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In a cross-sectional analysis of baseline data from a randomized clinical trial, we studied 198 adolescents and adults aged 15+ with sickle cell disease. Interest was in assessing the relative strengths of the relationship of vaso-occlusive crisis (VOC) pain domains of intensity, frequency, and duration, with health-related quality of life (HRQOL). Variation in psychosocial, physical function, and pain expression domains of HRQOL was partially explained by frequency, intensity, and duration of VOC pain, separately and together, over and above differences in age, sex, genotype, and organ system damage. However, no single domain measure accounted for more than an additional partial R2 of 12.5% alone. Vaso-occlusive crisis pain frequency explained the most variation, when simultaneously considering VOC intensity and duration, except for stiffness, where duration was most predictive. Yet VOC pain intensity, and even VOC duration, also contributed to variability in HRQOL. We recommend that for most purposes, because all 3 VOC pain domains contribute to variability in HRQOL, all 3 domains should be assessed and interventions should be targeted to improve all 3 domains to maximize HRQOL outcomes. [ABSTRACT FROM AUTHOR]

Summary: Background: Bone marrow transplantation (BMT) is a standard treatment for several haematologic conditions. Following BMT, patients may develop hepatobiliary complications that impact morbidity and mortality. The differential diagnosis may include drug‐induced liver injury (DILI), sepsis‐associated liver injury (SALI), sinusoidal obstruction syndrome (SOS), graft‐versus‐host disease (GVHD), viral hepatitis, ischaemic hepatitis, and fulminant hepatitis. Aims: To evaluate the frequency, clinical characteristics, and outcomes of patients with hepatobiliary alterations associated with BMT in a tertiary referral centre. Methods: This was a cross‐sectional study with data collected from the medical records of patients undergoing BMT between January 2017 and June 2022. We diagnosed hepatobiliary complications based on established criteria. Results: We included 377 patients; 55.7% had hepatobiliary complications. Female gender, pre‐BMT hepatobiliary alteration, and haploidentical allogeneic transplantation were associated with increased risk with odds ratios (OR) of 1.8 (p = 0.005), 1.72 (p = 0.013) and 3.25 (p = 0.003), respectively. Patients with hepatobiliary complications spent longer in the hospital than those without (27.7 × 19.3 days, respectively; p < 0.001). Among 210 patients with hepatobiliary complications, 28 died compared to 5 of 167 without complications (OR 4.98; p = 0.001). Conclusions: Hepatobiliary complications are frequent in patients undergoing BMT. There is a greater risk of their occurrence in women, people with pre‐BMT liver alterations, and in haploidentical transplants. The occurrence of these complications increases the length of stay and is associated with a higher risk of death. [ABSTRACT FROM AUTHOR]

Background & Aims: Patients with acute liver failure (ALF) awaiting liver transplantation (LT) may develop multiorgan failure, but organ failure does not impact waitlist prioritization. The aim of this study was to examine the impact of organ failure on waitlist mortality risk and post LT outcomes in patients with ALF. Methods: We studied adults waitlisted for ALF in the United Network for Organ Sharing (UNOS) database (2002–2019). Organ failures were defined using a previously described Chronic Liver Failure modified sequential organ failure score assessment adapted to UNOS data. Regression analyses of the primary endpoints, 30‐day waitlist mortality (Competing risk), and post‐LT mortality (Cox‐proportional hazards), were performed. Latent class analysis (LCA) was used to determine the organ failures most closely associated with 30‐day waitlist mortality. Results: About 3212 adults with ALF were waitlisted, for hepatotoxicity (41%), viral (12%) and unspecified (36%) etiologies. The median number of organ failures was three (interquartile range 1–3). Having ≥3 organ failures (vs. ≤2) was associated with a sub hazard ratio (HR) of 2.7 (95%CI 2.2–3.4)) and a HR of 1.5 (95%CI 1.1–2.5)) for waitlist and post‐LT mortality, respectively. LCA identified neurologic and respiratory failure as most impactful on 30‐day waitlist mortality. The odds ratios for both organ failures (vs. neither) were higher for mortality 4.5 (95% CI 3.4–5.9) and lower for delisting for spontaneous survival.5 (95%CI.4–.7) and LT.6 (95%CI.5–.7). Conclusion: Cumulative organ failure, especially neurologic and respiratory failure, significantly impacts waitlist and post‐LT mortality in patients with ALF and may inform risk‐prioritized allocation of organs. [ABSTRACT FROM AUTHOR]

Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only definitive curative option for β‐major thalassemia patients (β‐MT). Posterior reversible encephalopathy syndrome (PRES) is a pervasive neurological complication which typically occurs following HSCT. β‐MT patients are prone to a higher PRES incidence due to long‐term immunosuppression; thus, it is imperative that these patients are closely monitored for PRES after HSCT. Patients and methods: We included 148 pediatric patients with β‐MT who underwent HSCT between March 2015 and August 2022 in Children's Medical Center. Patients in this study were divided into two groups. The association between PRES and class of β‐MT and other risk factors were assessed and the overall survival rate was determined. Results: Fourteen out of 112 patients (12%) with class I and II β‐MT developed PRES. However, PRES occurred in 11 out of 36 patients (30.5%) with β‐MT‐III. Our results indicated that there was a significant association between class III β‐MT and the occurrence of (P =.004). Additionally, acute graft‐versus‐host disease (aGVHD) occurred in 80% and 44.7% of patients in the PRES and non‐PRES groups, respectively (P =.001). The results of the Kaplan‐Meier analysis revealed that the 5‐year overall survival (OS) was 75.6% in the PRES group versus 95% in the non‐PRES group, which was statistically significant (P =.001). Conclusion: Based on our results, pediatric β‐MT III patients are at a higher risk of developing PRES. Additionally, pediatric β‐MT patients with a history of aGVHD, regardless of disease class, are more likely to develop PRES. Considering these results, PRES has a higher chance of being the etiology of symptoms and should be considered more often in these patients. [ABSTRACT FROM AUTHOR]

In chronic liver disease, hepatic stellate cell activation and degeneration of liver sinusoidal endothelial cells lead to structural changes, which are secondary to fibrosis and the presence of regenerative nodules in the sinusoids, and to functional changes, which are related to vasoconstriction. The combination of such changes increases intrahepatic vascular resistance and causes portal hypertension. The subsequent increase in splanchnic and systemic hyperdynamic circulation further increases the portal blood flow, thereby exacerbating portal hypertension. In clinical practice, the hepatic venous pressure gradient is the gold-standard measure of portal hypertension; a value of ≥10 mm Hg is defined as clinically significant portal hypertension, which is severe and is associated with the risk of liver-related events. Hepatic venous pressure gradient measurement is somewhat invasive, so evidence on the utility of risk stratification by elastography and serum biomarkers is needed. The various stages of cirrhosis are associated with different outcomes. In viral hepatitis-related cirrhosis, viral suppression or elimination by nucleos(t)ide analog or directacting antivirals results in recompensation of liver function and portal pressure. However, careful follow-up should be continued, because some cases have residual clinically significant portal hypertension even after achieving sustained virologic response. In this study, we reviewed the current and future prospects for portal hypertension. [ABSTRACT FROM AUTHOR]

Background: Porto‐sinusoidal vascular disorder (PSVD) involves a group of rare vascular liver diseases of unknown aetiology that may lead to the development of portal hypertension and its life‐threatening complications. Its pathophysiology is not well understood, and animal models described to date do not fully recapitulate human disease. Methods: We developed three different PSVD rat models by either immunosensitization (repetitive intraportal LPS or intramuscular spleen extract injections) or toxic (Selfox: combination of FOLFOX and a selenium‐enriched diet) treatment and characterized them at haemodynamic, histological, biochemical and transcriptional levels. We compared these results to human data. Results: All three models developed significant portal hypertension, while only the LPS and the Selfox models displayed PSVD‐specific and nonspecific histological alterations in the absence of cirrhosis. Transcriptional comparison between rat models and human data showed that both LPS and Selfox models recapitulate the main transcriptional alterations observed in humans, especially regarding haemostasis, oxidative phosphorylation and cell cycle regulation. Reproducibility and feasibility was higher for the Selfox model. Conclusions: The Selfox rat model faithfully reproduces the main alterations described in PSVD. Its use as a preclinical model for drug testing in progressing PSVD can be a significant step forward towards the development of new therapeutic targets for this rare condition. [ABSTRACT FROM AUTHOR]

Hydroxyurea was the first prophylactic drug used for sickle cell disease management because it lowers the frequency and severity of vaso- occlusive crises. It increases hemoglobin which carries oxygen round the body by prolonging red blood cell life span, hydration, rheology (of?) and normalizes elevated white blood cells. Hydroxyurea reduces the need for hospitalization and blood transfusion in children and adult sickle cell patients. The aim of this study was to evaluate the effectiveness of hydroxyurea in the management of sickle cell patients in a study population. A descriptive cross-sectional study design was adopted using a sample of 59 patients with sickle cell disease receiving hydroxyurea at the Quality Control Unit of the Pharmacy Department of the University of Benin Teaching Hospital, Benin City. The questionnaire was both interviewer- and self-administered, and responses were entered and analyzed using Microsoft Excel. Results were represented as frequencies and percentages. Ethical considerations were observed. About 81.4% of the patients recruited were presently being treated with hydroxyurea, 45.8% were females and 50% were within 5 – 14 years of age. About 67.9% of patients using hydroxyurea had no pain crises, 83.0% had on blood transfusion in the last one year. Self- reported health improvement was high (75.5%) and 90.6% of the patients attested to the effectiveness of hydroxyurea. It can thus be concluded that hydroxyurea reduced the frequency of pain crises, hospitalization and blood transfusion among SCD patients. Morbidity and mortality associated with sickle cell disease had been reduced among SCD patients in this health facility. [ABSTRACT FROM AUTHOR]

Background: For the unclear pathogenesis of Sjogren's syndrome (SS), further exploration is necessary. Mesenchymal stem cells (MSCs) and derived exosomes (MSCs‐exo) have exhibited promising results in treating SS. Object: This study aimed to investigate the effect and mechanism of human umbilical cord MSCs (UC‐MSCs) on SS. Methods: Nonobese Diabetic (NOD) mouse splenic T cells were co‐cultured with UC‐MSCs and UC‐MSCs‐exo, and interferon‐gamma (IFN‐γ), interleukin (IL)‐6, IL‐10, prostaglandin E2 (PGE2), and transforming growth factor‐β1 (TGF‐β1) levels in the supernatant were assessed by quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay. Co‐cultured T cells were injected into NOD mice via the tail vein. The inflammatory cell infiltration in the intestine and the submandibular gland was characterized by hematoxylin‐eosin staining. Treg/Th17 homeostasis within the spleen was determined by flow cytometry. Gut microbiota was detected by 16S rRNA sequencing, and the relationship between differential microbiota and Treg/Th17 cytokines was analyzed by the Pearson correlation coefficient. Results: UC‐MSCs, UC‐MSCs‐exo, and NOD mouse splenic T cells were successfully cultured and identified. After T cells were co‐cultured with UC‐MSCs and UC‐MSCs‐exo, both IFN‐γ and IL‐6 were decreased while IL‐10, PGE2, and TGF‐β1 were increased in transcriptional and translational levels. UC‐MSCs and UC‐MSCs‐exo partially restored salivary secretion function, reduced Ro/SSA antibody and α‐Fodrin immunoglobulin A levels, reduced inflammatory cell infiltration in the intestine and submandibular gland, raised proportion of Treg cells, decreased IFN‐γ, IL‐6, IL‐2, IL‐17, lipopolysaccharide, and tumor necrosis factor‐alpha levels, and raised IL‐10, Foxp3, and TGF‐β1 levels by affecting co‐cultured T cells. The intervention of UC‐MSCs and UC‐MSCs‐exo improved intestinal homeostasis in NOD mice by increasing microbiota diversity and richness. Additionally, differential microbiota was significantly associated with Treg/Th17 cytokine levels. Conclusion: Human UC‐MSCs and UC‐MSCs‐exo improved disease characterization of SS in NOD mice through regulation of gut microbiota and Treg/Th17 cellular immunity. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with chromosomal rearrangements and multiple gene mutations and the impairment of normal hematopoiesis. Current efforts to improve AML outcomes have focused on developing targeted therapies that may allow for improved antileukemic effects while reducing toxicity significantly. Gemtuzumab ozogamicin (GO) is one of the most thoroughly studied molecularly targeted therapies in adults. GO is a monoclonal antibody against CD33 IgG4 linked to the cytotoxic drug calicheamicin DMH. The use of GO as a chemotherapeutic agent is not generalized for all patients who suffer from AML, particularly for those whose health prevents them from using intensive conventional chemotherapy, in which case it can be used on its own, and those who have suffered a first relapse, where its combination with other chemotherapeutic agents is possible. This systematic review aimed to comprehensively evaluate GO, focusing on its molecular structure, mode of action, pharmacokinetics, recommended dosage, resistance mechanisms, and associated toxicities to provide valuable information on the potential benefits and risks associated with its clinical use. A systematic review of eight scientific articles from 2018 to 2023 was conducted using PRISMA analysis. The results showed that GO treatment activates proapoptotic pathways and induces double-strand breaks, initiating DNA repair mechanisms. Cells defective in DNA repair pathways are susceptible to GO cytotoxicity. GO has recommended doses for newly diagnosed CD33+ AML in combination or as a single agent. Depending on the treatment regimen and patient status, GO doses vary for induction, consolidation, and continuation cycles. Multidrug resistance (MDR) involving P-glycoprotein (P-gp) is associated with GO resistance. The overexpression of P-gp reduces GO cytotoxicity; inhibitors of P-gp can restore sensitivity. Mitochondrial pathway activation and survival signaling pathways are linked to GO resistance. Other resistance mechanisms include altered pharmacokinetics, reduced binding ability, and anti-apoptotic mechanisms. GO has limited extramedullary toxicity compared to other AML treatments and may cause hepatic veno-occlusive disease (HVOD). The incidence of hepatic HVOD after GO therapy is higher in patients with high tumor burden. Hematological side effects and hepatotoxicity are prominent, with thrombocytopenia and neutropenia observed. In conclusion, GO's reintroduction in 2017 followed a thorough FDA review considering its altered dose, dosing schedule, and target population. The drug's mechanism involves CD33 targeting and calicheamicin-induced DNA damage, leading to apoptosis and resistance mechanisms, including MDR and survival signaling, which impact treatment outcomes. Despite limited extramedullary toxicity, GO is associated with hematological side effects and hepatotoxicity. [ABSTRACT FROM AUTHOR]

In patients with sarcoidosis, the development of pulmonary hypertension is associated with significant morbidity and mortality. The global prevalence of sarcoidosis-associated pulmonary hypertension (SAPH) reportedly ranges between 2.9% and 20% of sarcoidosis patients. Multiple factors may contribute to the development of SAPH, including advanced parenchymal lung disease, severe systolic and/or diastolic left ventricular dysfunction, veno-occlusive or thromboembolic disease, as well as extrinsic factors such as pulmonary vascular compression from enlarged lymph nodes, anemia, and liver disease. Early diagnosis of SAPH is important but rarely achieved primarily due to insufficiently accurate screening strategies, which rely entirely on non-invasive tests and clinical assessment. The definitive diagnosis of SAPH requires right heart catheterization (RHC), with transthoracic echocardiography as the recommended gatekeeper to RHC according to current guidelines. A 6-min walk test (6MWT) had the greatest prognostic value in SAPH patients based on recent registry outcomes, while advanced lung disease determined using a reduced DLCO (<35% predicted) was associated with reduced transplant-free survival in pre-capillary SAPH. Clinical management involves the identification and treatment of the underlying mechanism. Pulmonary vasodilators are useful in several scenarios, especially when a pulmonary vascular phenotype predominates. End-stage SAPH may warrant consideration for lung transplantation, which remains a high-risk option. Multi-centered randomized controlled trials are required to develop existing therapies further and improve the prognosis of SAPH patients. [ABSTRACT FROM AUTHOR]

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a rare liver vascular condition, potentially life-threatening, with clinical signs of portal hypertension, frequently reported in relation to bone marrow transplantation and possibly in non-transplantation-related chemotherapy. We report the case of a 65-year-old female patient who insidiously developed fatigue, mild tenderness of the right upper abdominal quadrant, hepato-splenomegaly and slight weight gain consecutive to ascites development, as well as persistent elevation of transaminases and mild thrombocytopenia. To note, she had a previous history of colorectal cancer (CRC) with liver metastases and several courses of chemotherapy. Abdominal duplex and elastography measurements made the diagnosis of cirrhosis improbable. A lot of lab work-ups were performed in order to rule out several diseases and conditions. Further, transjugular access was used to perform the measurement of the hepatic venous pressure gradient and liver biopsy that confirmed SOS/VOD. In late 2023, she was diagnosed with endometrial adenocarcinoma, requiring chemotherapy again. At present, the liver condition is stationary, but the prognosis is, however, uncertain. In conclusion, we presented the atypical case of a female patient who developed portal hypertension syndrome associated with the late onset of SOS/VOD, after 5-fluorouracil and oxaliplatin chemotherapy for CRC and liver metastases, subsequently diagnosed with endometrial adenocarcinoma, which posed many diagnostic and therapeutic challenges. Given the potentially bad outcome, an early diagnosis of SOS/VOD in patients receiving drugs of risk is important not only to stratify further risk, but also to initiate an appropriate therapy in order to improve the prognosis.

Purpose: Vessels encapsulating tumor clusters (VETC) is a novel vascular pattern structurally and functionally distinct from microvascular invasion (MVI) in hepatocellular carcinoma (HCC). This study aims to explore the prognostic value of VETC in patients receiving hepatic arterial infusion chemotherapy (HAIC) for unresectable HCC. Methods: From January 2016 to December 2017, 145 patients receiving HAIC as the initial treatment for unresectable HCC were enrolled and stratified into two groups according to their VETC status. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were evaluated. Results: The patients were divided into two groups: VETC+ (n = 31, 21.8%) and VETC− (n = 114, 78.2%). The patients in the VETC+ group had worse ORR and DCR than those in the VETC− group (RECIST: ORR: 25.8% vs. 47.4%, P = 0.031; DCR: 56.1% vs. 76.3%, P = 0.007; mRECIST: ORR: 41.0% vs. 52.6%, P = 0.008; DCR: 56.1% vs. 76.3%, P = 0.007). Patients with VETC+ had significantly shorter OS and PFS than those with VETC− (median OS: 10.2 vs. 21.6 months, P < 0.001; median PFS: 3.3 vs. 7.2 months, P < 0.001). Multivariate analysis revealed VETC status as an independent prognostic factor for OS (HR: 2.40; 95% CI: 1.46–3.94; P = 0.001) and PFS (HR: 1.97; 95% CI: 1.20–3.22; P = 0.007). Conclusion: VETC status correlates remarkably well with the tumor response and long-term survival in patients undergoing HAIC. It may be a promising efficacy predictor and help identify patients who will benefit from HAIC. [ABSTRACT FROM AUTHOR]

Introduction: Evidence for dual antidiabetic therapy in type 2 diabetes mellitus patients with cirrhosis is limited. This study compared 5-year mortality, composite hepatic decompensation risk, and hepatocellular carcinoma occurrence in patients with diabetes and cirrhosis who were either on metformin monotherapy or on dual metformin and sodium-glucose co-transporter-2 inhibitor (SGLT2-I) therapy. Methods: This retrospective study used the TriNetX Research Network to identify propensity score-matched patients treated with either metformin or dual metformin and SGLT2-I therapy. Our outcomes were all-cause mortality, a composite of hepatic decompensation events, and hepatocellular carcinoma (HCC) occurrence over 5 years. We estimated hazard ratios within each cohort with 95% confidence intervals (CI) and Kaplan-Meier estimates for time-to-event distributions with Log-rank tests. We were able to stratify our cohorts by age, sex, race, and ethnicity. We further investigated a subset of diabetic patients with cirrhosis due to MASH. Results: In our propensity score-matched cohorts of type 2 diabetes patients with cirrhosis, those on dual metformin and SGLT2-I therapy had decreased risk for mortality (HR 0.57, 95%CI 0.41–0.81), reduced composite risk of becoming decompensated (HR 0.63, 95%CI 0.43–0.93) and less than half the risk for developing HCC (HR 0.43, 95%CI 0.21–0.88) compared to those on mono metformin therapy. We did not find a difference between mono or dual therapy treatment for mortality, decompensation, or HCC risks in the subset of patients with MASH cirrhosis. Conclusion: Dual metformin and SGLT2-I treatment in type 2 diabetes patients with cirrhosis are associated with improved mortality and hepatic complications. [ABSTRACT FROM AUTHOR]

COVID-19 infections accelerate liver decompensation and serious liver-related co-morbidities. The aim is to evaluate the safety and impact of COVID vaccines on hepatic disease progression in patients with advanced liver disease and to identify parameters that predict the occurrence of complications. The study involved 70 patients with advanced liver disease who were vaccinated with different COVID vaccines from January 2021 to April 2022. They were evaluated clinically. The laboratory investigation included a complete blood count, liver and kidney function tests, calculation of CTP and MELD scores, plasma levels of ammonia, abdominal ultrasound, and upper GI endoscopy. Twenty patients had experienced complications 64 ± 12 days from the last dose of a vaccination. Twenty patients (28.6%) developed hepatic decompensation and hypothyroidism (n = 11, 15.7%), and five (7.14%) patients developed splanchnic thrombosis. There were no COVID-19 reinfections except for two patients who received Sinopharm and developed vaccine-associated enhanced disease (2.9%). Complications after COVID vaccinations were correlated with ALT (r = 0.279, p = 0.019), serum sodium (r = −0.30, p = 0.005), creatinine (r = 0.303, p = 0.011), liver volume (LV) (r = −0.640, p = 0.000), and MELD score (r = 0.439, p = 0.000). Multivariate logistic regression revealed that LV is the only independent predictor (p = 0.001). LV ≤ 682.3 has a sensitivity of 95.24% and a specificity of 85.71% in predicting complications with an AUC of 0.935, p < 0.001. In conclusion, the hepatic reserve and prognosis in liver cirrhosis should be evaluated prior to COVID vaccinations using the MELD score and liver volume as promising risk stratification criteria. In summary, the research proposes a novel triaging strategy that involves utilizing the MELD score and liver volume as risk stratification parameters of the hepatic reserve and prognosis of advanced liver cirrhosis prior to COVID immunization to determine who should not receive a COVID vaccination. [ABSTRACT FROM AUTHOR]

Background: Peripheral blood immunomarkers are associated with prognosis in patients with solid tumors receiving chemotherapy or immunotherapy. In this study, the associations of circulating neutrophil‐to‐lymphocyte ratio (NLR), monocyte‐to‐lymphocyte ratio (MLR), and platelet‐to‐lymphocyte ratio (PLR), as well as their dynamic changes were investigated in relation to the efficacy of immunotherapy in patients with primary liver cancer. Methods: Comparisons were made between NLR, MLR, and PLR among individuals exhibiting disease control (defined as the best response of partial response [PR] or stable disease [SD]) and those with progressive disease (PD). Additionally, disease control rate (DCR), overall survival (OS), and progression‐free survival (PFS) were compared between individuals with different NLR, MLR, and PLR levels before initiating palliative immunotherapy. Furthermore, comparisons were made between patients with different alterations in the ratios at the second cycle of immunotherapy compared to baseline. These analyses were performed using univariate and multivariate approaches. A total of 119 Chinese patients with liver cancer who underwent immunotherapy were included in this study, which focused on hepatocellular carcinoma (HCC). Results: In cases with HCC (n = 104), the cutoffs of NLR, MLR, and PLR to differentiate treatment responders from nonresponders were 3.38, 0.28, and 227.18, respectively. Patients with the best response of PR or SD had significantly lower NLR and MLR. Patients with NLR <3.38 and those with MLR <0.28 significantly had longer OS and PFS than their counterparts, and those with PLR <227.18 had significantly longer PFS, both in overall patients and in various patient subgroups. Lower NLR, MLR, or PLR was associated with earlier BCLC stage, fewer metastatic sites, less frequent extrahepatic metastasis, or better performance status. For individuals who had an unfavorable baseline NLR ≥3.38, MLR ≥0.28, or a favorable baseline PLR <227.18 prior to first immunotherapy, a decrease in NLR, MLR, or PLR at Cycle 2 of immunotherapy was significantly associated with a higher DCR. Conclusions: Among patients with HCC who received immunotherapy, lower NLR, and MLR at baseline in overall patients were significantly associated with better disease control and more favorable survival outcomes (both OS and PFS), and lower PLR was significantly associated with longer PFS. The findings of this research may offer useful hints foranoptimized selection of patients with liver cancer who may benefit more from immunotherapy. [ABSTRACT FROM AUTHOR]

Moyamoya disease (MMD) is a rare disorder of the cerebrovascular system. It is a steno‐occlusive disease that involves angiogenesis and blood–brain barrier (BBB) disruption. Bradykinin (BK), its metabolite des‐Arg9‐BK, and receptor (B1R) affect angiogenesis and BBB integrity. In this study, we aimed to investigate the changes in BK, B1R and des‐Arg9‐BK levels in the serum and brain tissues of patients with MMD and explore the underlying mechanism of these markers in MMD. We obtained the serum samples and superficial temporal artery (STA) tissue of patients with MMD from the Department of Neurosurgery of the Jining First People's Hospital. First, we measured BK, des‐Arg9‐BK and B1R levels in the serum of patients by means of ELISA. Next, we performed immunofluorescence to determine B1R expression in STA tissues. Finally, we determined the underlying mechanism through Western blot, angiogenesis assay, immunofluorescence, transendothelial electrical resistance and transcytosis assays. Our results demonstrated a significant increase in the BK, des‐Arg9‐BK and B1R levels in the serum of patients with MMD compared to healthy controls. Furthermore, an increase in the B1R expression level was observed in the STA tissues of patients with MMD. BK and des‐Arg9‐BK could promote the migratory and proliferative abilities of bEnd.3 cells and inhibited the formation of bEnd.3 cell tubes. In vitro BBB model showed that BK and des‐Arg9‐BK could reduce claudin‐5, ZO‐1 and occluding expression and BBB disruption. To the best of our knowledge, our results show an increase in BK and B1R levels in the serum and STA tissues of patients with MMD. BK and Des‐Arg9‐BK could inhibit angiogenesis, promote migratory and proliferative capacities of cells, and disrupt BBB integrity. Therefore, regulating BK, des‐Arg9‐BK and B1R levels in the serum and the brain could be potential strategies for treating patients with MMD. [ABSTRACT FROM AUTHOR]

Background and objectives: Limb ischemia or compartment syndrome, requiring surgery, are some of the frequent cannula-related complications in patients supported with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). The purpose of this exploratory study is to depict and evaluate the dynamic changes in the lower limb muscles with ultrasound shear wave elastography as marker for early lower limb ischemia. Methods: Eleven patients with VA-ECMO after cardiac arrest were included in this study. Seven patients received distal perfusion cannula (DPC) after implantation of the VA-ECMO, whereas 4 had no DPC after VA-ECMO. Compartment syndrome was clinically excluded in all patients. Both lower limbs, e.g., with and without arterial cannula, were monitored with near-infrared spectroscopy (NIRS) for the oxygen saturation of the local tissue. We performed ultrasound shear wave elastrography (SWE) to assess dynamic changes of the medial gastrocnemius muscle at maximum passive muscle stretch (exercise) of both legs. Color-coded duplexsonography was conducted to examine the blood flow velocity of the popliteal artery of the lower limb. Results: We found no difference between DPC and no DPC (p = 0.115) during use of VA-ECMO. However, we detected marked lower limb muscle perfusion deficits of cannulated (58.9 ± 13.5 kPa) vs. cannula-free limb (95.7 ± 27.9 kPa: p < 0.001), applying SWE. No relationship was detected between NIRS measurements and SWE values (kPa) of both lower limbs. The mean peak systolic velocity of the popliteal artery at the cannulated side (30.0 ± 11.7 cm/s) was reduced compared to the non-cannulated side (39.3 ± 18.6 cm/s; p = 0.054). Conclusions: Regardless of DPC after implantation of VA-ECMO, the gastrocnemius muscles seem to lose function due to cannula-related microcirculatory deficits. Muscle function analysis via SWE combined with NIRS might offer a sensitive indicator for early onset leg ischemia during VA-ECMO-related arterial cannulation. [ABSTRACT FROM AUTHOR]

Background: Spontaneous cervical artery dissection (sCeAD) is one of the prime causes of ischemic stroke in young adults. Based on vessel wall imaging, steno-occlusive or expansive wall hematomas can be distinguished. It is unclear whether these two distinct morphological phenotypes reflect different pathophysiological processes. Aim: We aim to evaluate differences in clinical characteristics and long-term recurrence between patients with expansive and steno-occlusive mural wall hematoma in the acute phase. Methods: Participants of the ReSect-study, one of the largest single-center cohort studies with long-term follow-up of sCeAD patients, with sufficient magnetic resonance imaging (MRI) were included. All available MRI scans were retrospectively evaluated for patients dichotomized to two groups: (1) mural hematoma causing steno-occlusive pathologies without expansion of total vessel diameter (steno-occlusive hematoma), and (2) mural hematoma causing vessel diameter expansion without lumen stenosis (expansive hematoma). Patients with mixed steno-occlusive and expansive vessel pathologies were excluded from the analysis. Results: In total, 221 individuals were available for analysis. The pathognomonic vessel wall hematoma was steno-occlusive in 187 (84.6%) and expansive in 34 (15.4%). No difference was seen in patient demographics, clinical status at admission, laboratory parameters, family history, or the frequency of clinical stigmata for connective tissue disorders. Both patients with expansive and steno-occlusive mural hematoma had a high likelihood of suffering cerebral ischemia (64.7 vs 79.7). Still, time from symptom onset to diagnosis was significantly longer in those with expansive dissection (17.8 vs 7.8 days, p = 0.02). Those with expansive dissections were more likely to have upper respiratory infection within 4 weeks prior to dissection (26.5% vs 12.3%, p = 0.03). Upon follow-up, functional outcome was identical and groups did not differ in rate of sCeAD recurrence, but those with expansive mural hematoma at baseline more frequently had residual aneurysmal formation (41.2% vs 11.5%, p < 0.01). Conclusions: As cerebral ischemia was frequent in both, our clinical results do not advise for differential treatment or follow-up based on the acute morphological phenotype. There was no clear evidence of a different aetiopathogenesis between patients with steno-occlusive or expansive mural hematoma in the acute phase. More mechanistic approaches are needed to elucidate potential differences in pathomechanism between both entities. Data access: Anonymized data not published within this article will be made available by request from any qualified investigator. [ABSTRACT FROM AUTHOR]

The Scimitar syndrome or pulmonary venolobar syndrome is a rare, complex and variable congenital anomaly of cardiopulmonary development characterised by an abnormal right-sided pulmonary venous drainage in the inferior vena cava, malformation of the right lung, abnormal arterial supply and sometimes cardiac malformations. These serious anomalies notwithstanding, their presentation is varied, ranging from asymptomatic to severe symptoms, particularly in the neonatal and early infantile period. Some symptomatic cases are misdiagnosed as recurrent lower respiratory tract infections or as heart failure, missing the underlying congenital anomaly. Considering associated serious complications such as pulmonary hypertension and a high mortality rate, accurate and timely diagnosis is mandatory. This requires a high index of suspicion, not only by clinicians but also by radiologists who encounter suggestive chest radiographs in asymptomatic children. Still, the classic radiological finding for which the condition is named is seen in only about 50% of all cases and only 10% in affected infants. We highlight this case to heighten clinicians' and radiologists' suspicions about Scimitar syndrome. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities. The prevalence of MetS has surged, transforming it into a pressing public health concern that could potentially affect around 20%–25% of the global population. As MetS continues its ascent, diverse interventions, pharmacological, nonpharmacological and combined have been deployed. Yet, a comprehensive remedy that fully eradicates MetS symptoms remains elusive, compounded by the risks of polypharmacy's emergence. Acknowledging the imperative to grasp MetS's intricate pathologies, deeper insights for future research and therapy optimisation become paramount. Conventional treatments often target specific syndrome elements. However, a novel approach emerges in mesenchymal stem cell‐derived extracellular vesicles (MSC‐EVs) therapy, promising a holistic shift. MSC‐EVs, tiny membranous vesicles secreted by mesenchymal stem cells, have garnered immense attention for their multifaceted bioactivity and regenerative potential. Their ability to modulate inflammation, enhance tissue repair and regulate metabolic pathways has prompted researchers to explore their therapeutic application in MetS. This review primarily aims to provide an overview of how MSC‐EVs therapy can improve metabolic parameters in subjects with MetS disease and also introduce the usefulness of NMR spectroscopy in assessing the efficacy of MSC‐EVs therapy for treating MetS. Significance statement: Given the significant public health implications of MetS, continuous research aiming to empower individuals in managing this condition is crucial. Rigorous investigation into MSC‐EVs therapy as a promising alternative to whole‐cell therapy is underway. Notably, MSC‐EVs treatment has been observed to induce various metabolic alterations in subjects with MetS, such as restoration of significant metabolic pathways and metabolite levels that are affected by MetS. NMR spectroscopy has played a pivotal role in identifying different biomarkers related to MetS and examining the physical characteristics of mesenchymal stem cells (MSCs). This review focuses on presenting the potential of MSC‐EVs in normalising metabolic parameters in MetS and emphasizes the value of NMR spectroscopy in studying intricate pharmacometabolomic aspects related to MSC‐EVs therapy. [ABSTRACT FROM AUTHOR]

Background: The inflammatory mediators produced after traumatic brain injury (TBI) are reaching peripheral organs causing organ and tissue damage, including the liver. Our study assessed the effect of intravenous (i.v.) infusion of oral mesenchymal stem cells (OMSCs) on TBI-induced liver damage by measuring liver inflammatory factors and liver oxidative stress. Methods: Twenty-eight adult male Wistar rats were divided into four groups: 1) sham control; 2) TBI alone (TBI); 3) TBI vehicle (Veh)-control; and 4) TBI with OMSC treatment (SC). OMSCs were obtained from oral mucosa biopsies. OMSCs were administered and administered i.v. at 1 and 24 h after TBI. Within 48 h after TBI, multiple parameters were analyzed, including inflammation, oxidative stress, and histopathological changes. Results: In comparison to sham controls, the TBI alone showed in liver significantly increased levels of interleukin-lß (IL-lß; P < 0.001), interleukin-6 (IL-6; P < 0.001), malondialdehyde (MDA; P < 0.001), and protein carbonyl (PC; P < 0.001). At the same time the TBI alone decreased the liver levels of superoxide dismutase (SOD; P < 0.001), total antioxidant capacity (TAC; P < 0.001), catalase (CAT; P < 0.001), and interleukin-10 (IL-10; P < 0.001). In comparison to the TBI alone group, the therapeutic group treated with i.v. infusion of OMSCs demonstrated significantly reduced changes of IL-lß (P < 0.001), IL-6 (P < 0.01), MDA (P < 0.01), PC (P < 0.05), SOD (P < 0.001), TAC (P < 0.01), CAT (P < 0.01), and IL-10 (P < 0.01). Histopathological evaluation showed in TBI alone group that the total score of liver tissue injury included extensive hydropic degeneration, lobular necrosis, inflammation as well as central vein congestion with subendothelial hemorrhage increased compared the sham group (P < 0.001). Administration of OMSC showed significantly smaller increase in the injury score compared to the TBI alone group (P < 0.001). Conclusion: Therapy with i.v. OMSCs administration after TBI reduces liver injury, as measured by inflammation and oxidative stress. The use of OMSCs can be considered for treatment of liver injury caused by TBI. [ABSTRACT FROM AUTHOR]

Aplastic anemia (AA) is a potentially fatal bone marrow failure syndrome characterized by a paucity of hematopoietic stem cells and progenitor cells with varying degrees of cytopenia and fatty infiltration of the bone marrow space. Recent advances in genomics have uncovered a link between somatic mutations and myeloid cancer in AA patients. At present, the impact of these mutations on AA patients remains uncertain. We retrospectively investigated 279 AA patients and 174 patients with myelodysplastic syndromes (MDS) and performed targeted sequencing of 22 genes on their bone marrow cells using next-generation sequencing (NGS). Associations of somatic mutations with prognostic relevance and response to treatment were analyzed. Of 279 AA patients, 25 (9.0%) patients had somatic mutations, and 20 (7.2%) patients had one mutation. The most frequently mutated genes were ASXL1(3.2% of the patients), DNMT3A (1.8%) and TET2 (1.8%). In the MDS group, somatic mutations were detected in 120 of 174 (69.0%) patients, and 81 patients (46.6%) had more than one mutation. The most frequently mutated genes were U2AF1 (24.7% of the patients), ASXL1 (18.4%) and TP53 (13.2%). Compared with MDS patients, AA patients had a significantly lower frequency of somatic mutations and mostly one mutation. Similarly, the median variant allele frequency was lower in AA patients than in MDS patients (6.9% vs. 28.4%). The overall response of 3 and 6 months in the somatic mutation (SM) group was 37.5% and 66.7%, respectively. Moreover, there was no significant difference compared with the no somatic mutation (N-SM) group. During the 2-years follow-up period, four (20%) deaths occurred in the SM group and 40 (18.1%) in the N-SM group, with no significant difference in overall survival and event-free survival between the two groups. Our data indicated that myeloid tumor-associated somatic mutations in AA patients were detected in only a minority of patients by NGS. AA and MDS patients had different gene mutation patterns. The somatic mutations in patients with AA were characterized by lower mutation frequency, mostly one mutation, and lower median allelic burden of mutations than MDS. Somatic mutations were a common finding in the elderly, and the frequency of mutations increases with age. The platelet count affected the treatment response at 3 months, and ferritin level affected the outcome at 6 months, while somatic mutations were not associated with treatment response or long-term survival. However, our cohort of patients with the mutation was small; this result needs to be further confirmed with large patient sample. [ABSTRACT FROM AUTHOR]

Portal hypertension (PH), defined as a pathological increase in the portal vein pressure, has different aetiologies and causes. Intrahepatic PH is mostly secondary to the presence of underlying liver disease leading to cirrhosis, characterized by parenchymal changes with deregulated accumulation of extracellular matrix and vascular abnormalities; liver sinusoidal endothelial cells and hepatic stellate cells are key players in PH progression, able to influence each other. However, PH may also develop independently of parenchymal damage, as occur in portosinusoidal vascular disorder (PSVD), a group of clinical and histological entities characterized by portal vasculature dysfunctions. In this particular group of disorders, the pathophysiology of PH is still poorly understood. In the last years, several genetic studies, based on genome‐wide association studies or whole‐exome sequencing analysis, have highlighted the importance of genetic heritability in PH pathogenesis, both in cirrhotic and non‐cirrhotic cases. The common PNPLA3 p.I148M variant, one of the main determinants of the susceptibility to steatotic liver disease, has also been associated with decompensation in patients with PH. Genetic variations at loci influencing coagulation, mainly the ABO locus, may directly contribute to the pathogenesis of PH. Rare genetic variants have been associated with familiar cases of progressive PSVD. In this review, we summarize the recent knowledges on genetic variants predisposing to PH development, contributing to better understand the role of genetic factors in PH pathogenesis. [ABSTRACT FROM AUTHOR]

Haematopoietic stem cell transplantation is a mainstay of therapy for numerous malignant and nonmalignant diseases. Endothelial activation and dysfunction occur after stem cell transplantation, driven by various patient‐ and transplant‐specific factors. This can manifest as one of the relatively uncommon endothelial injury syndromes, such as sinusoidal obstruction syndrome, transplant‐associated thrombotic microangiopathy, idiopathic pneumonia syndrome, capillary leak syndrome, engraftment syndrome or posterior reversible encephalopathy syndrome. This review focuses on the pathogenesis, classification and diagnosis of these disorders, as well as provides guidance on risk mitigation and treatment. [ABSTRACT FROM AUTHOR]

The clinical characteristics, risk factors and survival prognosis of pericardial effusion (PE) after haematopoietic stem cell transplantation (HSCT) in children were investigated. Clinical data of children who underwent HSCT at the Children's Hospital Affiliated with Chongqing Medical University from January 2016 to December 2022 were analysed retrospectively. Cox proportional hazards regression and the Kaplan-Meier method were used to analyse the risk factors for post-HSCT PE and its impact on outcomes, respectively. We enrolled 452 patients with HSCT: 307 males and 145 females, with a median age of 3.4 (1.8 to 6.5) years at transplantation. Forty-five patients (10%) had PE within a median time of 25 (10.5 to 44) days, 42 (93%) within 100 days. Three patients with large PE were treated with pericardiocentesis and drainage, while the others were treated conservatively. Of the 45 patients with PE, 24 survived, and their PE disappeared after treatment. Graft-versus-host disease (GVHD) grade, abnormal pre-HSCT electrocardiogram, hepatic veno-occlusive disease (HVOD), pulmonary infection and Epstein–Barr virus (EBV) infection were risk factors for PE. The overall survival (OS) rates at 1, 3, and 5 years were 86.0%, 84.2%, and 82.3%, respectively. PE had a significant negative effect on OS after HSCT (P < 0.0001). Particularly, one patient with large PE died of pericardial tamponade. Post-HSCT PE usually occurred within 100 days. GVHD grade, abnormal pre-HSCT electrocardiogram, HVOD, pulmonary infection and EBV infection were closely related to PE. PE had a significant negative effect on OS rate. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is characterized by a mutation in the beta-globin gene resulting in abnormal hemoglobin S (HgbS). The significant sequela of SCD include anemia and recurrent vaso-occlusive episodes (VOEs) which may effectuate patients to receive chronic blood transfusions. Current pharmacotherapy options for SCD include hydroxyurea, voxelotor, Lglutamine, and crizanlizumab. Simple and exchange transfusions are often utilized as prophylaxis to prevent emergency department (ED)/urgent care (UC) visits or hospitalizations from VOEs by reducing the level of sickled red blood cells (RBCs). In addition, the treatment of VOEs involves intravenous (IV) hydration and pain management. Studies have demonstrated that sickle cell infusion centers (SCIC) decrease hospital admissions for VOEs, and IV hydration and pain medications are the key components of management employed. Thus, we hypothesized that implementing a structured infusion protocol in the outpatient setting would reduce the incidence of VOEs. Here, we discuss two patients with SCD who were trialed on scheduled outpatient IV hydration and opioids with the goal of decreasing the frequency of VOEs in the setting of the current blood product shortage and the patients' refusal to receive exchange transfusions. Overall, the two patients had opposing outcomes- one demonstrated reduced frequency of VOEs, whereas the other had mixed results due to noncompliance to scheduled outpatient sessions. The use of outpatient SCICs may be an effective intervention for prevention of VOEs in patients with SCD, and further patient-centered research and quality improvement initiatives are needed to further quantify and understand the factors contributing to their efficacy. [ABSTRACT FROM AUTHOR]

Introduction: A positive association between benign prostate hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and metabolic syndrome (MetS) was reported in several studies, but studies from Asia often showed conflicting results. Materials and methods: Medical records were obtained from a health promotion center data-base between 2021 and 2022. Men without a history of treatment for LUTS were evaluated using the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), transrectal ultrasonography. Results: Of 1345 individuals, 603 (44.8%) had MetS. Older age, higher IPSS values, higher prevalence rates of BPH and overactive bladder, higher triiodothyronine, and lower testosterone and sex-hormone binding globulin were observed in individuals with MetS than in individuals without MetS. The severity of LUTS significantly increased in the individuals with MetS (p = .002). In individuals with MetS, age, HbA1c, and cerebrovascular disease (CVD) were associated with IPSS. For OABSS, age, HbA1c, thyroid-stimulating hormone (TSH), coronary artery occlusive disease, and CVD were identified as predictors. Conclusions: We confirmed the positive correlation between MetS and BPH/LUTS in Korean. Factors including TSH and atherosclerosis affected LUTS in individuals with MetS. These findings suggested a potential role of thyroid hormones and atherosclerosis in the etiology and treatment of BPH/LUTS in patients with MetS. [ABSTRACT FROM AUTHOR]

Introduction: Infantile hepatic hemangioma (IHH) is a common liver tumor in infants and shares the same characteristics as cutaneous infantile hemangioma (IH). Propranolol is effective for symptomatic IHH. The clinical features between cutaneous IH and IHH, and treatment efficacy of IHH (smaller than 4 cm) is unclear. To evaluate the correlation of clinical features between cutaneous IH and IHH, as well as efficacy of systemic propranolol in the treatment of cutaneous IH combined with IHH. Materials and Methods: The clinical data of infants with complicated cutaneous IH combined with IHH treated with systemic propranolol (1.5 ~ 2 mg/(kg d)) from January 2011 to October 2020 were retrospectively analyzed. Results: Forty‐five cases with IHH combined with complicated cutaneous IH were reviewed. Single cutaneous IH is more likely to be combined with focal IHH, cutaneous IH greater than 5, more likely to be combined with multiple IHH (Pearson = 0.546, p < 0.01). The mean age of focal and multiple IHH regression was 11.93 ± 14.42 months and 10.20 ± 9.15 months, respectively. Conclusions: The number of cutaneous IH were correlated with the number of IHH. There was no difference in the age of complete remission for focal and multiple IHH. [ABSTRACT FROM AUTHOR]

Hepatic sinusoidal obstruction syndrome (HSOS) is a death-dealing liver disease with a fatality rate of up to 67%. In the study present, we explored the efficacy of andrographolide (Andro), a diterpene lactone from Andrographis Herba, in ameliorating the monocrotaline (MCT)-induced HSOS and the underlying mechanism. The alleviation of Andro on MCT-induced rats HSOS was proved by biochemical index detection, electron microscope observation, and liver histological evaluation. Detection of hepatic ATP content, mitochondrial DNA (mtDNA) copy number, and protein expression of nuclear respiratory factor-1 (NRF1) and peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PPARGC1A) demonstrated that Andro strengthened mitochondrial biogenesis in livers from MCT-treated rats. Chromatin immunoprecipitation assay exhibited that Andro enhanced the occupation of nuclear factor erythroid 2-related factor 2 (NFE2L2, also known as NRF2) in the promoter regions of both PPARGC1A and NRF1. Andro also activated the NRF2-dependent anti-oxidative response and alleviated liver oxidative injury. In Nrf2 knock-out mice, MCT induced more severe liver damage, and Andro showed no alleviation in it. Furthermore, the Andro-activated mitochondrial biogenesis and anti-oxidative response were reduced in Nrf2 knock-out mice. Contrastingly, knocking out Kelch-like ECH-associated protein 1 (Keap1), a NRF2 repressor, reduced MCT-induced liver damage. Results from co-immunoprecipitation, molecular docking analysis, biotin-Andro pull-down, cellular thermal shift assay, and surface plasmon resonance assay showed that Andro hindered the NRF2-KEAP1 interaction via directly binding to KEAP1. In conclusion, our results revealed that NRF2-dependent liver mitochondrial biogenesis and anti-oxidative response were essential for the Andro-provided alleviation of the MCT-induced HSOS. Graphical Headlights: 1. Andro alleviated MCT-induced HSOS via activating antioxidative response and promoting mitochondrial biogenesis. 2. Andro-activated antioxidative response and mitochondrial biogenesis were NRF2-dependent. 3. Andro activated NRF2 via binding to KEAP1. [ABSTRACT FROM AUTHOR]

Background: Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality. Timely recognition of PPH, determining the cause, and initiating treatment is critical, as almost 90 percent of deaths due to PPH occur within four hours following delivery. Methods: This is a observational study over the period of 18 months. This study includes all cases of postpartum hemorrhage. Results and conclusion: : incidence of PPH in our study was 1.03% main type of PPH was atonic, seen in total 125 out of 151 cases ( 90.1%), while traumatic PPH was second most common cause noted among total 21 cases (7.9%) . Mortality was observed in those mothers who were having high risk factors like DIC, hepatic disease, severe anaemia and abnormal placentation. Prompt diagnosis and expertise and skillful intervention by senior obstetrician by performing internal iliac ligation and uterine compression sutures could save the mother from Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality. [ABSTRACT FROM AUTHOR]

The article focuses on liver transplantation as a curative strategy for Mahvash disease, an ultra-rare disorder caused by biallelic inactivating variants in the glucagon receptor gene (GCGR). Topics include the diagnosis of Mahvash disease through the identification of novel biallelic frameshift variants in GCGR, the manifestation of portal hypertension and recurrent encephalopathy in the absence of cirrhosis.

Mahvash disease is an exceedingly rare genetic disorder of glucagon signaling characterized by hyperglucagonemia, hyperaminoacidemia, and pancreatic a-cell hyperplasia. Although there is no known definitive treatment, octreotide has been used to decrease systemic glucagon levels. We describe a woman who presented to our medical center after three episodes of small-volume hematemesis. She was found to have hyperglucagonemia and pancreatic hypertrophy with genetically confirmed Mahvash disease and also had evidence of portal hypertension (recurrent portosystemic encephalopathy and variceal hemorrhage) in the absence of cirrhosis. These findings established a diagnosis of portosinusoidal vascular disease, a presinusoidal type of portal hypertension previously known as noncir-rhotic portal hypertension. Liver transplantation was followed by normalization of serum glucagon and ammonia levels, reversal of pancreatic hypertrophy, and resolution of recurrent encephalopathy and bleeding varices. Under normal physiologic conditions, glucagon is secreted by pancreatic a-cells in response to hypoglycemia and hyperaminoacidemia. This process establishes a catabolic state by stimulating gluconeogenesis and glycogen degradation while also inhibiting glycolysis and further glycogen synthesis, ultimately increasing blood glucose.1 Mahvash disease is an exceedingly rare disease characterized by pathogenic variants in the glucagon receptor gene (GCGR) that render hepatocytes unresponsive to glucagon. The loss of this feedback mechanism results in reactive pancreatic a-cell hyperplasia, which often leads to pancreatic neuroendocrine tumors and hyperaminoacidemia.2 Mahvash disease has traditionally been characterized by symptoms driven by pancreatic stimulation. However, here we describe a woman with Mahvash disease who was found to have portosinusoidal vascular disease (previously termed noncirrhotic portal hypertension) with variceal hemorrhage and portosystemic shunting leading to recurrent portosystemic encephalopathy. These findings indicate that portosinusoidal vascular disease may be an underlying feature of Mahvash disease. Liver transplantation resolved the patient's hyperglucagonemia by replacing defective hepatic glucagon receptors and instilling glucagon sensitivity. Replacing the liver, the site of increased portal-vein resistance, also resolved her intractable recurrent portosystemic encephalopathy and variceal hemorrhage. [ABSTRACT FROM AUTHOR]

Ascites is sometimes detected after allogeneic hematopoietic stem cell transplantation (allo-HSCT); however, since limited information is currently available, its clinical meaning remains unclear. Therefore, we herein examined potential factors for and the impact of ascites on the prognosis of patients after allo-HSCT at our institutes. Fifty-eight patients developed ascites within 90 days of allo-HSCT (small in 34 (16%), moderate-large in 24 (11%)). A multivariate analysis identified veno-occlusive disease/sinusoidal obstruction syndrome (p = 0.01) and myeloablative conditioning (p = 0.01) as significant potential factors for the development of small ascites. Thrombotic microangiopathy (TMA) (p < 0.01) was a significant potential factor for moderate-large ascites. The incidence of both small and moderate-large ascites correlated with lower overall survival (p = 0.03 for small ascites and p < 0.01 for moderate-large ascites) and higher non-relapse mortality rates (p = 0.03 for small ascites and p < 0.01 for moderate-large ascites). Lower OS and higher NRM rates correlated with the incidence of both small and moderate-large ascites. Further investigation is warranted to establish whether the clinical sign of ascites improves the diagnostic quality of TMA in a large-scale study. [ABSTRACT FROM AUTHOR]

Sinusoidal obstruction syndrome (SOS) is a serious liver disorder that occurs after liver transplantation, hematopoietic stem cell transplantation, and the administration of anticancer drugs. Since SOS is a life-threatening condition that can progress to liver failure, early detection and prompt treatment are required for the survival of patients with this condition. In this study, female CD1 mice were divided into treatment and control groups after the induction of an SOS model using monocrotaline (MCT, 270 mg/kg body weight intraperitoneally). The mice were analyzed at 0, 12, 24, and 48 h after MCT administration, and blood and liver samples were collected for assays and histopathology tests. SOS was observed in the livers 12 h after MCT injection. In addition, immunohistochemical findings demonstrated CD42b-positive platelet aggregations, positive signals for von Willebrand factor (VWF), and a disintegrin-like metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) in the MCT-exposed liver sinusoid. Although ADAMTS13's plasma concentrations peaked at 12 h, its enzyme activity continuously decreased by 75% at 48 h and, inversely and proportionally, concentrations in the VWF-A2 domain, in which the cleavage site of ADAMTS13 is located, increased after MCT injection. These findings suggest that the plasma concentration and activity of ADAMTS13 could be useful biomarkers for early detection and therapeutic intervention in patients with SOS. [ABSTRACT FROM AUTHOR]

Background: Oxaliplatin-based regimens are commonly used as adjuvant chemotherapy following surgery for colorectal cancer. Adverse events associated with oxaliplatin include blue liver, which is caused by sinusoidal dilation and diffuse peliosis hepatis. We report herein a case of localized peliosis hepatis closely resembling a metastatic liver tumor. Case presentation: The patient, a 50-year-old male, underwent a robotically assisted colectomy for rectosigmoid colon cancer, which was discovered when hematochezia occurred. The patient received a diagnosis of pStage IIIb and was treated with four courses of CAPOX as adjuvant chemotherapy starting at postoperative month 1. At postoperative month 4, contrast-enhanced computed tomography (CT) of the abdomen revealed a 20-mm, low-density area with heterogeneous internal structure in S6/7 of the liver. Abdominal ultrasound and gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) findings led to a diagnosis of metastatic liver tumor, for which a laparoscopic partial hepatectomy was performed. The resected lesion was a dark reddish-brown nodule with indistinct margins that appeared to be continuous with the surrounding area. Histopathological analysis revealed severe, localized dilatation of the sinusoids and congestion consistent with the gross nodule. Based on these findings, localized peliosis hepatis associated with oxaliplatin-induced sinusoidal damage was diagnosed. Conclusions: Localized peliosis hepatis associated with oxaliplatin use can be difficult to distinguish from a metastatic liver tumor on imaging studies. [ABSTRACT FROM AUTHOR]

Background: This study aimed to capture the implementation process of the ALIGN Study, (An individualized Pain Plan with Patient and Provider Access for Emergency Department care of Sickle Cell Disease). ALIGN aimed to embed Individualized Pain Plans in the electronic health record (E-IPP) and provide access to the plan for both adult patients with sickle cell disease (SCD) and emergency department providers when a person with SCD comes to the emergency department in vaso-occlusive crises. Methods: Semi-structured interviews were conducted with research teams from the 8 participating sites from the ALIGN study. Seventeen participants (principal investigators and study coordinators) shared their perspectives about the implementation of ALIGN in their sites. Data were analyzed in three phases using open coding steps adapted from grounded theory and qualitative content analysis. Results: A total of seven overarching themes were identified: (1) the E-IPP structure (location and upkeep) and collaboration with the informatics team, (2) the role of ED champion, (3) the role of research coordinators, (4) research team communication, and communication between research team and clinical team, (5) challenges with the study protocol, (6) provider feedback: addressing over-utilizers, patient mistrust, and the positive feedback about the intervention, and (7) COVID-19 and its effects on study implementation. Conclusions: Findings from this study contribute to learning how to implement E-IPPs for adult patients with SCD in ED. The study findings highlight the importance of early engagement with different team members, a champion from the emergency department, study coordinators with different skills and enhancement of communication and trust among team members. Further recommendations are outlined for hospitals aiming to implement E-IPP for patients with SCD in ED. [ABSTRACT FROM AUTHOR]

Systemic therapy remains the primary therapeutic approach for advanced hepatocellular carcinoma (HCC). Nonetheless, its efficacy in achieving control of intrahepatic lesions is constrained. Hepatic arterial infusion chemotherapy (HAIC) is a therapeutic approach that combines localized treatment with systemic antitumor effects, which aim is to effectively manage the progression of cancerous lesions within the liver, particularly in patients with portal vein tumor thrombosis (PVTT). Combining HAIC with anti-programmed cell death protein 1 (anti-PD-1) monoclonal antibody (mAb) immunotherapy is anticipated to emerge as a novel therapeutic approach aimed at augmenting the response inside the localized tumor site and achieving prolonged survival advantages. In order to assess the effectiveness, safety, and applicability of various therapeutic modalities and to address potential molecular mechanisms underlying the efficacy of HAIC-sensitizing immunotherapy, we reviewed the literature about the combination of HAIC with anti-PD-1 mAb therapies. [ABSTRACT FROM AUTHOR]

Introduction: Neuronal surface antibody syndromes (NSAS) encompass a growing set of autoimmune neurological disorders, with their predominant clinical presentation being autoimmune encephalitis (AE). The most extensively documented form within NSAS is anti-N-methyl-D-aspartate receptor (NMDAR) autoimmunity. In contrast, other NSAS, such as anti-metabotropic glutamate receptor-5 (mGluR5) autoimmunity, are less common and less comprehensively characterized, particularly in pediatric cases. Case description: In this instance, we present the case of a 7-year-old girl who exhibited abnormal behaviors following hematopoietic stem cell transplantation (HSCT). She received a diagnosis of anti-mGluR5 AE, and her Electroencephalogram (EEG) displayed an increased number of generalized slow waves during wakefulness. Treatment involved intravenous administration of gamma globulin and methylprednisolone, followed by oral prednisone tablets. Levetiracetam was introduced as an antiepileptic therapy during the pulse steroid therapy. Notably, the abnormal behaviors exhibited significant improvement after treatment. Conclusions: To the best of our knowledge, this is the first report of rare pediatric NSAS involving anti-mGluR5 AE following HSCT. Enhancing our understanding and characterization of this condition may facilitate its recognition and treatment in children. Serum antibody testing could enable early identification and treatment of anti-mGluR5 AE. [ABSTRACT FROM AUTHOR]

The article focuses on the pharmacology of chemotherapy and immunosuppressants, detailing their mechanisms of action and side effects. Topics include the classification of chemotherapeutic agents based on their mechanism of action, the cell cycle, and the anaesthetic implications of these drugs, including interactions with anaesthetic agents and their impact on cancer recurrence.

Aims: The aim of this study was to identify risk factors associated with acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT) by systematically reviewing the relevant literature. Methods: This meta-analysis surveyed relevant articles published in PubMed, Embase, and the Cochrane Library up to December 2022 to identify the reliable risk factors for AKI after HSCT, calculating odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results: Twenty studies with 4,378 patients were included. Umbilical cord blood transplantation (OR = 2.36; 95% CI: 1.77–3.15; p < 0.00001), calcineurin inhibitors (CNIs) (OR = 1.97; 95% CI: 1.06–3.67; p = 0.03), sinusoidal obstruction syndrome (SOS) (OR = 5.80; 95% CI: 3.96–8.51; p < 0.00001), allogeneic transplantation (OR = 4.27; 95% CI: 1.83–9.95; p = 0.0008), hypertension (OR = 2.07; 95% CI: 1.16–3.69; p = 0.01), amphotericin B (OR = 4.03; 95% CI: 2.54–6.40; p < 0.00001), vancomycin (OR = 2.19; 95% CI: 1.24–3.87; p = 0.007), and total body irradiation (TBI) (OR = 1.81; 95% CI: 1.27–2.57; p = 0.001) were risk factors for AKI. Conclusion: Umbilical cord blood transplantation, CNIs, SOS, allogeneic transplantation, hypertension, amphotericin B, vancomycin, and TBI were risk factors for AKI. It is important for clinical staff to be aware of these risk factors in their treatment planning with patients undergoing HSCT. [ABSTRACT FROM AUTHOR]

Acute hepatic porphyria (AHP) is caused by defects in hepatic heme biosynthesis, leading to disabling acute neurovisceral attacks and chronic symptoms. In ENVISION (NCT03338816), givosiran treatment for 6 months reduced attacks and other disease manifestations compared with placebo. Herein, we report data from the 36-month final analysis of ENVISION. Ninety-four patients with AHP (age ≥12 years) and recurrent attacks were randomized 1:1 to monthly double-blind subcutaneous givosiran 2.5 mg/kg (n = 48) or placebo (n = 46) for 6 months. In the open-label extension (OLE) period, 93 patients received givosiran 2.5 or 1.25 mg/kg for 6 months or more before transitioning to 2.5 mg/kg. Endpoints were exploratory unless otherwise noted. During givosiran treatment, the median annualized attack rate (AAR) was 0.4. Through Month 36, annualized days of hemin use remained low in the continuous givosiran group (median, 0.0 to 0.4) and decreased in the placebo crossover group (16.2 to 0.4). At end of OLE, in the continuous givosiran and placebo crossover groups, 86% and 92%, respectively, had 0 attacks. AAR was lower than historical AAR in 98% and 100%, respectively (post hoc analysis), and there were 0 days of hemin use in 88% and 90%, respectively. The 12-item short-form health survey physical and mental component summary scores increased by 8.6 and 8.1, respectively (continuous givosiran) and 9.4 and 3.2, respectively (placebo crossover). EQ-5D health-related questionnaire scores increased by 18.9 (continuous givosiran) and 9.9 (placebo crossover). Lower urinary delta-aminolevulinic acid and porphobilinogen levels were sustained. Safety findings demonstrated a continued positive risk/benefit profile for givosiran. Long-term monthly givosiran treatment provides sustained and continued improvement in clinical manifestations of AHP. NCT03338816. 2017-002432-17. Acute hepatic porphyria (AHP) is a group of rare, chronic, multisystem disorders associated with overproduction and accumulation of neurotoxic heme intermediates (delta-aminolevulinic acid and porphobilinogen), sometimes resulting in recurrent acute attacks and long-term complications. Givosiran, a small-interfering RNA that prevents accumulation of delta-aminolevulinic acid and porphobilinogen, is approved for the treatment of AHP. These final 36-month results of ENVISION, a phase III study of givosiran in patients with AHP and recurrent attacks, show that long-term monthly treatment with givosiran leads to continuous and sustained reductions in annualized attack rate and use of hemin over time, as well as improved quality of life, with an acceptable safety profile. These results are important for physicians, patients, families, and caregivers who are grappling with this debilitating and potentially life-threatening disease with few effective and tolerable treatment options. [Display omitted] • Givosiran treatment (≤36 months) resulted in sustained improvement in symptoms of AHP. • Median annualized attack rate during givosiran treatment (through Month 36) was 0.4. • Proportions of patients with 0 attacks or 0 days of hemin use increased over time. • Patients showed continued improvement in physical/mental health and quality of life. • Givosiran had an acceptable safety profile. [ABSTRACT FROM AUTHOR]

Background: In clinical practice, some patients with advanced intrahepatic cholangiocarcinoma (ICC) cannot tolerate or refuse chemotherapy due to the toxicity, necessitating alternative treatments. PD-1 blockade combined with lenvatinib showed promising results in phase II studies with small sample size, but there is a lack of data on the routine use with this regimen. This study aimed to evaluate the effectiveness and safety of the regimen in patients with advanced ICC, and to identify predictors for treatment response and prognosis. Methods: We conducted a retrospective cohort study of patients treated with PD-1 inhibitors plus lenvatinib for advanced ICC between July 2017 and August 2022. The study endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Biomarker analysis for CA19-9 and PD-L1 expression was performed. Exploratory analysis for genetic alternation was conducted. Results: The study included 103 patients. It demonstrated a median PFS of 5.9 months and a median OS of 11.4 months. ORR was 18.4% and DCR was 80.6%. The incidence of grade 3 or 4 adverse events was 50.5%. Positive PD-L1 expression (TPS ≥ 1%) was associated with higher ORR (P = 0.013) and prolonged PFS (P = 0.023). Elevated CA19-9 (> 37 U/ml) was associated with decreased ORR (P = 0.019), poorer PFS (P = 0.005) and OS (P = 0.034). Patients with IDH1 mutations exhibited a favorable response to the treatment (P = 0.011), and patients with TP53 mutations tended to have worse OS (P = 0.031). Conclusions: PD-1 blockade plus lenvatinib is effective and safe in routine practice. PD-L1 expression and CA19-9 level appear to predict the treatment efficacy. IDH1 mutations might indicate a better treatment response. Clinical trial registration: NCT03892577. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Treatment of recurrent myelodysplastic syndrome (MDS) after hematopoietic cell transplantation (HCT) remains challenging. We present a 4‐year‐old girl experiencing early MDS relapse post‐HCT treated with a multimodal strategy encompassing a second HCT and innovative targeted therapies. We underscore the potential of a comprehensive treatment approach in managing recurrent pediatric MDS. [ABSTRACT FROM AUTHOR]

Bilateral vertebral artery occlusive disease has been considered as a favorable condition with good collaterals. However, the prognosis of acute ischemic stroke secondary to symptomatic bilateral vertebral artery occlusion (BVAO) and endovascular treatment (EVT) has rarely been reported. We retrospectively selected patients with acute ischemic stroke admitted for symptomatic BVAO between January 2020 and February 2023. All patients with ischemic stroke were evaluated for ischemic lesion and arterial status using brain imaging and angiography. The prognosis of acute stroke with symptomatic BVAO was compared between EVT and conventional treatment. Outcomes were evaluated using modified Rankin Scale (mRS) score at 3 months follow-up. Within the study period, 17 of 2,655 acute ischemic stroke patients were diagnosed with ischemic stroke with symptomatic BVAO. The median age of these patients was 70 (interquartile range 44--89) years, and 13 (76%) were male. Seven patients received emergent EVT with stenting and 10 patients received conventional medical treatment only. Nine of 10 patients with conventional treatment had in-hospital stroke progression and developed new ischemic lesions in the pons and midbrain. Five patients with fetal and hypoplastic posterior communicating artery presented bilateral cerebral peduncular lesions. At 3 months follow-up, 6 patients (35%) had favorable outcomes (mRS 0-2), of which 5 were treated with vertebral artery stenting and 1 received conventional treatment. Ischemic stroke in patients with acute symptomatic BVAO is uncommon. However, stroke progression is common, and the prognosis of most patients is poor. Rescue management such as EVT might be considered for symptomatic BVAO. [ABSTRACT FROM AUTHOR]

• MARS therapy improved bilirubin, ammonia, urea, creatinine, INR, ALT, and AST. • Liver failure patients awaiting transplantation can benefit from MARS therapy. • MARS therapy can benefit patients with acute liver failure and chronic disease. Liver failure is associated with a high mortality rate, with many patients requiring transplant for definitive treatment. The Molecular Adsorbent Recirculating System (MARS) is a nonbiologic system that provides extracorporeal support. Literature on MARS therapy is mixed: outcomes support MARS therapy for patients with isolated acute liver failure, but data on patients with chronic disease is varied. Several case studies report success using MARS as a bridging treatment for patients awaiting transplant. The purpose of this case series is to present the outcomes of 44 patients who underwent MARS therapy for liver failure, 19 of whom used MARS therapy as a bridging therapy to transplant. This study retrospectively identified 44 patients who underwent MARS therapy for liver failure at Mayo Clinic, Jacksonville, between January 2014 and April 2021. Variables of interest included changes in laboratory markers of hepatic functioning, number and length of MARS therapy sessions, transplantation status, and mortality. Following MARS therapy, there were improvements in mean serum bilirubin, ammonia, urea, creatinine, International Normalized Ratio, alanine aminotransferase, and aspartate aminotransferase levels. Twenty-seven patients (61.36%) survived the hospital stay; 17 (38.63%) died in the hospital. The majority of surviving patients (n = 19; 73.07%) received liver transplant. Six did not require transplant (22.22%). All but 1 patient who received MARS as a bridging treatment to transplant survived the follow-up period (n = 18; 94.74%). Outcomes of these 44 cases suggest that MARS improves liver failure-associated laboratory parameters and may be effective therapy as a bridge to liver transplant. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Peliosis hepatis (PH) is a rare benign condition, characterized by hepatic sinusoidal dilatation and blood‐filled cystic cavities, often found incidentally, with still challenging diagnosis by imaging due to polymorphic appearance. Purpose: Based on a retrospective analysis of our series (12 patients) and systematic literature review (1990–2022), to organize data about PH and identify features to improve characterization. Study Type: Retrospective case series and systematic review. Population: Twelve patients (mean age 48 years, 55% female) with pathology‐proven PH and 49 patients (mean age 52 years, 67% female) identified in 33 studies from the literature (1990–2022). Field Strength/Sequence: 1,5‐T; T1‐weighted (T1W), T2‐weighted (T2W), diffusion‐weighted (DW), contrast‐enhanced (CE) T1W imaging. Assessment: We compared our series and literature data in terms of demographic (gender/age/ethnicity), clinical characteristics (symptoms/physical examination/liver test), associated conditions (malignancies/infectious/hematologic/genetic or chronic disorders/drugs or toxic exposure) percentage. On magnetic resonance imaging lesion numbers/shape/mean maximum diameter/location/mass effect/signal intensity were compared. PH pathological type/proposed imaging diagnosis/patient follow‐up were also considered. Statistical Tests: Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports/Series quality assessment. Intraclass correlation and Cohen's kappa coefficients for levels of inter/intrareader agreement in our experience. Results: Patients were mainly asymptomatic (92% vs. 70% in our study and literature) with associated conditions (83% vs. 80%). Lesions showed homogeneous T1W‐hypointensity (58% vs. 65%) and T2W‐hyperintensity (58% vs. 66%). Heterogeneous nonspecific (25% vs. 51%), centrifugal (34% vs. 8%), or rim‐like centripetal (25% vs. 23%) patterns of enhancement were most frequent, with hypointensity on the hepatobiliary phase (HBP), without restricted diffusivity. Good inter‐ and intrareader agreement was observed in our experience. Concerning JBI Checklist, 19 out of 31 case reports met at least 7 out of 8 criteria, whereas 2 case series fulfilled 5 and 6 out of 10 items respectively. Data Conclusion: A homogeneous, not well‐demarcated T1W‐hypointense and T2W‐hyperintense mass, with heterogeneous nonspecific or rim‐like centripetal or centrifugal pattern of enhancement, and hypointensity on HBP, may be helpful for PH diagnosis. Among associated conditions, malignancies and drug exposures were the most frequent. Level of Evidence: 4 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Background: Advanced hepatocellular carcinoma (HCC) shows poor prognosis. Combined hepatic artery infusion chemotherapy (HAIC) and lenvatinib and PD-1 antibody therapy show promising effects in treating advanced HCC, and salvage hepatectomy further promotes the overall survival in patients who were successfully converted after combined therapy. However, salvage major hepatectomy is not always amenable due to insufficient future liver remnant volume (FLV). Case presentation: We report the case of a 59-year-old man with a huge HCC as well as multiple intrahepatic foci and portal vein tumor thrombosis at his right hemi-liver. Genomic and pathologic analyses of HCC tissue revealed a TMBhigh, TPS, and CPS-high cancer, with mutated DNA damage repair gene FANCC. These results suggested that this patient may benefit from chemotherapy and immunotherapy. Thus, he received combined HAIC, lenvatinib, and PD-1 antibody treatment and showed a quick and durable response. After successful downstaging, this patient was evaluated as not suitable for salvage hepatectomy due to the low FLV. He then received simultaneous transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE). The FLV increased to meet the criteria of salvage hepatectomy. Finally, this patient underwent right hemi-hepatectomy without any severe perioperative complications. In addition, no tumor recurrence occurred during the 9-month follow-up period after surgery. Conclusion: Combined HAIC, lenvatinib, and PD-1 antibody therapy, followed by simultaneous TACE and PVE, is a safe and effective conversion therapy that promotes tumor necrosis and increase FLV in patients with advanced HCC. [ABSTRACT FROM AUTHOR]

Hepatic sinusoidal obstruction syndrome (SOS) is a severe and life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a multi-center retrospective study to evaluate the utility of our ultrasonographic scoring system for the diagnosis of SOS (HokUS-10) in predicting SOS-related mortality (SOS-RM). We analyzed a total of 42 patients who developed SOS after HSCT. The cumulative incidences of SOS-RM, non-relapse mortality (NRM), and overall survival at day 180 after the diagnosis of SOS were 26.4%, 28.8% and 54.5%, respectively. The area under the receiver operating characteristic curve analysis showed that the optimal cut-off value of HokUS-10 total score to predict SOS-RM was 8 points after the treatment of SOS. In the individual HokUS-10 score, ascites and portal vein flow-related scores (PV mean velocity and PV flow direction) after the treatment of SOS were shown as significant risk factors for SOS-RM. Our study suggested that US findings after the treatment can predict the treatment outcomes for SOS. [ABSTRACT FROM AUTHOR]