Investigation of Serum Albumin as a Dynamic Treatment-Specific Surrogate for Outcomes in Patients With Myelofibrosis Treated With Ruxolitinib.

PURPOSE: Ruxolitinib improves splenomegaly and disease-related symptoms in most patients with myelofibrosis (MF), and it has been associated with a survival benefit in higher-risk patients with splenomegaly. Spleen volume reduction has been associated with a survival benefit in ruxolitinib-treated patients; however, its use as a surrogate is limited. We hypothesized that an anti-inflammatory response to ruxolitinib would correlate with improved patient outcomes. METHODS: We interrogated serum albumin, an acute phase reactant and marker of nutritional status in 590 patients with MF and analyzed differential trajectories of albumin on the basis of ruxolitinib treatment. Additionally, we assessed the prognostic role of baseline albumin and change in albumin. RESULTS: We found that serum albumin levels tend to decrease in patients with MF; however, this tendency is abrogated by ruxolitinib treatment. To that end, baseline serum albumin level correlates with overall survival (OS) in patients with MF, independent of the variables that comprise the dynamic international prognostic scoring system; however, this correlation is limited to ruxolitinib-naïve patients. In ruxolitinib-treated patients, the change in serum albumin after ruxolitinib treatment, rather than the baseline value, is associated with improved OS, a finding not seen in ruxolitinib-naïve patients. CONCLUSION: These findings suggest that serum albumin, a ubiquitously available laboratory value, has specific relevance in patients with MF and reflects therapeutic response to ruxolitinib.

[Pathogenesis and Targeted Treatment Progress of Splenomegaly in Primary Myelofibrosis--Review].

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm with splenomegaly as the major clinical manifestation, which is commonly considered to be linked to splenic extramedullary hematopoiesis. Alteration of CXCL12/CXCR4 pathway can lead to the migration of hematopoietic stem cells and hematopoietic progenitor cells from bone marrow to spleen which results in splenic extramedullary hematopoiesis. In addition, low GATA1 expression and the abnormal secretion of cytokines were found to be significantly associated with splenomegaly. With the application of JAK1/2 inhibitors in clinical, the symptoms of splenomegaly have been significantly improved in PMF patients. This article will review the pathogenesis and targeted treatment progress of splenomegaly in PMF.

[Comparison of Clinical Characteristics of JAK2, CALR and Tri-Negative Driving Mutant Type in Patients with Essential Thrombocythemia].

OBJECTIVE: To investigate the relationship between mutated genes and clinical features in patients with essential thrombocythemia (ET). METHODS: The clinical data of 69 patients with ET from October 2018 to March 2022 were retrospectively analyzed. According to driver mutation type, patients were divided into JAK2 group, CALR group and triple-negative group. The sex, age, cardiovascular risk factors, thrombosis, splenomegaly, routine blood test and coagulation status of patients in three groups were analyzed. RESULTS: Among 69 ET patients, 46 cases were associated with JAK2 mutation, 14 cases with CALR mutation, 8 cases with triple-negative mutation, and one with MPL gene mutation. There were no significant differences in age and sex among the three groups (P >0.05). The highest thrombotic rate was 26.09% (12/46) in JAK2 group, then 12.5% (1/8) in triple-negative group, while no thrombotic events occurred in CALR group. The incidence of splenomegaly was the highest in JAK2 group (34.78%), while no splenomegaly occurred in triple-negative group. The white blood cell (WBC) count in JAK2 group was (9.00±4.86)×109/L, which was significantly higher than (6.03±2.32)×109/L in CALR group (P <0.05). The hemoglobin (Hb) and hematocrit (HCT) in JAK2 group were (148.42±18.79) g/L and (0.44±0.06)%, respectively, which were both significantly higher than (131.00±15.17) g/L and (0.39±0.05)% in triple-negative group (P <0.05). The platelet (PLT) in JAK2 group was (584.17±175.77)×109/L, which was significantly lower than (703.07±225.60)×109/L in CALR group (P <0.05). The fibrinogen (Fg) in JAK2 and triple-negative group were (2.64±0.69) g/L and (3.05±0.77) g/L, respectively, which were both significantly higher than (2.24±0.47) g/L in CALR group (P <0.05, P <0.01). The activated partial thromboplastin time (APTT) in triple-negative group was (28.61±1.99) s, which was significantly decreased compared with (31.45±3.35) s in CALR group (P <0.05). CONCLUSIONS: There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations. Among ET patients, JAK2 mutation is most common. Compared with CALR group, the thrombotic rate, WBC and Fg significantly increase in JAK2 group, while PLT decrease. Compared with triple-negative group, the incidence of splenomegaly and HCT significantly increase. Compared with CALR group, Fg significantly increases but APTT decreases in triple-negative group.

Assessing the diagnostic utility of the Gaucher Earlier Diagnosis Consensus (GED-C) scoring system using real-world data.

BACKGROUND: Gaucher disease (GD) is a rare autosomal recessive condition associated with clinical features such as splenomegaly, hepatomegaly, anemia, thrombocytopenia, and bone abnormalities. Three clinical forms of GD have been defined based on the absence (type 1, GD1) or presence (types 2 and 3) of neurological signs. Early diagnosis can reduce the likelihood of severe, often irreversible complications. The aim of this study was to validate the ability of factors from the Gaucher Earlier Diagnosis Consensus (GED-C) scoring system to discriminate between patients with GD1 and controls using real-world data from electronic patient medical records from Maccabi Healthcare Services, Israel's second-largest state-mandated healthcare provider. METHODS: We applied the GED-C scoring system to 265 confirmed cases of GD and 3445 non-GD controls matched for year of birth, sex, and socioeconomic status identified from 1998 to 2022. The analyses were based on two databases: (1) all available data and (2) all data except free-text notes. Features from the GED-C scoring system applicable to GD1 were extracted for each individual. Patients and controls were compared for the proportion of the specific features and overall GED-C scores. Decision tree and random forest models were trained to identify the main features distinguishing GD from non-GD controls. RESULTS: The GED-C scoring distinguished individuals with GD from controls using both databases. Decision tree models for the databases showed good accuracy (0.96 [95% CI 0.95-0.97] for Database 1; 0.95 [95% CI 0.94-0.96] for Database 2), high specificity (0.99 [95% CI 0.99-1]) for Database 1; 1.0 [95% CI 0.99-1] for Database 2), but relatively low sensitivity (0.53 [95% CI 0.46-0.59] for Database 1; 0.32 [95% CI 0.25-0.38]) for Database 2). The clinical features of splenomegaly, thrombocytopenia (< 50 × 109/L), and hyperferritinemia (300-1000 ng/mL) were found to be the three most accurate classifiers of GD in both databases. CONCLUSION: In this analysis of real-world patient data, certain individual features of the GED-C score discriminate more successfully between patients with GD and controls than the overall score. An enhanced diagnostic model may lead to earlier, reliable diagnoses of Gaucher disease, aiming to minimize the severe complications associated with this disease.

Caroli disease combined with Banti syndrome in a woman: a case report.

Caroli disease is a rare congenital malformation that predisposes to segmental cystic dilatation of the intrahepatic bile ducts. Banti syndrome is characterized by persistent splenomegaly due to chronic congestion, resulting in a low hematocrit and ultimately leading to pancytopenia. In this report, we describe a 29-year-old woman who presented with a >20-year history of hepatitis B surface antigen positivity and a >1-year history of recurrent fatigue and malaise. On examination, the patient had abdominal distension with marked splenomegaly (7 cm below the ribs) and ascites with tenderness of the abdominal muscles to palpation. A complete blood count showed a low white blood cell count, red blood cell count, and hemoglobin concentration. During the course of treatment, the patient developed multiple symptoms of pancytopenia and concomitant splenomegaly, and she was discharged after total splenectomy with good recovery. The combination of Banti syndrome and Caroli disease results in severe symptoms of portal hypertension.

Infectious Mononucleosis: An Updated Review.

BACKGROUND: Infectious mononucleosis is common among adolescents and young adults. Although the majority of cases resolve spontaneously, life-threatening manifestations, and complications have been recognised. OBJECTIVE: The purpose of this article is to familiarize clinicians with the clinical manifestations, evaluation, diagnosis, and management of infectious mononucleosis. METHODS: A search was conducted in October 2022 in PubMed Clinical Queries using the key terms "infectious mononucleosis" OR "Epstein-Barr virus" OR "EBV". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the aforementioned search was used in the compilation of the present article. RESULTS: Infectious mononucleosis, caused by Epstein-Barr virus, most commonly affects adolescents and adults aged 15 to 24 years. Epstein-Barr virus is transmitted primarily in saliva. Infectious mononucleosis is characterized by a triad of fever, tonsillar pharyngitis, and lymphadenopathy. Fatigue may be profound but tends to resolve within three months. Periorbital and/or palpebral edema, typically bilateral, occurs in one-third of patients. Splenomegaly and hepatomegaly occur in approximately 50% and 10% of cases, respectively. A skin rash, which is usually widely scattered, erythematous, and maculopapular, occurs in approximately 10 to 45% of cases. Peripheral blood leukocytosis is observed in most patients; lymphocytes make up at least 50% of the white blood cell differential count. Atypical lymphocytes constitute more than 10% of the total lymphocyte count. The classic test for infectious mononucleosis is the demonstration of heterophile antibodies. The monospot test is the most widely used method to detect the serum heterophile antibodies of infectious mononucleosis. When confirmation of the diagnosis of infectious mononucleosis is required in patients with mononucleosis-like illness and a negative mono-spot test, serologic testing for antibodies to viral capsid antigens is recommended. Infectious mononucleosis is a risk factor for chronic fatigue syndrome. Spontaneous splenic rupture occurs in 0.1 to 0.5% of patients with infectious mononucleosis and is potentially life-threatening. Treatment is mainly supportive. Reduction of activity and bed rest as tolerated are recommended. Patients should be advised to avoid contact sports or strenuous exercise for 8 weeks or while splenomegaly is still present. Most patients have an uneventful recovery. CONCLUSION: Infectious mononucleosis is generally a benign and self-limited disease. Prompt diagnosis is essential to avoid unnecessary investigations and treatments and to minimize complications. Splenic rupture is the most feared complication. As avoiding exposure to EBV is almost impossible, the most effective way to prevent EBV infection and infectious mononucleosis is the development of an effective, safe, and affordable EBV vaccine that can confer life-long immunity.

Are transplant indications changing for myelofibrosis?

Myelofibrosis is a devastating myeloid malignancy characterized by dysregulation of the JAK-STAT pathway, resulting in splenomegaly, constitutional symptoms, anemia, thrombocytopenia, leukocytosis, and an increased likelihood of progression to acute leukemia. The only curative option is allogeneic stem cell transplantation. The numbers of transplants have been increasing every year, and although there have been improvements in survival, there remain many unanswered questions. In this review, we will evaluate patient selection and appropriate timing for transplantation. We will cover the current prognostic scoring systems, which can aid in the decision of when to move forward with transplant. We will also review the different donor options, as well as the conditioning regimens. The peritransplant management of splenomegaly will be reviewed. We will discuss management of posttransplant complications such as loss of donor chimerism or disease relapse. Finally, we will review what is known about the outlook of patients who have undergone allogeneic stem cell transplant with regards to quality of life and long-term survival.

Clinical characteristics, treatment, and management of pembrolizumab induced hemophagocytic lymphohistiocytosis.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal adverse reaction to pembrolizumab. The clinical characteristics of pembrolizumab induced HLH are unknown. Exploring the clinical features of pembrolizumab induced HLH is crucial for the treatment and prevention of immune checkpoint inhibitor-induced HLH. METHODS: The literature related to pembrolizumab induced HLH was collected for retrospective analysis by searching the Chinese and English databases from inception until August 31, 2023. RESULTS: A total of 24 patients were included, including 17 men (70.8%) with a median age of 61 years (41,80). The time between the last infusion and the start of HLH ranged from 2 to 46 days, with a median time of 14 days. Fever (100%) was the most common symptom, accompanied by splenomegaly (14 cases, 58.3%) and hepatomegaly (6 cases, 25.0%). Laboratory examination revealed revealed anemia (18 cases, 75.0%), leukopenia (12 cases, 50.0%), thrombocytopenia (20 cases, 83.3%), hypertriglyceridemia (11 cases, 45.8%), hypofibrinogenemia (11 cases, 45.8%). decreased natural killer cell function (7 cases, 29.2%), and elevated soluble CD25(15 cases, 62.5%). All patients developed hyperferriinemia, with a median of 30,808 ng/mL (range 1303 ~ 100,000). Bone marrow biopsy showed hemophagocytosis (15 cases, 62.5%). After discontinuation of pembrolizumab and treatment with steroids, etoposide, intravenous immunoglobulin, cytokine blocking, and immunosuppression, 17 patients recovered or improved, and 5 patients eventually died. CONCLUSION: HLH should be suspected when unexplained fever, cytopenia, splenomegaly, and elevated aminotransferase occur in patients using pembrolizumab. Screening for risk factors before treatment with pembrolizumab may be necessary to prevent HLH.

A case of Hodgkin lymphoma-type Richter syndrome presenting as small-intestinal perforation.

Hodgkin lymphoma type of Richter syndrome (HL-type RS) is a rare disease that arises in patients with chronic lymphocytic leukemia (CLL). HL-type RS lesions can manifest in various sites and are often accompanied by related symptoms. This is the first case report to describe diagnosis of HL-type RS after emergency surgery for gastrointestinal perforation caused by the development of a HL-type RS lesion. A 47-year-old man diagnosed with CLL three years prior began treatment with ibrutinib due to worsening anemia and splenomegaly two months prior to the emergency department presentation. Although splenomegaly improved, lymphocytopenia, anemia, and a newly arising mesenteric lymphadenopathy continued to worsen. He presented to the emergency department with abdominal pain, and subsequent surgery revealed small intestinal perforation and mesenteric lymphadenopathy with HL-type RS confirmed by histopathological examination of the resected small intestine. He subsequently received brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A + AVD), which effectively managed the HL-type RS. If CLL clinical presentation deviates from the typical course, an early tissue biopsy should be considered to evaluate for HL-type RS. Given the adoption of the A + AVD regimen as the standard treatment for Hodgkin lymphoma, further research is needed to evaluate its efficacy in HL-type RS.

[Clinical features of non-cirrhotic portal hypertension in patients with common variable immunodeficiency].

We wished to summarize the clinical features of common variable immunodeficiency (CVID) complicated by non-cirrhotic portal hypertension (NCPH) and to deepen our understanding of it. The case data of CVID complicated with NCPH admitted to Peking Union Medical College Hospital from January 1983 to May 2021 were analyzed retrospectively to summarize their clinical characteristics. Six patients with CVID combined with NCPH (three of each sex; 16-45 years) were assessed. Four patients had portal hypertension. All patients had anemia, splenomegaly, a normal serum level of albumin and transaminases, and possibly increased levels of alkaline phosphatase and gamma-glutamyl transpeptidase. Two patients were diagnosed with esophagogastric fundic varices by gastroscopy. Two patients underwent splenectomy (which improved hematologic abnormalities partially). Four patients had autoimmune disease. Two cases were diagnosed with nodular regenerative hyperplasia (NRH) upon liver biopsy. Six patients were administered intravenous immunoglobulin-G (0.4-0.6 g/kg bodyweight) once every 3-4 weeks as basic therapy. Often, CVID complicated with NCPH has: (1) The manifestations of portal hypertension as the primary symptom. (2) Autoimmune-related manifestations. Imaging can provide important diagnostic clues. The etiology may be related to hepatic NRH and splenomegaly due to recurrent infections.

Analysis of Hematological Indices and Splenectomy Rates in 2,130 Patients with Hemoglobin H Diseases or ß-Thalassemia.

INTRODUCTION: Splenomegaly and hypersplenism are common complications of thalassemia patients due to the excessive clearance of defective red blood cells from the spleen. To date, splenectomy has been considered one of the most effective treatments for splenomegaly, reducing clinical severity among thalassemia patients. Thus, we aim to investigate the differences in splenectomy rates and hematological indices among thalassemia patients with different genotypes. METHOD: In this study, we analyzed the clinical data of thalassemia in 2,130 patients admitted to the 923rd Hospital of the People's Liberation Army from January 2006 to December 2020, and the statistical software SPSS 26.0 was applied to analyze the data. RESULT: Of the 2,130 patients with thalassemia, 265 patients underwent splenectomy. It was determined that significantly more patients with hemoglobin H (HbH) disease, a form of α-thalassemia, have undergone splenectomy than ß-thalassemia patients (20% vs. 7%). Further, HbH disease patients were diagnosed at a significantly older age than ß-thalassemia patients. CONCLUSION: The greater probability of HbH disease patients undergoing splenectomy is likely influenced by multiple factors, including their lower dependency on transfusion, leading to high spleen compensatory stress on the spleen, and the destruction of defective erythrocytes. In contrast, ß-thalassemia is clinically more severe and less tolerant of hemoglobin fluctuations. Based on these findings, clinicians are suggested to pay more attention to HbH disease patients as many of them are still under-transfused, which could lead to chronic hemolysis and more severe hepatosplenomegaly. These results might offer insight for improving the clinical management of patients with different types of thalassemia.

Large Volume Paracentesis in Patients with Liver Cirrhosis Temporarily Diminishes Blood Cell Count.

Background: Large-volume paracentesis is the preferred treatment for patients with severe and refractory ascites. Several complications were reported during therapeutical paracentesis. However, there are very few published studies on the change in blood cell count after paracentesis. This study aimed to evaluate any changes in blood cell counts after ascites fluid drainage. Methods: This study was conducted on patients with severe ascites and chronic liver disease who underwent large-volume paracentesis at Namazi Hospital, in Shiraz, Iran, between March 2021 and February 2022. A data gathering form containing the patient's medical history, cause of cirrhosis, ascites fluid volume, as well as routine tests including primarily sodium, potassium, and basal creatinine, was filled out. Before and after the surgery, the total blood cell count was measured. Before the procedure, adjustment was made in the case of coagulopathy and albumin deficiency. The effect of factors such as the volume of drained fluid, splenomegaly, antibiotics, and steroid use was assessed on the changes in the number of blood cells. Using the JAMOVI 2.3.9 software, a paired t test and multiple regression were applied for statistical analysis (P<0.001). Results: The study included 37 patients. After the paracentesis procedure, the number of blood cells significantly decreased in all groups (P<0.001). The followings are the amounts of each type of blood cells before and after the procedure: Platelet=153837±91862 and 115648±69136, red blood cells=3.53±0.784 and 3.22±0.705, white blood cells=12.3±7.78 and 8.6±5.5. None of the study variables, including drained volume, splenomegaly, antibiotics, and steroid use, were significant predictors of the changes in the blood cell count after paracentesis (P>0.001). Conclusion: The findings of the present study showed that children with tense ascites who had large-volume paracentesis might experience a sharp drop in blood cell count after the procedure, which was a transient physiological condition.

Splenomegaly and Splenic Pseudocyst in a Female Teenage Patient with Sickle Cell Anemia-A Case Report.

Splenomegaly is one of the complications of sickle cell disease (SCD) occurring in early childhood. This risk is reduced by the age of five years as the spleen undergoes auto splenectomy as a consequence of recurrent vasooclusion and splenic infarction. However, in some variants of SCD, the persistence of the spleen occurs. This can be complicated rarely by the formation of a splenic pseudocyst. We report a 17-year-old teenager with sickle cell anemia who presented with an 8-year history of gradually increasing left-sided abdominal swelling and a 2-month history of recurrent left upper abdominal pain. A computerized tomography scan revealed splenomegaly and multiple splenic cysts, not responsive to opioid analgesics which necessitated a total splenectomy. The histology report found an absence of epithelial lining confirming splenic pseudocysts. SCD patients with splenomegaly have underlying splenic infarction, which is a predisposition to splenic pseudocyst formation, though a rare occurrence. Many patients with splenic pseudocyst are usually asymptomatic and do not need intervention. However, the index patient developed serious symptoms indicating a need for a total splenectomy. A splenic pseudocyst is rare and found in <1% of splenectomies.

GAU-PED study for early diagnosis of Gaucher disease in children with splenomegaly and cytopenia.

BACKGROUND: Gaucher disease (GD) diagnosis can be delayed due to non-specific symptoms and lack of awareness, leading to unnecessary procedures and irreversible complications. GAU-PED study aims to assess GD prevalence in a high-risk pediatric population and the presence, if any, of novel clinical or biochemical markers associated with GD. MATERIALS AND METHODS: DBS samples were collected and tested for ß-glucocerebrosidase enzyme activity for 154 patients selected through the algorithm proposed by Di Rocco et al. Patients showing ß-glucocerebrosidase activity below normal values were recalled to confirm the enzyme deficiency with the gold standard essay on cellular homogenate. Patients tested positive at the gold standard analysis were evaluated through GBA1 gene sequencing. RESULTS: 14 out of 154 patients were diagnosed with GD, with a prevalence of 9.09% (5.06-14.78%, CI 95%). Hepatomegaly, thrombocytopenia, anemia, growth delay/deceleration, elevated serum ferritin, elevated Lyso-Gb1 and chitotriosidase were significantly associated with GD. CONCLUSIONS: GD prevalence in a pediatric population at high-risk appeared to be higher compared to high-risk adults. Lyso-Gb1 was associated with GD diagnosis. The algorithm proposed by Di Rocco et al. can potentially improve the diagnostic accuracy of pediatric GD, allowing the prompt start of therapy, aiming to reduce irreversible complications.

Spleen size change after hepatitis C treatment: a simple parameter to predict clinical outcomes.

Portal hypertension contributes to splenomegaly in cirrhotic patients. Reduction in spleen size may represent improvement in portal hypertension. The goal was to determine whether reduction in spleen size following sustained virologic response (SVR) in patients with hepatitis C virus (HCV) cirrhosis is associated with lower risk of liver-related adverse outcomes. A retrospective cohort study was performed regarding HCV-infected patients treated with direct-acting antiviral agents at the Iowa City Veterans Administration Medical Center between 2014 and 2019. Patients with cirrhosis and splenomegaly on baseline ultrasound were included. Spleen size, platelet counts, decompensations, hepatocellular carcinoma (HCC) status, and mortality were recorded through July 31, 2021. Decrease in spleen size ≥1.5 cm was regarded as significant. Intergroup comparisons were performed on SPSS 28. Eighty patients with cirrhosis and splenomegaly before SVR were identified. Spleen sizes decreased significantly after SVR in 31 patients over a median of 1 year (Group A), whereas 49 patients did not meet this endpoint (Group B). Lack of spleen size reduction was associated with the presence of varices before SVR (odds ratio (OR): 5.3, p < 0.01). Group A had significantly greater increases in platelet count after SVR than did Group B. Patients in Group B had greater risk of HCC (OR: 9.7, CI: 1.2-79; p = 0.03) and death (OR: 3.6, CI: 1.1-12; p = 0.04). Reduced spleen size in patients with HCV cirrhosis after SVR is associated with greater increment in platelet count, decreased risk of HCC, and reduced mortality compared to patients whose spleen size does not decrease.

Complement-Mediated Thrombotic Microangiopathy and Spontaneous Splenic Rupture Associated With Cytomegalovirus Infection.

This is a case report of a previously healthy female patient with complement-mediated thrombotic microangiopathy (TMA) caused by a systemic cytomegalovirus infection that was successfully treated with plasmapheresis, steroids, and parenteral valganciclovir. Complement-mediated TMA is the result of various genetic mutations leading to complement abnormalities with overactivation of alternate complement pathway in response to a triggering infection. She also had splenic rupture without splenomegaly and was managed successfully without splenectomy.

The Role of the Spleen in Portal Hypertension.

As liver disease progresses, intrahepatic vascular resistance increases (backward flow theory of portal hypertension) and collateral veins develop. Adequate portal hypertension is required to maintain portal flow into the liver through an increase in blood flow into the portal venous system (forward flow theory of portal hypertension). The splenic artery resistance index is significantly and selectively elevated in cirrhotic patients. In portal hypertension, a local hyperdynamic state occurs around the spleen. Splenomegaly is associated with a poor prognosis in cirrhosis and is caused by spleen congestion and by enlargement and hyperactivation of splenic lymphoid tissue. Hypersplenism can lead to thrombocytopenia caused by increased sequestering and breakdown of platelets in the spleen. The close relationship between the spleen and liver is reflected in the concept of the hepatosplenic axis. The spleen is a regulatory organ that maintains portal flow into the liver and is the key organ in the forward flow theory of portal hypertension. This review summarizes the literature on the role of the spleen in portal hypertension.

Spleen volume and length determined by computed tomography impact outcome after allogeneic stem cell transplantation for myelofibrosis.

Splenomegaly is a hallmark of myelofibrosis (MF), and reports on the impact of spleen size on the outcome of allo-HSCT have been conflicting, possibly due to differences in methods of assessment. We retrospectively analysed the impact of spleen volume and length measured by computed tomography on allo-HSCT outcome in 93 patients, 74% of whom had prior ruxolitinib treatment. Median spleen volume and length were 1.58 dm3 and 20 cm, respectively. We found a strong correlation between spleen volume and length (Pearson's r = 0.95, p < 0.001), Spearman (rho = 0.96, p < 0.001). After a median follow-up of 41.7 months, 5-year overall and disease-free survival were 66% and 59%, respectively. Spleen size did not impact overall survival or non-relapse mortality. Larger spleen volume and length as continuous variables were associated with slower platelet and leucocyte engraftment and a higher risk of disease relapse in univariate and multivariate analyses. Spleen length measured precisely by imaging is a good surrogate for spleen volume. In the era of JAK inhibitors, larger spleen size reflects advanced disease in MF and is associated with an increased risk of relapse but has no impact on non-relapse mortality and overall survival after allo-HSCT.

Myeloid-specific fatty acid transport protein 4 deficiency induces a sex-dimorphic susceptibility for nonalcoholic steatohepatitis in mice fed a high-fat, high-cholesterol diet.

Newborns with FATP4 mutations exhibit ichthyosis prematurity syndrome (IPS), and adult patients show skin hyperkeratosis, allergies, and eosinophilia. We have previously shown that the polarization of macrophages is altered by FATP4 deficiency; however, the role of myeloid FATP4 in the pathogenesis of nonalcoholic steatohepatitis (NASH) is not known. We herein phenotyped myeloid-specific Fatp4-deficient (Fatp4M-/-) mice under chow and high-fat, high-cholesterol (HFHC) diet. Bone-marrow-derived macrophages (BMDMs) from Fatp4M-/- mice showed significant reduction in cellular sphingolipids in males and females, and additionally phospholipids in females. BMDMs and Kupffer cells from Fatp4M-/- mice exhibited increased LPS-dependent activation of proinflammatory cytokines and transcription factors PPARγ, CEBPα, and p-FoxO1. Correspondingly, these mutants under chow diet displayed thrombocytopenia, splenomegaly, and elevated liver enzymes. After HFHC feeding, Fatp4M-/- mice showed increased MCP-1 expression in livers and subcutaneous fat. Plasma MCP-1, IL4, and IL13 levels were elevated in male and female mutants, and female mutants additionally showed elevation of IL5 and IL6. After HFHC feeding, male mutants showed an increase in hepatic steatosis and inflammation, whereas female mutants showed a greater severity in hepatic fibrosis associated with immune cell infiltration. Thus, myeloid-FATP4 deficiency led to steatotic and inflammatory NASH in males and females, respectively. Our work offers some implications for patients with FATP4 mutations and also highlights considerations in the design of sex-targeted therapies for NASH treatment.NEW & NOTEWORTHY FATP4 deficiency in BMDMs and Kupffer cells led to increased proinflammatory response. Fatp4M-/- mice displayed thrombocytopenia, splenomegaly, and elevated liver enzymes. In response to HFHC feeding, male mutants were prone to hepatic steatosis, whereas female mutants showed exaggerated fibrosis. Our study provides insights into a sex-dimorphic susceptibility to NASH by myeloid-FATP4 deficiency.

Clinical application of preoperative shear wave dispersion for prediction of post liver failure in patients with hepatocellular carcinoma after hepatectomy.

OBJECTIVE: The aim in this study was to determine the efficacy of shear wave dispersion (SWD) technique for the prediction of post hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma after hepatectomy and develop an SWD based risk prediction model. METHODS & MATERIALS: We prospectively enrolled 205 consecutive patients who were scheduled to undergo hepatectomy for hepatocellular carcinoma (HCC), pre-operative SWD examination, laboratory data and some other clinicopathological tests were collected. The risk factors of PHLF were identified according to univariate and multivariate analysis, a predictive model was established based on logistic regression analyses. RESULTS: SWD examination was successfully performed in 205 patients. PHLF occurred in 51 patients (24.9%), including 37/11/3 patients with Grade A/B/C, respectively. There was a high correlation between SWD value of liver and liver fibrosis stage (r = 0.873, p < 0.05). Patients with PHLF has a higher median SWD value of liver than patients without PHLF [17.4 vs 14.7 (m/s)/kHz, p < 0.05]. The SWD value of liver, total bilirubin (TB), international normalized ratio of prothrombin time (INR) and splenomegaly were significantly related to PHLF based on the multivariate analysis. A new prediction model (PM) for PHLF was established (PM = -12.918 + 0.183× SWD + 6.668× INR +0.100×TB+1.240×splenomegaly). The optimal cutoff value of SWD for predicting PHLF was 16.7 (m/s)/kHz. The area under the curve (AUC) of the PM for PHLF was 0.833, which was higher than that of SWD, INR, Forns, FIB4, APRI (p < 0.005, respectively). CONCLUSION: SWD is a promising and reliable method for PHLF prediction in patients with HCC who were undergoing hepatectomy. Compared with SWD, Forns, APRI and FIB-4, PM demonstrate better efficacy for preoperative PHLF prediction.