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Purpose Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs). Methods This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI). Results Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76–1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54–1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84–5.34). Conclusion There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols.

The prevalence of direct kidney involvement in novel coronavirus disease (COVID-19) is low, but such involvement is a marker of multiple organ dysfunction and severe disease. Here, we explore potential pathways of kidney damage and discuss the rationale for extracorporeal support with various blood purification strategies in patients who are critically ill with COVID-19.

The Varian Ethos system allows for online adaptive treatments through the utilization of artificial intelligence (AI) and deformable image registration which automates large parts of the anatomical contouring and plan optimization process. In this study, treatments of intact prostate and prostate bed, with and without nodes, were simulated for 182 online adaptive fractions, and then a further 184 clinical fractions were delivered on the Ethos system. Frequency and magnitude of contour edits were recorded, as well as a range of plan quality metrics. From the fractions analyzed, 11% of AI generated contours, known as influencer contours, required no change, and 81% required minor edits in any given fraction. The frequency of target and noninfluencer organs at risk (OAR) contour editing varied substantially between different targets and noninfluencer OARs, although across all targets 72% of cases required no edits. The adaptive plan was the preference in 95% of fractions. The adaptive plan met more goals than the scheduled plan in 78% of fractions, while in 15% of fractions the number of goals met was the same. The online adaptive recontouring and replanning process was carried out in 19 min on average. Significant improvements in dosimetry are possible with the Ethos online adaptive system in prostate radiotherapy.

The rapid adoption of robotic surgical systems across Europe has led to a critical gap in training and credentialing for gastrointestinal (GI) surgeons. Currently, there is no existing standardised curriculum to guide robotic training, assessment and certification for GI trainees. This manuscript describes the protocol to achieve a pan-European consensus on the essential components of a comprehensive training programme for GI robotic surgery through a five-stage process. In Stage 1, a Steering Committee, consisting of international experts, trainees and educationalists, has been established to lead and coordinate the consensus development process. In Stage 2, a systematic review of existing multi-specialty robotic training curricula will be performed to inform the formulation of key position statements. In Stage 3, a comprehensive survey will be disseminated across Europe to capture the current state of robotic training and identify potential challenges and opportunities for improvement. In Stage 4, an international panel of GI surgeons, trainees, and robotic theatre staff will participate in a three-round Delphi process, seeking [greater than or equal to] 70% agreement on crucial aspects of the training curriculum. Industry and patient representatives will be involved as external advisors throughout this process. In Stage 5, the robotic training curriculum for GI trainees will be finalised in a dedicated consensus meeting, culminating in the production of an Explanation and Elaboration (E&E) document.

Abstract Image guidance (IG) and robotics systems are becoming more widespread in their utilization and can be invaluable intraoperative adjuncts during spine surgery. Both are highly reliant upon stereotaxy and either pre- or intraoperative radiographic imaging. While user-operated IG systems have been commercially available longer and subsequently are more widely utilized across centers, robotics systems provide unique theoretical advantages over freehand and IG techniques for placing instrumentation within the spine. While there is a growing plethora of data showing that IG and robotic systems decrease the incidence of malpositioned screws, less is known about their impact on clinical outcomes. Both robotics and IG may be of particular value in cases of substantial deformity or complex anatomy. Indications for the use of these systems continue to expand with an increasing body of literature justifying their use in not only guiding thoracolumbar pedicle screw placement, but also in cases of cervical and pelvic instrumentation as well as spinal tumor resection. Both techniques also offer the potential benefit of reducing occupational exposures to ionizing radiation for the operating room staff, the surgeon, and the patient. As the use of IG and robotics in spine surgery continues to expand, these systems’ value in improving surgical accuracy and clinical outcomes must be weighed against concerns over cost and workflow. As newer systems incorporating both real-time IG and robotics become more utilized, further research is necessary to better elucidate situations where these systems may be particularly beneficial in spine surgery.

BackgroundMulti-organ dysfunction in critical illness is common and frequently involves the lungs and kidneys, often requiring organ support such as invasive mechanical ventilation (IMV), renal replacement therapy (RRT) and/or extracorporeal membrane oxygenation (ECMO).MethodsA consensus conference on the spectrum of lung–kidney interactions in critical illness was held under the auspices of the Acute Disease Quality Initiative (ADQI) in Innsbruck, Austria, in June 2018. Through review and critical appraisal of the available evidence, the current state of research, and both clinical and research recommendations were described on the following topics: epidemiology, pathophysiology and strategies to mitigate pulmonary dysfunction among patients with acute kidney injury and/or kidney dysfunction among patients with acute respiratory failure/acute respiratory distress syndrome. Furthermore, emphasis was put on patients receiving organ support (RRT, IMV and/or ECMO) and its impact on lung and kidney function.ConclusionThe ADQI 21 conference found significant knowledge gaps about organ crosstalk between lung and kidney and its relevance for critically ill patients. Lung protective ventilation, conservative fluid management and early recognition and treatment of pulmonary infections were the only clinical recommendations with higher quality of evidence. Recommendations for research were formulated, targeting lung–kidney interactions to improve care processes and outcomes in critical illness.

Pulse oximetry is universally used for monitoring patients in the critical care setting. This article updates the review on pulse oximetry that was published in 1999 in Critical Care . A summary of the recently developed multiwavelength pulse oximeters and their ability in detecting dyshemoglobins is provided. The impact of the latest signal processing techniques and reflectance technology on improving the performance of pulse oximeters during motion artifact and low perfusion conditions is critically examined. Finally, data regarding the effect of pulse oximetry on patient outcome are discussed.

Fixing cells with paraformaldehyde (PFA) is an essential step in numerous biological techniques as it is thought to preserve a snapshot of biomolecular transactions in living cells. Fixed-cell imaging techniques such as immunofluorescence have been widely used to detect liquid–liquid phase separation (LLPS) in vivo. Here, we compared images, before and after fixation, of cells expressing intrinsically disordered proteins that are able to undergo LLPS. Surprisingly, we found that PFA fixation can both enhance and diminish putative LLPS behaviors. For specific proteins, fixation can even cause their droplet-like puncta to artificially appear in cells that do not have any detectable puncta in the live condition. Fixing cells in the presence of glycine, a molecule that modulates fixation rates, can reverse the fixation effect from enhancing to diminishing LLPS appearance. We further established a kinetic model of fixation in the context of dynamic protein–protein interactions. Simulations based on the model suggest that protein localization in fixed cells depends on an intricate balance of protein–protein interaction dynamics, the overall rate of fixation, and notably, the difference between fixation rates of different proteins. Consistent with simulations, live-cell single-molecule imaging experiments showed that a fast overall rate of fixation relative to protein–protein interaction dynamics can minimize fixation artifacts. Our work reveals that PFA fixation changes the appearance of LLPS from living cells, presents a caveat in studying LLPS using fixation-based methods, and suggests a mechanism underlying the fixation artifact. A typical human cell is a crowded soup of thousands of different proteins. One way that the cell organizes this complex mix of contents is by creating separate droplets within the cell, like oil in water. These droplets can form through a process known as liquid-liquid phase separation, or LLPS, where specific proteins gather in high concentrations to carry out their cellular roles. The critical role of LLPS in cellular organization means that it is widely studied by biologists. To detect LLPS, researchers often subject the cells to treatments designed to hold all the proteins in place, creating a snapshot of their natural state. This process, known as fixing, allows scientists to easily label a protein with a fluorescent tag, take pictures of the cells, and look at whether the protein forms droplets in its natural state. This is often easier to do than imaging cells live, but it relies on LLPS being well-preserved upon fixation. To test if this is true, Irgen-Gioro, Yoshida et al. looked at protein droplets in live cells, and then fixed the cells to check whether the appearance of the droplets had changed. The images taken showed that fixation could alter the size and number of droplets depending on the protein being studied. To explain why the effects of fixing change depending on the protein, Irgen-Gioro, Yoshida et al. hypothesized that a faster fixation – relative to how quickly proteins can bind and unbind to their droplets – can better preserve the LLPS droplets. They verified their idea using a microscopy technique in which they imaged single molecules, allowing them to see how different fixation speeds relative to protein binding affected the droplets. The work of Irgen-Gioro, Yoshida et al. identifies an important caveat to using fixation for the study of LLPS in cells. Their findings suggest that researchers should be cautious when interpreting the results of such studies. Given that LLPS in cells is an area of research with a lot of interest, these results could benefit a broad range of biological and medical fields. In the future, Irgen-Gioro, Yoshida et al.’s findings could prompt scientists to develop new fixing methods that better preserve LLPS in cells.

Macrophages are diverse immune cells that reside in all tissues. Although macrophages have been implicated in mammary-gland function, their diversity has not been fully addressed. By exploiting high-resolution three-dimensional imaging and flow cytometry, we identified a unique population of tissue-resident ductal macrophages that form a contiguous network between the luminal and basal layers of the epithelial tree throughout postnatal development. Ductal macrophages are long lived and constantly survey the epithelium through dendrite movement, revealed via advanced intravital imaging. Although initially originating from embryonic precursors, ductal macrophages derive from circulating monocytes as they expand during puberty. Moreover, they undergo proliferation in pregnancy to maintain complete coverage of the epithelium in lactation, when they are poised to phagocytose milk-producing cells post-lactation and facilitate remodelling. Interestingly, ductal macrophages strongly resemble mammary tumour macrophages and form a network that pervades the tumour. Thus, the mammary epithelium programs specialized resident macrophages in both physiological and tumorigenic contexts.Dawson et al. characterize a macrophage population associated with mammary ducts that are long lived, derive from embryonic precursors and have multiple roles in pregnancy, lactation, involution and cancer.

Metodos Se recogieron y pesaron los componentes de 21 pruebas comerciales de flujo lateral de la enfermedad por coronavirus de 2019 (COVID-19) de los Estados Unidos de America, el Reino Unido de Gran Bretana e Irlanda del Norte, la Union Europea y el procedimiento de inclusion en la lista de uso de emergencia de la Organizacion Mundial de la Salud. Se desmontaron manualmente los kits de pruebas, se clasificaron los componentes y se pesaron por separado.