New Zealand White Rabbits Effectively Clear Borrelia burgdorferi B31 despite the Bacterium's Functional vlsE Antigenic Variation System.

Borrelia burgdorferi is a tick-borne bacterium responsible for approximately 300,000 annual cases of Lyme disease (LD) in the United States, with increasing incidences in other parts of the world. The debilitating nature of LD is mainly attributed to the ability of B. burgdorferi to persist in patients for many years despite strong anti-Borrelia antibody responses. Antimicrobial treatment of persistent infection is challenging. Similar to infection of humans, B. burgdorferi establishes long-term infection in various experimental animal models except for New Zealand White (NZW) rabbits, which clear the spirochete within 4 to 12 weeks. LD spirochetes have a highly evolved antigenic variation vls system, on the lp28-1 plasmid, where gene conversion results in surface expression of the antigenically variable VlsE protein. VlsE is required for B. burgdorferi to establish persistent infection by continually evading otherwise potent antibodies. Since the clearance of B. burgdorferi is mediated by humoral immunity in NZW rabbits, the previously reported results that LD spirochetes lose lp28-1 during rabbit infection could potentially explain the failure of B. burgdorferi to persist. However, the present study unequivocally disproves that previous finding by demonstrating that LD spirochetes retain the vls system. However, despite the vls system being fully functional, the spirochete fails to evade anti-Borrelia antibodies of NZW rabbits. In addition to being protective against homologous and heterologous challenges, the rabbit antibodies significantly ameliorate LD-induced arthritis in persistently infected mice. Overall, the current data indicate that NZW rabbits develop a protective antibody repertoire, whose specificities, once defined, will identify potential candidates for a much-anticipated LD vaccine.

Does Point-of-Care Ultrasonography Improve Clinical Outcomes in Emergency Department Patients With Undifferentiated Hypotension? An International Randomized Controlled Trial From the SHoC-ED Investigators.

STUDY OBJECTIVE: Point-of-care ultrasonography protocols are commonly used in the initial management of patients with undifferentiated hypotension in the emergency department (ED). There is little published evidence for any mortality benefit. We compare the effect of a point-of-care ultrasonography protocol versus standard care without point-of-care ultrasonography for survival and clinical outcomes. METHODS: This international, multicenter, randomized controlled trial recruited from 6 centers in North America and South Africa and included selected hypotensive patients (systolic blood pressure <100 mm Hg or shock index >1) randomized to early point-of-care ultrasonography plus standard care versus standard care without point-of-care ultrasonography. Diagnoses were recorded at 0 and 60 minutes. The primary outcome measure was survival to 30 days or hospital discharge. Secondary outcome measures included initial treatment and investigations, admissions, and length of stay. RESULTS: Follow-up was completed for 270 of 273 patients. The most common diagnosis in more than half the patients was occult sepsis. We found no important differences between groups for the primary outcome of survival (point-of-care ultrasonography group 104 of 136 patients versus standard care 102 of 134 patients; difference 0.35%; 95% binomial confidence interval [CI] -10.2% to 11.0%), survival in North America (point-of-care ultrasonography group 76 of 89 patients versus standard care 72 of 88 patients; difference 3.6%; CI -8.1% to 15.3%), and survival in South Africa (point-of-care ultrasonography group 28 of 47 patients versus standard care 30 of 46 patients; difference 5.6%; CI -15.2% to 26.0%). There were no important differences in rates of computed tomography (CT) scanning, inotrope or intravenous fluid use, and ICU or total length of stay. CONCLUSION: To our knowledge, this is the first randomized controlled trial to compare point-of-care ultrasonography to standard care without point-of-care ultrasonography in undifferentiated hypotensive ED patients. We did not find any benefits for survival, length of stay, rates of CT scanning, inotrope use, or fluid administration. The addition of a point-of-care ultrasonography protocol to standard care may not translate into a survival benefit in this group.

A traumatic tale of two cities: does EMS level of care and transportation model affect survival in patients with trauma at level 1 trauma centres in two neighbouring Canadian provinces?

BACKGROUND: Two distinct Emergency Medical Services (EMS) systems exist in Atlantic Canada. Nova Scotia operates an Advanced Emergency Medical System (AEMS) and New Brunswick operates a Basic Emergency Medical System (BEMS). We sought to determine if survival rates differed between the two systems. METHODS: This study examined patients with trauma who were transported directly to a level 1 trauma centre in New Brunswick or Nova Scotia between 1 April 2011 and 31 March 2013. Data were extracted from the respective provincial trauma registries; the lowest common Injury Severity Score (ISS) collected by both registries was ISS≥13. Survival to hospital and survival to discharge or 30 days were the primary endpoints. A separate analysis was performed on severely injured patients. Hypothesis testing was conducted using Fisher's exact test and the Student's t-test. RESULTS: 101 cases met inclusion criteria in New Brunswick and were compared with 251 cases in Nova Scotia. Overall mortality was low with 93% of patients surviving to hospital and 80% of patients surviving to discharge or 30 days. There was no difference in survival to hospital between the AEMS (232/251, 92%) and BEMS (97/101, 96%; OR 1.98, 95% CI 0.66 to 5.99; p=0.34) groups. Furthermore, when comparing patients with more severe injuries (ISS>24) there was no significant difference in survival (71/80, 89% vs 31/33, 94%; OR 1.96, 95% CI 0.40 to 9.63; p=0.50). CONCLUSION: Overall survival to hospital was the same between advanced and basic Canadian EMS systems. As numbers included are low, individual case benefit cannot be excluded.

Metabolic analysis of striatal tissues from Parkinson's disease-like rats by electrospray ionization ion mobility mass spectrometry.

Electrospray ionization ion mobility mass spectrometry (ESI-IMMS) was used to study the striatal metabolomes in a Parkinson's like disease (PD-like) rat model. Striatal tissue samples from Berlin Druckrey IV (BD-IV) with PD-like disease 20 dpn-affected and 15 dpn-affected rats (dpn: days postnatal) were investigated and compared with age-matched controls. An ion mobility mass spectrometer (IMMS) produced multidimensional spectra with mass to charge ratio (m/z), ion mobility drift time, and intensity information for each individual metabolite. Principle component analysis (PCA) was applied in this study for pattern recognition and significant metabolites selection (68% data was modeled in PCA). Both IMMS spectra and PCA results showed that there were clear global metabolic differences between PD-like samples and healthy controls. Nine metabolites were selected by PCA and identified as potential biomarkers using the Human Metabolome Database (HMDB). One targeted metabolite in this study was dopamine. Selected-mass mobility analysis indicated the absence of dopamine in PD-like striatal metabolomes. A major discovery of this work, however, was the existence of an isomer of dopamine. By using ion mobility spectrometry, the dopamine isomer, which has not previously been reported, was separated from dopamine.

Assessment of tumoral and peritumoral inflammatory reaction in cutaneous malignant melanomas.

Skin cancer is one of the most common types of cancer, with an increasing worldwide incidence in recent decades. The main risk factor for increasing the skin cancer incidence is ultraviolet (UV) radiation. Of the two major forms of skin cancer (melanomas and non-melanotic cancers), the cutaneous melanoma (CM) is the most aggressive form, causing about 80% of the deaths resulted from this type of tumor. Malignant melanoma develops through malignant transformation of melanocytes in the skin because of prolonged exposure to solar or artificial UV. The malignant transformation of the melanocytes in the skin is accompanied by the presence of a local inflammatory reaction that, in the initial stages of carcinogenesis, would oppose to tumor development. Chronic exposure to UV or other etiopathogenic factors induces chronic inflammation, which, by producing inflammatory molecules (cytokines, chemokines, prostaglandins), constitutes a tumoral microenvironment that favors carcinogenesis, tumor invasion, metastasis, and the presence of neoplastic "mutant cells" that avoid the protective action of the immune system. Using immunohistochemistry techniques, we assessed the intra- and peritumoral inflammatory infiltrate cells in CM. The chronic inflammatory infiltrate presented more intense in the peritumoral stroma compared to the intratumoral one, heterogenous, more intensely composed of lymphocytes, plasma cells, macrophages, and mast cells (MCs), the most numerous cells in the inflammatory infiltrate being T-lymphocytes, plasma cells and macrophages; B-lymphocytes and MCs were in a small number, especially intratumorally. Inflammatory cells had a direct contact with tumor cells, blood vessels, connective matrix, suggesting that the inflammatory microenvironment plays an important role in carcinogenesis, tumor invasion, local angiogenesis, and tumor metastasis.

Mechanisms of Altered Immune Response in Skin Melanoma.

Melanoma, a deadly form of skin cancer, poses significant challenges to the host immune system, allowing tumor cells to evade immune surveillance and persist. This complex interplay between melanoma and the immune system involves a multitude of mechanisms that impair immune recognition and promote tumor progression. This review summarizes the intricate strategies employed by melanoma cells to evade the immune response, including defective immune recognition, immune checkpoint activation, and the role of regulatory T-cells, myeloid-derived suppressor cells, and exosomes in suppressing anti-tumor immunity. Additionally, we discuss potential therapeutic targets aimed at reversing immune evasion in melanoma, highlighting the importance of understanding these mechanisms for developing more effective immunotherapies. Improved insights into the interactions between melanoma and the immune system will aid in the development of novel treatment strategies to enhance anti-tumor immune responses and improve patient outcomes.

The Impact of Competitive Sports on Oral Health: Exploring Their Relationship with Salivary Oxidative Stress in Children.

This article explores the correlation between salivary biomarkers, such as glutathione peroxidase (GPX), total antioxidant capacity (TAC), and superoxide dismutase (SOD), and their association with oral health for children in competitive sports. Saliva has emerged as a valuable resource for evaluating physiological and pathological conditions due to its non-invasive collection method and easy storage. This study examines the potential of GPX, TAC, and SOD as salivary biomarkers for assessing the impact of competitive sports on children's oral health. It discusses the potential implications of increased oxidative stress due to intense physical activity and the role of antioxidant defense mechanisms in maintaining oral health. In total, 173 children aged between 6 and 17 were divided into three groups, 58 hockey players, 55 football players, and 60 in the control group, and examined to assess their oral hygiene and dental and periodontal health. Saliva was collected, centrifuged, and the supernatant was analyzed for the relevant biomarkers. The findings seem to suggest that salivary biomarkers, like GPX, TAC, and SOD, might serve as indicators of the physiological response to competitive sports in children, as well as indicators of oral health, especially dental cavities, and periodontal disease. Statistical analysis showed significant differences between the groups, with better values for athletes, regardless of age, sex, or activity type. Understanding the relationship between salivary biomarkers and competitive sports in children can have significant implications for monitoring and optimizing the health and performance of young athletes. Further research is needed to establish the specific associations between these biomarkers and the effects of several types and intensities of sports activities on oral health in children.

Retrospective Study of a Patient with Multiple de Novo Skin Tumor Formations.

In Romania, the incidence of malignant melanocytic tumors is continuously increasing. According to the World Health Organization, the incidence of melanocytic and non-melanocytic skin neoplasms has increased considerably and globally, in the last decade. We present the case of a 49-year-old patient who, over the course of 7 years, came in the Plastic Surgery Clinic of the Emergency County Hospital of Craiova for the excision of a number of 25 skin tumor formations, located on the face, cervical region, trunk and upper limbs. Treatment included complete microsurgical excision and supervision. In the end, the patient's treatment compliance decreased significantly.

Potential role of α-synuclein in neurodegeneration: studies in a rat animal model.

Neuronal protein α-synuclein (α-syn) is an essential player in the development of neurodegenerative diseases called synucleinopathies. A spontaneous autosomal recessive rat model for neurodegeneration was developed in our laboratory. These rats demonstrate progressive increases in α-syn in the brain mesencephalon followed by loss of dopaminergic terminals in the basal ganglia (BG) and motor impairments. The severity of pathology is directly related to the overexpression of α-syn and parallel decrease in dopamine (DA) level in the striatum (ST) of affected rats. The neurodegeneration in this model is characterized by the presence of perikarya and neurites Lewis bodies (LB) and diffuse marked accumulation of perikaryal α-syn in the substantia nigra (SN), brain stem (BS), and striatum (ST) along with neuronal loss. Light and ultrastructural analyses revealed that the process of neuronal degeneration is a 'dying back' type. The disease process is accompanied by gliosis and release of inflammatory cytokines. This neurodegeneration is a multisystemic disease and implicate α-syn as a major factor in the pathogenesis of this inherited autosomal recessive animal model. Decrease dopamine (DA) and overexpression of α-syn in the brain mesencephalon may provide a naturally occurring animal model for Parkinson's disease (PD) and other synucleinopathies that reproduces significant pathological, neurochemical, and behavioral features of the human disease.

A mouse model of Down syndrome trisomic for all human chromosome 21 syntenic regions.

Down syndrome (DS) is caused by the presence of an extra copy of human chromosome 21 (Hsa21) and is the most common genetic cause for developmental cognitive disability. The regions on Hsa21 are syntenically conserved with three regions located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. In this report, we describe a new mouse model for DS that carries duplications spanning the entire Hsa21 syntenic regions on all three mouse chromosomes. This mouse mutant exhibits DS-related neurological defects, including impaired cognitive behaviors, reduced hippocampal long-term potentiation and hydrocephalus. These results suggest that when all the mouse orthologs of the Hsa21 genes are triplicated, an abnormal cognitively relevant phenotype is the final outcome of the elevated expressions of these orthologs as well as all the possible functional interactions among themselves and/or with other mouse genes. Because of its desirable genotype and phenotype, this mutant may have the potential to serve as one of the reference models for further understanding the developmental cognitive disability associated with DS and may also be used for developing novel therapeutic interventions for this clinical manifestation of the disorder.

Activation of AMP-activated protein kinase in cerebella of Atm-/- mice is attributable to accumulation of reactive oxygen species.

Ataxia telangiectasia (A-T) is an inherited disease, the most prominent feature of which is ataxia caused by degeneration of cerebellar neurons and synapses. The mechanisms underlying A-T neurodegeneration are still unclear, and many factors are likely to be involved. AMP-activated protein kinase (AMPK) is a sensor of energy balance, and research on its function in neural cells has gained momentum in the last decade. The dual roles of AMPK in neuroprotection and neurodegeneration are complex, and they need to be identified and characterized. Using an Atm (ataxia telangiectasia mutated) gene deficient mouse model, we showed here that: (a) upregulation of AMPK phosphorylation and elevation of reactive oxygen species (ROS) coordinately occur in the cerebella of Atm-/- mice; (b) hydrogen peroxide induces AMPK phosphorylation in primary mouse cerebellar astrocytes in an Atm-independent manner; (c) administration of the novel antioxidant monosodium luminol (MSL) to Atm-/- mice attenuates the upregulation of both phosphorylated-AMPK (p-AMPK) and ROS, and corrects the neuromotor deficits in these animals. Together, our results suggest that oxidative activation of AMPK in the cerebellum may contribute to the neurodegeneration in Atm-/- mice, and that ROS and AMPK signaling pathways are promising therapeutic targets for treatment of A-T and other neurodegenerative diseases.

Custom-Made Direct Metal Laser Sintering Titanium Subperiosteal Implants in Oral and Maxillofacial Surgery for Severe Bone-Deficient Patients-A Pilot Study.

BACKGROUND: Nowadays, a combination of classical subperiosteal implant designs with 3D imaging and printing allows one to reduce treatment time and provides support for fixed prostheses in cases where other techniques do not provide satisfactory results. This study aims to present a digital technique for the manufacturing of custom-made subperiosteal implants and what complications might appear after this type of surgery. METHODS: Sixteen patients treated with a custom-made DMLS titanium subperiosteal implant during the period between October 2021 and February 2022 were enrolled in the study. Orthopantomography (OPT) and cone-beam computer tomography (CBCT) were recorded for all patients. The measurements taken into account in this study were the fit and stability of implants, duration of surgery, implant survival, and early and late complications. RESULTS: The fit of the implants was extremely satisfactory, with a mean rating of 4 out of 5. The mean duration of the intervention was 86.18 min. At the end of the study, one implant was lost due to insufficient fit and recurrent, untreatable infections. Eleven implants (69%) were placed on the maxillary and five (31%) implants were placed on the mandible. CONCLUSIONS: Taking this into consideration, custom-made DMLS titanium subperiosteal implants could present satisfactory implant survival and low complication rates.

Ductus Venosus Agenesis and Portal System Anomalies-Association and Outcome.

To evaluate the prenatal diagnosis of agenesis of ductus venosus (ADV) and portal venous system (PVS) anomalies and describe the outcome of these cases, either isolated or associated. We evaluated the intrahepatic vascular system regarding the presence of normal umbilical drainage and PVS characteristics in the second and third trimester of pregnancy. The associated anomalies and umbilical venous drainage were noted. Follow-up was performed at six months follow-up. Ultrasonography was performed in 3517 cases. A total of 19 cases were prenatally diagnosed: 18 ADV cases, seven abnormal PVS cases, and six associations of the two anomalies. We noted an incidence of 5.1‱ and 1.9‱ for ADV and PVS anomalies, respectively. Out of the 18 ADV cases, 27.7% were isolated. Five cases (26.3%) presented genetic anomalies. PVS anomalies were found in 33.3% of the ADV cases. ADV was present in 85.7% of the PVS anomalies. DV and PVS abnormalities were found with a higher than reported frequency. Normal DV is involved in the normal development of the PVS. Additional fetal anomalies are the best predictor for the outcome of ADV cases. Evaluation of PVS represents a powerful predictor for ADV cases and addresses the long-term prognosis.

Multiple trials may yield exaggerated effect size estimates.

Published psychological research attempting to support the existence of small and medium effect sizes may not have enough participants to do so accurately, and thus, repeated trials or the use of multiple items may be used in an attempt to obtain significance. Through a series of Monte-Carlo simulations, this article describes the results of multiple trials or items on effect size estimates when the averages and aggregates of a dependent measure are analyzed. The simulations revealed a large increase in observed effect size estimates when the numbers of trials or items in an experiment were increased. Overestimation effects are mitigated by correlations between trials or items, but remain substantial in some cases. Some concepts, such as a P300 wave or a test score, are best defined as a composite of measures. Troubles may arise in more exploratory research where the interrelations among trials or items may not be well described.

Retrospective Study Over the Hypospadias Surgery in a Single Tertiary Center.

Hypospadias surgery is a common activity in every department for pediatric surgery, increased incidence of this condition contributing this aspect. For this purpose permanent review of the data of cases is probably necessary, in order to promptly evaluate short and long term results. MATERIAL AND METHODS: The authors are presenting this retrospective clinical and statistical study, enrolling 149 patients, hospitalized and operated in the Department of Pediatric Surgery and Orthopedics, between 2009 and 2018. several parameters were taken into consideration: moment of conception, type of hypospadias, associated malformations, use of meatoplasty, age at meatoplasty, age at urethroplasty, type of urethroplasty, postoperative incidents and complications. RESULTS: Most of the patients included in the study were classified as anterior type of hypospadias, associated malformations were present in 20,13% of the patients, and 80% of the associated malformations belonged to the urogenital system. Over 60% of the cases underwent meatoplasty as a tactical procedure. Mathieu was the most appreciated procedure (74,5%) for urethroplasty and over a half of the patients were operated after the age of 3 years. Early and late postoperative fistula formation was noted in 18,12% of cases. CONCLUSIONS: Better parameters to assess the exact type of hypospadias are needed to be introduced. Also, clear protocols for preoperative work-up in detection of other abnormalities, especially genito-urinary. Meatoplasty as a tactical procedure is having unclear influence for urethroplasty. Decreasing the age at urethroplasty should be the next goal. Some surgeons should really get overspecialized for this type of surgery.

Effect of curcumin and Meriva on the lung metastasis of murine mammary gland adenocarcinoma.

BACKGROUND: Curcumin is one of the most studied natural compounds which has been used as a feed additive for centuries. Curcumin exhibits low oral bioavailability in rodents and human. Curcumin formulated with phosphatidylcholine (Meriva) increases curcumin bioavailability five-fold compared to original curcumin. The aim of this study was to evaluate the efficacy of curcumin conjugated with phosphatidylcholine as an anticancer agent. MATERIALS AND METHODS: In this xenograft study, mammary gland tumor cell line (ENU1564) was inoculated into the mammary fat pad of athymic nude mice. The mice were treated orally with either curcumin or Meriva. The tumor and its lung metastasis were evaluated grossly, microscopically, and immunohistochemically. RESULTS: Meriva significantly reduced the expression of MMP-9 and lung metastasis of our cell line used in this experimental model. CONCLUSION: Curcumin conjugated with phosphatidylcholine increased the efficacy of curcumin as an anticancer agent.

Changes in nursing students' knowledge, attitudes and interest in caring for older adults: A longitudinal cohort study.

Nursing education programs have a responsibility to prepare future nurses to care for the growing number of older adults who will be accessing health care services. Preparation involves ensuring students have the knowledge, skills and desire to provide quality care to older adults. A longitudinal cohort study was conducted to collect data on students' knowledge of, attitudes towards, and interest in working with older adults during each year of an undergraduate nursing program. Data were collected using the Kogan Attitudes Towards Older People Scale, Palmore's Fact on Aging Quiz and a demographic instrument designed specifically for this study. Results showed slight improvements in students' overall attitudes towards older adults at the completion of their nursing degree. Increases in knowledge were seen in 12 of 24 areas measured. Gerontology as a preferred career choice was highest immediately following a clinical placement focusing on caring for older adults. Integrating gerontological clinical experiences into a beginning fundamental nursing course does not necessarily improve students' learning in the area of caring for older adults. Nursing programs have a responsibility to design, monitor and update curricula to ensure students are being adequately prepared to care for older adults.

Prenatal findings and pregnancy outcome in fetuses with right and double aortic arch. A 10-year experience at a tertiary center.

OBJECTIVE: Our objective was to evaluate the accuracy of the prenatal diagnosis and the relation between the type of right aortic arch (RAA) with other intra- or extracardiac (EC) and chromosomal anomalies. METHODS: A retrospective, observational study was conducted between 2011-2020 in a Romanian tertiary center. All RAA cases, including double aortic arch (DAA), were extracted from the databases and studied thoroughly. RESULTS: We detected 18 RAA cases: five (27.78%) type I (mirror image, "V" type), 11 (61.12%) type II ("U" type), and two (11.10%) DAA cases. Heart anomalies were associated in 38.89% (overall), 60% (type I), 36.37% (type II), and 0% (DAA) cases. Tetralogy of Fallot represented the most prevalent cardiac malformation (in 22.23% of cases). EC anomalies were present in 44.44% of fetuses (20% of type I, 54.55% of type II, and 50% of DAA cases). Genetic abnormalities were found in 41.17% of pregnancies, with 22q11.2 deletion in 23.53%. 55.55% of the cases had a good neonatal evolution and 44.45% of the pregnancies were terminated. An overall good outcome of pregnancy was noted in 40% of type I RAA, 63.64% of type II RAA, and 50% of DAA cases. All RAA cases examined in the first trimester were correctly diagnosed. CONCLUSIONS: RAA can be accurately diagnosed and classified by means of prenatal ultrasound since early pregnancy. A detailed anatomy scan and genetic testing, including 22q11 deletion, should be offered to all pregnancies when RAA is discovered. When isolated, RAA associates a good outcome, indifferently the anatomical type.

Peripheral adenopathies in children - an attempt of clinical morphological profile.

AIM: The authors have proposed to assess peripheral adenopathies in a series of hospitalized children in order to identify and define clinical and morphological profiles of different types of lymph node (LN) diseases. MATERIALS AND METHODS: The studied group consisted of 58 patients less than 18 years of age. The investigation algorithm included: gender, age, site, involvement, side, extension and histopathological (HP) type of LN lesions. Tissue fragments were processed using classical histological techniques (formalin fixation and paraffin embedment) and stained with Hematoxylin-Eosin (HE). In some cases (tuberculous lesions and lymphomas), special stainings (Ziehl-Neelsen) and immunohistochemistry were used. Stratification scales of cases were defined according to each parameter in order to compare the data. All obtained data were assessed individually, compared to each other and with similar data from the literature with the help of a statistical apparatus [χ² (chi-squared) test and analysis of variance (ANOVA) test] in some cases. RESULTS: The young patients were slightly more frequently boys, of all ages but with a mean age of 10 and half years. The affected LNs belonged most often to neck region, either on the left or on the right side but sometimes bilateral or even on the midline; usually, more than one LN was involved in the area. In most of the cases, the lesions were localized in only one LN area. HP picture was dominated by the inflammatory processes, firstly the nonspecific ones, followed by tuberculosis. DISCUSSIONS: Our observations fitted, for each parameter, with the wide ranges found in the literature. Comparisons between parameters' variations revealed differences, sometimes significant that we tried to organize in clinical and morphological profiles. CONCLUSIONS: The assessment of our data allowed us to define some clinical and morphological profiles of different types of adenopathy that, by improvement on studies including larger series, could be of real use in daily pediatric practice.

Does Point of Care Ultrasound Improve Resuscitation Markers in Undifferentiated Hypotension? An International Randomized Controlled Trial From The Sonography in Hypotension and Cardiac Arrest in the Emergency Department (SHoC-ED) Series.

Introduction Point of Care Ultrasound (PoCUS) protocols are commonly used to guide resuscitation for patients with undifferentiated hypotension, yet there is a paucity of evidence for any outcome benefit. We undertook an international multicenter randomized controlled trial (RCT) to assess the impact of a PoCUS protocol on key clinical outcomes. Here we report on resuscitation markers.  Methods Adult patients presenting to six emergency departments (ED) in Canada and South Africa with undifferentiated hypotension (systolic blood pressure (SBP) <100mmHg or a Shock Index >1.0) were randomized to receive a PoCUS protocol or standard care (control). Reported physiological markers include shock index (SI), and modified early warning score (MEWS), with biochemical markers including venous bicarbonate and lactate, at baseline and four hours.  Results A total of 273 patients were enrolled, with data collected for 270. Baseline characteristics were similar for each group. Improvements in mean values for each marker during initial treatment were similar between groups: Shock Index; mean reduction in Control 0.39, 95% CI 0.34 to 0.44 vs. PoCUS 0.33, 0.29 to 0.38; MEWS, mean reduction in Control 2.56, 2.22 to 2.89 vs. PoCUS 2.91, 2.49 to 3.32; Bicarbonate, mean reduction in Control 2.71 mmol/L, 2.12 to 3.30 mmol/L vs. PoCUS 2.30 mmol/L, 1.75 to 2.84 mmol/L, and venous lactate, mean reduction in Control 1.39 mmol/L, 0.93 to 1.85 mmol/L vs. PoCUS 1.31 mmol/L, 0.88 to 1.74 mmol/L. Conclusion We found no meaningful difference in physiological and biochemical resuscitation markers with or without the use of a PoCUS protocol in the resuscitation of undifferentiated hypotensive ED patients. We are unable to exclude improvements in individual patients or in specific shock types.