Disease Association of Anti‒Carboxyethyl Lysine Autoantibodies in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurring suppurating lesions of the intertriginous areas, resulting in a substantial impact on patients' QOL. HS pathogenesis remains poorly understood. An autoimmune component has been proposed, but disease-specific autoantibodies, autoantigens, or autoreactive T cells have yet to be described. In this study, we identify a high prevalence of IgM, IgG, and IgA antibodies directed against Nε-carboxyethyl lysine (CEL), a methylglyoxal-induced advanced glycation end-product, in the sera of patients with HS. Titers of anti-CEL IgG and IgA antibodies were highly elevated in HS compared with those in healthy controls and individuals with other inflammatory skin diseases. Strikingly, the majority of anti-CEL IgG was of the IgG2 subclass and correlated independently with both disease severity and duration. Both CEL and anti-CEL‒producing plasmablasts could be isolated directly from HS skin lesions, further confirming the disease relevance of this autoimmune response. Our data point to an aberration of the methylglyoxal pathway in HS and support an autoimmune axis in the pathogenesis of this debilitating disease.

The impact of delayed wound healing on patient-reported outcomes after breast cancer surgery.

PURPOSE: Postoperative complications after breast cancer surgery may be associated with decreased quality of life. It remains unclear whether oncoplastic breast-conserving surgery or mastectomy with reconstruction lead to more postoperative complications than conventional breast surgery (CBS). As delayed wound healing (DWH) is one of the most frequent minor complications, we sought to investigate the significance of DWH for patient-reported outcomes after oncoplastic, reconstructive, and CBS. METHODS: Our study is a retrospective cohort study of consecutive patients with stage I-II breast cancer who underwent oncoplastic or CBS performed by three breast surgeons at a single tertiary referral hospital from June 2011 until May 2019. Patient-reported outcomes were evaluated postoperatively using the BREAST-Q questionnaire. Comparisons were made between patients with and without DWH. RESULTS: A total of 229 patients who met the inclusion criteria and 28 (12%) of them developed DWH, 27/158 (17%) in the oncoplastic breast-conserving surgery and reconstruction group and 1/71 (1%) in the CBS group. The mean time from surgery to BREAST-Q assessment was comparable in both groups (29 months in the DWH vs. 33 months in the normal wound healing group). No statistically significant difference for any BREAST-Q scale was detected between patients with and without DWH. This includes physical (p = 0.183), psychosocial (p = 0.489), sexual well-being (p = 0.895), and satisfaction with breasts (p = 0.068). CONCLUSION: Our study confirms that oncoplastic breast-conserving surgery and mastectomy with reconstruction lead to significantly more DWH than CBS. However, neither quality of life nor patient-reported outcomes following state-of-the-art reconstructive or oncoplastic breast-conserving surgery at a specialized center seem to be compromised.

Comparison of patient-reported outcomes among different types of oncoplastic breast surgery procedures.

BACKGROUND: This study aims to compare patient-reported outcomes (PROs) after different types of oncoplastic surgery (OPS) procedures and correlate the results with previously published normative data from women with no prior history of breast cancer (BC) and breast surgery. METHODS: Cross-sectional study of patients with stage I-II BC undergoing a specific selection of OPS procedures from 04/2012 to 12/2018 by three breast surgeons at a single tertiary referral hospital in Switzerland. PROs were evaluated using the postoperative BREAST-Q questionnaire. RESULTS: One hundred twenty-seven patients met the inclusion criteria and were surveyed. All OPS techniques achieved comparably elevated scores in satisfaction with breasts, psychosocial, and sexual well-being. Compared to normative data of healthy women, all OPS groups postoperatively achieved significantly better satisfaction with breasts, psychosocial, and sexual well-being. CONCLUSION: This study shows high PROs across all types of OPS, which were superior to normative data from healthy women. Our findings confirm that OPS is associated with high quality of life and patient satisfaction.

Lipidomics Profiling of Hidradenitis Suppurativa Skin Lesions Reveals Lipoxygenase Pathway Dysregulation and Accumulation of Proinflammatory Leukotriene B4.

Hidradenitis suppurativa (HS) is a chronic, recurring inflammatory dermatosis characterized by abscesses, deep-seated nodules, sinus tracts, and fibrosis in skin lesions around hair follicles of the axillary, inguinal, and anogenital regions. Whereas the exact pathogenesis remains poorly defined, clear evidence suggests that HS is a multifactorial inflammatory disease characterized by innate and adaptive immune components. Bioactive lipids are important regulators of cutaneous homeostasis, inflammation, and resolution of inflammation. Alterations in the lipid mediator profile can lead to malfunction and cutaneous inflammation. We used targeted lipidomics to analyze selected omega-3 and omega-6 polyunsaturated fatty acids in skin of patients with HS and of healthy volunteers. Lesional HS skin displayed enrichment of 5-lipoxygenase (LO)‒derived metabolites, especially leukotriene B4. In addition, 15-LO‒derived metabolites were underrepresented in HS lesions. Changes in the lipid mediator profile were accompanied by transcriptomic dysregulation of the 5-LO and 15-LO pathways. Hyperactivation of the 5-LO pathway in lesional macrophages identified these cells as potential sources of leukotriene B4, which may cause neutrophil influx and activation. Furthermore, leukotriene B4-induced mediators and pathways were elevated in HS lesions, suggesting a contribution of this proinflammatory lipid meditator to the pathophysiology of HS.

Comparison of Anterolateral Thigh and Radial Forearm Free Flaps in Head and Neck Reconstruction.

BACKGROUND: The radial forearm flap (RFF) and the anterolateral thigh flap (ALT) are commonly used for the reconstruction of head and neck soft-tissue defects. The aim of the study was to investigate and compare the surgical outcomes, complications and systemic condition of the patient after reconstruction of extensive head and neck defects with ALT or RFF following cancer extirpation. PATIENTS AND METHODS: Between August 2011 and November 2013, a total of 36 patients affected by head and neck cancer (31 males and five females; mean age=64.7 years, range=40-86 years) underwent microsurgical reconstruction with 29 RFF and 10 ALT procedures. The surgical outcomes and complications among these two groups were retrospectively analyzed. RESULTS: The success rate was 97% for the RFF group and 90% for the ALT group, with one total flap loss in each group. Donor-site complications occurred in 6% of the RFF group and in 7% of the ALT group. Seven RFF-treated patients (24%) and two treated with ALT (20%) experienced systemic complications. Statistical analysis confirmed no significant difference between the two groups regarding the variables investigated (p>0.05). CONCLUSION: In our experience, ALT and RFF demonstrated analogous practicability and reliability for the reconstruction of head and neck soft-tissue defects, with similar local and systemic complications and donor-site morbidity rates.

Development of color vision discrimination during childhood: differences between Blue-Yellow, Red-Green, and achromatic thresholds.

Nonvisual demands of tests affect vision test results in children. 150 children (79 females and 71 males, 5.3-12.7 years of age) were examined. Isoluminant Blue, Yellow, Red, Green, and Black and White thresholds were established with a four-alternative forced-choice and pseudo-10-bit system with adaptive staircase and gaming elements. Where Threshold=b0+b1*age-1, b1 for RG=6.26±1.90 (95% confidence limits), Achr=3.96±1.07 and BY=12.48±2.76 were significantly different. The noncolor demands of the test are the same for RG, BY, and Achr, so the later development of BY discrimination is not an artifact of the test.

The Medial Sural Artery Perforator Flap: The First Choice for Soft-Tissue Reconstruction About the Knee.

BACKGROUND: The gastrocnemius muscle flap may be considered the first choice in many cases of soft-tissue reconstruction about the knee. Limited arc of rotation and reach of the flap as well as unsightly muscle bulk are major disadvantages and were the impetus to look for a local alternative. The aim of this study is to present a consecutive series of patients with a reconstruction about the knee involving the medial sural artery perforator flap (MSAPF). METHODS: A consecutive series of 17 cases of defect reconstructions about the knee using the MSAPF is described, with an emphasis on early postoperative complications. RESULTS: No major flap-related complications occurred except 1 case of tip necrosis that healed uneventfully after excision and secondary suture. Two patients with direct donor-site closure had a minor complication that required no revision, and 2 had partial skin-graft loss. CONCLUSIONS: In summary, use of this pedicled perforator flap represents a reliable technique for soft-tissue reconstruction about the knee with an acceptable complication rate and optimal contour reconstruction without the need for a skin graft and secondary debulking procedures. The range of motion associated with the MSAPF in comparison to the range associated with the gastrocnemius muscle flap is increased so that more proximal and lateral defects can be covered. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

A Simple, Reliable, and Inexpensive Intraoperative External Expansion System for Enhanced Autologous Structural Fat Grafting.

External volume expansion of the recipient site by suction has been proposed as a way of improving fat graft survival. The objective of this study was to present an innovative and simple intraoperative external expansion system to enhance small-volume autologous fat grafting (40-80 mL) and to discuss its background and its mechanism of action. In this system, expansion is performed using a complete vacuum delivery system known as the Kiwi VAC-6000M with a PalmPump (Clinical Innovations). The recipient site is rapidly expanded intraoperatively 10 times for 30 seconds each with a negative pressure of up to 550 mm Hg before autologous fat injection. During this repetitive stimulation, the tissues become grossly expanded, developing macroscopic swelling that regresses slowly over the course of hours following the cessation of the stimulus. The system sets various mechanisms in motion, including scar release, mechanical stimulation, edema, ischemia, and inflammation, which provide an environment conducive for cell proliferation and angiogenesis. In order to maintain the graft construct in its expansive state, all patients are encouraged postoperatively to use the Kiwi three times daily for one minute per session over the course of three days. The handling of this system is simple for both the patients and the surgeon. Satisfactory clinical outcomes have been achieved without significant complications.

Phase II metabolism in human skin: skin explants show full coverage for glucuronidation, sulfation, N-acetylation, catechol methylation, and glutathione conjugation.

Although skin is the largest organ of the human body, cutaneous drug metabolism is often overlooked, and existing experimental models are insufficiently validated. This proof-of-concept study investigated phase II biotransformation of 11 test substrates in fresh full-thickness human skin explants, a model containing all skin cell types. Results show that skin explants have significant capacity for glucuronidation, sulfation, N-acetylation, catechol methylation, and glutathione conjugation. Novel skin metabolites were identified, including acyl glucuronides of indomethacin and diclofenac, glucuronides of 17ß-estradiol, N-acetylprocainamide, and methoxy derivatives of 4-nitrocatechol and 2,3-dihydroxynaphthalene. Measured activities for 10 µM substrate incubations spanned a 1000-fold: from the highest 4.758 pmol·mg skin(-1)·h(-1) for p-toluidine N-acetylation to the lowest 0.006 pmol·mg skin(-1)·h(-1) for 17ß-estradiol 17-glucuronidation. Interindividual variability was 1.4- to 13.0-fold, the highest being 4-methylumbelliferone and diclofenac glucuronidation. Reaction rates were generally linear up to 4 hours, although 24-hour incubations enabled detection of metabolites in trace amounts. All reactions were unaffected by the inclusion of cosubstrates, and freezing of the fresh skin led to loss of glucuronidation activity. The predicted whole-skin intrinsic metabolic clearances were significantly lower compared with corresponding whole-liver intrinsic clearances, suggesting a relatively limited contribution of the skin to the body's total systemic phase II enzyme-mediated metabolic clearance. Nevertheless, the fresh full-thickness skin explants represent a suitable model to study cutaneous phase II metabolism not only in drug elimination but also in toxicity, as formation of acyl glucuronides and sulfate conjugates could play a role in skin adverse reactions.

Aldehyde oxidase activity in fresh human skin.

Human aldehyde oxidase (AO) is a molybdoflavoenzyme that commonly oxidizes azaheterocycles in therapeutic drugs. Although high metabolic clearance by AO resulted in several drug failures, existing in vitro-in vivo correlations are often poor and the extrahepatic role of AO practically unknown. This study investigated enzymatic activity of AO in fresh human skin, the largest organ of the body, frequently exposed to therapeutic drugs and xenobiotics. Fresh, full-thickness human skin was obtained from 13 individual donors and assayed with two specific AO substrates: carbazeran and zoniporide. Human skin explants from all donors metabolized carbazeran to 4-hydroxycarbazeran and zoniporide to 2-oxo-zoniporide. Average rates of carbazeran and zoniporide hydroxylations were 1.301 and 0.164 pmol⋅mg skin(-1)⋅h(-1), resulting in 13 and 2% substrate turnover, respectively, after 24 hours of incubation with 10 µM substrate. Hydroxylation activities for the two substrates were significantly correlated (r(2) = 0.769), with interindividual variability ranging from 3-fold (zoniporide) to 6-fold (carbazeran). Inclusion of hydralazine, an irreversible inhibitor of AO, resulted in concentration-dependent decrease of hydroxylation activities, exceeding 90% inhibition of carbazeran 4-hydroxylation at 100 µM inhibitor. Reaction rates were linear up to 4 hours and well described by Michaelis-Menten enzyme kinetics. Comparison of carbazeran and zoniporide hydroxylation with rates of triclosan glucuronidation and sulfation and p-toluidine N-acetylation showed that cutaneous AO activity is comparable to tested phase II metabolic reactions, indicating a significant role of AO in cutaneous drug metabolism. To our best knowledge, this is the first report of AO enzymatic activity in human skin.

Cognitive abilities of children on a gray seriation test.

PURPOSE: The importance of testing children's color vision, particularly to identify color vision deficiencies at an early age, has long been agreed on by teachers and color vision researchers and healthcare workers. The classic color vision tests were not necessarily developed for children's cognitive abilities, even though they are commonly used to assess children's color vision. Although, in the past, psychologists have studied color seriation abilities of children, they have not necessarily chosen isoluminous stimuli, which would minimize brightness cues. This investigation was designed to assess the ability of children to seriate a gray series. METHODS: Tests were constructed in the form of the Farnsworth-Munsell style of arrangement test with constant intervals of metric lightness (CIE L*). Four intervals (DeltaL* = 15, 10, 5, and 3) were used. The child was instructed to arrange the colors from darker to lighter (or vice versa). RESULTS: Errors were not made on the DeltaL* = 15 series. Only isolated errors were made on the DeltaL* = 10 series. Errors were made on the DeltaL* = 5 series that diminished with age to nil in the older groups. Errors were made on the DeltaL* = 3 series at all ages studied, which also diminished with increasing age. CONCLUSIONS: Children aged 5 to 12 have sufficiently grasped the concept of seriation. They are able to complete a series with DeltaL* = 5, hence are capable of performing color arrangement tests with similar color differences such as the Lanthony New Color Test and the Farnsworth-Munsell D-15. Given the large number of errors made on DeltaL* = 3 series, it may be concluded that children's performance on the 100-hue test, at least to the age of 12 years, could be unduly influenced by non-color vision factors.

Color vision in children and the Lanthony New Color Test.

Much is known about color vision in infants, adolescents, and adults, but very few studies report the changes, which occur in color perception of children in their early schooling years. There is also a shortage of suitable color vision tests for children. This study investigated the changes in color vision of school students between 5-12 years old using the Lanthony New Color Test (NCT). Subjects of all ages were able to complete a shortened form of this test adequately. The Vingrys and King-Smith (1988) method of panel test analysis and Adams and Rodic (1982) color confusion score were adapted to analyze their performance of the test. This study confirmed that there are changes in color perception occurring in this age group. Color perception abilities increased as a function of age and there was also an improvement in the performance on the NCT with age. This can be attributed to both cognitive development and changes occurring to the color vision system.