In vitro experiments showed that the release of curcumin from the HPMC mixture was significantly slower due to the sustained-release property of HPMC as a typical excipient. The release profile of curcumin from the HPMC mixture was relatively stable for a controlled release. SEM images show that the HPMC co-spray-dried powders have crumpled surfaces due to the large molecular weight of HPMC. DSC, XRD, FTIR, N2 adsorption, and TGA have been measured for the spray-dried curcumin materials. This work indicates that HPMC can be used as a controlled-release excipient for curcumin preparations.In order to achieve the controlled release of curcumin, HPMC (hydroxypropyl methyl cellulose) was spray dried with curcumin and lactose. The spray-dried materials were pressed into tablets with a diameter of 8 mm, and their release characteristics  Curcumin is a hydrophobic polyphenol extracted from the root and stem of turmeric. It has a variety of pharmacological properties, including antioxidant, anti-inflammatory, anticancer, and treatment of nerve diseases . HoweverHydroxypropyl methylcellulose (HPMC) is a semisynthetic dietary polymer based on cellulose. HPMC is used as a food ingredient and in the food industry as an emulsifier, suspension agent, film-forming agent, stabilizer, or thickener. In addition, HPMC is used as an excipient in pharmaceutical preparations to improve the solubility of active pharmaceutical ingredients and to control drug delivery –5.Many methods have been reported to increase the solubility of curcumin and promote its bioavailability. Relative techniques include the preparation of colloids, protein-based complexes, solid dispersions, nanoemulsions –8, and sConsidering the physical product stability and security problems, the experimental design used water as a dispersion medium and selected lactose, a commonly used drug-excipient, as the water-soluble carrier. HPMC was used as the studying excipient for the control the curcumin dissolution rate. After high-speed stirring of mixed suspension, the spray drying technique was used to dry the mixture.α-lactose monohydrate (purity > 99.9%) was purchased from Jiangsu Dawning Pharmaceutical Co., Ltd.; and curcumin (purity > 98.0%) was purchased from Tonghua Food & Chemical Co., Ltd.HPMC (SE-E5) was purchased from Anhui Sunhere Pharmaceutical Excipients Co., Ltd.; the pharmaceutical-grade In order to study the sustained-release effects of HPMC for curcumin, the experiment was carried out with spray drying of suspension A containing curcumin and lactose and suspension B containing curcumin, lactose, and HPMC, respectively. Suspension A contains 10% curcumin and 20% lactose in water, which were mixed at high stirring speed for 1 min. Suspension B contains 10% curcumin, 15% lactose, and 10% HPMC in water, after mixing by high-speed stirring, forming a foam-like mixture for spray drying. In the experiment, the same spray-drying parameters were used for the two suspensions. The spray dryer  was adjusted to the optimal parameters: an inlet air temperature of 140°C, outlet air temperature of 125°C, fan frequency of 50 Hz, peristaltic pump speed of 15 rpm/min, spray pressure of 0.65 MPa, and nozzle diameter of 1.0 mm. Suspensions A and B were spray dried, respectively, and the powders were collected in the collection vessel .2 as the purge gas. Heat flow as a function of increasing temperature was recorded for the analysis of each sample. Fourier transform infrared (FTIR) spectroscopy was used to investigate the production and the raw material . The specimen was mixed with KBr powder, tableted, and scanned for transmission sensitivity in a Nicolet 6700 FTIR spectrometer (Thermo Fisher Scientific). The FTIR spectra used a resolution of 1 cm−1 with 64 scans. The solid powder sample was placed on a carbon tape on an aluminum sample spike. The gold-plated particles were observed by using a JSM-7200F scanning electron microscope . Thermogravimetric analysis (TGA Q5000 V3.17 Build 265) was performed for the sample. Measurement was carried out on the sample loaded in small alumina pans with N2 as the balance gas. The temperature was set from 20°C to 350°C, with a constant heating rate of 5°C/min, under a flow of nitrogen gas in pyrolysis condition. XRD analysis was used to investigate the crystalline characteristics of the solid powder. Solid samples were loaded on powder holders and analyzed using a Siemens D5000 diffractometer. One gram of the sample was dispersed in the sample holder. The scanning region of diffraction angle (2θ) was set from 5 to 40° with a scanning rate of 1.2°/min, a scanning current of 30 mA, and a scanning voltage of 40 kV. The N2 adsorption was carried out for the powder sample to determine the porosity.The UV-vis absorption spectra were recorded in the range 350–450 nm  with a UIn order to further study the HPMC effect in a microsense, scanning electron microscopy (SEM) was used. As shown in Figures α-lactose peaks are observed at 2θ of 12.5°, 19.1°, 19.6°, and 19.9°. The spectra showed that the HPMC-contained sample was crystalline with sharp peaks observed. The changes in peak intensity and wavenumber shift were studied by FTIR (−1 indicates the presence of hydroxide, indicating the presence of water which agreed with the DSC result [The DSC curves  show tha by FTIR . The peaC result .2 adsorption-desorption isotherms for the HPMC-contained sample. The isotherms display class II behavior. In the process of increasing gas pressure, countermolecular layer adsorption and multimolecular layer adsorption are carried out simultaneously in which the “knee” point is not sharp. According to the BET result, the sample has a nonporous or macroporous structure. According to TGA analysis (BET  spectra analysis , HPMC diin vitro were measured. In vitro experiments showed that the release of curcumin from the HPMC mixture was significantly slower due to the sustained-release property of HPMC as a typical excipient. The release profile of curcumin from the HPMC mixture was relatively stable for a controlled release. SEM images show that the HPMC co-spray-dried powders have crumpled surfaces due to the large molecular weight of HPMC. DSC, XRD, FTIR, N2 adsorption, and TGA have been measured for the spray-dried curcumin materials. The work indicates that HPMC can be used as a controlled-release excipient for curcumin preparations.In this work, HPMC was spray dried with curcumin and lactose. The spray-dried materials were pressed into tablets, and its release characteristics


Dual in utero electroporation provides a precise and effective tool to label and manipulate gene expression in multiple neuronal populations within a circuit in a spatially and temporally regulated manner. In addition, this technique allows for morphophysiological investigations into neuronal development and connectivity following cell-specific gene manipulations. Here, we detail the dual  In utero electroporation (IUE) is a powerful tool to target specific neuronal populations in the developing cortex with temporal and spatial resolution . The proThis protocol can be utilized to target different cortical regions, such as the medial prefrontal cortex (mPFC), as well as the hippocampus. In the DNA-encoding vector, different promoters can be used to restrict gene expression in neurons while bypassing expression in neural progenitor cells  for electroporation.a. Use a plasmid encoding a fluorescent protein under the CAG promoter  pCAG-tdTomato or pCAG-GFP, to label neurons and detect efficient electroporation at birth in live mice.Timing: 15 min.LoxP-stop-LoxP-DsRed, called pCALNL-DsRed, addgene: #13769) together with pCAG-GFP and low concentration of pCAG-Cre to label a subset of GFP-expressing neurons within the electroporated region , then heat electrodes to 70.5 °C for these experiments. Use only the bottom electrode.5. Place the micropipette tip inside the 6 mm O.D. large round-tipped forceps and gently break off the tip to create an angle of about 45° . Break mTiming: 15 min.CRITICAL: If the micropipette tip is too dull, then it will not penetrate the embryonic sac. If the tip is too thin, then it will be challenging to deposit plasmid into the brain. If there is clear damage to the cortex after electroporation, then the tip is likely too thick .6. Autoclave large and small round-tipped forceps, needle driver, and scissors. This can be completed the day of or the night before.7. Place sterile 1x PBS into 30- or 50-ml syringes fitted with a 0.22 mm filter for surgeries.8. Sterilize fenestrated drapes and gauze.Timing: 1.5 h.1. Prewarm the heating pad in a microwave and PBS to 37°C in a water bath. Wipe down the surgical area with 70% ethanol.2. Just before beginning surgery, administer 0.1 mg/ kg body weight subcutaneous (s.c.) buprenorphine to timed-pregnant mice.3. Anesthetize a E13.5 timed-pregnant mouse by placing it in the isoflurane induction chamber.a. Turn on oxygen, and open primary and secondary flowmeters. Set the secondary flowmeter to ∼1.5 LPM.b. Turn on isoflurane to 4% and wait until the mouse is immobile, then decrease the level to 2%.4. After ∼3 min, take the mouse out of the chamber and shave the mouse’s belly with clippers while it is anesthetized.Timing: 0.5–1.0 h.Note: Suitable embryonic age can be differ depending on the regions.5. Move the mouse onto the heating pad with its abdomen exposed and place its nose into the nose cone.a. Put ophthalmic ointment on the eyes.b. Place 2.5% lidocaine prilocaine cream on its abdomen and tape the limbs down.6. Wipe down the abdomen using alternative swabs of prevantics and alcohol. Do this three times, starting with prevantics and ending with alcohol.7. Cover the abdomen with a piece of fenestrated sterile drape and gauze.a. Align the hole to be around the area of the incision.b. Drench the gauze with the warm, sterile PBS.8. Pinch the skin using the small ringed forceps and lift skin, make a skin incision of ∼2 cm long though the midline with scissors.9. Using the small ringed forceps, lift the muscle of abdominal wall and make an incision with scissors through the linea alba (white line) to avoid cutting of major blood vessels.CRITICAL: If the mouse starts waking up after completion of the shaving procedure, place it back in the induction chamber and repeat Step 3.10. Gently move the uterine horns out through the incision using the large ring forceps and lay the uterine horns on the top of the gauze with the number of embryos counted and write the sequence of embryos in a notebook . RegularCRITICAL: Lifting the muscle before the incision of abdominal wall is important to avoid injuries of organs and embryos underneath. Begin with a small cut to allow the air in to push apart the abdominal wall and tissue underneath.11. Inject 1–2 μL plasmid DNA solution into the lateral ventricle using a mouth-controlled micropipette, which consists of a 1 ml syringe sans plunger, 15″ aspirator tube assembly, 0.22 mm filter, and micropipette .CRITICAL: Carefully pull the uterine horns out of the abdominal cavity with the large ring forceps. Gently pull at the areas where embryos meet, rather than pulling directly on the embryos, to avoid damaging them. Alternatively, one can use fingers to gently move the embryos out while holding the peritoneum up and to the side with large ringed forceps.Note: The lateral ventricle should be filled with fast green if the injection is successful .CRITICAL: To increase survival rate after the second IUE, inject embryos in an alternating pattern.CRITICAL: Avoid placing too much of the micropipette tip inside the embryonic sac. Doing so leads to holes, which can cause amniotic fluid to leak and increase the risk of abortion.12. Place forceps-type electrodes (tweezertrode diameter: 2 mm) parallel to DNA-injected embryos (position and direction of electrodes depend on the desired target areas) and deliver 36 mV for 50 ms-long electric pulses with a 950 ms pulse interval.CRITICAL: Micropipette tips should not be reused for more than 10 embryos since the tip becomes blunt, which increases potential damage to embryos. Do not reuse electrodes across litters and conditions.Note: The electrodes should be placed in PBS-containing conical tube to keep them wet.CRITICAL: The tweezertrode anode should be placed to direct the DNA toward the progenitor cell population of interest. For the SSC, the tweezertrodes will be orthogonally oriented with the anode on the barrel cortex. The embryo should move slightly when electrical pulses are being applied.13. Repeat steps 11–12 for the desired embryos. Keep track of which embryos and hemispheres are electroporated.CRITICAL: Gently push the embryo towards the embryonic sac to ensure more efficient electroporation delivery. The limbs of embryo should move after each electric pulse.14. Reposition the horns carefully using the large ring forceps back into the abdominal cavity. Fill cavity with warm PBS.15. Suture the abdominal wall and skin with absorbable PDS suture line.16. Cover the skin incision with triple antibiotic.17. Administer 5 mg/ kg/s.c. Rimadyl (carprofen).18. Place the mouse in an empty cage on top of a heating pad until awake.19. Upon waking, move the mouse back to its home cage. Put moistened food in the cage.CRITICAL: Regularly drop warm PBS onto the uterine horns before moving to the next electroporation.20. Monitor mouse at 24 h post-surgery and administer 5 mg/kg/s.c. Rimadyl (carprofen).21. 48 h after the first IUE (E15.5), and 10 min prior to surgery, administer 0.1 mg/kg/s.c. Buprenorphine.Timing: 0.5–1.0 h.22. Anesthetize the mouse and repeat steps 1–7.23. Using the small ringed forceps to pinch and lift skin, cut the suture line from the first surgery and gently open the original skin and abdominal wall incision.CRITICAL: Performing the second IUE too soon  following the first IUE results in a larger degree of co-localization between electroporated cell populations .22. Anes24. Guide uterine horns out and lay them on the top of the gauze. Regularly wet uterine horns with warm PBS.25. Find the electroporated embryos from last surgery and inject 1–2 μL plasmid DNA solution into the lateral ventricle using a micropipette. Make sure the lateral ventricle is filled with fast green.26. Electroporate using forceps-type electrodes . Make sure the embryos move with the electrical pulses.27. After finishing the second IUE of the embryos, reposition the horns carefully using the large ring forceps into the abdominal cavity. Fill cavity with warm PBS.28. Suture the abdominal wall with absorbable PDS suture line. Next, place one suture in the middle of the incision on the skin and staple the skin closed using autowound clips.29. Repeat steps 16–19.30. Post-surgical care: monitor mouse every day for 72-h post-surgery and administer 5 mg/kg/s.c. Rimadyl (carprofen) daily.Optional: Trim the skin and abdominal wall if needed.in vitro experiments.Mice are typically born between E19 and E20. They can then be screened for fluorescence expression. IUE in CD1 mice are typically well-tolerated with 70–90% of electroporated pups being born. There could be some variability in the targeted region between mice and across litters. Practice can limit variability. In addition, including controls in the same litter is critical depending on the parameters  that are analyzed. Electroporated mice can be used for many purposes, including preparing fixed brain sections for imaging and morphological characterizations, preparing acute slices for electrophysiology, behavior analysis, and dissecting cells for Dual IUE can target cortical neurons within the same cortical region but in different layers or target neurons in different cortical regions and layers. However, dual IUE may have a reduced efficacy compared to single IUE. One must be gentle with the embryos to maximize survival. When researchers are beginning this procedure, begin with a single IUE in the desired cortical location. Once it is established, then transition to dual IUE.Cannot penetrate the embryonic sac with the micropipette.The micropipette tip is too dull or wide. Change to a sharper tip and repeat. Proceeding with a micropipette tip that is too dull or wide could damage the embryo .Cannot deposit the plasmid into the lateral ventricle.There could be multiple causes for this : The tipThe embryonic sac is leaking amniotic fluid.The micropipette tip may be too dull or wide. Adjust micropipette sharpness or thickness accordingly . The micPopping of the embryonic sac during handling.If this happened, the embryos will not likely survive. Handle the embryos more gently.The dam is bleeding.Although this procedure should not result in excessive bleeding, there could be blood between the skin and peritoneum. As long as it is only a small amount of blood, this will resolve as the surgery is completed. If an organ was ruptured, then there would be more blood within the peritoneal cavity. If so, euthanize the animal.Few or no electroporated pups are born.The experimenter was likely not gentle enough with the embryos during surgery. The experimenter should put less pressure on the embryos, deposit the DNA plasmids with less force, and consider altering micropipette sizes. In addition, pups at the top of the uterine horn (near the knots) and at the junction between the two uterine horns should not be electroporated otherwise this increases the chances of spontaneous abortions.Electroporated pups are born, but the fluorescent protein is expressed in subcortical or incorrect cortical locations.If the fluorescent reporter is in subcortical locations, then the micropipette was too deep. Ensure the plasmid DNA is properly injected into the lateral ventricle. If it is expressed in incorrect cortical locations, then adjust tweezertrode orientation to obtain the correct location.Electroporated pups are born, but there is noticeable damage to the cortex or hydrocephalus.If there is damage to the cortex, then the micropipette was too dull. Hydrocephalus can happen with IUE, but it is uncommon. This could occur for several reasons: 1) too much pressure when depositing the plasmid into the lateral ventricle, 2) from the micropipette injection causing bleeding inside the lateral ventricle, or 3) inflammation. Ensure sterilizing the surgical and IUE tools before start, and deposit plasmid DNA gently.Only some of the pups have dual IUE, while others have a single IUE.This is likely because one of the IUEs was unsuccessful, or the second IUE was performed out of sequence and did not target the electroporated embryos. Some embryos could die between the first and second IUE. A dying embryo has an opaque white-yellowish color prior to being fully resorbed. Be mindful to count all the embryos carefully during the first and second IUEs, and note which embryos are no longer healthy. Skip unhealthy or dying embryos, even if they were part of the first IUE. When skipping those dying embryos, make sure to remain in sequence with the previous IUE pattern so that all healthy embryos that received the first IUE (E13.3) also receive the second IUE (E15.5).


Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus. Careful and timely intervention is required to optimise glycaemic control and reduce the risk of mortality and devastating complications. Of these, cerebral oedema is the leading cause of death, with a mortality rate of approximately 25%. This article highlights the recent updates to UK fluid therapy guidelines for DKA and provides clinical context for the benefit of paediatricians and junior doctors in light of this new guidance. Updates to two UK guidelines in 2020 has improved concordance, with 0.9% sodium chloride and the Holliday-Segar formula used as a gold standard to calculate fluid maintenance requirement.Minor differences remain, such as the maximum weight for maintenance and the stratification of diabetic ketoacidosis or dehydration severity.Careful monitoring and adherence to these national guidelines is recommended and will hopefully contribute to a reduction in deaths secondary to cerebral oedema (CO).Further research is required to evaluate the efficacy of these new guidelines, and better understand the pathophysiology and risk factors for developing CO.Diabetic ketoacidosis (DKA) is a potentially life-threatening metabolic complication of type 1 diabetes mellitus. Despite interventions to reduce the incidence of DKA, the National Paediatric Diabetes Audit for 2018/2019 showed that overall 20.9% of all newly diagnosed patients in the United Kingdom (UK) presented in DKA, although there is considerable regional variability.1DKA is characterised by uncontrolled hyperglycaemia, ketosis and subsequent metabolic acidosis. As highlighted in 4Globally, the International Society for Paediatric and Adolescent Diabetes (ISPAD) guidelines are widely used for management of paediatric DKA.Specifically, the NICE 2015 guidelines were more conservative with fluid administration, in order to avoid rapid changes in osmolality. The BSPED guidelines permitted a more generous fluid allowance, and this raised concerns about precipitating CO. The conflicting advice generated challenges in the emergency setting, with arbitrary site-specific preference rather than evidence-based medicine taking precedence. In addition to generating uncertainty of treatment pathways increasing the risk of clinical error, the regional variability hampered service evaluation and audit of clinical practice.Unfortunately, there is little data to establish differences in their efficacy, especially surrounding the risk of CO in the paediatric population. However, inadequate resuscitation is likely to increase the risk of brain injury and thus must be avoided. Further research on a national scale is required to assess this.This article aims to highlight the considerable alterations made to the two main UK guidelines. Alongside these updates, this article will provide clinical context to paediatricians and junior doctors who are likely to treat these vulnerable groups.In January 2020, the BSPED published new guidance for the management of children with DKA.10 11Furthermore, there are clear risks associated with inadequate fluid replacement. A hypovolaemic state will result in systemic hypotension and ultimately, cerebral hypoperfusion which, particularly in the context of acidosis, will increase the risk of a brain injury.6In 2008, following three deaths from CO, the South Thames Retrieval Service introduced a ‘restrictive fluid’ DKA guideline in the region. Subsequently, no deaths have been reported, but this is insufficient evidence on which to make definitive recommendations or guidelines.12More recently, in December 2020, NICE released updated guidance on the management of DKA in CYP, which was broadly concordant with BSPED, particularly with respect to more liberal fluid restriction. This was prompted by new evidence identified by NICE’s surveillance team in a review of 12 studies set to determine optimal fluid therapy in CYP with DKA. The fluid protocols followed in the PECARN study were fundamental to these updates,Both BSPED and NICE recommend the following fluid maintenance requirements, using 0.9% sodium chloride without added glucose, and the Holliday-Segar formula:100 mL/kg for the first 10 kg (0–10 kg body weight).50 mL/kg for the second 10 kg (10–20 kg body weight).20 mL/kg for each subsequent kilogramme (>20 kg body weight).When calculating the total fluid replacement, subtract any initial bolus volumes from the total fluid deficit (unless the child or young person is in shock).For insulin and electrolyte replacement requirements, both recommendThe addition of 40 mmol/L potassium chloride to all fluids  unless the patient is anuric or hyperkalaemic. Include this before starting the insulin infusion if hypokalaemia is observed at presentation.0.9% sodium chloride should be used without added glucose unless the plasma glucose is <14 mmol/L.Initially assess for the presence of hyponatraemia, continue to monitor throughout treatment and treat as soon as blood glucose falls. Monitor sodium levels throughout treatment and calculate sodium initially to identify if hyponatraemia is present. This should be treated as soon as blood glucose falls. It is important to monitor as hyponatraemia and rapidly increasing sodium levels can both be signs of CO.Do not give intravenous sodium bicarbonate to CYP with DKA unless they have compromised cardiac contractility caused by life-threatening hyperkalaemia or severe acidosis, and you have discussed with paediatric intensivist.A soluble insulin infusion of between 0.05 units/kg/hour and 0.1 units/kg/hour, 1–2 hours after intravenous fluids have been commenced. BSPED stated that the 0.05 units/kg/hour should be sufficient unless the patient is suffering from severe DKA or is an adolescent. If they are attached to a ‘continuous subcutaneous insulin infusion’, disconnect when starting intravenous insulin therapy. For patients already on long-acting insulin, it may be continued, and in new patients consider commencing long-acting subcutaneous insulin alongside intravenous. Similarly, the NICE guidelines state that continuing subcutaneous basal insulin in a child or young person who was using a basal insulin before DKA may be continued in discussion with a diabetes specialist.Although these guidelines now have greater cohesion, a number of minor differences remainRegarding fluid replacement, NICE have included two levels of severity of DKA, while BSPED have subdivided the stratification to include three discrete categories for severity and subsequent dehydration status, as outlined in A difference remains between the maximum weight considered by the guidelines when calculating fluid deficit. Given that the maximum weight considered for each is 75 kg for NICE and 80 kg for BSPED, the maximum difference in deficit fluids could be 1850 mL (5%×75 kg=3750 mL for NICE compared with 7%×80 kg=5600 mL for BSPED).For patients who are clinically dehydrated, but not in shock, an intravenous 10 mL/kg bolus of 0.9% sodium chloride is recommended on admission. This should be administered over 30 min (NICE) or 60 min (BSPED). This volume is included in the fluid replacement when calculating the total fluid deficit. NICE recommend discussing with a paediatrician experienced in DKA management before giving more than one intravenous bolus. A second bolus should only be considered if needed to improve tissue perfusion and this must be done after reassessing their clinical status.A delicate balance between increasing the risk of osmolar shift secondary to rapid fluid administration, with the risk of dehydration and subsequent CO due to slower fluid administration, is the foundation for the initial discrepancy between the two guidelines. Guidance from the 2018 ISPAD consensus states that this should be administered between 30 min and 60 min, which falls between the two UK guidelines.In the presence of hypovolaemic shock, both NICE and BSPED recommend an intravenous 0.9% sodium chloride bolus of 20 mL/kg. BSPED recommend repeating these infusions over 15 min to a maximum of 40 mL/kg, before considering the introduction of inotropes, while NICE recommends administering it as soon as possible. In both guidelines, the bolus for shock is not subtracted from total fluid deficit.While the nomenclature varies between these two guidelines, in practice, it is likely that these will represent similar time frames. Administering a 20 mL/kg 0.9% sodium chloride bolus to treat shock as quickly as possible should provide the best therapy for the patient.When calculating fluid replacement, the NICE guidelines recommend a maximum weight of 75 kg, whereas BSPED recommend a maximum weight of 80 kg or 97th centile weight for age (whichever is lower).This discrepancy is unlikely to be encountered on a frequent basis in general paediatric practice. However, if the weight greatly exceeds 75 kg, it may be more appropriate for young people to be managed according to adult guidelines due to their increased body habitus. Additionally, identifying a CYP on the 97th centile can be difficult, especially in an emergency setting, and, therefore, this may be missed.The new guidelines released by both NICEThe most pertinent similarities between the BSPED and ISPAD guidelines include giving a bolus for shock (20 mL/kg), using the Holliday-Segar formula to determine the maintenance fluid requirements, using a maximum of 80 kg in weight for these calculations and stratifying the severity of DKA  compared with the two classifications used by NICE (mild/moderate and severe).In contrast to the NICE and BSPED guidelines, which state that a 0.9% sodium chloride solution must be used when considering fluid requirements, in the ISPAD guidance, either a 0.45% or 0.9% sodium chloride or a balanced salt solution  may be used. This is secondary to recent findings from randomised control trials showing no difference in cerebral injury in patients rehydrated at different rates with either 0.45% or 0.9% sodium chloride. Additionally, for those not in shock, these fluids should be infused over 30–60 min, which falls between the two 2020 guidelines (NICE states to give fluids over 30 min and BSPED states over 60 min). Regarding the fluid bolus for those in shock, as with the NICE 2020 guidelines, the ISPAD guidelines state that it should be given ‘as soon as possible’. Conversely, BSPED says this should be over 15 min. However, in practice, this difference in nomenclature is likely to be negligible. Also, in agreement with the NICE 2020 guidelines, the ISPAD guidelines recommend the prescription of insulin at between 0.05 units/kg/hour and 0.1 units/kg/hour, where 0.05 units/kg/hour is usually sufficient in mild DKA. When assessing glucose introduction, the ISPAD guidance recommends that healthcare professionals ‘consider adding glucose before 17 mmol/L if falling rapidly. Otherwise 5% glucose should be added when the plasma glucose falls to approximately 14–17 mmol/L’. This is in contrast to the NICE and BSPED guidelines, which only introduce 5% glucose when it has fallen below 14 mmol/L.The Royal Children’s Hospital (RCH) in Melbourne, Clinical Practice Guidelines for Diabetic Ketoacidosis, last updated in November 2018, have been adapted for statewide use with the support of the Victorian Paediatric Clinical Network. Although broadly similar, there are a few distinct differences between the RCH guidelines and those of NICE, BSPED and ISPAD. For those in shock, a 10 mL/kg 0.9% sodium chloride bolus can be given, half the volume of 20 mL/kg recommended by the other guidelines. Although initial fluid rates are based on a degree of dehydration , maintenance fluids are not calculated using the Holliday-Segar formula. Instead a detailed table is used, with the fluid requirements classified according to the different degrees of dehydration up to a maximum of 70 kg.However, as with the other guidelines, 40 mmol/L of potassium chloride is added to the fluid, as long as the child is not anuric or a serum potassium ≥5.5 mmol/L. If required, these can be increased to a maximum of 60 mmol/L, which is not specified in the other guidelines. Additionally, 5% glucose is added if the blood glucose is ≤15 mmol/L, which is comparable, although this can be increased to 10% glucose if blood glucose is falling rapidly or ≤5 mmol/L. Insulin infusion rate of 0.1 units/kg/hour is recommended unless treating children under 5 years of age, children undergoing inter-hospital transfer  or children with blood glucose <15 mmol/L at the time of commencement of the insulin infusion. This is placed at the upper end of the bracket of the other guidelines, where 0.1 units/kg/hour is recommended for those with severe DKA, adolescence or unresolved ketosis.The convergence of the NICE and BSPED guidelines is a welcome development in the emergency management of paediatric DKA. This will provide much needed clarity to the treating clinicians, reducing regional variation and decreasing the potential for error. Despite the pathophysiology of CO remaining uncertain, fluid therapy must be carefully controlled, as inadequate resuscitation is likely to increase the risk of brain injury and thus must be avoided.There is emerging evidence for a more judicious approach in the management of DKADespite this, it is imperative that the incidence of CO continues to be monitored following a change to the guidelines and, in addition, this may offer insights into the underlying pathophysiological basis and effective preventative measures.In the meantime, for junior clinicians treating DKA in CYP, close supervision by experienced paediatricians, careful monitoring and adherence to a single-set of evidence-based guidelines are likely to translate into better outcomes for this challenging condition.


A solitary fibrous tumour (SFT) is a rare neoplasm that commonly arises in the pleura and can occur in other extrathoracic sites. Extrapleural SFT, particularly in the sinonasal cavity, is extremely rare. There are no definite diagnostic criteria for sinonasal SFT as it is rare. Histologic analysis with immunohistochemistry plays an important role in diagnosing SFT.We report herein a case of SFT of the sinonasal cavity, which later spread to the oral cavity in a 67-year-old male with underlying papillary thyroid carcinoma (PTC) stage IV. He complained of recurrent epistaxis from a mass in his left nasal cavity for two weeks. The mass grew bigger, and spread to the oral cavity, causing dysphagia and upper airway obstruction. Tracheostomy was done under local anaesthesia and a biopsy of the mass was taken to rule out metastasis from the PTC. However, histopathological examination revealed a mesenchymal tumour of fibroblastic type, consistent with an SFT. He was planned for surgical resection of the tumour. However, he refused the operation and was lost to follow-up.We describe the clinical presentation of this rare tumour of the sinonasal and oral cavity, including upper airway obstruction, and the importance of immunohistochemical markers such as CD34 and BCL-2 in diagnosing SFT. Complete resection of the tumour is the definitive treatment for SFT.SFT of the sinonasal and oral cavity is extremely rare. Upper airway obstruction may occur due to the location of the tumour in the airway region. Immunohistochemistry is crucial to distinguish this tumour from other mesenchymal tumours. •Solitary fibrous tumour (SFT) in the nasal cavity and paranasal sinus is extremely rare. In our case, the tumour had spread to the oral cavity, causing upper airway obstruction.•Urgent trachestomy is needed in view of upper airway obstruction due the massive tumour in the upper airway.•Our patient also had double pathology, which was SFT of the sinonasal cavity with underlying papillary thyroid carcinoma (PTC) stage IV. Thus, we had to rule out metastasis from PTC to the sinonasal cavity.•Immunohistochemical studies are the most sensitive and specific method for diagnosing an SFT. Among the most sensitive first-line markers are CD34, BCL-2 and STAT6. It usua2A 67-year-old Malay male who worked as a rubber tapper presented with a two-week history of recurrent left epistaxis. He also complained of left-sided nasal blockage over the past 30 years, worsening over the past eight months. He started to notice a mass in his left nasal cavity eight months ago, associated with anosmia and ageusia. The nasal mass spread to the oral cavity, causing shortness of breath and dysphagia. He also had progressive left cheek fullness and left eye proptosis for four months. Nevertheless, his left eye vision was good, and there was no diplopia. He was already diagnosed with papillary thyroid carcinoma with spine metastasis the previous year, and was planned for a total thyroidectomy at that time, however, he refused surgical intervention. He did not take any drugs and did not have any allergy histories. He was an active cigarette smoker but did not take alcohol. Family history was unremarkable.On physical examination, a fleshy mass was seen protruding from the left nasal cavity, with left cheek swelling and left eye proptosis A. IntraoComputed tomography (CT) scan of the paranasal sinus and neck revealed heterogenous opacification of the left maxillary sinus, bilateral nasal cavities, bilateral ethmoid, sphenoid, and frontal sinuses A. The soHistopathological examination of the left nasal and gum mass showed tumour tissue composed of haphazardly arranged spindle-shaped cells of variable cellularity and spindled to oval nuclei with mild pleomorphism A. There A multidisciplinary team discussion was held between otorhinolaryngologist, oral and maxillofacial surgeon, ophthalmologist, radiologist and pathologist, and the patient was planned for surgical resection of the tumour. He was referred to a dietician for optimization of nutrition and to an anaesthetist for pre-operative assessment. However, he sadly refused the operation and was lost to follow-up.3SFT is a mesenchymal tumour that is mostly found in the pleura and the thoracic cavity. The extrapleural SFT rarely occurs in the head and neck area, only around 5–27%, mainly in orbit and the oral cavity . SFT is SFT is usually painless and gradually increases in size, therefore, the patient is often not aware of its presence until it has grown enough to cause symptoms and signs. Most patients with SFT of the sinonasal cavity presented with nasal blockage and other symptoms such as rhinorrhea and epistaxis . Some coSFTs are macroscopically well-circumscribed and partially encapsulated with a multinodular, whitish, firm cut surface . MicroscImmunohistochemical studies are the most sensitive and specific method for diagnosing an SFT. CD34 and BCL-2 are the most sensitive first-line markers for SFT diagnosis . CD34 exSFTs have isoattenuation with the surrounding muscles and soft tissue on computed tomography (CT) imaging. The attenuation increases with intravenous contrast administration . CT scanThe gold standard of treatment of SFT is surgical resection with negative margins . EndoscoLiterature has reported synchronous occurrence of SFT with another tumour, including papillary thyroid carcinoma (PTC), pituitary macroadenoma , and breIn terms of prognosis, a risk stratification system for predicting metastatic risk has been recently introduced, which incorporates four variables: patient's age, numbers of mitoses, tumour size, and tumour necrosis . In a va4SFTs of the head and neck region is rare, especially in the sinonasal region. The most common presenting symptoms are nasal blockage and epistaxis. Upper airway obstruction may occur in an extensive tumour involving the sinonasal and the oral cavity, needing tracheostomy. Immunohistochemical markers are essential in diagnosing SFT, in which CD34, BCL-2 and STAT6 are the most sensitive. The definitive treatment for SFT is complete resection, and its prognosis is generally favourable and mainly depends on the completeness of tumour resection.Not applicable.None.Nurul Anis: data collection and design of the study, drafting the article. Noor Idayu, Muhammad Nasri: data collection. Wan Faiziah, Sharifah Emilia, Ramiza Ramza: drafting the article and revising it critically for important intellectual content, final approval of the version to be submitted.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.Not applicable.Nurul Anis Mohd Fauzi.Not commissioned, externally peer-reviewed.None.


Delta-B-line was able to diagnose fluid non-responders with an area under the curve of 0.74 . The best threshold was two B-lines with a sensitivity of 80% and a specificity of 57%. The final Delta-B-line could predict postoperative pulmonary complications with an area under the curve of 0.74 . Delta-B-line of two or more detected in four lung ultrasound zones can be considered to be a marker of preload unresponsiveness after a fluid challenge in abdominal surgery.A fluid challenge can generate an infraclinical interstitial syndrome that may be detected by the appearance of B-lines by lung ultrasound. Our objective was to evaluate the appearance of B-lines as a diagnostic marker of preload unresponsiveness and postoperative complications in the operating theater. We conducted a prospective, bicentric, observational study. Adult patients undergoing abdominal surgery were included. Stroke volume (SV) was determined before and after a fluid challenge with 250 mL crystalloids (Delta-SV) using esophageal Doppler monitoring. Responders were defined by an increase of Delta-SV > 10% after fluid challenge. B-lines were collected at four bilateral predefined zones . Delta-B-line was defined as the number of newly appearing B-lines after a fluid challenge. Postoperative pulmonary complications were prospectively recorded according to European guidelines. In total, 197 patients were analyzed. After a first fluid challenge, 67% of patients were responders and 33% were non-responders. Delta-B-line was significantly higher in non-responders than responders [4 (2–7) The objectives and procedures of the study were registered at Clinicaltrials.gov . Current guidelines recommend guiding fluid titration by measuring stroke volume (SV) in high-risk surgical patients to obtain an unresponsiveness state, which corresponds to the absence of an increase in SV of more than 10% after a fluid challenge4. Application of such recommendations has reduced post-operative morbidity and the length of hospitalization.In major surgery, fluid overload has been shown to be associated with increased postoperative complications and length of hospital stay5 then emergency rooms6, cardiology7 and nephrology8. The final step of “fluid administration limited by lung sonography-protocol” (FALLS-protocol) consists of the visualization of ultrasound B-lines during fluid therapy9. The appearance of B-lines in an area where no B-line was present is diagnosed as a hydrostatic excess of the subpleural interstitial septa. Such appearance of B-lines takes place at an infra-clinical stage10. As lung ultrasound is a simple and real-time tool, could it be potentially used in the operative setting to guide fluid titration and avoid fluid overload?Based on the study of artifacts over the last 25 years, lung ultrasound has been increasingly used in intensive care units (ICUs)Our main objective was to study the relationship between the appearance of new B-lines (Delta-B-line) and the appearance of fluid unresponsiveness after fluid challenge in the operating theatre. Our secondary objective was to study the relationship between Delta-B-line at the end of surgery and the appearance of postoperative pulmonary complications.Comité de Protection des Personnes Hospital Group Pitié-Salpétrière, Paris, France; reference PI2017_843_0018) and was registered at Clinicaltrials.gov . The present report adheres to the applicable CONSORT guidelines and was drafted in accordance with the recommendations of the STROBE statement. All patients provided their informed consent prior to inclusion in the study. The study was conducted in accordance with the Declaration of Helsinki on ethical principles for medical research involving human subjects.The objectives and procedures of the study were approved by institutional review board , patients with a suspected or proven acute lung disease  or chronic interstitial lung disease , emergency surgery or patients who refused to sign the consent form.11. We remind that B-line is strictly defined as, always: comet-tail artifact, arising from the pleural line, moving in concert with lung sliding; almost always: long, well defined, erasing A-lines, hyperechoic. In a rib short axis view, three (or more) B-lines are called lung rockets and define interstitial syndrome12. Two B-lines are called pre-lung rockets and may indicate a preliminary step of hemodynamic interstitial edema  and a Philips sectorial, 1 to 5 MHz, wideband S5-1 cardiac probe . Gain was adjusted to maximize contrast. The A-line and B-line are artifacts recognized by international evidence-based recommendations6. In order to avoid any collection problem related to surgical drapes, we used an adaptation of the bedside lung ultrasound in emergency-points (BLUE-points), described in Fig. 114. Upper and lower BLUE-points are anterior. The lower BLUE-point, when laterally continued, determines a posterior point, the «posterolateral alveolar pleural syndrome-point» (PLAPS-point). In this study, we used a lateral point in between lower BLUE-point and PLAPS-point (roughly between anterior and posterior axillary lines). This lateral point had the advantage of being accessible in spite of the constraints of the operating field. In addition, at the PLAPS-point, B-lines are visible in up to ¼ of healthy subjects12.The zones of analysis were based on previous studies showing that fluid overload is detectable at the anterior chest wall2O PEEP for 20 s)15. A sufficient time between the end of the maneuver and the data collection in order to avoid any hemodynamic impact of the maneuver on the data (2 min).Number of B-lines were counted bilaterally and was the sum of B-lines at the upper BLUE-points and the lateral points, i.e., four points. The number of B-lines was counted in a rib short-axis scan between two ribs. Care was taken to apply the probe to the same precise area of the same patient during each collection. An alveolar recruitment maneuver was performed two minutes before each lung ultrasound collection  was analyzed a posteriori by two lung ultrasound experts blinded to the patient responsiveness status . An examiner was considered to be an expert if s/he had performed at least 50 lung ultrasounds−1) or cisatracurium (0.15 mg kg−1). All patients were intubated and then ventilated in volume-controlled mode. The tidal volume was adjusted to the ideal body weight  and the ventilatory rate was adjusted to achieve and maintain an end-tidal CO2 pressure of 35 to 37 mmHg. A positive end-expiratory pressure (PEEP) of 5 to 8 cmH2O was applied. An alveolar recruitment maneuver was carried out systematically after oro-tracheal intubation17.The study began when monitoring of SV was implemented during digestive, urological, and/or gynecological surgery under general anaesthesia. Anaesthesia was induced with propofol and sufentanil or remifentanil and then maintained using target-controlled infusions of propofol and the opioid used for tracheal intubation. Hypnotics and opioids were titrated using the bispectral index , with a target value of between 40 and 60. Neuromuscular blockade was achieved with rocuronium  was calculated according to the following formula: Delta-SV (%) = ((SVafter − SVbefore)/SVbefore) × 100. A patient was defined as a responder if the Delta-SV was more than 10% after fluid challenge. Fluid challenge was continued until the Delta-SV was < 10%, according to French guidelines3  distributed by Gamida. Collection of the SV was averaged over five cardiac cycles. After induction, an initial measurement of the SV and a first lung ultrasound collection in the four zones were performed and stored. Then, SV was measured, and the lung ultrasound collection performed and stored after each fluid challenge with 250 ml of crystalloids which was administered over 5 min2), and cardiac index. The following data were collected at the end of the intervention: number of patients treated with norepinephrine, total intraoperative dose of norepinephrine (µg kg-1), total intraoperative volume of fluid administered (ml kg - 1), arterial oxygen partial pressure to fractional inspired oxygen ratio (PaO2/FiO2) (mmHg), brain natriuretic peptide level, duration of the operation, length of hospitalization, and postoperative pulmonary complications.The following demographic data were collected: age, gender, body mass index, medical background, American Society of Anaesthesiology Physical Status score (ASA), and type of surgery. The following ventilatory and hemodynamic data were collected at baseline and after each fluid challenge: plateau pressure, PEEP, minute ventilation, heart rate (HR), mean arterial pressure (MAP), pulsed oxygen saturation Assessment of fluid unresponsiveness of Delta-B-line after the first fluid challenge.Assessment of fluid unresponsiveness of Delta-B-line considering all fluid challenges.Association between final Delta-B-line and pulmonary complications.The data analysis will consist of 3 parts:A data analysis and statistical plan was written and posted on a publicly accessible server [Clinicaltrials.gov (NCT03502460)] before data were accessed. A sample of 200 patients was calculated to be sufficient to demonstrate that Delta-B-line could diagnose fluid unresponsiveness with an area under the curve > 0.70, under the assumption of an expected sensitivity of 80%, a power of 80%, and an alpha risk of 0.05.The normality of the distribution of variables was verified using an Agostino-Pearson test. The data were expressed as the means ± standard deviation (SD), medians [interquartile interval (IQR)], or numbers (proportion in %), depending on the case. The Student t test, Mann–Whitney test, chi-squared test, or Fischer test were used to compare quantitative or qualitative variables between responding and non-responding patients and between patients developing complications and those who did not. The paired t test and Wilcoxon test were used to compare the variables before and after a 250-ml fluid challenge. Multivariable logistic regression was used to analyze the association between the occurrence of postoperative pulmonary complications and significant determinants in univariate analysis with a p-value < 0.05 and interactions between the centre and each variable. Diagnostic values for fluid unresponsiveness or postoperative pulmonary complications were assessed using a receiver operating characteristic curve and calculating the area under the curve. The best threshold was defined as that which provided the highest Youden index. Correlations between the Delta-SV and the Delta-B-line were tested using Spearman’s correlation rank analysis. Changes of the Delta-SV according of Delta-B-line were compared using one-way analysis of variance (ANOVA) with Tukey’s post hoc test. Differences with a p-value < 0.05 were considered statistically significant. Interobserver agreement between the two experts concerning qualitative ultrasound signs (signs present or absent) was evaluated using a Kappa concordance coefficient and agreement on quantitative evaluations (number of B-lines detected at the upper and lower sites) using an intraclass correlation coefficient.https://www.medcalc.org; 2021) was used for all statistical analyses.MedCalc Statistical Software version 19.7 . 200 patients undergoing digestive, urological, or gynecological surgery who required intraoperative hemodynamic optimization by fluid challenge titration were finally included. Two cases were excluded because of the impossibility of obtaining an esophageal Doppler monitoring signal and one because of local interference that impeded the obtention of lung ultrasound images of sufficient quality . Delta-B-line was able to diagnose fluid non-responders with an area under the curve of 0.74 . The best threshold for Delta-B-line was two . No patient received vasopressor before the first fluid challenge.The number of responding patients after the first fluid challenge  was 133 (67%) and 64 were non-responders (33%). There was a significant decrease in HR and a significant increase in cardiac index in responding patients (p < 0.01). The number of B-lines increased in responders and non-responders after this first fluid challenge (p < 0.01) (Table Delta-B-line=2 = 6.7% 95% CI (4.2 to 8.7) and Delta-SVDelta-B-line=3 = 6.4% 95% CI (3.8 to 7.6) vs Delta-SVDelta-B-line=0 = 14.5% 95% CI (12.9 to 16.7); p < 0.05) . When considering all fluid challenges administered, the Delta-SV values decrease significantly and below the threshold of 10% after the Delta-B-line ≥ 2 compared to Delta-B-line = 0  (Table Sixteen (8%) patients developed postoperative pulmonary complications: eight (50%) developed a respiratory infection, four 25%) respiratory failure, and four (25%) aspiration pneumonitis. The final Delta-B-line was significantly higher for patients with pulmonary complications than those without  Table .Table 3UInterobserver agreement was good, with a Kappa concordance coefficient of 0.87; 95% CI 0.67 to 0.99. The intraclass correlation coefficient for the agreement on quantitative evaluations was 0.90 (95% CI 0.80–0.96).Our study suggests that Delta-B-line ≥ 2 at four zones can diagnose fluid unresponsiveness in patients undergoing abdominal surgery. Our study also found that the final Delta-B-line was associated with the occurrence of postoperative pulmonary complications.12. An increase in interstitial fluid may be caused by two phenomena. (1) An increase in hydrostatic pressures between the capillary and lung interstitium. A predominance of A-lines may predict low pulmonary artery occlusion pressure (PAOP) with good specificity, whereas a predominance of anterior B-lines may predict that the underlying lung is "overloaded"20. Thus, B-lines can be considered as a sign of high cardiac filling pressure21. Moreover, anaesthesia-induced vasodilatation induces decreased clearance and an increase in the half-life of infused fluids in healthy patients22. This could promote the slower turnover of crystalloids and the accumulation of fluid in the interstitium23. (2) Changes in capillary permeability. Some authors advocated an absence of correlation between the number of B-lines and an increase in the PAOP24. This can be explained by deterioration of the alveolar-capillary membrane25. Note that our population had “healthy” lungs. In the same population, it has been shown that a single bolus of crystalloids can cause interstitial pulmonary edema associated with a decrease in the angiopoietin-1/angiopoietin-2 ratio, suggesting a proinflammatory effect26. Still in these patients, hypervolemia could increase the release of atrial natriuretic peptide and cause enhanced shedding of the endothelial glycocalyx. This deterioration has been shown to cause the shifting of fluids into the interstitial space27.B-lines result from an ultrasound reverberation phenomenon on subpleural inter-lobular septa and may reflect interstitial edema11. We can explain our low threshold by the fact that the anaesthetist in charge of the patient was present to detect interstitial edema at a very early stage, whereas patients with acute pulmonary edema are explored at a more advanced stage. Thus, excess interstitial fluid may invade one or two sub-pleural interlobular septa, which is detected in near real-time during fluid challenge, leaving the other septa empty. A previous study showed that pre-lung rockets (two B-lines) may indicate an early stage of pulmonary edema5.The threshold for diagnosing fluid unresponsiveness may seem low , whereas current knowledge indicates that the number of B-lines must be ≥ 3 for diagnosing pulmonary edema29. Studies have found that vascular filling in ICU patients with ARDS causes deterioration of lung aeration, visible by lung ultrasound. Such an excess of extravascular lung water has been shown to correlate with higher mortality30. In addition, the postoperative appearance of new B-lines following thoracic surgery has been shown to correlate with the development of postoperative pulmonary complications31. Moreover, it has been shown that the detection of B-lines in chronic hemodialysis patients is an independent factor of mortality and cardiovascular complications32. In our study, the median postoperative PaO2/FIO2 ratio for patients with complications was < 300 mmHg, which corresponds to “mild” ARDS according to the «Berlin definition», despite the absence of a significant difference relative to patients without complications33.Finally, we found that the final Delta-B-line can predict the occurrence of postoperative pulmonary complications. Avoid fluid overload by using indexes guiding vascular filling have resulted in a significant reduction in pulmonary complications34. Each monitor and index has its own advantages and limitations35. Finally, the adhesion and the weak compliance with the management protocol based on the monitoring tools of the SV currently, demonstrates the need to find indices based on tools already well used by the practitioners36. Lung ultrasound can therefore potentially be routinely used in the operating theatre to avoid fluid overload and thus reduce the occurrence of postoperative pulmonary complications. Lung ultrasound has several advantages. It is non-irradiating, noninvasive, and has a fast learning curve37. It is also worth remembering that B-lines are usually absent in euvolaemic patients and appear before clinical symptoms or signs of fluid overload38. Thus, it can allow continuous monitoring of B lines as soon as they appear, as well as dynamic reassessments of a patient's volume status. It is also a simple tool which the use is facilitated today by the development of portable devices. Moreover, it should be pointed out also that the ultrasound is cheap and is now available in many operating rooms. The interobserver agreement in this study was good, close to that of other studies39.The assessment of perioperative hemodynamic is challenging and, thus, several tools are used. In addition, the accuracy of cardiac output monitors and the preload dependency index is still only modestOur study had the following limitations. The first was the interpretation of B-lines that appear during surgery. Atelectasis occurring during the intervention was prevented by performing recruitment maneuvers. We were forced to remove patients with a suspected or proven acute lung disease or chronic interstitial lung disease to limit the occurrence of false positives and to avoid making it difficult to account of new B-lines appeared in case of many initial B-lines. However, in the case of our target population of elective surgery patients (excluding emergency surgery), trace patterns of incipiens pneumonia were a possible cause, although probably rare and anyway hard to prove currently.40. The results of this study should be understood with this critical point in mind.Second, we saw that the accuracy of lung ultrasound was good but not perfect. We expected such results, which indicated that either lung ultrasound was not perfect, or that the gold standard was not perfect too. Comparing a new test to an imperfect gold standard might unavoidably generate less than perfect results. Note that the esophageal Doppler monitoring probe, which is one of the cardiac output monitoring devices frequently used in the operating theatre, has its own limitations, including spatial instability in the esophagus and accuracy of measurement of the cardiac outputThirdly, we must keep in mind that a volume responsive patient may be intolerant to fluids, so while a Delta B line should definitely represent a fluid stop point, it may not represent volume unresponsiveness, which likely explains lung ultrasound being "imperfect" as a fluid responsiveness tool, which it isn't inherently. It is a marker of fluid tolerance and further studies should be carried out taking into account this endpoint.Finally, our results are based on an optimization by the variation of the stroke volume and not by the variation of the number of B lines in ultrasound because this method is not yet recognized. A randomized and multicenter study project will be set up to show the superiority in terms of postoperative complications of a fluid titration strategy based on delta-B-line versus stroke volume monitoring.This study showed that Delta-B-line of two or more detected in four lung ultrasound zones can be considered to be a marker of preload unresponsiveness after fluid challenge in abdominal surgery .Supplementary Information.


The wetting of surfacesis strongly influenced by adsorbate layers.Therefore, in this work, sessile drops and their interaction withadsorbate layers on surfaces were investigated by molecular dynamicssimulations. Binary fluid model mixtures were considered. The twocomponents of the fluid mixture have the same pure component parameters,but one component has a stronger and the other a weaker affinity tothe surface. Furthermore, the unlike interactions between both componentswere varied. All interactions were described by the Lennard-Jonestruncated and shifted potential with a cutoff radius of 2.5σ.The simulations were carried out at constant temperature for mixturesof different compositions. The parameters were varied systematicallyand chosen such that cases with partial wetting as well as cases withtotal wetting were obtained and the relation between the varied molecularparameters and the phenomenological behavior was elucidated. Dataon the contact angle as well as on the mole fraction and thicknessof the adsorbate layer were obtained, accompanied by information onliquid and gaseous bulk phases and the corresponding phase equilibrium.Also, the influence of the adsorbate layer on the wetting was studied:for a sufficiently thick adsorbate layer, the wall’s influenceon the wetting vanishes, which is then only determined by the adsorbatelayer. Thewetting of solids plays an important role in many processes.It is usually characterized by the contact angle θ of a sessiledrop on a surface and depends on the interactions between all componentsof the investigated system.2 Surfaces without adsorbate layers can only be obtained by special treatments such as plasma cleaningand storage in ultrahigh vacuum. The adsorbate layer leads to a changein the wetting behavior compared to the atomically clean surface3 and it has long been known that the adsorbatelayer strongly influences the contact angle of a sessile drop andmust not be neglected in studies of wetting of surfaces.4 In most situations, the underlying substratehas no direct influence on the sessile drop when the adsorbate layeris thicker than about 1–2 nm.6 In recent experimentalstudies on surfaces with adsorbate layer, that is, gold, steel, andtitanium, Heier et al.2 observed that thecontact angle depends only on the adsorbate layer composition foran adsorbate layer thicker than 1.4 nm.2 In contrast,the wetting is influenced by the underlying substrate directly whenthe adsorbate layer is thinner than about 1 nm.7Technical surfaces are always contaminatedby adsorbed residues,which form an adsorbate layer. The composition and thickness of thatadsorbate layer depend on the pretreatment of the surface, the surroundingfluid , and the underlying substrate and can, for example,be studied by X-ray photoelectron spectroscopy (XPS).Molecular simulations help gaining a detailed understandingofwetting phenomena and have been carried out by many authors, see forexample, refs −10 Molec20 Investigations of sessile drops of binary mixtures on planar wallshave been carried out during the last 10 years by several groups.29 Seveno et al.,22 Das and Binder,24 Jiang et al.,25 and Surblys et al.26 focused on methods for predicting the contactangle from the surface tensions, whereas Kumar and Errington28 describe methods for obtaining the contact angle by spreading anddrying coefficients from Monte Carlo simulations. Seveno et al.,22 Das and Binder,24 Jiang et al.,25 and Kumar and Errington28 investigatedthe contact angle on a solid in a system with two immiscible liquids,whereas Surblys et al.26 investigated thewetting of water–methanol or water–isopropyl alcoholmixtures with different alcohol mass fractions on a solid wall withmolecular dynamics (MD) simulations. Lundgren et al.29 investigated the wetting of a water–ethanol dropleton a solid graphite surface with MD simulations for different molefractions of ethanol.Wetting transitions, that is, prewetting ordemixing, on planarwalls have been studied previously by many authors using molecularsimulations.In contrast to these previous studies,we systematically investigatedthe influence of the adsorbate layer on the wetting. Thereby, binaryfluid mixtures with varying unlike fluid–fluid interactionswere used. Furthermore, the attraction of the wall differs for thetwo components of the mixtures, which leads to a different adsorptionof the two components.31 The same potential is used in the present work. The LJTS potentialdescribes properties of simple fluids for a wide range of states andits properties are well known,44 both for pure fluids and mixtures, and it has been used as a modelfluid for many studies, for example, see refs  potential with a cutoff radius of 2.5σ.see refs , 45−55. In the present work, the wetting of a planar LJTSwall by differentbinary LJTS fluid mixtures is investigated. The two components ofthe fluid had the same pure component parameters, only the parameterdescribing the unlike dispersive interactions was varied such thatdifferent types of fluid mixture behavior were obtained: a mixturewith a (low-boiling) hetero-azeotrope, an ideal mixture, and a mixturewith a high-boiling azeotrope. Furthermore, one of the fluid componentswas attracted more strongly by the solid than the other. The temperaturewas kept constant for all simulations conducted in the present work.From the simulation results, information on different propertieswas obtained: the adsorption , the contact angle, and bulk data of the liquiddrop and the surrounding vapor phase. Cases with total wetting andcases with partial wetting were observed.The paper is organizedstraightforwardly: first, the molecularmodel and simulation method are described, followed by the descriptionof the evaluation of the simulation data. Then, the results are presentedand discussed and the conclusions are drawn.In our work, only computer experiments were conducted.uLJTS was used for describing the interactionsbetween all particles. It is based on the Lennard-Jones (LJ) 12-6potential uLJr as the distancebetween two particles.56 The LJTS potentialwas truncated and shifted at a cutoff radius rc of 2.5σ throughout the present work.In this work, the LJTS 12-6 potential m of all fluids andthe solid were the same. Binary fluid mixtures consisting of two identicalfluid (f) components A and B were studied, that is, not only the sizeparameters but also the energy parameters εf of thefluids were the same.The sizeparameter σ and the mass 58 for the binary interaction energy and size parameteri and j indicate the components and ξij is the binary interaction parameter. ij, however, was varied.Three fluid mixtures A + B were considered. They vary in the binaryinteraction parameter ξAB, for which the numberswere: ξAB = 0.7, 1.0, and 1.25. The unlike fluid–fluidinteractions are unfavorable for ξAB = 0.7, idealfor ξAB = 1.0, and favorable for ξAB = 1.25. These binary interaction parameters lead to a mixture witha vapor–liquid–liquid equilibrium (VLLE) and a miscibilitygap (mixture I), an ideal mixture (mixture II), and a mixture witha high-boiling azeotrope (mixture III). Sketches of the phase behaviorof the three mixtures are shown in The unlike fluid–fluid interactionswere described usingthe modified Lorentz–Berthelot combination ruless =100εf and the solid wall had a crystal configurationwith a face-centered cubic lattice with the (100) surface exposedto the fluid. The crystal configuration remained unchanged duringthe simulation due to the high energy parameter of the solid. Thepresent choices lead to a lattice constant a = 1.55σand a density of the solid of ρs = 1.07σ–3.The energy parameter of the solid(s) was εsA = 0.10) than fluid component B (ξsB = 0.035). Thewetting behavior of the pure fluids A and B on the wall is known froma previous study of Becker et al.30 andcan be calculated by a correlation. This correlation leads to totalwetting for component A (θA = 0°) and to partialwetting for component B (θB = 123.8°) at thestudied temperature.The binary fluid mixtures interacted withthe solid wall, whereasfluid component A was attracted more strongly  ensemble with the massivelyparallel program ls1 mardyn.52 A snapshot of the simulation scenario used in this work is shownin 31 the scenario containedan atomistic wall, which was composed of six layers of LJTS sites.The atomistic wall was located in the x,z-plane of a Cartesian coordinate system and the y-coordinate was perpendicular to the wall’s surface. It wasfixed at the bottom of the simulation box by applying an externalpotential on the lowest layers of the solid, as described in detailin the Supporting Information. Periodicboundary conditions were applied in all directions. To avoid fluidlayer growth underneath the wall, a repulsive soft membrane with areset force of F = −20εfσ–2·Δy was applied at y = 65σ with Δy as the distancefrom particles above the membrane to the membrane. Even for largecontact angles of the droplet, the distance between the droplet andthe membrane was sufficiently large to avoid any influence of themembrane on the droplet. The size of the simulation box was the samefor all simulations: the height of the simulation box was Ly = 70σ, whereas thewidth and the depth were Lx = Lz = 125σ.For investigating the wetting andadsorption of the binary fluid mixtures, MD simulations were carriedout in the canonical .32 The equilibration time is determined by the equilibrationof the adsorbate layer and the liquid droplet and it is much longerthan for pure fluids, cf. refs (t = 0.0005(m/εf)1/2σ.All simulations started with a hemispherical liquid droplet(contactangle θ = 90°) on top of the wall in the middle of the cf. refs ,31. At l59 with a collision frequency of ν = 0.05.The total number of fluid particles varied between 61,000 and 90,000such that a sufficient number of particles of both components waspresent in the simulations to obtain acceptable statistics for allfluid regions, cf. refs .During the simulation, the temperature was kept constantindividuallyfor each of the fluids and the solid by an Andersen thermostatcf. refs ,31. The A″ and ρB″, the totalpressure p″, and the mole fraction of componentA xA″vapor phase(bulk): the component densities ρxA″,ads, the surface excess of both componentsΓA″ and ΓB″, and the adsorbate layer thickness of both components δA″ and δB″vapor phase adsorbatelayer: the average mole fractionof component A A′ and ρB′ and themole fraction of component A xA′liquid phase (bulk): the component densitiesρDepending on thesettings, two differentcases were observed in the present simulations: total wetting andpartial wetting. In the evaluation of the simulations, different regionswere distinguished, which are illustrated in Rd were also measured.The liquid phase adsorbate layer was not evaluated quantitativelyin the present work because the quantities of the liquid phase adsorbatelayer were influenced by the vapor–liquid interface for smalldroplets and could not be measured with sufficient accuracy. The vapor–liquidinterface as well as the three-phase contact were also not studiedquantitatively in the present work. The vapor–liquid interfaceof binary LJTS mixtures was comprehensively studied in previous workof our group.62 The total pressure in the liquid phase differs fromthat calculated for the vapor phase by the pressure difference forsmall droplets resulting from the Young–Laplace equation63 and was not determined in the present work.Detailed information on the calculation of the quantities stated aboveare given in the Appendix.For the case of partialwetting, the contact angle θ andthe droplet radius y-axis of that coordinate system is parallelto the y-axis of the Cartesian system but goes throughthe symmetry axis of the droplet; cf. y = 0σ is at the lower end of the wall. The cylindrical coordinatesystem is convenient for the simulations with partial wetting andis basically the same as that used by Becker et al.30 in their work with simulations of droplets at walls. Forconsistency, the cylindrical coordinate system was also used for theevaluation of the simulations with total wetting. Due to the cylindricalcoordinate system, the corners of the simulation box are not consideredin the data evaluation.For the evaluation of the simulationresults, not the Cartesiancoordinate system shown in A and ρB were sampled as block averagewith a block size of 500,000time steps during the simulation run via binning in the cylindricalcoordinate system. 466 bins of equal size were used both in y- and r-direction. The density was sampledby counting the particles per bin. The density fields were used todetermine the liquid phase quantities as well as the contact angleand the droplet radius by calculating the vapor–liquid interfaceof the droplet; cf. the Appendix.Component density fields ρi(y) with i = A, B were used here.These profiles were calculated by averaging the density fields ρi over r. For total wetting, the density fields were averaged overall r. For partial wetting, however, the influenceof the three-phase region is excluded by 5σ in each direction.This results in vapor side density profiles ρiv(y) for (Rd + 5σ) < r < 62.5σ and droplet side density profiles ρid(y) for 0 < r < (Rd – 5σ).For characterizing the vaporphase and liquid phase adsorbate layers,fluid component density profiles ρThe droplet sidedensity profiles were used in the present workto gain a qualitative insight into the liquid phase adsorbate layer;they were not used quantitatively. The calculation of the vapor phasebulk and vapor phase adsorbate layer quantities was based on the vaporside density profiles. They were also used to give qualitative insightsinto the vapor phase adsorbate layer.A and ρBand the corresponding density profiles ρA(y) and ρB(y) for a partialwetting case. All ρi(y) show a layering at the wall. ρBd(y) shows the layeringof a liquid adsorption, followed by a plateau of the component densityin the liquid droplet, which corresponds to the bulk liquid properties.For larger y, a smooth decrease to the componentdensity in the vapor phase is observed. This decrease simply resultsfrom the averaging over r and the increasing amountof vapor phase in the considered volume as the y-coordinateapproaches the droplet top. On the vapor side for ρAv(y) and ρBv(y), typical vapor phase adsorption density profilesare observed.xA″, xA′, xA″,ads, p″, ρA″, ρA′, ρB″, ρB′, θ, ΓA″, ΓB″, δA″, and δB″, was estimatedto be three times the standard deviation of five block averages ofthe production run . Fluid component densityfields and profiles that are shown in the following were averagedover 2,500,000 time steps. The averaged fluid component density profilesand the corresponding uncertainties are given for all simulationsin an Excel spreadsheet in the Supporting Information.In this work, the uncertainty of the calculated quantities,thatis, In the presentwork, simulations for three fluid mixtures withdifferent unlike fluid–fluid interactions and with varyingcomposition of the fluid were carried out. The numerical results aregiven in NA andcomponent B NB in the simulation volume.Here, the total number of fluid particles was chosen such that a sufficientnumber of particles of both components was available to obtain acceptablestatistics, cf. refs (NA/(NA + NB), that is, an average over allregions with fluid particles. Instead, we prefer using the mole fraction xA″ in the bulk vapor phase, which is easier to interpret. It givesa more direct information on the studied scenario and is independentof the simulation box size.The composition of the fluid wasvaried by varying the overallratio of particles of component A cf. refs ,31. For The simulation results are discussedin the following subsections.rc = 2.5σ was introduced first by Heier et al.54 for pure fluids and extended to binary mixtures by Stephanet al.36 It shows a good agreement withmolecular simulation results for pure fluids and for mixtures.61The bulk vapor phaseand liquid phase propertiesobtained from the simulations for the cases with partial and totalwetting were compared to phase diagrams calculated with the perturbedtruncated and shifted (PeTS) equation of state (EOS). The PeTS EOSfor the LJTS fluid with a cutoff radius AB = 1.0 (xA″ = xA′.The vapor–liquid equilibrium(VLE) of the ideal mixture(mixture II) with ξAB = 1.0 5, middleAB = 0.7 are shown on the right side of The results formixture III (with ξA = 0° and θB = 123.8°) are also shown(stars). The pure component contact angle values were determined witha correlation from Becker et al.30 Thestraight lines shown in Supporting Information.The contact angle results obtained inthe simulations of the present work are summarized in xA′, startingfrom the value for pure component B, that is, xA′ = 0 molmol–1. The slopes differ for the different mixtures,leading to different xA′, for which cos(θ) becomes1 . For cos(θ) = 1, the empirical correlationleads to mixture I: xA′ = 0.0425 mol mol–1, mixture II: xA′ = 0.2470 mol mol–1, and mixture III: xA′ = 0.5986 mol mol–1. The strongest influence of increasing xA′ on thecontact angle is observed for mixture I (ξAB = 0.7),in which the unlike fluid–fluid interactions are unfavorable;the weakest influence is observed for mixture III (ξAB = 1.25) with favorable unlike fluid–fluid interactions. Thiscan be understood as a consequence of the stronger depletion of componentB in the adsorbate layer, which leads to a stronger shielding of componentB of the solid, for the unfavorable unlike fluid–fluid interactions.The depletion of component B is discussed in more detail in the followingsections.Remarkably simple trends were found. For all studied mixtures,cos(θ) increases linearly with i obtained from the simulations with the ideal mixture  are shown in i(y) are shown in A =0° and θB = 123.8°.Density fieldsρsA > ξsB.The inspection of the three partial wetting simulationsin A(y) and ρB(y) (cf. The correspondingdensity profiles ρB(y) cf. 8 give adxA″. This effect levels outwith increasing distance from the wall’s surface; see, forexample, the case with xA″ = 0.508 mol mol–1 for total wetting. From the third layer, that is, a distance largerthan the cutoff radius of 2.5σ from the surface, no direct influenceof the wall is present and the density profiles of component A andB are identical. The composition from the third layer of the vaporphase adsorbate layer is the same for both components and is determinedby the fluid–fluid interaction. For partial wetting and a distancebetween the droplet and the wall’s surface smaller than thecutoff radius, the droplet is influenced by the solid wall as wellas by the underlying adsorbate layer. For a distance larger than thecutoff radius, however, the droplet is only influenced by the adsorbatelayer and not directly by the solid wall. The present simulationswith mixture II show a distance between the droplet and the wall’ssurface smaller than the cutoff radius and as a consequence, the dropletis influenced by both the wall and the underlying adsorbate layer.The distance of 2.5σ corresponds to 0.85 nm for argon with asize parameter of σAr = 0.33916 nm.32 These findings are in good agreement with experimentaldata, which do not show any influence of the substrate on the wettingfor adsorbate layers thicker than 1 – 2 nm; cf. ref lead to the density fields ρi shown in i(y) shown in xA″, basicallya drop of component B is sitting on an adsorbate layer, which is richin component A; cf. xA″, the contact angle decreasesand, beyond a certain point, total wetting is observed.The simulationswith the hetero-azeotropic mixture I (ξi(y)  cf. 10 show txA″. This transitiondoes not take place simultaneously with the transition from partialwetting to total wetting, as observed for mixture II.The vapor phase adsorbate layer shows a continuoustransition fromthin-film to thick-film adsorption, that is, the adsorbate layer thicknessincreases steadily with increasing i obtained from the simulations with mixture III (ξAB = 1.25), which forms a low-boiling azeotrope, are shownin i(y) are shown in xA″, the contact angle decreases and total wetting is observed. Forthis mixture, total wetting is observed for the highest value of xA″. This results from the phase behavior of the high-boiling azeotrope,where for xA″ > 0.5 mol mol–1 itis xA′ < xA″ and therefore, component A hasless influence on the droplet than for the other mixtures with same xA″.The densityfields ρi(y) shown in xA″,component B is richer in the first adsorbate layer than componentA. This results not only from the small xA″ but alsofrom the favorable unlike fluid–fluid interaction. For higher xA″, it can be seen that the first adsorbate layer is still rich incomponent A and component B is still depleted, however, not as muchas for mixture I and II. For this mixture, the distance between thedroplet and the surface is smaller than the cutoff radius and as aconsequence, the droplet is influenced by both the solid wall andthe adsorbate layer underneath the droplet. This is similar to mostsimulations in the present work except for one simulation with mixtureI. The influence of the wall on the droplet decreases with increasing xA″.The corresponding density profiles ρAs already observed for mixture II for the vapor phase adsorbatelayer, a discontinuous transition from thin-film to thick-film isobserved. This change in the adsorbate layer thickness takes placesimultaneously with the transition from partial to total wetting.i″ (cf. pA″ and pB″ in the vapor phase can be defined as pA″ = xA″·p″ and pB″ = (1 – xA″)p″. In the diagram on the left side of The vapor phase adsorption datafor the cases with partial and total wetting were used to determineadsorption isotherms. The adsorption isotherms for both fluid componentsobtained from the results for the three mixtures studied here areshown in We start with the discussion of the results forpartial wetting13, left.pB″, the surface excess of component Bincreases. For mixtures II and III, a different behavior is observed:with increasing surface excess of component A, the ideal or favorablefluid–fluid interaction leads to an increasing surface excessof component B, even though pB″ is decreasing; componentB is attracted by component A. For most simulations conducted in thepresent work, the amount of component A in the first adsorbate layerwas much larger than that of component B. For these cases, the influenceof the solid on component B is shielded by component A. However, forthe simulations with xA″ = 0.0081 and 0.041 mol mol–1 of mixture III  are as expected: withincreasing Theinformation obtained for the adsorption isotherms for the totalwetting case is patchy cf. 13, but ai″ of each component were also obtained. The layer thicknessshows the same behavior as the adsorption isotherms of component Aand δA and δB are the same. Theresults of the adsorbate layer thickness are presented in the Supporting Information.In the present work, results for theadsorbate layer thicknessδIn sA and ξsB.In the McCabe–Thiele diagram on the right side of The results obtained from the simulations with totalwetting (fullsymbols) are different than those obtained for the simulations withpartial wetting. They lie in the vicinity of the corresponding bulkvalues determined by the PeTS EOS and show a decreased separationof component A between the bulk vapor and the adsorbate. This resultsfrom the thick-film adsorbate layer appearing in the simulations withtotal wetting. The thick-film adsorbate layer leads, due to its thickness,to an increased influence of the fluid–fluid interaction andto a decreased influence of the solid–fluid interaction . Therefore, density profiles ata constant y-value ρi are plottedas function of r. Here, these profiles are shownfor the first three density maxima of the adsorbate layers, that is,at y = 5.663, 6.534, and 7.436σ. As expected,the density on the droplet side is always larger than that on thevapor side for both components. For y = 6.534σ(green) and y = 7.436σ (red), the transitionfrom the liquid to the vapor side for each mixture is rather similarto the vapor–liquid interface observed for these mixtures forplanar interfaces. For mixture I, an enrichment of component A atthe interface is observed, whereas for mixtures II and III, no enrichmentis observed. This is in good agreement with the findings of Stephanet al.,61 who investigatedthe vapor–liquid interfaces of binary LJTS fluid mixtures withdensity gradient theory and MD simulations. They found an enrichmentfor low-boiling azeotropic mixtures and no enrichment for high-boilingazeotropic mixtures and a quasi-ideal mixture. In contrast to thetwo upper layers, for mixture I in the three-phase contact, that is, y = 5.663σ (blue), no enrichment of component A atthe interface is observed. This layer close to the wall is stronglyinfluenced by the solid–fluid interaction such that the vapor–liquidinterface is superimposed in the three-phase contact by the solid–fluidinteraction. This superimposing decreases with increasing distancefrom the wall’s surface. For mixtures II and III for y = 5.663σ (blue), a strong influence of the solid–fluidinteraction is also observed. However, the interfacial behavior staysthe same.The three-phase contact separatesthe adsorbate layer into a vapor phase adsorbate layer and a liquidphase adsorbate layer. The transition from the liquid to the vaporphase adsorbate layer at the three-phase contact is shown in detailin Inthe present study, the wetting of a planar wall with binaryfluid mixtures was investigated with MD simulations. Three differentmixtures were studied: while the pure components A and B were identical,the unlike fluid–fluid interaction was varied, resulting ina mixture with a (low-boiling) hetero-azeotrope, an ideal mixture,and a mixture with a high-boiling azeotrope. Furthermore, the compositionof the binary mixtures was varied. Component A was attracted morestrongly by the wall than component B. All interactions  were described by a LJTSpotential with a cutoff radius of 2.5σ.The simulationresults can be classified into two cases: partialwetting  andtotal wetting . Remarkably simple results were obtained for the contact angle:starting from the contact angle for pure component B, the cosine ofthe contact angle increases linearly with the concentration of componentA in the liquid phase for all studied mixtures. The decrease of thecontact angle is stronger for the hetero-azeotropic mixture with unfavorableunlike fluid–fluid interactions than for the mixture with thehigh-boiling azeotrope with favorable unlike fluid–fluid interactions,that is, total wetting is reached for lower concentrations of A forthe hetero-azeotropic mixture.Due to the strong preferenceof component A, high concentrationsof component A in the first adsorbate layer and a depletion of componentB in that layer are observed. This effect levels out with increasingdistance from the wall’s surface and vanishes at distancesabove 2.5σ from the surface. Then, only the fluid–fluidinteractions determine the wetting. The strong adsorption of componentA leads to a shielding of component B from the solid. Both, thin-filmand thick-film adsorption from the vapor phase were observed. Totalwetting always resulted in thick-film adsorption and partial wettingmostly in thin-film adsorption, except for the hetero-azeotropic mixtureand high concentrations of component A. There, thick-film adsorptionwas observed. For this mixture, the transition from thin-film to thick-filmtook place continuously. For the other two mixtures, it took placein a discrete manner upon the transition from partial to total wetting.The surface excess of component A shows no influence of the strengthof the unlike fluid–fluid interactions; however, this is notthe case for the surface excess of component B, which depends stronglyon the unlike fluid–fluid interactions.An unexpectedbehavior was observed in the McCabe–Thielediagram relating the vapor phase adsorbate layer mole fraction tothat in the bulk vapor phase: for partial wetting, all simulationresults lie on one curve, independent of the mixture. This means thatthe mole fraction of the vapor phase adsorbate layer can be predictedfrom that of the vapor phase without taking into account the strengthof the unlike fluid–fluid interactions; it is determined onlyby the solid–fluid interactions. For total wetting, the compositionof the adsorbate layer is more liquid-like and the separation of componentA is decreased compared to partial wetting.In the three-phasecontact, the behavior of the vapor–liquidinterface is superimposed by the solid–fluid interaction. Foran increasing distance from the solid, the corresponding vapor–liquidinterface of each mixture was observed.Molecular simulationstudies enable systematic studies of the influenceof molecular parameters on the adsorption and wetting of mixtures.Only a very simple scenario was investigated here: the attractiveinteractions were dispersive, the two pure fluids were identical,and only two molecular parameters were varied. Despite this, a wealthof phenomena was observed and could be explained. The approach canobviously be extended to many other interesting cases.