Inhibition of PIM kinase in tumor associated macrophages suppresses inflammasome activation and sensitizes prostate cancer to immunotherapy.

Immunotherapy has changed the treatment paradigm for many types of cancer, but immune checkpoint inhibitors (ICIs) have not shown benefit in prostate cancer (PCa). Chronic inflammation contributes to the immunosuppressive prostate tumor microenvironment (TME) and is associated with poor response to ICIs. The primary source of inflammatory cytokine production is the inflammasome. Here, we identify PIM kinases as important regulators of inflammasome activation in tumor associated macrophages (TAMs). Analysis of clinical data from a cohort of treatment naïve, hormone responsive PCa patients revealed that tumors from patients with high PIM1/2/3 display an immunosuppressive TME characterized by high inflammation (IL-1ß and TNFα) and a high density of repressive immune cells, most notably TAMs. Strikingly, macrophage-specific knockout of PIM reduced tumor growth in syngeneic models of prostate cancer. Transcriptional analyses indicate that eliminating PIM from macrophages enhanced the adaptive immune response and increased cytotoxic immune cells. Combined treatment with PIM inhibitors and ICIs synergistically reduced tumor growth. Immune profiling revealed that PIM inhibitors sensitized PCa tumors to ICIs by increasing tumor suppressive TAMs and increasing the activation of cytotoxic T cells. Collectively, our data implicate macrophage PIM as a driver of inflammation that limits the potency of ICIs and provides preclinical evidence that PIM inhibitors are an effective strategy to improve the efficacy of immunotherapy in prostate cancer.

Non-functional muscle-invasive bladder paraganglioma-a case report.

Background: Extra-adrenal pheochromocytoma (paraganglioma) of the urinary bladder is a rare tumor, accounting for 0.05% of bladder tumors and less than 1% of all paragangliomas. In the genitourinary tract, paragangliomas are most commonly found in the bladder. These tumors have aggressive malignant potential, so complete surgical resection for localized disease is important. Paragangliomas may be non-functional or functional with catecholamine secretions. Although these tumors are rare and difficult to distinguish from urothelial carcinoma (UC), intraoperative manipulation of these tumors may lead to a catecholamine surge and intraoperative complications. Preoperative or early intraoperative recognition of this tumor would facilitate appropriate alpha blockade to minimize morbidity. Case Description: Herein we report a rare non-functional paraganglioma arising from the bladder of a 46-year-old male. This case is notable for the location of the mass, requiring a 70-degree cystoscopic lens for complete visualization near the bladder neck, and for the identification of a golden-yellow sessile mass during the resection. Upon visualization of this mass, the operation should be paused for close hemodynamic monitoring and assess for signs of hypertensive crisis prior to continuing without alpha blockade. Conclusions: Suspected localized bladder paraganglioma cases should be optimized hemodynamically and managed surgically. Visualization of a sessile bladder mass on gross examination with golden-yellow tumor during the resection should prompt suspicion for a paraganglioma. Biochemical evaluation with serum or urine catecholamines, metanephrines, and normetanephrines should be performed to assess for tumor functionality.

Is the Change in Prevalence of High Myopia Compared to That of Myopia Really Disproportionate?

Purpose: It has been noted that, at higher prevalences, the rate of change in the prevalence of high myopia seems to be disproportionately greater compared with the rate of change in the prevalence of myopia. A simple, evidence-based explanation for this relationship is offered. Methods: Using a convenience sample of 41 datasets with prevalence estimates for at least two refractive error thresholds (e.g., -0.50 and -6.00 D) the common slope of the logit vs. refractive threshold was applied to model expected rates of high myopia across the myopia prevalence range and the corresponding ratio of change in high myopia to myopia prevalence. Results: The logit of high myopia is related linearly to the logit of myopia. The ratio of increase in high myopia prevalence to that for myopia prevalence increases with underlying prevalence. For example, an increase in myopia prevalence from 19% to 20% is modelled to be accompanied by a 0.1% increase in the prevalence of high myopia from 1.55% to 1.65%-a ratio of 0.1. Conversely, an increase in myopia prevalence from 79% to 80% is predicted to result in a 1% increase in the prevalence of high myopia from 20.6% to 21.6%-a ratio of 1.0. Conclusions: The increase in the prevalence of high myopia compared with that of myopia as the latter increases is merely a function of the underlying nature of refractive error probability distributions and requires no further investigation as to its origin. Translational Relevance: This study shows how the prevalence of myopia and high myopia are inter-related. A widespread effort to slow myopia progression will affect the prevalence of high myopia but not myopia in general. In contrast, efforts to delay myopia onset will affect both.

Nonlinear geometric phase coded ferroelectric nematic fluids for nonlinear soft-matter photonics.

Simultaneous manipulation of multiple degrees of freedom of light lies at the heart of photonics. Nonlinear wavefront shaping offers an exceptional way to achieve this goal by converting incident light into beams of new frequencies with spatially varied phase, amplitude, and angular momenta. Nevertheless, the reconfigurable control over structured light fields for advanced multimode nonlinear photonics remains a grand challenge. Here, we propose the concept of nonlinear geometric phase in an emerging ferroelectric nematic fluid, of which the second-order nonlinear susceptibility carries spin-dependent nonlinearity phase. A case study with photopatterned q-plates demonstrates the generation of second-harmonic optical vortices with spin-locked topological charges by using cascaded linear and nonlinear optical spin-orbit interactions. Furthermore, we present the dynamic tunability of second-harmonic structured light through temperature, electric field, and twisted elastic force. The proposed strategy opens new avenues for reconfigurable nonlinear photonics, with potential applications in optical communications, quantum computing, high-resolution imaging, etc.

Efficacy in myopia control-The impact of rebound.

PURPOSE: When myopia control treatment is discontinued, progression will increase, but does it revert to expected values based on the age and race of the child or does it accelerate further? The latter scenario is considered a rebound. METHODS: A PubMed search was conducted with the words 'rebound' and 'myopia control', identifying further papers from reviews. Inclusion was limited to prospective studies with ≥6 months of treatment, ≥3 months of data following cessation and with axial length data, which allowed calculation of rebound. Nineteen studies were identified, comprising 24 treatment groups. In 10 studies, untreated control children were followed both throughout the treatment and cessation periods, allowing for a concurrent comparison group. In three studies, a control group was followed for 1 or 2 years and thereafter received the treatment under evaluation. Later, treatment ceased in the originally treated children. Finally, six studies were cross-over designs. For these latter two study designs, initial axial elongation and myopia progression in the control group were extrapolated to the cessation period, accounting for annual slowing. Values from durations of <1 year were annualised. RESULTS: The mean annualised rebound was +0.05 ± 0.10 mm and -0.09 ± 0.24 D for axial length and myopia progression, respectively, and these were correlated (r2 = 0.59, p < 0.001). Rebound was associated with 1-year treatment efficacy (r2 = 0.43, p < 0.001). The mean annualised rebound with optical corrections was -0.01 ± 0.03 mm. Five of the six highest rebound values (≥0.14 mm) were from red light therapy and atropine studies. Rebound ranged from +0.03 to +0.14 mm for overnight orthokeratology. CONCLUSIONS: Consistent with previous statements, no evidence for rebound was found for myopia control spectacles and soft contact lenses. Future research should explore the influence of age and magnitude of treatment efficacy on rebound.

Can we really distinguish 'responders' from 'non-responders' to myopia control interventions?

PURPOSE: It is common to hear talk of 'responders' and 'non-responders' with respect to myopia control interventions. We consider the reality of distinguishing these sub-groups using data from the first year of the Low-concentration Atropine for Myopia Progression (LAMP) study. METHODS: The first year of the LAMP study was a robustly designed, placebo-controlled trial of three different low concentrations of atropine using a large sample size (N > 100 randomised to each group). The authors subsequently published mean axial elongation and myopia progression rates by age group. We used these data to calculate efficacy in terms of both absolute reduction in myopic progression and absolute reduction in axial elongation for each of the different atropine concentrations at each age group. We then compared these efficacy data to the overall progression for each of the two progression metrics. RESULTS: Plotting efficacy as a function of overall myopia progression and axial elongation for each of the different atropine concentrations demonstrates the invariant nature of efficacy, in terms of clinically meaningful reduction in progression, despite a substantial range of underlying overall progression. That is, faster progressors-the so-called non-responders-achieved similar reduction in axial elongation and myopia progression as the slower progressors-the so-called responders-within the various atropine treatment groups. CONCLUSION: The use of the terms, responders and non-responders, during myopia progression interventions is not supported by evidence. Those designated as such may simply be slower or faster progressors, who, on average achieve the same benefit from treatment.

Influence of age and race on axial elongation in myopic children: A systematic review and meta-regression.

PURPOSE: Axial elongation is the basis of progression in primary myopia and the preferred metric to monitor its evolution. We conducted a meta-regression to model axial elongation and its associated factors in children with low to moderate myopia. METHODS: A comprehensive electronic systematic search was performed using Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials of studies conducted up until October 2021. The mean rate of axial elongation was analyzed using a multivariate linear mixed-effects meta-regression model, with backward stepwise elimination of nonsignificant covariates. The model included three levels of random effects, allowing both prediction and confidence intervals to be estimated. RESULTS: A total of 64 studies with 83 subpopulations and 142 evaluations of mean axial change from baseline met our inclusion criteria and had no missing significant covariates in the final model. A separate analysis including all populations with axial length data (202 evaluations) but missing variance or covariate data produced a similar model to that for the analysis with complete data. The mean axial elongation is 38% greater in Asian children (95% confidence interval, 19 to 61%; p<0.01) compared with non-Asians, but both groups show a 15% decline per year as age increases (95% confidence interval, 12 to 17% p<0.0001). Prediction intervals indicate substantial variability around the axial elongation estimates. CONCLUSIONS: This analysis provides mean values of axial elongation for evaluation of efficacy of myopia control. The broad prediction intervals emphasize the large range of individual axial elongation rates in the population, illustrating the challenge in managing individual children. Interpretation of the analysis is limited by the use of aggregated data rather than individual subject data.

Pharmacodynamics of taniborbactam in combination with cefepime studied in an in vitro model of infection.

OBJECTIVES: To define the in vitro pharmacodynamics of taniborbactam against Enterobacterales with CTXM-15, KPC, AmpC, and OXA-48 ß-lactamases. METHODS: An in vitro pharmacokinetic model was used to simulate serum concentrations associated with cefepime 2G by 1 h infusion 8 h. Taniborbactam was given in exposure ranging and fractionation simulations. Reduction in viable count at 24 h (Δ 24) was the primary end point and four strains were used: Escherichia coli expressing CTXM-15 or AmpC and Klebsiella pneumoniae expressing KPC or OXA-48 enzymes. RESULTS: Taniborbactam was administered as continuous infusions; ≥4 log kill was attained with taniborbactam concentrations of ≥0.01 mg/L against CTXM-15 E. coli, ≥0.5 mg/L against KPC- and OXA-48 K. pneumoniae, and ≥4 mg/L against AmpC E. coli. Analyses were conducted to determine the pharmacokinetic/dynamic driver for each strain. For E. coli (CTXM-15) and E. coli (AmpC), area under the concentration-time curve (AUC) was best related to change in viable count (R20.74 and 0.72, respectively). For K. pneumoniae (KPC) AUC and T > 0.25 mg/L were equally related to bacterial clearance (R20.72 for both), and for K. pneumoniae (OXA-48) T > 0.25 mg/L was the best predictor (R20.94). The taniborbactam AUC range to produce a 1-log10 reduction in viable count was 4.4-11.2 mg·h/L. Analysis of data from all strains indicated T > MIC divided by 4 was best related to change in viable count; however, curve fit was poor R2 < 0.49. CONCLUSIONS: Taniborbactam was effective in combination with cefepime in producing bacterial clearance for B lactam resistant Enterobacterales. The primary pharmacodynamic driver was AUC or time > threshold, both being closely related to antibacterial effect.

Navigating uncertainty in maximum body size in marine metazoans.

Body size is a fundamental biological trait shaping ecological interactions, evolutionary processes, and our understanding of the structure and dynamics of marine communities on a global scale. Accurately defining a species' body size, despite the ease of measurement, poses significant challenges due to varied methodologies, tool usage, and subjectivity among researchers, resulting in multiple, often discrepant size estimates. These discrepancies, stemming from diverse measurement approaches and inherent variability, could substantially impact the reliability and precision of ecological and evolutionary studies reliant on body size data across extensive species datasets. This study examines the variation in reported maximum body sizes across 69,570 individual measurements of maximum size, ranging from <0.2 µm to >45 m, for 27,271 species of marine metazoans. The research aims to investigate how reported maximum size variations within species relate to organism size, taxonomy, habitat, and the presence of skeletal structures. The investigation particularly focuses on understanding why discrepancies in maximum size estimates arise and their potential implications for broader ecological and evolutionary studies relying on body size data. Variation in reported maximum sizes is zero for 38% of species, and low for most species, although it exceeds two orders of magnitude for some species. The likelihood of zero variation in maximum size decreased with more measurements and increased in larger species, though this varied across phyla and habitats. Pelagic organisms consistently had low maximum size range values, while small species with unspecified habitats had the highest variation. Variations in maximum size within a species were notably smaller than interspecific variation at higher taxonomic levels. Significant variation in maximum size estimates exists within marine species, and partially explained by organism size, taxonomic group, and habitat. Variation in maximum size could be reduced by standardized measurement protocols and improved meta-data. Despite the variation, egregious errors in published maximum size measurements are rare, and their impact on comparative macroecological and macroevolutionary research is likely minimal.

Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.

BACKGROUND: The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1. METHODS: Tissues from animal pulmonary hypertension models as well as human pulmonary artery endothelial cells from patients with PAH exhibited increased vascular UCHL1 staining and protein expression. Exposure to LDN57444, a UCHL1-specific inhibitor, reduced human pulmonary artery endothelial cell and smooth muscle cell proliferation. Across 3 preclinical PAH models, LDN57444-exposed animals, Uchl1 knockout rats (Uchl1-/-), and conditional Uchl1 knockout mice (Tie2Cre-Uchl1fl/fl) demonstrated reduced right ventricular hypertrophy, right ventricular systolic pressures, and obliterative vascular remodeling. Lungs and pulmonary artery endothelial cells isolated from Uchl1-/- animals exhibited reduced total and activated Akt with increased ubiquitinated Akt levels. UCHL1-silenced human pulmonary artery endothelial cells displayed reduced lysine(K)63-linked and increased K48-linked AKT1 levels. RESULTS: Supporting experimental data, we found that rs9321, a variant in a GC-enriched region of the UCHL1 gene, is associated with reduced methylation (n=5133), increased UCHL1 gene expression in lungs (n=815), and reduced cardiac index in patients (n=796). In addition, Gadd45α (an established demethylating gene) knockout mice (Gadd45α-/-) exhibited reduced lung vascular UCHL1 and AKT1 expression along with attenuated hypoxic pulmonary hypertension. CONCLUSIONS: Our findings suggest that UCHL1 deficiency results in PAH attenuation by means of reduced AKT1, highlighting a novel therapeutic pathway in PAH.

Myopia control: Seeing beyond efficacy.

SIGNIFICANCE: The availability of a range of effective myopia control modalities enables the clinician to exercise judgment when discussing the treatment plan with the patient and their parents. This article outlines important considerations beyond efficacy.Clinically meaningful myopia control may be attained with some spectacle lenses, select soft contact lenses, some concentrations of atropine, and overnight orthokeratology. Given that satisfactory efficacy can be achieved with a range of modalities, other factors should be considered when deciding upon the best intervention for a given child. Four key factors-compliance, quality of vision, quality of life, and safety-are discussed in this review. Compliance directly impacts efficacy regardless of the modality and is the most important consideration, as it is influenced by quality of vision and comfort. Daily disposal myopia control contact lenses and overnight orthokeratology are generally associated with high compliance, provide better vision-related quality of life than spectacles, and carry a very low risk when used appropriately. A further benefit of overnight orthokeratology is the elimination of a need for optical correction during the day.

Overcoming Understaging and Undergrading in Upper Tract Urothelial Carcinoma. Comment on Ghoreifi et al. Modern Kidney-Sparing Management of Upper Tract Urothelial Carcinoma. Cancers 2023, 15, 4495.

Kidney-sparing management for upper tract urothelial carcinoma (UTUC) has become more common but is still most limited by inaccurate histopathologic diagnosis [...].

Outcomes of Short and Long Tibial Stems for Primary Total Knee Arthroplasty in a Population of Obese Patients at Two-Year Follow-Up: A Clinical and Biomechanical Study.

BACKGROUND: Obesity can be a source of higher failure rates and inferior clinical outcomes after total knee arthroplasty (TKA). The aim of this study was to compare outcomes, failure rates, and stress distributions of TKA in obese patients using a short, long, or no tibial stem. METHODS: A matching process based on the type of stem used and the age allowed included 180 patients who had a body mass index (BMI) > 30 and underwent a TKA between January 2010 and December 2019, with a minimum follow-up of 2 years. They were classified as moderately obese (MO: 30 < BMI < 35, N = 90) and severely obese (SO: BMI > 35, N = 90). For each, 3 subgroups were defined: thirty patients received a 30 mm short stem (SS), thirty received a 100 mm long stem (LS), and thirty received no stem (NS). Patients were assessed preoperatively and postoperatively using the Knee Society Score (KSS). A finite element model was developed to evaluate the biomechanical effects of the tibial stem on stress distribution in the subchondral bone based on BMI. RESULTS: The SS patients had significantly higher postoperative KSS knee score [MO: 88.9 (SS) versus 79 (LS) versus 80.6 (NS); SO: 84.5 versus 72.4 versus 78.2] (P < .0001) and function score [MO: 90.4 (SS) versus 78.4 (LS) versus 68.5 (NS); SO: 85.5 versus 73 versus 61.8] (P < .0001) compared to LS and NS patients. The biomechanical study demonstrated a BMI-dependent increase in stress in the subchondral bone in contact with the tibial components. These stresses were mainly distributed at the tibial cut for NS and along the stem for SS and LS. CONCLUSIONS: A short, cemented tibial stem offers better functional outcomes without increasing failure rates compared to a longer stem during primary TKA in a population of obese patients at two-year follow-up. A short tibial stem does not lead to increased stress compared to an LS, at least for certain BMI categories.

New examples of ferroelectric nematic materials showing evidence for the antiferroelectric smectic-Z phase.

We present a new ferroelectric nematic material, 4-((4'-((trans)-5-ethyloxan-2-yl)-2',3,5,6'-tetrafluoro-[1,1'-biphenyl]-4-yl)difluoromethoxy)-2,6-difluorobenzonitrile (AUUQU-2-N) and its higher homologues, the molecular structures of which include fluorinated building blocks, an oxane ring, and a terminal cyano group, all contributing to a large molecular dipole moment of about 12.5 D. We observed that AUUQU-2-N has three distinct liquid crystal phases, two of which were found to be polar phases with a spontaneous electric polarization Ps of up to 6 µC cm-2. The highest temperature phase is a common enantiotropic nematic (N) exhibiting only field-induced polarization. The lowest-temperature, monotropic phase proved to be a new example of the ferroelectric nematic phase (NF), evidenced by a single-peak polarization reversal current response, a giant imaginary dielectric permittivity on the order of 103, and the absence of any smectic layer X-ray diffraction peaks. The ordinary nematic phase N and the ferroelectric nematic phase NF are separated by an antiferroelectric liquid crystal phase which has low permittivity and a polarization reversal current exhibiting a characteristic double-peak response. In the polarizing light microscope, this antiferroelectric phase shows characteristic zig-zag defects, evidence of a layered structure. These observations suggest that this is another example of the recently discovered smectic ZA (SmZA) phase, having smectic layers with the molecular director parallel to the layer planes. The diffraction peaks from the smectic layering have not been observed to date but detailed 2D X-ray studies indicate the presence of additional short-range structures including smectic C-type correlations in all three phases-N, SmZA and NF-which may shed new light on the understanding of polar and antipolar order in these phases.

Juvenile-onset myopia-who to treat and how to evaluate success.

The risk of eye diseases such as myopic macular degeneration increases with the level of myopia, but there is no safe level of myopia and the burden of lower degrees of myopia remains considerable. Effective treatments are available that slow progression and thus limit the final degree of myopia. In this review, the rationale for slowing progression is summarized, and a case made for treating all myopic children. Measurement of refractive error and axial length is reviewed, stressing the precision of optical biometry, but also the need for cycloplegic autorefraction. The factors influencing progression are considered and the available tools for interpretation of progression rate are discussed. Finally, the need to set attainable treatment goals is emphasized.

PIM1 targeted degradation prevents the emergence of chemoresistance in prostate cancer.

PIM kinases have important pro-tumorigenic roles and mediate several oncogenic traits, including cell proliferation, survival, and chemotherapeutic resistance. As a result, multiple PIM inhibitors have been pursued as investigational new drugs in cancer; however, response to PIM inhibitors in solid tumors has fallen short of expectations. We found that inhibition of PIM kinase activity stabilizes protein levels of all three PIM isoforms (PIM1/2/3), and this can promote resistance to PIM inhibitors and chemotherapy. To overcome this effect, we designed PIM proteolysis targeting chimeras (PROTACs) to target PIM for degradation. PIM PROTACs effectively downmodulated PIM levels through the ubiquitin-proteasome pathway. Importantly, degradation of PIM kinases was more potent than inhibition of catalytic activity at inducing apoptosis in prostate cancer cell line models. In conclusion, we provide evidence of the advantages of degrading PIM kinases versus inhibiting their catalytic activity to target the oncogenic functions of PIM kinases.

PIM1 drives lipid droplet accumulation to promote proliferation and survival in prostate cancer.

Lipid droplets (LDs) are dynamic organelles with a neutral lipid core surrounded by a phospholipid monolayer. Solid tumors exhibit LD accumulation, and it is believed that LDs promote cell survival by providing an energy source during energy deprivation. However, the precise mechanisms controlling LD accumulation and utilization in prostate cancer are not well known. Here, we show peroxisome proliferator-activated receptor α (PPARα) acts downstream of PIM1 kinase to accelerate LD accumulation and promote cell proliferation in prostate cancer. Mechanistically, PIM1 inactivates glycogen synthase kinase 3 beta (GSK3ß) via serine 9 phosphorylation. GSK3ß inhibition stabilizes PPARα and enhances the transcription of genes linked to peroxisomal biogenesis (PEX3 and PEX5) and LD growth (Tip47). The effects of PIM1 on LD accumulation are abrogated with GW6471, a specific inhibitor for PPARα. Notably, LD accumulation downstream of PIM1 provides a significant survival advantage for prostate cancer cells during nutrient stress, such as glucose depletion. Inhibiting PIM reduces LD accumulation in vivo alongside slow tumor growth and proliferation. Furthermore, TKO mice, lacking PIM isoforms, exhibit suppression in circulating triglycerides. Overall, our findings establish PIM1 as an important regulator of LD accumulation through GSK3ß-PPARα signaling axis to promote cell proliferation and survival during nutrient stress.

Registro colombiano de trasplante cardíaco: año 1985-2021 / Colombian Heart Transplant Registry: 1985-2021

Resumen Introducción: El trasplante cardíaco tiene como objetivo principal mejorar la calidad de vida y la sobrevida de los pacientes con falla cardiaca avanzada. Pocos países en Latinoamérica tienen un sistema nacional de registro de trasplante de órganos sólidos, incluido corazón. En el caso de Colombia, cada institución maneja sus propias estadísticas. Objetivo: Describir la evolución de los trasplantes cardíacos realizados en Colombia desde sus inicios, como parte de la estrategia de implementación de un registro nacional de trasplante cardíaco. Materiales y método: Estudio descriptivo acerca de los trasplantes cardíacos realizados en las instituciones de Colombia que han hecho trasplante cardíaco en cualquier momento, desde el 01 de enero del 1985 hasta el 31 de diciembre del 2021. La información fue recolectada en un formato electrónico a través del capítulo de Falla Cardiaca, Trasplante Cardíaco e Hipertensión Pulmonar de la Asociación Sociedad Colombiana de Cardiología y Cirugía Cardiovascular. Resultados: se identificaron 10 instituciones que han realizado al menos un procedimiento de trasplante cardíaco en un período de 36 años (1985 a 2021), para un total de 1.451 trasplantes cardíacos. De estos procedimientos, 1.327 (91%) se realizaron en población adulta, 124 (9%) en población pediátrica y 80% en población masculina. Por otro lado, se han hecho 26 trasplantes cardíacos combinados (23 corazón/riñón y 3 corazón/pulmón) y 16 retrasplantes cardíacos. Conclusión: El número de trasplantes cardíacos que se realizan en Colombia es cada vez mayor. A pesar de las dificultades económicas, geográficas, logísticas, de disponibilidad de donantes, entre muchas otras, las instituciones trasplantadoras de Colombia, junto con el Instituto Nacional de Salud, continúan trabajando para lograr una mejor y mayor cobertura en salud de la población con falla cardíaca avanzada que requiere trasplante cardíaco y de los pacientes que son llevados a trasplante cardíaco. Este artículo pretende ser el inicio de un registro nacional de trasplante cardíaco.

Abstract Introduction: the main goal of heart transplantation is to improve the quality of life and survival of patients with advanced heart failure. Few Latin American countries have a national registry of solid organ transplants, including heart transplants. In Colombia, each institution handles its own statistics. Objective: To describe the development of heart transplantation in Colombia from its beginning, as part of the strategy for implementing a national heart transplant registry. Materials and method: a descriptive study of the heart transplants performed in all Colombian institutions that performed heart transplants at any time between January 1, 1985, and December 31, 2021. The information was gathered in an electronic format through the Heart Failure, Heart Transplant and Pulmonary Hypertension Chapter of the Asociación Sociedad Colombiana de Cardiología y Cirugía Cardiovascular [Colombian Society of Cardiology and Cardiovascular Surgery Association]. Results: ten institutions were found in which at least one heart transplant had been performed over a 36-year period (1985 to 2021), for a total of 1,451 heart transplants. Of these procedures, 1,327 (91%) were in adults, 124 (9%) in children, and 80% in males. Furthermore, 26 combined heart transplants have been performed (23 heart/kidney and three heart/lung) as well as 16 heart retransplants. Conclusion: the number of heart transplants performed in Colombia is growing. Despite economical, geographical, logistical and donor availability difficulties, among many others, the Colombian transplant institutions, together with the Instituto Nacional de Salud [National Institute of Health], continue to work toward a better and fuller healthcare coverage for those with advanced heart failure requiring heart transplantation and for patients undergoing heart transplantation. This article seeks to initiate a national heart transplant registry.

Reduced strength and increased variability of extinction selectivity during mass extinctions.

Two of the traits most often observed to correlate with extinction risk in marine animals are geographical range and body size. However, the relative effects of these two traits on extinction risk have not been investigated systematically for either background times or during mass extinctions. To close this knowledge gap, we measure and compare extinction selectivity of geographical range and body size of genera within five classes of benthic marine animals across the Phanerozoic using capture-mark-recapture models. During background intervals, narrow geographical range is strongly associated with greater extinction probability, whereas smaller body size is more weakly associated with greater extinction probability. During mass extinctions, the association between geographical range and extinction probability is reduced in every class and fully eliminated in some, whereas the association between body size and extinction probability varies in strength and direction across classes. While geographical range is universally the stronger predictor of survival during background intervals, variation among classes during mass extinction suggests a fundamental shift in extinction processes during these global catastrophes.