Dramatic Impact of Centralization and a Multidisciplinary Bladder Cancer Program in Reducing Mortality: The CABEM Project

PURPOSE Muscle-invasive bladder cancer (MIBC) is an aggressive disease with a complex treatment. In Brazil, as in most developing countries, data are scarce, but mortality seems exceedingly high. We have created a centralization program involving a multidisciplinary clinic in a region comprising seven municipalities. The aim of this study is to evaluate the impact of a multidisciplinary clinic and a centralization-of-care program (CABEM program) on MIBC treatment in Brazil. PATIENTS AND METHODS A total of 116 consecutive patients were evaluated. In group 1, 58 patients treated for MIBC before establishing a bladder cancer program from 2011 to 2017 were retrospectively evaluated. Group 2 represented 58 patients treated for MIBC after the implementation of the CABEM centralization program. Age, sex, staging, comorbidity indexes, mortality rates, type of treatment, and perioperative outcomes were compared. RESULTS Patients from group 2 versus 1 were older (68 v 64.2 years, P = .02) with a higher body mass index (25.5 v 22.6 kg/m2, P = .017) and had more comorbidities according to both age-adjusted Charlson Comorbidity Index (4.2 v 2.8, P = .0007) and Isbarn index (60.6 v 43.9, P = .0027). Radical cystectomy (RC) was the only treatment modality for patients in group 1, whereas in group 2, there were 31 (53%) RC; three (5%) partial cystectomies; seven (12%) trimodal therapies; 13 (22%) palliative chemotherapies; and three (5%) exclusive transurethral resections of the bladder tumor. No patient in group 1 received neoadjuvant chemotherapy, whereas it was offered to 69% of patients treated with RC. Ninety-day mortality rates were 34.5% versus 5% for groups 1 versus 2 ( P < .002). One-year mortality was also lower in group 2. CONCLUSION Our data support that a centralization program, a structured bladder clinic associated with protocols, a multidisciplinary team, and inclusion of chemotherapy and radiotherapy treatments can pleasingly improve outcomes for patients with MIBC.

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The effect of obturator nerve blockade on oncological outcomes of patients with lateral wall localized non-muscle invasive bladder cancer

10.22541/au.162036218.88606882/v1 ◽

2021 ◽

Author(s):

Ozan Horsanali ◽

Huseyin Eren ◽

Eyup Dil ◽

Alper Çaglayan ◽

Ozgur Erdogan ◽

...

Keyword(s):

Bladder Cancer ◽

Lateral Wall ◽

Obturator Nerve ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Nerve Blockade ◽

Oncological Outcomes ◽

Group 2 ◽

Muscle Invasive ◽

Group 1

Objective: To investigate the effect of obturator nerve blockade on oncological outcomes of patients with a diagnosis of lateral wall localized non-muscle invasive bladder cancer. Materials and Methods: One hundred six patients diagnosed with lateral wall localized non-invasive bladder cancer were evaluated between January 2015 and March 2020 in this retrospective, cross-sectional observational study. The patients were divided into two groups: patients receiving only spinal anaesthesia and those receiving spinal anaesthesia combined with ultrasound-guided obturator nerve blockade. Oncological outcomes of the groups were compared statistically. Results: We observed recurrent tumours in 25 patients (45.5%) in Group 1 and 11 patients (21.6%) in Group 2. In addition, we observed tumour progression in eight patients (14.5%) in Group 1 and two patients (3.9%) in Group 2. We observed statistical significance in differences between groups regarding tumour size, recurrence rate, adequate muscle tissue sampling, the ability for complete resection and persistent obturator reflex. The efficacy rate of obturator blockade was 92.1% in Group 2. One-year recurrence-free survival (RFS) was 98.0% and five-year RFS was 23.5% for Group 1, while they were, respectively, 97.4% and 57.2% for Group 2. Conclusion: The obturator reflex is a common and challenging reflex that may cause major complications and result in unintended consequences such as incomplete resection or tumour recurrence with transurethral resection of bladder tumours. In this study, we demonstrated that combining spinal anaesthesia with obturator nerve blockade for lateral wall localized non-muscle invasive bladder cancer may prevent tumour recurrence and reduce perioperative complications.

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Comparing the efficacies of neoadjuvant non-cisplatin-based and cisplatin-based chemotherapies in obtaining pathologic complete remissions in muscle-invasive bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15577 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15577-e15577

Author(s):

Praveen Sivakumaran ◽

Vishal Navnitray Ranpura ◽

David John Perry

Keyword(s):

Bladder Cancer ◽

Treatment Group ◽

Neoadjuvant Chemotherapy ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Group 2 ◽

Muscle Invasive ◽

To Receive ◽

Group 1 ◽

Hospital Center

e15577 Background: Muscle-invasive bladder cancer (MIBC) is an aggressive disease and cisplatin-based neoadjvuant chemotherapy is standard therapy. Because of renal insufficiency, many patients are unfit to receive cisplatin and, instead receive carboplatin-based chemotherapy. The efficacy of carboplatin-based chemotherapy has not been studied in this setting. We performed a study comparing the efficacies of neoadjuvant carboplatin-containing and cisplatin-containing chemotherapies in achieving pathologic complete responses (pCR) in MIBC. Overall survival (OS) was also calculated. Methods: Medical records for all patients who underwent cystectomy at MedStar Washington Hospital Center between January 1, 2002 and December 31, 2011 were reviewed to determine which neoadjuvant chemotherapy was given and whether a pCR was reached at the time of cystectomy. OS was also calculated. Results: 232 patients qualified for study. 13 received neoadjuvant cisplatin-based treatment (Group 1) and 12 received neoadjuvant carboplatin-based treatment (Group 2). pCR rates were 53.8% and 41.7% in Groups 1 and 2, respectively. 5-year OS for Groups 1 and 2 were 69% and 75%, respectively. Conclusions: Given the limitations of this small retrospective analysis, carboplatin-based neoadjuvant chemotherapy prior to cystectomy for MIBC appears to be comparable in efficacy to cisplatin-based neoadjuvant chemotherapy.

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Perioperative outcomes of aspirin use in partial nephrectomy.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.698 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 698-698

Author(s):

Matthew D. Ingham ◽

Ross Erik Krasnow ◽

Matthew Mossanen ◽

Ye Wang ◽

Adam B. Althaus ◽

...

Keyword(s):

Minimally Invasive ◽

Partial Nephrectomy ◽

Surgical Approach ◽

Major Complication ◽

Perioperative Outcomes ◽

Complication Rates ◽

Hospital Outcomes ◽

Group 2 ◽

The Impact ◽

Group 1

698 Background: Increasing cardiovascular disease has led to increases in the patient population on anti-platelet therapy who require urologic surgery. We sought to study perioperative outcomes for those undergoing partial nephrectomy (PN) while taking or not taking perioperative aspirin (pASA). Methods: A retrospective review of those undergoing PN was performed on the Premier Hospital Database from 2003 to 2015, with survey projection weighting resulting in a cohort of 10,807 patients. Two groups were formed – those continued on pASA (group 1, n = 774) and those with no pASA (group 2, n = 10,033). In-hospital complication rates were studied: major bleeding, overall transfusion, day-of-surgery transfusion, prolonged ( > 4 days) length of stay (LOS), and prolonged ( > 285 minutes) operative time. We also assessed 90-day rates of: cardiovascular catastrophe, readmission, major complication, and DVT/PE. Unadjusted rates were calculated for all PN patients and further subdivided into open and minimally invasive PN. Adjusted odds ratios (OR) were then calculated between groups 1 and 2. Results: Group 1 was older (58% vs 38% ≥65 years, p < 0.0001), largely male (73.1% vs 58.7%, p = 0.001), and less healthy (34.8% vs 18.4% with a CCI score ≥2, p = 0.003) than to group 2. For in-hospital outcomes, no significant differences were noted. Stratifying by surgical approach, those in group 1 undergoing minimally invasive PN were slightly less likely to require a day-of-surgery transfusion (OR 0.29, CI [0.05-0.99], p < 0.05). For 90-day outcomes, group 1 were far more likely to suffer a cardiovascular catastrophe (OR 7.56, CI [3.38-16.92], p < 0.001) regardless of surgical approach. Conversely, group 1 was slightly less likely to experience readmission (OR 0.48, CI [0.24-0.94], p < 0.05) and was likely driven by those undergoing minimally invasive PN. Conclusions: This large review of academic and community hospitals provides insight into the impact perioperative ASA has on PN outcomes. As noted, in-hospital outcomes were largely equivalent between groups while 90-day cardiovascular catastrophe rates were much higher in the ASA group. Despite this, this study lends support to the belief that pASA should not be considered an absolute contraindication to PN.

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Perioperative outcomes of aspirin use in radical prostatectomy.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.150 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 150-150

Author(s):

Matthew D. Ingham ◽

Ross E Krasnow ◽

Matthew Mossanen ◽

Ye Wang ◽

Steven Lee Chang

Keyword(s):

Radical Prostatectomy ◽

Minimally Invasive ◽

Major Complication ◽

Perioperative Outcomes ◽

Complication Rates ◽

Hospital Outcomes ◽

Group 2 ◽

The Impact ◽

To Receive ◽

Group 1

150 Background: Increasing cardiovascular disease has led to increases in the patient population on anti-platelet therapy who require urologic surgery. We sought to study perioperative outcomes for those undergoing radical prostatectomy (RP) while taking or not taking perioperative aspirin (pASA). Methods: A retrospective review of patients undergoing RP was performed on the Premier Hospital Database from 2003 to 2015, with survey projection weighting resulting in a cohort of 157,674 patients. Two groups were formed – those continued on pASA (group 1, n = 4400) and those with no pASA (group 2, n = 153,274). In-hospital complication rates were studied: major bleeding, overall transfusion, day-of-surgery transfusion, prolonged ( > 4 days) length of stay (LOS), and prolonged ( > 285 minutes) operative time. We also assessed 90-day rates of: cardiovascular catastrophe, readmission, major complication, and DVT/PE. Unadjusted rates were calculated for all RP patients and further subdivided into open and minimally invasive RP. Adjusted odds ratios (OR) were then calculated between groups 1 and 2. Results: Group 1 was older (51.5% vs 41.8% ≥65 years, p = 0.002) and less healthy (13.8% vs 5.3% with a CCI score ≥2, p < 0.0001) vs those in group 2. Group 1 patients were more likely to receive an open RP (42.3% vs 28.1%, p < 0.0001). For in-hospital outcomes for all RPs, no significant differences were noted regardless of surgical approach. For 90-day outcomes, those in group 1 were more likely to suffer a MI (OR 5.88, CI [3.4-10.18], p < 0.001), major complication (OR2.95, CI [1.58-5.5], p < 0.001), or be readmitted (OR 1.63, CI [1.18-2.26], p < 0.05). The disparity in both MI and major complication rates appeared to be largely driven by those undergoing minimally invasive RPs, with an OR of 7.92 and 4.02 noted, respectively. Conclusions: This large, retrospective, database review of both academic and community hospitals provides an important assessment of the impact pASA has on RP outcomes. In-hospital outcomes were equivalent between groups but those on pASA saw increased rates of MI, major complication, and readmission. Despite this, this study lends support to the belief that pASA should likely not be considered an absolute contraindication to RP.

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

Journal of Perinatal Medicine ◽

10.1515/jpm-2020-0156 ◽

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.

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

World Journal of Emergency Surgery ◽

10.1186/s13017-021-00382-z ◽

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.

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

Neuro-Oncology ◽

10.1093/neuonc/noaa222.704 ◽

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.

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

Scientific Reports ◽

10.1038/s41598-021-85692-7 ◽

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.

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Comparison of Thulium Laser Resection of Bladder Tumors and Conventional Transurethral Resection of Bladder Tumors for Non-Muscle-Invasive Bladder Cancer

Urologia Internationalis ◽

10.1159/000514042 ◽

2021 ◽

pp. 1-6

Author(s):

Zheng Liu ◽

Yucong Zhang ◽

Guoliang Sun ◽

Wei Ouyang ◽

Shen Wang ◽

...

Keyword(s):

Bladder Cancer ◽

Transurethral Resection ◽

Invasive Bladder Cancer ◽

Perioperative Outcomes ◽

Thulium Laser ◽

Bladder Tumors ◽

Muscle Invasive Bladder Cancer ◽

Laser Resection ◽

Baseline Characteristics ◽

Muscle Invasive

Introduction: The thulium laser resection of bladder tumors (TmLRBT) was increasingly used in the treatment of non-muscle-invasive bladder cancer (NMIBC) recently, and here we report the relevant outcomes of our institution to evaluate its efficacy and safety. Methods: We retrospectively collected the data of NMIBC patients who underwent either TmLRBT or transurethral resection of bladder tumor (TURBT). The baseline characteristics and perioperative outcomes were compared in these 2 groups. Results: The TmLRBT had a higher rate of detrusor identification than TURBT (97.4 vs. 87.6%, p = 0.001). After screening, 134 patients who underwent TmLRBT and 152 patients who received TURBT were enrolled in the analysis, and their baseline characteristics were similar. During the TURBT, 24 (15.8%) obturator nerve reflexes and 9 (5.9%) bladder perforations occurred, while none happened during the TmLRBT. After surgery, TmLRBT patients had fewer postoperative gross hematuria (38.1 vs. 96.7%, p < 0.001) and postoperative irrigation (27.6 vs. 92.7%, p < 0.001), and its irrigation duration was significantly shorter (2.3 vs. 3.3 day, p < 0.001). During the follow-up, no significant difference in the recurrence rate was detected (p = 0.315). Conclusions: TmLRBT is a safer technique than conventional TURBT in the treatment of NMIBC, and it could offer better specimens for pathologic assessment while the cancer control was not compromised.

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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2100 ◽

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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