Sofosbuvir-velpatasvir in children 3-17 years old with hepatitis C virus infection.

BACKGROUND: The safety and efficacy of sofosbuvir-velpatasvir in children aged 3-17 years with chronic hepatitis C virus (HCV) infection of any genotype were evaluated. METHODS: In this Phase 2, multicenter, open-label study, patients received once daily for 12 weeks either sofosbuvir-velpatasvir 400/100 mg tablet (12-17 years), 200/50 mg low dose tablet or oral granules (3-11 years and ≥17 kg), or 150/37.5 mg oral granules (3-5 years and <17 kg). The efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Dose appropriateness was confirmed by intensive pharmacokinetics in each age group. FINDINGS: Among 216 patients treated, 76% had HCV genotype 1% and 12% had genotype 3. Rates of SVR12 were 83% (34/41) among 3-5-year-olds, 93% (68/73) among 6-11-year-olds, and 95% (97/102) among 12-17-year-olds. Only two patients experienced virologic failure. The most common adverse events were headache, fatigue, and nausea in 12-17-year-olds; vomiting, cough, and headache in 6-11-year-olds; and vomiting in 3-5-year-olds. Three patients discontinued treatment because of adverse events. Four patients had serious adverse events; all except auditory hallucination (n = 1) were considered unrelated to study drug. Exposures of sofosbuvir, its metabolite GS-331007, and velpatasvir were comparable to those in adults in prior Phase 2/3 studies. Population pharmacokinetic simulations supported weight-based dosing for children in this age range. INTERPRETATION: The pangenotypic regimen of sofosbuvir-velpatasvir is highly effective and safe in treating children 3-17 years with chronic HCV infection.

Diagnosis and Follow-up of Incidental Liver Lesions in Children.

ABSTRACT: Incidental liver lesions are identified in children without underlying liver disease or increased risk of hepatic malignancy in childhood. Clinical and imaging evaluation of incidental liver lesions can be complex and may require a multidisciplinary approach. This review aims to summarize the diagnostic process and follow-up of incidental liver lesions based on review of the literature, use of state-of-the-art imaging, and our institutional experience. Age at presentation, gender, alpha fetoprotein levels, tumor size, and imaging characteristics should all be taken into consideration to optimize diagnosis process. Some lesions, such as simple liver cyst, infantile hemangioma, focal nodular hyperplasia (FNH), and focal fatty lesions, have specific imaging characteristics. Recently, contrast-enhanced ultrasound (CEUS) was Food and Drug Administration (FDA)-approved for the evaluation of pediatric liver lesions. CEUS is most specific in lesions smaller than 3 cm and is most useful in the diagnosis of infantile hemangioma, FNH, and focal fatty lesions. The use of hepatobiliary contrast in MRI increases specificity in the diagnosis of FNH. Recently, lesion characteristics in MRI were found to correlate with subtypes of hepatocellular adenomas and associated risk for hemorrhage and malignant transformation. Biopsy should be considered when there are no specific imaging characteristics of a benign lesion. Surveillance with imaging and alpha fetoprotein (AFP) should be performed to confirm the stability of lesions when the diagnosis cannot be determined, and whenever biopsy is not feasible.

Ledipasvir-Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C.

For children under 12 years of age who have chronic hepatitis C virus (HCV) infection, there are currently no approved treatments with direct-acting antiviral agents. We therefore evaluated the safety and efficacy of ledipasvir-sofosbuvir in HCV-infected children aged 3 to <6 years. In an open-label study, patients 3 to <6 years old chronically infected with HCV genotype 1 (n = 33) or 4 (n = 1) received weight-based doses of combined ledipasvir-sofosbuvir as granules (33.75 mg/150 mg for weights <17 kg or 45 mg/200 mg for weights ≥17 kg) for 12 weeks. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12). For the first 14 patients, intensive pharmacokinetic sampling was done on day 10 of treatment. All patients had been infected through perinatal transmission and were treatment naïve. No patients had known cirrhosis. Ten patients (29%) weighed <17 kg. SVR12 was achieved in 97% of patients (33 of 34); the patient who did not achieve SVR12 was 3 years old and discontinued treatment after 5 days because of an adverse event "abnormal drug taste." The most common adverse events were vomiting (24% of patients), cough (21%), and pyrexia (21%). No patients experienced a serious adverse event. Intensive pharmacokinetic analysis of 13 patients for whom data were evaluable confirmed that the doses selected were appropriate. Conclusion: Ledipasvir-sofosbuvir was well tolerated and highly effective in children 3 to <6 years old with chronic HCV infection.

Practice variation in the immediate postoperative care of pediatric liver transplant patients: Framework for a national consensus.

Advancements in critical care management have led to improvement in pediatric LT outcomes. However, there are no specific guidelines for many aspects of immediate post-LT care. This survey examines practice variations in the immediate postoperative care of pediatric LT patients at a large number of active US centers. This study is a cross-sectional survey of medical directors at PALISI-affiliated PICU in the United States. Centers performing pediatric LT were analyzed. Study measures included PICU practices regarding staffing, composition of the multidisciplinary team, early post-LT graft and patient monitoring, and anticoagulation. Of the thirty-five responding centers, twenty-five had a LT program which accounted for one-half of all US pediatric LTs. For analysis, centers were categorized by volume: high (7), medium (11), and low (7). The majority of PICU teams included an intensivist (80%) and hepatologist (84%). High-volume centers were less likely to have 24-hour in-house attending coverage (29%, compared to 64% (medium) and 100% (low)). High-volume centers were most likely to have pre-printed orders, but least likely to have written PICU management protocols. Most centers utilize routine daily liver ultrasound. Routine prophylactic anticoagulation, and the agent of choice, was variable. There is marked inconsistency in post-LT practice across PALISI centers in regards to team composition and immediate post-LT management. A national US consensus for post-LT PICU practices would facilitate outcomes research and would establish a platform for multicenter studies.

Inadequate Bowel Preparation in Pediatric Colonoscopy-Prospective Study of Potential Causes.

OBJECTIVES: Inadequate bowel preparation (IBP) for colonoscopy leads to missed diagnosis, longer anesthesia time, higher chance of complications and increased costs. Adult studies have demonstrated that patient characteristics such as male gender and obesity are associated with IBP. Little is known about factors affecting bowel preparation in children. Our aim was to determine factors associated with IBP in children. METHODS: We prospectively enrolled children undergoing outpatient colonoscopy. Quality of bowel preparation was assessed using Boston Bowel Preparation Scale (BBPS) score (range 0-9). Data collected included patient demographics, indication, and type of insurance. Patients were divided into two groups based on BBPS score-adequate (BBPS score > 5) and inadequate (BBPS score < 5) and groups were compared using Student t-test and chi-square test. Possible predictors were analyzed using multivariate logistic regression models. RESULTS: A total of 334 children were prospectively enrolled of whom 321 were studied further (age range 2-18 years; mean age 12.4 years; 60.4% female; 85.9% Caucasian). The mean BBPS score was 6.8 (standard deviation of ±2). IBP was reported in 12.8% (41/321). Multivariable logistic regression analysis did not show statistical differences between the groups in studied patient factors including age, gender, obesity, race, insurance type, and indication for colonoscopy. CONCLUSION: Contrary to several adult studies, the results of our prospective study did not show any relationship between examined patient factors and IBP in children. Interestingly, IBP was less prevalent in our pediatric study compared to published adult data (12.8% vs 20-40%).

The value of transmandibular approach to total maxillectomy in the management of T3-T4 carcinoma of the maxillary sinus.

Surgical excision of the maxilla either as a primary procedure or after radiotherapy continues to play an important role in the management of carcinoma of the maxillary sinus. A majority of these cancers are seen in T3-T4 stage. Recurrence at the infratemporal fossa has been recognized as a major cause of failure. Although the importance of inclusion of the pterygopalatine fossa in the field of excision has been recognized, there is no uniform approach for en bloc removal of the pterygopalatine fossa. Transmandibular approach has been described for purpose and practiced at the Bangalore Institute of Oncology for the past 8 years with success. This paper presents the technique used, its benefits and the results obtained.

All India Ophthalmological Society - Indian Journal of Ophthalmology consensus statement on preferred practices during the COVID-19 pandemic.

The COVID-19 pandemic has taken tragic proportions and has disrupted lives globally. In the wake of governmental lockdowns, ophthalmologists need practical and actionable guidelines based on advisories from national health departments on how to conduct their duties during nationwide lockdowns and after these are lifted. In this paper, we present a preferred practice pattern (PPP) based on consensus discussions between leading ophthalmologists and health care professionals in India including representatives from major governmental and private institutions as well as the All India Ophthalmological Society leadership. In this document, the expert panel clearly defines the range of activities for Indian ophthalmologists during the ongoing lockdown phase and precautions to be taken once the lockdown is lifted. Guidelines for triage, governmental guidelines for use of personal protective equipment from ophthalmologists' point of view, precautions to be taken in the OPD and operating room as well as care of various ophthalmic equipment have been described in detail. These guidelines will be applicable to all practice settings including tertiary institutions, corporate and group practices and individual eye clinics and should help Indian ophthalmologists in performing their professional responsibilities without being foci of disease transmission.

Management of Acute Liver Failure: A Pediatric Perspective.

PURPOSE OF REVIEW: Pediatric acute liver failure is a rare, complex, rapidly progressing, and life-threatening illness. Majority of pediatric acute liver failures have unknown etiology. This review intends to discuss the current literature on the challenging aspects of management of acute liver failure. RECENT FINDINGS: Collaborative multidisciplinary approach for management of patients with pediatric acute liver failure with upfront involvement of transplant hepatologist and critical care specialists can improve outcomes of this fatal disease. Extensive but systematic diagnostic evaluation can help to identify etiology and guide management. Early referral to a transplant center with prompt liver transplant, if indicated, can lead to improved survival in these patients. SUMMARY: Prompt identification and aggressive management of pediatric acute liver failure and related comorbidities can lead to increased transplant-free survival and improved post-transplant outcomes, thus decreasing mortality and morbidity associated with this potential fatal condition.

Antral balloon sinus elevation and grafting prior to dental implant placement: review of 34 cases.

PURPOSE: The objective of this study was to assess the antral balloon technique for sinus elevation followed by bone graft and implant placement. MATERIALS AND METHODS: A total of 34 patients with atrophic edentulous posterior maxillary ridges underwent antral balloon sinus elevation followed by bone grafting (autogenous bone retrieved from the chin mixed with platelet-rich plasma) and implant placement. RESULTS: The population consisted of 26 male and 8 female patients with a mean age of 42 years (range, 33 to 56 years). Successful sinus membrane balloon elevation was performed in all 34 patients, and 62 implants were placed. A membrane tear in one patient was managed intraoperatively by placement of a collagen membrane. Two implants failed within 6 months, and the survival rate of the other 60 implants was 100% after 3 years of follow-up. The mean inflated balloon volume was 1.96 mL and the mean elevated sinus height by balloon was 11.6 mm. An average bone gain of 7.5 mm (range, 5.2 to 10.5 mm) was observed. CONCLUSIONS: This case series demonstrates the feasibility of antral balloon sinus membrane elevation followed by bone augmentation and implant placement. This technique offers optimal assurance for membrane safety, and it is less invasive than the routine lateral window technique, safe, and associated with less postoperative bleeding and discomfort. This method is predictable, easy to learn, and associated with low complication rates. However, large comparative studies with other techniques are required.

Flare up of choroiditis and choroidal neovasculazation associated with punctate inner choroidopathy during early pregnancy.

A 28-year-old, healthy female, who had a recent repeated history of miscarriage, presented with bilateral choroidal neovascular membranes (CNVM), for which she received photodynamic therapy with three doses of lucentis, at intervals of one month each, to which she responded. After five months, the patient again presented with complaints of diminution of vision since 15 days. She had a history of miscarriage two days before presenting to our clinic. CNVM was scarred at this time and the fundus picture showed multiple small punctate spots around the fovea at the level of the choroid, which showed early hyperfluroscence on fundus fluorescein angiography, suggestive of punctate inner choroidopathy. She was advised systemic steroids, to which she responded dramatically.