Case report: First documented case of cerebral angiostrongyliasis caused by Angiostrongylus costaricensis in a free-ranging opossum.

Angiostrongylus costaricensis is a metastrongyloid nematode that primarily infects the mesenteric arteries of wild rodents. This parasite is endemic in several regions of the American continent, and in humans, causes a disease known as abdominal angiostrongyliasis. Despite the important health implications of this nematode, there are limited studies investigating the involvement of wild animals in its life cycle. In this study, we present the clinical manifestations, pathologic findings, and molecular diagnosis, to the best of our current knowledge, of the first documented onset of cerebral angiostrongyliasis because of A. costaricensis infection in a juvenile free-ranging opossum (Didelphis marsupialis). Histopathological findings stress the presence of eosinophilic meningoencephalitis with nematodes present within the lesions, and PCR was positive for cox1 and ITS1 reactions. The obtained sequences for a 279 bp fragment of ITS1 were 100% identical to A. costaricensis from Costa Rica. This case highlights the substantial difficulties in diagnosing neuroangiostrongyliasis, yet underscores the importance of considering A. costaricensis as a potential culprit behind neurological conditions in wild marsupials. It acts as an urgent call to action to improve surveillance programs tracking infectious and parasitic diseases causing mortality in wildlife populations.

Spinocerebellar ataxia type 2 has multiple ancestral origins.

INTRODUCTION: Spinocerebellar ataxia type 2 (SCA2) is a dominant neurodegenerative disorder due to expansions of a CAG repeat tract (CAGexp) at the ATXN2 gene. Previous studies found only one ancestral haplotype worldwide, with a C allele at rs695871. This homogeneity was unexpected, given the severe anticipations related to SCA2. We aimed to describe informative ancestral haplotypes found in South American SCA2 families. METHODS: Seventy-seven SCA2 index cases were recruited from Brazil, Peru, and Uruguay; 263 normal chromosomes were used as controls. The SNPs rs9300319, rs3809274, rs695871, rs1236900 and rs593226, and the STRs D12S1329, D12S1333, D12S1672 and D12S1332, were used to reconstruct haplotypes. RESULTS: Eleven ancestral haplotypes were found in SCA2 families. The most frequent ones were A-G-C-C-C (46.7 % of families), G-C-C-C-C (24.6 %) and A-C-C-C-C (10.3 %) and their mean (sd) CAGexp were 41.68 (3.55), 40.42 (4.11) and 45.67 (9.70) (p = 0.055), respectively. In contrast, the mean (sd) CAG lengths at normal alleles grouped per haplotypes G-C-G-A-T, A-G-C-C-C and G-C-C-C-C were 22.97 (3.93), 23.85 (3.59), and 30.81 (4.27) (p < 0.001), respectively. The other SCA2 haplotypes were rare: among them, a G-C-G-A-T lineage was found, evidencing a G allele in rs695871. CONCLUSION: We identified several distinct ancestral haplotypes in SCA2 families, including an unexpected lineage with a G allele at rs695871, a variation never found in hundreds of SCA2 patients studied worldwide. SCA2 has multiple origins in South America, and more studies should be done in other regions of the world.

Una Actualización de la Enseñanza de la Anatomía Humana: Análisis Comparativo de Aula Invertida y Modelo tradicional / An Update on the Teaching of Human Anatomy: Comparative Analysis of the Flipped Classroom and the Traditional Model

La enseñanza de la Anatomía humana es trascendental para toda profesión del área de la salud. En el contexto de Chile, ésta se caracteriza por ser principalmente corte tradicional con transferencia unidireccional de la información. Actualmente se propone lograr un aprendizaje más significativo, con la ayuda de modelos como Aula invertida. El objetivo de este estudio es comparar el rendimiento académico entre el modelo tradicional (MT) y Aula invertida (AI). Se intervinieron 2 cursos de 1° año, de las carreras de Nutrición y Odontología año 2022 de la Universidad de La Frontera, en los que se aplicó MT y AI, comparando el rendimiento con un test post clase en Nutrición, y un trabajo grupal en Odontología. Se realizaron análisis estadísticos descriptivos y pruebas que compararon las notas obtenidas. En uno de los grupos se segmentaron los estudiantes por rendimiento para analizar cómo afecta cada modelo dependiendo del tipo de estudiante. Se obtuvo mejor promedio post test con AI en Nutrición; 4,9 ±1,3, en contraste con un promedio de 4,2 ±1,3 para MT (escala 1,0 a 7,0). La prueba T de Student arrojó diferencias estadísticamente significativas (p0,05) en las calificaciones de los trabajos grupales con MT y AI. Es imperante actualizar la enseñanza de la Anatomía en favor de lograr un aprendizaje significativo, mediado por el trabajo de pares y el estudiante como protagonista que propone AI, que a su vez beneficia a aquellas personas con rendimientos más bajos al comienzo.

SUMMARY: The teaching of anatomy is transcendental for every profession in the health care area. In the Chilean context, this is characterized by being mainly traditional with a one-way transfer of information. Currently, it is proposed to achieve a more significant learning, with based models such as Flipped Classroom. The objective of this study is to compare the academic performance between the traditional model (TM) and the flipped classroom (FP). Two 1st year courses were intervened, from the Nutrition and Dentistry degrees at Universidad de La Frontera in 2022, in which TM and FP were applied, comparing the performance with a post-class test in Nutrition, and workgroup in Denistry. Descriptive statistical analyzes and tests that compared the grades obtained were performed. In one of the groups, the students were segmented by performance to analyze how each model affects the type of student. A better post-test average was obtained with FP in Nutrition; 4.9 ±1.3, in contrast to an average of 4.2 ±1.3 for TM (1.0 to 7.0 scale). Student's t test showed statistically significant differences (p0.05) in the evaluations of the workgroup with TM and FP. It is imperative to improve the Anatomy´s teaching in favor of achieving significant learning, mediated by peer work and the student as the protagonist proposing FP, which in turn benefits individuals with lower performances at the beginning.

Self-Healing of Trotter Error in Digital Adiabatic State Preparation.

Adiabatic time evolution can be used to prepare a complicated quantum many-body state from one that is easier to synthesize and Trotterization can be used to implement such an evolution digitally. The complex interplay between nonadiabaticity and digitization influences the infidelity of this process. We prove that the first-order Trotterization of a complete adiabatic evolution has a cumulative infidelity that scales as O(T^{-2}δt^{2}) instead of O(T^{2}δt^{2}) expected from general Trotter error bounds, where δt is the time step and T is the total time. This result suggests a self-healing mechanism and explains why, despite increasing T, infidelities for fixed-δt digitized evolutions still decrease for a wide variety of Hamiltonians. It also establishes a correspondence between the quantum approximate optimization algorithm and digitized quantum annealing.

Paired microbiome and metabolome analyses associate bile acid changes with colorectal cancer progression.

Colorectal cancer (CRC) is driven by genomic alterations in concert with dietary influences, with the gut microbiome implicated as an effector in disease development and progression. While meta-analyses have provided mechanistic insight into patients with CRC, study heterogeneity has limited causal associations. Using multi-omics studies on genetically controlled cohorts of mice, we identify diet as the major driver of microbial and metabolomic differences, with reductions in α diversity and widespread changes in cecal metabolites seen in high-fat diet (HFD)-fed mice. In addition, non-classic amino acid conjugation of the bile acid cholic acid (AA-CA) increased with HFD. We show that AA-CAs impact intestinal stem cell growth and demonstrate that Ileibacterium valens and Ruminococcus gnavus are able to synthesize these AA-CAs. This multi-omics dataset implicates diet-induced shifts in the microbiome and the metabolome in disease progression and has potential utility in future diagnostic and therapeutic developments.

Neurological Phenotypes of IRF2BPL Gene Variants: A Report of Four Novel Variants.

IRF2BPL gene variants have recently been associated to developmental disability and epilepsy in children and movement disorders in adults. So far, only few cases have been reported; here we present four novel cases identified by exome sequencing, while investigating developmental delay, adult-onset cerebellar ataxia or regression.

Evolución del parto por cesárea en la provincia del Neuquén, 2000-2020 / Caesarean section rate evolution in Neuquén province, 2000 to 2020

RESUMEN INTRODUCCIÓN: El nacimiento por cesárea se encuentra en aumento en todo el mundo, con diferencias significativas entre regiones. El objetivo fue determinar la situación del porcentaje de cesárea en mujeres con parto en la provincia del Neuquén en 2000-2020, buscando diferencias entre subsectores, zonas sanitarias, localidades e instituciones de salud . MÉTODOS: Se analizaron las estadísticas del Sistema Informático Perinatal referentes a vía de parto, recién nacidos y mujeres con partos entre 2000 y 2020. Se realizó un análisis estratificado del porcentaje de cesáreas, describiendo medidas de tendencia central, de dispersión y velocidad promedio de incremento anual . RESULTADOS: Las características sociodemográficas de madres gestantes se han modificado, con un descenso del embarazo adolescente y un aumento de madres de más de 35 años. Se observó un mayor porcentaje de bajo peso al nacer en el subsector privado y una importante disminución de la tasa bruta de natalidad, con mayor descenso en el interior provincial. Se encontró un aumento sostenido, así como diferencias crecientes y muy significativas entre subsectores (y dentro de estos entre las distintas instituciones) . DISCUSIÓN: Existen diferencias muy significativas en los resultados si se comparan los diferentes subsectores e instituciones respecto al nacimiento por cesárea. Estos resultados son un aporte para la construcción de políticas acordes a la realidad epidemiológica de la provincia y de cada institución de salud.

ABSTRACT INTRODUCTION: Cesarean delivery is increasing all over the world, with significant differences between regions. The aim was to determine the cesarean section rate in women giving birth between 2000 and 2020 in Neuquén province, seeking for differences between sub-sectors, health zones, cities and health institutions . METHODS: Statistics from the Perinatal Information System were analyzed regarding type of delivery, newborns and women delivering between 2000 and 2020. A stratified analysis of the cesarean section rate was conducted, describing central tendency and dispersion measures, and the average annual rate of increase . RESULTS: Maternal sociodemographic characteristics have changed, with adolescent pregnancy decrease and a higher number of mothers older than 35 years of age. The percentage of low birth weight was higher in the private sub-sector, with a significant decrease of gross birth rate, mainly inside the province. There was a steady increase as well as growing and very significant differences between sub-sectors (and within them between the different institutions) . DISCUSSION: The results show very significant differences when comparing sub-sectors and institutions regarding cesarean birth, and contribute to building policies tailored to the epidemiological situation of the province and each health institution.

An Exploratory Survey on the Care for Ataxic Patients in the American Continents and the Caribbean.

Little is known about access of rare disease carriers to health care. To increase this knowledge, the Pan American Hereditary Ataxia Network (PAHAN) conducted an exploratory survey about care for hereditary ataxias in American continents and the Caribbean. A questionnaire was sent to health professionals about the hereditary ataxias identified; access to care; and local teaching and research. The number of ataxics under current care per 100,000 inhabitants was subtracted from the expected overall prevalence of 6/100,000, to estimate the prevalence of uncovered ataxic patients. Local Human Development Indexes (HDI) were used to measure socio-economic factors. Twenty-six sites participated. Twelve sites had very high, 13 had high, and one site had medium HDI. Participants reported on 2239 and 602 patients with spinocerebellar ataxias and recessive forms under current care. The number of patients under current care per inhabitants varied between 0.14 and 12/100,000. The estimated prevalence of uncovered ataxic patients was inversely proportional to HDIs (rho = 0.665, p = 0.003). Access to diagnosis, pre-symptomatic tests, and rehabilitation were associated with HDIs. More and better molecular diagnostic tools, protocols and guidelines, and professional training for ataxia care were the top priorities common to all respondents. Evidence of inequalities was confirmed. Lower HDIs were associated with high potential numbers of uncovered ataxic subjects, and with lack of molecular diagnosis, pre-symptomatic testing, and rehabilitation. More and better diagnostic tools, guidelines, and professional training were priorities to all sites. PAHAN consortium might help with the last two tasks.

Passive epidemiological surveillance in wildlife in Costa Rica identifies pathogens of zoonotic and conservation importance.

Epidemiological surveillance systems for pathogens in wild species have been proposed as a preventive measure for epidemic events. These systems can minimize the detrimental effects of an outbreak, but most importantly, passive surveillance systems are the best adapted to countries with limited resources. Therefore, this research aimed to evaluate the technical and infrastructural feasibility of establishing this type of scheme in Costa Rica by implementing a pilot program targeting the detection of pathogens of zoonotic and conservation importance in wildlife. Between 2018 and 2020, 85 carcasses of free-ranging vertebrates were admitted for post-mortem and microbiology analysis. However, we encountered obstacles mainly related to the initial identification of cases and limited local logistics capacity. Nevertheless, this epidemiological surveillance scheme allowed us to estimate the general state of health of the country's wildlife by establishing the causes of death according to pathological findings. For instance, 60% (51/85) of the deaths were not directly associated with an infectious agent. Though in 37.6% (32/85) of these cases an infectious agent associated or not with disease was detected. In 27.1% (23/85) of the cases, death was directly related to infectious agents. Furthermore, 12.9% (11/85), the cause of death was not determined. Likewise, this wildlife health monitoring program allowed the detection of relevant pathogens such as Canine Distemper Virus, Klebsiella pneumoniae, Angiostrongylus spp., Baylisascaris spp., among others. Our research demonstrated that this passive surveillance scheme is cost-effective and feasible in countries with limited resources. This passive surveillance can be adapted to the infrastructure dedicated to monitoring diseases in productive animals according to the scope and objectives of monitoring wildlife specific to each region. The information generated from the experience of the initial establishment of a WHMP is critical to meeting the challenges involved in developing this type of scheme in regions with limited resources and established as hotspots for emerging infectious diseases.

An untargeted metabolomics analysis of exogenous chemicals in human milk and transfer to the infant.

Human milk is the optimal infant nutrition. However, although human-derived metabolites (such as lipids and oligosaccharides) in human milk are regularly reported, the presence of exogenous chemicals (such as drugs, food, and synthetic compounds) are often not addressed. To understand the types of exogenous compounds that might be present, human milk (n = 996) was analyzed by untargeted metabolomics. This analysis revealed that lifestyle molecules, such as medications and their metabolites, and industrial sources, such as plasticizers, cosmetics, and other personal care products, are found in human milk. We provide further evidence that some of these lifestyle molecules are also detectable in the newborn's stool. Thus, this study gives important insight into the types of exposures infants receiving human milk might ingest due to the lifestyle choices, exposure, or medical status of the lactating parent.

Diverse mutational spectrum in the 13q14 chromosomal region in a Brazilian cohort of retinoblastoma.

Retinoblastoma is a rare childhood tumor caused by the inactivation of both copies of the RB1 gene. Early diagnosis and identification of heritable RB1 mutation carriers can improve the disease outcome and management via genetic counseling. We used the Multiplex Ligation-dependent Probe Amplification (MLPA) method to analyze the RB1 gene and flanking regions in blood samples from 159 retinoblastoma patients previously negative for RB1 point mutations via Sanger sequencing. We detected a wide spectrum of germline chromosomal alterations, ranging from partial loss or duplication of RB1 to large deletions spanning RB1 and adjacent genes. Mutations were validated via karyotyping, fluorescent in situ hybridization (FISH), SNP-arrays (Single Nucleotide Polymorphism-arrays) and/or quantitative relative real-time PCR. Patients with leukocoria as a presenting symptom showed reduced death rate (p = 0.013) and this sign occurred more frequently among carriers of two breakpoints within RB1 (p = 0.05). All unilateral cases presented both breakpoints outside of RB1 (p = 0.0075). Patients with one breakpoint within RB1 were diagnosed at earlier ages (p = 0.017). Our findings characterize the mutational spectrum of a Brazilian cohort of retinoblastoma patients and point to a possible relationship between the mutation breakpoint location and tumor outcome, contributing to a better prospect of the genotype/phenotype correlation and adding to the wide diversity of germline mutations involving RB1 and adjacent regions in retinoblastoma.

Fracturas de la base del quinto metatarsiano: ¿es útil mi tornillo de esponjosa con rosca parcial? Experiencia de 10 años / Fractures of the base of the fifth metatarsal bone: is my partially-threaded cancellous screw useful? 10-year experience

OBJETIVO Evaluar el resultado quirúrgico de fracturas de las zonas 2 y 3 de la base del quinto metatarsiano usando tornillos de esponjosa de diámetro de 4,0 mm con rosca parcial. MATERIALES Y MÉTODOS Evaluación retrospectiva de pacientes operados entre 2010 a 2019. Incluimos todos los casos sintetizados con este dispositivo con seguimiento mínimo de tresmeses, y excluimos casos operados con otros dispositivos y seguimiento menor a tres meses. Evaluamos la consolidació n y la presencia de complicaciones. Determinamos el largo del tornillo, el diámetro del canal endomedular, la distancia entre el borde proximal de la tuberosidad y la fractura, y la distancia de paso de la rosca sobre el rasgo de la fractura en radiografías anteroposterior (AP) y oblicua del pie. RESULTADOS Evaluamos 39 casos, y la muestra tenía una edad promedio de 27 años, y predominio del sexo masculino. El largo de tornillo más usado fue el de 45 mm, y los diámetros promedios del canal endomedular medidos en las radiografías AP y oblicua fueron de 4,6 mm y 3,96 mm, respectivamente. La distancia del borde de la tuberosidad hasta la fractura fue de 25,8 mm, y la distancia de paso de la rosca sobre el rasgo de la fractura fue en promedio de 24 mm. Hubo 100% de consolidación, en un promedio de 9,4 semanas, y 3 casos de retardo de consolidación, 2 de retroceso de tornillo, 1 de rosca intrafoco, y 1 de fractura cortical superior. No hubo retiros de tornillos a la fecha. DISCUSION No existe consenso respecto al tornillo ideal. La literatura internacional recomienda dispositivos intramedulares de diámetro de al menos 4,5 mm. Existen pocos reportes del uso de tornillos de diámetro de 4,0 mm. CONCLUSIONES El tornillo de esponjosa de diámetro de 4,0 mm con rosca parcial es una alternativa eficaz, segura y con baja tasa de complicaciones para el manejo de estas fracturas en nuestra población.

OBJETIVE To evaluate the surgical result of zone-2 and -3 fractures of the base of the fifth metatarsal bone using partially-threaded cancellous screws with a diameter of 4.0 mm. MATERIALS AND METHODS A retrospective evaluation of patients submitted to surgery between 2010 and 2019. We included all of the cases synthesized with this device with a minimum follow-up of three months, and excluded the cases operated on with other devices and follow-up shorter than three months. We evaluated the consolidation and the presence of complications, and determined, screw length, diameter of the endomedullary canal, the distance between the proximal edge of tuberosity and the fracture, and thread pitch over the fracture line on anteroposterior (AP) and oblique radiographs. RESULTS We evaluated 39 cases, and the sample had an average age of 27 years and male predominance. The most used screw length was 45 mm, and the average diameters of the medullary canal measured on the AP and oblique radiographs were of 4.6 mm and 3.96 mm respectively. The distance from the edge of the tuberosity to the fracture was of 25.8 mm, and the thread pitch over the fracture line was on average 24 mm. The rate of consolidation was of 100%, occurring in an average of 9.4 weeks, and there were 3 cases of consolidation delay, 2 of screw recoil, 1 of intrafocus thread, and 1 of superior cortex fracture. To date, there have been no cases of screw removal. DISCUSSION There is no consensus regarding the ideal screw. The international literature recommends intramedullary devices with a diameter of at least 4.5 mm. There are few reports of the use of screws with 4.0 mm in diameter. CONCLUSIONS The partially-threaded cancellous screw with a diameter of 4.0 mm is an effective and safe option, with a low complication rate for the management of these fractures.

Enhancing untargeted metabolomics using metadata-based source annotation.

Human untargeted metabolomics studies annotate only ~10% of molecular features. We introduce reference-data-driven analysis to match metabolomics tandem mass spectrometry (MS/MS) data against metadata-annotated source data as a pseudo-MS/MS reference library. Applying this approach to food source data, we show that it increases MS/MS spectral usage 5.1-fold over conventional structural MS/MS library matches and allows empirical assessment of dietary patterns from untargeted data.

Multiomic Analyses of Nascent Preterm Infant Microbiomes Differentiation Suggest Opportunities for Targeted Intervention.

The first week after birth is a critical time for the establishment of microbial communities for infants. Preterm infants face unique environmental impacts on their newly acquired microbiomes, including increased incidence of cesarean section delivery and exposure to antibiotics as well as delayed enteral feeding and reduced human interaction during their intensive care unit stay. Using contextualized paired metabolomics and 16S sequencing data, the development of the gut, skin, and oral microbiomes of infants is profiled daily for the first week after birth, and it is found that the skin microbiome appears robust to early life perturbation, while direct exposure of infants to antibiotics, rather than presumed maternal transmission, delays microbiome development and prevents the early differentiation based on body site regardless of delivery mode. Metabolomic analyses identify the development of all gut metabolomes of preterm infants toward full-term infant profiles, but a significant increase of primary bile acid metabolism only in the non-antibiotic treated vaginally birthed late preterm infants. This study provides a framework for future multi-omic, multibody site analyses on these high-risk preterm infant populations and suggests opportunities for monitoring and intervention, with infant antibiotic exposure as the primary driver of delays in microbiome development.

A Prebiotic Diet Alters the Fecal Microbiome and Improves Sleep in Response to Sleep Disruption in Rats.

Sleep disruption is a challenging and exceedingly common physiological state that contributes to a wide range of biochemical and molecular perturbations and has been linked to numerous adverse health outcomes. Modern society exerts significant pressure on the sleep/wake cycle via myriad factors, including exposure to electric light, psychological stressors, technological interconnection, jet travel, shift work, and widespread use of sleep-affecting compounds. Interestingly, recent research has identified a link between the microbiome and the regulation of sleep, suggesting that interventions targeting the microbiome may offer unique therapeutic approaches to challenges posed by sleep disruption. In this study, we test the hypothesis that administration of a prebiotic diet containing galactooligosaccharides (GOS) and polydextrose (PDX) in adult male rats improves sleep in response to repeated sleep disruption and during recovery sleep. We found that animals fed the GOS/PDX prebiotic diet for 4 weeks exhibit increased non-rapid eye movement (NREM) and rapid eye movement (REM) sleep during 5 days of sleep disruption and increased total sleep time during 24 h of recovery from sleep disruption compared to animals fed a control diet, despite similar baseline sleep characteristics. Further, the GOS/PDX prebiotic diet led to significant changes in the fecal microbiome. Consistent with previous reports, the prebiotic diet increased the relative abundance of the species Parabacteroides distasonis, which positively correlated with sleep parameters during recovery sleep. Taken together, these findings suggest that the GOS/PDX prebiotic diet may offer an approach to improve resilience to the physiologic challenge of sleep disruption, in part through impacts on the microbiome.

The Host-Microbiome Response to Hyperbaric Oxygen Therapy in Ulcerative Colitis Patients.

BACKGROUND & AIMS: Hyperbaric oxygen therapy (HBOT) is a promising treatment for moderate-to-severe ulcerative colitis. However, our current understanding of the host and microbial response to HBOT remains unclear. This study examined the molecular mechanisms underpinning HBOT using a multi-omic strategy. METHODS: Pre- and post-intervention mucosal biopsies, tissue, and fecal samples were collected from HBOT phase 2 clinical trials. Biopsies and fecal samples were subjected to shotgun metaproteomics, metabolomics, 16s rRNA sequencing, and metagenomics. Tissue was subjected to bulk RNA sequencing and digital spatial profiling (DSP) for single-cell RNA and protein analysis, and immunohistochemistry was performed. Fecal samples were also used for colonization experiments in IL10-/- germ-free UC mouse models. RESULTS: Proteomics identified negative associations between HBOT response and neutrophil azurophilic granule abundance. DSP identified an HBOT-specific reduction of neutrophil STAT3, which was confirmed by immunohistochemistry. HBOT decreased microbial diversity with a proportional increase in Firmicutes and a secondary bile acid lithocholic acid. A major source of the reduction in diversity was the loss of mucus-adherent taxa, resulting in increased MUC2 levels post-HBOT. Targeted database searching revealed strain-level associations between Akkermansia muciniphila and HBOT response status. Colonization of IL10-/- with stool obtained from HBOT responders resulted in lower colitis activity compared with non-responders, with no differences in STAT3 expression, suggesting complementary but independent host and microbial responses. CONCLUSIONS: HBOT reduces host neutrophil STAT3 and azurophilic granule activity in UC patients and changes in microbial composition and metabolism in ways that improve colitis activity. Intestinal microbiota, especially strain level variations in A muciniphila, may contribute to HBOT non-response.

An international analysis evaluating frontline bendamustine with rituximab in extranodal marginal zone lymphoma.

Extranodal marginal zone lymphoma (EMZL) is a heterogeneous non-Hodgkin lymphoma. No consensus exists regarding the standard-of-care in patients with advanced-stage disease. Current recommendations are largely adapted from follicular lymphoma, for which bendamustine with rituximab (BR) is an established approach. We analyzed the safety and efficacy of frontline BR in EMZL using a large international consortium. We included 237 patients with a median age of 63 years (range, 21-85). Most patients presented with Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (n = 228; 96.2%), stage III/IV (n = 179; 75.5%), and intermediate (49.8%) or high (33.3%) Mucosa Associated Lymphoid Tissue International Prognosis Index (MALT-IPI). Patients received a median of 6 (range, 1-8) cycles of BR, and 20.3% (n = 48) received rituximab maintenance. Thirteen percent experienced infectious complications during BR therapy; herpes zoster (4%) was the most common. Overall response rate was 93.2% with 81% complete responses. Estimated 5-year progression-free survival (PFS) and overall survival (OS) were 80.5% (95% CI, 73.1% to 86%) and 89.6% (95% CI, 83.1% to 93.6%), respectively. MALT-IPI failed to predict outcomes. In the multivariable model, the presence of B symptoms was associated with shorter PFS. Rituximab maintenance was associated with longer PFS (hazard ratio = 0.16; 95% CI, 0.04-0.71; P = .016) but did not impact OS. BR is a highly effective upfront regimen in EMZL, providing durable remissions and overcoming known adverse prognosis factors. This regimen is associated with occurrence of herpes zoster; thus, prophylactic treatment may be considered.

Análisis comparativo de la visualización del canal mandibular mediante tomografía computarizada cone beam en humanos / Comparative analysis of the visualization of the mandibular canal by cone beam computed tomography in humans

RESUMEN: Una de las estructuras de mayor interés en la región maxilofacial es el canal mandibular, donde su preservación optimiza el éxito de los procedimientos clínicos. Por su disposición al interior de la mandíbula, la visualización in vivo requiere el uso de técnicas radiográficas, entre las que destaca el Cone Beam CT (CBCT). El objetivo de este trabajo es comparar la visualización del canal mandibular humano mediante imágenes en CBCT con distintos observadores y programas de radiación. Mediante imágenes generadas con CBCT en mandíbulas secas con distintos programas de adquisición, se obtuvieron cortes coronales en los sectores anterior, medio y posterior del canal mandibular, con un total 240 mediciones, las que incluyeron dos tamaños de voxel y dos dosis de radiación distintos. Cada una de las imágenes fue evaluada por un Cirujano Dentista, Máster en Anatomía y Especialista en radiología Máxilofacial. Se obtuvieron porcentajes de visualización según observador para cada programa de adquisición de imágenes. La prueba de Q de Cochran arrojó diferencias entre los observadores (p0,05). El grado de experticia del observador influye en la visualización y su precisión. A su vez, utilizar un programa de adquisición de imagen con distinto voxel y/o dosis no afecta a la visualización, siendo esta dependiente de la anatomía propia de la estructura. Podría utilizarse un protocolo con menor radiación para el usuario cumpliendo con la premisa ALARA (As Low As Reasonably Achievable).

SUMMARY: One of the structures of greatest interest in the maxillofacial region is the mandibular canal, where its preservation optimizes the success of clinical procedures. Due to its disposition inside the mandible, in vivo visualization requires the use of radiographic techniques, among which the Cone Beam CT (CBCT) stands out. The objective of this work is to compare the visualization of the human mandibular canal by means of CBCT images with different observers and radiation programs. Using images generated with CBCT in dry mandibles with different acquisition programs, coronal slices were obtained in the anterior, middle and posterior sectors of the mandibular canal, with a total of 240 measurements, which included two voxel sizes and two doses different radiation sources. Each of the images was evaluated by a Dentist, an Anatomy Master's degree and a specialist in Oral & Maxillofacial Radiology. Percentages of visualization according to observer were obtained for each image acquisition program. The Cochran Q test yielded differences between the observers (p 0.05). The degree of expertise of the observer influences the visualization and its precision. In turn, using an image acquisition program with a different voxel/radiation dose not affect the visualization, since it depends on the anatomy of the structure itself. A protocol with less radiation could be used in patients complying with the ALARA ("As Low As Reasonably Achievable") premise.