Apalutamide-Induced Toxic Epidermal Necrolysis in a Caucasian Patient with Metastatic Castration-Sensitive Prostate Cancer: A Case Report and Review of the Literature.

Apalutamide is a novel nonsteroidal androgen receptor inhibitor that has been shown to improve outcomes for patients with nonmetastatic castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer when combined with androgen deprivation therapy. Apalutamide-induced skin rash occurred commonly in clinical trials, with 23.8-27.1% of patients experiencing a rash of any grade, and 5.2-6.3% experiencing a rash of grade three or higher. There were no cases of severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) reported in clinical trials; however, there are rare cases reported in the literature with the majority occurring in Asian patients. An 83-year-old Caucasian male was commenced on apalutamide, combined with degarelix, for the management of metastatic castration-sensitive prostate cancer. During week five of apalutamide treatment, the patient developed a widespread erythematous maculopapular rash. On presentation, the rash affected 80% of his body surface area (BSA) and a diagnosis of a severe cutaneous drug eruption was made. He was commenced on methylprednisolone (MP) therapy. Despite 5 days of MP, the rash continued to deteriorate involving 95% of his BSA. Nikolsky's sign was positive. A diagnosis of overlap SJS/TEN was made, supported by skin biopsy. His SCORTEN score was three. He was then commenced on intravenous immunoglobulin and transferred to the intensive care unit. Over the coming days, the rash began to stabilise, and his steroid dose was weaned. He was discharged from hospital 38 days after rash onset. We report the first suggested case of apalutamide-induced SJS/TEN in a Caucasian patient. We discuss other cases of apalutamide-induced SCARs reported in the literature. Risk factors seem to include low body weight and Japanese race, as well as short time to onset of rash.

Pediatric Oncology Palliative Care Programs in Central America: Pathways to Success.

Palliative care offers children who have life-limiting and life-threatening oncologic illnesses and their families improved quality of life. In some instances, impeccable symptom control can lead to improved survival. Cultural and financial barriers to palliative care in oncology patients occur in all countries, and those located in Central America are no exception. In this article, we summarize how the programs participating in the Asociación de Hemato-Oncólogos Pediatras de Centro America (AHOPCA) have developed dedicated oncology palliative care programs. The experience in Guatemala, El Salvador, Costa Rica, Panama, Dominican Republic and Haiti is detailed, with a focus on history, the barriers that have impeded progress, and achievements. Future directions, which, of course, may be impacted by the COVID-19 pandemic, are described as well.

Tracking gene expression, metabolic profiles, and biochemical analysis in the halotolerant basidiomycetous yeast Rhodotorula mucilaginosa EXF-1630 during benzo[a]pyrene and phenanthrene biodegradation under hypersaline conditions.

Polyaromatic phenanthrene (Phe) and benzo[a]pyrene (BaP) are highly toxic, mutagenic, and carcinogenic contaminants widely dispersed in nature, including saline environments. Polyextremotolerant Rhodotorula mucilaginosa EXF-1630, isolated from Arctic sea ice, was grown on a huge concentration range -10 to 500 ppm- of Phe and BaP as sole carbon sources at hypersaline conditions (1 M NaCl). Selected polycyclic aromatic hydrocarbons (PAHs) supported growth as well as glucose, even at high PAH concentrations. Initially, up to 40% of Phe and BaP were adsorbed, followed by biodegradation, resulting in 80% removal in 10 days. While extracellular laccase, peroxidase, and un-specific peroxygenase activities were not detected, NADPH-cytochrome c reductase activity peaked at 4 days. The successful removal of PAHs and the absence of toxic metabolites were confirmed by toxicological tests on moss Physcomitrium patens, bacterium Aliivibrio fischeri, human erythrocytes, and pulmonary epithelial cells (A549). Metabolic profiles were determined at the midpoint of the biodegradation exponential phase, with added Phe and BaP (100 ppm) and 1 M NaCl. Different hydroxylated products were found in the culture medium, while the conjugative metabolite 1-phenanthryl-ß-D-glucopyranose was detected in the medium and in the cells. Transcriptome analysis resulted in 870 upregulated and 2,288 downregulated transcripts on PAHs, in comparison to glucose. Genomic mining of 61 available yeast genomes showed a widespread distribution of 31 xenobiotic degradation pathways in different yeast lineages. Two distributions with similar metabolic capacities included black yeasts and mainly members of the Sporidiobolaceae family (including EXF-1630), respectively. This is the first work describing a metabolic profile and transcriptomic analysis of PAH degradation by yeast.

Isolation and characterization of yeasts associated with plants growing in heavy-metal- and arsenic-contaminated soils.

Yeasts were quantified and isolated from the rhizospheres of 5 plant species grown at 2 sites of a Mexican region contaminated with arsenic, lead, and other heavy metals. Yeast abundance was about 10(2) CFU/g of soil and 31 isolates were obtained. On the basis of the phylogenetic analysis of 26S rRNA and internal transcribed spacer fragment, 6 species were identified within the following 5 genera: Cryptococcus (80.64%), Rhodotorula (6.45%), Exophiala (6.45%), Trichosporon (3.22%), and Cystobasidium (3.22%). Cryptococcus spp. was the predominant group. Pectinases (51.6%), proteases (51.6%), and xylanases (41.9%) were the enzymes most common, while poor production of siderophores (16.1%) and indole acetic acid (9.67%) was detected. Isolates of Rhodotorula mucilaginosa and Cystobasidium sloffiae could promote plant growth and seed germination in a bioassay using Brassica juncea. Resistance of isolates by arsenic and heavy metals was as follows: As(3+) ≥ 100 mmol/L, As(5+) ≥ 30 mmol/L, Zn(2+) ≥ 2 mmol/L, Pb(2+) ≥ 1.2 mmol/L, and Cu(2+) ≥ 0.5 mmol/L. Strains of Cryptococcus albidus were able to reduce arsenate (As(5+)) into arsenite (As(3+)), but no isolate was capable of oxidizing As(3+). This is the first study on the abundance and identification of rhizosphere yeasts in a heavy-metal- and arsenic-contaminated soil, and of the reduction of arsenate by the species C. albidus.

Efectividad de higiene broncopulmonar en la resolución de atelectasia en pacientes pediátricos sometidos a ventilación mecánica / Efficiency of bronchopulmonar hygiene in the resolution of atelectasy in pediatric patients submitted to mechanical ventilation

Introducción: La utilización de la ventilación mecánica en el paciente crítico conlleva implícito riesgo de complicaciones, con el agravante de la mayor dificultad de la ventilación en el niño, tanto por las características propias de la edad pediátrica, como de los ventiladores mecánicos utilizados. Existen una series de complicaciones que son inducidas por la ventilación mecánica entre las cuales se puede mencionar: barotrauma, volutrauma, ateletrauma y biotrauma. Las atelectasias ocupan un lugar importante entre las complicaciones que ocurren en los pacientes pediátricos sometidos a ventilación mecánica. Para la resolución de la misma el personal de enfermería aplica medidas que facilitan la eliminación de las secreciones y otros detritos situados en la vía aérea artificial, mediante el uso de la higiene broncopulmonar consistente en las aplicaciones de todas aquellas medidas destinadas a mantener limpias y permeables las vías aéreas. Objetivos: evaluar la efectividad de la higiene broncopulmonar en la resolución de atelectasia en pacientes pediátricos sometidos a ventilación mecánica. Métodos: la muestra estuvo conformada por 30 pacientes (24 por ciento) en edades comprendidas desde un mes a catorce años ingresados al servicio de cuidados intensivos pediátricos del Hospital "J. M. de los Ríos" de Caracas durante los meses de junio a octubre de 2005. Los criterios de inclusión son de pacientes que presenta clínica y radiológicamente atelectasia. Resultados: en la distribución anatómica lobular de las atelectasias predominó la lobar izquierda, el tiempo de resolución en menos horas fue la global izquierda. Conclusiones: aunque la evidencia no sustenta la hipótesis inicial clínicamente es importante para el personal de salud que labora en el Servicio de Cuidados Intensivos Pediátricos en la aplicación de las técnicas de (HBP) en pacientes sometidos a ventilación mecánica.

Factores predictivos de litiasis coledociana / Predictive factors of Choledocholithiasis

Antecedentes: Existen factores clínicos y ecográficos considerados predictivos de litiasis canalicular; su efectividad permitiría plantear el uso sistemático o selectivo de la colangiografía intraoperatoria. Objetivo: Correlacionar el incremento de los valores de laboratorio y ecográficos como factores predictivos con los hallazgos intraoperatorios y la colangiografía sistemática. Método: Descriptivo de corte transversal. Resultados: Se analizaron 147 historias clínicas (97 mujeres). 124 cumplieron con los criterios de inclusión. Se encontraron 24 pacientes con litiasis coledociana; de estos 10 presentaron aumento de todas las enzimas y del diámetro de la vía biliar principal por ecografía. En 5 pacientes no se encontró ningún factor predictivo y en los 9 restantes, se encontraron alteraciones de uno o más factores predictivos. Conclusiones: -Los distintos factores predictivos han mostrado en nuestros pacientes baja sensibilidad; ninguno de ellos aislado llega al 70 por ciento. -El estudio escográfico de la vía biliar ha mostrado una especificidad de 91 por ciento, pero baja sensibilidad para el diagnóstico de litiasis coledociana; esto podría estar relacionado con la tardanza en la cirugía a la que se vieron obligados algunos pacientes. -Ninguno de los factores predictivos (FAL, gGT, Bilirrubina, Ecografía) pueden reemplazar, el uso sistemático de la CIO.