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Background Previous reports about risk factors for linezolid-induced thrombocytopenia have been insufficient, often due to the variability in study design and population, and some factors have not yet been studied. Aim The aims of this study are to determine potential risk factors for linezolid-induced thrombocytopenia, and to analyze the influencing factors of different thrombocytopenia definitions. Method This retrospective study involved patients who were administered intravenous linezolid for ≥ 1 day between January 1, 2015 and January 1, 2021. Their demographic and clinical data were extracted from electronic medical records. Thrombocytopenia was defined as: ①thrombocytopenia with platelet count

Summary Crosstalk between endothelial cells (ECs) and pericytes or vascular smooth muscle cells (VSMCs) is essential for the proper functioning of blood vessels. This balance is disrupted in several vascular diseases but there are few experimental models which recapitulate this vascular cell dialogue in humans. Here, we developed a robust multi-cell type 3D vessel-on-chip (VoC) model based entirely on human induced pluripotent stem cells (hiPSCs). Within a fibrin hydrogel microenvironment, the hiPSC-derived vascular cells self-organized to form stable microvascular networks reproducibly, in which the vessels were lumenized and functional, responding as expected to vasoactive stimulation. Vascular organization and intracellular Ca2+ release kinetics in VSMCs could be quantified using automated image analysis based on open-source software CellProfiler and ImageJ on widefield or confocal images, setting the stage for use of the platform to study vascular (patho)physiology and therapy., Graphical abstract, Highlights • 3D VoC formed by hiPSC-ECs and hiPSC-VSMCs • Vascular organization in 3D VoC formed by hiPSC-VSMC and primary mural cells • Functional responses of hiPSC-VSMCs in 3D VoC • Automated analysis of microvascular network morphology and Ca2+ release in VSMCs, In this article, Orlova and colleagues describe the generation of an entirely human induced pluripotent stem cells (hiPSC)-derived vessel-on-chip composed with endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Changes in microvascular network architecture and intracellular Ca2+ release kinetics could be quantified during vascular organization or upon drug treatment providing a useful platform to study vascular development and disease.

Smooth muscle cells (SMCs) usually express a contractile phenotype in the healthy aorta. However, aortic SMCs have the ability to undergo profound changes in phenotype in response to changes in their extracellular environment, as occurs in ascending thoracic aortic aneurysms (ATAA). Accordingly, there is a pressing need to quantify the mechanobiological effects of these changes at single cell level. To address this need, we applied Traction Force Microscopy (TFM) on 759 cells coming from three primary healthy (AoPrim) human SMC lineages and three primary aneurysmal (AnevPrim) human SMC lineages, from age and gender matched donors. We measured the basal traction forces applied by each of these cells onto compliant hydrogels of different stiffness (4, 8, 12, 25 kPa). Although the range of force generation by SMCs suggested some heterogeneity, we observed that: 1. the traction forces were significantly larger on substrates of larger stiffness; 2. traction forces in AnevPrim were significantly higher than in AoPrim cells. We modelled computationally the dynamic force generation process in SMCs using the motor-clutch model and found that it accounts well for the stiffness-dependent traction forces. The existence of larger traction forces in the AnevPrim SMCs were related to the larger size of cells in these lineages. We conclude that phenotype changes occurring in ATAA, which were previously known to reduce the expression of elongated and contractile SMCs (rendering SMCs less responsive to vasoactive agents), tend also to induce stronger SMCs. Future work aims at understanding the causes of this alteration process in aortic aneurysms. Supplementary information The online version of this article (10.1007/s10237-020-01412-6) contains supplementary material, which is available to authorized users.

COVID 19 pandemic has affected the world for more than one year now. It has had impact on children as well, but the numbers have been fewer than adults, with lesser morbidity. Children have been commonly asymptomatic and are suspected to be the spreaders to the more susceptible part of the community. Nasopharyngeal swab testing is difficult and challenging in smaller children, and therefore their results should be interpreted with caution. Multisystem involvement has been seen in some children who required ICU admission. Most centers treated these cases as a multisystem inflammatory syndrome and used vasoactive agents for support. Overall, children showed lower morbidity and mortality all over the world.

Background: The role of vasoactive medications in septic shock is well-defined, but the appropriate time of initiation of these medications in reference to fluid boluses is not clear. We planned to study prospectively the practices and outcome of initiation of vasoactive infusions with respect to resuscitation fluids boluses in pediatric septic shock. Patients and methods: Children aged 1 month to 18 years diagnosed with septic shock were enrolled to receive fluid resuscitation boluses along with vasoactive drugs. The primary outcome was to look at various practices of the initiation of vasoactive infusions; accordingly, patients were categorized into three groups: N1 received vasoactive infusions after completion of the first bolus (20 mL/kg), N2 after the second (40 mL/kg), and N3 after the third fluid (60 mL/kg) bolus. Secondary outcomes were to compare the time taken, amount of fluid required to achieve hemodynamic stability, total fluid required, and complications in the first 24 hours of treatment and mortality. Results: Hundred children were enrolled and grouped into N1, N2, and N3 with 46, 10, and 44 patients, respectively. The volume of fluid required to achieve the resolution of shock in N1 (40 ± 10 mL/kg) was significantly less than in N2 (70 ± 10 mL/kg) and N3 (70 ± 20 mL/kg); p = 0.02. The time taken to achieve hemodynamic stability was significantly less in N1 (115 ± 45 minutes) than in N2 (196 ± 32 minutes) and N3 (212 ± 44 minutes); p = 0.02. The volume of intravenous fluid required in the first 24 hours (p = 0.02) and complications were lower in the N1 group (p = 0.04). No statistical difference in mortality was seen. Conclusion: Early initiation of vasoactive infusions (after the first bolus) resulted in less total fluid volume, lesser time to achieve hemodynamic stability, less fluid boluses, less length of stay in the pediatric intensive care unit, and lesser complications in the first 24 hours. Highlight: Early initiation of vasoactive infusions—after completion of the first fluid bolus resulted in less need for further fluid boluses, lesser time for shock resolution, lesser fluid overload, and less PICU stay—in pediatric septic shock. How to cite this article: Karanvir, Gupta S, Kumar V. Practices of Initiation of Vasoactive Drugs in Relation to Resuscitation Fluids in Children with Septic Shock: A Prospective Observational Study. Indian J Crit Care Med 2021;25(8):928–933.

Background Hoof disease is one of the three major diseases that often occur in dairy cows. The impact of this disease on dairy farming is second only to mastitis. Laminitis is a diffuse, aseptic, serous, non-purulent inflammation of the dermal papillae and vascular layers of the cow’s hoof wall. In the pasture, laminitis occurs mostly in the laminae, that is, inside the hoof shell. No lesions can be seen on the surface. Therefore, laminitis cannot attract the attention of veterinarians. However, laminitis has become a major factor that seriously affects the health and welfare of dairy cows, making it an important cause of hindering the performance of dairy cows. Methods The study was conducted at a dairy farm in Harbin, Heilongjiang province, China. We selected a sample of the laminitis cows based on the veterinary diagnosis, took blood from the jugular vein and then separated the plasma, and measured the index with the Elisa kit. In this study, the markers of inflammatory and vasoactive substances status in dairy cows consisted of subclinical laminitis (SCL, n = 20), chronic laminitis (CL, n = 20) and healthy dairy cows (CON, n = 20) under the local management conditions were investigated. Results Compared with healthy cattle, HIS, IL-6, LPS, and TNF-α in subclinical laminitis group significantly increased (P P P P P P Conclusion This study reported for the first time that pasture laminitis was divided into subclinical laminitis and clinical chronic laminitis. Through research on the inflammatory factors and vasoactive substances of dairy cows, it is found that there is a close relationship between them, which affects the metabolic cycle of dairy cows. These indicators are abnormally expressed and cause hoof microcirculation disorders.

Introduction. It is known that liver cirrhosis (LC) is a chronic diffuse liver disease, the severity of which is manifested by the restructuring of its parenchyma in the form of nodular transformation and fibrosis due to necrosis of hepatocytes, the appearance of shunts between the portal and central veins and liver failure. Oxidative stress is one of the primary pathogenetic links of the LC onset. The aim of study. To determine the content of some endothelium-dependent vasoactive substances in the blood of patients, depending on the liver cirrhosis severity and the organism’s redox system state. Materials and methods. 81 patients (26 females (32.1 %), 55 males (67.9 %) aged 27 to 73 years (mean age – 46.9 ± 10.8 years) were included in the randomized trial with the preliminary stratification by the presence of LC (experimental group – EG). All of them were hospitalized and treated at the Department of Internal Medicine N 1 at Danylo Halytsky Lviv National Medical University and the Gastroenterology Department of Lviv Regional Clinical Hospital – Lviv Regional Hepatology Center. We also examined 20 practically healthy persons (8 females (40.0 %), 12 males (60.0 %)) aged 19 to 70 years (mean age – 41.8 ± 4.2 years) from which a control group (CG) was formed. All patients underwent a comprehensive clinical laboratory and instrumental examination of all organs and systems in accordance with the requirements of the modern medicine. According to the results of the examinations, all the patients of the EG were divided into 3 groups, according to the LC severity by the criteria of C. H. Child – R. N. Pugh – in the first (class A) was 19, in the second (class B) – 29, in the third (class C) – 27 persons. To study the concentration of some endothelium-dependent vasoactive substances in blood of the cirrhotic patients, the content of endothelin-1, cyclic guanosine monophosphate (cGMP), renin, aldosterone, and also natriuretic peptide were determined using standard methods. The activity of catalase and content of thiobarbituric acid (TBA) products, including malondialdehyde (MDA), was studied to determine the redox system state. The actual material was handled on a personal computer in Exel 2010, Statistica 6.0, RStudio v. 1.1.442 and R Commander v.2.4-4 using descriptive statistics. The results obtained in the case of normal distribution were presented as M ± σ, n – the number of patients examined in the group, in case of abnormal distribution – Me [25,0 %; 75.0 %]. The difference was considered statistically significant if p < 0.05. Results. In accordance with the results of the study, it was found that the activity of catalase in the cirrhotic patients significantly (p < 0.001) decreased, and content of MDA content significantly (p < 0.001) increased with the LC severity increase according to the criteria of C. H. Child – R. N. Pugh. It testifies the reduction of antioxidant activity and enhancement of the reactive oxygen species activity with the formation of such toxic substances as MDA in the blood of this category of persons confirming the redox homeostasis disorders. It leads to the impaired functioning of the endothelial cells that are one of the most sensitive to the reactive oxygen species cells. As a result, NO-dependent vasodilatation, increased endothelin-1 synthesis, activation of the renin-aldosterone system, whose effect is negligible, since the decreased sensitivity of the vascular receptors to the influence of endogenous vasoconstrictors, increase of the content of natriuretic peptide, due to the inhibition of renin and aldosterone secretion, as well as a direct effect on the smooth muscle cells of the vascular wall. This is confirmed by the increase of the content of endothelin-1, cGMP, renin, aldosterone, natriuretic peptide in the blood of this category of patients with the LC increasing severity according to the criteria of C. H. Child – R. N. Pugh. Conclusions. The liver significantly influences the endothelium state due to the role of oxidative stress in the metabolisms of NO, endothelin-1, natriuretic peptide, renin-aldosterone system. The cirrhotic patients revealed the increase in malondialdehyde and the decrease in catalase activity with the disease severity increase according to the criteria of C. H. Child – R. N. Pugh. It evidences the significant abnormalities in the redox homeostasis of such patients, and subsequently leads to the endothelial dysfunction with impaired metabolism of vasoactive humoral-metabolic substances in the blood of patients. In particular, them become the prerequisite for the occurrence of extrahepatic comorbid syntropic lesions, that significantly complicate the underlying disease course.

A lateralized distribution of neuropeptidase activities in the frontal cortex of normotensive and hypertensive rats has been described depending on the use of some vasoactive drugs and linked to certain mood disorders. Asymmetrical neuroperipheral connections involving neuropeptidases from the left or right hemisphere and aminopeptidases from the heart or plasma have been suggested to play a role in this asymmetry. We hypothesize that such asymmetries could be extended to the connection between the brain and physiologic parameters and metabolic factors from plasma and urine. To assess this hypothesis, we analyzed the possible correlation between neuropeptidases from the left and right frontal cortex with peripheral parameters in normotensive (Wistar Kyoto [WKY]) rats and hypertensive rats (spontaneously hypertensive rats [SHR]) untreated or treated with vasoactive drugs such as captopril, propranolol and L-nitro-arginine methyl ester. Neuropeptidase activities from the frontal cortex were analyzed fluorometrically using arylamide derivatives as substrates. Physiological parameters and metabolic factors from plasma and urine were determined using routine laboratory techniques. Vasoactive drug treatments differentially modified the asymmetrical neuroperipheral pattern by changing the predominance of the correlations between peripheral parameters and central neuropeptidase activities of the left and right frontal cortex. The response pattern also differed between SHR and WKY rats. These results support an asymmetric integrative function of the organism and suggest the possibility of a different neurometabolic response coupled to particular mood disorders, depending on the selected vasoactive drug., This work was supported by the Ministry of Science and Innovation through project no. SAF 2008 04685 C02 01.

Spontaneous and sensory-evoked activity propagates across varying spatial scales in the mammalian cortex, but technical challenges have limited conceptual links between the function of local neuronal circuits and brain-wide network dynamics. We present a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake mice. Our multi-scale approach employs an orthogonal axis design where the mesoscopic objective is oriented above the brain and the two-photon objective is oriented horizontally, with imaging performed through a microprism. We also introduce a viral method for robust and widespread gene delivery in the mouse brain. These approaches allow us to identify the behavioral state-dependent functional connectivity of pyramidal neurons and vasoactive intestinal peptide (VIP)-expressing interneurons with long-range cortical networks. Our novel imaging system provides a powerful strategy for investigating cortical architecture across a wide range of spatial scales., Reporting summary Further information on research design is available in the Life Sciences Reporting Summary linked to this article.

The aim was to translationally compare a pharmacologic strategy versus treatment with the Impella RP in profound RV cardiogenic shock (CS). The pigs were allocated to either vasoactive therapy with norepinephrine (0.10 μg/kg/min) for the first 30 min, supplemented by an infusion of milrinone (0.4 μg/kg/min) for additional 150 min, or treatment with the Impella RP device for 180 min. Total RV workload (Pressure-volume-area × heart rate*103(mmHg/min)) remained unaffected upon treatment with the Impella RP and increased in the vasoactive group (CS 179[147;228] to norepinephrine 268[247;306](p = 0.002 compared to Impella RP) and norepinephrine + milrinone 366[329;422] (p = 0.002 compared to Impella RP). A trend towards higher venous cerebral oxygen saturation was observed with norepinephrine than Impella RP (Impella RP 51[47;61]% vs norepinephrine 62[57;71]%; p = 0.07), which became significantly higher with the addition of milrinone (Impella RP 45[32;63]% vs norepinephrine + milrinone 73[66;81]%; p = 0.002). The Impella RP unloaded the failing RV. In contrast, vasoactive treatment led to enhanced cerebral venous oxygen saturation.

Background\ud Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications.\ud Methods\ud We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements.\ud Results\ud The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care.\ud Conclusion\ud The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.

ObjectivesTo evaluate whether early intensive care transthoracic echocardiography (TTE) can improve the prognosis of patients with mechanical ventilation (MV).DesignA retrospective cohort study.SettingPatients undergoing MV for more than 48 hours, based on the Medical Information Mart for Intensive Care III (MIMIC-III) database and the eICU Collaborative Research Database (eICU-CRD), were selected.Participants2931 and 6236 patients were recruited from the MIMIC-III database and the eICU database, respectively.Primary and secondary outcome measuresThe primary outcome was in-hospital mortality. Secondary outcomes were 30-day mortality from the date of ICU admission, days free of MV and vasopressors 30 days after ICU admission, use of vasoactive drugs, total intravenous fluid and ventilator settings during the first day of MV.ResultsWe used propensity score matching to analyse the association between early TTE and in-hospital mortality and sensitivity analysis, including the inverse probability weighting model and covariate balancing propensity score model, to ensure the robustness of our findings. The adjusted OR showed a favourable effect between the early TTE group and in-hospital mortality (MIMIC: OR 0.78; 95% CI 0.65 to 0.94, p=0.01; eICU-CRD: OR 0.76; 95% CI 0.67 to 0.86, pConclusionsEarly application of critical care TTE during MV is beneficial for improving in-hospital mortality. Further investigation with prospectively collected data is required to validate this relationship.

The brain is supplied by an elaborate vascular network that originates extracranially and reaches deep into the brain. The concept of the neurovascular unit provides a useful framework to investigate how neuronal signals regulate nearby microvessels to support the metabolic needs of the brain, but it does not consider the role of larger cerebral arteries and systemic vasoactive signals. Furthermore, the recently emerged molecular heterogeneity of cerebrovascular cells indicates that there is no prototypical neurovascular unit replicated at all levels of the vascular network. Here, we examine the cellular and molecular diversity of the cerebrovascular tree and the relative contribution of systemic and brain-intrinsic factors to neurovascular function. Evidence supports the concept of a 'neurovascular complex' composed of segmentally diverse functional modules that implement coordinated vascular responses to central and peripheral signals to maintain homeostasis of the brain. This concept has major implications for neurovascular regulation in health and disease and for brain imaging.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of vasoactive drugs versus placebo or no intervention, or versus another vasoactive drug, or versus a plasma expander during or after paracentesis in people with cirrhosis and large ascites.

Neuroendocrine tumors (NETs) are unusual neoplasms with a diverse spectrum of clinical presentations. There is a lack of literature on cases of 2 primary histologically distinct NETs. We report a case of a 40-year-old man who presented with chronic diarrhea. A colonoscopy was performed which discovered a rectal polyp, with pathology showing a well-differentiated NET. A subsequent somatostatin scan revealed a pancreatic tail mass. Biopsy showed a histologically distinct well-differentiated vasoactive intestinal peptide-producing NET. Given that pancreatic and rectal NETs come from different embryonic origins, the diagnosis of 2 primary NETs presents a unique case.

Helicopter Emergency Medical Services (HEMS) often provide post-resuscitation care. Our aims were to investigate whether physicians' frequent exposure to prehospital post-resuscitation care is associated with differences in (1) medical management, (2) achieving treatment targets recommended by resuscitation guidelines, (3) survival.We conducted a retrospective cohort study using data from a national HEMS quality register. We included patients between January 1st, 2012 and September 9th, 2019 who received post-resuscitation care by a HEMS physician. We excluded patients16 years old. For each patient we determined the number of post-resuscitation cases the physician had attended in the previous 12 months. Patients were divided in to three groups: low (0-5), intermediate (6-11) and high exposure (≥12 cases). Medical management and proportions within treatment targets were compared. Survival at 30-days and 1-year was analysed by multivariate logistic regression analysis, controlling for known prognostic factors.2272 patients were analysed. Patients in the high exposure group had mechanical ventilation and vasoactive medications initiated more often (P 0.001 and P = 0.008, respectively) and on-scene times were longer (P 0.001). The target for blood pressure was achieved more often in this group (P = 0.026), but targets for oxygenation and ventilation were not. We did not see an association between survival and physicians' exposure to post-resuscitation care (odds ratio 0.96, 95% confidence interval 0.70-1.33 for low and 0.78, 0.56-1.08 for intermediate, compared to high exposure).Physicians with more, frequent exposure take a more active approach to post-resuscitation care, but this does not seem to improve survival.

RationaleLittle is known on the use of noninvasive ventilation (NIPPV) in pediatric hematopoietic cell transplant (HCT) patients.ObjectiveWe sought to describe the landscape of NIPPV use and to identify risk factors for failure to inform future investigation or quality improvement.MethodsThis is a multicenter, retrospective observational cohort of 153 consecutive children post-HCT requiring NIPPV from 2010-2016.Results97 (63%) failed NIPPV. Factors associated with failure on univariate analysis included: longer oxygen use prior to NIPPV (p=0.04), vasoactive agent use (p40 at 4 hours [aOR=6.3 9(95% CI: 2.4, 16.4), pConclusionsIn this cohort respiratory rate at 4 hours and vasoactive use are independent risk factors of NIPPV failure. An objective model to predict which children may benefit from a trial of NIPPV, may also inform the timing of both NIPPV initiation and uncomplicated intubation.

Introduction Erectile dysfunction (ED) is associated with various comorbidities and an early diagnosis and treatment is necessary to avoid the development of these comorbidities. Unfortunately, there is no biochemical marker that can be used for early diagnosis of ED. Nitric oxide (NO) is released by nerve and endothelial cells in the corpora cavernosa of the penis and is believed to be the main vasoactive chemical mediator of penile erection. Adropin is a regulatory peptide which has effects on NO bioavailability and energy homeostasis. We hypothesized that adropin may contribute to the pathogenesis of ED because of the presence of both metabolic effects and the influence on NO bioavailability. To confirm this hypothesis, we investigated the relationship between ED and serum adropin and NO levels. Material and methods Seventy-five ED patients were enrolled for this study and the patients were divided into two groups according to angiographic scoring. Serum NO and adropin levels were measured by the Griess reaction and ELISA method, respectively. Results Serum adropin and NO levels were found to be lower in the group which has higher angiographic score and the difference in NO was statistically significant. Also, adropin has a significant correlation between IIEF scores in ED patients. Conclusions This is the first study in the literature investigating the levels of adropin in ED patients having coronary artery disease. The adropin molecule shows a promising future in clarifying the etiopathogenesis of ED. More comprehensive and multicenter studies are needed to reveal the role of adropin in ED and the effects of treatment on this molecule.

Objective: The aim of this study is to investigate the current status of the diagnosis and treatment of patients with pancreatic neuroendocrine neoplasms (pNENs) undergoing surgery in China. Methods: This is a multicenter cross-sectional study performed in China. Data from patients with pNENs undergoing surgery at 33 high-volume medical centers, where the number of pancreatectomies exceeds 20 cases per year, were collected and analyzed between March 1, 2016 and February 28, 2017. Results: In total, 392 patients with pNENs were enrolled. The male to female ratio was 1.4. The majority of patients were aged between 40 and 70 years. 65.6% of the patients had non-functional tumors. Among those with functional tumors, the percentages of insulinomas, gastrinomas, glucagonomas, and vasoactive intestinal peptide-secreting tumors were 94.8%, 1.5%, 2.2%, and 1.5%, respectively. Multidisciplinary team (MDT) discussion was conducted for 39.0% of the patients. Minimally invasive surgery was performed on 31.1 % of the 392 patients. The incidence of grade B/C pancreatic fistula formation was 4.4%. A total of 89.0% of the surgeries achieved R0 resection, and 41.6% of the tumors were well differentiated. Lymph node metastasis was present in 8.9% of the patients. The percentages of patients with grades G1, G2, and G3 disease were 49.2%, 45.7%, and 5.1%, respectively. Conclusion: This multicenter cross-sectional study systematically presents the current status of the diagnosis and treatment of patients with pNENs undergoing surgery in China. MDT consultation for pNENs has not been widely implemented in China. Although the incidence of surgical complications is relatively low, minimally invasive procedures should be further promoted. This study shows us how to improve the outcomes of these patients. Key words: China; Current status; Pancreatic neuroendocrine neoplasms; Pancreatic surgery

Introduction:The fact that critically ill pediatric patients have hemodynamic and metabolic characteristics different from that in adults plays a key role in the selection of vasoactive agent. The aim of this study was to compare the effects of vasoactive agent and agent groups on hemodynamics in order to effectively regulate impaired hemodynamics in critically ill pediatric patients, to provide early diagnosis, time-sensitive and targeted treatment and reduce side effects. Methods:Disease severity, vital signs, renal function, and laboratory data of 103 patients aged 1 to 18 years, who were treated in the pediatric intensive care unit and administered one or more vasoactive agents, were evaluated.Results:The average Pediatric Risk of Mortality (PRISM III-24) score in the dobutamine group was significantly higher than in the adrenalin-dobutamine group (p=0.048), and no statistically significant difference was observed between the other groups (p>0.05). There was a statistically significant difference in the mean cardıac apex beat between dopamine, dobutamine, dopamine-dobutamine and dopamine-adrenaline groups (p=0.0001, p=0.0001 p=0.007 and p=0.011, reespectively). A statistically significant difference was observed in systolic blood pressure (SAB) between dopamine-dobutamine, dopamine-adrenaline and dopamine-dobutamine-adrenaline groups (p=0.003, p=0.00 and p=0.005, respectively). The S0 lactate levels in the adrenaline group were found to be statistically significantly higher than those in dopamine and adrenaline-dobutamine and dopamine-dobutamine-adrenaline groups (p=0.048, p=0.036 and p=0.045. There was a significant difference in S4 lactate values between dopamine-adrenaline and adrenaline-dobutamine groups and between dobutamine and adrenaline groups (p=0.045 and p=0.047, respectively). There was no statistically significant difference in the average central venous oxygen saturation (ScVO2) between dopamine, dobutamine, dopamine-dobutamine, dopamine-adrenaline, adrenaline-dobutamine, dopamine-dobutamine-adrenaline, dopamine-dobutamine-adrenaline-noradrenaline and adrenaline groups (p>0.05). A statistically significant difference was observed between the mean amounts of urine S0, S24 and S48 in the dobutamine group (p=0.002). The average S0 urine volume in the dobutamine group was found to be statistically significantly lower than the average S24, S48 urine volume (p=0.01 and p=0.03, respectively). No statistically significant difference was observed between the other times and groups (p>0.05).Conclusion:Blood lactate levels were significantly higher in the adrenaline group than in the other groups, while no significant difference was found in cardiac apex beat, SAB, ScVO2 and amount of urine between the groups. This elevation was limited to the first 4 hours, and the use of adrenaline together with dopamine and/or dobutamine significantly reduced the incidence of hyperlactatemia compared to the use of adrenaline alone. The use of dobutamine alone significantly increased the amount of urine within hours.

Complex regional pain syndrome (CRPS) is a perplexing painful syndrome of the extremities usually following a harmful event. It is distinguished in two types, mainly depending on the presence of nerve injury. Although its prevalence may vary depending on social and ethnic factors, middle-aged women seem to suffer most often and the upper limb is the most commonly affected extremity. Apart from pain, which is the dominating feature, the clinical picture unfolds across several domains: sensory, motor, autonomic and trophic. This syndrome develops in two phases, the acute (warm) phase, with the classic symptoms of inflammation, and the chronic (cold) phase, often characterized by trophic changes of the soft tissues and even bones. Although the syndrome has been studied for over two decades, no imaging or laboratory test has been established for the diagnosis and recently proposed diagnostic criteria have not yet been validated and are only occasionally applied. Its pathophysiology is still quite obscure, although the most likely mechanisms involve the classic and neurogenic paths of inflammation mediated by cytokines and neuropeptides, intertwined with changes of the autonomic and central nervous system, psychological mechanisms and, perhaps, autoimmunity. Although plenty of treatment modalities have been tried, none has been proven unequivocally efficacious. Apart from information and education, which should be offered to all patients, the most effective pharmacological treatments seem to be bisphosphonates, glucocorticoids and vasoactive mediators, while physical therapy and rehabilitation therapy also make part of the treatment.

Background/objective: A prospective cohort study aimed to evaluate the clinical efficacy of a specific vasoactive herbal formula, Huo Xue Tong Luo capsule (HXTL capsule), for the treatment of patients with asymptomatic osteonecrosis of femoral head (ONFH). Methods: We evaluated a clinical trial of 55 patients (59 hips) with asymptomatic ONFH (no joint collapse) evaluated by Steinberg staging system and necrosis range classification criteria. Then, they were given HXTL capsule under specific protocol. Among them, 39 males and 16 females with an average age of 36.4 ± 10.1 years were followed up for an average of 4.38 years during treatment. The aggravation of clinical and imaging results was assessed by initial pain and joint collapse. The clinical and imaging outcomes of these patients were compared with those of a historical control group from the literature under critical inclusion criteria. Results: At the latest follow-up, initial pain occurred in five of 59 (8.5%) hips of patients taking HXTL capsule compared with 31 of 81 (38.3%) controls (p

Movement has a prominent impact on activity in sensory cortex, but has opposing effects on visual and auditory cortex. Both cortical areas feature a vasoactive intestinal peptide-expressing (VIP) disinhibitory circuit, which in visual cortex contributes to the effect of running. In auditory cortex, however, the role of VIP circuitry in running effects remains poorly understood. Running and optogenetic VIP activation are known to differentially modulate sound-evoked activity in auditory cortex, but it is unknown how these effects vary across cortical layers, and whether laminar differences in the roles of VIP circuitry could contribute to the substantial diversity that has been observed in the effects of both movement and VIP activation. Here we asked whether VIP neurons contribute to the effects of running, across the layers of auditory cortex. We found that both running and optogenetic activation of VIP neurons produced diverse changes in the firing rates of auditory cortical neurons, but with distinct effects on spontaneous and evoked activity and with different patterns across cortical layers. On average, running increased spontaneous firing rates but decreased evoked firing rates, resulting in a reduction of the neuronal encoding of sound. This reduction in sound encoding was observed in all cortical layers, but was most pronounced in layer 2/3. In contrast, VIP activation increased both spontaneous and evoked firing rates, and had no net population-wide effect on sound encoding, but strongly suppressed sound encoding in layer 4 narrow-spiking neurons. These results suggest that VIP activation and running act independently, which we then tested by comparing the arithmetic sum of the two effects measured separately to the actual combined effect of running and VIP activation, which were closely matched. We conclude that the effects of locomotion in auditory cortex are not mediated by the VIP network.

Coronavirus SARS-CoV-2 is responsible for the COVID-19 pandemic, and headache is reported in 6.5% to 34% of all cases. There is little published evidence on the pharmacological treatment of COVID-19 headache. This case series presents six COVID-19 infected patients with refractory headache, in which intranasal bedside Sphenopalatine Ganglion Block was performed for analgesia. All patients had a reduction in headache intensity from severe pain to mild or no pain after the procedure with minor transient side effects. Proposed mechanisms of action include reduction of local autonomic stimuli, intracranial vasoconstriction, and reduction of vasoactive substances release in the pterygopalatine fossa.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation Unrestricted research grant from Abiomed Background No strong evidence exists regarding the treatment of cardiogenic shock (CS) caused by acute right ventricular (RV) failure which has mainly consisted of vasoactive drugs. There is expert agreement that treatment with the recently developed Impella RP is feasible, but no previous studies have compared vasoactive treatment strategies with the Impella RP in terms of cardiac unloading and end-organ perfusion. Hypothesis Treatment with the Impella RP device will be associated with lower RV myocardial workload (pressure-volume area) compared to vasoactive treatment strategies and can furthermore be achieved without compromising organ perfusion. Methods CS was induced by a stepwise injection of polyvinyl alcohol microspheres into the right coronary artery in twenty adult female Danish landrace pigs weighing 75-80 kg. After induction of CS, the pigs were allocated to one of the two interventions for 180 minutes: 1) vasoactive therapy comprised a continuous infusion of norepinephrine (0.1 µg/kg/min) for the first 30 minutes, supplemented by an infusion of milrinone (0.4 µg/kg/min) for the remaining 150 minutes or 2) immediate insertion of and treatment with the Impella RP. The results are presented as median [Q1;Q3]. Results Treatment with the Impella RP was associated with a lower RV workload compared to the vasoactive group, while no difference was observed with regards to left ventricular workload among intervention groups, Figure 1. Renal venous oxygen saturation increased to a similar degree following both interventions compared to the state of CS. A trend towards a higher cerebral venous oxygen saturation was observed with norepinephrine compared to Impella RP (Impella RP 51 [47;61] % vs Norepinephrine 62 [57;71] % ; p = 0.07), which became significantly higher with the addition of milrinone (Impella RP 45 [32;63] % vs Norepinephrine +Milrinone 73 [66;81] %; p = 0.002). Conclusion In this large animal model of profound CS caused by predominantly RV failure the Impella RP unloaded the failing RV. The vasoactive treatment, however, caused a higher cerebral venous oxygen saturation, while both interventions increased renal venous oxygen saturation to a similar degree. Abstract Figure 1

Vasoactive and inotropic medications are essential for sepsis management, however, the association between the maximum Vasoactive-Inotropic score (VISmax) and clinical outcomes is unknown in adult patients with sepsis. We investigated the VISmax as a predictor for mortality among such patients in the emergency department (ED) and compared its prognostic value with that of the sequential organ failure assessment (SOFA) score. This single-center retrospective study included 910 patients diagnosed with sepsis between January 2016 and March 2020. We calculated the VISmax using the highest doses of vasopressors and inotropes administered during the first 6 h on ED admission and categorized it as 0–5, 6–15, 16–30, 31–45, and &gt, 45 points. The primary outcome was 30-day mortality. VISmax for 30-day mortality was significantly higher in non-survivors than in survivors. The mortality rates in the five VISmax groups were 17.2%, 20.8%, 33.3%, 54.6%, and 70.0%, respectively. The optimal cut-off value of VISmax to predict 30-day mortality was 31. VISmax had better prognostic value than the cardiovascular component of the SOFA score and initial lactate levels. VISmax was comparable to the APACHE II score in predicting 30-day mortality. Multivariable analysis showed that VISmax 16–30, 31–45, and &gt, 45 were independent risk factors for 30-day mortality. VISmax in ED could help clinicians to identify sepsis patients with poor prognosis.

Neurogenic erectile dysfunction (NED) can be defined as the inability to achieve or maintain an erection due to central or peripheral neurologic disease. Neurologic diseases can also affect the physical ability and psychological status of the patient. All these factors may lead to a primary or secondary NED. Medication history plays an important role since there are many drugs commonly used in neurologic patients that can lead to ED. The assessment of NED in these patients is generally evolving with the application of evoked potentials technology in the test of somatic and autonomic nerves, and functional magnetic resonance imaging. With the electrophysiological examinations, neurogenic causes can be determined. These tools allow to categorize neurologic lesion and assess the patient prognosis. The first-line treatment for NED is phosphodiesterase inhibitors. Second-line treatments include intracavernous and intraurethral vasoactive injections. Third-line treatments are penile prostheses. The efficacy and safety of each treatment modality depend on the specific neurologic condition. This review discusses the physiology, pathophysiology, diagnosis, and treatment of ED in multiple peripheral and central neurologic conditions, as well as for future research.