Potential of ileal bile acid transporter inhibition as a therapeutic target in Alagille syndrome and progressive familial intrahepatic cholestasis

Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) are rare, inherited cholestatic liver disorders that manifest in infants and children and are associated with impaired bile flow (ie cholestasis), pruritus and potentially fatal liver disease. There are no effective or approved pharmacologic treatments for these diseases (standard medical treatments are supportive only), and new, noninvasive options would be valuable. Typically, bile acids undergo biliary secretion and intestinal reabsorption (ie enterohepatic circulation). However, in these diseases, disrupted secretion of bile acids leads to their accumulation in the liver, which is thought to underlie pruritus and liver‐damaging inflammation. One approach to reducing pathologic bile acid accumulation in the body is surgical biliary diversion, which interrupts the enterohepatic circulation (eg by diverting bile acids to an external stoma). These procedures can normalize serum bile acids, reduce pruritus and liver injury and improve quality of life. A novel, nonsurgical approach to interrupting the enterohepatic circulation is inhibition of the ileal bile acid transporter (IBAT), a key molecule in the enterohepatic circulation that reabsorbs bile acids from the intestine. IBAT inhibition has been shown to reduce serum bile acids and pruritus in trials of paediatric cholestatic liver diseases. This review explores the rationale of inhibition of the IBAT as a therapeutic target, describes IBAT inhibitors in development and summarizes the current data on interrupting the enterohepatic circulation as treatment for cholestatic liver diseases including ALGS and PFIC.     

Changing clinico-laboratory profile of encephalitis patients in the eastern Uttar Pradesh region of India

A cross-sectional study was done on 100 consecutive paediatric patients presenting with acute encephalitis syndrome. The clinico-laboratory features of all patients were recorded in a prestructured performa. Cerebrospinal fluid and serum samples were tested for: Japanese encephalitis (JE) virus; Chandipura virus; coxsackie virus; dengue virus; enterovirus 76; and West Nile virus. Twenty-two (22.0%) patients were confirmed JE cases and 17% had parasitic or bacteriological aetiology. The remaining 61 cases (61.0%) in which no viral aetiological agent was found were grouped as non-JE cases. Peripheral vascular failure, splenomegaly and hypotonia were distinguishing clinical features found in the non-JE patients. A high mortality of 26.5% was seen in patients with confirmed or presumptive viral encephalitis (22/83). A fatal outcome was independently associated with peripheral vascular failure and pallor at the time of admission. Early recognition of these signs may help clinicians to manage these cases.     

Recurrent CEOT of the maxilla

Calcifying epithelial odontogenic tumor (CEOT) is a rare benign, but locally infiltrating odontogenic neoplasm. It accounts for less than 1% of all odontogenic tumors. This is a case report of recurrent CEOT in the maxilla. A 35-year-old patient reported after three years of surgical excision of the lesion, with a recurrence. It is of particular concern because of its anatomic location in the maxilla. Maxillary tumors tend to be more aggressive and rapidly spreading and may involve the surrounding vital structures. Adequate resection of the lesion with disease-free surgical margins and long-term follow-up is recommended.     

Unusual intraosseous transmigration of impacted tooth

Transmigration of an impacted tooth through the symphyseal suture is a rare and special developmental anomaly of unknown etiology that is unique to the mandibular canine. Maxillary canine transmigration is even rarer. Transmigrated canines are particularly significant due to the aesthetic and functional importance. A maxillary lateral incisor crossing the mid-palatal suture has never been reported in the literature. The aim of this report is to present the first case of simultaneous transmigration of a lateral incisor and canine in the maxilla. The paper also reports four unusual cases of unilateral canine transmigration in the maxilla and mandible and successful eruption of one of the transmigrated mandibular canines following orthodontic traction. Etiology of transmigration and its clinical considerations are also discussed.     

Olfaction and apathy in Alzheimer's disease,mild cognitive impairment,and healthy older adults

Objectives: Apathy is a prevalent neuropsychiatric manifestation in individuals with Alzheimer's disease (AD) that is associated with decreased social functioning and increased caregiver burden. Olfactory deficits are also commonly observed in AD, and prior work has indicated a link between increased apathy and olfactory dysfunction in individuals with Parkinson's disease. Here, we examined odor identification performance in patients with probable AD (n = 172), individuals with mild cognitive impairment (MCI; n = 112), and neurologically and psychiatrically healthy older adults (n = 132) and its relation to apathy, depression, and overall psychopathology. Method: Participants were administered the Sniffin’ Sticks odor identification test and measures assessing severity of apathy, depression, and overall neuropsychiatric symptomatology. Results: Consistent with previous research, AD and MCI patients were significantly worse at identifying odors than healthy older adults. Additionally, a sex by diagnosis interaction was observed. AD patients had significantly higher levels of apathy relative to MCI and control participants. Of note, across the entire sample odor identification deficits were correlated with level of apathy at the level of p < 0.01, but not with depression or neuropsychiatric symptom severity, when controlling for Mini-Mental State Examination (MMSE) score. Conclusion: Collectively, these data suggest that olfactory disturbance and apathy in AD may result from the progression of disease pathology in shared neural substrates.