Comparison of Controlled Hypotension Due to the Use of Dexmedetomidine, Magnesium Sulfate, and Esmolol in Craniotomy Surgery

Introduction: Craniotomy includes the temporary removal of bone flap from calvarium to access the intracranial contents, which is usually used to reduce intracranial pressure. Induced or controlled hypotension is a method by which arterial blood pressure is predictably reduced, thus reducing bleeding. Therefore, the present study aimed to compare the dexmedetomidine, magnesium sulfate, and esmolol in controlled hypotension in craniotomy of patients with brain injury. Materials and methods: In this randomized double-blind clinical trial, 45 patients entered into study based on inclusion criteria. All patients were monitored when entering operating room. The questionnaire was completed by all groups, in which PR, MAP (Mean Arterial Pressure), mean bleeding score, mean of received packed cells, controlled hypotension and bradycardia, and survival of patients were recorded. Data were analyzed using spss software version 19, and ANOVA and T-Test were used for statistical significance analysis. Results: The mean age and standard deviations of the three groups of dexmedetomidine, esmolol and magnesium sulfate were 36.78±10.32, 34.47±10.58, and 39.67±11.99 years, respectively. There was no significant difference between the three groups in terms of age, gender, initial heart rate and baseline blood pressure (BP). The MAP and bleeding score (P=0.04 and P=0.0001) was significantly lower in the dexmedetomidine group than in the other two groups. Although the heart rate in the esmolol group was lower than the other two groups, the difference was not significant (P = 0.128). Unlike esmolol and magnesium sulfate groups, GOS did not decrease in the dexmedetomidine group. Conclusion: Comparison of the three groups in controlled hypotension in craniotomy surgery showed that the MAP and bleeding score of dexmedetomidine group was significantly lower than the other two groups, and the GOS didn’t decrease in this group. In general, dexmedetomidine would be a better choice for controlled hypotension in craniotomy.

Evaluating Clinical Outcomes and Potential Prognostic Factors Among 308 Children and Adolescents with Immune Thrombocytopenia (ITP): An 11-Year Retrospective Cohort Study

Background: Immune thrombocytopenia (ITP) usually is a mild and self-limited disease; however, 25-30% of children develop chronic ITP. Nordic score is a validated clinical prediction tool, yet its use in children is limited and evidence for other prognostic factors is unclear. Purpose: To evaluate clinical outcomes among pediatric ITP patients, and examine their relationship to patient characteristics, including Nordic score. We hypothesized that Nordic score and patient characteristics will be predictive of ITP resolution or development of chronic ITP. Methods: We conducted a retrospective chart review of all children diagnosed with ITP at our institution between May 2008 to May 2019. Data extraction included patients' age, sex, presenting signs and symptoms, laboratory values, treatment decisions, and clinical outcomes. Nordic score calculated with 6 clinical features from diagnosis: abrupt onset <14 days, age < 10 years, preceding infection <1 month, platelet count < 5x10 9/L, wet purpura, and male sex. High scores (10-14) predict a brief disease course (<3 months), whereas low scores (0-4) predict a more prolonged course. Primary outcomes included complete response (CR) (platelets 100 x10 9/L on 2 occasions >7 days apart), recurrence (platelets < 100 after achieving CR), development of chronic ITP, and resolution (long term normal platelet count). Secondary outcomes included early response (platelets 30 x10 9/L in <1 week), time to CR, duration of CR (months between CR and recurrence), and time to resolution. Data presented as odds ratio (OR) with 95% confidence intervals. OR for Nordic score presented per 5-unit increase correlating with Nordic score categories (low 0-4, moderate 5-9, high 10-14). Results: A total of 308 patients were included (median age 5 years, IQR 2.0-10.8; 54.5% male) (Table 1). About 56% presented with platelets < 10 x10 9/L and 42% had bleeding at diagnosis (bleeding score 3 or higher), only 3% were severe. Median Nordic score was 10 (IQR 6-11). Overall, 64% of patients were treated upfront, majority (98%) receiving intravenous immunoglobulin (IVIG). Treatment at diagnosis was more likely for patients with platelets < 10 x10 9/L (OR 21, 10.4-42.5), bleeding score 3 or higher (OR 2.0, 1-4), and higher Nordic score (OR 6.2, 5.6-6.9) (Table 2). Treatment was predictive only of early response in multivariate analysis, not of CR, recurrence, development of chronic ITP, or disease resolution. Additionally, treatment at diagnosis was not associated with reduction in ITP-related complications, such as major bleeding episodes, need for platelet or red cell transfusions, or iron deficiency anemia. Overall rate of CR was 90% over a median of 1 month (IQR 0.3-4 months), while 13% had recurrence after median 19 months (IQR 8.3-26.0 months) and 32% developed chronic ITP. Overall, 80% of all study patients had resolution of ITP after median 1 month (IQR 0.3-5), with 86% achieving this before 12 months. About 36% of patients with chronic ITP had disease resolution over median 25 months (IQR 16.3-46.5 months). Univariate analysis showed significant variation across subgroups for age, viral symptoms, abrupt onset, Nordic score, hospital admission at diagnosis, platelet count, and treatment. Using multivariate regression analysis adjusted for the above variables, Nordic score was the only independent predictor of all primary outcomes. Higher Nordic score group had increased likelihood of CR (OR 6.2, 5.6-6.8) and disease resolution (OR 6.8, 5.1-8.9). Lower Nordic score group was associated with increased likelihood of recurrence (OR 6.5, 5.3-6.9) and development of chronic ITP (OR 8.6, 6.5-11.4). Additionally, higher Nordic score group was associated with increased time to recurrence and duration of response, decreased time to CR and resolution. Conclusions: In our cohort, low platelet count and bleeding symptoms were drivers of upfront treatment in pediatric ITP. Treatment initiation, associated with Nordic score, was predictive of faster increase in platelet count; however, it had no impact on overall disease trajectory or likelihood of complications. Our analysis demonstrate that Nordic score is an independent predictor of CR, resolution, recurrence, and development chronic ITP. Nordic score is a useful, simple prognostic tool that has the potential to help predict clinical course of pediatric ITP and identifying patients who may benefit from closer monitoring. Figure 1 Figure 1. Disclosures Badawy: Bluebird Bio Inc: Consultancy; Sanofi Genzyme: Consultancy; Vertex Pharmaceuticals Inc: Consultancy.

Comparing Exercise-Induced Musculoskeletal Bleeding in Murine Models of Hemophilia A and B

Background: Hemophilia A and B are recessive X-linked bleeding disorders characterized by the deficiency in coagulation factor VIII and factor IX. Patients with the severe form of the disease can experience bleeding into the joints and muscle either spontaneously or after provoking events including sporting injuries of different degree. Patients are prone to bleeding in the musculoskeletal system. While most research is focused on hemarthrosis, muscle hematomas are not well studied although being the second most common complication of hemophilia, accounting for 10-25% of diagnosed bleeding episodes. There is limited consensus regarding optimal diagnosis and treatment of muscle hematomas in patients with hemophilia. We are investigating the effect of physical activity on muscle and joint bleeds in mouse models of hemophilia. Aim: The objective of this study was to compare the severity of exercise-induced skeletal bleedings in two mouse models of hemophilia A and B. Methods: Hemophiliac F8-KO and F9-KO mice, aged from 8-12 weeks old, were subjected to either mild or moderate daily treadmill exercise for 5 days. The speed was set at 10 meters per minute for the mild intensity group and 15 meters per minute for the moderate intensity group; and the animals were exercised for 30 minutes daily. Mechanical stimulus with a brush was used to encourage the animals to run. Animals were monitored daily and on day 6 (24 hours after the treadmill exercise) the animals were sacrificed to assess bleeding events. The mice skin was carefully removed and the body was macroscopically evaluated for presence of bleeds. If muscle bleedings were present, they were assigned a score in accordance with a previously published protocol (Tranholm M et al., JTH 2015 Jan;13(1):82-91) with minor modifications. Results: The animals were closely monitored during the study periods, and all completed the study. Normal behaviour and appearances were observed. No external bleeding was recorded. No muscle hematoma was observed in the wild-type C57-strain, thus the group received the bleeding score of 0. For the mild exercise group, the mean muscle bleeding score of F8-KO strain was 5.50 (standard error = 2.81), while the mean muscle bleeding score of F9-KO strain was 1 (standard error: 2). The two-tailed P value between the hemophilia A and B group was significant (p<0.01). For the moderate exercise group, the mean muscle bleeding score of F8-KO strain was 4.667 (standard error = 3.51), while the mean muscle bleeding score of F9-KO strain was 2.8 (standard error = 2.86). The two-tailed P value between the hemophilia A and B group was 0.33. Discussions: The preliminary analysis of our data showed that musculoskeletal bleeding induced by exercise appears to be more severe in hemophilia A mice than hemophilia B. This is in accordance with previous observations that hemophilia B may be clinically milder than hemophilia A. In our study, there appears to be a more significant difference between the hemophilia A and B mice when the mice were subject to milder form of exercise. No statistical significance was found between the two groups when moderate exercise was given. Overall, this exercise model can be a useful tool to study the pathophysiology of musculoskeletal bleeding as well as to evaluate new therapeutic strategies in the prevention and management of muscle hematomas in hemophilia. Figure 1 Figure 1. Disclosures Gross: Leo Pharma: Honoraria; Bayer: Honoraria; BMS-Pfizer: Honoraria; Valeo: Honoraria. Matino: Bayer: Membership on an entity's Board of Directors or advisory committees, Other: research grants and personal fees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: research grants and personal fees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Other: research grants and personal fees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: research grants and personal fees; Spark: Other: research grants; Octopharma: Membership on an entity's Board of Directors or advisory committees, Other: research grants and personal fees; Sobi: Membership on an entity's Board of Directors or advisory committees, Other: personal fees.

Standardizing the Diagnostic and Therapeutic Approach to Newly Diagnosed Children with ITP: An ITP Consortium of North America (ICON) Quality Improvement Initiative

BACKGROUND Pediatric immune thrombocytopenia (ITP) is an acquired disorder of platelet destruction that is associated with an increased risk of bleeding. Despite published guidelines for the management of ITP, the available evidence is of low grade, leading to practice variation in different settings. The use of validated bleeding scores to guide clinical decision making is inconsistent. In addition, many children are initially treated with medications despite the recommendation for observation in newly diagnosed children with ITP and no or mild bleeding symptoms. This approach leads to over-utilization of healthcare resources including hospitalizations, medication administration, and medical encounters for management-related side effects. In 2020, a quality improvement (QI) project of the Pediatric ITP Consortium of North America (ICON) was initiated to improve consistency in clinical practice at ICON sites using national ITP guidelines. DESIGN/METHODS Within the ICON QI subcommittee, a standardized clinical care pathway (Figure 1) for newly diagnosed childhood ITP was developed based on the American Society of Hematology (ASH) 2019 guidelines. The goal was to unify approach to management, decrease practice variation, identify and learn from deviations in decision making, and decrease resource utilization by increasing observation rates in low-risk pediatric ITP patients. Site investigators shared the care pathway to update institutional providers on national guidelines. For Aim 1 of this project, sites completed a multi-center, retrospective analysis documenting the pre-QI pathway management of children, ages 1-16 years, diagnosed with ITP from January to December 2019. Statistical analysis was performed using R version 4.0.2. For Aim 2, after local dissemination and education of the clinical care pathway, clinicians at all participating sites will review the pathway at the time of managing newly diagnosed children and then complete a short survey documenting a bleeding score and management decisions. RESULTS Current data from the retrospective review is summarized in Figure 1. 98 patients across four ICON institutions are included in this analysis. The median age at diagnosis was 6 years (IQR 2.7, 9.2) with 61% being male. 43 (44%) patients had their first hematology encounter in the inpatient setting, 40 (41%) in the outpatient clinic, and 14 (14%) in the emergency room. Buchanan and Adix bleeding scores were obtained from only one patient (1%) at diagnosis. Treatment strategies varied including observation in 47 (48%) patients, IVIG in 40 (41%), corticosteroids in 9 (9%), and anti-D globulin in 3 (3%). 53 (54%) patients were admitted at the time of diagnosis. The prospective QI pathway is being utilized by six ICON institutions and 20 patients have been followed on the pathway since November 2020. An additional seven sites are in various phases of study activation. DISCUSSION Evidence-based ITP guidelines and an expert consensus report have been recently published. For children with newly diagnosed ITP and a platelet count <20 x 10 9/L who have no or mild bleeding, ASH guidelines suggest against admission to the hospital and suggest observation rather than treatment with corticosteroids. Retrospective analysis of the management at four ICON centers demonstrates the variation in approach to treatment. However, although guidelines suggest initial management based on objective assessment of bleeding symptoms, only one patient (1%) had a documented bleeding score at presentation, suggesting a lack of a standard approach to management and practice variation. These data support the need for this quality initiative, which involves clinicians reviewing the pathway while managing patients and answering a survey at the time of clinical visits to report on bleeding symptoms and management. This initiative will be expanded to include a total of 13 institutions across the United States. Data will be analyzed every 1-2 years and changes will be made to the pathway with the goal of improving care. Further quality initiatives may help to standardize the management approach of pediatric ITP patients and optimize health outcomes in this patient population. Figure 1 Figure 1. Disclosures Badawy: Bluebird Bio Inc: Consultancy; Sanofi Genzyme: Consultancy; Vertex Pharmaceuticals Inc: Consultancy. Grace: Novartis: Research Funding; Dova: Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Research Funding; Principia: Membership on an entity's Board of Directors or advisory committees. Nakano: Novartis: Consultancy.

The influence of laser-microgrooved implant and abutment surfaces on mean crestal bone levels and peri-implant soft tissue healing: a 3-year longitudinal randomized controlled clinical trial

Purpose The study aimed to compare clinical and radiographic parameters of peri-implant site of laser-microgrooved implants with either laser-microgrooved or regular machined prosthetic abutment post 3 years of early loading. Method Twenty edentulous sites of systemically and periodontally healthy individuals were allocated into two groups in this prospective, two-armed, randomized double-blinded clinical trial in 1:1 ratio, wherein each site received laser-microgrooved implants with either laser-microgrooved or machined prosthetic abutments. Outcome measures included full-mouth plaque (FMPS%) and bleeding score (FMBS%), site-specific plaque (SPS%) and bleeding score (SBS%), peri-implant sulcus depth (PISD mm), and mean crestal bone loss (MCBL mm) evaluated at baseline (6 weeks), 1 and 3 years post-early loading. Mean and standard deviation of all parameters were estimated, between groups and at different time points using independent and paired t-test, respectively, Normality was checked using Kolmogorov–Smirnov test and Shapiro–Wilk test, P value ≤ 0.05 was considered as statistically significant. Results Three-year follow-up of test group showed statistically significant reduction in SPS, SBS, PISD (P value ≤ 0.001). The MCBL reduced from 1.93 mm to 0.61 mm (P value ≤ 0.001); in other words, a bone gain of 0.15 mm was obtained in the test group. Conclusion Within the limitations of the present study, laser-microgrooved implants loaded with laser-microgrooved prosthetic abutments showed superior results clinically and radiographically when compared to loading with machined abutments.

Coculture Strategy for Developing Lactobacillus paracasei PS23 Fermented Milk with Anti-Colitis Effect

Few studies have documented the effects of fermented milk on intestinal colitis, which are mediated by regulating various microbial and inflammatory processes. Here, we investigated the effects of fermented milk with Lactobacillus paracasei PS23 on intestinal epithelial cells in vitro and dextran sulfate sodium (DSS)-induced colitis in vivo. As L. paracasei PS23 grew poorly in milk, a coculture strategy with yogurt culture was provided to produce fermented milk (FM). The results indicated that the coculture exhibited a symbiotic effect, contributing to the better microbial and physicochemical property of the fermented milk products. We further evaluated the anti-colitis effect of fermented milk with L. paracasei PS23 in vitro. Both PS23-fermented milk (PS23 FM) and its heat-killed counterpart (HK PS23 FM) could protect or reverse the increased epithelial permeability by strengthening the epithelial barrier function in vitro by increasing transepithelial electrical resistance (TEER). In vivo analysis of the regulation of intestinal physiology demonstrated that low-dose L. paracasei PS23-fermented ameliorated DSS-induced colitis, with a significant attenuation of the bleeding score and reduction of fecal calprotectin levels. This anti-colitis effect may be exerted by deactivating the inflammatory cascade and strengthening the tight junction through the modification of specific cecal bacteria and upregulation of short-chain fatty acids. Our findings can clarify the role of L. paracasei PS23 in FM products when cocultured with yogurt culture and can elucidate the mechanisms of the anti-colitis effect of L. paracasei PS23 FM, which may be considered for therapeutic intervention.

Management of Gingival Bleeding in Periodontal Patients with Domiciliary Use of Toothpastes Containing Hyaluronic Acid, Lactoferrin, or Paraprobiotics: A Randomized Controlled Clinical Trial

Periodontitis is an irreversible oral disease causing the destruction of tooth-supporting tissues. In addition to scaling and root planing (SRP) procedures, patients should achieve a correct domiciliary oral hygiene in order to maintain a healthy status. The aim of the present study was to evaluate the efficacy of different toothpastes in reducing gingival bleeding in periodontal patients. In addition to a professional treatment of SRP, 80 patients were randomly divided into four groups according to the toothpaste assigned for the daily domiciliary use using an electric toothbrush: Group 1 (Biorepair Gum Protection), Group 2 (Biorepair Plus Parodontgel), Group 3 (Biorepair Peribioma PRO), and Group 4 (Meridol Gum Protection) (control group). After baseline (T0), patients were visited after 15 days (T1), 3 months (T2), and 6 months (T3). At each appointment, the following periodontal indexes were assessed: bleeding on probing (BoP), full-mouth bleeding score (FMBS), and modified sulcus bleeding index (mSBI). All the experimental toothpastes caused an immediate significant modification of the three clinical indexes measured, except for the control product. Biorepair Peribioma PRO, with its paraprobiotic content, was also the only toothpaste causing a prolonged effect, reducing BoP even at T3. Accordingly, both hyaluronic acid and lactoferrin appear as reliable supports for the domiciliary management of periodontal disease. In spite of this, paraprobiotics are likely to show the most important benefit thanks to their immunomodulating mechanism of action.

Association of Dephosphorylated-Uncarboxylated Matrix Gla Protein and Risk of Major Bleeding in Patients Presenting with Acute Myocardial Infarction

The “Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines” (CRUSADE) score emerged as a predictor of major bleeding in patients presenting with the acute coronary syndrome. On the other hand, previous studies established the association of dephosphorylated-uncarboxylated Matrix Gla protein (dp-ucMGP) and vitamin K, as well as their subsequent impact on coagulation cascade and bleeding tendency. Therefore, in the present study, we explored if dp-ucMGP plasma levels were associated with CRUSADE bleeding score. In this cross-sectional study, physical examination and clinical data, including plasma dp-ucMGP levels, were obtained from 80 consecutive patients with acute myocardial infarction (AMI). A significant positive correlation was found between CRUSADE bleeding score and both dp-ucMGP plasma levels (r = 0.442, p < 0.001) and risk score of in-hospital mortality (r = 0.520, p < 0.001), respectively. In comparing the three risk groups of risk for in-hospital bleeding, the high/very high-risk group had significantly higher dp-ucMGP levels from both very low/low group (1277 vs. 794 pmol/L, p < 0.001) and the moderate group (1277 vs. 941 pmol/L, p = 0.047). Overall, since higher dp-ucMGP levels were associated with elevated CRUSADE score and prolonged hemostasis parameters, this may suggest that there is a biological link between dp-ucMGP plasma levels and the risk of bleeding in patients who present with AMI.