Rewiring Photosynthesis by Water-Soluble Fullerene Derivatives for Solar-Powered Electricity Generation.

Natural photosynthesis holds great potential to generate clean electricity from solar energy. In order to utilize this process for power generation, it is necessary to rewire photosynthetic electron transport chains (PETCs) of living photosynthetic organisms to redirect more electron flux toward an extracellular electrode. In this study, a semi-artificial rewiring strategy, which use a water-soluble fullerene derivative to capture electrons from PETCs and donate them for electrical current generation, is proposed. A positively charged fullerene derivative, functionalized with N,N-dimethyl pyrrolidinium iodide, is found to be efficiently taken up by the cyanobacterium Synechocystis sp. PCC 6803. The distribution of this fullerene derivative near the thylakoid membrane, as well as site-specific inhibitor assays and transient absorption spectroscopy, suggest that it can directly interact with the redox centers in the PETCs, particularly the acceptor side of photosystem I (PSI). The internalized fullerene derivatives facilitate the extraction of photosynthetic electrons and significantly enhance the photocurrent density of Synechocystis by approximately tenfold. This work opens up new possibility for the application of fullerenes as an excellent 3D electron carrier in living biophotovoltaics.

Cross-reactive CD8+ T cell responses to tumor-associated antigens (TAAs) and homologous microbiota-derived antigens (MoAs).

BACKGROUND: We have recently shown extensive sequence and conformational homology between tumor-associated antigens (TAAs) and antigens derived from microorganisms (MoAs). The present study aimed to assess the breadth of T-cell recognition specific to MoAs and the corresponding TAAs in healthy subjects (HS) and patients with cancer (CP). METHOD: A library of > 100 peptide-MHC (pMHC) combinations was used to generate DNA-barcode labelled multimers. Homologous peptides were selected from the Cancer Antigenic Peptide Database, as well as Bacteroidetes/Firmicutes-derived peptides. They were incubated with CD8 + T cells from the peripheral blood of HLA-A*02:01 healthy individuals (n = 10) and cancer patients (n = 16). T cell recognition was identified using tetramer-staining analysis. Cytotoxicity assay was performed using as target cells TAP-deficient T2 cells loaded with MoA or the paired TuA. RESULTS: A total of 66 unique pMHC recognized by CD8+ T cells across all groups were identified. Of these, 21 epitopes from microbiota were identified as novel immunological targets. Reactivity against selected TAAs was observed for both HS and CP. pMHC tetramer staining confirmed CD8+ T cell populations cross-reacting with CTA SSX2 and paired microbiota epitopes. Moreover, PBMCs activated with the MoA where shown to release IFNγ as well as to exert cytotoxic activity against cells presenting the paired TuA. CONCLUSIONS: Several predicted microbiota-derived MoAs are recognized by T cells in HS and CP. Reactivity against TAAs was observed also in HS, primed by the homologous bacterial antigens. CD8+ T cells cross-reacting with MAGE-A1 and paired microbiota epitopes were identified in three subjects. Therefore, the microbiota can elicit an extensive repertoire of natural memory T cells to TAAs, possibly able to control tumor growth ("natural anti-cancer vaccination"). In addition, non-self MoAs can be included in preventive/therapeutic off-the-shelf cancer vaccines with more potent anti-tumor efficacy than those based on TAAs.

Diversity of US participants in AstraZeneca-sponsored clinical trials.

BACKGROUND: To develop medicines that are safe and efficacious to all patients, clinical trials must enroll appropriate target populations, but imbalances related to race, ethnicity and sex have been reported. A comprehensive analysis and improvement in understanding representativeness of patient enrollment in industry-sponsored trials are key public health needs. METHODS: We assessed race/ethnicity and sex representation in AstraZeneca (AZ)-sponsored clinical trials in the United States (US) from 2010 to 2022, compared with the 2019 US Census. RESULTS: In total, 246 trials representing 95,372 patients with complete race/ethnicity and sex records were analyzed. The proportions of different race/ethnicity subgroups in AZ-sponsored clinical trials and the US Census were similar (White: 69.5% vs 60.1%, Black or African American: 13.3% vs 12.5%, Asian: 1.8% vs 5.8%, Hispanic: 14.4% vs 18.5%). We also observed parity in the proportions of males and females between AZ clinical trials and US Census (males: 52.4% vs 49.2%, females: 47.6% vs 50.8%). Comparisons of four distinct therapy areas within AZ (Respiratory and Immunology [R&I]; Cardiovascular, Renal, and Metabolism [CVRM]; Solid Tumors; and Hematological Malignancies), including by trial phases, revealed greater variability, with proportions observed above and below US Census levels. CONCLUSION: This analysis provides the first detailed insights into the representativeness of AZ trials. Overall, the proportions of different race/ethnicity and sex subgroups in AZ-sponsored clinical trials were broadly aligned with the US Census. We outline some of AZ's planned health equity initiatives that are intended to continue to improve equitable patient enrollment.

Evaluation of a microencapsulated form of zinc oxide on weanling pig growth performance, fecal zinc excretion, and small intestinal morphology.

A total of 300 pigs (DNA 200 × 400; initially 6.0 ±â€…0.08 kg body weight [BW]) were used in a 42-d study to evaluate a microencapsulated form of zinc oxide. At weaning, pigs were randomly allocated to pens, and pens were randomly assigned to dietary treatments with 5 pigs per pen and 12 pens per treatment. Dietary treatments were 1) negative control (CON; standard nursery diet containing 110 ppm Zn in the form of zinc sulfate from trace mineral premix); 2) control diet with 400 ppm added Zn from ZnO included in phases 1 and 2 (Low-ZnO); 3) control diet with 3,000 ppm added Zn from ZnO included in phase 1 and 2,000 ppm added Zn from ZnO included in phase 2 (High-ZnO); 4) control diet with 400 ppm added Zn from microencapsulated ZnO included in phases 1 and 2 (Low-MZnO; Vetagro S.p.A., Reggio Emilia, Italy); 5) control diet with 3,000 ppm added Zn from microencapsulated ZnO in phase 1 and 2,000 ppm added Zn from microencapsulated ZnO in phase 2 (high-MZnO; Vetagro S.p.A., Reggio Emilia, Italy). On days 10 and 28, fecal samples from 2 pigs per pen were collected for fecal Zn concentrations, and on day 28, 30 pigs (n = 6) were euthanized, and small intestinal tissues were collected to evaluate morphology. For the entire treatment period (days 0 to 28) there was no evidence of differences in average daily gain (ADG), average daily feed intake (ADFI), or G:F (P > 0.05). During the common phase 3 (days 28 to 42) pigs fed the negative control, High-MZnO, or Low-MZnO had improved (P < 0.0001) ADG and ADFI compared to pigs fed High- or Low-ZnO. For the entire experiment (days 0 to 42), pigs fed Low-ZnO or High-ZnO had reduced (P < 0.0001) ADG compared to those fed the negative control. A significant treatment × day interaction (P = 0.04) was observed for fecal Zn concentrations, where the level of Zn excreted in the feces was dependent on the sampling day in pigs fed a low level of ZnO or low level of microencapsulated ZnO. There was no evidence (P > 0.05) that small intestinal morphology differed significantly between treatments. In summary, feeding a microencapsulated form of ZnO did not alter piglet growth performance during the treatment period. Pigs fed a low level of ZnO or microencapsulated ZnO had reduced fecal Zn excretion by the end of the feeding period, but no significant impacts were observed on piglet small intestinal morphology.

Milk replacer feeding once or twice a day did not change the ruminal metabolomic profile and the microbial diversity of dairy calves from birth to weaning.

In commercial dairy production systems, feeding calves once a day could be an alternative to reduce labor expenses. Several studies comparing once (OAD) versus twice (TAD) a day milk feeding systems have not evidenced differences in calf growth, rumen development, blood parameters or health scores, but impact on ruminal microbiota remains to be investigated. The objective of this study was to determine the effects of OAD or TAD on the establishment of the ruminal microbiota and its metabolic activity. Sixteen male calves (45.9 ± 5.7 kg at birth) were involved in the trial from birth to weaning (63 d). After the colostrum phase, 2 feeding programs based on a milk replacer were tested and calves were allocated to these programs on d 5. To study the establishment of the bacterial community, ruminal fluid was obtained from each calf one hour after the morning meal at 7 (d 7), 35 (d 35) and 63 (d 63) days of age. The ruminal metabolome was evaluated at a 7 d interval from d 1 to d 63. Ruminal microbiota and metabolite profiles were characterized by 16 S rRNA gene sequencing- and by H-NMR spectroscopy, respectively. Our results showed that feeding milk replacer once or twice a day did not change the ruminal microbiota and metabolites of dairy calves from birth to weaning. Microbial data showed that diversity and richness increased with age, suggesting a shift from an heterogeneous and less diverse community after birth (d 7) to a more diverse but homogeneous community at 35 and 63 d. These findings suggest that feeding milk once a day can be successfully applied to a calf feeding system without compromising microbial establishment and functions.

Meta-analysis prediction intervals are under reported in sport and exercise medicine.

AIM: Prediction intervals are a useful measure of uncertainty for meta-analyses that capture the likely effect size of a new (similar) study based on the included studies. In comparison, confidence intervals reflect the uncertainty around the point estimate but provide an incomplete summary of the underlying heterogeneity in the meta-analysis. This study aimed to estimate (i) the proportion of meta-analysis studies that report a prediction interval in sports medicine; and (ii) the proportion of studies with a discrepancy between the reported confidence interval and a calculated prediction interval. METHODS: We screened, at random, 1500 meta-analysis studies published between 2012 and 2022 in highly ranked sports medicine and medical journals. Articles that used a random effect meta-analysis model were included in the study. We randomly selected one meta-analysis from each article to extract data from, which included the number of estimates, the pooled effect, and the confidence and prediction interval. RESULTS: Of the 1500 articles screened, 866 (514 from sports medicine) used a random effect model. The probability of a prediction interval being reported in sports medicine was 1.7% (95% CI = 0.9%, 3.3%). In medicine the probability was 3.9% (95% CI = 2.4%, 6.6%). A prediction interval was able to be calculated for 220 sports medicine studies. For 60% of these studies, there was a discrepancy in study findings between the reported confidence interval and the calculated prediction interval. Prediction intervals were 3.4 times wider than confidence intervals. CONCLUSION: Very few meta-analyses report prediction intervals and hence are prone to missing the impact of between-study heterogeneity on the overall conclusions. The widespread misinterpretation of random effect meta-analyses could mean that potentially harmful treatments, or those lacking a sufficient evidence base, are being used in practice. Authors, reviewers, and editors should be aware of the importance of prediction intervals.

¿Tiene el tratamiento previo con inhibidores de la 5-alfa reductasa repercusión en la enucleación prostática con láser holmium? Resultados de un estudio prospectivo observacional y revisión de la literatura / Evaluating the effects of preoperative treatment with 5-alpha reductase inhibitors in holmium laser enucleation of the prostate

Introducción y objetivos Los pacientes tratados con HoLEP frecuentemente han recibido tratamientos previos, incluyendo los inhibidores de la 5-alfa-reductasa (5ARI). Nuestro objetivo es evaluar el efecto del tratamiento previo con 5ARI en los parámetros perioperatorios y del postoperatorio immediato en pacientes tratados con HoLEP. Materiales y métodos Se ha llevado a cabo un estudio retrospectivo utilizando una base de datos recogida prospectivamente, de todos los pacientes tratados con HoLEP en nuestro centro entre enero de 2017 y enero de 2023. Se han analizado los gramos de resección, la eficiencia de enucleación y morcelación (gramos enucleados/tiempo de enucleación y gramos de morcelación/tiempo de morcelación), las complicaciones postoperatorias, el tiempo de hospitalización y el descenso de hemoglobina. Resultados Se han incluido 327 pacientes; 173 de ellos (52,9%) fueron tratados con 5ARI. Entre los parámetros perioperatorios estudiados para determinar la eficiencia no se encontraron diferencias. No se observaron diferencias en las complicaciones peri o postoperatorias, estancia hospitalaria o descenso de hemoglobina. Conclusiones El uso de 5ARI no tuvo repercusión en el postoperatorio immediato de los pacientes tratados con HoLEP. En nuestra cohorte el uso de 5ARI no ha demostrado alterar la eficiencia quirúrgica, ni en la enucleación ni en la morcelación. Futuros estudios multicéntricos serán necesarios para corroborar estos hallazgos. (AU)

Introduction and aim Patients treated with HoLEP are frequently treated with previous treatments, including 5-alpha-reductase inhibitors (5-ARIs). We investigated the impact of pretreatment with 5-ARIs on perioperative and immediate postoperative parameters in patients treated with HoLEP. Material and Methods A retrospective study was performed using a prospectively collected database including all patients treated with HoLEP at our center between January 2017 and January 2023. The resected tissue weight, enucleation and morcellation efficiency (enucleation weight/time and morcellation weight/ time), postoperative complications, hospital stay and hemoglobin drop have been analyzed. Results A total of 327 patients were included. Of these, 173 (52.9%) were treated with 5-ARIs. No differences were found among the perioperative parameters investigated to determine efficiency. No differences were observed in peri- or postoperative complications, hospital stay or hemoglobin drop. Conclusions Therapy with 5-ARIs had no impact on the immediate postoperative outcomes of patients treated with HoLEP. In our cohort, we observed that the use of 5-ARIs did not affect surgical efficiency, enucleation or morcellation. Further multicenter studies will be necessary to validate these findings. (AU)

100% Orange Juice Consumption is Associated with Socioeconomic Status, Improved Nutrient Adequacy, and Higher Bioactive Compounds Intake: Results from Brazilian National Dietary Survey 2017-2018.

OBJECTIVE: The consumption of 100% orange juice (OJ) has been associated with nutrient adequacy and better diet quality. To date, there are few analyses exploring 100% OJ consumption patterns across populations, with no data from Brazil. We aimed to explore the associations between 100% OJ consumption, sociodemographic factors, and nutrient intake in a representative sample of the Brazilian general population aged 10 years or older. METHODS: Data were obtained from the National Dietary Survey 2017-2018, a cross-sectional study including data on individual food intake of 46,164 subjects aged ≥10 years collected using two 24-h dietary recalls. RESULTS: 100% OJ was consumed by 11% of the population, with a mean intake of 43.0 ml/d. Males were more frequent consumers compared to females, and the percentage of consumers increased with education and income. 100% OJ consumption was associated with higher intakes of energy, vitamin C, folate, calcium, magnesium, potassium, polyphenols, and carotenoids. There is no significant difference in fiber intake between consumers and non-consumers. 100% OJ consumers had a higher percentage of the population meeting the Estimated Average Requirement for vitamin A, vitamin C, vitamin D, folate, calcium, and magnesium. CONCLUSION: Our results suggest that 100% OJ could be a component of a healthy diet, helping individuals to achieve nutrient recommendations.

Skill acquisition interventions for the learning of sports-related skills: A scoping review of randomised controlled trials.

BACKGROUND: Skill acquisition science is the study of how motor skills are acquired, developed and/or learned. There is substantive evidence for general motor skill acquisition in controlled laboratory settings yet the literature on the learning of sports-related skills is typically less conclusive. OBJECTIVES: This scoping review aimed to summarise the current literature on skill acquisition intervention studies examining the learning of sports-related skills as part of a randomised controlled trial, by synthesizing and extracting the most relevant features. METHODS: Four electronic databases (PsychINFO, PubMed, SPORTDiscus and Web of Science) were searched for relevant studies. The sample characteristics of these studies were extracted, and summarised. Two systematic searches of the literature were conducted. In the first search, eighty-six studies were retained. A second search was conducted in July 2022 to include new studies and specifically focused on the inclusion of within-subject design studies, resulting in the inclusion of 35 additional studies. A third search was conducted in May 2023 to include new studies resulting in the inclusion of 10 additional studies. RESULTS: One hundred and thirty studies across 29 sports were included in the review. The vast majority of the studies in this scoping review (n = 104) examined the learning of a sport-related skill in participants with no experience. Twenty-eight percent of all retained studies (n = 35) considered only the learning of a golf skill, and all studies were practiced in a laboratory environment, examining closed motor skills (n = 130). The most common intervention categories reported were attention (n = 22), instruction and demonstration (n = 20), practice design (n = 20), and perceptual training (n = 19). Nearly half of all studies used an immediate retention test within 48 h of the cessation of practice (n = 63), and just over one quarter of studies (n = 34) reported incorporating some form of transfer test. Eighty-six percent (n = 112) reported positive findings. CONCLUSIONS: The skewed focus on golf skills across a small number of skill acquisition interventions, the inconsistent use and reporting of performance measures, practice durations and measures of learning alongside the relatively small sample sizes consisting mostly of inexperienced learners and the skewed publication of positive findings should warrant caution. More empirical studies across a broader range of sports and with more consistent methodologies are needed to develop a robust pool of literature that can support academics and practitioners interested in which skill acquisition interventions could be used to influence the learning of sports-related skills.

Exploring potooxidative degradation pathways of harmol and harmalol alkaloids in water: effects of pH, excitation sources and atmospheric conditions.

This work explores the photochemical degradation of cationic species of 7-hydroxy-1-methyl-2H-pyrido[3,4-b]indole or harmol (1C) and the corresponding partially hydrogenated derivative 7-hydroxy-1-methyl-3,4-dihydro-2H-pyrido[3,4-b]indole or harmalol (2C) in aqueous solution. UV-visible absorption and fluorescence emission spectroscopy coupled with multivariate data analysis (MCR-ALS and PARAFAC), HPLC and HRESI-MS techniques were used for both quantitative and qualitative analysis. The formation of hydrogen peroxide reactive oxygen species (ROS) was quantified, and the influence of pH, oxygen partial pressure and photoexcitation source on the photochemical degradation of both compounds was assessed. The potential implications on the biosynthesis of ßCs and their biological role in living systems are discussed.

Chronic Viral Infections and Cancer, Openings for Therapies and Vaccines.

Infections are responsible for approximately one out of six cases of cancer worldwide [...].

Triclabendazole efficacy, prevalence, and re-infection of Fasciola hepatica in bovine and ovine naturally infected in the Andes of Ecuador.

Fasciola spp., infections are distributed worldwide including the Andes region of Ecuador, affecting cattle, sheep, porcine, humans, and other herbivores. Triclabendazole (TCBZ) is commonly used to treat animal infections. However, prospective studies on TCBZ efficacy and fascioliosis prevalence have not been studied in the highlands of Ecuador. This study was performed in a rural community at central of the Ecuadorian Andes in freely roaming bovine and ovine aimed to 1) evaluate the efficacy of TCBZ by administering a single oral dose of 12 mg/kg body weight, 2) assess the prevalence of F. hepatica infection and 3) to monitor re-infections for a follow-up period of five months. In total, 122, 86, 111, 110, 89, and 90 and 49, 34, 47, 28, 27, and 31 stool samples were collected each month from bovines and ovine, respectively. Besides, 32 stool samples from porcine were also collected at the beginning of the study. Stools were microscopically analyzed by formalin-ether concentration method to detect F. hepatica ova. The prevalence of F. hepatica infections before treatment was 55,7% and 63,3% for bovine and ovine, respectively. The infection prevalence was of 22% in porcine. The efficacity of triclabendazole was 83% and 97% in bovines and ovine, respectively, at 30 days post-treatment. The re-infection reaches to 54,4% in bovines and 61,3% in ovine after five months. TCBZ had a high efficacy and could be used for bovines and ovine Fasciola infections in the study region; however, re-infections reach the initial prevalence after five months. Therefore, we recommend integrated control strategies, including chemotherapy with a single oral dose of TCBZ, vector control, and future drug resistance studies.

Distribution of photoactive ß-carboline alkaloids across Passiflora caerulea floral organs.

This study reports valuable information regarding the presence and concentration of a series of photoactive ß-carboline (ßCs) alkaloids (norharmane, harmane, harmine, harmol, harmaline, and harmalol) and their distribution across the floral age and organs of Passiflora caerulea. UHPLC-MS/MS data reported herein reveal that the ßCs' content ranged from 1 to 110 µg kg-1 , depending on the floral organ and age. In certain physiologically relevant organs, such as anthers, ßCs' content was one order of magnitude higher than in other organs, suggesting a special role for ßCs in this specific organ. ßCs' content also varied in a structure-dependent manner. Alkaloids bearing a hydroxyl group at position C(7) of the main ßC ring were present at concentrations one order of magnitude higher than other ßC derivatives investigated. UV-visible and fluorescence spectroscopy of the flower extracts provided complementary information regarding other biologically relevant groups of chromophores (phenolic/indolic derivatives, flavonoids/carotenes, and chlorophylls). Since flowers are constantly exposed to solar radiation, the presence of photoactive ßCs in floral organs may have several (photo)biological implications that are further discussed.

Evaluating the effects of preoperative treatment with 5-alpha reductase inhibitors in holmium laser enucleation of the prostate.

INTRODUCTION AND AIM: Patients treated with HoLEP are frequently treated with previous treatments, including 5-alpha-reductase inhibitors (5-ARIs). We investigated the impact of pretreatment with 5-ARIs on perioperative and immediate postoperative parameters in patients treated with HoLEP. MATERIAL AND METHODS: A retrospective study was performed using a prospectively collected database including all patients treated with HoLEP at our center between January 2017 and January 2023. The resected tissue weight, enucleation and morcellation efficiency (enucleation weight/time and morcellation weight/ time), postoperative complications, hospital stay and hemoglobin drop have been analyzed. RESULTS: A total of 327 patients were included. Of these, 173 (52.9%) were treated with 5-ARIs. No differences were found among the perioperative parameters investigated to determine efficiency. No differences were observed in peri- or postoperative complications, hospital stay or hemoglobin drop. CONCLUSIONS: Therapy with 5-ARIs had no impact on the immediate postoperative outcomes of patients treated with HoLEP. In our cohort, we observed that the use of 5-ARIs did not affect surgical efficiency, enucleation or morcellation. Further multicenter studies will be necessary to validate these findings.

Anti-tumor necrosis factor α: originators versus biosimilars, comparison in clinical response assessment in a multicenter cohort of patients with inflammatory arthropathies.

OBJECTIVE: To compare etanercept and adalimumab biosimilars (SB4 and ABP501) and respective bioriginators in terms of safety and efficacy in a real-life contest. METHODS: We consequently enrolled patients affected by rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with SB4, and ABP501, or with corresponding originators, belonging to the main biological prescribing centers in the Lazio region (Italy), from 2017 to 2020. Data were collected at recruitment and after 4, 8, 12, and 24 months of therapy. RESULTS: The multicenter cohort was composed by 455 patients treated with biosimilars [SB4/ABP501 276/179; female/male 307/146; biologic disease-modifying anti-rheumatic drug (b-DMARD) naïve 56%, median age/ interquartile range 55/46-65 years] and 436 treated with originators (etanercept/adalimumab 186/259, female/ male 279/157, b-DMARD naïve 67,2%, median age/interquartile range 53/43-62 years). No differences were found about safety, but the biosimilar group presented more discontinuations due to inefficacy (p<0.001). Female gender, being a smoker, and being b-DMARD naïve were predictive factors of reduced drug survival (p=0.05, p=0.046, p=0.001 respectively). The retention rate at 24 months was 81.1% for bioriginators and 76.5% for biosimilars (median retention time of 20.7 and 18.9 months, respectively) (p=0.002). Patients with remission/low disease activity achievement at 4 months showed a cumulative survival of 90% to biosimilar therapy until 24 months (p=0.001); early adverse reactions instead represented a cause of subsequent drug discontinuation (p=0.001). CONCLUSIONS: Real-life data demonstrated a similar safety profile between biosimilars and originators, but a reduced biosimilar retention rate at 24 months. Biosimilars could be considered a valid, safe, and less expensive alternative to originators, allowing access to treatments for a wider patient population.

Integrated plasma metabolomics and lipidomics profiling highlights distinctive signature of hepatocellular carcinoma in HCV patients.

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) is essential towards the improvement of prognosis and patient survival. Circulating markers such as α-fetoprotein (AFP) and micro-RNAs represent useful tools but still have limitations. Identifying new markers can be fundamental to improve both diagnosis and prognosis. In this approach, we harness the potential of metabolomics and lipidomics to uncover potential signatures of HCC. METHODS: A combined untargeted metabolomics and lipidomics plasma profiling of 102 HCV-positive patients was performed by HILIC and RP-UHPLC coupled to Mass Spectrometry. Biochemical parameters of liver function (AST, ALT, GGT) and liver cancer biomarkers (AFP, CA19.9 e CEA) were evaluated by standard assays. RESULTS: HCC was characterized by an elevation of short and long-chain acylcarnitines, asymmetric dimethylarginine, methylguanine, isoleucylproline and a global reduction of lysophosphatidylcholines. A supervised PLS-DA model showed that the predictive accuracy for HCC class of metabolomics and lipidomics was superior to AFP for the test set (100.00% and 94.40% vs 55.00%). Additionally, the model was applied to HCC patients with AFP values < 20 ng/mL, and, by using only the top 20 variables selected by VIP scores achieved an Area Under Curve (AUC) performance of 0.94. CONCLUSION: These exploratory findings highlight how metabo-lipidomics enables the distinction of HCC from chronic HCV conditions. The identified biomarkers have high diagnostic potential and could represent a viable tool to support and assist in HCC diagnosis, including AFP-negative patients.

Trasplante cardíaco y autólogo de células progenitoras hematopoyéticas en pacientes con amiloidosis AL / Cardiac and autologous stem cell transplantation hematopoietic in patients with AL amyloidosis

Resumen Objetivo: Describir la evolución de las cadenas livianas libres séricas (CLL) en el período comprendido entre el trasplante cardíaco ortotópico (TCO) y el trasplante de células progenitoras hematopoyéticas (TCPH), la respuesta hematológica al año tras el TCPH y el tratamiento quimioterápico e inmunosupresor en pacientes con amiloidosis AL. Método: Serie de casos de pacientes consecutivos con diagnóstico de amiloidosis AL que recibieron TCO seguido de TCPH del Registro Institucional de Amiloidosis del Hospital Italiano de Buenos Aires, entre enero de 2010 y noviembre de 2021. Se reportaron los valores de CLL entre trasplantes y al año del TCPH. Las variables cuantitativas se describieron como mediana e intervalo intercuartil, y las variables categóricas como frecuencias absolutas y relativas. Resultados: De 106 pacientes con amiloidosis AL, seis tuvieron TCO seguido de TCPH. La mediana de edad fue de 55 años. La mayoría eran hombres (n = 5). En el período entre trasplantes, la CLL involucrada disminuyó en dos pacientes y se mantuvo estable en tres. Todos lograron la remisión hematológica completa al año del TCPH. Un solo paciente presentó recaída en el órgano sólido trasplantado. Tacrolimus, micofenolato de mofetilo y corticoides fue el esquema inmunosupresor utilizado después del TCO. Conclusiones: El TCO representa una opción de tratamiento en pacientes con falla cardíaca grave por amiloidosis, permitiendo luego un tratamiento intensivo con quimioterapia de inducción y TCPH. Si bien faltan estudios, la terapia inmunosupresora después del TCO podría tener algún efecto sobre las células plasmáticas clonales.

Abstract Objective: To describe the evolution of serum free light chains (FLC) in the period between orthotopic heart transplantation (OHT) and autologous stem cell transplantation (ASCT), the hematological response one year after ASCT and chemotherapy and immunosuppressive treatment in patients with AL amyloidosis. Method: Case series of consecutive patients diagnosed with AL amyloidosis who received OHT followed by ASCT from the Institutional Registry of Amyloidosis of the Italian Hospital of Buenos Aires, between January 2010 and November 2021. FLC values between transplants and at year post ASCT. Quantitative variables were described with their median and interquartile range. Categorical variables as absolute and relative frequencies. Results: Of 106 patients with AL amyloidosis, 6 had an OHT followed by ASCT. The median age was 55 years. Most were men (n = 5). In the period between transplants, the involved CLL decreased in two patients and remained stable in three. All achieved complete hematologic remission 1 year after ASCT. A single patient presented relapse in the transplanted solid organ. Tacrolimus, mycophenolate mofetil, and corticosteroids were the immunosuppressive regimen used after OHT. Conclusions: OHT represents a treatment option in patients with severe heart failure due to amyloidosis, allowing later intensive treatment with induction chemotherapy and ASCT. Although studies are lacking, immunosuppressive therapy after OHT might have some effect on clonal plasma cells.

Incidence of Rapidly Progressive Osteoarthritis Following Intra-articular Hip Corticosteroid Injection: A Systematic Review and Meta-Analysis.

Background: The American Academy of Orthopedic Surgery recommends intra-articular corticosteroid injections (CSIs) for managing hip osteoarthritis (OA) based on short-term, prospective studies. Recent retrospective studies have raised concerns that CSIs may lead to rapidly progressive OA (RPOA). We sought to systematically review the literature of CSIs for hip OA to estimate the incidence of RPOA. Methods: MEDLINE, Embase, and Cochrane Library were searched to identify original research of hip OA patients receiving CSIs. Overall, 27 articles involving 5831 patients published from 1988 to 2022 were included. Study design, patient characteristics, CSI details, follow-up, and cases of RPOA were recorded. Studies were classified by their ability to detect RPOA based on follow-up. Random effects meta-analysis was used to calculate the incidence of RPOA for studies able to detect RPOA. Results: The meta-analytic estimate of RPOA incidence was 6% (95% confidence interval, 3%-9%) based on 10 articles classified as able to detect RPOA. RPOA definitions varied from progression of OA within 6 months to the presence of destructive changes. These studies were subject to bias from excluding patients with missing post-CSI radiographs. The remaining 17 articles were classified as unable to detect RPOA, including all of the studies cited in the American Academy of Orthopedic Surgery recommendation. Conclusions: The incidence of RPOA after CSIs remains unknown due to variation in definitions and follow-up. While RPOA following CSIs may be 6%, many cases are not severe, and this may reflect selection bias. Further research is needed to understand whether clinically significant RPOA is incident enough to limit CSI use.

Cardiac and autologous stem cell transplantation hematopoietic in patients with AL amyloidosis.

OBJECTIVE: To describe the evolution of serum free light chains (FLC) in the period between orthotopic heart transplantation (OHT) and autologous stem cell transplantation (ASCT), the hematological response one year after ASCT and chemotherapy and immunosuppressive treatment in patients with AL amyloidosis. METHOD: Case series of consecutive patients diagnosed with AL amyloidosis who received OHT followed by ASCT from the Institutional Registry of Amyloidosis of the Italian Hospital of Buenos Aires, between January 2010 and November 2021. FLC values between transplants and at year post ASCT. Quantitative variables were described with their median and interquartile range. Categorical variables as absolute and relative frequencies. RESULTS: Of 106 patients with AL amyloidosis, 6 had an OHT followed by ASCT. The median age was 55 years. Most were men (n = 5). In the period between transplants, the involved CLL decreased in two patients and remained stable in three. All achieved complete hematologic remission 1 year after ASCT. A single patient presented relapse in the transplanted solid organ. Tacrolimus, mycophenolate mofetil, and corticosteroids were the immunosuppressive regimen used after OHT. CONCLUSIONS: OHT represents a treatment option in patients with severe heart failure due to amyloidosis, allowing later intensive treatment with induction chemotherapy and ASCT. Although studies are lacking, immunosuppressive therapy after OHT might have some effect on clonal plasma cells.

OBJETIVO: Describir la evolución de las cadenas livianas libres séricas (CLL) en el período comprendido entre el trasplante cardíaco ortotópico (TCO) y el trasplante de células progenitoras hematopoyéticas (TCPH), la respuesta hematológica al año tras el TCPH y el tratamiento quimioterápico e inmunosupresor en pacientes con amiloidosis AL. MÉTODO: Serie de casos de pacientes consecutivos con diagnóstico de amiloidosis AL que recibieron TCO seguido de TCPH del Registro Institucional de Amiloidosis del Hospital Italiano de Buenos Aires, entre enero de 2010 y noviembre de 2021. Se reportaron los valores de CLL entre trasplantes y al año del TCPH. Las variables cuantitativas se describieron como mediana e intervalo intercuartil, y las variables categóricas como frecuencias absolutas y relativas. RESULTADOS: De 106 pacientes con amiloidosis AL, seis tuvieron TCO seguido de TCPH. La mediana de edad fue de 55 años. La mayoría eran hombres (n = 5). En el período entre trasplantes, la CLL involucrada disminuyó en dos pacientes y se mantuvo estable en tres. Todos lograron la remisión hematológica completa al año del TCPH. Un solo paciente presentó recaída en el órgano sólido trasplantado. Tacrolimus, micofenolato de mofetilo y corticoides fue el esquema inmunosupresor utilizado después del TCO. CONCLUSIONES: El TCO representa una opción de tratamiento en pacientes con falla cardíaca grave por amiloidosis, permitiendo luego un tratamiento intensivo con quimioterapia de inducción y TCPH. Si bien faltan estudios, la terapia inmunosupresora después del TCO podría tener algún efecto sobre las células plasmáticas clonales.