Scalable Generation of 3D Pancreatic Islet Organoids from Human Pluripotent Stem Cells in Suspension Bioreactors.

We describe a scalable method for the robust generation of 3D pancreatic islet-like organoids from human pluripotent stem cells using suspension bioreactors. Our protocol involves a 6-stage, 20-day directed differentiation process, resulting in the production of 104-105 organoids. These organoids comprise α- and ß-like cells that exhibit glucose-responsive insulin and glucagon secretion. We detail methods for culturing, passaging, and cryopreserving stem cells as suspended clusters and for differentiating them through specific growth media and exogenous factors added in a stepwise manner. Additionally, we address quality control measures, troubleshooting strategies, and functional assays for research applications.

Evolving patterns and clinical outcome of genetic studies performed at diagnosis in acute myeloid leukemia patients: Real life data from the PETHEMA Registry.

BACKGROUND: There are no studies assessing the evolution and patterns of genetic studies performed at diagnosis in acute myeloid leukemia (AML) patients. Such studies could help to identify potential gaps in our present diagnostic practices, especially in the context of increasingly complex procedures and classifications. METHODS: The REALMOL study (NCT05541224) evaluated the evolution, patterns, and clinical impact of performing main genetic and molecular studies performed at diagnosis in 7285 adult AML patients included in the PETHEMA AML registry (NCT02607059) between 2000 and 2021. RESULTS: Screening rates increased for all tests across different time periods (2000-2007, 2008-2016, and 2017-2021) and was the most influential factor for NPM1, FLT3-ITD, and next-generation sequencing (NGS) determinations: NPM1 testing increased from 28.9% to 72.8% and 95.2% (p < .001), whereas FLT3-ITD testing increased from 38.1% to 74.1% and 95.9% (p < .0001). NGS testing was not performed between 2000-2007 and only reached 3.5% in 2008-2016, but significantly increased to 72% in 2017-2021 (p < .001). Treatment decision was the most influential factor to perform karyotype (odds ratio [OR], 6.057; 95% confidence interval [CI], 4.702-7.802), and fluorescence in situ hybridation (OR, 2.273; 95% CI, 1.901-2.719) studies. Patients ≥70 years old or with an Eastern Cooperative Oncology Group ≥2 were less likely to undergo these diagnostic procedures. Performing genetic studies were associated with a favorable impact on overall survival, especially in patients who received intensive chemotherapy. CONCLUSIONS: This unique study provides relevant information about the evolving landscape of genetic and molecular diagnosis for adult AML patients in real-world setting, highlighting the increased complexity of genetic diagnosis over the past 2 decades.

[Frailty as a predictor of 3-year mortality in older adult patients in long-term care in Mexico]. / Fragilidad como predictor de mortalidad a 3 años en los pacientes adultos mayores en cuidados de largo plazo en México.

INTRODUCTION: The objective of our study was to evaluate the long-term association between mortality and frailty in institutionalized patients in Mexico. Worldwide, there are limited lines of research in this population of geriatric patients and this entity generates a significant impact on the quality of life and prognosis of our patients. MATERIAL AND METHODS: It is a prospective cohort study of 81 patients in long-term care who met the selection criteria. Frailty was determined using the FRAIL scale. Data on mortality were collected during the follow-up period, and diagnosis was monitored. The risk of presenting this event was determined by logistic regression, Kaplan-Meier, and Cox proportional hazards analysis, adjusted for age and sex. RESULTS: The mean follow-up time of the patients was 36 months (1094 days), during which 33 subjects died (40.7%). In our population, at the beginning of the study the vast majority of frail patients had pathologies that independently generate risk of adverse events, disability (Barthel=30.9; SD 28.8), sarcopenia (n=40; 71.4%), one to 3 falls in the last year (n=17; 63%), ≥4 falls (n=4; 57.1%). Frail participants had a higher adjusted risk of mortality (HR 2.93; 95% CI 1.33-6.43; p=0.007). CONCLUSIONS: The frailty entity is associated in the long term with mortality in institutionalized patients in Mexico. Timely treatment and approach may allow a good prognosis and quality of life.

Symptomatology and knowledge regarding pelvic floor dysfunctions and influence of gender stereotypes in female athletes.

Pelvic floor dysfunctions (PFD) are highly prevalent among females who do athletics, a sport requiring jumping, strength, and running. Although educational approaches are useful options, the educational need for this particular population remains unknown. The objective of the present study was to describe the level of knowledge regarding PFD and its relationship with symptomatology and gender stereotypes in female athletes in Spain. A total of 255 female athletes completed an anonymous online survey to explore their knowledge regarding urinary incontinence (UI), pelvic organ prolapse (POP), anal incontinence (AI), and sexual dysfunction (SexD), as well as their PFD symptoms and gender stereotyped beliefs related to sport. Educational level and sports characteristics (training volume, experience, and athletic modality) were also explored. Participants demonstrated a low level of knowledge in terms of POP (52.5%), AI (64.0%), and SexD (40%), but not for UI (70.8%). The proportion of PFD complaints was 63.5% for dyspareunia, 51.8% for urine leakage, 42.4% for pelvic pain, 17.3% for AI, and 9.0% for POP, with no associations with knowledge (p > 0.05). Lower knowledge about UI and SexD was related to greater gender stereotypes (p < 0.05) and rejection of professional healthcare (p = 0.010). As a conclusion, the level of knowledge about PFD was low in female athletes who train and compete in athletics in Spain, mainly with regard to sexual dysfunction. Although 63.5% of athletes had dyspareunia and 51.8% urinary leakages, symptomatology was not associated with level of knowledge. However, a lower level of knowledge was associated with more stereotyped beliefs and rejection of professional healthcare for PFD. These findings confirm the need to design appropriate educational interventions to disseminate information on all the types of PFD, particularly sexual contents. The potential influence of gender stereotypes makes it appropriate to include the gender perspective in these interventions.

Spontaneous Remission of Blastic Plasmacytoid Dendritic Cell Neoplasm: A Case Report.

Spontaneous remissions (SRs) in blastic plasmacytoid dendritic cell neoplasms (BPDCNs) are infrequent, poorly documented, and transient. We report a 40-year-old man presenting with bycitopenia and soft tissue infection. The bone marrow exhibited 3% abnormal cells. Immunophenotyping of these cells revealed the antigens CD45+ (dim), CD34+, CD117+, CD123+ (bright), HLA-DR+ (bimodal), CD56+ (bright), CD33+, CD13+, CD2+, and CD22+ (dim) and the partial expression of the CD10+, CD36+, and CD7+ antigens. All other myeloid, monocytic, and lymphoid antigens were negative. Genetic studies showed a complex karyotype and mutations in the TP53R337C and KRASG12D genes. On hospital admission, the patient showed a subcutaneous nodule on the right hand and left lower limb. Flow cytometry multiparameter (FCM) analysis showed the presence of 29% abnormal cells with the previously described immunophenotype. The patient was diagnosed with BPDCN. The patient was treated with broad-spectrum antibiotics for soft tissue infection, which delayed therapy for BPDCN. No steroids or chemotherapeutic or hypomethylating agents were administered. His blood cell counts improved and skin lesions disappeared, until the patient relapsed five months after achieving spontaneous remission. About 60% of abnormal cells were identified. No changes in immunophenotype or the results of genetic studies were observed. The patient underwent a HyperCVAD chemotherapy regimen for six cycles. Consolidation therapy was performed via allogeneic bone marrow transplantation with an HLA-unrelated donor. One year after the bone marrow transplant, the patient died due to the progression of his underlying disease, coinciding with a respiratory infection caused by SARS-CoV-2. In the available literature, SRs are often linked to infections or other stimulators of the immune system, suggesting that powerful immune activation could play a role in controlling the leukemic clone. Nevertheless, the underlying mechanism of this phenomenon is not clearly understood. We hypothesize that the immune system would force the leukemic stem cell (LSC) to undergo a state of quiescence. This loss of replication causes the LSC progeny to die off, resulting in the SR of BPDCN.

Conventional Versus Traction-Assisted Endoscopic Submucosal Dissection for Esophageal, Gastric, and Colorectal Neoplasms: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Endoscopic submucosal dissection (ESD) is increasingly being utilized for the resection of superficial gastrointestinal neoplasms. However, the long procedure time poses a technical challenge for conventional ESD (C-ESD). Traction-assisted ESD (T-ESD) was developed to facilitate the procedure by reducing its duration. This study compares the efficacy and safety of C-ESD versus T-ESD in the treatment of esophageal, gastric, and colorectal neoplasms. Nine randomized controlled trials (RCTs) were analyzed. Traction-assisted ESD exhibited shorter mean dissection times for the esophagus and colorectal regions and lower perforation rates in colorectal cases. No significant differences were observed in en bloc resection or bleeding rates. Traction-assisted ESD proves to be more efficient in mean procedure time for esophageal and colorectal cases and safer in perforation rates for colorectal cases, but similar rates are noted for en bloc resection or bleeding.

Validation of mutated CEBPA bZIP as a distinct prognosis entity in acute myeloid leukemia: a study by the Spanish PETHEMA registry.

Not available.

Extended septal myectomy versus alcohol septal ablation: clinical results at a national referral centre.

OBJECTIVES: Extended septal myectomy and alcohol septal ablation are 2 invasive treatments for hypertrophic obstructive cardiomyopathy. Our goal was to compare which of these techniques achieved a higher reduction in gradients, improvement in New York Heart Association (NYHA) functional class and reduction in medical treatment. METHODS: It is a single-centre observational and retrospective analysis. We used multivariable regression analyses to assess the association of ablation/myectomy with different outcomes. The odds ratio or coefficient along with the 95% confidence interval was estimated according to the group and adjusted for the corresponding preprocedural variables and EuroSCORE II. RESULTS: A total of 78 patients underwent septal myectomy, and 25 patients underwent alcohol septal ablation. Basal and Valsalva gradients after myectomy were reduced to a higher degree in comparison to ablation: 21.0 mmHg [P < 0.001, 95% confidence interval -30.7; -11.3], and 34.3 mmHg (P < 0.001, -49.1; -19.5) respectively. Those patients who received a myectomy had a lower probability of having moderate mitral regurgitation (odds ratio = 0.18, P = 0.054). Patients after septal myectomy were more likely to be NYHA functional class I (80.4%), whereas patients after ablation were more likely to be NYHA functional class III (48%). Both groups continued with beta-blocker therapy, but disopyramide could be discontinued after the myectomy in more cases (20%-36% vs 59%-1.3%; P < 0.001), and there was a tendency to discontinue calcium channel blockers (48%-16% vs 15.4-3.8%; P = 0.054). CONCLUSIONS: After adjustment using preprocedural gradients and EuroSCORE II, myectomy achieves greater reduction in left ventricular outflow tract gradients compared to septal ablation.

Specialization of amygdala subregions in emotion processing.

The amygdala is important for human fear processing. However, recent research has failed to reveal specificity, with evidence that the amygdala also responds to other emotions. A more nuanced understanding of the amygdala's role in emotion processing, particularly relating to fear, is needed given the importance of effective emotional functioning for everyday function and mental health. We studied 86 healthy participants (44 females), aged 18-49 (mean 26.12 ± 6.6) years, who underwent multiband functional magnetic resonance imaging. We specifically examined the reactivity of four amygdala subregions (using regions of interest analysis) and related brain connectivity networks (using generalized psycho-physiological interaction) to fear, angry, and happy facial stimuli using an emotional face-matching task. All amygdala subregions responded to all stimuli (p-FDR < .05), with this reactivity strongly driven by the superficial and centromedial amygdala (p-FDR < .001). Yet amygdala subregions selectively showed strong functional connectivity with other occipitotemporal and inferior frontal brain regions with particular sensitivity to fear recognition and strongly driven by the basolateral amygdala (p-FDR < .05). These findings suggest that amygdala specialization to fear may not be reflected in its local activity but in its connectivity with other brain regions within a specific face-processing network.

Cyborg islets: implanted flexible electronics reveal principles of human islet electrical maturation.

Flexible electronics implanted during tissue formation enable chronic studies of tissue-wide electrophysiology. Here, we integrate tissue-like stretchable electronics during organogenesis of human stem cell-derived pancreatic islets, stably tracing single-cell extracellular spike bursting dynamics over months of functional maturation. Adapting spike sorting methods from neural studies reveals maturation-dependent electrical patterns of α and ß-like (SC-α and ß) cells, and their stimulus-coupled dynamics. We identified two major electrical states for both SC-α and ß cells, distinguished by their glucose threshold for action potential firing. We find that improved hormone stimulation capacity during extended culture reflects increasing numbers of SC-α/ß cells in low basal firing states, linked to energy and hormone metabolism gene upregulation. Continuous recording during further maturation by entrainment to daily feeding cycles reveals that circadian islet-level hormone secretion rhythms reflect sustained and coordinate oscillation of cell-level SC-α and ß electrical activities. We find that this correlates with cell-cell communication and exocytic network induction, indicating a role for circadian rhythms in coordinating system-level stimulus-coupled responses. Cyborg islets thus reveal principles of electrical maturation that will be useful to build fully functional in vitro islets for research and therapeutic applications.

Music Listening in Stem Cell Transplantation and Acute Myeloid Leukemia: A Randomized Clinical Trial.

CONTEXT: Music listening (ML) has been shown to have a beneficial effect on patients with cancer. However, novel intervention approaches are needed. OBJECTIVES: We aimed to determine whether ML based on the iso-principle, conducted using a mobile application (GloMus), improves symptom burden, quality of life (QoL), anxiety, and depression in patients undergoing stem cell transplantation (SCT) and intensive induction chemotherapy for acute myeloid leukemia (AML). METHODS: In this randomized controlled clinical trial, we assigned 71 patients to the ML or standard care (SC) groups, stratified by the reason for admission (AML, allogeneic-SCT, or inpatient/outpatient autologous-SCT). Upon admission, participants in the ML groups were invited to undergo daily ML sessions designed to change negative moods into positive ones (iso-principle). The intervention consisted of listening to pre-recorded classical music ordered by beats per minute and tonality. Symptom burden (Edmonton Symptom Assessment System-Revised) was assessed in the ML groups before and after each session. Anxiety, depression (Hospital Anxiety and Depression Scale), and QoL (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation/Leukemia) were measured weekly in the ML and SC groups. RESULTS: Symptom burden in both allogeneic- and inpatient autologous-SCT ML groups reduced after the intervention. In all experimental groups, clinically important improvements were observed after ML sessions. No differences were found between the groups (ML vs. SC) at different weeks of admission regarding anxiety, depression, and QoL. CONCLUSIONS: ML based on our innovative iso-principle strategy, conducted using GloMus, reduced the symptom burden in patients undergoing allogeneic- and inpatient autologous-SCT (ClinicalTrials.gov number, NCT05696457).

First-in-human study of JNJ-67571244, a CD33 × CD3 bispecific antibody, in relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome.

Relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) outcomes remain poor. A targeted cluster of differentiation (CD)33 × CD3 bispecific antibody, JNJ-67571244, was assessed to identify the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety and tolerability, and preliminary clinical activity in patients with r/rAML or r/rMDS. This first-in-human, open-label, phase I, dose-escalation/dose-expansion study included patients with r/rAML or r/rMDS who were ineligible for or had exhausted standard therapeutic options. JNJ-67571244 was administered intravenously or subcutaneously using step-up dosing until ≥1 discontinuation condition was met. Outcomes included safety/tolerability, preliminary clinical activity, and systemic pharmacokinetics and pharmacodynamics. The study was terminated after evaluating 10 dose-escalation cohorts (n = 68) and before starting dose-expansion. Overall, 11 (16.2%) patients experienced ≥1 dose-limiting toxicity; all experienced ≥1 treatment-emergent adverse event (TEAE; treatment related: 60 [88.2%]); and 64 (94.1%) experienced ≥1 TEAE of Grade ≥3 toxicity (treatment related: 28 [41.2%]). Although some patients had temporary disease burden reductions, no responses were seen. JNJ-67571244 administration increased multiple cytokines, which coincided with incidence of cytokine release syndrome, infusion-related reactions, and elevated liver function tests. A prolonged step-up strategy was tested to improve tolerability, though this approach did not prevent hepatotoxicity. T-cell activation following treatment suggested target engagement but did not correlate with clinical activity. Safely reaching the projected exposure level for JNJ-67571244 efficacy was not achieved, thus MTD and RP2D were not determined.

Non-Tuberculous Mycobacterial isolates from Panama: A retrospective 5-year analysis (2017-2021).

BACKGROUND: The genus Mycobacterium includes well-known bacteria such as M. tuberculosis causing tuberculosis and M. leprae causing leprosy. Additionally, various species collectively termed non-tuberculous mycobacteria (NTM) can cause infections in humans and animals, affecting individuals across all age groups and health conditions. However, information on NTM infection prevalence in Panama is limited. METHODS: This study conducted a retrospective analysis of clinical records from 2017 to 2021, specifically focusing on patients with NTM isolates. Data were categorized by variables like sex, age, HIV status, and sample source. RESULTS: Among the 4430 clinical records analyzed, 698 were linked to patients with NTM isolates. Of these patients, 397 were male, and 301 were female. Most female patients with NTM isolates (n = 190) were aged >45 to 85 years, while most male patients (n = 334) fell in the >25 to 75 years age group. A noteworthy proportion of male patients (n = 65) were aged 25-35 years. A significant age difference between male (median [min-max] = 53 years [3-90]) and female (median [61 years [6-94]) patients was observed (p < 0.001). Regarding HIV status, 77 positive individuals were male, and 19 were female (p < 0.001). Most samples (n = 566) were sputum samples, with additional pulmonary-associated samples such as broncho-alveolar lavage, tracheal secretions, and pleural fluid samples. Among extrapulmonary isolates (n = 48), sources included catheter secretions, intracellular fluids, peritoneal fluid, blood cultures, cerebrospinal fluid, bone marrow samples, and capillary transplant lesions. Specifically, the analysis identified the pathogenic microorganisms responsible for mycobacteriosis in Panama during the specific period 2017-2021, as M. fortuitum (34.4%), M. intracellulare (20.06%), and M. abscessus (13.75%), respectively. CONCLUSIONS: This study highlights the growing public health concern of NTM infections in Panama. The research provides valuable insights into the prevalence and distribution of NTM species in the country, offering a foundation for the development and implementation of effective prevention and control strategies for NTM infections in Panama.

Diferencias clínicas entre la amiloidosis cardiaca por transtirretina y la cardiopatía hipertensiva / Clinical differences between transthyretin cardiac amyloidosis and hypertensive heart disease

Introducción: Un porcentaje importante de pacientes finalmente diagnosticados de amiloidosis cardIaca por transtirretina (ATTR) fueron previamente diagnosticados de cardiopatía hipertensiva (CHTA), ya que ambas enfermedades suelen cursar con insuficiencia cardíaca (IC) con fracción de eyección preservada (ICFEp) e hipertrofia ventricular. Nuestros objetivos fueron evaluar las diferencias clínicas, electrocardiográficas y ecocardiográficas, y analizar si existe un pronóstico diferencial entre ambas entidades nosológicas. Material y métodos: Se incluyeron retrospectivamente todos los pacientes con CHTA a los que se solicitó una gammagrafía cardíaca con 99mTc-Difosfonatos (GDPD) y estudio de cadenas ligeras en sangre y orina para despistaje de ATTR en nuestro centro, en el periodo 2016-2021. Para el análisis, se excluyeron aquellos diagnosticados de otros tipos de amiloidosis. Resultados: Se analizaron un total de 72 pacientes: 33 fueron diagnosticados de ATTR y 39 de CHTA, finalmente. Los pacientes con ATTR presentaron mayores niveles de troponina I ultrasensible (TnI-US) y propéptido natriurético cerebral N-terminal (NT-ProBNP); en electrocardiograma (ECG) presentaron más frecuentemente patrón de seudoinfarto y alteraciones de la conducción; en ecocardiograma transtorácico (ETT) presentaron mayor grado de hipertrofia ventricular, disfunción ventricular izquierda y parámetros de peor función diastólica, con presiones de llenado más elevadas. En el seguimiento a 4 años, el grupo de ATTR mostró mayor necesidad de marcapasos (MCP), sin evidenciarse evidencias en cuanto a mortalidad, desarrollo de fibrilación auricular o más ingresos por IC. Conclusiones: En nuestra serie, los pacientes con ATTR presentaron diferencias clínicas, electrocardiográficas y ecocardiográficas respecto a aquellos con CHTA, con mayor riesgo necesidad de MCP en el seguimiento.(AU)

Introduction: A significant percentage of patients eventually diagnosed with cardiac transthyretin amyloidosis (TTRA) was previously diagnosed with hypertensive heart disease (HHD), since both conditions usually present with heart failure (HF) with preserved ejection fraction (HFpEF) and ventricular hypertrophy. Our objectives were to evaluate the clinical, electrocardiographic and echocardiographic differences, and to analyse whether there exists a differential prognosis between these two nosological entities. Materials and methods: We retrospectively included all patients with HHD for whom a cardiac scintigraphy with 99mTc-diphosphonate (GDPD) and a free light chains test in blood and urine were ordered for ATTR screening in our centre, in the period between 2016 and 2021. Those diagnosed with other types of amyloidosis were excluded from the analysis. Results: A total of 72 patients were analyzed: 33 were finally diagnosed with TTRA and 39 with CHTA. Patients with TTRA had higher levels of ultrasensitive troponin I (TnI-US) and N-terminal brain natriuretic propeptide (NT-ProBNP); in electrocardiography (ECG) they presented a pseudo-infarction pattern more frequently as well as conduction disturbances; in echocardiography (TTE) they presented a higher degree of ventricular hypertrophy, left ventricular dysfunction and worse diastolic function parameters, with elevated filling pressures. In the 4-year follow-up, the ATTR group showed greater need for pacemaker (PCM), with no evidence regarding mortality, development of atrial fibrillation (AF), or more admissions for heart failure (HF). Conclusions: In our series, patients with TTRA showed clinical, electrocardiographic and echocardiographic differences compared to patients with HHD, with increased risk of need for PCM.(AU)

Characteristics and risk factors associated with mortality during the first cycle of prone secondary to ARDS due to SARS-CoV-2 pneumonia / Características y factores de riesgo asociados a mortalidad durante el primer ciclo de prono por SDRA secundario a neumonía por SARS-CoV-2

Objective To analyze characteristics, changes in oxygenation, and pulmonary mechanics, in mechanically ventilated patients with ARDS due to SARS-CoV-2 treated with prone position and evaluate the response to this maneuver.Design Cohort study including patients with PaO2/FiO2 <150mmHg requiring prone position over 18 months. We classified patients according to PaO2/FiO2 changes from basal to 24h after the first prone cycle as: 1) no increase 2) increase <25%, 3) 25%–50% increase 4) increase >50%. Setting 33-bed medical-surgical Intensive Care Unit (ICU) in Argentina. Patients 273 patients. Interventions None. Main variables of interest Epidemiological characteristics, respiratory mechanics and oxygenation were compared between survivors and non-survivors. Independent factors associated with in-hospital mortality were identified. Results Baseline PaO2/FiO2 was 116 [97–135]mmHg (115 [94–136] in survivors vs. 117 [98–134] in non-survivors; p=0.50). After prone positioning, 22 patients (8%) had similar PaO2/FiO2 values; 46(16%) increased PaO2/FiO2 ≤25%; 55 (21%) increased it 25%–50%; and 150 (55%), >50%. Mortality was 86%, 87%, 72% and 50% respectively (p<0.001). Baseline PaO2/FiO2, <100mmHg did not imply that patients were refractory to prone position. Factors independently associated with mortality were age, percentage increase in PaO2/FiO2 after 24h being in prone, and number of prone cycles. Conclusions Older patients unable to improve PaO2/FiO2 after 24h in prone position and who require >1 cycle might early receive additional treatments for refractory hypoxemia. After the first 24h in the prone position, a low percentage of PaO2/FiO2 increase over baseline, beyond the initial value, was independently associated with higher mortality. (AU)

Objetivo Analizar las características, cambios en la oxigenación y mecánica pulmonar, en pacientes ventilados mecánicamente con SDRA por SARS-CoV-2 tratados con posición prona, y evaluar la respuesta a esta maniobra. Diseño Estudio de cohorte que incluyó pacientes con PaO2/FiO2 <150mmHg que requirieron posición prona durante 18 meses. Se clasificaron los pacientes según los cambios de PaO2/FiO2 desde el basal y 24horas después del primer ciclo prono como: 1) Sin aumento 2) Aumento <25%, 3) 25–50% de aumento 4) Aumento >50%. Ambito Unidad de Cuidados Intensivos (UCI) médico-quirúrgica de 33 camas en Argentina. Pacientes 273 pacientes. Intervenciones Ninguna. Principales variables de interés Se compararon características epidemiológicas, mecánica respiratoria y oxigenación entre sobrevivientes y no sobrevivientes. Se identificaron factores independientes asociados a la mortalidad hospitalaria. Resultados La PaO2/FiO2 basal fue de 116 [97–135]mmHg (115 [94–136] en sobrevivientes vs. 117 [98–134] en no sobrevivientes; p=0,50). Después de la posición prona, 22 pacientes (8%) tenían valores similares de PaO2/FiO2; 46 (16%) aumentaron PaO2/FiO2 ≤25%; 55 (21%) lo aumentaron 25%–50%; y 150 (55%), >50%. La mortalidad fue de 86%, 87%, 72% y 50% respectivamente (p<0,001). La PaO2/FiO2 basal, <100mmHg no implicó que los pacientes fueran refractarios a la posición prona. Los factores asociados independientemente con la mortalidad fueron la edad, el aumento porcentual de PaO2/FiO2 después de 24horas en prona, y el número de ciclos prono. Conclusiones Los pacientes mayores que no pueden mejorar PaO2/FiO2 después de 24 horas en posición prona y que requieren más de 1 ciclo podrían recibir tratamientos adicionales para la hipoxemia refractaria. Después de las primeras 24horas en decúbito prono, un bajo porcentaje de aumento de PaO2/FiO2 sobre el valor basal, más allá del valor inicial, se asoció de forma independiente con una mayor mortalidad. (AU)

The Fabaceae in Northeastern Mexico (Subfamily Caesalpinioideae, Mimosoideae Clade, Tribes Mimoseae, Acacieae, and Ingeae).

A synoptic compendium of the legumes of the Mimosoideae clade in northeastern Mexico is presented for the first time, including changes in their botanical nomenclature and retypification of genera. Furthermore, based on new information recently published, the taxonomic limits of several new genera segregated from Acacia (Acaciella, Mariosousa, Senegalia, and Vachellia) and Prosopis (Neltuma and Strombocarpa) are clarified and included. Based on field work, collection of botanical samples over the past 30 years, and reviewing botanical materials in national and international herbaria, we have completed the diversity of legumes of the Mimosoideae clade of northeastern Mexico. Three tribes (Acacieae, Ingeae, and Mimosaeae), 22 genera, 92 species, and 19 infraspecific categories were recorded. Only the genus Painteria is endemic to Mexico. Eighty-eight species are native to Mexico, and four are exotic: Acacia salicina, Neptunia prostrata, Neltuma chilensis and Albizia lebbeck. Twenty-eight species are endemic to Mexico, nine species are endemic to northeastern Mexico, and four species are endemic to only one state in Mexico. The 22 registered genera represent 44% and 65% of the generic flora of the Mimosoideae clade for Mexico and the planet, respectively, while the 92 species registered represent 3% and 18% of the species of the clade Mimosoideae for the planet and Mexico, respectively. According to the new nomenclature of legumes, the number of genera in the Mimosoideae clade in northern Mexico has increased from 19 to 24.

Valve Hemodynamics by Valve Size and 1-Year Survival Following Implantation of the Portico Valve in the Multicenter CONFIDENCE Registry.

Background: The CONtrolled delivery For ImproveD outcomEs with cliNiCal Evidence registry was initiated to characterize the clinical safety and device performance from experienced transcatheter aortic valve implantation (TAVI) centers in Europe and Australia that use the Portico valve to treat patients with severe aortic stenosis. We herein report for the first time the valve performance at 30-day across all implanted valve sizes and the 1-year survival from this registry. Methods: This was a prospective, multicenter, single-arm observational clinical investigation of patients clinically indicated for implantation of a Portico valve in experienced TAVI centers. Patients were treated with a commercially available valve (size 23, 25, 27, or 29 mm) using either the first-generation delivery system (DS) (n = 501) or the second-generation (FlexNav) DS (n = 500). Adverse events were adjudicated by an independent clinical events committee according to Valve Academic Research Consortium-2 criteria. Echocardiographic outcomes were assessed at 30 days by an independent core laboratory, and a survival check was performed at 1 year. Results: We enrolled 1001 patients (82.0 years, 62.5% female, 63.7% New York Heart Association functional class III/IV at baseline) from 27 clinical sites in 8 countries across Europe and one site in Australia. Implantation of a single valve was successful in 97.5% of subjects. Valve hemodynamics at 30 days were substantially improved relative to baseline, with large aortic valve areas and low mean gradients across all implanted valve sizes (aortic valve areas were 1.7 ± 0.4, 1.7 ± 0.5, 1.8 ± 0.5, and 2.0 ± 0.5 cm2, and mean gradients were 7.0 ± 2.7, 7.5 ± 4.7, 7.3 ± 3.3, and 6.4 ± 3.3 mmHg for 23, 25, 27, and 29 mm valve sizes, respectively). Across all implanted valve sizes, most patients (77.1%) had no patient-prosthesis mismatch. Death from any cause within 1 year occurred in 13.7% of the patients in the first-generation DS group as compared with 11.0% in the second-generation DS group (p = 0.2). Conclusions: The Portico valve demonstrated excellent hemodynamic performance across all valve sizes in a large cohort of subjects implanted in experienced TAVI centers. One-year survival rates were favorable when using both the first-generation and second-generation (FlexNav) DSs in this high-risk cohort. ClinicalTrialsgov Identifier: NCT03752866.

Characteristics and risk factors associated with mortality during the first cycle of prone secondary to ARDS due to SARS-CoV-2 pneumonia.

OBJECTIVE: To analyze characteristics, changes in oxygenation, and pulmonary mechanics, in mechanically ventilated patients with ARDS due to SARS-CoV-2 treated with prone position and evaluate the response to this maneuver. DESIGN: Cohort study including patients with PaO2/FiO2 <150mmHg requiring prone position over 18 months. We classified patients according to PaO2/FiO2 changes from basal to 24h after the first prone cycle as: 1) no increase 2) increase <25%, 3) 25%-50% increase 4) increase >50%. SETTING: 33-bed medical-surgical Intensive Care Unit (ICU) in Argentina. PATIENTS: 273 patients. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Epidemiological characteristics, respiratory mechanics and oxygenation were compared between survivors and non-survivors. Independent factors associated with in-hospital mortality were identified. RESULTS: Baseline PaO2/FiO2 was 116 [97-135]mmHg (115 [94-136] in survivors vs. 117 [98-134] in non-survivors; p=0.50). After prone positioning, 22 patients (8%) had similar PaO2/FiO2 values; 46(16%) increased PaO2/FiO2 ≤25%; 55 (21%) increased it 25%-50%; and 150 (55%), >50%. Mortality was 86%, 87%, 72% and 50% respectively (p<0.001). Baseline PaO2/FiO2, <100mmHg did not imply that patients were refractory to prone position. Factors independently associated with mortality were age, percentage increase in PaO2/FiO2 after 24h being in prone, and number of prone cycles. CONCLUSIONS: Older patients unable to improve PaO2/FiO2 after 24h in prone position and who require >1 cycle might early receive additional treatments for refractory hypoxemia. After the first 24h in the prone position, a low percentage of PaO2/FiO2 increase over baseline, beyond the initial value, was independently associated with higher mortality.