Multiple neurosurgical treatments for different members of the same family with Currarino syndrome

Introduction

Currarino's syndrome (CS) is an autosomal dominant disorder of embryonic development causing a rare malformating syndrome characterized by a triad of an anorectal malformations, presacral mass (most commonly an anterior sacral meningocele) and sacral bony defects. Mutations of the HLXB9 gene have been identified in most CS cases, but a precise genotype-phenotype correlation has not been described so far. Family screening is obligatory. The diagnosis is usually made during childhood and rarely in adulthood. In this context, imaging, and especially MRI plays a major role in the diagnosis of this syndrome. Surgical management is provided by pediatric surgeons or neurosurgeons.

Physician visits and the timing of skeletal-related events among men newly diagnosed with metastatic prostate cancer: A cohort analysis

Introduction

Men diagnosed with metastatic prostate cancer (PCa) are at increased risk for skeletal complications which are associated with significant morbidity and mortality. Although both the urologist and the medical oncologist play important roles in the management of patients with advanced PCa, there is limited information regarding their role in the context of skeletal complications. The current study investigated these relationships among newly diagnosed metastatic patients with PCa.

Therapeutic drug monitoring in inflammatory bowel disease: The dawn of reactive monitoring

Inflammatory bowel disease (IBD) is a chronic condition that significantly affects the quality of life of its patients. Biologic drugs have been the mainstay treatment in the management of IBD patients but despite their significant contribution, there remains a proportion of patients that do not respond or lose response to treatment. Therapeutic drug monitoring (TDM) involves measuring levels of serum drug concentrations and anti-drug antibodies. TDM of biologic drugs initially emerged to understand treatment failure in other immune mediated inflammatory diseases. This was then introduced in IBD to rationalize primary non-response or secondary loss of response, given that low serum drug concentrations or the formation of anti-drug antibodies are variably associated with treatment failure. The aim of this narrative review is to provide an overview regarding the current use of TDM in clinical practice and to present the evidence available regarding its use in both proactive and reactive clinical settings in preventing and managing treatment failure. This review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations, in everyday practice. A narrative review of published articles and conference abstracts regarding the use of TDM in IBD management, through an electronic search using PubMed and ScienceDirect. TDM has proven to be superior and more cost effective in guiding management of patients with treatment failure compared to empiric dose escalation or change in treatment. Despite a trend towards an association between clinical outcomes and drug concentrations, proactive TDM based strategies have not been shown to achieve clear benefit in long-term outcomes. In the clinical setting, TDM has proven to be useful in managing IBD patients, and its use in the reactive setting, as an additional tool to help manage patients with treatment failure, is being promoted as newer guidelines and consensus groups implement TDM as part of the management plan.     

CYP3A activity in severe liver cirrhosis correlates with Child–Pugh and model for end-stage liver disease (MELD) scores

Aims

Impaired liver function often necessitates drug dose adjustment to avoid excessive drug accumulation and adverse events, but a marker for the extent of the required adjustment is lacking. The aim of this study was to investigate whether Child–Pugh (CP) and model for end-stage liver disease (MELD) scores correlate with drug clearance.

Methods

Midazolam was used as a CYP3A probe and its pharmacokinetics were analyzed in 24 patients with mild to severe liver cirrhosis (n = 4, 10 and 10 with CP class A, B and C, respectively) and six patients without liver disease.

Results

Both scores correlated well with unbound midazolam clearance (CL_u), unbound midazolam fraction and half-life (all P < 0.01), whereas the unbound steady-state volume of distribution was not significantly changed. In patients with severe liver cirrhosis unbound midazolam clearance was only 14% of controls (CP C: CL_u = 843 ± 346 l h⁻¹, MELD ≥ 15: CL_u = 805 ± 474 l h⁻¹, controls: CL_u = 5815 ± 2649 l h⁻¹, P < 0.01).

Conclusion

The correlation with unbound midazolam clearance suggests that either score predicts the metabolic capacity of CYP3A, the most relevant drug metabolizing enzyme subfamily in humans.     

Comparison of the antibacterial activity of calcium silicate- and epoxy resin-based endodontic sealers against Enterococcus faecalis biofilms: a confocal laser-scanning microscopy analysis

Odontology - This study assessed the antibacterial activity of BioRoot RCS in comparison with that of the Totalfill BC and AH Plus sealers against Enterococcus faecalis biofilms in dentinal tubules...