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Yellow phosphorus ingestion causing acute fulminant hepatic failure is a serious condition. The establishment of health measures to monitor and prevent yellow phosphorus poisoning is of utmost importance because there is no known cure for the condition. To prevent phosphorus poisoning, it is crucial to raise awareness among the general population about its potential fatality, educate primary care physicians about the delayed onset toxidrome, and take precautions to ensure careful monitoring and reporting. Herein, we present a case of a 33-year-old male who consumed 30 grams of rat poison {Yellow Phosphorus (YP)} while under the influence of alcohol. He presented to us on day 5 with icterus and bilateral subconjunctival haemorrhage. Laboratory investigations revealed severely deranged liver function tests and raised Prothrombin Time (PT)/International Normalised Ratio (INR), indicating acute fulminant hepatic failure. The patient was started on N-acetyl cysteine, vitamin K, and received fresh frozen plasma transfusion. Despite treatment, on day 3, the patient developed grade 4 Hepatic Encephalopathy (HE) and the laboratory parameters worsened. Close monitoring revealed further deterioration, leading to the decision for emergency orthotopic Liver Transplantation (LT) on day 7. Following the transplant, the patient's liver function tests showed improvement. The subconjunctival haemorrhage and icterus resolved completely on day 3 post-transplantation. The patient was extubated on day 3 and discharged on day 5 post-transplantation. Regular follow-up appointments were uneventful. In conclusion, the present case report highlights the successful management of a patient with acute fulminant hepatic failure through early hepatic transplantation. It emphasizes the importance of prompt recognition, appropriate treatment, and timely transplantation in improving patient outcomes. [ABSTRACT FROM AUTHOR]

This document is a letter published in the Annals of Hematology discussing the diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS). VOD/SOS is a rare endothelial disease that can occur after hematopoietic cell transplantation or other forms of endothelial damage. The letter presents a case study of a patient who developed late-onset VOD/SOS and highlights the challenges in diagnosing the condition. The authors recommend preemptive treatment for suspected cases and suggest that early biopsy may be necessary for a definitive diagnosis. They also call for further research to develop more specific diagnostic criteria for VOD/SOS. [Extracted from the article]

The article presents a case study of a 52 year old female patient with poorly differentiated clear cell renal cell carcinoma (ccRCC) who experienced severe liver toxicity (CHILI Grade 3) following immunotherapy with pembrolizumab. It is reported that the patient developed jaundice, pruritus, and abnormal liver function tests five weeks after a single administration of pembrolizumab. It is further noted that despite immunosuppression, the patient's liver condition worsened.

Personalized medicine is a dynamic and rapidly developing approach in clinical practice that involves utilizing innovative technologies to make decisions in the screening, prevention, diagnosis, and treatment of disease. Chronic liver disease is a progressive deterioration of hepatic functions and a continuous process of inflammation, destruction, and regeneration of liver parenchyma, resulting in fibrosis and cirrhosis. Additionally, personalized medicine helps prevent diseases from occurring by providing patients with earlier intervention and treatment opportunities, thereby reducing the risk and recurrence rate of diseases. [Extracted from the article]

To the Editor, Nontuberculous mycobacteria (NTM) are widely distributed in the environment and can pose a diagnostic challenge as a potential cause of neutropenic fever in patients with hematologic malignancies.[1] The incidence of NTM infection after allogeneic hematopoietic stem cell transplantation (HSCT) varies depending on the type of transplant, with reported rates ranging from 0.4%[2] to as high as 9.7% in a cohort where two-thirds of patients underwent T-cell depletion.[3] Despite accumulating evidence from studies conducted in the post-HSCT setting, only two case reports have described patients who underwent HSCT complicated with NTM infection prior to the transplantation.[[4]] Specifically, there are no published reports of disseminated NTM infection before HSCT, which has been associated with a poor outcome and a mortality rate of 60.3% in immunocompromised populations.[6] Herein, we present a case of successful cord blood transplantation (CBT) with concurrent antimycobacterial treatment to address pulmonary and bloodstream I Mycobacterium kansasii i infection during the peri-HSCT period. This suggests that the duration of NTM treatment during the pre-HSCT period should be individualized to avoid delaying the timing of HSCT once the infection is under control. [Extracted from the article]

IVC syndrome caused by malignant neoplasms usually occurs later in the clinical course of the tumor; therefore, the survival duration of patients with malignant IVC syndrome is generally short, and treatment options are limited to palliative care. Secondary Budd-Chiari syndrome caused by adult T-cell leukemia/lymphoma Abbreviations IVC inferior vena cava ATL adult T-cell leukemia/lymphoma VCAP vincristine, cyclophosphamide, doxorubicin, and predonisone AMP doxorubicin, ranimustine, and predonisone VECP vindesine, etoposide, carboplatin, and predonisone PET-CT positron emission tomography-computed tomography Budd-Chiari syndrome is a disorder defined as hepatic venous outflow tract obstruction, regardless of the level of obstruction, that is not due to pericardial/cardiac diseases or sinusoidal obstruction syndrome (veno-occlusive disease).[1] Primary Budd-Chiari syndrome is defined as obstruction due to a predominantly venous process (thrombosis or phlebitis).[1] In contrast, secondary Budd-Chiari syndrome is defined as compression or invasion of the hepatic veins and/or the inferior vena cava (IVC) by a lesion that originates outside the vein (e.g., a malignant neoplasm).[1] Most Budd-Chiari syndrome cases are primary, and approximately half the patients harbor myeloproliferative neoplasms (e.g., polycythemia vera and essential thrombocythemia) because these disorders usually demonstrate hypercoagulability.[1] We herein report an autopsy case of secondary Budd-Chiari syndrome caused by adult T-cell leukemia/lymphoma (ATL), which resulted in sudden death by refractory shock. [Extracted from the article]

This article discusses a case report of a patient with pulmonary veno-occlusive disease (PVOD) who underwent lung transplantation despite not showing hemodynamic changes. The patient had radiographic findings consistent with PVOD but did not have low oxygen levels or abnormal pulmonary vascular resistance. The patient's condition worsened quickly, leading to lung transplantation before respiratory failure. The article highlights the importance of early referral for transplantation in suspected cases of PVOD, even without hemodynamic changes. It also covers the radiographic findings, diagnostic methods, and treatment options for sarcoidosis-associated PVOD. The text emphasizes the need to consider PVOD in patients with a history of sarcoidosis, even without active sarcoidosis markers. [Extracted from the article]

BACKGROUND: Inotuzumab ozogamicin (InO) is an antibody-drug conjugate used for adults with relapsed/refractory B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The INotuzumab Ozogamicin trial to inVestigAte Tolerability and Efficacy (INO-VATE) previously reported improved outcomes with InO versus standard-of-care (SoC) chemotherapy. This article reports the final INO-VATE results (≥2 years of follow-up) and additional analyses of patient characteristics associated with improved outcomes. METHODS: Between August 27, 2012, and January 4, 2015, this multicenter, parallel, open-label, phase 3 trial randomized 326 adults with relapsed/refractory ALL to InO (n = 164) or SoC (n = 162); 307 received 1 or more doses of the study drug (164 in the InO arm and 143 in the SoC arm). RESULTS: The complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) rate was higher with InO versus SoC (73.8% vs 30.9%; 1-sided P

In the present research, we reported an acute myeloid leukemia subject. The patient was treated with Cytarabine 200 mg/m2 per day with continuous IV infusion on days 1, 2, 3, 4, Etoposide 100 mg/m2 per day with continuous IV infusion on days 1, 2, 3, 4, Idarubicin 12 mg/m2 as a 4-hour IV infusion on days 2, 4, 6, and Mitoxantrone 10 mg/m2 as a 30-minute IV infusion on days 1, 2, 3. During treatment, the patient suffered from 3 life-threatening complications caused by chemotherapy drugs include sinusoidal obstruction syndrome (SOS), refractory thrombocytopenia, and pericardial effusion with pericardiocentesis limitation. To this end, we tried three novel approaches for patient management by Corticosteroid and Colchicine. Intravenous immunoglobulin infusion and oral prednisolone (2 mg/kg/d) were not effective in thrombocytopenia. However, eltrombopag (25 mg/kg/d) response was dramatic. Moreover, pericardial effusion and respiratory distress during the first chemotherapy course were managed with Lasix (2 mg/kg/d) and Spironolactone (25 mg/d); meanwhile, the massive pericardial effusion during the second chemotherapy course was managed with Colchicine (0.5 mg/d) through the mentioned treatment. Fortunately, these approaches were effective and life-saving.

This article, published in Pulmonary Circulation, discusses the potential benefits of combined chemotherapy and immunotherapy in improving the course of pulmonary arterial hypertension (PAH). The article presents a case study of a patient with PAH associated with connective tissue disease who received chemotherapy and immunotherapy for metastatic lung adenocarcinoma. The patient experienced improvement in functional class and risk score while on treatment, but experienced clinical deterioration after discontinuation. The article acknowledges the limitations of a single case study and the difficulty in determining the specific effects of the treatment on PAH. However, it provides valuable insights into the potential effects of antineoplastic and immunomodulatory therapy in PAH and calls for further research in this area. [Extracted from the article]

Background: Hepatoblastoma is the most common primary malignancy of hepatic origin in children, with an estimated incidence of 0.5–1.5 per million children. Hepatoblastoma classically has an intraparenchymal location, and pedunculated hepatoblastoma is a relatively rare entity. Accurate diagnosis can be challenging due to its extrahepatic location and possibly its thin peduncle, which is not easily identified in imaging. Case presentation: Here, we report a case of asymptomatic giant palpable hepatoblastoma in the LUQ of a four-month-old male infant, initially suspected of neuroblastoma based on abdominal ultrasound findings. The final diagnosis of giant pedunculated hepatoblastoma was made based on the abdominal CT scan and the diagnosis was confirmed by percutaneous biopsy. Due to the size of the tumor, complete removal of the tumor was not initially possible. Therefore, the patient was treated with several courses of chemotherapy. The tumor was shrunk and then completely removed. The patient was treated, and no complications were found in the 6-month follow-up. Conclusion: Pedunculated hepatoblastoma is rare but should be considered as a possibility in the case of a perihepatic mass in a pediatric patient that can be confused with other upper abdominal masses such as an adrenal mass. Therefore, in such cases, we must look for the vascular pedicle in the imaging and keep the AFP check in mind. [ABSTRACT FROM AUTHOR]

Background: Porto-sinusoidal vascular disease (PSVD) is a novel nomenclature to describe non-cirrhotic portal hypertension and characteristic histology without portal vein thrombosis (PVT). It is a more inclusive definition than the previously well-recognized entity idiopathic non-cirrhotic portal hypertension. There is a paucity of data on PSVD patients. Methods: A total of 33 patients diagnosed with PSVD and portal hypertension (PH) between 2005 and 2021 were included. Data were retrieved from electronic medical record system and analyzed. Results: Of the 33 patients, 6 (18%) occurred in post-transplant allograft liver. After a median follow-up of 96 months (interquartile range, IQR [52, 139]), 14 deaths occurred (42%), 4 directly related to decompensated liver disease. The Kaplan–Meier survival estimates at 1, 5, and 10 years were 94%, 87% and 58%. PVT occurred in 10 patients (30%). The Nelson–Aalen cumulative risk estimate for PVT at 1, 5 and 10 years were 16%, 25% and 48%. The median model for end-stage liver disease and Child–Pugh score at initial presentation were 8 (IQR [7–12]) and 5 [5–6], and increased to 13 [8, 18] and 7 [5, 8], respectively, at the end of follow-up. Of the 11 patients who presented with splenomegaly and no specific sign of PH, 7 (64%) developed varices and 3 (27%) ascites at a median follow-up of 100 months. Conclusions: PSVD with PH is not a benign entity. Mortality, PVT and hepatic decompensation are common. Patients with PSVD must be closely monitored, including those who only have non-specific clinical signs (e.g., splenomegaly) of PH. [ABSTRACT FROM AUTHOR]

EC-IC bypasses have been performed to treat complex aneurysms or moyamoya disease or atherosclerotic steno-occlusive disease. We report the three cases that underwent EC-IC revascularization of the IMA-M2 bypass using the radial artery graft concurrently after the STA-MCA anastomosis to prevent potential ischemic damage during the operation and augment more flow in terminal internal carotid artery stenosis. All patients experienced neither perioperative complications nor further events for a 3-month follow-up. The double-barreled IMA-M2 and STA-MCA bypass is a good option for substantial amount of EC-IC revascularization with minimizing ischemic injury and maximizing flow amount in patients with severe hemodynamic compromise. [ABSTRACT FROM AUTHOR]

Background and Aims: The definitive treatment for pyrrolizidine alkaloids (PAs)‐induced hepatic sinusoidal obstruction syndrome (HSOS) is not available. The effectiveness of anticoagulation therapy remains controversial. The efficacy of low molecular weight heparin (LMWH) should be investigated in patients and animal models, and the underlying mechanism should be explored. Methods: The prognosis of patients with PAs‐HSOS who received anticoagulation therapy was retrospectively analysed. The effect of enoxaparin on the liver injury was determined in animal models of monocrotaline (MCT)‐induced HSOS was determined, and the underlying mechanism was investigated using a murine model. Results: The cumulative survival rate of patients with PAs‐induced HSOS was 60.00% and 90.90% in the non‐anticoagulation group and anticoagulation group. Enoxaparin attenuated liver injury effectively in a rat model of MCT‐induced HSOS. Additionally, the improvement of severe liver injury was observed in MCT‐treated mice after the administration of enoxaparin (40 mg/kg). The alleviation of liver injury was observed in mice with hepatocyte‐specific deletion of oncostatin M (Osm△Hep). In MCT‐treated mice administrated with enoxaparin, no significant differences in liver injury were observed between Osm△Hep mice and Osmflox/flox mice. Additionally, adenovirus‐mediated overexpression of Osm resulted in severe liver injury in MCT‐induced mice after the administration of enoxaparin. Conclusions: LMWH attenuated severe liver injury in patients with PAs‐Induced HSOS and animal models of MCT‐induced HSOS, which provides a rationale for the application of anticoagulation therapy. [ABSTRACT FROM AUTHOR]

Background: Partial liver transplantation has recently been proposed to alleviate organ shortages. However, transplantation of a small-for-size graft is associated with an increased risk of posttransplant hepatic dysfunction, commonly referred to as small-for-size syndrome (SFSS). This review describes the etiology, pathological features, clinical manifestations, and diagnostic criteria of SFSS. Moreover, we summarize strategies to improve graft function, focusing on graft inflow modulation techniques. Finally, unmet needs and future perspectives are discussed. Summary: In fact, posttransplant SFSS can be attributed to various factors such as preoperative status of the recipients, surgical techniques, donor age, and graft quality, except for graft size. With targeted improvement measures, satisfactory clinical outcomes can be achieved in recipients at increased risk of SFSS. Given the critical role of relative portal hyperperfusion in the pathogenesis of SFSS, various pharmacological and surgical treatments have been established to reduce or partially divert excessive portal inflow, and recipients will benefit from individualized therapeutic regimens after careful evaluation of benefits against potential risks. However, there remain unmet needs for further research into different aspects of SFSS to better understand the correlation between portal hemodynamics and patient outcomes. Key Messages: Contemporary transplant surgeons should consider various donor and recipient factors and develop case-specific prevention and treatment strategies to improve graft and recipient survival rates. [ABSTRACT FROM AUTHOR]

Purpose: Appropriate pre-transplant strategies in patients with myelodysplastic syndromes (MDS) remain challenging. We sought to assess the effect of different pre-transplant therapies and transplantation interval times on patient prognosis. Methods: We retrospectively analysed clinical data for 371 consecutive MDS patients after myeloablative transplantation between 2007 and 2019. Results: The median age of the patients was 38 years (range, 12–64 years). A total of 114 patients (31%) received supportive care (SC), 108 (29%) hypomethylating agents (HMAs), and 149 (40%) chemotherapy-based therapy before transplantation. In patients who received HMA or SC, there was no significant difference in overall survival (OS; P=0.151) or relapse-free survival (RFS; P=0.330), except that HMA-treated patients had a lower rate of non-relapse mortality (5- year NRM: 18% vs. 32%, P=0.035). However, compared with patients who received HMA, those who received chemotherapy-based therapy had a lower 5-year OS rate (56% vs. 69%, P=0.020) and a slightly higher 5-year NRM rate (28% vs. 18%, P=0.067). Compared to the delayed transplant group (transplant interval ≥6 months), the early transplant group (transplant interval <6 months) had a superior 5-year OS (66% vs. 51%, P=0.001) and a lower 5-year cumulative incidence of NRM (22% vs. 36%, P=0.001). Conclusion: The findings of the study indicate that receiving an appropriate pre transplant strategy (SC/HMA + <6 months) significantly improves OS and decreases NRM in MDS patients after myeloablative transplantation. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury, also known as drug-induced hepatotoxicity (DILI), is a major cause of medicine withdrawal (prescription or over-the-counter) from the market. Thus, the authors focused on unfolding existing in vitro models for studying DILI-induced chronic liver failure, from the traditional 2D culture system to organoid technology, as well as emerging technological methods for evaluating chronic DILI, such as microfluidic devices and organ-on-chip models, which are now considered new tools for pharmaceutical and toxicological applications. This is a particularly interesting result given that for many years, the pg130 pathway and Il11 were both considered to have a protective role in mouse models of liver injury; in line with more recent articles [[5]], the authors showed that aggregate gp130 signaling and Il11 upregulation in a damaged liver are toxic and antiregenerative after APAP treatment [[3]]. Its toxicity, whether via accidental or intentional overdose, is an ongoing global problem that continues to result in severe cases of hepatotoxicity, acute liver failure, and even irreversible liver injury necessitating liver transplantation. [Extracted from the article]

Background. Oxaliplatin (OX)-based chemotherapy induces sinusoidal obstruction syndrome (SOS) in the nontumorous liver parenchyma, which can increase the risk of liver resection due to colorectal liver metastasis (CRLM). The extracellular volume (ECV) calculated from contrast-enhanced computed tomography (CT) has been reported to reflect the morphological change of hepatic fibrosis. The present retrospective study aimed to evaluate the ECV fraction as a predictive factor for OX-induced SOS. Methods. Our study included 26 patients who underwent liver resection for CRLM after OX-based chemotherapy with a preoperative dynamic CT of appropriate quality. We investigated the relationship between the pathological SOS grade and the ECV fraction. Results. Overall, 26 specimens from the patients were graded with the SOS classification of Rubbia-Brandt et al. as follows: grade 0, n = 17 (65.4%); grade 1, n = 4 (15.4%); and grade 2, n = 5 (19.2%). No specimens showed grade 3 SOS. In a univariate analysis, the ECV fraction in grade 0 SOS was significantly lower than that in grade 1 + 2 SOS (26.3 ± 3.4% vs. 30.6 ± 7.0%; P = 0.025). The cutoff value and AUC value of the ECV fraction to distinguish between grades 0 and 1 + 2 were 27.5% and 0.771, respectively. Conclusions. Measurement of the ECV fraction was found to be a potential noninvasive diagnostic method for determining early-stage histopathological sinusoidal injury induced by OX-based chemotherapy. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to evaluate the therapeutic efficacy and safety of endovascular treatment aorto-iliac occlusive disease (AIOD) with TransAtlantic Inter-Society Consensus II (TASC II) C and D lesions. In addition, 10 years of experience with interventional procedures and treatment options in our center were also worthy of further discussion. Methods: Between January 2011 and December 2020, a total of 26 consecutive AIOD patients with TASC-II C and D lesions treated endovascular approach were enrolled in this study. Patients' demographic and clinical data were collected, and the safety and efficacy of endovascular therapy were evaluated. In addition, operation procedures were also described. Results: The mean age of patients was 62.2 ± 7 years (49–57 years), and the mean body mass index of patients was 24.2 ± 2.6 kg/m2. Fifteen patients (57.7%) were Rutherford 4, 5 each (19.2%) were Rutherford 3 and 5, and 1 (3.8%) was Rutherford 2. No other serious complications occurred except death in 3 patients. Most of the patients (73.1%) had a history of smoking, and hypertension and hyperlipidemia were common comorbidities. Endovascular therapy was successfully performed in 25 patients, and the technical success rate was 96.2%. The patient's ankle-brachial index improved significantly postoperatively compared with preoperatively (preoperative 0.33 ± 0.14 vs 1.0 ± 0.09, P < 0.001). The primary patency rates were 100%, 95.7%, and 91.3% at 1, 3, and 5 years, while the secondary patency rates were 100%. No treatment-related deaths or serious complications occurred. Conclusions: Endovascular treatment of AIOD patients with TASC-II C and D lesions might be safe and have a high rate of middle-term and long-term primary patency. [ABSTRACT FROM AUTHOR]

Aim: Sinusoidal obstruction syndrome (SOS) induced by oxaliplatin‐including chemotherapies (OXCx) is associated with impaired hepatic reserve and higher morbidity after hepatic resection. However, in the absence of an appropriate animal experimental model, little is known about its pathophysiology. This study aimed to establish a clinically relevant reproducible model of FOLFOX‐induced SOS and to compare the clinical/histopathological features between the clinical and animal SOS settings. Methods: We performed clinical/pathological analyses of colorectal liver metastasis (CRLM) patients who underwent hepatectomy with/without preoperative treatment of FOLFOX (n = 22/18). Male micro‐minipigs were treated with 50% of the standard human dosage of the FOLFOX regimen. Results: In contrast to the monocrotaline‐induced SOS model in rats, hepatomegaly, ascites, congestion, and coagulative necrosis of hepatocytes were absent in patients with CRLM with OXCx pretreatment and OXCx‐treated micro‐minipigs. In parallel to CRLM cases with OXCx pretreatment, OXCx‐challenged micro‐minipigs exhibited deteriorated indocyanine green clearance, morphological alteration of liver sinusoidal endothelial cells, and upregulated matrix metalloproteinase‐9. Using our novel porcine SOS model, we identified the hepatoprotective influence of recombinant human soluble thrombomodulin in OXCx‐SOS. Conclusions: With distinct differences between monocrotaline‐induced rat SOS and human/pig OXCx‐SOS, our pig OXCx‐SOS model serves as a preclinical platform for future investigations to dissect the pathophysiology of OXCx‐SOS and seek preventive strategies. [ABSTRACT FROM AUTHOR]

Objectives: Management of patients undergoing coronary artery bypass grafting (CABG) with obstructive disease of the carotid arteries is still a matter of debate. We compared the results of staged carotid artery stenting (CAS) before CABG in patients with carotid lesions. Materials and Method: Patients with significant carotid artery disease who were deemed to simultaneously suffer from an obstructive coronary artery disease requiring CABG from 2008 to 2018 were screened and enrolled in this study. We performed a staged CAS in cases with ≥60% stenosis and neurological symptoms or asymptomatic patients with ≥80% carotid artery stenosis. Patients with bilateral carotid lesions received sequential CAS within three weeks. Six weeks after the CAS procedure, all patients underwent CABG. Results: A total of 142 patients were included. Eighty-five of these had neurological symptoms, while the remaining 40% were asymptomatic. Thirty-one patients underwent sequential CAS for bilateral lesions. The cerebrovascular event (CVE) following CAS (3 patients) and CABG (3 patients) was 4.2%. There was only a single case of mortality in this cohort. Although it was not statistically significant, CVE after CABG was more frequent in patients with bilateral carotid disease. Conclusions: Our results showed that staged CAS could be performed with minimal adverse outcomes in patients suffering from a simultaneous occlusive disease of carotids and coronary arteries before CABG. Bilateral CAS will further decrease cerebrovascular events and could be performed consequently or concomitantly. [ABSTRACT FROM AUTHOR]

Background: Early recognition and specific therapy facilitate a favorable disease course in hepatic venous-occlusive disease (HVOD) following hematopoietic stem cell transplantation (HCT). Diagnostic and classification criteria, published by the European Society for Blood and Marrow Transplantation (EBMT), better account for clinical differences in disease presentation in pediatric populations. Objectives: To compare the course of HVOD in children before and after the implementation of new EBMT criteria. Material and methods: The study retrospectively evaluates 26 HVODs in 179 children treated in a single HCT unit (Slovakia) comparing the period of 2014–2017 using the Baltimore and modified Seattle criteria with the period of 2018–2021, when new EBMT criteria were adopted. Results: No difference in HVOD incidence (11.2% vs. 14.8%, p = 0.46) and in time of diagnosis post-HCT (15.6 days vs. 15.7 days, p = 0.75) was found. With EBMT criteria we observed more frequent anicteric disease at diagnosis (50% vs. 87.5%, p = 0.04), lower serum bilirubin at diagnosis (3.4 mg/dL vs. 1.23 mg/dL, p = 0.045), and non-significant trends of shorter defibrotide treatment (21.7 days vs. 15.6 days, p = 0.73), decreased mortality (30% vs. 6.2%, p = 0.10) and shorter hospitalization (73.1 days vs. 59.6 days, p = 0.54). Conclusions: Different time periods around the implementation of new criteria are evaluated, underling that pediatric EBMT criteria for post-transplant HVOD diagnosis appear more sensitive. [ABSTRACT FROM AUTHOR]

Background and aim: Oxaliplatin can lead to hepatic sinusoidal injury, called hepatic sinusoidal obstruction syndrome (SOS), resulting in portal hypertension-related complications. This could worsen the clinical course of the patients treated with oxaliplatin. Early diagnosis is challenging. We explored predictive markers of oxaliplatin-induced collateral vessels. Methods: Patients who received oxaliplatin-based chemotherapy were retrospectively screened. We evaluated their laboratory findings and spleen size on computed tomography immediately before oxaliplatin-based chemotherapy and after 6 months of treatment. The primary outcome was collateral vessel development, as a surrogate marker for oxaliplatin-induced SOS in patients who underwent oxaliplatin-based chemotherapy. The secondary outcome was the identification of factors that predicted the development of collateral vessels. Results: We enrolled 161 patients who received oxaliplatin-based chemotherapy. They had a median age of 69 years, and 63.3% were men. Collateral vessels developed in nine (5.6%) patients during the study period. After oxaliplatin-based chemotherapy, the spleen size increased in 104 patients (64.6%), with a ≥ 30% increase in 19.4% of the patients. Univariate analysis showed that the Fibrosis-4 (FIB-4) index (≥ 1.76; OR 9.17), aspartate aminotransferase:platelet ratio index (APRI) (≥ 0.193; OR 9.62), cumulative dose of oxaliplatin (≥ 1000 mg; OR 8.43), and increase in spleen size (≥ 30%; OR 6.01) were significant risk factors for collateral vessel development. Multivariate analysis after stepwise selection revealed that the FIB-4 index and spleen size were significant independent predictive factors. Conclusion: A ≥ 1.76 increase in the FIB-4 index and a ≥ 30% increase in spleen size after 6 months of oxaliplatin-based chemotherapy were significant predictive markers for collateral vessel development. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a predictive model to identify individuals most likely to derive overall survival (OS) benefit from adjuvant chemotherapy (AC) after hepatic resection of intrahepatic cholangiocarcinoma (ICC). Patients who underwent hepatic resection of ICC between 1990 and 2020 were identified from a multi-institutional database. Factors associated with worse OS were identified and incorporated into an online predictive model to identify patients most likely to benefit from AC. Among 726 patients, 189 (26.0%) individuals received AC. Factors associated with OS on multivariable analysis included CA19-9 (Hazard Ratio [HR]1.17, 95%CI 1.04–1.31), tumor burden score (HR1.09, 95%CI 1.04–1.15), T-category (T2/3/4, HR1.73, 95%CI 1.73–2.64), nodal disease (N1, HR3.80, 95%CI 2.02–7.15), tumor grade (HR1.88, 95%CI 1.00–3.55), and morphological subtype (HR2.19, 95%CI 1.08–4.46). A weighted predictive score was devised and made available online (https://yutaka-endo.shinyapps.io/ICCrisk%5fmodel%5ffor%5fAC/). Receipt of AC was associated with a survival benefit among patients at high/medium-risk (high: no AC, 0% vs. AC, 20.6%; medium: no AC, 36.4% vs. 40.8%; both p < 0.05) but not low-risk (low: no AC, 65.1% vs. AC, 65.1%; p = 0.73) tumors. An online predictive model based on tumor characteristics may help identify which patients may benefit the most from AC following resection of ICC. [ABSTRACT FROM AUTHOR]

Hematopoietic cell transplantation is an established curative treatment option for various hematological malignant, and non-malignant diseases. However, the success of HCT is still limited by life-threatening early complications post-HCT, such as Graft Versus Host Disease (GVHD), Sinusoidal Obstruction Syndrome (SOS), and transplant-associated microangiopathy, to name a few. A decade of research in the discovery and validation of novel blood-based biomarkers aims to manage these early complications by using them for diagnosis or prognosis. Advances in this field have also led to predictive biomarkers to identify patients' likelihood of response to therapy. Although biomarkers have been extensively evaluated for different complications, these are yet to be used in routine clinical practice. This review provides a detailed summary of various biomarkers for individual early complications post-HCT, their discovery, validation, ongoing clinical trials, and their limitations. Furthermore, this review also provides insights into the biology of biomarkers and the challenge of obtaining a universal cut-off value for biomarkers. [ABSTRACT FROM AUTHOR]

Bone marrow transplantation (BMT) is the standard treatment for several hematologic pathologies. Post-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, ischemic and fulminant hepatitis, among others. Defining the etiology of hepatobiliary injury is challenging due to the overlapping symptoms. Thus, it is necessary to be aware of and understand the clinical characteristics of these hepatobiliary complications and provide adequate management with possible better outcomes. We reviewed the scientific literature focused on early hepatobiliary complications associated with BMT. We searched the PubMed database using the following descriptors: hepatic complications, drug-induced liver disease, graft-versus-host disease, cholestasis, sepsis, sinusoidal obstruction syndrome, cytomegalovirus, viral hepatitis, bone marrow transplantation, and hematopoietic stem cell transplantation. Post-BMT hepatobiliary complications comprise several differential diagnoses and are challenges for the hepatologist's clinical practice. When evaluating these patients, it is necessary to consider the temporality between the use of certain medications, the increase in liver enzymes, and the presence of infection, in addition to applying diagnostic criteria and complementary tests for a specific diagnosis. [ABSTRACT FROM AUTHOR]

Background: Tumor embolization due to venous infiltration of breast cancer pulmonary metastases is very rare. Case presentation: A 72-year-old female was diagnosed with triple-negative breast cancer. Neoadjuvant chemotherapy was discontinued because of progressive disease, and a right mastectomy with sentinel lymph node biopsy was performed. The pathological analysis of surgical specimens revealed carcinoma with cartilaginous and/or osseous metaplasia. At 22 months after surgery, lung metastasis was observed, and 6 months after initiating treatment for lung metastases, she complained of sudden numbness in the left-lower limb with trouble walking. Ultrasonography showed an embolism in the left popliteal artery, and contrast computed tomography showed enlarged lung metastases and infiltration of the left-upper lobe disease into the left superior pulmonary vein and left atrium. Acute arterial occlusive disease in the left-lower limb caused by the tumor embolism was suspected, so an endovascular thrombectomy was performed. Tumor emboli were removed by embolectomy catheter. Conclusion: This report of lung metastasis from breast cancer with cartilaginous and/or osseous metaplasia and acute lower-limb artery occlusion due to a tumor thrombus adds useful information to the literature on these extremely rare cases. [ABSTRACT FROM AUTHOR]

Aims: Long non-coding RNAs (lncRNAs) contribute to the regulation of vital physiological processes and play a role in the pathogenesis of many diseases. Monocrotaline (MCT) can cause large-scale outbreaks of toxic liver disease in humans and animals in the form of hepatic sinusoidal obstruction syndrome (HSOS). Although many experiments have been carried out to explain the pathogenesis of Monocrotaline-induced hepatic sinusoidal obstruction syndrome and to develop treatments for it, no studies have examined the role of Long non-coding RNAs in this condition. This study aimed to investigate the Long noncoding RNAs-mRNA regulation network in Monocrotaline-induced hepatic sinusoidal obstruction syndrome in rats. Main methods: We established a model for MCT-induced hepatic sinusoidal obstruction syndrome, and then carried out microarray for liver tissues of SD rats in amodel of early hepatic sinusoidal obstruction syndrome(12 h Monocrotaline treatment vs. control group) to investigate the differentially expressed Long non-coding RNAs and mRNAs in early hepatotoxicity. This was followed by RT-PCR analysis of selected Long non-coding RNAs, which were markedly altered. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome analyses were also conducted. Key findings: 176 Long non-coding RNAs (63 downregulated and 113 upregulated) and 4,221mRNAs (2,385 downregulated and 1836 upregulated)were differentially expressed in the Monocrotaline-treated group compared to the control group. The biological processes identified in GO enrichment analysis as playing a role in hepatotoxicity were positive regulation of guanosine triphosphate phosphohydrolase, liver development, and the oxidation-reduction process. Pathway analysis revealed that the metabolism pathways, gap junction, and ribosome biogenesis in eukaryotes were closely related to Monocrotaline-induced hepatotoxicity. According to these analyses, LOC102552718 might play an essential role in hepatotoxicity mechanisms by regulating the expression of inositol 1,4,5-trisphosphate receptor-1 (Itpr-1). Significance: This study provides a basis for further research on the molecular mechanisms underlying Monocrotaline-induced hepatotoxicity and its treatment, especially in the early stage, when successful treatment is critical before irreversible liver damage occurs. [ABSTRACT FROM AUTHOR]

Background: Pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD) belongs to Group 1 pulmonary hypertension. Pulmonary veno-occlusive disease (PVOD), which is characterized by venous system aberrations, has been previously reported in CTD-PAH; however, it has rarely been observed in Sjogren's syndrome (SS). Case presentation: Our 28-year-old female patient was admitted to the hospital with recurrent shortness of breath even after minimal physical activity. Her chest high-resolution CT scan demonstrated pulmonary artery dilatation and bilateral ground-glass nodules. A subsequent right heart catheterization confirmed pulmonary hypertension because her mean pulmonary arterial pressure was 62 mmHg. Our inquisitive genomic assessment identified a novel EIF2AK4 mutation at c.1021 C > T (p. Gln341*), the dominant causal gene of PVOD. Histological examination demonstrated stenosis and occlusions in the pulmonary veins. Because she presented with features such as dry eyes and Raynaud's phenomenon, we performed a biopsy on the labial salivary gland, which confirmed SS. Her treatment regimen included PAH-targeted therapies (tadalafil and macitentan) in combination with hydroxychloroquine. Although she was hospitalized several times due to acute exacerbation of PAH, her disease progression was under control, and she did not demonstrate any signs of pulmonary edema even after a three-year treatment period. Conclusion: Here, we report the case of an SS-PAH patient with PVOD who carried a novel biallelic EIF2AK4 mutation, and PAH-targeted therapies were well tolerated by our patient. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction underlies many of the major complications following hematopoietic cell transplantation (HCT), including transplant-associated thrombotic microangiopathy (TA-TMA), veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), and engraftment syndrome (ES). Emerging evidence similarly implicates endothelitis and microangiopathy in severe COVID-19-related multi-system organ dysfunction. Given the overlap in these two illness states, we hypothesize that prior COVID-19 infection may increase risk for HCT-related endotheliopathies. This retrospective, multicenter study included patients aged 0-25 years who underwent autologous or allogeneic HCT for any indication between January 1, 2020 and September 21, 2021, with close attention to those infected with COVID-19 in either the six months prior to transplant or twelve months following transplant. Incidences of TA-TMA, VOD/SOS, and ES were compared among patients with COVID-19 infection pre-HCT and post-HCT, as well as with historical controls who were never infected with SARS-CoV-2. Those who underwent HCT following COVID-19 infection displayed significantly increased rates of TA-TMA compared to those who were never infected. Additionally, our data suggests a similar trend for increased VOD/SOS and ES rates, although this did not reach statistical significance. Therefore, a history of COVID-19 infection prior to undergoing HCT may be a nonmodifiable risk factor for endothelial-related complications following HCT. Further studies are warranted to better clarify this relationship among larger cohorts and in the era of the Omicron SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

The primary hyperoxalurias (PHs) are a group of diseases characterized by kidney stones, nephrocalcinosis, and chronic kidney disease. At stages of advanced kidney disease, glomerular filtration of oxalate becomes insufficient, plasma levels increase, and tissue deposition may occur. Hemodialysis is often unable to overcome the excess hepatic oxalate production. The current surgical management of primary hyperoxaluria type 1 (PH1) is combined liver kidney transplantation. In a subset of PH1 patients who respond to pyridoxine, kidney-only transplantation has been successfully performed. Recently, kidney-only transplantation has also been performed in PH1 patients receiving a small interfering RNA therapy called lumasiran. This drug targets the hepatic overproduction of oxalate, making kidney-only transplantation a potentially practical novel approach for managing PH1 patients with advanced kidney disease. It is unknown if similar effects could be seen with a different small interfering RNA agent called nedosiran. This article will briefly review PH1, describe the small interfering RNA therapies being used to treat PH, summarize the reported cases of kidney-only transplantation performed with lumasiran, and detail a case of kidney-only transplantation performed in a PH1 patient receiving nedosiran. [ABSTRACT FROM AUTHOR]

Background: Wedge hepatic vein pressure (WHVP) accurately estimates the portal pressure (PP) in chronic sinusoidal portal hypertension patients. Whether this applies to patients with acute portal hypertension due to hepatic sinusoidal obstruction syndrome (HSOS) is unclear. Our aim was to assess the agreement between WHVP and PP in patients with HSOS by comparing them to decompensated cirrhosis patients. Methods: From December 2013 to December 2021, patients with pyrrolidine alkaloid-induced HSOS (PA-HSOS) receiving hepatic venous pressure gradient (HVPG) measurement and transjugular intrahepatic portosystem shunt (TIPS) were retrospectively collected and matched with those of patients with virus- or alcohol-related cirrhosis as a cirrhosis group. Pearson's correlation (R), intraclass correlation coefficient (ICC), scatter plots, and the Bland–Altman method were performed for agreement evaluation. Results: A total of 64 patients were analyzed (30 PA-HSOS and 34 cirrhosis groups). The correlation between WHVP and PP was moderate in the PA-HSOS group (R: 0.58, p = 0.001; ICC: 0.68, p = 0.002) but good in the cirrhosis group (R: 0.81, p < 0.001; ICC: 0.90, p < 0.001). The percentage of patients with inconsistent WHVP and PP in the two groups was 13 (43.3%) and 15 (26.5%) (p = 0.156), respectively, and an overestimation of PP was more common in the PA-HSOS group (33.3% vs. 2.9%, p = 0.004). HVPG and portal pressure gradient (PPG) consistency was poor in both groups (R: 0.51 vs. 0.26; ICC: 0.65 vs. 0.41; p < 0.05). Conclusions: WHVP in patients with PA-HSOS did not estimate PP as accurately as in patients with virus- or alcohol-related cirrhosis, which was mainly due to PP overestimation. [ABSTRACT FROM AUTHOR]

Background: Elevated serum ferritin is a common condition in critically ill patients. It is well known that hyperferritinemia constitutes a good biomarker for hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. However, further differential diagnoses of hyperferritinemia in adult critically ill patients remain poorly investigated. We sought to systematically investigate hyperferritinemia in adult critically ill patients without HLH. Methods: In this secondary analysis of a retrospective observational study, patients ≥18 years admitted to at least one adult intensive care unit at Charité–Universitätsmedizin Berlin between January 2006 and August 2018, and with hyperferritinemia of ≥500 μg/L were included. Patients with HLH were excluded. All patients were categorized into non-sepsis, sepsis, and septic shock. They were also classified into 17 disease groups, based on their ICD-10 codes, and pre-existing immunosuppression was determined. Uni- and multivariable linear regression analyses were performed in all patients. Results: A total of 2583 patients were analyzed. Multivariable linear regression analysis revealed positive associations of maximum SOFA score, sepsis or septic shock, liver disease (except hepatitis), and hematological malignancy with maximum ferritin. T/NK cell lymphoma, acute myeloblastic leukemia, Kaposi's sarcoma, acute or subacute liver failure, and hepatic veno-occlusive disease were positively associated with maximum ferritin in post-hoc multivariable linear regression analysis. Conclusions: Sepsis or septic shock, liver disease (except hepatitis) and hematological malignancy are important differential diagnoses in hyperferritinemic adult critically ill patients without HLH. Together with HLH, they complete the quartet of important differential diagnoses of hyperferritinemia in adult critically ill patients. As these conditions are also related to HLH, it is important to apply HLH-2004 criteria for exclusion of HLH in hyperferritinemic patients. Hyperferritinemic critically ill patients without HLH require quick investigation of differential diagnoses. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Angiogenesis, the process of formation of new blood vessels, is required for cancer cells to obtain nutrients and oxygen. HCC is a typical hypervascular solid tumor with an aberrant vascular network and angiogenesis that contribute to its growth, progression, invasion, and metastasis. Current anti-angiogenic therapies target mainly tyrosine kinases, vascular endothelial growth factor receptor (VEGFR), and plateletderived growth factor receptor (PDGFR), and are considered effective strategies for HCC, particularly advanced HCC. However, because the survival benefits conferred by these anti-angiogenic therapies are modest, new anti-angiogenic targets must be identified. Several recent studies have determined the underlying molecular mechanisms, including pro-angiogenic factors secreted by HCC cells, the tumor microenvironment, and cancer stem cells. In this review, we summarize the roles of pro-angiogenic factors; the involvement of endothelial cells, hepatic stellate cells, tumor-associated macrophages, and tumor-associated neutrophils present in the tumor microenvironment; and the regulatory influence of cancer stem cells on angiogenesis in HCC. Furthermore, we discuss some of the clinically approved anti-angiogenic therapies and potential novel therapeutic targets for angiogenesis in HCC. A better understanding of the mechanisms underlying angiogenesis may lead to the development of more optimized anti-angiogenic treatment modalities for HCC. [ABSTRACT FROM AUTHOR]

Late‐onset HOVD should be taken into consideration when patients develop liver dysfunction and/or weight gain no matter how long post‐HSCT. Solid organ transplantation offers a valuable therapeutic option for selected patients with single organ failure after HSCT without adverse impact on graft function or overall outcomes. This late‐onset HOVD case occurred beyond 16 months post‐HSCT indicating that late‐onset HOVD should be taken into consideration when patients developed related clinical signs no matter how long post‐HSCT. Solid organ transplantation offers valuable therapeutic options for patients with single organ failure after HSCT without adverse impact on overall outcomes. [ABSTRACT FROM AUTHOR]

Background: The use of venovenous extra corporeal membrane oxygenation (VV-Ecmo) in severe hypoxemic respiratory failure from coronavirus disease 2019 has been described but reported utilization and outcomes are variable and detailed data on patient characteristics is lacking. Objective: Our study aimed to evaluate the effect of extra-corporeal membrane oxygenation (ECMO) when compared to the traditional conventional protective lung strategy mechanical ventilation for Covid-19 ARDS associated Respiratory failure. Patients and Methods: This is a prospective study with 1:1 randomization for either to go through ECMO or keep on conventional mechanical ventilation with protective lung strategy for patient Covid-ARDS associated with respiratory failure. One hundred patients were randomized in each group. Results: Hundred patients were in each group. Age was 48.4 ± 9.0 in the standard care mechanical ventilation group versus 47.8 ± 8.3 in the ECMO group, 54 males and 46 females in the standard care group and 59 males and 41 females in the ECMO group. Vasopressor weaning was in 40 cases in the standard care group and 64 patients in the ECMO group with a significant statistical difference in favor of the ECMO group (p-value < 0.001). Also, weaning from mechanical ventilation was 29 patients versus 66 patients in the standard care group and in the ECMO group respectively (P-value <0.001). Also the inflammatory markers like CRP, D-dimer, procalcitonin, IL-6 and ferritin were more improved in the ECMO group, more than in the standard care group with a significant statistical difference (p-value <0.001), Conclusion: ECMO in Covid-19 ARDS respiratory failure patients was associated with weaning from mechanical ventilation & vasopressors and more improvement in the markers profile, together with the radiological point of view and arterial blood gases parameters when compared to the standard care group together with a great reduction in the length of stay in the intensive care unit with decrease in the mortality. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a chronic disorder and is one of the most common endocrine disorders in women of a reproductive age. The prevalence of PCOS is growing globally; 52% of women in Southeast Asia alone suffer from this disorder. This disorder is caused by chronic hyperandrogenism, which hinders folliculogenesis. There is also a close relationship between hyperandrogenism and hyperinsulinemia/insulin resistance (IR), and it is estimated that 40–80% of PCOS patients suffer from insulin resistance (IR). Mesenchymal stem cells (MSCs) and their secretomes have been shown to alleviate PCOS symptoms by decreasing IR and androgen secretion by reducing inflammation. This study aimed to systematically review the literature to study the reported potential of MSCs and their secretomes in decreasing inflammation markers in PCOS treatment. Methods: A systematic literature search was performed on EMBASE, PubMed (MEDLINE), and the Cochrane Library with the terms insulin-resistant PCOS, mesenchymal stem cells, and secretome or conditioned medium as the search keywords. A total of 317 articles were reviewed. Four articles were identified as relevant for this systematic review. Results: The results of this study supported the use of mesenchymal stem cells and their secretions in decreasing inflammatory markers in the treatment of polycystic ovary syndrome. Conclusions: This review provided evidence that treatment with mesenchymal stem cells and their secretomes has the potential to treat PCOS due to its ability to downregulate androgen levels and increase insulin sensitivity, which thereby lowers the level of proinflammatory factors. [ABSTRACT FROM AUTHOR]

Current pharmacotherapy options of drug-induced liver injury (DILI) remain under discussion and are now evaluated in this analysis. Needless to say, the use of the offending drug must be stopped as soon as DILI is suspected. Normal dosed drugs may cause idiosyncratic DILI, and drugs taken in overdose commonly lead to intrinsic DILI. Empirically used but not substantiated regarding efficiency by randomized controlled trials (RCTs) is the intravenous antidote treatment with N-acetylcysteine (NAC) in patients with intrinsic DILI by N-acetyl-p-aminophenol (APAP) overdose. Good data recommending pharmacotherapy in idiosyncratic DILI caused by hundreds of different drugs are lacking. Indeed, a recent analysis revealed that just eight RCTs have been published, and in only two out of eight trials were DILI cases evaluated for causality by the worldwide used Roussel Uclaf Causality Assessment Method (RUCAM), representing overall a significant methodology flaw, as results of DILI RCTs lacking RUCAM are misleading since many DILI cases are known to be attributable erroneously to nondrug alternative causes. In line with these major shortcomings and mostly based on anecdotal reports, glucocorticoids (GCs) and other immuno-suppressants may be given empirically in carefully selected patients with idiosyncratic DILI exhibiting autoimmune features or caused by immune checkpoint inhibitors (ICIs), while some patients with cholestatic DILI may benefit from ursodeoxycholic acid use; in other patients with drug-induced hepatic sinusoidal obstruction syndrome (HSOS) and coagulopathy risks, the indication for anticoagulants should be considered. In view of many other mechanistic factors such as the hepatic microsomal cytochrome P450 with a generation of reactive oxygen species (ROS), ferroptosis with toxicity of intracellular iron, and modification of the gut microbiome, additional therapy options may be available in the future. In summation, stopping the offending drug is still the first line of therapy for most instances of acute DILI, while various therapies are applied empirically and not based on good data from RCTs awaiting further trials using the updated RUCAM that asks for strict exclusion and inclusion details like liver injury criteria and provides valid causality rankings of probable and highly probable grades. [ABSTRACT FROM AUTHOR]

Background/Aims Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is one of the most fatal complications of hematopoietic cell transplantation (HCT), and defibrotide is the only curative drug. We conducted this study to confirm the survival rate of VOD/SOS patients diagnosed in Korea and assess the efficacy of defibrotide. Methods Patients diagnosed with VOD/SOS after allogenic HCT between 2003 and 2020 were enrolled. We investigated day +100 survival rates and associated risk factors in patients who satisfied the modified Seattle criteria within 50 days of HCT. Results A total of 110 patients satisfied the modified Seattle criteria, of which 65.5% satisfied the Baltimore criteria. Thirty-seven patients were treated with defibrotide. The day +100 survival rate of the 110 patients was 65.3%. The survival rates in patients who did not meet the Baltimore criteria and in those who did were 86.8% and 53.7%, respectively (p = 0.001). The day +100 survival rate of patients treated with defibrotide was 50.5%. Among the patients receiving defibrotide, those whose creatinine levels were more than 1.2 times the baseline had a significantly lower survival rate at 26.7% (p = 0.014). On multivariate regression analysis, the hazard ratio of satisfaction of the Baltimore criteria was 4.54 (95% confidence interval [CI], 1.69 to 12.21; p = 0.003). In patients treated with defibrotide, the hazard ratio was 8.70 (95% CI, 2.26 to 33.45; p = 0.002), when creatinine was more than 1.2 times the baseline on administration. Conclusions The day +100 survival rate was significantly lower when the Baltimore criteria were satisfied, and when there was an increase in creatinine at the time of defibrotide administration.

The article presents the case study of 38-year-old woman with dyspnea on exertion, myalgias, and mild lower extremity claudication. Topics include revealing precapillary pulmonary hypertension, ground glass on chest computed tomography (CT), and a very low diffusing capacity for carbon monoxide; and unexpectedly revealing elevated fluorodeoxyglucose (FDG) uptake most prominently in the aorta.

Previous studies have reported patients with VEXAS being transplanted in the absence of a prior diagnosis, including one of the patients we report here (P4). Keywords: allogeneic haematopoietic stem cell transplantation; chronic myelomonocytic leukaemia; myelodysplastic syndrome; VEXAS syndrome EN allogeneic haematopoietic stem cell transplantation chronic myelomonocytic leukaemia myelodysplastic syndrome VEXAS syndrome 777 781 5 11/24/22 20221201 NES 221201 Vacuoles, E1-ligase, X-linked, Auto-inflammatory, Somatic (VEXAS) syndrome, is an acquired, progressive systemic auto-inflammatory disorder with overlapping rheumatological and haematological features.1,2 It is caused by myeloid-restricted somatic mutations in ubiquitin-like modifier-activating enzyme 1 ( I UBA1 i ), the gene that encodes E1 ubiquitin ligase. Very few patients had any inflammatory symptoms or disease manifestations classically associated with VEXAS (Table 2).2,5 The MDS features were also different. [Extracted from the article]

Simple Summary: For patients undergoing multimodal treatment for colorectal liver metastases (CLM), the development of sinusoidal obstruction syndrome (SOS) as a side effect of oxaliplatin-based chemotherapy may endanger the prospects after liver resection. In this study, we aimed to investigate possible protective effects of an additional preoperative inhibition of vascular endothelial growth factor (VEGF) on the occurrence of SOS and its implications on liver function and regeneration after liver resection. After successful establishment of a novel murine model of SOS, we were able to show a reduced incidence of SOS after additive treatment with a VEGF inhibitor. Changes in the VEGF pathway, namely in the expression of VEGF receptor-2 (VEGF-R2), may be responsible for these findings. By preventing the incidence of SOS, the inhibition of VEGF may help to reduce morbidity after liver resection for patients with CLM. Further clinical studies are needed to corroborate our results. (1) Background: Sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy is associated with unfavorable outcomes after partial hepatectomy for colorectal liver metastases (CLM). Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), may prevent SOS development. We investigated the impact of VEGF-inhibition on the development of SOS in a murine model. (2) Methods: Male wild-type and CD39-null mice received oxaliplatin, additional anti-VEGF (OxAV), or controls, and were sacrificed or subjected to major partial hepatectomy (MH). Specimen were used for histological analysis of SOS. Liver damage was assessed by plasma transaminases. The VEGF pathway was elucidated by quantitative PCR of liver tissue and protein analysis of plasma. (3) Results: Mice treated with oxaliplatin developed SOS. Concomitant anti-VEGF facilitated a reduced incidence of SOS, but not in CD39-null mice. SOS was associated with increased plasma VEGF-A and decreased hepatocyte growth factor (HGF). After OxAV treatment, VEGF-R2 was upregulated in wild-type but downregulated in CD39-null mice. Oxaliplatin alone was associated with higher liver damage after MH than in mice with concomitant VEGF-inhibition. (4) Conclusions: We established a murine model of oxaliplatin-induced SOS and provided novel evidence on the protective effect of VEGF-inhibition against the development of SOS that may be associated with changes in the pathway of VEGF and its receptor VEGF-R2. [ABSTRACT FROM AUTHOR]

Numb chin syndrome (NCS) is a rare sensory neuropathy resulting from inferior alveolar or mental nerve injury. It manifests as hypoesthesia, paraesthesia, or, rarely, as pain in the chin and lower lip. Several case reports suggest that sickle cell disease (SCD) could be a cause of NCS. However, information about NCS is scarce in this population. Our objectives were to synthesize all the available literature relevant to NCS in SCD and to propose recommendations for diagnosis and management based on the best available evidence. A systematic review was performed on several databases to identify all relevant publications on NCS in adults and children with SCD. We identified 73 publications; fourteen reports met the inclusion/exclusion criteria. These described 33 unique patients. Most episodes of NCS occurred in the context of typical veno-occlusive crises that involved the mandibular area. Radiological signs of bone infarction were found on some imaging, but not all. Neuropathy management was mostly directed toward the underlying cause. Overall, these observations suggest that vaso-occlusion and bone infarction could be important pathophysiological mechanisms of NCS. However, depending on the individual context, we recommend a careful evaluation to rule out differential causes, including infections, local tumors, metastatic disease, and stroke. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to review the incidence, spectrum and investigation of liver masses presenting to our tertiary liver unit. Methods: A retrospective single-centre cohort study of paediatric patients (age < 16 years) diagnosed with a liver mass who were investigated at a UK paediatric hepatobiliary tertiary referral centre. Data relating to the clinical findings at presentation, source of referral, diagnostic investigations and histopathology findings were recorded and analysed. Results: 107 patients were identified between July 2012 and July 2019 (55 females). 69 (64%) patients had benign liver lesions, whereas the remaining 38 (36%) were found to have malignant masses. The liver lesions were most commonly detected incidentally (33%) with the second most common presentation being with palpable mass (29%). 82 (77%) patients were referred from other hospitals. All patients underwent USS, 74% MRI, 36% CT, 5% CEUS, 1% PET and 5% HIDA scan with 47% ultimately undergoing biopsy. 72% of patients had AFP measured. The most common benign liver masses were haemangioma 33 (48%), hepatic cyst 17 (25%) and FNH 12 (19%). Amongst the malignant lesions, 29 (76%) were hepatoblastoma and 3 (8%) were hepatocellular carcinoma. Conclusions: This large review series demonstrates that just over 1/3 of patients presenting to a paediatric tertiary referral centre with a focal liver lesion had neoplastic liver lesions, despite the published literature commonly stating that 2/3 of paediatric liver masses are malignant. [ABSTRACT FROM AUTHOR]