Metabolic disorders are a common cause of acute liver failure (ALF) in infants and children. Several key metabolic disorders that can cause ALF include neonatal hemochromatosis, type 1 tyrosinemia, mitochondrial cytopathies such as fatty acid oxidation defects and respiratory chain disorders, galactosemia, and urea cycle defects. Timely diagnosis and specific treatment of the underlying metabolic etiology are important for improving outcomes in pediatric ALF.
Interpret tests for metabolic diseases talk sk yachhaSanjeev Kumar
Clinical suspicion of inborn errors of metabolism should arise with parental consanguinity, positive family history, unexplained sibling deaths, or recurrent issues like hypoglycemia, acidosis, or encephalopathy. Initial screening tests available in India can help identify aminoaciduria, organic acidemias, or fatty acid oxidation defects while definitive testing requires samples not readily available, like fresh tissue, to analyze specific enzyme activities. Managing treatable conditions like hereditary fructose intolerance or some organic acidemias can improve outcomes.
Metabolic Liver Disease definitions by Dr. Ashish BavdekarSanjeev Kumar
This document discusses metabolic liver disease (MLD), including:
1. MLDs can be classified based on their effects, ranging from no harm to the liver to significant liver injury.
2. Data from Indian hospitals shows MLD cases are increasing and now represent a significant portion of liver diseases seen.
3. MLDs can present early in infancy with features like galactosemia, tyrosinemia, or cystic fibrosis or later with glycogen storage disease, Wilson's disease, or lipid storage disorders.
4. Diagnosing MLD can be challenging due to non-specific signs, genetic heterogeneity, and lack of diagnostic facilities in some areas.
Glycogen storage disorder case presentation1Sanjeev Kumar
This document summarizes the medical history and treatment of a 4-month-old male child diagnosed with Glycogen Storage Disorder Type 1B (GSD 1B). The child had a history of multiple hospital admissions for infections, hypoglycemia, metabolic acidosis, hepatomegaly, and failure to thrive. Genetic testing confirmed a homozygous deletion in the glucose-6-phosphate translocase gene. The child was started on a specialized diet but continued having infections and developmental delays. Sadly, the child passed away at 10 months after developing severe metabolic acidosis and respiratory distress during an episode of acute gastroenteritis.
Progressiv familial intrahepatic cholestasis type 1 case presentationSanjeev Kumar
This document describes the case of a 4-year-old male child presenting with itching, jaundice, and diarrhea for 3 months. He had a family history of similar cases resulting in death from liver disease. Liver tests showed elevated alkaline phosphatase. A liver biopsy showed mild degeneration and normal bile ducts. Immunostaining was positive for BSEP and MRP3. Based on the clinical features and test results, the child was diagnosed with Progressive Familial Intrahepatic Cholestasis type 1.
This document summarizes information presented by two public health nutrition students about Glycogen Storage Disease type 1 (von Gierke's disease). It defines GSD1 as a genetic metabolic disorder caused by an inability to break down glycogen into glucose. This puts patients at risk for hypoglycemia. The major forms are type 1a, caused by a deficiency in glucose-6-phosphatase, and type 1b, caused by a defect in glucose-6-phosphate translocase. Successful treatment requires maintaining normal blood glucose through frequent intake of complex carbohydrates. Left untreated, GSD1 can cause serious health issues; but with proper nutrition management, patients can experience normal growth and development.
This document discusses the approach to a case of neonatal liver failure. It begins by describing the case presentation and initial workup. Key points include that metabolic diseases are a common cause of neonatal liver failure. The document then discusses priorities in management, which include stabilizing life-threatening issues and pursuing diagnostic testing. Common causes like galactosemia, tyrosinemia, and HSV hepatitis are discussed. The case is ultimately diagnosed as mitochondrial DNA depletion syndrome based on genetic testing. Important lessons are around promptly considering and evaluating for metabolic etiologies in neonatal liver failure cases.
Interpret tests for metabolic diseases talk sk yachhaSanjeev Kumar
Clinical suspicion of inborn errors of metabolism should arise with parental consanguinity, positive family history, unexplained sibling deaths, or recurrent issues like hypoglycemia, acidosis, or encephalopathy. Initial screening tests available in India can help identify aminoaciduria, organic acidemias, or fatty acid oxidation defects while definitive testing requires samples not readily available, like fresh tissue, to analyze specific enzyme activities. Managing treatable conditions like hereditary fructose intolerance or some organic acidemias can improve outcomes.
Metabolic Liver Disease definitions by Dr. Ashish BavdekarSanjeev Kumar
This document discusses metabolic liver disease (MLD), including:
1. MLDs can be classified based on their effects, ranging from no harm to the liver to significant liver injury.
2. Data from Indian hospitals shows MLD cases are increasing and now represent a significant portion of liver diseases seen.
3. MLDs can present early in infancy with features like galactosemia, tyrosinemia, or cystic fibrosis or later with glycogen storage disease, Wilson's disease, or lipid storage disorders.
4. Diagnosing MLD can be challenging due to non-specific signs, genetic heterogeneity, and lack of diagnostic facilities in some areas.
Glycogen storage disorder case presentation1Sanjeev Kumar
This document summarizes the medical history and treatment of a 4-month-old male child diagnosed with Glycogen Storage Disorder Type 1B (GSD 1B). The child had a history of multiple hospital admissions for infections, hypoglycemia, metabolic acidosis, hepatomegaly, and failure to thrive. Genetic testing confirmed a homozygous deletion in the glucose-6-phosphate translocase gene. The child was started on a specialized diet but continued having infections and developmental delays. Sadly, the child passed away at 10 months after developing severe metabolic acidosis and respiratory distress during an episode of acute gastroenteritis.
Progressiv familial intrahepatic cholestasis type 1 case presentationSanjeev Kumar
This document describes the case of a 4-year-old male child presenting with itching, jaundice, and diarrhea for 3 months. He had a family history of similar cases resulting in death from liver disease. Liver tests showed elevated alkaline phosphatase. A liver biopsy showed mild degeneration and normal bile ducts. Immunostaining was positive for BSEP and MRP3. Based on the clinical features and test results, the child was diagnosed with Progressive Familial Intrahepatic Cholestasis type 1.
This document summarizes information presented by two public health nutrition students about Glycogen Storage Disease type 1 (von Gierke's disease). It defines GSD1 as a genetic metabolic disorder caused by an inability to break down glycogen into glucose. This puts patients at risk for hypoglycemia. The major forms are type 1a, caused by a deficiency in glucose-6-phosphatase, and type 1b, caused by a defect in glucose-6-phosphate translocase. Successful treatment requires maintaining normal blood glucose through frequent intake of complex carbohydrates. Left untreated, GSD1 can cause serious health issues; but with proper nutrition management, patients can experience normal growth and development.
This document discusses the approach to a case of neonatal liver failure. It begins by describing the case presentation and initial workup. Key points include that metabolic diseases are a common cause of neonatal liver failure. The document then discusses priorities in management, which include stabilizing life-threatening issues and pursuing diagnostic testing. Common causes like galactosemia, tyrosinemia, and HSV hepatitis are discussed. The case is ultimately diagnosed as mitochondrial DNA depletion syndrome based on genetic testing. Important lessons are around promptly considering and evaluating for metabolic etiologies in neonatal liver failure cases.
Metabolic liver disease presenting with cholestasis talk anshu srivastavaSanjeev Kumar
This document discusses metabolic liver disease presenting with cholestasis. It begins by defining cholestasis and describing the differences between intrahepatic and extrahepatic cholestasis. In neonates, a metabolic etiology is often the cause of cholestasis and can include conditions like galactosemia or tyrosinemia. The document then examines various etiologies of cholestasis across different age groups. It provides details on progressive familial intrahepatic cholestasis (PFIC), benign recurrent intrahepatic cholestasis (BRIC), and intrahepatic cholestasis of pregnancy. The document emphasizes the importance of early identification of treatable metabolic causes of chole
This document provides information about Progressive Familial Intrahepatic Cholestasis (PFIC), a rare genetic liver disease. It defines what PFIC is, describes potential symptoms, diagnostic testing and treatment options. It also outlines the three main subtypes of PFIC, defined by the gene that is mutated. Each subtype can present with different levels of itching and liver abnormalities, and may progress to complications like liver failure if left untreated. Close monitoring by medical experts and potential surgical interventions or liver transplant are important for managing PFIC.
Jaundice in pregnancy can be caused by hemolytic, hepatocellular, or obstructive factors. Hemolytic jaundice may be due to blood transfusion incompatibility or infection, hepatocellular jaundice can result from viral hepatitis, preeclampsia, acute fatty liver of pregnancy, or drugs/alcohol, and obstructive jaundice may be from cholestasis of pregnancy, gallstones, or other conditions. Cholestasis of pregnancy is caused by estrogen sensitivity and shows a familial tendency, with symptoms of itching and mild jaundice. It can lead to complications like postpartum hemorrhage, premature labor, and stillbirth, so induction of labor is
This document discusses jaundice in multiple patients and the underlying causes. It begins by summarizing different causes of jaundice, including unconjugated hyperbilirubinemia from excessive production or failure of conjugation, and conjugated hyperbilirubinemia from hepatocellular damage or obstruction of bile flow.
It then analyzes several case studies: three with unconjugated hyperbilirubinemia from megaloblastic anemia, hereditary spherocytosis, and an unknown cause; two with conjugated hyperbilirubinemia, one from hepatocellular damage and one from obstruction; and one with malaria-induced cholestasis.
The document emphasizes different
Direct hyperbilirubinaemia in neonate by Dr. Tareq Rahmantareq rahman
This document discusses neonatal cholestasis, defined as prolonged conjugated hyperbilirubinemia in newborns. It reviews definitions, pathophysiology, prevalence, etiologies, evaluation, management, and prognosis. The most common causes are neonatal hepatitis, biliary atresia, and idiopathic neonatal hepatitis. Evaluation involves initial labs and imaging to determine if the cause is intrahepatic or extrahepatic. Specific treatments depend on the underlying condition, such as surgery for biliary atresia or liver transplantation for decompensated liver disease. Prognosis depends on factors like etiology, age at treatment, and progression to cirrhosis.
The document summarizes various liver conditions that can cause jaundice in pregnancy. It discusses physiological changes in the liver during pregnancy and various causes of jaundice related and unrelated to pregnancy. These include viral hepatitis, intrahepatic cholestasis of pregnancy (ICP), preeclampsia, HELLP syndrome, and acute fatty liver of pregnancy (AFLP). It provides details on pathogenesis, clinical presentation, management and prognosis for these conditions. Pregnancy-related liver disorders can affect both mother and fetus, so prompt diagnosis and treatment are important.
Liver disease in pregnancy can have severe maternal and fetal effects. Unique conditions include hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome, and acute fatty liver of pregnancy. Physiological changes occur in hepatic parameters during pregnancy. Conditions like viral hepatitis and cirrhosis may impact an existing pregnancy. Accurate diagnosis and management of liver conditions is important to optimize outcomes.
Dr Anil Arora address the liver diseases that are specific during pregnancy. The presentation contains case discussions on diagnosis, treatments & take home messages
Presented by:
Ahmad mukhtar
MD.,M.B.B.Ch., M.Sc Obstetrics and GynecologyConsultant and Lecturer of Obstetrics and Gynecology, Faculty of
MEDICINE, Zagazig University.
Acute Fatty Liver of Pregnancy (AFLP) is a rare but serious condition that affects 1 in 7,000-11,000 pregnancies. It is characterized by fatty infiltration and cellular dysfunction in the liver during late pregnancy or early postpartum. Prompt delivery is the recommended treatment as the condition does not typically improve until after delivery, and maternal and fetal mortality rates are high if not treated properly. Diagnosis is based on clinical presentation and lab tests in the absence of a definitive causative agent or diagnostic test. Close monitoring of future pregnancies is advised for women previously affected by AFLP.
Evaluation of proteinuria in children - by Dr.B.Sivakanthbsivakanth
1) Proteinuria, or excess protein in the urine, is a common finding in children that requires evaluation to determine the cause. Transient or orthostatic proteinuria are generally benign, while persistent proteinuria may indicate kidney disease.
2) Evaluation of a child with proteinuria includes a history, physical exam, urinalysis, and tests to assess kidney function. Distinguishing transient, orthostatic, and persistent proteinuria guides further testing and management.
3) For persistent proteinuria, additional tests are needed to identify potential causes like glomerular disease, tubular disorders, or infection and determine if nephrology referral is required. Ongoing monitoring is important to classify the
This document discusses liver disease in pregnancy. It begins by noting that liver disorders can take a more serious course during pregnancy and may have severe effects on the mother and fetus. It then reviews normal physiological changes in liver parameters during pregnancy. The document goes on to classify different types of liver diseases that can occur during pregnancy, including those unique to pregnancy and those that coincide or preexist. It presents two case reports, one involving acute fatty liver of pregnancy and another involving intrahepatic cholestasis of pregnancy. It concludes by discussing various viral hepatitises, fulminant hepatitis, and other chronic liver conditions that may occur during pregnancy.
The document discusses liver disease in pregnancy. It notes physiological changes in pregnancy that can affect the liver such as increased alkaline phosphatase levels. It describes different types of liver diseases that can occur including those induced by pregnancy like hyperemesis gravidarum or coinciding with pregnancy like viral hepatitis. It provides details on obstetric cholestasis including its causes, clinical features, investigations, management, and maternal and perinatal prognosis. Management of obstetric cholestasis includes monitoring liver function tests, inducing labor at 38 weeks, fetal surveillance during labor, administering vitamin K, and using ursodeoxycholic acid or cholestyramine to relieve symptoms and normalize liver tests.
1) A 36-year-old pregnant woman presents with jaundice, nausea, vomiting and abdominal pain. Laboratory tests show elevated bilirubin and mildly decreased platelets.
2) The diagnosis is acute fatty liver of pregnancy (AFLP), a rare but serious condition where toxic fatty acid metabolites build up in the liver. AFLP occurs in the third trimester and is associated with obesity, multiple pregnancies, and male fetuses.
3) AFLP and HELLP syndrome share some similarities but AFLP typically causes more severe liver dysfunction. Treatment involves urgent delivery of the baby combined with intensive maternal care including glucose supplementation, antibiotics, and reversal of coagulopathy. Complications can be life
This document discusses investigations for jaundice, including liver function tests (LFTs), CT scan, MRI scan, ERCP, and EUS. It provides detailed information on various LFTs such as aminotransferases, alkaline phosphatase, bilirubin, and GGT. It describes characteristic patterns seen in different liver diseases and notes that additional tests may include hepatitis markers, iron studies, tumor markers, and endoscopic ultrasound. Reference sources include medical textbooks and Wikipedia.
A 7 month old female infant presented with persistent jaundice since 2 weeks of life, high colored urine, and normal colored stools. On examination, she had deep icterus, hepatomegaly, and failure to thrive. Initial tests showed conjugated hyperbilirubinemia. Further workup included normal thyroid function, urine tests, TORCH titers, and alpha-1 antitrypsin level. Liver function tests showed elevated enzymes. Imaging showed hepatomegaly. Differentials included genetic and infectious causes of neonatal cholestasis.
This document summarizes the approach to a child presenting with splenohepatomegaly and developmental delay. Initial testing suggested Gaucher disease but further evaluation found no GBA gene mutation. Bone marrow showed foam cells. The child later developed neurological symptoms. Genetic testing found a pathogenic NP-C mutation, confirming the diagnosis as Niemann-Pick type C, a rare lysosomal storage disorder. Differential diagnoses discussed included Saposin-C deficiency and prosaposin deficiency based on initial findings.
Una persona ofrece sus datos de contacto que incluyen una dirección, un número de celular y una ubicación, posiblemente para vender cupcakes. El mensaje concluye diciendo que aunque no se puede comprar la felicidad directamente, un cupcake puede acercarse.
Metabolic liver disease presenting with cholestasis talk anshu srivastavaSanjeev Kumar
This document discusses metabolic liver disease presenting with cholestasis. It begins by defining cholestasis and describing the differences between intrahepatic and extrahepatic cholestasis. In neonates, a metabolic etiology is often the cause of cholestasis and can include conditions like galactosemia or tyrosinemia. The document then examines various etiologies of cholestasis across different age groups. It provides details on progressive familial intrahepatic cholestasis (PFIC), benign recurrent intrahepatic cholestasis (BRIC), and intrahepatic cholestasis of pregnancy. The document emphasizes the importance of early identification of treatable metabolic causes of chole
This document provides information about Progressive Familial Intrahepatic Cholestasis (PFIC), a rare genetic liver disease. It defines what PFIC is, describes potential symptoms, diagnostic testing and treatment options. It also outlines the three main subtypes of PFIC, defined by the gene that is mutated. Each subtype can present with different levels of itching and liver abnormalities, and may progress to complications like liver failure if left untreated. Close monitoring by medical experts and potential surgical interventions or liver transplant are important for managing PFIC.
Jaundice in pregnancy can be caused by hemolytic, hepatocellular, or obstructive factors. Hemolytic jaundice may be due to blood transfusion incompatibility or infection, hepatocellular jaundice can result from viral hepatitis, preeclampsia, acute fatty liver of pregnancy, or drugs/alcohol, and obstructive jaundice may be from cholestasis of pregnancy, gallstones, or other conditions. Cholestasis of pregnancy is caused by estrogen sensitivity and shows a familial tendency, with symptoms of itching and mild jaundice. It can lead to complications like postpartum hemorrhage, premature labor, and stillbirth, so induction of labor is
This document discusses jaundice in multiple patients and the underlying causes. It begins by summarizing different causes of jaundice, including unconjugated hyperbilirubinemia from excessive production or failure of conjugation, and conjugated hyperbilirubinemia from hepatocellular damage or obstruction of bile flow.
It then analyzes several case studies: three with unconjugated hyperbilirubinemia from megaloblastic anemia, hereditary spherocytosis, and an unknown cause; two with conjugated hyperbilirubinemia, one from hepatocellular damage and one from obstruction; and one with malaria-induced cholestasis.
The document emphasizes different
Direct hyperbilirubinaemia in neonate by Dr. Tareq Rahmantareq rahman
This document discusses neonatal cholestasis, defined as prolonged conjugated hyperbilirubinemia in newborns. It reviews definitions, pathophysiology, prevalence, etiologies, evaluation, management, and prognosis. The most common causes are neonatal hepatitis, biliary atresia, and idiopathic neonatal hepatitis. Evaluation involves initial labs and imaging to determine if the cause is intrahepatic or extrahepatic. Specific treatments depend on the underlying condition, such as surgery for biliary atresia or liver transplantation for decompensated liver disease. Prognosis depends on factors like etiology, age at treatment, and progression to cirrhosis.
The document summarizes various liver conditions that can cause jaundice in pregnancy. It discusses physiological changes in the liver during pregnancy and various causes of jaundice related and unrelated to pregnancy. These include viral hepatitis, intrahepatic cholestasis of pregnancy (ICP), preeclampsia, HELLP syndrome, and acute fatty liver of pregnancy (AFLP). It provides details on pathogenesis, clinical presentation, management and prognosis for these conditions. Pregnancy-related liver disorders can affect both mother and fetus, so prompt diagnosis and treatment are important.
Liver disease in pregnancy can have severe maternal and fetal effects. Unique conditions include hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome, and acute fatty liver of pregnancy. Physiological changes occur in hepatic parameters during pregnancy. Conditions like viral hepatitis and cirrhosis may impact an existing pregnancy. Accurate diagnosis and management of liver conditions is important to optimize outcomes.
Dr Anil Arora address the liver diseases that are specific during pregnancy. The presentation contains case discussions on diagnosis, treatments & take home messages
Presented by:
Ahmad mukhtar
MD.,M.B.B.Ch., M.Sc Obstetrics and GynecologyConsultant and Lecturer of Obstetrics and Gynecology, Faculty of
MEDICINE, Zagazig University.
Acute Fatty Liver of Pregnancy (AFLP) is a rare but serious condition that affects 1 in 7,000-11,000 pregnancies. It is characterized by fatty infiltration and cellular dysfunction in the liver during late pregnancy or early postpartum. Prompt delivery is the recommended treatment as the condition does not typically improve until after delivery, and maternal and fetal mortality rates are high if not treated properly. Diagnosis is based on clinical presentation and lab tests in the absence of a definitive causative agent or diagnostic test. Close monitoring of future pregnancies is advised for women previously affected by AFLP.
Evaluation of proteinuria in children - by Dr.B.Sivakanthbsivakanth
1) Proteinuria, or excess protein in the urine, is a common finding in children that requires evaluation to determine the cause. Transient or orthostatic proteinuria are generally benign, while persistent proteinuria may indicate kidney disease.
2) Evaluation of a child with proteinuria includes a history, physical exam, urinalysis, and tests to assess kidney function. Distinguishing transient, orthostatic, and persistent proteinuria guides further testing and management.
3) For persistent proteinuria, additional tests are needed to identify potential causes like glomerular disease, tubular disorders, or infection and determine if nephrology referral is required. Ongoing monitoring is important to classify the
This document discusses liver disease in pregnancy. It begins by noting that liver disorders can take a more serious course during pregnancy and may have severe effects on the mother and fetus. It then reviews normal physiological changes in liver parameters during pregnancy. The document goes on to classify different types of liver diseases that can occur during pregnancy, including those unique to pregnancy and those that coincide or preexist. It presents two case reports, one involving acute fatty liver of pregnancy and another involving intrahepatic cholestasis of pregnancy. It concludes by discussing various viral hepatitises, fulminant hepatitis, and other chronic liver conditions that may occur during pregnancy.
The document discusses liver disease in pregnancy. It notes physiological changes in pregnancy that can affect the liver such as increased alkaline phosphatase levels. It describes different types of liver diseases that can occur including those induced by pregnancy like hyperemesis gravidarum or coinciding with pregnancy like viral hepatitis. It provides details on obstetric cholestasis including its causes, clinical features, investigations, management, and maternal and perinatal prognosis. Management of obstetric cholestasis includes monitoring liver function tests, inducing labor at 38 weeks, fetal surveillance during labor, administering vitamin K, and using ursodeoxycholic acid or cholestyramine to relieve symptoms and normalize liver tests.
1) A 36-year-old pregnant woman presents with jaundice, nausea, vomiting and abdominal pain. Laboratory tests show elevated bilirubin and mildly decreased platelets.
2) The diagnosis is acute fatty liver of pregnancy (AFLP), a rare but serious condition where toxic fatty acid metabolites build up in the liver. AFLP occurs in the third trimester and is associated with obesity, multiple pregnancies, and male fetuses.
3) AFLP and HELLP syndrome share some similarities but AFLP typically causes more severe liver dysfunction. Treatment involves urgent delivery of the baby combined with intensive maternal care including glucose supplementation, antibiotics, and reversal of coagulopathy. Complications can be life
This document discusses investigations for jaundice, including liver function tests (LFTs), CT scan, MRI scan, ERCP, and EUS. It provides detailed information on various LFTs such as aminotransferases, alkaline phosphatase, bilirubin, and GGT. It describes characteristic patterns seen in different liver diseases and notes that additional tests may include hepatitis markers, iron studies, tumor markers, and endoscopic ultrasound. Reference sources include medical textbooks and Wikipedia.
A 7 month old female infant presented with persistent jaundice since 2 weeks of life, high colored urine, and normal colored stools. On examination, she had deep icterus, hepatomegaly, and failure to thrive. Initial tests showed conjugated hyperbilirubinemia. Further workup included normal thyroid function, urine tests, TORCH titers, and alpha-1 antitrypsin level. Liver function tests showed elevated enzymes. Imaging showed hepatomegaly. Differentials included genetic and infectious causes of neonatal cholestasis.
This document summarizes the approach to a child presenting with splenohepatomegaly and developmental delay. Initial testing suggested Gaucher disease but further evaluation found no GBA gene mutation. Bone marrow showed foam cells. The child later developed neurological symptoms. Genetic testing found a pathogenic NP-C mutation, confirming the diagnosis as Niemann-Pick type C, a rare lysosomal storage disorder. Differential diagnoses discussed included Saposin-C deficiency and prosaposin deficiency based on initial findings.
Una persona ofrece sus datos de contacto que incluyen una dirección, un número de celular y una ubicación, posiblemente para vender cupcakes. El mensaje concluye diciendo que aunque no se puede comprar la felicidad directamente, un cupcake puede acercarse.
January 2014 - New products from General MillsGeneralMillsPR
General Mills is launching more than 50 new items from the company’s U.S. Retail business with dozens more rolling out in international markets during the second-half of the company’s fiscal 2014, which ends in May.
This document provides information on neonatal hypoglycemia including its definition, mechanisms, risk factors, screening, management, and differential diagnosis. Some key points include:
- Neonatal hypoglycemia is defined as a blood glucose level less than 45 mg/dL.
- Common risk factors include prematurity, low birth weight, and infants of diabetic mothers.
- At risk infants should be screened every 2-6 hours initially. Symptomatic infants are screened more frequently.
- Treatment for asymptomatic hypoglycemia involves feeding while symptomatic cases receive IV dextrose.
- Resistant hypoglycemia may be caused by conditions like hyperinsulinism and adrenal insufficiency and requires additional testing and medications like hydro
Critical Care Summit Egypt 2015 Common Arrhythmias in the ICUDr.Mahmoud Abbas
Lecture presented by Dr Khaled Farouk at Egyptian Critical Care Summit 2015, the leading ICU event and medical exhibition in Egypt. www.criticalcareegypt.com
Hemophagocytic Lymphohistiocytosis (HLH) is an aggressive and life threatening syndrome which results from excessive immune activation, that can rapidly deteriorate and lead to multiple organ failure and death.
ACUTE LIVER FAILURE - APPROACH AND MANAGEMENTNishant Yadav
Acute liver failure is a clinical syndrome resulting from massive necrosis or impairment of hepatocytes, leaving insufficient liver function. It impairs synthetic, excretory, and detoxifying liver functions. Pediatric acute liver failure is defined by evidence of liver dysfunction within 8 weeks, uncorrectable coagulopathy, and no evidence of chronic liver disease. Causes include viral infections, drugs, and metabolic disorders. Management involves transport to a specialized center, intensive care, supportive care, measures for raised intracranial pressure, coagulopathy, sepsis, and potential liver transplantation.
Protocol based approach to metabolic liver disease seema alamSanjeev Kumar
This document outlines a protocol-based approach to identifying metabolic liver disease (MLD) as the cause of unexplained liver conditions in children. Key points include:
- MLD accounts for a significant percentage of pediatric liver disease cases that were previously classified as cryptogenic or of unknown etiology.
- The most common presentation of MLD is organomegaly.
- Following a series of diagnostic protocols tailored to different clinical presentations can help detect many treatable or palliative MLD cases that may otherwise go undiagnosed.
- Applying these protocols at a large pediatric liver disease center in India reduced the percentage of cases classified as cryptogenic or indeterminate from over 25% to under
A 3 month old child presented with neonatal hepatitis and ascites. Initial tests showed liver damage and worsening liver function. Further testing found very high levels of sialic acid in the urine, suggesting Salla disease. Salla disease is a rare lysosomal storage disorder caused by a defect in sialic acid metabolism, characterized by ascites and liver involvement. The child was treated supportively but died from complications within two weeks.
The document defines acute liver failure in children and discusses its causes, presentation, management, and complications. Acute liver failure is characterized by liver dysfunction within 8 weeks without preexisting liver disease and includes coagulopathy and hepatic encephalopathy. Common causes include viral hepatitis, acetaminophen toxicity, and idiosyncratic drug reactions. Management involves supportive care to maintain organ function, treatment of specific causes, and potentially liver transplantation for severe cases.
New Born Screening Notes 072109 Dr Galidovarun10anshu
1. The document discusses newborn screening, which primarily detects inborn errors of metabolism and genetic disorders that can be treated if detected early.
2. The mandatory newborn screening tests in the Philippines screen for 5 conditions: congenital adrenal hyperplasia, congenital hypothyroidism, phenylketonuria, galactosemia, and G6PD deficiency.
3. Each condition is described in 1-2 sentences, including what it is, how it is tested for in newborns, and its potential consequences if untreated. The document provides brief but comprehensive overviews of the key genetic disorders included in newborn screening.
Congenital hypothyroidism is caused by insufficient thyroid hormone secretion and occurs in approximately 1 in 4000 births. It is most commonly due to thyroid dysgenesis resulting in thyroid gland abnormalities. Clinical features are non-specific in early life but can include prolonged jaundice, constipation, hypotonia, and developmental delay. It is diagnosed through newborn screening and treated with levothyroxine replacement therapy. Without treatment, it can lead to cretinism.
1. Neonatal cholestasis is defined as conjugated hyperbilirubinemia in a newborn. It can be caused by intrahepatic or extrahepatic conditions.
2. Common etiologies include biliary atresia, metabolic diseases like galactosemia, and infections. Biliary atresia is the most common cause of extrahepatic cholestasis.
3. Evaluation involves history, physical exam, lab tests including liver function tests and imaging, and may require liver biopsy. Treatment depends on the underlying cause but may include surgical intervention or lifestyle changes.
Acute fatty liver of pregnancy is a rare but potentially lethal condition that affects 1 in 7,000 to 20,000 pregnancies. It commonly presents after 30 weeks of pregnancy with nausea, vomiting, abdominal pain and jaundice. Liver function tests show elevated enzymes and hypoglycemia is present in 70% of cases. Prompt delivery improves outcomes for both mother and baby, with supportive care including treatment of coagulopathy and hypoglycemia before delivery. Recurrence is possible in subsequent pregnancies if the mother has an underlying fatty acid oxidation disorder.
A 41-year-old female was hospitalized in the oncology clinic with a history of spontaneous fractures over the past four years and recent poor appetite, nausea, and vomiting. Her lab results showed elevated calcium, low phosphorus, and elevated alkaline phosphatase. This suggests either primary hyperparathyroidism or hypercalcemia of malignancy as the most important diagnosis, with PTH testing needed to confirm.
This document defines and describes Fulminant Hepatic Failure (FHF), also known as Acute Liver Failure (ALF). It provides definitions for different types of liver failure based on duration and presence of pre-existing liver disease. The document discusses the etiology, pathogenesis, clinical manifestations and stages of hepatic encephalopathy in FHF. It outlines the diagnostic workup and management approach for FHF, including initial stabilization, monitoring for complications, supportive care to maximize survival, and consideration of liver transplantation.
This document discusses congenital adrenal hyperplasia (CAH), which results from a genetic defect in adrenal steroid biosynthesis. It causes decreased cortisol production and increased production of other hormones. The most common type is 21-hydroxylase deficiency, which can present as salt-wasting or simple virilizing CAH. Diagnosis is made through newborn screening, physical exam, and lab tests. Treatment involves hydrocortisone and fludrocortisone supplementation as well as stress dosing during illness to prevent adrenal crisis. Outcomes have improved with newborn screening and lifelong medical management.
This document presents a case of a 4-year-old boy with 1 month of intermittent high fever and pallor who was found to have severe anemia, jaundice, hepatosplenomegaly, and bone marrow findings consistent with hemophagocytic lymphohistiocytosis (HLH). HLH is a life-threatening syndrome characterized by uncontrolled activation of macrophages and T-cells leading to hyperinflammation. It can be primary/familial or secondary to infections, malignancies, or autoimmune conditions. The case report reviews the diagnostic criteria, associated infections, clinical manifestations, bone marrow findings, treatment including chemotherapy and stem cell transplant, and prognosis of HLH.
This document discusses neonatal jaundice and hyperbilirubinemia. It begins by defining jaundice and hyperbilirubinemia. It then describes the metabolism of bilirubin, including transport to the liver, hepatic uptake, conjugation in the liver, and excretion in bile and stool. Causes of increased bilirubin production are discussed, including increased red blood cell production or breakdown. The document also discusses approaches to evaluating and managing neonatal jaundice and hyperbilirubinemia, including assessing risk factors, monitoring bilirubin levels, and guidelines for initiating phototherapy.
This document describes a case of omphalitis, an infection of the umbilical stump, in a 7-day-old male infant. The infant presented with fever, yellowish umbilical discharge, and hypoactivity. Laboratory tests showed elevated white blood cell count and C-reactive protein. The infant was diagnosed with omphalitis and sepsis and started on intravenous antibiotics and supportive care. Omphalitis is a potentially serious infection in neonates that requires prompt treatment with antibiotics and sometimes surgery.
1. Nephrotic syndrome is characterized by massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia. The majority of cases in children are idiopathic or minimal change disease.
2. Secondary causes include systemic diseases, infections, medications, and genetic conditions.
3. Treatment involves corticosteroids as first line, with recurrence being common in minimal change disease. Kidney biopsy may be needed to identify secondary causes or steroid resistance.
This document discusses a case of neonatal liver failure that was ultimately diagnosed as neonatal hemochromatosis. It provides background on neonatal liver failure and outlines the diagnostic challenges. It describes the patient's presentation and initial workup. Additional testing revealed elevated ferritin and iron saturation levels suggestive of hemochromatosis, though initial MRI and liver biopsy were negative. Confirmation came from a salivary gland biopsy showing iron deposits. The discussion reviews genetic and metabolic causes of neonatal liver failure and highlights the difficulty in diagnosis given tests may not be fully sensitive or specific.
Similar to MLD presenting with ALF Talk by Dr SK Yachha (20)
1. An 8-year-old male presented with resistant rickets and bony deformities. Initial workup found hypocalcemia, hypophosphatemia, elevated alkaline phosphatase, and normal parathyroid hormone.
2. Further testing revealed proximal renal tubular acidosis, hypokalemia, and firm hepatomegaly. Wilson's disease was suspected and confirmed with elevated urinary copper levels.
3. The patient was diagnosed with Wilson's disease presenting as resistant rickets and proximal renal tubular acidosis. He was started on chelating agents and potassium citrate to treat the Wilson's disease and renal tubular acidosis respectively.
Wilson Disease - Beyond the liver and brain…- Dr Ujjal PoddarSanjeev Kumar
This document discusses the non-hepatic and non-neurological manifestations of Wilson's disease. It summarizes several studies that found the majority of Wilson's disease patients presented with hepatic or neurological symptoms, while a minority exhibited other manifestations. These included bone, joint, eye, heart, blood, kidney, skin and endocrine issues. Specifically, it notes that bone and joint pain can be early presenting symptoms and unexplained hemolysis in young adults should raise suspicion for Wilson's disease screening. The document concludes that while uncommon, recognition of non-hepatic manifestations is important for fully characterizing and managing Wilson's disease.
This document discusses the role of liver biopsy in determining the stage and cause of liver disease. A liver biopsy can reveal the stage of disease, whether it is caused by autoimmune, metabolic, or viral factors. Early stage disease may show minor changes like mild steatosis, while later stages show features like portal inflammation, interface hepatitis, steatosis, glycogenated nuclei, Mallory bodies, and copper accumulation. Copper stains on biopsy tissue can help determine if Wilson's disease is present, shown by red-orange or black-brown copper deposits. The document also describes several case examples where liver biopsy aided in diagnosis, such as diagnosing Wilson's disease in an 8-year old male based on cirrhosis and
Key publications on wilson disease in last 3 yearsSanjeev Kumar
This document summarizes key publications on Wilson disease from the last 3 years. It discusses clinical profiles of Wilson disease patients, patient and graft survival rates post-liver transplantation, issues with immunosuppressive regimens post-transplant, and experimental adenoviral gene therapy providing long-term correction of copper metabolism in a mouse model of Wilson disease. It also presents studies finding that increased levels of non-ceruloplasmin bound and exchangeable copper are associated with oxidative stress and neurological worsening in Wilson disease patients.
This document summarizes a case discussion of a 10-year-old female patient presenting with acute liver failure and hemolysis who was potentially in need of a liver transplant. The patient had symptoms for 4 weeks and was initially evaluated at a nearby hospital before being referred for further evaluation. On examination, she had pallor, icterus, periorbital puffiness, distended abdomen, and enlarged liver and spleen. Investigations showed abnormal liver function tests and signs of hemolysis. Based on further testing, she was diagnosed with Wilson's disease. Due to developing grade 2 encephalopathy, she underwent living-related liver transplantation with her mother as the donor. She recovered well after the transplant.
When does one use zinc alone - Dr Vinay GoyalSanjeev Kumar
This document discusses the use of zinc alone in treating Wilson's disease. Zinc is the preferred initial treatment as it is nontoxic and prevents copper absorption in the intestine. It works by inducing intestinal metallothionein and blocking copper absorption and resorption from the gastrointestinal tract. Zinc can be used long-term for maintenance therapy in Wilson's disease patients, including during pregnancy where it has been shown to be safe. The document also discusses combinations of zinc and penicillamine, noting some studies have found higher mortality with this combination compared to other therapies.
The panel discussion focused on developmental, speech, psychiatric and counseling issues related to Wilson's disease. The panelists were experts in neurology, speech pathology, psychiatry and counseling. Key topics discussed included:
- Common neurological and psychiatric manifestations of Wilson's disease including movement disorders, dysarthria, and behavioral/mood changes.
- The importance of considering Wilson's disease in young patients presenting with recent neuropsychiatric symptoms that are treatment resistant.
- Challenges in diagnosing and managing dominant psychiatric presentations of Wilson's disease.
- The role of various specialists like speech therapists and counselors in addressing issues related to speech, behavior, rehabilitation and quality of life in patients with Wilson's
Hepatic and Neuro Wilson disease - Is there a difference? - Dr John MatthaiSanjeev Kumar
This document discusses the differences between hepatic and neurological involvement in Wilson disease. It notes that the pathophysiology of how copper overload leads to liver vs. brain disease is not fully understood. The document then lists several clinical observations that may provide clues about the pathophysiology: 1) Not all copper overload syndromes affect both the liver and brain. 2) Neurological disease can sometimes occur without liver involvement in Wilson disease patients. 3) Copper chelating treatments can improve both liver and neurological symptoms.
Diagnostic challenges in Wilson disease: do scoring systems help? - Dr Harsha...Sanjeev Kumar
This document discusses diagnostic challenges in Wilson disease and whether scoring systems help. It summarizes that experts view hepatic and neuropsychiatric Wilson disease differently. It then discusses several prognostic scoring systems used for acute liver failure, including Child-Pugh, MELD, and Nazer scores. Data is presented on etiologies of acute liver failure from studies in India. Scoring systems for Wilson disease are also discussed, noting they have variable sensitivity and many patients who died could not undergo testing. The take home message is that appropriate combinations of symptoms, signs, and screening tests are usually adequate for diagnosis, and the main challenge is considering Wilson disease initially.
Panel Discussion - Genetics - Is there a role in clinical practice? - Dr Seem...Sanjeev Kumar
Genetic testing plays an important role in the diagnosis and management of Wilson disease (WD), though it cannot replace standard biochemical tests. In the presented cases:
1) Genetic testing confirmed diagnosis in a child with classic WD, and showed that a negative result did not rule out WD given genetic heterogeneity.
2) It was useful for family screening and managing a fulminant case.
3) It was the preferred method for screening asymptomatic siblings.
4) While it did not replace liver biopsy, it provided additional information in inconclusive cases.
5) Treatment should not be based on genetic results alone without biochemical abnormalities.
Genetic counseling was recommended for families planning pregnancy due
Choice and Monitoring of drug therapy - Dr Ashish BavdekarSanjeev Kumar
Wilson's disease is treated with chelating agents like penicillamine or trientine to reduce copper levels over 6-12 months. Zinc is used long-term to maintain a negative copper balance. Patients require lifelong monitoring clinically and through liver enzymes and urinary/serum copper levels to determine treatment effectiveness, compliance, and adverse effects. Biochemical improvement can take variable times from months to years.
Copper in health and disease - Dr Srinivas SankaranarayananSanjeev Kumar
Copper is an essential trace element that plays an important role in many biological processes as a co-factor in enzymes. Both copper deficiency and toxicity can cause disease. Copper homeostasis is tightly regulated in the body by transport proteins like ATP7A and ATP7B, as free copper above certain levels can be toxic. Genetic mutations in ATP7B can cause Wilson's disease, characterized by copper accumulation in tissues. While Indian Childhood Cirrhosis was once thought to be caused by excess copper intake, it has disappeared as copper utensils were replaced, suggesting other etiologies. There is increasing evidence for the role of copper in neurodegenerative diseases like Alzheimer's through oxidative stress mechanisms.
Why did d-penicillamine disappear from the market?Sanjeev Kumar
This document summarizes a talk on the shortage of the drug penicillamine in India. It discusses that penicillamine disappeared from the market in mid-2016 due to lack of raw material supply from China. The official reason was that the raw material supplier was unavailable, but the actual reasons may have been that the drug came under price control and suppliers did not want to provide raw materials at a competitive price. It also discusses the roles of the Central Drugs Standard Control Organization and National Pharmaceutical Pricing Authority in regulating drug prices and availability in India. The real issue highlighted is India's increasing dependence on China for drug ingredients and the need to support domestic bulk drug manufacturing.
Role of MRI in Wilson disease - Dr Sanjib SinhaSanjeev Kumar
Wilson's disease is a rare genetic disorder that causes copper to accumulate in the brain and other vital organs. MRI plays an important role in evaluating patients with suspected Wilson's disease. Key findings on MRI include signal changes in the basal ganglia, midbrain, pons, and cerebral white matter. Characteristic signs include T1 hyperintensity of the globus pallidus, the "face of the giant panda" sign, and CPM-like changes resembling osmotic demyelination. Serial MRI can show improvement in many patients responding to treatment, while extensive changes correlate with poorer prognosis. Advanced techniques like DTI reveal more widespread white matter abnormalities than conventional MRI and help assess disease severity.
Complications of drug therapy - Dr Malathi SathiyasekaranSanjeev Kumar
1) The document discusses various drug therapies for Wilson disease including penicillamine, zinc, trientine, and tetrathiomolybdate.
2) Penicillamine has severe side effects in 30% of patients including kidney toxicity, lupus-like syndrome, and bone marrow suppression. Its complications can be both direct chemical toxicity or immune-mediated.
3) Zinc has very few side effects but can cause gastric irritation. It is less likely than other drugs to cause neurological deterioration.
How do we monitor neurological improvement - Dr Rukmini MridulaSanjeev Kumar
This document discusses monitoring neurological improvement in patients with Wilson's disease undergoing treatment. It outlines several scales that can be used to stage and monitor patients, including the Chu staging scale and the Global Assessment Scale for Wilson's Disease. When monitoring therapy, clinicians should watch for worsening of symptoms and slowly titrate medications to avoid deterioration. Investigations like urinary copper levels and serum markers can provide information on treatment compliance and effectiveness, while repeat neuroimaging and clinical exams over time assess neurological recovery. Persisting tremors may require additional interventions like thalamotomy.
Wilsons disease and hepatitis dr. abhamoni baroSanjeev Kumar
Case: Prolonged acute hepatitis – is there more to it?
Presenter: Abhamoni Baro
Moderator: Ashish Bavdekar
Panelists: Prakash Vaidya, Harshad Devarbhavi, Seema Alam
Child with acute liver failure dr. kirtichandra kodaliSanjeev Kumar
A 3-year-old boy presented with fever, cough, loose stools and increasing drowsiness over the past few days. On examination, he showed signs of dehydration and liver enlargement. Laboratory tests found elevated liver enzymes and ammonia levels, indicating acute liver failure. The cause was determined to be paracetamol toxicity from an accidental overdose, as serum paracetamol levels were found to be toxic. The patient was treated with N-acetyl cysteine and supportive care, and his condition improved such that his liver function normalized and he was discharged.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
Summer is a time for fun in the sun, but the heat and humidity can also wreak havoc on your skin. From itchy rashes to unwanted pigmentation, several skin conditions become more prevalent during these warmer months.
Lecture 6 -- Memory 2015.pptlearning occurs when a stimulus (unconditioned st...AyushGadhvi1
learning occurs when a stimulus (unconditioned stimulus) eliciting a response (unconditioned response) • is paired with another stimulus (conditioned stimulus)
Co-Chairs, Val J. Lowe, MD, and Cyrus A. Raji, MD, PhD, prepared useful Practice Aids pertaining to Alzheimer’s disease for this CME/AAPA activity titled “Alzheimer’s Disease Case Conference: Gearing Up for the Expanding Role of Neuroradiology in Diagnosis and Treatment.” For the full presentation, downloadable Practice Aids, and complete CME/AAPA information, and to apply for credit, please visit us at https://bit.ly/3PvVY25. CME/AAPA credit will be available until June 28, 2025.
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Breast cancer: Post menopausal endocrine therapyDr. Sumit KUMAR
Breast cancer in postmenopausal women with hormone receptor-positive (HR+) status is a common and complex condition that necessitates a multifaceted approach to management. HR+ breast cancer means that the cancer cells grow in response to hormones such as estrogen and progesterone. This subtype is prevalent among postmenopausal women and typically exhibits a more indolent course compared to other forms of breast cancer, which allows for a variety of treatment options.
Diagnosis and Staging
The diagnosis of HR+ breast cancer begins with clinical evaluation, imaging, and biopsy. Imaging modalities such as mammography, ultrasound, and MRI help in assessing the extent of the disease. Histopathological examination and immunohistochemical staining of the biopsy sample confirm the diagnosis and hormone receptor status by identifying the presence of estrogen receptors (ER) and progesterone receptors (PR) on the tumor cells.
Staging involves determining the size of the tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). The American Joint Committee on Cancer (AJCC) staging system is commonly used. Accurate staging is critical as it guides treatment decisions.
Treatment Options
Endocrine Therapy
Endocrine therapy is the cornerstone of treatment for HR+ breast cancer in postmenopausal women. The primary goal is to reduce the levels of estrogen or block its effects on cancer cells. Commonly used agents include:
Selective Estrogen Receptor Modulators (SERMs): Tamoxifen is a SERM that binds to estrogen receptors, blocking estrogen from stimulating breast cancer cells. It is effective but may have side effects such as increased risk of endometrial cancer and thromboembolic events.
Aromatase Inhibitors (AIs): These drugs, including anastrozole, letrozole, and exemestane, lower estrogen levels by inhibiting the aromatase enzyme, which converts androgens to estrogen in peripheral tissues. AIs are generally preferred in postmenopausal women due to their efficacy and safety profile compared to tamoxifen.
Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant is a SERD that degrades estrogen receptors and is used in cases where resistance to other endocrine therapies develops.
Combination Therapies
Combining endocrine therapy with other treatments enhances efficacy. Examples include:
Endocrine Therapy with CDK4/6 Inhibitors: Palbociclib, ribociclib, and abemaciclib are CDK4/6 inhibitors that, when combined with endocrine therapy, significantly improve progression-free survival in advanced HR+ breast cancer.
Endocrine Therapy with mTOR Inhibitors: Everolimus, an mTOR inhibitor, can be added to endocrine therapy for patients who have developed resistance to aromatase inhibitors.
Chemotherapy
Chemotherapy is generally reserved for patients with high-risk features, such as large tumor size, high-grade histology, or extensive lymph node involvement. Regimens often include anthracyclines and taxanes.
Kosmoderma Academy, a leading institution in the field of dermatology and aesthetics, offers comprehensive courses in cosmetology and trichology. Our specialized courses on PRP (Hair), DR+Growth Factor, GFC, and Qr678 are designed to equip practitioners with advanced skills and knowledge to excel in hair restoration and growth treatments.
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdfrightmanforbloodline
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
1. Surender K Yachha
Professor and Head
Department of Pediatric Gastroenterology
Sanjay Gandhi Postgraduate Institute
of Medical sciences, Lucknow, India
2. Definition
Acute liver failure
Encephalopathy
within 8 weeks of
Jaundice*
Trey C, Davidson CS. Bucuvalas J et al
Prog liver Ds,1970;3:282-98 Clin Liver Dis. 2006 ;10:149-68
3.
4. Metabolic etiology of ALF (N= 36, 10%)
Etiology < 3 years of age (n=23) > 3 years of age (n=13)
Respiratory chain defect 7 0
FAOD 4 13 0
Mitochondrial cytopathy 2 2
Tyrosenemia 4 6 0
Galactosemia 2 0
A-1 AT deficiency 1 0
Fructose-intolerance 1 0
Niemann-Pick type C 1 0
Urea cycle defect 1 1
Reyes Syndrome 0 1
Wilson’s disease 0 9
5. Metabolic causes of ALF in neonates
N= 31(%) Year 2008
Neonatal: Causes PALFSG data set
Neonatal Hemochromatosis 15 (71%)
Metabolic:
Galactosemia 4 (13)
Tyrosinemia
Mitochondrial cytopathy
Dhawan A. Liver Transplantation 2008; 14: S80- S84
6. Causes of ALF in 80 infants
Causes of ALF (n = 80) Total number (%)
Metabolic disorders 34 (42.5%)
Type I tyrosinemia 12
Mitochondrial cytopathy 17
Urea cycle disorder
Ornithine carbamyl-transferase deficiency (1) 2
Argininosuccinic aciduria (1)
Galactosemia 2
Hereditary fructose intolerance 1
Neonatal hemochromatosis 13 (16.2%)
7. Clues to etiology by evaluating
clinical features
Maternal history as clue’s to etiology: Mother an important link
Sib death especially with jaundice NH, tyrosinemia, galactosemia,
mitochondrial cytopathy, HLH,
Niemann- Pick
Placental edema, intrauterine hydrops NH, Mitochondrial & HLH
Clues as per timing of presentation
At birth or soon after
NH, mitochondrial hepatopathy, tyrosinemia, galactosemia.
8. Clues to etiology by evaluating
clinical features
Clues to etiology by examining the baby
• IUGR: NH, mitochondrial cytopathy
• Cataract: Galactosemia
• Abnormal odor: tyrosinemia , Fatty acid oxidation defects
• Skin rash: HLH, Fatty acid oxidation defects
• Large spleen: HLH, Leukemia, Niemann-Pick
• Seizure: HSV, HLH, secondary sepsis
9. Stages of encephalopathy
Stage Clinical Reflexes Neurological sign
Inconsolable crying, Normal or
I inattention to task; child is hyper-reflexic
not acting like self to Difficult or
parents impossible to test
II same as in stage I same as in adequately
stage I
Somnolence, stupor, Hyper-reflexic
III combativenes
Comatose, arouses with Decerebrate or
IV painful stimuli (4a) or Absent decorticate
no response (4b)
10. Neonatal Hemochromatosis (NH)
• Onset of organ damage in utero
• Abnormal iron deposition in liver,
pancreas, heart, CNS and salivary glands
• End stage liver disease present by birth
• Possible pathogenesis gestational alloimmune.
Clinical features:
• Maternal : Still births, previous sib deaths; antenatal period : IUGR,
oligohydramnios, placental edema; small for date baby.
• Presents usually few hours to sometimes weeks after birth
• Hypoglycemia, coagulopathy, jaundice, anemia, ascites, anasarca,
splenomegaly with shrunken liver.
11. Neonatal Hemochromatosis (NH)
Investigations: Low to normal transaminases, hypoalbuminemia,
hypofibrinogenemia, thrombocytopenia.
Diagnosis:
High serum ferritin median 2448 (415 -100,000) μg/L for screening,
Low serum transferrin, high transferrin saturation (95 % to 100 %
up to 157 % vs. normal newborn 80%)
Lip biopsy: salivary gland biopsy showing iron deposition on staining
(best for Indian situations) OR
MRI pancreas with low signal intensity on T2 imaging confirms the
diagnosis.
12. Type 1 Tyrosinemia
Inborn error of tyrosine metabolism, inheritance: autosomal recessive;
involves liver, kidneys and peripheral nerves.
Presents as acute hepatic crisis or chronic liver disease. 60 % present
as ALF in first 2 years of life including neonatal period.
Presentation:
Cogaulopathy, mildly raised transaminases and no jaundice in the
neonate
Neonatal cholestasis with liver failure
“Boiled cabbage” or “rotten mushroom” odour
Hypoglycemia, coagulopathy, hepatomegaly, ascites
Rapid decompensation with death unless promptly treated
13. Type 1 Tyrosinemia
Diagnosis
Screening: high alpha-fetoprotein:
mean level: 160,000 µg/mL
vs.
normal full-term baby 84,000 µg/ml
Confirmation: Increased urinary succinylacetone
29. IVIG during pregnancy in NH
Regimen widely practiced at present
Reduction in NH: at-risk pregnancies
administration of intravenous immunoglobulin
at 1 g/kg of body weight weekly from week 18
until the end of gestation
32. Algorithm of management of
infants and younger children with
ALF
Suspect ALF
• Jaundice (conjugated)
• Coagulopathy (even isolated) as per PALFSG definition
• Hepatomegaly and/or splenomegaly
• Ascites
34. Algorithm of management
Start treatment
• Stop oral feeds
• Broad spectrum antibiotics
• Fluconazole iv
• Consider iv acyclovir for suspected Herpes simplex.
Best is to start till investigations are available as the
condition is potentially treatable and common.
•Treat fast if suspicion of neonatal hemochromatosis is high.
• Albumin infusion if serum levels low
• Avoid fluid overload
• Correction for losses: warmer/ventilator
• Euglycemia, Na, K, Ca, Mg, phosphate
• Coagulopathy: Fresh frozen plasma,
exchange transfusion if necessary
36. Wilson disease (ALF)
Difficulty in diagnosis
Usual diagnostic criteria…
Diagnostic difficulty in WD: ALF
S Ceruloplasmin: Acute phase reactant … falsely normal
45% renal failure: Urinary Cu cannot be assessed (less)
S Cu and urinary Cu not readily available, time consuming
Liver biopsy cannot be done: transjugular may be possible
KF ring: absent in 50 % of WD patients with ALF and
not a bedside test
37. Wilson Disease presenting as ALF
When to suspect?
Modest elevations of transaminases (<2000 IU/L)
Normal or subnormal alkaline phosphatase (<40 IU/L)
Coomb’s negative hemolytic anemia
Renal failure (45%)
AASLD Guidelines. Hepatology 2008
38. How to Diagnose?
Test Value Sensitivity Specificity
ALP/ Bilirubin <4 94% 96%
AST/ ALT > 2.2 94% 86%
Combined: above two 100% 100%
Serum Cu > 200 mcg/dL 75% 96%
S Ceruloplasmin < 20 mg/dL 21% 84%
Hemoglobin < 10g/dL 94% 74%
Korman et al. Hepat 2008
39. Caveats
• Parameters: Adult studies
• Children ALP/ Bilirubin ratio <1
Sensitivity 86%, Specificity 50%
Tiesseres. Ped Crit Med 2005
40. Treatment options
Medical management
D- Pencillamine/ Trientine (20mg/kg/d)
41. OLT in whom?
New Wilson Index
Score ≥11/20: Transplant Sensitivity: 93%
Score <11/20: Medical Mx Specificity: 98%
Dhawan et al. Liv transpl 2005
Fischer. 6 WD Score >11 in 3 cases
JPGN 2011 All alive 2 survived without OLT. 1 OLT
Score 10: 1 patients received OLT.
42. Outcome in WD with ALF
Case series No of cases Outcome
Emre. 11 FHF All transplanted
Tranpl 2001 9 had I/V 1 year patient survival rate: 87.5%
hemolysis
Elsenbch OLT 3 survived
WJG 2007 7 FHF No OLT: 4 survived (3: D- Pen, 1:Trientine)
Korman. OLT 13 survived
Hepat 2008 16 FHF Without OLT 3 died
43. WD: ALF with IV Hemolysis
Case series Cases with Coomb’s Percentage
negative hemolytic anemia
Emre.Tranpl 2001 9/11 transplanted cases 81.8%
Wang L. Ped Neonat 2010 2/11 18%
Chapoy P. Sem Hop 1979 1/6 16.6%
44. LDH : 2723
10yr boy Plasma Hb: high
IV Hemolysis PS: hemolysis
HAV-
Hb:11 Hb:12 HEV-
HBV-
PRBC G6PD normal
Hb:6
Grade II DCT/ICT -
INR:5
INR: 3
INR: 1.8
No SGPGI
Prodrome TB/DB: 3.2/1.5
Jaundice 10days AST/ALT:58/44
Cola col. urine ALP: 266
D- Pen
Pallor
May 2011 June 2011 Aug 2011
45. International scenario of
Reyes syndrome
No. of Period Age Association
cases
USA 172 1986-99 6-7yr
(Belay et al,1999) 93% antecedent
UK 2600 1977-99 10-15 mo viral illness
(Newton and Hall)
Australia 8 1993-2001 1yr-19yr
(Halpin 2003) 5-100%: aspirin
Peak in 1970-80
Decrease in 30 yrs
1970-80 2010