Deep Shave Removal of Suspected Basal Cell Carcinoma: A Prospective Study.

BACKGROUND: Diagnosis and treatment of basal cell carcinoma (BCC) in the same visit by shave removal may decrease health care spending and promote patient satisfaction. OBJECTIVE: To prospectively evaluate deep shave removal of lesions clinically suspicious for low-risk BCC on the trunk or extremities in immunocompetent patients. MATERIALS AND METHODS: Deep shave removal with the intent to remove the entire tumor was performed from January 2015 to June 2016, and patients were followed prospectively for clinical evidence of tumor recurrence. RESULTS: Seventy-seven lesions were removed from 51 patients, including 29 (37%) superficial and nodular BCCs, 27 (35%) superficial BCCs, 16 (21%) nodular BCCs, and 5 (6%) non-BCCs. Fifteen BCCs (21%) had positive residual margins after deep shave removal, which was significantly more likely to occur in nodular compared with superficial BCCs (odds ratio = 7.8, 95% confidence interval = 1.4-43), and underwent re-excision. Fourteen specimens initially reported to have negative margins after deep shave underwent resectioning, which revealed positive margins in 4 specimens (28.6%). No BCCs have recurred clinically after an average follow-up of 50 months (SE 3.2). CONCLUSION: Consider deep shave removal for low-risk BCCs on the trunk or extremities in immunocompetent patients hoping to avoid a second treatment visit.

The asymmetric function of Dph1-Dph2 heterodimer in diphthamide biosynthesis.

Diphthamide, the target of diphtheria toxin, is a post-translationally modified histidine residue found in archaeal and eukaryotic translation elongation factor 2 (EF2). In the first step of diphthamide biosynthesis, a [4Fe-4S] cluster-containing radical SAM enzyme, Dph1-Dph2 heterodimer in eukaryotes or Dph2 homodimer in archaea, cleaves S-adenosylmethionine and transfers the 3-amino-3-carboxypropyl group to EF2. It was demonstrated previously that for the archaeal Dph2 homodimer, only one [4Fe-4S] cluster is necessary for the in vitro activity. Here, we demonstrate that for the eukaryotic Dph1-Dph2 heterodimer, the [4Fe-4S] cluster-binding cysteine residues in each subunit are required for diphthamide biosynthesis to occur in vivo. Furthermore, our in vitro reconstitution experiments with Dph1-Dph2 mutants suggested that the Dph1 cluster serves a catalytic role, while the Dph2 cluster facilitates the reduction of the Dph1 cluster by the physiological reducing system Dph3/Cbr1/NADH. Our results reveal the asymmetric functional roles of the Dph1-Dph2 heterodimer and may help to understand how the Fe-S clusters in radical SAM enzymes are reduced in biology.

The rise of transcutaneous drug delivery for the management of alopecia: a review of existing literature and an eye towards the future.

Introduction: Fractional lasers and microneedling devices are increasingly used with topical drugs to treat various conditions, including alopecia, as they grant access to dermal structures such as hair follicles and cutaneous vasculature. Objective: To perform a comprehensive review on transcutaneous drug delivery for the management of alopecia. Methods: PubMed, Embase, and Ovid Medline databases were searched using terms including: alopecia, microneedling, lasers, androgenetic alopecia (AGA), alopecia areata (AA), drug delivery. Articles were examined for inclusion criteria: diagnosis of alopecia regardless of type, use of fractional laser or microneedling devices, and subsequent administration of topical medication. Results: 8 studies, 6 prospective clinical trials and 2 case series, examining either AA or AGA were identified. For AA, five studies examined microneedling together with topical triamcinolone in three of these, while two studies used photodynamic therapy. Regarding AGA, two studies used topical minoxidil plus microneedling, and one examined topical finasteride with fractional erbium glass laser. Improvement was seen in 6 of the 8 studies. Discussion: Transcutaneous drug delivery via fractional laser and microneedling is a promising modality with preliminary evidence for increased hair regrowth over topical therapy alone. Further studies are needed to elucidate treatment parameters and appropriate device selection for drug delivery.

A Cost-Utility Analysis of 5 Strategies for the Management of Acute Otitis Media in Children.

OBJECTIVE: To assess whether antimicrobial therapy in young children with acute otitis media reduces time to resolution of symptoms, overall symptom burden, and persistence of otoscopic evidence of infection. We used a cost-utility model to evaluate whether immediate antimicrobial treatment seems to be worthwhile, and if so, which antimicrobial agent is most cost effective. STUDY DESIGN: We compared the cost per quality-adjusted life-day of 5 treatment regimens in children younger than 2 years of age with acute otitis media: immediate amoxicillin/clavulanate, immediate amoxicillin, immediate cefdinir, watchful waiting, and delayed prescription (DP) for antibiotic. RESULTS: The 5 treatment regimens, listed in order from least effective to most effective were DP, watchful waiting, immediate cefdinir, immediate amoxicillin, and immediate amoxicillin/clavulanate. Listed in order from least costly to most costly, the regimens were DP, immediate amoxicillin, watchful waiting, immediate amoxicillin/clavulanate, and immediate cefdinir. The incremental cost-utility ratio of immediate amoxicillin compared with DP was $101.07 per quality-adjusted life-day gained. The incremental cost-utility ratio of immediate amoxicillin/clavulanate compared with amoxicillin was $2331.28 per quality-adjusted life-day gained. CONCLUSIONS: In children younger than 2 years of age with acute otitis media and no recent antibiotic exposure, immediate amoxicillin seems to be the most cost-effective initial treatment.

Dph3 is an electron donor for Dph1-Dph2 in the first step of eukaryotic diphthamide biosynthesis.

Diphthamide, the target of diphtheria toxin, is a unique posttranslational modification on translation elongation factor 2 (EF2) in archaea and eukaryotes. The biosynthesis of diphthamide was proposed to involve three steps. The first step is the transfer of the 3-amino-3-carboxypropyl group from S-adenosyl-l-methionine (SAM) to the histidine residue of EF2, forming a C-C bond. Previous genetic studies showed this step requires four proteins in eukaryotes, Dph1-Dph4. However, the exact molecular functions for the four proteins are unknown. Previous study showed that Pyrococcus horikoshii Dph2 (PhDph2), a novel iron-sulfur cluster-containing enzyme, forms a homodimer and is sufficient for the first step of diphthamide biosynthesis in vitro. Here we demonstrate by in vitro reconstitution that yeast Dph1 and Dph2 form a complex (Dph1-Dph2) that is equivalent to the homodimer of PhDph2 and is sufficient to catalyze the first step in vitro in the presence of dithionite as the reductant. We further demonstrate that yeast Dph3 (also known as KTI11), a CSL-type zinc finger protein, can bind iron and in the reduced state can serve as an electron donor to reduce the Fe-S cluster in Dph1-Dph2. Our study thus firmly establishes the functions for three of the proteins involved in eukaryotic diphthamide biosynthesis. For most radical SAM enzymes in bacteria, flavodoxins and flavodoxin reductases are believed to serve as electron donors for the Fe-S clusters. The finding that Dph3 is an electron donor for the Fe-S clusters in Dph1-Dph2 is thus interesting and opens up new avenues of research on electron transfer to Fe-S proteins in eukaryotic cells.