Increased Longevity of a Novel Gas Exchanger System for Low-Flow Veno-Venous Extracorporeal CO2 Removal in Acute Hypercapnic Respiratory Failure

Introduction: Low-flow veno-venous extracorporeal CO2 removal (ECCO2R) is an adjunctive therapy to support lung protective ventilation or maintain spontaneous breathing in hypercapnic respiratory failure. Low-flow ECCO2R is less invasive compared to higher flow systems, while potentially compromising efficiency and membrane lifetime. To counteract this shortcoming, a high-longevity system has recently been developed. Our hypotheses were that the novel membrane system provides runtimes up to 120 h, and CO2 removal remains constant throughout membrane system lifetime. Methods: Seventy patients with pH ≤ 7.25 and/or PaCO2 ≥9 kPa exceeding lung protective ventilation limits, or experiencing respiratory exhaustion during spontaneous breathing, were treated with the high-longevity ProLUNG system or in a control group using the original gas exchanger. Treatment parameters, gas exchanger runtime, and sweep-gas VCO2 were recorded across 9,806 treatment-hours and retrospectively analyzed. Results: 25/33 and 23/37 patients were mechanically ventilated as opposed to awake spontaneously breathing in both groups. The high-longevity system increased gas exchanger runtime from 29 ± 16 to 48 ± 36 h in ventilated and from 22 ± 14 to 31 ± 31 h in awake patients (p < 0.0001), with longer runtime in the former (p < 0.01). VCO2 remained constant at 86 ± 34 mL/min (p = 0.11). Overall, PaCO2 decreased from 9.1 ± 2.0 to 7.9 ± 1.9 kPa within 1 h (p < 0.001). Tidal volume could be maintained at 5.4 ± 1.8 versus 5.7 ± 2.2 mL/kg at 120 h (p = 0.60), and peak airway pressure could be reduced from 31.1 ± 5.1 to 27.5 ± 6.8 mbar (p < 0.01). Conclusion: Using a high-longevity gas exchanger system, membrane lifetime in low-flow ECCO2R could be extended in comparison to previous systems but remained below 120 h, especially in spontaneously breathing patients. Extracorporeal VCO2 remained constant throughout gas exchanger system runtime and was consistent with removal of approximately 50% of expected CO2 production, enabling lung protective ventilation despite hypercapnic respiratory failure

Nitroglycerin challenge identifies microcirculatory target for improved resuscitation in patients with circulatory shock

Background Circulatory shock and multi-organ failure remain major contributors to morbidity and mortality in critically ill patients and are associated with insufficient oxygen availability in the tissue. Intrinsic mechanisms to improve tissue perfusion, such as up-regulation of functional capillary density (FCD) and red blood cell velocity (RBCv), have been identified as maneuvers to improve oxygen extraction by the tissues; however, their role in circulatory shock and potential use as resuscitation targets remains unknown. To fill this gap, we examined the baseline and maximum recruitable FCD and RBCv in response to a topical nitroglycerin stimulus (FCD$_{NG}$, RBCv$_{NG}$) in patients with and without circulatory shock to test whether this may be a method to identify the presence and magnitude of a microcirculatory reserve capacity important for identifying a resuscitation target. Methods Sublingual handheld vital microscopy was performed after initial resuscitation in mechanically ventilated patients consecutively admitted to a tertiary medical ICU. FCD and RBCv were quantified using an automated computer vision algorithm (MicroTools). Patients with circulatory shock were retrospectively identified via standardized hemodynamic and clinical criteria and compared to patients without circulatory shock. Results 54 patients (57 ± 14y, BMI 26.3 ± 4.9 kg/m$^{2}$, SAPS 56 ± 19, 65% male) were included, 13 of whom presented with circulatory shock. Both groups had similar cardiac index, mean arterial pressure, RBCv, and RBCv$_{NG}$. Heart rate (p < 0.001), central venous pressure (p = 0.02), lactate (p < 0.001), capillary refill time (p < 0.01), and Mottling score (p < 0.001) were higher in circulatory shock after initial resuscitation, while FCD and FCD$_{NG}$ were 10% lower (16.9 ± 4.2 and 18.9 ± 3.2, p < 0.01; 19.3 ± 3.1 and 21.3 ± 2.9, p = 0.03). Nitroglycerin response was similar in both groups, and circulatory shock patients reached FCD$_{NG}$ similar to baseline FCD found in patients without shock. Conclusion Critically ill patients suffering from circulatory shock were found to present with a lower sublingual FCD. The preserved nitroglycerin response suggests a dysfunction of intrinsic regulation mechanisms to increase the microcirculatory oxygen extraction capacity associated with circulatory shock and identifies a potential resuscitation target. These differences in microcirculatory hemodynamic function between patients with and without circulatory shock were not reflected in blood pressure or cardiac index

Nitroglycerin challenge identifies microcirculatory target for improved resuscitation in patients with circulatory shock

Background: Circulatory shock and multi-organ failure remain major contributors to morbidity and mortality in critically ill patients and are associated with insufficient oxygen availability in the tissue. Intrinsic mechanisms to improve tissue perfusion, such as up-regulation of functional capillary density (FCD) and red blood cell velocity (RBCv), have been identified as maneuvers to improve oxygen extraction by the tissues; however, their role in circulatory shock and potential use as resuscitation targets remains unknown. To fill this gap, we examined the baseline and maximum recruitable FCD and RBCv in response to a topical nitroglycerin stimulus (FCDNG, RBCvNG) in patients with and without circulatory shock to test whether this may be a method to identify the presence and magnitude of a microcirculatory reserve capacity important for identifying a resuscitation target. Methods: Sublingual handheld vital microscopy was performed after initial resuscitation in mechanically ventilated patients consecutively admitted to a tertiary medical ICU. FCD and RBCv were quantified using an automated computer vision algorithm (MicroTools). Patients with circulatory shock were retrospectively identified via standardized hemodynamic and clinical criteria and compared to patients without circulatory shock. Results: 54 patients (57 ± 14y, BMI 26.3 ± 4.9 kg/m2, SAPS 56 ± 19, 65% male) were included, 13 of whom presented with circulatory shock. Both groups had similar cardiac index, mean arterial pressure, RBCv, and RBCvNG. Heart rate (p &lt; 0.001), central venous pressure (p = 0.02), lactate (p &lt; 0.001), capillary refill time (p &lt; 0.01), and Mottling score (p &lt; 0.001) were higher in circulatory shock after initial resuscitation, while FCD and FCDNG were 10% lower (16.9 ± 4.2 and 18.9 ± 3.2, p &lt; 0.01; 19.3 ± 3.1 and 21.3 ± 2.9, p = 0.03). Nitroglycerin response was similar in both groups, and circulatory shock patients reached FCDNG similar to baseline FCD found in patients without shock. Conclusion: Critically ill patients suffering from circulatory shock were found to present with a lower sublingual FCD. The preserved nitroglycerin response suggests a dysfunction of intrinsic regulation mechanisms to increase the microcirculatory oxygen extraction capacity associated with circulatory shock and identifies a potential resuscitation target. These differences in microcirculatory hemodynamic function between patients with and without circulatory shock were not reflected in blood pressure or cardiac index.</p

LRR-RLK family from two Citrus species: Genome-wide identification and evolutionary aspects

Background: Leucine-rich repeat receptor-like kinases (LRR-RLKs) represent the largest subfamily of plant RLKs. The functions of most LRR-RLKs have remained undiscovered, and a few that have been experimentally characterized have been shown to have important roles in growth and development as well as in defense responses. Although RLK subfamilies have been previously studied in many plants, no comprehensive study has been performed on this gene family in Citrus species, which have high economic importance and are frequent targets for emerging pathogens. In this study, we performed in silico analysis to identify and classify LRR-RLK homologues in the predicted proteomes of Citrus clementina (clementine) and Citrus sinensis (sweet orange). In addition, we used large-scale phylogenetic approaches to elucidate the evolutionary relationships of the LRR-RLKs and further narrowed the analysis to the LRR-XII group, which contains several previously described cell surface immune receptors. Results: We built integrative protein signature databases for Citrus clementina and Citrus sinensis using all predicted protein sequences obtained from whole genomes. A total of 300 and 297 proteins were identified as LRR-RLKs in C. clementina and C. sinensis, respectively. Maximum-likelihood phylogenetic trees were estimated using Arabidopsis LRR-RLK as a template and they allowed us to classify Citrus LRR- 34 RLKs into 16 groups. The LRR-XII group showed a remarkable expansion, containing approximately 150 paralogs encoded in each Citrus genome. Phylogenetic analysis also demonstrated the existence of two distinct LRR-XII clades, each one constituted mainly by RD and non-RD kinases. We identified 68 orthologous pairs from the C. clementina and C. sinensis LRR-XII genes. In addition, among the paralogs, we identified a subset of 78 and 62 clustered genes probably derived from tandem duplication events in the genomes of C. clementina and C. sinensis, respectively. Conclusions: This work provided the first comprehensive evolutionary analysis of the LRR-RLKs in Citrus. A large expansion of LRR-XII in Citrus genomes suggests that it might play a key role in adaptive responses in host-pathogen co-evolution, related to the perennial life cycle and domestication of the citrus crop species

Volumen de pulverización, dosis y horario de aplicación de glifosato en el control de Urochloa brizantha

In order to optimize machinery use, the application of herbicides has been performed at different times of the day and night. Therefore, knowledge about the pesticide that will be used and how the spray volume and time of application affect the effectiveness of the product is very important. Thus, the objective of this work was to study the influence of spray volume and different time of application on the control of Urochloa brizantha by different doses of glyphosate. The treatments were arranged in a 5 x 3 x 2 factorial scheme in a randomized block design with four replications. Five doses of glyphosate (0; 1080; 1440; 1800 and 2160 g∙ha-1∙a.e.), three times of application (morning, afternoon and evening) and two spray volumes (50 and 100 L·ha-1) were evaluated. A control assessment was performed at 21 days after application, in addition to the accumulation of dry matter and the leaf area index on the regrowth. A satisfactory control of the grass was obtained for applications performed in the morning and afternoon, without interference of the volume applied and the doses tested. Evening application reduces the effectiveness of glyphosate in Urochloa brizantha burndown.Con el fin de optimizar el uso de la maquinaria, la aplicación de herbicidas se ha realizado en diferentes momentos del día y de la noche. Sin embargo, es muy importante el conocimiento sobre el pesticida que se utilizará y cómo el volumen de pulverización y el horario de aplicación pueden afectar la eficacia del tratamiento. Así, el objetivo de este trabajo fue estudiar la influencia del volumen de aspersión y los diferentes horarios de aplicación en el control de Urochloa brizantha para distintas dosis de glifosato. Los tratamientos se organizaron en un arreglo factorial de 5 x 3 x 2 en un diseño de bloques al azar con cuatro repeticiones. Se evaluaron cinco dosis de glifosato (0; 1080; 1440; 1800 y 2160 g∙ha-1∙e.a.), tres horarios de aplicación (mañana, tarde y noche) y dos volúmenes de aspersión (50 y 100 L·ha-1). Se realizó una evaluación de control a los 21 días después de la aplicación, además de la acumulación de materia seca y el índice de área foliar en el rebrote. Se obtuvo un control satisfactorio de la hierba en las aplicaciones realizadas por la mañana y por la tarde, sin interferencia del volumen aplicado y las dosis probadas. La aplicación nocturna reduce la eficacia del control del glifosato sobre Urochloa brizantha

Effects of enhanced adsorption haemofiltration versus haemoadsorption in severe, refractory septic shock with high levels of endotoxemia: the ENDoX bicentric, randomized, controlled trial

Background Endotoxin adsorption is a promising but controversial therapy in severe, refractory septic shock and conflicting results exist on the effective capacity of available devices to reduce circulating endotoxin and inflammatory cytokine levels. Methods Multiarm, randomized, controlled trial in two Swiss intensive care units, with a 1:1:1 randomization of patients suffering severe, refractory septic shock with high levels of endotoxemia, defined as an endotoxin activity ≥ 0.6, a vasopressor dependency index ≥ 3, volume resuscitation of at least 30 ml/kg/24 h and at least single organ failure, to a haemoadsorption (Toraymyxin), an enhanced adsorption haemofiltration (oXiris) or a control intervention. Primary endpoint was the difference in endotoxin activity at 72-h post-intervention to baseline. In addition, inflammatory cytokine, vasopressor dependency index and SOFA-Score dynamics over the initial 72 h were assessed inter alia. Results In the 30, out of 437 screened, randomized patients (10 Standard of care, 10 oXiris, 10 Toraymyxin), endotoxin reduction at 72-h post-intervention-start did not differ among interventions (Standard of Care: 12 [1–42]%, oXiris: 21 [10–51]%, Toraymyxin: 23 [10–36]%, p = 0.82). Furthermore, no difference between groups could be observed neither for reduction of inflammatory cytokine levels (p = 0.58), nor for vasopressor weaning (p = 0.95) or reversal of organ injury (p = 0.22). Conclusions In a highly endotoxemic, severe, refractory septic shock population neither the Toraymyxin adsorber nor the oXiris membrane could show a reduction in circulating endotoxin or cytokine levels over standard of care

Úlcera de perna: um estudo de casos em Juiz de Fora-MG (Brasil) e região

BACKGROUND: Leg ulcers are characterized as tissue loss in the lower extremities, generally caused by vascular dysfunction.OBJECTIVES: Verify the clinical and epidemiological profiles of the population sample with leg ulcers treated at the health centers of Juiz deFora (Brazil).MATERIAL ANDMETHODS: 124 leg-wound patients were evaluated between January 1999 and August 2001 and submitted to aclinical protocol.RESULTS: The mean age was 64 years, with females in the majority (65.3%). The mean family composition was 3.7 persons, and family inco-me was around US$200.00 (86.8OBJETIVOS: Caracterizar clínica e epidemiologicamente a amostra populacional com UP atendida nos centros de saúde de Juiz de Fora. PACIENTES E MÉTODOS: Submetidos ao protocolo clínico 124 pacientes com UP, de Juiz de Fora e região de janeiro/1999 a agosto/2001. RESULTADOS: A média de idade foi 64 anos, 65,3$540,00 (86,8%). Associavam-se às úlceras insuficiência venosa (90,3%), hipertensão arterial sistêmica (54%), obesidade (20,2%) e diabetes mellitus (16,1%). A associação insuficiência venosa e hipertensão arterial foi freqüente (43,7%) e significante (p5cm) em cerca de 90% da amostra, com médias de 8,7cm e 9,6cm para os eixos vertical e horizontal, respectivamente. Estavam acompanhadas de hipercromia (92,7%), lipodermatoesclerose (68,5%) e varicosidades (66,9%), com duração média de 94,2 meses, e 50% das úlceras eram recidivantes. CONCLUSÕES: Os dados sugerem que a úlcera de perna seja doença crônica significativa na população idosa e de baixa renda de Juiz de Fora e região

Participação Feminina na Produção Científica em Finanças nos EnANPAD’s de 2000 a 2010

Este artigo teve por objetivo investigar a participa&ccedil;&atilde;o feminina na produ&ccedil;&atilde;o cient&iacute;fica da divis&atilde;o de finan&ccedil;as publicada nos EnANPAD&rsquo;s de 2000 a 2010. Trata-se de uma pesquisa bibliom&eacute;trica, quantitativa, que aborda a Lei de Lotka utilizando-se o modelo Lagrangiano de Poisson, em que foram analisados 506 artigos. Destes, 27 s&atilde;o de autoria exclusivamente feminina e 184 de autoria mista (feminino e masculino). Contudo, houve supremacia masculina. A maior prefer&ecirc;ncia feminina foi pela sub&aacute;rea de finan&ccedil;as corporativas e, a masculina, de mercados financeiros e de capitais. Nas pesquisas em conjunto o mainstream foi em finan&ccedil;as corporativas; seguida de mercados financeiros e de capitais; de investimentos; derivativos e gest&atilde;o de riscos e; finan&ccedil;as internacionais. Os temas mais abordados foram governan&ccedil;a corporativa e agency, pol&iacute;ticas de financiamento e estrutura de capital, gest&atilde;o de fundos ou carteiras e asset pricing. A an&aacute;lise da produtividade dos autores, por g&ecirc;nero, revelou que, tanto feminina quanto masculina, n&atilde;o tiveram ader&ecirc;ncia &agrave; distribui&ccedil;&atilde;o de Poisson e &agrave; Lei. E, parece haver uma tend&ecirc;ncia de crescimento positivo da participa&ccedil;&atilde;o das mulheres nas publica&ccedil;&otilde;es em finan&ccedil;as, sugerindo que elas t&ecirc;m conquistado espa&ccedil;o em uma &aacute;rea matem&aacute;tica com forte vi&eacute;s masculino, como acontece em outras &aacute;reas

Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding

OBJECTIVES: To assess the risk of venous thromboembolic events (VTEs) and bleeding with or without thromboprophylaxis during neoadjuvant chemotherapy in bladder cancer patients scheduled for radical cystectomy. MATERIALS AND METHODS: We conducted a retrospective cohort study in 4886 patients with non-metastatic bladder cancer undergoing cystectomy across 28 centres in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis on VTE and bleeding. RESULTS: In 147 patients (3%) VTEs were recorded within the first year. These occurred a median (interquartile range [IQR]) of 127 (82-198) days after bladder cancer diagnosis. Bleeding events occurred in 131 patients (3%) within the first year. These occurred a median (IQR) of 101 (83-171) days after cancer diagnosis. In inverse probability weighting analyses, compared to patients without thromboprophylaxis during chemotherapy, patients with thromboprophylaxis had not only a lower risk of VTE (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12-0.81; P = 0.016) but also a lower bleeding risk (HR 0.03, 95% CI 0.09-0.12; P <0.0001). The retrospective nature of the study was its main limitation. CONCLUSIONS: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomised trials in other malignancies. Our data suggest thromboprophylaxis is protective against VTEs and should be the standard of care during neoadjuvant chemotherapy