Critical warm ischemia time point for cardiac donation after circulatory death.

Donation after circulatory death (DCD) represents a promising opportunity to overcome the relative shortage of donors for heart transplantation. However, the necessary period of warm ischemia is a concern. This study aims to determine the critical warm ischemia time based on in vivo biochemical changes. Sixteen DCD non-cardiac donors, without cardiovascular disease, underwent serial endomyocardial biopsies immediately before withdrawal of life-sustaining therapy (WLST), at circulatory arrest (CA) and every 2 min thereafter. Samples were processed into representative pools to assess calcium homeostasis, mitochondrial function and cellular viability. Compared to baseline, no significant deterioration was observed in any studied parameter at the time of CA (median: 9 min; IQR: 7-13 min; range: 4-19 min). Ten min after CA, phosphorylation of cAMP-dependent protein kinase-A on Thr197 and SERCA2 decreased markedly; and parallelly, mitochondrial complex II and IV activities decreased, and caspase 3/7 activity raised significantly. These results did not differ when donors with higher WLST to CA times (≥9 min) were analyzed separately. In human cardiomyocytes, the period from WLST to CA and the first 10 min after CA were not associated with a significant compromise in cellular function or viability. These findings may help to incorporate DCD into heart transplant programs.

A real-world evidence study of nabiximols in multiple sclerosis patients with resistant spasticity: Analysis in relation to the newly described 'spasticity-plus syndrome'.

BACKGROUND AND PURPOSE: Nabiximols is a therapeutic option for patients with multiple sclerosis (MS) spasticity whose symptoms are poorly controlled by conventional oral first-line medications. This study aimed to assess the relationship between changes in spasticity severity (measured on the 0-10 numeric rating scale [NRS]) and the presence of associated symptoms in patients treated with nabiximols, and to investigate the presence of the newly described 'spasticity-plus syndrome'. METHODS: We analyzed real-world data from the Italian Medicines Agency e-Registry on 1138 patients with MS spasticity who began treatment with nabiximols. Evaluation time points were baseline, 4 weeks, and 3, 6, 12 and 18 months after treatment start. RESULTS: Common symptoms associated with MS spasticity in this cohort were pain (38.4% at baseline), sleep disturbances (32.7%), and spasms/cramps (28.5%). Pain was frequently clustered with sleep disturbances (57.2% of pain cases) and spasms/cramps (43.9%). Approximately one-third of patients with data at all evaluation time points maintained treatment at 18 months. Nabiximols reduced the baseline mean spasticity 0-10 NRS score by 24.6% at Week 4, and by 33.9% at 18 months in treatment continuers. Nabiximols resolved a range of MS spasticity-associated symptoms at Week 4, and after 18 months in treatment continuers. CONCLUSION: This real-world analysis supports the concept of a spasticity-plus syndrome and suggests that nabiximols can favorably impact a range of spasticity-associated symptoms.

Chemical characterization and microencapsulation of extracellular fungal pigments.

In this work, extracellular colored metabolites obtained from the filamentous fungi Talaromyces australis and Penicillium murcianum, isolated in the Andean-Patagonian native forests of Chile, were studied as prospect compounds to increase the sustainability of cosmetic products. The chemical and antioxidant properties of these natural pigments were characterized and strategies for their microencapsulation were also studied. UHPLC/MS-MS analyses indicated that the predominant metabolites detected in the cultures of P. murcianum were monascin (m/z = 411.15) and monashexenone (m/z = 319.10), while athrorosin H (m/z = 458.20) and damnacanthal (m/z = 281.05) were detected in cultures of T. australis. ORAC tests revealed that P. murcianum's metabolites had the greatest antioxidant properties with values higher than 2000 µmol of trolox equivalents/g. The fungal metabolites were successfully microencapsulated by ionic gelation into structures made of 1.3% sodium alginate, 0.2% chitosan, and 0.07% hyaluronic acid. The microencapsulation process generated structures of 543.57 ± 0.13 µm of mean diameter (d50) with an efficiency of 30% for P. murcianum, and 329.59 ± 0.15 µm of mean diameter (d50) and 40% efficiency, for T. australis. The chemical and biological characterization show the biotechnological potential of these fungal species to obtain pigments with antioxidant activity that could be useful in the cosmetic industry. The encapsulation process enables the production of easy-to-handle dry powder from the fungal metabolites, which could be potentially marketed as a functional cosmetic ingredient. KEY POINTS: • The predominant fungal pigments were of azaphilone and anthraquinoid classes. • The fungal pigments showed high antioxidant activity by ORAC assay. • Fungal pigment microcapsules obtained by ionic gelation were characterized.

Botulinum Toxin Injection Plus Topical Diltiazem for Chronic Anal Fissure: A Randomized Double-Blind Clinical Trial and Long-term Outcome.

BACKGROUND: Chemical sphincterotomy avoids the risk of permanent incontinence in the treatment of chronic anal fissure, but it does not reach the efficacy of surgery and recurrence is high. Drug combination has been proposed to overcome these drawbacks. OBJECTIVE: This study aimed to compare the clinical, morphological, and functional effects of combined therapy with botulinum toxin injection and topical diltiazem in chronic anal fissure and to assess the long-term outcome after healing. DESIGN: This is a randomized, controlled, double-blind, 2-arm, parallel-group trial with a long-term follow-up. SETTINGS: This study was conducted at a tertiary care center. PATIENTS: A total of 70 consecutive patients were referred to the gastroenterology department of a hospital in Valencia, Spain. INTERVENTION: After botulinum toxin injection (20 IU), patients were randomly assigned to local diltiazem (diltiazem group) or placebo gel (placebo group) for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome was fissure healing (evaluated by video register by 3 independent physicians). Secondary outcomes included symptomatic relief (30-day diary), effect on anal sphincters (manometry), safety, and long-term recurrence (24 months and 10 years). RESULTS: Healing was achieved per protocol in 13 of 25 (52%) patients of the diltiazem group and 11 of 30 (36.7%) patients of the placebo group (p = 0.25); on an intention-to-treat basis in 37.1% and 31.4% (p = 0.61). Both groups displayed significant reduction of anal pressures. Thirty percent reported minor and transitory incontinence, without differences between groups. Nine (69.2%) of the diltiazem group and 6 (54.5%) of the placebo group experienced a relapse at 24 months (p = 0.67). The overall recurrence rate at 10 years was 83.3% (20/24 patients). LIMITATIONS: This study was limited by the loss of patients during the trial. The low healing rate led to a small cohort to assess recurrence. CONCLUSIONS: Combined botulinum toxin injection and topical diltiazem is not superior to botulinum toxin injection in the treatment of chronic anal fissure. Both options offer suboptimal healing rates. Long-term recurrence is high (>80% at 10 years) and might appear at any time after healing. See Video Abstract at http://links.lww.com/DCR/B527. INYECCIN DE TOXINA BOTULNICA MS DILTIAZEM TPICO EN FISURA ANAL CRNICA UN ENSAYO CLNICO ALEATORIZADO DOBLE CIEGO Y RESULTADOS A LARGO PLAZO: ANTECEDENTES:La esfinterotomía química evita el riesgo de incontinencia permanente en el tratamiento de la fisura anal crónica, pero no alcanza la eficacia de la cirugía y la recurrencia es alta. Se ha propuesto la combinación de fármacos para superar estos inconvenientes.OBJETIVO:Comparar los efectos clínicos, morfológicos y funcionales de la terapia combinada con inyección de toxina botulínica y diltiazem tópico en fisura anal crónica y evaluar el resultado a largo plazo después de la cicatrización.DISEÑO:Ensayo aleatorizado, controlado, doble ciego, de dos brazos, de grupos paralelos con un seguimiento a largo plazo.ESCENARIO:Estudio realizado en un centro de atención terciaria.PACIENTES:Un total de 70 pacientes consecutivos referidos al servicio de gastroenterología de un hospital de Valencia, España.INTERVENCIÓN:Después de la inyección de toxina botulínica (20UI), los pacientes fueron asignados al azar a diltiazem local (grupo de diltiazem) o gel de placebo (grupo de placebo) durante 12 semanas.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la cicatrización de la fisura (evaluado por registro de video por tres médicos independientes). Los resultados secundarios incluyeron alivio sintomático (diario de 30 días), efecto sobre los esfínteres anales (manometría), seguridad y recurrencia a largo plazo (24 meses y 10 años).RESULTADOS:La curación se logró por protocolo en 13/25 (52%) en el grupo de Diltiazem y 11/30 (36,7%) en el grupo de Placebo (p = 0.25); por intención de tratar en el 37.1% y el 31.4%, respectivamente (p = 0.61). Ambos grupos mostraron una reducción significativa de las presiones anales. El 30% refirió incontinencia leve y transitoria, sin diferencias entre grupos. 9 (69.2%) del grupo de Diltiazem y 6 (54.5%) del grupo de placebo recurrieron a los 24 meses (p = 0.67). La tasa global de recurrencia a los 10 años fue del 83.3% (20/24 pacientes).LIMITACIONES:La pérdida de pacientes a lo largo del ensayo. La baja tasa de curación llevó a una pequeña cohorte para evaluar la recurrencia.CONCLUSIONES:La inyección combinada de toxina botulínica y diltiazem tópico no es superior a la inyección de TB en el tratamiento de la fisura anal crónica. Ambas opciones ofrecen tasas de curación subóptimas. La recurrencia a largo plazo es alta (> 80% a los 10 años) y puede aparecer en cualquier momento después de la curación. Consulte Video Resumen en http://links.lww.com/DCR/B527.

Estimation of the second ventilatory threshold through ventricular repolarization profile analysis.

Under the hypothesis that sympathetic control of ventricular repolarization may change once the second ventilatory threshold (VT2) has been reached, a novel methodology for non-invasive VT2 estimation based on the analysis of the T wave from the electrocardiogram (ECG) is proposed, and potential underlying physiological mechanisms are suggested. 25 volunteers (33.4 ± 5.2 years) underwent an incremental power cycle ergometer test (25 W/minute). During the test, respiratory gas exchange and multi-lead ECG were acquired. The former was employed to determine VT2, used here as a reference, whereas the latter was used to compute the temporal profiles of an index of ventricular repolarization instability (dT) and its low-frequency (LF) oscillations (LFdT). The sudden increases observed in dT and LFdT profiles above an established heart rate threshold were employed to derive VT2 estimates, referred to as VT2d T and VT2LF d T , respectively. Estimation errors of -4.7 ± 25.2 W were obtained when considering VT2d T . Errors were lower than the one-minute power increment of 25 W in 68% of the subjects and lower than 50 W in 89.5% of them. When using VT2LF d T , estimation error was of 15.3 ± 32.4 W. Most of the subjects shared common characteristic dT and LFdT profiles, which could be reflecting changes in the autonomic control of ventricular repolarization before and after reaching VT2. The analysis of ventricular repolarization dynamics during exercise allows non-invasive ECG-based estimation of VT2, possibly in relation to changes in the autonomic control of ventricular electrical activity when VT2 is reached.

Validity of the Polar H7 Heart Rate Sensor for Heart Rate Variability Analysis during Exercise in Different Age, Body Composition and Fitness Level Groups.

This work aims to validate the Polar H7 heart rate (HR) sensor for heart rate variability (HRV) analysis at rest and during various exercise intensities in a cohort of male volunteers with different age, body composition and fitness level. Cluster analysis was carried out to evaluate how these phenotypic characteristics influenced HR and HRV measurements. For this purpose, sixty-seven volunteers performed a test consisting of the following consecutive segments: sitting rest, three submaximal exercise intensities in cycle-ergometer and sitting recovery. The agreement between HRV indices derived from Polar H7 and a simultaneous electrocardiogram (ECG) was assessed using concordance correlation coefficient (CCC). The percentage of subjects not reaching excellent agreement (CCC > 0.90) was higher for high-frequency power (PHF) than for low-frequency power (PLF) of HRV and increased with exercise intensity. A cluster of unfit and not young volunteers with high trunk fat percentage showed the highest error in HRV indices. This study indicates that Polar H7 and ECG were interchangeable at rest. During exercise, HR and PLF showed excellent agreement between devices. However, during the highest exercise intensity, CCC for PHF was lower than 0.90 in as many as 60% of the volunteers. During recovery, HR but not HRV measurements were accurate. As a conclusion, phenotypic differences between subjects can represent one of the causes for disagreement between HR sensors and ECG devices, which should be considered specifically when using Polar H7 and, generally, in the validation of any HR sensor for HRV analysis.

[Influence of the labor quality of life on the employeeperformance of public hospitals from Mexico: a vision based on the team management]. / Influencia de la calidad de vida laboral sobre el desempeño de trabajadores de hospitales públicos de México: una visión desde la gestión directiva.

OBJECTIVE: To assess the relationship between labor quality of life (LQL) and organizational workers performance (OWP) from seven public hospitals, analyzing the influence of the personnel management (PM) as mediator of this relationship. MATERIALS AND METHODS: A cross-sectional study was conducted in 866 professionals and managers of public hospitals from Tlaxcala and Mexico City. The LQL was assessed with a validated questionnaire, OWP with 34 indicators, and PM with an instrument designed for this study. RESULTS: Mean scores of LQL, were significantly lower among workers from Tlaxcala. Participants who perceived an adequate PM, they increased at 2.7 times their likelihood of having highest LQL, and participants categorized in the high LQL presented 69% higher likelihood of having an adequate OWP. CONCLUSIONS: The appropriate PM was associated with greater LQL, showing to be a mediator variable between the positive relationship of CVL and the OWP.

OBJETIVO: Evaluar la relación entre calidad de vida laboral (CVL) y el desempeño organizacional (DO) de trabajadores de siete hospitales públicos, a partir del análisis de la influencia de la gestión directiva (GD) como mediadora de esta relación. MATERIAL Y MÉTODOS: Se realizó un estudio transversal en 866 profesionales y directivos de hospitales públicos de Tlaxcala y de la Ciudad de México. La CVL fue medida con un instrumento validado, el DO con 34 indicadores y la GD con un instrumento diseñado para este estudio. RESULTADOS: Los puntajes de gestión directiva, CVL, DO y GD fueron sig- nificativamente menores en los trabajadores de Tlaxcala. Los participantes que percibieron adecuada GD incrementaron 2.7 veces más la probabilidad de percibir elevada CVL y los participantes categorizados en elevada CVL presentaron 69% mayor probabilidad de tener adecuado DO. CONCLUSIONES: La adecuada GD se asoció con una mejor CVL, lo que mostró ser una variable mediadora de la relación positiva entre CVL y DO.

Physical Activity and Sedentary Behavior at the End of the Human Lifespan.

To objectively assess physical activity levels and sedentary behavior in a cohort of Spanish centenarians and their nonagenarian peers. Physical activity and sedentary behavior patterns were objectively measured by an ActiGraph GT3X accelerometer in centenarians (n = 18; 83% women; 100.8 ± 0.8 [100-103] years) and nonagenarians (n = 11; 91% women; 93.3 ± 2.5 [90-98] years). Centenarians showed less counts per minute (17.6 ± 7.1 vs. 46.1 ± 23.7, p = .003, d = 1.851) and steps per day (455 ± 237 vs. 1,249 ± 776, p = .007, d = 1.587) than nonagenarians. The daily number of sedentary breaks was also lower in the former (5.0 ± 1.5 vs. 6.7 ± 2.0, p = .019, d = 0.971). When observing time distribution, the most active day period in both groups was the morning, with a peak between 10:00 and 11:59. This data suggest that the decline in physical activity levels continues to worsen until the end of the human lifespan.

Talaromyces australis and Penicillium murcianum pigment production in optimized liquid cultures and evaluation of their cytotoxicity in textile applications.

In this work Talaromyces australis and Penicillium murcianum pigment production in liquid cultures and the cytotoxic effect of such pigments on skin model cells were studied. Response surface methodology (RSM) was used to optimize culture conditions aiming to increase pigment production in malt extract and peptone-glucose-yeast extract medium. Cytotoxicity of fungal pigments and also from lixiviates of wool fabrics dyed with T. australis and P. murcianum pigment was evaluated on mammalian cell lines HEK293 and NIH/3T3. Results showed that variations on initial pH, NaCl and peptone, resulted in increments up to 188.2% for red pigment of T. australis and 107.4% for yellow pigment of P. murcianum, regarding non-optimized conditions. Tested fungi also showed great differences in culture conditions for the maximum pigment production, with P. murcianum requiring an alkaline medium (initial pH 9) supplemented with NaCl and T. australis an acidic medium (initial pH 5) without addition of salt. The cytotoxicity assays provided evidences on the safe nature of these natural pigments when used for textile applications. The cytotoxicity assay showed that the threshold of toxicity, given by the lowest IC50 value (0.21 g L-1) was more than double of the concentration of pigment required to dye the wool samples. In addition, cytotoxicity of lixiviates depicted no toxic effect over tested cells.

[Validation of a scale to assess the labour quality of life in public hospitals from Tlaxcala]. / Validación de una escala para medir la calidad de vida laboral en hospitales públicos de Tlaxcala.

OBJECTIVE:: To validate a scale for assessing the labour quality of life in public hospitals (LQL-PH) from Tlaxcala, Mexico. MATERIALS AND METHODS:: The instrument was validated among 669 health workers from six hospitals from the Ministry of Health of Tlaxcala, Mexico. Content validity was by inquiry to experts, construct validity by factor analysis, criterion validity by comparing with other scales, and reliability with Cronbach's Alpha. RESULTS:: The factor analysis uncovered four dimensions: "individual welfare", "conditions and labour environment", "organization", and "well-being accomplished by the work"; reliability was 0.921. Workers who perceibed better LQL-PH were: under 50 years old, with temporary contract, with less seniority in job, with work schedule at daytime of weekends, and those with academic degree. CONCLUSIONS:: LQL-PH showed to be an instrument phsycometrically valid and reliable. It's recommendable to prove this scale in other public and private health institutions, as well as its relationship with key health care indicators of labour performance and management.

Improving phosphorus uptake and wheat productivity by phosphoric acid application in alkaline calcareous soils.

BACKGROUND: Low phosphorus (P) efficiency from existing granular fertilisers necessitates searching for efficient alternatives to improve wheat productivity in calcareous soil. RESULTS: Multi-location trials have shown that phosphoric acid (PA) produced 16% higher wheat grain over commercial P fertilisers, i.e. diammonium phosphate (DAP) and triple superphosphate (TSP). Methods of P application significantly influenced grain yield and the efficiency of methods was observed in the order: PA placement below seed > PA, DAP or TSP fertigation > DAP or TSP broadcast. The sub-surface application of PA produced highest grain yields (mean of all rates), i.e. 4669, 4158 and 3910 kg ha(-1) in Bagh, Bhalwal and Shahpur soil series, respectively. Phosphoric acid at 66 kg P2 O5 ha(-1) was found more effective in increasing gain yield over that of control. Trend in grain P uptake was found similar to that observed for grain yield. Maximum P uptake by grain was recorded at the highest P rate and the lowest at zero P. The significant increase in P uptake with P rates was generally related to the increase in yield rather than its concentration in grain. Phosphorus agronomic efficiency (PAE) and phosphorus recovery efficiency (PRE) were found higher at lower P rate (44 kg P2 O5 ha(-1) ) and decreased with P application. However, PA applied by the either method resulted in higher PAE and PRE compared to DAP and TSP. CONCLUSION: Phosphoric acid is suggested as an efficient alternative to commercial granular P fertilisers for wheat production in alkaline calcareous soils. © 2015 Society of Chemical Industry.

Participation and detection rates by age and sex for colonoscopy versus fecal immunochemical testing in colorectal cancer screening.

PURPOSE: To compare two strategies for colorectal cancer screening: one-time colonoscopy versus fecal immunochemical testing (FIT) (and colonoscopy for positive) every 2 years, in order to determine which strategy provides the highest participation and detection rates in groups of sex and age. METHODS: This analysis was performed with data from the first screening round within the COLONPREV study, a population-based, multicenter, nationwide trial carried out in Spain. Several logistic regression models were applied to identify the influence of the screening test on participation rates and detection of proximal and distal neoplasms, as well to identify the influence of age and sex: women aged 50-59 years, women aged 60-69 years, men aged 50-59 years, and men aged 60-69 years. RESULTS: Participation was higher in women than in men, especially among women aged 50-59 years (25.91 % for colonoscopy and 35.81 % for FIT). Crossover from colonoscopy to FIT was higher among women than men, especially among those aged 60-69 years (30.37 %). In general, detection of any neoplasm and advanced adenoma was higher with colonoscopy than with FIT, but no significant differences were found between the two strategies for colorectal cancer detection. Detection of advanced adenoma in both arms was lower in women [specifically in women aged 50-59 years (OR 0.31; 95 % CI 0.25-0.38) than in men aged 60-69 years]. Women aged 50-59 years in the colonoscopy arm had a higher probability of detection of advanced adenoma (OR 4.49; 95 % CI 3.18-6.35), as well as of detection of neoplasms in proximal and distal locations (proximal OR 19.34; 95 % CI 12.07-31.00; distal OR 11.04; 95 % CI 8.13-15.01) than women of the same age in the FIT arm. These differences were also observed in the remaining groups but to a lesser extent. CONCLUSION: Women were more likely to participate in a FIT-based strategy, especially those aged 50-59 years. The likelihood of detection of any neoplasm was higher in the colonoscopy arm for all the population groups studied, especially in women aged 50-59 years. Distinct population groups should be informed of the benefits of each screening strategy so that they may take informed decisions.

N-terminal pro-B-type natriuretic peptide post-discharge monitoring in the management of patients with heart failure and preserved ejection fraction - a randomized trial: The NICE study.

AIMS: There is a lack of specific studies assessing the impact of natriuretic peptide monitoring in the post-discharge management of patients with heart failure (HF) and preserved ejection fraction (HFpEF), throughout the vulnerable phase following acute HF hospitalization. The NICE study aims to assess the clinical benefit of incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) into the post-discharge management of HFpEF patients. METHODS AND RESULTS: Individuals admitted with HFpEF (left ventricular ejection fraction >50%) were included in a multicentre randomized controlled study employing an open-label design with event blinding (NCT02807168). Upon discharge, 157 patients were randomly allocated to either NT-proBNP monitoring (n = 79) or no access to NT-proBNP (control group, n = 78) during pre-scheduled visits at 2, 4 and 12 weeks. Clinical endpoints were evaluated at 6 months. The primary endpoint of HF rehospitalizations occurred in 12.1% patients, without significant differences observed between the NT-proBNP monitoring group (12.8%) and the control group (11.4%) (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.47-2.81, p = 0.760). Regarding secondary endpoints, the NT-proBNP monitoring group demonstrated a significantly lower risk of death (1.3% vs. 10.1%; HR 0.12, 95% CI 0.02-0.98; p = 0.048), whereas non-HF hospitalizations (12.8% vs. 19.0%, p = 0.171) and any adverse clinical event (26.9% vs. 36.7%, p = 0.17) did not reach statistical significance [Correction added on 29 April 2024, after first online publication: In the preceding sentence, "95% CI 0.02 - 0.09" has been corrected to "95% CI 0.02 - 0.98; p = 0.048" in this version.]. Awareness of NT-proBNP levels were associated with higher doses of diuretics and renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers) in the NT-proBNP monitoring group. CONCLUSIONS: Post-discharge monitoring of NT-proBNP in HFpEF patients did not exhibit an association with reduced rates of HF hospitalization in this study. Nonetheless, it appears to enhance global clinical management by optimizing medical therapies and contributing to improved overall survival.

Withdrawal of drug therapy in responders to cardiac resynchronization therapy: rationale and design of the REMOVE trial.

INTRODUCTION AND OBJECTIVES: Cardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients. METHODS: The REMOVE trial is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF >10% (provided the LVEF is <50%); b) a reduction in LVEF >10% accompanied by an increase >15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted. CONCLUSIONS: The results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients. Registred at ClinicalTrials.gov (Identifier: NCT05151861).

Refractory anorexia nervosa in adulthood and nucleus accumbens deep brain stimulation.

Background: Anorexia Nervosa is a life-threatening mental illness with numerous consequences. Some cases are chronic and refractory to multiple treatments. Consequently, there is great interest in therapeutic alternatives that may improve severe patients. We present an adult patient with anorexia nervosa that underwent to bilateral nucleus accumbens deep brain stimulation (NAc-DBS). Case description: The patient was a healthy 46-year-old woman with higher education and an adequate premorbid socio-labour situation. Her disease had a late onset (25 years). The patient never presented clinical remission or weight stability. In recent years, the patient's body mass index (BMI) was 13.16 (32kg). The case was evaluated with multiple neuropsychological tests as well as the BMI before and after surgery. The clinical follow-up was 50 months. After bilateral NAc-DBS the patient experienced an important clinical benefit and significant improvement in neuropsychological tests and weight (BMI 17.28, 42 kg; 50th month) Programming: 4,5V, 130Hz, 210 µs. Conclusion: Despite the patient´s age and the long duration of the disease, our results suggest that bilateral nucleus accumbens stimulation may be a useful and effective therapeutic strategy for cases such as the one presented. Additionally, this case presents a surgical midlife patient with both the latest disease onset and the longest follow-up after treatment in the literature.

Multidecadal fluctuations in green turtle hatchling production related to climate variability.

The state of Campeche, Mexico, harbors one of the largest green turtle (Chelonia mydas) rookeries of the Wider Caribbean Region. Since the 1970s, harvesting of this population was common practice, but it has since ceased, and the population is rebounding as a consequence. In this rookery, during the past 37 years (1984-2020), the positive relationship between the annual number of nesting females and the number of hatchlings they produce has revealed a long-term population signal that we postulate could be related to environmental factors. To investigate this relationship more deeply, we adopt a stock-recruitment (SR) approach, which is commonly used in fisheries. Regression analysis methods for the SR relationship, including a dynamic version of the model that incorporates the effect of sea surface temperature, show that the number of recruits produced and the number of hatchlings per unit nester were significantly and inversely correlated with a 26-year cycle of the Atlantic Multidecadal Oscillation (AMO) with a three year lag. A possible explanation for this finding is that environmental conditions during warming periods of the 26-year AMO cycle may negatively affect hatchling production by altering the nest moisture content during the incubation period, and increasing embryonic mortality, while the annual female abundance at nesting beaches may decrease due to trophic effects. The time series of abundance corresponding to other population units of green turtles as well as other species of sea turtles in the Gulf of Mexico present a similar behavior to that evaluated here, suggesting a basin-wide environmental effect.

Value of increased soluble suppressor tumorigenicity biomarker 2 (sST2) on admission as an indicator of severity in patients with COVID-19.

BACKGROUND: Soluble suppressor of tumorigenicity-2 (sST2) is a biomarker for heart failure and pulmonary injury. We hypothesize that sST2 could help predict severity of SARS-CoV-2 infections. METHODS: sST2 was analyzed in patients consecutively admitted for SARS-CoV-2 pneumonia. Other prognostic markers were also measured. In-hospital complications were registered, including death, ICU admission, and respiratory support requirements. RESULTS: 495 patients were studied (53% male, age: 57.6±17.6). At admission, median sST2 concentrations was 48.5ng/mL [IQR, 30.6-83.1ng/mL] and correlated with male gender, older age, comorbidities, other severity biomarkers, and respiratory support requirements. sST2 levels were higher in patients who died (n=45, 9.1%) (45.6 [28.0, 75.9]ng/mL vs. 144 [82.6, 319] ng/mL, p<0.001) and those admitted to ICU (n=46, 9.3%) (44.7 [27.5, 71.3] ng/mL vs. 125 [69.0, 262]ng/mL, p<0.001). sST2 levels>210ng/mL were a strong predictor of complicated in-hospital courses, with higher risk of death (OR, 39.3, CI95% 15.9, 103) and death/ICU (OR 38.3, CI95% 16.3-97.5) after adjusting for all other risk factors. The addition of sST2 enhanced the predictive capacity of mortality risk models. CONCLUSIONS: sST2 represents a robust severity predictor in COVID-19 and could be an important tool for identifying at-risk patients who may benefit from closer follow-up and specific therapies.

Increased risk of hospitalization and death in Mexican children and adolescents with COVID-19 and comorbidities.

BACKGROUND: Although COVID-19 (coronavirus disease 2019) in children is usually mild, they need hospitalization and intensive care in exceptional cases. Adverse outcomes have been observed mainly among children with comorbidities, justifying their vaccination. This study aimed to assess the risk of hospitalization and death in Mexican children and adolescents with COVID-19 and comorbidities. METHODS: A cross-sectional study was performed on 366,542 confirmed COVID-19 cases under 18 years, reported by the Mexican Ministry of Health up to July 9, 2022. Logistic regression models were performed. RESULTS: The mean age was 10.98 years, 50.6% were male, and 7.3% reported at least one comorbidity. The percentage of hospitalization and death in COVID-19 patients with and without comorbidities was 3.52%, and 0.20%, respectively; children with comorbidities presented a higher percentage of hospitalization (14.0%) and death (1.9%). The probability of hospitalization was 5.6 times greater in pediatric patients with COVID-19 and comorbidities, and the comorbidities that showed the greatest risk were immunosuppression (odds ratio (OR) 22.06), chronic kidney disease (CKD) (11.36), and cardiovascular diseases (5.66). The probability of death in patients with comorbidities was 11.01 times higher than in those without diseases, and the highest risk was observed in those with CKD (OR 12.57), cardiovascular diseases (6.87), and diabetes (5.83). CONCLUSIONS: Pediatric patients with comorbidities presented a higher risk of severe COVID-19. It is suggested that vaccination should be promoted with greater emphasis on pediatric patients with comorbidities.

INTRODUCCIÓN: Aunque COVID-19 (enfermedad por coronavirus 2019) en niños es usualmente leve, en casos excepcionales requieren hospitalización y cuidados intensivos. Los resultados adversos han sido observados principalmente en los niños con comorbilidades, justificando su vacunación. El objetivo de este estudio fue evaluar el riesgo de hospitalización y muerte en niños y adolescentes mexicanos con COVID-19 y comorbilidades. MÉTODOS: Estudio transversal en 366,542 casos de COVID-19 confirmados, menores de 18 años y reportados por la Secretaría de Salud de México, hasta el 9 de julio del 2022. Se ejecutaron modelos multivariados de regresión logística. RESULTADOS: El promedio de edad fue de 10.98 años, 50.6% de sexo masculino, y 7.3% reportaron al menos una comorbilidad. El porcentaje de hospitalización y muerte en pacientes con COVID-19 sin comorbilidades fue 3.52% y 0.20%, respectivamente; mientras que los pacientes con comorbilidades presentaron más elevados porcentajes de hospitalización (14.0%) y muerte (1.9%). La probabilidad de hospitalización fue 5.6 veces más en los pacientes con COVID-19 y comorbilidades, comparando con aquellos sin comorbilidades. Las comorbilidades que mostraron más riesgo fueron inmunosupresión (razón de momios (RM) 22.06), enfermedad renal crónica (ERC) (RM 11.36) y enfermedades cardiovasculares (RM 5.66). La probabilidad de muerte en los pacientes con comorbilidades fue 11.01 veces más que en aquellos sin enfermedades, y fue más elevado en aquellos con ERC (RM 12.57), enfermedades cardiovasculares (RM 6.87) y diabetes (RM 5.83). CONCLUSIONES: Los pacientes pediátricos con comorbilidades presentaron mayor riesgo de COVID-19 severo, por lo que se sugiere promover con mayor énfasis la vacunación en ellos.

Carbapenemase-Encoding Genes and Colistin Resistance in Gram-Negative Bacteria During the COVID-19 Pandemic in Mexico: Results from the Invifar Network.

In this study, we report the carbapenemase-encoding genes and colistin resistance in Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa in the second year of the COVID-19 pandemic. Clinical isolates included carbapenem-resistant K. pneumoniae, carbapenem-resistant E. coli, carbapenem-resistant A. baumannii, and carbapenem-resistant P. aeruginosa. Carbapenemase-encoding genes were detected by PCR. Carbapenem-resistant K. pneumoniae and carbapenem-resistant E. coli isolates were analyzed using the Rapid Polymyxin NP assay. mcr genes were screened by PCR. Pulsed-field gel electrophoresis and whole-genome sequencing were performed on representative isolates. A total of 80 carbapenem-resistant E. coli, 103 carbapenem-resistant K. pneumoniae, 284 carbapenem-resistant A. baumannii, and 129 carbapenem-resistant P. aeruginosa isolates were recovered. All carbapenem-resistant E. coli and carbapenem-resistant K. pneumoniae isolates were included for further analysis. A selection of carbapenem-resistant A. baumannii and carbapenem-resistant P. aeruginosa strains was further analyzed (86 carbapenem-resistant A. baumannii and 82 carbapenem-resistant P. aeruginosa). Among carbapenem-resistant K. pneumoniae and carbapenem-resistant E. coli isolates, the most frequent gene was blaNDM (86/103 [83.5%] and 72/80 [90%], respectively). For carbapenem-resistant A. baumannii, the most frequently detected gene was blaOXA-40 (52/86, 60.5%), and for carbapenem-resistant P. aeruginosa, was blaVIM (19/82, 23.2%). For carbapenem-resistant A. baumannii, five indistinguishable pulsotypes were detected. Circulation of K. pneumoniae New Delhi metallo-ß-lactamase (NDM) and E. coli NDM was detected in Mexico. High virulence sequence types (STs), such as K. pneumoniae ST307, E. coli ST167, P. aeruginosa ST111, and A. baumannii ST2, were detected. Among K. pneumoniae isolates, 18/101 (17.8%) were positive for the Polymyxin NP test (two, 11.0% positive for the mcr-1 gene, and one, 5.6% with disruption of the mgrB gene). All E. coli isolates were negative for the Polymyxin NP test. In conclusion, K. pneumoniae NDM and E. coli NDM were detected in Mexico, with the circulation of highly virulent STs. These results are relevant in clinical practice to guide antibiotic therapies considering the molecular mechanisms of resistance to carbapenems.