Scar versus shape: patient-reported outcome after different surgical approaches to gynecomastia measured by modified BREAST Q®.

OBJECTIVES: The challenge in the operative therapy for enlargement of the male breast is to deal with the skin excess. Shape and scars are the major parameters after which patients assess their operative result. Therefore, we assessed the satisfaction rate among patients undergoing subcutaneous mastectomy at our institution with special regard to scar tissue formation and the postoperative appearance of the chest wall in dependence of the surgical approach (periarolar versus inframammary fold). METHODS: The study includes n = 36 male patients who underwent subcutaneous mastectomy at AGAPLESION Markus Hospital Frankfurt/Main. Patient's satisfaction dependent with the appearance of the chest wall and scar formation was evaluated by a modified BREAST Q® questionnaire plus two male-based additional questions. RESULTS: There is no statistically significant difference in satisfaction with the operative result depending on the pattern of incision (periareolar versus submammary periareolar; 81.9% versus 75.5%) with the operative result. Evaluation of additional questions of the modified BREAST Q® questionnaire showed that 86% of the patients (n = 31) would rather have more scars and a flatter chest wall. A BMI >25 kg/m2 is accompanied by a higher risk for complications (p = 0.04). CONCLUSIONS: Periareolar incision is still the method of choice, if promising an aesthetic appealing result. When reaching its limits though, we showed that a flat and male-shaped appearance of the chest wall is priority for the patients and should therefore be for the surgeon as well.

A distinct M2 macrophage infiltrate and transcriptomic profile decisively influence adipocyte differentiation in lipedema.

Lipedema is a chronic and progressive adipose tissue disorder, characterized by the painful and disproportionate increase of the subcutaneous fat in the lower and/or upper extremities. While distinct immune cell infiltration is a known hallmark of the disease, its role in the onset and development of lipedema remains unclear. To analyze the macrophage composition and involved signaling pathways, anatomically matched lipedema and control tissue samples were collected intra-operatively from gender- and BMI-matched patients, and the Stromal Vascular Fraction (SVF) was used for Cytometry by Time-of-Flight (CyTOF) and RNA sequencing. The phenotypic characterization of the immune component of lipedema versus control SVF using CyTOF revealed significantly increased numbers of CD163 macrophages. To gain further insight into this macrophage composition and molecular pathways, RNA sequencing of isolated CD11b+ cells was performed. The analysis suggested a significant modification of distinct gene ontology clusters in lipedema, including cytokine-mediated signaling activity, interleukin-1 receptor activity, extracellular matrix organization, and regulation of androgen receptor signaling. As distinct macrophage populations are known to affect adipose tissue differentiation and metabolism, we evaluated the effect of M2 to M1 macrophage polarization in lipedema using the selective PI3Kγ inhibitor IPI-549. Surprisingly, the differentiation of adipose tissue-derived stem cells with conditioned medium from IPI-549 treated SVF resulted in a significant decreased accumulation of lipids in lipedema versus control SVF. In conclusion, our results indicate that CD163+ macrophages are a critical component in lipedema and re-polarization of lipedema macrophages can normalize the differentiation of adipose-derived stem cells in vitro evaluated by the cellular lipid accumulation. These data open a new chapter in understanding lipedema pathophysiology and may indicate potential treatment options.

Differential role of cytosolic Hsp70s in longevity assurance and protein quality control.

70 kDa heat shock proteins (Hsp70) are essential chaperones of the protein quality control network; vital for cellular fitness and longevity. The four cytosolic Hsp70's in yeast, Ssa1-4, are thought to be functionally redundant but the absence of Ssa1 and Ssa2 causes a severe reduction in cellular reproduction and accelerates replicative aging. In our efforts to identify which Hsp70 activities are most important for longevity assurance, we systematically investigated the capacity of Ssa4 to carry out the different activities performed by Ssa1/2 by overproducing Ssa4 in cells lacking these Hsp70 chaperones. We found that Ssa4, when overproduced in cells lacking Ssa1/2, rescued growth, mitigated aggregate formation, restored spatial deposition of aggregates into protein inclusions, and promoted protein degradation. In contrast, Ssa4 overproduction in the Hsp70 deficient cells failed to restore the recruitment of the disaggregase Hsp104 to misfolded/aggregated proteins, to fully restore clearance of protein aggregates, and to bring back the formation of the nucleolus-associated aggregation compartment. Exchanging the nucleotide-binding domain of Ssa4 with that of Ssa1 suppressed this 'defect' of Ssa4. Interestingly, Ssa4 overproduction extended the short lifespan of ssa1Δ ssa2Δ mutant cells to a lifespan comparable to, or even longer than, wild type cells, demonstrating that Hsp104-dependent aggregate clearance is not a prerequisite for longevity assurance in yeast.

Microsurgical Phalloplasty in Nontranssexual Patients - Considerations After a Retrospective Single-center Analysis of 23 Cases.

OBJECTIVE: To evaluate the outcome of a single-center series of penile reconstruction using the radial free forearm flap in rare indications. MATERIALS AND METHODS: From April 1993 until September 2016, 23 nontranssexual patients underwent phallic reconstruction by the use of a neuromicrovascular free radial forearm flap in our clinic. Patient-specific characteristics, surgical techniques, complications, and outcomes were retrospectively evaluated and interpreted. RESULTS: The indications for surgery were: disorders of sex development (34.8%), reconstruction after oncologic surgery (34.8%), automutilation (8.7%), iatrogenic (8.7%), microphallus (8.7%), and 1 case of priapism (4.3%). Two patients (8.7%) had a total flap necrosis and 2 patients (8.7%) had a partial flap necrosis; 3 out of these 4 patients were heavy smokers. Urinary fistulae and strictures were frequent but were successfully managed by urologists in all cases. There was no statistically significant correlation between smoking, comorbidities, number of venous anastomoses, and complications. CONCLUSION: In departments experienced in microsurgery, the goals of penile reconstruction could also be achieved in patients with rare indications by the use of the neuromicrovascular free radial forearm flap. Despite the high rate of postoperative complications, penile reconstruction with the free radial forearm flap yields satisfying results. An intensive cooperation between the plastic-reconstructive team and the urological team is a prerequisite to achieve the best surgical result.

Multimodal Evaluation of Functional Nerve Regeneration in Transgender Individuals After Phalloplasty With a Free Radial Forearm Flap.

BACKGROUND: Constructing a sensitive phallus is a key objective in sex affirmation surgery, but still there is a major lack of evidence in outcome analysis of postoperative sensibility of the newly constructed body part. AIM: To evaluate the innervation and sensibility of a forearm free-flap neophallus with nerve coaptation by a broad-spectrum follow-up. METHODS: The phallic sensibility of 20 transgender individuals who underwent phalloplasty with a free radial forearm flap was evaluated by a standardized multimodal approach, examining 5 main sensory modalities. Measurements were performed in defined areas at the phallus and at the unoperated forearm as a control area. Additionally, all patients were asked to complete a questionnaire about their subjective quality of life and ability to orgasm. OUTCOME: This study evaluated the following parameters: perception of pressure (Semmes-Weinstein monofilaments) and vibration (C64 Hz tuning fork), static two-point discrimination, sharp-blunt and hot-cold discrimination at the phallus and the forearm, sum score of calculated life satisfaction, and ability to orgasm. RESULTS: Most of the patients (n = 14) were able to perceive 2 or more sensory modalities tested at the newly constructed phallus. 2 patients did not develop any sensibility. Interestingly, the median values for vibration perception were similar for the phallus and the unoperated forearm. Pressure sensibility was present at the phallus, but less than at the forearm. Moreover, sharp-blunt sensibility was present in 11 patients. In contrast, clear cold-warm discrimination could not be achieved, although the majority of patients detected the cold stimulus. A two-point discrimination of up to 23 mm could not be detected in either body part. 15 patients experienced orgasms without difficulty after 23 months (n = 20 after 54 months). CLINICAL IMPLICATIONS: We observed successful recovery of sensibility at the phalli for the majority of patients, including the preservation of orgasm. STRENGTHS & LIMITATIONS: Our institution is one of the few centers regularly performing phalloplasties in transgender patients, especially preferring the technique of Gottlieb and Levine. This study contributes to the few studies that perform sensory testing at the phallus and is unique in its kind in that it uses a multimodal approach. A limitation of this study is the limited number of cases and the limited validity of vibratory testing. CONCLUSION: Confirming a promising tactile sensibility after phalloplasty with a neurovascular radial forearm flap, the next step would be to identify whether this reinnervation effectively develops due to nerve coaptation or spontaneous sprouting. Küenzlen L, Nasim S, van Neerven S, et al. Multimodal Evaluation of Functional Nerve Regeneration in Transgender Individuals After Phalloplasty With a Free Radial Forearm Flap. J Sex Med 2020;17:1012-1024.

Long-term results measured by BREAST-Q reveal higher patient satisfaction after "autoimplant-mastopexy" than augmentation-mastopexy.

BACKGROUND: The aim of a mastopexy is to raise the breast projection, tighten the skin envelope, and place the nipples in an optimal position in projection to the inframammary fold. This procedure is often combined with prosthetic implants or an autoimplant. Given the current increasing demand for the use of autologous tissue, we evaluated mastopexies combined with either an autoimplant or prosthetic implant in terms of patient satisfaction and long-term results. METHODS: We evaluated 34 patients who underwent a mastopexy with simultaneous breast prosthesis or an autoimplant. During follow-ups we obtained standardized breast measurements, BREAST-Q score, and pre- and postoperative photographs to perform photometric measurements. RESULTS: BREAST-Q score of patients that underwent autoimplant-mastopexies revealed a higher patient satisfaction with significant differences in satisfaction with breast appearance (69±18 vs. 55±16, P=0.03) and outcome (71±18 vs. 48±26, P=0.009). Regarding breast shape, photometric evaluations presented a significantly different breast shape with higher upper pole fullness in augmentation-mastopexy patients. No statistical significance between long-term results and complication rates could be observed in either patient groups. CONCLUSIONS: The BREAST-Q score implies a higher overall long-term satisfaction in patients that received autoimplant-mastopexy with similar long-term results compared with augmentation-mastopexy. Nevertheless, individual decision-making is necessary and should be based on the degree of ptosis, existing breast volume, previous operations, and patients' preferences regarding postoperative breast shape and projection.

Yeast and human Ysl2p/hMon2 interact with Gga adaptors and mediate their subcellular distribution.

The Gga proteins represent a family of ubiquitously expressed clathrin adaptors engaged in vesicle budding at the tubular endosomal network/trans Golgi network. Their membrane recruitment is commonly thought to involve interactions with Arf and signals in cargo through the so-called VHS domain. For yeast Gga proteins, however, partners binding to its VHS domain have remained elusive and Gga localization does not absolutely depend on Arf. Here, we demonstrate that yeast Gga recruitment relies on a network of interactions between the scaffold Ysl2p/Mon2p, the small GTPase Arl1p, and the flippase Neo1p. Deletion of either YSL2 or ARL1 causes mislocalization of Gga2p, whereas a neo1-69 mutant accumulates Gga2p on aberrant structures. Remarkably, Ysl2p directly interacts with human and yeast Ggas through the VHS domain, and binding to Gga proteins is also found for the human Ysl2p orthologue hMon2. Thus, Ysl2p represents an essential, evolutionarily conserved member of a network controlling direct binding and membrane docking of Ggas. Because activated Arl1p is part of the network that binds Gga2p, Arf and Arf-like GTPases may interact in a regulatory cascade.