Pre-Existence of Prothrombotic State in Patients with Atrial Fibrillation Despite Therapy with New and Traditional Anti-Coagulant Drugs

Abstract Background: Oral anticoagulants such as warfarin (W) have been conventionally used for the management of atrial fibrillation (AF). Despite the effectiveness of W, its use in AF patients requiring anticoagulation is suboptimal with an even greater underuse seen in elderly patients who are at higher risk of stroke. New oral anticoagulants such as rivaroxaban (R) and apixaban (A) have been approved to manage thrombotic and cardiovascular disorders including AF. The newer anticoagulants do not require continuous monitoring like W does and are much more convenient for patients with AF. Objective: To profile the baseline level of circulating thrombogenic biomarkers von Willebrand Factor (vWF), prothrombin fragment 1.2 (F1+2), microparticle bound tissue factor (MP-TF) and plasminogen activator inhibitor (PAI-1) in patients with AF. Additionally, the effect of both newer (R and A) and traditional (W) anticoagulants on the levels of thrombogenic biomarkers in patients with AF will be assessed. Materials: Citrated blood was drawn from thirty AF patients prior to ablation surgery and spun at 3000 rpm to obtain platelet poor plasma. Normal plasma samples from healthy controls were purchased from a commercial source (George King Biomedical, Overland Park, KS). The plasma samples were analyzed using a biochip array (Randox, London, UK) for metabolic syndrome biomarkers including PAI-1 and ELISA kits for vWF, MP-TF (Hyphen BioMed, Nueville-Sur-Oise, France) and prothrombin F1+2 (Siemens, Newark, DE). Results: Circulating levels of vWF, MP-TF and PAI-1 were statistically increased in patients with AF compared to normal (P<0.0001, P<0.0001, and P=0.0014, respectively). Circulating levels of prothrombin F1+2 showed no difference between the AF and normal group (P=0.2696). AF patients (n=30) were divided into two groups based on their usage (Group 1, n=21) and non-usage (Group 2, n=9) of any anticoagulant. Furthermore, those on anticoagulants were divided based on their use of newer (R and A, Group 3, n=16) or traditional (W, Group 4, n=4) anticoagulants. A statistical increase in vWF (P<0.0001), MP-TF (P<0.0001) and PAI-1 (P=0.011) remained in Group 1 compared to normal while a statistical increase in prothrombin F1+2 (P=0.0343) and PAI-1 (P=0.0040) were noted in Group 2 compared to normal. vWF (P=0.0036) and MP-TF (P=0.0059) were elevated in Group 1 compared to Group 2 while prothrombin F1+2 (P=0.0697) and PAI-1 (P=0.4548) showed no difference between the two groups. Furthermore, there was no statistical difference in the level of any thrombogenic biomarker in AF patients between Group 3 (R and A) and Group 4 (W). (Table 1) Discussion: Elevated levels of vWF, MP-TF and PAI-1 seen in AF patients compared to normal provide insight into an additional risk of thrombogenesis associated with AF which is not targeted by current anticoagulant medications. Most patients are assessed using a stroke risk stratification scale (CHA2DS2VASc, CHADS2, CHADS-VASC, or CHADS) to determine if anti-coagulants should be used to prevent stroke associated with AF. Of the 30 patients examined in this study, 8/9 (89%) patients who were not on anticoagulants had a stroke risk stratification score of 0 while 20/21(95%) patients who were on anticoagulants had a score of >1. This data supports studies which suggest that adding levels of prothrombotic biomarkers to current risk stratification scales could be more effective in assessing the risk of stroke of patients with AF. This data also suggests that although very effective in lowering prothrombin F1+2 levels in AF, the newer anticoagulants, R and A, and the traditional anticoagulant, W, still leave additional prothrombotic biomarkers unaffected. These unaffected biomarkers could be the potential target of future drug therapies which could lower the risk of stroke in patients with AF even more than the use of newer/traditional anticoagulants alone.Table 1.Biomarkers of Thrombogenesis in AF and Normal GroupsGroupvWF (concentration %)Prothrombin F1+2 (pmol/L)MP-TF (pg/mL)PAI-1 (ng/mL)Normal4140 ± 919 n=46106.1 ± 52.7 n=500.38 ± 0.25 n=483.21 ± 4.13 n=25AF Group 1 Anticoagulant n=216616 ± 1173107.9 ± 61.20.93 ± 0.715.69 ± 4.15Group 2 Non-Anticoagulant n=94788 ± 1338162.5 ± 93.30.51 ± 0.136.49 ± 3.14Group 3 New Anticoagulants (R and A) n=166721 ± 1127103.5 ± 37.60.76 ± 0.345.68 ± 4.53Group 4 Traditional Anticoagulants (W) n=46387 ± 158075.2 ± 52.60.94 ± 0.335.63 ± 3.52 Disclosures No relevant conflicts of interest to declare.

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Persistent Prothrombotic State in Atrial Fibrillation Despite Use of Novel Oral Anti-Coagulants

Blood ◽

10.1182/blood.v128.22.3832.3832 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3832-3832

Author(s):

Jeffrey Liles ◽

Christopher Wanderling ◽

Abigail M Otto ◽

Jordan Liles ◽

Debra Hoppensteadt ◽

...

Keyword(s):

Atrial Fibrillation ◽

Risk Stratification ◽

Oral Anticoagulants ◽

Control Group ◽

Plasma Samples ◽

Group 2 ◽

Newer Anticoagulants ◽

Circulating Levels ◽

Pai 1 ◽

Group 1

Abstract Background: Oral anticoagulants such as warfarin have been conventionally used for the management of atrial fibrillation (AF). Despite the effectiveness of warfarin, its use in AF patients requiring anticoagulation is suboptimal with an even greater underuse seen in elderly patients who are at higher risk of stroke. New oral anticoagulants such as rivaroxaban(R), apixaban (A), dabigitran (D) and edoxaban (E) have been approved to manage thrombotic and cardiovascular disorders including AF. The newer anticoagulants do not require continuous monitoring like warfarin and are much more convenient for patients with AF. Objective: To profile the baseline level of circulating thrombotic biomarkers plasminogen activator inhibitor (PAI-1), von Willebrand Factor (vWF), microparticle bound tissue factor (MP-TF) and prothrombin fragment 1.2 (F1.2) in patients with AF. Additionally, the effect of novel oral anticoagulants (R, A, D and E) on the levels of thrombotic biomarkers in patients with AF is assessed. Materials and Methods: Citrated blood samples were drawn from 30 patients (21 male and 9 female; mean age 59.1) prior to ablation surgery for AF at Loyola University Medical Center in Maywood, Illinois. Citrated blood was spun at 3000 rpm to obtain platelet poor plasma. Normal plasma samples from healthy controls (24 male and 24 female; mean age 33) were purchased from a commercial source (George King Biomedical, Overland Park, KS). The plasma samples were analyzed using a biochip array (Randox, London, UK) for metabolic syndrome biomarkers including PAI-1 and ELISA kits for vWF, MP-TF (Hyphen BioMed, Nueville-Sur-Oise, France) and prothrombin F1.2 (Siemens, Newark, DE). Results: Compared to the control group, circulating levels of vWF, MP-TF and PAI-1 were statistically increased in patients with AF (P<0.0001, P<0.0001, and P=0.0014, respectively). Circulating levels of prothrombin F1.2 showed no difference between the AF and the control group (P=0.2696). AF patients (n=30) were divided into two groups based on their usage (Group 1, n=17) and non-usage (Group 2, n=10) of any novel oral anticoagulant (R, A, D and E). Three patients on warfarin were excluded from this section of data analysis. A statistical increase in vWF (P=0.0018) and MP-TF (P=0.0039) remained in those taking novel oral anticoagulants compared to group 2. No difference was seen in PAI-1 (P=0.333) or F1.2 (P=0.31) between groups 1 and 2. Percent change from the normal mean was also calculated for PAI-1, vWF, MP-TF and F1.2 in group 1 (78%, 61.1%, 142%, 8.9%, respectively) and group 2 (113.6%, 16.9%, 31.7%, 41.4%, respectively) as seen in table 1. Discussion: Elevated levels of PAI-1, vWF and MP-TF seen in AF patients compared to normal provide insight into an additional risk of thrombogenesis associated with AF which is not targeted by current anticoagulant medications. Most AF patients are assessed using a stroke risk stratification scale (CHA2DS2VASc) to determine if anti-coagulants should be used to prevent stroke associated with AF. Patients in group 1 had a mean CHA2DS2VASc score of 1.15 compared to 2.18 see in group 2. This data supports studies which suggest that including levels of prothrombotic biomarkers to current risk stratification scales could be more effective in assessing the risk of stroke of patients with AF. This data also suggests that although very effective in lowering prothrombin F1.2 levels in AF, the newer anticoagulants, R,A,D and E still leave additional prothrombotic biomarkers unaffected. These unaffected biomarkers could be the potential target of future drug therapies which could lower the risk of stroke in patients with AF even more than the use of newer anticoagulants alone. Disclosures No relevant conflicts of interest to declare.

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Application of Long-Acting VLHL PAI-1 during Sutureless Partial Nephrectomy in Mice Reduces Bleeding

BioMed Research International ◽

10.1155/2015/392862 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7

Author(s):

Khaled Shahrour ◽

Rick Keck ◽

Jerzy Jankun

Keyword(s):

Partial Nephrectomy ◽

Blood Clot ◽

Treated Group ◽

Group 4 ◽

Final Weight ◽

Group 3 ◽

Group 2 ◽

Long Acting ◽

Pai 1 ◽

Group 1

PAI-1 prevents lysis of blood clot by inhibiting the urokinase and tPA induced conversion of plasminogen to plasmin. VLHL PAI-1 protein mutant was created to extend half-life over 700 hours. The objective of this paper was to test VLHL PAI-1 effects on bleeding during partial nephrectomy in mice. All animals had a left partial nephrectomy after intravenous infusion of saline or tPA. The animals were divided into four groups. Group 1 was infused with saline and kidney was exposed to saline too; Group 2 was infused with saline and kidney was exposed to PAI-1. Group 3 was infused with tPA and kidney was exposed to saline, while Group 4 was infused with tPA and kidney was exposed to PAI-1. Preweighed gauze containing PAI-1 or saline was then applied to the kidney for 30 minutes. The gauze was afterward weighed and blood loss was measured by subtracting the preweight of gauze from the final weight. We have observed a statistically significant (P≤0.05) reduction of bleeding in PAI-1-treated group in comparison to saline and tPA-treated groups. Based on these results we propose that VLHL PAI-1 can be used therapeutically in limiting the flow of blood from renal wounds.

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In-vivo evaluation of the effect of cyanoacrylate on prosthetic vascular graft infection – does cyanoacrylate increase the severity of infection?

VASA ◽

10.1024/0301-1526/a000867 ◽

2020 ◽

Vol 49 (4) ◽

pp. 281-284

Author(s):

Atıf Yolgosteren ◽

Gencehan Kumtepe ◽

Melda Payaslioglu ◽

Cuneyt Ozakin

Keyword(s):

Vascular Graft ◽

Graft Infection ◽

Vascular Graft Infection ◽

Group 4 ◽

Significant Difference ◽

Group 3 ◽

Group 2 ◽

Prosthetic Vascular Graft Infection ◽

Group 1

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.

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Does Perioperative Hemoglobin A1c Level Affect the Incidence, Pattern and Mortality of Lower Extremity Amputation?

Current Vascular Pharmacology ◽

10.2174/1570161116666180123112529 ◽

2019 ◽

Vol 17 (4) ◽

pp. 354-364

Author(s):

Hassan Al-Thani ◽

Moamena El-Matbouly ◽

Maryam Al-Sulaiti ◽

Noora Al-Thani ◽

Mohammad Asim ◽

...

Keyword(s):

Glycemic Control ◽

Lower Extremity ◽

Hazard Ratio ◽

Lower Extremity Amputation ◽

Group 4 ◽

Group 3 ◽

Group 5 ◽

Group 2 ◽

Extremity Amputation ◽

Group 1

Background: We hypothesized that perioperative HbA1c influenced the pattern and outcomes of Lower Extremity Amputation (LEA). Methods: A retrospective analysis was conducted for all patients who underwent LEA between 2000 and 2013. Patients were categorized into 5 groups according to their perioperative HbA1c values [Group 1 (<6.5%), Group 2 (6.5-7.4%), Group 3 (7.5-8.4%), Group 4 (8.5-9.4%) and Group 5 (≥9.5%)]. We identified 848 patients with LEA; perioperative HbA1c levels were available in 547 cases (Group 1: 18.8%, Group 2: 17.7%, Group 3: 15.0%, Group 4: 13.5% and Group 5: 34.9%). Major amputation was performed in 35%, 32%, 22%, 10.8% and 13.6%, respectively. Results: The overall mortality was 36.5%; of that one quarter occurred during the index hospitalization. Mortality was higher in Group 1 (57.4%) compared with Groups 2-5 (46.9%, 38.3%, 36.1% and 31.2%, respectively, p=0.001). Cox regression analysis showed that poor glycemic control (Group 4 and 5) had lower risk of mortality post-LEA [hazard ratio 0.57 (95% CI 0.35-0.93) and hazard ratio 0.46 (95% CI 0.31-0.69)]; this mortality risk persisted even after adjustment for age and sex but was statistically insignificant. The rate of LEA was greater among poor glycemic control patients; however, the mortality was higher among patients with tight control. Conclusion: The effects of HbA1c on the immediate and long-term LEA outcomes and its therapeutic implications need further investigation.

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Association between cervical disc disease and lesions of multiple sclerosis

The Neuroradiology Journal ◽

10.1177/1971400920983565 ◽

2021 ◽

pp. 197140092098356

Author(s):

Marwan Alkrenawi ◽

Michael Osherov ◽

Azaria Simonovich ◽

Jonathan Droujin ◽

Ron Milo ◽

...

Keyword(s):

Spinal Cord ◽

Cervical Disc ◽

Cervical Disc Disease ◽

Disc Disease ◽

Group 4 ◽

Demyelinating Lesions ◽

Grade Ii ◽

Group 3 ◽

Group 2 ◽

Group 1

Background Cervical discopathy and demyelinating lesions often co-exist in patients with multiple sclerosis (MS). Our study examines the possible association between these two pathologies. Methods Medical records and cervical magnetic resonance imaging scans of MS patients with cervical discopathy who were seen at our MS clinic during 2018 were retrospectively reviewed. The severity of the disc disease was classified as grade I (no compression), grade II (compression of the dural sac) and grade III (cord compression). The spinal cord in each scan was divided into six segments corresponding to the intervertebral space of the spine (C1–C6). Each segment was defined as containing demyelinating lesion and disc pathology (group 1), demyelinating lesion without disc pathology (group 2), disc pathology without demyelinating lesion (group 3) and no demyelinating lesion or disc pathology (group 4). Fisher’s exact test was used to test the association between demyelinating lesions and disc pathology. Results Thirty-four MS patients with cervical discopathy were included in the study (26 females; average age 42.9 ± 13.7 years; average disease duration 8.4 ± 5.4 years). A total of 204 spinal cord segments were evaluated. Twenty-four segments were classified as group 1, 27 segments as group 2, 52 segments as group 3 and 101 segments as group 4. There was no association between demyelinating lesions and the grade of disc disease ( p = 0.1 for grade I, p = 0.3 for grade II and p = 1 for grade III disc disease). Conclusion Our study did not find any association between cervical disc disease and demyelinating spinal cord lesion.

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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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Control of Vulval Competence and Centering in the Nematode Oscheius sp. 1 CEW1

Genetics ◽

10.1093/genetics/163.1.133 ◽

2003 ◽

Vol 163 (1) ◽

pp. 133-146 ◽

Cited By ~ 1

Author(s):

Sophie Louvet-Vallée ◽

Irina Kolotuev ◽

Benjamin Podbilewicz ◽

Marie-Anne Félix

Keyword(s):

Germ Line ◽

Specific Mechanism ◽

C Elegans ◽

Group 4 ◽

Cell Ablation ◽

Group 3 ◽

Group 2 ◽

P Cells ◽

Large Category ◽

Group 1

Abstract To compare vulva development mechanisms in the nematode Oscheius sp. 1 to those known in Caenorhabditis elegans, we performed a genetic screen for vulva mutants in Oscheius sp. 1 CEW1. Here we present one large category of mutations that we call cov, which affect the specification of the Pn.p ventral epidermal cells along the antero-posterior axis. The Pn.p cells are numbered from 1 to 12 from anterior to posterior. In wild-type Oscheius sp. 1 CEW1, the P(4-8).p cells are competent to form the vulva and the progeny of P(5-7).p actually form the vulva, with the descendants of P6.p adopting a central vulval fate. Among the 17 mutations (defining 13 genes) that we characterize here, group 1 mutations completely or partially abolish P(4-8).p competence, and this correlates with early fusion of the Pn.p cells to the epidermal syncytium. In this group, we found a putative null mutation in the lin-39 HOM-C homolog, the associated phenotype of which could be weakly mimicked by injection of a morpholino against Osp1-lin-39 in the mother’s germ line. Using cell ablation in a partially penetrant competence mutant, we show that vulval competence is partially controlled by a gonadal signal. Most other mutants found in the screen display phenotypes unknown in C. elegans. Group 2 mutants show a partial penetrance of Pn.p competence loss and an abnormal centering of the vulva on P5.p, suggesting that these two processes are coregulated by the same pathway in Oscheius sp. 1. Group 3 mutants display an enlarged competence group that includes P3.p, thus demonstrating the existence of a specific mechanism inhibiting P3.p competence. Group 4 mutants display an abnormal centering of the vulval pattern on P7.p and suggest that a specific mechanism centers the vulval pattern on a single Pn.p cell.

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Hypertrophy of unaffected cardiomyocytes correlates with severity of cardiomyopathy in female patients with Fabry disease

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01803-7 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Cristina Chimenti ◽

Romina Verardo ◽

Andrea Frustaci

Keyword(s):

Fabry Disease ◽

Wall Thickness ◽

Left Ventricular ◽

Female Patients ◽

Maximal Wall Thickness ◽

Group 4 ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract Aim To investigate the contribution of unaffected cardiomyocytes in Fabry disease cardiomyopathy. Findings Left ventricular (LV) endomyocardial biopsies from twenty-four females (mean age 53 ± 11 ys) with Fabry disease cardiomyopathy were studied. Diagnosis of FD was based on the presence of pathogenic GLA mutation, Patients were divided in four groups according with LV maximal wall thickness (MWT): group 1 MWT ≤ 10.5 mm, group 2 MWT 10.5–15 mm, group 3 MWT 16–20 mm, group 4 MWT > 20 mm. At histology mosaic of affected and unaffected cardiomyocytes was documented. Unaffected myocytes’ size ranged from normal to severe hypertrophy. Hypertrophy of unaffected cardiomyocytes correlated with severity of MWT (p < 0.0001, Sperman r 0,95). Hypertrophy of unaffected myocytes appear to concur to progression and severity of FDCM. It is likely a paracrine role from neighboring affected myocytes.

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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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Vermal Length and Transcerebellar Diameter in Gestational Age Estimation: A Guide to Forensic Expert

National Journal of Clinical Anatomy ◽

10.1055/s-0039-1697895 ◽

2019 ◽

Vol 08 (03) ◽

pp. 101-105

Author(s):

Nadia Ahmad ◽

S. L. Jethani ◽

Deepa Singh ◽

Ruchira Nautiyal

Keyword(s):

Gestational Age ◽

Age Determination ◽

Linear Increase ◽

Group 4 ◽

Age Regression ◽

Group 3 ◽

Group 2 ◽

Gestational Age Estimation ◽

Formalin Fixed ◽

Group 1

Abstract Background Transcerebellar diameter is one of the reliable, constant predicting parameters to assess the gestational age and fetal growth. Other than this, measurements of vermis, mostly the vermal length (height), have also been mentioned by authors to assess gestational age. Establishing a correlation between parameters and advancing gestation would be helpful in estimating the gestational age of fetus. Aims and Objectives To establish a correlation of vermal length and transcerebellar diameter with gestational age. Materials and Methods An observational and descriptive study conducted on 60 formalin-fixed human cerebellums. Fetuses with gross congenital/neurological abnormality were excluded. Fetuses were grouped into four groups—group 1 (13–17 weeks), group 2 (18–22 weeks), group 3 (23–27 weeks), and group 4 (28–32 weeks of gestation). Vermal length and transcerebellar diameter were measured with help of Vernier calipers. The data obtained were analyzed using statistical software SPSS version 20.0 and one-way analysis of variance. Observation A linear increase in vermal length parameters and transcerebellar diameter were seen with increasing gestational age. Regression analysis was done and regression equation was derived for each parameter. Conclusion Such correlations would help in fetal age determination in the field of forensic studies.

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