Genotype correlates with clinical course and outcome of children with tight junction protein 2 (TJP2) deficiency-related cholestasis.

BACKGROUND AND AIMS: The study aimed to describe the clinical course and outcomes, and analyze the genotype-phenotype correlation in patients with tight junction protein 2 (TJP2) deficiency. APPROACH AND RESULTS: Data from all children with chronic cholestasis and either homozygous or compound heterozygous mutations in TJP2 were extracted and analyzed. The patients were categorized into 3 genotypes: TJP2-A (missense mutations on both alleles), TJP2-B (missense mutation on one allele and a predicted protein-truncating mutation [PPTM] on the other), and TJP2-C (PPTMs on both alleles). A total of 278 cases of genetic intrahepatic cholestasis were studied, with TJP2 deficiency accounting for 44 cases (15.8%). Of these, 29 were homozygous and 15 were compound heterozygous variants of TJP2 . TJP2-A genotype was identified in 21 (47.7%), TJP2-B in 7 cases (15.9%), and TJP2-C in 16 cases (36.4%), respectively. Patients with the TJP2-C genotype were more likely to experience early infantile cholestasis (87.5% vs. 53.5%, p =0.033), less likely to clear jaundice (12.5% vs. 52.2%, p =0.037), more likely to develop ascites, and had higher serum bile acids. Patients with the TJP2-C genotype were more likely to die or require liver transplantation (native liver survival: 12.5% vs. 78.6%, p <0.001), with a median age at death/liver transplantation of 2.5 years. Cox regression analysis revealed that TJP2-C mutations ( p =0.003) and failure to resolve jaundice ( p =0.049) were independent predictors of poor outcomes. CONCLUSIONS: Patients with the TJP2-C genotype carrying PPTMs in both alleles had a rapidly progressive course, leading to early decompensation and death if they did not receive timely liver transplantation.

Therapeutic Enteral Formulas in Children.

PURPOSE: A variety of enteral formulas for various diseases have become available in India in the last few years. Awareness among pediatricians about the availability and indications for these therapeutic formulas is low. METHODS: A literature search was conducted in PUBMED and relevant data collected from all English language publications available. Data on the commercial preparations was sourced from the individual companies, the Diet 4 life initiative as well as FSSAI (Food safety and standards authority of India). CONCLUSIONS: Therapeutic enteral formulas, which are indicated in various disease states belong to four categories - lactose modified, hydrolyzed, MCT based and metabolic disease specific formulas. Lactose modified formulas which are used in temporary or permanent lactose intolerance and Galactosemia are either casein or soy protein based. Hydrolyzed formulas could be partially hydrolyzed, extensively hydrolyzed or amino acid based. Only extensively hydrolyzed formula should be recommended in milk protein allergy. Amino acid (elemental) formulas are mainly indicated in patients with diffuse intestinal mucosal disease. MCT formulas are used in chronic liver disease with cholestasis, and have 30 to 80% MCT. Formulas for inborn errors of metabolism are free of specific carbohydrate, amino acid or fatty acid. Proprietary formulas presently available in India with their specifications have been listed.

Severe liver dysfunction in an infant with cystic fibrosis masquerading as metabolic liver disease.

We present a rare presentation of cystic fibrosis with neonatal cholestasis. Histological features of mucoviscidosis were present in liver involving the biliary tract, intestinal mucosa, pancreas, and lung. Besides, there was a rare association with autosomal dominant type of polycystic renal disease.

Gastrointestinal Fistulization in Amebic Liver Abscess.

BACKGROUND: Liver abscess is a common deep seated abscess in children; amebic liver abscess is associated with more local complications. CASE CHARACTERISTICS: We report two preschool children presenting with short history of pain, fever and right upper quadrant pain. The abscess communicated with gastro-intestinal tract (ascending colon in case 1 and duodenum in case 2), and diagnosis of amebic liver abscess was confirmed by DNA PCR. OUTCOME: Both children were successfully managed with intravenous antibiotics and catheter drainage. MESSAGE: Gastrointestinal fistulization may be rarely seen in amebic liver abscess. Conservative management with antibiotics, catheter drainage and supportive care may suffice.

Ganga hospital open injury score in management of open injuries.

INTRODUCTION: Open injuries of the limbs offer challenges in management as there are still many grey zones in decision making regarding salvage, timing and type of reconstruction. As a result, there is still an unacceptable rate of secondary amputations which lead to tremendous waste of resources and psychological devastation of the patient and his family. Gustilo Anderson's classification was a major milestone in grading the severity of injury but however suffers from the disadvantages of imprecise definition, a poor interobserver correlation, inability to address the issue of salvage and inclusion of a wide spectrum of injuries in Type IIIb category. Numerous scores such as Mangled Extremity Severity Score, the Predictive Salvage Index, the Limb Salvage Index, Hannover Fracture Scale-97 etc have been proposed but all have the disadvantage of retrospective evaluation, inadequate sample sizes and poor sensitivity and specificity to amputation, especially in IIIb injuries. METHODS: The Ganga Hospital Open Injury Score (GHOIS) was proposed in 2004 and is designed to specifically address the outcome in IIIb injuries of the tibia without vascular deficit. It evaluates the severity of injury to the three components of the limb--the skin, the bone and the musculotendinous structures separately on a grade from 0 to 5. Seven comorbid factors which influence the treatment and the outcome are included in the score with two marks each. The application of the total score and the individual tissue scores in management of IIIB injuries is discussed. RESULTS: The total score was shown to predict salvage when the value was 14 or less; amputation when the score was 17 and more. A grey zone of 15 and 16 is provided where the decision making had to be made on a case to case basis. The additional value of GHOIS was its ability to guide the timing and type of reconstruction. A skin score of more than 3 always required a flap and hence it indicated the need for an orthoplastic approach from the index procedure. Bone score of 4 and 5 will require complex reconstruction procedures like bone transport, extensive bone grafting or free fibular graft. Regarding the timing of reconstruction, injuries with a score of 9 or less indicated a low violence trauma and were amenable for early soft tissue reconstruction whereas injuries with a score of 10 or more indicated high violence injuries where a staged reconstruction policy must be followed. CONCLUSIONS: Ganga Hospital Open Injury Score was found to be highly useful in decision making regarding salvage in IIIB injuries. The individual tissue scores were also useful to provide guidance regarding the timing and type of bone and soft tissue reconstruction.

Primary lung abscess in early infancy.

BACKGROUND: Lung abscess is rare in early infancy. CASE CHARACTERISTICS: We report two infants with lung abscess, who presented with short respiratory llness. INTERVENTION: Infants were managed with broad spectrum antibiotics including Clindamycin. Needle aspiration was attempted in one case. MESSAGE: High index of suspicion in infants with respiratory distress of prolonged duration can help in reaching the diagnosis.

Neglected patellar tendon ruptures: a simple modified reconstruction using hamstrings tendon graft.

PURPOSE: We hereby describe a cost effective and simple anatomical reconstruction without requirement for allograft or implants for neglected chronic patellar tendon injuries. This has been validated in seven patients with an average follow up of greater than three years resulting in good outcome. METHODS: Seven patients (six males, one female) of mean age 41.8 years (range up to 57 years) presented with neglected patellar tendon injury. The time since injury ranged between three months and three years (average nine months). Active extension was not possible in three patients, and four patients had an extensor lag between 40° and 80° (average 62.5°). Four patients had quadriceps strength of grade 2/5 and three patients had grade 3/5. All patients had severe functional limitation with an average IKDC score of 46.8 (range 39-57). They all underwent patellar tendon reconstruction using hamstrings tendon autograft. RESULTS: Postoperatively with a mean follow up of 40.7 months (range 31-52 months), all patients had a stable knee with mean flexion of 125° (range 120°-130°) and without any extension lag. Quadriceps power was regained in five cases to 5/5 and in two cases to 4/5. With an improvement in the IKDC score to 86.8 (range 80-92), excellent outcome was noted in five patients and good outcome in two patients. The average postoperative Lysholm score was 92.4 (range 89-95) and the average Kujala score was 94.5 (range 92-97). CONCLUSION: Patellar tendon reconstruction using hamstrings autograft for neglected patellar tendon injuries provides good stability and excellent outcome. Compared to previous techniques described, our technique is unique in being cost effective and a simple anatomical reconstruction without the requirement for allograft or implants.