Search

Purpose: The aim of this study was to compare liver size measurements in different conventional B‐mode ultrasound image (US) field views using magnetic resonance imaging (MRI) measurement as a reference. Methods: After receiving Institutional Review Board approval and informed consent, three operators measured the largest sagittal and transverse dimensions of adult livers on three US image field views (90°, 120°, and 140°) with a single curvilinear transducer. We analyzed the differences in liver size across three image field views using one‐way analysis of variance (ANOVA) and examined the correlations between MRI and ultrasound measurements using Spearman regression. We used 95% Bland–Altman limits of agreement (95% LOA) to analyze the confidence interval for liver size measurements between MRI and US. Intra‐observer and inter‐observer reliability in measuring liver size were assessed using intraclass correlation coefficient (ICC). Results: Based on sagittal liver length, 28 adult participants (7 men and 21 women, mean age 43 years) were divided into Group 1 (<17 cm, n = 10) or Group 2 (≥17 cm, n = 18). There was a significant difference in the liver size measurements across the three image field views (P <.001) in both groups. The highest correlation in liver size measurements between MRI and US was with ultra‐wide‐view (R2 =.87 in sagittal; R2 =.79 in transverse). Bland–Altman LOA also indicated good agreement between MRI and ultra‐wide‐view measurements. Intra‐observer and inter‐observer reliability in measuring liver size were good (ICC = 0.82–0.98). Conclusion: The study suggests that ultrasound ultra‐wide‐view provides the most accurate liver size measurement and good intra‐ and inter‐operator reliability. [ABSTRACT FROM AUTHOR]

Clinical manifestations of congenital syphilis (CS) include liver disease with/without impaired liver function, identified as syphilitic hepatitis. Hepatic involvement may be dramatic; therefore, early diagnosis is crucial to provide treatment and prevent fatal outcomes. A new resurgence of CS cases has been described in recent years worldwide. We reported our experience with a case series of infants hospitalized for liver disease with a final diagnosis of CS, highlighting the wide spectrum of liver involvement, the rapid progression in cases with late diagnosis, and the pitfalls of the management of this forgotten but reemerging disease. A retrospective analysis of CS patients with hepatic presentation in the period 2008–2023 was conducted. We collected five cases (three female) with a median age of 13.8 days (range 1–84 days). In three cases, mothers were not screened for syphilis during pregnancy, and in two cases, they were seronegative in the first trimester screening. None practiced specific therapy during pregnancy. Hepatic involvement was characterized by hepatosplenomegaly, in four cases associated with cholestatic jaundice and in three cases with liver failure. Rapid plasma reagin (RPR) and Treponema pallidum hemagglutination assay (TPHA) were positive in all cases in mothers and infants. CS presented with multiorgan involvement and was fatal in one case. Conclusions: It is important to consider CS in infants with cholestasis and acute liver failure, but also in sick infants with isolated hepatomegaly. Early recognition of infants with CS is critical to identify missed cases during pregnancy and to start early treatment. What is known: • In recent years, it has been seen an increase of congenital syphilis cases in both low- and middle-income countries. • In most cases, infants born to mothers untreated for syphilis appear normal without signs of infection at birth but may develop manifestations of the disease after months or years if left untreated. • What is new: • Congenital syphilis is an emerging problem that may result in multiorgan involvement with liver disease predominant at onset. • It is important to consider congenital syphilis in infants with cholestasis and liver failure, but also in sick infants with isolated hepatomegaly. [ABSTRACT FROM AUTHOR]

Background/Aim: Transileocolic portal vein embolization (TIPE) may reduce the risk of liver failure after massive hepatectomy. However, convincing evidence of its usefulness in this regard is yet to be reported. Therefore, this study aimed to investigate the use of TIPE after massive hepatectomy. Patients and Methods: Twelve patients who underwent TIPE were included. Pre- and postoperative liver volumetry was determined using a 3D simulator with computed tomography. Results: After TIPE, the percent change in total liver volume was 104.0%±13.1% (p=0.08). Conversely, the percent increase in remnant liver volume (ml)/total liver volume (ml) and remnant liver volume (ml)/standard liver volume (ml) was 122.9%±18.6% (p<0.001) and 132.2%±19.6% (p<0.001), respectively. TIPE operation time was 125±84.6 min, with minimal blood loss in all cases. Postoperative hospitalization duration during TIPE was 4.5±2.6 days. No TIPE-related complications occurred in any patient. Conclusion: TIPE is beneficial and safe when preoperative volumetry indicates that the remaining liver volume is inadequate and inoperable. [ABSTRACT FROM AUTHOR]

Dengue fever, a mosquito-borne viral infection, poses a significant global health threat, and early diagnosis is crucial for effective disease management. Human infection typically occurs through infected Aedes mosquitoes, such as Aedes aegypti or Aedes albopictus. The disease spectrum ranges from asymptomatic infection and mild febrile illness (dengue fever) to more severe conditions, such as dengue hemorrhagic fever and dengue shock syndrome. Dengue fever is characterized by severe headache, high fever, skin rash, muscle and joint pain, nausea, and vomiting. Dengue hemorrhagic fever is marked by high fever, an enlarged liver, hemorrhagic phenomena, shock, and often cardiovascular disorders. Dengue fever is transmitted through urban (human transmission cycle) and sylvatic (animal transmission cycle) cycles. The demand for early detection of this virus has increased to control the spread of infectious diseases and protect humankind from its harmful effects. Various methods can be employed for the laboratory diagnosis of this virus to detect the virus itself, viral nucleic acids, antibodies, or antigens, or a combination of these approaches. Recently, biosensors have emerged as a potential tool for detecting and quantifying viruses, offering fast detection, relative cost-effectiveness, and high sensitivity and selectivity compared to conventional diagnostic methods such as immunological and molecular techniques. Most biosensors employ electrochemical detection techniques with transducers, owing to their easy construction, low cost, ease of use, and portability. [ABSTRACT FROM AUTHOR]

Background and Aims: Interdigitating dendritic cell tumour/sarcoma (IDCS) is an exceedingly uncommon and aggressive tumour with a dismal prognosis. IDCS arises from antigen-presenting cells, which involve nodal and extranodal sites. The aim of the study is to evaluate a case of IDCS and its diagnostic challenges. Methods: A 21-year-old female with no comorbidities, a bone marrow aspirate and biopsy and an excision biopsy of the lymph node shows atypical mononuclear infiltrates that were immunohistochemically positive for S100-diffuse, CD68, LCA and Ki67. Results: Here, we report a single case of IDCS with a tumour arising from the lymph node and bone marrow infiltration. Discussion: IDCS is an aggressive disease with uncertain behaviour; strong suspicion is required to establish a diagnosis. [ABSTRACT FROM AUTHOR]

Background: Liver abscesses continue to present a significant diagnostic and therapeutic challenge to the medical community. Early clinical distinction between an amoebic and a pyogenic liver abscess is challenging due to their overlapping clinical presentations. Aim: The present study was undertaken to evaluate the clinical characteristics, lab parameters as well as management in patients suspected of liver abscess. Methods: A retrospective study was carried out in 60 consecutive patients presenting with liver abscess, admitted at tertiary care hospital. Lab investigations were carried out. All patients underwent ultrasound-guided aspiration of a liver abscess either by percutaneous needle or by a pigtail catheter. Patients were monitored during the period of hospital stay to note their outcome. The data variables collected were compiled by using an excel spreadsheet and later analysed using Medcalc (version 20.118). Results: The commonly observed clinical presentation was abdominal pain (95%) followed by fever (57%) and jaundice (7%). On examination, 60% of the liver abscess cases had right hypochondrial tenderness while Hepatomegaly was observed in about 17% of the subjects. Leucocytosis was observed in 67% of the cases in view of underlying infectious etiology. The size of the majority (60%) of the liver abscess were in the range of 5.1 to 9.9 cms and right lobe was the most affected region (75.2%). Conclusion: Early recognition of symptoms, institution of antibiotic and amoebicidal therapy and drainage of abscess via appropriate modality improves the prognosis of liver abscess.

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and non-stigmatising, and can improve awareness and patient identification.

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms nonalcoholic and fatty were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.

Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, is widely prescribed for hyperlipidemia management. Recent studies also showed that it has therapeutic potential in various liver diseases. However, its effects on hepatomegaly and liver regeneration and the involved mechanisms remain unclear. Here, the study showed that fenofibrate significantly promoted liver enlargement and regeneration post-partial hepatectomy in mice, which was dependent on hepatocyte-expressed PPARα. Yes-associated protein (YAP) is pivotal in manipulating liver growth and regeneration. We further identified that fenofibrate activated YAP signaling by suppressing its K48-linked ubiquitination, promoting its K63-linked ubiquitination, and enhancing the interaction and transcriptional activity of the YAP–TEAD complex. Pharmacological inhibition of YAP–TEAD interaction using verteporfin or suppression of YAP using AAV Yap shRNA in mice significantly attenuated fenofibrate-induced hepatomegaly. Other factors, such as MYC, KRT23, RAS, and RHOA, might also participate in fenofibrate-promoted hepatomegaly and liver regeneration. These studies demonstrate that fenofibrate-promoted liver enlargement and regeneration are PPARα-dependent and partially through activating the YAP signaling, with clinical implications of fenofibrate as a novel therapeutic agent for promoting liver regeneration.

Introduction: Hemophagocytic lymphohistiocytosis characterized by hemophagocytosis leading to uncontrolled inflammation; the most common etiology in secondary cases of hemophagocytic lymphohistiocytosis is viral infections, especially Epstein–Barr virus. Visceral leishmaniasis is a vectorborne protozoal disease caused by Leishmania donovani complex. It is common in tropical and subtropical regions, with 50,000–90,000 new cases annually. Case presentation: A 15-month-old Arab female was admitted to our hospital with 15 days of fever and decreased weight. On clinical examination, she had a markedly enlarged liver and spleen that were palpable 4 cm and 6 cm below the costal margin, respectively. The peripheral blood smear showed hypochromic microcytic anemia, poikilocytosis, reactive lymphocytosis, and mild thrombocytopenia. Bone marrow aspiration did not show malignancy or any other pathological findings. The patient was put on antibiotic therapy without improvement. Repeated bone marrow aspiration showed erythrophagocytosis; intracellular small round organisms looked like the amastigote form of Leishmania (Donovan bodies) with no evidence of malignancies. Her lab values showed ferritin greater than 500 ug/L, pancytopenia, and hypertriglyceridemia. The patient was diagnosed with hemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis. Conclusion: Hemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis is an extensively rare phenomenon in the medical literature that causes challenges in diagnosis and management. Steroids should be used wisely to not cover the symptoms of infections or malignancy, and amphotericin B resistance should be kept in mind in unresponsive Leishmania cases. [ABSTRACT FROM AUTHOR]

Background: Aborted bariatric surgeries are an undesirable experience for patients as they are subjected to potential physical harm and emotional distress. A thorough investigation of aborted bariatric surgeries has not been previously reported. This information may allow the discovery of opportunities to mitigate the risk of aborting some bariatric operations. Methods: Data from the Michigan Bariatric Surgery Collaborative, a statewide bariatric surgery registry, were used to identify all aborted primary bariatric operations from June 2006 through January 2023. The reasons for aborting surgery were divided into seven categories. Stepwise logistic regression was performed to identify independent predictors of aborted procedures for potentially modifiable factors. Results: A total of 115,004 patients underwent bariatric surgery with 555 (0.48%) procedures aborted. Of those having an aborted operation the mean age was 52 years and mean BMI was 49.8 with females accounting for 72%. Sleeve gastrectomy had the lowest aborted rate (0.38%) as compared to gastric bypass, adjustable gastric banding, and biliopancreatic diversion (p < 0.0001). The most common aborted surgery reason categories included adhesions and hernias, tumors and anatomic anomalies, and inadequate visualization due to either hepatomegaly or abdominal wall thickness. The most significant (p < 0.0001) independent predictors of aborted surgeries due to hepatomegaly or abdominal wall thickness were BMI ≥ 60 (OR 10.7), BMI 50 to 59 (OR 3.1) and diabetes mellitus (OR 2.7). Preoperative weight loss was a protective factor for aborting surgery due to hepatomegaly or abdominal wall thickness (OR 0.9; p < 0.0001). Conclusions: Aborted surgeries are uncommon and occur in approximately 1 in 200 primary bariatric operations with the lowest rate identified in sleeve gastrectomy. Nearly 20% of operations are aborted due to hepatomegaly or abdominal wall thickness and targeting patients with elevated BMIs and diabetes mellitus for preoperative weight loss might reduce the risk of these types of aborted procedures. [ABSTRACT FROM AUTHOR]

Purpose: To assess liver and spleen characteristics of a population with Gaucher disease (GD) using multiparametric MRI and MR elastography (MRE) for evaluation of diffuse liver and spleen disease, which includes liver fat fraction, liver and spleen volume and iron deposition, and liver and spleen stiffness correlated with DS3 Severity Scoring System for Gaucher disease (GD-DS3). Methods: We prospectively evaluated 41 patients with type 1 Gaucher disease using a 3.0 T MRI and MRE between January 2019 and February 2020. Clinical, laboratory, and imaging data was collected. Mann–Whitney, Kruskal–Wallis, and Spearman's correlation were applied to evaluate liver and spleen MRI and MRE, clinical and laboratory variables, and GD-DS3. ERT and SRT treatment groups were compared. Results: Hepatomegaly was seen in 15% and splenomegaly in 42% of the population. Moderate and strong and correlations were found between liver and spleen iron overload (rho = 0.537; p = 0.002); between liver and spleen volume (rho = 0.692, p < 0.001) and between liver and spleen stiffness (rho = 0.453, p = 0.006). Moderate correlations were found between liver stiffness and GD-DS3 (rho = 0.559; p < 0.001) and between splenic volume and GD-DS3 (rho = 0.524; p = 0.001). Conclusion: The prevalence of hepatosplenomegaly, liver fibrosis, and liver iron overload in treated patients with GD is low, which may be related to the beneficial effect of treatment. Liver MRE and splenic volume correlate with severity score and may be biomarkers of disease severity. [ABSTRACT FROM AUTHOR]

Introduction: Biliary atresia (BA) is a condition of progressive sclerosis in the extrahepatic biliary tract which if left untreated, can lead to cirrhosis and liver failure. The diagnosis of BA must be done promptly because it is associated with a better prognosis if treatment is done earlier. We aimed to determine the accuracy of clinical features (hepatomegaly, splenomegaly, and pale stools), and laboratory findings (gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP)) for diagnosis of BA. Methods: We analyzed the medical records of BA patients and cholestatic non-BA patients as controls who were admitted to our hospital from 2009 to 2017. Results: We ascertained 34 BA patients and 39 cholestatic non-BA subjects. The sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of clinical features (combination of hepatomegaly, splenomegaly, and pale stools) and laboratory findings (combination of GGT and ALP) were 62.5%, 48.6%, 51.3%, and 60%, and 93.3%, 22.2%, 50%, and 80%, respectively; while the Sn, Sp, PPV, and NPV for combination of clinical and laboratory findings were 58.6%, 62.9%, 56.7%, and 64.7%. Conclusion: A combination of clinical features and laboratory findings show a moderate accuracy for the diagnosis of BA. These findings imply that BA diagnosis might be early established using very simple and routine examination; therefore, suspicious BA patients can be referred to the pediatric surgical center for diagnosis establishment and treatment can be performed earlier accordingly. Our study provides a comprehensive analysis of clinical and laboratory findings as potential early detection tools for BA. [ABSTRACT FROM AUTHOR]

Pediatric MASLD (previously referred to as NAFLD) incidence has continued to rise along with the obesity pandemic. Pediatric MASLD increases the risk of liver fibrosis and cirrhosis in adulthood. Early detection and intervention can prevent and reduce complications. Liver biopsy remains the gold standard for diagnosis, although imaging modalities are increasingly being used. We performed a retrospective study of 202 children seen in a pediatric gastroenterology clinic with a complaint of abdominal pain, elevated liver enzymes or MASLD, or a combination of the three to evaluate screening methods for MASLD. A total of 134 of the 202 patients included in the study underwent laboratory testing and abdominal ultrasound. Ultrasound images were reviewed with attention to liver size and echotexture by a fellowship-trained pediatric radiologist for liver size and echotexture. Overall, 76.2% of the initial radiology reports correctly identified hepatomegaly based on age and 75.4% of the initial radiology reports correctly described hepatic echogenicity that was consistent with increased hepatic fat deposition. Use of screening ultrasound in concert with other clinical evaluations can be helpful to identify children at risk of MASLD. Utilizing ranges for liver span according to age can help to diagnose hepatomegaly, and understanding how to identify hepatic echogenicity is important for identifying possible hepatic steatosis. [ABSTRACT FROM AUTHOR]

The objectives of the study were to present the experience of diagnosis, management, and therapy with IL-1 inhibitors in patients with Schnitzler's syndrome (SchS) according to a multicenter Russian cohort. An observational retrospective study for a 10-year period (2012–2022) involved 17 patients with SchS who were admitted to the hospital or were observed on an outpatient basis (eight women and nine men). The diagnosis of all of them corresponded to the Strasbourg diagnostic criteria. The age of patients ranged from 25 to 81 years (Me 53[46; 56]). The age at the time of the onset of the disease ranged from 20 to 72 years (Me 46[39; 54]), the duration of the disease before diagnosis ranged from 1 to 35 years (Me 6.5[3; 6]), in three patients it exceeded 10 years, in the rest it ranged from 1 to 8 years. Infectious and lymphoproliferative diseases, monogenic AIDs (CAPS, TRAPS, and HIDS) were excluded from all patients at the prehospital stage. The referral diagnosis for all of them was Still 's disease in adults. Clinical manifestations of the disease in all patients included fatigue, lethargy, fatigue, rash, and fever. In all patients, skin elements were urticular and were accompanied by itching in 6 (37.5%) patients. Bone pain was observed in 12 (70.6%) patients; arthralgias, in 16 (94.1%); arthritis, in 9 (52.9%); myalgia, in 7 (41.2%); and weight loss, in 4 (23.5%). Lymphadenopathy was detected in 6 (35.3%) patients; enlarged liver, in 6 (35.3%); pericarditis, in 4 (23.5%); angioedema, in 6 (35.3); redness and dryness in the eyes, in 3 (17.6%); sore throat, in 2 (11.8%); abdominal pain, in 1 (5.9%), distal polyneuropathy, in 2 (11.8%); paraesthesia, in 1 (5.9%); and chondritis of the auricles, in 1 (5.9%). Monoclonal gammopathy was detected in all patients with a secretion level of 2.9–15.1 g/L: IgMk (n = 10, 64.7%), less often IgMλ (n = 2), IgGk (n = 2), IgGλ (n = 1), and IgAλ (n = 1). Ben-Jones protein was not detected in any of them. All patients had an increased level of ESR and CRP. Before inclusion in the study, 16 patients received GCs (94.1%) with a temporary effect that disappeared with dose reduction or cancellation. Seven patients received cDMARDs, including methotrexate (5), hydroxychloroquine (2), and cyclophosphamide (1). All patients received NSAIDs and antihistamines, as well as biologics, including the anti-B-cell drug rituximab (1), monoclonal ABs to IgE omalizumab (2, 1 without effect and 1 with partial effect), IL-1i canakinumab (n = 10, 58.8%) subcutaneously once every 8 weeks, and anakinra (n = 4, 23.5%) subcutaneously daily. The duration of taking anakinra, which was prescribed in the test mode, ranged from 1 week to 2.5 months with a further switch to canakinumab in 3 patients. The duration of taking canakinumab at the time of analysis ranged from 7 months to 8 years. Against the background of treatment with IL-1i, 10 out of 11 (90.9%) patients received a complete response in terms of the clinical manifestations of the disease and a decrease in the level of ESR and CRP within a few days. In one patient, a partial response to the administration of anakinra was detected; however, after switching to canakinumab, the effect of treatment was finally lost. One patient received IL-6i for 8 months with an incomplete effect and a positive dynamics after switching to anakinra. Thus, anakinra was initially prescribed to four patients and changed to canakinumab in two of them; canakinumab was started as the first drug in seven patients. Treatment with anakinra was continued in two patients; with canakinumab, in nine patients. In one patient, due to the persistent absence of relapses, the interval between canakinumab injections was increased to 5 months without signs of reactivation; however, subsequently, against the background of stress and relapses of the disease, the intervals were reduced to 4 months. A healthy child was born by the same patient on the background of treatment. The tolerability of therapy was satisfactory in all patients, no SAEs were noted. SchS is a rare multifactorial/non-monogenic AID that should be differentiated from a number of rheumatic diseases and other AIDs. The onset in adulthood, the presence of recurrent urticarial rashes in combination with fever and other manifestations of a systemic inflammatory response are indications for examination for monoclonal secretion. The use of short- or long-acting IL-1i is a highly effective and safe option in the treatment of such patients. [ABSTRACT FROM AUTHOR]

Human pregnane X receptor (PXR) is critical for regulating the expression of key drug‐metabolizing enzymes such as CYP3A and CYP2C. Our recent study revealed that treatment with rodent‐specific PXR agonist pregnenolone‐16α‐carbonitrile (PCN) significantly induced hepatomegaly and promoted liver regeneration after two‐thirds partial hepatectomy (PHx) in mice. However, it remains unclear whether PXR activation induces hepatomegaly and liver regeneration and simultaneously promotes metabolic function of the liver. Here, we investigated the metabolism activity of CYP1A2, CYP3A1/2 and CYP2C6/11 during PXR activation‐induced liver enlargement and regeneration in rats after cocktail dosing of CYP probe drugs. For PCN‐induced hepatomegaly, a notable increase in the metabolic activity of CYP3A1/2 and CYP2C6/11, as evidenced by the plasma exposure of probe substrates and the AUC ratios of the characteristic metabolites to its corresponding probe substrates. The metabolic activity of CYP1A2, CYP3A1/2 and CYP2C6/11 decreased significantly after PHx. However, PCN treatment obviously enhanced the metabolic activity of CYP2C6/11 and CYP3A1/2 in PHx rats. Furthermore, the protein expression levels of CYP3A1/2 and CYP2C6/11 in liver were up‐regulated. Taken together, this study demonstrates that PXR activation not only induces hepatomegaly and liver regeneration in rats, but also promotes the protein expression and metabolic activity of the PXR downstream metabolizing enzymes such as CYP3A1/2 and CYP2C6/11 in the body. [ABSTRACT FROM AUTHOR]

Simple Summary: Winter-associated mortalities at Atlantic salmon marine aquaculture sites have been reported in the last decade in Atlantic Canada and Iceland. Some fish species develop a condition known as 'Winter Syndrome' or 'Winter Disease' (WS/WD) when held at cold temperatures that is associated with enlarged and pale livers (fatty liver disease; FLD). To determine if salmon can develop FLD, we measured liver fat content and composition, and the expression of 34 molecular biomarkers of FLD in fish held long-term at 3 °C. Total fat and triacylglycerol levels were 50% higher in fish that showed symptoms of FLD, compared with healthy fish. Also, the expression level of 32 of the 34 selected biomarkers changed in fish with symptoms of FLD. Our results show that prolonged exposure to cold temperatures can lead to the development of FLD in some Atlantic salmon, and suggest that the development of new diets may improve the health and welfare of salmon during the winter. Large-scale mortality events have occurred during the winter in Atlantic salmon sea cages in Eastern Canada and Iceland. Thus, in salmon held at 3 °C that were apparently healthy (i.e., asymptomatic) and that had 'early' and 'advanced' symptoms of 'winter syndrome'/'winter disease' (WS/WD), we measured hepatic lipid classes and fatty acid levels, and the transcript expression of 34 molecular markers of fatty liver disease (FLD; a clinical sign of WS/WD). In addition, we correlated our results with previously reported characteristics associated with this disease's progression in these same individuals. Total lipid and triacylglycerol (TAG) levels increased by ~50%, and the expression of 32 of the 34 genes was dysregulated, in fish with symptoms of FLD. TAG was positively correlated with markers of inflammation (5loxa, saa5), hepatosomatic index (HSI), and plasma aspartate aminotransferase levels, but negatively correlated with genes related to lipid metabolism (elovl5b, fabp3a, cd36c), oxidative stress (catc), and growth (igf1). Multivariate analyses clearly showed that the three groups of fish were different, and that saa5 was the largest contributor to differences. Our results provide a number of biomarkers for FLD in salmon, and very strong evidence that prolonged cold exposure can trigger FLD in this ecologically and economically important species. [ABSTRACT FROM AUTHOR]

Fenofibrate, a peroxisome proliferator-activated receptor α (PPAR α) agonist, is widely prescribed for hyperlipidemia management. Recent studies also showed that it has therapeutic potential in various liver diseases. However, its effects on hepatomegaly and liver regeneration and the involved mechanisms remain unclear. Here, the study showed that fenofibrate significantly promoted liver enlargement and regeneration post-partial hepatectomy in mice, which was dependent on hepatocyte-expressed PPAR α. Yes-associated protein (YAP) is pivotal in manipulating liver growth and regeneration. We further identified that fenofibrate activated YAP signaling by suppressing its K48-linked ubiquitination, promoting its K63-linked ubiquitination, and enhancing the interaction and transcriptional activity of the YAP–TEAD complex. Pharmacological inhibition of YAP–TEAD interaction using verteporfin or suppression of YAP using AAV Yap shRNA in mice significantly attenuated fenofibrate-induced hepatomegaly. Other factors, such as MYC, KRT23, RAS, and RHOA, might also participate in fenofibrate-promoted hepatomegaly and liver regeneration. These studies demonstrate that fenofibrate-promoted liver enlargement and regeneration are PPAR α -dependent and partially through activating the YAP signaling, with clinical implications of fenofibrate as a novel therapeutic agent for promoting liver regeneration. Fenofibrate-promoted liver enlargement and regeneration are PPAR α -dependent and partially through activating the YAP signaling, which indicates the clinical implications of fenofibrate as a novel therapeutic agent for promoting liver regeneration. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Revista de Investigación e Innovación en Ciencias de la Salud (RIICS) is the property of Fundacion Universitaria Maria Cano and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Insulin inhibits gluconeogenesis and stimulates glucose conversion to glycogen and lipids. How these activities are coordinated to prevent hypoglycemia and hepatosteatosis is unclear. Fructose-1,6-bisphosphatase (FBP1) is rate controlling for gluconeogenesis. However, inborn human FBP1 deficiency does not cause hypoglycemia unless accompanied by fasting or starvation, which also trigger paradoxical hepatomegaly, hepatosteatosis, and hyperlipidemia. Hepatocyte FBP1-ablated mice exhibit identical fasting-conditional pathologies along with AKT hyperactivation, whose inhibition reversed hepatomegaly, hepatosteatosis, and hyperlipidemia but not hypoglycemia. Surprisingly, fasting-mediated AKT hyperactivation is insulin dependent. Independently of its catalytic activity, FBP1 prevents insulin hyperresponsiveness by forming a stable complex with AKT, PP2A-C, and aldolase B (ALDOB), which specifically accelerates AKT dephosphorylation. Enhanced by fasting and weakened by elevated insulin, FBP1:PP2A-C:ALDOB:AKT complex formation, which is disrupted by human FBP1 deficiency mutations or a C-terminal FBP1 truncation, prevents insulin-triggered liver pathologies and maintains lipid and glucose homeostasis. Conversely, an FBP1-derived complex disrupting peptide reverses diet-induced insulin resistance.

Hereditary fructose intolerance is a rare genetic disorder that is inherited in an autosomal recessive manner, with mutations sometimes occurring spontaneously. Consuming fructose triggers biochemical abnormalities, disrupting liver processes like glycogenolysis and gluconeogenesis. Recent studies have revealed elevated intrahepatic fat levels in affected individuals. Symptoms include aversion to fructose-containing foods, hypoglycemia, liver and kidney dysfunction, and growth delays, with severe cases leading to liver enlargement, fatty liver disease, kidney failure, and life-threatening hypoglycemia. In this case study, we present a 20-month-old child with symptoms including difficulty passing stool, abdominal rigidity, abdominal pain with bloating and hypoglycemia. Initial clinical findings revealed elevated liver enzymes, a mildly enlarged hyperechoic liver, hypercholesterolemia, and borderline alpha-fetoprotein values. Diagnostic assessments identified hereditary fructose intolerance (HFI) with pathogenic variants in the ALDOB gene, along with a diagnosis of celiac disease. Genetic testing of the parents revealed carrier status for pathological aldolase B genes. This case underscores the importance of comprehensive clinical evaluation and genetic testing in pediatric patients with complex metabolic presentations. [ABSTRACT FROM AUTHOR]

The liver, given its role as the central metabolic organ, is involved in many inherited metabolic disorders, including lysosomal storage diseases (LSDs). The aim of this manuscript was to provide a comprehensive overview on liver involvement in LSDs, focusing on clinical manifestation and its pathomechanisms. Gaucher disease, acid sphingomyelinase deficiency, and lysosomal acid lipase deficiency were thoroughly reviewed, with hepatic manifestation being a dominant clinical phenotype. The natural history of liver disease in the above-mentioned lysosomal disorders was delineated. The importance of Niemann–Pick type C disease as a cause of cholestatic jaundice, preceding neurological manifestation, was also highlighted. Diagnostic methods and current therapeutic management of LSDs were also discussed in the context of liver involvement. [ABSTRACT FROM AUTHOR]

The activation of pregnane X receptor (PXR) or peroxisome proliferator-activated receptor α (PPARα) can induce liver enlargement. Recently, we reported that PXR or PPARα activation-induced hepatomegaly depends on yes-associated protein (YAP) signaling and is characterized by hepatocyte hypertrophy around the central vein area and hepatocyte proliferation around the portal vein area. However, it remains unclear whether PXR or PPARα activation-induced hepatomegaly can be reversed after the withdrawal of their agonists. In this study, we investigated the regression of enlarged liver to normal size following the withdrawal of PCN or WY-14643 (typical agonists of mouse PXR or PPARα) in C57BL/6 mice. The immunohistochemistry analysis of CTNNB1 and KI67 showed a reversal of hepatocyte size and a decrease in hepatocyte proliferation after the withdrawal of agonists. In details, the expression of PXR or PPARα downstream proteins (CYP3A11, CYP2B10, ACOX1, and CYP4A) and the expression of proliferation-related proteins (CCNA1, CCND1, and PCNA) returned to the normal levels. Furthermore, YAP and its downstream proteins (CTGF, CYR61, and ANKRD1) also restored to the normal states, which was consistent with the change in liver size. These findings demonstrate the reversibility of PXR or PPARα activation-induced hepatomegaly and provide new data for the safety of PXR and PPARα as drug targets. • PXR or PPARα activation-induced hepatomegaly is reversible. • The hepatocyte size and proliferation return to normal state after the reversal. • Protein levels altered by PXR or PPARα activation are restored after the reversal. [ABSTRACT FROM AUTHOR]

• Benign massive hepatomegaly with quality of life impairment symptoms may be an indication of liver transplantation. • Polycystic liver disease and giant hemangioma are the most common etiologies. • Performing total hepatectomy of enlarged livers is challenging. • The left-to-right piggyback approach is a useful technique in this situation. • Previous liver cysts manipulation may lead to massive abdominal adhesions and increased bleeding in polycystic liver disease. Polycystic liver disease and giant hepatic hemangioma may present with severe symptom burden and indicate orthotopic liver transplantation. The left-to-right piggyback approach is a useful technique for performing total hepatectomy of enlarged livers. The purpose of this study is to analyze the results of liver transplantation in patients with benign massive hepatomegaly. This is a single-center retrospective study involving all adult patients who underwent liver transplantation due to benign massive hepatomegaly from January 2002 to June 2023. A total of 22 patients underwent liver transplantation (21 cases of polycystic live disease and 1 case of giant hepatic hemangioma). During the same time, there were 2075 transplants; therefore, benign massive hepatomegaly accounted for 1.06% of cases. Most patients (59.09%) were transplanted using the left-to-right piggyback technique. Seven patients had previous attempted treatment of hepatic cysts. Another patient previously underwent bilateral nephrectomy and living-donor kidney transplantation. Among these patients, in 5 cases there were massive abdominal adhesions with increased bleeding. Four of these 8 patients died in the very early perioperative period. In comparison to patients without previous cysts manipulation, massive adhesions and perioperative death were significantly higher in those cases (62.5 vs 0%, P =.002 and 50% vs 0%, P =.004, respectively). Liver transplantation due to polycystic liver disease and giant hemangioma is a rare event. Total hepatectomy is challenging due to the enlarged native liver. The left-to-right piggyback technique is useful, because it avoids vena cava twisting and avulsion of its branches. Massive adhesions due to previous cysts manipulation may lead to increased bleeding, being a risk factor for mortality. [ABSTRACT FROM AUTHOR]

Deficiency of citrin, the liver-type aspartate-glutamate carrier, arises from biallelic mutations of the gene SLC25A13. Although citrin deficiency (CD) is associated with higher risk of hepatocellular carcinoma (HCC) in adult patients, this association remains inconclusive in pediatric cases. The patient in this paper had been diagnosed to have CD by SLC25A13 analysis at the age 10 months, and then in response to dietary therapy, her prolonged jaundice and marked hepatosplenomegaly resolved gradually. However, she was referred to the hospital once again due to recurrent abdominal distention for 2 weeks at her age 4 years and 9 months, when prominently enlarged liver and spleen were palpated, along with a strikingly elevated serum alpha-fetoprotein (AFP) level of 27605 ng/mL as well as a large mass in the right liver lobe and a suspected tumor thrombus within the portal vein on enhanced computed tomography. After 4 rounds of adjuvant chemotherapy, right hepatic lobectomy and portal venous embolectomy were performed at her age 5 years and 3 months, and metastatic hepatoblastoma was confirmed by histopathological analysis. Afterwards, the patient underwent 5 additional cycles of chemotherapy and her condition remained stable for 7 months after surgery. Unfortunately, hepatoblastoma recurred in the left lobe at the age 5 years and 10 months, which progressed rapidly into liver failure, and led to death at the age 6 years and 1 month. As far as we know, this is the the first case of hepatoblastoma in a patient with CD, raising the possibility of an association between these two conditions. [ABSTRACT FROM AUTHOR]

Ascites is a pathological collection of free fluid in the peritoneal cavity, which is a common complication in patients with cirrhosis, an advanced liver disease. Bacterial infection increases the mortality rate of hospitalized patients with cirrhosis, irrespective of the severity of the liver disease. Around 60% of patients with compensated cirrhosis developed ascites within 10 years during the course of their disease. The in-hospital mortality rate due to spontaneous bacterial peritonitis (SBP) could exceed 90%, but with early diagnosis and prompt antibiotic therapy, this rate has been shown to decrease to 20%. Here, we enrolled adult (age ≥ 18) patients with liver disease with evidence of cirrhosis who developed ascites and assessed the presence of spontaneous ascites fluid infection (SAFI) in these patients. Of the total 218 patients, 22.9% (50/218) develop ascites infection. The liver organ function tests like alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin were found to be significantly (P < 0.05) higher in patients with ascites fluid infection compared to patients with non-ascites fluid infection. Of the gram-negative bacteria, K. pneumonia and E. coli were isolated and found to be 100% resistant to amoxicillin and clavulanate. From the gram-positive bacterial isolates, S. aureus was only resistant to penicillin, whereas Str. viridans was resistant to ceftriaxone, cefotaxime, cefepime, and penicillin. On the other hand, clinical features such as a history of jaundice, low arterial blood pressure, and ultrasound results such as a shrunken liver and enlarged spleen were also independent predictors of spontaneous bacterial peritonitis. In conclusion, given the high probability of death following SAFI, early detection, and treatment, as well as knowledge of the microbial agent, resistance profile, and predictive markers in various contexts, are essential for the timely diagnosis and management of SAFI in these patients. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Thalassemia and hemoglobin (Hb) variants are the most common hereditary red blood cell disorders worldwide. Alpha-thalassemia and alpha-globin variants are caused by mutations of the alpha-globin genes (HBA2 and HBA1), resulting in impaired alpha-globin production and structurally abnormal globin, respectively. Clinical severity of alpha-thalassemia correlates with the number of affected alpha-globin genes, yielding a spectrum of clinical manifestations from mild to severe anemia. Routine diagnosis involves Hb analysis and PCR-based methods, yet identifying rare variants necessitates comprehensive clinical and hematologic laboratory data. The knowledge of phenotype and genotype correlation is useful for genetic counseling and treatment planning. Case Report: A 59-year-old Thai woman presented with chronic anemia. Her baseline Hb level ranged between 8.0 and 9.0 g/dL, with no history of transfusion. Physical examination showed mild pallor, without enlarged liver and spleen. Laboratory investigations showed microcytic, hypochromic anemia and abnormal Hb peak by Hb analysis (retention time 4.58 min by HPLC method). Common alpha-globin gene deletions, including the Southeast-Asian/Thai 3.7 kb and 4.2 kb deletions were tested using gap-PCR, with none of these deletions detected. Direct DNA sequencing revealed a compound heterozygosity of Hb Jax (HBA2: c.44G>C) and Hb Constant Spring (HBA2: c.427T>C). Conclusions: Compound heterozygosity of Hb Jax and Hb Constant Spring results in microcytic anemia. Hb Jax can be identified by Hb analysis, and diagnosis can be confirmed by direct DNA sequencing method. Coinheritance of Hb Jax and alpha-globin variants should be considered in cases with microcytic anemia and a specific Hb peak seen in Hb chromatogram. [ABSTRACT FROM AUTHOR]

Pediatricians face a diagnostic dilemma when young patients with sickle cell disease (SCD) have prolonged fevers. SCD is a potential immunocompromised state because of functional asplenia. Most children with hemoglobin variant SS (Hb SS) have decreased or absent splenic function by the age of 2 years. These patients are at substantial risk of life-threatening infections, especially with encapsulated organisms and serious complications such as vaso-occlusive crisis and acute chest syndrome. We present a 3-year-old male, diagnosed with SCD with symptoms of fever, rash, and enlarged spleen and liver. Despite a 6-day course of intravenous (IV) antibiotics, his fevers persisted, and the inflammatory markers remained elevated. This clinical presentation prompted further investigations into a potential systemic etiology. [ABSTRACT FROM AUTHOR]

Chromobacterium violaceum is associated with severe sepsis leading to cutaneous and visceral organ abscesses, with mortality rates up to 73%. Around 200 cases of C. violaceum infection have been reported globally. We report a case of a 27-year-old female U.S. Marine recruit who presented with fever, chills, myalgias, arthralgias, headache, and nodules on her extremities. Physical examination revealed multiple small skin abscesses on her extremities. Abdominal imaging with contrast revealed large liver abscesses requiring drainage. Both blood and wound cultures grew C. violaceum. The patient was successfully treated with meropenem and ciprofloxacin. At 3 months, symptoms had resolved, and labs and imaging were normal. Though rare, C. violaceum infection rates are increasing. Severe infection develops rapidly and invasive disease is not uncommon. Early detection and appropriate antibiotic treatment are key in preventing mortality. [ABSTRACT FROM AUTHOR]

Aim: The aim is to study the various histopathological changes in the liver in pediatric patients with choledochal cyst (CC) and correlate with the presentation and type of cyst. Methods: In a prospective observational study including all pediatric patients who underwent CC excision, histopathological changes of the liver in the form of cholestasis (CHS), portal inflammation (PI), bile duct proliferation (BDP), and fibrosis were studied and graded using a scoring system. They were analyzed in relation to age, sex, symptoms, and type of the cyst. Results: All 30 patients of CC showed various degrees of histopathological changes in the liver in the form of CHS, PI, BDP, and liver fibrosis. Patients <1 years had 9/13 (69.2%) cystic variety and those >1 years had 17/17 (100%) fusiform variety of CC (P < 0.001). Patients <1 years frequently presented with jaundice and hepatomegaly and those >1 years presented with pain abdomen (P < 0.002). Higher grades of liver fibrosis and BDP were seen in the cystic variety compared to the fusiform variety (P < 0.001). However, no significant association was found with CHS and PI (P > 1.23). Conclusions: Histopathological changes in the liver of varying grades are seen in all patients of CC. Patients of CC <1 year presented frequently with jaundice, had the cystic type, and had a higher degree of liver damage on histopathology. [ABSTRACT FROM AUTHOR]

The hepatic deletion of Rbpjκ (RbpjF/F::AlbCre) in the mouse leads to exhibition of the Alagille syndrome phenotype during early postnatal liver development with hyperlipidemia and cholestasis due to attenuated disruption of NOTCH signaling. Given the roles of NRF2 signaling in the regulation of lipid metabolism and bile ductal formation, it was anticipated that these symptoms could be alleviated by enhancing NRF2 signaling in the RbpjF/F::AlbCre mouse by hepatic deletion of Keap1 in compound Keap1F/F::RbpjF/F::AlbCre mice. Unexpectedly, these mice developed higher hepatic and plasma cholesterol levels with more severe cholestatic liver damage during the pre-weaning period than in the RbpjF/F::AlbCre mice. In addition, hypercholesterolemia and hepatic damage were sustained throughout the growth period unlike in the RbpjF/F::AlbCre mouse. These enhanced abnormalities in lipid metabolism appear to be due to NRF2-dependent changes in gene expression related to cholesterol synthetic and subsequent bile acid production pathways. Notably, the hepatic expression of Cyp1A7 and Abcb11 genes involved in bile acid homeostasis was significantly reduced in Keap1F/F::RbpjF/F::AlbCre compared to RbpjF/F::AlbCre mice. The accumulation of liver cholesterol and the weakened capacity for bile excretion during the 3 pre-weaning weeks in the Keap1F/F::RbpjF/F::AlbCre mice may aggravate hepatocellular damage level caused by both excessive cholesterol and residual bile acid toxicity in hepatocytes. These results indicate that a tuned balance of NOTCH and NRF2 signaling is of biological importance for early liver development after birth. [ABSTRACT FROM AUTHOR]

Background: Metabolic liver diseases (MLDs) in children can present with a wide range of clinical features. Aims and Objectives: This study aims to increase the high index of suspicion among physicians and awareness among caregivers regarding early diagnosis of MLD. Materials and Methods: This hospital-based prospective observational study has been conducted in the Paediatric Outpatient Department and Inpatient Department of RG Kar Medical College, Kolkata, over 2 years from 2021 to 2023. A total of 47 children aged up to 12 years were diagnosed as various MLDs who fulfilled inclusion and exclusion criteria were included in the study. Template was generated and analysis was done on SPSS software. Results: The study sample was 47 children with MLDs. Mean age was 4.21±3.81 years. Males: female ratio was approximately 2.35:1. History of consanguinity among parents was present in 23.40% cases which affirmed the autosomal recessive mode of inheritance in most of the MLD. History of sibling deaths was there in 10 cases. The most common symptom was yellowish discoloration 21 (44.68%) followed by abdominal distension 12 (25.53%). There were diverse modes of presentations. The most common presentations were hepatomegaly 47 (100%) and splenomegaly 30 (63.83%). Of 47 MLDs, Wilson disease cases were maximum (27.66%) followed by glycogen storage disease (23.40%). Conclusion: High index of suspicion should be prevalent among physicians for early diagnosis of cases to reduce disease mortality and morbidity. [ABSTRACT FROM AUTHOR]

An outbreak of suspected Kikuyu grass (Cenchrus clandestinus) intoxication among dairy cattle occurred on the island of Terceira in the Azores (Portugal), in October 2022. The animals affected were non-lactating dairy cows and heifers from five small farms grazing (free or tethered) a Kikuyu-dominant pasture. Of the 29 animals exposed, 17 were affected, and eight (five heifers and three adult cows) died, resulting in a morbidity rate of 58%, a mortality rate of 28% and a case mortality rate of 47%. The clinical signs were non-specific and inconsistent, and included dry faeces, some with dark red blood; apathy and prostration; abdominal dilatation; tachycardia; tachypnoea; pale or jaundiced mucous membranes; sham drinking; sialorrhoea; and moderate to severe dehydration. Symptomatic treatment was provided but was ineffective. Haematology and serum biochemistry revealed an acute inflammatory leukogram, increased alkaline phosphatase (ALP) activity, decreased gamma-glutamyl transferase (GGT) activity, and azotaemia. The most consistent necropsy findings were haemorrhages in the epicardium and endocardium, an enlarged liver with rounded edges, non-perforated abomasal ulcers, and haemorrhagic lesions in the small and large intestines. Histopathology indicated myocarditis, hepatitis, interstitial nephritis, enteritis and colitis. Several fungal species were isolated from grass samples taken from affected pastures including several Fusarium spp., the genus implicated in Kikuyu toxicosis. Immediate removal of the animals from the pasture with Kikuyu was the only measure that prevented new cases and resulted in the recovery of some of the less affected animals. The epidemiological features of this outbreak and the clinical signs and micro– and macroscopic lesions observed were highly suggestive of Kikuyu grass poisoning. Although the weather conditions varied from other published cases, the grazing conditions (almost exclusive Kikuyu grass) and the post-mortem findings were very similar to those described in the literature, particularly the haemorrhages in the epicardium and endocardium. Kikuyu grass is very invasive and presents many desirable characteristics as cattle feed. Thus, an increase in cases of intoxication may be expected. Practitioners and farmers in areas where Kikuyu grass is abundant should be aware of the potential risks of grazing cattle exclusively on these pastures. They should also be aware of the early and subtle signs of Kikuyu intoxication to allow for timely removal of the animals from pasture. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) caused more deaths in 2017 than breast cancer, prostate, and brain cancers combined. This is primarily due to their aggressive metastatic nature, leading to more fatal rates of cancer patients. Despite this condition, there are no clinically approved drugs that can target metastasis. The NSCLC with EGFR T790M-overexpressing HER2 shows the resistance to osimertinib and trastuzumab starting 10--18 months after the therapy, and thus prospects are grim to these patients. To target the recalcitrant ERBB2 driver oncogene, we developed two engineered destabilizing 3'UTR ERBB2 constructs that degrade the endogenous ERBB2 transcript and proteins by overwriting the encoded endogenous ERBB2 mRNA with the destabilizing message. When iron oxide nanocages (IO nanocages) were used as vehicles to deliver them to tumors and whole tissues in mice bearing tumors, it was well tolerated and safe and caused no genome rearrangement whereas they were integrated into genome deserts (non-coding regions). We achieved significant reduction of the primary tumor volume with desARE3'UTRERBB2-30, achieving 50% complete tumor lysis and inhibiting 60%--80% of liver metastasis, hepatomegaly, and 90% of lung metastasis, through ERBB2 downregulation. These constructs were distributed robustly into tumors, livers, lungs, kidneys, and spleen and mildly in the brain and not in the heart. They caused no abnormality in both short- and long-term administrations as well as in healthy mice. In summary, we accomplished significant breakthrough for the therapeutics of intractable lung cancer patients whose cancers become resistant and metastasize. [ABSTRACT FROM AUTHOR]

Abdominal mass in a toddler is a common condition encountered in clinical practice. The nature of abdominal mass in toddlers can be a developmental cyst or benign and malignant tumours from various intraabdominal organs. Round blue cell tumours arising from the kidney, adrenals, pancreas, and liver in toddlers present as abdominal masses and are potentially fatal even with systematic treatment. Hepatoblastoma, a small round blue cell tumour of childhood, is a rare hepatic tumour. We report a case of hepatoblastoma in a toddler in view of its diagnostic challenge. [ABSTRACT FROM AUTHOR]

Recurrent infections in children are alarming symptoms that require further investigation, particularly for various immunodeficiency syndromes. However, concomitant physical examination and laboratory findings, along with detailed investigations on the nature of these infections, might be useful to identify further pathologies, such as neutropenia, which might be the underlying reason behind recurrent infections. In this case report, we aimed to provide a different perspective on recurrent infections in childhood and to highlight the importance of accompanying physical examination findings and careful history-taking. In addition, by using glycogen storage disease type 1b as a model disease, we aim to raise awareness of inborn errors of metabolism as possible differential diagnoses and to prove that through certain therapeutic measures such as drug repurposing, these diseases can be controlled, possibly leading to decreased morbidity and mortality in this patient group, which was once thought to have a devastating prognosis. [ABSTRACT FROM AUTHOR]

Organ dysfunction and failure increase the morbidity and mortality following major burn. Alteration of liver morphology and function is common following major burns; however, it has not received much attention. In this study we have assessed the impact of thermal burn on liver in relation with mortality. 55 patients (33 female and 22 males) with TBSA 10–90% and age ranged from 18 to 75 years were included. A bed side serial ultrasonography to assess the volume of liver and liver function tests was done on the 2nd, 9th and 16th day following burn. Baseline demographic and clinical information such as age, gender, burn size and outcome of patient were also collected. 8 patients died during 2nd week following burn and 47 survived. The mean TBSA for survivors was 37% and for non survivors 80%. Mean liver volume in survivors steadily decreased from 1693.70 cm3 to 1631.31 cm3 over 3 weeks. Mean liver volume in non- survivors steadily increased from 1855.88 cm3 to 2028.50 cm3 over 2 weeks. Liver function test in survivors steadily improved while in non survivors it deteriorated over 2 weeks. There is a correlation between altered liver morphology and function with mortality among severely burnt patients however liver volume did not show statistical significance. A decreasing trend of liver dysfunction parameters and hepatomegaly following burn is associated with good prognosis. • Alteration of liver morphology and function is common following major burns. • There is correlation between altered liver morphology and biomarkers and mortality among severely burned patients. • A decreasing trend of liver biomarkers and hepatomegaly is associated with good prognosis among severely burned patients. [ABSTRACT FROM AUTHOR]

Amyloidosis is a rare, polymorphic and serious disease. AL amyloidosis, the most common form, results from deposits of insoluble fibrils made up of immunoglobulin light chains in different organs. A symptomatic liver damage is present in approximately 30 % of patients and affects the prognosis. A particular rare form of icteric liver damage with a rapid increase of bilirubin level has a terrible prognosis. Myocardial damage, also prognostic, can be responsible for a cardiac liver. Digestive tract involvement is often concerned, which can be asymptomatic or cause various problems including hemorrhage or perforation. The diagnosis of amyloidosis is histological, using specific congo red staining associated with typing of amyloid deposits by direct immunofluorescence or immunohistochemistry. The biopsy is preferably performed in the salivary glands or abdominal fat. Treatment is currently based on immuno-chemotherapy. A particular form of amyloidosis, transthyretin-TTR, produced by the liver, may require liver transplantation in cases of serious cardiac or neurological damage, even if this indication is disappearing thanks to new specific treatments. [ABSTRACT FROM AUTHOR]

Congenital hepatic fibrosis (CHF) is a rare condition characterized by abnormal accumulation of fibrous tissue in the liver, leading to liver dysfunction. While CHF has been documented in various animal species, it has rarely been reported in cattle. This report presents a case of CHF in an aborted Holstein-Friesian fetus. During the necropsy, the most notable macroscopic findings included an enlarged liver with an irregular "cobblestone appearance" on the surface and firm parenchyma, as well as moderate ascites. Histopathological examination revealed extensive hepatic fibrosis in the portal areas, accompanied by bridging fibrosis extending between portal tracts and bile duct proliferation within the fibrous tissue. Screening for infectious agents as the cause of abortion or liver lesions was unremarkable. The necropsy and histopathological findings confirmed CHF, constituting the first case described in Holstein-Friesian calves in Serbia. Further research is required to determine whether this condition has a genetic basis or is influenced by yet to be identified factors in Holstein-Friesian cattle. [ABSTRACT FROM AUTHOR]

This commentary responds to a case about diethylene glycol-contaminated glycerin in cough syrup. Glycerin is a commonly used excipient in medicines to improve texture and taste. Excipients are typically pharmacologically inactive ingredients contained in prescription and over-the-counter drugs that play a critical role in the delivery, effectiveness, and stability of active drug substances. The commentary first canvasses how contaminants enter the excipient supply chains. One way is by misleading labeling or intentional adulteration by manufacturers or suppliers. Another way is by human or systemic error. This commentary then discusses quality control testing and suggests the ethical and clinical importance of increased transparency in excipient supply chains. [ABSTRACT FROM AUTHOR]

Introduction: Measles is a highly contagious viral disease. In recent years, there has been an alarming increase in measles cases in Europe. Most patients were not vaccinated. The aim of this study was to analyse the clinical manifestation of measles in paediatric patients, considering the differences between infants and older children. Material and methods: This was a retrospective observational study, for which data were collected from the medical records of paediatric patients hospitalised due to measles January 2017 - December 2019. Stratification was based on age. In the younger group (infants), children under 13 months of age were included. Results: In total 84 children were enrolled in the study, including 26 infants (30.95%) and 58 older children (69.5%). In 67/84 (79.76%) participants no history of measles vaccination was reported. Among those not vaccinated, there were 28/67 (41.79%) children too young for vaccination. Fever and erythema occurred in all patients. The disease was complicated by pneumonia in 39/84 (46.43%) and acute otitis media in 19/84 (22.62%) children. Antibiotics were administered in 45/84 (69.05%) cases, of which 10/58 (17.24%) had 2 or more. The infants had significantly less frequent photophobia (p = 0.041693), lymphadenopathy (p = 0.005229), hepatomegaly (p = 0.030619), and splenomegaly (p = 0.019469), Instead, they were significantly more likely to have acute otitis media (p = 0.020141). Conclusions: Measles is a serious disease that most commonly affects unvaccinated children. The most common symptoms include fever and rash. Otitis media and pneumonia were the most common measles complications. The variations in symptoms and complications of measles differ significantly between infants and older children. [ABSTRACT FROM AUTHOR]

Copyright of Revista Pediatría de Atención Primaria is the property of LUA Ediciones 3.0 S.L. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Viral Hepatitis Journal / Viral Hepatit Dergisi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Splenomegaly is the enlargement of spleen. Splenomegaly is a sign seen in various disease processes in infants and children. So, an attempt was made in the present study to know the various etiological factors and clinical features and clinical outcome of splenomegaly in the cases admitted in Prathima institute of medical sciences, Nagunoor, Karimnagar Aim and objectives: 1. To establish the possible etiology of Splenomegaly in children by clinical and laboratory methods Material and methods: 100 children from 3 months to 18years, with varying grades of Splenomegaly of different etiologies, admitted to paediatric wards of Prathima Institute of Medical Sciences, Karimnagar were studied in this observational study between Decembers 2015 to November 2017. Detailed study of each case including history, thorough physical examination and necessary investigations were done to reach the diagnosis. Results: Male preponderance was seen in present study. Maximum incidence of Splenomegaly was seen between 3 months to 6 years age group (62%). Majority of the cases had moderate Splenomegaly (62%). Fever was the most common presenting feature associated with Splenomegaly. Hepatomegaly was the most common association with Splenomegaly. Infections (42%) were the most common cause of Splenomegaly, followed by hematologic (25%) causes. Conclusions: Infections was the most common cause of Splenomegaly in present study. Male preponderance was seen; majority of cases had moderate Splenomegaly and belonged to preschool age group. [ABSTRACT FROM AUTHOR]