A Pilot Study Characterizing Factors in Adherence to Cutaneous Lupus Treatment.

Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease that manifests as scarring, dyspigmentation, erythema, and pain. Topical corticosteroids are a mainstay of treatment. Irritation, messiness, and tediousness may deter use. Thus, nonadherence, rather than nonresponse, can result in treatment failure. Prior adherence studies were limited to systemic lupus erythematosus. We performed a single-center, open-label pilot study to assess adherence to topical medication in patients with CLE. CLE adherence to topical medications is suboptimal and declines over time. Shorter treatment duration and greater patient perception of disease severity may contribute to higher adherence. Improving adherence to existing treatments could be as or more valuable than new therapies for the disease.

Non-response to Interleukin-1 Antagonist Canakinumab in Two Patients with Refractory Pyoderma Gangrenosum and Hidradenitis Suppurativa.

Pyoderma gangrenosum and hidradenitis suppurativa are skin conditions characterized by an intense neutrophil-mediated inflammatory response that is often difficult to effectively treat. Successful use of interleukin (IL)-1ß inhibition using canakinumab and anakinra has been reported in patients with concomitant pyoderma gangrenosum and hidradenitis suppurativa. We report two cases where targeted therapy with canakinumab failed to lead to improvement for patients with pyoderma gangrenosum and hidradenitis suppurativa. The reason behind the non-response to IL-1ß blockade seen in these patients is unclear. Our report suggests that further controlled studies are warranted to help clinicians predict treatment responses to anti-IL-1 therapies in these challenging patients.

Cost-Effectiveness Analysis of Breast Reconstruction Options in the Setting of Postmastectomy Radiotherapy Using the BREAST-Q.

BACKGROUND: A consensus is lacking on a uniform reconstructive algorithm for patients with locally advanced breast cancer who require postmastectomy radiotherapy. Both delayed autologous and immediate prosthetic techniques have inherent advantages and complications. The study hypothesis is that implants are more cost effective than autologous reconstruction in the setting of postmastectomy radiotherapy because of immediate restoration of the breast mound. METHODS: A cost-effectiveness analysis model using the payer perspective was created comparing delayed autologous and immediate prosthetic techniques against the do-nothing option of mastectomy without reconstruction. Costs were obtained from the 2010 Nationwide Inpatient Sample database. Effectiveness was determined using the BREAST-Q patient-reported outcome measure. A breast quality-adjusted life-year value was considered 1 year of perfect breast health-related quality of life. The incremental cost-effectiveness ratio was calculated for both treatments compared with the do-nothing option. RESULTS: BREAST-Q scores were obtained from patients who underwent immediate prosthetic reconstruction (n = 196), delayed autologous reconstruction (n = 76), and mastectomy alone (n = 71). The incremental cost-effectiveness ratios for immediate prosthetic and delayed autologous reconstruction compared with mastectomy alone were $57,906 and $102,509, respectively. Sensitivity analysis showed that the incremental cost-effectiveness ratio for both treatment options decreased with increasing life expectancy. CONCLUSIONS: For patients with advanced breast cancer who require postmastectomy radiotherapy, immediate prosthetic-based breast reconstruction is a cost-effective approach. Despite high complication rates, implant use can be rationalized based on low cost and health-related quality-of-life benefit derived from early breast mound restoration. If greater life expectancy is anticipated, autologous transfer is cost effective as well and may be a superior option.

Safety of the supraclavicular artery island flap in the setting of neck dissection and radiation therapy.

BACKGROUND: The supraclavicular artery island flap (SAIF) has recently been repopularized as a versatile and reliable option for reconstruction of oncological head and neck defects. Prior ipsilateral neck dissection or irradiation is considered a relative contraindication to its use. The aim of this study was to describe the safety and utility of the SAIF for head and neck reconstruction in the setting of neck dissection and radiation. METHODS: A retrospective chart review was performed of consecutive SAIF reconstructions at two institutions between May 2011 and 2014. In addition to demographic data, comorbidities, indications, surgical characteristics, data about radiation treatment, and neck dissection were specifically recorded. Donor and recipient site complications were noted. Fisher exact test was performed to analyze if neck dissection or radiation were associated with complications. RESULTS: A total of 22 patients underwent SAIF reconstruction for an array of head and neck defects. Donor site infection was noted in one patient. Recipient site complications included, wound dehiscence (n = 2), orocutaneous fistula (n = 1), carotid blowout (n = 1), and total flap loss (n = 1). There was no association between prior neck dissection or radiation treatment and flap loss (p = 1.00). CONCLUSION: The SAIF is safe for use in patients who have had an ipsilateral neck dissection involving level IV or V lymph nodes and/or radiation treatment to the neck. It can be used alone or in combination with other flaps for closure of a variety of head and neck defects.

Cost-effectiveness analysis of implants versus autologous perforator flaps using the BREAST-Q.

BACKGROUND: Reimbursement has been recognized as a physician barrier to autologous reconstruction. Autologous reconstructions are more expensive than prosthetic reconstructions, but provide greater health-related quality of life. The authors' hypothesis is that autologous tissue reconstructions are cost-effective compared with prosthetic techniques when considering health-related quality of life and patient satisfaction. METHODS: A cost-effectiveness analysis from the payer perspective, including patient input, was performed for unilateral and bilateral reconstructions with deep inferior epigastric perforator (DIEP) flaps and implants. The effectiveness measure was derived using the BREAST-Q and interpreted as the cost for obtaining 1 year of perfect breast health-related quality-adjusted life-year. Costs were obtained from the 2010 Nationwide Inpatient Sample. The incremental cost-effectiveness ratio was generated. A sensitivity analysis for age and stage at diagnosis was performed. RESULTS: BREAST-Q scores from 309 patients with implants and 217 DIEP flap reconstructions were included. The additional cost for obtaining 1 year of perfect breast-related health for a unilateral DIEP flap compared with implant reconstruction was $11,941. For bilateral DIEP flaps compared with implant reconstructions, the cost for an additional breast health-related quality-adjusted life-year was $28,017. The sensitivity analysis demonstrated that the cost for an additional breast health-related quality-adjusted life-year for DIEP flaps compared with implants was less for younger patients and earlier stage breast cancer. CONCLUSIONS: DIEP flaps are cost-effective compared with implants, especially for unilateral reconstructions. Cost-effectiveness of autologous techniques is maximized in women with longer life expectancy. Patient-reported outcomes findings can be incorporated into cost-effectiveness analyses to demonstrate the relative value of reconstructive procedures.

Phosphorylated RPA recruits PALB2 to stalled DNA replication forks to facilitate fork recovery.

Phosphorylation of replication protein A (RPA) by Cdk2 and the checkpoint kinase ATR (ATM and Rad3 related) during replication fork stalling stabilizes the replisome, but how these modifications safeguard the fork is not understood. To address this question, we used single-molecule fiber analysis in cells expressing a phosphorylation-defective RPA2 subunit or lacking phosphatase activity toward RPA2. Deregulation of RPA phosphorylation reduced synthesis at forks both during replication stress and recovery from stress. The ability of phosphorylated RPA to stimulate fork recovery is mediated through the PALB2 tumor suppressor protein. RPA phosphorylation increased localization of PALB2 and BRCA2 to RPA-bound nuclear foci in cells experiencing replication stress. Phosphorylated RPA also stimulated recruitment of PALB2 to single-strand deoxyribonucleic acid (DNA) in a cell-free system. Expression of mutant RPA2 or loss of PALB2 expression led to significant DNA damage after replication stress, a defect accentuated by poly-ADP (adenosine diphosphate) ribose polymerase inhibitors. These data demonstrate that phosphorylated RPA recruits repair factors to stalled forks, thereby enhancing fork integrity during replication stress.