Search

The characteristics of coronavirus disease 2019 (COVID-19) pneumonia caused by the severe acute respiratory syndrome coronavirus 2 Omicron variant have not been fully described. Unlike other variants, the Omicron variant replicates rapidly in the bronchus. Therefore, we hypothesized that it would have different computed tomography (CT) findings from non-Omicron variants.

Bleeding manifestations in primary immune thrombocytopenia (ITP) range from skin petechiae to life-threatening intracranial hemorrhage (ICH). However, the relation between these various bleeding manifestations and the platelet count in ITP remains poorly characterized. Using a nationwide database of patients with ITP during the years 2005 to 2014 (10 years) in Japan, we analyzed 19 415 adult patients newly diagnosed with ITP, including 222 with ICH. The frequency of skin purpura was 64.8%, and this increased linearly with thrombocytopenia without a specific platelet count threshold. In contrast, mucosal bleeding (epistaxis and gingival bleeding) and organ bleeding (melena, hematuria, and ICH) increased exponentially with thrombocytopenia at a platelet count threshold of 10 to 15 × 109/L. Age showed a much weaker correlation than platelet count with skin and mucosal bleeding. However, the incidence of organ bleeding increased exponentially above 60 years of age. Multivariate analysis showed that the presence of mucosal bleeding was a risk factor for occurrence of melena and hematuria but not for ICH. The frequency of ICH was 1.1% and risk factors for ICH were age ≥60 years (odds ratio [OR], 3.09; 95% confidence interval [CI], 2.13-4.47; P < .001), platelet count <10 × 109/L (OR, 2.96; 95% CI, 2.11-4.15; P < .001), and the presence of hematuria (OR, 1.56; 95% CI, 1.04-2.35; P = .033). The relation between ICH and platelet count varied with age. This large-scale analysis of risk factors for bleeding in ITP has revealed distinct characteristics of skin, mucosal, and organ bleeding in adult patients with newly diagnosed ITP, thus indicating those who are at a high risk of severe organ bleeding.

Bleeding manifestations in primary immune thrombocytopenia (ITP) range from skin petechiae to life-threatening intracranial hemorrhage (ICH). However, the relation between these various bleeding manifestations and the platelet count in ITP remains poorly characterized. Using a nationwide database of patients with ITP during the years 2005 to 2014 (10 years) in Japan, we analyzed 19 415 adult patients newly diagnosed with ITP, including 222 with ICH. The frequency of skin purpura was 64.8%, and this increased linearly with thrombocytopenia without a specific platelet count threshold. In contrast, mucosal bleeding (epistaxis and gingival bleeding) and organ bleeding (melena, hematuria, and ICH) increased exponentially with thrombocytopenia at a platelet count threshold of 10 to 15 × 109/L. Age showed a much weaker correlation than platelet count with skin and mucosal bleeding. However, the incidence of organ bleeding increased exponentially above 60 years of age. Multivariate analysis showed that the presence of mucosal bleeding was a risk factor for occurrence of melena and hematuria but not for ICH. The frequency of ICH was 1.1% and risk factors for ICH were age ≥60 years (odds ratio [OR], 3.09; 95% confidence interval [CI], 2.13-4.47; P< .001), platelet count <10 × 109/L (OR, 2.96; 95% CI, 2.11-4.15; P< .001), and the presence of hematuria (OR, 1.56; 95% CI, 1.04-2.35; P= .033). The relation between ICH and platelet count varied with age. This large-scale analysis of risk factors for bleeding in ITP has revealed distinct characteristics of skin, mucosal, and organ bleeding in adult patients with newly diagnosed ITP, thus indicating those who are at a high risk of severe organ bleeding.

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia due to accelerated platelet destruction and impaired platelet production. Diagnosis of ITP is still challenging because ITP has been diagnosed by exclusion. Exclusion of thrombocytopenia due to bone marrow failure is especially important in Japan because of high prevalence of aplastic anemia compared to Western countries. Hence, we propose new diagnostic criteria involving the measurement of plasma thrombopoietin (TPO) levels and percentage of immature platelet fraction (RP% or IPF%) as shown in Fig. 1. These biomarkers reflect the pathology of ITP, in which shortened platelet lifespan associated with increased platelet destruction and relatively maintained platelet production.

The binding of von Willebrand factor (VWF) to glycoprotein (GP) Ib-IX-V stimulates transmembrane signaling events that lead to platelet adhesion and aggregation. Recent studies have implied that activation of Src family kinases is involved in GPIb-mediated platelet activation, although the related signal transduction pathway remains poorly defined. This study presents evidence for an important role of Src and GPIb association. In platelet lysates containing Complete, a broad-spectrum protease inhibitor mixture, Src and Lyn dynamically associated with GPIb on VWF-botrocetin stimulation. Cytochalasin D, which inhibits translocation of Src kinases to the cytoskeleton, further increased Src and GPIb association. Similar results were obtained with botrocetin and monomeric A1 domain, instead of intact VWF, with induction of both Src activation and association between GPIb and Src. These findings suggest that ligand binding of GPIb, without receptor clustering, is sufficient to activate Src. Immunoprecipitation studies demonstrated that Src, phosphoinositide 3– kinase (PI 3–kinase), and GPIb form a complex in GPIb-stimulated platelets. When the p85 subunit of PI 3–kinase was immunodepleted, association of Src with GPIb was abrogated. However, wortmannin, a specific PI 3–kinase inhibitor, failed to block complex formation between Src and GPIb. The Src-SH3 domain as a glutathione S-transferase (GST)–fusion protein coprecipitated the p85 subunit of PI 3–kinase and GPIb. These findings taken together suggest that the p85 subunit of PI 3–kinase mediates GPIb-related activation signals and activates Src independently of the enzymatic activity of PI 3– kinase.

The binding of von Willebrand factor (VWF) to glycoprotein (GP) Ib-IX-V stimulates transmembrane signaling events that lead to platelet adhesion and aggregation. Recent studies have implied that activation of Src family kinases is involved in GPIb-mediated platelet activation, although the related signal transduction pathway remains poorly defined. This study presents evidence for an important role of Src and GPIb association. In platelet lysates containing Complete, a broad-spectrum protease inhibitor mixture, Src and Lyn dynamically associated with GPIb on VWF-botrocetin stimulation. Cytochalasin D, which inhibits translocation of Src kinases to the cytoskeleton, further increased Src and GPIb association. Similar results were obtained with botrocetin and monomeric A1 domain, instead of intact VWF, with induction of both Src activation and association between GPIb and Src. These findings suggest that ligand binding of GPIb, without receptor clustering, is sufficient to activate Src. Immunoprecipitation studies demonstrated that Src, phosphoinositide 3– kinase (PI 3–kinase), and GPIb form a complex in GPIb-stimulated platelets. When the p85 subunit of PI 3–kinase was immunodepleted, association of Src with GPIb was abrogated. However, wortmannin, a specific PI 3–kinase inhibitor, failed to block complex formation between Src and GPIb. The Src-SH3 domain as a glutathione S-transferase (GST)–fusion protein coprecipitated the p85 subunit of PI 3–kinase and GPIb. These findings taken together suggest that the p85 subunit of PI 3–kinase mediates GPIb-related activation signals and activates Src independently of the enzymatic activity of PI 3– kinase.

Casirivimab and imdevimab are effective in preventing hospitalization in outpatients with coronavirus disease 2019 (COVID-19); however, disease progression after casirivimab and imdevimab administration has been reported. This study aimed to elucidate the risk factors for disease progression after casirivimab and imdevimab administration.

The platelet glycoprotein Ib (GpIb) complex is composed of four polypeptides: the disulfide-linked GpIba and GpIbß and the noncovalently associated GpIX and GpV. GpIba contains binding sites for von Willebrand factor and for thrombin and mediates platelet adhesion to the subendothelium under conditions of high shear stress. We have previously shown the presence of GpIba and GpIbß mRNA and protein in cultured human umbilical vein endothelial cells (HUVECs) as well as the presence of GpIba mRNA and protein in tonsillar endothelium. We, therefore, probed ECs for the presence of the other components of the GpIb/IX/V complex. We have identified the presence of GpIX and GpV mRNA in cultured HUVEC monolayers. The sequence of HUVEC GpIX cDNA was identical to the previously published human erythroleukemia (HEL) cell GpIX cDNA sequence. Two species of GpV mRNA, one of 3 kb and one of 4.4 kb, were found in HUVECs, whereas HEL cells displayed only the 4.4-kb species and the megakaryocytic cell line CHRF-288 contained only the 3-kb species. We previously showed that EC GpIba protein is identical in molecular weight to platelet GpIba. HUVEC GpIbß, in contrast to its platelet counterpart, has a molecular weight of 50 kD and forms a correspondingly larger disulfide-bonded complex with EC GpIba. The molecular weights of GpIX and GpV were 22 and 88 kD, respectively, identical to the corresponding platelet polypeptides. Furthermore, we have identified all four components of the complex in tonsillar vessels. Using flow cytometry, we have established that all four polypeptides of the GpIb/IX/V complex are expressed on the surface membranes of cultured HUVECs and adult aortic ECs. Furthermore, using two-color fluorescence, we have shown that all ECs expressing GpIba also express GpIX and GpV on their surface. The ratio of GpIba:GpIX:GpV is 1:1:0.5, which is identical to the ratio present in platelets. None of the polypeptides of the GpIb complex could be identified on the surface of human smooth muscle cells or lymphocytes. The presence of all members of the GpIb complex in the EC membrane suggests that this complex may play a role in endothelial function in vivo.

No relevant conflicts of interest to declare.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease caused by the SFTS bunyavirus, which is carried by ticks, and presents various symptoms such as fever, fatigue, digestive symptoms, and hemophagocytic lymphhistiocytosis (HLH). Since the first case was reported from China in 2011, there has been a rapid increase of newly diagnosed patients in Japan. Because the mortality rate has remained high (10-30%), there is an urgent need to establish a management strategy for SFTS.

Primary pyomyositis is a bacterial infection of the skeletal muscle commonly affecting children with Staphylococcus aureus most often isolated as a pathogen. However, pyomyositis caused by anaerobic bacteria is rare in adults. Here, we report a case of solitary Pyomyositis of the left rhomboideus muscle in an immunocompetent person. A 70-year-old Japanese male presented with high fever and left shoulder pain. His muscle below the lower edge of the left scapula was tender and swollen. His laboratory examinations revealed severe inflammation. Computed tomography showed a solitary low-density area around a contrast enhancement in the left rhomboideus muscle. He was diagnosed as having solitary pyomyositis. Although his symptoms did not improve despite empiric intravenous administration of antibiotics, an incision was performed. Streptococcus anginosus and Streptococcus intermedius were isolated from the culture of drainage fluid. His symptoms gradually disappeared after the incisional drainage and continuous administration of antibiotics. Pyomyositis did not recur after his discharge. To the best of our knowledge, this is the first report on anaerobic pyomyositis of the shoulder muscle.

Radioimmunotherapy (RIT) with 90Y-ibritumomab tiuxetan has been used for the treatment of relapsed or refractory indolent B-cell lymphoma. Early prediction of response to the therapy may offer the potential to identify patients who will benefit this therapy. We evaluated the efficacy of fluorine 18 fluorodeoxyglucose (FDG) combined positron emission tomographic-computed tomographic (FDG-PET/CT) imaging for assessment of therapy and predicting outcome in 90Y-ibritumomab tiuxetan radioimmunotherapy.Radioimmunotherapy with 90Y-ibritumomab tiuxetan was preformed in 52 patients with relapsed or refractory indolent B cell lymphoma (follicular lymphoma, 45; mucosa-associated lymphoid tissue lymphoma, 5; lymphoplasmacytic lymphoma, 2) at Hyogo College of Medicine Hospital from June 2009 through August 2012. FDG-PET/CT scanning was performed at two weeks and the later after 90Y-ibritumomab tiuxetan therapy.In FDG-PET at 2 weeks after 90Y-ibritumomab therapy, 26 (50%) showed complete response (defined as early CR), 20 (38%) showed partial response (PR-2W) and 6 (12%) showed non response (NR-2W). Further follow-up revealed 10 later CR (8 CR out of 20 PR-2W and 2 CR out of 6 NR-2W), showing 69 %(36) of overall CR rate. Relapse was occurred in 4(17%) of 26 early CR and in 6 (60%) of 10 later CR, indicating significantly low relapse late in early CR (P= 0.0074, by Chi-square test). Patients with early CR (CR in 2 weeks after the RIT) showed significantly better progression free survival than those with later CR (P=0.0046, by Logrank test). In contrast, analysis at six weeks after the RIT showed 36 CR patients (10 of which eventually relapse), but failed to discriminate patients who had high risk of relapse.Our results suggest that CR assessed by FDG-PET/CT at 2 weeks after 90Y-ibritumomab tiuxetan therapy discriminates good responder to the RIT and predicts better progression free survival in relapsed or refractory indolent B cell lymphoma.No relevant conflicts of interest to declare.

Abstract 3648