bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complete Remission Represents the Major Surrogate Marker of Long Survival in Multiple Myeloma.
Authors: Wang Michael , Delasalle Kay , Thomas Sheeba , Giralt Sergio , Alexanian Raymond 
Published: April 2020

Abstract
The impact of complete remission of myeloma on long term outcome remains controversial. Between January 1987 and May 2006, we evaluated frequencies of partial and complete remission, and survival from onset of therapy, for 721 consecutive, newly diagnosed patients who received a high-dose, dexamethasone-based combination as primary treatment. Only patients &lt;65 for whom intensive therapy was a uniform option were included; 45 patients with nonsecretory myeloma protein or with &lt;50 mg/day of only Bence Jones protein were excluded in order to provide a valid myeloma protein marker in all patients. Criteria for partial response (PR) required reduction of serum myeloma protein level by &gt;50% and of Bence Jones protein by &gt;90%; complete remission (CR) was defined by negative findings on immunofixation. Among 721 previously untreated patients, the initial response rate was 57%, including 8% with CR. Within 12 months, 397 patients received intensive therapy with a high-dose, melphalan-based regimen supported by autologous stem cells. In comparison with non-transplanted patients, intensified patients were younger (median 52 vs 56 yrs), more anemic (median 10.3 vs 11.3 gms/dl), and had more patients with stage 3 disease by ISS criteria (37% vs 25%) (p&lt;.01). Intensive therapy converted PR to CR in 34%, resistant disease (NR) to PR in 51%, and NR to CR in 14% of patients. For 209 patients with persistent resistant disease, the median survival was 2 yrs. Among 384 patients who achieved PR as maximum benefit, median survival times were significantly longer for 164 patients who received only primary treatment (4.3 yrs) and for 67 patients converted from NR to PR by intensive treatment (4.3 yrs) (p&lt;.01); survival was even longer for 153 patients with persistent PR after intensive therapy (5.9 yrs) (p&lt;.01), an outcome attributed to the high frequency of further moderate reduction of responsive myeloma after high-dose therapy even without CR. For 124 patients who achieved CR after only primary therapy or after intensive therapy of PR or NR, the median time to CR was 3 months (range 1–12 months) and median survival times of 10–14 yrs were similar; the median survival of 9 yrs for 32 patients intensified in CR was also similar, suggesting that high-dose therapy provided no further benefit after CR had been achieved with initial therapy. A randomized trial may be useful to clarify this question. Among the patients who died in CR, the cause of death was unrelated to myeloma in 20%, justifying future analyses of disease-related survival for such patients. Prolongation of survival was evident primarily when intensive therapy induced a major reduction of the myeloma and especially to CR. The sensitivity of myeloma to intensive therapy declined progressively for patients treated in NR, PR, or CR.
Clinical Outcomes of Off-Label Use of Recombinant Activated Factor VII (rFVIIa) at Teaching Hospitals Affiliated with a Medical School.
Authors: Cheng Yijun , Baxter Melissa S. , Schroeder Walter S. , Bernstein Zale P. 
Published: April 2020

Abstract
BACKGROUND: Recombinant factor VIIa (rFVIIa), NovoSeven®, is currently licensed in the United States for treatment of bleeding in hemophilia patients with acquired coagulation factor inhibitors. The off-label uses of this medication have expanded dramatically in past few years. Here we report our experience with the off-label use of rFVIIa at University at Buffalo affiliated teaching hospitals which include a level III trauma and major cardiothoracic centers.
PATIENTS AND METHODS: We reviewed the clinical, laboratory, and radiographic data of a consecutive series of 43 patients who received off-label rFVIIa between December 2001 and September 2005.
RESULTS: The indications for off-label rFVIIa use included CNS bleeding (17 patients), cardiothoracic and vascular surgery (9 patients), trauma (7 patients), GI bleeding (4 patients), coagulopathy (2 patients) and prophylaxis for surgery (4 patients). The dosage ranged from 32 to 150 mcg/kg with most patients receiving 90 mcg/kg. While a majority of patients received a single dose of rFVIIa (29 patients), one received a total of 22 doses. Overall 21 patients (49%) were alive at discharge. Those patients who received rFVIIa to stop severe bleeding from trauma or surgery appeared to have the worst outcome. The patient who received 22 doses of rFVIIa appeared to derive some clinical benefit after his initial doses, but became non-responsive to additional therapies. Successful hemostasis with rFVIIa was achieved in 100% of patients with preoperative prophylactic use. There were no thromboembolic events attributed to rFVIIa treatment.
CONCLUSIONS: The outcome of off-label use of rFVIIa appears to correlate with clinical indications, with prophylactic use having greatest benefit and surgical hemorrhage, the worst. Our findings were used to revise guidelines to allow for more efficacious use of off-label rFVIIa.
Heterogeneous Expression of Protein C (PC), Protein S (PS) and Thrombomodulin (TM) in Human Colon Cancer Tissue.
Authors: Wojtukiewicz Marek , Sierko Ewa , Zawadzki Roman J. , Zimnoch Lech , Klsiel Walter 
Published: April 2020

Abstract
Colon cancer is often complicated by thromboembolic episodes. It has been recognized that blood coagulation proteins play a role in malignant tumor progression and metastatic dissemination. An important inhibitory mechanism is provided by protein C (PC) system consisting of protein C, protein S (PS) and thrombomodulin (TM). Thrombin binds to membrane-bound TM and consequently activates PC. Active PC together with its cofactor - PS inactivates coagulation factors Va and VIIIa. Recently novel biological activities have been desribed for protein C system components that do not relate to its hemostatic functions. Active protein C exerts antiapoptotic activity towards endothelial cells (ECs) and activates proteolytic enzymes. It induces proliferation of ECs and angiogenesis. Protein S was documented to inhibit apoptosis as well as inflammatory and immunologic response.
The purpose of the study was to elucidate the solid phase interactions between colon cancer tissue and components of protein C system that may contribute to tumor progression. The tissues from colon cancer were obtained at surgical resection during radical treatment of 66 patients. The patients undergoing surgery have not received any previous anticancer therapy. Tumor fragments were processed acc. to AMeX method and than embedded in paraffin. Immunohistochemical studies (avidin-biotin complex-ABC - technique) were performed using polyclonal antibodies against PC, PS and TM.
Weak expression of PC was observed in cancer cells of two thirds of the examined specimens while in 4/66 cases there was no staining for PC in cancer cell bodies. One third of colon cancer fragments revealed strong expression of PC. Presence of PS was demonstrated in 64 cases of colon cancer, however its expression was irregular: a weak staining was observed in 60 cases and strong one - only in 4 cases. Two cases of colon cancer tissue have not revealed any staining for PS in cancer cells. Weak expression of TM was observed in two thirds of the examined cases, while a strong staining was revealed in one third of colon cancer tissues. However the expression of TM was inconsistent: not all cell bodies were TM-positive. The presence of PC and PS, but not TM was demonstrated in tumor associated macrophages. Furthermore, PS and TM antigens were localized in tumor stroma. Heterogeneous expression of PC system components in colon cancer tissue may indicate that their biological activity, exerted via their interplay with coagulation/fibrinolysis and regardless of their function in hemostasis, may modulate tumor growth.
Dielectric Barrier Discharge Plasma in Coagulation and Sterilization.
Authors: Balasubramanian Manjula , Sebastian Anita , Peddinghaus Marie , Fridman Gregory , Fridman Alexander , Gutsol Alexander , Friedman Gregory , Ari Brooks 
Published: April 2020

Abstract
Rapid loss of blood, in the operating room or trauma, necessitates a need for hastening coagulation Attempts to hasten coagulation include electrocautery based on thermal plasma discharges. Although there have been other effective attempts to prevent further loss of blood via coagulation, tissue damage and dessication can occur as a result of the high temperatures 2. Our group has developed a method to initiate rapid coagulation with dielectric plasma discharge (cold). Initial experiments were performed using fresh blood from volunteers to compare time for coagulation of whole blood exposed to plasma, one minute versus 10 minutes. We tried same experiments on cut cadaver organs such as spleen and placenta which showed evidence of rapid coagulation compared to control without evidence of tissue damage.
Our research team has developed a novel method using non-thermal dielectric barrier discharge plasma (DBD plasma) to coagulate blood and sterilize tissues without causing thermal damage. This treatment would be safe to patients because no exposed electrodes are involved and high frequency current (under 10 KHz) is kept below mili-ampere. Our experiments have shown that such plasma treatment hastens blood coagulation and causes simultaneous wound sterilization via a large concentration of chemically active species in plasma that are ions, radicals (O, OH, N) and electronically-excited atoms and molecules.
A kinetic model of blood coagulation under influence of DBD plasma was constructed. The model assumes contact flux of positive ions from DBD plasma into the surface of the blood being treated. Once at the surface, these ions recombine, leading to formation of aqueous Hydrogen ions which catalyze the release of Calcium ions into the blood. The addition of Calcium ions to blood speeds up the coagulation process proportionally to the amount of ions added. The model demonstrates thrombin formation in the presence of DBD plasma peaking and occurring within significantly less time compared to thrombin formation without DBD plasma3. Such medically relevant demonstrations and mathematical explanations have allowed us to develop a portable device that may prove useful in situations where control of bleeding is crucial. In addition, because of the potential for simultaneous sterilization, this device may also help to decrease infections. This pioneering technology will find applicability in many clinical situations: sterilization of human tissue surfaces prior to surgery and sterilization of catheters, a well-known cause of morbidity in hospitals.
Major Obstetric Haemorrhage in Late Termination of Pregnancy in Eight Women.
Authors: Sekhar Mallika , Narat Santosh , Le Dieu Rifca , Luqmani Asad , Hollamby Suzie , AlObaidi Magda , Hughes George 
Published: April 2020

Abstract
Eight patients were referred from a private clinic between August 2003 and May 2004 for management of severe uncontrolled bleeding after late second trimester termination of pregnancy (TOP). TOP was perfomed at a mean gestation period of 21.4 weeks (median 21 weeks, 21–23 weeks) and was performed in 2 stages. Stage 1 comprised cervical dilatation, rupture of membrane, severing the cord and insertion of laminara. 24 hours later a dilatation and evacuation procedure was carried out. Mean age was 24.25 years (range 17–35). None of the women had any previous bleeding problems. Mean pre-operative Haemoglobin was 10.5 gm/dl (8.7 to 12.2 gm/dl). 1 patient had a preoperative clotting screen and this was normal. The pattern of bleeding was as follows: PV bleed 8/8, generalised bleed 2/8, haemodynamic failure 5/8. Median time to onset of bleeding after the second stage was 1.5 hours and median time to control bleeding was 9.5 hours. Details of coagulation screen and transfusion support are provided in tables 1 and 2. Factor VIIa was not approved for use in the hospital at that time.
table 1 coagulation parameters UPN nadir fibrinogen (1.8–4.5 g/l) hours to nadir from TOP hours to normal fibrinogen PT (9.6–11.6 secs) APTT (24–32 secs) platelets (150–400 × 109/l) 1 0.44 8 18 16.7 37.2 203 2 0.19 2 7 22.6 54.8 108 3 0.67 7 13 16.8 38 44 4 0.21 5 11 23.4 34.2 145 5 0.35 5 6 21.5 78 47 6 0.5 6 12 31 37.2 141 7 0.57 3 5 15.6 42.7 88 8 0.94 5 12.8 37.7 144 table 2 blood product support UPN cryoppt (units) FFP(units) RBC(units) platelets(units) 1 12 2 2 2 20 4 14 1 3 15 4 9 4 40 4 12 5 20 5 17 2 6 10 3 8 7 18 4 6 1 8 2 2
Obstetric interventions included hysterectomy (1), balloon occlusion (2) ERPC (1), hysterotomy (1), cervical tear repair (2) and vaginal pack (2). Obstetric cause of haemorrhage was identified to be uterine atony (4), retained products (2), uterine injury (2) and no identifiable cause (2). All women recovered fully.
Results: The profound coagulopathy in these women was characterised by a reduction in fibrinogen that was out of proportion to the anomalies in other clotting parameters and platelet counts. Treatment with cryoprecipitate reversed this reduction and controlled the haemorrhage although 5/8 patients required significant surgical intervention.
Conclusions:The coagulation anomalies in these women are indicative of a defibrination syndrome that differs from DIC in the disproportionate reduction in fibrinogen level and the relatively rapid and complete resolution with blood product replacement and treating uterine pathology.Two stage TOPs in late second trimester is associated with significant morbidity.
Rituximab Use in Four Patients with Acquired vonWillebrand’s Syndrome.
Authors: Singh Priya C. , Siegel Jamie E. , Caro Jaime , Besa Emmanuel C. 
Published: April 2020

Abstract
Treating Acquired von Willebrand’s Syndrome (AVWS) is a challenge requiring multiple therapeutic modalities to achieve success in controlling and preventing bleeding episodes. From review of the literature, clinical use of rituximab, an anti-CD20 monoclonal antibody, in AVWS has not been reported. We present our experience with four patients treated with rituximab for steroid or intravenous immunoglobulin (IVIG) refractory and/or dependent AVWS associated with IgG monoclonal gammopathy of undetermined significance. Rituximab at a dose of 375mg/m2 was administered intravenously weekly for 4 consecutive weeks in the first patient. After 3 cycles of rituximab, we observed a correction of her bleeding time to normal, improvement of her prolonged aPTT, a decrease in her monoclonal IgG and cessation of her bleeding episodes for 29 months. She relapsed and was retreated with rituximab at the same dose for 3 cycles with no improvement in aPTT and bleeding time. She has had no further bleeding episodes after compliance with epsilon aminocaproic acid for one year. The second patient received rituximab intravenously at a dose of 375 mg/m2 weekly for 4 weeks. Prolonged aPTT was unchanged after treatment. He was asymptomatic for 8 months and then received prophylactic IVIG and von Willebrand Factor concentrate (Humate-P) for elective hand surgery. The third patient had a concomitant worsening idiopathic neuropathy and received rituximab 375mg/m2 intravenously daily for 2 consecutive days two weeks apart for his neuropathy. His neuropathy and prolonged aPTT did not improve and he developed gastrointestinal bleeding 1.5 months later. The fourth patient received rituximab 150mg/m2 intravenously weekly for 4 consecutive weeks. Prolonged aPTT was unchanged after treatment. He experienced no bleeding symptoms for 38 months. Factor VIII, Ristocetin Cofactor, von Willebrand Antigen and IgG levels were not significantly affected by rituximab use in cases 2–4. Rituximab seemed to be most effective in the first and fourth cases. The dosing and number of cycles is unclear. Success in the first case with multiple cycles of therapy may be needed for response and warrants further evaluation. Additionally, it appears therapy needs to be reinforced with other agents to prevent or stop bleeding. It was well tolerated with no infectious complications in our patients. Only one patient had an infusion related reaction, which did not require stopping therapy. Further prospective studies are needed to evaluate the efficacy of rituximab and establish the dosing and treatment duration in AVWS.
French Multicenter Study for Post-Marketing Survey of WILFACTIN®: A Von Willebrand Factor Concentrate with a Low FVIII Content.
Authors: Borel-Derlon Annie , Goudemand Jenny , Rothschild Chantal , Chatelanaz Catherine , Bridey Françoise ,   French Post-Marketing Study Group5
Published: April 2020

Abstract
This non-interventional study is designed to evaluate the safety and efficacy of WILFACTIN® when used for up to 3 years of treatment of bleeding episodes at hospital, for home-self treatment or prevention of surgical bleeding by patients with von Willebrand disease (VWD). The study is set up according to the Note for guidance CPMP/BPWG/220/02. Thirty six French centers enrolled 65 patients. Data from 48 patients (26 females, 22 males) were available for this 19-month interim analysis. Patients ages ranged from 11 months to 83.5 years (median, 38.5 years): 8 had type 1, 25 type 2, and 15 type 3 VWD. Baseline VWF:RCo and FVIII:C levels were less than 20 IU/dl in 37 and 20 patients respectively. The mean observation period was 155 days. A total of 1094 infusions were administered in 39 patients, 15% for spontaneous or trauma bleeds, 23% for invasive or surgical procedures, 59% for long-term prophylaxis and 3% short-term prophylaxis. The mean infusion dosage (VWF:RCo IU/kg body weight) ranged from 35.5 to 77.7 for 10 major bleeds, 23.9 to 53.2 for 25 surgeries and 27.2 to 58.2 for 8 patients with long-term prophylaxis treatment. The majority of subjects for long-term prophylaxis had type 3 VWD (6/8) and all were more than 12 years old. Indications for prophylaxis have included mucosal bleeds for 5 patients and joint bleeds for 3 patients. The number of prophylactic infusions ranged between 1 to 3 per week and these regimens, guided by the bleeding pattern of each patient, yielded favorable results in the prevention of bleeding episodes. Only 7 bleeds occurred less than 72 hours following infusion (7/642 infusions). To date (April 2006), one patient experienced 2 non serious possibly drug-related adverse events: moderate blood pressure increase with chest pain. No cases of thrombosis were reported following treatment. No cases of VWF inhibitor development. The results of this interim analysis of post-marketing survey confirm the safety and efficacy of WILFACTIN® for treatment of VWD, particularly for home self-treatment including long-term prophylaxis, and validate the results documented in previously reported clinical trials.
Rituximab as a Treatment Option for Acquired Inhibitors.
Authors: de Souza Jonas A. , Escobar Miguel A. 
Published: April 2020

Abstract
The incidence of acquired Factor VIII (FVIII) inhibitors is 0.2–1.0 case/million/year with a mortality range of 7.9 to 22%. Management consists of treating the bleeding episode and eradicating the autoantibody. First line therapy for the latter includes immunosuppressive agents with all of their potentially serious side effects. On this study, we add 5 patients to the scant published literature of individuals treated with Rituximab, a monoclonal antibody against CD20+ B cells. The patients had bleeding episodes from moderate to severe and presented with a prolonged partial thromboplastin time (PTT) that did not correct with a 1:1 mix with normal plasma. Inhibitors were confirmed by a low FVIII level and the Bethesda assay. Summarized clinical and laboratory data are shown in the table below. All the patients received Rituximab 375 mg/m2 once weekly × 4 doses. Patients 2–5 received Rituximab exclusively and patient 1 received two initial weeks of prednisone and cyclophosphamide followed by Rituximab. There were no adverse reactions to Rituximab. Complete remission was defined as clinical improvement associated with disappearance of the FVIII antibody and normalization of the factor VIII level. All the patients are currently in complete remission with no relapse, and with a post Rituximab time of more than 36 months for patients 1 and 5, and 12 months for patients 2–4. Rituximab appears to be a safe and well tolerated alternative to cytotoxic agents and it should be studied more thoroughly in prospective randomized studies.
Age/Sex/Race FVIII:C FVIII inhibitor (BU) Underlying Disorders Bleeding Treatment BU= Bethesda Units; HTN=Hypertension; CHF= Congestive Heart Failure; SLE= Systemic Lupus Erythematous; DM= Diabetes Mellitus; CRF= Chronic Renal Failure; rFVIIa=Recombinant activated factor VII. 1 80/M/Cauc &lt; 1% 33 HTN, CHF rFVIIa 2 37/M/Hisp &lt; 1% 68.4 None rFVIIa 3 45/F/Cauc &lt; 1% 58.4 SLE None 4 70/M/Hisp &lt; 1% 17 DM, CRF rFVIIa 5 83/M/AA 1% 6.8 HTN, DM rFVIIa
Efficacy of Peri- and Postoperative Treatment in 95 Patients with Von Willebrand’s Disease.
Authors: von Auer Charis , Lotter Kathrin , Heinsdorf Sandra , Scharrer Inge 
Published: April 2020

Abstract
Von Willebrand’s disease (VWD) is the most common inherited bleeding disorder in humans, exhibiting quantitative and qualitative defects in the von Willebrand factor. To investigate the quality of treatment during the peri- and postoperative course of patients with VWD, we conducted a retrospective data analysis. We analyzed data of 95 patients with VWD who went for 173 surgical interventions in our center between 1981 and 2003. Peri- and postoperative courses with regard of bleeding complications were reviewd. 59 Patients had type1 VWD (two severe, three moderate, 54 mild). 16 patients had type 2 VWD (14 2A, one 2B, one 2N) and 11 patients type 3 VWD. Nine patients with type1 VWD had an additional factor deficiency (five FXII-, two FVII- and two FV-deficiencies). We analyzed the course of 54 orthopedic surgeries, 41 abdominal surgeries, 15 angiographies, 12 endoscopic surgeries, 10 ear-nose-throat interventions, 11 mamma surgeries, 10 neurological surgeries, 8 soft tissue surgeries, 7 thorax surgeries, 3 thyroid gland surgeries and 2 biopsies. Most patients (108/173) were treated with Humate P, 33 patients with DDAVP (33/173) and 9 patients received both products during the pre- peri- and postoperative period. Three patients received other plasmatic FVIII- concentrates, 20 patients had no therapy for their coagulation disorder. 16 patients (9, 2%) had peri- or postoperative bleeding complications. Most of them were seen in patients with VWD type 2B and 3 and in patients who underwent major surgery and who received only DDAVP. Humate P was used for 9 interventions (9/108 = 8, 3%) and DDAVP for four interventions (4/33 = 12, 1%) with bleeding complications, three patients had no therapy. Most of these complications were reported in thoracic surgery (2/7 = 28%), gynecological (3/11 = 27%) and otolaryngological surgery (2/10 = 20%). Retrospectively 15 bleeding complications could be explained by surgical technique, thromboprophylaxis, inefficient substitution therapy or additional thrombocytopenia. In conclusion our findings show a low frequency of bleeding complications in VWS patients with surgical interventions. Our evaluation reveals the necessity of special hemostaseologic care and laboratory controls for these patients. Substitution therapy should depend on type of VWD and type of surgical intervention. Especially during thoracic surgery, gynecological and otolaryngological surgery a careful peri- and postoperative hemostaseologic management as well as careful hemostyptic techniques of the surgeon are required.