ResearchPad - Hematology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Clinical, Laboratory, and Bone Marrow Findings of 31 Patients With Waldenström Macroglobulinemia]]> https://www.researchpad.co/product?articleinfo=Ncf03617d-0fcc-47fd-9e77-46f2747c453d

Background

Waldenström macroglobulinemia (WM) is a subset of lymphoplasmacytic lymphoma (LPL) with bone marrow (BM) involvement and an IgM monoclonal gammopathy of any level. We aimed to identify the clinical, laboratory, and BM findings of patients with WM and to evaluate the usefulness of CD154 for the diagnosis and prognosis of WM.

Methods

We reviewed the medical records and BM studies and/or flow cytometric immunotyping of 31 patients with untreated WM. Semiquantitative immunohistochemistry (CD20, CD138, tryptase, and CD154) of BM was performed.

Results

Only six patients presented with symptoms of hyperviscosity syndrome. Eleven patients had solid cancer and/or another hematologic malignancy. Mast cells (MC) increased in all samples, with some in close contact with tumor cells. Tryptase-positive MC (17.1/ high-power fields [HPF], 1.2–72.0/HPF) and CD154-positive MC (8.6/HPF, 0.1–31.1/HPF) were observed. The high CD154-positive MC (≥8.6/HPF) group showed a lower overall five-year survival rate than the low CD154-positive MC (<8.6/HPF) group (71.9% vs. 100.0%; P=0.012). Flow cytometric immunophenotyping of BM aspirates showed increased B lymphocytes and plasma cells with a normal phenotype (CD138+/CD38+/CD19+/CD45+/CD56).

Conclusions

Approximately one third of WM patients showed other malignancies and all patients had increased MC. Immunohistochemistry and flow cytometric immunophenotyping are useful for diagnosing WM, and increased CD154-positive MC can indicate poor prognosis.

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<![CDATA[The First Korean Case of High-Molecular-Weight Kininogen Deficiency, With a Novel Variant, c.488delG, in the KNG1 Gene]]> https://www.researchpad.co/product?articleinfo=N7444a83d-c557-4944-8543-34fe71ce3a78 ]]> <![CDATA[Effective Management of Femur Fracture Using Damage Control Orthopedics Following Fat Embolism Syndrome]]> https://www.researchpad.co/product?articleinfo=Naa27dcb2-d804-4974-ba25-4e93e2f9c52d

Fat embolism syndrome (FES) is a rare event following a traumatic injury, and its pathophysiologic mechanism continues to be elusive. Fat embolism syndrome generally occurs when a bone marrow fat enters the bloodstream resulting in a cascade of inflammatory response, hyper-coagulation, and an array of symptoms that generally begin within 24-48 hours. FES early symptoms include petechial rash, shortness of breath, altered mental status, seizures, fever, and may result in decreased urine output. The common etiologies of a fat embolism include long bone fractures, mainly femoral and pelvic fractures. 

There are multiple management methods described in the literature to help prevent FES and other long bone fracture complications from occurring. Although not universally adopted, the damage control orthopedics (DCO) has been the major management option for patients with a long bone fracture. DCO is entertained by provisional immobilization of patients with long bone fractures and those who are considered severely traumatized patients (STP). Thus, immobilization can help minimize the traumatic effect and the subsequent second hit by performing non-life saving surgical procedures.

In this case, a patient with a transverse femur fracture suffered disconcerting symptoms of fat embolism prior to definitive femur repair. Hence, damage control orthopedics was entertained with a postponement of his femur repair to facilitate stabilization. The use of damage control orthopedics was successful in this patient with no long term complications.

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<![CDATA[Osteonecrosis Mandibular Extended to Bisphosphonates: A Very Rare Extensive Case]]> https://www.researchpad.co/product?articleinfo=N037685f4-90f6-41f6-a826-98b21a001021

After the first report of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in 2003, it has increased significantly since then. We report a very rare extensive case never seen before in our experience of bone exposure with necrosis reaching the mandibular inferior border. Although the treatment modalities are not yet established, most researchers have recommended conservative approaches. The surgery was to be as conservative as possible, with a resection of the mandibular range followed by reconstruction using titanium plate with space maintainer. The authors would like to share their approach, management, and awareness.

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<![CDATA[Cardiovascular Risk Profile of Chimeric Antigen Receptor T-cell Therapy]]> https://www.researchpad.co/product?articleinfo=Nfc26de66-cdcd-4135-ae5d-ec20c8a2c79c

Chimeric antigen receptor (CAR) T-cell therapy is a novel form of immunotherapy that has been recently introduced in clinical practice for the treatment of leukemias and lymphomas after being approved by United States Food and Drug Administration (USFDA). The risk profile of this treatment modality is not yet fully explored. As the survival of cancer patients is expected to rise due to new therapies being brought into practice, physicians are going to encounter side effects of these therapies. This may include both short-term and long-term effects. Having a good knowledge of these side effects can help the physicians recognize in advance the at-risk population and risk stratify them accordingly. Cardiac oncology is a growing field that involves the study of interaction between novel immunotherapies and their cardiac side effects. Knowing the cardiotoxicity profile of CAR T-cell therapy will help us choose the most appropriate patient population (those who can benefit the most without being at risk of harmful effects including cardiotoxicity) for the therapy. It will also help us recognize various cardiac complications, as they arise later during the lifetime of these cancer survivors. 

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<![CDATA[Protein C Deficiency as a Risk Factor for Stroke in Young Adults: A Review]]> https://www.researchpad.co/product?articleinfo=N29a8fdd1-5512-482c-a77f-66c37c8e449f

Protein C (PC) is a 62-kD vitamin K dependent glycoprotein produced by the liver as a zymogen and is activated by binding to the thrombin-thrombomodulin complex, with protein S (PS) acting as a cofactor. Among its various functions, PC acts as a naturally occurring anticoagulant and its deficiency, either homozygous or heterozygous, predisposes the individual to a state of thrombosis, particularly venous thromboembolism, and mainfests as myocardial infarction (MI), deep venous thrombosis, pulmonary embolism, or stroke. This review discusses the pathophysiology of the anticoagulatory effect of PC, mode of inheritance of its deficiency, the arterial and venous involvement in patients with stroke, and its risk factors. A detailed analysis of published case reports on PC deficiency as a causative agent of stroke in young adults has also been included along with the management of such patients.

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<![CDATA[Physicochemical and biological evaluation of JR-131 as a biosimilar to a long-acting erythropoiesis-stimulating agent darbepoetin alfa]]> https://www.researchpad.co/product?articleinfo=Na789b0ff-1b14-409c-afa6-0c7a70fc7c42

Renal anemia is predominantly caused by a relative deficiency in erythropoietin (EPO). Conventional treatment for renal anemia includes the use of recombinant human EPO (rhEPO) or a long-acting erythropoiesis-activating agent named darbepoetin alfa, which is a modified rhEPO with a carbohydrate chain structure that differs from native hEPO. We have developed a biosimilar to darbepoetin alfa designated JR-131. Here, we comprehensively compare the physicochemical and biological characteristics of JR-131 to darbepoetin alfa. JR-131 demonstrated similar protein structure to the originator, darbepoetin alfa, by peptide mapping and circular dichroism spectroscopy. Additionally, mass spectroscopic analyses and capillary zone electrophoresis revealed similar glycosylation patterns between the two products. Human bone marrow-derived erythroblasts differentiated and proliferated to form colonies with JR-131 to a similar degree as darbepoetin alfa. Finally, JR-131 stimulated erythropoiesis and improved anemia in rats similarly to darbepoetin alfa. Our data show the similarity in physicochemical and biological properties of JR-131 to those of darbepoetin alfa, and JR-131 therefore represents a biosimilar for use in the treatment of renal anemia.

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<![CDATA[Nocturnal hypercapnia with daytime normocapnia in patients with advanced pulmonary arterial hypertension awaiting lung transplantation]]> https://www.researchpad.co/product?articleinfo=Nacc6463a-eb28-4f4a-acf0-c81fc9df01f4

Background

Pulmonary arterial hypertension (PAH) is frequently complicated by sleep disordered breathing (SDB), and previous studies have largely focused on hypoxemic SDB. Even though nocturnal hypercapnia was shown to exacerbate pulmonary hypertension, the clinical significance of nocturnal hypercapnia among PAH patients has been scarcely investigated.

Method

Seventeen patients with PAH were identified from 246 consecutive patients referred to Kyoto University Hospital for the evaluation of lung transplant registration from January 2010 to December 2017. Included in this study were 13 patients whose nocturnal transcutaneous carbon dioxide partial pressure (PtcCO2) monitoring data were available. Nocturnal hypercapnia was diagnosed according to the guidelines of the American Academy of Sleep Medicine. Associations of nocturnal PtcCO2 measurements with clinical features, the findings of right heart catheterization and pulmonary function parameters were evaluated.

Results

Nocturnal hypercapnia was diagnosed in six patients (46.2%), while no patient had daytime hypercapnia. Of note, nocturnal hypercapnia was found for 5 out of 6 patients with idiopathic PAH (83.3%). Mean nocturnal PtcCO2 levels correlated negatively with the percentage of predicted total lung capacity (TLC), and positively with cardiac output and cardiac index.

Conclusion

Nocturnal hypercapnia was prevalent among advanced PAH patients who were waiting for lung transplantation, and associated with %TLC. Nocturnal hypercapnia was associated with the increase in cardiac output, which might potentially worsen pulmonary hypertension especially during sleep. Further studies are needed to investigate hemodynamics during sleep and to clarify whether nocturnal hypercapnia can be a therapeutic target for PAH patients.

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<![CDATA[Effects of amotosalen treatment on human platelet lysate bioactivity: A proof-of-concept study]]> https://www.researchpad.co/product?articleinfo=Ne8e94533-b9bd-43e3-83be-324d5eb7ad87

Background

Clinical application of mesenchymal stromal cells (MSCs) usually requires an in vitro expansion step to reach clinically relevant numbers. In vitro cell expansion necessitates supplementation of basal mammalian cell culture medium with growth factors. To avoid using supplements containing animal substances, human platelet lysates (hPL) produced from expired and pathogen inactivated platelet concentrates can be used in place of fetal bovine serum. However, globally, most transfusion units are currently not pathogen inactivated. As blood banks are the sole source of platelet concentrates for hPL production, it is important to ensure product safety and standardized production methods. In this proof-of-concept study we assessed the feasibility of producing hPL from expired platelet concentrates with pathogen inactivation applied after platelet lysis by evaluating the retention of growth factors, cytokines, and the ability to support MSC proliferation and tri-lineage differentiation.

Methodology/Principal findings

Bone marrow-derived MSCs (BM-MSCs) were expanded and differentiated using hPL derived from pathogen inactivated platelet lysates (hPL-PIPL), with pathogen inactivation by amotosalen/ultraviolet A treatment applied after lysis of expired platelets. Results were compared to those using hPL produced from conventional expired pathogen inactivated platelet concentrates (hPL-PIPC), with pathogen inactivation applied after blood donation. hPL-PIPL treatment had lower concentrations of soluble growth factors and cytokines than hPL-PIPC treatment. When used as supplementation in cell culture, BM-MSCs proliferated at a reduced rate, but more consistently, in hPL-PIPL than in hPL-PIPC. The ability to support tri-lineage differentiation was comparable between lysates.

Conclusion/Significance

These results suggest that functional hPL can be produced from expired and untreated platelet lysates by applying pathogen inactivation after platelet lysis. When carried out post-expiration, pathogen inactivation may provide a valuable solution for further standardizing global hPL production methods, increasing the pool of starting material, and meeting future demand for animal-free supplements in human cell culturing.

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<![CDATA[Isoniazid Induced Pure Red Blood Cell Aplasia]]> https://www.researchpad.co/product?articleinfo=Nb1c63667-9043-4dcf-8239-06ce9e59873c

Pure red blood cell aplasia (PRCA) is one of the uncommon causes of anemia. Drug-induced PRCA is even more infrequent. Only a few drugs are implicated in PRCA. Isoniazid is a widely used drug for the treatment of tuberculosis all over the world. It is known to cause hepatotoxicity, but in rare instances, it can lead to PRCA. 

A 72-year-old Caucasian male, who was started on isoniazid after the diagnosis of latent tuberculosis, presented two months later with episodes of syncope to primary care physician’s office. The initial blood work showed severe anemia. There were no signs of acute or chronic gastrointestinal blood loss, and the stool hemoccult test was negative. Iron, vitamin B12, folate, lactate dehydrogenase, bilirubin, transaminases, and erythropoietin were within normal limits. Peripheral blood smear showed normochromic and normocytic anemia. A reticulocyte count was less than 1,000 per microliter. Thymoma, human immunodeficiency virus, and parvovirus B19 were ruled out. Further work-up with bone marrow biopsy confirmed pure red blood cell aplasia. A detailed review of recently started medications revealed isoniazid as the offending drug. Isoniazid was stopped. Reticulocyte count and bone marrow recovered a few days after stopping with eventual improvement in hemoglobin level, thus confirming the diagnosis of isoniazid induced red blood cell aplasia.

Isoniazid is the first-line therapy for tuberculosis. Rarely, it can cause pure red blood cell suppression and severe anemia, an untoward effect, worth remembering.

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<![CDATA[Association of Blood Type With Postsurgical Mucosal Bleeding in Pediatric Patients Undergoing Tonsillectomy With or Without Adenoidectomy]]> https://www.researchpad.co/product?articleinfo=N94e7580b-d8ce-4c0c-8c33-3f9fa80b3a3f

Key Points

Question

Is blood type O associated with a higher prevalence hemorrhage in children after tonsillectomy with or without adenoidectomy?

Findings

In this cohort study of nearly 15 000 children who underwent tonsillectomy with or without adenoidectomy, the hemorrhage rate following surgery was 3.9%. In the cohort of children for whom a blood type was known, those with blood type O experienced bleeding as frequently as those with non-O types, despite having significantly lower baseline von Willebrand factor values.

Meaning

The findings of this study indicate that bleeding rates after tonsillectomy with or without adenoidectomy are similar in children with blood type O and those with non-O types.

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<![CDATA[Fusobacterium necrophorum Septicemia Leading to Lemierre’s Syndrome in an Immunocompetent Individual: A Case Report]]> https://www.researchpad.co/product?articleinfo=Naef1cec0-ed96-497d-8d22-318e0b032456

Lemierre syndrome is a life-threatening condition associated with infection by obligate anaerobes residing in oropharyngeal mucosa. The most common organism responsible is Fusobacterium necrophorum. We report a case in a 69-year-old gentleman. The man with past medical history of hypertension, anxiety and chronic alcohol abuse was brought in by his family for altered mental status and fever. He had a complicated stay with septic shock on multiple pressors, his blood cultures grew Fusobacterium necrophorum and neck ultrasound showed acute thrombus of the right internal jugular vein (IJV). The patient had received intravenous antibiotics throughout stay but had poor prognosis and eventually expired after a complicated hospital stay.

Lemierre syndrome is a rare syndrome usually associated with an acute oropharyngeal infection due to anaerobic bacteria leading to secondary septic thrombophlebitis of the internal jugular vein. The characteristic clinical picture noticed is a hematogenous progression to distant septic emboli. It is a life-threatening condition and a prompt diagnosis is critical for preventing fatal consequences.

The purpose of this case report is to increase awareness about this clinical condition among medical professionals.

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<![CDATA[Bone marrow transplantation for thalassemia]]> https://www.researchpad.co/product?articleinfo=N824f5c04-2e04-434a-842f-85bd6f9ef774

Early trials of allogeneic bone marrow transplantation (BMT) for homozygous beta-thalassemia and the analyses of results of transplantation in patients less then 16 years old have allowed us to identify three classes of risk using the criteria of degree of hepatomegaly, the degree of portal fibrosis and the quality of the chelation treatment given before the transplant. Patients for whom all three criteria were adverse constituted class 3, patients with none of the adverse criteria constituted class one and patients with one or various association of the adverse criteria formed Class 2. Most patients older than 16 years have disease characteristics that place them in class 3 with very few in class 2. For all the patients with an HLA identical donor we are actually using two Protocols for BMT to whom the patients are assigned on the base of the class they belong to at the time of BMT and independently on the age of the patient. For class 1, class 2 and for class 3 the probabilities of survival and of event-free-survival are respectively of 98% and 94%, 87% and 84%, 100% and 67%. For those patients that were older than 16 years at the time of the transplant, the probabilities of survival are 82% and the probabilities of event-free survival are 79%.

Bone marrow transplantation is a new form of radical treatment of thalassemia in those patients with an HLA identical donor.

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<![CDATA[Rosuvastatin Use Implicated in the Drug Reaction with Eosinophilia and Systemic Symptoms]]> https://www.researchpad.co/product?articleinfo=N6dcb7abc-ecc3-408b-abb7-e8dc20d57b5f

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a life-threatening drug-induced hypersensitivity reaction that is most closely associated with antiepileptics and antibiotics. While cases of DRESS are rare, here we present a case of DRESS in an adult male following administration of rosuvastatin who presented with fevers, generalized rash, and facial fullness. Vitals on presentation were temperature 102oF, pulse 95/min, blood pressure 95/47 mmHg, and respiratory rate of 14/min. His physical examination revealed scleral icterus, generalized blanching maculopapular rash, facial fullness, and right upper quadrant tenderness. Laboratory investigations found hemoglobin 10 gm/dl, white blood cell count 16.0 K/uL, peripheral eosinophil count 1,700 K/uL, alkaline phosphatase 2,501 U/L, aspartate transaminase 620 U/L, alanine transaminase 680 U/L, total bilirubin 13.2 mg/dl with a direct component of 9 mg/dl, blood urea nitrogen 66 mg/dl, creatinine 5.20 mg/dl, glomerular filtration rate 8 ml/min, and immunoglobulin E level 623 IU/mL. Serology for viral hepatitis, Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 was negative. Computed tomographic scan of chest, abdomen, and pelvis showed generalized lymphadenopathy. Over the next week, the patient deteriorated clinically with worsening transaminitis and oliguric acute renal failure requiring renal replacement therapy. As per the European Registry of Severe Cutaneous Adverse Reaction Criteria (RegiSCAR), the probability of rosuvastatin-induced DRESS syndrome was scored as “definite.” He was treated with systemic and topical glucocorticoids leading to a gradual improvement in his symptoms. Skin biopsy was suggestive of DRESS syndrome as well. Since DRESS carries such a significant risk of mortality between 10% and 20%, DRESS must be recognized and treated as soon as symptoms present. Clinicians should also be aware that statins, one of the most commonly prescribed drugs, are also a potential cause DRESS.

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<![CDATA[The Role of Blood Viscosity in Infectious Diseases]]> https://www.researchpad.co/product?articleinfo=N58238e42-440f-487e-977a-3cd53c206269

Blood viscosity is increased by elevated concentrations of acute phase reactants and hypergammaglobulinemia in inflammation. These increase blood viscosity by increasing plasma viscosity and fostering erythrocyte aggregation. Blood viscosity is also increased by decreased erythrocyte deformability, as occurs in malaria. Increased blood viscosity contributes to the association of acute infections with myocardial infarction (MI), venous thrombosis, and venous thromboembolism. It also increases vascular resistance, which decreases tissue perfusion and activates stretch receptors in the left ventricle, thereby initiating the systemic vascular resistance response. This compensates for the increased vascular resistance by vasodilation, lowering hematocrit, and decreasing intravascular volume. This physiological response causes the anemias associated with malaria, chronic inflammation, and other chronic diseases. Since tissue perfusion is inversely proportional to blood viscosity, anemia may be beneficial as it increases tissue perfusion when erythrocyte aggregating factors or erythrocytes with decreased deformability are present in the blood.

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<![CDATA[Iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood]]> https://www.researchpad.co/product?articleinfo=N9158e50b-6372-4968-9c34-a70f2648acea

Background

Iron overload is one of common complications of β-thalassemia. Systemic iron homeostasis is regulated by iron-regulatory hormone, hepcidin, which inhibits intestinal iron absorption and iron recycling by reticuloendothelial system. In addition, body iron status and requirement can be altered with age. In adolescence, iron requirement is increased due to blood volume expansion and growth spurt. Heterozygous β-globin knockout mice (Hbbth3/+; BKO) is a mouse model of thalassemia widely used to study iron homeostasis under this pathological condition. However, effects of age on iron homeostasis, particularly the expression of genes involved in hemoglobin metabolism as well as erythroid regulators in the spleen, during adolescence have not been explored in this mouse model.

Methods

Iron parameters as well as the mRNA expression of hepcidin and genes involved in iron transport and metabolism in wildtype (WT) and BKO mice during adolescence (6–7 weeks old) and adulthood (16–20 weeks old) were analyzed and compared by 2-way ANOVA.

Results

The transition of adolescence to adulthood was associated with reductions in duodenal iron transporter mRNA expression and serum iron levels of both WT and BKO mice. Erythrocyte parameters in BKO mice remained abnormal in both age groups despite persistent induction of genes involved in hemoglobin metabolism in the spleen and progressively increased extramedullary erythropiesis. In BKO mice, adulthood was associated with increased liver hepcidin and ferroportin mRNA expression along with splenic erythroferrone mRNA suppression compared to adolescence.

Conclusion

Our results demonstrate that iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood. The present study underscores the importance of the age of thalassemic mice in the study of molecular or pathophysiological changes under thalassemic condition.

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<![CDATA[Identification of key gene modules and hub genes of human mantle cell lymphoma by coexpression network analysis]]> https://www.researchpad.co/product?articleinfo=N430ea83f-4a22-409a-b9d1-a8aa4046804e

Purpose

Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin lymphoma that is incurable with standard therapies. The use of gene expression analysis has been of interest, recently, to detect biomarkers for cancer. There is a great need for systemic coexpression network analysis of MCL and this study aims to establish a gene coexpression network to forecast key genes related to the pathogenesis and prognosis of MCL.

Methods

The microarray dataset GSE93291 was downloaded from the Gene Expression Omnibus database. We systematically identified coexpression modules using the weighted gene coexpression network analysis method (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were performed on the modules deemed important. The protein–protein interaction networks were constructed and visualized using Cytoscape software on the basis of the STRING website; the hub genes in the top weighted network were identified. Survival data were analyzed using the Kaplan–Meier method and were compared using the log-rank test.

Results

Seven coexpression modules consisting of different genes were applied to 5,000 genes in the 121 human MCL samples using WGCNA software. GO and KEGG enrichment analysis identified the blue module as one of the most important modules; the most critical pathways identified were the ribosome, oxidative phosphorylation and proteasome pathways. The hub genes in the top weighted network were regarded as real hub genes (IL2RB, CD3D, RPL26L1, POLR2K, KIF11, CDC20, CCNB1, CCNA2, PUF60, SNRNP70, AKT1 and PRPF40A). Survival analysis revealed that seven genes (KIF11, CDC20, CCNB1, CCNA2, PRPF40A, CD3D and PUF60) were associated with overall survival time (p < 0.05).

Conclusions

The blue module may play a vital role in the pathogenesis of MCL. Five real hub genes (KIF11, CDC20, CCNB1, CCNA2 and PUF60) were identified as potential prognostic biomarkers as well as therapeutic targets with clinical utility for MCL.

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<![CDATA[Agreement of stall‐side and laboratory major crossmatch tests with the reference standard method in horses]]> https://www.researchpad.co/product?articleinfo=Ne5c2f006-1372-403b-9633-cc73c039d7bd

Abstract

Background

Crossmatching is used to prevent life‐threatening transfusion reactions in horses. Laboratory methods are laborious and technically challenging, which is impractical during emergencies.

Hypothesis/Objectives

Evaluate agreement between a stall‐side crossmatch kit (KIT) and a laboratory method (LAB) in horses with known and unknown blood types.

Animals

Twenty‐four blood‐typed and alloantibody‐screened healthy adult horses (Aim 1) and 156 adult horses of unknown blood type (Aim 2).

Methods

Prospective, blinded study. Expected positive (n = 35) and negative (n = 36) crossmatches among 24 antibody and blood‐typed horses were used to determine sensitivity and specificity of KIT and LAB against the reference method. Agreement in 156 untyped horses was evaluated by reciprocal crossmatch (n = 156).

Results

Sensitivity (95% confidence interval [CI]) for LAB and KIT compared with expected reactions was 77.1% (59.9%‐90.0%) and 91.4% (77.0%‐98.2%), and specificity 77.8% (60.9%‐89.9%) and 73.5% (55.6%‐87.1%), respectively. The KIT was 100% sensitive for Aa reactions; LAB was 100% sensitive for Qab; and both were 100% sensitive for Ca. Cohen's κ agreement for LAB and KIT with expected positive and negative reactions (n = 71) was moderate (0.55 [0.36‐0.74]) and substantial (0.65 [0.47‐0.82]), respectively. Agreement was fair comparing LAB with KIT in Aim 1 (0.30 [0.08‐0.52]) and in untyped horses in Aim 2 (0.26 [0.11‐0.41]).

Conclusions and Clinical Importance

Agreement between KIT and LAB with expected reactions was blood type dependent. Performance of both methods depends on blood type prevalence.

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<![CDATA[Plasma disposition of gabapentin after the intragastric administration of escalating doses to adult horses]]> https://www.researchpad.co/product?articleinfo=Nc6ed3fd9-4440-4123-9313-e9287b824446

Abstract

Background

In humans, gabapentin an analgesic, undergoes non‐proportional pharmacokinetics which can alter efficacy. No information exists on the pharmacokinetics of dosages >20 mg/kg, escalating dosages or dose proportionality of gabapentin in horses.

Hypothesis and Objectives

Gabapentin exposure in plasma would not increase proportionally relative to the dose in horses receiving dosages ≥20 mg/kg. To assess the plasma pharmacokinetics of gabapentin after nasogastric administration of gabapentin at dosages of 10 to 160 mg/kg in adult horses.

Animals

Nine clinically healthy adult Arabian and Quarter Horses.

Methods

In a randomized blinded trial, gabapentin was administered by nasogastric intubation to horses at 10, 20 mg/kg (n = 3) and 60, 80, 120, 160 mg/kg (n = 6). Plasma was collected before and at regular times over 64 hours after administration of gabapentin. Gabapentin was quantified using a validated chromatographic method. Dose proportionality was estimated using a power model. Pharmacokinetic parameters were estimated using compartmental pharmacokinetic analysis.

Results

Plasma pharmacokinetics parameters of gabapentin were estimated after nasogastric administration at dosages of 10 to 160 mg/kg. Gabapentin plasma concentration increased with dose increments. However, the area under the concentration curve from zero to infinity and maximal plasma concentration did not increase proportionally relative to the dose in horses.

Conclusions and Clinical Importance

Gabapentin exposure in plasma is not proportional relative to the dose in horses receiving nasogastric dosages of 10 to 160 mg/kg.

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<![CDATA[Platelet aggregometry testing during aspirin or clopidogrel treatment and measurement of clopidogrel metabolite concentrations in dogs with protein‐losing nephropathy]]> https://www.researchpad.co/product?articleinfo=Nd5f2d8af-edf6-49d8-990d-6756b2faaae2

Abstract

Background

Dogs with protein‐losing nephropathy (PLN) are treated with antiplatelet drugs for thromboprophylaxis but no standardized method exists to measure drug response. It is also unknown if clopidogrel metabolite concentrations [CM] differ between healthy and PLN dogs.

Objectives

Assess response to aspirin or clopidogrel in PLN dogs using platelet aggregometry (PA) and compare [CM] between healthy and PLN dogs.

Animals

Six healthy and 14 PLN dogs.

Methods

Platelet aggregometry using adenosine diphosphate (ADP), arachidonic acid (AA), and saline was performed in healthy dogs at baseline and 1‐week postclopidogrel administration to identify responders or nonresponders. A decrease of ≥60% for ADP or ≥30% for AA at 1 or 3 hours postpill was used to define a responder. At 1 and 3 hours postclopidogrel, [CM] and PA were measured in healthy and PLN dogs. Platelet aggregometry was performed in PLN dogs at baseline, 1, 6, and 12 weeks after clopidogrel or aspirin administration.

Results

In PLN dogs receiving clopidogrel, PA differed from baseline at all time points for ADP but not for AA at any time point. Most dogs responded at 1 or both time points except for 1 dog that showed no response. For PLN dogs receiving aspirin, no differences from baseline were observed at any time point for either ADP or AA. No differences in [CM] were found at either time point between healthy and PLN dogs.

Conclusions and Clinical Importance

Platelet aggregometry may represent an objective method to evaluate response to clopidogrel or aspirin treatment and PLN dogs appear to metabolize clopidogrel similarly to healthy dogs.

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