bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-Xa Levels in Critically Ill Patients Receiving Dalteparin for Thromboprophylaxis.
Authors: McDonald Ellen , Dale Craig , Pleasance Susan , McNeill Andrea , Harvey Johanne , Wynne Christine , Duffett Mark , Provost Louise , Rioux Anik , LaRouche Genevieve , Davidson Carson , Watpool Irene , McCardle Tracy , Foxall Julia , Bouwers Kim , Jo Mary , Zytaruk Nicole , Griffith Lauren , Crowther Mark , Cook Deborah ,   for the PROTECT Investigatorsand the Canadian Critical Care Trials Group
Published: April 2020

Abstract
Rationale: Despite the efficacy and safety of low molecular weight heparin (LWMH) compared to unfractionated (UFH) in many patients, LMWH may bioaccumulate in patients with renal insufficiency which could cause an increased risk of bleeding. If LMWH thromboprophylaxis is safe in ICU patients with renal insufficiency, this could reduce the risk of DVT and HIT. Since the extent to which LMWH bioaccumulates in critically ill patients in prophylactic rather than therapeutic doses is unclear, our objective was to measure peak and trough anti-Xa levels during a multicenter randomized pilot trial of LMWH vs UFH for thromboprophylaxis in the medical-surgical ICU setting.
Methods: We included 128 patients ≥18 years with an expected ICU stay ≥72h. We excluded patients with trauma, orthopedic, cardiac, or neurosurgery, severe hypertension, DVT, PE or hemorrhage within 3 mos, INR &gt;2ULN, PTT &gt;2ULN, platelets &lt;100 x109/L, and if creatinine clearance was &lt;30 ml/min on ICU admission. Trough anti-Xa levels were drawn when patients developed creatinine clearance &lt;30ml/min, trough and peak anti-Xa levels were drawn on Tuesdays and Thursdays regardless of serum creatinine, and random anti-Xa levels were drawn if patients had a bleeding event.
Results: No differences were found in the 2 groups (median anti-Xa levels) as shown below.
Conclusions: We did not observe LWMH or UFH bioaccumulation when administered in prophylactic doses in these critically ill patients with a range of renal dysfunction.
Anti-Xa Levels
Allocation Cr Cl &lt;30 (trough) Tues & Thurs (trough) Tues & Thurs (peak) Bleeding (random) Group A 8 tests in 2 pts 17 tests in 9 pts 17 tests in 9 pts 7 tests in 4 pts Group A 0.1 IU/mL 0.09 IU/mL 0.11 IU/mL 0.1 IU/mL Group B 23 tests in 5 pts 46 tests in 12 pts 46 tests in 12 pts 10 tests in 8 pts Group B 0.1 IU/mL 0.09 IU/mL 0.11 IU/mL 0.1 IU/mL
Safety and Efficacy of Venous Thromboembolism Prophylaxis with Low Molecular Weight Heparin in Hospitalised Patients with Acute Medical Illness and Renal Failure.
Authors: Tincani Enrico , Mannucci Caterina , Casolari Barbara , Turrini Fabrizio , Crowther Mark A. , Ferrari Patrizia , Cenci Anna Maria , Bondi Marco 
Published: April 2020

Abstract
Objectives: To study the incidence of bleeding complications during thromboprophylaxis with dalteparin in patients with acute medical illness and renal failure.
Design: Prospective, cohort study.
Setting: Community Hospital.
Main outcome: The primary safety outcome was the incidence of major and minor bleeding, while the primary efficacy outcomes were objectively verified symptomatic DVT, pulmonary embolism, and objectively verified asymptomatic DVT detected on routine compression ultrasonography. Secondary outcomes included anti-Xa heparin levels.
Patients: 56 consecutives patients (29 males, age 77.86±10.27 y, 27 females, age 84.60±6,78 y) admitted with acute medical illness were considered for the study. Eligible patients were 18 years or older and had none of the following: hepatic failure (prothrombin time &lt;50%), platelet count &lt;100.000/ml, chronic use of warfarin, or an ongoing requirement for anticoagulation. Two doses of dalteparin were prescribed as dictated by a venous thromboembolism risk score. 44 patients judged to be at high risk (age &gt;75 y, 44 of 56, 78%, active cancer, 5 of 56, 8.9%, previous venous thromboembolism, 1 of 56, 1.8%) received a dose of 5.000 IU daily; the other 12 received 2.500 IU daily. Dalteparin was given at 8 am for 6 days. The timing of anti-Xa activity determination and of compression ultrasound examination of leg veins is shown in table 1.
Methods
Results: there was 1 case (1 of 56, 1.8%) of nose bleeding at the third day of treatment in a patient with moderate renal failure. The bled was easily stopped. None of the following variables: dose of dalteparin, age, sex, creatinine clearance, and anti-Xa activity when entered in a regression model were able to predict the hemorrhagic complication. There were no cases of venous thromboembolism. Though, peak anti-Xa activity was higher in patients with marked renal impairment, it never reached therapeutic levels (&gt;0.5 IU/mL).
anti-Xa activity at day 6
Conclusions: The modest (and not significant) increase in anti-Xa activity in patients with reduced creatinine clearance was not associated with a clinically apparent risk of bleeding. Thromboprophylaxis with dalteparin appears safe even in acutely ill medical patients with renal failure.
day 0 Creatinine Clearance anti-Xa activity before Dalteparin CUS day 6 Creatinine Clearance anti-Xa activity 4 h after Dalteparin CUS CrCl &gt;90 ml/min CrCl &gt;89–60 ml/min CrCl &gt;59–30 ml/min CrCl &lt;29 ml/min p=0.45 Patients 5 12 26 13 anti-Xa activity IU/mL 0.012±0.02 0.016±0.054 0.066±0.12 0.20±0.66
The Influence of Prior Oral Anticoagulation Therapy on the Anticoagulant Effect of Low Molecular Weight Heparin.
Authors: Rouby Soumaya El , Patel Urvashi , Patsh Marsha , Cohen Marc , Zucker Marcia L. , Pan Chi-Miau , LaDuca Frank M. 
Published: April 2020

Abstract
Low Molecular Weight Heparins (LMWHs) have been suggested by the ACCP as an alternative to UFH for the anticoagulation of patients on chronic oral anticoagulation therapy (OAT) with warfarin. However, the optimal way to manage these patients remains to be established particularly for high-risk patients who require any type of general surgery or urgent invasive PCI procedures.
The purpose of this study is to evaluate the LMWH point-of-care (POC) HEMONOXTM assay (Edison, NJ) in patients on chronic OAT. This clot-based test uses rTF reagents and the Hemochron Jr. Signature+ system. The Hemonox clotting time (CT) was analyzed at baseline and at peak response post enoxaparin treatment.
Following IRB approval, blood samples from patients on chronic OAT (5 to 20 years, n=13) were evaluated with the Hemonox assay within 12– 18 hours of their last warfarin dose, patients were evaluated weekly for 4 –12 consecutive weeks. In vitro enoxaparin dose response was evaluated by adding 1 U/ml to blood samples obtained from the OAT patients. In supplemental clinical evaluation, 2 PCI cases on OAT were performed at Newark Beth Israel Medical Center, Newark, NJ. Patients were anticoagulated during their PCI procedure with enoxaparin at a final IV dose of 0.5 mg/kg
Hemonox CT baseline response was patient specific and the same response profile was obtained for each patient on OAT who underwent consecutive weekly testing. The majority of patients on OAT (9/13; 69%) exhibited elevated Hemonox baseline CT (150–350 secs) when compared to the previously reported range for PCI patients without prior OAT (baseline CT &lt; 100 secs in 100% of cases, Mean = 71.2 ± 9.0, n= 39). Three patients on OAT (23%) showed CT≤150 secs, and only one patient (8%) yielded a baseline &lt; 100 secs. When the blood of the patient with baseline &lt; 100 sec (baseline value = 70 secs) was spiked in vitro with 1 U/ml enoxaparin, the Hemonox CT was 339 secs which was comparable with the peak response (386 and 308 secs; anti-Xa activity = 0.70 ± 0.01 U/ml; concentration of enoxaparin in the circulation = 0.77± 0.13) observed in the PCI patients receiving enoxaparin (0.5 mg/kg IV) and with a prior OAT who showed similar baseline values. Spiked samples from clinic patients with Hemonox baseline &gt; 150 secs were &gt; 700 secs.
Our results demonstrate that prior to administration of LMWH, baseline monitoring may be helpful in patients on OAT to alert clinicians to appropriate alterations of enoxaparin dosing and target anticoagulation times due to the influence of warfarin.
Gene Therapy for X-Linked Chronic Granulomatous Disease.
Authors: Ott Marion G. , Stein Stefan , Koehl Ulrike , Schilz Andrea , Kuhlcke Klaus , Schmidt Manfred , von Kalle Christof , Hassan Moustapha , Siler Ulrich , Hoelzer Dieter , Seger Reinhard , Grez Manuel 
Published: April 2020

Abstract
Chronic Granulomatous Disease (CGD) is a primary immunodeficiency in which phagocytic cells of affected patients have impaired antimicrobial activity due to a defect in the production of reactive oxygen species (ROS). CGD is caused by mutations in any one of four genes encoding for the subunits of the NADPH oxidase complex. CGD is an ideal target for a gene replacement therapy, since females carriers of CGD with as low as 5-10% NADPH oxidase activity are healthy. Based on our preclinical work, we initiated a Phase I/II trial in January 2004. Two X-CGD patients, 26 and 25 years old, were recruited based on their long history of recurrent and life-threatening bacterial and fungal infections. G-CSF mobilized CD34+ cells were transduced with a monocistronic gp91phox retroviral vector. The transduction efficiency was 45% for Pat.1 and 40% for Pat. 2. The number of CD34+ cells reinfused was 1.2x10e7 per kg for Pat.1 and 0.9x10e7 per kg for Pat. 2. Before reinfusion, the patients were conditioned with liposomal busulphan given i.v. at a dose of 4 mg/kg at two consecutive days, starting at day -3. The treatment was well tolerated and no adverse effects have been observed. Neutrophil counts declined to less than 100 cells per μl at day 15 post reinfusion in both patients and recovered to more than 500 cells per μl at day 30 for Pat. 1 and day 20 for Pat. 2. A significant fraction of gene marked cells has been detected in peripheral blood of both patients since day +21. Similarly, therapeutically relevant levels of ROS production have been observed. In conclusion, the protocol we have used allows for stable engraftment of gene transduced hematopoietic cells under conditions in which gene corrected cells lack a selective advantage over non-corrected cells.
Freeze-Drying Human Red Blood Cells: Effect of Hematocrit and Composition of the Freeze-Drying Medium on Red Cell Survival.
Authors: Satpathy Gyana R. , Torok Zsolt , Banerjee Mitali , Bali Rachna , Little Erika , Crowe John H. , Tsvetkova Nelly M. , Tablin Fern 
Published: April 2020

Abstract
A wide variety of medical procedures require transfusion of red blood cells (RBCs). RBCs are currently preserved either at 4°C, at a higher hematocrit (70%) for up to 7–12 weeks or in a frozen state in the presence of glycerol at −80°C for several years. However, each procedure has its demerits. Storage in the dry state offers a possibility for storing the cells for long periods of time under conditions that are far easier to maintain (i.e. room temperature), making the transport to sites of immediate need feasible. We developed a method for freeze-drying RBCs using 15% hematocrit, resulting in a survival of 40% after rehydration, as assessed by the percent hemolysis. In this work, we report the effect of cell hematocrit, concentration of trehalose, salts and overall osmolality of the freeze-drying medium on the survival after freeze-drying and rehydration. Decreasing the percent hematocrit and trehalose in the freeze-drying buffer resulted in about 20% improvement in the post-rehydration survival. Freeze-dried and rehydrated RBCs showed high levels of ATP, 2,3-DPG and low percent methemoglobin. These data are discussed in terms of the glass transition properties of the freeze-drying buffer. This work provides an important step in formulating a freeze drying medium that will provide optimum RBC survival after freeze drying and rehydration.
Ex Vivo Gene Therapy of a Preadolescent with X-Linked Severe Combined Immunodeficiency.
Authors: Chinen Javier , Puck Jennifer M. , Davis Joie , Linton Gilda F. , Whiting-Theobald Narda L. , Woltz Patricia C. , Buckley Rebecca H. , Malech Harry L. 
Published: April 2020

Abstract
X-linked severe combined immunodeficiency (XSCID) results from mutations in IL2RG, which encodes the common gamma chain (γc) shared by receptors for IL-2, 4, 7, 9, 15 and 21. XSCID is best treated with bone marrow transplantation (BMT) from an HLA-matched sibling. Patients lacking a matched sibling can benefit from a T-cell depleted haploidentical BMT, but some do not achieve adequate immune reconstitution. Ex vivo autologous hematopoietic stem cell (HSC) gene therapy may be an alternative to haploidentical BMT. In a French trial, 9 of 10 XSCID infants had immune reconstitution following ex vivo transduction of autologous HSC with a retroviral vector encoding γc. Selective development and expansion of T, NK and B cells from progenitors expressing γc was important to the success of this therapy. However, the 2 youngest patients, treated at 1 and 3 months of age, later developed T cell leukemias associated with retrovirus insertions that activated the LMO2 transcription factor. Young age at treatment might have had a role in the development of these adverse events. We have developed an XSCID gene transfer protocol as salvage treatment for older patients who have failed haploidentical BMT. An 11 year-old XSCID patient with no detectable engraftment from prior haploidentical BMTs had lymphocytopenia, growth failure, infections, chronic diarrhea and skin rashes. After G-CSF mobilization and harvest by apheresis, his purified autologous peripheral blood CD34+ cells were transduced daily for 4 days with GALV-MFGS-γc retrovirus in the presence of growth factors and Retronectin®. Eighty million cells/kg (80% CD34+; 40% γc transgene positive) were reinfused. At 1, 2 and 3 months after treatment, provirus marking by PCR of unseparated blood leukocytes was 1.4%, 2.3% and &lt;0.01%, respectively. At 4.5 months, marking reappeared in lineages dependent on IL2RG expression: 0.5% in T cells, 0.1% in NK cells and 0.05% in B cells. This lineage-specific marking persisted at the same level at 6 months. LAM PCR showed polyclonal marking. T-lymphocytes have not yet increased above 300/μl. However, from 2 months after gene therapy the patient experienced a sustained improvement in well-being with resolution of lifelong diarrhea and rashes. No infections have occurred except one episode of otitis externa 3 months post therapy that resolved promptly to oral antibiotics. At six months submandibular lymph nodes were palpable for the first time in his life. Thymus size on chest CT images increased from 1.8 cm3 to 3.2 cm3. Additional follow up is necessary to know if gene marking and clinical improvement persist and if significant expansion of corrected lymphocytes occurs. Our preliminary results suggest that ex vivo retrovirus-mediated gene therapy, targeting CD34+ cells from peripheral blood, may benefit older children with XSCID who have failed haploidentical BMT.
Pharmacokinetics (PK) and Pharmacodynamics (PD) of Epoetin Alfa in Anemic Cancer Patients Receiving Cycling Chemotherapy.
Authors: Cheung Wing K. , Danneman Brian , Wacholtz Mary , Lau Henry , Miller Denis 
Published: April 2020

Abstract
Epoetin alfa is a recombinant human erythropoietin (EPO). The objective of this study was to compare the PK/PD of epoetin alfa after a fixed dose (40,000 IU) once weekly (QW) regimen to those after the weight based (150 IU/kg) 3 times per week (TIW) regimen for 4 weeks in healthy subjects and for 6 weeks in anemic cancer patients. In this randomized, open-label, parallel, multi-center study, PK profiles were determined during Week 1 and Week 3 in healthy subjects. For cancer patients, PK profiles were determined during Week 1 when patients were receiving chemotherapy and an optional one during Week 3 when patients were not receiving chemotherapy. Of the 33 enrolled cancer patients who received as least one dose of Epoetin alfa (safety population), 29 were evaluable for PK and 27 were evaluable for PD. Of the safety population (82% had solid tumors), ECOG scores were 0 (48%), 1 (42%), and 2 (9%). None of the patients had bone or kidney metastasis. Their ages and body weights ranged from 31–77 yrs (mean 59.2 yrs) and 50.9 –94.1 kg (mean 70.8 kg), respectively. Mean serum EPO concentrations in the cancer patients during Week 1 were higher than during Week 3. In general, the concentration-time profiles and PK parameters of anemic cancer subjects were different from those in healthy subjects during Week 1 but similar to healthy subjects during Week 3. Mean (SD) PK parameters are listed in following table. Epoetin alfa was safe and well tolerated after the two regimens in this study. The 40,000 IU QW regimen had a higher Cmax, higher exposure to epoetin alfa/erythropoietin in serum (in terms of AUC0-7days), and a lower clearance (CL/F) than the 150 IU/kg TIW regimen. Despite these PK differences, time-profiles of changes in PD parameters and their AUC (% reticulocytes, hemoglobin, and total RBCs) were similar. Mean (SD) PK parameters
150 IU/kg TIW 150 IU/kg TIW 40,000 IU QW 40,000 IU QW 1st Week 3rd Week 1st Week 3rd Week a n=3 for Week 1 and n=2 for Week 3; b n=11 for Week 1 and n=7 for Week 3. Cancer Patients (n=14) (n=4) (n=18) (n=7) Cmax, IU/mL 414 (312) 178 (58) 1077 (510) 897 (322) AUC0-7days, mIU.h/mL 43014(37270) 21082(6909) 84205(46999) 48254(17658) CL/F, mL/h/kg 20.2(15.9) 23.6(9.5) 9.16(4.69) 13.9(7.6) T1/2, h 43.7(3.9) 41.9(14.8)a 41.9(14.8)a 38.8(11.0)b Healthy Subjects (n=6) (n=6) (n=6) (n=6) Cmax, mIU/mL 163 (54) 125 (32) 1036 (238) 909 (398) AUC0-7days, mIU.h/mL 15708(4327) 12913(3249) 47469(13301) 32969(7945) CL/F, mL/h/kg 31.2 (11.5) 36.9 (10.0) 12.6 (3.1) 17.8 (3.7) T1/2, h 25.0 (7.1) 26.0 (8.9) 28.8 (8.1) 23.7 (8.5)
Need To Register Consanguinity To Avoid Transfusions in Random Fashion among Close Relatives.
Authors: Fernandez Jose , Fridman Sergio , Acevedo Mirta , Benzadon Ricardo , Dupont Juan , Garay Guy , Riveros Dardo , Cacchione Roberto 
Published: April 2020

Abstract
Transfusion associated graft versus host disease (TGVHD) is a complication of transfusion (T) among close relatives but this event is not usually registered. In a search in Medline, since 1966 to present, no references where found on the need to register consanguinity between donors and receptors. The object of this research was to determine the importance of recording consanguinity (C) transfusions in a random fashion to avoid TGVHD. Between January 2001 and June 2003 the presence of C between blood donors and patients (P) on the Donor’s Book and in the mother and satellite blood bags for platelets were registered. Donations (D) were directed (DD) or non-directed (ND). 10,827 D were registered, from which 18,406 units (U) of cellular hemocomponents (CH) apt for transfusion were obtained. Of these, 1,868 D (17.3%) were C with the P and 3,324 (18%) U of CH apt for transfusion were obtained. In order to investigate the chance of a random transfusion of CH to C we excluded from the probability analysis the following U: 1) ABO/Rh incompatible: 157 (4,7%). 2) Already transfused or discarded at the moment of the transfusion order: 304 (9,1%). 3) Not donated at the time of the transfusion order: 504 (15,2%). 4) Irradiated hemocomponents (for C, DD, inmunodeficiencies, etc.): 624 (18,8%). 5) Non-transfused because of absence of transfusion order for the C patient: 846 (25,5%). U from C donors ready for transfusion to a C patient was 889 from 3.324 (26,7%). According to the Accountant Book, at the moment of transfusion the pondered S from C donors was 1.067 U. In the same way, at the moment of transfusion for C receptors, the pondered S of all balance of CH not belonging to C donors was: 28,720 U. In this study the chance that a patient receives at least one U of CH from C donors in a random fashion was [1.067 /28.720 + 1.067] x 100 = 3,6 %. Although the incidence of TGVHD is unknown it is thought to be very low. The chance of 3.6% of receiving at least one U of CH from a C donor in a random way is high and justifies largely considering this event to be registered. This percentage could suffer significant variations for different modalities of Blood Banks with regards to donation, storage and supplying of CH.
Influence of Homemade and Commercial Fibrin Sealant on Alveolar Bone Healing - an Experimental Study.
Authors: Correa Maria Elvira P. , Almeida Oslei P. , Peres Danyel , Alves Marcelo C. , Costa Fernando F. , Annechinno-Bizzachi Joyce M. , Barjas-Castro Maria Lourdes 
Published: April 2020

Abstract
The beneficial aspects of fibrin sealants for soft tissues are well documented, but studies of their direct influence on bone healing and their effectiveness in augmenting bone graft healing have produced conflicting results. The aim of this study was to evaluate the influence of fibrin sealants (FS) in the alveolar bone healing process during a period of up to 28 days. Seventy-five Wistar rats were submitted to a superior incisor extraction after intramuscular anesthesia (kentamine chloridrate 10% – 10mg/kg and tiazina chloridrate-5mg/kg). The rats were divided into tree different groups and the sealants were introduced into the alveolar bone. The first group (25) received human homemade fibrin glue, the second group (25) FS associated to factor XIII and aprotinin (Beriplast; Aventis-Beringher) and the third group (25) was the control. Animals were sacrificed by prolonged diethyl inhalation on days 7, 14 and 28 after surgery. Animal craniums were dissected and submitted to a decalcification, and preparated for H&E light microscopy. The morphometric study was performed by means of an interactive computerized image analysis system KS400 (Zeiss, Jena). New bone formation was carefully delimited in four different alveolar regions (apical, two middle areas and cervical) of each specimen. The data were statistically analyzed using multiple regression, ANOVA and Tukey test. Results showed that the amount of alveolar bone formation (μm) in the control group and commercial sealant was statistically similar. However, alveolus receiving homemade sealant presented less amount of new bone formation comparing to commercial sealant and control group (p=0.0034) (figure 1). The present study demonstrated that homemade fibrin sealant delays osteogenic formation. Commercial sealant did not improve alveolar repair however, the amount of new bone formation was slightly higher comparing to the control, probably due to the factor XIII present in this sealant.
Figure Figure