Risk factors and outcome of Chimeric Antigen Receptor T-Cell patients admitted to Pediatric Intensive Care Unit: CART-PICU study.

Introduction: Chimeric antigen receptor (CAR)T-cell CD19 therapy is an effective treatment for relapsed/refractory B-cell acute lymphoblastic leukemia. It can be associated with life-threatening toxicities which often require PICU admission. Purpose: to describe clinical characteristics, treatment and outcome of these patients. Methods: Prospective observational cohort study conducted in a tertiary pediatric hospital from 2016-2021. Children who received CAR-T admitted to PICU were included. We collected epidemiological, clinical characteristics, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), treatment, length of stay and mortality. Results: CAR T-cells (4-1BB constructs) were infused in 59 patients. Twenty-four (40.7%) required PICU admission, length of stay was 4 days (IQR 3-6). Median age was 8.3 years (range 4-24). Patients admitted to PICU presented higher disease burden before infusion: 24% blasts in bone marrow (IQR 5-72) vs. 0 (0-6.9), p<0.001. No patients with <5% blasts were admitted to PICU. Main reasons for admissions were CRS (n=20, 83.3%) and ICANS (n=3, 12.5%). Fourteen patients (58.3%) required inotropic support, 14(58.3%) respiratory. Sixteen patients (66.6%) received tocilizumab, 10(41.6%) steroids, 6(25.0%) anakinra, and 5(20.8%) siltuximab. Ten patients (41.6%) presented neurotoxicity, six of them severe (ICANS 3-4). Two patients died at PICU (8.3%) because of refractory CRS-hemophagocytic lymphohistyocitosis (carHLH) syndrome. There were no significant differences in relapse rate after CAR-T in patients requiring PICU, it was more frequently CD19 negative (p=0.344). Discussion: PICU admission after CAR-T therapy was mainly due to CRS. Supportive treatment allowed effective management and high survival. Some patients presenting with carHLH, can suffer a fulminant course.

Molecular Characterization of Salmonella spp. Isolates from Wild Colombian Babilla (Caiman crocodilus fuscus) Isolated In Situ.

Salmonella enterica is a pathogen capable of colonizing various environments, including the intestinal tract of different animals such as mammals, birds, and reptiles, which can act as carriers. S. enterica infection induces different clinical diseases, gastroenteritis being the most common, which in some cases, can evolve to septicemia and meningitis. Reptiles and amphibians have been reported as a reservoir of Salmonella, and transmission of the pathogen to humans has been documented. This study aimed to determine the presence of virulence genes and characterize the genotypic antibiotic resistance profile in Salmonella strains isolated from Caiman crocodilus fuscus obtained in situ (natural habitat) in Prado, Tolima, Colombia in a previous study and stored in a strain bank in our laboratory. Fifteen Salmonella strains were evaluated through endpoint PCR to determine the presence of resistance genes and virulence genes. The genes blaTEM, strB, and sul1 were detected in all the strains that confer resistance to ampicillin, streptomycin, and sulfamethoxazole, as well as the virulence genes invA, pefA, prgH, spaN, tolC, sipB, sitC, pagC, msgA, spiA, sopB, sifA, lpfA, csgA, hilA, orgA, iroN, avrA, and sivH, indicating the possible role of babilla (Caiman crocodilus fuscus) as a carrier of multidrug-resistant bacteria.

Sensibilidad del test de diagnóstico rápido SARS-CoV-2 Panbio en Atención Primaria / Sensitivity of the Panbio COVID-19 rapid antigen detection test in primary care

Introducción y objetivos: los pediatras de Atención Primaria necesitamos técnicas de diagnóstico rápido (TDR) fiables para prevenir la propagación de la enfermedad COVID-19 mediante un cribado temprano y eficaz a la espera de una vacuna. El objetivo de este trabajo fue evaluar como novedad en Atención Primaria, tanto en adultos como niños, sintomáticos y contactos asintomáticos, la sensibilidad (S) de los test de antígeno SARS-CoV-2 Panbio del laboratorio Abbott respecto a la reacción en cadena de la polimerasa (PCR).Pacientes y métodos: se incluyeron 591 pacientes (222 menores de 14 años) (249 sintomáticos y 342 contactos). Se calculó la sensibilidad (S) y la especificidad (E) junto con sus intervalos de confianza (IC) del 95%. La independencia de los dos resultados ha sido analizada mediante el test de McNemar.Resultados: la S del test en adultos fue del 81% (IC 95%: 66,16-96,34) y en niños del 80% (IC 95%: 34,94-100) dentro de los 5 primeros días. En contactos se evaluó la S en los cinco primeros días, en adultos (68%; IC 95%: 51,13-86,37), del 5.º al 9.º día (85%) y en niños (66%; IC 95%: 30,31-100). El tipo de contacto más frecuente fue domiciliario en un 52% de los casos. La E fue 100% en todos los casos.Conclusiones: el test rápido de antígeno SARS-CoV-2 Panbio puede ser útil para diagnóstico de adultos y niños los primeros cinco días de inicio de síntomas, así como entre el 5.º y 9.º día tras el contacto con positivo COVID-19 confirmado, pendiente de interpretar en futuros estudios. (AU)

Introduction and objectives: primary care paediatricians need reliable rapid diagnostic techniques (RDTs) to prevent the spread of coronavirus disease 19 (COVID-19) through early and effective screening while awaiting a vaccine. The objective of this study was to evaluate the sensitivity (Sen) of the Abbott laboratory SARS-CoV-2 Panbio antigen test, newly introduced in primary care, in both adults and children (symptomatic and asymptomatic contacts) in comparison to the polymerase chain reaction (PCR) test.Sample and methods: the study included 591 patients (222 aged less than 14 years) from 7 primary care centres; of who 249 were symptomatic and 342 asymptomatic contacts. We calculated the Sen and specificity (Spe) with their 95% confidence intervals (CIs). We assessed the independence of the two results with the McNemar test.Results: the Sen of the test within 5 days from onset was 81% in adults (95% CI, 66.16-96.34) and 80% in children (95% CI: 34.94-100). In contacts, we assessed the Sen within 5 days, in adults (68%; 95% CI: 51.13- 86.37), in 5 to 9 days (85%) and in children (66%; 95% CI: 30.31-100). The most frequent source of exposure were household contacts (52% of the cases). The Spe was 100% in every case.Conclusions: the Panbio SARS-CoV-2 rapid antigen test can be useful for diagnosis in adults and children within 5 days of onset, and from days 5 to 9 in contacts of confirmed COVID 19 cases. Further studies are required for adequate interpretation of the latter result. (AU)

Transepithelial Corneal Crosslinking Using a Novel Ultraviolet Light-Emitting Contact Lens Device: A Pilot Study.

Purpose: To evaluate the feasibility of a novel, on-eye UVA light-emitting contact lens device driven by fiber optics for the corneal crosslinking (CXL) of patients with keratoconus. Methods: In nine corneal transplant candidates with advanced keratoconus a scleral contact lens reservoir containing 0.007% benzalkonium chloride preserved with 0.25% riboflavin-monophosphate was placed on the eye for 30 minutes. The reservoir lens was removed and replaced with the CXLens UVA light-emitting contact lens. A 375-nm UVA light at 4 mW/cm2 intensity was delivered for 30 minutes for a dose of 7.2 J/cm2. A one-sided paired t-test was used to evaluate mean differences in maximum keratometry, thinnest corneal thickness, and endothelial cell density between screening and 6 months after CXL. A two-sided paired t-test was used to evaluate differences in best-corrected distance visual acuity between screening and 6 months after CXL. Results: All patients received the treatment as per protocol and adhered to follow-up testing. At 6 months after CXL, treated eyes had an average -1.0 ± 1.6 diopters decrease in the maximum keratometry (P = 0.049), a nonsignificant 2.3 ± 7.5 letter improvement in best-corrected distance visual acuity (P = 0.19), a nonsignificant -17 ± 14 µm decrease in thinnest corneal thickness (P < 0.01), and a nonsignificant -86 ± 266 cells/mm2 decrease in endothelial cell density (P = 0.20). Conclusions: Our pilot study demonstrated the feasibility of the novel CXL device for the treatment of keratoconus and indicates the device is ready for larger scale studies with longer follow-up periods. Translational Relevance: The novel CXLens on-eye UVA light-emitting contact lens device offers the potential for efficient, high-throughput transepithelial corneal CXL.

Identification and Control of Latent Bacteria in in vitro Cultures of Sweetpotato [Ipomoea batatas (L.) Lam].

Bacterial microorganisms which are latent in in vitro cultures can limit the efficiency of in vitro methods for the conservation of genetic resources. In this study we screened 2,373 accessions from the in vitro sweetpotato germplasm collection of the International Potato Center in Lima, Peru for bacteria associated with plantlets in tissue culture through a combination of morphological methods and partial 16S rDNA sequencing. Bacteria were detected in 240 accessions (10% of the accessions screened) and we were able to isolate 184 different bacterial isolates from 177 different accessions. These corresponded to at least nineteen Operational Taxonomic Units (OTUs) of bacteria, belonging to the genera Sphingomonas, Bacillus, Paenibacillus, Methylobacterium, Brevibacterium, Acinetobacter, Microbacterium, Streptomyces, Staphylococcus, and Janibacter. Specific primers were developed for PCR based diagnostic tests that were able to rapidly detect these bacteria directly from tissue culture plants, without the need of microbial sub-culturing. Based on PCR screening the largest bacterial OTUs corresponded to a Paenibacillus sp. closely related to Paenibacillus taichungensis (41.67%), and Bacillus sp. closely related to Bacillus cereus (22.22%), and Bacillus pumilus (16.67%). Since in vitro plant genetic resources must be microbe-free for international distribution and use, any microbial presence is considered a contamination and therefore it is critical to clean all cultures of these latent-appearing bacteria. To accomplish this, plantlets from in vitro were transferred to soil, watered with Dimanin® (2 ml/l) weekly and then reintroduced into in vitro. Of the 191 accessions processed for bacterial elimination, 100% tested bacteria-free after treatment. It is suspected that these bacteria may be endosymbionts and some may be beneficial for the plants.

Mutation in ROBO3 Gene in Patients with Horizontal Gaze Palsy with Progressive Scoliosis Syndrome: A Systematic Review.

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, inherited disorder characterized by a congenital absence of conjugate horizontal eye movements with progressive scoliosis developing in childhood and adolescence. Mutations in the Roundabout (ROBO3) gene located on chromosome 11q23-25 are responsible for the development of horizontal gaze palsy and progressive scoliosis. However, some studies redefined the locus responsible for this pathology to a 9-cM region. This study carried out a systematic review in which 25 documents were analyzed, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. The search was made in the following electronic databases from January 1995 to October 2019: PubMed, Scopus, Web of Science, PEDRO, SPORT Discus, and CINAHL. HGPPS requires a multidisciplinary diagnostic approach, in which magnetic resonance imaging might be the first technique to suggest the diagnosis, which should be verified by an analysis of the ROBO3 gene. This is important to allow for adequate ocular follow up, apply supportive therapies to prevent the rapid progression of scoliosis, and lead to appropriate genetic counseling.

Metal-containing Particulate Matter and Associated Reduced Olfactory Identification Ability in Children from an Area of High Atmospheric Exposure in Mexico City.

Air pollution has been linked to poor olfactory function in human adults. Among pollutants, particulate matter (PM) is especially relevant, as it may contain toxic metal ions that can reach the brain via olfactory pathways. Our purpose was to investigate the relation between atmospheric PM and olfactory identification performance in children. Using a validated method, we tested the olfactory identification performance of 120 children, 6-12 years old, from two locations in Mexico City: a focal group (n = 60) from a region with high PM levels and a control group of equal size and similar socioeconomic level from a region with markedly lower PM concentrations. Groups were matched for age and sex. Concentrations of manganese and lead in the hair of participants were determined as biomarkers of exposure. Daily outdoor PM levels were obtained from official records, and indoor PM levels were measured in the children's classrooms. Official records confirmed higher levels of outdoor PM in the focal region during the days of testing. We also found higher classroom PM concentrations at the focal site. Children from the focal site had on average significantly lower olfactory identification scores than controls, and hair analysis showed significantly higher levels of manganese for the focal children but no difference in lead. Children appear to be vulnerable to the effects of air pollution on olfactory identification performance, and metal-containing particles likely play a role in this. Olfactory tests provide a sensitive, noninvasive means to assess central nervous function in populations facing poor air quality.

Prenatal exposure to particulate matter and ozone: Bulky DNA adducts, plasma isoprostanes, allele risk variants, and neonate susceptibility in the Mexico City Metropolitan Area.

Mexico City's Metropolitan Area (MCMA) includes Mexico City and 60 municipalities of the neighbor states. Inhabitants are exposed to emissions from over five million vehicles and stationary sources of air pollutants such as particulate matter (PM) and ozone. MCMA PM contains elemental carbon and organic carbon (OC). OCs include polycyclic aromatic hydrocarbons (PAHs), many of which induce mutagenic and carcinogenic DNA adducts. Gestational exposure to air pollution has been associated with increased risk of intrauterine growth restriction, preterm birth or low birth weight risk, and PAH-DNA adducts. These effects also depend on the presence of risk alleles. We investigated the presence of bulky PAH-DNA adducts, plasma 8-iso-PGF2α (8-iso-prostaglandin F2α ) and risk allele variants in neonates cord blood and their non-smoking mothers' leucocytes from families that were living in a highly polluted area during 2014-2015. The presence of adducts was significantly associated with both PM2.5 and PM10 levels, mainly during the last trimester of gestation in both neonates and mothers, while the last month of pregnancy was significant for the association between ozone levels and maternal plasma 8-iso-PGF2α . Fetal CYP1B1*3 risk allele was associated with increased adduct levels in neonates while the presence of the maternal allele significantly reduced the levels of fetal adducts. Maternal NQO1*2 was associated with lower maternal levels of adducts. Our findings suggest the need to reduce actual PM limits in MCMA. We did not observe a clear association between PM and/or adduct levels and neonate weight, length, body mass index, Apgar or Capurro score. Environ. Mol. Mutagen. 60:428-442, 2019. © 2019 Wiley Periodicals, Inc.

Stacking three late blight resistance genes from wild species directly into African highland potato varieties confers complete field resistance to local blight races.

Considered responsible for one million deaths in Ireland and widespread famine in the European continent during the 1840s, late blight, caused by Phytophthora infestans, remains the most devastating disease of potato (Solanum tuberosum L.) with about 15%-30% annual yield loss in sub-Saharan Africa, affecting mainly smallholder farmers. We show here that the transfer of three resistance (R) genes from wild relatives [RB, Rpi-blb2 from Solanum bulbocastanum and Rpi-vnt1.1 from S. venturii] into potato provided complete resistance in the field over several seasons. We observed that the stacking of the three R genes produced a high frequency of transgenic events with resistance to late blight. In the field, 13 resistant transgenic events with the 3R-gene stack from the potato varieties 'Desiree' and 'Victoria' grew normally without showing pathogen damage and without any fungicide spray, whereas their non-transgenic equivalent varieties were rapidly killed. Characteristics of the local pathogen population suggest that the resistance to late blight may be long-lasting because it has low diversity, and essentially consists of the single lineage, 2_A1, which expresses the cognate avirulence effector genes. Yields of two transgenic events from 'Desiree' and 'Victoria' grown without fungicide to reflect small-scale farm holders were estimated to be 29 and 45 t/ha respectively. This represents a three to four-fold increase over the national average. Thus, these late blight resistant potato varieties, which are the farmers' preferred varieties, could be rapidly adopted and bring significant income to smallholder farmers in sub-Saharan Africa.

Tumores endobronquiales benignos infrecuentes / Rare benign endobronchial tumors

Las neoplasias pulmonares pueden manifestarse en forma de nódulo solitario, masa o tumoración endobronquial. Los tumores endobronquiales benignos son muy poco frecuentes, pero también forman parte del diagnóstico diferencial de las neoplasias de pulmón. En este trabajo describimos dos de ellos especialmente infrecuentes: un lipoma endobronquial, que era el responsable de una atelectasia, y un schwannoma o neurilemmoma, que fue un hallazgo endoscópico casual(AU)

Lung cancer can present as a solitary nodule, a mass or an endobronchial lesion. Benign tumors of the endobronchial tree are uncommon but are included in the differential diagnosis of lung cancer. We present two particularly rare benign endobronchial tumours — an endobronchial lipoma causing atelectasis and an asymptomatic schwannoma or neurilemmomma, discovered on endoscopy(AU)

[A dangerous combination for stroke in young patient: assimilation of the atlas and anti beta2-glycoprotein I antibodies]. / Asimilación del atlas y anticuerpos anti beta2 microglobulina I: una combinación peligrosa para enfermedad vascular cerebral en un paciente joven.

A 45 year old male was admitted to the hospital for unsteady gait and dizziness. The brain CT showed bilateral cerebellar ischemic stroke. The MRI corroborated the stroke in the cerebellum with a third acute ischemic stroke in the pons. The laboratory work up showed a positive anti beta2-glycoprotein I antibodies. The cerebral angiogram showed the territories occluded and also a rare malformation of the cranium vertebral junction called assimilation of the atlas. We concluded that due to the turbulence created in the V3 segment of the vertebral artery surrounding the atlas, the presence of the anti beta2-glycoprotein was the cause of the infarction in this patient.

Molecular and physiological adaptation to prolonged drought stress in the leaves of two Andean potato genotypes.

Responses to prolonged drought and recovery from drought of two South American potato (Solanum tuberosum L. ssp. andigena (Juz & Buk) Hawkes) landraces, Sullu and Ccompis were compared under field conditions. Physiological and biomass measurements, yield analysis, the results of hybridisation to a potato microarray platform (44 000 probes) and metabolite profiling were used to characterise responses to water deficit. Drought affected shoot and root biomass negatively in Ccompis but not in Sullu, whereas both genotypes maintained tuber yield under water stress. Ccompis showed stronger reduction in maximum quantum yield under stress than Sullu, and less decrease in stomatal resistance. Genes associated with PSII functions were activated during recovery in Sullu only. Evidence for sucrose accumulation in Sullu only during maximum stress and recovery was observed, in addition to increases in cell wall biosynthesis. A depression in the abundance of plastid superoxide dismutase transcripts was observed under maximum stress in Ccompis. Both sucrose and the regulatory molecule trehalose accumulated in the leaves of Sullu only. In contrast, in Ccompis, the raffinose oligosaccharide family pathway was activated, whereas low levels of sucrose and minor stress-mediated changes in trehalose were observed. Proline, and expression of the associated genes, rose in both genotypes under drought, with a 3-fold higher increase in Sullu than in Ccompis. The results demonstrate the presence of distinct molecular and biochemical drought responses in the two potato landraces leading to yield maintenance but differential biomass accumulation in vegetative tissues.

Transient thyroiditis after treatment with lenalidomide in a patient with metastatic renal cell carcinoma.

Lenalidomide, a recently developed immunomodulatory drug, shares the antiangiogenic and antitumor properties of thalidomide. While there is a known association between thalidomide and hypothyroidism, to our knowledge, there have been no prior reports of thyrotoxicosis associated with thalidomide or lenalidomide treatment. Herein, we report the case of a patient who developed transient thyrotoxicosis while receiving lenalidomide in a clinical trial for metastatic renal cell carcinoma. The time course and biochemical features of this patient's presentation are most consistent with immune-mediated subacute destructive thyroiditis. This case highlights the importance of monitoring thyroid function in the growing number of patients being treated with lenalidomide.