Circulating bioactive bacterial DNA is associated with immune activation and complications in common variable immunodeficiency.

Common variable immunodeficiency (CVID) is characterized by profound primary antibody defects and frequent infections, yet autoimmune/inflammatory complications of unclear origin occur in 50% of individuals and lead to increased mortality. Here, we show that circulating bacterial 16S rDNA belonging to gut commensals was significantly increased in CVID serum (P < 0.0001), especially in patients with inflammatory manifestations (P = 0.0007). Levels of serum bacterial DNA were associated with parameters of systemic immune activation, increased serum IFN-γ, and the lowest numbers of isotype-switched memory B cells. Bacterial DNA was bioactive in vitro and induced robust host IFN-γ responses, especially among patients with CVID with inflammatory manifestations. Patients with X-linked agammaglobulinemia (Bruton tyrosine kinase [BTK] deficiency) also had increased circulating bacterial 16S rDNA but did not exhibit prominent immune activation, suggesting that BTK may be a host modifier, dampening immune responses to microbial translocation. These data reveal a mechanism for chronic immune activation in CVID and potential therapeutic strategies to modify the clinical outcomes of this disease.

Serological evidence of avian HEV antibodies in apparently healthy chickens in southwest Nigeria.

Avian hepatitis E virus (aHEV) is associated with hepatitis-splenomegaly syndrome, big liver and spleen disease and hepatic rupture haemorrhage syndrome. However, the knowledge about aHEV in commercial layer chickens in Nigeria is scarce. In this study, 460 serum samples obtained from 36 apparently healthy commercial layer chicken flocks in three states (Ogun, Osun and Oyo States) of southwestern Nigeria were analysed by enzyme linked immunosorbent assay for the presence of anti-aHEV immunoglobulin Y (IgY) antibodies. In total, the overall seroprevalence of anti-aHEV antibodies was 14.6%. The serological analysis revealed that 75% of the flocks examined were positive for anti-aHEV IgY antibodies from chickens of various ages in all three states. The percentage of the seropositive chickens in the three states varied from flock to flock ranging from 60% to 88.8% and seropositive chickens were detected at any age (24-52 weeks of age) without significant differences between the age groups. This is the first report assessing the presence of aHEV antibodies in chickens from Nigeria. The detection of anti-aHEV antibodies in commercial layer chickens in this study emphasizes the importance of serosurveillance in disease monitoring due to the economic threat posed by aHEV as a result of decreased egg production and increased mortality in affected commercial layer chicken farms. However, further studies are essential to reveal the clinical implications and to assess the real burden of aHEV in Nigeria.

Post-transfusion hemoglobin response in patients with cirrhosis: Can we expect a 1 g/dL rise per unit transfused?

BACKGROUND: A patient's hemoglobin is typically expected to rise by 1 g/dL/unit transfused PRBCs. However, it has been theorized that mechanisms such as hyperbilirubinemia and splenomegaly might lead to either a direct lysis or sequestration of red blood cells that could decrease this proportionate response. STUDY DESIGN AND METHODS: Patients with resolved GI bleeding but still requiring transfusion to correct anemia were compared in cirrhosis and control groups. A retrospective chart review between 2015 and 2020 was conducted at a single institution. Data collected included age, sex, BMI, GI bleed diagnosis, number of PRBCs transfused, presence of splenomegaly and spleen size, alcohol use history, type of cirrhosis, MELD-Na at admission, GFR, and pre-and post-transfusion labs: total bilirubin, ALT, hemoglobin, hematocrit. A logic regression was performed for each group looking at which factors were associated with a successful response (defined as >0.9 g/dL hemoglobin per unit transfused). RESULTS: Mean change in hemoglobin was 0.77 g/dL in patients with cirrhosis compared to 1.46 g/dL in patients without (P < .001, N = 103). Odds ratios for presence of splenomegaly (0.22, N = 78) and female sex (4.39, N = 102) in predicting adequate response (>0.9 g/dL/unit) were both significant (P = .002) as well as portal hypertensive bleed diagnosis (0.28, N = 85, P = .0015). Factors that did not contribute included: age, race, BMI, alcohol use, GFR, change in ALT, and change in total bilirubin. CONCLUSIONS: Patients with cirrhosis have an approximately 50% decreased response to transfusion with PRBCs after resolution of a gastrointestinal bleed in comparison to patients without cirrhosis. Risk factors included splenomegaly, portal hypertension, and male sex.

Clinical Sequelae Associated with Unresolved Tropical Splenomegaly in a Cohort of Recently Resettled Congolese Refugees in the United States-Multiple States, 2015-2018.

Tropical splenomegaly is often associated with malaria and schistosomiasis. In 2014 and 2015, 145 Congolese refugees in western Uganda diagnosed with splenomegaly during predeparture medical examinations underwent enhanced screening for various etiologies. After anecdotal reports of unresolved splenomegaly and complications after U.S. arrival, patients were reassessed to describe long-term clinical progression after arrival in the United States. Post-arrival medical information was obtained through medical chart abstraction in collaboration with state health partners in nine participating states. We evaluated observed splenomegaly duration and associated clinical sequelae between 130 case patients from eastern Congo and 102 controls through adjusted hierarchical Poisson models, accounting for familial clustering. Of the 130 case patients, 95 (73.1%) had detectable splenomegaly after arrival. Of the 85 patients with records beyond 6 months, 45 (52.9%) had persistent splenomegaly, with a median persistence of 14.7 months (range 6.0-27.9 months). Of the 112 patients with available results, 65 (58.0%) patients had evidence of malaria infection, and the mean splenomegaly duration did not differ by Plasmodium species. Refugees with splenomegaly on arrival were 43% more likely to have anemia (adjusted relative risk [aRR]: 1.43, 95% CI: 1.04-1.97). Those with persistent splenomegaly were 60% more likely (adjusted relative risk [aRR]: 1.60, 95% CI: 1.15-2.23) to have a hematologic abnormality, particularly thrombocytopenia (aRR: 5.53, 95% CI: 1.73-17.62), and elevated alkaline phosphatase (aRR: 1.57, 95% CI: 1.03-2.40). Many patients experienced persistent splenomegaly, contradicting literature describing resolution after treatment and removal from an endemic setting. Other possible etiologies should be investigated and effective treatment, beyond treatment for malaria and schistosomiasis, explored.

A novel etiologic factor of highly elevated cholestanol levels: progressive familial intrahepatic cholestasis.

Background Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an uncommon cholestatic liver disease caused by mutations in the ATP binding cassette subfamily B member 4 (ABCB4) gene. Although PFIC3 is frequently identified in childhood, ABCB4 disease-causing alleles have been described in adults affected by intrahepatic cholestasis of pregnancy, hormone-induced cholestasis, low-phospholipid-associated cholelithiasis syndrome or juvenile cholelithiasis, cholangiocarcinoma and in sporadic forms of primary biliary cirrhosis. Cholestanol is a biomarker which is elevated especially in cerebrotendinous xanthomatosis and rarely in primary biliary cirrhosis (PBC) and Niemann Pick type C. Case presentation Here we report a Turkish patient with compound heterozygous mutations in the ABCB4 gene, who has hepatosplenomegaly, low level of high-density lipoprotein, cholestasis and high level of cholestanol. Conclusion This is the first PFIC3 case with a high cholestanol level described in the literature. There are very few diseases linked to increased cholestanol levels, two of which are CTX and PBC. From this case, we can conclude that a high cholestanol level might be another indicator of PFIC type 3.

The Importance of Characterizing the Hemoglobin Instability of New Variants: The Case of Hb Dompierre [ß29(B11)Gly→Arg, HBB: c.88G>C].

Hb Dompierre [ß29(B11)Gly→Arg, HBB: c.88G>C] is a rare ß-globin gene variant that was previously described in the heterozygous state in a 24-year-old female patient. It is defined in the HbVar database as being clinically and biologically asymptomatic. A few years after the first description, we had an opportunity of reassessing the index case because she presented with splenomegaly and clinical and biological manifestations of hemolysis. After ruling out the most common causes of hemolysis, further analyses on the variant hemoglobin (Hb) using brilliant cresyl blue staining, indicated that it showed mild instability, which may explain the clinical and biological manifestations. A structural bioinformatic analysis on the Hb variant suggested that the amino acid replacement may be deleterious to the integrity of the Hb. This report confirms the importance of completely characterizing all new Hb variants in order to guide the patients' clinical management and follow-up, as well as to provide the probands and their family members with appropriate genetic counseling.

Partial Splenic Artery Embolization in 35 Cancer Patients: Results of a Single Institution Retrospective Study.

PURPOSE: To evaluate the safety and efficacy of partial splenic embolization (PSE) in cancer patients with different etiologies of splenomegaly/hypersplenism. MATERIALS AND METHODS: The medical records of 35 cancer patients who underwent 39 PSE procedures were analyzed. The splenomegaly/hypersplenism was due to chemotherapy (n = 17), portal hypertension (n = 10), or hematologic malignancy (n = 8). After the first 11 PSEs, celiac plexus neurolysis, corticosteroids, and non-steroid anti-inflammatory drugs (NSAIDs) were included in the post-procedural management. RESULTS: PSE led to 59 ± 16% (mean ± standard deviation) splenic infarcts. The infarct volume per 1 mL 300-500 µm tris-acryl gelatin microspheres was not significantly different between the chemotherapy-induced group (264 ± 89 cm3) and the portal hypertension group (285 ± 139 cm3) but was significantly higher in the hematology group (582 ± 345 cm3). Platelet count increased from 65.7 ± 19.7 k/µl to a peak platelet count of 221 ± 83 k/µl at 2 weeks after PSE. Patients with a follow-up period of more than 1 year had the most recent platelet count of 174 ± 113 k/µl. Platelet count increase was significantly higher in the chemotherapy-induced group than the portal hypertension group. Adding celiac plexus neurolysis, corticosteroids, and NSAIDs to the post-procedural management resulted in a decreased rate of major complications from 73% to 46% and a decrease in the rate of moderate or severe pain from 92% to 20%. CONCLUSIONS: PSE improved platelet counts in cancer patients despite different etiologies of splenomegaly. The addition of celiac plexus neurolysis, corticosteroids, and NSAIDS to the post-PSE treatment protocol reduced complications. Data from this study could help to predict the amount of 300-500 µm tris-acryl gelatin microspheres required to achieve a planned infarct size.

Ruxolitinib in adult patients with secondary haemophagocytic lymphohistiocytosis: an open-label, single-centre, pilot trial.

BACKGROUND: Hemophagocytic lymphohistiocytosis is a cytokine-driven inflammatory syndrome that is associated with substantial morbidity and mortality. Overall survival in adult patients with secondary haemophagocytic lymphohistiocytosis remains suboptimal, and novel therapeutic strategies are needed. The phosphorylation-dependent activation of the Janus family kinases JAK1 and JAK2 are hallmarks of the final common pathway in this disease. We therefore aimed to determine the activity and safety of ruxolitinib, a JAK inhibitor, in adults with secondary haemophagocytic lymphohistiocytosis. METHODS: We performed an open-label, single-centre, pilot study of ruxolitinib in adults with secondary haemophagocytic lymphohistiocytosis at the University of Michigan Rogel Cancer Center (Ann Arbor, MI, USA). We included patients aged 18 years or more who fulfilled at least five of the eight HLH-2004 criteria for hemophagocytic lymphohistiocytosis. Discontinuation of corticosteroids was not required for enrolment in this study. Patients received oral ruxolitinib (15 mg twice a day) on a continuous 28-day cycle, or until disease progression or unacceptable toxicity. The primary endpoint was overall survival at 2 months from the first dose of ruxolitinib. Secondary endpoints included the assessment of adverse events, response (defined as the assessment of all quantifiable signs and laboratory abnormalities included in the diagnostic criteria for haemophagocytic lymphohistiocytosis), and pharmacodynamic biomarkers. Analyses were done in all treated patients with available data. This study is registered with ClinicalTrials.gov, number NCT02400463, and is still recruiting. FINDINGS: As of Feb 7, 2019, five patients had been enrolled. The first patient was enrolled in February, 2016. No deaths were recorded, with a median follow-up of 490 days (IQR 190-1075). 2-month overall survival was 100% (95% CI 57-100). Regarding response, resolution of symptoms (either partial or complete) and disease-associated laboratory abnormalities was observed in all five patients. Cytopenias improved in all patients within the first week of treatment, leading to relatively rapid transfusion independence, discontinuation of corticosteroids, and hospital discharge. A single serious adverse event (ie, grade 4 febrile neutropenia) was reported. One patient discontinued treatment because of grade 2 extremity pain and no treatment-related deaths were observed. Improvements in inflammatory markers (eg, ferritin, soluble IL-2 receptor) and T cells and monocytes activation (ie, decreased STAT1 phosphorylation) were observed following treatment. INTERPRETATION: These preliminary data suggest that ruxolitinib is active, well tolerated, and manageable in the outpatient setting in patients with secondary haemophagocytic lymphohistiocytosis. Given the paucity of effective, non-myelosuppressive therapies, these preliminary findings have important therapeutic implications for patients with haemophagocytic lymphohistiocytosis and other cytokine-release syndromes and warrant further investigation. FUNDING: National Cancer Institute, the University of Michigan Rogel Cancer Center, and Incyte Corporation.

Aberrant progranulin, YKL-40, cathepsin D and cathepsin S in Gaucher disease.

In Gaucher disease, several macrophage-specific biomarkers have been validated for use in the clinic. However, Gaucher disease is more complex involving system-wide pathophysiology beyond the macrophage, and based on gene array analysis in our Gaucher disease mouse model and other emerging pathophysiologic insights, we evaluated serum levels of cathepsins D and S, YKL-40 and progranulin in Gaucher disease patients. We assessed their biomarker potential in Gaucher disease and compared them to established Gaucher disease biomarkers, chitotriosidase, chemokine ligand 18 (CCL18), and other indicators of disease severity and response to therapy. Mean YKL-40 and cathepsin D and S levels were significantly higher in Gaucher disease patients compared to healthy controls; in contrast, mean progranulin levels were lower in Gaucher disease patients compared to healthy controls. Enzyme replacement therapy resulted in a significant reversal of elevated cathepsin D and S but there was no change in progranulin and YKL-40 levels. Patients with persistent splenomegaly after long-term enzyme replacement therapy had significantly higher serum YKL-40 than patients with smaller spleens (63.0 ±â€¯6.4 ng/ml vs. 46.4 ±â€¯4.3 ng/ml, p = .03). Serum YKL-40 levels were higher in subjects with severe bone involvement (Hermann Score 3 to 5) compared to those with milder bone involvement (Hermann Score 1 to 2) (70.1 ±â€¯4.3 ng/ml vs. 48.1 ±â€¯3.7 ng/ml, p = .0002). YKL-40 was only weakly associated with chitotriosidase (r = 0.2, p = .008) and CCL18 (r = 0.3, p = .0004), and cathepsin S was moderately associated with chitotriosidase (r = 0.4, p = .01) and CCL18 (r = 0.6, p < .0001). Receiver operating curves for progranulin and YKL-40 demonstrated areas under the curves of 0.80 and 0.70, respectively. In conclusion, while these biomarkers do not meet robust properties of established macrophage-specific biomarkers, they may inform severity of skeletal disease, contribution of fibrosis to residual splenomegaly, and other disease manifestations. These findings, including markedly low progranulin levels that do not change upon enzyme replacement therapy, are intriguing to prompt further investigations to decipher their role in pathophysiology and relevance to diverse phenotypes of Gaucher disease.

Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice.

BACKGROUND: Glyphosate is the most widely used herbicide in the USA and worldwide. There has been considerable debate about its carcinogenicity. Epidemiological studies suggest that multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) have a positive and statistically significant association with glyphosate exposure. As a B cell genome mutator, activation-induced cytidine deaminase (AID) is a key pathogenic player in both MM and B cell NHL. METHODS: Vk*MYC is a mouse line with sporadic MYC activation in germinal center B cells and considered as the best available MM animal model. We treated Vk*MYC mice and wild-type mice with drinking water containing 1000 mg/L of glyphosate and examined animals after 72 weeks. RESULTS: Vk*MYC mice under glyphosate exposure developed progressive hematological abnormalities and plasma cell neoplasms such as splenomegaly, anemia, and high serum IgG. Moreover, glyphosate caused multiple organ dysfunction, including lytic bone lesions and renal damage in Vk*MYC mice. Glyphosate-treated wild-type mice developed benign monoclonal gammopathy with increased serum IgG, anemia, and plasma cell presence in the spleen and bone marrow. Finally, glyphosate upregulated AID in the spleen and bone marrow of both wild-type and Vk*MYC mice. CONCLUSIONS: These data support glyphosate as an environmental risk factor for MM and potentially NHL and implicate a mechanism underlying the B cell-specificity of glyphosate-induced carcinogenesis observed epidemiologically.

Factors Affecting Persistent Splenomegaly After Adult-to-Adult Living Donor Liver Transplantation Using a Left Lobe.

BACKGROUND: The aim of the present study was to evaluate spleen volume (SV) and the factors influencing it after adult-to-adult living donor liver transplantation (A2LDLT) using a left lobe. METHODS: Pretransplant computed tomography (CT) and post-transplant CT 2 years after A2LDLT were examined by volumetric analysis in 24 patients. We divided the recipients into the following 2 groups according to the post-transplant SV: >500 mL (Group A) and ≤500 mL (Group B). The factors affecting the change in post-transplant SV were compared between the 2 groups. RESULTS: The mean pretransplant SV decreased significantly after A2LDLT. Platelet counts after living donor liver transplantation increased significantly relative to the pretransplant values. Post-transplant SV was >500 mL in 9 patients (Group A) and ≤500 mL in 15 (Group B). Pretransplant SV, platelet count, anhepatic time, operative time, intraoperative blood loss, post-transplant portal vein pressure >20 mm Hg, and post-transplant portal vein flow >250 mL/min/100 g graft weight showed significant differences between the 2 groups. Actual graft volume (GV) and GV/standard liver volume ratio showed no intergroup differences. Multivariate analysis showed that the only significant factor related to a post-transplant SV of >500 mL was the pretransplant SV. Post-transplant platelet counts were significantly increased from the pretransplant values in both Group A and Group B. CONCLUSIONS: Pretransplant SV is the only significant factor predicting a SV of >500 mL after A2LDLT. However, even in patients with a SV of >500 mL, the platelet count increased significantly from the pretransplant value.

Clinical presentation and hematological profile among young and old chronic lymphocytic leukemia patients in Sudan.

OBJECTIVE: To assess the clinical presentation and hematological profile among young (≤ 55 years) and old (> 55 years) chronic lymphocytic leukemia patients in Sudan. RESULT: In the present cross-sectional descriptive study, out of 110 cases studied, among them 31 (28.2%) were young (≤ 55 years) patients with mean age 48 years, and 79 (71.8%) were elder patients (> 55 years) with mean age 66 years, the overall mean age was 62.97 ± 12.06 with range (22-85 years), and 79 (71.8%) were males and 31 (28.2%) were females (M:F = 2.6:1) (P = 0.000). (7.3%) were asymptomatic, 61 (55.5%) presented with nonspecific complains. Generalized lymphadenopathy was seen in 52 (47.27%) with elder predominance (P = 0.03). Splenomegaly, hepatomegaly, thrombocytopenia and anemia were seen in 54 (49.1%), 14 (12.7%), 43 (39.1%) and 38 (34.5%) of patients respectively with male predominance. 54 (49.1%) and 42 (38.18%) of patients presented at Rai high risk and Binet C stages respectively with nearly same age and sex distribution. CLL in Sudan is a disease of elders, same as seen in literature, with high male to female ratio. In general hematological parameters means were noted to be distributed equally according to age and sex groups. Majority of patients were presented with nonspecific symptoms and nearly half of patients presented at late stages as reported in most developing countries.

Correlation between the values of circulating blood elements with the size of spleen in the presence of schistosomal splenomegaly

Abstract Purpose: To evaluate a possible relationship between the size of the spleen and values of circulating blood elements in patients with schistosomatic splenomegaly. Methods: ixty one patients with hepatosplenic schistosomiasis mansoni underwent a clinical exam and peripheral venous blood was collected for a hemogram. The erythrocyte, hemoglobin, hematocrit, leukocyte, and platelet values were determined. All patients underwent abdominal ultrasound to measure the spleen. The hematological test results were compared to the size of the spleen. Results: The size of the spleen varied from 14.0 to 28.4 (19.9 ± 3.7) cm according to the ultrasound image. Thrombocytopenia was observed 58 (95%) patients, leukopenia in 55 (90%) patients, and anemia in 32 (52.4%) patients. Leukopenia was proportional to splenomegaly. Conclusion: Schistosomal splenomegaly leads to leukopenia in direct proportion to the size of the spleen.

Distribution characteristics of cells in splenomegaly due to hepatitis B-related cirrhotic portal hypertension and their clinical importance.

Objectives To investigate peripheral cytopenia in patients with splenomegaly due to hepatitis B-related cirrhotic portal hypertension (HBRCPH) by comparing blood cell counts from enlarged spleens with peripheral blood. Methods This prospective study involved patients undergoing splenectomy at the Nangfang Hospital from June 2013 to December 2015. Blood cell counts from peripheral blood were compared with those from splenic blood taken during splenectomies. Results Clinical data were available from 30 patients. White blood cell (WBC), red blood cell (RBC) and platelet counts were statistically significantly lower in peripheral blood compared with splenic blood. After splenectomy, peripheral blood cell counts increased significantly compared with pre-operative levels. Platelet and WBC counts in the lower spleen were significantly higher than those in the porta lienis (middle segment) and upper spleen. Conclusions In patients with splenomegaly due to HBRCPH, the counts of three blood cell lineages were significantly higher in the spleen than in peripheral blood. Splenectomy can aid the return of peripheral blood cell counts to normal levels. The most significant retention of platelets and WBCs occurred in the lower spleen which may be useful information for surgeons performing partial splenectomies.

Correlation between the values of circulating blood elements with the size of spleen in the presence of schistosomal splenomegaly.

PURPOSE: To evaluate a possible relationship between the size of the spleen and values of circulating blood elements in patients with schistosomatic splenomegaly. METHODS: ixty one patients with hepatosplenic schistosomiasis mansoni underwent a clinical exam and peripheral venous blood was collected for a hemogram. The erythrocyte, hemoglobin, hematocrit, leukocyte, and platelet values were determined. All patients underwent abdominal ultrasound to measure the spleen. The hematological test results were compared to the size of the spleen. RESULTS: The size of the spleen varied from 14.0 to 28.4 (19.9 ± 3.7) cm according to the ultrasound image. Thrombocytopenia was observed 58 (95%) patients, leukopenia in 55 (90%) patients, and anemia in 32 (52.4%) patients. Leukopenia was proportional to splenomegaly. CONCLUSION: Schistosomal splenomegaly leads to leukopenia in direct proportion to the size of the spleen.

Causes of peripheral cytopenia in hepatitic cirrhosis and portal hypertensive splenomegaly.

The clinical data of 183 patients with hepatitic cirrhosis and portal hypertensive splenomegaly complicated by peripheral cytopenia were retrospectively analyzed to investigate the causes of peripheral cytopenia, as well as the proportion of the causes in these patients. All patients underwent splenectomy. Before operation, these patients had one or more types of peripheral cytopenia (cumulative cytopenia: 390 patient-times). After splenectomy, blood counts in 79.2% (309/390) returned to normal, while in 15.9% (62/390) they increased but failed to reach to normal levels, and in 4.9% (19/390) they became lower than before the operations. For the last group of patients ( n = 19), long-term follow-up showed that blood counts returned to normal in five patients. In other words, in 80.5% [(309 + 5)/390 or 314/390] of patient-times, the peripheral cytopenia was due to hypersplenism, in 15.9% it was due to a combination of factors, and in 3.6% [14/390] it had nothing to do with the hypersplenism. Thus, hypersplenism is a major cause, but not the only cause, of peripheral cytopenia in patients with hepatic cirrhosis and portal hypertensive splenomegaly, and splenectormy is an effective treatment for these patients. Impact statement For a long time, the development of peripheral cytopenias as a complication to cirrhotic portal hypertension has been attributed to hypersplenism; however, this has never been fully demonstrated. Dameshek summarized that hypersplenism should be diagnosed by the presence of four conditions: (a) mono- or multi-lineage peripheral cytopenias; (b) compensatory hyperplasia of bone marrow; (c) splenomegaly; and (d) correction of cytopenias after splenectomy. We retrospectively analyzed the clinical data from 183 surgical patients, and found that 80.5% of peripheral cytopenias was caused by hypersplenism, 16% by a combination of factors, and 3.5% by other factors unrelated to hypersplenism. As the first quantitative findings in this field, our results verify that hypersplenism is a major, but not exclusive, cause of peripheral cytopenias, and provides important clinical evidence for investigating the cause of peripheral cytopenias.

Splenomegaly and Its Associations with Genetic Polymorphisms and Treatment Outcome in Colorectal Cancer Patients Treated with Adjuvant FOLFOX.

PURPOSE: Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients. MATERIALS AND METHODS: Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells. RESULTS: Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, -42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly. CONCLUSION: Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly.

A multicentre observational study for early diagnosis of Gaucher disease in patients with Splenomegaly and/or Thrombocytopenia.

Gaucher disease (GD) is the most common lysosomal disorder resulting from deficient activity of the ß-glucosidase enzyme that causes accumulation of glucosylceramide in the macrophage-monocyte system. Notably, because of non-specific symptoms and a lack of awareness, patients with GD experience long diagnostic delays. The aim of this study was to apply a diagnostic algorithm to identify GD type 1 among adults subjects referred to Italian haematology outpatient units because of splenomegaly and/or thrombocytopenia and, eventually, to estimate the prevalence of GD in this selected population. One hundred and ninety-six subjects (61 females, 135 males; mean age 47.8 ± 18.2 years) have been enrolled in the study and tested for ß-glucosidase enzyme activity on dried blood spot (DBS). Seven of 196 patients have been diagnosed with GD, (5 females and 2 males) with mean age 31.8 ± 8.2 years, with a prevalence of 3.6% (with a prevalence of 3.6% (I95% CI 1.4-7.2; 1/28 patients) in this population. These results show that the use of an appropriate diagnostic algorithm and a simple diagnostic method, such as DBS, are important tools to facilitate the diagnosis of a rare disease even for not disease-expert physicians.