Switching from immediate- to extended-release cysteamine in patients with nephropathic cystinosis: from clinical trials to clinical practice.

Background: The purpose of this study is to evaluate the effectiveness and safety of switching from immediate-release (IR) to extended-release (ER) cysteamine in patients with nephropathic cystinosis (NC) in Spain. Methods: We conducted an observational, retrospective, multicentre study in NC patients who received IR cysteamine for at least 12 months, switched to ER cysteamine, and received it for at least 6 months before inclusion. Results: Data were collected from nine patients (four children, five adults) 36 months before and after the switch. Despite the highly selected population, an improvement in growth, particularly in children and a significant reduction in hospitalization days was observed. A decrease in halitosis, body odour and gastrointestinal effects was reported in most of the patients who suffered before the switch, and the use of proton pump inhibitors (PPIs) decreased in some patients. The estimated glomerular filtration rate (eGFR) remained stable in patients with preserved kidney function. No significant changes in white blood cell (WBC) cystine levels were observed after the switch. There was no significant difference in the cysteamine dose received. However, some patients were receiving <50% of the recommended dose of cysteamine before and after the switch and showed elevated levels of WBC cystine. Conclusions: Switching from IR to ER cysteamine in clinical practice reduces hospital stays, improves nutritional status and growth in paediatric patients and could help to enhance treatment tolerability by reducing side effects. Furthermore, the dosing of ER cysteamine could promote therapeutic compliance and positively affect the quality of life of the NC population.

The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.

The retina is the sensory tissue responsible for the first stages of visual processing, with a conserved anatomy and functional architecture among vertebrates. To date, retinal eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and others, affect nearly 170 million people worldwide, resulting in vision loss and blindness. To tackle retinal disorders, the developing retina has been explored as a versatile model to study intercellular signaling, as it presents a broad neurochemical repertoire that has been approached in the last decades in terms of signaling and diseases. Retina, dissociated and arranged as typical cultures, as mixed or neuron- and glia-enriched, and/or organized as neurospheres and/or as organoids, are valuable to understand both neuronal and glial compartments, which have contributed to revealing roles and mechanisms between transmitter systems as well as antioxidants, trophic factors, and extracellular matrix proteins. Overall, contributions in understanding neurogenesis, tissue development, differentiation, connectivity, plasticity, and cell death are widely described. A complete access to the genome of several vertebrates, as well as the recent transcriptome at the single cell level at different stages of development, also anticipates future advances in providing cues to target blinding diseases or retinal dysfunctions.

Cell cycle regulation by ADP and IGF-1 in cultured late developing glia progenitors of the avian retina.

In the avian retina, ADP induces the proliferation of late developing glia progenitors. Here, we show that in serum-containing retinal cell cultures, ADP-induced increase in [3H]-thymidine incorporation can be prevented by the IGF-1 receptor antagonists AG1024 and I-OMe-Tyrphostin AG 538, suggesting the participation of IGF-1 in ADP-mediated progenitor proliferation. In contrast, no increase in [3H]-thymidine incorporation is observed in retinal cultures treated only with IGF-1. Under serum starvation, while no increase in cell proliferation is detected in cultures treated only with ADP or IGF-1, a significant increase in [3H]-thymidine incorporation and number of PCNA expressing cells is observed in cultures treated concomitantly with ADP plus IGF-1, suggesting that both molecules are required to induce proliferation of retinal progenitors. In serum-starved cultures, although an increase in cell viability is detected by MTT assays in IGF-1-treated cultures, no significant increase in viability of [3H]-thymidine labeled progenitors is observed, suggesting that IGF-1 may contribute to survival of postmitotic cells in culture. While only ADP increases intracellular calcium, only IGF-1 induces the phosphorylation of Akt in the retinal cultures. IGF-1 through the PI3K/Akt pathway induces a significant increase in the transcription and expression of CDK1 with a decrease in phospho-histone H3 expression that is concomitant with an increase in the expression of cyclins D1 and E and CDK2. These findings suggest that IGF-1 stimulates CDK-1 mRNA and protein expression that enable progenitors to progress through the cell cycle. However, signaling of ADP in the presence IGF-I seems to be required for DNA synthesis.

Legius Syndrome and Inflammatory Bowel Disease: A Pediatric Case Report.

Legius syndrome (LS) is a rare and underrecognized disorder that is often misdiagnosed as neurofibromatosis type 1 (NF1). It is characterized by café-au-lait macules without the tumoral manifestations of NF1. We report the case of an 11-year-old patient with multiple café-au-lait macules and intertriginous freckling who was admitted for bloody stools, joint pain, and weight loss. His clinical and endoscopic findings were consistent with inflammatory bowel disease (IBD). He also met the clinical diagnostic criteria for NF1 but not for LS. Genetic testing played a pivotal role in the differential diagnosis and revealed a loss-of-function mutation in the SPRED1 gene, confirming the diagnosis of LS. This is the first reported case of a patient with IBD and LS. The subtle manifestations of LS make it an underdiagnosed disease, which reduces the likelihood of it being diagnosed in association with other diseases, such as IBD. There are, however, 10 published case reports linking IBD and NF1, and some pathophysiological mechanisms have been proposed. Continued reporting will help clarify the relationship between IBD and RASopathies such as NF1 and LS.

Association of apoptosis-related variants to malaria infection and parasite density in individuals from the Brazilian Amazon.

BACKGROUND: In malaria infection, apoptosis acts as an important immunomodulatory mechanism that leads to the elimination of parasitized cells, thus reducing the parasite density and controlling immune cell populations. Here, it was investigated the association of INDEL variants in apoptotic genes-rs10562972 (FAS), rs4197 (FADD), rs3834129 and rs59308963 (CASP8), rs61079693 (CASP9), rs4647655 (CASP3), rs11269260 (BCL-2), and rs17880560 (TP53)-and the influence of genetic ancestry with susceptibility to malaria and parasite density in an admixed population from the Brazilian Amazon. METHODS: Total DNA was extracted from 126 malaria patients and 101 uninfected individuals for investigation of genetic ancestries and genotypic distribution of apoptosis-related variants by Multiplex PCR. Association analyses consisted of multivariate logistic regressions, considering the following comparisons: (i) DEL/DEL genotype vs. INS/DEL + INS/INS; and (ii) INS/INS vs. INS/DEL + DEL/DEL. RESULTS: Individuals infected by Plasmodium falciparum had significantly higher African ancestry proportions in comparison to uninfected controls, Plasmodium vivax, and mixed infections. The INS/INS genotype of rs3834129 (CASP8) seemed to increase the risk for P. falciparum infection (P = 0.038; OR = 1.867; 95% CI 0.736-3.725), while the DEL/DEL genotype presented a significant protective effect against infection by P. falciparum (P = 0.049; OR = 0.446; 95% CI 0.185-0.944) and mixed infection (P = 0.026; OR = 0.545; 95% CI 0.281-0.996), and was associated with lower parasite density in P. falciparum malaria (P = 0.009; OR = 0.383; 95% CI 0.113-1.295). Additionally, the INS/INS genotype of rs10562972 (FAS) was more frequent among individuals infected with P. vivax compared to P. falciparum (P = 0.036; OR = 2.493; 95% CI 1.104-4.551), and the DEL/DEL genotype of rs17880560 (TP53) was significantly more present in patients with mono-infection by P. vivax than in individuals with mixed infection (P = 0.029; OR = 0.667; 95% CI 0.211-1.669). CONCLUSIONS: In conclusion, variants in apoptosis genes are associated with malaria susceptibility and parasite density, indicating the role of apoptosis-related genetic profiles in immune responses against malaria infection.

Management of immunosuppressive therapy in kidney transplant recipients with COVID-19. A multicentre national study derived from the Spanish Society of Nephrology COVID registry.

INTRODUCTION: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated. OBJECTIVES: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis. MATERIAL AND METHODS: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis. RESULTS: renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years. The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased. Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7 ±â€¯0.8, 2.1 ±â€¯1.2 and 1.8 ±â€¯1 mg/dl respectively (p < 0.001). 56.9% of the patients (N = 350) were monitored for anti-HLA antibodies. 94% (N = 329) had no anti-HLA changes, while 6% (N = 21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N = 9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant. CONCLUSIONS: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.

Rational Design, Synthesis, and Characterization of a Solid Δ9-Tetrahydrocannabinol Nanoformulation Suitable for "Microdosing" Applications.

Background: This article highlights the formulation of a solid Δ9-tetrahydrocannabinol (THC)-loaded ingestible prepared from pure THC distillate. Methods: A THC-containing ethanol-assisted cannabinoid nanoemulsion (EACNE) was created using a solvent displacement technique. Subsequently, the EACNE was converted to a solid powdery material while still retaining its THC potency, a format uniquely suited for "microdosing" applications. Results: EACNE had an average lipid droplet size of ∼190 nm, with a polydispersity index of 0.15, and an average droplet ζ potential of -49±10 mV. The nanoemulsion (NE) was colloidally stable for at least 6 weeks, with no meaningful change in cannabinoid potency over the experimental period, as determined by high-performance liquid chromatography analysis. The EACNE remained stable when subjected to physical stresses such as heat, freeze/thaw cycles, carbonation, dilution to beverage concentrations, high sucrose concentrations, and a pH range between 5 and 8. The microencapsulated EACNE demonstrated limited free-flowing behavior but was freely redispersible in water without any visible phase separation. Conclusions: We report the design, creation, and characterization of a THC NE generated without the use of specialized equipment, such as a microfluidizer or a high-pressure homogenizer. This emulsion could readily be converted to a water-redispersible powder. This embodiment is particularly suited for THC "microdosing," a practice that might decouple the health benefits of THC from its psychotropic effects.

A Review of the Popular Uses, Anatomical, Chemical, and Biological Aspects of Kalanchoe (Crassulaceae): A Genus of Plants Known as "Miracle Leaf".

Species of the genus Kalanchoe have a long history of therapeutic use in ethnomedicine linked to their remarkable healing properties. Several species have chemical and anatomical similarities, often leading to confusion when they are used in folk medicine. This review aims to provide an overview and discussion of the reported traditional uses, botanical aspects, chemical constituents, and pharmacological potential of the Kalanchoe species. Published scientific materials were collected from the PubMed and SciFinder databases without restriction regarding the year of publication through April 2023. Ethnopharmacological knowledge suggests that these species have been used to treat infections, inflammation, injuries, and other disorders. Typically, all parts of the plant are used for medicinal purposes either as crude extract or juice. Botanical evaluation can clarify species differentiation and can enable correct identification and validation of the scientific data. Flavonoids are the most common classes of secondary metabolites identified from Kalanchoe species and can be correlated with some biological studies (antioxidant, anti-inflammatory, and antimicrobial potential). This review summarizes several topics related to the Kalanchoe genus, supporting future studies regarding other unexplored research areas. The need to conduct further studies to confirm the popular uses and biological activities of bioactive compounds is also highlighted.

Catastrophic Antiphospholipid Syndrome and Renal Failure: An Unexpected Recovery After Three Years on Dialysis.

Catastrophic antiphospholipid syndrome (CAPS) is a rare and life-threatening disorder characterised by arterial or venous thrombotic events, involving three or more organs in a short period of time, in the presence of persistent antiphospholipid antibodies. Long-term anticoagulation with warfarin is the standard of care to prevent recurrent vascular events. Besides supportive care, optimal management of CAPS is unclear and consensus among experts is lacking. We describe a patient with primary antiphospholipid syndrome who experienced probable CAPS after receiving rivaroxaban, resulting in extensive cutaneous ulceration, acute coronary syndrome and dialysis-dependent renal failure. Anticoagulation, glucocorticoids and plasmapheresis were started. In the haemodialysis period, he maintained treatment with long-term vitamin K antagonist. The international normalized ratio target was optimized to 3.5-4. This strategy was associated with the healing of skin lesions, regression of cardiac lesions and recovery of renal function after three years on dialysis.

Cell lipid droplet heterogeneity and altered biophysical properties induced by cell stress and metabolic imbalance.

Lipid droplets (LD) are important regulators of lipid metabolism and are implicated in several diseases. However, the mechanisms underlying the roles of LD in cell pathophysiology remain elusive. Hence, new approaches that enable better characterization of LD are essential. This study establishes that Laurdan, a widely used fluorescent probe, can be used to label, quantify, and characterize changes in cell LD properties. Using lipid mixtures containing artificial LD we show that Laurdan GP depends on LD composition. Accordingly, enrichment in cholesterol esters (CE) shifts Laurdan GP from ∼0.60 to ∼0.70. Moreover, live-cell confocal microscopy shows that cells present multiple LD populations with distinctive biophysical features. The hydrophobicity and fraction of each LD population are cell type dependent and change differently in response to nutrient imbalance, cell density, and upon inhibition of LD biogenesis. The results show that cellular stress caused by increased cell density and nutrient overload increased the number of LD and their hydrophobicity and contributed to the formation of LD with very high GP values, likely enriched in CE. In contrast, nutrient deprivation was accompanied by decreased LD hydrophobicity and alterations in cell plasma membrane properties. In addition, we show that cancer cells present highly hydrophobic LD, compatible with a CE enrichment of these organelles. The distinct biophysical properties of LD contribute to the diversity of these organelles, suggesting that the specific alterations in their properties might be one of the mechanisms triggering LD pathophysiological actions and/or be related to the different mechanisms underlying LD metabolism.

NMDA Receptor Activation and Ca2+/PKC Signaling in Nicotine-Induced GABA Transport Shift in Embryonic Chick Retina.

Nicotinic receptors are present in the retina of different vertebrates, and in the chick retina, it is present during early development throughout to post-hatching. These receptors are activated by nicotine, an alkaloid with addictive and neurotransmitter release modulation properties, such as GABA signaling. Here we evaluated the mechanisms of nicotine signaling in the avian retina during the development of neuron-glia cells at a stage where synapses are peaking. Nicotine almost halved [3H]-GABA uptake, reducing it by 45% whilst increasing more than two-fold [3H]-GABA release in E12 embryonic chick retinas. Additionally, nicotine mediated a 33% increase in [3H]-D-aspartate release. MK-801 50 µM blocked 66% of nicotine-induced [3H]-GABA release and Gö 6983 100 nM prevented the nicotine-induced reduction in [3H]-GABA uptake by rescuing 40% of this neurotransmitter uptake, implicating NMDAR and PKC (respectively) in the nicotinic responses. In addition, NO-711 prevented [3H]-GABA uptake and release induced by nicotine. Furthermore, the relevance of calcium influx for PKC activation was evidenced through fura-2 imaging. We conclude that the shift of GABA transport mediated by nicotine promotes GABA release by inducing transporter reversal via nicotine-induced EAA release through EAATs, or by a direct effect of nicotine in activating nicotinic receptors permeable to calcium and promoting PKC pathway activation and shifting GAT-1 activity, both prompting calcium influx, and activation of the PKC pathway and shifting GAT-1 activity.

Espiritualidade e religiosidade: influência na terapêutica e bem-estar no câncer / Spirituality and religiosity: influence on cancer therapy and well-being / Espiritualidad y religiosidad: influencia en la terapia y el bienestar en el cáncer

Resumo A religiosidade e a espiritualidade proporcionam força e confiança a pacientes com neoplasia para encarar situações difíceis ao longo do processo da busca pela cura, indicando que o uso da fé é importante nesse momento. O estudo buscou analisar, por meio de revisão sistemática de literatura, a produção científica nacional e internacional para aferir se práticas religiosas e espirituais facilitam a adesão terapêutica e melhoram a qualidade de vida da população com câncer. O sistema Grades of Recommendation, Assessment, Development and Evaluation foi empregado para classificar o nível de evidência dos estudos. Alguns artigos demonstraram que espiritualidade e religiosidade influenciam positivamente no tratamento e bem-estar dos pacientes. Com base nos resultados, conclui-se que pacientes com câncer que utilizam a religiosidade e espiritualidade como estratégia apresentam maior esperança no tratamento, entretanto são necessários estudos mais aprofundados na área para garantir a eficácia dessa utilização.

Abstract Religiosity and spirituality provide cancer patients with strength and confidence to face difficult situations during the process of seeking a cure, indicating that faith is an important element at this time. This systematic literature review analyzed the national and international scientific production to assess whether religious and spiritual practices facilitate therapeutic adherence and improve the quality of life of cancer patients. Level of evidence was classified using the Grades of Recommendation, Assessment, Development and Evaluation approach. Some articles showed that spirituality and religiosity positively influence treatment and patient well-being. In conclusion, cancer patients who use religiosity and spirituality as a strategy have grater hope in treatment; however, further in-depth studies are needed to ensure its effectiveness.

Resumen La religiosidad y la espiritualidad aportan fuerza y confianza a los pacientes con cáncer para enfrentar situaciones difíciles en la búsqueda de la cura, lo que muestra que la fe es importante en este momento. Desde una revisión sistemática de la literatura, este estudio analizó la producción científica nacional e internacional para identificar si las prácticas religiosas y espirituales facilitan la adherencia terapéutica y mejoran la calidad de vida de los pacientes con cáncer. El sistema Grades of Recommendation, Assessment, Development and Evaluation se utilizó para calificar el nivel de evidencia. Algunos artículos indican que la espiritualidad y la religiosidad influyen positivamente en el tratamiento y el bienestar de los pacientes. Los hallazgos permiten concluir que los pacientes con cáncer que usan como estrategia la religiosidad y la espiritualidad tienen mayor esperanza en el tratamiento, sin embargo, se necesitan más estudios para asegurar la efectividad de este uso.

Níveis séricos de vitamina D e alterações hepáticas em pacientes com malária na região Amazônica / Serum levels of vitamin d and hepatic changes in patients with malaria in the Amazon region / Niveles séricos de vitamina d y alteraciones hepáticas en pacientes con malaria en la Amazonia

Vários estudos sugerem a importância da vitamina D ­ 25(OH)D ­ na evolução clínica dos pacientes com malária. Entretanto, a prevalência de deficiência de 25(OH)D na população amazônica é pouco conhecida, havendo também poucos estudos com pacientes diagnosticados com malária. Assim, o objetivo deste estudo foi avaliar os níveis séricos de 25(OH)D em pacientes com malária e sua relação com dados epidemiológicos, parasitológico e provas de função hepática. Para tanto, foi realizado um estudo transversal analítico com um grupo de pacientes com malária e um grupo controle no município de Itaituba (PA), Brasil, no período de janeiro de 2018 a outubro de 2019. Elaborou-se um protocolo para avaliação dos dados sociodemográficos, parasitológicos e laboratoriais, adotando-se o nível de significância de 5%. A prevalência de deficiência de 25(OH)D foi observada nos pacientes com malária (28,5%) e no grupo controle (24,6%), sem diferença estatística; porém, entre os residentes no garimpo, os níveis séricos foram estatisticamente menores nos pacientes com malária. Os níveis séricos de transaminase glutâmico-pirúvica (TGP) apresentaram correlação inversa com os de 25(OH)D. As provas de função hepática foram significativamente maiores no grupo com malária. Dessa forma, este estudo evidenciou a deficiência de 25(OH)D em Itaituba. Alterações hepáticas pela infecção plasmodial podem ter contribuído para a correlação inversa observada entre os níveis de TGP e 25(OH)D.

Several studies suggest the importance of vitamin D ­ 25(OH)D ­ in the clinical evolution of patients with malaria. However, the prevalence of 25(OH)D deficiency in the Amazonian population is little known, and studies with patients diagnosed with malaria are scarce. Thus the objective of this study is to evaluate the serum levels of 25(OH)D in patients with malaria and its relationship with epidemiological and parasitological data and liver function tests. To that end, an analytical cross-sectional study was carried out with a group of patients with malaria and a control group in the municipality of Itaituba (PA), Brazil, from January 2018 to October 2019. A protocol was elaborated for the evaluation of sociodemographic, parasitological, and laboratory data, adopting a significance level of 5%. Results: The prevalence of 25(OH)D deficiency was observed in patients with malaria (28.5%) and in the control group (24.6%), with no statistical difference; however, among residents in the mining, serum levels were statistically lower in patients with malaria. The glutamic-pyruvic transaminase (GPT) serum levels showed an inverse correlation with 25(OH)D levels. Liver function tests were significantly higher in the malaria group. Thus, this study evidenced 25(OH)D deficiency in Itaituba. Hepatic changes due to plasmodial infection may have contributed to the inverse correlation observed between GPT and 25(OH)D levels.

Diversos estudios sugieren la importancia de la vitamina D ­[25(OH)D]­ en la evolución clínica de pacientes con malaria. Sin embargo, la prevalencia de la deficiencia de 25(OH)D en la población amazónica es poco conocida y existen pocos estudios en pacientes con malaria. Ante esto, el objetivo de este estudio fue evaluar los niveles séricos de 25(OH)D en pacientes con malaria y su relación con datos epidemiológicos, parasitológicos y pruebas de función hepática. Para ello, se realizó un estudio transversal analítico en el grupo de pacientes con malaria y en un grupo control en el municipio de Itaituba (PA), Brasil, de enero de 2018 a octubre de 2019. Se elaboró un protocolo para la evaluación de datos sociodemográficos, parasitológicos y de laboratorio, adoptando un nivel de significancia del 5%. La prevalencia de deficiencia de 25(OH)D se observó en pacientes con malaria (28,5%) y en el grupo control (24,6%), sin diferencia estadística; sin embargo, entre los residentes en la minería, los niveles séricos fueron estadísticamente inferiores en pacientes con malaria. Los niveles séricos de transaminasa glutámico pirúvica (TGP) mostraron una correlación inversa con los niveles de 25(OH)D. Las pruebas de función hepática fueron significativamente más altas en el grupo de malaria. De esta manera, se evidenció deficiencia de 25(OH)D en la población de Itaituba. Los cambios hepáticos debido a la infección plasmodial pueden haber contribuido a la correlación inversa observada entre los niveles de TGP y 25(OH)D.

Combined Liver-Kidney Transplantation in High Immunologic Risk Recipients: Kidney Graft Evolution.

BACKGROUND: Candidates for combined liver-kidney transplant frequently present pretransplant HLA sensitization in most cases related to elevated prior transfusion requirements. The urgency criterion and the evidence of the protective effect at the immunologic level of the liver graft open the possibility of carrying out the combined transplant in patients with an incompatible crossmatch. The single-center experience presented here describes the patient profile and kidney graft evolution observed in this highly sensitized group. METHODS: Descriptive study of a series of 4 cases of patients with positive crossmatch results who received a simultaneous liver-kidney transplant at our center. Demographic characteristics and clinical information were collected and detailed. RESULTS: Before the transplant, 2 patients presented HLA class I antibodies and the other 2 showed both class I and II. The post-transplant crossmatch result was negative in 2 of the 4 patients. All received induction with Thymoglobulin. In the 2 patients in whom the crossmatch remained positive, treatment with plasmapheresis, intravenous immunoglobulins and rituximab was initiated, after which the crossmatch resulted negative. During follow-up, anti-HLA antibodies were monitored, with the presence of mainly class I antibodies with variable mean fluorescence intensity being detected in all but 1 patient. Renal graft function remained stable throughout the tracing without objectifying histologic signs of rejection during the first 6 months of evolution. CONCLUSIONS: In our experience, combined liver-kidney transplant in sensitized patients with an incompatible crossmatching test has presented satisfactory outcomes. Close clinical and analytical monitoring is essential.

Estrategias de regulación emocional de niños/as en el aprendizaje de la escritura en situación de clase y de entrevista / Strategies for emotional regulation of children in learning to write in class and interview situations

Resumen El presente estudio se propone contribuir al campo de la autorregulación temprana desde un enfoque ecológico y situado y, al mismo tiempo, al campo del aprendizaje de la escritura. Sus objetivos son: (1) identificar eventos emocionalmente desafiantes en el aprendizaje de la escritura de niños/as; (2) indagar el despliegue de sus estrategias de regulación emocional; y (3) analizar la variación de dichas estrategias en situación de clase y de entrevista. Participaron 10 niños/as de primer grado de 6 y 7 años de la ciudad de San Carlos de Bariloche (Argentina). Se realizaron observaciones de clases de Lengua focalizadas en escritura y entrevistas individuales. Las entrevistas se originaron en videos-elicitación cortos de niños/as actuando en eventos emocionalmente desafiantes en momentos de aprendizaje de la escritura: la percatación de una brecha entre el saber/poder y las demandas de una tarea, la exposición social y el entorno distractor. Se identificaron siete eventos emocionalmente desafiantes en total, sumándose cuatro a los propuestos en los videos-elicitación: la adecuación a normas externas, la corrección, la dificultad con el material y la equivocación. Asimismo, se documentó un amplio repertorio de estrategias de regulación emocional. Las más frecuentes fueron la modificación de la situación social, la comunicación y la expresión. Las observaciones permitieron hallar la modificación de la situación física, el control y el habla privada. En las entrevistas se pudo registrar la actividad alternativa, la respiración, la comunicación y la revaluación cognitiva. Se concluyó que la complementación de técnicas resulta promisoria para el estudio de la regulación emocional en el aprendizaje de la escritura.

Abstract Learning to write involves the challenge to understand and regulate one's own emotions in situation, such as frustration, anxiety and different moods. In recent years, the study of emotion regulation in children through different methodological tools, such as interviews, questionnaires or observations, has increased. However, to date there are few studies that complement these techniques. The present study seeks to contribute to early emotion regulation in learning to write from a sociocultural, ecological and situated approach, through the combination of interviews and class observations. The aims are to: (1) identify emotionally challenging events in children's learning to write; (2) describe the deployment of their strategies of emotion regulation; and (3) analyze the variation of these strategies in class and interview situations. Participants were 10 first graders from a school located in the urban area at San Carlos de Bariloche (Argentina). The school was selected because communication and regulation of emotions is part of the educational project. Observations of language classes and individual interviews were conducted over Zoom in the COVID-19 pandemic context. Ten observations focused on the class interaction between the teacher and children in learning to write situations were analyzed. The individual interview is based on video-elicitation technique. Three videos were designated ad hoc. Each video elicited emotionally challenging events in learning to write: (1) the awareness of a gap between knowledge/power and the demands of a task (child represented difficulties in writing and erasing, showing emotional affectation); (2) social exposure (child was reading alone and an adult asked her about what she was reading, after which the girl looked down and pursed her lips); and (3) the distracting environment (two girls were chatting and making noise as two boys were writing in their notebooks). Beyond the three emotionally challenging events presented in the video-elicitation, another four were found: the adaptation to external norms, the revision of the own text, the difficulty with the material, and the acknowledge the own mistakes. Additionally, children deployed a wide repertoire of strategies according to the emotion regulation model of Gross (2015) and the specific literature. Overall, the most frequent strategies were the modification of the situation in a social way, communication and expression. In the observations, modification of the situation in physical form, control and private speech were found. In the interviews, the alternative activity, breathing, communication and cognitive reappraisal were observed. Finally, it was concluded that the complementation of research methods, class observations and interviews, is promising for the study of children's emotion regulation in learning to write.

Reflexões éticas na atenção à saúde de pacientes com HIV / Ethical reflections on the health care of HIV patients / Reflexiones éticas en la asistencia sanitaria a pacientes con VIH

Resumo Neste trabalho, pretendeu-se analisar aspectos éticos no seguimento terapêutico de pacientes com HIV mediante revisão sistemática de literatura, realizada por meio de pesquisas nas bases PubMed, LILACS e MEDLINE, usando descritores em inglês e português, com 169 publicações de 2011 a 2021. Para evitar viés, foi utilizado o método Prisma e consideradas as recomendações estabelecidas pelo sistema Grading of Recommendations Assessment, Development and Evaluation para classificação do nível de evidência. O bem-estar de pacientes com HIV está associado ao nível de relações interpessoais, qualidade do tratamento e crenças pessoais. A estigmatização e o medo da divulgação da doença nos grupos em que convivem são os principais motivos de aflição. Com isso, é fundamental um maior apoio aos pacientes durante o diagnóstico e tratamento da doença, para que possam elaborar melhor suas estratégias de enfrentamento.

Abstract This study analyzed ethical aspects in the therapeutic follow-up of patients with HIV via a systematic literature review conducted by searching the PubMed, LILACS and MEDLINE databases, using descriptors in English and Portuguese language, with 169 publications from 2011 to 2021. To avoid bias, the Prisma guidelines were used and the recommendations established by the Grading of Recommendations Assessment, Development and Evaluation system were considered to classify the level of evidence. The well-being of HIV patients is associated with the level of interpersonal relationships, quality of treatment and personal beliefs. Stigmatization and fear of the dissemination of the disease in the groups in which they live are the main reasons for distress. Support to patients during the diagnosis and treatment of the disease are fundamental, so that they can better apply their coping strategies.

Resumen Este trabajo propone analizar los aspectos éticos en el seguimiento terapéutico de pacientes con VIH a través de una revisión sistemática de la literatura en las bases de datos PubMed, LILACS y MEDLINE, utilizando descriptores en inglés y portugués, lo que resultó en 169 publicaciones entre 2011 y 2021. Para evitar sesgos se utilizó el método Prisma y, para clasificar el nivel de evidencia, se consideraron las recomendaciones establecidas por el sistema Grading of Recommendations Assessment, Development and Evaluation. El bienestar de los pacientes con VIH estuvo asociado al nivel de relaciones interpersonales, calidad del tratamiento y creencias personales. El estigma y el miedo a propagar la enfermedad en los grupos con los cuales conviven fueron los principales motivos de preocupación. Por lo tanto, es fundamental brindar un mayor apoyo a los pacientes durante el diagnóstico y tratamiento de la enfermedad para que puedan desarrollar mejor sus estrategias de afrontamiento.

[Management of immunosuppressive therapy in kidney transplant recipients with COVID19. A multicentre national study derived form the S.E.N. COVID registry.] / Manejo de la inmunosupresión en pacientes trasplantados de riñón con COVID19. Estudio multicéntrico nacional derivado del registro COVID de la S.E.N.

INTRODUCTION: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated. OBJECTIVES: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis. MATERIAL AND METHODS: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis. RESULTS: 615 renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years.The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased.Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7±0.8, 2.1±1.2 and 1.8±1 mg/dl respectively (p<0.001).56.9% of the patients (N=350) were monitored for anti-HLA antibodies. 94% (N=329) had no anti-HLA changes, while 6% (N=21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N=9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant. CONCLUSIONS: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.

Radio-cephalic fistula recovered with drainage to median basilic vein by straightening of the forearm cephalic vein: A case report.

The distal arteriovenous fistula (AVF) has less complications and better patency than the proximal fistula, when it works properly. The complications of outflow of the fistula are complex, and it is necessary to analyze all solutions to solve the problem. We introduce a novel approach to solve outflow problems of a radio-cephalic AVF by straightening of the forearm cephalic vein with drainage into the median basilic vein.

Association between vitamin D serum levels and clinical, laboratory, and parasitological parameters in patients with malaria from an endemic area of the Amazon.

BACKGROUND: Some studies have suggested the importance of vitamin D [25(OH)D] in malaria clinical practice. The prevalence of 25(OH)D deficiency in the Amazon population is not well known, and there are few studies in patients with malaria. This study aimed to evaluate 25(OH)D serum levels in patients with malaria and determine their relationships with epidemiological, clinical, laboratory, and parasitemia data. METHODS: An analytical cross-sectional study of 123 patients with malaria and 122 individuals without malaria was performed in Itaituba, Pará, Brazil, from January 2018 to October 2019, by evaluating sociodemographic, clinical-epidemiological, parasitological, and laboratory data and adopting a 5% significance level. Parametric tests (Student's t-test), non-parametric tests (Mann-Whitney U), and Spearman's correlation ([rs], for non-parametric variables) were used according to the nature of the distribution of the variables. For the qualitative variables, Pearson's chi-square test, Fisher's exact test, and the G test were used. Spearman's correlation was used to compare the results of the 25(OH)D levels and blood counts performed among patients and the control group. RESULTS: Malaria patients residing in a mining area had 25(OH)D serum levels that were significantly lower than those in the control group residing in the mining area, though both were within normal levels. Red blood cell counts had an inverse correlation with parasitemia (Plasmodium falciparum), and platelet levels had an inverse correlation with parasitemia (Plasmodium vivax). 25(OH)D deficiency was evidenced in Itaituba, in the state of Pará, which is an endemic area of malaria in the Amazon region.

O Impacto da COVID-19 no Diagnóstico de Doenças Cardíacas na América Latina Uma Subanálise do INCAPS COVID / The Impact of COVID-19 on Diagnosis of Heart Disease in Latin America an INCAPS COVID Sub-analysis

Resumo Fundamento A pandemia de COVID-19 interferiu na prestação de atendimento a doenças cardiovasculares na América Latina. No entanto, o efeito da pandemia nos volumes de procedimentos cardíacos diagnósticos ainda não foi quantificado. Objetivo Avaliar (1) o impacto de COVID-19 nos volumes de diagnóstico cardíaco na América Latina e (2) determinar sua relação com a incidência de casos de COVID-19 e as medidas de distanciamento social. Métodos A International Atomic Energy Agency realizou uma pesquisa mundial avaliando mudanças nos volumes diagnósticos cardíacos decorrentes da COVID-19. Foram obtidos os volumes diagnósticos cardíacos dos locais participantes para março e abril de 2020 e comparados com março de 2019. Foram coletados dados de distanciamento social a partir dos Relatórios de mobilidade da comunidade de Google e a incidência de COVID-19 por país a partir de Our World in Data. Resultados Foram realizadas pesquisas em 194 centros que realizam procedimentos diagnósticos cardíacos, em 19 países da América Latina. Em comparação com o mês de março de 2019, os volumes dos procedimentos diagnósticos cardíacos diminuíram 36% em março de 2020 e 82% em abril de 2020.As maiores reduções ocorreram em relação aos testes de estresse ecocardiográfico (91%), testes ergométricos de esteira (88%) e escore de cálcio por tomografia computadorizada (87%), com pequenas variações entre as sub-regiões da América Latina. As mudanças em padrões de distanciamento social (p < 0,001) estavam mais fortemente associadas com a redução do volume do que a incidência de COVID-19 (p = 0,003). Conclusões A COVID-19 foi associada a uma redução significativa de procedimentos diagnósticos cardíacos na América Latina, a qual foi mais relacionada ao distanciamento social do que ao aumento da incidência da COVID-19. São necessários melhor equilíbrio e timing de medidas de distanciamento social e planejamento para manter o acesso ao atendimento médico durante um surto pandêmico, especialmente em regiões com alta mortalidade cardiovascular.

Abstract Background The COVID-19 pandemic has disrupted the delivery of care for cardiovascular diseases in Latin America. However, the effect of the pandemic on the cardiac diagnostic procedure volumes has not been quantified. Objective To assess (1) the impact of COVID-19 on cardiac diagnostic volumes in Latin America and (2) determine its relationship with COVID-19 case incidence and social distancing measures. Methods The International Atomic Energy Agency conducted a worldwide survey assessing changes in cardiac diagnostic volumes resulting from COVID-19. Cardiac diagnostic volumes were obtained from participating sites for March and April 2020 and compared to March 2019. Social distancing data were collected from Google COVID-19 community mobility reports and COVID-19 incidence per country from the Our World in Data. Results Surveys were conducted in 194 centers performing cardiac diagnostic procedures, in 19 countries in Latin America. Procedure volumes decreased 36% from March 2019 to March 2020, and 82% from March 2019 to April 2020. The greatest decreases occurred in echocardiogram stress tests (91%), exercise treadmill tests (88%), and computed tomography calcium scores (87%), with slight variations between sub-regions of Latin America. Changes in social distancing patterns (p < 0.001) were more strongly associated with volume reduction than COVID-19 incidence (p = 0.003). Conclusions COVID-19 was associated with a significant reduction in cardiac diagnostic procedures in Latin America, which was more related to social distancing than to the COVID-19 incidence. Better balance and timing of social distancing measures and planning to maintain access to medical care is warranted during a pandemic surge, especially in regions with high cardiovascular mortality.