Impact of letermovir prophylaxis in CMV reactivation and disease after allogenic hematopoietic cell transplantation: a real-world, observational study.

Letermovir for CMV prevention in CMV-seropositive adults undergoing allo-HCT was implemented at our program in 2021. This study investigates the results from the use of letermovir. The study includes all the 140 CMV-seropositive patients who underwent an allo-HCT during the years 2020, 2021, and 2022 at our institution. Thirty-eight (27.4%) of these patients received letermovir, administered from day + 7 to day + 100 and restarted if patients were on treatment with steroids. The day + 180 and 1-year cumulative incidences of CMV reactivation were 5.3% and 12.1% for patients who received letermovir and 52.9% and 53.9% for those who did not (P < 0.001) (HR 0.19, P < 0.001). Four (10.5%) of these thirty-eight patients had a CMV reactivation, but only 2 (5.3%) cases occurred during the administration of letermovir. During the first year after allo-HCT, 13 (9.2%) patients had CMV disease; the day + 180 and 1-year cumulative incidences were 2.6% and 6.0% for patients who received letermovir and 9.9% and 12.3% for those who did not (P = 0.254) (HR 1.01, P = 0.458). Two (4.2%) of the patients included in the letermovir group had CMV disease, but both of them after letermovir discontinuation. Letermovir induced a protective effect on CMV reactivation risk, but its use was not associated with a significant reduction of CMV disease. The fact that the CMV disease in patients who received letermovir occurred after the discontinuation of the drug, questions whether CMV prophylaxis should be used in patients with high risk for CMV reactivation or disease.

Use of probiotic yeasts with biocontrol activity for fermentation of ewe's milk.

BACKGROUND: There are sufficient scienctific studies that support the benefit that fermented dairy products produce in those who consume them. Traditionally, cow's milk has been the most commonly used milk but there is a growing interest in the development of new dairy products, substituting cow's milk with milk from other sources, as well as in the use of microorganisms in fermentation to replace artificial preservatives or treatments that may affect the chemical and organoleptic characteristics of the product. For these reasons, the aim of the present work was to understand the behavior of five potential probiotic yeasts during the fermentation of ewe's milk and to consider their potential use as biocontrol agents. RESULTS: Saccharomyces cerevisiae 3 and Hanseniaspora osmophila 1056 provided the most promising kinetic parameters in the different salt, temperature and pH conditions tested in their technological characterization. The profiles of organic acids and volatile compounds after the fermentation period was noteworthy for contributing to the final aroma of the dairy product. Sensory analysis revealed the sour taste of all samples, and S. cerevisiae 3, Lachancea thermotolerans 1039, and H. osmophila 1056 stood out for an accentuated cheese flavor. In addition, all strains showed biocontrol activity; they reduced the mycelium of the mycotoxigenic molds. CONCLUSION: Saccharomyces cerevisiae 3 and H. osmophila 1056 could be inoculated along with bacterial starters to provide a functional fermented beverage with improved flavor. These strains also have an added value as they act as biocontrol agents. © 2022 Society of Chemical Industry.

Impact of Early Intrapatient Variability of Tacrolimus Concentrations on the Risk of Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation Using High-Dose Post-Transplant Cyclophosphamide.

Tacrolimus (Tac) is a pivotal immunosuppressant agent used to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloHSCT). Tac is characterized by a narrow therapeutic window and a high inter-patient and intra-patient pharmacokinetic variability (IPV). Although high IPV of Tac concentrations has been associated with adverse post-transplant outcomes following solid organ transplantation, the effects of Tac IPV on alloHSCT recipients have not been determined. Tac IPV was therefore retrospectively evaluated in 128 alloHSCT recipients receiving high-dose post-transplant cyclophosphamide (PTCy) and the effects of Tac IPV on the occurrence of acute GVHD (aGVHD) were analyzed. Tac IPV was calculated from pre-dose concentrations (C0) measured during the first month after Tac initiation. The cumulative rates of grades II-IV and grades III-IV aGVHD at day +100 were 22.7% and 7%, respectively. Higher Tac IPV was associated with a greater risk of developing GVHD, with patients having IPV > 50th percentile having significantly higher rates of grades II-IV (34.9% vs. 10.8%; hazard ratio [HR] 3.858, p < 0.001) and grades III-IV (12.7% vs. 1.5%; HR 9.69, p = 0.033) aGVHD than patients having IPV ≤ 50th percentile. Similarly, patients with IPV > 75th percentile had higher rates of grades II-IV (41.9% vs. 16.5%; HR 3.30, p < 0.001) and grades III-IV (16.1% vs. 4.1%; HR 4.99, p = 0.012) aGVHD than patients with IPV ≤ 75th percentile. Multivariate analyses showed that high Tac IPV (>50th percentile) was an independent risk factor for grades II-IV (HR 2.99, p = 0.018) and grades III-IV (HR 9.12, p = 0.047) aGVHD. Determination of Tac IPV soon after alloHSCT could be useful in identifying patients at greater risk of aGVHD.

Safety Evaluation of Yeasts With Probiotic Potential.

This work has evaluated the safety aspects of 20 yeast strains, isolated from food environments, selected in previous works due to their probiotic potential. Among the different strains, there are Saccharomyces and non-Saccharomyces yeasts. Before safety evaluation, differentiation of Saccharomyces cerevisiae strains was done by PCR amplification of inter-δ region with pairs of primers δ2-12 and δ12-21, which showed that they were all different from each other and also had different profiles to Saccharomyces boulardii (the only commercial probiotic yeast). The non-Saccharomyces ones were already known. The evaluation tests carried out were antibiotic and antifungal resistance, production of biogenic amines, deconjugation activity of bile salts, and different enzymatic activities: coagulase, deoxyribonuclease, hemolysin, proteolytic, and phospholipase. None of the studied strains demonstrated coagulase, hemolytic or DNase capacity (clear virulence factors), although all of them showed protease activity, some showed phospholipase activity, and half of the yeasts were capable of conjugating bile salts. Regarding antimicrobial compounds, all were resistant to antibiotics but showed sensitivity to the antimycotics used. Nevertheless, only one strain of Hanseniaspora osmophila was excluded for use in the food industry, due to its high production of tyramine.

[Intestinal lymphangiectasia in a patient with Sanfilippo B syndrome]. / Linfangiectasia intestinal en un paciente afectado de síndrome de Sanfilippo B.

Mucopolysaccharidosis type IIIB is a lysosomal storage disease caused by a deficiency of the N-acetyl-alpha-d-glucosaminidase enzyme involved in the catabolism of heparan sulfate, causing its accumulation in various tissues. We present an 8-year-old patient with mucopolysaccharidosis type IIIB, with a history of chronic diarrhea and endoscopic and histological findings compatible with intestinal lymphangiectasia. After a dietary treatment with a low-fat diet supplemented with mediumchain triglyceride, our patient presents clinical improvement until today. The pathogenesis of chronic diarrhea in patients with mucopolysaccharidosis type IIIB is still unknown. The Linfangiectasia intestinal en un paciente afectado de síndrome de Sanfilippo B Intestinal lymphangiectasia in a patient with Sanfilippo B syndrome presence of intestinal lymphangiectasia in these patients should be investigated, and appropriate dietary treatment should be initiated, if confirmed, to improve their quality of life.

La mucopolisacaridosis tipo III B es una enfermedad de depósito lisosomal causada por la deficiencia de la enzima N-acetil-alfad- glucosaminidasa, implicada en el catabolismo del heparán sulfato, que produce su acúmulo en diversos tejidos. Se presenta a un paciente de 8 años, afectado de mucopolisacaridosis tipo III B, con historia de diarrea crónica y hallazgos endoscópicos e histológicos compatibles con linfangiectasia intestinal. Tras tratamiento dietético con restricción de ácidos grasos de cadena larga y rica en triglicéridos de cadena media, presentó mejoría clínica, mantenida hasta la actualidad. La patogenia de la diarrea crónica en pacientes con mucopolisacaridosis tipo III B es aún desconocida. Debe investigarse la presencia de linfangiectasia intestinal en estos pacientes e iniciar, en caso de confirmarse, un tratamiento dietético adecuado para mejorar así su calidad de vida.

Influencia de los factores ambientales-analíticos sobre el fenotipo de esclerosis lateral amiotrófica en un medio rural / Environmental-analytical risk factors influence on the phenotype of amyotrophic lateral sclerosis in a rural setting

Introducción. Existen discrepancias en los diversos estudios que intentan correlacionar los factores de riesgo de desarrollar esclerosis lateral amiotrófica (ELA) y el impacto en su pronóstico. Algunos de dichos factores son intrínsecos al medio de vida rural. Por ello, proponemos estudiar si alguno de éstos influye sobre el inicio o el pronóstico de la enfermedad en la región sanitaria de Lleida, un ámbito predominantemente rural. Pacientes y métodos. Se recogieron y analizaron variables relacionadas con factores generales, clínicos, ambientales y de laboratorio en el momento del diagnóstico de ELA en 38 pacientes, y se relacionaron retrospectivamente con el inicio de la enfermedad y su supervivencia. Resultados. Los antecedentes familiares de ELA (p < 0,02) y la creatincinasa elevada (p < 0,0001) se asociaron a mayor supervivencia. El tabaquismo (p < 0,04), el trabajo físico (p < 0,03), la creatinina baja (p < 0,03) y la creatincinasa elevada (p = 0,0005) se asociaron a un inicio precoz de la enfermedad de modo estadísticamente significativo. La forma de inicio bulbar se relacionó significativamente con un inicio tardío de la enfermedad (p < 0,01). El colesterol total y la proteína C reactiva no influyeron en el inicio ni en el curso de la ELA en nuestra muestra. Existe una tendencia estadísticamente no significativa a favor de que el ejercicio físico moderado se asocia con un inicio más tardío, mientras que el ejercicio intenso se asocia con un inicio precoz de la ELA. Conclusiones. Los resultados apuntan a que existe una serie de factores que influye en el desarrollo y pronóstico de la ELA, y alguno de éstos es más prevalente en el ámbito rural, como el trabajo físico (AU)

Introduction. There are discrepancies in the different studies that attempt to correlate the risk factors of developing amyotrophic lateral sclerosis (ALS) and the impact on their prognosis. Some of these factors are intrinsic to the rural livelihood. Therefore, we propose to study if any of these influence the onset and/or prognosis of the disease in the health region of Lleida, a predominantly rural area. Patients and methods. Variables related to general factors, clinical, environmental and laboratory were collected and analyzed at the time of diagnosis of ALS in 38 patients and were retrospectively related to the onset of the disease and its survival. Results. The family history of ALS (p < 0.02) and elevated CK (p < 0.0001) were associated with increased survival. Smoking (p < 0.04), physical work (p < 0.03), low creatinine (p < 0.03), elevated CK (p = 0.0005) were associated with an early onset of the disease. The bulbar onset form was significantly related to a late onset of the disease (p < 0,01). Total cholesterol and PCR did not influence the onset or course of ALS. There is a non-significant trend at statistical level in favor of moderate physical exercise being associated with a later onset, while intense exercise at an early onset of ALS. Conclusions. The results suggest that there are a number of factors that influence the development and prognosis of ALS, some of which are more prevalent in rural areas, such as physical work (AU)