Everolimus for cardiac rhabdomyomas in children with tuberous sclerosis. The ORACLE study protocol (everOlimus for caRdiac rhAbdomyomas in tuberous sCLErosis): a randomised, multicentre, placebo-controlled, double-blind phase II trial.

INTRODUCTION: Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma. METHODS: ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure. CONCLUSIONS: ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.

The Efficacy and Safety of Pimecrolimus in Patients With Facial Seborrheic Dermatitis: A Systematic Review of Randomized Controlled Trials.

Facial seborrheic dermatitis (SD) is a chronic inflammatory skin condition that can affect the quality of life with frequent recurrences. There is no medication as yet to cure this disease completely. There are four general categories of agents that are used to treat SD: antifungal agents, keratolytics, corticosteroids, and lastly calcineurin inhibitors. Topical therapies are the mainstream line of treatment to be used for this skin condition. The objective of this article is to critically review the published data in the literature on the use of topical pimecrolimus 1% topical cream as an option for treating facial SD. The final purpose of this review is to answer two questions: whether pimecrolimus topical cream is effective for the treatment of SD compared to the conventional current treatments and how safe is this treatment.  The PubMed, Clinicaltrials.gov, MEDLINE + Embase, and Cochrane library databases were searched for original randomized clinical trials (RCTs) evaluating pimecrolimus 1% topical cream and comparing it with other topical treatments for SD. A systematic review and meta-analysis were then conducted on the selected studies by grading the evidence and qualitative comparison of results among and within studies. A total of five studies were included in the review; however, only four were eligible for inclusion in the meta-analysis, in which pimecrolimus was compared with other treatments for the management of facial SD. Pimecrolimus was found to be an effective topical treatment for facial SD, as it showed considerable desirable control of the symptoms in patients with facial SD clinically, in addition to a lower recurrence or relapsing rates; however, it had more side effects compared to other topical treatments, but the side effects were mild and tolerable.

How often should percutaneous gastrostomy feeding tubes be replaced? A single-institute retrospective study.

OBJECTIVE: Percutaneous gastrostomy (PG) is a common procedure that enables long-term enteral nutrition. However, data on the durability of individual tube types are insufficient. We conducted this study to compare the longevities and features of different PG tube types. DESIGN: We performed a 5-year retrospective analysis of patients who underwent endoscopic and radiologic PG-related feeding tube procedures. The primary and secondary outcomes were tube exchange intervals and revenue costs, respectively. Demographic factors, underlying diseases, operator expertise, materials used, and complication profiles were assessed. RESULTS: A total of 599 PG-related procedures for inserting pull-type PG (PGP), balloon-type PG (PGB), PG jejunal MIC* (PGJM; gastrojejunostomy type), and PG jejunal Levin (PGJL) tubes were assessed. On univariate Kaplan-Meier analysis, PGP tubes showed longer median exchange intervals than PGB tubes (405 days (95% CI: 315 to 537) vs 210 days (95% CI: 188 to 238); p<0.001). Larger PGB tubes diameters were associated with longer durations than smaller counterparts (24 Fr: 262 days (95% CI: 201 to NA), 20 Fr: 216 days (95% CI: 189 to 239), and 18 Fr: 148 days (95% CI: 100 to 245)). The PGJL tubes lasted longer than PGJM counterparts (median durations: 168 days (95% CI: 72 to 372) vs 13 days (95% CI: 23 to 65); p<0.001). Multivariate Cox proportional regression analysis revealed that PGJL tubes had significantly lower failure rates than PGJM tubes (OR 2.97 (95% CI: 1.17 to 7.53); p=0.022). PGB tube insertion by general practitioners was the least costly, while PGP tube insertion by endoscopists was 2.9-fold more expensive; endoscopic PGJM tubes were the most expensive at two times the cost of PGJL tubes. CONCLUSION: PGP tubes require replacement less often than PGB tubes, but the latter are more cost-effective. Moreover, PGJL tubes last longer than PGJM counterparts and, owing to lower failure rates, may be more suitable for high-risk patients.

The coexistence of anterior communicating artery aneurysm and meningioma: A literature review and illustrative case.

Background: Anterior communicating artery (Acom) aneurysm has an association with many types of intracranial lesions. However, its association with meningioma can be challenging, which is not well addressed in the literature. Herein, we described a literature review focused on the association between Acom aneurysm and meningioma, explicitly highlighting the spatial presence between these two pathologies. We analyzed the literature according to that association with particular emphasis on location-based challenges. Furthermore, we present an illustrative case of surgically treating both lesions in one surgery utilizing the same approach. Methods: A Medline database search was conducted by the following combined formula: (Meningioma [Title/ Abstract]) AND (Aneurysm [Title/Abstract]) AND (((Anterior communicating artery [Title/Abstract]) OR (Acom [Title/Abstract])) OR Acomm [Title/Abstract]))). Additional resources were added after screening the references of the included papers. Results: Nine patients with coexistence of Acom aneurysm and meningioma were found in the literature. The coexistence of both pathologies was found in seven females and two males. The presence of an aneurysm was found to be solitary in 66.67% (n = 6/9). Furthermore, meningioma was found to be an isolated lesion in all included cases, and in 22.2% (n = 2/9), they were located ipsilaterally. The location of the meningioma to the aneurysm seems to be in proximity. Conclusion: Acom aneurysm can coexist with intracranial meningioma; this association can be spatially related intracranially. Such coexistence entails a variety of nuances and challenges that neurosurgeons encounter during the management of these complex lesions.