A new model of diffuse brain injury in rats

1994 ◽  
Vol 80 (2) ◽  
pp. 291-300 ◽  
Author(s):  
Anthony Marmarou ◽  
Montasser A. Abd-Elfattah Foda ◽  
Wimer van den Brink ◽  
J. Campbell ◽  
H. Kita ◽  
...  
Keyword(s):  
Brain Injury ◽  
Mortality Rate ◽  
Cause Of Death ◽  
Skull Fracture ◽  
Guide Tube ◽  
Diffuse Brain Injury ◽  
Group 2 ◽  
The Impact ◽  
Diffuse Brain ◽  
Group 1

✓ This report describes the development of an experimental head injury model capable of producing diffuse brain injury in the rodent. A total of 161 anesthetized adult rats were injured utilizing a simple weight-drop device consisting of a segmented brass weight free-falling through a Plexiglas guide tube. Skull fracture was prevented by cementing a small stainless-steel disc on the calvaria. Two groups of rats were tested: Group 1, consisting of 54 rats, to establish fracture threshold; and Group 2, consisting of 107 animals, to determine the primary cause of death at severe injury levels. Data from Group 1 animals showed that a 450-gm weight falling from a 2-m height (0.9 kg-m) resulted in a mortality rate of 44% with a low incidence (12.5%) of skull fracture. Impact was followed by apnea, convulsions, and moderate hypertension. The surviving rats developed decortication flexion deformity of the forelimbs, with behavioral depression and loss of muscle tone. Data from Group 2 animals suggested that the cause of death was due to central respiratory depression; the mortality rate decreased markedly in animals mechanically ventilated during the impact. Analysis of mathematical models showed that this mass-height combination resulted in a brain acceleration of 900 G and a brain compression gradient of 0.28 mm. It is concluded that this simple model is capable of producing a graded brain injury in the rodent without a massive hypertensive surge or excessive brain-stem damage.

A new model of diffuse brain injury in rats

1994 ◽  
Vol 80 (2) ◽  
pp. 301-313 ◽  
Author(s):  
Montasser A. Abd-Elfattah Foda ◽  
Anthony Marmarou
Keyword(s):  
Brain Injury ◽  
Brain Stem ◽  
Content Type ◽  
Diffuse Brain Injury ◽  
Weight Drop ◽  
Group 2 ◽  
The Brain ◽  
Fine Print ◽  
Diffuse Brain ◽  
Group 1

✓ A new model producing diffuse brain injury, without focal brain lesions, has been developed in rats. This has been achieved by allowing a weight of 450 gm to fall onto a metallic disc fixed to the intact skull of the animal which is supported by a foam bed. Two levels of injury were examined by adjusting the height of the falling weight to either 1 m or 2 m. Two groups of animals were studied. Group 1 animals were separated into three subgroups: 10 received a 1-m weight drop, 58 received a 2-m weight drop, and 13 served as controls; all were allowed to breathe spontaneously. Group 2 animals were separated into the same subgroups: four received a 1-m weight drop, six received a 2-m weight drop, and four served as controls; all of these were mechanically ventilated during the procedure. In Group 1, morphological studies using light and electron microscopy were performed at 1, 6, 24, or 72 hours, or 10 days after insult; all Group 2 rats were studied at 24 hours after injury. Results from Group 1 animals showed that no mortality occurred with the 1-m level injury, while 59% mortality was seen with the 2-m level injury. On the other hand, no mortality occurred in Group 2 animals regardless of the level of trauma induced. However, the morphological changes observed in both groups were similar. Gross pathological examination did not reveal any supratentorial focal brain lesion regardless of the severity of the trauma. Petechial hemorrhages were noticed in the brain stem at the 2-m level injury. Microscopically, the model produced a graded widespread injury of the neurons, axons, and microvasculature. Neuronal injury was mainly observed bilaterally in the cerebral cortex. Brain edema, in the form of pericapillary astrocytic swelling, was also noted in these areas of the cerebral cortex and in the brain stem. Most importantly, the trauma resulted in a massive diffuse axonal injury that primarily involved the corpus callosum, internal capsule, optic tracts, cerebral and cerebellar peduncles, and the long tracts in the brain stem. It is concluded that this model would be suitable for studying neuronal, axonal, and vascular changes associated with diffuse brain injury.

scholarly journals Beyond the visible world: the role of microscopy in the study of past human conditions

2013 ◽  
Vol 19 (S4) ◽  
pp. 41-42
Author(s):  
S. Assis ◽  
A. Keenleyside ◽  
A.L. Santos
Keyword(s):  
Cause Of Death ◽  
Bone Lesion ◽  
Bone Lesions ◽  
Tissue Quality ◽  
Histological Techniques ◽  
Infectious Origin ◽  
Bone Changes ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Paleopathology, summarily defined as the study of past diseases, has on the differential diagnosis a major challenge. Histological techniques offered the possibility to look inside the microstructure of both normal and abnormal body tissues to diagnose diseases that affected past populations, leading to the development of a new field of research - paleohistology or paleohistopathology. However, and contrary to paleopathology whose journey is well-established, in paleohistopathology there are many gaps that need to be filled. This occurrence is probably the result of a nonsystematic and non-standardized approach to the microscopic study of skeletal abnormalities, especially those of infectious origin involving periosteal new bone formation (PNBF). The aims of this work were: (1) to search for differences in the microstructure of PNBF with regard to the cause of death of the individual; (2) to infer differences between the macroscopic and microscopic proprieties of bone lesions, and (3) to ascertain the impact of diagenetic changes in the bone microstructure. For histological examination under transmitted and polarized light, a total of 34 dry bone specimens: 26 belonging to 23 individuals from the Human Identified Skeletal Collection from the Bocage Museum (Lisbon, Portugal), and eight from archaeological skeletons were prepared. The documented bone samples were collected from individuals who died from tuberculosis-TB (Group 1), non-TB infectious diseases (Group 2), and conditions other than those of TB and non-TB infectious origin (Group 3).With regard to the diagnosis of pathological conditions, differences in the microstructure of PNBF were seen between Group 1 and Group 2 of cause of death and within groups. Multiple layers of “appositional bone” enclosing numerous primary vascular canals were the pattern most commonly observed (n=4) in the samples from Group 1. This type of PNBF seems to mimic the appositional growth that characterizes the modeling process of the periosteal and endosteal membranes (PEM) during rapid growth periods. An abnormal stimulation of growth factors, especially of the vascular endothelial growth factor (VEGF) may eventually explain the extensive hypervascularization observed (Fig. 1 A-B). Periosteal lesions on ribs are normally associated with pulmonary infection (e.g. TB) disseminated from the lungs (via pleura) to the ribs. However, three samples (one from Group 1, two from Group 2) presented a microstructure compatible with subperiosteal hematomas (Fig. 1 C-D). Repetitive microtrauma (e.g. chest wall vibration) that causes detachment of the periosteum may have leaded to subperiosteal bleeding and hematoma formation. These observations suggest that beyond pulmonary diseases other mechanisms may stimulate PNBF on the visceral surface of ribs. Histological analysis was also fundamental in the description and characterization of bone changes. For example, of the five samples with “consolidated” fracture callus, only two presented a truly mature and remodeled microstructure. This means that the outer surface of a bone lesion may not give a complete picture of the tissues response (Fig. 2 A-B). In spite of the good preservation of some bone samples, massive diagenetic changes due to the action of bacteria and fungi were observed at microscopic level. This clearly suggests that gross inspection is not a good measure of the bone tissue quality. In contrast, microscopy is essential to differentiate between pseudopathology and physiological or pathological signs.Microscopy revealed surprising results that reinforce the pertinence of applying histological techniques in the description and diagnosis of bone changes in human remains.This research was supported by Fundação para a Ciência e Tecnologia, Portugal [SFRH/BD/36739/2007, Sandra Assis].

scholarly journals Diabetes Mellitus: An Independent Risk Factor of In-Hospital Mortality in Patients with Infective Endocarditis in a New Era of Clinical Practice

2019 ◽  
Vol 16 (12) ◽  
pp. 2248 ◽  
Author(s):  
Lin ◽  
Chua ◽  
Chung ◽  
Hang ◽  
Tsai
Keyword(s):  
Diabetes Mellitus ◽  
Infective Endocarditis ◽  
Mortality Rate ◽  
Hospital Mortality ◽  
Early Identification ◽  
Multivariable Analysis ◽  
Increased Risk ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Infective endocarditis (IE) is a severe disease with a hospital mortality rate of 17%–25%. Early identification of IE patients with high risk of mortality may improve their clinical outcomes. Patients with diabetes mellitus (DM) who develop infective diseases are associated with worse outcomes. This study aimed to define the impact of DM on long-term mortality in IE patients. A total of 412 patients with definite IE from February 1999 to June 2012 were enrolled in this observational study and divided into 2 groups: group 1, patients with DM (n = 72) and group 2, patients without DM (n = 340). The overall in-hospital mortality rate for both groups combined was 20.2% and was higher in group 1 than in group 2 (41.7% vs. 16.5%, p < 0.01). Compared to patients without DM, patients with DM were older and associated with higher incidence of chronic diseases, less drug abuse, higher creatinine levels, and increased risk of Staphylococcus aureus infection (all p < 0.05). Moreover, they were more likely to have atypical clinical presentation and were associated with longer IE diagnosis time (all p < 0.05). In multivariable analysis, DM is an independent and significant predictor of mortality. The prognosis of IE patients with DM is still poor. Early identification and more aggressive treatment may be considered in IE patients with DM.

scholarly journals Influence of Skull Fracture on Traumatic Brain Injury Risk Induced by Blunt Impact

2020 ◽  
Vol 17 (7) ◽  
pp. 2392 ◽  
Author(s):  
Lihai Ren ◽  
Dangdang Wang ◽  
Xi Liu ◽  
Huili Yu ◽  
Chengyue Jiang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Injury Risk ◽  
Skull Fracture ◽  
Human Model ◽  
Damage Modeling ◽  
Diffuse Brain Injury ◽  
Blunt Impact ◽  
Ground Impact ◽  
Diffuse Brain

This study is aimed at investigating the influence of skull fractures on traumatic brain injury induced by blunt impact via numerous studies of head–ground impacts. First, finite element (FE) damage modeling was implemented in the skull of the Total HUman Model for Safety (THUMS), and the skull fracture prediction performance was validated against a head–ground impact experiment. Then, the original head model of the THUMS was assigned as the control model without skull element damage modeling. Eighteen (18) head–ground impact models were established using these two FE head models, with three head impact locations (frontal, parietal, and occipital regions) and three impact velocities (25, 35, and 45 km/h). The predicted maximum principal strain and cumulative strain damage measure of the brain tissue were employed to evaluate the effect of skull fracture on the cerebral contusion and diffuse brain injury risks, respectively. Simulation results showed that the skull fracture could reduce the risk of diffuse brain injury risk under medium and high velocities significantly, while it could increase the risk of brain contusion under high-impact velocity.

scholarly journals Spatial distribution of neuropathology and neuroinflammation elucidate the biomechanics of fluid percussion injury

2020 ◽  
Author(s):  
Joshua A. Beitchman ◽  
Jonathan Lifshitz ◽  
Neil G. Harris ◽  
Theresa C. Thomas ◽  
Audrey D. Lafrenaye ◽  
...  
Keyword(s):  
Brain Injury ◽  
Sensorimotor Cortex ◽  
List Type ◽  
Mechanical Forces ◽  
Diffuse Brain Injury ◽  
Biomechanical Models ◽  
Fluid Percussion ◽  
Fluid Percussion Injury ◽  
The Impact ◽  
Diffuse Brain

AbstractDiffuse brain injury is better described as multi-focal, where pathology can be found adjacent to seemingly uninjured neural tissue. In experimental diffuse brain injury, pathology and pathophysiology have been reported far more lateral than predicted by the impact site. Finite element biomechanical models of diffuse brain injury predict regions of maximum stress and strain. However, the application of a skull with uniform thickness may mask the pathophysiology due to varying thickness of human and animal skulls. Force applied to the intact skull would diffuse the forces, whereas forces applied through an open skull are distributed along paths of least resistance within and then exiting the skull. We hypothesized that the local thickening of the rodent skull at the temporal ridges serves to focus the intracranial mechanical forces experienced during brain injury and generate predictable pathology in underlying cortical tissue. We demonstrated local thickening of the skull at the temporal ridges using contour analysis of coronal skull sections and oblique sectioning on MRI. After diffuse brain injury induced by midline fluid percussion injury (mFPI), pathological foci along the anterior-posterior length of cortex under the temporal ridges were evident acutely (1, 2, 7 days) and chronically (28 days) post-injury by deposition of argyophilic reaction product. Area CA3 of the hippocampus and lateral nuclei of the thalamus showed pathological change, suggesting that mechanical forces to or from the temporal ridges shear subcortical regions. A proposed model of mFPI biomechanics suggests that injury force vectors reflect off the skull base and radiate toward the temporal ridge due to the material properties of the skull based on thickness, thereby injuring ventral thalamus, dorsolateral hippocampus, and sensorimotor cortex. Surgically thinning the temporal ridge prior to injury reduced the injury-induced inflammation in sensorimotor cortex. These data build evidence for the temporal ridges of the rodent skull to contribute to the observed pathology, whether by focusing extracranial forces to enter the cranium or intracranial forces to escape the cranium. Pre-clinical investigations can take advantage of the predicted pathology to explore injury mechanisms and treatment efficacy.HighlightsThe temporal ridge is 75% thicker than the adjacent skull of the rodentExperimental diffuse TBI neuropathology occurs beneath the length of the temporal ridgeNeuropathology encompasses sensorimotor cortex, somatosensory thalamus, and dorsolateral hippocampusProposed mechanism of biomechanical injury forces include the temporal ridge

CD34 immunostain increases sensitivity of the diagnosis of fetal vascular malperfusion in placentas from ex-utero intrapartum treatment

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Jerzy Stanek
Keyword(s):  
Statistical Significance ◽  
Treatment Procedure ◽  
Fetal Survival ◽  
Ex Utero Intrapartum Treatment ◽  
Life Threatening ◽  
Group 2 ◽  
Cd34 Immunostain ◽  
The Impact ◽  
Diaphragmatic Hernias ◽  
Group 1

AbstractShort CommunicationsEXIT (ex-utero intrapartum treatment) procedure is a fetal survival-increasing modification of cesarean section. Previously we found an increase incidence of fetal vascular malperfusion (FVM) in placentas from EXIT procedures which indicates the underlying stasis of fetal blood flow in such cases. This retrospective analysis analyzes the impact of the recently introduced CD34 immunostain for the FVM diagnosis in placentas from EXIT procedures.Objectives and MethodsA total of 105 placentas from EXIT procedures (48 to airway, 43 to ECMO and 14 to resection) were studied. In 73 older cases, the placental histological diagnosis of segmental FVM was made on H&E stained placental sections only (segmental villous avascularity) (Group 1), while in 32 most recent cases, the CD34 component of a double E-cadherin/CD34 immunostain slides was also routinely used to detect the early FVM (endothelial fragmentation, villous hypovascularity) (Group 2). 23 clinical and 47 independent placental phenotypes were compared by χ2 or ANOVA, where appropriate.ResultsThere was no statistical significance between the groups in rates of segmental villous avascularity (29 vs. 34%), but performing CD34 immunostain resulted in adding and/or upgrading 12 more cases of segmental FVM in Group 2, thus increasing the sensitivity of placental examination for FVM by 37%. There were no other statistically significantly differences in clinical (except for congenital diaphragmatic hernias statistically significantly more common in Group 2, 34 vs 56%, p=0.03) and placental phenotypes, proving the otherwise comparability of the groups.ConclusionsThe use of CD34 immunostain increases the sensitivity of placental examination for FVM by 1/3, which may improve the neonatal management by revealing the increased likelihood of the potentially life-threatening neonatal complications.

scholarly journals The negative effects of COVID-19 and national lockdown on emergency surgery morbidity due to delayed access

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Francesco A. Ciarleglio ◽  
Marta Rigoni ◽  
Liliana Mereu ◽  
Cai Tommaso ◽  
Alessandro Carrara ◽  
...  
Keyword(s):  
Emergency Department ◽  
Blood Transfusion ◽  
Emergency Surgery ◽  
Surgical Care ◽  
Close Correlation ◽  
Negative Effects ◽  
Group 2 ◽  
Retrospective Comparative Study ◽  
The Impact ◽  
Group 1

Abstract Background The aim of this retrospective comparative study was to assess the impact of COVID-19 and delayed emergency department access on emergency surgery outcomes, by comparing the main clinical outcomes in the period March–May 2019 (group 1) with the same period during the national COVID-19 lockdown in Italy (March–May 2020, group 2). Methods A comparison (groups 1 versus 2) and subgroup analysis were performed between patients’ demographic, medical history, surgical, clinical and management characteristics. Results Two-hundred forty-six patients were included, 137 in group 1 and 109 in group 2 (p = 0.03). No significant differences were observed in the peri-operative characteristics of the two groups. A declared delay in access to hospital and preoperative SARS-CoV-2 infection rates were 15.5% and 5.8%, respectively in group 2. The overall morbidity (OR = 2.22, 95% CI 1.08–4.55, p = 0.03) and 30-day mortality (OR = 1.34, 95% CI 0.33–5.50, =0.68) were significantly higher in group 2. The delayed access cohort showed a close correlation with increased morbidity (OR = 3.19, 95% CI 0.89–11.44, p = 0.07), blood transfusion (OR = 5.13, 95% CI 1.05–25.15, p = 0.04) and 30-day mortality risk (OR = 8.00, 95% CI 1.01–63.23, p = 0.05). SARS-CoV-2-positive patients had higher risk of blood transfusion (20% vs 7.8%, p = 0.37) and ICU admissions (20% vs 2.6%, p = 0.17) and a longer median LOS (9 days vs 4 days, p = 0.11). Conclusions This article provides enhanced understanding of the effects of the COVID-19 pandemic on patient access to emergency surgical care. Our findings suggest that COVID-19 changed the quality of surgical care with poorer prognosis and higher morbidity rates. Delayed emergency department access and a “filter effect” induced by a fear of COVID-19 infection in the population resulted in only the most severe cases reaching the emergency department in time.

scholarly journals QOL-49. THE IMPACT OF OTOTOXICITY AND VISUAL IMPAIRMENT ON EDUCATION IN CHILDREN TREATED FOR CNS TUMOURS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii440-iii440
Author(s):  
Harriet Dulson ◽  
Rachel McAndrew ◽  
Mark Brougham
Keyword(s):  
Visual Impairment ◽  
Impaired Hearing ◽  
Cranial Radiotherapy ◽  
Radiotherapy Group ◽  
Platinum Based Chemotherapy ◽  
Cns Tumours ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Abstract INTRODUCTION Children treated for CNS tumours experience a very high burden of adverse effects. Platinum-based chemotherapy and cranial radiotherapy can cause ototoxicity, which may be particularly problematic in patients who have impaired vision and cognition as a result of their tumour and associated treatment. This study assessed the prevalence of impaired hearing and vision and how this may impact upon education. METHODS 53 patients diagnosed with solid tumours in Edinburgh, UK between August 2013–2018 were included in the study. Patients were split into three groups according to treatment received: Group 1 – cisplatin-based chemotherapy and cranial radiotherapy; Group 2 - platinum-based chemotherapy, no cranial radiotherapy; Group 3 – benign brain tumours treated with surgery only. Data was collected retrospectively from patient notes. RESULTS Overall 69.5% of those treated with platinum-based chemotherapy experienced ototoxicity as assessed by Brock grading and 5.9% of patients had reduced visual acuity. Patients in Group 1 had the highest prevalence of both. 44.4% of patients in Group 1 needed increased educational support following treatment, either with extra support in the classroom or being unable to continue in mainstream school. 12.5% of Group 2 patients required such support and 31.3% in Group 3. CONCLUSIONS Children with CNS tumours frequently require support for future education but those treated with both platinum-based chemotherapy and cranial radiotherapy are at particular risk, which may be compounded by co-existent ototoxicity and visual impairment. It is essential to provide appropriate support for this patient cohort in order to maximise their educational potential.

scholarly journals Association between serum oestradiol level on the hCG administration day and neonatal birthweight after IVF-ET among 3659 singleton live births

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Liu ◽  
Jing Li ◽  
Wanyu Zhang ◽  
Yihong Guo
Keyword(s):  
Birth Weight ◽  
Ovarian Stimulation ◽  
Group 4 ◽  
Group 6 ◽  
Group 3 ◽  
Group 5 ◽  
Group 2 ◽  
The Impact ◽  
Ivf Et ◽  
Group 1

AbstractOestradiol, an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization-embryo transfer (IVF-ET) cycles. A supraphysiologic E2 level is inevitable during controlled ovarian hyper-stimulation (COH), and its effect on the outcome of IVF-ET is controversial. The aim of this retrospective study is to evaluate the association between elevated serum oestradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and neonatal birthweight after IVF-ET cycles. The data of 3659 infertile patients with fresh IVF-ET cycles were analysed retrospectively between August 2009 and February 2017 in First Hospital of Zhengzhou University. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels ≤ 1000 pg/mL, n = 230), group 2 (serum E2 levels between 1001 and 2000 pg/mL, n = 524), group 3 (serum E2 levels between 2001 and 3000 pg/mL, n = 783), group 4 (serum E2 levels between 3001 and 4000 pg/mL, n = 721), group 5 (serum E2 levels between 4001 and 5000 pg/mL, n = 548 ), and group 6 (serum E2 levels > 5000 pg/mL, n = 852). Univariate linear regression was used to evaluate the independent correlation between each factor and outcome index. Multiple logistic regression was used to adjust for confounding factors. The LBW rates were as follows: 3.0% (group 1), 2.9% (group 2), 1.9% (group 3), 2.9% (group 4), 2.9% (group 5), and 2.0% (group 6) (P = 0.629), respectively. There were no statistically significant differences in the incidences of neonatal LBW among the six groups. We did not detect an association between peak serum E2 level during ovarian stimulation and neonatal birthweight after IVF-ET. The results of this retrospective cohort study showed that serum E2 peak levels during ovarian stimulation were not associated with birth weight during IVF cycles. In addition, no association was found between higher E2 levels and increased LBW risk. Our observations suggest that the hyper-oestrogenic milieu during COS does not seem to have adverse effects on the birthweight of offspring after IVF. Although this study provides some reference, the obstetric-related factors were not included due to historical reasons. The impact of the high estrogen environment during COS on the birth weight of IVF offspring still needs future research.

scholarly journals THU0227 CAFFEINE INTAKE MODULATES DISEASE ACTIVITY AND CYTOKINES LEVELS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 340.2-341
Author(s):  
V. Orefice ◽  
F. Ceccarelli ◽  
C. Barbati ◽  
R. Lucchetti ◽  
G. Olivieri ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Caffeine Intake ◽  
Caffeine Consumption ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease mainly affecting women of childbearing age. The interplay between genetic and environmental factors may contribute to disease pathogenesis1. At today, no robust data are available about the possible contribute of diet in SLE. Caffeine, one of the most widely consumed products in the world, seems to interact with multiple components of the immune system by acting as a non-specific phosphodiesterase inhibitor2.In vitrodose-dependent treatment with caffeine seems to down-regulate mRNA levels of key inflammation-related genes and similarly reduce levels of different pro-inflammatory cytokines3.Objectives:We evaluated the impact of caffeine consumption on SLE-related disease phenotype and activity, in terms of clinimetric assessment and cytokines levels.Methods:We performed a cross-sectional study, enrolling consecutive patients and reporting their clinical and laboratory data. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2k)4. Caffeine intake was evaluated by a 7-day food frequency questionnaire, including all the main sources of caffeine. As previously reported, patients were divided in four groups according to the daily caffeine intake: <29.1 mg/day (group 1), 29.2-153.7 mg/day (group 2), 153.8-376.5 mg/day (group 3) and >376.6 mg/day (group 4)5. At the end of questionnaire filling, blood samples were collected from each patient to assess cytokines levels. These were assessed by using a panel by Bio-Plex assays to measure the levels of IL-6, IL-10, IL-17, IL-27, IFN-γ, IFN-α and Blys.Results:We enrolled 89 SLE patients (F/M 87/2, median age 46 years, IQR 14; median disease duration 144 months, IQR 150). The median intake of caffeine was 195 mg/day (IQR 160.5). At the time of the enrollment, 8 patients (8.9%) referred a caffeine intake < 29.1 mg/day (group 1), 27 patients (30.3%) between 29.2 and 153.7 mg/day (group 2), 45 patients (51%) between 153.8 and 376.5 mg/day (group 3) and 9 patients (10.1%) >376.6 mg/day (group 4). A negative correlation between the levels of caffeine and disease activity, evaluated with SLEDAI-2K, was observed (p=0.01, r=-0.26). By comparing the four groups, a significant higher prevalence of lupus nephritis, neuropsychiatric involvement, haematological manifestations, hypocomplementemia and anti-dsDNA positivity was observed in patients with less intake of caffeine (figure 1 A-E). Furthermore, patients with less intake of caffeine showed a significant more frequent use of glucocorticoids [group 4: 22.2%,versusgroup 1 (50.0%, p=0.0001), group 2 (55.5%, p=0.0001), group 3 (40.0%, p=0.009)]. Moving on cytokines analysis, a negative correlation between daily caffeine consumption and serum level of IFNγ was found (p=0.03, r=-0.2) (figure 2A); furthermore, patients with more caffeine intake showed significant lower levels of IFNα (p=0.02, figure 2B), IL-17 (p=0.01, figure 2C) and IL-6 (p=0.003, figure 2D).Conclusion:This is the first report demonstrating the impact of caffeine on SLE disease activity status, as demonstrated by the inverse correlation between its intake and both SLEDAI-2k values and cytokines levels. Moreover, in our cohort, patients with less caffeine consumption seems to have a more severe disease phenotype, especially in terms of renal and neuropsychiatric involvement. Our results seem to suggest a possible immunoregulatory dose-dependent effect of caffeine, through the modulation of serum cytokine levels, as already suggested byin vitroanalysis.References:[1]Kaul et alNat. Rev. Dis. Prim.2016; 2. Aronsen et alEurop Joul of Pharm2014; 3. Iris et alClin Immun.2018; 4. Gladman et al J Rheumatol. 2002; 5. Mikuls et alArth Rheum2002Disclosure of Interests:Valeria Orefice: None declared, Fulvia Ceccarelli: None declared, cristiana barbati: None declared, Ramona Lucchetti: None declared, Giulio Olivieri: None declared, enrica cipriano: None declared, Francesco Natalucci: None declared, Carlo Perricone: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, Fabrizio Conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi

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