17ß-estradiol induces hyperresponsiveness in guinea pig airway smooth muscle by inhibiting the plasma membrane Ca2+-ATPase.

High serum estrogen concentrations are associated with asthma development and severity, suggesting a link between estradiol and airway hyperresponsiveness (AHR). 17ß-estradiol (E2) has non-genomic effects via Ca2+ regulatory mechanisms; however, its effect on the plasma membrane Ca2+-ATPases (PMCA1 and 4) and sarcoplasmic reticulum Ca2+-ATPase (SERCA) is unknown. Hence, in the present study, we aim to demonstrate if E2 favors AHR by increasing intracellular Ca2+ concentrations in guinea pig airway smooth muscle (ASM) through a mechanism involving Ca2+-ATPases. In guinea pig ASM, Ca2+ microfluorometry, muscle contraction, and Western blot were evaluated. Then, we performed molecular docking analysis between the estrogens and Ca2+ ATPases. In tracheal rings, E2 produced AHR to carbachol. In guinea pig myocytes, acute exposure to physiological levels of E2 modified the transient Ca2+ peak induced by caffeine to a Ca2+ plateau. The incubation with PMCA inhibitors (lanthanum and carboxyeosin, CE) partially reversed the E2-induced sustained plateau in the caffeine response. In contrast, cyclopiazonic acid (SERCA inhibitor), U-0126 (an inhibitor of ERK 1/2), and choline chloride did not modify the Ca2+ plateau produced by E2. The mitochondrial uniporter activity and the capacitative Ca2+ entry were unaffected by E2. In guinea pig ASM, Western blot analysis demonstrated PMCA1 and PMCA4 expression. The results from the docking modeling demonstrate that E2 binds to both plasma membrane ATPases. In guinea pig tracheal smooth muscle, inhibiting the PMCA with CE, induced hyperresponsiveness to carbachol. 17ß-estradiol produces hyperresponsiveness by inhibiting the PMCA in the ASM and could be one of the mechanisms responsible for the increase in asthmatic crisis in women.

Design and Biocompatibility of a Novel, Flexible Artificial Cornea.

Purpose: We sought to introduce the materials, design, and biocompatibility of a flexible and suturable artificial corneal device. Methods: Single-piece, fully synthetic, optic-skirt design devices were made from compact perfluoroalkoxy alkane. The skirt and the optic wall surfaces were lined with a porous tissue ingrowth material using expanded polytetrafluoroethylene. Full-thickness macroapertures around the skirt perimeter were placed to facilitate nutrition of the recipient cornea. Material properties including the skirt's modulus of elasticity and bending stiffness, optic light transmission, wetting behavior, topical drug penetrance, and degradation profile were evaluated. Results: The final prototype suitable for human use has a transparent optic with a diameter of 4.60 mm anteriorly, 4.28 mm posteriorly, and a skirt outer diameter of 6.8 mm. The biomechanical and optical properties of the device closely align with the native human cornea with an average normalized device skirt-bending stiffness of 4.7 kPa·mm4 and light transmission in the visible spectrum ranging between 92% and 96%. No optical damage was seen in the 36 devices tested in fouling experiments. No significant difference was observed in topical drug penetrance into the anterior chamber of the device implanted eye compared with the naïve rabbit eye. Conclusions: The flexibility and biocompatibility of our artificial cornea device may offer enhanced tissue integration and decreased inflammation, leading to improved retention compared with rigid keratoprosthesis designs. Translational Relevance: We have developed a fully synthetic, flexible, suturable, optic-skirt design prototype artificial cornea that is ready to be tested in early human feasibility studies.

Donor Lung Preservation at 10°C: Clinical and Logistical Impact.

INTRODUCTION: Cold static donor lung preservation at 10°C appears to be a promising method to safely extend the cold ischemic time (CIT) and improve lung transplant (LTx) logistics. METHODS: LTx from November 2021 to February 2023 were included in this single institution, prospective, non-randomized study comparing prolonged preservation at 10°C versus standard preservation on ice. The inclusion criteria for 10°C preservation were suitable grafts for LTx without any donor retrieval concerns. PRIMARY ENDPOINT: primary graft dysfunction (PGD) grade-3 at 72-h. Secondary endpoints: clinical outcomes, cytokine profile and logistical impact. RESULTS: Thirty-three out of fifty-seven cases were preserved at 10°C. Donor and recipient characteristics were similar across the groups. Total preservation times (h:min) were longer (p<0.001) in the 10°C group [1st lung: median 12:09 (IQR 9:23-13:29); 2nd: 14:24 (12:00-16:20)] vs. standard group [1st lung: median 5:47 (IQR 5:18-6:40); 2nd: 7:15 (6:33-7:40)]. PGD grade-3 at 72-h was 9.4% in 10°C group vs. 12.5% in standard group (p=0.440). Length of mechanical ventilation (MV), ICU and hospital stays were similar in both groups. Thirty and ninety-day mortality rates were 0% in 10°C group (vs. 4.2% in standard group). IL-8 concentration was significantly higher 6-h post-LTx in the standard group (p=0.025) and IL-10 concentration was increased 72-h post-LTx in the 10°C group (p=0.045). CONCLUSIONS: Preservation at 10°C may represent a safe and feasible strategy to intentionally prolong the CIT. In our center, extending the CIT at 10°C may allow for semi-elective LTx and improve logistics with similar outcomes compared to the current standard preservation on ice.

Safety of helicopter transport in patients with acute coronary syndrome / Seguridad del transporte en helicóptero en pacientes con síndrome coronario agudo

Abstract Background: ST-elevation myocardial infarction (STEMI) systems of care have reduced inter-hospital transfer times and facilitated timely reperfusion goals. Helicopters may be an option when land transportation is not feasible; however, the safety of air transport in patients with acute coronary syndrome (ACS) is a factor to consider. Objetives: The aim of this study was to evaluate the safety of helicopter transport for patients with ACS. Methods: Prospective, observational, and descriptive study including patients diagnosed with ACS within the STEMI network of a metropolitan city transferred by helicopter to a large cardiovascular center to undergo percutaneous coronary intervention. The primary outcome of the study was the incidence of air-travel-related complications defined as IV dislodgement, hypoxia, arrhythmia, angina, anxiety, bleeding, and hypothermia. Secondary outcomes included the individual components of the primary outcome. Results: A total of 106 patients were included in the study; the mean age was 54 years and 84.9% were male. The most frequent diagnosis was STEMI after successful fibrinolysis (51.8%), followed by STEMI with failed fibrinolysis (23.7%) and non-reperfused STEMI (9.4%). Five patients (4.7%) developed at least one complication: IV dislodgement (1.8%) and hypoxemia (1.8%) in two patients and an episode of angina during flight (0.9%). A flight altitude of > 10,000 ft was not associated with complications. Conclusions: The results of this study suggest that helicopter transportation is safe in patients undergoing acute coronary syndrome, despite the altitude of a metropolitan area.

Resumen Antecedentes: Los sistemas de atención de IAMCEST han reducido los tiempos de transferencia interhospitalaria y han facilitado las metas de reperfusión oportuna. Los helicópteros pueden ser una opción cuando el transporte terrestre no es factible; sin embargo, la seguridad del transporte aéreo en pacientes con síndrome coronario agudo (SICA) es un factor a considerar. Objetivos: Evaluar la seguridad del transporte en helicóptero para pacientes con SICA. Métodos: Estudio prospectivo, observacional, descriptivo. Se incluyeron pacientes con diagnóstico de SICA dentro de la red IAMCEST en metrópolis extensa, trasladados en helicóptero a un centro cardiovascular. El resultado primario del estudio fue la incidencia de complicaciones relacionadas con los viajes aéreos definidas cómo desalojo de catéter intravenoso, hipoxia, arritmia, angina, ansiedad, sangrado e hipotermia. Resultados: Total de 106 pacientes; la edad media fue de 54 años y 84,9% eran hombres. La altitud media de vuelo fue de 10,100 pies y la distancia media de vuelo fue de 50,0 km. El diagnóstico más frecuente fue IAMCEST tras fibrinolisis exitosa (51,8%), seguido de IAMCEST con fibrinolisis fallida (23,7%). Cinco pacientes (4,7%) desarrollaron una complicación: desalojo IV (1,8%) e hipoxemia (1,8%) en dos pacientes y un episodio de angina durante el vuelo (0,9%). Una altitud de vuelo mayor de 10,000 pies no se asoció a complicaciones. Conclusiones: Los resultados de este estudio sugieren que el transporte en helicóptero es seguro en pacientes con SICA, incluso en altitudes > 10,000 pies.

Safety of helicopter transport in patients with acute coronary syndrome.

BACKGROUND: ST-elevation myocardial infarction (STEMI) systems of care have reduced inter-hospital transfer times and facilitated timely reperfusion goals. Helicopters may be an option when land transportation is not feasible; however, the safety of air transport in patients with acute coronary syndrome (ACS) is a factor to consider. OBJETIVES: The aim of this study was to evaluate the safety of helicopter transport for patients with ACS. METHODS: Prospective, observational, and descriptive study including patients diagnosed with ACS within the STEMI network of a metropolitan city transferred by helicopter to a large cardiovascular center to undergo percutaneous coronary intervention. The primary outcome of the study was the incidence of air-travel-related complications defined as IV dislodgement, hypoxia, arrhythmia, angina, anxiety, bleeding, and hypothermia. Secondary outcomes included the individual components of the primary outcome. RESULTS: A total of 106 patients were included in the study; the mean age was 54 years and 84.9% were male. The most frequent diagnosis was STEMI after successful fibrinolysis (51.8%), followed by STEMI with failed fibrinolysis (23.7%) and non-reperfused STEMI (9.4%). Five patients (4.7%) developed at least one complication: IV dislodgement (1.8%) and hypoxemia (1.8%) in two patients and an episode of angina during flight (0.9%). A flight altitude of > 10,000 ft was not associated with complications. CONCLUSIONS: The results of this study suggest that helicopter transportation is safe in patients undergoing acute coronary syndrome, despite the altitude of a metropolitan area.

ANTECEDENTES: Los sistemas de atención de IAMCEST han reducido los tiempos de transferencia interhospitalaria y han facilitado las metas de reperfusión oportuna. Los helicópteros pueden ser una opción cuando el transporte terrestre no es factible; sin embargo, la seguridad del transporte aéreo en pacientes con síndrome coronario agudo (SICA) es un factor a considerar. OBJETIVOS: Evaluar la seguridad del transporte en helicóptero para pacientes con SICA. MÉTODOS: Estudio prospectivo, observacional, descriptivo. Se incluyeron pacientes con diagnóstico de SICA dentro de la red IAMCEST en metrópolis extensa, trasladados en helicóptero a un centro cardiovascular. El resultado primario del estudio fue la incidencia de complicaciones relacionadas con los viajes aéreos definidas cómo desalojo de catéter intravenoso, hipoxia, arritmia, angina, ansiedad, sangrado e hipotermia. RESULTADOS: Total de 106 pacientes; la edad media fue de 54 años y 84,9% eran hombres. La altitud media de vuelo fue de 10,100 pies y la distancia media de vuelo fue de 50,0 km. El diagnóstico más frecuente fue IAMCEST tras fibrinolisis exitosa (51,8%), seguido de IAMCEST con fibrinolisis fallida (23,7%). Cinco pacientes (4,7%) desarrollaron una complicación: desalojo IV (1,8%) e hipoxemia (1,8%) en dos pacientes y un episodio de angina durante el vuelo (0,9%). Una altitud de vuelo mayor de 10,000 pies no se asoció a complicaciones. CONCLUSIONES: Los resultados de este estudio sugieren que el transporte en helicóptero es seguro en pacientes con SICA, incluso en altitudes > 10,000 pies.

Multidisciplinary approach for locally advanced non-small cell lung cancer (NSCLC): 2023 expert consensus of the Spanish Lung Cancer Group GECP.

INTRODUCTION: Recent advances in the treatment of locally advanced NSCLC have led to changes in the standard of care for this disease. For the selection of the best approach strategy for each patient, it is necessary the homogenization of diagnostic and therapeutic interventions, as well as the promotion of the evaluation of patients by a multidisciplinary oncology team. OBJECTIVE: Development of an expert consensus document with suggestions for the approach and treatment of locally advanced NSCLC leaded by Spanish Lung Cancer Group GECP. METHODS: Between March and July 2023, a panel of 28 experts was formed. Using a mixed technique (Delphi/nominal group) under the guidance of a coordinating group, consensus was reached in 4 phases: 1. Literature review and definition of discussion topics 2. First round of voting 3. Communicating the results and second round of voting 4. Definition of conclusions in nominal group meeting. Responses were consolidated using medians and interquartile ranges. The threshold for agreement was defined as 85% of the votes. RESULTS: New and controversial situations regarding the diagnosis and management of locally advanced NSCLC were analyzed and reconciled based on evidence and clinical experience. Discussion issues included: molecular diagnosis and biomarkers, radiologic and surgical diagnosis, mediastinal staging, role of the multidisciplinary thoracic committee, neoadjuvant treatment indications, evaluation of response to neoadjuvant treatment, postoperative evaluation, and follow-up. CONCLUSIONS: Consensus clinical suggestions were generated on the most relevant scenarios such as diagnosis, staging and treatment of locally advanced lung cancer, which will serve to support decision-making in daily practice.

Outcomes after lung transplantation from selected donors older than 70 years in a single centre: time to close the debate?

OBJECTIVES: The aim of this study was to compare the outcomes of lung transplantations using grafts from donors aged over 70 years against those performed using younger donors. METHODS: This retrospective single-centre analysis includes lung transplants conducted at our institution from January 2014 to June 2022. Lung recipients were classified into 2 groups based on donor age (group A <70 years; group B ≥70 years). Variables regarding demographics, peri and postoperative outcomes and survival were included. The statistical analysis approach included univariable analysis, propensity score matching to address imbalances in donor variables (smoking status), recipient characteristics (sex, age, diagnosis and lung allocation score) and calendar period and survival analysis. RESULTS: A total of 353 lung transplants were performed in this period, 47 (13.3%) using grafts from donors aged over 70 years. Donors in group B were more frequently women (70.2% vs 51.6%, P = 0.017), with less smoking history (22% vs 43%, P = 0.002) and longer mechanical ventilation time (3 vs 2 days, P = 0.025). Recipients in group B had a higher lung allocation score (37.5 vs 35, P = 0.035). Postoperative variables were comparable between both groups, except for pulmonary function tests. Group B demonstrated lower forced expiratory volume 1 s levels (2070 vs 2580 ml, P = 0.001). The propensity score matching showed a lower chance of chronic lung allograft dysfunction by 12% for group B. One-, three- and five-year survival was equal between the groups. CONCLUSIONS: The use of selected expanded-criteria donors aged over 70 years did not result in increased postoperative morbidity, early mortality or survival in this study.

Influencia del antecedente de intervención coronaria percutánea sobre los desenlaces angiográficos y clínicos en pacientes con infarto agudo de miocardio con elevación del segmento ST / Impact of previous percutaneous coronary intervention on angiographic and clinical outcomes in patients with ST-segment elevation myocardial infarction

Resumen Antecedentes: El pronóstico de los pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) y antecedente de intervención coronaria percutánea (ICP) es incierto. Objetivos: Evaluar si la ICP previa en pacientes con IAMCEST incrementa el riesgo de eventos cardiovasculares mayores y si el flujo final epicárdico varía según la estrategia de reperfusión. Material y métodos: Subestudio de PHASE-MX, observacional, longitudinal y comparativo, de pacientes con IAMCEST reperfundidos en menos de 12 horas de iniciados los síntomas, divididos conforme el antecedente de ICP. El acaecimiento del criterio de valoración principal (muerte cardiovascular, reinfarto, insuficiencia cardíaca y choque cardiogénico) dentro de los 30 días se comparó con estimaciones de Kaplan-Meier, prueba de rangos logarítmicos y modelo de riesgos proporcionales de Cox. El flujo epicárdico final se evaluó con el sistema de clasificación del flujo TIMI después de la reperfusión. Resultados: Se incluyeron 935 pacientes, 85.6 % del sexo masculino, 6.9 % de los cuales tenía antecedente de ICP; 53 % recibió terapia farmacoinvasiva y 47 %, ICP primaria. La incidencia del criterio de valoración principal en pacientes con ICP previa fue de 9.8 % versus 13.3 % en aquellos sin ese antecedente (p = 0.06); 87.1 % de los pacientes con ICP previa obtuvo flujo final de grado TIMI 3 versus 75 % del grupo con estrategia farmacoinvasiva (p = 0.235). Conclusiones: El antecedente de ICP no incrementa el riesgo de eventos cardiovasculares mayores a los 30 días en pacientes con IAMCEST; sin embargo, impacta negativamente en el flujo sanguíneo angiográfico final de los pacientes que recibieron terapia farmacoinvasiva (en comparación con ICP primaria).

Abstract Background: The prognosis of patients with ST-segment elevation myocardial infarction (STEMI) and previous percutaneous coronary intervention (PCI) is uncertain. Objectives: To evaluate if previous PCI in patients with STEMI increases the risk of major cardiovascular events, and if final epicardial blood flow differs according to the reperfusion strategy. Material and methods: Observational, longitudinal, comparative sub-study of the PHASE-MX trial that included patients with STEMI and reperfusion within 12 hours of symptom onset, who were divided according to their history of PCI. The occurrence of the composite primary endpoint (cardiovascular death, re-infarction, congestive heart failure and cardiogenic shock) within 30 days was evaluated using Kaplan-Meier estimates, log-rank test and Cox proportional hazards model. Final epicardial blood flow was assessed using the TIMI grading system after reperfusion. Results: A total of 935 patients were included; 85.6% were males, and 6.9% had a history of PCI; 53% underwent pharmacoinvasive therapy, and 47%, primary PCI. The incidence of the composite primary endpoint at 30 days in patients with a history of PCI was 9.8% vs. 13.3% in those with no previous PCI (p = 0.06). Among the patients with previous PCI, 87.1% reached a final TIMI grade 3 flow after primary PCI vs. 75% in the group with pharmacoinvasive strategy (p = 0.235). Conclusions: A history of PCI does not increase the risk of major cardiovascular events at 30 days; however, it impacted negatively on the final angiographic blood flow of patients that received pharmacoinvasive therapy (compared to primary PCI).

Long-Term Outcomes of Pharmacoinvasive Strategy Versus Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction: A Study from Mexico City.

Although primary percutaneous coronary intervention (pPCI) is the treatment of choice in ST-elevation myocardial infarction (STEMI), challenges may arise in accessing this intervention for certain geodemographic groups. Pharmacoinvasive strategy (PIs) has demonstrated comparable outcomes when delays in pPCI are anticipated, but real-world data on long-term outcomes are limited. The aim of the present study was to compare long-term outcomes among real-world patients with STEMI who underwent either PIs or pPCI. This was a prospective registry including patients with STEMI who received reperfusion during the first 12 hours from symptom onset. The primary objective was cardiovascular mortality at 12 months according to the reperfusion strategy (pPCI vs PIs) and major cardiovascular events (cardiogenic shock, recurrent myocardial infarction, and congestive heart failure), and Bleeding Academic Research Consortium type 3 to 5 bleeding events were also evaluated. A total of 799 patients with STEMI were included; 49.1% underwent pPCI and 50.9% received PIs. Patients in the PIs group presented with more heart failure on admission (Killip-Kimbal >I 48.1 vs 39.7, p = 0.02) and had a lower proportion of pre-existing heart failure (0.2% vs 1.8%, p = 0.02) and atrial fibrillation (0.25% vs 1.2%, p = 0.02). No statistically significant difference was observed in cardiovascular mortality at the 12-month follow-up (hazard ratio for PIs 0.74, 95% confidence interval 0.42 to 1.30, log-rank p = 0.30) according to the reperfusion strategy used. The composite of major cardiovascular events (hazard ratio for PIs 0.98, 95% confidence interval 0.75 to 1.29, p = 0.92) and Bleeding Academic Research Consortium type 3 to 5 bleeding rates were also comparable. A low socioeconomic status, Killip-Kimball >2, age >60 years, and admission creatinine >2.0 mg/100 ml were predictors of the composite end point after multivariate analysis. In conclusion, this prospective real-world registry provides additional support that long-term major cardiovascular outcomes and bleeding are not different between patients who underwent PIs versus primary PCI.

Novel Management of Ocular Surface Inflammation in Patients With Ocular Graft-Versus-Host Disease in the Setting of Cataract Surgery.

PURPOSE: To report the outcomes of cataract surgery in patients with ocular graft-versus-host disease (oGVHD) using a novel preoperative immunomodulatory regimen in a collaborative subspecialty care setting. METHODS: Retrospective case series of patients with oGVHD who underwent cataract surgery using a novel preoperative immunomodulatory regimen in a collaborative care setting. A preoperative regimen consisting of pooled human immune globulin 1%, autologous serum 50%, and methylprednisolone 1% eye drops was prescribed. Outcome measures included visual acuity (VA), ocular surface disease index (OSDI) score, lissamine green staining, and complications with a minimum of 2 years of follow-up. RESULTS: Thirty-five eyes from 20 patients with oGVHD were studied. The mean age was 59 years (range 30-70 years). A healthy comparison group included 35 eyes from 24 patients with a mean age of 63 years (range 44-74 years). At the 2-year follow-up, the mean corneal staining score was 2.3/15, the mean OSDI score was 37.5, and the mean VA was 20/30 (logarithm of the minimal angle of resolution 0.17). The global complication rate was 2.8% at the last follow-up with no difference versus a healthy comparison group. CONCLUSIONS: A collaborative care model improving ocular surface health before cataract surgery with dry eye and cataract subspecialists can optimize outcomes in patients with oGVHD.

Nanoporous graphene-based thin-film microelectrodes for in vivo high-resolution neural recording and stimulation.

One of the critical factors determining the performance of neural interfaces is the electrode material used to establish electrical communication with the neural tissue, which needs to meet strict electrical, electrochemical, mechanical, biological and microfabrication compatibility requirements. This work presents a nanoporous graphene-based thin-film technology and its engineering to form flexible neural interfaces. The developed technology allows the fabrication of small microelectrodes (25 µm diameter) while achieving low impedance (∼25 kΩ) and high charge injection (3-5 mC cm-2). In vivo brain recording performance assessed in rodents reveals high-fidelity recordings (signal-to-noise ratio >10 dB for local field potentials), while stimulation performance assessed with an intrafascicular implant demonstrates low current thresholds (<100 µA) and high selectivity (>0.8) for activating subsets of axons within the rat sciatic nerve innervating tibialis anterior and plantar interosseous muscles. Furthermore, the tissue biocompatibility of the devices was validated by chronic epicortical (12 week) and intraneural (8 week) implantation. This work describes a graphene-based thin-film microelectrode technology and demonstrates its potential for high-precision and high-resolution neural interfacing.

Extending the age criteria of lung transplant donors to 70+ years old does not significantly affect recipient survival.

OBJECTIVES: To determine the impact of older donor age (70+ years) on long-term survival and freedom from chronic lung allograft dysfunction in lung transplant (LTx) recipients. METHODS: A retrospective single-center study was performed on all LTx recipients from 2002 to 2017 and a modern subgroup from 2013 to 2017. Recipients were stratified into 4 groups based on donor lung age (<18, 18-55, 56-69, ≥70 years). Donor and recipient characteristics were compared using χ2 tests for differences in proportions and analysis of variance for differences in means. Univariable and multivariable Cox regression was used to describe differences in long-term survival and freedom from chronic lung allograft dysfunction. RESULTS: Between 2002 and 2017, 1600 LTx were performed, 98 of which were performed from donors aged 70 years or older. Recipients of 70+ years donor lungs were significantly older with a mean age of 55.5 ± 12.9 years old (P = .001) and had more Status 3 (urgent) recipients (37.4%, P = .002). After multivariable regression, there were no significant differences in survival or freedom from chronic lung allograft dysfunction between the 4 strata of recipients. CONCLUSIONS: Lung transplantation using donors 70 years old or older can be considered when all other parameters suggest excellent donor lung function without compromising short- or long-term outcomes.

Trypanosoma cruzi in Mexican Neotropical vectors and mammals: wildlife, livestock, pets, and human population.

OBJECTIVE: To provide primary evidence of Trypanosoma cruzi landscape genetics in the Mexican Neotropics. MATERIALS AND METHODS: Trypanosoma cruzi and discrete typing units (DTU) prevalence were analyzed in landscape communities of vectors, wildlife, livestock, pets, and sympatric human populations using endpoint PCR and sequencing of all relevant amplicons from mitochondrial (kDNA) and nuclear (ME, 18S, 24Sα) gene markers. RESULTS: Although 98% of the infected sample-set (N=2 963) contained single or mixed infections of DTUI (TcI, 96.2%) and TcVI (22.6%), TcIV and TcII were also identified. Sensitivity of individual markers varied and was dependent on host taxon; kDNA, ME and 18S combined identified 95% of infections. ME genotyped 90% of vector infections, but 60% of mammals (36% wildlife), while neither 18S nor 24Sα typed more than 20% of mammal infections. CONCLUSION: Available gene fragments to identify or genotype T. cruzi are not universally sensitive for all landscape parasite populations, highlighting important T. cruzi heteroge- neity among mammal reservoir taxa and triatomine species.

Real-World Evaluation of a Pharmacoinvasive Strategy for STEMI in Latin America: A Cost-Effective Approach with Short-Term Benefits.

Purpose: While pharmacoinvasive strategy (PI) is a safe and effective approach whenever access to primary percutaneous intervention (pPCI) is limited, data on each strategy's economic cost and impact on in-hospital stay are scarce. The objective is to compare the cost-effectiveness of a PI with that of pPCI for the treatment of ST-elevation myocardial infarction (STEMI) in a Latin-American country. Patients and Methods: A total of 1747 patients were included, of whom 470 (26.9%) received PI, 433 (24.7%) pPCI, and 844 (48.3%) NR. The study's primary outcome was the incremental cost-effectiveness ratio (ICER) for PI compared with those for pPCI and non-reperfused (NR), calculated for 30-day major cardiovascular events (MACE), 30-day mortality, and length of stay. Results: For PI, the ICER estimates for MACE showed a decrease of $-35.81/per 1% (95 confidence interval, -114.73 to 64.81) compared with pPCI and a decrease of $-271.60/per 1% (95% CI, -1086.10 to -144.93) compared with NR. Also, in mortality, PI had an ICER decrease of $-129.50 (95% CI, -810.57, 455.06) compared to pPCI and $-165.27 (-224.06, -123.52) with NR. Finally, length of stay had an ICER reduction of -765.99 (-4020.68, 3141.65) and -283.40 (-304.95, -252.76) compared to pPCI and NR, respectively. Conclusion: The findings of this study suggest that PI may be a more efficient treatment approach for STEMI in regions where access to pPCI is limited or where patient and system delays are expected.

Conversion in a Resectable Tumor after Denosumab Neoadjuvant in a Large Dorsal Giant Cells Tumor: A Case Report and a Literature Review.

Giant cell tumors of bone are a rare entity, usually occurring in young patients and characteristically arising in the long bones. The spinal location is rare and usually presents with pain and/or neurological symptoms. The treatment of choice is surgery. Treatment with Denosumab, a bisphosphonate inhibitor of RANK-L, which is highly expressed in these tumors, has shown extensive activity in unresectable patients or those undergoing incomplete surgery. Preoperative treatment with this drug is gaining increasing interest, as its high potency in tumor reduction in this subtype of neoplasm has allowed resectability in selected patients. We present the case of a young patient with a large spinal tumor who, after neoadjuvant Denosumab, underwent complete en bloc surgery with clean margins and a great pathological response.

Silver and Copper Nitride Cooperate for CO Electroreduction to Propanol.

The need of carbon sources for the chemical industry, alternative to fossil sources, has pointed to CO2 as a possible feedstock. While CO2 electroreduction (CO2 R) allows production of interesting organic compounds, it suffers from large carbon losses, mainly due to carbonate formation. This is why, quite recently, tandem CO2 R, a two-step process, with first CO2 R to CO using a solid oxide electrolysis cell followed by CO electroreduction (COR), has been considered, since no carbon is lost as carbonate in either step. Here we report a novel copper-based catalyst, silver-doped copper nitride, with record selectivity for formation of propanol (Faradaic efficiency: 45 %), an industrially relevant compound, from CO electroreduction in gas-fed flow cells. Selective propanol formation occurs at metallic copper atoms derived from copper nitride and is promoted by silver doping as shown experimentally and computationally. In addition, the selectivity for C2+ liquid products (Faradaic efficiency: 80 %) is among the highest reported so far. These findings open new perspectives regarding the design of catalysts for production of C3 compounds from CO2 .

Unraveling the Neuroprotective Effect of Natural Bioactive Compounds Involved in the Modulation of Ischemic Stroke by Network Pharmacology.

Ischemic stroke (IS) is one of the leading causes of mortality worldwide. It is characterized by the partial or total occlusion of arteries that supply blood to the brain, leading to the death of brain cells. In recent years, natural bioactive compounds (NBCs) have shown properties that ameliorate the injury after IS and improve the patient's outcome, which has proven to be a potential therapeutic strategy due to their neuroprotective effects. Hence, in the present study, we use both systems pharmacology and chemoinformatic analyses to identify which NBCs have the most potential to be used against IS in clinics. Our results identify that flavonoids and terpenoids are the most studied NBCs, and, mainly, salidrosides, ginkgolides A, B, C, and K, cordycepin, curcumin, baicalin, resveratrol, fucose, and cannabidiol, target the main pathological processes occurring in IS. However, the medicinal chemistry properties of such compounds demonstrate that only six fulfill such criteria. However, only cordycepin and salidroside possess properties as leader molecules, suggesting that these compounds may be considered in developing novel drugs against IS.

[Acute myocardial infarction patients without COVID-19 manifestations in the pandemic may have high thrombus burden]. / Pacientes con infarto agudo de miocardio sin manifestaciones de COVID-19 pueden tener alta carga de trombo.

Objective: The objective of the study is to identify clinical and angiographic characteristics of patients with ST-segment elevation myocardial infarction (STEMI) but without clinical manifestations of COVID-19 infection during the pandemic, compared with patients 1 year before the pandemic. Methods: Observational study that included 138 consecutive patients hospitalized with STEMI who underwent primary percutaneous coronary intervention (PCI) without COVID-19 infection during the 2020 pandemic. A group of 175 STEMI patients treated with PCI in the year before the pandemic served as the control group. Results: During the periods analyzed, compared with the control group, patients admitted during the pandemic without clinical manifestations of COVID-19 did not have significant differences in demographic characteristics, comorbidities, or delayed time and location of the acute myocardial infarction. Furthermore, there were no differences between the two groups concerning levels of CK-MB and NT-proBNP, or in inflammation markers and left ventricular ejection fraction. In patients without COVID-19 during the pandemic compared with control, we found a higher intracoronary thrombus burden (thrombus grade 5; 78.3% vs. 62.9%, respectively. p = 0.002). Accordingly, the use of glycoprotein IIB/IIIa inhibitors (37.7% vs. 26.3%, p = 0.03) was higher in these patients. Conclusions: This study demonstrates an increased thrombus burden in STEMI patients without clinical manifestation of COVID-19 during the pandemic compared with the same time period in the previous year.

Objetivo: Identificar las características clínicas y angiográficas de los pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) sin manifestaciones clínicas de COVID-19 durante la pandemia y compararlos con los pacientes en el año previo. Métodos: Estudio observacional que incluyó 138 pacientes consecutivos que fueron hospitalizados por IAMCEST y que fueron tratados con angioplastía primaria (ACTP) sin manifestaciones clínicas de COVID-19 durante la pandemia de 2020. Se seleccionó a un grupo control de 175 pacientes con IAMCEST tratados con ACTP en el año previo a la pandemia. Resultados: Los pacientes atendidos durante la pandemia no tuvieron diferencias significativas en cuanto a las características clínicas, demográficas, comorbilidades, tiempo de retraso y localización del infarto. Además, no hubo diferencias entre ambos grupos en los niveles de CK-MB, NT-proBNP, marcadores de inflamación ni en la fracción de eyección del ventrículo izquierdo. En los pacientes sin COVID-19 tratados durante la pandemia encontramos mayor carga trombótica intracoronaria (trombo grado 5; 78.3% vs. 62.9%, respectivamente. p = 0.002). De igual manera, el uso de inhibidores de la glucoproteina IIB/IIIa (37.7% vs. 26.3%, p = 0.03) fue mayor. Conclusiones: Este studio demostró un aumento en la carga trombótica en los pacientes con IAMCEST sin manifestaciones clínicas de COVID-19 durante la pandemia al compararlos con los pacientes tratados por la misma patología en el año previo.

Twelve-Month Clinical and Histopathological Performance of a Novel Synthetic Cornea Device in Rabbit Model.

Purpose: To report the biological stability and postoperative outcomes of a second-generation, single-piece, flexible synthetic cornea in a rabbit model. Methods: Device materials and design were amended to enhance biointegration. Optic skirt design devices were made from compact perfluoroalkoxy alkane with porous expanded polytetrafluoroethylene ingrowth surface overlying the skirt and optic wall. Sixteen devices were implanted into intrastromal pocket in rabbit eyes. Rabbits were randomly assigned to 6- and 12-month follow-up cohorts (n = 8 in each) postoperatively. Monthly examinations and optical coherence tomography assessed cornea-device integration, iridocorneal angle, optic nerve, and retina. Results: There were no intraoperative complications. All devices were in situ at exit, with clear optics. No retroprosthetic membrane, glaucoma, cataract formation, or retinal detachment was observed. Two rabbits in the 6-month group had mild, focal anterior lamella thinning without retraction adjacent to the optic near tight sutures. Three postoperative complications occurred in the 12-month group. One rabbit diagnosed with endophthalmitis was euthanized on day 228. Mild sterile focal retraction of anterior lamella occurred in two rabbits, which were terminated on days 225 and 315. Light microscopic examination of enucleated globes demonstrated fibroplasia with new collagen deposition into the porous scaffold without significant inflammation, encapsulation, or granuloma formation. Conclusions: Clinical evaluations, imaging, and histopathological findings indicate favorable outcomes of this synthetic corneal device in a rabbit model. Early feasibility studies in humans are being planned. Translational Relevance: Favorable 12-month results of the device in rabbits demonstrate vision-restoring potential in corneally blind individuals at high risk of failure with donor keratoplasty.

Venous excess ultrasound score and acute kidney injury in patients with acute coronary syndrome.

AIMS: Systemic venous congestion is associated with an increased risk of acute kidney injury (AKI) in critically ill patients. Venous Excess Ultrasound Score (VExUS) has been proposed as a non-invasive score to assess systemic venous congestion. We aimed to evaluate the association between VExUS and AKI in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: This is a prospective study including patients with the diagnosis of ACS (both ST elevation and non-ST elevation ACS). VExUS was performed during the first 24 h of hospital stay. Patients were classified according to the presence of systemic congestion (VExUS 0/≥1). The primary objective of the study was to determine the occurrence of AKI, defined by KDIGO criteria. A total of 77 patients were included. After ultrasound assessment, 31 (40.2%) patients were categorized as VExUS ≥1. VExUS ≥1 was more frequently found in inferior vs. anterior myocardial infarction/non-ST-segment elevation acute myocardial infarction (48.3 vs. 25.8 and 22.5%, P = 0.031). At each increasing degree of VExUS, a higher proportion of patients developed AKI: VExUS = 0 (10.8%), VExUS = 1 (23.8%), VExUS = 2 (75.0%), and VExUS = 3 (100%; P < 0.001). A significant association between VExUS ≥1 and AKI was found [odds ratio (OR): 6.75, 95% confidence interval (CI): 2.21-23.7, P = 0.001]. After multivariable analysis, only VExUS ≥1 (OR: 6.15; 95% CI: 1.26-29.94, P = 0.02) remained significantly associated with AKI. CONCLUSION: In patients hospitalized with ACS, VExUS is associated with the occurrence of AKI. Further studies are needed to clarify the role of VExUS assessment in patients with ACS.