Endovascular Embolization Techniques in a Novel Swine Model of Fatal Uncontrolled Solid Organ Hemorrhage and Coagulopathy.

BACKGROUND: Endovascular embolization is increasingly used in treating traumatic hemorrhage and other applications. No endovascular-capable translational large animal models exist and coagulopathy's effect on embolization techniques is unknown. We developed a coagulation-adaptable solid organ hemorrhage model in swine for investigation of embolization techniques. METHODS: Anesthetized swine (n = 26, 45 ± 3 kg) had laparotomy and splenic externalization. Half underwent 50% isovolemic hemodilution with 6% hetastarch and cooling to 33-35°C (COAG group). All had controlled 20 mL/kg hemorrhage and endovascular access to the proximal splenic artery with a 4F catheter via a right femoral sheath. Splenic transection and 5 min free bleeding were followed by treatment (n = 5/group) with 5 mL gelfoam slurry, three 6-mm coils, or no treatment (n = 3, control). Animals received 15 mL/kg plasma resuscitation and were monitored for 6 hr. Splenic blood loss was continuously measured and angiograms were performed at specified times. RESULTS: Coagulopathy was successfully established in COAG animals. Pre-treatment blood loss was greater in COAG (11 ± 6 mL/kg) than non-COAG (7 ± 3 mL/kg, P = 0.04) animals. Splenic hemorrhage was universally fatal without treatment. Non-COAG coil survival was 4/5 (326 ± 75 min) and non-COAG Gelfoam 3/5 (311 ± 67 min) versus non-COAG Control 0/3 (82 ± 18 min, P < 0.05 for both). Neither COAG Coil (0/5, 195 ± 117 min) nor COAG Gelfoam (0/5, 125 ± 32 min) treatment improved survival over COAG Control (0/3, 56 ± 19 min). Post-treatment blood loss was 4.6 ± 3.4 mL/kg in non-COAG Coil and 4.6 ± 2.9 mL/kg in non-COAG Gelfoam, both lower than non-COAG Control (18 ± 1.3 mL/kg, P = 0.05). Neither COAG Coil (8.4 ± 5.4 mL/kg) nor COAG Gelfoam (15 ± 11 ml/kg) had significantly less blood loss than COAG Control (20 ± 1.2 mL/kg). Both non-COAG treatment groups had minimal blood loss during observation, while COAG groups had ongoing slow blood loss. In the COAG Gelfoam group, there was an increase in hemorrhage between 30 and 60 min following treatment. CONCLUSIONS: A swine model of coagulation-adaptable fatal splenic hemorrhage suitable for endovascular treatment was developed. Coagulopathy had profound negative effects on coil and gelfoam efficacy in controlling bleeding, with implications for trauma and elective embolization procedures.

Is thrombocytosis always an indicator of autosplenectomy in patients with systemic lupus erythematosus?

In systemic lupus erythematosus (SLE), the most commonly encountered finding related to platelets is thrombocytopenia whereas thrombocytosis is rarely reported. Our aim here was to reveal the type and the frequency of thrombocytosis in SLE patients along with its causes. Data of patients were evaluated retrospectively. Patients who had a platelet count of > 450,000/mm3 (> 450 × 109/L) in at least two subsequent counts and lasting more than 6 months during the follow-up were considered to have "persistent thrombocytosis". Peripheral smear results of patients with thrombocytosis were analyzed, and spleen imaging was performed for autosplenectomy/hyposplenism to patients with persistent thrombocytosis. A total of 205 patients with SLE were included in the study [196 (95.6%) female, mean age 41.5 years]. Out of 12 patients (5.9%) with thrombocytosis, 9 (4.3%) had transient thrombocytosis and 3 patients (1.4%) had persistent thrombocytosis. Of those with transient thrombocytosis, 5 were associated with iron deficiency anemia (IDA), 2 to polyarthritis, and the remaining 2 to digital ischemia and/or cutaneous vasculitis. Of three patients with persistent thrombocytosis, one was identified to have had splenectomy due to resistant immune thrombocytopenic purpura, and the other two (0.9%) patients had autosplenectomy. The only independent risk factor for the development of thrombocytosis was the presence of cutaneous vasculitis (OR 10.79 (95% CI 2.14-54.47), p = 0.0004). During the course of SLE, frequency of thrombocytosis is similar to that of the general population and the most common cause is reactive thrombocytosis. If the thrombocytosis was persistent, rheumatologist must consider that the patient may have autosplenectomy/asplenia/hyposplenism.

Recurrent spontaneous splenic rupture in a patient with congenital factor XIII deficiency.

We describe an unusual presentation of factor XIII (FXIII) deficiency in a 17-year-old boy who was diagnosed with this congenital deficiency at the age of 18 months. He had a history of spontaneous splenic rupture 8 years ago, which was managed conservatively. He now presented with sudden severe abdominal and left shoulder pain for 1 day, with no history of antecedent trauma. He was in shock, and examination revealed diffuse peritonitis. A computed tomography scan showed a grade IV splenic laceration. He was taken as an emergency to the operating room where he was found to have a shattered spleen, and a splenectomy was performed. He received cryoprecipitate transfusions perioperatively. After an uneventful recovery, the patient was discharged. To the best of our knowledge, this is the first described case of a recurrent splenic rupture in a patient with FXIII deficiency.

Evaluation of clopidogrel, hypercoagulability, and platelet count in dogs undergoing splenectomy for splenic masses.

Dogs that had splenectomy are predisposed to fatal thrombotic conditions, and thrombocytosis is a risk factor for post-splenectomy hypercoagulability. However, in veterinary medicine, there are no specific therapeutic approaches for managing this hypercoagulability. This study aimed to determine the preventive effect of clopidogrel on post-operative hypercoagulability during the first 2 weeks post-splenectomy in dogs with splenic masses. This study included 12 dogs that had splenectomy. Seven dogs received no treatment (group A), and five were treated with clopidogrel (group B). Clopidogrel was loaded at 10 mg/kg on day 2 and continued at 2 mg/kg until day 14. Blood samples were collected on the day of surgery and 2, 7, and 14 days after splenectomy in both groups. In group B, thromboelastography (TEG) was performed on the same days. In group A, there was significant elevation of platelet counts on days 7 (p = 0.007) and 14 (p = 0.001) compared to day 0. In group B, the platelet counts were significantly elevated on day 7 (p = 0.032) but no significant difference was found on day 14 compared to day 0. Platelet counts on day 14 were significantly higher in group A than in group B (p = 0.03). The lower platelet counts were correlated with alterations in TEG parameters, and no significant differences were found in the K and α-angle values at all postoperative assessment points compared to day 0. Our study suggests that clopidogrel may reduce post-operative thrombocytosis and hypercoagulability in dogs that undergo splenectomy for splenic masses.

Hyposplenism revealed by Plasmodium malariae infection.

BACKGROUND: Hyposplenism, due to splenectomy, inherited red blood cell disorders or acquired conditions such as celiac disease, has an important impact on the severity of malaria, especially in non-immune patients. Conversely, that malaria may reveal functional hyposplenism has not been described previously. METHODS: A 31-year old gardener was diagnosed with an uncomplicated attack of Plasmodium malariae 11 years after leaving the endemic area. In addition to trophozoites and schizonts, thick and thin smears also showed Howell-Jolly bodies, pointing to functional hyposplenism. This was later confirmed by the presence of a calcified spleen in the context of S/ß + sickle-cell syndrome in a patient previously unaware of this condition. CONCLUSION: Malaria may reveal hyposplenism. Although Howell-Jolly bodies are morphologically similar to nuclei of young Plasmodium trophozoite, distinction on smears is based on the absence of cytoplasm and irregular size of Howell-Jolly bodies. In the patient reported here, hyposplenism was revealed by the occurrence of P. malariae infection relatively late in life. Timely diagnosis of hyposplenism resulted in the implementation of appropriate measures to prevent overwhelming infection with capsulated bacteria. This observation highlights the importance of diagnosing hyposplenism in patients with malaria despite the morphological similarities between ring nuclei and Howell-Jolly bodies on thick smears.

Hyposplenism: comparison of different methods for determining splenic function.

Asplenic patients are at risk for pneumococcal sepsis. Patients with hyposplenic function, such as associated with sickle cell disease (SCD), are also at risk. However, tests to assess splenic function are either unavailable or lacking standardization. The aim of this study was to compare different methods for determining splenic function. Eighteen patients with SCD (i.e., 10 heterozygous (SC) and 8 homozygous (SS) SCD patients), and eight splenectomized patients were compared to 10 controls. All subjects underwent spleen scintigraphy, after which functional splenic volumes (FSV) were calculated. FSV was compared to immunological function and B cell-subsets, as well as phagocytic function represented by the presence of Howell Jolly bodies (HJB) and percentages of pitted red cells (PIT). Heterozygous SCD (SC) patients had increased splenic volumes, but diminished FSV, homozygous SCD (SS) patients were asplenic. Splenectomized and SS patients had a strongly reduced phagocytic and immunological function. SC patients had reduced anti-polysaccharide responses without an increase in PIT. FSV correlated significantly with phagocytic and immunological function. HJB were indicative of splenic dysfunction, HJB absence was not indicative of normal functioning splenic tissue. Although visualizing HJB is methodologically advantageous to PIT, both are valid biomarkers of splenic dysfunction. The amount of non-switched memory B cells is strongly correlated to FSV.

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.

Correlation of biological serum markers with the degree of hepatic fibrosis and necroinflammatory activity in hepatitis C and schistosomiasis patients.

Liver biopsy is the gold-standard method to stage fibrosis; however, it is an invasive procedure and is potentially dangerous. The main objective of this study was to evaluate biological markers, such as cytokines IL-13, IFN-gamma, TNF-alpha and TGF-beta, platelets, bilirubins (Bil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total proteins, gamma-glutamil transferase (gamma-GT) and alkaline phosphatase (AP), that could be used to predict the severity of hepatic fibrosis in schistosomiasis and hepatitis C (HC) as isolated diseases or co-infections. The following patient groups were selected: HC (n = 39), HC/hepatosplenic schistosomiasis (HSS) (n = 19), HSS (n = 22) and a control group (n = 13). ANOVA and ROC curves were used for statistical analysis. P < 0.05 was considered significant. With HC patients we showed that TNF-alpha (p = 0.020) and AP (p = 0.005) could differentiate mild and severe fibrosis. With regard to necroinflammatory activity, AST (p = 0.002), gamma-GT (p = 0.034) and AP (p = 0.001) were the best markers to differentiate mild and severe activity. In HC + HSS patients, total Bil (p = 0.008) was capable of differentiating between mild and severe fibrosis. In conclusion, our study was able to suggest biological markers that are non-invasive candidates to evaluate fibrosis and necroinflammatory activity in HC and HC + HSS.

Localized hepatosplenic sarcoidosis with an elevated serum CA-125 level.

Sarcoidosis, a granulomatous disorder of unknown etiology, primarily affects the lungs and lymph nodes. Extrapulmonary disease without any pulmonary involvement is rare. Sarcoidosis with an elevated serum CA-125 level has only been reported five times in the literature. We describe a case of localized hepatosplenic sarcoidosis, confirmed by biopsy, with associated CA-125 elevation. In our review of the current literature, this is the first reported case of localized hepatosplenic sarcoidosis with associated serum CA-125 elevation.

[The spleen: between mysteries and discoveries]. / La rate: entre mystères et découvertes.

Mainly because it is possible to live without it, the spleen has always been considered a secondary and mysterious organ. However, recent observations have revealed new unsuspected functions for this organ whose patho-physiological importance should be reconsidered. Much less known than the hypersplenism, the hyposplenism corresponds historically to the loss or the insufficiency of the two principal functions of spleen: the filtration of faded or senescent elements from the blood and the fight against infections. In this article, after a short recall of the physiological functions of spleen, three innovations relating to hyposplenism will be explored: the vascular complications, the loss of the splenic pool of regenerating monocytes and the loss of the splenic pool of pluripotent mesenchymal stem cell.

Potential role of Howell-Jolly bodies in identifying functional hyposplenism: a prospective single-institute study.

Although patients with cancer and immunosuppression are at a risk of functional hyposplenism, how to detect it promptly remains unclear. Since hyposplenism allows erythrocytes with nuclear remnants (Howell-Jolly bodies [HJBs]) to appear in the peripheral blood, HJB detection by a routine microscopic examination may help identify patients with functional hyposplenism. This prospective study was thus performed to determine the underlying diseases in patients who presented with HJBs. Of 100 consecutive patients presenting with HJBs, 73 had a history of splenectomy. The remaining 27 had hematologic cancer (n = 6, 22%), non-hematologic cancer (n = 8, 30%), hepatic disorders (n = 4, 15%), premature neonates (n = 3, 11%), hemolytic anemia (n = 2, 7%), autoimmune disorders (n = 2, 7%) and miscellaneous diseases (n = 2, 7%), and their prior treatments included chemotherapy (n = 8, 30%), steroids (n = 7, 26%) and molecular-targeted therapy (n = 3, 11%). Among the 27 patients, 22 had computed tomography scans available: 3 (14%) had underlying diseases in the spleen, and the remaining 19 (86%) were all found to have a decreased splenic volume, including 11 (50%) with more than 50% of the ideal value. The present findings suggest that HJB detection identifies patients with potentially functional hyposplenism who should receive appropriate interventional treatment, such as vaccination and prophylactic antibiotics.

Carbohydrate antigen 19-9 elevation without evidence of malignant or pancreatobiliary diseases.

Although carbohydrate antigen 19-9 (CA 19-9) may be elevated in benign diseases, elevated CA 19-9 may cause a fear of cancer and unnecessary follow-up studies. Research on how to approach systematically in this case is very limited. The purpose of this study was to analyze the clinical features and the causes of CA 19-9 elevation without evidence of malignant or pancreatobiliary diseases. We retrospectively reviewed the medical records of patients who had CA 19-9 elevation (≥80 U/mL) and were found to be unrelated to cancer after follow-up. After exclusion, 192 patients were included in this study. The median level of CA 19-9 was 136.5 U/mL. The causes of CA 19-9 elevation were determined in 147 (76.6%) patients, and that was unknown in 45 (23.4%). The estimated causative diseases were hepatic diseases in 63 patients, pulmonary diseases in 32, gynecologic diseases in 38, endocrine diseases in 13, and spleen disease in 1. Of 45 patients with unknown cause, 35 had normalization of CA 19-9 and 10 had persistently elevated CA 19-9. In conclusion, CA 19-9 elevation without malignancies or pancreatobiliary diseases should be systematically evaluated and followed up. We suggest an algorithm to investigate the causes and follow up these patients.

A case of ruptured splenic cyst with elevated serum levels of CEA treated by laparoscopic unroofing.

Splenic cysts are rare and tend to have elevated tumor markers, of which carbohydrate antigen (CA) 19-9 is the most frequently elevated. Therefore, splenic cysts with elevated serum carcinoembryonic antigen (CEA) levels and without CA19-9 elevation are extremely rare. A 26-year-old woman presented with sudden upper abdominal pain while sleeping. Contrast-enhanced computed tomography (CT) showed an 85-mm simple splenic cyst in the upper pole and a moderate amount of ascites around the spleen. The serum levels of CEA, but not CA19-9, were elevated. Spontaneous rupture of a splenic cyst was diagnosed. We performed elective laparoscopic unroofing. The histological findings revealed a stratified squamous epithelium on the inner surface of the cystic wall. On immunohistochemical examination, the squamous epithelium was found to be positive for cytokeratin (CK)7, negative for calretinin, and positive for CEA. The histological diagnosis was an epidermoid cyst. Three months after the operation, the elevated serum tumor marker levels of CEA were normalized. Splenic cysts with high levels of CEA and low levels of CA19-9 are extremely rare. Laparoscopic unroofing is a useful operative procedure for ruptured splenic cysts with elevated levels of serum tumor markers.

Rifaximin Reduces Markers of Inflammation and Bacterial 16S rRNA in Zambian Adults with Hepatosplenic Schistosomiasis: A Randomized Control Trial.

Cirrhosis is the dominant cause of portal hypertension globally but may be overshadowed by hepatosplenic schistosomiasis (HSS) in the tropics. In Zambia, schistosomiasis seroprevalence can reach 88% in endemic areas. Bacterial translocation (BT) drives portal hypertension in cirrhosis contributing to mortality but remains unexplored in HSS. Rifaximin, a non-absorbable antibiotic may reduce BT. We aimed to explore the influence of rifaximin on BT, inflammation, and fibrosis in HSS. In this phase II open-label trial (ISRCTN67590499), 186 patients with HSS in Zambia were evaluated and 85 were randomized to standard care with or without rifaximin for 42 days. Changes in markers of inflammation, BT, and fibrosis were the primary outcomes. BT was measured using plasma 16S rRNA, lipopolysaccharide-binding protein, and lipopolysaccharide, whereas hyaluronan was used to measure fibrosis. Tumor necrosis factor receptor 1 (TNFR1) and soluble cluster of differentiation 14 (sCD14) assessed inflammation. 16S rRNA reduced from baseline (median 146 copies/µL, interquartile range [IQR] 9, 537) to day 42 in the rifaximin group (median 63 copies/µL, IQR 12, 196), P < 0.01. The rise in sCD14 was lower (P < 0.01) in the rifaximin group (median rise 122 ng/mL, IQR-184, 783) than in the non-rifaximin group (median rise 832 ng/mL, IQR 530, 967). TNFR1 decreased (P < 0.01) in the rifaximin group (median -39 ng/mL IQR-306, 563) but increased in the non-rifaximin group (median 166 ng/mL, IQR 3, 337). Other markers remained unaffected. Rifaximin led to a reduction of inflammatory markers and bacterial 16S rRNA which may implicate BT in the inflammation in HSS.

Study on the relationship between serum high density lipoprotein and Pi-deficiency syndrome in patients with coronary heart disease.

OBJECTIVE: To explore the relationship of Pi-deficiency syndrome in TCM with the change of serum high density lipoprotein (HDL) in blood lipid metabolic disorder. METHODS: Sixty-eight patients with confirmed coronary heart disease (CHD) were selected for TCM syndrome typing into Pi-deficiency (PD) group and non-Pi-deficiency (NPD) group. Routine blood lipids and serum lipoprotein electrophoretogram (SLPG) were determined in all patients to analyze the total content of HDL and its relative contents of sub-components HDL(1-5), as well as their relation with PD syndrome. Besides, a healthy control group (62 cases) was set up. RESULTS: The level of serum HDL-C was lowered, SLPG abnormality rate increased in the patients with CHD, with total HDL and the relative contents of subcomponent HDL(1) and HDL(3) significantly lower than those in the healthy control group (P<0.01). The total HDL, HDL(1) and HDL(3) in the PD group were also lower than those in the NPD group (P<0.05, P<0.01). CONCLUSION: Serum HDL and its sub-components showed a definite relation with TCM PD syndrome type, therefore, further exploring the granular specificity of HDL and its sub-components as well as their influence on reverse cholesterol transport (RCT) may hopefully provide clues for developing RCT regulatory Chinese new drugs and for CHD prevention and treatment.

Benign splenic epithelial cyst accompanied by elevated Ca 19-9 level: a case report.

We report the case of a 30-year-old woman with a benign epidermoid splenic cyst and a high CA 19-9 serum level (268 U/mL). The patient underwent resection of the cyst and splenectomy. After removal of the cyst, the serum CA 19-9 level decreased to a normal level within 6 weeks. True non-parasitic splenic cysts are rare. Approximately 30 cases of benign true splenic cysts with a high CA 19-9 serum level have been published.

Detection of systemic amyloidosis in the pig-tailed macaque (Macaca nemestrina).

Secondary amyloidosis is a progressive systemic disease for which there is no reliable diagnostic assay, preventive measure, or treatment. In an attempt to elucidate an antemortem diagnosis, 30 female pig-tailed macaques (Macaca nemestrina) at the Washington National Primate Research Center were surveyed for amyloidosis. Amyloid was demonstrated histologically in 47% (14 of 30) of the animals. The distribution and severity of amyloid deposition was variable. Affected animals had a mean age (+/-1 standard deviation) of 13.2 +/- 4.9 y, which was significantly greater than the mean age of unaffected animals (9.3 +/- 4.1) y. Twelve tests were evaluated for detection of amyloidosis; the diagnostic value of each was determined through comparison of histologically positive and histologically negative animals. Diagnostic tests evaluated were endoscopic examination and biopsy of the stomach and colon, abdominal ultrasonography, hepatic radiology, serum amyloid A (SAA), endothelin 1, alpha-fetal protein, aspartate aminotransferase (AST), alanine aminotransferase, gamma-glutamyltransferase (GGT), alkaline phosphatase, cholesterol, blood urea nitrogen, total bilirubin, C-reactive proteins, and erythrocyte sedimentation rate. Amyloidotic animals demonstrated a distinctive serologic profile: elevated SAA, GGT, and AST in combination with decreased total protein and albumin. Radiology demonstrated hepatomegaly in animals with hepatic amyloid deposition. In the absence of known infection or trauma, an amyloidotic serologic profile and radiologic hepatomegaly are consistent with systemic amyloidosis in M. nemestrina.