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Introduction There is subgroup analysis suggesting a lack of benefit of daratumumab use in multiple myeloma (MM) and hepatic disease (HD). The objectives of this study were to conduct a systematic review and interpretation of daratumumab-based regimen efficacy in transplant-ineligible patients with untreated MM and HD. Methods A systematic search in Pubmed® database about randomized clinical trials (RCTs) with subgroup analysis regarding hepatic function for overall survival (OS) or progression-free survival (PFS) were developed. Two methodologies were applied. One of them considered statistical interaction, prespecification, biological support and consistency of subgroup results. Second methodology was two-part validated tool: preliminary questions to reject subset analysis without minimal relevance, and a checklist relating a recommendation for applicability in clinical practice. Results It was included three records. About first methodology, statistical interaction among subgroups was found for PFS in one RCT. Subsets were prespecified in all RCTs. Biological support of efficacy differences could be reasonable. Inconsistent results were found. Second methology directly rejected applicability of subset analysis in two records. Checklist recommended “null” application of results in the remaining RCT. Conclusions No consistent heterogeneity for daratumumab-based regimen efficacy was observed among subgroups regarding hepatic function in transplant-ineligible patients with untreated MM. Patients with normal hepatic function and HD could benefit from these treatments.

The history of asparaginase clinical use is inextricably linked to the improvement of treatment programs for acute lymphoblastic leukaemia (ALL). Asparaginase, obtained from E. coli, has become the crucial part in the protocols for the treatment of ALL in children and adults since the 1960s-1970s due to its antitumor effect on lymphoid leukemia cells. Despite the evolution of therapeutic approaches in ALL management, changes in used chemotherapeutic agents, their administration regimens and doses, the asparaginase remains one of the leading therapeutic agents in ALL patients. With time ideas about the asparaginase mechanisms have expanded, new data have been accumulated on adverse effects (allergic reactions, thrombotic complications, pancreatitis, hepatic dysfunction, etc.). The asparaginase obtained from Erwinia chrysanthemi and PEGylated forms of the drug were used to reduce the frequency of any of such adverse effects. This literature review provides current concepts on the mechanism of L-asparaginase dosage forms action, describes side effects associated with the use of this medication. We also present our own clinical case of L-asparaginase (obtained from Erwinia chrysanthemi) administration in ALL patient with allergic reaction to PEG-L-asparaginase.

Background Oxygen delivery during cardiopulmonary bypass (CPB) is closely related to postoperative acute kidney injury (AKI). The value of critical indexed oxygen delivery (DO2i) is a key indicator to reflect oxygen supply in cardiovascular surgery. However, the target DO2i value for neonates undergoing hypothermic CPB remains unclear. Methods One hundred and twenty-six consecutive newborns (≤28 days) undergoing arterial switch operations were retrospectively divided into two groups according to AKI occurrence. Baseline characteristics, intraoperative variables, and clinical outcomes were collected. Multivariate logistic regression analysis and receiver-operating characteristic curve were performed to investigate the association between DO2i and AKI. Results Neonates in the no-AKI group (n = 67) had significantly higher nadir bypass flow and DO2i during the hypothermic phase compared with the AKI group (n = 59). AKI group had remarkably higher incidences of hepatic dysfunction and peritoneal dialysis requirement compared with newborns without AKI. Mixed venous oxygen saturation (SvO2) was comparable between the two groups. Base excess (BE)(P = 0.011) value during the hypothermic phase of the AKI group was higher than the no-AKI group. Multivariate analysis showed that hypothermic DO2i was negatively associated with AKI. The cut-off value of hypothermic DO2i was 269 mL min-1 m-2. Conclusions The importance of hypothermic DO2i should be highlighted, even when SvO2 was satisfactory. A lower threshold of DO2i > 269 mL min-1 m-2 may help protect neonates from the risk of postoperative AKI. Impact The key message of our article is that the lower threshold of DO2i > 269 mL min-1 m-2 may help protect neonates from the risk of AKI after on-pump hypothermic cardiovascular surgery. The critical DO2i value for neonates undergoing hypothermic CPB remains unclear, and our study may add new evidence for this matter based on the 6-year experience of our center. In this study, the lowest critical value of DO2i in neonatal hypothermic CPB is determined for the first time, which provides a reference for intra-CPB management strategy to improve the postoperative outcomes of newborns.

Toxicity related to acetaminophen is most encountered with the acute ingestion of large doses. However, toxicity may also result from chronic ingestion, even when recommended doses are administered over a prolonged period of time. We present the case of a 20-month-old female toddler who received therapeutic recommended doses of acetaminophen (oral or intravenous) following multiple surgical interventions for treatment of a tracheo-esophageal fistula following ingestion of a button battery. The potential role of chronic acetaminophen administration in the etiology of hepatoxicity is discussed and prevention strategies are presented.

Background The coronavirus disease 2019 (COVID-19), a pandemic contributing to more than 105 million cases and more than 2.3 million deaths worldwide, was described to be frequently accompanied by extrapulmonary manifestations, including liver dysfunction. Liver dysfunction and elevated liver enzymes were observed in about 53% of COVID-19 patients. Aim To gain insight into transcriptional abnormalities in liver tissue of severe COVID-19 patients that may result in liver dysfunction. Methods The transcriptome of liver autopsy samples from severe COVID-19 patients against those of non-COVID donors was analyzed. Differentially expressed genes were identified from normalized RNA-seq data and analyzed for the enrichment of functional clusters and pathways. The differentially expressed genes were then compared against the genetic signatures of liver diseases including cirrhosis, fibrosis, non-alcoholic fatty liver disease (NAFLD), and hepatitis A/B/C. Gene expression of some differentially expressed genes was assessed in the blood samples of severe COVID-19 patients with liver dysfunction using qRT-PCR. Results Analysis of the differential transcriptome of the liver tissue of severe COVID-19 patients revealed a significant upregulation of transcripts implicated in tissue remodeling including G-coupled protein receptors family genes, DNAJB1, IGF2, EGFR, and HDGF. Concordantly, the differential transcriptome of severe COVID-19 liver tissues substantially overlapped with the disease signature of liver diseases characterized with pathological tissue remodeling (liver cirrhosis, Fibrosis, NAFLD, and hepatitis A/B/C). Moreover, we observed a significant suppression of transcripts implicated in metabolic pathways as well as mitochondrial function, including cytochrome P450 family members, ACAD11, CIDEB, GNMT, and GPAM. Consequently, drug and xenobiotics metabolism pathways are significantly suppressed suggesting a decrease in liver detoxification capacity. In correspondence with the RNA-seq data analysis, we observed a significant upregulation of DNAJB1 and HSP90AB1 as well as significant downregulation of CYP39A1 in the blood plasma of severe COVID-19 patients with liver dysfunction. Conclusion Severe COVID-19 patients appear to experience significant transcriptional shift that may ensue tissue remodeling, mitochondrial dysfunction and lower hepatic detoxification resulting in the clinically observed liver dysfunction.

Background Hypertension, proteinuria, and hepatic dysfunction have been described as manifestations of coronavirus disease 2019 (COVID-19) and are generally accepted as poor prognostic factors. However, these same findings can also occur in pregnant women with preeclampsia, thus creating a diagnostic challenge. Case We report a case of COVID-19 infection in an otherwise healthy pregnant patient with secondary hypertension, proteinuria, and significant hepatic dysfunction. Maternal placental growth factor (PlGF) testing was used to rule out preeclampsia. The patient received supportive care and improved significantly. She went on to have a spontaneous vaginal term delivery of a healthy male baby. Conclusion COVID-19 infection in pregnancy may present as preeclampsia-like syndrome. PlGF testing can be used to differentiate preeclampsia from COVID-19 and facilitate appropriate management.

Arsenic exposure causes immense health distress by increasing risk of cardiovascular abnormalities, diabetes mellitus, neurotoxicity, and nephrotoxicity. The present study explored the role of inducible nitric oxide synthase (iNOS) inhibitors against sodium arsenite-induced renal and hepatic dysfunction in rats. Female Sprague Dawley rats were subjected to arsenic toxicity by administering sodium arsenite (5 mg/kg/day, oral) for 4 weeks. The iNOS inhibitors, S-methylisothiourea (10 mg/kg, i.p.) and aminoguanidine (100 mg/kg, i.p.) were given one hour before sodium arsenite administration in rats for 4 weeks. Sodium arsenite led rise in serum creatinine, urea, uric acid, electrolytes (potassium, fractional excretion of sodium), microproteinuria, and decreased creatinine clearance (

Introduction: Dengue is the most rapidly spreading mosquito-borne viral disease. Liver is the most commonly affected organ and manifests as asymptomatic transaminitis to acute liver failure. Aim: (1) To study the clinical and biochemical profile of liver involvement. (2) To find the association between severity of hepatic dysfunction, morbidity and mortality in the admitted patients. Method and Material: This was a prospective study involving confirmed dengue fever cases admitted in Tata Main Hospital from January 2018 to December 2019. Cases were classified into non-severe dengue and severe dengue based on 2009 WHO classification. Severity of hepatic dysfunction was divided into grades A, B, C and D and correlation with various outcomes which included length of stay, complications and mortality was studied through relevant investigations. Results: Out of the 175 cases, Non-severe Dengue (NSD) was seen among 72.6% patients while severe dengue (SD) in 28.5% patients. Normal liver function was found in 68.6%, Grade B liver injury in 8% while Grade C and Grade D liver injury in 16.6% and 16.8% patients respectively. Mean AST levels were found to be higher than those of ALT levels. Longer hospital stay, complications like shock, acute kidney injury (AKI), thrombocytopenia and mortality were significantly more in patients with higher grades of liver dysfunction (p=0.03), while ARDS and MODS were seen only in patients with Grade C and Grade D liver injury. Conclusion: AST and ALT levels were statistically higher in Dengue fever patients with worse outcome. They can thus, serve as prognostic markers of severe Dengue.

Background Dogs with portosystemic shunts have an altered blood amino acid profile, with an abnormal branched-chained amino acid (BCAA)-to-aromatic amino acid (AAA) ratio being the most common abnormality. Different liver diseases have distinctive amino acid profiles. Objectives Determine the changes in plasma amino acid profiles in dogs with extrahepatic portosystemic shunts (EHPSS) from diagnosis to complete closure. Animals Ten client-owned dogs with EHPSS closed after surgical attenuation. Methods Prospective cohort study. Medical treatment was instituted in dogs diagnosed with EHPSS. At least 4 weeks later, gradual surgical attenuation was performed. Three months postoperatively, EHPSS closure was confirmed by transsplenic portal scintigraphy. Clinical signs were scored and blood was taken before institution of medical treatment, at time of surgery, and 3 months postoperatively. At the end of the study, the plasma amino acid profiles were analyzed in batch. Results The median BCAA-to-AAA ratio was extremely low (0.6) at time of diagnosis and remained low (0.5) at time of surgery, despite the fact that median neurological score significantly improved from 22 to 2 after starting medical treatment (P = .04). Three months after surgical attenuation, a significantly higher BCAA-to-AAA ratio (1.5) was observed (P < .001). Conclusions and Clinical Importance Medical treatment does not improve the BCAA-to-AAA ratio in dogs with EHPSS, despite substantial clinical improvement. Although the ratio significantly increased after EHPSS closure, it was still indicative of moderate to severe hepatic dysfunction in all dogs.

Introduction Improvements in glycemic control and hepatic function are clinically important goals in the treatment of patients with type 2 diabetes mellitus (T2DM) complicated by hepatic dysfunction. The favorable effects of the sodium–glucose co-transporter inhibitor luseogliflozin on hepatic dysfunction were anticipated for humans. Nevertheless, few clinical studies have confirmed its real-world efficacy on hepatic dysfunction. This trial assessed the efficacy and safety of luseogliflozin in patients with T2DM complicated by hepatic dysfunction. Methods This prospective, single-site, single-arm, open-label, exploratory trial included 55 subjects with T2DM complicated by hepatic dysfunction. Subjects were administered luseogliflozin and observed for 52 weeks. The primary endpoints were the change in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), and hemoglobin A1c (HbA1c) from baseline to week 52. The secondary endpoints included body weight, body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG), homeostatic model assessment beta (HOMA-β), homeostatic model assessment of insulin resistance (HOMA-IR), ferritin, Mac-2 binding protein (M2-BP), fatty liver index (FLI), fibrosis-4 (FIB-4) index, type IV collagen 7S domain, nonalcoholic fatty liver disease (NAFLD) fibrosis score, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6). Results AST, ALT, γ-GTP, and HbA1c significantly decreased from baseline to week 52. Body weight, BMI, waist circumference, and FPG also significantly decreased. HOMA-IR significantly decreased but HOMA-β was unchanged. FLI, ferritin, M2-BP, and NAFLD fibrosis scores significantly decreased whereas the FIB-4 index and type IV collagen 7S domain did not significantly change. The hs-CRP and IL-6 levels did not significantly change. Conclusion Luseogliflozin administration in patients with T2DM complicated by hepatic dysfunction was well tolerated, did not worsen the hepatic condition, and might even be beneficial to improve hepatic function, reduce liver fat, and attenuate liver injury and fibrosis. Trial Registration This study was registered under the University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR) (No. UMIN000025808) and the Japan Registry of Clinical Trials (jRCT) (No. jRCTs021180017).

Purpose of review This article describes the clinical presentation, relevant diagnostic investigations, and treatment of metabolic and toxic myelopathies. Recent findings Metabolic myelopathies, including those due to deficiency of vitamin B12, folate, copper, or vitamin E, are preventable and typically respond to supplementation. In metabolic myelopathy, early recognition and treatment are important to reduce morbidity, particularly due to subacute combined degeneration of the spinal cord. Toxic myelopathies, including those due to medical interventions (eg, methotrexate, radiation), dietary toxins (eg, lathyrism, konzo), and drugs of abuse (eg, heroin), typically result in permanent neurologic deficits. Toxic myelopathy due to hepatic dysfunction may be reversible if patients receive early intervention, whereas nitrous oxide myelopathy responds to vitamin B12 replacement and cessation of exposure. In toxic myelopathy, it is best to avoid the provoking factor when possible or attempt to mitigate risk by identifying risk factors for developing myelopathy. Summary Metabolic and toxic myelopathies are important causes of morbidity that require a high index of suspicion for diagnosis.

Introduction: Intestinal failure-associated liver disease (IFALD) refers to hepatic dysfunction that results from prolonged parenteral nutrition (PN) use. IFALD is multifactorial in origin and remains a major cause of morbidity and mortality. Prior to 2004, IFALD was associated with mortality as high as 90% in infants who remained on PN greater than 1 year. The advent of new strategies for intravenous lipid emulsion (ILE) administration and improved catheter care now allow many patients to remain on PN and recover from this once fatal condition. Several additional treatment modalities are often used to further improve outcomes for IFALD patients and they are reviewed here.Areas covered: The etiology of IFALD is presented, as well as the rationale behind the use of ILEs that contain fish oil. Other management strategies are addressed, including the effects of several pharmacologic and nutritional interventions.Expert opinion: Like its etiology, the management of IFALD is multifactorial. Prompt recognition of patients at risk, avoiding macronutrient excess, and preventing central line associated bloodstream infections will improve outcomes. In patients who develop IFALD, the use of fish oil monotherapy seems to be efficacious. The most effective intervention, however, continues to be discontinuation of PN and achieving full enteral feedings.

Background Coronavirus disease 2019 (COVID-19) is a pandemic disease spreading all over the world and has aroused global concerns. The increasing mortality has revealed its severity. It is important to distinguish severe patients and provide appropriate treatment and care to prevent damages. Diabetes is reported to be a common comorbidity in COVID-19 patients and associated with higher mortality. We attempted to clarify the relationship between diabetes and COVID-19 patients' severity. Aim To determine the role of type 2 diabetes in COVID-19 patients. Methods To study the relationship between diabetes and COVID-19, we retrospectively collected 61 patients' data from a tertiary medical center in Wuhan. All the patients were diagnosed with laboratory-confirmed COVID-19 and admitted to the center from February 13 to March 1, 2020. Patients' age, sex, laboratory tests, chest computed tomography findings, capillary blood glucose (BG), and treatments were collected and analyzed. Fisher exact test was used for categorical data. Univariate and multivariate logistic regressions were used to explore the relationship between clinical characteristics and patients' severity. Results In the 61 patients, the comorbidity of type 2 diabetes, hypertension, and heart diseases were 24.6% (15 out of 61), 37.7% (23 out of 61), and 11.5% (7 out of 61), respectively. The diabetic group was related to more invasive treatments (P = 0.02) and severe status (P = 0.003). In univariate logistic regression, histories of diabetes (OR = 7.13, P = 0.003), hypertension (OR = 3.41, P = 0.039), and hepatic dysfunction (OR = 7.69, P = 0.002) were predictors of patients' severity while heart disease (OR = 4.21, P = 0.083) and large lung involvement (OR = 2.70, P = 0.093) also slightly exacerbated patients' conditions. In the multivariate analysis, diabetes (OR = 6.29, P = 0.016) and hepatic dysfunction (OR = 5.88, P = 0.018) were risk factors for severe patients. Diabetic patients showed elevated BG in 61.7% of preprandial tests and 33.3% of postprandial tests, revealing the limited control of glycemia in COVID-19 patients. Conclusion A history of type 2 diabetes is correlated with invasive treatments and severe status. Suboptimal glycemic control and hepatic dysfunction have negative effects on severity status and may lead to the exacerbation of COVID-19 patients.

In this article we are providing a theoretical background for understanding different types of hepatotoxicities induced by drugs. Drug induced hepatotoxicity a potential complication of nearly every medication that is prescribed, because the liver is central to the metabolic disposition of virtually all drugs and foreign substances. Although drugs are metabolised without injury to the liver, many fatal and near fatal drug reactions occur each year. More than 900 drugs have been implicated in causing liver injury and it is the most common reason for a drug to be withdrawn from the market. Keywords: Hepatotoxicity, Hepatic dysfunction, Jaundice, Liver failure.

Objectives To present a case report of succesfully metyrapone treatment of a neonatal patient with McCune–Albrigth syndrome (MAS), a rare disease caused by a genetically mosaic disorder and is characterized by variable hyperfunctional endocrinopathies, bone dysplasia, and café-au-lait spots. Case presentation A preterm newborn was admitted to hospital and she presented difficulty controlling hypertension, café-au-lait spots, and failure to thrive. An abdominal ultrasound and a magnetic resonance showed a high volume of both suprarenal glands. Therefore, MAS was suspected. Laboratory data confirmed adrenocorticotropic hormone-independent Cushing’s syndrome with hepatic dysfunction and metyrapone treatment was initiated. A progressive normalization of cortisol levels was achieved despite poor oral tolerance. Conclusion Our case shows that metyrapone is useful in the management of neonatal Cushing’s syndrome due to McCune–Albright syndrome.

Background Stauffer Syndrome (SS) is a paraneoplastic disorder associated with renal cell carcinoma (RCC). First described by Herbert Maurice Stauffer in 1961, it is characterized by hepatic dysfunction in the absence of metastasis, and elevated alkaline phosphatase, aminotransferases and prolonged prothrombin time. Initial reports did not include jaundice as an inclusion criterion. We aim to report the rare SS jaundice variant in a patient with a small renal mass and review the literature to determine if the size of the renal mass could influence the development of the SS. Case presentation The aim of this article is to present the case of a 53-year-old male with Stauffer syndrome jaundice variant secondary to a 2.5 cm renal mass, treated with laparoscopic radical nephrectomy with complete resolution of the syndrome. Conclusions This syndrome is yet to be fully understood, and as far as the evidence shows, size does not matter. This entity should always be in mind when encountered with a patient with liver dysfunction and jaundice with a suspicion or confirmed diagnosis of a renal mass. To date, and to our knowledge, there have been eleven reported cases of paraneoplastic cholestatic jaundice syndrome including the current case. Six cases presented in patients with small renal mases (

Atherosclerosis, a disease which affects large and medium sized arteries, is now a leading cause of death in many developed countries. High serum LDL (low density lipoproteins) and VLDL (very low density lipoproteins) levels are considered as atherogenic, whereas high HDL (High Density Lipoproteins) over 60 mg/Dl has a protective effect.Literature reviews were conducted by me from different articles on hypolipidemic drugs and the present review looking forward ideal hypolipidemic drugs with their target of action in the treatment of atherosclerosis.Statins are the first line antilipidemic drugs which possess dose dependent adverse effects like muscle pain, neuropathy, hepatic dysfunction and rhabdomyolysis. Reducing the statin dose, adding drug like proproteinconvertasesubtilisin/kexin type 9 inhibitors, supplements with coenzyme Q10 and L-carnitinie are some of the approaches to reduce statin advderse effects. In future for those patients who cannot tolerate statin and for those who can’t achieve LDL target, squalene synthase inhibitors are the best choice. We focused on current existing hypolipidemic drugs, their targets and mechanism of actions and also the new ideal antilipidemic drugs of future. Ideal antilipidemic drug is one which should produce target lipid level, cause fewer side effects and drug interactions.

Children with leukemia commonly receive red blood cell (RBC) transfusions and transfusion-related iron overload (TRIO) is a major complication. However, few studies have evaluated TRIO in children with leukemia and no guidelines for screening exist. This retrospective, observational cohort study in children with acute leukemia evaluates the prevalence of TRIO and its impact on end-organ function.The study included 139 patients; 60% standard-risk acute lymphoblastic leukemia (ALL), 32% high-risk (HR) ALL, and 9% acute myeloid leukemia (AML). The mean age at diagnosis was 6 years (range: 5 mo to 18 y). Patients with HR-ALL and AML were more likely to be transfused with ≥10 RBC units (59% and 92%, respectively) compared with those with standard-risk ALL (18%) (P0.0001). Ferritin levels were measured in 68% patients and elevated (1000 mcg/L) in 23%. Endocrinopathies were the most common end-organ abnormality. Hepatic dysfunction was significantly higher in patients with ≥10 RBC units transfused compared with those with10 units (P=0.008).Although the RBC transfusion burden is highest in patients with AML and HR-ALL, TRIO screening was not commonly performed. Patients who receive ≥10 RBC units are at risk for hepatic and endocrine dysfunction. We recommend routine screening for TRIO in children with leukemia, who are at risk for a higher transfusion burden.

Спонтаниот бактериски перитонитис (СБП) кај пациентите со црнодробна цироза е новонастаната, спонтана бактериска инфекција на стерилна асцитна течност, во отсуство на интраабдоминални извори на инфекција или малигнитет. Најсензитивен показател за поставување на дијагнозата е бројот на полиморфонуклеарни клетки (ПМНК) ≥250 во 1 мл асцитна течност (рачно микроскопско или автоматизирано пребројување) и/или кога во микробиолошката култура биде изолиран еден бактериски вид. Цел на трудот е да се одреди концентрацијата на калпротектин во асцит кај пациентите со СБП и не-СБП, да се споредат просечните вредности на Turcotte-Pugh II и MELD скорот кај пациентите со СБП и не-СБП и просечните вредности на C-реактивниот протеин во серум и во асцит во испитуваните групи. Материјали и методи. Во оваа проспективно-аналитичко-опсервациска пилот студија беа вклучени 30 пациенти со црнодробна цироза и асцит, поделени во две групи, СБП и не-СБП. Квантитативното мерење на калпротектин во асцит се вршеше со тестот Quantum Blue Calprotectin Ascites (LF-ASC25). Тестот е дизајниран за селективно мерење на антигенот на калпротектинот (MRP8/14) со директен сендвич имуноесеј. Примероците од асцитот се разредуваа со Chase Buffer во однос 1:5 и по 12 минути инкубација на собна температура, интензитетот на сигналот на линијата за тестирање и контролната линија се мереа квантитативно со BÜHLMANN Quantum Blue®Reader. Собраните податоци се обработија со помош на статистичкиот програм SPSS 23 за Windows. Резултати. Во нашата студија просечната вредност на калпротектин кај пациентите со СБП изнесуваше 1,4 μg/mL. Најниската вредност на калпротектин во испитуваната група беше регистрирана кај еден пациент со вредност од 0,61 μg/mL, додека највисока вредност од 1,81μg/mL кај четири пациенти. Резултатите покажаа повисоки вредности на калпротектин во асцит кај пациентите со алкохолна болест на црниот дроб во споредба со останатите етиологии. Рефракторен асцит се регистрира кај 60,0% од испитаниците, а само кај еден пациент (6,7%) се регистрира Klepsiella pneumoniae во микробиолошката анализа на асцитот. Според Child-Turcotte-PughII класификација сите пациенти од испитуваната група беа класа C, додека просечната вредност на MELD скорот изнесуваше 29,8±6,14. Разликата помеѓу просечните вредности наC-реактивниот протеин во серум и во асцит кај пациентите со СБП беше статистички сигнификантна во споредба со не-СБП. Заклучок. Kвантитативното одредување на калпротектинот во асцит со тестот Quantum Blue Calprotectin Ascites(LF-ASC25) може да се користи како алтернатива наполиморфонуклеарните клетки (ПМНК) во асцит. СБП се јавува кај пациенти со сериозна црнодробна дисфункција пресметана според Child-Pugh II скорот и MELD скорот. Вредноста на C-реaктивниот протеин во серум и во асцит кај пациентите со СБП немаше високи вредности ,но сепак беше утврдена сигнификантна разлика во споредба со пациентите со не-СБП.

Background Liver is one of a common site of metastasis in metastatic breast cancer, and associated with visceral crisis in breast cancer. The clinical course and prognosis of breast cancer with liver metastasis (BCLM) is quite different with other solid cancers presenting with liver metastasis. BCLM patients frequently develop hepatic failure due to liver metastasis, but there are no clinicopathologic or radiologic parameters estimating the prognosis of BCLM during their clinical course. In this study, we analyzed the relationship of radiologic, clinicopathologic characteristics and survival outcomes in BCLM patients. Methods Between January 2009 to May 2019, 156 BCLM patients were analyzed. Baseline and final abdomen CT scan or liver MRI during treatment was reviewed by experienced radiologist. The pattern of liver metastasis was classified as oligometasis (3 or less metastatic lesions), non-confluent mass formation, confluent mass formation, infiltrative and pseudocirrhosis pattern. Clinicopathologic characteristics including child-pugh score (CPS) and survival outcomes including liver metastasis associated overall survival (LMOS) was analyzed Results Among 156 patients, 77 patients were initially presented with oligometastasis, 58 patients with non-confluent mass-forming pattern, 14 patients with confluent mass formation, and 7 patients with infiltrative liver metastasis. Patients who showed liver metastasis at initial recurrence or metastasis showed confluent mass-forming (9 patients, 64.3%) or infiltrative liver metastasis (6 patients, 85.7%) as presentation. At patient’s death, initial confluent mass-forming or infiltrative liver metastasis patients showed hepatic dysfunction with CPS 2 or 3. Patients with oligometastasis showed superior LMOS compared to non-confluent mass-forming, confluent mass-forming and infiltrative liver metastasis with worst survival outcome (median LMOS 55.03 months vs. 36.87, 36.93 and 8.8 months, P=0.0021). In luminal B patients, radiologic liver metastasis pattern at patient’s death or last follow-up were associated to cause of patient’s death such as hepatic failure (P=0.044). There were no survival benefit of patients who received local treatment for liver metastasis, compared to patients who only received systemic chemotherapy. Conclusion Initial hepatic metastasis pattern were associated with LMOS, especially infiltrative liver metastasis associated to poor survival outcome. There were no survival benefit of local treatment of liver metastasis during follow-up. Authors are planning on subsequent analysis based on pathologic classification of liver metastasis. Citation Format: Jieun Lee, Moon Hyung Choi, Ahwon Lee, Sung Hak Lee. Pattern of hepatic metastasis as a prognostic index in breast cancer liver metastasis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-54.

Objective: To investigate the incidence, clinical characteristics and outcomes of early hyperbilirubinemia in critically ill patients. Design and Setting: This is a post hoc analysis of a prospective multicenter cohort study. Patients: Patients with measured bilirubin levels within the first 2 days after ICU admission were eligible. Patients with liver cirrhosis were excluded. Endpoints: The primary endpoint was the incidence of early hyperbilirubinemia, defined as bilirubin ≥33 μmol/L within 2 days after ICU admission. Secondary endpoints included clinical characteristics of patients with versus patients without early hyperbilirubinemia, and outcomes up to day 30. Results: Of 4,836 patients, 559 (11.6%) patients had early hyperbilirubinemia. Compared to patients without early hyperbilirubinemia, patients with early hyperbilirubinemia presented with higher severity of illness scores, and higher incidences of sepsis and organ failure. After adjustment for confounding variables, early hyperbilirubinemia remained associated with mortality at day 30 (odds ratio, 1.31 [95%–confidence interval 1.06–1.60]; P = 0.018). Patients with early hyperbilirubinemia and thrombocytopenia (interaction P-value = 0.005) had a higher likelihood of death within 30 days (odds ratio, 2.61 [95%–confidence interval 2.08–3.27]; P < 0.001) than patients with early hyperbilirubinemia and a normal platelet count (odds ratio, 1.09 [95%–confidence interval 0.75–1.55]; P = 0.655). Conclusions: Early hyperbilirubinemia occurs frequently in the critically ill, and these patients present with higher disease severity and more often with sepsis and organ failures. Early hyperbilirubinemia has an association with mortality, albeit this association was only found in patients with concomitant thrombocytopenia.

The aim of the present study was to clarify the effect of recombinant human erythropoietin (EPO) and low molecular weight heparin (LMWH) on a rat model of lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC). Experimental DIC was induced by sustained infusion of 5 mg/kg LPS for 4 h. EPO or LMWH was then administered to the LPS-induced DIC model. LPS-induced consumption coagulopathy, hemostatic activation and plasma TNF elevation remained unaltered in the LPS+EPO group, except for the D-dimer levels, and these abnormalities were significantly improved in the LPS+LMWH group. Plasma alanine aminotransferase (ALT) levels were markedly reduced in the LPS+EPO group, accompanied by a significant suppression of hepatocellular apoptosis. In the LPS+LMWH group, plasma creatinine levels and glomerular fibrin deposition were significantly attenuated, along with plasma ALT levels and hepatocellular apoptosis. Thus, a single administration of EPO may improve hepatic dysfunction by primarily exerting an anti-apoptotic, not anticoagulant, effect in the LPS-induced DIC model.

Background: This study was aimed to investigate the incidence, risk factors, and outcomes of patients with postoperative hepatic dysfunction (PHD) after frozen elephant trunk (FET) for type A aortic dissection (TAAD).Method: A retrospective study was performed with 492 patients who underwent FET for TAAD between 2015 and 2019. Independent risk factors for PHD were determined by multivariate mixed-effect logistic analysis with surgeon-specific factor as a random effect.Results: The incidence of PHD was 25.4% (n = 125) in our cohort. Patients with PHD presented higher early mortality (10.4 vs. 1.1%, p < 0.001), rates of acute kidney injury (42.4 vs. 12.8%, p < 0.001), and newly required dialysis (23.2 vs. 3.0%, p < 0.001) compared with those without PHD. Moreover, with the median follow-up period of 41.3 months, the survival curve was worse in patients with PHD compared with no PHD group (log-rank p < 0.001), whereas it was similar after excluding patients who died within 30 days (log-rank p = 0.761). Multivariable analyses suggested that PHD was predicted by preoperative aspartate transferase [odds ratio (OR), 1.057; 95% confidence intervals (CI), 1.036–1.079; p < 0.001], celiac trunk malperfusion (OR, 3.121; 95% CI, 1.008–9.662; p = 0.048), and cardiopulmonary bypass time (OR, 1.014; 95% CI, 1.005–1.023; p = 0.003). Retrograde perfusion (OR, 0.474; 95% CI, 0.268–0.837; p = 0.010) was associated with a reduced risk of PHD. Celiac trunk malperfusion was an independent predictor for PHD but not associated with early mortality and midterm survival.Conclusions: PHD was associated with increased early mortality and morbidity, but not with late death in midterm survival. PHD was predicted by preoperative aspartate transferase, celiac trunk malperfusion, and cardiopulmonary bypass (CPB) time, and retrograde perfusion was associated with a reduced risk of PHD.

Background Hepatic dysfunction (HD) increases the morbidity and mortality rates after cardiac surgery. However, few studies have investigated the association between HD and acute DeBakey type I aortic dissection (ADIAD) surgery. This retrospective study aimed to identify risk factors for developing HD in patients who received acute type I aortic dissection repair and its consequences. Methods A total of 830 consecutive patients who received ADIAD surgery from January 2014 to December 2019 at our center were screened for this study. The End-Stage Liver Disease (MELD) score more than 14 was applied to identify postoperative HD. Logistic regression model was applied to identify risk factors for postoperative HD, Kaplan–Meier survival analysis and Cox proportional hazards regression assay were conducted to analyze the association between HD and postoperative long-term survival. Results Among 634 patients who eventually enrolled in this study, 401 (63.2%) experienced postoperative HD with a 30-Day mortality of 15.5%. Preoperative plasma fibrinogen level (PFL) [odds ratio (OR): 0.581, 95% confidence interval (CI): 0.362–0.933, P = 0.025], serum creatinine (sCr) on admission (OR: 1.050, 95% CI 1.022–1.079, P P = 0.039), and postoperative mechanical ventilation (MV) duration (OR: 1.019, 95% CI 1.003–1.035, P = 0.020) were identified as independent risk factors for developing postoperative HD by multivariate analyses. In addition, the Kaplan–Meier analysis indicated that the long-term survival rate was significantly different between patients with or without postoperative HD. However, the hazard ratios of long-term survival for these two groups were not significantly different. Conclusions HD was a common complication after ADIAD surgery and associated with an increasing 30-Day mortality rate. Decreased PFL, elevated sCr, prolonged CPB duration, and longer postoperative MV time were independent risk factors for postoperative HD.

An 18-year-old male patient presented to our ambulatory services due to a 3-month course of progressive dyspnea and non-productive cough. Symptoms were present even at rest, and he exhibited severe limitation at physical activity. He had a diagnosis of glycogen storage disease (GSD) type IV attained by liver biopsy since three years of age, when he developed hepatomegaly and mild hepatic dysfunction. At the time, histopathological examination showed grade 2 fibrosis along with numerous intracytoplasmic PAS-positive deposits that were resistant [...]

Background Peroxisome biogenesis disorders (PBD) are a heterogeneous group of autosomal recessive disorders that affect multiple organ systems. Approximately 80% of PBD patients are classifiedin the Zellweger syndrome spectrum, which is generally caused by mutations in the PEX1, PEX6, PEX10, PEX12, or PEX26 genes. Methods We present the clinical characteristics of three male members with cholestatic hepatopathy and developmental delay. Next-Generation Sequencing (NGS) was used to analyze 52 genes responsible for hereditary diseases with cholestasis. The variant was confirmed by Sanger sequencing. Dried blood spot (DBS) samples of 537 newborns from Dagestan were tested for the presence of that mutation. The frequency of the mutant allele in the population of Dagestan wasestimated using the Hardy–Weinberg equilibrium. Results Symptoms of disease manifested from the first months of life as severe hepatic dysfunction and developmental delay. Physical examination showed jaundice, hepatosplenomegaly, coagulopathy, and normal or slightly elevated level of gamma-glutamyltransferase (GGT), similar to progressive familial intrahepatic cholestasis. The level of C26 and ratio of C26/C22 in plasma were increased. A nucleotide variant in the PEX26 gene was identified: NM_017929.6:c.347 T>A, p.(Leu116Gln) in a homozygous state. Parents and healthy siblings were heterozygous for the mutant allele. This variant was not described in the Database of Single Nucleotide Polymorphism (dbSNP), it is not registered in the Human Gene Mutation Database (HGMD) v. 2020.1. The frequency of the mutant allele in the population of Dagestan is estimated to be less than 0.000931 (99% CI, 0.000929–0.000934). Conclusions Our clinical cases from Dagestan describe the phenotype associated with the c.347 T>A,p.(Leu116Gln), variant in the PEX26 gene. We show that the onset of the clinical picture in patients with Zellweger syndrome spectrum could start with severe hepatic dysfunction and cholestasis. We suggest that biochemical screening of PBD in infants with cholestasis is necessary.

Background: Rickettsial fever is a major health concern in different districts of Karnataka with serious complications, including morbidity and mortality, if diagnosed late. Objective: The objective of the present study was to know the clinical profile of Rickettsial fever in children. Materials and Methods: A descriptive study was conducted on all the laboratory-confirmed cases of Rickettsial fever in children admitted to a tertiary care hospital from December 2018 to November 2019. Results: Among 103 children studied, majority were males (66%) in the age group of 3–6 years. All the children presented with history of fever (100%) followed by decreased appetite (94%). The least common symptoms noticed were altered sensorium (1.9%), breathlessness (6.5%), and bleeding tendencies (6.5%). The most serious complications seen were shock (38.8%), hepatic dysfunction (7.7%), and myocarditis (3%). There were no deaths reported. The least common complication was renal failure. A single case had cranial nerve palsy with meningitis. Conclusion: It was concluded that male children in the age group of 3–6 years were more affected. The common symptoms observed were fever, decreased appetite, abdominal distension, and skin rash and the common complications were shock and myocarditis.

Der kardiogene Schock ist ein lebensbedrohlicher Zustand, der haufig mit einer akuten Organdysfunktion der Leber einhergeht. Infolge einer verminderten kardialen Pumpleistung mit konsekutiver Hypoperfusion und inadaquater Sauerstoffversorgung der Leber konnen sich verschiedene Formen einer akuten Leberfunktionsstorung entwickeln, so etwa eine hypoxische Hepatitis oder akute Leberinsuffizienz. Eine gefurchtete lebensbedrohliche Komplikation ist die sekundar sklerosierende Cholangitis. Wesentliche Therapiemasnahmen beinhalten die Stabilisierung der hamodynamischen Situation mit Optimierung der kardialen Auswurfleistung zur Verbesserung der systemischen Perfusion sowie die Verbesserung der hepatischen Sauerstoffversorgung. Insgesamt ist das kombinierte Auftreten eines kardiogenen Schocks und einer schweren hepatischen Dysfunktion mit einer schlechten Prognose assoziiert.

Although catfish are found worldwide and commonly consumed in the southern United States, fatal infections from catfish are rare. Edwardsiella tarda is a bacterium known to cause gastrointestinal distress most commonly, but extraintestinal infections are a rarely considered danger for those acquiring, preparing, and consuming aquatic animals. Susceptible to all gram-negative active antibiotics, it is easily treated except in immunocompromised hosts, such as those with malignancy, diabetes, and hepatic dysfunction.

Background: Dengue, the most common arboviral disease worldwide is usually endemic but several epidemics have been recorded. Global incidence of dengue has grown dramatically in recent decades; about half of the world's population is now at risk. The situation in India is reflected by occurrence of major disease outbreaks from time to time over the last few decades. Objectives: The objective of the present study was to observe the various clinical manifestations and complications of dengue fever. Materials and Methods: Study included 100 patients admitted to medicine ward in medical college hospital for a period of 6 months with symptoms and signs suggestive of dengue fever and those positive for NS1Ag, IgM and IgG dengue antibodies using Rapid strip test. Results: Among 100 patients observed, majority cases were dengue fever (92%) with no mortality, 5% were dengue hemorrhagic fever (DHF) with mortality 20% and 3% were dengue shock syndrome (DSS) with mortality 67%. 71 were males and 29 were females with sex ratio 2.5:1. Maximum patients were in the age group of 18-30years. Most common clinical manifestations were fever (100%), headache (90%), abdominal pain (72%), arthralgia (65%), myalgia (64%), hepatomegaly (52%) and splenomegaly (41%). Thrombocytopenia (84%) is the most common hematological abnormality observed. Among serology positivity, majority were positive for NS1 antigen (81%), followed by IgM antibodies (7%) and mixed positivity (12%). Most common complication observed was hepatic dysfunction (33%). Conclusion: Dengue infection is common viral infection with varying clinical manifestations from region to region and epidemic to epidemic. Even though no specific treatment available for dengue fever but early diagnosis and timely intervention will prevent complications and mortality from dengue hemorrhagic fever and dengue shock syndrome.

Background: Malaria continues to be a huge socioeconomic burden despite various measures taken to curb the spread worldwide. It is also a global concern and more so in countries with a resource-limited setting. This inspired us to look at variables that could represent a severe disease in those limited settings, one such parameter being thrombocytopenia in malaria. Aims and Objectives: To find the relationship between thrombocytopenia and renal failure, hepatic dysfunction and cerebral malaria (severe malaria) and to identify if thrombocytopenia on the first day of admission increases the likelihood of severe malaria. Methods: The study included 85 patients admitted in Yenepoya medical college hospital with fever and peripheral smear or malarial parasite fluorescent test (MPFT) positive for Plasmodium species. Results: A total of 85 patients were included in the study. It was noted that the patients with profound thrombocytopenia (

Aim. To provide a current view on the tolerability and safety of statin therapy. Materials and methods. The data of 73 scientific sources from Russian and foreign literature published within 1996-2018 are considered. Results. It is generally accepted that statins are first-line therapeutic agents for hypercholesterolemia and combined hyperlipidemia. Today there in growing evidence that lowering of low-density lipoprotein cholesterol levels prevents atherosclerotic diseases and reduces a risk of cardiovascular and overall mortality. Main issues of current statin therapy include a use of inadequate dosage for atherosclerotic diseases prevention, low treatment compliance and drug intolerance. In recent years the issue of statin intolerance has become of great importance. Criteria were proposed for determining an inability to tolerate statins, some experts suggest replacing definition of “statin intolerance” with the term “statin-associated side-effects”. Most discussed adverse effects due to statins include muscle-related symptoms (myalgia/myopathy), hepatotoxicity (hepatic hyperenzymemia) new-onset diabetes, dementia and cognitive impairment. Mechanisms of development of these adverse effects are still unclear. Certain factors and conditions capable of triggering some adverse effects as well as absolute contraindications to statin therapy were established. Some factors and conditions capable of triggering some adverse effects as well as absolute contraindications to statin therapy were identified. Occurrence of statin-associated side-effects depends on statin dose, a patient's age, gender, comorbidity and concomitant therapy. Many adverse effects of statins are drug class effect. At the same time each of statins has specific features of its structure, metabolism, drug interactions and pharmacokinetics. Pitavastatin belongs to the last generation of statins and it has distinct pharmacological features and neutral diabetogenic effects, etc. Risk of adverse effects due to statins is often exaggerated while benefit from the use of statins for preventing atherosclerotic diseases outweighs potential risks. Real occurrence of some adverse effects due to statin therapy requires additional evidence. Conclusion. Overall, statins have a good tolerability profile and are approved for use in the vast majority of patients who required lipid-lowering therapy.

BackgroundThe rate of toxic deaths related to induction chemotherapy in the treatment of locally advanced head and neck cancers is unacceptable and calls into question this therapeutic strategy, which is however highly effective in terms of rate and speed of response. The purpose of the study was to investigate predictive factors of toxicity of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) in locally advanced head and neck cancers (LAHNC).MethodsBetween June 2009 and December 2017, 113 patients treated consecutively with TPF were included retrospectively. Patients were receiving induction chemotherapy for either an inoperable cancer or laryngeal preservation. For inoperable cancer, induction chemotherapy was proposed to patients presenting either a large tumor with strong symptoms (dyspnea, dysphagia, pain) or a tumor with rapid progression. Risk factors were chosen among the initial patient and tumour characteristics and chemotherapy modalities.ResultsEighty-nine patients (79%) were male; the median age was 58 years [32–71]. Sixty-nine (61%) patients were treated for inoperable cancer and 44 (39%) for laryngeal preservation. 45% had stage IVa cancer, 28% stage III and 25% stage IVb. Sixty percent of patients had a partial response after TPF, 22% had a complete response, 12% were stable, 5% were progressing, and 1% had a discordant response. Thirty-four patients (30%) received enteral feeding during induction chemotherapy with TPF. The possibility of oral feeding without a tube was predictive of a better response (p = 0.003). Seven (6%) patients died during TPF. There was an increased risk of death with preexisting liver dysfunction (liver dysmorphia on imaging or decrease prothrombin rate) (p = 0.032). There was an increased risk of grade ≥ 3 infection if an enteral feeding occurred during the period of induction chemotherapy (p = 0.03).ConclusionsTPF induction chemotherapy had an 82% objective response rate with 6% toxic deaths. Nutritional status and the presence of hepatic dysfunction are significant risk factors to be taken into account in therapeutic decisions.

In Scrunb Typhus, hepatotoxicity is an important, yet understudied, manifestation. We reviewed studies on scrub typhus, published in the last five years (2014–2019), which evaluated its clinico-epidemiological factors in India, and concentrated on its hepatic involvement. Nine studies were found, and no Indian study exclusively evaluated hepatic dysfunction. Thus, comments from a few international studies were also included. We conclude that liver dysfunction in the form of elevated serum transaminase levels is a common manifestation of scrub typhus, which may herald progress to fulminant hepatic failure.

Drug-induced liver injury significantly caused by synthetic drugs, and other xenobiotics contribute to clinical hepatic dysfunction, which has been a substantial challenge for both patients and physicians. Traditional medicines used as an alternative therapy because of their pharmacological benefits, less or no side effects, and enormous availability in nature. Phytochemicals are essential ingredients of plants that reduce necrotic cell death, restore the antioxidant defence mechanism, limit oxidative stress, and prevent the inflammation of tissue and dysfunction of the mitochondria. In this review, we principally focused on the potential effect of the herbal plants and their phytochemicals in treating drug-induced hepatotoxicity.

The incidence of newly diagnosed hepatocellular carcinoma is approaching nearly 1 million cases per year. Treatment of this disease is a particularly challenging clinical problem as the majority of patients have underlying liver disease. Treatment options for patients with hepatocellular carcinoma have expanded over the last two decades and interventions are selected based on tumor staging and the degree of hepatic dysfunction. Numerous improvements have been made in intraoperative ultrasonography and ablation technologies and these innovations have allowed for the development of a well-tolerated procedure that focuses on destroying the tumor with minimal injury to the surrounding liver parenchyma. With advances in laparoscopic surgery the implementation of ablative technologies has expanded the opportunity to successfully treat patients with hepatocellular carcinoma and cirrhosis who previously had no therapeutic option. The following chapter outlines the approach to successfully treat the patient who has a diagnosis of hepatocellular carcinoma. It outlines the clinical steps taken before surgery, in the operating room and tumor surveillance after the ablation. It also includes troubleshooting approaches at various stages while managing the patient.

Background and Aims: Recent reports have indicated that hepatic dysfunction occurred in a proportion of patients with coronavirus disease 2019 (COVID-19). We aimed to compare and describe the liver biomarkers in different subtypes of COVID-19 patients.Methods: This study enrolled 288 COVID-19 patients in Huangshi Hospital of Traditional Chinese Medicine. All patients were divided into ordinary, severe, and critical groups according to the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7). Demographic, clinical characteristics and liver biomarkers were compared among the three groups.Results: During hospitalization, AST, TBiL, and ALP levels in ordinary and severe patients fluctuated within the normal range with a rising trend in critical patients except AST. ALT and GGT levels fluctuated within the normal range showing an upward trend, while LDH levels in the critical group exceeded the normal range. Prealbumin showed an upward trend, especially in the severe group. At discharge, AST and LDH levels in ordinary and severe groups were lower than their baselines but increased in the critical group. In contrast to albumin, TBiL levels were increased in ordinary and critical groups while decreased in the severe group. The stratified analysis revealed factors affecting liver function in critical cases included highest temperature ≥38.0°C, age ≥60 and symptom of hypoxemia.Conclusions: COVID-19 can cause severe hepatic dysfunction in critical patients, requiring early monitoring and intervention. LDH, ALP, GGT, TBiL, prealbumin, and albumin may be helpful for evaluating and predicting disease prognosis due to their correlation with disease severity in COVID-19.

Background Solitary fibrous tumour/haemangiopericytoma (SFT-HPC) is a rare fibroblastic mesenchymal neoplasm that develops as a result of the uncontrolled proliferation of mesenchymal fibroblasts and occurs rarely during pregnancy. Case Presentation A 26-year-old woman (G2P1) with an intrauterine pregnancy at 34+4weeks presented at a university hospital with a history of nausea and vomiting since 20 weeks. Other symptoms included slight headache and 5-kg weight loss. She had attended and been admitted to several hospitals during that time. Laboratory evaluation revealed evidence of hepatic dysfunction with elevated liver enzymes. The patient's headache worsened, and magnetic resonance imaging (MRI) showed an extra-axial mass in the right tentorial and supratentorial spaces, with brain herniation. Caesarean section and brain tumour resection were performed under general anaesthesia at the same time. Histopathological analysis revealed HPC (World Health Organization [WHO] grade III). Nausea and vomiting symptoms gradually improved. Postoperatively, the patient underwent fractional external radiotherapy (total amount 50 Gy). There was no evidence of local recurrence of metastases in the follow-up 6 months after surgery. Conclusions Nausea and vomiting are commonly experienced during pregnancy. This often makes patients ignore other aetiologies that cause nausea and vomiting. Central nervous system tumours can mimic the common pregnancy complaint of nausea and vomiting. Although rare in pregnancy, they can adversely affect maternal and fetal survival if untreated. Clinicians should exclude other pathology when the onset of nausea and vomiting is after the first trimester., Highlights • Haemangiopericytoma is a rare and aggressive type of soft tissue sarcoma that arises from pericytes of the capillaries and involves mostly the musculoskeletal system. • Its presentation [[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]] in the central nervous system is very rare. • Diagnosis was made at 34 weeks of pregnancy after several hospital admissions for nausea and vomiting starting at 20 weeks gestation. • There should be a suspicion of pathology when the onset of nausea and vomiting is after the first trimester.

Purpose: Hyperbilirubinemia is frequent in patients with hematological malignancies admitted to the intensive care unit (ICU). Literature about hepatic dysfunction (HD) in this context is scarce. Methods: We investigated the prognostic impact of HD analyzing a prospective multicenter cohort of 893 critically ill hematology patients. Two groups were defined: patients with HD (total bilirubin ≥33 μmol/L at ICU admission) and patients without HD. Results: Twenty one percent of patients were found to have HD at ICU admission. Cyclosporine, antimicrobials before ICU admission, abdominal symptoms, ascites, history of liver disease, neutropenia, increased serum creatinine and myeloma were independently associated with HD. Etiology remained undetermined in 73% of patients. Hospital mortality was 56.3% and 36.3% respectively in patients with and without HD (p < 0.0001). Prognostic factors independently associated with hospital mortality in HD group were, performance status >1 (OR = 2.07, 95% CI = 1.49–2.87, p < 0.0001), invasive mechanical ventilation (OR = 3.92, 95% CI = 2.69–5.71, p < 0.0001), renal replacement therapy (OR = 1.74, 95% CI = 1.22–2.47, p = 0.002), vasoactive drug (OR = 1.81, 95% CI = 1.21–2.71, p = 0.004) and SOFA score without bilirubin level at ICU admission (OR = 1.09, 95% CI = 1.04–1.14, p < 0.0001). Conclusions: HD is common, underestimated, infrequently investigated, and is associated with impaired outcome in critically ill hematology patients. HD should be considered upon ICU admission and managed as other organ dysfunctions., SCOPUS: ar.j, info:eu-repo/semantics/published

Background:Acute kidney injury (AKI) is the main clinical concern resulted from ischemia-reperfusion injury (IRI). Ample clinical data indicates that AKI is associated with distant organ dysfunctions and poor patients’ outcomes. Oxidative stress and inflammation have a critical role in the pathogenesis of organ injuries following IRI. The objectives of this study were to determine the impact of Gamma Oryzanol (GO), extracted from rice bran oil, on distant organs in rats after IRI.Methods:Twelve out of 24 Wistar rats were treated by one dosage of GO (100mg/kg) 1 h before I/R induction through both oral gavage and intraperitoneal injection. Then, the AKI model rats were induced by IRI. Oxidative stress and antioxidant protein levels were assessed in the brain, heart, and liver tissues in the experimental groups. Furthermore, the effects of GO on IRI-induced liver dysfunction, apoptosis, and inflammation were measured by Western blot.Results:GO pretreatment could significantly restore the levels and activity of antioxidant proteins in the brain, heart, and liver tissues (P < 0.05). Moreover, GO pretreatment could decrease the inflammatory cytokine (IL-1, IL-6, and TNF-α) in the liver (P < 0.01). By reducing Bax/Bcl-2 ratio and down-regulating caspase-3, GO could significantly diminish apoptosis in the liver tissue after the kidney I/R (P < 0.01). Additionally, GO could significantly diminish the deterioration of liver function in the kidney I/R model.Conclusion:GO protects distant organs against renal IRI-induced oxidative stress. Furthermore, it ameliorates liver function and remarkably exerts anti-oxidative, anti-inflammatory, and anti-apoptotic roles in the liver as an important detoxifying organ.

Hepatic dysfunction secondary to cardiac causes is a challenging clinical scenario which is often multifactorial and requires meticulous...

Background Abnormalities in liver function tests commonly occur in patients with acute heart failure (AHF). The Fibrosis-4 (FIB4) index, a non-invasive and easily calculated marker, has been used for hepatic diseases and reflects adverse prognosis. It is not clearly established whether the FIB4 index at admission can predict adverse outcomes in patients with AHF. Methods and results From a multicenter AHF registry, we retrospectively evaluated 1162 consecutive patients admitted due to AHF (median age 78 [69–85] years and 702 patients [60.4%] were male). The FIB4 index at admission was calculated as: age (yrs) × aspartate aminotransferase [U/L]/(platelets count [103/μL] × √alanine aminotransferase [U/L]. The median value of the FIB4 index at admission was 2.79. All-cause mortality and rehospitalization due to HF at 12 months were investigated as a composite endpoint and occurred in 142 (12.2%) patients and 232 (20%) patients, respectively. Kaplan-Meyer analysis shows a significant increase in the composite endpoint from the first to fourth quartile group of the FIB4 index values (log-rank, p Conclusions Hepatic dysfunction evaluated with the FIB4 index at admission is a predictor of the composite endpoint of all-cause mortality and rehospitalization in AHF patients.

Given the visibility of cutaneous findings, skin manifestations are often a presenting symptom of underlying systemic disease, including chronic liver disease. Many cutaneous signs and symptoms that correlate with chronic liver disease are common physical examination findings in patients with no history of liver disease. It is nonetheless important to be aware that these cutaneous findings may be an indication of underlying liver disease and often occur in the setting of such hepatic dysfunction. This article covers general cutaneous signs that may correlate with various liver diseases and describes specific cutaneous signs as they relate to more specific liver diseases.

Background This study evaluated the safety and efficacy of pazopanib in patients with metastatic soft tissue sarcoma in routine clinical use in Japan. Methods It was a multicentre, centrally registered and uncontrolled observational study in patients who received pazopanib for metastatic soft tissue sarcoma, with an observation period of 1 year after the start of drug administration. The study was conducted at 378 investigational sites in Japan from September 2012 to September 2019. Progression-free survival (PFS) and overall survival (OS) were the efficacy endpoints of the study. Results A total of 1970 patients were enrolled. Of these, 680 with finalized study forms were included in the analysis. Overall, 649 patients were included in the safety analysis set, and 569 were included in the efficacy analysis set. Most of the patients (81.97%) experienced at least one adverse drug reaction (ADR); 22.34% of patients reported serious ADRs and 34.98% of patients experienced grade ≥ 3 ADRs in the safety set. Hypertension (40.37%) and hepatic dysfunction (26.50%) were the two most common ADRs. A total of 262 deaths were reported, of which 12 were due to ADRs. The median PFS was 3.09 months, whereas the median OS was not reached at the end of the 1-year observation period. Conclusions The safety and efficacy profiles in this postmarketing observational study were consistent with prior data and registration clinical trials. No new safety signals were observed while treating patients with metastatic soft tissue sarcoma with pazopanib.

Background It is rare for hepatolenticular degeneration [Wilson’s disease (WD)] to occur along with keratoconus (KC). In our report, a teenager was diagnosed with WD because of the discovery of Kayser–Fleischer (KF) ring in the cornea, and concomitant KC was found. Case presentation A 19-year-old male was diagnosed with KC due to a rapid decline in visual acuity within a short period of time. Ocular examination revealed the presence of ring-shaped, dense, brown sediment at the Descemet membrane of the bilateral limbus cornea, exhibiting characteristics similar to those of KF ring. Then, the patient was referred to the Department of Neurology and diagnosed with asymptomatic WD. During the next 5 years of follow-up, the patient has worn RGP lenses, routinely taken drugs that inhibit copper absorption and promote copper excretion, and maintained a low-copper diet. He has never exhibited obvious systemic symptoms associated with WD, such as neurological, mental, or hepatic dysfunction, and the color of the KF ring has grown obviously lighter. Moreover, the morphology of the cornea has stabilized. Conclusion Only one report of WD combined with KC was found in the literature. So far, there is no evidence of a correlation between the occurrence of the two diseases. However, a low-copper diet and active copper-reducing therapy may have played a role in stabilizing the patient’s condition in this case.

Background: To study liver function test in dengue fever patients. Methods: This study was hospital based prospective study, which included 100 cases of dengue fever. Results: 28 patients had ALT >1-3 ×UNL (upper normal limit), 18 patients had ALT >3-10×UNL and 6 patients had >10×UNL. 24 patients had AST >1-3×UNL, 23 patients had AST >3-10×UNL and 11 patients had >10×UNL. Conclusion: The aspartate aminotransferase (AST) levels in dengue patients was higher than alanine aminotransferase(ALT) levels. This differs from the pattern in viral hepatitis but is similar to that seen in alcoholic hepatitis.