRC screening programs should combine various methods tailored to specific population needs, aiming for early detection and reduced mortality rates.

Objectives: The presence of macro-B12 is a cause of factual hypervitaminemia B12. Precipitation with polyethylene glycol (PEG) is a simple method of removing high-molecular-weight biomolecules. However, "free" molecule may co-precipitate. This fact requires the establishment of reference intervals for the post-precipitation result. The main aims of the study were to: 1) establish post-PEG RIs for vitamin B12; 2) compare the two criteria for defining the presence of macro-B12; 3) evaluate the joint usefulness of percentage post-PEG vitamin B12 recovery and post-PEG RIs to inform the real vitamin B12 status; and 4), propose interpretative comments for ease of interpretation., Methods: Prospective study in which 488 serum samples from "healthy" individuals were included and analyzed to determine recovery and RIs following PEG precipitation. Subsequently, a retrospective analysis was carried out in order to evaluate the joint usefulness of both definitions for a suspicion of macro-B12. A total of 297 cases were included., Results: Recovery and post-PEG RIs determined on an Alinity i platform ranged from 60 to 107 % and from 118 to 506 pmol/L, respectively. McNemar's test revealed statistically significant differences between both criteria for estimating interference. However, both methodologies showed good agreement. In 27 cases, the presence of macro-B12 coexisted with true hypervitaminemia B12. No case of coexistence of macro-B12 with vitamin B12 deficiency was detected in our series., Conclusions: Laboratory reports should include total vitamin B12 concentration, recovery and post-PEG vitamin B12 concentration with their adjusted RIs to better assess the body vitamin status., Competing Interests: Competing interests: The authors state no conflicts of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Respiratory viruses contribute to high morbidity and mortality in Africa. In 2020, the Ohio State University's Global One Health Initiative, in collaboration with the Ethiopian Public Health Institute and the US Centers for Disease Control and Prevention, took action to strengthen Ethiopia's existing respiratory virus surveillance system through decentralization of laboratory testing and scale-up of national and regional capacity for detecting respiratory viruses. In August 2022, four regional laboratories were established, thereby raising the number of reference laboratories conducting respiratory virus surveillance to five. This article highlights lessons learned during implementation and outlines processes undertaken for laboratory scale-up and decentralization., (Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene 2024.)

Objective: To assess the real-world, long-term effectiveness of rituximab (RTX) as a rescue therapy in patients with antisynthetase syndrome and progressive interstitial lung disease (ASS-ILD)., Methods: Multicentre observational retrospective longitudinal study of a cohort of patients with ASS-ILD that started treatment with RTX due to recurrent or ongoing progressive ILD despite therapy with glucocorticoids and immunosuppressants., Results: Twenty-eight patients were analyzed. Examining the entire study population, before treatment with RTX the mean decline in %pFVC and %pDLCO from the ASS-ILD diagnosis to the initiation of RTX treatment (T0) was -6.44% and -14.85%, respectively. After six months of treatment, RTX reversed the decline in pulmonary function test (PFT) parameters: ∆%pFVC +6.29% (95% CI: -10.07 to 2.51; p=0.002 compared to T0) and ∆%pDLCO +6.15% (95% CI: -10.86 to -1.43; p=0.013). Twenty-four patients completed one year of therapy and 22 two years, maintaining the response in PFT: ∆%pFVC: +9.93% (95% CI: -15.61 to -4.25; p=0.002) and ∆%pDLCO: +7.66% (95% CI: -11.67 to -3.65; p<0.001). In addition, there was a significant reduction in the median dose of prednisone, and it could be suspended in 18% of cases. In 33% of patients who required oxygen therapy at the start of treatment, it could be discontinued. The frequency of adverse events reached 28.5% of cases., Conclusion: Based on our results, RTX appears to be effective as rescue therapy in most patients with recurrent or progressive ASS-ILD unresponsive to conventional treatment. The use of RTX was well tolerated in the majority of patients., (© 2024. The Author(s).)

Introduction: The assessment of the cervical spine (CS) in axial spondyloarthritis (axSpA) and its radiographic characteristics, including the zygapophyseal joints (ZJ), may be helpful for an accurate diagnosis, establishing a prognosis and enhancing treatment decisions., Objectives: To describe the prevalence and characteristics of CS involvement in patients with axSpA and perform a comparison between groups according to cervical radiographic damage., Methods: Patients who fulfilled the Assessment of SpondyloArthritis International Society classification criteria were included from January 2011 to January 2021. Sociodemographic, clinical, radiographic and treatment variables were gathered. Patients were categorised into 'CS group' (Bath Ankylosing Spondylitis Radiology Index ≥2 or De Vlam score ≥3 for ZJ) and 'no CS group' as controls. ZJ fusion and interobserver reliability in ZJ scoring were analysed., Results: A total of 340 patients were included, 244 (71.7%) men, with mean age 57±15 years. CS involvement was observed in 181 (53.2%) patients. Patients in the CS group, as compared with no CS group, were predominantly men, older, had a higher body mass index, higher prevalence of smoking, showed higher disease activity, worse functionality and mobility, as well as more structural damage. Sixty-nine patients with CS involvement had ZJ fusion at some level. These patients showed worse mobility and more radiographic damage. Overall, ZJ involvement was observed in 99 patients (29.1%), 20 of whom did not present with vertebral body involvement., Conclusion: Radiographic evaluation of CS is relevant in patients with axSpA and should be assessed routinely. Evaluation of the ZJ is particularly significant, as it is related to higher disease activity and worse function., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

One of the problems that most seriously affects oenology today is enzymatic browning, especially when grapes are infected by grey rot. We studied the capacity of glutathione (GSH) and a specific inactivated dry yeast rich in glutathione (IDY-GSH) to protect white grape must from browning compared to that of sulphur dioxide (SO 2 ). The results indicate that SO 2 drastically reduces the oxygen consumption rate (by around 72%), protects hydroxycinnamic acids from oxidation and prevents grape must against browning even in the presence of laccase. Specifically, the presence of SO 2 reduced the colour's blue-yellow component ( b *) by around 91% in control conditions and around 76% in the presence of laccase. GSH, pure or in the form of IDY-GSH, also reduces the oxygen consumption rate (by 23% and 36%, respectively) but to a lesser extent than SO 2 . GSH also favours the formation of grape reaction product (GRP) from hydroxycinnamic acids and effectively protects grape must against browning in healthy grape conditions. Specifically, the presence of GSH reduced b * by around 81% in control conditions. Nevertheless, in the presence of laccase, it was not effective enough, reducing b * by around 39% in the case of pure GSH and 24% in the case of IDY-GSH. Therefore, both forms of GSH can be considered as interesting alternative tools to SO 2 for preventing browning in white grape must, but only when the grapes are healthy.

Objective: To investigate the usefulness of 18 F-FDG PET-CT for assessing large-vessel (LV) involvement in patients with suspected giant cell arteritis (GCA) and a negative temporal artery biopsy (TAB)., Methods: A retrospective review of our hospital databases was conducted to identify patients with suspected GCA and negative TAB who underwent an 18 F-FDG PET-CT in an attempt to confirm the diagnosis. The gold standard for GCA diagnosis was clinical confirmation after a follow-up period of at least 12 months., Results: Out of the 127 patients included in the study, 73 were diagnosed with GCA after a detailed review of their medical records. Of the 73 patients finally diagnosed with GCA, 18 F-FDG PET-CT was considered positive in 61 cases (83.5%). Among the 54 patients without GCA, 18 F-FDG PET-CT was considered positive in only eight cases (14.8%), which included 1 case of Erdheim-Chester disease, 3 cases of IgG4-related disease, 1 case of sarcoidosis, and 3 cases of isolated aortitis. Overall, the diagnostic performance of 18 F-FDG PET-CT for assessing LV involvement in patients finally diagnosed with GCA and negative TAB yielded a sensitivity of 83.5%, specificity of 85.1%, and a diagnostic accuracy of 84% with an area under the ROC curve of 0.844 (95% CI: 0.752 to 0.936). The sensitivity was 89% in occult systemic GCA and 100% in extracranial LV-GCA., Conclusion: Our study confirms the utility of 18 F-FDG PET-CT in patients presenting with suspected GCA and a negative TAB by demonstrating the presence of LV involvement across different subsets of the disease., (© 2024. The Author(s).)

Graphene-based Field-Effect Transistors (FETs) integrated with microstrip patch antennas offer a promising approach for terahertz signal radiation. In this study, a dual-stage simulation methodology is employed to comprehensively investigate the device's performance. The initial stage, executed in MATLAB, delves into charge transport dynamics within a FET under asymmetric boundary conditions, employing hydrodynamic equations for electron transport in the graphene channel. Electromagnetic field interactions are modeled via Finite-Difference Time-Domain (FDTD) techniques. The second stage, conducted in COMSOL Multiphysics, focuses on the microstrip patch antenna's radiative characteristics. Notably, analysis of the S11 curve reveals minimal reflections at the FET's resonant frequency of 1.34672 THz, indicating efficient impedance matching. Examination of the radiation pattern demonstrates the antenna's favorable directional properties. This research underscores the potential of graphene-based FETs for terahertz applications, offering tunable impedance matching and high radiation efficiency for future terahertz devices.

Despite emerging evidence and advances in the management of atopic dermatitis there a lack of consensus regarding the diagnostic criteria, therapeutic approach, method to assess severity, and patient follow-up for this condition. An expert consensus study was conducted to provide recommendations on the management of patients with moderate-to-severe atopic dermatitis. The study used Delphi-like methodology based on a literature review, a summary of the scientific evidence, and a 2-round survey. The agreement of 60 panellists on 21 statements was evaluated. Consensus was pre-defined as ≥ 80% agreement of all respondents. In the first round 6 statements reached consensus. Unanimous consensus was achieved regarding therapeutic goals and patient satisfaction (maintained in the long term and periodic goals reassessment recommended every 3-6 months). In the second round, half of the statements reached consensus, all related to patient follow-up, treatment goals, and atopic comorbidities. The statements that did not reach consensus were related to diagnosis (biomarkers, allergy, and food testing) and starting patients on conventional systemic treatment rather than advanced treatment. The study assessed expert opinion regarding a variety of topics related to the clinical approach to patients with moderate-to-severe atopic dermatitis, in order to provide guidance on the diagnosis and management of patients with atopic dermatitis.

Introduction: The expansion of higher education is a worldwide phenomenon. To our knowledge, there are no studies analyzing the trends in demands of enrollment in health-related studies in Spain. Therefore, the objective was to analyze the change in demand (the number of requests for enrollment divided by the number of offered places) for undergraduate health-related studies in Spain during the period 2015-2021 as well as compare the change by region in the pre (2015-2019) and pandemic (2020-2021) period., Methods: This is an observational (ecological type) study with temporal series analyses using data from public (non-for-profit) higher education institutions from the Integrated University Information System. For the analysis by region, we calculated the demand of all twelve undergraduate health-related degrees and the percentages of change between both periods using the Wilcoxon test. The Joinpoint Regression program was used to analyze the trends in demand for each degree during the 7-year period., Results: Significant ( p < 0.001) increases in demand during the pandemic period were observed in all regions. During the pandemic, medicine, biomedicine, nursing, odontology and pharmacy presented a higher demand in comparison with data collected before the pandemic started. In contrast, this pattern was not confirmed in the following cases: physiotherapy, occupational therapy, podiatry, psychology, social work, human nutrition and dietetics. By regions, Navarra, Asturias, and La Rioja presented the most drastic changes. In regions with the biggest number of universities, such as Catalonia, Andalusia and Madrid, the change observed was smaller., Competing Interests: The authors declare that they have no competing interests., (© 2023 Jerez-Roig et al.)

Background: Staphylococcus aureus causes a wide range of infections from mild skin and soft tissue to severe life-threatening bacteremia. The pathogenicity of S. aureus infections is related to various bacterial surface components and extracellular proteins such as toxic-shock syndrome (TSS) toxin and Panton-Valentine leukocidin (PVL). In this study we determine the antimicrobial resistance of isolated strains and their virulence genes in Ethiopia., Methods: A total of 190 archived S. aureus isolates from four Ethiopia Antimicrobial Resistance (AMR) Surveillance sites were analyzed. The identification of S. aureus was done by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF Biotyper) and antimicrobial susceptibility test (AST) was done using VITEK ® 2. Multiplex PCR was used to detect mecA, mecC, pvl and spa genes and super-antigens ( sea, seb, sec, seh and sej staphylococcal enterotoxins)., Results: A total of 172 isolates were confirmed as S. aureus , 9 (5.23%) were methicillin-resistant S. aureus (MRSA) and 163 (94.76%) were methicillin-susceptible S. aureus (MSSA). AST showed that 152 (88.4%) isolates were resistant to penicillin; 90 (52.32%) resistant to trimethoprim-sulfamethoxazole; and 45 (26.16%) resistant to tetracycline. A total of 66 (38.37%) isolates harbored at least one staphylococcal enterotoxin gene and 31 (46.96%) isolates had more than one. The most frequent enterotoxin gene encountered was seb 28 (16.28%). The TSST-1 gene was detected in 23 (13.37%). Presence of staphylococcal enterotoxin gene showed significant association with antibiotic resistance to cefoxitin, benzylpenicillin, oxacillin, erythromycin, clindamycin, tetracycline and SXT. The pvl gene was detected in 102 (59.3%) of isolates. Isolates from patients below 15 years of age showed significantly high numbers of pvl gene (P = 0.02). Presence of sej (P = 0.011) and TSST-1 (P <0.001) genes were associated with the presence of pvl gene., Conclusion: In this study, isolates were highly resistant to oral antibiotics and the pvl, seb, sea and TSST-1 genes were prevalent., Competing Interests: Dr Joan-Miquel Balada-Llasat reports grants, personal fees from BioMerieux, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2023 Ibrahim et al.)

Diagnostic tools that can rapidly identify and characterize microbes growing in blood cultures are important components of clinical microbiology practice because they help to provide timely information that can be used to optimize patient management. This publication describes the bioMérieux BIOFIRE Blood Culture Identification 2 (BCID2) Panel clinical study that was submitted to the U.S. Food & Drug Administration. Results obtained with the BIOFIRE BCID2 Panel were compared to standard-of-care (SoC) results, sequencing results, PCR results, and reference laboratory antimicrobial susceptibility testing results to evaluate the accuracy of its performance. Results for 1,093 retrospectively and prospectively collected positive blood culture samples were initially enrolled, and 1,074 samples met the study criteria and were included in the final analyses. The BIOFIRE BCID2 Panel demonstrated an overall sensitivity of 98.9% (1,712/1,731) and an overall specificity of 99.6% (33,592/33,711) for Gram-positive bacteria, Gram-negative bacteria and yeast targets which the panel is designed to detect. One hundred eighteen off-panel organisms, which the BIOFIRE BCID2 Panel is not designed to detect, were identified by SoC in 10.6% (114/1,074) of samples. The BIOFIRE BCID2 Panel also demonstrated an overall positive percent agreement (PPA) of 97.9% (325/332) and an overall negative percent agreement (NPA) of 99.9% (2,465/2,767) for antimicrobial resistance determinants which the panel is designed to detect. The presence or absence of resistance markers in Enterobacterales correlated closely with phenotypic susceptibility and resistance. We conclude that the BIOFIRE BCID2 Panel produced accurate results in this clinical trial., Competing Interests: The authors declare a conflict of interest. This info is included in the body of the manuscript: Authors received research funds paid to their institutions from BIOFIRE Diagnostics, LLC, which is now known as bioMérieux, Inc. K.H., B.K., and D.Y.L. are employed by the study sponsor. D.D.R. was employed by University Hospitals Cleveland Medical Center during this study. D.D.R. has received research support from Altona, BD, bioMérieux, Bio-Rad, Cepheid, Cleveland Diagnostics, Luminex, HelixBind, Hologic, Qiagen, Q-Linea, Specific Diagnostics, Thermo Fisher, and Vela; and D.D.R. has or has had advisory relationships with Luminex, Next Gen Diagnostics, Renascent Diagnostics, Roche, and Seegene. A.L. has received research funding from BIOFIRE, Cepheid, and Luminex. J.-M.B.-L. has served as a consultant for bioMérieux and also participated in other BIOFIRE clinical studies. A.H. has received industry sponsored grant funding from bioMérieux (BIOFIRE), and Beckman Coulter, and she has consulted for Bio-Rad. G.J.B. has given educational seminars sponsored by BIOFIRE and has also served on a BIOFIRE advisory panel. R.S. has received honoraria from bioMérieux for speaking engagements.

The aim of this study was to determine whether the pandemic has reinforced the choice of pursuing health-related bachelor's degrees, and to identify underlying factors that could contribute to that impact. This is a cross-sectional study using an online survey of 2,344 students of nursing, physiotherapy, medicine, psychology and podiatry who started health-related bachelor's degrees after the COVID-19 outbreak in Spanish higher education institutions. The pandemic influenced the choice of these studies by increasing the desire to help others (33.2%), by increasing citizenship values (28.4%), and by increasing the desire to contribute to improving the situation of the country (27.5%). Women had a significantly greater influence on the increase in social values related to the practice of the profession produced by the pandemic, whereas men and the bachelor's degree in podiatry were more influenced by salary prospects. An increased desire to help others was significantly higher among women and nursing and medical students. Podiatry and psychology were the degrees were most influenced by the pandemic, as more students decided to pursue them, something they had previously doubted, while in nursing, psychology, and medicine the pandemic reinforced their interest in pursuing the degree the most. Students personally affected by COVID-19 reported being more influenced in reconsidering their professional path and in reinforcing their desire to pursue the health-related studies., (© 2023. The Author(s).)

Purpose: Cholangiocarcinoma (CCA) is usually diagnosed at advanced stages, with limited therapeutic options. Preclinical models focused on unresectable metastatic CCA are necessary to develop rational treatments. Pathogenic mutations in IDH1/2, ARID1A/B, BAP1, and BRCA1/2 have been identified in 30%-50% of patients with CCA. Several types of tumor cells harboring these mutations exhibit homologous recombination deficiency (HRD) phenotype with enhanced sensitivity to PARP inhibitors (PARPi). However, PARPi treatment has not yet been tested for effectiveness in patient-derived models of advanced CCA., Experimental Design: We have established a collection of patient-derived xenografts from patients with unresectable metastatic CCA (CCA&#95;PDX). The CCA&#95;PDXs were characterized at both histopathologic and genomic levels. We optimized a protocol to generate CCA tumoroids from CCA&#95;PDXs. We tested the effects of PARPis in both CCA tumoroids and CCA&#95;PDXs. Finally, we used the RAD51 assay to evaluate the HRD status of CCA tissues., Results: This collection of CCA&#95;PDXs recapitulates the histopathologic and molecular features of their original tumors. PARPi treatments inhibited the growth of CCA tumoroids and CCA&#95;PDXs with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1. In line with these findings, only CCA&#95;PDX and CCA patient biopsy samples with mutations of BRCA2 showed RAD51 scores compatible with HRD., Conclusions: Our results suggest that patients with advanced CCA with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1, are likely to benefit from PARPi therapy. This collection of CCA&#95;PDXs provides new opportunities for evaluating drug response and prioritizing clinical trials., (©2022 The Authors; Published by the American Association for Cancer Research.)

Timely administration of appropriate antibiotic therapy is associated with better patient outcomes and lower costs of care compared to delayed appropriate therapy, yet initial treatment is often empiric since causal pathogens are typically unknown upon presentation. The challenge for clinicians is balancing selection of adequate coverage treatment regimens, adherence to antimicrobial stewardship principles to deter resistance, and financial constraints. This retrospective cohort study aimed to assess the magnitude and impact of delayed appropriate antibiotic therapy among patients hospitalized with septic arthritis (SA) in the U.S. from 2017 to 2019 using healthcare encounter data. Timely appropriate therapy was defined as the receipt of antibiotic(s) with in vitro activity against identified pathogens within two days of admission; all other patients were assumed to have received delayed appropriate therapy. Of the 517 patients admitted to hospital for SA who met all selection criteria, 26 (5.0%) received delayed appropriate therapy. In inverse-probability-treatment-weighting-adjusted analyses, the receipt of delayed appropriate therapy was associated with an additional 1.1 days of antibiotic therapy, 1.4 days in length of stay, and $3531 in hospital costs (all vs. timely appropriate therapy; all p ≤ 0.02). Timely appropriate therapy was associated with a twofold increased likelihood of antibiotic de-escalation during the SA admission.

Background: The lysis of platelets during in vitro coagulation leads to increased potassium concentrations.We aimed to establish the cut-off value for platelet count interfering serum potassium and to estimate the percentage of cases of pseudohyperkalemia and pseudonormokalemia in our hospital., Materials and Methods: Individuals diagnosed with essential thrombocytosis (2010-2019) based on the WHO criteria for the classification of myeloid neoplasms and acute leukemia were considered.The cut-off value for the interference of platelet count on serum potassium results was calculated using the reference change value. Sensitivity and specificity were calculated using a ROC-curve, and the size of the effect by the Cohen's d.The clinical impact of both phenomena was assessed by reviewing the medical records of individuals classified as such, and also looking for potential cases in 2019 on the laboratory information system., Results: Fifty-four individuals with essential thrombocytosis were included. Potassium concentration correlated with platelet count (P-value<0.001; Spearman's ρ =0.394) in serum. The cut-off value of platelet count interfering potassium was 598x10 3 /μL [CI95%: 533-662x10 3 /μL], with an associated sensitivity and specificity of 0.67 [CI95%:0.52-0.80] and 0.58 [CI95%:0.42-0.72] respectively.The medical records of patients classified as pseudohyperkalemia or pseudonormokalemia did not include any medical action for the modification of potassium levels. In 2019, up to 0.14% of the total serum potassium determinations were susceptible to be pseudohyperkalemia or pseudonormokalemia., Conclusion: This study provides a cut-off value for platelet count interfering serum potassium concentrations, and brings to light not only pseudohyperkalemia-related issues, but also the pseudonormokalemia phenomenon, which usually goes unnoticed., Competing Interests: Declaration of competing interests All authors declare no conflicts of interest., (Copyright © 2022 International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). All rights reserved.)

Introduction: Staphylococcus infection-associated glomerulonephritis (SAGN), is an autoimmune sequela of infection affecting a subset of infected patients without specific predictive factors, frequently presenting with acute nephritic syndrome and propensity for chronic kidney disease. We performed a comparative genotypic and phenotypic analysis of S. aureus isolates from patients that did and those that did not develop SAGN., Methods: We had 22 culture-proven cases of SAGN from Ohio State University Wexner Medical Center (OSUWMC) from 2004 to 2016, 9 of 22 being blood cultures, with archived isolates. These, along with blood culture isolates from 12 patients with no clinical evidence of SAGN (between ages 40 to 80 years) over the same period were used for genotyping. For host demographic comparison, we used all available SAGN cases ( n  = 85, including those with positive cultures other than blood; and patients with kidney biopsies received from referring hospitals) and all OSUWMC patients with positive Staphylococcus cultures without glomerulonephritis (GN) ( n  = 23,496)., Results: Multiple sequence types (STs) suggesting strain diversity was seen in the GN isolates with mainly clonal complexes (CC) 5 and 59. Mutations in the agr operon were identified in significantly higher number of the GN isolates (83%) than non-GN isolates (16%). Significant differences in β-hemolysis and biofilm formation was also observed between the groups., Conclusion: The functionality of these agr mutants remains to be seen, but the presently known effects of reduced agr function, namely increased surface adhesins, biofilm formation, and persistent bacteremia could be important microbial factors predisposing to SAGN and testing for them early during infection could help to predict its development., (© 2022 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)

Rationale: Abnormal values of hypercoagulability biomarkers, such as D-dimer, have been described in Coronavirus Disease 2019 (COVID-19), which has also been associated with disease severity and in-hospital mortality. COVID-19 patients with pneumonia are at greater risk of pulmonary embolism (PE). However, the real incidence of PE is not yet clear, since studies have been limited in size, mostly retrospective, and PE diagnostic procedures were only performed when PE was clinically suspected., Objectives: (1) To determine the incidence, clinical, radiological, and biological characteristics, and clinical outcomes of PE among patients hospitalized for COVID-19 pneumonia with D-dimer > 1,000 ng/mL. (2) To develop a prognostic model to predict PE in these patients., Methods: Single-center prospective cohort study. Consecutive confirmed cases of COVID-19 pneumonia with D-dimer > 1,000 ng/mL underwent computed tomography pulmonary angiography (CTPA). Demographic and laboratory data, comorbidities, CTPA scores, treatments administered, and clinical outcomes were analyzed and compared between patients with and without PE. A risk score was constructed from all these variables., Results: Between 6 April 2020 and 2 February 2021, 179 consecutive patients were included. The overall incidence of PE was 39.7% (71 patients) (CI 95%, 32-47%). In patients with PE, emboli were located mainly in segmental/subsegmental arteries (67%). Patients with PE did not differ from the non-PE group in sex, age, or risk factors for thromboembolic disease. Higher urea, D-Dimer, D-dimer-to-ferritin and D-dimer-to-lactate dehydrogenase (LDH) ratios, platelet distribution width (PDW), and neutrophil-to-lymphocyte ratio (NLR) values were found in patients with PE when compared to patients with non-PE. Besides, lymphocyte counts turned out to be lower in patients with PE. A score for PE prediction was constructed with excellent overall performance [area under the ROC curve-receiver operating characteristic (AUC-ROC) 0.81 (95% CI: 0.73-0.89)]. The PATCOM score stands for Pulmonary Artery Thrombosis in COVID-19 Mallorca and includes platelet count, PDW, urea concentration, and D-dimer-to-ferritin ratio., Conclusion: COVID-19 patients with pneumonia and D-dimer values > 1,000 ng/mL were presented with a very high incidence of PE, regardless of clinical suspicion. Significant differences in urea, D-dimer, PDW, NLR, and lymphocyte count were found between patients with PE and non-PE. The PATCOM score is presented in this study as a promising PE prediction rule, although validation in further studies is required., Competing Interests: AA-F reports personal fees from Astrazeneca, GSK, Chiesi, and Menarini, from outside the submitted work. JS reports personal fees, as a speaker, from Roche and Boehringer-Ingelheim, with no relationship with the submitted work. ES-L reports personal fees from Astrazeneca, GSK, and Boehringer-Ingelheim, personal and advisory board fees from MSD, and grants, personal, and advisory board fees from Actelion and Janssen, from outside the submitted work. BN reports personal fees from Roche, Brystol, and Boehringer-Ingelheim, with no relationship with the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Suarez Castillejo, Toledo-Pons, Calvo, Ramon-Clar, Martínez, Hermoso de Mendoza, Morell-García, Bauça, Berga, Núñez, Preda, Sauleda, Argente Castillo, Ballesteros, Martín, Sala-Llinas and Alonso-Fernández.)

Aluminum enters the body primarily through diet or occupational exposure, and is cleared through urine. However, this trace element may accumulate and cause toxicity in subjects with renal insufficiency, and even in dialysis patients. The mechanism of aluminum toxicity is related to increased oxidative and inflammatory stress, iron and calcium dyshomeostasis, or cholinergic dysregulation, among other. A review was conducted on the specimens and analytical methods used to determine aluminum in biological specimens and dialysis water. This paper describes the most relevant aspects related to quality assurance. This is a practical guideline for the development and implementation of a reliable method for determination of aluminum in the clinical laboratory. Serum aluminum is the main biomarker of toxicity. For cases of chronic exposure, urine testing is recommended. At present, inductively coupled plasma mass spectrometry (ICP-MS) is the gold-standard determination method, since it has been proven to have the best quantification limits, selectivity and robustness. Clear recommendations are provided in relation to the specimens used for aluminum determination. Relevant pre-analytical, analytical, and post-analytical considerations are also presented., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2022 Sonia Pérez San Martín et al., published by De Gruyter, Berlin/Boston.)

Objectives: Most errors in laboratory medicine occur in the pre- and post-analytical phases of the total testing process (TTP). In 2014, the Spanish Society of Laboratory Medicine (SEQC ML ) started the current Preanalytical Phase EQA Programme, with the objective of providing a tool for the improvement of the preanalytical phase. The aim of this study was to review the evolution of quality indicators (QI) and the comparability of established performance specifications (PS) with other EQA programmes., Methods: In the SEQC ML programme, participants were asked to register rejections of the main specimens and the causes for rejections. Data collected from 2014 to 2017, and then reviewed biennially (2018-2019), was used to calculate the percentiles; p25, p50, p75, and p90 for every round, and their means were set as PS. These PS were compared with the results of other programmes., Results: The evolution of QI results for 2018-2019 period showed general maintenance or improvement, e.g., a significant decrease in the number of serum samples with a haemolytic index ≥0.5 g/L, except for EDTA and citrate samples handle, maybe for an improvement in detection. The comparison with PS for the QI of the IFCC Working Group "Laboratory Errors and Patient Safety" and the Key Incident Management and Monitoring System (KIMMS) programme of the RCPA showed comparable results, supporting the validity of the established specifications., Conclusions: The PS obtained are a helpful tool for benchmarking and to identify processes of the preanalytical phase whose improvement should be set as a priority., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2022 Andrea Caballero et al., published by De Gruyter, Berlin/Boston.)

Antimicrobial resistance is a global public health threat, and gram-negative bacteria, such as Enterobacterales and Pseudomonas aeruginosa, are particularly problematic with difficult-to-treat resistance phenotypes. To reduce morbidity and mortality, a reduction in the time to effective antimicrobial therapy (TTET) is needed, especially among critically ill patients. The antibiogram is an effective clinical tool that can provide accurate antimicrobial susceptibility information and facilitate early antimicrobial optimization, decrease TTET, and improve outcomes such as mortality, hospital length of stay, and costs. Guidance is lacking on how to validate the susceptibility to new antibacterial agents. Commonly used traditional and combination antibiograms may not adequately assist clinicians in making treatment decisions. Challenges with the current susceptibility testing of new β-lactam/β-lactamase inhibitor combinations persist, impacting the appropriate antibacterial choice and patient outcomes. Novel antibiograms such as syndromic antibiograms that incorporate resistant gram-negative phenotypes and/or minimum inhibitory concentration distributions may assist in determining the need for earlier susceptibility testing or help define an earlier optimal use of the new β-lactam/β-lactamase inhibitors. The purpose of this review is to emphasize novel antibiogram approaches that are capable of improving the time to susceptibility testing and administration for new β-lactam/β-lactamase inhibitors so that they are earlier in a patient's treatment course.

Wilson's disease (WD) is an inherited disorder of copper metabolism caused by mutations in the ATP7B gene. This condition is characterized by the accumulation of copper in the liver and other organs and tissues causing hepatic and neuropsychiatric manifestations. This paper reviews the diagnostic performance and limitations of the biochemical tests commonly used to detect this underdiagnosed disease. It also provides some recommendations and suggests a set of standardized laboratory comments. At present, a rapid, simple, reliable biochemical test that confirms diagnosis of WD is not available. However, diagnosis can be established based on serum ceruloplasmin and urinary copper excretion. Total serum copper should be employed with caution, since it has a low negative predictive value. The use of estimated non-ceruloplasmin-bound copper is not recommended. Nevertheless, measured relative exchangeable copper has very high sensitivity and specificity and emerges as a potential gold standard for the biochemical diagnosis of WD. The development of novel assays for WD detection makes this disorder a potential candidate to be included in newborn screening programs., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2022 Eduardo Martínez-Morillo and Josep Miquel Bauça, published by De Gruyter, Berlin/Boston.)

Purpose: Treatment options for advanced cholangiocarcinoma are limited and prognosis is poor. Cholangiocarcinomas are highly heterogeneous at the molecular level, with divergent patterns between intrahepatic and extrahepatic forms, intrahepatic being particularly rich in actionable alterations. We compared survival in patients with advanced cholangiocarcinoma harboring alterations matched to targeted drugs, with patients harboring nonactionable alterations., Experimental Design: Patients with cholangiocarcinoma treated between 2011 and 2020 at one institution, with available molecular analyses, were retrospectively reviewed. Genomic alteration actionability was classified according to the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) and correlated with efficacy endpoints., Results: Of 327 patients included, 78.9% had intrahepatic cholangiocarcinoma, 97.9% had received chemotherapy for metastatic disease. Actionable molecular alterations per ESCAT were identified in 184 patients (56.3%), including IDH1 mutations and FGFR2 fusions (23.1% and 8.0% of patients with intrahepatic cholangiocarcinoma, respectively). Median overall survival in 50 patients with ESCAT I-IV alterations who received matched therapy (48 with intrahepatic cholangiocarcinoma) was 22.6 months [95% confidence interval (CI), 20.1-32.8], compared with 14.3 months (95% CI 11.9-18.1) in 130 patients without actionable ESCAT alterations (HR, 0.58; 95% CI, 0.40-0.85; P = 0.005). Among patients receiving matched targeted therapy, median progression-free survival was longer for patients with alterations classified as ESCAT I-II compared with ESCAT III-IV (5.0 vs. 1.9 months; HR, 0.36; 95% CI, 0.15-0.87; P = 0.02)., Conclusions: ESCAT represents a tool to guide clinicians in fine-tuning use of molecular profiling data to choose matched targeted therapies. Our data demonstrate that targeted treatment administered per alteration actionability according to ESCAT is associated with improved survival in cholangiocarcinoma, particularly in ESCAT I-II intrahepatic cholangiocarcinoma., (©2022 American Association for Cancer Research.)

Background: The first years of university can be very challenging for students. Previous research has focused on the study of the prevalence of burnout and of psychological distress in medical students. The aim of this study was to investigate the prevalence of psychological symptoms and burnout reported by first-year students, the relationship between these variables and their academic performance, and the differences between health and non-health sciences students., Methods: An observational study with a cross-sectional design was performed. Students of health sciences (medicine, nursing, physiotherapy, psychology), and non-health sciences (biology, social sciences, business management, and engineering) undergraduate programs completed the Brief Symptom Inventory (BSI-18) and the Maslach Burnout Inventory-Student Survey (MBI-SS). Students' grades for the first semester were collected., Results: A sample of 506 students participated. Prevalence of psychological distress was 27.1% and burnout was 7.3%. Academic performance was unaffected in relation to either psychological distress or burnout. Non-health sciences students showed a greater risk of depression., Conclusions: This study provides evidence of the high prevalence of psychological distress in the first year of college. Even when burnout prevalence was low, the results suggest the need to introduce prevention programs to improve the psychological wellbeing of these students.

Background: A description of individuals with SARS-CoV-2 infection comparing the first and second waves could help adapt health services to manage this highly transmissible infection., Objective: We aimed to describe the epidemiology of individuals with suspected SARS-CoV-2 infection, and the characteristics of patients with a positive test comparing the first and second waves in Catalonia, Spain., Methods: This study had 2 stages. First, we analyzed daily updated data on SARS-CoV-2 infection in individuals from Girona (Catalonia). Second, we compared 2 retrospective cohorts of patients with a positive reverse-transcription polymerase chain reaction or rapid antigen test for SARS-CoV-2. The severity of patients with a positive test was defined by their admission to hospital, admission to intermediate respiratory care, admission to the intensive care unit, or death. The first wave was from March 1, 2020, to June 24, 2020, and the second wave was from June 25, 2020, to December 8, 2020., Results: The numbers of tests and cases were lower in the first wave than in the second wave (26,096 tests and 3140 cases in the first wave versus 140,332 tests and 11,800 cases in the second wave), but the percentage of positive results was higher in the first wave than in the second wave (12.0% versus 8.4%). Among individuals with a positive diagnostic test, 818 needed hospitalization in the first wave and 680 in the second; however, the percentage of hospitalized individuals was higher in the first wave than in the second wave (26.1% versus 5.8%). The group that was not admitted to hospital included older people and those with a higher percentage of comorbidities in the first wave, whereas the characteristics of the groups admitted to hospital were more alike., Conclusions: Screening systems for SARS-CoV-2 infection were scarce during the first wave, but were more adequate during the second wave, reflecting the usefulness of surveillance systems to detect a high number of asymptomatic infected individuals and their contacts, to help control this pandemic. The characteristics of individuals with SARS-CoV-2 infection in the first and second waves differed substantially; individuals in the first wave were older and had a worse health condition., (©Lia Alves-Cabratosa, Marc Comas-Cufí, Jordi Blanch, Ruth Martí-Lluch, Anna Ponjoan, Antoni Castro-Guardiola, Abelardo Hurtado-Ganoza, Ana Pérez-Jaén, Maria Rexach-Fumaña, Delfi Faixedas-Brunsoms, Maria Angels Gispert-Ametller, Anna Guell-Cargol, Maria Rodriguez-Batista, Ferran Santaularia-Font, Ramon Orriols, Marc Bonnin-Vilaplana, Juan Carlos Calderón López, Gladis Sabater-Talaverano, Francesc Xavier Queralt Moles, Sara Rodriguez-Requejo, Esteve Avellana-Revuelta, Elisabet Balló, Ester Fages-Masmiquel, Josep-Maria Sirvent, Carol Lorencio, Josep Miquel Morales-Pedrosa, Patricia Ortiz-Ballujera, Rafel Ramos. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 06.01.2022.)

Objective: To describe the maternal, neonatal and pregnancy characteristics related to inhibition of lactation (IL) with cabergoline., Method: We assessed 20,965 occasions of breastfeeding initiation, according to data collected from obstetric records at the Hospital Clinic of Barcelona (Spain) between January 2011 and December 2017., Results: IL decreased over the study period from 8.78% to 6.18% (odds ratio [OR]: 0.93 per year; 95% confidence interval [95%CI]: 0.90-0.95). Women with a lower educational level (OR: 2.5; 95%CI: 2.0-3.0), mothers living in more depressed areas (OR: 1.08 per 10 extra points over 100; 95%CI: 1.04-1.12), smokers (OR: 2.2; 95%CI: 1.9-2.6), and those with more children (OR: 1.2 for each sibling; 95%CI: 1.1-1.3), preterm birth (OR: 1.8; 95%CI: 1.4-2.3), multiple births (OR: 1.6; 95%CI: 1.2-2.1) and a higher risk pregnancy (OR: 1.3 per risk point; 95%CI: 1.2-1.4) showed a higher prevalence of IL. Compared to women born in Spain, IL was less likely in all other women with the exception of Chinese women (OR: 7.0; 95%CI: 5.7-8.6). These disparities remained during the study period., Conclusions: Factors related to lower socioeconomic status and poor health were more likely to be associated with IL. The overall use of cabergoline decreased during the study period while inequalities persisted. Taking these inequalities into account is the first step to addressing them., (Copyright © 2021 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: Pancreatic cancer (PC) is one of the deadliest malignancies. The aim of this study was to determine the usefulness of the carbohydrate antigen 19.9 (CA19.9)/ carcinoembryonic antigen (CEA) ratio as a diagnostic tool., Methods: This was a retrospective observational study (2015-2019), including laboratory requests with increased CA19.9 and CEA but no previous neoplasia. Receiver operating characteristic (ROC) curve analyses were performed for the CA19.9/CEA ratio and for CA19.9 and CEA alone for the detection of PC, and cutoff values for all strategies were selected separately and in combination., Results: A total of 373 individuals were included. The area under the curve (AUC) for CA19.9/CEA was 0.872, whereas the AUC for CA19.9 was 0.847 and for CEA was 0.554. Cutoff values with the greatest diagnostic power were CA19.9/CEA >40, CA19.9 >1130 U/mL, and CEA > 14.5 U/mL. The combination of CA19.9/CEA > 40 with CA19.9 > 550 U/mL maximized the diagnostic accuracy for PC., Conclusion: Our results highlight the relevance of the measurement of serum CA19.9 and CEA in the detection of PC., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Tumour heterogeneity impacts the efficacy of metastatic cancer treatment even if actionable mutations are identified. Clinicians need to understand if assessing one lesion provides reliable information to drive a therapeutic decision in non-small-cell lung cancer (NSCLC) patients., Methods: We analysed inter-tumour heterogeneity from five autopsied individuals with NSCLC-harbouring mutations in the epidermal growth factor receptor (EGFR), treated with EGFR tyrosine kinase inhibitors (TKIs). Through a comprehensive next-generation sequencing (NGS) oncopanel, and an EGFR panel for digital droplet PCR (ddPCR), we compared metastases within individuals, longitudinal biopsies from the same lesions and, whenever possible, the primary naive tumour., Results: Analysis of 22 necropsies from five patients revealed homogeneity in pathogenic mutations and TKI-resistance mechanisms within each patient in four of them. In-depth analysis by whole-exome sequencing from patient 1 confirmed homogeneity in clonal mutations, but heterogeneity in passenger subclonal alterations. Different resistance mechanisms were detected depending on the patient and line of treatment. Three patients treated with a c-MET inhibitor in combination with TKI lost MET amplification upon progression., Conclusion: At a given point and under selective TKI pressure, a single metastasis biopsy in disseminated tumours from EGFR-mutated NSCLC patients could provide a reasonable assessment of actionable alterations useful for therapeutic decisions., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Plant viruses can evolve towards new pathogenic entities that may eventually cause outbreaks and become epidemics or even pandemics. Seven years ago, tomato brown rugose fruit virus (ToBRFV) emerged, overcoming the genetic resistance that had been employed for more than sixty years against tobamoviruses in tomato. Since then, ToBRFV has spread worldwide, producing significant losses in tomato crops. While new resistances are deployed, the only means of control is the implementation of effective prevention and eradication strategies. For this purpose, in this work, we have designed, assessed, and compared an array of tests for the specific and sensitive detection of the ToBRFV in leaf samples. First, two monoclonal antibodies were generated against a singular peptide of the ToBRFV coat protein; antibodies were utilized to devise a double-antibody-sandwich enzyme-linked immunosorbent assay (DAS-ELISA) test that sensitively detects this virus and has no cross-reactivity with other related tobamoviruses. Second, a real-time quantitative PCR (RT-qPCR) test targeting the RNA-dependent replicase open reading frame (ORF) was designed, and its performance and specificity validated in comparison with the CaTa28 and CSP1325 tests recommended by plant protection authorities in Europe. Third, in line with the tendency to use field-deployable diagnostic techniques, we developed and tested two sets of loop-mediated isothermal amplification (LAMP) primers to double-check the detection of the movement protein ORF of ToBRFV, and one set that works as an internal control. Finally, we compared all of these methods by employing a collection of samples with different ToBRFV loads to evaluate the overall performance of each test.

Recent growth and institutionalization in the field of mixed methods research has provided fertile ground for a wide range of thoughtful criticism of how this research approach has been developed and conceptualized by some members of the mixed methods community. This criticism reflects the increasing maturity of the field as well as the different theoretical perspectives and methodological practices of researchers in different disciplines. While debates addressing these criticisms are likely to lead to valuable insights, no empirical studies have been carried out to date that have investigated researchers' critical views on the development and conceptualization of mixed methods research. This study examines the criticisms of the mixed methods field raised by a cross-national sample of researchers in education, nursing, psychology, and sociology. We carried out a secondary analysis of semi-structured interviews with 42 researchers and identified 11 different criticisms, which we classified in four domains: essence of mixed methods, philosophy, procedures, and politics. The criticisms related to the procedures domain were equally distributed among the four disciplines, while those related to the essence, philosophy and politics domains were more common among sociologists. Based on our findings, we argue that the divergence of views on foundational issues in this field reflects researchers' affiliation to different communities of practice, each having its own principles, values, and interests. We suggest that a greater awareness of this divergence of perspectives could help researchers establish effective collaboration and anticipate potential challenges when working with researchers having different methodological approaches., Competing Interests: The authors have declared that no competing interests exist.

Background: Proper specimen collection is central to improving patient care by ensuring optimal yield of diagnostic tests, guiding appropriate management, and targeting treatment. The purpose of this article is to describe the development and implementation of a training-of-trainers educational program designed to improve clinical culture specimen collection among healthcare personnel (HCP) in Ethiopia., Methods: A Clinical Specimen Collection training package was created consisting of a Trainer's Manual, Reference Manual, Assessment Tools, Step-by-Step Instruction Guides (i.e., job aides), and Core Module PowerPoint Slides., Results: A two-day course was used in training 16 master trainers and 47 facility-based trainers responsible for cascading trainings on clinical specimen collection to HCP at the pre-service, in-service, or national-levels. The Clinical Specimen Collection Package is offered online via The Ohio State University's CANVAS online platform., Conclusions: The training-of-trainers approach may be an effective model for development of enhanced specimen collection practices in low-resource countries.

Background: In other healthcare professions, there has been extensive research into students' motivation, but studies aiming to determine what leads individuals to choose a degree in physiotherapy are scarce. This research study had three main objectives: to obtain a sociodemographic profile of first-year physiotherapy students in Catalonia; to determine the factors that lead individuals to choose a degree in physiotherapy; and to determine potential differences, according to gender and country of origin., Methods: This is an observational, cross-sectional, multicentre study. Data were collected by means of a self-administered, ad-hoc questionnaire, consisting of 15 Likert scale questions, options ranging from "not influencing at all -1-" to "extremely influencing -5-". Ten out of the twelve universities in Catalonia (Spain) that offer a degree in physiotherapy participated in this study. The sample consisted of 941 first-year physiotherapy students (55.2% men; mean age 20.1, SD: 3.4)., Results: The most determinant factors leading individuals to pursue a degree in physiotherapy were: helping others (95.6%); the relationship between physiotherapy and sports (79%); physiotherapy involving manual work (76.4%); and it being perceived as providing multiple job opportunities (75.9%). Male and French students were attracted due to its relation to sports (MD = 0.369, p  < 0.001 and MD = 0.130, p  < 0.027), perception of it being an easy degree (MD = 0.148, p  < 0.001 and MD = 0.091, p  < 0.037), admiration for a known physiotherapist (MD = 0.223, p  = 0.006 and MD = 0.265, p  = 0.001), employability (MD = 0.297, p  < 0.001 and MD = 0.706, p  < 0.001), good income (MD = 0.190, p  = 0.002 and MD = 0.609, p  < 0.001) and social recognition (MD = 0.164, p  = 0.011 and MD = 0.286, p  < 0.001). Helping others (MD = -0.149, p  < 0.001) and interest in the sciences (MD = -0.164, p  = 0.030) were more determinant for female students. Male students were more guided by recommendation (MD = 0.234, p  = 0.001) and to complement previous studies (MD = 0.237, p  = 0.016). French students tended to present more interest in the selection of physiotherapy as a wish since childhood (MD = 0.595, p  < 0.001), due to its multiple job opportunities (MD = 0.427, p  < 0.001) and because of manual work, and did not choose it to complement previous studies (MD = -1.122, p  < 0.001)., Conclusions: The desire to help and care for others, the relation to sports, and involving manual work are the predominant factors that lead students to pursue a degree in physiotherapy. Female students favour helping others and science, whereas male students favour its relation to sports, complementing studies, social factors (admiration, recommendation, friendship) and socioeconomic determinants such as employability, good income or social recognition. When compared to Spanish students, French students were more motivated by its connection to sports, social and socioeconomic factors and some vocational determinants such as being a wish since childhood and interest in a manual profession., Competing Interests: The authors declare there are no competing interests., (©2021 Fuente-Vidal et al.)

Background-Aim: Diabetes mellitus is one of the most prevalent diseases worldwide. According to the ADA 2020 guidelines, individuals with unstable glycemic control should be monitored every three months by measuring glycated hemoglobin (HbA1c). The aim of this study was to evaluate the demand adequacy for HbA1c in the monitoring of patients with diabetes mellitus with a highly unstable glycemic control., Methods: Retrospective observational study (2016-2019). All HbA1c tests from individuals ≥18 years requested by hospital physicians were considered.Highly unstable glycemic control was defined as HbA1c≥10.0%, and their monitoring was classified as: optimal, out of recommendations (if>3months) and lack of monitoring if no further HbA1c measurement was performed by the laboratory.For individuals classified as lack of monitoring , medical records were reviewed and further re-classified as: [1] due to patient's responsibility, [2] attributable to the requesting physician, [3] monitored by POCT, [4] unfeasibility of monitoring or [5] referral outside our area for follow-up., Results: During the assessed period, 1,156 patients had an HbA1c value≥10.0%. 67.5% of them were monitored either in the clinical laboratory or as POCT (33.7% optimal monitoring), whereas 21.0% patients were not monitored due to preventable situations., Conclusion: Lack of monitoring due to physician's reasons or patient's responsibility highlights the urgent need for an improvement., Competing Interests: Conflicts of interest All authors declare no conflicts of interest., (Copyright © 2021 International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). All rights reserved.)

Newborn Screening Programs (NSP) in Spain were born in the city of Granada in 1968. Till the 1980s, they were developed around the so-called "National Plan for Preventing Subnormality", covering up to 30% of the Spanish newborns. From 1982, when the health system management was transferred to the different autonomous regions, the NSP began to expand, and the bases to transform them into an organized and multidisciplinary activity, integrated and coordinated from the National Health System were settled. Despite this expansion, it is not until the 1990s when their coverage reaches almost 100% newborns in Spain. NSP grew up asymmetrically across the different autonomous regions. In 2005 and 2006 the scientific societies SEQC (Spanish Society of Clinical Chemistry) and AECNE (Spanish Society of Newborn Screening), coordinated by the Health Promotion Area of the General Directorate of Public Health, gathered together the necessary information to elaborate a report on the NSP in Spain addressed to the Interterritorial Council of the National Health System. In July 2013, that Council approved the seven diseases that should be part of each region newborn screening panel, being the first step towards the NSP harmonization in Spain. Currently, the NSP include between 8 and 29 diseases in their panels, thus more still more efforts are needed in order to achieve a higher uniformity.

Background: Improved point-of-care diagnostic tests for tuberculosis (TB) in severe immune suppressed people living with HIV (PLWH) are needed to decrease morbidity and mortality outcomes. The aim of the study is to evaluate the performance of the lipoarabinomannan antigen test (LAM-test) with and without α-mannosidase pre-treated urine in a cohort of PLWH in primary care clinics in Guatemala. We further determined TB incidence, and mortality rates and its risk factors in PLWH with TB symptoms., Methods: Prospective longitudinal study of PLWH with TB symptoms. Urine samples were collected at 2 HIV sites to test the sensitivity of the LAM-test in urine with and without α-mannosidase pre-treatment. A composite reference standard of either a positive Mycobacterium tuberculosis complex culture and/or GeneXpert ® MTB/RIF (Xpert, Cepheid, Sunnyvale, CA, USA) results was used in the LAM-test diagnostic accuracy studies. Cox proportional hazards regression was used to study mortality predictors., Results: The overall sensitivity of the LAM-test was of 56.1% with 95% CI of (43.3-68.3). There were no differences in the LAM-test sensitivity neither by hospital nor by CD4 T cell values. LAM-test sensitivity in PLWH with < 200 CD4 T cells/µl was of 62.2% (95% CI 46.5-76.2). There were no significant differences in sensitivity when comparing LAM-test results obtained from untreated vs. α-mannosidase treated urine [55.2% (95% CI 42.6-67.4) vs. 56.9% (95% CI 44-69.2), respectively]. TB incidence in our cohort was of 21.4/100 person years (PYs) (95% CI 16.6-27.6), and mortality rate was of 11.1/100 PYs (95% CI 8.2-15.0). Importantly, PLWH with a positive LAM-test result had an adjusted hazard ratio (aHR) of death of 1.98 (1.0-3.8) with a significant p value of 0.044 when compared to PLWH with a negative LAM-test result., Conclusions: In this study, α-mannosidase treatment of urine did not significantly increase the LAM-test performance, however; this needs to be further evaluated in a large-scale study due to our study limitations. Importantly, high rates of TB incidence and mortality were found, and a positive LAM-test result predicted mortality in PLWH with TB clinical symptoms.