Longitudinal outcome over four decades of allogeneic stem cell transplantation: a single center experience.

This 45-year study (1978-2022) at a single institution evaluated HSCT outcomes and complications, emphasizing recent advances, with to provide insights into HSCT's evolving field and ongoing efforts to enhance patient outcomes. Involving 1707 patients, the study revealed an initial phase (1978-1987) with a limited activity that yielded modest outcomes, a nearly three-decade span (1988-2016) with a substantial increase in transplant activity, emphasizing umbilical cord blood transplantation (UCBT) for patients lacking a suitable matched sibling donor. In addition to a gradual increase in recipient age, significant improvement in outcomes emerged in the recent period (2017-2022), marked by UCBT replacement with haploidentical transplants, introduction of PTCY-based GVHD prophylaxis for all type of transplants, and increased use of conditioning regimens with thiotepa, busulfan, and fludarabine. In this period, reductions in GVHD, non-relapse mortality, and relapse rates significantly contributed to improved overall survival, event-free survival, and GVHD-free/relapse-free survival. The study identified specific factors, including GVHD prophylaxis and donor selection changes, associated with these positive trends. This four-decade study provides a unique perspective on allogeneic HSCT, showcasing the dynamic evolution of transplantation practices and their impact on outcomes, offering valuable insights for personalized treatment approaches and emphasizing continual innovation in this critical therapeutic modality.

Nature or Nurture: Is the Digestive System of the Pontoporia blainvillei Influenced or Determined by Its Diet?

The Franciscana (also known as the La Plata River Dolphin) is a small dolphin that lives in the coastal waters of Brazil, Uruguay, and Argentina. This species is considered the most endangered marine mammal in the western South Atlantic Ocean. Anatomic dissection of the digestive system of 19 animals of different ages, including 2 neonates, 12 juveniles, and 5 adults, was performed. Parameters related to length, breadth, weight, and diameter of the digestive viscera were considered in each case. Our results show that the Franciscana dolphin presents differential characteristics in relation to several parts of the digestive system, including, specifically, the tongue, the teeth, the stomach, and the small intestine. Thus, this paper add precious information to the actual knowledge of this vulnerable marine mammal species in order to improve conservation efforts.

Comprehensive detection of CRLF2 alterations in acute lymphoblastic leukemia: a rapid and accurate novel approach.

Introduction: Acute lymphoblastic leukemia (ALL) is a prevalent childhood cancer with high cure rate, but poses a significant medical challenge in adults and relapsed patients. Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype, with approximately half of cases characterized by CRLF2 overexpression and frequent concomitant IKZF1 deletions. Methods: To address the need for efficient, rapid, and cost-effective detection of CRLF2 alterations, we developed a novel RT-qPCR technique combining SYBR Green and highresolution melting analysis on a single plate. Results: The method successfully identified CRLF2 expression, P2RY8::CRLF2 fusions, and CRLF2 and JAK2 variants, achieving a 100% sensitivity and specificity. Application of this method across 61 samples revealed that 24.59% exhibited CRLF2 overexpression, predominantly driven by IGH::CRLF2 (73.33%). High Resolution Melting analysis unveiled concurrent CRLF2 or JAK2 variants in 8.19% of samples, as well as a dynamic nature of CRLF2 alterations during disease progression. Discussion: Overall, this approach provides an accurate identification of CRLF2 alterations, enabling improved diagnostic and facilitating therapeutic decision-making.

The Application of 3D Anatomy for Teaching Veterinary Clinical Neurology.

Neuroanatomy is always a challenging topic for veterinary students. It is widely accepted that understanding the anatomy of the central nervous system (CNS) is essential to explain many of the pathological processes that affect the brain. Although its study has varied over time to achieve this goal, in human and veterinary medicine it is difficult to find a teaching method that associates normal anatomy with pathological alterations of the brain. For the first time, we have created an educational tool that combines neuroanatomy and neuropathology, using different magnetic resonance (MR) images as a basis and EspINA software as analyzer, to obtain segmented structures and 3D reconstructions of the dog brain. We demonstrate that this combination is an optimal tool to help anatomists to understand the encephalon, and additionally to help clinicians to recognize illness including a multitude of neurological problems. In addition, we have tried to see whether photogrammetry, which is a common technique in other sciences, for example geology, could be useful to teach veterinary neuroanatomy. Although we still need further investigations, we have been able to generate 3D reconstructions of the whole brain, with very promising results to date.

Incidence and Risk Factors for Development of Cardiac Toxicity in Adult Patients with Newly Diagnosed Acute Myeloid Leukemia.

The incidence of cardiac morbimortality in acute myeloid leukemia (AML) is not well known. We aim to estimate the cumulative incidence (CI) of cardiac events in AML patients and to identify risk factors for their occurrence. Among 571 newly diagnosed AML patients, 26 (4.6%) developed fatal cardiac events, and among 525 treated patients, 19 (3.6%) experienced fatal cardiac events (CI: 2% at 6 months; 6.7% at 9 years). Prior heart disease was associated with the development of fatal cardiac events (hazard ratio (HR) = 6.9). The CI of non-fatal cardiac events was 43.7% at 6 months and 56.9% at 9 years. Age ≥ 65 (HR = 2.2), relevant cardiac antecedents (HR = 1.4), and non-intensive chemotherapy (HR = 1.8) were associated with non-fatal cardiac events. The 9-year CI of grade 1-2 QTcF prolongation was 11.2%, grade 3 was 2.7%, and no patient had grade 4-5 events. The 9-year CI of grade 1-2 cardiac failure was 1.3%, grade 3-4 was 15%, and grade 5 was 2.1%; of grade 1-2, arrhythmia was 1.9%, grade 3-4 was 9.1%, and grade 5 was 1%. Among 285 intensive therapy patients, median overall survival decreased in those experiencing grade 3-4 cardiac events (p < 0.001). We observed a high incidence of cardiac toxicity associated with significant mortality in AML.

The Respiratory System of the Arctocephalus australis in Comparison to the Dog as a Land-Carnivore: Are There Adaptations to Marine Life?

Marine mammals are divided into three groups, with similar adaptations resulting from their aquatic lifestyle: sirenians, pinnipeds, and cetaceans. The present work focused on the South American fur seal, or Arctocephalus australis, a carnivore included in the pinnipeds group. We assessed whether the anatomical features of the Arctocephalus australis' respiratory system are comparable to those of other land-carnivores or whether these individuals show anatomical adaptations related to their ability to dive or their breath-holding capacities. We studied 11 cadavers of Arctocephalus australis, which included adult (n = 2) and juvenile (n = 9) individuals, by anatomically dissecting their isolated entire respiratory system. Although it is generally similar to that in land-carnivores, we demonstrated that the Arctocephalus australis's respiratory apparatus shows several specific characteristics. Therefore, our results are of great importance for clinical diagnostic and wildlife conservation purposes.

Connections between postparotid terminal branches of the facial nerve: An immunohistochemistry study.

It has been assumed that connections between the postparotid terminal branches of the facial nerve are purely motor. However, the nature of their fibers remains unexplored. The aim of this study is to determine whether these connections comprise motor fibers exclusively. In total 17 connections between terminal facial nerve branches were obtained from 13 different facial nerves. Choline acetyltransferase antibody (ChAT) was used to stain the fibers in the connections and determine whether or not all of them were motor. All connections contained ChAT positive and negative fibers. The average number of fibers overall was 287 (84-587) and the average proportion of positive fibers was 63% (37.7%-91.5%). In 29% of the nerves, >75% of the fibers were ChAT+ (strongly positive); in 52.94%, 50%-75% were ChAT+ (intermediately positive); and in 17.65%, <50% were ChAT+ (weakly positive). Fibers traveling inside the postparotid terminal cranial nerve VII branch connections are not exclusively motor.

An approach to the evaluation of the potency of cannabis resin in Madrid: A health hazard? / Aproximación a la evaluación de la potencia de la resina de cannabis en Madrid: ¿Un riesgo para la salud?

The present study investigates the concentration of Delta (9)-tetrahidrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) in 60 samples of cannabis resin acquired on the streets of Madrid region and its potential danger to consumers' health. Additionally, we study the possible correlation between the potency of samples and their organoleptic characteristics. The analysis of cannabinoids was carried out using a high performance liquid chromatography (RP-HPLC-UV). To classify samples, a strength scale based on THC content was established. THC content in 76.7% of the samples was higher than 15%. This potency allows these samples to be classified as Schedule I or drugs with "unacceptable risk" for human health. THC content in 36.7% of the samples was 28.8% on average, which means very high potency. The mean CBD content was 5%, while the correlation between the CBD/THC ratio and potency was negative. The mean content of CBN was 1.74% and the CBN/THC ratio also showed a negative correlation in respect to potency. When investigating the possible correlation between sample potency and organoleptic characteristics, those samples which simultaneously presented sticky texture, high elasticity and light brown colour had very high potency, with an average THC content of 28.7%. Our study shows that the THC content of most of the cannabis that can be purchased in Madrid region is over 15% and poses a health hazard. Additionally, we demonstrate for the first time that only those samples with very high potency can be directly associated with certain organoleptic characteristics.

El presente estudio investiga la concentración de Delta(9)-tetrahidrocannabinol (THC), cannabidiol (CBD) y cannabinol (CBN) en 60 muestras de resina de cannabis adquiridas en las calles de Madrid y su potencial riesgo para la salud del consumidor. Adicionalmente, estudiamos la posible asociación entre la potencia de las muestras y sus características organolépticas. El análisis de cannabinoides se llevó a cabo mediante cromatografía líquida de alta resolución (RP-HPLC-UV). Atendiendo al contenido en THC se estableció una escala de potencia para clasificar las muestras. El 76,7% de las muestras tenía un contenido en THC superior al 15%, esta potencia las cataloga como drogas de Grado I con "riesgo inaceptable" para la salud. El 36,7% de las muestras presentaron un contenido medio en THC del 28,8% (potencia muy alta). El contenido medio en CBD fue del 5% y el de CBN 1,74%; ambas ratios, CBD/THC y CBN/THC, mostraron una correlación negativa con la potencia. Al investigar la posible asociación entra potencia y características organolépticas, se observó que las muestras que presentaban a la vez una textura pegajosa, una elasticidad alta y un color marrón claro, tenían una potencia muy alta, con un contenido medio en THC del 28.7%. Nuestro estudio muestra que el contenido en THC de la mayoría de la resina de cannabis que puede adquirirse en Madrid es superior al 15% y supone un elevado riesgo para la salud. Adicionalmente, demostramos por primera vez que solo aquellas muestras con una potencia muy alta pueden asociarse directamente con ciertas características organolépticas.

The Digestive System of the Arctocephalus australis in Comparison to the Dog as a Land-Carnivore Model.

Marine mammals play a critical ecological role as both predator and prey. They are divided into three groups that share similar adaptations to their aquatic life, but that have very different origins and life patterns: sirenians, pinnipeds, cetaceans. The species object of our interest is the South American fur seal or Arctocephalus australis, a carnivore classified within the group of pinnipeds. The objective of the present study was to evaluate whether the anatomical characteristics of the Arctocephalus australis' digestive system are similar to that of other land-carnivores or if, on the contrary, this species shows anatomical adaptations related to their life in the ocean. The study was carried out on 11 cadavers of the species Arctocephalus australis, made up of two adults and nine juveniles, by means of the anatomical dissection of their entire isolated digestive system. We demonstrate that, with several exceptions, the anatomical characteristics of the digestive system of the Arctocephalus australis are similar to those in other carnivores. Therefore, our data constitute an important contribution for clinical diagnostic and conservation purposes, for both veterinarians and biologists.

A Morphological and Morphometric Dental Analysis as a Forensic Tool to Identify the Iberian Wolf (Canis Lupus Signatus).

Depredation by the Iberian wolf (Canis lupus signatus) is currently thought to be a problem in some areas of Spain. However, there are few technically validated forensic tools available to determine the veracity of claims with a high degree of scientific confidence, which is important given that such attacks may lead to compensation. The analysis of bite marks on attacked animals could provide scientific evidence to help identify the offender. Thus, the aim of this study was to assess the morphological and morphometric characteristics of Iberian wolf dentition. This data collection would serve as a base-point for a more accurate identification of the wolves thorough their bite marks. For the first time, 36 dental variables have been studied in wolves' skulls, employing univariate and multivariate analyses. The general morphological dental characteristics of wolves are very similar in terms of their dental formula and tooth structure to other canids, like domestic dogs. Sex differentiation was evident, principally in terms of the maxillary distance between the palatal surfaces of the canine teeth (UbC) and the width of the left mandibular canine teeth (LlCWd). New morphometric reference information was obtained that can aid the forensic identification of bite marks caused by the Iberian wolf with greater confidence.

The Human Laryngeal Innervation Revisited-The Role of the Neural Connections.

In spite that vascular inconvenients or immunological rejections have been solved in relation with larynx transplant, a successful functional reinnervation has not been achieved. Some studies have suggested that laryngeal nerve connection may contain motor fibers, which could explain unexpected evoked responses in electromyographic studies or the different positions adopted of the vocal folds after similar nerve lesions. Ten patients with unexpected evoked responses after laryngeal nerve stimulation were selected. All the patients underwent a total laryngectomy due to oncological causes. In every case, laryngeal nerve connections were observed. All of them were morphologic and histologic processed for choline-acetyltransferase immunohistochemistry. The presence of motor axons in the nerve connections has been demonstrated, which would explain that the motor innervation to the laryngeal muscles could be dual through these variable connections. This also would justify the difficulty of carrying out laryngeal nerve reinnervation procedures. Anat Rec, 302:646-651, 2019. © 2018 Wiley Periodicals, Inc.