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Although postoperative portal vein thrombosis (PVT) is a frequent complication of splenectomy, few studies have examined PVT after simultaneous hepatectomy and splenectomy (HS). The aim of this study was to clarify the risk factors for and characteristics of PVT after HS. This retrospective observational study included 102 patients, including 76 with liver cirrhosis (LC) and 26 without, who underwent HS between April 2004 and April 2021. The incidence and location of postoperative PVT detected on contrast-enhanced CT 1 week after surgery were analyzed. In addition, pre- and intraoperative parameters were compared between patients with postoperative PVT and those without in order to determine risk factors for PVT after HS. Among the 102 patients, 29 (28.4 %), including 32.9 % with LC and 15.4 % without LC, developed PVT after surgery. Among the 29 patients with PVT, 21 (72.4 %), 4 (13.8 %), and 4 (13.8 %) developed thrombus in the intrahepatic portal vein only, extrahepatic portal vein only, and both the extra- and intrahepatic portal veins, respectively. Multivariable analysis showed that preoperative splenic vein dilatation was an independent risk factor for PVT after HS (odds ratio: 1.53, 95 % confidence interval: 1.156–2.026, P = 0.003). Our results suggest that splenic vein dilatation is an independent risk factor for PVT after simultaneous HS, and that PVT after HS occurs more frequently in the intrahepatic portal vein. After HS for cases with dilated splenic veins, we should pay particular attention to the PVT development in the intrahepatic portal vein regardless of the type of liver resection. [ABSTRACT FROM AUTHOR]

Introduction: Portal hypertension combined with hypersplenism (PHcH) is the main cause of hypocytosis and esophagogastric variceal hemorrhage in patients with liver cirrhosis. Activated macrophages that destroy excess blood cells are the main cause of hypersplenism, but the activating pathway is not very clear. This study aims to investigate the activation types of splenic macrophages and their activation mechanisms, to provide experimental evidence for the biological treatment of splenomegaly, and to find a strategy to improve liver fibrosis and inflammation by intervening in splenic immune cells. This study revealed the occurrence of M2-like polarization of macrophages and upregulation of c-Myc gene expression in the PH spleen. Methods: RNAseq, protein chip, western blot, and chip-seq were performed on macrophages and the in vitro MEK inhibitor rafametinib was used. Carbon tetrachloride and thioacetamide induced mouse cirrhosis models were separately constructed. Results: c-Myc gene knockout in splenic macrophages reduced M2-like polarization and exacerbated liver fibrosis inflammation. c-Myc activated the MAPK signaling pathway and upregulated the expression of IL-4 and M2-like related genes in PH hypersplenism through the MEK-ERK-c-Myc axis. In addition, the c-Myc gene exerted anti-inflammatory effects by upregulating IL-4-mediated signal transduction to promote M2-like differentiation and anti-inflammatory cytokine secretion. Conclusions: Activation of MEK‐ERK‐c‐MYC signaling pathway promotes splenic M2-like macrophage polarization to inhibit PHcH-liver cirrhosis. Therefore, the induction of macrophage depolarization might represent a new therapeutic approach in the cure of PH hypersplenism, making c-Myc a potential candidate for macrophage polarization therapy. [ABSTRACT FROM AUTHOR]

Thrombocytopenia is one of the common complications after liver transplantation, with pathophysiological mechanisms including insufficient platelet production and increased platelet consumption, which severely affects the prognosis of liver transplant recipients. Various factors such as preoperative hepatitis virus infection, intraoperative ischemic injury, and postoperative use of immunosuppressive drugs may lead to thrombocytopenia after liver transplantation. Early detection and effective treatment of thrombocytopenia after liver transplantation are currently hot topics of research. Based on the existing literature, this article reviews the definition, pathophysiological mechanisms, risk factors, treatment, and prevention of thrombocytopenia, and discusses the occurrence and development of thrombocytopenia after liver transplantation and related diagnosis and treatment strategies, aiming to optimize the existing treatment opinions, reduce the risk of thrombocytopenia after transplantation and improve the prognosis of liver transplant recipients. [ABSTRACT FROM AUTHOR]

The clearance of senescent and altered red blood cells (RBCs) in the red pulp of the human spleen involves sequential processes of prefiltration, filtration, and postfiltration. While prior work has elucidated the mechanisms underlying the first two processes, biomechanical processes driving the postfiltration phagocytosis of RBCs retained at interendothelial slits (IES) are still poorly understood. We present here a unique computational model of macrophages to study the role of cell biomechanics in modulating the kinetics of phagocytosis of aged and diseased RBCs retained in the spleen. After validating the macrophage model using in vitro phagocytosis experiments, we employ it to probe the mechanisms underlying the kinetics of phagocytosis of mechanically altered RBCs, such as heated RBCs and abnormal RBCs in hereditary spherocytosis (HS) and sickle cell disease (SCD). Our simulations show pronounced deformation of the flexible and healthy RBCs in contrast to minimal shape changes in altered RBCs. Simulations also show that less deformable RBCs are engulfed faster and at lower adhesive strength than flexible RBCs, consistent with our experimental measurements. This efficient sensing and engulfment by macrophages of stiff RBCs retained at IES are expected to temper splenic congestion, a common pathogenic process in malaria, HS, and SCD. Altogether, our combined computational and in vitro experimental studies suggest that mechanical alterations of retained RBCs may suffice to enhance their phagocytosis, thereby adapting the kinetics of their elimination to the kinetics of their mechanical retention, an equilibrium essential for adequately cleaning the splenic filter to preserve its function. [ABSTRACT FROM AUTHOR]

Background: The prognosis comparison between endoscopic therapy + partial splenic embolization (PSE) and Hassab's operation is unclear in the treatment of esophageal variceal bleeding in patients with liver cirrhosis. This study aimed to compare the outcome of endoscopic therapy + PSE (EP) with a combination of splenectomy + pericardial devascularization procedure, known as Hassab's operation (SH) for esophageal variceal bleeding in patients with liver cirrhosis with hypersplenism. Methods: We enrolled 328 patients, including 125 and 203 patients who underwent EP and SH, respectively. Each group consisted of 110 patients after propensity score matching (PSM). Subsequently, we recorded and analyzed bleeding episodes and mortality in 6 months and 1, 2, and 5 years after therapies. Results: The median follow-up time in the EP and SH groups was 53 and 64 months, respectively. Bleeding incidence 6 months after therapies in the EP group was lower than that in the SH group (1.8% vs. 10.0%, P = 0.010). Additionally, complications in the perioperative period were not significantly different (0% vs. 3.6%, P = 0.008). However, the bleeding rate between the two groups was not significantly different at 1, 2, and 5 years after therapies (7.3% vs. 12.7%, P = 0.157; 10.9% vs. 16.4%, P = 0.205; 30.6% vs. 31.8%, P = 0.801), as well as mortality rate (4.5% vs 7.3%, P = 0.571). Conclusion: Compared with SH therapy, the bleeding rate 6 months after EP therapy was lower, but the long-term bleeding rate was similar. [ABSTRACT FROM AUTHOR]

Background: Although postoperative portal vein thrombosis (PVT) is a frequent complication of splenectomy, few studies have examined PVT after simultaneous hepatectomy and splenectomy (HS). The aim of this study was to clarify the risk factors for and characteristics of PVT after HS. Methods: This retrospective observational study included 102 patients, including 76 with liver cirrhosis (LC) and 26 without, who underwent HS between April 2004 and April 2021. The incidence and location of postoperative PVT detected on contrast-enhanced CT 1 week after surgery were analyzed. In addition, pre- and intraoperative parameters were compared between patients with postoperative PVT and those without in order to determine risk factors for PVT after HS. Results: Among the 102 patients, 29 (28.4 %), including 32.9 % with LC and 15.4 % without LC, developed PVT after surgery. Among the 29 patients with PVT, 21 (72.4 %), 4 (13.8 %), and 4 (13.8 %) developed thrombus in the intrahepatic portal vein only, extrahepatic portal vein only, and both the extra- and intrahepatic portal veins, respectively. Multivariable analysis showed that preoperative splenic vein dilatation was an independent risk factor for PVT after HS (odds ratio: 1.53, 95 % confidence interval: 1.156–2.026, P = 0.003). Conclusion: Our results suggest that splenic vein dilatation is an independent risk factor for PVT after simultaneous HS, and that PVT after HS occurs more frequently in the intrahepatic portal vein. After HS for cases with dilated splenic veins, we should pay particular attention to the PVT development in the intrahepatic portal vein regardless of the type of liver resection.

The clinical course of patients with chronic hemolytic anemia can be complicated by the development of splenomegaly and consequent hypersplenism. This may warrant management by medical or surgical methods. Furthermore, in some patients, splenic manipulation may be warranted in the absence of hypersplenism, spleen being the primary site of red cell destruction. Wherever possible, splenectomy is avoided or deferred in view of the life-long risks of infection and thrombosis associated with this procedure. Optimal management in hemolytic anemia, therefore, incorporates prevention of hypersplenism as one of the key treatment goals.

Objective: Unusual clinical course Background: Hypersplenism, the rapid and premature destruction of blood cells, encompasses a triad of splenomegaly, cytopenias (anemia, leukopenia, or thrombocytopenia), and compensatory bone marrow proliferation. Secondary hypersplenism results from non-intrinsic splenic diseases, such as hemoglobinopathies. Sickle cell disease consists of a group of genotypes, where hemoglobin sickle C disease (HbSC) is the inheritance of hemoglobin S with hemoglobin C. Most homozygous genotypes undergo complete auto-splenectomy by age 6 years, whereas those with HbSC disease rarely do. We report a rare case of hypersplenism and massive splenomegaly in an adult with sickle cell disease, the HbSC genotype, requiring splenectomy. Case Report: A 41-year-old woman with known splenomegaly initially presented to the general surgery clinic for management of abdominal pain. She was found to have anemia, indicating cytopenia likely from hypersplenism. Consequently, she underwent splenic artery embolization, followed by an exploratory laparotomy and splenectomy, with an unremarkable postoperative course. Conclusions: Acute splenic sequestration crisis can result from hypersplenism, a potentially fatal complication of sickle hemoglobinemia. The continuous cycle of sickled cell entrapment and stasis causes numerous splenic infarctions, forming splenic parenchymal scar tissue which reduces the spleen’s size and functionality – the process of auto-splenectomy. Adults rarely experience these crises past adolescence, which are secondary to the scarring and atrophy from premature auto-splenectomy. Our patient’s spleen measured 21.1 cm, larger than the average adult’s spleen. In our case, adjunctive preoperative splenic artery embolization likely contributed to decreased intraoperative blood loss during splenectomy, mitigating the need for perioperative transfusions. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated portal hypertension (PHT) and its predictors among native liver survivors (NLS) of biliary atresia (BA) after Kasai portoenterostomy (KPE). Methods: This was a multicenter study using prospectively collected data. The subjects were patients who remained transplant-free for 5 years after KPE. Their status of PHT was evaluated and variables that predicted PHT were determined by regression analysis and receiver operating characteristic (ROC) curve. Results: Six centers from East Asia participated in this study and 320 subjects with KPE between 1980 to 2018 were analyzed. The mean follow-up period was 10.6 ± 6.2 years. At the 5th year after KPE, PHT was found in 37.8% of the subjects (n = 121). Patients with KPE done before day 41 of life had the lowest percentage of PHT compared to operation at older age. At 12 months after KPE, PHT + ve subjects had a higher bilirubin level (27.1 ± 11.7 vs 12.3 ± 7.9 µmol/L, p = 0.000) and persistent jaundice conferred a higher risk for PHT (OR = 12.9 [9.2–15.4], p = 0.000). ROC analysis demonstrated that a bilirubin level above 38 µmol/L at 12 months after KPE predicted PHT development (sensitivity: 78%, specificity: 60%, AUROC: 0.75). Conclusions: In BA, early KPE protects against the development of PHT among NLSs. Patients with persistent cholestasis at one year after KPE are at a higher risk of this complication. They should receive a more vigilant follow-up. Level of evidence: Level III [ABSTRACT FROM AUTHOR]

IntroductionPortal hypertension combined with hypersplenism (PHcH) is the main cause of hypocytosis and esophagogastric variceal hemorrhage in patients with liver cirrhosis. Activated macrophages that destroy excess blood cells are the main cause of hypersplenism, but the activating pathway is not very clear. This study aims to investigate the activation types of splenic macrophages and their activation mechanisms, to provide experimental evidence for the biological treatment of splenomegaly, and to find a strategy to improve liver fibrosis and inflammation by intervening in splenic immune cells. This study revealed the occurrence of M2-like polarization of macrophages and upregulation of c-Myc gene expression in the PH spleen.MethodsRNAseq, protein chip, western blot, and chip-seq were performed on macrophages and the in vitro MEK inhibitor rafametinib was used. Carbon tetrachloride and thioacetamide induced mouse cirrhosis models were separately constructed.Resultsc-Myc gene knockout in splenic macrophages reduced M2-like polarization and exacerbated liver fibrosis inflammation. c-Myc activated the MAPK signaling pathway and upregulated the expression of IL-4 and M2-like related genes in PH hypersplenism through the MEK-ERK-c-Myc axis. In addition, the c-Myc gene exerted anti-inflammatory effects by upregulating IL-4-mediated signal transduction to promote M2-like differentiation and anti-inflammatory cytokine secretion.ConclusionsActivation of MEK‐ERK‐c‐MYC signaling pathway promotes splenic M2-like macrophage polarization to inhibit PHcH-liver cirrhosis. Therefore, the induction of macrophage depolarization might represent a new therapeutic approach in the cure of PH hypersplenism, making c-Myc a potential candidate for macrophage polarization therapy.

Wei Hong,1,2 Zizhuo Wang,1,2 Wei Yao,1,2 Xin Zhang,1,2 Lijie Zhang,1,2 Bin Liang1,2 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Hubei Key Laboratory of Molecular Imaging, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Bin Liang, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, People’s Republic of China, Tel +86 27 85726432, Fax +86 27 85727002, Email bliang@hust.edu.cnAim: Partial splenic embolization (PSE) combined with transarterial chemoembolization (TACE) has been reported in treatment of hepatocellular carcinoma (HCC) with cirrhotic hypersplenism and thrombocytopenia. However, efficacy and safety of repeated PSE when required are unclear. This study aims to investigate post-procedural changes in peripheral blood cell and hepatic function, progression-free survival (PFS), and safety of HCC patients with hypersplenism received TACE and repeated PSE compared to those received TACE alone.Methods: This retrospective study included 102 HCC patients with hypersplenism who received TACE (n = 73) or TACE+PSE (n = 29) from January 2014 to December 2021. Changes in peripheral blood cell and hepatic function were investigated at 1 week, 2, 6, 12, 18, and 24 months. TACE procedure sessions and adverse events were recorded. PFS and prognostic factors were analyzed.Results: Despite response to initial PSE being limited, repeated PSE increased platelet (PLT) again, which peaked at 18 months. It also continued to improve red blood cell (RBC) and hemoglobin, which showed significant differences in changes from baseline between two groups until 24 months, as well as Child-Pugh scores at 12 and 18 months. Mean TACE procedure sessions were significantly higher in TACE+PSE group than that in TACE alone group (4.55 vs 3.26, P = 0.019). TACE+PSE group had longer median PFS (19.4 vs 9.5 months, P = 0.023) than TACE alone group, where PSE was an independent protective factor (HR, 0.508; P = 0.014). Initial and repeated PSE showed no significant differences in safety.Conclusion: Repeated PSE is effective in increasing PLT again and improving RBC, hemoglobin and liver function. It contributed to performing serial TACE procedures thereafter. TACE combined with repeated PSE has significantly longer PFS than TACE alone, where PSE was an independent protective factor. Moreover, the safety of repeated PSE was comparable to initial PSE.Keywords: hepatocellular carcinoma, hypersplenism, transarterial chemoembolization, partial splenic embolization

Portal hypertension refers to a range of complications that arise from elevated pressure in the portal vein system, which can be caused by various factors. The primary causes of portal hypertension are cirrhosis induced by viral hepatitis and non-cirrhotic factors such as Budd-Chiari syndrome, portal cavernous transformation, and regional portal hypertension. Patients with portal hypertension experience increased blood flow and resistance in the portal vein, leading to enlargement of the spleen and increased splenic function. This, in turn, can result in a decrease in blood cells and an overgrowth of bone marrow hematopoietic cells, leading to complications like anemia, bleeding, and infection. The treatment for splenomegaly induced by portal hypertension involves both medical and surgical approaches, with surgical treatment being the primary method. This article provides an overview of the common treatment options for splenomegaly caused by portal hypertension. [ABSTRACT FROM AUTHOR]

Alterations in blood cell counts are the most prominent and recurrent clinical findings among patients suffering from both acute and chronic liver disease. These changes are an important marker of liver failure and often play a key role in the evaluation and management of these patients. Together with the prolongation of coagulation tests, thrombocytopenia is the most common disorder among these individuals. This condition, as well as leukopenia, is largely attributable to hypersplenism, a disorder in which the spleen retains and destroys blood cells, including platelets. However, when the platelet count drops below 10x103/µl, it is essential to consider other causes, such as autoimmune factors that may be contributing to the development of thrombocytopenia. Anemia, defined as a decrease in red blood cell count or hemoglobin levels, is another common characteristic of liver disease. Although in most cases macrocytic anemia occurs, in some situations it can be secondary to hemolytic events, as observed in Zieve's syndrome. This wide range of manifestations of anemia among liver patients highlights the complex interaction between liver and blood components. Despite advances in understanding the underlying causes of these cytopenias, treatment options remain limited. Therapeutic options generally focus on the transfusion of blood products to compensate for deficiencies in cell counts or on the use of thrombopoietin (TPO) analogues to temporarily stimulate platelet production in the bone marrow. However, these treatments tend to address the symptoms rather than the root causes of hematologic disorders in liver disease. The persistence and worsening of these disorders may serve as early indicators of the progression of liver failure. The complicated relationship between liver and hematological homeostasis remains the subject of research. A deeper understanding of these mechanisms could potentially open the door toward more targeted and effective therapeutic approaches to address cytopenias in the context of liver disease. [ABSTRACT FROM AUTHOR]

Abstract Background Visceral leishmaniasis (VL), or kala-azar, is a common comorbidity in patients with AIDS in endemic areas. Many patients continue to experiences relapses of VL despite virological control, but with immunological failure. These patients remain chronically symptomatic with hypersplenism, for example with anemia, leukopenia, and thrombocytopenia, and are at risk of severe co-infection due to low CD4+ count. Therefore, in this study, splenectomized patients with VL and HIV infection were investigated to understand why the CD4+ count fails to recover in these patients, evaluating the importance of spleen mass for hypersplenism and immunological failure. Methods From a retrospective open cohort of 13 patients who had previously undergone splenectomy as salvage therapy for relapsing VL, 11 patients with HIV infection were investigated. This study compared the patients’ complete blood cell count (CBC) and CD4+ and CD8+ cell counts before and after splenectomy with respect to spleen weight. Results CBC was substantially improved after splenectomy, indicating hypersplenism. However, to the best of our knowledge, this is the first study to show that spleen mass is strongly and negatively correlated with CD4+ cell count (ρ = −0.71, P = 0.015). Conclusions This finding was unexpected, as the spleen is the most extensive lymphoid tissue and T-lymphocyte source. After reviewing the literature and reasoning, we hypothesized that the immunological failure was secondary to CD4+ loss initially by apoptosis in the spleen induced by productive HIV infection and, subsequently, by pyroptosis sustained by parasitic infection in spleen macrophages. Graphical Abstract

Cardia cancer patients complicated with cirrhosis，hypersplenism，and portal hypertension constantly have contraindications to systemic drugs such as chemotherapy due to poor liver function，and surgery has become the preferred treatment for patients with such cardia tumors. Evaluation of surgical indications，optimization of surgical regimen，and perioperative management strategy are key factors for safe and successful implementation of these surgeries. Here，we reported a 65-year-old male patient undergoing laparoscopic splenectomy plus pericardiac vascularization combined with radical resection of cardiac carcinoma. Satisfactory clinical efficacy was obtained. He could eat semi-liquid diet at 2 weeks after surgery. During over 1-year follow-up，the patient was generally in good condition，could eat normal diet，and the white blood cell，red blood cell and platelet were restored normal. Liver function was normal，and no thrombosis was seen on portal ultrasound. This case prompts that for cardia cancer patients complicated with cirrhosis，hypersplenism，esophago-gas-tric fundal varices，esophageal stricture，this surgical regimen provides novel therapeutic ideas，which can be utilized as a safe and effective treatment option.

PURPOSE: Portal hypertension (PHT) and its sequelae are the most clinically important manifestations in cystic fibrosis-related liver disease (CFLD). This paper aimed to evaluate the safety and efficacy of a pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) to prevent PHT-related complications in pediatric patients with CFLD. METHODS: This was a prospective single-arm study on pediatric patients with CFLD, signs of PHT, and preserved liver function who underwent a pre-emptive TIPS in a single tertiary CF center between 2007 and 2012. The long-term safety and clinical efficacy were assessed. RESULTS: A pre-emptive TIPS was performed on seven patients with a mean age of 9.2 years (± standard deviation: 2.2). The procedure was technically successful in all patients, with an estimated median primary patency of 10.7 years [interquartile range (IQR) 0.5–10.7)]. No variceal bleeding was observed during the median follow-up of 9 years (IQR 8.1–12.9). In two patients with advanced PHT and rapidly progressive liver disease, severe thrombocytopenia could not be stopped. Subsequent liver transplantation revealed biliary cirrhosis in both patients. In the remaining patients with early PHT and milder porto-sinusoidal vascular disease, symptomatic hypersplenism did not occur, and liver function remained stable until the end of the follow-up. Inclusion for pre-emptive TIPS was discontinued in 2013 following an episode of severe hepatic encephalopathy. CONCLUSION: TIPS is a feasible treatment with encouraging long-term primary patency to avoid variceal bleeding in selected patients with CF and PHT. However, as the progression of liver fibrosis, thrombocytopenia, and splenomegaly is inevitable, the clinical benefits due to pre-emptive placement appear to be minor.

Background and Aims: The transjugular intrahepatic portosystemic shunt has controversial survival benefits; thus, patient screening should be performed preoperatively. In this study, we aimed to develop a model to predict post-transjugular intrahepatic portosystemic shunt mortality to aid clinical decision making. Methods: A total of 811 patients undergoing transjugular intrahepatic portosystemic shunt from five hospitals were divided into the training and external validation data sets. A modified prediction model of post-transjugular intrahepatic portosystemic shunt mortality (ModelMT) was built after performing logistic regression. To verify the improved performance of ModelMT, we compared it with seven previous models, both in discrimination and calibration. Furthermore, patients were stratified into low-, medium-, high- and extremely high-risk subgroups. Results: ModelMT demonstrated a satisfying predictive efficiency in both discrimination and calibration, with an area under the curve of .875 in the training set and .852 in the validation set. Compared to previous models (ALBI, BILI-PLT, MELD-Na, MOTS, FIPS, MELD, CLIF-C AD), ModelMT showed superior performance in discrimination by statistical difference in the Delong test, net reclassification improvement and integrated discrimination improvement (all p < .050). Similar results were observed in calibration. Low-, medium-, high- and extremely high-risk groups were defined by scores of ≤160, 160--180, 180--200 and >200, respectively. To facilitate future clinical application, we also built an applet for ModelMT. Conclusions: We successfully developed a predictive model with improved performance to assist in decision making for transjugular intrahepatic portosystemic shunt according to survival benefits. [ABSTRACT FROM AUTHOR]

Objective NR5A1 is a key regulator of sex differentiation and has been implicated in spleen development through transcription activation of TLX1. Concerns exist about hypo- or asplenism in individuals who have a difference of sex development (DSD) due to an NR5A1 disease-causing variant. We aimed to assess spleen anatomy and function in a clinical cohort of such individuals and in their asymptomatic family member carriers. Design Cross-sectional assessment in 22 patients with a DSD or primary ovarian insufficiency and 5 asymptomatic carriers from 18 families, harboring 14 different NR5A1 variants. Methods Spleen anatomy was assessed by ultrasound, spleen function by peripheral blood cell count, white blood cell differentiation, percentage of nonswitched memory B cells, specific pneumococcal antibody response, % pitted red blood cells, and Howell–Jolly bodies. Results Patients and asymptomatic heterozygous individuals had significantly decreased nonswitched memory B cells compared to healthy controls, but higher than asplenic patients. Thrombocytosis and spleen hypoplasia were present in 50% of heterozygous individuals. Four out of 5 individuals homozygous for the previously described p.(Arg103Gln) variant had asplenia. Conclusions Individuals harboring a heterozygous NR5A1 variant that may cause DSD have a considerable risk for functional hyposplenism, irrespective of their gonadal phenotype. Splenic function should be assessed in these individuals, and if affected or unknown, prophylaxis is recommended to prevent invasive encapsulated bacterial infections. The splenic phenotype associated with NR5A1 variants is more severe in homozygous individuals and is, at least for the p.(Arg103Gln) variant, associated with asplenism. [ABSTRACT FROM AUTHOR]

Cardia cancer patients complicated with cirrhosis, hypersplenism, and portal hypertension constantly have contraindications to systemic drugs such as chemotherapy due to poor liver function, and surgery has become the preferred treatment for patients with such cardia tumors. Evaluation of surgical indications, optimization of surgical regimen, and perioperative management strategy are key factors for safe and successful implementation of these surgeries. Here, we reported a 65-year-old male patient undergoing laparoscopic splenectomy plus pericardiac vascularization combined with radical resection of cardiac carcinoma. Satisfactory clinical efficacy was obtained. He could eat semi-liquid diet at 2 weeks after surgery. During over 1-year follow-up, the patient was generally in good condition, could eat normal diet, and the white blood cell, red blood cell and platelet were restored normal. Liver function was normal, and no thrombosis was seen on portal ultrasound. This case prompts that for cardia cancer patients complicated with cirrhosis, hypersplenism, esophago-gas-tric fundal varices, esophageal stricture, this surgical regimen provides novel therapeutic ideas, which can be utilized as a safe and effective treatment option. [ABSTRACT FROM AUTHOR]

PURPOSE Portal hypertension (PHT) and its sequelae are the most clinically important manifestations in cystic fibrosis-related liver disease (CFLD). This paper aimed to evaluate the safety and efficacy of a pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) to prevent PHT-related complications in pediatric patients with CFLD. METHODS This was a prospective single-arm study on pediatric patients with CFLD, signs of PHT, and preserved liver function who underwent a pre-emptive TIPS in a single tertiary CF center between 2007 and 2012. The long-term safety and clinical efficacy were assessed. RESULTS A pre-emptive TIPS was performed on seven patients with a mean age of 9.2 years (± standard deviation: 2.2). The procedure was technically successful in all patients, with an estimated median primary patency of 10.7 years [interquartile range (IQR) 0.5-10.7)]. No variceal bleeding was observed during the median follow-up of 9 years (IQR 8.1-12.9). In two patients with advanced PHT and rapidly progressive liver disease, severe thrombocytopenia could not be stopped. Subsequent liver transplantation revealed biliary cirrhosis in both patients. In the remaining patients with early PHT and milder porto-sinusoidal vascular disease, symptomatic hypersplenism did not occur, and liver function remained stable until the end of the follow-up. Inclusion for pre-emptive TIPS was discontinued in 2013 following an episode of severe hepatic encephalopathy. CONCLUSION TIPS is a feasible treatment with encouraging long-term primary patency to avoid variceal bleeding in selected patients with CF and PHT. However, as the progression of liver fibrosis, thrombocytopenia, and splenomegaly is inevitable, the clinical benefits due to pre-emptive placement appear to be minor. [ABSTRACT FROM AUTHOR]

Splenic artery embolization plays an important role in the management of various medical and surgical conditions that are non-traumatic in etiology, in addition to its well-established and widely discussed role in managing splenic trauma. In nontraumatic emergencies of catastrophic bleeding originating from the spleen or splenic artery, splenic artery embolization can be effective in achieving hemostasis as a definitive management, temporary stabilizing measure, or preoperative optimization technique. In addition to emergency clinical conditions, splenic artery embolization can be performed electively as an alternative to splenectomy for managing patients with hypersplenism. Herein, we report 6 cases of splenic artery embolization performed at our center to highlight its various indications. This article aims to demonstrate the role of splenic artery embolization in different clinical scenarios and the considerations behind the techniques employed through illustrative cases.

In this study, we report an unprecedented case of graft failure following hematopoietic stem cell transplantation (HSCT) in a patient with a myeloproliferative neoplasm (MPN) who had achieved bone marrow (BM) remission. We outline the intricate cellular components of splenic hematopoiesis, which are derived from both the recipient and the donor, underpinning the persistence of fibrosis. Our investigation characterizes the distinct cellular populations that play a pivotal role in graft exhaustion and introduces an unusual hypothesis regarding the perpetuation of a malignant niche in extramedullary sites within the context of HSCT.

Hypersplenism, although a rare hematological complication seen in chronic kidney disease patients, poses a significant challenge for successful kidney transplantation due to potential complications such as cytopenias and inadequate immunosuppressive therapy. We present a 40-year old end-stage kidney disease patient on dialysis with hypersplenism who underwent a laparoscopic splenectomy prior to high immunological risk renal transplantation. Post-splenectomy, there was a remarkable improvement in cytopenias, and effective immunosuppressive therapy could be administered prior to renal transplantation. Splenectomy remains a valuable strategy for managing hypersplenism, ensuring correction of cytopenias, for optimal immunosuppression prior to kidney transplantation. Pre-transplant vaccination further mitigates the risk infections with capsulated organisms. Our case underscores the importance of a multidisciplinary approach in decision-making and highlights splenectomy as a safe and effective intervention to address cytopenias due to hypersplenism prior to renal transplantation. [ABSTRACT FROM AUTHOR]

Background: Sickle cell disease (SCD) patients encounter various complications, such as acute splenic sequestration crisis and hypersplenism that may require splenectomy. This systematic review and meta-analysis aims to clarify differences between total splenectomy (TS) or partial splenectomy (PS) in terms of hematological and postoperative outcomes., Methods: We identified studies involving SCD patients who underwent PS or TS, whether open or laparoscopic, and whose hematological and operative outcomes were evaluated, through searching PubMed, Web of Science, Scopus, Embase and Cochrane databases from inception until June 2024., Primary Outcomes: hemoglobin concentration and reticulocytes %., Secondary Outcomes: operative blood transfusion need, length of hospital stay (LoS), postoperative infections, overwhelming postsplenectomy sepsis (OPSS), acute chest syndrome (ACS), thromboembolic events and mortality., Results: Eighteen studies were included; 17 cohort and one case series. Seven studies collected data from the same SICHA institutions, so a total of 756 SCD patients is included. According to the most recent study, no significant changes in hemoglobin (preoperative 10.5 ± 0.3 vs 9.6 ± 0.4 one year postoperative in 24 PS cases, and 9.7 ± 0.1 vs 9.7 ± 0.2 in 73 TS cases), however, both TS and PS significantly decreased reticulocyte by 2 % (0.8-3.2 %). Proportional analysis of short-term infection revealed a lower incidence in TS 2.71 % vs 8.64 % in PS, and similarly for ACS, it is 6.97 % in TS vs 14.90 % in PS., Conclusion: This first systematic review and meta-analysis shows that TS and PS have no or minimal effect on hemoglobin but a strong lowering effect on reticulocyte %. Proportional analysis reveals lower short-term infections and ACS following TS than PS. However, further clinical trials are necessary to draw definite conclusions and improve surgical decision making., Type of Study: Systematic review and meta-analysis of cohort studies., Level of Evidence: II., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The clearance of senescent and altered red blood cells (RBCs) in the red pulp of the human spleen involves sequential processes of prefiltration, filtration, and postfiltration. While prior work has elucidated the mechanisms underlying the first two processes, biomechanical processes driving the postfiltration phagocytosis of RBCs retained at interendothelial slits (IES) are still poorly understood. We present here a unique computational model of macrophages to study the role of cell biomechanics in modulating the kinetics of phagocytosis of aged and diseased RBCs retained in the spleen. After validating the macrophage model using in vitro phagocytosis experiments, we employ it to probe the mechanisms underlying the kinetics of phagocytosis of mechanically altered RBCs, such as heated RBCs and abnormal RBCs in hereditary spherocytosis (HS) and sickle cell disease (SCD). Our simulations show pronounced deformation of the flexible and healthy RBCs in contrast to minimal shape changes in altered RBCs. Simulations also show that less deformable RBCs are engulfed faster and at lower adhesive strength than flexible RBCs, consistent with our experimental measurements. This efficient sensing and engulfment by macrophages of stiff RBCs retained at IES are expected to temper splenic congestion, a common pathogenic process in malaria, HS, and SCD. Altogether, our combined computational and in vitro experimental studies suggest that mechanical alterations of retained RBCs may suffice to enhance their phagocytosis, thereby adapting the kinetics of their elimination to the kinetics of their mechanical retention, an equilibrium essential for adequately cleaning the splenic filter to preserve its function., Competing Interests: Competing interests statement:The authors declare no competing interest.

Rationale and Objectives: A consensus has not yet been reached regarding the optimal timing for the combination of transjugular intrahepatic portosystemic shunt (TIPS) and partial splenic embolization (PSE) in patients with cirrhosis-related variceal bleeding and hypersplenism. This study aimed to compare the clinical outcomes of patients who underwent either an early or late combination of TIPS and PSE., Methods: A total of 84 consecutive patients with cirrhosis-related variceal bleeding and hypersplenism who underwent TIPS and PSE between September 2016 and April 2023 were included in this retrospective multicenter study. These patients were subsequently divided into early combination (n = 36) and late combination (n = 48) groups based on the timing of the combination therapy., Results: Kaplan-Meier curves revealed a significant increase in cumulative survival in the late combination group, compared with that in the early combination group (log-rank P = 0.018). Additionally, the late combination group exhibited a lower cumulative incidence of overt hepatic encephalopathy (OHE), compared with the early combination group (log-rank P = 0.002). In Cox regression models, noninfarcted splenic volume (hazard ratio [HR] = 0.995, 95% confidence interval [CI] = 0.991-0.999, P = 0.044) and grouping (HR = 0.101, 95% CI = 0.011-0.921, P = 0.034) were identified as independent risk factors for mortality. Furthermore, the independent risk factors for OHE were serum albumin (ALB) level (P = 0.032) and grouping (P = 0.028)., Conclusion: The early combination of TIPS and PSE was associated with higher risks of death and OHE than the late combination., Competing Interests: Declaration of Competing Interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: To delineate the natural history of splenic complications other than loss of splenic function in children with sickle cell disease (SCD), we performed a retrospective chart review of patients with SCD treated at the Texas Children's Hospital., Methods: We determined the dates of diagnoses of splenic complications, the number of acute splenic sequestration crises (ASSC), and hydroxyurea treatment in pediatric patients with SCD. We also examined the association of hydroxyurea therapy with the onset and severity of ASSC., Results: The cumulative prevalence of splenic complications was 24.7% for splenomegaly, 24.2% for ASSC, 9.6% for hypersplenism, and 5.6% for splenectomy. The cumulative prevalence of splenic complications was highest in patients with hemoglobin Sβ 0 (69.2%), intermediate in hemoglobin SS (33.3%), low in hemoglobin SC (9.0%), and non-existent in hemoglobin Sβ + . The overall event rate of ASSC was 8.3 per 100 patient-years. The event-rate was 28.4 for hemoglobin Sβ 0 , 10.9 for hemoglobin SS, and 3.5 for hemoglobin SC. Patients with hemoglobin SS and hemoglobin Sβ 0 on hydroxyurea therapy had a significantly higher occurrence of ASSC than those who were not, with event rates of 14.2 and 3.1, respectively. The event rate was also higher for children who started hydroxyurea before age 2 years than for those who started after this age (19.8 and 9.2, respectively)., Conclusions: The prevalence and severity of splenic problems vary widely between different sickle cell genotypes, with hemoglobin Sβ 0 having the most severe complications. Hydroxyurea therapy is associated with increased incidence of ASSC, particularly when initiated before 2 years of age., (© 2024 Wiley Periodicals LLC.)

Partial splenic artery embolization (PSAE) is an alternative treatment modality for managing hypersplenism secondary to portal hypertension. We are presenting a case series of patients with portal hypertension who underwent PSAE for symptomatic hypersplenism. We included patients with portal hypertension who underwent PSAE from January 2022 to December 2022. Patients' characteristics and procedure related complications were noted. Data were analyzed for improvement in the hematological parameters. A total of 11 (7 women, median age 34 [18–56] years) patients were included. Three patients were cirrhotic (hepatitis B-2, metabolic dysfunction–associated steatotic liver disease −1) and 8 were non-cirrhotic (extra-hepatic portal vein obstruction-5, Non cirrhotic portal fibrosis-3). Splenic artery aneurysm was concomitantly present in 5 cases. Technical success was achieved in all cases. Post embolization, hemoglobin, white blood cells and platelet counts improved at 4 weeks, 12 weeks and 24 weeks along with symptomatic improvement. All patients had post-embolization syndrome. One patient developed transient ascites and secondary bacterial peritonitis which was managed conservatively. One patient died due to splenic abscess and septicemia. Although, hematological parameters and symptoms improve post procedure, PSAE is associated with major complications and should be performed judiciously in selected cases only. Graphical abstract is presented in Figure 1. [ABSTRACT FROM AUTHOR]

Aneurysms of the splenic artery are the third most common type of intra-abdominal aneurysms and the most common type of visceral aneurysms. Portal hypertension is a significant risk factor for development of these aneurysms. We report the case of a white, female, 52-year-old patient with multiple splenic artery aneurysms and hypersplenism secondary to portal hypertension and cirrhosis. Abdominal angiotomography identified six splenic aneurysms. In this scenario, an endovascular intervention was scheduled to conduct embolization using controlled release coils and Onyx™ embolization agent. The three largest aneurysms were treated. Control angiographs showed good exclusion of the aneurysms. The endovascular technique therefore proved to be a good choice considering the patient's comorbidities and blood disorders. In this case, the procedure was successful. There were no immediate or long-term complications. The patient recovered well and is in clinical follow-up., Competing Interests: Conflicts of interest: No conflicts of interest declared concerning the publication of this article., (Copyright© 2024 The authors.)

Introduction Beta thalassemia is a hemoglobinopathy characterized by defective production of the beta chain of hemoglobin, leading to irreversible destruction of RBCs, splenomegaly, pancytopenia, and a requirement for multiple transfusions. This condition necessitates iron chelation therapy, and splenectomy is often performed to manage hypersplenism. Methods This report includes a series of seven diagnosed cases of beta thalassemia with hypersplenism, all of whom underwent open splenectomy. Preoperative transfusions were administered to achieve target hemoglobin and platelet counts of 9 g/dL and 50,000/µL, respectively. Results The study included seven patients diagnosed with beta thalassemia, all of whom underwent open splenectomy. Among these, three patients also had concomitant cholecystectomy due to the presence of gallstones. The primary indication for performing splenectomy was hypersplenism. Preoperative transfusions were administered to ensure target hemoglobin levels of 9 g/dL and platelet counts of 50,000/µL. All patients were successfully discharged with minimal morbidity and no reported mortality. The longest follow-up period observed in this series was 10 months post-splenectomy, which limited the assessment of long-term effects. Conclusion Open splenectomy for hypersplenism in patients with beta thalassemia appears to be a safe and effective procedure with minimal short-term morbidity and no mortality observed in this series. However, due to the limited follow-up duration, the long-term effects of splenectomy in these patients could not be evaluated. Further studies with longer follow-up are needed to assess the long-term outcomes of splenectomy in beta thalassemia patients., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Tata Main Hospital Institutional Ethical Committee (TMH/IEC) issued approval TMH/IEC/MAY/150/2024. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kumar et al.)

Splenic artery embolization plays an important role in the management of various medical and surgical conditions that are non-traumatic in etiology, in addition to its well-established and widely discussed role in managing splenic trauma. In nontraumatic emergencies of catastrophic bleeding originating from the spleen or splenic artery, splenic artery embolization can be effective in achieving hemostasis as a definitive management, temporary stabilizing measure, or preoperative optimization technique. In addition to emergency clinical conditions, splenic artery embolization can be performed electively as an alternative to splenectomy for managing patients with hypersplenism. Herein, we report 6 cases of splenic artery embolization performed at our center to highlight its various indications. This article aims to demonstrate the role of splenic artery embolization in different clinical scenarios and the considerations behind the techniques employed through illustrative cases.

Background: Partial splenic embolization (PSE) has been proposed to treat the consequences of hypersplenism in the context of portal hypertension, especially thrombocytopenia. However, a high morbidity/mortality rate has made this technique unpopular. We conducted a multicenter retrospective nationwide French study to reevaluate efficacy and tolerance., Methods: All consecutive patients who underwent PSE for hypersplenism and portal hypertension in 7 tertiary liver centers between 1998 and 2023 were included., Results: The study population consisted of 91 procedures in 90 patients, with a median age of 55.5 years [range 18-83]. The main cause of portal hypertension was cirrhosis (84.6 %). The main indications for PSE were (1) an indication of medical treatment or radiological/surgical procedure in the context a severe thrombocytopenia (59.3 %), (2) a chronic hemorrhagic disorder associated with a severe thrombocytopenia (18.7 %), and (3) a chronic pain associated with a major splenomegaly (9.9 %). PSE was associated with a transjugular intrahepatic portosystemic shunt in 20 cases. Median follow-up after PSE was 41.9 months [0.5-270.5]. Platelet count increased from a median of 48.0 G/L [IQR 37.0; 60.0] to 100.0 G/L [75.0; 148]. Forty-eight patients (52.7 %) had complications after PSE; 25 cases were considered severe (including 7 deaths). A Child-Pugh B-C score (p < 0.02) was significantly associated with all complications, a history of portal vein thrombosis (p < 0.01), and the absence of prophylactic antibiotherapy (p < 0.05) with severe complications., Conclusion: Our results strongly confirm that PSE is very effective, for a long time, although a quarter of the patients experienced severe complications. Improved patient selection (exclusion of patients with portal vein thrombosis and decompensated cirrhosis) and systematic prophylactic antibiotherapy could reduce morbidity and early mortality in the future., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objective: To compare clinical outcomes of superior versus inferior splenic artery embolization in partial splenic embolization (PSE) and identify predictors of major complications. Material and methods: This retrospective case-control study included 73 patients who underwent PSE between May 2005 and April 2021. They were divided into two groups: the superior and middle splenic artery embolization group (Group A, n  = 37) and the inferior and middle splenic artery embolization group (Group B, n  = 36). Outcome differences and major complications between the groups were assessed. Logistic regression was used to analyze potential predictors of major complications, and the optimal cutoff value for splenic embolization rates was determined using the Youden index. Results: There were no significant differences in laboratory and radiological outcomes between the two groups. Group A had a significantly lower incidence of major complications than Group B ( p  = 0.049), a lower Visual Analog Scale (VAS) score for pain ( p  = 0.036), and a shorter hospital stay ( p  = 0.022). Independent risk factors for major complications included inferior and middle splenic artery embolization (odds ratio [OR] = 3.672; 95% confidence interval [CI] = 1.028-13.120; p  = 0.045) and a higher spleen embolization rate (OR = 1.108; 95% CI = 1.003-1.224; p  = 0.044). The optimal cutoff for spleen embolization rate to predict major complications was 59.93% (sensitivity 77.8%, specificity 63.6%). Conclusion: Using 500-700 µm microspheres for PSE, targeting the middle and superior splenic artery yields similar effects to targeting the middle and inferior artery, but results in lower rates of major complications and shorter hospital stays. To effectively minimize the risk of major complications, the embolization rate should be kept below 59.93%, regardless of the target vessel.

Background: Total and partial splenectomy are used in pediatric patients with hereditary spherocytosis to resolve anemia and hemolytic complications., Procedure: Data from the Healthcare Cost and Utilization Project's Kid's Inpatient Database was used to profile and describe temporal trends in pediatric (≤18 years) hospital admissions in the United States from 2000 to 2019 data release years. Survey sampling methods were used to produce national estimates., Results: From 2000 to 2019, the use of splenectomy declined overall, from 427 to 206 weighted procedures (difference = 222, 95% confidence interval [CI]: 124-320; p < .0001); the risk of undergoing splenectomy during admission also declined from 56.7% to 38.7% (risk difference = 17.9 percentage points [p.p.], 95% CI: 9.7-26.1; p < .0001). Total splenectomy was mostly used. Age at time of splenectomy increased 10.2 years (difference = 1.6 years, 95% CI: 0.6-2.7; p = .0018). The risk of splenectomy increased with age until 10 years, then leveled off until 18 years. The proportion of children aged ≤5 years undergoing splenectomy decreased from 27.7% to 11.2% in 2019 (risk difference: 16.5 p.p., 95% CI: 7.3-25.7; p = .0004). The strongest clinical predictors of splenectomy, adjusting for patient- and hospital-level characteristics, were a co-diagnosis of symptomatic cholelithiasis (adjusted odds ratio [aOR] = 3.18, 95% CI: 1.92-5.28; p < .0001) and splenomegaly or hypersplenism (aOR = 2.52, 95% CI: 1.74-3.65; p < .0001). Risk of splenectomy with splenomegaly or hypersplenism increased over time., Conclusion: Splenectomy was delayed until age greater than 10 years. Older age, co-diagnosis with splenomegaly or hypersplenism, or symptomatic cholelithiasis were strongest clinical predictors of splenectomy. Conservative management of hereditary spherocytosis appears to be more common., (© 2024 Wiley Periodicals LLC.)

Despite the efficacy of splenectomy for chronic immune thrombocytopenia (ITP), its considerable failure rate and its possible related complications prove the need for further research into potential predictors of response. The platelet sequestration site determined by 111 In-labelled autologous platelet scintigraphy has been proposed to predict splenectomy outcome, but without standardisation in clinical practice. Here, we conducted a single-centre study by analysing a cohort of splenectomised patients with ITP in whom 111 In-scintigraphy was performed at La Paz University Hospital in Madrid to evaluate the predictive value of the platelet kinetic studies. We also studied other factors that could impact the splenectomy outcome, such as patient and platelet characteristics. A total of 51 patients were splenectomised, and 82.3% responded. The splenic sequestration pattern predicted a higher rate of complete response up to 12 months after splenectomy (p = 0.005), with 90% sensitivity and 77% specificity. Neither age, comorbidities, therapy lines nor previous response to them showed any association with response. Results from the platelet characteristics analysis revealed a significant loss of sialic acid in platelets from the non-responding patients compared with those who maintained a response (p = 0.0017). Our findings highlight the value of splenic sequestration as an independent predictor of splenectomy response., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)