Reduction In Hemoglobin Research Articles

221. Intravenous and oral tranexamic acid are equivalent at reducing blood loss in thoracolumbar spinal fusion: a prospective randomized trial phase II

BACKGROUND CONTEXT The use of antifibrinolytic agents such as tranexamic acid (TXA) to decrease operative blood loss and allogenic blood transfusions is well documented in the literature. While evidence supports the use of intravenous (IV) and topical formulations of TXA in spine surgery, the use of oral (PO) TXA has not been studied. PURPOSE The objective of the study is to compare perioperative blood loss in patients undergoing elective posterior thoracolumbar fusion who were treated with IV vs PO TXA. STUDY DESIGN/SETTING A prospective randomized trial of patients enrolled at a university affiliated tertiary medical center between February 2017 and October 2018. PATIENT SAMPLE Enrolled patients were randomly assigned between the 2 treatment groups of IV and oral TXA using a random number algorithm. 90 patients received IV TXA and 81 patients received PO TXA. OUTCOME MEASURES The primary outcome was the reduction of hemoglobin. Secondary outcomes included calculated blood loss, drain output, postoperative transfusion, complications, and length of hospital stay. METHODS A total of 171 patients undergoing thoracolumbar fusion were randomized to receive 1.95g of PO TXA 2 hours preoperatively or 2g IV TXA (1g before incision and 1g before wound closure) intraoperatively. The sample was further stratified into 3 categories based on number of levels fused (1-2 level fusions, 3-5, and >5). Equivalence analysis was performed with a two one-sided test (TOST). A P-value of RESULTS Patient demographic factors were similar between groups except for age, weight and BMI. The mean reduction of hemoglobin was similar between IV and PO groups (3.48 g/dL vs 3.19 g/dL, respectively; P = 0.004, equivalence). Similarly, the calculated blood loss was equivalent (1274 mL vs 1206 mL, respectively; P = 0.001, equivalence). A total of 21 patients (23%) in IV TXA group received a transfusion compared with 10 patients in PO TXA group (13%) (P = 0.07). Two patients (2% and 3% in IV and PO, respectively) in each group experienced a DVT/PE (P = 0.90). CONCLUSIONS Patients treated with IV and PO TXA experienced the same perioperative blood loss after spinal fusions. Given its lower cost, PO TXA represents an excellent alternative to IV TXA in patients undergoing elective posterior thoracolumbar fusion and may improve health care cost-efficiency in the studied population. FDA DEVICE/DRUG STATUS Unavailable from authors at time of publication.

The haematological consequences of Plasmodium vivax malaria after chloroquine treatment with and without primaquine: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis

BackgroundMalaria causes a reduction in haemoglobin that is compounded by primaquine, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The aim of this study was to determine the relative contributions to red cell loss of malaria and primaquine in patients with uncomplicated Plasmodium vivax.MethodsA systematic review identified P. vivax efficacy studies of chloroquine with or without primaquine published between January 2000 and March 2017. Individual patient data were pooled using standardised methodology, and the haematological response versus time was quantified using a multivariable linear mixed effects model with non-linear terms for time. Mean differences in haemoglobin between treatment groups at day of nadir and day 42 were estimated from this model.ResultsIn total, 3421 patients from 29 studies were included: 1692 (49.5%) with normal G6PD status, 1701 (49.7%) with unknown status and 28 (0.8%) deficient or borderline individuals. Of 1975 patients treated with chloroquine alone, the mean haemoglobin fell from 12.22 g/dL [95% CI 11.93, 12.50] on day 0 to a nadir of 11.64 g/dL [11.36, 11.93] on day 2, before rising to 12.88 g/dL [12.60, 13.17] on day 42. In comparison to chloroquine alone, the mean haemoglobin in 1446 patients treated with chloroquine plus primaquine was − 0.13 g/dL [− 0.27, 0.01] lower at day of nadir (p = 0.072), but 0.49 g/dL [0.28, 0.69] higher by day 42 (p < 0.001). On day 42, patients with recurrent parasitaemia had a mean haemoglobin concentration − 0.72 g/dL [− 0.90, − 0.54] lower than patients without recurrence (p < 0.001). Seven days after starting primaquine, G6PD normal patients had a 0.3% (1/389) risk of clinically significant haemolysis (fall in haemoglobin > 25% to < 7 g/dL) and a 1% (4/389) risk of a fall in haemoglobin > 5 g/dL.ConclusionsPrimaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia. Its widespread implementation will require accurate diagnosis of G6PD deficiency to reduce the risk of drug-induced haemolysis in vulnerable individuals.Trial registrationThis trial was registered with PROSPERO: CRD42016053312. The date of the first registration was 23 December 2016.

Intravenous tranexamic acid reduces blood transfusions in revision total hip arthroplasty: a meta-analysis.

Aim: We performed a meta-analysis to systematically assess the efficacy and safety of intravenous tranexamic acid in revision total hip arthroplasty. Method: Potential academic articles were identified from Cochrane Library, Medline, PubMed, EMBASE, ScienceDirect and other databases. The time range we retrieved from was that from the inception of electronic databases to February 2019. Gray studies were identified from the references of included literature reports. STATA version 11.0 was used to analyze the pooled data. Results: A total of eight articles were involved in our study. The overall participants of tranexamic acid (TXA) group were 3533, whereas it was 11,007 in the control group. Our meta-analysis showed that TXA is preferable for revision total hip arthroplasty because of its lower value of hemoglobin reduction (weighted mean difference= -1.277-1.405; 95% CI: -1.996 to -0.559; p< 0.001), the rate of blood transfusion (odds ratio: 0.233; 95% CI: 0.129-0.422; p< 0.001) and the number of red blood cell units transfused (weighted mean difference= -0.978; 95% CI= -1.631 to -0.324; p = 0.003). However, there was no difference in calculated blood loss (p = 0.075), operation duration (p= 0.569) and venous thromboembolism complications (p = 0.338). Conclusion: Based on available evidence, use of intravenous TXA for patients undergoing revision arthroplasty may reduce hemoglobin reduction, number of red blood cell units transfused and blood transfusion rate without increasing the risk of venous thromboembolism and length of operation duration. Given the relevant possible biases in our study, adequately powered and better-designed studies with long-term follow-up are required to reach a firmer conclusion.

Cangrelor -Safe and Effective Agent for Treating Pump Thrombosis in LVAD Patients

Background Pump thrombosis (PT) is a major complication of Left Ventricular Assist Device (LVAD). One of the early markers of PT is elevation in Lactate Dehydrogenase (LDH). Aggressive anti coagulation regimen can sometimes decrease LDH levels and prevent surgical need for pump exchange. Several treatment strategies have been utilized including escalating anti thrombotic therapy. There is minimal data regarding the role of Cangrelor for treatment of PT. Purpose Cangrelor, which is a novel antiplatelet agent in the treatment of PT. Method Review of cases of suspected pump thrombosis as evidenced by elevated LDH and Plasma free hemoglobin, who were treated with Cangrelor at University Medical Center from October 2018 to March 2019. We found two cases that were treated with Cangrelor. Results First patient had Heart Mate implanted 02/01/2017. She had undergone pump exchange for pump thrombosis 03/16/2018. She was not a candidate for further pump exchange or transplant due to socioeconomic issues. She was admitted with elevated LDH of 1400. She was initially started on heparin and integrillin drips with no significant change in LDH for 3 days (1097,1466,1541). There was also ongoing increase in Plasma free hemoglobin (62,82, 107). At this point it was decided to discontinue Integrilin and start Cangrelor. The LDH level started decreasing immediately and was back to baseline level of nearly 600 in 4 days. Free hemoglobin normalized in 5 days. She had no major bleeding complications. She was discharged from the hospital without any major events. Second patient had Heart Mate II implanted January 2017. He had suffered subarachnoid hemorrhage, when treated with heparin and Integrilin drip for elevated LDH. He subsequently underwent LVAD exchange on 8/29/2018. Patient did well for few months after the pump exchange. However, he started having intermittent flash pulmonary edema, power fluctuations and was subsequently hospitalized for transplant evaluation. While admitted he was noted to have elevated LDH to more than 1000 with increase in plasma free hemoglobin. Due to his history of subarachnoid hemorrhage with Integrilin, we chose to use Cangrelor with standard dose heparin drip for treatment of pump thrombosis. He was initially given 4mcgm/kg/min with rapid reduction in LDH and free hemoglobin. He was then maintained on 0.75mcgm/kg/min. This dose was increased to 1.5mcg/kg/min as LDH started to rebound. Patient went on to get heart transplant and did well without any bleeding complications. Conclusions Cangrelor can be used along with heparin for pump thrombosis. It has been used effectively in decreasing the LDH levels without any major bleeding complications. It may be considered as safe alternative to other modalities of anticoagulation.

41-Year-Old Man With Fever and Bloody Diarrhea

41-Year-Old Man With Fever and Bloody Diarrhea

Effectiveness and Safety of Hydroxychloroquine compared to Teneligliptin in uncontrolled T2DM patients as add-on Therapy.

ObjectivesHydroxychloroquine (HCQ) 400 mg is approved by the Drug Controller General of India (DCGI) and recommended by the Research Society for the Study of Diabetes in India (RSSDI) clinical practice recommendations 2017 as add-on therapy after metformin and sulfonylurea in Type 2 Diabetes (T2DM) patients. The aim of this observational study is to compare the efficacy and safety of hydroxychloroquine 400 mg and teneligliptin 20 mg when used as add-on therapy in Indian Type 2 DM patients who were inadequately controlled (HbA1c ≥7.5%) with metformin 1000 mg and glimepiride 2 mg combination.MethodologyThis study is a prospective observational study to be conducted in 2 diabetic centres of Patna city between October 2017 and May 2018 involving 180 patients followed up for 6 months. One group (N=90) of patients received hydroxychloroquine 400 mg + metformin 1000 mg + glimepiride 2 mg, the other group (N=90) received teneligliptin 20 mg + metformin 1000 mg + glimepiride 2 mg. Efficacy was assessed by fasting blood glucose (FBG), post prandial blood glucose (PPBG) and glycated haemoglobin (HbA1c) reduction. Safety was evaluated by the number of hypoglycaemic events and changes in serum creatinine levels. Home based glucose monitoring was used to detect the hypoglycaemic events. Patients who had any type of retinopathy/maculopathy were excluded.ResultsMean age of entire population was 66±8 years with mean 6±2 years of DM with 102 males. Mean body weight was 71±12 kg. Baseline HbA1c was 8.1±0.3 in the hydroxychloroquine group and 8.2±0.2 in the teneligliptin group.At 24 weeks there were statistically significant reductions in mean HbA1c in the hydroxychloroquine group (1.1±0.3) as compared to the teneligliptin group (0.82±0.3) (P≤0.001). The mean FBG and PPBG was 169±18 mg/dl and 232±18 mg/dl respectively in hydroxychloroquine group which was reduced to 121±15 mg/dl and 161±19 mg/dl at the end of 24 weeks. In the teneligliptin group, FBG and PPBG was 171±16 mg/dl and 239±21 mg/dl at baseline, which was reduced to 121±15 mg/dl and 161±19 mg/dl respectively in same period of time (P≤ 0.005). There were 4 incidences of hypoglycaemic events in the hydroxychloroquine group (4.4%) and 6 in the teneligliptin group (6.67%). No patients required medical assistance for hypoglycaemic events. There was no statistically significant change in body weight in both the groups. No marked changes in creatinine levels were found in patients in both the groups.ConclusionIn conclusion, treatment with hydroxychloroquine 400 mg for 24 weeks reduces glycaemic parameters more aggressively than teneligliptin 20 mg in Indian type 2 diabetes patients.

Comparison of the accelerometer-based navigation system with conventional instruments for total knee arthroplasty: a propensity score-matched analysis

BackgroundThe accelerometer-based navigation (ABN) system is an emerging navigation system for total knee arthroplasty (TKA). This study aimed to determine whether the ABN system could improve the accuracy of mechanical alignment, component positioning, and short-term clinical outcomes for TKA when compared to conventional instruments (CON).MethodsA total of 204 patients were selected and divided into two groups (CON: 135, ABN: 69) after applying the inclusion and exclusion criteria. Then, 1:1 propensity score matching was performed for age, gender, body mass index, hip-knee-ankle angle (HKA), Knee Society Score (KSS), Western Ontario and McMaster Universities (WOMAC) score, and follow-up times. A total of 82 consecutive patients (82 knees) underwent total knee arthroplasty using ABN (n = 41) or CON (n = 41) were enrolled in this study. The postoperative HKA, frontal femoral component (FFC) angle, frontal tibial component (FTC) angle, lateral femoral flexion (LFF) angle, and lateral tibial component (LTC) angle were compared between the two groups to evaluate mechanical alignment and component positioning. Additional clinical parameters, including haemoglobin reduction, the KSS, and the WOMAC score, were assessed at the final follow-up (the mean follow-up period was 20.9 months in the CON group and 21.2 months in the ABN group).ResultsThe ABN group had a significantly improved mean absolute deviation of HKA (P = 0.033), FFC (P = 0.004), FTC (P = 0.017), LFF (P = 0.023), and LTC (P = 0.031) compared to those of the CON group. The numbers of FFCs and LTCs within 3° were significantly different (P = 0.021, P = 0.023, respectively) between the two groups. However, no differences in the numbers of FTCs within 3° (P = 0.166) and LFF within 3° (P = 0.556) were found. The ABN group had a significantly higher KS function score (P = 0.032), and the pain and stiffness scores were significantly different (P = 0.034, P = 0.020, respectively) between the two groups. Moreover, the ABN system could reduce hidden blood loss postoperatively. However, no difference was found in the KS knee score and the total WOMAC score between the two groups.ConclusionThis study demonstrates that ABN system improved TKA mechanical alignment and component positioning and decreased the hidden blood loss postoperatively compared to conventional instruments. However, no significant differences were found in short-term clinical outcomes between ABN and conventional instruments at the final follow-up. However, whether this system contributes to revision rates and long-term clinical outcomes requires further study.

The clinical efficacy of flexible ureteroscopy and minimally invasive percutaneous nephrolithotomy for renal calculus of 2-4 cm and its influence on the renal indicators

Objective To discuss the clinical efficacy of staged flexible ureteroscopy holmium laser lithotripsy (FURL) and Minimally invasive percutaneous nephrolithotomy (MPCNL) for renal calculus of 2-4 cm and its influence on the renal indicators. Methods The clinical data of 125 renal calculus patients in our hospital form January 2017 to February 2018 were retrospectively analyzed. All patients were divided into the staged FURL group (68 cases) and the M PCNL group (57 cases) according to the different ways of treatment, and the clinical indicators during and after operation, renal function and renal blood flow indicators, postoperative complications and stone clearance were recorded and compared. Results The operative time, total treatment time, hospitalization expenses of the staged FURL group were significantly higher than the MPCNL group, and the intraoperative blood loss, hospitalization time, hemoglobin reduction were significantly lower than the MPCNL group, which were statistically significant (P 0.05). After treatment the RI value of the staged FURL group was significantly lower than the MPCNL group, the S/D value, Vmax were significantly higher than the MPCNL group, which were statistically significant (P 0.05). The incidence of postoperative complications of the staged FURL group[7.35%(5/68)] was significantly lower than the MPCNL group[17.54%(10/57)], which was statistically significant (P 0.05). Conclusions The efficacy and safety of staged FURL in the treatment of 2-4 cm renal calculus is better, which is beneficial to the recovery of renal blood flow after operation, and the incidence of postoperative complications is lower, it is worthy of popularization and application. Key words: Kidney Calculi; Lasers, Solid-State; Lithotripsy; Nephrostomy, Percutaneous; Ureteroscopy

Ultrasonographic Features of Uterine Scar after Laparoscopic and Laparoscopy-Assisted Minilaparotomy Myomectomy: A Comparative Study

To evaluate uterine scar features after laparoscopic myomectomy (LM) compared with myomectomy performed by laparoscopy initially and then completed with minilaparotomy (LAM). Prospective cohort study. An academic center for advanced endoscopic gynecologic surgery. Sixty-nine symptomatic women who underwent myomectomy between July and December 2018. Patients underwent LM or LAM and 3-month follow-up ultrasonography. Forty-four patients underwent LM and 25 underwent LAM. Demographic data, intraoperative parameters, and postoperative outcomes were collected. Two-dimensional color Doppler ultrasound was done at a 3-month follow-up to evaluate myomectomy scar features, myometrial thickness, and the presence of and vascularity of a heterogeneous mass. These features were compared with those of the intact myometrium on the opposite wall of the patient's uterus. The 2 groups had similar demographic characteristics, and there were no significant between-group differences in the number, maximum diameter, type, or location of myomas. The mean myometrial thickness at the scar site was 18.9 ± 3.22 mm in the LM group and 19.7 ± 3.50 mm in the LAM group, with no significant difference between the 2 groups. There was no meaningful difference in vascularity between the scar and normal myometrium. Heterogeneous masses were detected in 23% of patients in the LM group and in 24% of those in the LAM group. Other than mean operative time (207 minutes for LM vs 150 minutes for LAM; p < .001) and mean postoperative reduction in hemoglobin (1.77 mg/dL for LM vs 2.35 mg/dL for LAM; p = .023), there were no other statistical differences between the 2 groups. One patient in the LM group experienced a bowel injury resulting from morcellation. There were no differences in myometrial scar features after LM compared with after LAM, implying effective suturing via both approaches.

Abstract 3905: Translational efficacy and safety modeling and simulation to support the clinical development of JNJ-64619178, a PRMT5 inhibitor

Abstract Protein arginine methyltransferase 5 (PRMT5) is an epigenetic enzyme with oncogenic properties. JNJ-64619178 (JNJ178) is a potent, selective, structurally unique PRMT5 inhibitor with good preclinical efficacy in inhibiting the growth of hematologic and solid tumor cell lines. Toxicology studies showed that JNJ178 decreased reticulocytes and neutrophils in rats and dogs. The objectives of translational modeling and simulation were to understand the exposure-response relationship of both safety and efficacy and provide guidance to the first-in-human clinical development of JNJ178. Experimental data for the PK/PD (Pharmacokinetics/Pharmacodynamics) modeling included: plasma concentration after single dose of JNJ178 in non-tumor bearing mice, plasma concentration and PD markers of dimethylation of arginine (%SDMA in plasma and %SMD1/3-Me2 in tumor, respectively) after multiple doses (1 to 10 mg/kg) QD (once daily) of JNJ178 in H1048 (human small cell lung carcinoma) xenografts, and tumor volume in four xenograft mouse models (A427, human lung carcinoma; H441, human lung adenocarcinoma; H520, human squamous cell lung carcinoma; and H1048). Plasma PK were first described by a standard two-compartment model and used as a driver of PD and tumor volume (efficacy). Plasma and tumor PD were modeled using an indirect response model. A hybrid tumor growth coupled with transit compartment mediated tumor killing model was used to fit the tumor volume data. To predict the safety profile of JNJ178, lifespan based indirect response model for erythropoiesis and Friberg myelosuppression model were used to simulate hemoglobin and neutrophil kinetics in human. The PK/PD model described the data well and validated the hypothesis that PD is driven by trough concentration. Based on the exposure-response relationship from the four xenograft models, the trough concentration needed to achieve tumor stasis for mouse was determined. In addition, the level of inhibition in tumor and plasma PD marker that was associated with tumor stasis was identified. Together with human PK parameters scaled using allometry, the dose range needed to achieve target therapeutic exposure for a typical human subject was predicted. Simulation results from erythropoiesis and Friberg myelosuppression models informed the optimal doing schedules for certain dose levels that would allow hematological toxicity to be manageable with &amp;lt;40% reduction in hemoglobin and &amp;gt;1.0 x 109/L neutrophil counts at all times. Overall, a translational modeling and simulation approach that considers safety and efficacy has been instrumental in the design of the first-in-human clinical development of PRMT5 inhibitor JNJ178 regarding selection of dose and schedule. Citation Format: Yue Guo, Nahor Haddish-Berhane, Hillary J. Millar, Tinne Verhulst, Tony Greway, Junguo Zhou, Loeckie DeZwart, Dana Gaffney, Joseph Portale, Dirk Brehmer, An Boeckx, Erika Van Heerde, Daniele Ouellet. Translational efficacy and safety modeling and simulation to support the clinical development of JNJ-64619178, a PRMT5 inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3905.

2019 Mark Coventry Award: A multicentre randomized clinical trial of tranexamic acid in revision total knee arthroplasty: does the dosing regimen matter?.

Tranexamic acid (TXA) is proven to reduce blood loss following total knee arthroplasty (TKA), but there are limited data on the impact of similar dosing regimens in revision TKA. The purpose of this multicentre randomized clinical trial was to determine the optimal regimen to maximize the blood-sparing properties of TXA in revision TKA. From six-centres, 233 revision TKAs were randomized to one of four regimens: 1 g of intravenous (IV) TXA given prior to the skin incision, a double-dose regimen of 1 g IV TXA given both prior to skin incision and at time of wound closure, a combination of 1 g IV TXA given prior to skin incision and 1 g of intraoperative topical TXA, or three doses of 1950 mg oral TXA given two hours preoperatively, six hours postoperatively, and on the morning of postoperative day one. Randomization was performed based on the type of revision procedure to ensure equivalent distribution among groups. Power analysis determined that 40 patients per group were necessary to identify a 1 g/dl difference in the reduction of haemoglobin postoperatively between groups with an alpha of 0.05 and power of 0.80. Per-protocol analysis involved regression analysis and two one-sided t-tests for equivalence. In total, one patient withdrew, five did not undergo surgery, 16 were screening failures, and 25 did not receive the assigned treatment, leaving 186 patients for analysis. There was no significant difference in haemoglobin reduction among treatments (2.8 g/dl for single-dose IV TXA, 2.6 g/dl for double-dose IV TXA, 2.6 g/dl for combined IV/topical TXA, 2.9 g/dl for oral TXA; p = 0.38). Similarly, calculated blood loss (p = 0.65) and transfusion rates (p = 0.95) were not significantly different between groups. Equivalence testing assuming a 1 g/dl difference in haemoglobin change as clinically relevant showed that all possible pairings were statistically equivalent. Despite the higher risk of blood loss in revision TKA, all TXA regimens tested had equivalent blood-sparing properties. Surgeons should consider using the lowest effective dose and least costly TXA regimen in revision TKA. Cite this article: Bone Joint J 2019;101-B(Supple 7):10-16.

Abstract 3730: 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol mitigates the hematopoietic syndrome of lethal acute radiation syndrome in mice

Abstract The acute radiation syndrome (ARS) is a broad term used to describe a range of signs and symptoms that reflect severe damage to specific organ systems and that can lead to death within hours or several months after exposure. In this study, we investigated the efficacy of EC-18 for the development of a medical countermeasure for ARS by analyzing IR-induced mortality and morbidity. First, we established a murine model of the ARS by exposing eleven week old male and female BALB/c mice to 6.0-6.5 Gy doses of total body irradiation (TBI; γ-ray, 60Co, 1553 R/min ), and assessed for 30 day survival, mean survival time and lethality dose (LD). The LD70/30 with confidence interval (CI) was 6.11Gy (5.98-6.22Gy). To determine the efficacy of EC-18 in IR-induced mortality, we exposed BALB/c mice to a 6.11Gy dose (LD70/30) of TBI and orally administered 10-250 mg/kg/day of EC-18, starting one day after irradiation. As a result, 6.11Gy of γ-radiation caused the death of 80% of the animals of positive control group within 23 days, with an average life span (ALS) of 17.9 days. The percentages of survival of the irradiated mice with EC-18 10, 50, and 250 mg/kg were 20%, 40%, and 80% with ALS of 19.3, 22.3, and 28.2 days, respectively. Moreover, the LD70/30 dose of γ-ray irradiation caused a substantial decrease in the body weight of the mice. The administration of EC-18 effectively prevented severe weight loss induced by irradiation. Next, we investigated the efficacy of EC-18 for hematopoietic ARS (H-ARS) by analyzing the kinetics of white blood cells (WBC), red blood cells (RBC), and platelets. A single whole body exposure of γ-radiation (6.11Gy) rapidly exhausted all kinds of WBC counts, and the administration of EC-18 significantly attenuated γ-radiation-induced depletion of WBCs in the irradiated mice. Especially, the administration of EC-18 substantially reduced γ-radiation-induced reduction of the ANC. The mean first day of neutropenia (ANC&amp;lt;500cells/μL) of control and EC-18-treated cohorts was 1.8±1.09 and 2.2±1.09 days, respectively. Although EC-18 did not protect the irradiated mice from experiencing severe neutropenia, it effectively reduced the duration of severe neutropenia from 13.0 days to 7.2±1.79 days. In addition, EC-18 significantly increased the mean nadir of ANC after γ-ray irradiation from 4.0±5.48 cells/μL to 20.0±10.00 cells/μL. In addition, the administration of EC-18 in the irradiated mice remarkably attenuated the rapid reduction of RBCs and hemoglobin. When exposed to a supra-lethal dose (8Gy) of γ-radiation, the two of five mice in the control cohort experienced severe skin discoloration and edema formation on the front right feet and hemorrhagic telangiectasia on the tales on day 10. EC-18 remarkably improved γ-radiation-induced skin damage in the irradiated mice. Based on the observations in this study, we concluded that EC-18 has potential as a medial countermeasure for ARS. Citation Format: Yong-Jae Kim, Jinseon Jeong, Ki-Young Sohn, Do Young Lee, Sun Young Yoon, Jae Wha Kim. 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol mitigates the hematopoietic syndrome of lethal acute radiation syndrome in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3730.

Risk factors for ribavirin treatment failure in Asian organ transplant recipients with chronic hepatitis E infection.

BACKGROUNDHepatitis E virus (HEV) infection is a cause of chronic hepatitis in immunosuppressed patients. Sustained virologic response rates to a 12-wk course of ribavirin therapy were reported to be > 70% in the West. This study describes the outcome of HEV treatment in a transplant center in Singapore.AIMTo study the outcome of ribavirin treatment in a series of chronic HEV patients, and the cause of treatment failure.METHODSWe studied all of the transplant recipients who were diagnosed with HEV infection between 2012 to 2015. The outcome of therapy and virologic relapse are monitored for three years after the end of therapy.RESULTSTen transplant recipients (4 liver, 5 kidney, and 1 bone marrow transplantation) with positive HEV RNA were studied. Nine patients received at least 12 wk of ribavirin therapy, and the remaining patient resolved after reducing immunosuppression therapy. Two subjects had prolonged viremia that lasted more than one year, despite continuous ribavirin therapy. Four ribavirin-treated patients (44.4%) had HEV RNA relapse after achieving a virologic response by the end of treatment. The overall failure rate is 66.7%. Being a kidney transplant recipient is the strongest risk factor for not achieving an initial sustained virologic response (0/5 treated, Chi-Square test, P < 0.05). The most common side effect of ribavirin is anemia (100%) (haemoglobin reduction of 3-6.2 g/dL). Seven patients required either a blood transfusion or erythropoietin therapy.CONCLUSIONThe sustained virologic response rate of 12-wk ribavirin therapy for HEV infection in this Asian series was lower than expected. Kidney transplant recipients had a higher rate of treatment failure due to higher immunosuppression requirements and adverse effects.

Patient Blood Management During Lumbar Spinal Fusion Surgery

Patient blood management (PBM) is defined as treatment of a patient who is at risk of transfusion to minimize the need for transfusion and improve the probability of an optimal clinical outcome. We performed the present study to examine the effects of PBM in spinal fusion surgery. A total of 154 patients who had undergone 1- and 2-level posterior lumbar interbody fusion for degenerative lumbar disease were included. We retrospectively reviewed the data from 101 patients from 2012 to 2016 as the pre-PBM group. We recruited 53 patients from 2017 to 2018 for the post-PBM group. Intravenous iron was administered 2-4 weeks before surgery, and intravenous tranexamic acid was administered intraoperatively in the post-PBM group. The primary outcome was the reduction of hemoglobin (Hb). The secondary outcomes included perioperative blood loss, Hemovac drain output, postoperative transfusion, complications, and length of hospital stay. Intravenous iron was administered 17.4 days before surgery in the post-PBM group. The reduction in Hb was not significantly different statistically between the 2 groups (3.06 vs. 3.33 g/dL; P > 0.05). Of the 101 patients in the pre-PBM group, 24 (24%) underwent transfusion. In contrast, no patient in the post-PBM group had required a transfusion (P < 0.001). The average hospital stay was 10.15 days in the pre-PBM group and 8.33 days in the post-PBM group (P= 0.02). The average operative time was 146 minutes in the pre-PBM group and 133 minutes in the post-PBM group (P= 0.03). The Hb decrease and total Hemovac drain output did not differ significantly between the 2groups. Implementation of PBM is an effective strategy for reducing the rate of transfusion in patients undergoing lumbar spinal fusion surgery without significant complications.

Safety and efficacy of intraoperative administration of intravenous tranexamic acid in transurethral resection of prostate: A double-blind, randomised, placebo-controlled trial

Purpose: The purpose of this article is to evaluate and compare the effect of intravenous tranexamic acid (TXA) with placebo on haemorrhage and quality of vision during and post-transurethral resection of the prostate (TURP). Methods: For nine months (September 2016 until June 2017), a randomised clinical trial was conducted with 70 patients, age 50–80 years, who were included in the study according to inclusion criteria (patients who required surgical intervention because of benign prostatic hyperplasia, prostate weight (&lt;100 cc), American Society of Anesthesiologists score ⩽II, etc.) and enrolled randomly one to one in two study groups, and who underwent TURP in Shahid Beheshti Hospital of Hamadan University of Medical Sciences by a single surgeon. Interventions: The study group participants received 500 mg TXA in 500 ml ringer serum (concentration of 1 mg/ml, infusion rate 100 mg/min, maximum dose of 15 mg/kg), whereas the control group received only ringer serum during surgery. The results were then compared for the variables operation time, amount of haematocrit (HCT)-haemoglobin (Hb) reduction following surgery and surgeon satisfaction. Results: Both groups had no difference in age, weight and prostate weight. Surgeon satisfaction was evaluated at the end of the operation. The frequency of high satisfaction in case and control groups was 74.3% and 8.65%, whereas low satisfaction was 0% and 42.69%, respectively ( p &lt; 0.05). The mean time of operation was 53.57±16.43 vs 120.71±47.76 minutes in the case and control group, respectively ( p &lt; 0.05). The mean HCT-Hb decrease ( p = 0.00) and the amount of infused volume before and after the operation ( p = 0.03) between both groups were significantly different. None of the patients experienced TXA side effects. Conclusions: Intravenous TXA can prevent haemorrhage and higher Hb and HCT reduction following TURP, shortening the operation time and improving surgeon vision during TURP. Level of evidence: 1b

Glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes:real-world evidence from a Mediterranean area

Aims: To assess clinical characteristics and factors associated with glycated hemoglobin (HbA1c) reduction in type 2 diabetes (T2DM) patients initiating glucagon-like peptide-1 receptor agonists (GLP-1RAs).Methods: Retrospective cohort study in patients with T2DM who initiated GLP-1RAs between 2007 and 2014 in primary health care centers in Catalonia (Spain). We evaluated changes in HbA1c and body weight at 6–12 months, and factors independently associated with achieving ≥1% HbA1c target reduction.Results: Overall, 4242 patients (47.9% male; mean BMI 37.5 kg/m2) initiated a GLP-1RA. At 6–12 months, the mean HbA1c level decreased from the baseline 8.8% to 7.7% (−1.0%; SD = 1.6). A 1% reduction in HbA1c was observed in 47.2% of patients. Patients lost a mean of 3.6 kg (SD = 6.2). Sixty percent of patients reduced both HbA1c and body weight, and 17% achieved only one of these targets. Independent determinants of a 1% HbA1c reduction were baseline HbA1c, age, diabetes duration and being on insulin treatment. Reduction in weight or HbA1c and the proportion of patients achieving a HbA1c reduction of ≥1% was significantly larger among subjects prescribed liraglutide than exenatide and lixisenatide.Conclusions: In this real-world, retrospective study, the magnitude of HbA1c and body weight reductions after addition of a GLP-1RA were similar to those observed in randomized controlled trials. Approximately 60% of patients attained reductions in both HbA1c and body weight, and there were significant differences among different drugs from this therapeutic group.

Efficacy of Ormeloxifene vs Norethisterone in the Management of Perimenopausal DUB

Background: Disorders of menstruation are the most common reason for a gynaecological consultation among women of reproductive age group. Dysfunctional Uterine Bleeding is defined as abnormal uterine bleeding in the absence of organic, systemic or iatrogenic causes. It can be managed both medically and surgically. In medical management, several drugs have been used. However there is lack of studies suggesting the most appropriate drug. The objective of our study is to compare the treatment efficacy of Norethisterone acetate (a progesterone derivative) versus Ormeloxifene (selective estrogen receptor modulator) in the treatment of DUB. Methodology: Total of 100 perimenopausal women with DUB were enrolled in our prospective study. They were randomly assigned into group A and group B. Group A was treated with 60mg Ormeloxifene two times a week for 3 months followed by once a week for another 3months. Group B was treated with Norethisterone 5 mg two times a day from Day5 to Day26 for 6 months. Primary outcome parameters noted were reduction in menstrual blood loss that was measured by fall in Pictorial Blood Loss Assessment Chart (PBAC) score, increase in haemoglobin, and decrease in endometrial thickness at the end of study. Results: In our study, the reduction in mean PBAC score with Ormeloxifene was significantly more than that seen with norethisterone after 6 months of therapy. There was a significant increase in hemoglobin level and reduction in endometrial thickness with Ormeloxifene compared to norethisterone. Patients were more compliant to Ormeloxifene because of better tolerance and convenient dosage schedule. Conclusion: In our study Ormeloxifene was found to be more effective than Norethisterone in reducing blood loss, improving haemoglobin level and reducing endometrial thickness in DUB patients.

Glycemic Control, Preexisting Cardiovascular Disease, and Risk of Major Cardiovascular Events in Patients with Type 2 Diabetes Mellitus: Systematic Review With Meta-Analysis of Cardiovascular Outcome Trials and Intensive Glucose Control Trials.

BackgroundThe value of glycemic control and preexisting cardiovascular disease in determining the risk of major cardiovascular events (MACE) in type 2 diabetes mellitus is uncertain. Intensive glucose control trials suggest that the 9% lower risk of MACE associated with intensive glycemic control, as compared with conventional glycemic control, is only driven by patients with type 2 diabetes mellitus without cardiovascular disease at baseline.Methods and ResultsWe did a meta‐analysis of cardiovascular outcome trials dividing patients with or without preexisting cardiovascular disease; we found that the lower risk of MACE is confined to patients with cardiovascular disease at baseline. Compared with placebo, the use of both glucagon‐like peptide‐1 receptor agonists and sodium‐glucose cotransporter‐2 inhibitors was associated with a significant 14% lower MACE risk in patients with preexisting cardiovascular disease and with a nonsignificant 2% higher MACE risk in those without preexisting cardiovascular disease (P for interaction=0.021). The meta‐regression analysis of all 12 trials demonstrated a significant (P=0.002) association between reductions of glycated hemoglobin in glycated hemoglobin A1C. Accordingly, the reduction of MACE expected if all cardiovascular outcome trials had achieved a 0.9% glycated hemoglobin reduction would have been 33%. Routine clinical care data complement the results of cardiovascular outcome trials but with some differences: the lower risk of MACE with sodium‐glucose cotransporter‐2 inhibitor use is evident in patients with type 2 diabetes mellitus with or without preexisting cardiovascular disease.ConclusionsSodium‐glucose cotransporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists should be included in the therapeutic plan of patients with type 2 diabetes mellitus and overt cardiovascular disease, with due attention paid to improvement of glycemic control, which may amplify their benefit on MACE.

Intravenous and Oral Tranexamic Acid Are Equivalent at Reducing Blood Loss in Thoracolumbar Spinal Fusion: A Prospective Randomized Trial.

A prospective randomized trial of patients enrolled at a university affiliated tertiary medical center between February and December 2017. To compare perioperative blood loss in patients undergoing elective posterior thoracolumbar fusion who were treated with intravenous (IV) versus oral (PO) tranexamic acid (TXA). The use of antifibrinolytic agents such as TXA to decrease operative blood loss and allogenic blood transfusions is well documented in the literature. While evidence supports the use of IV and topical formulations of TXA in spine surgery, the use of PO TXA has not been studied. Eighty-three patients undergoing thoracolumbar fusion were randomized to receive 1.95 g of PO TXA 2 hours preoperatively or 2 g IV TXA (1 g before incision and 1 g before wound closure) intraoperatively. The sample was further stratified into three categories based on number of levels fused (1-2 level fusions, 3-5, and >5). The primary outcome was the reduction of hemoglobin. Secondary outcomes included calculated blood loss, drain output, postoperative transfusion, complications, and length of hospital stay. Equivalence analysis was performed with a two one-sided test (TOST). A P-value of <0.05 suggested equivalence between treatments. Fourty three patients received IV TXA and 40 patients received PO TXA. Patient demographic factors were similar between groups except for body mass index (BMI). The mean reduction of hemoglobin was similar between IV and PO groups (3.36 g/dL vs. 3.43 g/dL, respectively; P = 0.01, equivalence). Similarly, the calculated blood loss was equivalent (1235 mL vs. 1312 mL, respectively; P = 0.02, equivalence). Eight patients (19%) in IV TXA group received a transfusion compared with five patients in PO TXA group (13%) (P = 0.44). One patient (2% and 3% in IV and PO, respectively) in each group experienced a deep venous thrombosis/pulmonary embolism (P = 0.96). Patients treated with IV and PO TXA experienced the same perioperative blood loss after spinal fusions. Given its lower cost, PO TXA represents an excellent alternative to IV TXA in patients undergoing elective posterior thoracolumbar fusion and may improve healthcare cost-efficiency in the studied population. 1.

Greater Combined Reductions in Hba1C ≥1.0% and Weight ≥5.0% with Semaglutide Versus Comparators in type 2 Diabetes

Objective: Semaglutide is a glucagon-like peptide 1 (GLP-1) analog for the once-weekly treatment of type 2 diabetes (T2D). In the global SUSTAIN clinical trial program, semaglutide demonstrated superior glycated hemoglobin (HbA1c) and body weight reductions versus comparators. This post hoc analysis compared the proportion of patients achieving combined reductions in glycemia and body weight versus comparators. Methods: A total of 5,119 subjects with T2D in the phase 3 SUSTAIN 1 through 5 and 7 trials, from 33 countries, were included in this post hoc analysis. Subjects received subcutaneous semaglutide 0.5 or 1.0 mg, placebo or active comparator (sitagliptin 100 mg, exenatide extended release 2.0 mg, insulin glargine, dulaglutide 0.75 or 1.5 mg). The main endpoint was a composite of ≥1.0% HbA1c reduction and ≥5.0% weight loss at end of treatment. Results: Significantly greater proportions of subjects achieved the composite endpoint with semaglutide 0.5 (25 to 38%) and 1.0 mg (38 to 59%) versus comparators (2 to 23%). More subjects treated with semaglutide versus comparators achieved ≥1.0% HbA1c reductions (58 to 77% and 75 to 83% for semaglutide 0.5 and 1.0 mg versus 12 to 68%) and ≥5.0% weight loss (37 to 46%, 45 to 66% versus 4 to 30%). Proportions of subjects achieving targets were significantly higher with semaglutide 1.0 versus 0.5 mg in four of five trials. Semaglutide was well tolerated, with a safety profile similar to other GLP-1 receptor agonists. Conclusion: Significantly more subjects achieved both ≥1.0% HbA1c reduction and ≥5.0% weight loss with once-weekly subcutaneous semaglutide treatment versus comparators in the SUSTAIN trials. A dose-dependent effect was observed with semaglutide. Abbreviations: AE = adverse event; CV = cardiovascular; ER = extended release; GLP-1 = glucagon-like peptide 1; GLP-1 RA = glucagon-like peptide 1 receptor agonist; HbA1c = glycated hemoglobin; OAD = oral antidiabetic drug; sc = subcutaneous; T2D = type 2 diabetes.