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BackgroundClogging is characterized by a progressive impairment of transmembrane patency in renal replacement devices and occurs due to obstruction of pores by unknown molecules. If citrate-based anti-coagulation is used, clogging can manifest as a metabolic alkalosis accompanied by hypernatremia and hypercalcemia, primarily a consequence of Na3Citrate infusion. An increased incidence of clogging has been observed during the COVID-19 pandemic. However, precise factors contributing to the formation remain uncertain. This investigation aimed to analyze its incidence and assessed time-varying trajectories of associated factors in critically ill patients on continuous renal replacement therapy (CRRT).MethodsIn this retrospective, single-center data analysis, we evaluated COVID-19 patients undergoing CRRT and admitted to critical care between March 2020 and December 2021. We assessed the proportional incidence of clogging surrogates in the overall population and subgroups based on the specific CRRT devices employed at our institution, including multiFiltrate (Fresenius Medical Care) and Prismaflex System (Baxter). Moderate and severe clogging were defined as Na > 145 or ≥ 150 mmol/l and HCO3− > 28.0 or ≥ 30 mmol/l, respectively, with a total albumin-corrected calcium > 2.54 mmol/l. A mixed effect model was introduced to investigate factors associated with development of clogging.ResultsFifty-three patients with 240 CRRT runs were analyzed. Moderate and severe clogging occurred in 15% (8/53) and 19% (10/53) of patients, respectively. Twenty-seven percent (37/136) of CRRTs conducted with a multiFiltrate device met the criteria for clogging, whereas no clogging could be observed in patients dialyzed with the Prismaflex System. Occurrence of clogging was associated with elevated triglyceride plasma levels at filter start (p = 0.013), amount of enteral nutrition (p = 0.002) and an increasing white blood cell count over time (p = 0.002).ConclusionsClogging seems to be a frequently observed phenomenon in critically ill COVID-19 patients. The presence of hypertriglyceridemia, combined with systemic inflammation, may facilitate the development of an impermeable secondary membrane within filters, thereby contributing to compromised membrane patency.

ObjectiveVeno-venous (V-V) extracorporeal membrane oxygenation (ECMO) is increasingly used to support patients with severe acute respiratory distress syndrome (ARDS). In case of additional cardio-circulatory failure, some experienced centers upgrade the V-V ECMO with an additional arterial return cannula (termed V-VA ECMO). Here we analyzed short- and long-term outcome together with potential predictors of mortality.DesignMulticenter, retrospective analysis between January 2008 and September 2021.SettingThree tertiary care ECMO centers in Germany (Hannover, Bonn) and Switzerland (Zurich).PatientsSeventy-three V-V ECMO patients with ARDS and additional acute cardio-circulatory deterioration required an upgrade to V-VA ECMO were included in this study.Measurements and main resultsFifty-three patients required an upgrade from V-V to V-VA and 20 patients were directly triple cannulated. Median (Interquartile Range) age was 49 (28–57) years and SOFA score was 14 (12–17) at V-VA ECMO upgrade. Vasoactive-inotropic score decreased from 53 (12–123) at V-VA ECMO upgrade to 9 (3–37) after 24 h of V-VA ECMO support. Weaning from V-VA and V-V ECMO was successful in 47 (64%) and 40 (55%) patients, respectively. Duration of ECMO support was 12 (6–22) days and ICU length of stay was 32 (16–46) days. Overall ICU mortality was 48% and hospital mortality 51%. Two additional patients died after hospital discharge while the remaining patients survived up to two years (with six patients being lost to follow-up). The vast majority of patients was free from higher degree persistent organ dysfunction at follow-up. A SOFA score > 14 and higher lactate concentrations at the day of V-VA upgrade were independent predictors of mortality in the multivariate regression analysis.ConclusionIn this analysis, the use of V-VA ECMO in patients with ARDS and concomitant cardiocirculatory failure was associated with a hospital survival of about 50%, and most of these patients survived up to 2 years. A SOFA score > 14 and elevated lactate levels at the day of V-VA upgrade predict unfavorable outcome.

Background Regional citrate anticoagulation (RCA) is the recommended anticoagulation strategy for continuous kidney replacement therapy (CKRT). However, the safety of RCA in patients with liver dysfunction and/or shock remains controversial due to the risk of citrate accumulation. This study assesses the associations of citrate accumulation with liver dysfunction, circulatory shock, and mortality, and investigates lactate and the vasoactive inotropic score (VIS) as early predictors. Methods This retrospective cohort study included critically ill patients requiring RCA-based CKRT between January 2018 and March 2022. Lactate, VIS and parameters of organ failure were investigated as predictors of citrate accumulation. An albumin-corrected total calcium to ionized calcium ratio ≥ 2.5 was used to define citrate accumulation. Regression models were employed to investigate the association of predictors with outcomes. Results Nine hundred eleven patients were included, citrate accumulation was observed in 159 individuals (17%). Factors related to liver dysfunction, but not circulatory shock, were attributed to citrate accumulation. After multivariable adjustment, citrate accumulation was not associated with mortality. Lactate measured before onset of CKRT showed an improved discriminative performance compared to the VIS. The odds of citrate accumulation increased by 2.34 (CI 1.94–2.85, p  < 0.001) for each one-unit increase in lactate on the logarithmic scale (log mmol/L). The probability for citrate accumulation ranged from 3.3 (CI 2.06–5.28) % at lactate levels of 0.3 mmol/L to 59.8 (CI 48.88–69.78) % at levels of 25 mmol/L. Conclusion Lactate is a reliable predictor for assessing the risk of citrate accumulation in patients undergoing CKRT. Further research is needed to develop and validate predictive algorithms for various anticoagulation strategies to offer reliable support for personalized decision-making in clinical practice.

The continued digitalization of medicine has led to an increased availability of longitudinal patient data that allows the investigation of novel and known diseases in unprecedented detail. However, to accurately describe any underlying pathophysiology and allow inter-patient comparisons, individual patient trajectories have to be synchronized based on temporal markers. In this pilot study, we use longitudinal data from critically ill ICU COVID-19 patients to compare the commonly used alignment markers “onset of symptoms,” “hospital admission,” and “ICU admission” with a novel objective method based on the peak value of the inflammatory marker C-reactive protein (CRP). By applying our CRP-based method to align the progression of neutrophils and lymphocytes, we were able to define a pathophysiological window that improved mortality risk stratification in our COVID-19 patient cohort. Our data highlights that proper synchronization of longitudinal patient data is crucial for accurate interpatient comparisons and the definition of relevant subgroups. The use of objective temporal disease markers will facilitate both translational research efforts and multicenter trials.

Elucidation of the mechanisms involved in long-distance water transport in trees requires knowledge of the water distribution within the sapwood and heartwood of the stem as well as of the earlywood and latewood of an annual ring. X-ray computed tomography is a powerful tool for measuring density distributions and water contents in the xylem with high spatial resolution. Ten- to 20-year-old spruce (Picea abies L. KARST.) and oak (Quercus robur) trees grown in the field were used throughout the experiments. Stem and branch discs were collected from different tree heights, immediately deep frozen, and used for the tomographic determinations of spatial water distributions. Results are presented for single-tree individuals, demonstrating heartwood and sapwood distribution throughout their entire length as well as the water relations in single annual rings of both types of wood. Tree rings of the sapwood show steep water gradients from latewood to earlywood, whereas those of the heartwood reflect water deficiency in both species. Although only the latest two annual rings of the ringporous species are generally assumed to transport water, we found similar amounts of water and no tyloses in all rings of the oak sapwood, which indicates that at least water storage is important in the whole sapwood.

Hyperammonemia is a life-threatening condition, the prognosis of which depends on a rapid reduction of ammonia. If a hepatic cause is excluded, the differential diagnosis is broad and even in adulthood includes hereditary metabolic diseases. Here, the case of a 25-year-old female patient with severe hyperammonemia refractory to standard therapy is described and the relevance of extracorporeal elimination of ammonia emphasized.

In 2019, the dominant greenhouse gases released into Earth’s atmosphere continued to increase. The annual global average carbon dioxide concentration at Earth’s surface was 409.8 ± 0.1 ppm, an increase of 2.5 ± 0.1 ppm over 2018, and the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contributed 3.14 W m−2 to radiative forcing, representing a 45% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. The annual net global uptake of ∼2.4 billion metric tons of carbon dioxide by oceans was the highest in the record dating to 1982 and 33% higher than the 1997–2017 average. A weak El Niño at the beginning of 2019 transitioned to ENSO-neutral conditions by mid-year. Even so, the annual global surface temperature across land and oceans was still among the three highest in records dating to the mid- to late 1800s. July 2019 was Earth’s hottest month on record. Well over a dozen countries across Africa, Europe, Asia, Australia, and the Caribbean reported record high annual temperatures. In North America, Alaska experienced its warmest year on record, while the high northern latitudes that encompass the Arctic were second warmest, behind only 2016. Stations in several countries, including Vietnam, the Netherlands, Belgium, Luxembourg, France, and the United Kingdom, set new all-time daily high temperature records for their nations. Australia set a new nationally averaged daily maximum temperature record of 41.9°C on 18 December, breaking the previous record set in 2013 by 1.6°C. Daily temperatures surpassed 40°C for the first time in Belgium and the Netherlands. Lake temperatures increased on average across the globe in 2019; observed lakes in the Northern Hemisphere were covered in ice seven days fewer than the 1981–2010 average, according to phenological indicators. Over land, the growing season was an average of eight days longer than the 2000–10 average in the NH. Above Earth’s surface, the annual lower troposphere temperature was third highest to record high, and the lower stratosphere temperature was third lowest to record low, depending on the dataset analyzed. Middle- and upper-stratospheric temperatures were lowest on record since satellite records began in 1979. In September, Antarctica experienced a dramatic upper-atmosphere warming event that led to the smallest ozone hole since the early 1980s. Below-average Antarctic sea ice extent persisted throughout 2019, continuing a trend that began in September 2016. Net sea ice extent was below the 1981–2010 average for all days of the year, and January and June each set a new low monthly mean sea ice extent record. The Antarctic ice sheet continued to lose mass, with the highest rates of loss occurring in West Antarctica and Wilkes Land, East Antarctica. Across the cryosphere, alpine glaciers continued to lose mass for the 32nd consecutive year. Permafrost temperatures in the European Alps were slightly below the record temperatures measured in 2015, while record high permafrost temperatures were observed at a majority of the observation sites across the high northern latitudes. For the first time in the observational record at 26 sites in interior Alaska and the Seward Peninsula, the active layer did not freeze completely, a result of long-term permafrost warming and back-to-back relatively mild and snowy winters. In March, when Arctic sea ice reached its annual maximum extent, thin, first-year ice comprised ∼77% of all ice, compared to about 55% in the 1980s. In September, the minimum sea ice extent tied for the second smallest extent in the 41-year satellite record. In the Bering Sea, increasing ocean temperatures and reduced sea ice—which was the lowest on record there for the second consecutive winter—are leading to shifts in fish distributions within some of the most valuable fisheries in the world. Larger and more abundant boreal species, as opposed to smaller and less abundant Arctic species, dominated a large portion of the Arctic shelf in 2018 and 2019. During the 2019 melt season, the extent and magnitude of ice loss over the Greenland ice sheet rivaled 2012, the previous year of record ice loss. Melting of glaciers and ice sheets, along with warming oceans, account for the trend in rising global mean sea level. In 2019, global mean sea level set a new record for the eighth consecutive year, reaching 87.6 mm above the 1993 average when satellite measurements began, with an annual average increase of 6.1 mm from 2018. Ocean heat content measured to 700 m depth was record high, and the globally averaged sea surface temperature was the second highest on record, surpassed only by the record El Niño year of 2016. In October, the Indian Ocean dipole exhibited its greatest magnitude since 1997, associated with dramatic upper ocean warming in the western Indian Ocean basin. While ENSO conditions during 2019 appeared to have limited impacts, many climate events were influenced by the strong positive IOD, which contributed to a large rainfall deficit from the eastern Indian Ocean to the South Pacific Ocean east of Australia. Record heat and dryness in Australia intensified drought conditions already in place following below-average rainfall in 2017 and 2018, leading to severe impacts during late austral spring and summer, including catastrophic wildfires. Smoke from these wildfires, along with the volcanic eruptions of Raikoke (Russia) and Ulawun (Papua New Guinea), helped load the stratosphere with aerosol levels unprecedented since the post-Mt. Pinatubo era of the early 1990s. Indonesia also suffered severe drought and extreme wildfires toward the end of 2019; no rainfall was observed in the East Sumba District of the East Nusa Tenggara Province for 263 days. Conversely, the positive IOD also contributed to excess rainfall over the Horn of Africa from August through December, resulting in widespread flooding across East Africa. Elsewhere, India experienced one of its heaviest summer monsoon rains since 1995 despite a delayed and suppressed monsoon during June. In the United States, rapid snowmelt in the spring, as well as heavy and frequent precipitation in the first half of the year, contributed to extensive flooding in the Midwest throughout spring and summer, notably the Mississippi and Missouri basins. Dry conditions persisted over large parts of western South Africa, in some locations having continued for approximately seven years. Antecedent dry conditions and extreme summer heat waves pushed most of Europe into extreme drought. Due in part to precipitation deficits during December 2018 to January 2019—the peak of the rainy season—wildfires scorched vast areas of the southern Amazonian forests in Bolivia, Brazil, and Peru, as well as in northern Paraguay, later in 2019. Millions of trees and animals perished, with some local extinctions reported. In Siberia, fire activity during the summer was both strong and farther north than usual. This led to a new record of 27 teragrams (1012 g) of carbon emitted from fires in the Arctic, which was more than twice as high than in any preceding year. Closer to the equator, 96 named tropical storms were observed during the Northern and Southern Hemisphere storm seasons, well above the 1981–2010 average of 82. Five tropical cyclones reached Saffir–Simpson scale Category 5 intensity. In the North Atlantic basin, Hurricane Dorian caused unprecedented and tremendous devastation, with over 70 fatalities and damages totaling $3.4 billion (U.S. dollars) in The Bahamas. Tropical Cyclones Idai and Kenneth severely impacted southeastern Africa in March and April, respectively. Idai resulted in total damages of at least $2.2 billion (U.S. dollars), the costliest storm on record for the South Indian Ocean basin, as well as the deadliest with over 1200 fatalities across Mozambique, Zimbabwe, Malawi, and Madagascar.

Zusammenfassung Die Hyperammonämie ist ein lebensbedrohliches Krankheitsbild, dessen Prognose von einer raschen Senkung des Ammoniaks abhängt. Ist eine hepatische Ursache ausgeschlossen, ist die Differenzialdiagnose breit und umfasst auch im Erwachsenenalter hereditäre Stoffwechselerkrankungen. Hier beschreiben wir den Fall einer 25-jährigen Patientin mit einer schweren, therapierefraktären Hyperammonämie und betonen die Relevanz der extrakorporalen Elimination des Ammoniaks.