bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimated Annual Number of US Acute-Care Hospital Inpatients Meeting ACCP Criteria for Venous Thromboembolism (VTE) Prophylaxis.
Authors: Anderson Frederick A. , Zayaruzny Max , Heit John A. , Cohen Alexander T. ,   On Behalf of the VTE Impact Assessment Group
Published: April 2020

Abstract
Background While consensus guidelines regarding VTE prophylaxis for hospital inpatients have been available for more than 15 years, the number of US inpatients who are potentially eligible for prophylaxis is unknown. Such data are required for estimating the potential costs and benefits of prophylaxis in reducing VTE incidence. Objective To estimate the number of Y2002 US acute-care hospital inpatients who are potentially eligible for VTE prophylaxis.
Methods We applied the 7th (2004) American College of Chest Physician (ACCP) Consensus Conference VTE prophylaxis guidelines (Geerts et al. Chest2004;126:338S–400S) to inpatients with hospital discharge International Classification of Disease (ICD-9) codes for major surgery or medical illness identified from the Healthcare Utilization and Cost Database (HCUP), a national acute-care hospital database supported by the US Agency for Health Care Quality Research.
Results Of a total of 37.8 million inpatients discharged from US acute-care hospitals in Y2002, 13.4 million (35%) met ACCP guideline criteria for VTE prophylaxis (Table).
Table. Inpatients Discharged from US Acute-Care Hospitals with ACCP Guideline Defined Risk of VTE in Y2002 Surgical VTE Risk N Highest risk surgery 744,465 High risk surgery 3,031,318 Moderate risk surgery 2,019,696 Surgical subtotal 5,795,479 Medical VTE Risk N Heart failure 1,867,576 Cancer 1,017,356 Stroke 515,370 Other medical conditions 4,196,343 Medical subtotal 7,596,645 Grand Total 13,392,124
Among the 37.8 million Y2002 discharged inpatinets, 7.7 million were defined by HCUP criteria as having had a major operative procedure. When ACCP surgical risk criteria were applied to this population, 1.9 (25%) were at low VTE risk, while 5.8 million (75%) were at moderate (26%), high (39%) or highest (10%) VTE risk. Among the patients without a major operative procedure, 7.6 million met the ACCP criteria for VTE prophylaxis based on medical illness risk factors.
Conclusions In total, 13.4 million US residents meet ACCP criteria for VTE prophylaxis annually due to hospitalization for either major surgery or medical illness. Given that almost 60% of all VTE events occurring in the community are related to recent acute-care hospitalization, providing universal, safe and effective VTE prophylaxis to this population affords an important opportunity to significantly reduce the incidence of VTE. These data provide support for developing and monitoring compliance with hospital-wide guidelines for VTE prevention.
Low Dose Warfarin Is Effective Prophylaxis Against Deep Vein Thrombosis Following Total Hip Arthroplasty.
Authors: Bern Murray M. , Deshmukh Rahul V. , Nelson Russell , Bierbaum Benjamin , Losina Elena , Katz Jeffrey N. , Sevier Nancy , Howie Noreen 
Published: April 2020

Abstract
Thromboembolic disease (TED) including deep vein thrombosis (DVT) and pulmonary embolus (PE) remain major complications following total hip arthoplasty. Warfarin is an important pharmacologic prophylaxis against these complications. How to optimally use warfarin remains a sourse of debate. This retrospective patient report extends eariler observations that low dose warfarin is effective prophylaxis against symptomatic thromboembolic disease. Patients planned for elective unilateral total hip replacement were given 1 mg of warfarin for 7 days prior to surgery. Patients were excluded from this regimen if they had a coagulopathy, platelet count less than 140,000/mm3, previous TED, cancer, or were in need of long term anticogulation for other reasons. Prothrombin times were measured on the morning of surgery. The night following surgery they were prescribed variable dose warfarin which was continued while in hospital, with target INR 1.5–2.0. They were discharged to rehabilitation centers or home taking 1 mg daily until their 4–6 week followup visit. All patients received post-operative pneumatic compression stockings, followed by elastic compression stockings when ambulatory. Patients were encouraged to begin isometric exercises immediately after surgery and were mobilized on day 1 or 2 following surgery. Hospital and clinic charts for 13 months of consecutive patients were reviewed for any evidence of TED. Auxiliary data basis were probed for any additional evidence of TED, including the hospital logs of Radiology Department, Orthopedic Department Morbidity and Mortality rounds, Adverse Events, Medical Records Department, and Case Management. There were 833 primary and 170 revision total hip athroplasties. Of the 1003 patients studied, 3 had TED (0.3%, 95% CI 0.0–0.6), including 2 with DVT and l with nonfatel PE. The followup rate was 98.9%, with 11 patients lost to follow-up. Complications from the warfarin were minimal. The prothrombin times on the morning of surgery were below INR 1.4 for 98.9% of the patients. Two patients with INR greater than 1.49 on day of surgery received fresh frozen plasma. Seven patients had post-operative wound hematomas, one of which had INR greater than 1.5. Very low warfarin when started preopartively, continued as variable dose in the immediate postoperative period, and continued at 1 mg until the patient is fully ambulatory, combined with the mechanical tools listed, is effective and safe prophylaxis against TED.
A Variant of Congenital Neutropenia Is Caused by a 3′-UTR Mutation in the Gene Encoding the Endosomal Adaptor Protein p14 (MAPBPIP).
Authors: Bohn Georg , Allroth Anna , Thiel Jens , Schäffer Alejandro A. , Brandes Gudrun , Glocker Erik , Teis David , Taub Nicole , Zeidler Cornelia , Geffers Robert , Buer Jan , Huber Lukas A. , Welte Karl , Grimbacher Bodo , Klein Christoph 
Published: April 2020

Abstract
We have investigated the molecular etiology of autosomal recessive congenital neutropenia in a pedigree of 15 members with four affected children. Combining genome wide linkage analysis and a transcriptional profiling approach, we identified a homozygous mutation in the 3′-UTR of p14 (MAPBPIP), a recently identified adaptor molecule controlling late endosomal signaling by the MP1-MAPK complex. The mutation segregated with the disease, and neutrophils from all patients showed decreased RNA and protein levels of p14. To further assess the significance of this point mutation, we designed firefly luciferase reporter plasmids carrying either wildtype or mutated 3′-UTRs and cotransfected these constructs together with renilla luciferase expression plasmids into CHO cells. The specific luciferase activity was consistently decreased in the mutated constructs, suggesting that the mutated 3′-UTR is associated with decreased RNA levels in a heterologous system. Mechanistically, we excluded aberrant splicing and aberrant polyadenylation as a cause for decreased RNA levels. However, an increased ratio of unprocessed to processed nuclear RNA in transfected cells suggests a defect in RNA processing. Decreased levels of p14 lead to an abnormal configuration of lysosomes in granulocytes as shown by transmission electron microscopy. Whereas phagocytosis capacity is normal, killing of pathogenic bacteria is reduced in p14-deficient granulocytes. This defect is reversed upon retroviral p14 gene transfer into hematopoietic stem cells and subsequent differentiation into neutrophils in vitro. In summary, we provide evidence that decreased levels of p14 cause neutropenia. Furthermore, our report extends the small list of hereditary diseases associated with 3′-UTR mutations.
Rituximab Maintenance Prolongs Response Duration after Salvage Therapy with R-FCM in Patients with Relapsed Follicular Lymphomas and Mantle Cell Lymphomas: Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG).
Authors: Hiddemann Wolfgang , Forstpointner Roswitha , Dreyling Martin , Gramatzki Martin , Böck Hans-Peter , Hänel Mathias , Seymour John , Planker Manfred , Dührsen Ulrich , Wilms Klaus , Clemens Martin , Ludwig Wolf-Dieter , Wandt Hannes , Pasold Rita , Unterhalt Michael 
Published: April 2020

Abstract
Preceding studies have shown that Rituximab prolongs the time to treatment failure (TTF) and response duration (RD) in follicular lymphoma (FL) when given either together with chemotherapy or as maintenance after a no R containing therapy. In the current study the impact of R maintenance on RD was evaluated after remission induction by an R-chemo combination. Patients with advanced stage relapsed or refractory FL and mantle cell lymphoma (MCL) were eligible. The study design comprized a first randomization between 4 courses of chemotherapy with Fludarabine (25mg/m2/d days 1–3), Cyclophosphamide (200mg/m2/d days 1–3) and Mitoxantrone (8mg/m2/d day 1) (FCM) versus FCM plus Rituximab (375mg/m2/d on day 0) (R-FCM). Patients entering a complete (CR) or partial remission (PR) underwent a second randomzation for observation only versus R maintenance with 4 weekly doses of R (375mg/m2/d) to be given at three and nine month after end of therapy. Both randomizations were stratified for histology and preceding therapy. The first randomization was stopped after 147 patients demonstrating a significant improvement for the R-FCM therapy in initial response, progression free survival and even overall survival (OS). So all subsequent patients received R-FCM.
174 cases are currently evaluable for the second randomization, 136 of whom had received R-FCM for remission induction. In these patients the median RD has not been reached in the R-maintenance arm whereas it is 17 months in patients with no further treatment after R-FCM (p=0.0024). This improvement was seen both in FL and MCL. This study demonstrates that R maintenance after R-FCM salvage therapy is highly effective and improves the outcome of patients with relapsed FL and MCL.
The Addition of Rituximab to Dose-Adjusted EPOCH with HAART Suspension Is Highly Effective and Tolerable in AIDS-Related Lymphoma (ARL) and Allows the Delivery of Abbreviated Chemotherapy.
Authors: Dunleavy Kieron , Wayne Alan , Little Richard , Grant Nicole , Steinberg Seth , Jaffe Elaine S. , Pittaluga Stefania , Yarchoan Robert , Carrasquillo Jorge , Janik John , Wilson Wyndham H. 
Published: April 2020

Abstract
In ARL, the addition of Rituximab ® to CHOP chemotherapy may improve tumor response but the benefit appears offset by increased infectious deaths (Kaplan et al. Blood 2005; May 24: Epub). We hypothesized R with DA-EPOCH may enhance tumor kill, enabling fewer treatment cycles and lowering toxicity compared to DA-EPOCH alone. Pts received DA-EPOCH-R (in mg/m2/d etoposide 50, vincristine 0.4 and doxorubicin 10 all CIV d 1–4; and in mg/m2 cyclophosphamide 750 IV day 5, prednisone 60 po days 1–4 and rituximab 375 IV d 1, 5; and G-CSF sc d 6–15). Prophylactic IT MTX x 6 was administered and HAART was discontinued on all cycles. Cyclophosphamide was adjusted based on ANC nadir. Response was assessed by CT and PET and pts received 1 cycle beyond CR for a minimum of 3 cycles. Characteristics of 27 pts include median (range) age 41 (9–61) years; IPI 3 (0–4); ECOG PS 1 (1–4), CD-4 212 (0–674) cells/mm3; HIV viral load 58,700 (0–6,080,000) RNA copies/mL; male sex 22 (81%); LDH &gt; N 19 (70%); stage IV 18 (67%) and histology DLBCL 25 (93%) and Burkitt lymphoma 2 (7%). Of 24 evaluable pts (2 NE, 1 TE), median (range) cycles is 3 (3–5) with CR/Cru in 21 (88%) and PR 1 (4%) pts. At 25 mos median follow-up, PFS and OS are 77% and 72%, respectively. Shown below are PFS and OS for the entire group and PFS in pts with CD4 &gt; and &lt; 100 cells/mm3. In pts with CD4 &gt; and &lt; 100 cells/mm3, OS was 92% and 48%, respectively, indicating a relatively low probability of non-tumor related deaths at 2 yrs among pts in remission. IPI did not impact OS or PFS. The predictive value of early PET (after cycle 2 or 3) for progression was evaluated in 21 pts in remission. None of 11 pts with a negative PET progressed (100% negative predictive value) whereas only 2 of 10 pts with a positive PET progressed (20% positive predictive value). Toxicity on 81 cycles included ANC &lt; 500/mm3 on 33 (41%); platelets &lt; 50000/mm3 on 20 (25%) and; fever/neutropenia on 27 (33%). No treatment related deaths occurred. Short course DA-EPOCH-R is highly effective and tolerable in all subgroups of ARL with significantly fewer treatment cycles (median 3 versus 6 cycles) compared to DA-EPOCH alone. CD4 cells decreased a median of 42 cells/mm3 (range +271 to − 320) by end of therapy with DA-EPOCH-R compared to 189 cells/mm3 (range +19 to −973) with DA-EPOCH alone. While a negative PET scan reliably predicted a disease-free state, a positive PET scan only predicted treatment failure in 20% of pts in remission. Although this study was not designed to assess the benefit of rituximab, a comparison to DA-EPOCH (Blood101:4653, 2003) suggests rituximab may enhance tumor kill and reduce immune suppression. Accrual continues.
Figure Figure Figure Figure
Results of a Pilot Trial of Fludarabine, Mitoxantrone and Rituxan in Mantle Cell Lymphoma.
Authors: Levine Alexandra M. , Tulpule Anil , Smith Lynne , Espina Byron M. , Mohrbacher Ann F. , Feinstein Donald I. 
Published: April 2020

Abstract
Mantle cell lymphoma is an aggressive B cell tumor, with a median survival of approximately 3 years, despite treatment. While intensive therapy may be curative in some patients, the median age at diagnosis is in the 60’s, and such therapy is not always feasible. We developed a regimen of fludarabine, mitoxantrone and rituximab, comprised of fludarabine, 25 mg/m2, IV on days 1–3; mitoxantrone, 10mg/m2, IV on day 1, every 28 days for 6 cycles, along with rituximab, 375 mg/m2 given on day 1, of cycles 2 through 6, and then given alone for 3 weekly doses as cycle 7. To date, 14 male and 7 female patients with a median age of 60 years (range 41–87) have been accrued. Five patients (24 %) relapsed from prior systemic chemotherapy including stem cell transplantation in 1. All but 1 patient had either stage III (n=2) or stage IV disease (n=20). Sites of extranodal disease included bone marrow in 15 (71%), pleural effusions in 5 (24 %), and GI tract involvement in 3 (14 %) patients. Eight patients (38 %) had an intermediate or high IPI score. B symptoms were present in 7. On pathologic assessment, no patient had blastoid morphology. Cyclin D1 was expressed in 19 of 21 tissues tested. Treatment has been well tolerated; the most common side effect was transient grade 3 or 4 neutropenia reported in 17 (81 %) patients; transient grade 3 or 4 thrombocytopenia in 3 patients; and anemia observed in 6 patients. No grade 3 or 4 non-hematologic toxicity has been reported. Of 20 evaluable patients, complete remissions (CR) have been documented in 18 (90 %). The median duration of complete remission is 17.4 months (range 1.1–29.9). Thirteen patients have relapsed after 1.1 to 29.9 months in CR. All 20 of the evaluable patients remain alive after a median follow-up of 16.4+ mos (range 1.0–39.6+). Combination therapy with fludarabine, mitoxantrone, and rituxan is a well tolerated regimen and is highly active in patients with both newly diagnosed and relapsed mantle cell lymphoma. While relapse is seen in the majority, the regimen is capable of inducing CR in 90 % and can be used safely in elderly patients and those who have relapsed or are not eligible for stem cell transplant.
Validation Studies in European Blood Centers To Evaluate Processing Whole-Blood-Derived or Apheresis Plasma Using the INTERCEPT Blood System Intended for Commercialization.
Authors: Singh Y. , Hervig T. , Schlenke P. , Cazenave J.P. , Pinkoski L. , Corash L. 
Published: April 2020

Abstract
Introduction: INTERCEPT plasma (I-FFP) for transfusion is prepared with a photochemical treatment (PCT) system using amotosalen (S-59) and long-wavelength UVA light to inactivate a broad spectrum of blood-borne pathogens. For Phase 3 clinical trials, 6 US blood centers prepared an inventory of ~10,000 I-FFP units by processing ~250 mL whole blood-derived (WB) or apheresis (APH) plasma units using a prototype PCT system. In these trials, I-FFP effectively supported patients with congenital and acquired coagulopathies or TTP. The prototype PCT system has been modified to treat up to 635 mL of plasma in a single PCT process, yielding up to three ~200 mL doses while maintaining pathogen inactivation efficacy. This modified PCT system intended for commercialization was evaluated in process validation studies in 3 European blood centers under routine operating conditions. After processing with the commercial PCT system, the effect on coagulation factor activity and retention was assessed in APH plasma (Blood2004;104:746a) and, as reported here, in WB plasma.
Methods: Whole blood and/or APH plasma units were collected at 3 European blood centers. Three-unit pools (~600 mL) of WB plasma were prepared. APH plasma (~600 mL) was collected using Autopheresis C (Baxter) or MCS+(Haemonetics) devices. Blood bank personnel processed a total of 60 WB plasma pools and 90 APH plasma units using the commercial PCT system. Baseline and I-FFP plasma samples were collected, frozen below -60°C, and sent to Cerus for assay of factors I (fibrinogen), II, V, VII, VIII, IX, X, XI, and XIII, proteins C (PC) and S (PS), and antithrombin III (AT). Alpha-2 antiplasmin (AP) was assayed by a reference laboratory. Comparative data from a representative subset of I-FFP units prepared for the Phase 3 trials using the prototype PCT system were obtained from samples collected during PCT processing and stored at ≤−70°C. Retention of activity is expressed as the proportion (%) of pre-treatment (baseline) activity remaining after PCT.
Results: Retention of coagulation factor activity in WB and APH I-FFP prepared with the commercial PCT system (Comm) was 73–76% of baseline fibrinogen and FVIII activity, and 80–97% of baseline for factors II, V, VII, IX, X, XI, XIII, PC, PS, AT, and AP (Table). Retention of activity in I-FFP prepared with the commercial PCT system was similar to that of I-FFP prepared with the clinical prototype.
Conclusion: The PCT system intended for commercialization provides multiple I-FFP doses with a single PCT process. Retention of coagulation factor activity in WB and APH plasma processed with the commercial PCT system was similar to that of I-FFP used in Phase 3 trials to effectively support patients with congenital and acquired coagulopathies or TTP.
Retention of Coagulation Factor Activity in I-FFP
A Fully-Automated Screening Method for Anti-HLA Antibodies: Implications for Screening Plasma Donations To Prevent Transfusion-Related Acute Lung Injury (TRALI).
Authors: Culler Elizabeth , Barclay Sheilagh B. , Bray Robert A. , Gebel Howard M. , Hillyer Christopher D. , Roback John D. 
Published: April 2020

Abstract
Background: TRALI is a potentially fatal complication of transfusion. Although the pathogenesis is not completely understood, and may involve a “multi-hit” mechanism, transfusion of donor plasma containing anti-HLA and/or anti-neutrophil antibodies appears to play an important role. In previous studies, up to 22% of all blood components were found to contain HLA antibodies (Bray et al, Human Immunology, 65, 240–4, 2004). Based on the possible involvement of HLA antibodies in TRALI, some blood services no longer provide plasma from female donors for transfusion, since these donors are more likely to have these antibodies due to pregnancy. An alternative, more specific approach to prevent transfusion of HLA antibody-containing plasma, and possibly reduce the risk of TRALI, is to screen plasma prior transfusion. However, no automated method is yet available with sufficient throughput to screen blood donors for HLA antibodies.
Methods: The 3Ti Aegis is a novel open-architecture automated blood typing platform that uses fluorescence cytometry. The Aegis was readily configured for detecting anti-HLA Class I antibodies in donor plasma by modifying the commercially-available FlowPRA Class I Screening Test (One Lambda, Canoga Park, CA) to include a phycoerythrin (PE)-labeled secondary antibody. Positive and negative control samples, as well as patient specimens previously demonstrated to contain HLA antibodies, were evaluated to determine the accuracy of the automated Aegis method.
Results: Positive and negative controls were readily distinguished from one another whether testing was performed manually (according to manufacturer’s instructions) and acquired on a BD FACScan cytometer, or performed using the fully-automated method on the 3Ti Aegis. For the Aegis, the mean fluorescence intensities for positive and negative controls were 156.2 and 14.4, respectively. For the manual method, the signal to noise separation was comparable (692.5 and 28.9, respectively). Six additional patient samples, which had previously identified anti-Class I antibodies, also tested positive with the Aegis system. Estimated staining and acquisition times on the Aegis for 96 samples are 2 hours and 1.5 hours, respectively, which is comparable to the times for manual testing
Conclusions: The Aegis can perform accurate, high throughput, completely automated screening of plasma donations for HLA Class I antibodies prior to transfusion. Future work will focus on developing combined Class I and II screening beads, as well as beads for detecting common anti-neutrophil antibodies, to produce a comprehensive TRALI antibody detection package for the Aegis platform. The Aegis is the first device to make pretransfusion HLA antibody testing practical, and may reduce the incidence of TRALI and accompanying transfusion fatalities.