Search Results (74)

Background: Congenital hepatic hemangiomas (CHHs) are typically considered rapidly involuting tumors, similar to their cutaneous counterparts (RICHs). However, non-involuting tumors remain poorly characterized. This study examines the evolutionary patterns and management strategies for non-involuting congenital hepatic hemangiomas (NICHHs). Methods: We conducted a retrospective review of clinical, imaging, histological, and genetic data of children diagnosed with NICHH—defined as showing no signs of involution for at least 18 months—between 1991 and 2022. Results: Seven patients (five females, two males) were identified. The median age at diagnosis was 42 days (range: 0–1440). Five patients had asymptomatic lesions, predominantly located in the right hepatic lobe. Histologic confirmation was available in three cases, and a GNAQ gene mutation was identified in one. The median follow-up period was 75 months (range: 35–191). Three patients with giant NICHH were treated with sirolimus, resulting in partial response in two cases and lesion stabilization in one. The four untreated patients showed diverse evolutionary patterns, including delayed involution and tardive growth. Conclusions: NICHH lesions demonstrate distinct long-term evolution. Accurate diagnosis and regular monitoring are essential to avoid unnecessary interventions. Sirolimus may offer a promising non-surgical treatment for select patients, particularly those with giant lesions. Full article

Ciliopathies are disorders that affect primary or secondary cellular cilia or structures associated with ciliary function. Primary cilia (PC) are essential for metabolic regulation and embryonic development, and pathogenic variants in cilia-related genes are linked to several pediatric conditions, including renal-hepatic diseases and congenital defects. Biliary atresia (BA) is a progressive infantile cholangiopathy and the leading cause of pediatric liver transplantation. Although the exact etiology of BA remains unclear, evidence suggests a multifactorial pathogenesis influenced by both genetic and environmental factors. Patients with BA and laterality defects exhibit genetic variants associated with ciliopathies. Interestingly, even isolated BA without extrahepatic anomalies presents morphological and functional ciliary abnormalities, suggesting that environmental triggers may disrupt the ciliary function. Among these factors, hypoxia has emerged as a potential modulator of this dysfunction. Hypoxia-inducible factor 1-alpha (HIF-1α) plays a central role in hepatic responses to oxygen deprivation, influencing bile duct remodeling and fibrosis, which are key processes in BA progression. This review explores the crosstalk between hypoxia and hepatic ciliopathies, with a focus on BA. It discusses the molecular mechanisms through which hypoxia may drive disease progression and examines the therapeutic potential of targeting hypoxia-related pathways. Understanding how oxygen deprivation influences ciliary function may open new avenues for treating biliary ciliopathies and improving patient outcomes. Full article

Background/Objectives: A functional liver is vital for normal protein metabolism. Alterations of circulating amino acid (AA) concentrations have previously been reported in dogs with hepatocellular carcinoma, chronic hepatitis, and hepatocutaneous syndrome. The purpose of this study was to compare serum AA profiles between dogs with a congenital portosystemic shunt (CPSS) and healthy control dogs. Methods: Serum samples were collected from 50 dogs with an extrahepatic congenital portosystemic shunt (eCPSS) and 10 dogs with an intrahepatic congenital portosystemic shunt (iCPSS) at time of surgical intervention and from 21 healthy control dogs. Serum AA and other nitrogenous compounds were measured with a dedicated amino acid analyzer. The concentration of each AA was compared between groups using a Kruskal–Wallis test followed by Dunn’s multiple comparisons tests, as appropriate. The Benjamini–Hochberg procedure was used to control for false discovery. Significance was set at q < 0.05. Results: Compared to healthy controls, dogs with a CPSS had significantly increased serum concentrations of ammonia, asparagine, glutamic acid, histidine, phenylalanine, serine, and tyrosine and had significantly decreased concentrations of isoleucine, leucine, threonine, urea, and valine. There were no significant differences in serum AA concentrations between dogs with an eCPSS and dogs with an iCPSS. Conclusions: Dogs with a CPSS had altered serum AA concentrations compared to healthy control dogs, including decreased branched-chain amino acids (BCAAs) and increased aromatic amino acids (AAAs). In summary, serum AA profiles can differentiate dogs with a CPSS from healthy dogs but not dogs with an eCPSS from dogs with an iCPSS. Full article

Short bowel syndrome (SBS), usually resulting from massive small bowel resections or congenital defects, may lead to intestinal failure (IF), requiring intravenous fluids and parenteral nutrition to preserve patients’ nutritional status. Approximately 15% to 40% of subjects with SBS and IF develop chronic hepatic damage during their life, a condition referred to as intestinal-failure-associated liver disease (IFALD), which ranges from steatosis to fibrosis or end-stage liver disease. Parenteral nutrition has been largely pointed out as the main pathogenetic factor for IFALD. However, other elements, such as inflammation, bile acid metabolism, bacterial overgrowth and gut dysbiosis also contribute to the development of liver damage and may deserve specific treatment strategies. Indeed, in our review, we aim to explore IFALD pathogenesis beyond parenteral nutrition. By critically analyzing recent literature, we seek to delve with molecular mechanisms and metabolic pathways underlying liver damage in such a complex set of patients. Full article

Reports on patients with a gastrophrenic shunt treated with cellophane banding without attenuation are scarce. This case series evaluated the outcomes of cellophane banding without intraoperative attenuation in patients with a congenital left gastrophrenic shunt. Seven client-owned dogs and five client-owned cats with congenital left gastrophrenic shunt were included. Data collected from the medical records included signalment, history, physical examination, clinicopathologic testing, diagnostic imaging (pre and postoperative), perioperative complications, hepatic histopathological evaluation, and clinical outcomes. The application of a cellophane band without intraoperative attenuation of congenital left gastrophrenic shunts resulted in complete closure in 10/11 patients at a median follow-up of 60 days (range: 33–174) based on ultrasound. The mean shunt diameter was 6.1 mm (range: 4.2–8). One dog had partial closure of the shunt at 3 months but was lost to follow-up. One dog died perioperatively from seizures. One cat experienced post-attenuation neurologic signs that completely resolved. Cellophane banding without intraoperative attenuation appeared to be a safe and potentially effective approach for managing gastrophrenic shunts. The percentage of shunt closure observed in this cases series is higher than that historically reported for other shunt localizations. Shunt localization may influence closure. Residual shunting may not be associated with shunt diameter. Further studies with larger sample sizes and standardized follow-ups are needed to confirm its efficacy. Full article

Background: The Fontan procedure has provided pediatric patients suffering from severe congenital heart disease the opportunity to reach adulthood. Increasingly, we encounter the liver repercussions of Fontan circulation, alongside a decline in heart function and exercise performance. This study aims to identify the univentricular heart malformations that are most susceptible to liver dysfunction; assess which markers of liver injury are essential for multidisciplinary clinical follow-up of Fontan patients; determine the optimal approach for evaluating liver function in Fontan patients; and explore how a congenital cardiology team can interpret the data and respond effectively to signs of organ failure. Methods: Cross-sectional clinical study including patients who underwent a Fontan procedure at the University Hospital of Padua between 1982 and 2017. Patients were admitted for elective hospitalization between June 2021 and June 2022 and underwent clinical assessment, laboratory tests, and instrumental examinations. Results: Seventy patients were included in the study. On admission, 48 patients (72%) were in New York Heart Association (NYHA) functional class I, and the cardiopulmonary exercise test was normal for age and gender. At laboratory tests, 56% of patients showed changes in NTproBNP values, most of whom had right-sided ventricular morphology. Liver function tests showed abnormal Gamma-Glutamyl Transferase (GGT) blood levels in 68%. On cardiac imaging, at least moderate atrioventricular valve insufficiency was found in 9% of cases. Fibroscan showed altered hepatic stiffness values in 25% of cases. Statistical analysis showed that systemic atrioventricular valve (SAVV) dysfunction was significantly associated with a reduction of maximum oxygen consumption (VO₂ max) and hepatic stiffness. Conclusions: SAVV dysfunction is significantly responsible for worse functional outcomes and the development of hepatic fibrosis due to an increase in venous congestion. Setting up a careful multidisciplinary follow-up in these patients is mandatory for early detection of complications, prompt treatment, and better outcomes. Full article

Varicella-zoster virus is an α-herpes virus with a double-stranded DNA genome, which causes two main clinical pictures: varicella or chickenpox and herpes zoster. Chickenpox is the primary infection, predominantly affecting children, and it presents with fever and a cutaneous eruption consisting of a vesicular, pruritic, and painful rash. Herpes zoster is a viral infection that typically develops in adulthood as a result of the reactivation of the varicella-zoster virus. If acquired during pregnancy, chickenpox may be responsible for serious complications for the mother, the fetus, or the newborn. The most frequent complication of primary varicella-zoster virus infection in mothers is varicella pneumonia, while encephalitis and hepatitis are rare. The effects on the fetus due to chickenpox infection depend on the stage of pregnancy when the mother becomes infected. If the infection occurs during the first trimester, it does not increase the risk of miscarriage. However, if the infection occurs during the first or second trimester, it may cause fetal varicella syndrome or congenital varicella syndrome. During pregnancy, if the varicella-zoster virus reactivates, it usually does not cause harm to the fetus or lead to any birth defects. However, it may increase maternal morbidity due to herpes zoster and its complications. In the case of primary varicella-zoster virus infection in pregnant women, about 20% of newborns may get neonatal or infantile herpes zoster without any complications. However, it is recommended to start early treatment of herpes zoster in pregnant women as it is believed to accelerate the healing process of skin lesions and alleviate pain, reducing both its duration and severity. Through this narrative review, we discuss the approach to the optimal management of varicella-zoster virus infection during pregnancy. Full article

Hepatic encephalopathy (HE) in dogs is a metabolic disorder of the central nervous system that occurs secondarily to liver dysfunctions, whether due to acquired or congenital causes. A portosystemic shunt is the presence of abnormal communications between the hepatic vessels (portal and suprahepatic veins). As a result of this, the blood brought from the digestive tract through the portal vein bypasses the liver, and the unmetabolized components of the portal bloodstream enter directly into systemic circulation, causing clinical symptoms of metabolic encephalopathy (HE). A 3-month-old Bichon canine patient with a history of seizures secondarily to a portosystemic shunt (PS), confirmed through color Doppler ultrasound exam and computed tomography, was presented for evaluation. The typical electroencephalographic (EEG) traces recorded were characterized by the presence of bilateral symmetrical triphasic waves, resembling non-convulsive status epilepticus. The presence of this EEG pattern is useful in choosing the best therapeutic option in order to not accentuate the HE sings and, consequently, to decrease the mortality risk due to a prolonged status epilepticus. Full article

Background: Pregnant women with congenital heart disease carry a high risk of complications, especially when cardiac function is suboptimal. Increasing evidence suggests that impaired right ventricular (RV) function has a negative effect on placental function, possibly through venous congestion. We report a case series of hepatic and renal venous flow patterns in pregnant women with right ventricular dysfunction after repaired Tetralogy of Fallot (ToF), relative to those observed in normal pregnancy and preeclampsia. Methods: At 20–24 weeks pregnancy, RV function was measured by echocardiography and by cardiovascular magnetic resonance in women with repaired ToF. Combined Doppler-ECG of the hepatic and renal interlobular veins were performed in three women with asymptomatic right ventricular dysfunction. Venous impedance index and pulse transit time were measured and classified as abnormal at >75th and <25th reference percentile, respectively. Results: All three women showed dilated RV and mildly impaired RV function. Both hepatic and intrarenal Doppler flow waves were abnormal and very much resembled the patterns seen in preeclampsia. One of the three women had complications including ventricular tachycardia, intrauterine growth restriction, antenatal bleeding, emergency cesarean section and acute heart failure 2 days postpartum. Conclusions: Pregnant women with mild right ventricular dysfunction after repaired ToF show abnormal venous Doppler flow waves in the liver and kidneys, similar to those observed in preeclampsia. These findings are in line with reported observations on the association between impaired RV function, abnormal return of venous blood, venous congestion and organ dysfunction. The parallel with venous Doppler flow observations in preeclampsia suggest that the venous compartment might play an important role in the etiology of preeclampsia-induced organ dysfunction. Whether this phenomenon directly affects the uteroplacental circulation is to be assessed in future research. Full article

Consuming a “modern” Western diet and overnutrition may increase insulin secretion. Additionally, nutrition-mediated hyperinsulinemia is a major driver of ectopic fat deposition. The global prevalence of metabolic syndrome is high and growing. Within this context, people with congenital lipodystrophy often experience a severe form of metabolic syndrome. Evidence is increasingly supporting that subtle partial lipodystrophy plays an important role in the development of metabolic syndrome in the general population. In individuals in the general population with subtle partial lipodystrophy, as well as in those with congenital lipodystrophy, the subcutaneous adipose tissues are unable to accommodate surplus energy intake. In both conditions, (excess) fat is directed toward the liver, pancreas, and muscles, where it is deposited as ectopic fat, as this fat can no longer be stored in the “safe” subcutaneous fat depots. Ectopic fat depositions cause insulin resistance in the liver and muscles, as well as β-cell dysfunction in the pancreas. Support of a direct pathological role of ectopic fat deposition in this condition is further provided by the rapid normalization of hepatic insulin sensitivity and improvement in pancreatic β-cell function after marked reductions in ectopic fat depositions. Thus, ectopic fat deposition in the liver, pancreas, and muscles may play a causal role in the pathogenesis of metabolic syndrome even in the general population. As such, the prevention of ectopic fat deposition may reduce the risk of metabolic syndrome and mitigate its effects. Full article

Viruses are the most common congenital infections in humans and an important cause of foetal malformations, neonatal morbidity, and mortality. The effects of these infections, which are transmitted in utero (transplacentally), during childbirth or in the puerperium depend on the timing of the infections. These vary from miscarriages (usually with infections in very early pregnancy), congenital malformations (when the infections occur during organogenesis) and morbidity (with infections occurring late in pregnancy, during childbirth or after delivery). The most common of these viruses are cytomegalovirus, hepatitis, herpes simplex type-2, parvovirus B19, rubella, varicella zoster and zika viruses. There are currently very few efficacious antiviral agents licensed for use in pregnancy. For most of these infections, therefore, prevention is mainly by vaccination (where there is a vaccine). The administration of immunoglobulins to those exposed to the virus to offer passive immunity or appropriate measures to avoid being infected would be options to minimise the infections and their consequences. In this review, we discuss some of the congenital and perinatal infections and their consequences on both the mother and fetus and their management focusing mainly on prevention. Full article

Toxoplasmosis is a disease caused by the intracellular protozoan Toxoplasma gondii, which has infected a third of the global population. Immunocompromised individuals and children with congenital disorders are most likely to be impacted by toxoplasmosis, and accurate diagnosis is essential. Toxoplasmosis is associated with HIV, schizophrenia, and diabetes. However, few studies have analyzed the association with other microorganisms. The purpose of this study was to determine the prevalence of coinfection of Toxoplasma gondii with other pathogens. From November 1997 to June 2024, PubMed, Science Direct, LAT index, Web of Science, Google Scholar, and Research Gate were searched. The keywords used were “Toxoplasma and microorganism coinfection”, “Toxoplasma coinfection and parasites”, “Toxoplasma coinfection and Protozoans or Bacteria or Helminths or Nematodes or Trematodes or Mycobacterium”, “Toxoplasma gondii in coinfection with virus”, and “Human Toxoplasmosis and coinfection”. Next, OpenMeta Analyst Software version 12.11 was used for meta-analysis, creating forest plots, and determining heterogeneity I². A total of 17,535 patients in 48 articles, of whom 5848 were seropositive to T. gondii, were included in this review. Population studies showed that the prevalence of virus infection was most frequent (32%), followed by parasites (18.4%), bacteria (29.7%), and fungi (5.8%). The pooled prevalence of coinfection was found to be 29.1%, with a lower bound of 0.232, an upper bound of 0.350, a standard error of 0.030, and p < 0.001. Heterogeneity (I²) was 99.12%, p < 0.001, with a global variance tau2 = 0.042. Toxoplasma gondii is an opportunist that mainly affects immunocompromised populations. The main coinfections were found to be viral infections, with HIV ranking first, followed by cytomegalovirus, hepatitis B and C, rubella, herpes simplex 1 and 2, SARS-CoV-2, and coxsackie virus. Full article

The HNF1B gene, located on chromosome 17q12, encodes a transcription factor essential for the development of several organs. It regulates the expression of multiple genes in renal, pancreatic, hepatic, neurological, and genitourinary tissues during prenatal and postnatal development, influencing processes such as nephrogenesis, cellular polarity, tight junction formation, cilia development, ion transport in the renal tubule, and renal metabolism. Mutations that alter the function of Hnf1b deregulate those processes, leading to various pathologies characterized by both renal and extrarenal manifestations. The main renal diseases that develop are polycystic kidney disease, hypoplastic or dysplastic kidneys, structural abnormalities, Congenital Anomalies of the Kidney and Urinary Tract (CAKUT), and electrolyte imbalances such as hyperuricemia and hypomagnesemia. Extrarenal manifestations include Maturity-Onset Diabetes of the Young (MODY), hypertransaminasemia, genital and urinary tract malformations, Autism Spectrum Disorder (ASD), and other neurodevelopmental disorders. Patients with HNF1B alterations typically carry either punctual mutations or a monoallelic microdeletion in the 17q12 region. Future research on the molecular mechanisms and genotype–phenotype correlations in HNF1B-related conditions will enhance our understanding, leading to improved clinical management, genetic counseling, monitoring, and patient care. Full article

This study examined the seropositivity of T. gondii and coinfections with other TORCH pathogens among pregnant women attending 17 Basic Health Units (UBS) in Araçatuba, SP, Brazil. Of the 711 pregnant women seen at these UBS, only 297 were tested for T. gondii. Of the women tested for T. gondii (n = 297), 26.9% had IgG antibodies, 6.7% had IgM, and 32.0% tested positive for either or both. Only 1.4% showed both IgG and IgM antibodies, while 67.7% were non-reactive. The seropositivity was 17.1% for syphilis, 63.2% for rubella, 0.9% for hepatitis C, 0.9% for dengue, 17.9% for COVID-19, and 0.9% for herpes simplex (types 1/2). Coinfections with syphilis, rubella, and herpes simplex were also noted. Higher education levels appeared to protect against T. gondii seropositivity. The findings highlight a significant prevalence of T. gondii among pregnant women, with variation across UBSs, pointing to socioeconomic, behavioral, and environmental factors as influential. We also observed co-occurrence with other infections, such as syphilis, rubella, and herpes simplex. The study underscores the need for targeted public health interventions to reduce the risks of congenital infections. Full article

Cardiovascular diseases (CVDs) continue to be a major global health concern, representing a leading cause of morbidity and mortality. This review provides a comprehensive examination of CVDs, encompassing their pathophysiology, diagnostic biomarkers, advanced imaging techniques, pharmacological treatments, surgical interventions, and the emerging role of herbal remedies. The review covers various cardiovascular conditions such as coronary artery disease, atherosclerosis, peripheral artery disease, deep vein thrombosis, pulmonary embolism, cardiomyopathy, rheumatic heart disease, hypertension, ischemic heart disease, heart failure, cerebrovascular diseases, and congenital heart defects. The review presents a wide range of cardiac biomarkers such as troponins, C-reactive protein, CKMB, BNP, NT-proBNP, galectin, adiponectin, IL-6, TNF-α, miRNAs, and oxylipins. Advanced molecular imaging techniques, including chest X-ray, ECG, ultrasound, CT, SPECT, PET, and MRI, have significantly enhanced our ability to visualize myocardial perfusion, plaque characterization, and cardiac function. Various synthetic drugs including statins, ACE inhibitors, ARBs, β-blockers, calcium channel blockers, antihypertensives, anticoagulants, and antiarrhythmics are fundamental in managing CVDs. Nonetheless, their side effects such as hepatic dysfunction, renal impairment, and bleeding risks necessitate careful monitoring and personalized treatment strategies. In addition to conventional therapies, herbal remedies have garnered attention for their potential cardiovascular benefits. Plant extracts and their bioactive compounds, such as flavonoids, phenolic acids, saponins, and alkaloids, offer promising cardioprotective effects and enhanced cardiovascular health. This review underscores the value of combining traditional and modern therapeutic approaches to improve cardiovascular outcomes. This review serves as a vital resource for researchers by integrating a broad spectrum of information on CVDs, diagnostic tools, imaging techniques, pharmacological treatments and their side effects, and the potential of herbal remedies. Full article