Modafinil is a wake-promoting agent approved by the Federal Drug Administration for the treatment of narcolepsy. Preliminary evidence indicates that modafinil may improve fatigue and excessive sleepiness associated with a variety of conditions. The purpose of this study was to investigate the utility of modafinil as an adjunctive treatment of depressed patients. Subjects with a history of major depression with partial response on a stable therapeutic dose of an antidepressant were eligible to participate. All subjects endorsed complaints of significant fatigue and/or excessive sleepiness on clinical assessment. Modafinil was added to their existing regimen at a dose of 100 to 400 mg/d for 4 weeks. Subjects were assessed at 2-week intervals for improvement using the standard depression scales (HDRS, BDI, CGI), fatigue scales (VASF, FSI), and a neuropsychologic battery. Thirty-five subjects were entered and 31 subjects completed the 4-week trial. Significant improvements were seen across all 3 measures of depression (HDRS, BDI, CGIS) and both measures of fatigue (VASF, FSI). On the neurocognitive battery, significant gains in the Stroop Interference Test were seen at 4 weeks, whereas the other cognitive tests showed no change. Modafinil may be a useful and a well-tolerated adjunctive agent to standard antidepressants in the treatment of major depression.

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Neuroblastoma is the most common extracranial childhood solid tumor. Treatment of high risk tumors require intense multicycle chemotherapies, resulting in short-and long-term toxicities. Here, we present treatment of an orthotopic neuroblastoma mouse model, with silk fibroin materials loaded with vincristine, doxorubicin or the combination as a intratumoral, sustained release system. The materials, loaded with vincristine with or without doxorubicin, significantly decreased neuroblastoma tumor growth compared to materials loaded without drug or doxorubicin only as well as intravenous (IV) drug treatment. The intratumoral drug concentration was significantly higher with intratumoral delivery versus IV. Furthermore, intratumor delivery decreased the maximum plasma concentration compared to IV delivery, reducing systemic exposure and possibly reduing long-term side effects of chemotherapy exposure. Histopathologically, tumors with remission periods >25 days before recurrence transformed from a "small-round-blue cell" (SBRC) to predominantly "large cell" neuroblastoma (LCN) histopathology, a more aggressive tumor subtype with unfavorable clinical outcomes. These results show that intratumoral chemotherapy delivery may be a treatment strategy for pediatric neuroblastoma, potentially translatable to other focal tumors types. Furthermore, this treatment modality allows for a clinically relevant mouse model of tumor transformation that may be used for studying the phenotypical tumor recurrence and developing more effective treatment strategies for recurrent tumors.Neuroblastoma represents the most common extracranial solid tumor in the pediatric population and accounts for 15% of pediatric oncologic deaths.1 This tumor is derived from neural crest cells, and the location of the tumor can vary, including the adrenal medulla, sympathetic chain and thoracic cavity.

Background: Direct-to-implant breast reconstruction offers the intuitive advantages of shortening the reconstructive process and reducing costs. In the authors’ practice, direct-to-implant breast reconstruction has evolved from dual-plane to prepectoral implant placement. The authors sought to understand postoperative complications and aesthetic outcomes and identify differences in the dual-plane and prepectoral direct-to-implant subcohorts. Methods: A retrospective review of a prospectively maintained database was conducted from November of 2014 to March of 2018. Postoperative complication data, reoperation, and aesthetic outcomes were reviewed. Aesthetic outcomes were evaluated by a blinded panel of practitioners using standardized photographs. Results: One hundred thirty-four direct-to-implant reconstructions were performed in 81 women: 42.5 percent were dual-plane (n = 57) and 57.5 percent were prepectoral (n = 77). Statistical analysis was limited to patients with at least 1 year of follow-up. Total complications were low overall (8 percent), although the incidence of prepectoral complications [n = 1 (2 percent)] was lower than the incidence of dual-plane complications [n = 7 (12 percent)], with the difference approaching statistical significance (p = 0.07). Panel evaluation for aesthetic outcomes favored prepectoral reconstruction. Pectoralis animation deformity was completely eliminated in the prepectoral cohort. Conclusions: The authors present the largest comparative direct-to-implant series using acellular dermal matrix to date. Transition to prepectoral direct-to-implant reconstruction has not resulted in increased complications, degradation of aesthetic results, or an increase in revision procedures. Prepectoral reconstruction is a viable reconstructive option with elimination of animation deformity and potential for enhanced aesthetic results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.