Herpes Simplex Virus type 1 infects Langerhans cells and the novel epidermal dendritic cell, Epi-cDC2s, via different entry pathways.

Skin mononuclear phagocytes (MNPs) provide the first interactions of invading viruses with the immune system. In addition to Langerhans cells (LCs), we recently described a second epidermal MNP population, Epi-cDC2s, in human anogenital epidermis that is closely related to dermal conventional dendritic cells type 2 (cDC2) and can be preferentially infected by HIV. Here we show that in epidermal explants topically infected with herpes simplex virus (HSV-1), both LCs and Epi-cDC2s interact with HSV-1 particles and infected keratinocytes. Isolated Epi-cDC2s support higher levels of infection than LCs in vitro, inhibited by acyclovir, but both MNP subtypes express similar levels of the HSV entry receptors nectin-1 and HVEM, and show similar levels of initial uptake. Using inhibitors of endosomal acidification, actin and cholesterol, we found that HSV-1 utilises different entry pathways in each cell type. HSV-1 predominantly infects LCs, and monocyte-derived MNPs, via a pH-dependent pathway. In contrast, Epi-cDC2s are mainly infected via a pH-independent pathway which may contribute to the enhanced infection of Epi-cDC2s. Both cells underwent apoptosis suggesting that Epi-cDC2s may follow the same dermal migration and uptake by dermal MNPs that we have previously shown for LCs. Thus, we hypothesize that the uptake of HSV and infection of Epi-cDC2s will stimulate immune responses via a different pathway to LCs, which in future may help guide HSV vaccine development and adjuvant targeting.

Herpes simplex virus type 2-infected dendritic cells produce TNF-α, which enhances CCR5 expression and stimulates HIV production from adjacent infected cells.

Prior HSV-2 infection enhances the acquisition of HIV-1 >3-fold. In genital herpes lesions, the superficial layers of stratified squamous epithelium are disrupted, allowing easier access of HIV-1 to Langerhans cells (LC) in the epidermis and perhaps even dendritic cells (DCs) in the outer dermis, as well as to lesion infiltrating activated T lymphocytes and macrophages. Therefore, we examined the effects of coinfection with HIV-1 and HSV-2 on monocyte-derived DCs (MDDC). With simultaneous coinfection, HSV-2 significantly stimulated HIV-1 DNA production 5-fold compared with HIV-1 infection alone. Because <1% of cells were dually infected, this was a field effect. Virus-stripped supernatants from HSV-2-infected MDDCs were shown to enhance HIV-1 infection, as measured by HIV-1-DNA and p24 Ag in MDDCs. Furthermore these supernatants markedly stimulated CCR5 expression on both MDDCs and LCs. TNF-α was by far the most prominent cytokine in the supernatant and also within HSV-2-infected MDDCs. HSV-2 infection of isolated immature epidermal LCs, but not keratinocytes, also produced TNF-α (and low levels of IFN-ß). Neutralizing Ab to TNF-α and its receptor, TNF-R1, on MDDCs markedly inhibited the CCR5-stimulating effect of the supernatant. Therefore, these results suggest that HSV-2 infection of DCs in the skin during primary or recurrent genital herpes may enhance HIV-1 infection of adjacent DCs, thus contributing to acquisition of HIV-1 through herpetic lesions.

The capsular hammock flap for correction of breast implant ptosis.

UNLABELLED: A well-defined inframammary fold (IMF) is essential in providing an aesthetically pleasing and stable result in breast procedures. The position of the IMF on the chest wall determines the "footprint" of the breast, and hence the breast and chest aesthetic as a whole. Implant malposition is reported in the literature to occur in 5-8 % of primary breast augmentation patients. This occurs most commonly in a caudal direction, which is the most difficult problem to correct, as reported by Tebbett (Clin Plast Surg 28:425-434, 2001). Numerous surgical techniques to correct the malpositioned IMF have been described, including periosteal anchorage techniques as reported by Persichetti et al. (Ann Plast Surg 70:636-638, 2013), periareolar approaches that secure the IMF to the rib cage, and superiorly based capsular flaps. Here we describe a novel simple capsular flap technique using the lower anterior capsule, which is divided and formed into an inferiorly based flap and used as a "hammock" to re-establish the IMF and support the implant. As the capsule is made of a compact fibrous shell with a dense collagen network and excellent blood supply, using it as a flap to reposition and maintain the implant is ideal. Previous studies and tests have shown the reliability of capsule-based flap reconstruction due to the capsule's intrinsic strength and good vascularity, as shown by Rubino et al. (Ann Plast Surg 46:95-102, 2001). We describe our series of 12 primary breast augmentation patients with caudal implant malposition who underwent IMF reconstruction and implant repositioning with this technique. We explain our simple and repeatable technique that shows a stable and very durable result in repositioning the IMF and implant, with no recurrence of implant ptosis. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Abdominoplasty Improves Low Back Pain and Urinary Incontinence.

BACKGROUND: The authors studied the incidence of low back pain and urinary incontinence in the postpartum population presenting for abdominoplasty, and the extent of improvement following the operation. METHODS: This multicenter prospective study used validated questionnaires: the Oswestry Disability Index for back pain and the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form for urinary incontinence. Questionnaires were administered preoperatively and at 6 weeks and 6 months postoperatively. RESULTS: Results cover 214 patients from nine centers. The mean age was 42.1 years, the mean parity was 2.5, and the mean body mass index was 26.3 kg/m. The mean surgical statistics were as follows: weight removed, 1222 g; liposuction volume, 795 ml; and diastasis, 4.5 cm. Eighty-seven percent of the abdominoplasties were either radical, high lateral tension, or high oblique tension. The mean Oswestry Disability Index score preoperatively was 21.6 percent, and 8.8 percent had no back pain. The mean score was 8 percent at 6 weeks and 3.2 percent at 6 months. These results are statistically significant. The mean International Consultation on Incontinence Questionnaire score preoperatively was 6.5; of the patients assessed, 27.5 percent had no incontinence. This score fell to 1.6 at 6 weeks, and the same, 1.6, at 6 months. These results are also statistically significant. Preoperative predictors of back pain were body mass index greater than 25 kg/m and umbilical hernia; predictors of incontinence were age older than 40 years and vaginal deliveries. There were no significant predictors of postoperative back pain or urinary incontinence improvement at 6 months. All methods of abdominoplasty produced similar improvement. CONCLUSION: Abdominoplasty with rectus repair creates a significant improvement in the functional symptoms of low back pain and urinary incontinence. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Chronic biofilm infection in breast implants is associated with an increased T-cell lymphocytic infiltrate: implications for breast implant-associated lymphoma.

BACKGROUND: Biofilm infection of breast implants significantly potentiates capsular contracture. This study investigated whether chronic biofilm infection could promote T-cell hyperplasia. METHODS: In the pig study, 12 textured and 12 smooth implants were inserted into three adult pigs. Implants were left in situ for a mean period of 8.75 months. In the human study, 57 capsules from patients with Baker grade IV contracture were collected prospectively over a 4-year period. Biofilm and surrounding lymphocytes were analyzed using culture, nucleic acid, and visualization techniques. RESULTS: In the pig study, all samples were positive for bacterial biofilm. There was a significant correlation between the bacterial numbers and grade of capsular contracture (p = 0.04). Quantitative real-time polymerase chain reaction showed that all lymphocytes were significantly more numerous on textured compared with smooth implants (p < 0.001). T cells accounted for the majority of the lymphocytic infiltrate. Imaging confirmed the presence of activated lymphocytes. In the human study, all capsules were positive for biofilm. Analysis of lymphocyte numbers showed a T-cell predominance (p < 0.001). There was a significant linear correlation between the number of T and B cells and the number of detected bacteria (p < 0.001). Subset analysis showed a significantly higher number of bacteria for polyurethane implants (p < 0.005). CONCLUSIONS: Chronic biofilm infection around breast prostheses produces an increased T-cell response both in the pig and in humans. A possible link between bacterial biofilm and T-cell hyperplasia is significant in light of breast implant-associated anaplastic large-cell lymphoma. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.