S100A8-mediated metabolic adaptation controls HIV-1 persistence in macrophages in vivo.

HIV-1 eradication is hindered by viral persistence in cell reservoirs, established not only in circulatory CD4+T-cells but also in tissue-resident macrophages. The nature of macrophage reservoirs and mechanisms of persistence despite combined anti-retroviral therapy (cART) remain unclear. Using genital mucosa from cART-suppressed HIV-1-infected individuals, we evaluated the implication of macrophage immunometabolic pathways in HIV-1 persistence. We demonstrate that ex vivo, macrophage tissue reservoirs contain transcriptionally active HIV-1 and viral particles accumulated in virus-containing compartments, and harbor an inflammatory IL-1R+S100A8+MMP7+M4-phenotype prone to glycolysis. Reactivation of infectious virus production and release from these reservoirs in vitro are induced by the alarmin S100A8, an endogenous factor produced by M4-macrophages and implicated in "sterile" inflammation. This process metabolically depends on glycolysis. Altogether, inflammatory M4-macrophages form a major tissue reservoir of replication-competent HIV-1, which reactivate viral production upon autocrine/paracrine S100A8-mediated glycolytic stimulation. This HIV-1 persistence pathway needs to be targeted in future HIV eradication strategies.

The modified serratus anterior fascia flap improves satisfaction and long-term results in immediate implant-based breast reconstruction: A retrospective study.

After immediate implant-based breast reconstruction (IIBR) following skin-sparing mastectomy, postoperative complications such as implant exposure or badly defined mammary folds can occur. Acellular dermal matrix can provide good esthetic outcomes but remain expensive. This study evaluates a new technique of one-stage IIBR by using a modified serratus anterior fascia flap (MSFF group), providing lower implant coverage, as compared to the classical submuscular technique. In this retrospective study, we included all patients who underwent IIBR using either the MSFF technique or the classic technique between November 2012 and February 2015. We collected data regarding demographics, perioperative factors, postoperative complications, patient satisfaction (Breast-Q score), and esthetic outcomes. One hundred twenty-three patients who underwent IIBR, of which 61 breasts (59 patients) using the MSFF and 67 breasts (64 patients) the classical technique, were included. The size of the implants used were significantly higher in the MSFF group (p = 0.036). There were no statistically significant differences between the two groups with regard to the immediate complications rate. After a mean follow-up of 43.9 months, we observed more capsular contractures in the classic group (p < 0.001). In the classic group, patients required more revision surgeries (p = 0.008), more implant changes (p < 0.001), and higher volume of additional lipofilling (p < 0.001). According to the Breast Q scores, patients' satisfaction was better in the MSFF group regarding their breasts (p = 0.001) and the outcomes (p = 0.009). The MSFF is a simple, safe, effective, and inexpensive autologous technique for IIBR, which improves implant coverage with a vascularized flap and provides satisfying outcomes as compared to classic IIBR, with less complications.

ALGINATE versus NPWT in the Preparation of Surgical Excisions for an STSG: ATEC Trial.

A calcium alginate dressing (ALGINATE) and negative pressure wound therapy (NPWT) are frequently used to treat wounds which heal by secondary intention. This trial compared the healing efficacy and safety of these 2 treatments. METHODS: This randomized, non-inferiority trial enrolled patients who underwent skin excision (>30 cm2), which was left open to heal by secondary intention. They received ALGINATE or NPWT by a centralized randomization. Follow-up was performed weekly until optimal granulation tissue was obtained. The primary outcome was time to obtain optimal granulation tissue for a split thickness skin graft take (non-inferiority margin: 4 days). Secondary outcomes were occurrence of adverse events (AEs) and impact of the treatments on the patient's daily life. RESULTS: ALGINATE and NPWT were applied to 47 and 48 patients, respectively. The mean time to optimal granulation was 19.98 days (95% CI, 17.7-22.3) with ALGINATE and 20.54 (95% CI, 17.6-23.5) with NPWT. Between group difference was -0.56 days (95% CI -4.22 to 3.10). The non-inferiority of ALGINATE versus NPWT was demonstrated. No AE related to the treatment occurred with ALGINATE versus 14 AEs with NPWT. There was no difference in the impact of the treatments on the patient's daily life. CONCLUSION: This trial demonstrates that ALGINATE has a similar healing efficacy to that of NPWT and that is markedly better with regard to patient safety.

Lower rates of lipofilling sessions in latissimus dorsi flap breast reconstruction with initial higher volume transfer by preservation of subfascial fat: A 3D camera-assisted volumetric case series.

Breast reconstruction with latissimus dorsi flap (LDF) is a well-known technique, but the crucial goal is to achieve a satisfying final volume restoration. Our hypothesis is that LDF reconstruction with the preservation of subfascial fat can achieve a higher volume in a one-time procedure than that achieved in a classic LDF harvest. The aim of the study was to quantify the volume resorption in LDF reconstructions with the preservation of subfascial fat. Fifteen breasts were reconstructed with a simple LDF and the remaining 15 with an LDF with the preservation of the subfascial fat between January 2016 and May 2017. Secondly, every patient underwent a lipofilling procedure. A supplemental lipofilling procedure was performed in unsatisfying cases. A Structure-Sensor camera manufactured by OccipitalⓇ was used. Each patient received a 3D measurement during immediate postoperative care and then after 3 and 6 months of follow-up. This study shows no difference in volume retention at follow-up between the 2 techniques. The gain of an immediate and stable fatty layer in LDF + subfascial fat technique leads to breast volume improvement in one surgical step. Breast reconstruction with LDF and subfascial fat can be defined as a reliable solution, which provides an optimal result with a reduced number of surgical interventions when compared with a simple LDF.

[Decision-making in gender reassignment surgery]. / La décision en chirurgie de réassignation génitale.

The prescribing of hormones and the performing of gender reassignment surgery on a healthy body are dangerous and irreversible acts. To ensure patients' safety, endocrinologists and surgeons must use the skills of experienced psychiatrists to create a differential diagnosis, evaluate any frailties and weigh up the risk-benefit ratio. Therapeutic decisions are made as part of multidisciplinary consultation meetings. A minimum two-year observation period must be respected for the treatment to be covered by social security.

HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy.

Human immunodeficiency virus type 1 (HIV-1) eradication is prevented by the establishment on infection of cellular HIV-1 reservoirs that are not fully characterized, especially in genital mucosal tissues (the main HIV-1 entry portal on sexual transmission). Here, we show, using penile tissues from HIV-1-infected individuals under suppressive combination antiretroviral therapy, that urethral macrophages contain integrated HIV-1 DNA, RNA, proteins and intact virions in virus-containing compartment-like structures, whereas viral components remain undetectable in urethral T cells. Moreover, urethral cells specifically release replication-competent infectious HIV-1 following reactivation with the macrophage activator lipopolysaccharide, while the T-cell activator phytohaemagglutinin is ineffective. HIV-1 urethral reservoirs localize preferentially in a subset of polarized macrophages that highly expresses the interleukin-1 receptor, CD206 and interleukin-4 receptor, but not CD163. To our knowledge, these results are the first evidence that human urethral tissue macrophages constitute a principal HIV-1 reservoir. Such findings are determinant for therapeutic strategies aimed at HIV-1 eradication.

Reconstruction of Full-Thickness Lower Lid Defects Using Texier's Procedure: Retrospective Assessment of the Indications.

PURPOSE: Lower lid defects involving more than 75% of the lid's length or affecting the cheek are usually reconstructed with a Mustardé rotational cheek flap. This solution often induces postoperative ectropion. The Texier procedure (an upper lid myocutaneous flap and a chondromucosal alar graft) is usually indicated for 1-step reconstruction of full-thickness defects involving less than 50% of the lower lid. This retrospective study evaluated larger indications for the Texier procedure for full-thickness defects of the lower lid, results of lid defects longer than 50 or even 75%, and the use of a chondromucosal nasal septal graft for lid defects longer than 75%. MATERIALS AND METHODS: All lower lid reconstructions using the Texier procedure over a period of 29 months were retrospectively included. Data on postoperative complications and patient satisfaction were collected. RESULTS: Fifteen patients were included; one third had a defect involving no more than 50% of the lower lid, one third presented with a defect of 50 to 75%, and one third had a defect of at least 75%. In this last group, reconstruction included a septal graft. Mean follow-up was 35 months. Transitory palpebral edema was present in 100% of patients and lasted 8 months on average. No postoperative ectropion or nasal alar retraction of the graft donor site was observed. Mean satisfaction score was 2.86 of 3. CONCLUSIONS: The Texier procedure can be used as first-line treatment to reconstruct most full-thickness defects of the lower lid, including subtotal defects.

Three-stage folded forehead flap for nasal reconstruction: Objective and subjective measurements of aesthetic and functional outcomes.

BACKGROUND: The three-stage folded forehead flap (FFF) proved to be a simple and readily available method of lining replacement. To date, no clinical trial has evaluated the outcomes of the FFF on the nose shape and function. METHODS: Patients undergoing a full-thickness unilateral alar reconstruction with a forehead flap between January of 2010 and December of 2015 were included for analysis. Patients were divided into two groups: The FFF group included patients that had a unilateral alar reconstruction using a three-stage FFF; the standard forehead flap (SFF) group included patients that had a reconstruction using a two-stage forehead flap in combination with another method for lining reconstruction. The following objective measurements were performed: the alar thickness, nostril and hemi-nose areas, and nostril height. Subjective evaluation of the results was performed using the NAFEQ score. Independent raters also evaluated the appearance of the nose. RESULTS: Thirty-one patients were included: 15 in the FFF group and 16 in the SFF group. In both groups, the reconstructed ala was thicker than that on the normal side, the reconstructed nostril was smaller than the normal nostril, and the reconstructed hemi-nose was bigger than the normal side. Moreover, 84% of the patients were satisfied with their total nasal functioning. All the patients were satisfied with their total nasal appearance. CONCLUSION: The FFF showed objective, subjective, aesthetic, and functional results comparable to other lining reconstruction techniques.

Salvage of an osteocutaneous thermonecrosis secondary to tibial reaming by the induced membrane procedure.

Osteocutaneous thermonecrosis is a rare but devastating complication of tibial reaming, which can cause large and infected bone and cutaneous defects. The case presented here illustrates that the induced membrane technique described by Masquelet is a valuable option in treating this complication.

Efficacy of ultrasound, mammography and magnetic resonance imaging in detecting breast implant rupture: A retrospective study of 175 reconstructive and aesthetic sub-pectoral breast augmentation cases.

To date, the effectiveness of radiological imaging in detecting silicone breast implant rupture is uncertain. The purpose of this study is to retrospectively evaluate the effectiveness of radiological imaging when diagnosing a rupture. In this study, 175 patients with 242 breast implants were included, of which 168 and 74 implants were used for breast reconstruction and aesthetic augmentation, respectively. All patients who underwent revision surgery, between January 2015 and June 2016, following breast augmentation or reconstruction were included, regardless of any pre-operative diagnosis of rupture that had been made. The diagnosis of intracapsular rupture was verified intraoperatively and compared to the pre-operative findings. With regard to pre-operative diagnostic imaging methods, we compared magnetic resonance imaging (MRI), mammography, and ultrasonography (US) findings. Among the 242 implants that were explanted, 35 clinical ruptures were confirmed and compared with the related radiological findings. We reported 22 false positives and 15 false negatives. US was the least specific and least accurate method because of its lowest positive predictive value (PPV) and negative predictive value (NPV). Mammography was the most specific and most accurate method, with the highest PPV (96%). Surprisingly, MRI was the most sensitive; however, it was neither the most specific nor the most accurate method despite having the highest NPV (98%). After comparing these three radiological techniques, we conclude that US along with MRI can be useful for young patients. Mammography, which was characterised by high specificity and accuracy, could be useful along with MRI in investigating patients over the age of 40.

Correction of tuberous breast deformity: A retrospective study comparing lipofilling versus breast implant augmentation.

Breast implants and, more recently, autologous fat grafting are the two most common treatments used to correct tuberous breast deformity (TBD). The post-surgical quality of life between the two techniques is not well demonstrated. This study aimed to compare satisfaction and health-related quality of life in patients affected by TBD between these two techniques. All TBD patients operated between January 2008 and May 2015 were retrospectively identified, and only those treated with implants or lipofilling were included. Satisfaction was evaluated at least 6 months after surgery with the postoperative Breast-Q® augmentation module. From January 2008 to May 2015, 62 patients were recruited in our study, and 37 patients were evaluated using a Breast-Q questionnaire after at least 6 months of follow-up. Breast implant-augmented patients were significantly more satisfied concerning the "satisfaction with breasts" module (p = 0.002) and the "satisfaction with outcome" module (p = 0.00008). A question-by-question analysis revealed several interesting and significant differences, showing higher scores in most of the questions in the breast implant group. Patients in the lipofilling group, interestingly, had a mean of 1.6 interventions compared to the mean 1.36 interventions in the implant group (p = 0.23). This reflects the need to perform more surgical sessions in the lipofilling group to achieve a satisfactory result. Our study demonstrated that tuberous breast correction with implants can achieve better satisfaction along with good outcomes than lipofilling usually does.

The Human Penis Is a Genuine Immunological Effector Site.

The human penis is a main portal of entry for numerous pathogens, and vaccines able to control resulting infections locally are highly desirable. However, in contrast to the gastrointestinal or vaginal mucosa, the penile immune system and mechanisms inducing a penile immune response remain elusive. In this descriptive study, using multiparametric flow cytometry and immunohistochemistry, we characterized mucosal immune cells such as B, T, and natural killer (NK) cells from the urethra, fossa, and glans of human adult penile tissues. We show that memory B lymphocytes and CD138+ plasma cells are detected in all penile compartments. CD4+ and CD8+ T lymphocytes reside in the epithelium and lamina propria of the penile regions and have mostly a resting memory phenotype. All penile regions contain CD56dim NK cells surface expressing the natural cytotoxicity receptor NKp44 and the antibody-dependent cell cytotoxicity receptor CD16. These cells are also able to spontaneously secrete pro- and anti-inflammatory cytokines, such as IL-17 and IL-22. Finally, CCR10 is the main homing receptor detected in these penile cells although, together with CCR3, CCR6, and CCR9, their expression level differs between penile compartments. Unlike antigen-presenting cells which type differ between penile regions as we reported earlier, urethral, fossa, and glans content in immune B, T, and NK cells is comparable. However, median values per each analysis suggest that the glans, containing higher number and more activated NK cells together with higher number of terminally differentiate effector CD8+ T cells, is a superior effector site than the urethra and the fossa. Thus, the human penis is an immunologically active tissue containing the cellular machinery required to induce and produce a specific and effective response against mucosal pathogens. It can therefore be considered as a classic mucosal effector site, a feature that must be taken into account for the elaboration of efficient strategies, including vaccines, against sexually transmitted infections.

Lipofilling: A New Therapeutic Option for the Treatment of Lupus Panniculitis-Induced Atrophy.

Lupus panniculitis is a rare manifestation of cutaneous lupus erythematosus, which may lead to major aesthetic sequelae with a severe impact on patients' quality of life. We report 2 cases supporting the short- and long-term efficacy and safety of lipofilling in the treatment of lupus panniculitis-induced atrophy. These observations pave the way for prospective, larger-scale studies in patients with scarring lupus panniculitis, provided that the autoimmune pathogenic process is in complete, stable remission.

Perforator-based chimaeric thoracodorsal flap for foot reconstruction.

The reconstruction of severe defects of the ankle and foot is a challenge. The ideal solution should combine a thin skin flap on the dorsum to allow shoe fitting and a muscle flap with a split-thickness skin graft on the weight-bearing area. Perforator-based thoracodorsal chimaeric flaps allow us to achieve these two goals with minimal donor-site morbidity. We present a reconstruction of an extended circumferential defect of the ankle with an exposed heel using a chimaeric thoracodorsal perforator flap with a serratus muscle flap. The skin flap was transferred on the dorsal foot, whereas the serratus anterior muscle was transferred on the exposed heel. Postoperative recovery was uneventful and the patient began full weight bearing after 3 months. Twelve months after reconstruction, natural shape and walking function were successfully achieved.

A review of 105 subscapular-based flaps harvested using a new dorsal decubitus position: how far can we go?

OBJECTIVE: Interest in flaps based on the subscapular vascular system has decreased because of the need for intraoperative patient repositioning and the inability to employ a simultaneous 2-team approach. The aims of this study are to review our experience using dorsal decubitus patient positioning for subscapular-based flap harvest and to demonstrate the effectiveness and safety of this approach. METHODS: A retrospective review of all subscapular-based flap cases performed by the senior author at 2 hospital centers from 1995 to 2010 was conducted. Variables studied included indications for reconstruction, flap characteristics, and postoperative complications. A longitudinal roll placed between the scapulae as well as an optional perpendicularly placed shoulder roll are used to achieve dorsal decubitus patient positioning. RESULTS: One hundred five flaps were performed during the study period, and dorsal decubitus positioning was used in all cases. Eighty-four flaps were free and 21 were pedicled. Indications for reconstruction included cancer resection (n = 58), trauma (n = 32), infection (n = 9), and others (n = 6). A simultaneous 2-team approach was carried out in 70 cases. Major complications included 9 cases of arterial or venous thrombosis/insufficiency, 2 of which resulted in total flap failure. Intraoperative conversion to lateral decubitus positioning was never required. CONCLUSIONS: Dorsal decubitus harvesting for subscapular-based flaps is a practical and effective technique that enables a simultaneous 2-team approach in complex reconstructive cases. Previous limitations of these highly versatile flaps, such as the need for intraoperative patient repositioning, can thus be avoided. This approach is employed for all subscapular-based flap reconstructions performed by the senior author.

A new dorsal decubitus position for raising subscapular-based flaps.

Flaps based on the subscapular vascular system are reliable and versatile tools that provide excellent coverage for a wide range of tissue deficits. Raising these flaps in the described dorsal decubitus position permits two surgical teams to work simultaneously while obviating the need for intra-operative position changes. In cases where a subscapular-based flap is deemed the most suitable option for reconstruction, the dorsal decubitus technique eliminates many of the limitations associated with the traditional lateral decubitus approach without compromising the range of tissue obtainable.

Dorsal decubitus positioning: a novel method to harvest the latissimus dorsi flap for massive upper extremity defect reconstruction.

The latissimus dorsi, whether taken as a muscle or with a skin paddle, is one of the most useful flaps in the reconstructive surgeon's arsenal. With its predictable type V vascular pedicle, this broad muscle can be elevated on its dominant thoracodorsal pedicle or used in a reverse manner on its secondary thoracic and lumbar perforators. Traditionally harvested in a lateral decubitus position, over the last 10 years we have chosen to elevate this muscle in a dorsal decubitus position, enabling 2 surgical teams to operate simultaneously. With only one cushion placed along the vertebral column between the scapulas, each element of the subscapular system, including scapular bone, can be used to reconstruct complex upper limb defects. A vertical incision in front of the anterior axillary line is performed to identify the anterior border of the muscle, followed by a dissection in the submuscular plane to reveal the thoracodorsal pedicle and its branches. When a more complex chimeric flap is required, scapular bone, serratus muscle, and scapular or parascapular fasciocutaneous flaps are all available. To achieve the longest length possible, the pedicle can be isolated from the axillary vessels. The most common complications are related to donor site, with seroma and delayed wound healing being the most prevalent. Complaints of shoulder pain and functional disability were rare and mostly encountered in the first 2 weeks postoperatively.

Highly sensitive multivariable assay detection of melanocytic differentiation antigens and angiogenesis biomarkers in sentinel lymph nodes with melanoma micrometastases.

OBJECTIVES: To evaluate the prognostic value of melanocytic differentiation antigens and angiogenesis biomarkers in sentinel lymph nodes (SLNs) with melanoma micrometastases. DESIGN: Prognostic study of an inception cohort. SETTING: Academic research. Patients Between July 1, 1999, and July 31, 2002, all patients who had primary cutaneous or mucosal melanomas that have a Breslow depth of 1.5 mm or greater, ulceration, or Clark level IV or V, or had SLN biopsies. MAIN OUTCOME MEASURES: By the use of quantitative reverse transcription-polymerase chain reaction, the expression of the following was analyzed in SLNs: 2 melanocytic differentiation antigens (tyrosinase [P17646] and melanoma antigen recognized by T cells [MART-1; Q16655]) and genes involved in angiogenesis (VEGF [NM_001025366] and VEGFR2 [AF035121]), lymphangiogenesis (VEGFC [NM_005429], VEGFR3 [X68203], LYVE1 [NM_016164], and PROX1 [002763]), and invasion (uPA [NM_002658], PAI1 [NM_00602], and EMMPRIN [L10240]). Outcome measures were the association of these melanocytic differentiation antigens and angiogenesis biomarkers with clinicopathologic characteristics of patients, and an evaluation of the prognostic value for relapse-free survival and overall survival. RESULTS: Ninety-one patients were included, with a median follow-up period of 41 months. Micrometastases were present in 15% (14 of 91) of patients. Tyrosinase (P < .001), MART-1 (P < .001), vascular endothelial growth factor 121 (VEGF(121)) (P = .007), and PAI1 (P = .02) expression was significantly associated with micrometastasis. In univariate analysis, histologic findings and tyrosinase and MART-1 expression were significantly associated with relapse-free survival. Tyrosinase and MART-1 expression was associated with overall survival. A multiple Cox proportional hazards regression model identified negative histologic findings and tyrosinase expression that exceeded 27 copies/copy of TATA box-binding protein (third quartile) as significantly associated with an increased risk of relapse or death. CONCLUSIONS: Quantitative assessment of melanocytic differentiation antigens in SLNs, which has prognostic value, is more specific than qualitative assessment. Prognosis may be more effectively predicted by the combination of quantitative assessment of melanocytic differentiation antigens in SLNs with histologic assessment. A significant association was found between the presence of micrometastases and the expression of angiogenesis biomarkers.