Normothermic and hypothermic machine perfusion preservation versus static cold storage for deceased donor kidney transplantation.

BACKGROUND: Kidney transplantation is the optimal treatment for kidney failure. Donation, transport and transplant of kidney grafts leads to significant ischaemia reperfusion injury. Static cold storage (SCS), whereby the kidney is stored on ice after removal from the donor until the time of implantation, represents the simplest preservation method. However, technology is now available to perfuse or "pump" the kidney during the transport phase ("continuous") or at the recipient centre ("end-ischaemic"). This can be done at a variety of temperatures and using different perfusates. The effectiveness of these treatments manifests as improved kidney function post-transplant. OBJECTIVES: To compare machine perfusion (MP) technologies (hypothermic machine perfusion (HMP) and (sub) normothermic machine perfusion (NMP)) with each other and with standard SCS. SEARCH METHODS: We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies until 15 June 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs comparing machine perfusion techniques with each other or versus SCS for deceased donor kidney transplantation were eligible for inclusion. All donor types were included (donor after circulatory death (DCD) and brainstem death (DBD), standard and extended/expanded criteria donors). Both paired and unpaired studies were eligible for inclusion. DATA COLLECTION AND ANALYSIS: The results of the literature search were screened, and a standard data extraction form was used to collect data. Both of these steps were performed by two independent authors. Dichotomous outcome results were expressed as risk ratios (RR) with 95% confidence intervals (CI). Survival analyses (time-to-event) were performed with the generic inverse variance meta-analysis of hazard ratios (HR). Continuous scales of measurement were expressed as a mean difference (MD). Random effects models were used for data analysis. The primary outcome was the incidence of delayed graft function (DGF). Secondary outcomes included graft survival, incidence of primary non-function (PNF), DGF duration, economic implications, graft function, patient survival and incidence of acute rejection. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Twenty-two studies (4007 participants) were included. The risk of bias was generally low across all studies and bias domains. The majority of the evidence compared non-oxygenated HMP with standard SCS (19 studies). The use of non-oxygenated HMP reduces the rate of DGF compared to SCS (16 studies, 3078 participants: RR 0.78, 95% CI 0.69 to 0.88; P < 0.0001; I2 = 31%; high certainty evidence). Subgroup analysis revealed that continuous (from donor hospital to implanting centre) HMP reduces DGF (high certainty evidence). In contrast, this benefit over SCS was not seen when non-oxygenated HMP was not performed continuously (low certainty evidence). Non-oxygenated HMP reduces DGF in both DCD and DBD settings in studies performed in the 'modern era' and when cold ischaemia times (CIT) were short. The number of perfusions required to prevent one episode of DGF was 7.69 and 12.5 in DCD and DBD grafts, respectively. Continuous non-oxygenated HMP versus SCS also improves one-year graft survival (3 studies, 1056 participants: HR 0.46, 0.29 to 0.75; P = 0.002; I2 = 0%; high certainty evidence). Assessing graft survival at maximal follow-up confirmed a benefit of continuous non-oxygenated HMP over SCS (4 studies, 1124 participants (follow-up 1 to 10 years): HR 0.55, 95% CI 0.40 to 0.77; P = 0.0005; I2 = 0%; high certainty evidence). This effect was not seen in studies where HMP was not continuous. The effect of non-oxygenated HMP on our other outcomes (PNF, incidence of acute rejection, patient survival, hospital stay, long-term graft function, duration of DGF) remains uncertain. Studies performing economic analyses suggest that HMP is either cost-saving (USA and European settings) or cost-effective (Brazil). One study investigated continuous oxygenated HMP versus non-oxygenated HMP (low risk of bias in all domains); the simple addition of oxygen during continuous HMP leads to additional benefits over non-oxygenated HMP in DCD donors (> 50 years), including further improvements in graft survival, improved one-year kidney function, and reduced acute rejection. One large, high-quality study investigated end-ischaemic oxygenated HMP versus SCS and found end-ischaemic oxygenated HMP (median machine perfusion time 4.6 hours) demonstrated no benefit compared to SCS. The impact of longer periods of end-ischaemic HMP is unknown. One study investigated NMP versus SCS (low risk of bias in all domains). One hour of end ischaemic NMP did not improve DGF compared with SCS alone. An indirect comparison revealed that continuous non-oxygenated HMP (the most studied intervention) was associated with improved graft survival compared with end-ischaemic NMP (indirect HR 0.31, 95% CI 0.11 to 0.92; P = 0.03). No studies investigated normothermic regional perfusion (NRP) or included any donors undergoing NRP. AUTHORS' CONCLUSIONS: Continuous non-oxygenated HMP is superior to SCS in deceased donor kidney transplantation, reducing DGF, improving graft survival and proving cost-effective. This is true for both DBD and DCD kidneys, both short and long CITs, and remains true in the modern era (studies performed after 2008). In DCD donors (> 50 years), the simple addition of oxygen to continuous HMP further improves graft survival, kidney function and acute rejection rate compared to non-oxygenated HMP. Timing of HMP is important, and benefits have not been demonstrated with short periods (median 4.6 hours) of end-ischaemic HMP. End-ischaemic NMP (one hour) does not confer meaningful benefits over SCS alone and is inferior to continuous HMP in an indirect comparison of graft survival. Further studies assessing NMP for viability assessment and therapeutic delivery are warranted and in progress.

Morphological comparison of the larynx and trachea of Chelonia mydas (Linnaeus, 1758), Caiman yacare (Daudin, 1802) and Caiman latirostris (Daudin, 1802).

The larynx is in the lower respiratory tract and has the function of protecting the airways, controlling, and modulating breathing, assisting the circulatory system, and vocalizing. This study aims to describe the anatomy and histology of the skeleton of the larynx and trachea of the species Chelonia mydas, Caiman yacare and Caiman latirostris. The study was conducted at the Federal University of Espírito Santo (UFES), using nine specimens of Ch. mydas, 20 of Ca. yacare and four of Ca. latirostris. Samples of the larynx and trachea were collected, fixed, and sent for dissection of the structures and subsequent macroscopic analysis. For histology, samples were processed by the routine paraffin embedding method and stained with hematoxylin-eosin and Verhoeff. For the three species, two arytenoid cartilages, a cricoid cartilage, a hyoid apparatus composed of a base and two horns were found. In Ch. mydas, two structures called thyroid wings were observed, not found in crocodilians. The trachea of crocodilians presented incomplete tracheal rings and musculature, while the trachea of Ch. mydas presented complete tracheal rings. Histologically, the entire cartilaginous skeleton of the larynx of the three species, as well as the tracheal rings, are constituted by hyaline cartilage.

Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction: The DEFENDER Randomized Clinical Trial.

Importance: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown. Objective: To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023. Intervention: Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models. Results: Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group. Conclusion and Relevance: The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin. Trial Registration: ClinicalTrials.gov Identifier: NCT05558098.

Prospective, randomized, controlled trial assessing the effects of a driving pressure-limiting strategy for patients with acute respiratory distress syndrome due to community-acquired pneumonia (STAMINA trial): protocol and statistical analysis plan.

BACKGROUND: Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress syndrome. Whether a driving pressure-limiting strategy can improve clinical outcomes is unclear. OBJECTIVE: To describe the protocol and statistical analysis plan that will be used to test whether a driving pressure-limiting strategy including positive end-expiratory pressure titration according to the best respiratory compliance and reduction in tidal volume is superior to a standard strategy involving the use of the ARDSNet low-positive end-expiratory pressure table in terms of increasing the number of ventilator-free days in patients with acute respiratory distress syndrome due to community-acquired pneumonia. METHODS: The ventilator STrAtegy for coMmunIty acquired pNeumoniA (STAMINA) study is a randomized, multicenter, open-label trial that compares a driving pressure-limiting strategy to the ARDSnet low-positive end-expiratory pressure table in patients with moderate-to-severe acute respiratory distress syndrome due to community-acquired pneumonia admitted to intensive care units. We expect to recruit 500 patients from 20 Brazilian and 2 Colombian intensive care units. They will be randomized to a driving pressure-limiting strategy group or to a standard strategy using the ARDSNet low-positive end-expiratory pressure table. In the driving pressure-limiting strategy group, positive end-expiratory pressure will be titrated according to the best respiratory system compliance. OUTCOMES: The primary outcome is the number of ventilator-free days within 28 days. The secondary outcomes are in-hospital and intensive care unit mortality and the need for rescue therapies such as extracorporeal life support, recruitment maneuvers and inhaled nitric oxide. CONCLUSION: STAMINA is designed to provide evidence on whether a driving pressure-limiting strategy is superior to the ARDSNet low-positive end-expiratory pressure table strategy for increasing the number of ventilator-free days within 28 days in patients with moderate-to-severe acute respiratory distress syndrome. Here, we describe the rationale, design and status of the trial.

Does Time to Asystole in Donors After Circulatory Death Impact Recipient Outcome in Liver Transplantation?

BACKGROUND: The agonal phase can vary following treatment withdrawal in donor after circulatory death (DCD). There is little evidence to support when procurement teams should stand down in relation to donor time to death (TTD). We assessed what impact TTD had on outcomes following DCD liver transplantation. METHODS: Data were extracted from the UK Transplant Registry on DCD liver transplant recipients from 2006 to 2021. TTD was the time from withdrawal of life-sustaining treatment to asystole, and functional warm ischemia time was the time from donor systolic blood pressure and/or oxygen saturation falling below 50 mm Hg and 70%, respectively, to aortic perfusion. The primary endpoint was 1-y graft survival. Potential predictors were fitted into Cox proportional hazards models. Adjusted restricted cubic spline models were generated to further delineate the relationship between TTD and outcome. RESULTS: One thousand five hundred fifty-eight recipients of a DCD liver graft were included. Median TTD in the entire cohort was 13 min (interquartile range, 9-17 min). Restricted cubic splines revealed that the risk of graft loss was significantly greater when TTD ≤14 min. After 14 min, there was no impact on graft loss. Prolonged hepatectomy time was significantly associated with graft loss (hazard ratio, 1.87; 95% confidence interval, 1.23-2.83; P = 0.003); however, functional warm ischemia time had no impact (hazard ratio, 1.00; 95% confidence interval, 0.44-2.27; P > 0.9). CONCLUSIONS: A very short TTD was associated with increased risk of graft loss, possibly because of such donors being more unstable and/or experiencing brain stem death as well as circulatory death. Expanding the stand down times may increase the utilization of donor livers without significantly impairing graft outcome.

Redescription of three fossil baleen whale skulls from the Miocene of Portugal reveals new cetotheriid phylogenetic insights.

Cetotheriidae is a family of baleen whales that went nearly extinct during the Pleistocene (excluding Caperea marginata). For a long time, the Cetotheriidae family has been seen as a problematic clade, but in the past two decades there have been various studies trying to resolve the phylogeny of this group. In 1831, Alexandre Vandelli described three cetotheriid skulls, found during a gold exploration at Adiça beach (Portugal). These specimens constituted the first Portuguese vertebrate fossils ever published in the literature. Another skull was added to the "Vandelli skulls" by Jacinto Pedro Gomes, in 1914, during a survey of the Museu Nacional de História Natural collections without giving information on the origin of this skull. In 1941, Remington Kellogg states that one of the original "Vandelli skulls" is no longer present in the Museu Nacional de História Natural collections. Until today, there is no information on how, or exactly when, the fourth skull and one of the original three "Vandelli skulls" appeared and disappeared, respectively. Since their discovery, all the attempts to describe these specimens were not based on direct observations and no comprehensive phylogenetic analysis have included the three skulls. Here we provide a detailed anatomic description, a new phylogenetic analysis and a palaeoecological reconstruction of these specimens, clarifying their relationships within the Cetotheriidae family and fostering the importance of these historical specimens to the modern comprehension of fossil whale evolution. In addition, our results support that Cephalotropis nectus is a valid species with an emended diagnosis. We also concluded that two specimens belong to a new genus, forming two new fossil species (new combinations).

Convolutional neural network misclassification analysis in oral lesions: an error evaluation criterion by image characteristics.

OBJECTIVE: This retrospective study analyzed the errors generated by a convolutional neural network (CNN) when performing automated classification of oral lesions according to their clinical characteristics, seeking to identify patterns in systemic errors in the intermediate layers of the CNN. STUDY DESIGN: A cross-sectional analysis nested in a previous trial in which automated classification by a CNN model of elementary lesions from clinical images of oral lesions was performed. The resulting CNN classification errors formed the dataset for this study. A total of 116 real outputs were identified that diverged from the estimated outputs, representing 7.6% of the total images analyzed by the CNN. RESULTS: The discrepancies between the real and estimated outputs were associated with problems relating to image sharpness, resolution, and focus; human errors; and the impact of data augmentation. CONCLUSIONS: From qualitative analysis of errors in the process of automated classification of clinical images, it was possible to confirm the impact of image quality, as well as identify the strong impact of the data augmentation process. Knowledge of the factors that models evaluate to make decisions can increase confidence in the high classification potential of CNNs.

Prospective, randomized, controlled trial assessing the effects of a driving pressure-limiting strategy for patients with acute respiratory distress syndrome due to community-acquired pneumonia (STAMINA trial): protocol and statistical analysis plan / Estudo randomizado prospectivo e controlado de avaliação dos efeitos de uma estratégia de limitação da driving pressure em pacientes com síndrome do desconforto respiratório agudo devido à pneumonia adquirida na comunidade (estudo STAMINA): protocolo e plano de análise estatística

ABSTRACT Background: Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress syndrome. Whether a driving pressure-limiting strategy can improve clinical outcomes is unclear. Objective: To describe the protocol and statistical analysis plan that will be used to test whether a driving pressure-limiting strategy including positive end-expiratory pressure titration according to the best respiratory compliance and reduction in tidal volume is superior to a standard strategy involving the use of the ARDSNet low-positive end-expiratory pressure table in terms of increasing the number of ventilator-free days in patients with acute respiratory distress syndrome due to community-acquired pneumonia. Methods: The ventilator STrAtegy for coMmunIty acquired pNeumoniA (STAMINA) study is a randomized, multicenter, open-label trial that compares a driving pressure-limiting strategy to the ARDSnet low-positive end-expiratory pressure table in patients with moderate-to-severe acute respiratory distress syndrome due to community-acquired pneumonia admitted to intensive care units. We expect to recruit 500 patients from 20 Brazilian and 2 Colombian intensive care units. They will be randomized to a driving pressure-limiting strategy group or to a standard strategy using the ARDSNet low-positive end-expiratory pressure table. In the driving pressure-limiting strategy group, positive end-expiratory pressure will be titrated according to the best respiratory system compliance. Outcomes: The primary outcome is the number of ventilator-free days within 28 days. The secondary outcomes are in-hospital and intensive care unit mortality and the need for rescue therapies such as extracorporeal life support, recruitment maneuvers and inhaled nitric oxide. Conclusion: STAMINA is designed to provide evidence on whether a driving pressure-limiting strategy is superior to the ARDSNet low-positive end-expiratory pressure table strategy for increasing the number of ventilator-free days within 28 days in patients with moderate-to-severe acute respiratory distress syndrome. Here, we describe the rationale, design and status of the trial.

RESUMO Contexto: Em estudos observacionais sobre a síndrome do desconforto respiratório agudo, sugeriu-se que a driving pressure é o principal fator de lesão pulmonar induzida por ventilador e de mortalidade. Não está claro se uma estratégia de limitação da driving pressure pode melhorar os desfechos clínicos. Objetivo: Descrever o protocolo e o plano de análise estatística que serão usados para testar se uma estratégia de limitação da driving pressure envolvendo a titulação da pressão positiva expiratória final de acordo com a melhor complacência respiratória e a redução do volume corrente é superior a uma estratégia padrão envolvendo o uso da tabela de pressão positiva expiratória final baixa do protocolo ARDSNet, em termos de aumento do número de dias sem ventilador em pacientes com síndrome do desconforto respiratório agudo devido à pneumonia adquirida na comunidade. Métodos: O estudo STAMINA (ventilator STrAtegy for coMmunIty acquired pNeumoniA) é randomizado, multicêntrico e aberto e compara uma estratégia de limitação da driving pressure com a tabela de pressão positiva expiratória final baixa do protocolo ARDSnet em pacientes com síndrome do desconforto respiratório agudo moderada a grave devido à pneumonia adquirida na comunidade internados em unidades de terapia intensiva. Esperamos recrutar 500 pacientes de 20 unidades de terapia intensiva brasileiras e duas colombianas. Eles serão randomizados para um grupo da estratégia de limitação da driving pressure ou para um grupo de estratégia padrão usando a tabela de pressão positiva expiratória final baixa do protocolo ARDSnet. No grupo da estratégia de limitação da driving pressure, a pressão positiva expiratória final será titulada de acordo com a melhor complacência do sistema respiratório. Desfechos: O desfecho primário é o número de dias sem ventilador em 28 dias. Os desfechos secundários são a mortalidade hospitalar e na unidade de terapia intensiva e a necessidade de terapias de resgate, como suporte de vida extracorpóreo, manobras de recrutamento e óxido nítrico inalado. Conclusão: O STAMINA foi projetado para fornecer evidências sobre se uma estratégia de limitação da driving pressure é superior à estratégia da tabela de pressão positiva expiratória final baixa do protocolo ARDSnet para aumentar o número de dias sem ventilador em 28 dias em pacientes com síndrome do desconforto respiratório agudo moderada a grave. Aqui, descrevemos a justificativa, o desenho e o status do estudo.

First record of insect-plant interaction in Late Cretaceous fossils from Nelson Island (South Shetland Islands Archipelago), Antarctica.

Despite the enormous paleobotanical record on different islands of the Antarctic Peninsula, the evidence of insect activity associated with fossilized plants is scarce. Here we report the first evidence of insect-plant interaction from Cretaceous deposits, more precisely from a new locality at the Rip Point area, Nelson Island (Antarctic Peninsula). The macrofossil assemblage includes isolated Nothofagus sp. leaf impressions, a common component of the Antarctic paleoflora. Two hundred leaves were examined, of which 15 showed evidence of insect activity, displaying variations in size, shape, and preservation. Two types of interaction damage, galls and mines, were identified. A single specimen retained a circular scar recognized as galling scar, while meandering tracks were considered mines. These traces of herbivore insect activity, correspond to the oldest known record of this type of interaction of West Antarctica and the oldest record of insect-plant interaction in Nothofagus sp. reported so far.

Machine perfusion in liver transplantation.

BACKGROUND: Liver transplantation is the only chance of cure for people with end-stage liver disease and some people with advanced liver cancers or acute liver failure. The increasing prevalence of these conditions drives demand and necessitates the increasing use of donated livers which have traditionally been considered suboptimal. Several novel machine perfusion preservation technologies have been developed, which attempt to ameliorate some of the deleterious effects of ischaemia reperfusion injury. Machine perfusion technology aims to improve organ quality, thereby improving outcomes in recipients of suboptimal livers when compared to traditional static cold storage (SCS; ice box). OBJECTIVES: To evaluate the effects of different methods of machine perfusion (including hypothermic oxygenated machine perfusion (HOPE), normothermic machine perfusion (NMP), controlled oxygenated rewarming, and normothermic regional perfusion) versus each other or versus static cold storage (SCS) in people undergoing liver transplantation. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 10 January 2023. SELECTION CRITERIA: We included randomised clinical trials which compared different methods of machine perfusion, either with each other or with SCS. Studies comparing HOPE via both hepatic artery and portal vein, or via portal vein only, were grouped. The protocol detailed that we also planned to include quasi-randomised studies to assess treatment harms. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. overall participant survival, 2. quality of life, and 3. serious adverse events. Secondary outcomes were 4. graft survival, 5. ischaemic biliary complications, 6. primary non-function of the graft, 7. early allograft function, 8. non-serious adverse events, 9. transplant utilisation, and 10. transaminase release during the first week post-transplant. We assessed bias using Cochrane's RoB 2 tool and used GRADE to assess certainty of evidence. MAIN RESULTS: We included seven randomised trials (1024 transplant recipients from 1301 randomised/included livers). All trials were parallel two-group trials; four compared HOPE versus SCS, and three compared NMP versus SCS. No trials used normothermic regional perfusion. When compared with SCS, it was uncertain whether overall participant survival was improved with either HOPE (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.42 to 1.98; P = 0.81, I2 = 0%; 4 trials, 482 recipients; low-certainty evidence due to imprecision because of low number of events) or NMP (HR 1.08, 95% CI 0.31 to 3.80; P = 0.90; 1 trial, 222 recipients; very low-certainty evidence due to imprecision and risk of bias). No trials reported quality of life. When compared with SCS alone, HOPE was associated with improvement in the following clinically relevant outcomes: graft survival (HR 0.45, 95% CI 0.23 to 0.87; P = 0.02, I2 = 0%; 4 trials, 482 recipients; high-certainty evidence), serious adverse events in extended criteria DBD liver transplants (OR 0.45, 95% CI 0.22 to 0.91; P = 0.03, I2 = 0%; 2 trials, 156 participants; moderate-certainty evidence) and clinically significant ischaemic cholangiopathy in recipients of DCD livers (OR 0.31, 95% CI 0.11 to 0.92; P = 0.03; 1 trial, 156 recipients; high-certainty evidence). In contrast, NMP was not associated with improvement in any of these clinically relevant outcomes. NMP was associated with improved utilisation compared with SCS (one trial found a 50% lower rate of organ discard; P = 0.008), but the reasons underlying this effect are unknown. We identified 11 ongoing studies investigating machine perfusion technologies. AUTHORS' CONCLUSIONS: In situations where the decision has been made to transplant a liver donated after circulatory death or donated following brain death, end-ischaemic HOPE will provide superior clinically relevant outcomes compared with SCS alone. Specifically, graft survival is improved (high-certainty evidence), serious adverse events are reduced (moderate-certainty evidence), and in donors after circulatory death, clinically relevant ischaemic biliary complications are reduced (high-certainty evidence). There is no good evidence that NMP has the same benefits over SCS in terms of these clinically relevant outcomes. NMP does appear to improve utilisation of grafts that would otherwise be discarded with SCS; however, the reasons for this, and whether this effect is specific to NMP, is not clear. Further studies into NMP viability criteria and utilisation, as well as head-to-head trials with other perfusion technologies are needed. In the setting of donation following circulatory death transplantation, further trials are needed to assess the effect of these ex situ machine perfusion methods against, or in combination with, normothermic regional perfusion.

A new species of Comahuesuchus Bonaparte, 1991 (Crocodyliformes: Notosuchia) from the Upper Cretaceous of Neuquén, Lake Barreales, Patagonia, Argentina.

Notosuchian crocodyliforms were major components of the South American Cretaceous biota and, for over 125 years, paleontological fieldwork in this continent recovered several well-preserved fossils of these animals. They are largely recognized for terrestrial life and specialized feeding habits, frequently presenting bizarre taxa such as Comahuesuchus. A new species, Comahuesuchus bonapartei n. sp. (MUCPv 597; cast MN), is described from geological strata of Sierra Barrosa Formation (Upper Turonian) and Portezuelo Formation (Lower Coniacian) of Lake Barreales, Patagonia, Argentina. The new fossil comprises a right dentary bone that shares important and unique anatomical features with specimens of Comahuesuchus brachybuccalis, such as the presence of a well-marked shelf on the lateral surface of the bone; a flat, low, and wide mandibular symphysis; an enlarged, labiolingually compressed caniniform tooth at caudal position in the dentary; the presence of serrated mesial and distal carinae in the caniniform with a faceted labial surface, and the absence or extremely reduction in number of the postcaniniform dentition. C. bonapartei differs from C. brachybuccalis in having individual dentary alveoli, rather a dentition set in groove. Phylogenetic analyses support a sister-relationship between both species, which are well nested within notosuchians.

Assessment of inter-centre agreement across multidisciplinary team meetings for patients with retroperitoneal sarcoma.

BACKGROUND: Decision-making in the management of patients with retroperitoneal sarcoma is complex and requires input from a number of different specialists. The aim of this study was to evaluate the levels of agreement in terms of resectability, treatment allocation, and organs proposed to be resected across different retroperitoneal sarcoma multidisciplinary team meetings. METHODS: The CT scans and clinical information of 21 anonymized retroperitoneal sarcoma patients were sent to all of the retroperitoneal sarcoma multidisciplinary team meetings in Great Britain, which were asked to give an opinion about resectability, treatment allocation, and organs proposed to be resected. The main outcome was inter-centre reliability, which was quantified using overall agreement, as well as the chance-corrected Krippendorff's alpha statistic. Based on the latter, the level of agreement was classified as: 'slight' (0.00-0.20), 'fair' (0.21-0.40), 'moderate' (0.41-0.60), 'substantial' (0.61-0.80), or 'near-perfect' (>0.80). RESULTS: Twenty-one patients were reviewed at 12 retroperitoneal sarcoma multidisciplinary team meetings, giving a total of 252 assessments for analysis. Consistency between centres was only 'slight' to 'fair', with rates of overall agreement and Krippendorff's alpha statistics of 85.4 per cent (211 of 247) and 0.37 (95 per cent c.i. 0.11 to 0.57) for resectability; 80.4 per cent (201 of 250) and 0.39 (95 per cent c.i. 0.33 to 0.45) for treatment allocation; and 53.0 per cent (131 of 247) and 0.20 (95 per cent c.i. 0.17 to 0.23) for the organs proposed to be resected. Depending on the centre that they had attended, 12 of 21 patients could either have been deemed resectable or unresectable, and 10 of 21 could have received either potentially curative or palliative treatment. CONCLUSIONS: Inter-centre agreement between retroperitoneal sarcoma multidisciplinary team meetings was low. Multidisciplinary team meetings may not provide the same standard of care for patients with retroperitoneal sarcoma across Great Britain.

Attributable mortality due to nosocomial sepsis in Brazilian hospitals: a case-control study.

BACKGROUND: Nosocomial sepsis is a major healthcare issue, but there are few data on estimates of its attributable mortality. We aimed to estimate attributable mortality fraction (AF) due to nosocomial sepsis. METHODS: Matched 1:1 case-control study in 37 hospitals in Brazil. Hospitalized patients in participating hospitals were included. Cases were hospital non-survivors and controls were hospital survivors, which were matched by admission type and date of discharge. Exposure was defined as occurrence of nosocomial sepsis, defined as antibiotic prescription plus presence of organ dysfunction attributed to sepsis without an alternative reason for organ failure; alternative definitions were explored. Main outcome measurement was nosocomial sepsis-attributable fractions, estimated using inversed-weight probabilities methods using generalized mixed model considering time-dependency of sepsis occurrence. RESULTS: 3588 patients from 37 hospitals were included. Mean age was 63 years and 48.8% were female at birth. 470 sepsis episodes occurred in 388 patients (311 in cases and 77 in control group), with pneumonia being the most common source of infection (44.3%). Average AF for sepsis mortality was 0.076 (95% CI 0.068-0.084) for medical admissions; 0.043 (95% CI 0.032-0.055) for elective surgical admissions; and 0.036 (95% CI 0.017-0.055) for emergency surgeries. In a time-dependent analysis, AF for sepsis rose linearly for medical admissions, reaching close to 0.12 on day 28; AF plateaued earlier for other admission types (0.04 for elective surgery and 0.07 for urgent surgery). Alternative sepsis definitions yield different estimates. CONCLUSION: The impact of nosocomial sepsis on outcome is more pronounced in medical admissions and tends to increase over time. The results, however, are sensitive to sepsis definitions.

Use of Artificial Intelligence in the Classification of Elementary Oral Lesions from Clinical Images.

OBJECTIVES: Artificial intelligence has generated a significant impact in the health field. The aim of this study was to perform the training and validation of a convolutional neural network (CNN)-based model to automatically classify six clinical representation categories of oral lesion images. METHOD: The CNN model was developed with the objective of automatically classifying the images into six categories of elementary lesions: (1) papule/nodule; (2) macule/spot; (3) vesicle/bullous; (4) erosion; (5) ulcer and (6) plaque. We selected four architectures and using our dataset we decided to test the following architectures: ResNet-50, VGG16, InceptionV3 and Xception. We used the confusion matrix as the main metric for the CNN evaluation and discussion. RESULTS: A total of 5069 images of oral mucosa lesions were used. The oral elementary lesions classification reached the best result using an architecture based on InceptionV3. After hyperparameter optimization, we reached more than 71% correct predictions in all six lesion classes. The classification achieved an average accuracy of 95.09% in our dataset. CONCLUSIONS: We reported the development of an artificial intelligence model for the automated classification of elementary lesions from oral clinical images, achieving satisfactory performance. Future directions include the study of including trained layers to establish patterns of characteristics that determine benign, potentially malignant and malignant lesions.

Conditional Treatment Effect Analysis of Two Infusion Rates for Fluid Challenges in Critically Ill Patients: A Secondary Analysis of Balanced Solution versus Saline in Intensive Care Study (BaSICS) Trial.

Rationale: Optimal infusion rate for fluid challenges in critically ill patients is unknown. A large clinical trial comparing two different infusion rates yielded neutral results. Conditional average treatment effect (CATE) assessment may aid in tailoring therapy. Objectives: To estimate CATE in patients enrolled in the BaSICS trial and to assess the effects of receiving CATE model-recommended treatment in terms of hospital mortality. Methods: Post hoc analysis of the BaSICS trial assessing the effect of two infusion rates for the fluid challenge (fast, 999 ml/h, control group; vs. slow, 333 ml/h, intervention group) on hospital mortality. CATE was estimated as the difference in outcome for treatment arms in counterfactuals obtained from a Bayesian model trained in the first half of the trial adjusted for predictors hypothesized to interact with the intervention. The model recommended slow or fast infusion or made no recommendation in the second half. A threshold greater than 0.90 probability of benefit was considered. Results: A total of 10,465 patients were analyzed. The model was trained in 5,230 patients and tested in 5,235 patients. A recommendation could be made in the test set in 19% of patients (14% were recommended the control group and 5% the treatment group); for 81% of patients, no recommendation could be made. Slow infusion was more frequently recommended in cases of planned admissions in younger patients; fast infusion was recommended for older patients with sepsis. Slow infusion rate in the subgroup of patients in the test set in which slow infusion was recommended by the model was associated with an odds ratio of 0.58 (95% credible interval of 0.32-0.90; 0.99 posterior probability of benefit) for hospital mortality. Fast infusion in the subgroup in which the model recommended fast infusion was associated with an odds ratio of 0.72 (credible intervals from 0.54 to 0.91; probability of benefit >0.99). Conclusions: Estimation of CATEs from counterfactual probabilities in data from BaSICS provided additional information on trial data. Agreement between treatment recommendation and actual treatment was associated with lower hospital mortality. Clinical trial registered with clinicaltrials.gov (NCT02875873).

Study of the phytoremediation potential of native plant species identified in an area contaminated by volatile organic compounds: a systematic review.

Phytoremediation is a process that uses plants in situ to promote remediation of environments contaminated by organic or inorganic compounds. Phytoremediating species develop methods such as phytoextraction, rhizofiltration, phytodegradation, and phytovolatilization, which can manifest themselves individually or together in a single plant. This study aims to evaluate, through a systematic review, the potential phytoremediation techniques of the genera Syagrus (Mart.), Nephrolepis, Cyperus (L.), Mimosa (L.), Schinus (L.), Brachiaria, and Eryngium (L.) found in a humid area of Rio Grande do Sul, Brazil. The genera that presented significant numbers in the databases consulted were Cyperus and Brachiaria, followed by Nephrolepis. The first two are considered the most promising for phytoremediation processes. The other genera mentioned obtained favorable results for organic contaminants. The studies around these genera are still recent. It is necessary, in research, to highlight which phytoremediation processes the plants exert in relation to the contaminant of the place. In addition, priority should be given to native species that can establish themselves in the environment and that would not unbalance and harm the surrounding biota and ecosystem.

The research presents a survey of two decades in four multidisciplinary and international databases, identifying the limitation of research related to volatile and semi-volatile organic compounds, as well as contributing to the identification of native plant species that perform phytoremediation mechanisms.

Use of Deep Neural Networks in the Detection and Automated Classification of Lesions Using Clinical Images in Ophthalmology, Dermatology, and Oral Medicine-A Systematic Review.

Artificial neural networks (ANN) are artificial intelligence (AI) techniques used in the automated recognition and classification of pathological changes from clinical images in areas such as ophthalmology, dermatology, and oral medicine. The combination of enterprise imaging and AI is gaining notoriety for its potential benefits in healthcare areas such as cardiology, dermatology, ophthalmology, pathology, physiatry, radiation oncology, radiology, and endoscopic. The present study aimed to analyze, through a systematic literature review, the application of performance of ANN and deep learning in the recognition and automated classification of lesions from clinical images, when comparing to the human performance. The PRISMA 2020 approach (Preferred Reporting Items for Systematic Reviews and Meta-analyses) was used by searching four databases of studies that reference the use of IA to define the diagnosis of lesions in ophthalmology, dermatology, and oral medicine areas. A quantitative and qualitative analyses of the articles that met the inclusion criteria were performed. The search yielded the inclusion of 60 studies. It was found that the interest in the topic has increased, especially in the last 3 years. We observed that the performance of IA models is promising, with high accuracy, sensitivity, and specificity, most of them had outcomes equivalent to human comparators. The reproducibility of the performance of models in real-life practice has been reported as a critical point. Study designs and results have been progressively improved. IA resources have the potential to contribute to several areas of health. In the coming years, it is likely to be incorporated into everyday life, contributing to the precision and reducing the time required by the diagnostic process.

IMPACTO-MR: um estudo brasileiro de plataforma nacional para avaliar infecções e multirresistência em unidades de terapia intensiva / IMPACTO-MR: a Brazilian nationwide platform study to assess infections and multidrug resistance in intensive care units

RESUMO Objetivo: Descrever o IMPACTO-MR, um estudo brasileiro de plataforma nacional em unidades de terapia intensiva focado no impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. Métodos: Descrevemos a plataforma IMPACTO-MR, seu desenvolvimento, critérios para seleção das unidades de terapia intensiva, caracterização da coleta de dados, objetivos e projetos de pesquisa futuros a serem realizados na plataforma. Resultados: Os dados principais foram coletados por meio do Epimed Monitor System® e consistiram em dados demográficos, dados de comorbidades, estado funcional, escores clínicos, diagnóstico de internação e diagnósticos secundários, dados laboratoriais, clínicos e microbiológicos e suporte de órgãos durante a internação na unidade de terapia intensiva, entre outros. De outubro de 2019 a dezembro de 2020, 33.983 pacientes de 51 unidades de terapia intensiva foram incluídos no banco de dados principal. Conclusão: A plataforma IMPACTO-MR é um banco de dados clínico brasileiro de unidades de terapia intensiva focado na pesquisa do impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. Essa plataforma fornece dados para o desenvolvimento e pesquisa de unidades de terapia intensiva individuais e ensaios clínicos observacionais e prospectivos multicêntricos.

ABSTRACT Objective: To describe the IMPACTO-MR, a Brazilian nationwide intensive care unit platform study focused on the impact of health care-associated infections due to multidrug-resistant bacteria. Methods: We described the IMPACTO-MR platform, its development, criteria for intensive care unit selection, characterization of core data collection, objectives, and future research projects to be held within the platform. Results: The core data were collected using the Epimed Monitor System® and consisted of demographic data, comorbidity data, functional status, clinical scores, admission diagnosis and secondary diagnoses, laboratory, clinical, and microbiological data, and organ support during intensive care unit stay, among others. From October 2019 to December 2020, 33,983 patients from 51 intensive care units were included in the core database. Conclusion: The IMPACTO-MR platform is a nationwide Brazilian intensive care unit clinical database focused on researching the impact of health care-associated infections due to multidrug-resistant bacteria. This platform provides data for individual intensive care unit development and research and multicenter observational and prospective trials.