Tape strips detect molecular alterations and cutaneous biomarkers in skin of patients with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) has a high unmet need for better treatments. Biopsies are considered the gold standard for studying molecular alterations in skin. A reproducible, minimally invasive approach is needed for longitudinal monitoring in trials and in pediatric populations. OBJECTIVE: To determine whether skin tape strips can detect molecular alterations in HS and identify biomarkers of disease activity. METHODS: We performed RNA sequencing on tape strips collected from lesional and healthy-appearing (nonlesional) HS skin (n = 22) and healthy controls (n = 21). We correlated the expression of skin biomarkers between tape strips and a previously published gene-signature of HS biopsies. RESULTS: Tape strips detected upregulation of known HS biomarkers (eg, Interleukin[IL]-17A) in nonlesional and/or lesional skin and also identified novel clinically actionable targets, including OX40 and JAK3. The expression of Th17 and tumor necrosis factor-α pathways were highly correlated between tape strips and biopsies. HS clinical severity was significantly associated with expression of biomarkers (eg tumor necrosis factor-α , IL-17 A/F, OX40, JAK1-3, IL-4R) in HS lesional and/or nonlesional skin. LIMITATIONS: Sample size. Tape stripping is limited in depth. CONCLUSION: This study validates tape strips as a minimally-invasive approach to identify cutaneous biomarkers in HS. This provides a novel avenue for monitoring treatment efficacy and a potential step toward individualized therapy in HS.

Association of Spironolactone Use With Risk of Cancer: A Systematic Review and Meta-analysis.

IMPORTANCE: While originally approved for the management of heart failure, hypertension, and edema, spironolactone is commonly used off label in the management of acne, hidradenitis, androgenetic alopecia, and hirsutism. However, spironolactone carries an official warning from the US Food and Drug Administration regarding potential for tumorigenicity. OBJECTIVE: To determine the pooled occurrence of cancers, in particular breast and prostate cancers, among those who were ever treated with spironolactone. DATA SOURCES: PubMed, Cochrane Library, Embase, and Web of Science were searched from inception through June 11, 2021. The search was restricted to studies in the English language. STUDY SELECTION: Included studies reported the occurrence of cancers in men and women 18 years and older who were exposed to spironolactone. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers (K.B. and H.H.) selected studies, extracted data, and appraised the risk of bias using the Newcastle-Ottawa Scale. Studies were synthesized using random effects meta-analysis. MAIN OUTCOMES AND MEASURES: Cancer occurrence, with a focus on breast and prostate cancers. RESULTS: Seven studies met eligibility criteria, with sample sizes ranging from 18 035 to 2.3 million and a total population of 4 528 332 individuals (mean age, 62.6-72.0 years; in the studies without stratification by sex, women accounted for 17.2%-54.4%). All studies were considered to be of low risk of bias. No statistically significant association was observed between spironolactone use and risk of breast cancer (risk ratio [RR], 1.04; 95% CI, 0.86-1.22; certainty of evidence very low). There was an association between spironolactone use and decreased risk of prostate cancer (RR, 0.79; 95% CI, 0.68-0.90; certainty of evidence very low). There was no statistically significant association between spironolactone use and risk of ovarian cancer (RR, 1.52; 95% CI, 0.84-2.20; certainty of evidence very low), bladder cancer (RR, 0.89; 95% CI, 0.71-1.07; certainty of evidence very low), kidney cancer (RR, 0.96; 95% CI, 0.85-1.07; certainty of evidence low), gastric cancer (RR, 1.02; 95% CI, 0.80-1.24; certainty of evidence low), or esophageal cancer (RR, 1.09; 95% CI, 0.91-1.27; certainty of evidence low). CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, spironolactone use was not associated with a substantial increased risk of cancer and was associated with a decreased risk of prostate cancer. However, the certainty of the evidence was low and future studies are needed, including among diverse populations such as younger individuals and those with acne or hirsutism.

Change in Rheologic Properties of Facial Soft-Tissue Fillers across the Physiologic Angular Frequency Spectrum.

BACKGROUND: The number of soft-tissue filler injections performed in the United States is constantly increasing and reflects the high demand for enhanced facial and body attractiveness. The objective of the present study was to measure the viscoelastic properties of soft-tissue fillers when subjected to different testing frequencies. The range of tested frequencies represents clinically different facial areas with more [lips (high frequency)] or less [zygomatic arch (low frequency)] soft-tissue movement. METHODS: A total of 35 randomly selected hyaluronic acid-based dermal filler products were tested in an independent laboratory for their values of G', G″, tan δ, and G* at angular frequencies between 0.1 and 100 radian/second. RESULTS: The results of the objective analyses revealed that the viscoelastic properties of all tested products changed between 0.1 and 100 radian/second angular frequency. Changes in G' ranged from 48.5 to 3116 percent, representing an increase in their initial elastic modulus, whereas changes in G″ ranged from -53.3 percent (i.e., decrease in G″) to 7741 percent (i.e., increase in G″), indicating both an increase and a decrease in their fluidity, respectively. CONCLUSIONS: The increase in G' would indicate the transition from a "softer" to a "harder" filler, and the observed decrease in G″ would indicate an increase in the filler's "fluidity." Changes in the frequency of applied shear forces such as those occurring in the medial versus the lateral face will influence the aesthetic outcome of soft-tissue filler injections.

Soft tissue distribution pattern of facial soft tissue fillers with different viscoelastic properties.

BACKGROUND: Soft tissue filler product distribution and tissue integration have been shown to depend on myriad factors including the injector type, injector size, and injection angle. AIM: This study aims to investigate the magnitude of product spread across fascial soft tissue layers in relation to product viscoelastic properties. PATIENTS/METHODS: A total of 168 injection procedures were conducted in two female Caucasian body donors with a mean age of 80 years (range: 79-81) and a mean body mass index of 23.6 kg/m2 (range: 21.0-26.6). The injection procedures were performed in the forehead, scalp, zygomatic arch, mandible, clavicle, and sternum. The injected materials included Belotero® Soft, Belotero® Balance, Belotero® Intense, Belotero® Volume, Radiesse® , and Radiesse® Plus. Layer-by-layer dissections were performed to investigate the vertical distribution of the injected product. RESULTS: The mean product spread was for Belotero® Soft 4.54 ± 0.91; Belotero® Balance 3.85 ± 1.19; Belotero® Intense 3.04 ± 1.34; Belotero® Volume 2.58 ± 1.27; Radiesse® 1.31 ± 0.47; and Radiesse® Plus 1.27 ± 0.45 with P < .001. Bivariate correlations between product spread and storage modulus (G') revealed an inverse relationship of moderate strength with rp  = -0.651 and P < .001. CONCLUSION: The results of the present study revealed that products that were more fluid and less viscous distributed into more superficial fascial layers than products that were less fluid and more viscous (P < .001). This relationship held true irrespective of injected location.

Subperiosteal injections during facial soft tissue filler injections-Is it possible?

BACKGROUND: It can be hypothesized that safety during soft tissue filler injection could be enhanced if the product could be positioned between the periosteum and the bone surface i.e. subperiosteal. AIM: This study investigated the feasibilityof subperiosteal injections. PATIENTS/METHODS: We analysed 126 injection procedures performed in seven Caucasian body donors (4 males, 3 females) with a mean age of 75.29 ± 4.95 years [range: 70 - 87] and a mean body mass index of 23.53 ± 3.96 kg/m2 [range: 16.46 - 32.23]. The injection procedures were performed in the forehead, scalp, zygomatic arch and the mandible bilaterally. Injection procedures were conducted using 25G, 27G and 30G sharp-tip needles (TSK Laboratory, Tochigi, Japan) and at various angles from the bone surface measured with a goniometer: 90 degrees (perpendicular), 45 degrees and 10 degrees (as tangential as possible to bone surface). RESULTS: Cadaveric dissections of the injection sites showed that no product was located deep to the periosteum in any of the investigated regions. This indicates that all performed injection procedures positioned the product superficial to the periosteum (100%) with a zero-success rate of subperiosteal injections. CONCLUSION: In the setting of this cadaveric investigation, despite varying needle size and injection angle, subperiosteal injection could not be achieved. This indicates that the product can spread uncontrolled into more superficial layers yielding an increased risk for adverse aesthetic and vascular events.

How to best utilize the line of ligaments and the surface volume coefficient in facial soft tissue filler injections.

BACKGROUND: Recent advances in facial anatomy have increased our understanding of facial aging and where to best position facial soft tissue fillers. AIM: Aim of this study was to investigate a novel injection protocol which makes use of concepts like the line of ligaments or the surface - volume coefficient. MATERIALS AND METHODS: A total of 306 Caucasian patients (270 females, mean age 45.1 ± 11.4 years; 36 males, mean age 45.9 ± 11.6 years) were retrospectively investigated after the injection following a standardized protocol. This protocol comprised a total of six boluses and one retrograde fanning injections in the infraorbital area utilizing a 22G and a 25G blunt-tip cannula, respectively. Medial midfacial distances were measured using skin surface landmarks and compared after the injection of the partial and the total algorithm. RESULTS: Distances between the dermal location of the lateral SOOF and the dermal location of the mandibular ligament increased by 0.17 ± 0.11 mm with P < .001, to the corner of the mouth by 0.20 ± 0.09 mm with P < .001 and to the nasal ala by 0.20 ± 0.11 mm with P < .001. The repositioning of the facial soft tissues resulted also in a decrease of the height of the lower eyelid by 0.49 ± 0.13 mm with P < .001. CONCLUSION: The results revealed that utilizing these novel anatomic concepts, a mean amount of 0.32 cc high G-prime soft tissue filler injected in the lateral SOOF can change midfacial distances by an average of 0.19 mm.

Can smiling influence the blood flow in the facial vein?-An experimental study.

BACKGROUND: The understanding of functional facial anatomy and the interplay between facial structures is crucial for safe and effective minimally invasive and cosmetic surgical procedures. AIM: In this experimental study, we investigate the hypothesis that smiling can alter the blood flow in the angular/facial vein. MATERIALS AND METHODS: Twenty-six observations from 15 healthy volunteers (6 men, 9 women) with a mean age of 50.53 ± 13.27 (range: 24-66) were obtained. Doppler ultrasound imaging of the infraorbital segment of the angular vein (cranial to the zygomaticus major muscle) was performed and the venous flow was measured in a smiling and a resting, nonsmiling facial position. RESULTS: A statistically significant change in venous blood flow was detected upon smiling: a reduction in flow from 6.12 ± 3.0 cm/s to 0.52 ± 1.3 cm/s (P = .001). After three seconds, 80.8% of the observations had a blood flow of 0.0 cm/s. Increasing age was significantly correlated with a persistent blood flow during smiling (rp  = .469; P = .016). No differences between gender and sides of the face were observed. CONCLUSION: The results of this experimental study reveal that smiling can significantly reduce the venous flow in the angular/facial vein. Contraction of the zygomaticus major muscle compresses the vein against the underlying maxilla. Both minimally invasive and surgical procedures that alter the SMAS, the periocular musculature or the deep midfacial fat compartments might affect angular/facial venous flow.

Influence of needle size and injection angle on the distribution pattern of facial soft tissue fillers.

BACKGROUND: Soft tissue filler injections are performed using either sharp-tip needles or blunt-tip cannulas. Product can change planes in an uncontrolled manner during needle injections, potentially leading to unintentional intra-arterial placement. There is a paucity of data on the influence of injection angle on the dispersion patterns of soft tissue fillers. MATERIALS AND METHODS: A total of 126 injection procedures were conducted in seven Caucasian body donors (four males, three females) with a mean age of 75.29 ± 4.95 years and a mean body mass index of 23.53 ± 3.96 kg/m2 . Injection procedures were performed in various facial regions (forehead, scalp, zygomatic arch, mandibular angle), utilizing different needle sizes (25G, 27G, 30G) and different angles (90°, 45°, 10°). Layer-by-layer dissections were performed to verify the location of the injected product. Dissections were facilitated by the colored material. RESULTS: Utilizing a 30G needle (compared to a 25G needle) reduces the superficial spread with OR 0.70 (95% CI, 0.48-0.99) and P = 0.049, whereas injecting at 90° (vs 10° with the bevel down) increases the odds for superficial spread with OR 10.0 (95% CI, 7.11-14.09) and P < 0.001. CONCLUSION: Precision during soft tissue filler injections, defined as the product remaining in the plane of intended implantation, can be enhanced by changing the needle size and the injection angle. Utilizing a 30G needle and injecting at a 10° angle with bevel facing down reduces the uncontrolled product distribution into superficial fascial layers.

Extra-articular Metacarpal Fractures: Closed Reduction and Percutaneous Pinning Versus Open Reduction and Internal Fixation.

BACKGROUND: There is no consensus on the optimal operative treatment of isolated closed metacarpal fractures as every technique is associated with advantages and shortcomings. This retrospective study aims to compare the outcomes of single metacarpal, extra-articular fractures treated with closed reduction and percutaneous pinning (CRPP) versus open reduction and internal fixation (ORIF). METHODS: The charts of all patients who underwent surgical repair of closed metacarpal fractures at our institutions from 2009 to 2016 were reviewed. 70 patients met the inclusion criteria, 44 had undergone CRPP and 26 ORIF with plate or lag screws. Subgroup analyses of all patients stratified by both fracture pattern and fracture location were performed. Additionally, subgroup analyses of outcomes based on the time from injury to surgery were conducted. Clinical outcomes included immobilization time, total active motion, stiffness, complication and reoperation rates, as well as occupational therapy referral rates and duration. Functional outcomes were determined using the Quick-DASH (Disabilities of the Arm, Shoulder and Hand) score via telephone questionnaire administered retrospectively. RESULTS: Overall, there was no significant difference in functional outcome parameters including total active motion (CRPP 91% of normal vs. ORIF 87% of normal), stiffness, therapy referrals, and complications between treatment groups. Patients treated with CRPP, regardless of fracture pattern or location, were operated on earlier than those treated with ORIF (avg. 7 days vs. 15 days). The immobilization time for patients treated with ORIF was significantly less than those treated with CRPP (19.7 vs. 30.7 days; p=0.001). This difference in the immobilization time also reflected the outcomes of the subgroup analyses based on the post-injury time of surgery. When transverse shaft fractures were examined independently as a subgroup, ORIF resulted in improved post-operative range of motion vs. CRPP (100% normal vs. 91% normal). The mean DASH score for each group was satisfactory and the difference was not statistically significant (16.3 for the CRPP and 18.7 for the ORIF group, p=0.805). CONCLUSION: Both CRPP and ORIF are viable techniques with good clinical outcomes and low complication rates. ORIF of closed metacarpal fractures allowed for earlier mobilization when compared with CRPP without compromising fracture stability, clinical or functional short-term outcomes.

Influences of Age, Gender, and Body Mass Index on the Thickness of the Abdominal Fatty Layers and its Relevance for Abdominal Liposuction and Abdominoplasty.

BACKGROUND: Liposuction and lipoabdominoplasty procedures frequently involve the treatment of the superficial and deep fatty layers of the abdomen. OBJECTIVES: The aim of the present investigation was to provide comprehensive data on the thickness of the abdominal fatty layers in relation to age, gender, and body mass index (BMI). METHODS: The study investigated 150 Caucasian individuals; there was an equal distribution of males and females (each n = 75) and a balanced distribution of age (n = 30 per decade: 20-29, 30-39, 40-49, 50-59, and 60-69 years) and BMI (n = 50 per group: BMI ≤24.9, 25.0-29.9, and ≥30 kg/m2). Ultrasound-based measurements of the superficial and deep abdominal fatty layers were performed. RESULTS: An increase in BMI was associated with an increase in total abdominal wall fat thickness. The measured increase was related more to the thickness of the deep fatty layer than to the thickness of the superficial fatty layer (Z = 1.80, P = 0.036). An increase in age was associated with a decrease in thickness of the superficial fatty layer (rp = -0.104, P = 0.071) but with an increase in thickness of the deep fatty layer (rp = 0.197, P = 0.001). CONCLUSIONS: Age and BMI can change the thickness of both the superficial and deep fatty layers of the anterior abdominal wall, thus influencing the plan and conduct of cosmetic surgical procedures. Knowledge of the layered anatomy of the anterior abdominal wall, as well as its associated blood supply, is important for surgeons performing procedures in this area.

Influence of Age, Sex, and Body Mass Index on the Depth of the Superficial Fascia in the Face and Neck.

BACKGROUND: Nonsurgical skin-tightening procedures are increasing in popularity, as patients seek aesthetic interventions that are safe with minimal downtime. OBJECTIVE: This study was designed to provide precise data on the depth of the superficial fascia-the structure of action-of the face and neck. METHODS: One hundred fifty Caucasian individuals (75 men and 75 women) were investigated with a balanced distribution of age (n = 30 per decade: 20-29, 30-39, 40-49, 50-59, and 60-69 years) and body mass index (BMI) (n = 50 per group: BMI ≤ 24.9 kg/m, BMI between 25.0 and 29.9 kg/m, and BMI ≥ 30 kg/m). The distance between skin surface and the superficial fascia was measured through ultrasound in the buccal region, premasseteric region, and lateral neck. RESULTS: The mean distance between skin surface and superficial fascia was for the buccal region 4.82 ± 0.9 mm, range (2.60-6.90); for the premasseteric region 4.25 ± 0.6 mm, range (2.60-5.80); and for the lateral neck 3.71 ± 0.5 mm, range (2.0-5.0). The depth of the superficial fascia increased with increasing BMI, whereas it decreased with advanced age. CONCLUSION: Knowing the precise depth of the superficial fascia for nonsurgical skin-tightening procedures will guide practitioners toward safer and more effective outcomes.

Abdominoplasty in the Obese Patient: Risk versus Reward.

BACKGROUND: The incidence of obesity is on the rise worldwide. Many surgeons elect not to perform abdominoplasty on patients with a high body mass index, fearing an increased risk of perioperative complications. In this study, the authors compare the outcomes of obese and nonobese patients who underwent abdominoplasty. METHODS: A retrospective chart analysis was performed on all patients who underwent abdominoplasty by a single surgeon from 2009 to 2016. Complication rates were compared in obese and nonobese patients. Patients were excluded if they did not undergo a full abdominoplasty, underwent a combined surgical procedure, or underwent liposuction in an area outside of the abdomen or flanks at the time of the abdominoplasty. RESULTS: A total of 83 patients were included: 62 nonobese and 21 obese patients. The obese group had a higher average body mass index (34. 9 kg/m versus 25.1 kg/m; p < 0.001). Follow-up time was similar (310 days versus 265 days; p = 0.468). No significant differences were seen with regard to perioperative seroma formation (14.2 percent versus 22.5 percent; p = 0.419)), wound dehiscence (9.5 percent versus 11.29 percent; p = 0.822), hematoma formation (4.7 percent versus 1.6 percent; p = 0.438), or surgical-site infection (9.5 percent versus 8.0 percent; p = 0.835). No instances of venous thromboembolism were observed. CONCLUSIONS: Abdominoplasty, with or without concurrent liposuction, in obese patients, is a safe and effective procedure with similar perioperative complication rates as the nonobese patient population. No significant differences were observed in perioperative complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Structural Gender Dimorphism and the Biomechanics of the Gluteal Subcutaneous Tissue: Implications for the Pathophysiology of Cellulite.

BACKGROUND: This study was performed to investigate gender differences in gluteal subcutaneous architecture and biomechanics to better understand the pathophysiology underlying the mattress-like appearance of cellulite. METHODS: Ten male and 10 female body donors [mean age, 76 ± 16.47 years (range, 36 to 92 years); mean body mass index, 25.27 ± 6.24 kg/m (range, 16.69 to 40.76 kg/m)] were used to generate full-thickness longitudinal and transverse gluteal slices. In the superficial and deep fatty layers, fat lobule number, height, and width were investigated. The force needed to cause septal breakage between the dermis and superficial fascia was measured using biomechanical testing. RESULTS: Increased age was significantly related to decreased dermal thickness, independent of sex (OR, 0.997, 95 percent CI, 0.996 to 0.998; p < 0.0001). The mean number of subdermal fat lobules was significantly higher in male body donors (10.05 ± 2.3) than in female body donors (7.51 ± 2.7; p = 0.003), indicating more septal connections between the superficial fascia and dermis in men. Female sex and increased body mass index were associated with increased height of superficial fat lobules. The force needed to cause septal breakage in male body donors (38.46 ± 26.3 N) was significantly greater than in female body donors (23.26 ± 10.2 N; p = 0.021). CONCLUSIONS: The interplay of dermal support, septal morphology, and underlying fat architecture contributes to the biomechanical properties of the subdermal junction. This is influenced by sex, age, and body mass index. Cellulite can be understood as an imbalance between containment and extrusion forces at the subdermal junction; aged women with high body mass index have the greatest risk of developing (or worsening of) cellulite.

The posterior temporal supraSMAS minimally invasive lifting technique using soft-tissue fillers.

BACKGROUND: To investigate the effectiveness of the posterior temporal supraSMAS minimally invasive lifting technique and compared it to experiments performed in fresh human body donors by applying skin vector displacement measurement technology. MATERIALS AND METHODS: A total of 15 patients (14 females/1 male) with a mean age of 37.1 ± 9.4 years and a mean body mass index of 21.4 ± 3.3 kg/m2 were included into this observational analysis. The injection procedure was additionally performed in 2 male and 1 female fresh body donors with a mean age of 85.67 ± 9.7 years and a mean body mass index of 23.83 ± 4.7 kg/m2 . Different grades of skin laxity, variable amounts of product, and the application with and without subcision were tested and measured via three-dimensional reconstructions and surface displacement vectors using Vectra software with VAM module. RESULTS: Esthetic outcome was rated by an independent professional observer and by the patient immediately after the treatment (76.67% ± 17.6% vs 66.67% ± 18.1%) (P = 0.001) and after 1 month (80.00% ± 14.0% vs 75.00% ± 21.1%) (P = 0.19). Skin laxity, subcision, and the application of more than 1.0 cc per side resulted in our experimental setting in a smaller magnitude of skin displacement vectors indicating a reduced lifting effect. CONCLUSION: The posterior temporal supraSMAS minimally invasive lifting procedure seems to be a valid technique to treat temporal volume loss and to reduce the signs of age-related changes in the middle and lower face, ie "marionett line" and jowl deformity.

The layered anatomy of the jawline.

BACKGROUND: To investigate the layered anatomy of the jawline and to provide anatomic background for the formation of the labiomandibular sulcus, the jowl deformity, and the "double-chin" for safe and effective minimally invasive procedures. MATERIALS AND METHODS: Seventy-two fresh-frozen human cephalic cadavers (32 males, 40 females; mean age 75.2 ± 10.9 years, BMI 24.2 ± 6.6 kg/m2 , 99% Caucasian ethnicity) were investigated by layer-by-layer anatomical dissection. Magnet resonance and computed tomographic imaging was additionally carried out to support the anatomical findings. RESULTS: No major neuro-vascular structures were found to run in the subdermal plane or in the subcutaneous fat. The jowl deformity was identified to be caused by the loose adherence of the platysma to the mandible, which occurs posterior (but not anterior) to the mandibular ligament. The formation of the submental sulcus was identified to be caused by the submental septum, an osteo-cutaneous adhesion spanning all facial layers in the submental area. The formation of the labiomandibular sulcus was caused by the change in the subcutaneous fibro-connective arrangement rather than by an underlying adhesion or ligament. CONCLUSION: The layered arrangement of the jawline predisposes this region for subdermal and subcutaneous treatment options located superficial to the platysma. Subdermal subcision procedures might have a beneficial effect on the labiomandibular sulcus as the boundary between the different types of subcutaneous arrangement, which form the sulcus, is being smoothened.