- Spleen enlargement assessment using computed tomography: which coefficient correlates the strongest with the real volume of the spleen? [Journal Article]
- ARAbdom Radiol (NY) 2018 Feb 19
- CONCLUSIONS: Coefficient calculated from maximal length, vertical height and hilum thickness correlates the strongest with spleen volume and can be utilized for monitoring of spleen volume instead of obsolete splenic index. The most suitable for quick splenomegaly screening is two-dimensional coefficient (maximal length × vertical height), with the cut-off 115 cm2.
- Enlarged spleen is associated with low neutrophil and platelet engraftment rates and poor survival after allogeneic stem cell transplantation in patients with acute myeloid leukemia and myelodysplastic syndrome. [Journal Article]
- AHAnn Hematol 2018 Feb 17
- Primary graft failure can be a cause of early morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), as it leads to a high risk of severe infections and bleeding. Sp...
Primary graft failure can be a cause of early morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), as it leads to a high risk of severe infections and bleeding. Splenomegaly is associated with primary graft failure in patients of myelofibrosis, but the association between splenomegaly and outcomes after HSCT in patients with myeloid malignancies has not been previously evaluated. The aim of this study was to investigate the effect of spleen volume on engraftment kinetics in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We enrolled 85 patients. The median spleen volume was 146 cm3(quartile 88-201 cm3). The adjusted hazard ratios for neutrophil and platelet engraftments were 0.17 (0.07-0.40, p < 0.001) and 0.19 (0.05-0.69, p = 0.011), respectively, for the high-risk group, at a cutoff splenic volume of 320 cm3. Overall survival at 3 years after HSCT was significantly poor in the high-risk group with an adjusted hazard ratio of 13.8 (2.61-72.4, p = 0.002). Enlarged spleen was associated with low neutrophil and platelet engraftment rates and poor survival after allogeneic HSCT in patients of AML and MDS.
- The cat did it: erythema nodosum and additional atypical presentations ofBartonella henselaeinfection in immunocompetent hosts. [Journal Article]
- BCBMJ Case Rep 2018 Feb 16; 2018
- A healthy patient presented with painful skin lesions on the anterior surface of her legs. Erythema nodosum was diagnosed but all the usual causes were ruled out. The finding of bilateral enlarged ax...
A healthy patient presented with painful skin lesions on the anterior surface of her legs. Erythema nodosum was diagnosed but all the usual causes were ruled out. The finding of bilateral enlarged axillary lymph nodes with necrosis and granulomas led to the diagnosis ofBartonellainfection, an unusual cause of erythema nodosum. Imaging also revealed splenomegaly and small para-aortic lymph nodes. Up to one quarter of the patients with cat-scratch disease present atypically, a considerably higher prevalence than previously reported. A comprehensive review of the literature (PubMed, since inception, all languages) revealed a remarkable array of unusual presentations which are summarised and briefly discussed.
- Should rituximab replace splenectomy in the management of splenic marginal zone lymphoma? [Review]
- BPBest Pract Res Clin Haematol 2018; 31(1):65-72
- SMZL is a relatively rare low grade B-cell lymphoma, characterized usually by an indolent clinical behavior. Since there is no prospective randomized trials to establish the best treatment approach, ...
SMZL is a relatively rare low grade B-cell lymphoma, characterized usually by an indolent clinical behavior. Since there is no prospective randomized trials to establish the best treatment approach, decision on therapeutic management should be based on the available retrospective series. Based on these data, rituximab and splenectomy appear to be the most effective. Splenectomy represented the standard treatment modality until early 2000s. More than 90% of the patients present quick amelioration of splenomegaly related symptoms along with improvement of cytopenias related to hypersplenism. The median progression free survival was 8.25 years in the largest series of patients published so far, while the median 5- and 10- year OS were 84% and 67%, respectively. Responses to splenectomy are not complete since extrasplenic disease persists. Patients with heavy bone marrow infiltration, lymphadenopathy or other disease localization besides the spleen are not good candidates for splenectomy. Furthermore splenectomy is a major surgical procedure accompanied by acute perioperative complications as well as late toxicities mainly due to infections. For that reasons splenectomy is not appropriate for elderly patients or patients with comorbidities with a high surgical risk. On the other hand rituximab monotherapy displays high efficacy with minimal toxicity. Several published series have shown an ORR more than 90%, with high CR rates (∼50%). The 10-year PFS and OS were 63% and 85%, respectively in a series of 104 SMZL patients. The role of rituximab maintenance has been investigated by only one group. Based on these data, maintenance with rituximab further improved the quality of responses by increasing significantly the CR rates (from 42% at the end of induction to 71% at the end of maintenance treatment), as well as the duration of responses: 7-year PFS was 75% for those patients who received maintenance vs 39% for those who did not (p < 0.0004). However no difference in OS has been noticed between the two groups, so far. Summarizing the above data, it is obvious that Rituximab monotherapy is associated with high response rates, long response duration and favorable safety profile, rendering it as the treatment of choice in SMZL.
- Babesia microti Infection Changes Host Spleen Architecture and Is Cleared by a Th1 Immune Response. [Journal Article]
- FMFront Microbiol 2018; 9:85
- Babesia microtiis a malaria-like parasite, which infects ∼2000 people annually, such that babesiosis is now a notifiable disease in the United States. Immunocompetent individuals ...
Babesia microtiis a malaria-like parasite, which infects ∼2000 people annually, such that babesiosis is now a notifiable disease in the United States. Immunocompetent individuals often remain asymptomatic and are tested only after they feel ill. Susceptible C3H/HeJ mice show several human-like disease manifestations and are ideal to study pathogenesis ofBabesiaspecies. In this study, we examined parasitemia ofB. microtiat different time points and assessed its impact on hemoglobin levels in blood, on spleen pathology and overall immune response in C3H/HeJ mice. Peak parasitemia of 42.5% was immediately followed by diminished hemoglobin level. Parasitemia at 21 days of infection was barely detectable by microscopy presented 5.7 × 108to 5.9 × 109B. microtiDNA copies confirming the sensitivity of our qPCR. We hypothesize that qPCR detects DNA released from recently lysed parasites or from extracellularB. microtiin blood, which are not easily detected in blood smears and might result in under-diagnosis of babesiosis in patients. Splenectomized patients have been reported to show increased babesiosis severity and result in high morbidity and mortality. These results emphasize the importance of splenic immunity in resolution ofB. microtiinfection. Splenomegaly in infected mice associated with destruction of marginal zone with lysed erythrocytes and releasedB. microtilife forms in our experiments support this premise. At conclusion of the experiment at 21 days post-infection, significant splenic B and T cells depletion and increase in macrophages levels were observed inB. microtiinfected mice suggesting a role of macrophage in disease resolution. Infected mice also showed significantly higher plasmatic concentration of CD4 Th1 cells secreted cytokines such as IL-2 and IFN-γ while cytokines such as IL-4, IL-5, and IL-13 secreted by Th2 cells increase was not always significant. Thus, Th1 cells-mediated immunity appears to be important in clearance of this intracellular pathogen. Significant increase in IL-6 that promotes differentiation of Th17 cells was observed but it resulted in only moderate change in IL-17A, IL-17F, IL-21, and IL-22, all secreted by Th17 cells. A similar immune response to Trypanosoma infection has been reported to influence the clearance of this protozoan, and co-infecting pathogen(s).
- Inactivation of TRPM7 kinase in mice results in enlarged spleens, reduced T-cell proliferation and diminished store-operated calcium entry. [Journal Article]
- SRSci Rep 2018 Feb 14; 8(1):3023
- T lymphocytes enlarge (blast) and proliferate in response to antigens in a multistep program that involves obligatory cytosolic calcium elevations. Store-operated calcium entry (SOCE) pathway is the ...
T lymphocytes enlarge (blast) and proliferate in response to antigens in a multistep program that involves obligatory cytosolic calcium elevations. Store-operated calcium entry (SOCE) pathway is the primary source of Ca2+in these cells. Here, we describe a novel modulator of blastogenesis, proliferation and SOCE: the TRPM7 channel kinase. TRPM7 kinase-dead (KD) K1646R knock-in mice exhibited splenomegaly and impaired blastogenic responses elicited by PMA/ionomycin or anti-CD3/CD28 antibodies. Splenic T-cell proliferation in vitro was weaker in the mutant compared to wildtype littermates. TRPM7 current magnitudes in WT and KD mouse T cells were, however, similar. We tested the dependence of T-cell proliferation on external Ca2+and Mg2+concentrations. At a fixed [Mg2+o] of ~0.4 mM, Ca2+ostimulated proliferation with a steep concentration dependence and vice versa, at a fixed [Ca2+o] of ~0.4 mM, Mg2+opositively regulated proliferation but with a shallower dependence. Proliferation was significantly lower in KD mouse than in wildtype at all Ca2+and Mg2+concentrations. Ca2+elevations elicited by anti-CD3 antibody were diminished in KD mutant T cells and SOCE measured in activated KD splenocytes was reduced. These results demonstrate that a functional TRPM7 kinase supports robust SOCE, blastogenesis and proliferation, whereas its inactivation suppresses these cellular events.
- Talaromycosis (Penicilliosis) in a Cynomolgus Macaque. [Journal Article]
- VPVet Pathol 2018 Jan 01; :300985818758468
- A sexually mature Chinese-origin female Macaca fascicularis assigned to the high-dose group in a 26-week toxicology study with an experimental immunomodulatory therapeutic antibody (a CD40 L antagoni...
A sexually mature Chinese-origin female Macaca fascicularis assigned to the high-dose group in a 26-week toxicology study with an experimental immunomodulatory therapeutic antibody (a CD40 L antagonist fusion protein) was euthanized at the scheduled terminal sacrifice on study day 192. The animal was healthy at study initiation and remained clinically normal throughout the study. On study day 141, abnormal clinical pathology changes were found during a scheduled evaluation; splenomegaly was detected on study day 149 and supported by ultrasound examination. At the scheduled necropsy, there was marked splenomegaly with a nodular and discolored appearance. Cytologic examination of a splenic impression smear revealed yeast-like organisms within macrophages. Histologically, there was disseminated systemic granulomatous inflammation with 2- to 3-μm oval, intracytoplasmic yeast-like organisms in multiple organs identified as Talaromyces (Penicillium) marneffei. This organism, not previously reported as a pathogen in macaques, causes an important opportunistic infection in immunosuppressed humans in specific global geographic locations.
- Chronic neutrophilic leukemia: new science and new diagnostic criteria. [Review]
- BCBlood Cancer J 2018 Feb 13; 8(2):19
- Chronic neutrophilic leukemia (CNL) is a distinct myeloproliferative neoplasm defined by persistent, predominantly mature neutrophil proliferation, marrow granulocyte hyperplasia, and frequent spleno...
Chronic neutrophilic leukemia (CNL) is a distinct myeloproliferative neoplasm defined by persistent, predominantly mature neutrophil proliferation, marrow granulocyte hyperplasia, and frequent splenomegaly. The seminal discovery of oncogenic driver mutations in CSF3R in the majority of patients with CNL in 2013 generated a new scientific framework for this disease as it deepened our understanding of its molecular pathogenesis, provided a biomarker for diagnosis, and rationalized management using novel targeted therapies. Consequently, in 2016, the World Health Organization (WHO) revised the diagnostic criteria for CNL to reflect such changes in its genomic landscape, now including the presence of disease-defining activating CSF3R mutations as a key diagnostic component of CNL. In this communication, we provide a background on the history of CNL, its clinical and hemopathologic features, and its molecular anatomy, including relevant additional genetic lesions and their significance. We also outline the recently updated WHO diagnostic criteria for CNL. Further, the natural history of the disease is reviewed as well as potential prognostic variables. Finally, we summarize and discuss current treatment options as well as prospective novel therapeutic targets in hopes that they will yield meaningful improvements in patient management and outcomes.
- Lupus-like autoimmune disease caused by a lack of Xkr8, a caspase-dependent phospholipid scramblase. [Journal Article]
- PNProc Natl Acad Sci U S A 2018 Feb 12
- Apoptotic cells expose phosphatidylserine (PtdSer) on their cell surface and are recognized by macrophages for clearance. Xkr8 is a scramblase that exposes PtdSer in a caspase-dependent manner. Here,...
Apoptotic cells expose phosphatidylserine (PtdSer) on their cell surface and are recognized by macrophages for clearance. Xkr8 is a scramblase that exposes PtdSer in a caspase-dependent manner. Here, we found that among the three Xkr members with caspase-dependent scramblase activity, mouse hematopoietic cells express only Xkr8. The PtdSer exposure of apoptotic thymocytes, splenocytes, and neutrophils was strongly reduced when Xkr8 was absent. While wild-type apoptotic lymphocytes and neutrophils were efficiently engulfed in vitro by phagocytes expressing Tim4 and MerTK,Xkr8-deficient apoptotic cells were hardly engulfed by these phagocytes. Accordingly, the number of apoptotic thymocytes in the thymus and neutrophils in the peritoneal cavity of the zymosan-treated mice was significantly increased inXkr8-deficient mice. The percentage of CD62Llosenescent neutrophils was increased in the spleen ofXkr8-null mice, especially after the treatment with granulocyte colony-stimulating factor.Xkr8-null mice on an MRL background showed high levels of autoantibodies, splenomegaly with high levels of effector CD4 T cells, and glomerulonephritis development with immune-complex deposition at glomeruli. These results indicate that the Xkr8-mediated PtdSer exposure in apoptotic lymphocytes and aged neutrophils is essential for their clearance, and its defect activates the immune system, leading to lupus-like autoimmune disease.
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- Immature platelet fraction and thrombopoietin in patients with liver cirrhosis: A cohort study. [Journal Article]
- PlosPLoS One 2018; 13(2):e0192271
- CONCLUSIONS: On closer examination of the three compartments known to have an influence on platelet count splenomegaly seems to be the major cause of thrombocytopenia in patients with cirrhosis according to current knowledge. Higher IPF% in patients with thrombocytopenia indicates peripheral consumption of platelets. The relation between spleen diameter and platelet count indicates the spleen to be the major place of platelets' consumption. TPO did not differ between patients with and without thrombocytopenia. Furthermore, we cannot exclude an influence of impaired thrombopoietin synthesis on platelet counts. The association between IPF% and platelet count suggests that there is physiological regulation of platelets in patients with cirrhosis. In our study IPF% is associated with esophageal varices and the stage of cirrhosis. Further studies are needed to confirm these results.