Intra-Articular Application of Autologous, Fat-Derived Orthobiologics in the Treatment of Knee Osteoarthritis: A Systematic Review.

The aim of this study was to review the current literature regarding the effects of intra-articularly applied, fat-derived orthobiologics (FDO) in the treatment of primary knee osteoarthritis over a mid-term follow-up period. A systematic literature search was conducted on the online databases of Scopus, PubMed, Ovid MEDLINE, and Cochrane Library. Studies investigating intra-articularly applied FDO with a minimum number of 10 knee osteoarthritis patients, a follow-up period of at least 2 years, and at least 1 reported functional parameter (pain level or Patient-Reported Outcome Measures) were included. Exclusion criteria encompassed focal chondral defects and techniques including additional arthroscopic bone marrow stimulation. In 28 of 29 studies, FDO showed a subjective improvement in symptoms (pain and Patient-Reported Outcome Measures) up to a maximum follow-up of 7.2 years. Radiographic cartilage regeneration up to 3 years postoperatively, as well as macroscopic cartilage regeneration investigated via second-look arthroscopy, may corroborate the favorable clinical findings in patients with knee osteoarthritis. The methodological heterogeneity in FDO treatments leads to variations in cell composition and represents a limitation in the current state of knowledge. However, this systematic review suggests that FDO injection leads to beneficial mid-term results including symptom reduction and preservation of the affected joint in knee osteoarthritis patients.

The Triple Adipose-Derived Stem Cell Exosome Technology as a Potential Tool for Treating Triple-Negative Breast Cancer.

BACKGROUND: Extracellular vesicles are pivotal mediators in intercellular communication, facilitating the exchange of biological information among healthy, pathological and tumor cells. Between the diverse subtypes of extracellular vesicles, exosomes have unique properties and clinical and therapeutical applications. Breast cancer ranks as one of the most prevalent malignancies across the globe. Both the tumor core and its surrounding microenvironment engage in a complex, orchestrated interaction that facilitates cancer's growth and spread. METHODS: The most significant PubMed literature about extracellular vesicles and Adipose-Derived Stem Cell Exosomes and breast cancer was selected in order to report their biological properties and potential applications, in particular in treating triple-negative breast cancer. RESULTS: Adipose-Derived Stem Cell Exosomes represent a potential tool in targeting triple-negative breast cancer cells at three main levels: the tumor core, the tumor microenvironment and surrounding tissues, including metastases. CONCLUSIONS: The possibility of impacting triple-negative breast cancer cells with engineered Adipose-Derived Stem Cell Exosomes is real. The opportunity to translate our current in vitro analyses into a future in vivo scenario is even more challenging.

Cosmetic Breast Augmentation with Autologous Ex Vivo-Expanded Adipose-Derived Mesenchymal Stem/Stromal Cell (Stemform®)-Enriched Fat Grafts: A Study of the First Twenty-Two Real-World Patients.

BACKGROUND: Fat grafting is commonly utilized in breast surgery, and since it was first described, clinicians and researchers have stridden towards improvement of graft retention. Current advancements include adding adipose-derived mesenchymal stem/stromal cells (MSC(AT)s), which have demonstrated promise for improved graft retention. OBJECTIVES: This study reports outcomes for the first twenty-two patients undergoing breast augmentation (Stemform BA) or artificial implant replacement (Stemform AIR) with MSC(AT)-enriched fat in a real-world setting. METHODS: Autologous MSC(AT)s were isolated and expanded ex vivo, then mixed with lipoaspirate and injected as enriched fat for Stemform BA and AIR. The breast volume was measured preoperatively and at 3 and 12 months postoperative using a 3D Infinity Dual-Lens Camera and LifeVizApp software. Additionally, independent plastic surgeons evaluated clinical images, and patient satisfaction was obtained at equal time points. RESULTS: Twenty-two patients were included. All completed 3 and 12 months clinical follow-up and 3 months volume measurements. Nineteen patients completed 12 months volume measurements. The median fat graft retention at 12 months was 95.7% (IQR = 82.44-103.12%) for Stemform BA patients and 113.0% (IQR = 94.8-131.2%) for Stemform AIR patients. The Stemform BA patients had a median breast enlargement of 172.0% (IQR = 156.7-241.0%). The implant replacement volume of Stemform AIR patients was 102% (IQR = 85.1-130.3%). The patient reported 92.8% and 100% would elect to repeat treatment if they had the opportunity for Stemform BA and Stemform AIR, respectively. CONCLUSION: Breast augmentation and breast implant replacement patients receiving ex vivo-expanded MSC(AT)-enriched fat grafts had high graft retention and patient satisfaction scores. The paper confirms the clinical efficacy of using ex vivo-expanded MSC(AT)s. 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 .

The Ponytail Lift: 22 Years of Experience in 600 Cases of Endoscopic Deep Plane Facial Rejuvenation.

BACKGROUND: During aging, the face loses volume with progressive sagging of the soft tissues, while the neck demonstrates skin laxity and muscle banding. The treatment of facial and neck aging usually involves a traditional facelift, which can cause noticeable scarring and distortion of anatomy. OBJECTIVES: Modern facelift surgery must avoid such shortcomings and still address aging in all layers of the face. To achieve this goal a novel surgical technique was developed and coined the "Ponytail Lift" (PTL). When global facial rejuvenation is indicated, this procedure is combined with neck skin excision and referred to as the "Ponytail Facelift" (PTFL). METHODS: A retrospective analysis of 600 consecutive cases over 22 years (2000-2022) undergoing facial rejuvenation employing the endoscopic techniques PTL and PTFL was performed. Patients were followed for at least 12 months postoperatively. Demographics, surgical data as well as complications were recorded and analyzed. Additionally, technical details of the PTL and PTFL are discussed. RESULTS: There were no instances of postoperative skin flap necrosis and no permanent nerve injuries were recorded. An additional surgical touch up procedure to address unsatisfied aesthetic needs was performed in 20 cases. CONCLUSIONS: The Ponytail procedures offer a step-wise approach matched to the extent of the problem and are intended to refresh or transform the face with minimal incisions. Representing a deep plane facelift without the scar burden the incisions are hidden in the temple scalp, post-auricular and posterior scalp. The described techniques are safe and effective while providing reliable and satisfying results.

Nagor Impleo Round Silicone Gel Breast Implants: Early Outcome Analysis after 340 Primary Breast Augmentations.

For decades, implant-based breast augmentation has been one of the most performed surgical procedures for cosmetic purposes around the world. Hence, novel manufactured implants should be critically investigated to prove them safe and effective. Here, the authors describe the first independently conducted clinical study on Nagor Impleo textured round breast implants. For this retrospective study, outcomes of 340 consecutive female patients undergoing primary cosmetic breast augmentation were analyzed. Demographic and surgical data as well as outcomes and complications were evaluated. Furthermore, a survey concerning effectiveness and aesthetic satisfaction after breast augmentation was examined. All 680 implants were placed in a submuscular plane with incisions at the inframammary fold. The main indications for surgery were hypoplasia and hypoplasia with asymmetry. The mean implant volume was 390 cc and the main type of projection was high profile. The most common complications were hematoma and capsular contracture (0.9 percent, respectively). The overall revision rate for complications was 2.4%. Additionally, almost all patients showed increased quality of life and aesthetic satisfaction after a breast augmentation. Hence, all patients would undergo breast augmentation again with these newly launched devices. Nagor Impleo implants demonstrate a low complication rate and high safety profile. Although high aesthetic satisfaction and quality of life results were achieved, analysis of an even larger series over a longer period of time would be beneficial to evaluate the reliability of this implant.

Augmentation-Mastopexy: Analysis of 95 Consecutive Patients and Critical Appraisal of the Procedure.

Single-stage mastopexy-augmentation has been demonstrated to be a safe procedure. However, revisions may still be necessary. We evaluate 95 consecutive patients undergoing mastopexy-augmentation and introduce a new surgical technique for the procedure: the modified dual plane technique. In this retrospective study, 95 patients (mean age 34 ± 11 years) underwent mastopexy-augmentation between 2009 and 2019. The procedures were classified as subglandular, dual plane, or modified dual plane technique. The outcome measures included major and minor complications. A total of 19 patients underwent a subglandular procedure, 32 patients a dual plane procedure, and 44 patients a modified dual plane procedure. We observed a high overall complication rate in the subglandular group (n = 12, 63%), dual plane group (n = 15, 47%), and modified dual plane group (n = 10, 23%). Complications leading to implant loss/change occurred in seven patients in the subglandular group (37%), six patients in the dual plane group (19%), and no patient in the modified dual plane group. While we observed a high complication rate in patients undergoing mastopexy-augmentations, the modified dual plane technique was associated with a lower complication rate.

Effect of Music on the Efficiency of Performing a Microsurgical Arterial Anastomosis: A Prospective Randomized Study.

Introduction Music is commonly played in operating rooms. Because microsurgery demands utmost concentration and precise motor control, we conducted the present study to investigate a potentially beneficial impact of music on performing a microsurgical anastomosis. Materials and Methods We included a novice group (15 inexperienced medical students) and a professional group (15 experienced microsurgeons) in our study. Simple randomization was performed to allocate participants to the music-playing first or music-playing second cohort. Each participant performed two end-to-end anastomoses on a chicken thigh model. Participant demographics, their subjective preference for work environment (music/no music), and time to completion were noted. The performance of the participants was assessed using the Stanford Microsurgery and Resident Training (SMaRT) scale by an independent examiner, and the final anastomoses were evaluated according to the anastomosis lapse index. Results Listening to music had no significant effect on time to completion, SMaRT scale, and anastomosis lapse index scores in both novice and professional cohorts. However, the subjective preference to work while listening to music correlated with high SMaRT scale scores within the professional cohort ( p = 0.044). Conclusion Playing their preferred music in the operating room improves the performance scores of surgeons, but only if they subjectively appreciate working with background music.

A Novel Hair Restoration Technology Counteracts Androgenic Hair Loss and Promotes Hair Growth in A Blinded Clinical Trial.

Androgenic alopecia (AGA) is a genetically predetermined condition that occurs as a result of stepwise miniaturization of the dermal papilla. During this process, the hair follicle suffers from increasing malnutrition and eventually dies, causing progressive hair loss. We recently highlighted that HIF-1α modulation may counteract hair loss. Here, we aim to demonstrate the positive influence of Tomorrowlabs HIF strengthening factor [HSF] hair restoration technology on hair biology in a monocentric blinded clinical trial over a total period of 9 months. A trial with 20 subjects (4 female and 16 male) and once-daily application of [HSF] hair restoration technology to the scalp was conducted. To assess the tolerability and efficacy of [HSF], testing included dermatological assessment, determination of hair loss by counting after combing, macro images of the head and TrichoScan evaluation of hair density as well as the proportion of anagen hair versus telogen hair. The clinical data show Tomorrowlabs [HSF] hair restoration to be safe and effective to counteract AGA. The use of Tomorrowlabs [HSF] hair restoration resulted in improvements in the clinical parameters of hair quality such as thickness (+7.2%), hair density (+14.3%) and shine and elasticity (+20.3%) during the test period. The effectiveness of the test product was further determined by a significant reduction in hair loss of an average of 66.8% in treatment-responsive subjects after 6 months and an increase in hair growth reaching up to 32.5%, with an average percentage change of 8.4% in all participants and 10.8% in the responsive patients (85% of the study cohort) after 9 months on TrichoScan evaluation. The hair growth cycle was harmonized with the result of an average anagen hair percentage increase of +8.0% and telogen hair percentage reduction of -14.0% shown in the test area. Applicable for both sexes in an alcohol-free formulation, beneficial to scalp health and free of complications or side effects, this novel product provides objectively measurable results counteracting hair loss paired with an improved look and feel of the hair.

Advanced Endoscopic Techniques in Asian Facial Rejuvenation.

Asian anatomy and concepts of beauty differ from whites. Traditional SMAS face-lifts are developed based on a white patient population and not ideal to achieve the aesthetic goals of Asian patients. The characteristics of the ideal facial rejuvenation techniques for Asians comprise hidden incisions to avoid hypertrophic scarring and cultural stigma. The authors' approach addresses the Asian face in all dimensions using minimally invasive modalities combined with skin regenerative methods. This surgical technique is called the "Ponytail Lift." It simulates the vertical lift of the face when having the hair pulled up in a high ponytail.

Arthroscopy with Lipoaspirate and Plasma Infiltration Using Adipose-Derived Stem Cells Plus Platelet-Rich Plasma: Harvesting and Injection for Arthroscopic Treatment of Cartilage Defects of the Knee.

Osteoarthritis, predominantly of the knee, is a highly prevalent disease leading to pain, reduced quality of life, and significantly reduced ability to work. With autologous orthobiologic options, new regenerative treatment methods have emerged, offering an alternative to early surgical intervention. Supercharged Liparthroplasty combines arthroscopy with lipoaspirate and plasma infiltration of the joint. Lipoaspirate contains high levels of adipose-derived stem cells, which show chondroprotective and anti-inflammatory qualities. Intra-articular injection, combined with platelet-rich plasma administration for accelerated cartilage metabolism, thus provides an optional approach in osteoarthritis treatment. This article aims to provide in detail our regimen for Supercharged Liparthroplasty, including tissue harvesting and preparation of the injectables, therefore enabling physicians to adopt this point-of-care technique.

Naming the Barriers between Anti-CCR5 Therapy, Breast Cancer and Its Microenvironment.

Breast cancer represents the most common malignancy among women in the world. Although immuno-, chemo- and radiation therapy are widely recognized as the therapeutic trifecta, new strategies in the fight against breast cancer are continually explored. The local microenvironment around the tumor plays a great role in cancer progression and invasion, representing a promising therapeutic target. CCL5 is a potent chemokine with a physiological role of immune cell attraction and has gained particular attention in R&D for breast cancer treatment. Its receptor, CCR5, is a well-known co-factor for HIV entry through the cell membrane. Interestingly, biology research is unusually unified in describing CCL5 as a pro-oncogenic factor, especially in breast cancer. In silico, in vitro and in vivo studies blocking the CCL5/CCR5 axis show cancer cells become less invasive and less malignant, and the extracellular matrices produced are less oncogenic. At present, CCR5 blocking is a mainstay of HIV treatment, but despite its promising role in cancer treatment, CCR5 blocking in breast cancer remains unperformed. This review presents the role of the CCL5/CCR5 axis and its effector mechanisms, and names the most prominent hurdles for the clinical adoption of anti-CCR5 drugs in cancer.

Liparthroplasty for Thumb Carpometacarpal Joint Osteoarthritis: A Case Series with Median 5 Years of Follow-Up.

Liparthroplasty has recently been discussed as a promising bridging therapy after failed conservative treatment options to postpone arthroplasty surgery of the thumb carpometacarpal joint as long as possible. The current study investigates the sustainability of this method in seven stage II and twenty-four stage III osteoarthritis patients (twenty-seven female and four male cases). Data were evaluated preinterventionally, six months postinterventionally, and two years postinterventionally, as well as a final follow-up assessment after median 5.1 years. We found a significant reduction of all postinterventional disabilities of the arm, shoulder, and hand (dash) scores and pain levels compared to the ones prior to liparthroplasty. Moreover, we even detected a reduction in both parameters within the postinterventional course, so that the DASH scores of our final investigation were significantly lower than the values after six months. Furthermore, 12 of our 31 cases demanded a surgical conversion due to recurrence of symptoms. A binary regression analysis found smokers to have 11 times higher odds for therapy failure, leading to surgical conversion. Seventeen out of nineteen patients in our final assessment stated that they were pleased with liparthroplasty. Due to favorable mid-term outcomes of 61% of the 31 initially treated patients, we recommend liparthroplasty as a reliable bridging therapy for preserving joint integrity as long as possible, especially in non-smoking patients.

Irradiated Triple-Negative Breast Cancer Co-Culture Produces a Less Oncogenic Extracellular Matrix.

Triple-negative breast cancer is the most common and most deadly cancer among women. Radiation is a mainstay of treatment, administered after surgery, and used in the hope that any remaining cancer cells will be destroyed. While the cancer cell response is normally the focus of radiation therapy, little is known about the tumor microenvironment response after irradiation. It is widely reported that increased collagen expression and deposition are associated with cancer progression and poor prognosis in breast cancer patients. Aside from the classical fibrotic response, ratios of collagen isoforms have not been studied in a radiated tumor microenvironment. Here, we created one healthy co-culture of stromal fibroblasts and adipose-derived stem cells, and one triple-negative breast cancer co-culture, made of stromal fibroblasts, adipose derived stem cells, and triple-negative breast cancer cells. After irradiation, growth and decellularization of co-cultures, we reseeded the breast cancer cells for 24 h and analyzed the samples using mass spectrometry. Proteomic analysis revealed that collagen VI, a highly oncogenic collagen isoform linked to breast cancer, was decreased in the irradiated cancer co-culture. This indicates that the anti-cancer impact of radiation may be not only cell ablative, but also influential in creating a less oncogenic microenvironment.

The Three-Hour Lower Body Lift: Evolution of a Technique and Personal Experience after 155 Consecutive Cases.

BACKGROUND: Body-contouring is a surgical field in growing demand, as the number of massive weight loss patients following bariatric surgery is increasing. The purpose of this study was to provide a straightforward and time-efficient circumferential body lift technique to achieve optimal lower truncal contouring. PATIENTS AND METHODS: A total of 155 massive weight loss patients (133 women and 22 men) underwent lower body lift surgery between 2006 and 2018. The mean preoperative weight reduction and body mass indices were 56.5 ± 16.6 kg and 26.7 ± 4.7 kg/m2, respectively. The preoperative markings focused on the back and gluteal region, and the modified surgical technique are described. Additionally, improvements of intra-operative repositioning of the patient and how to deal with sterilization and dressings are elucidated. RESULTS: The average intra-operative time was 178 ± 54.6 minutes. The mean follow-up of all patients was 8.2 ± 2.4 years. The most common complications were related to wound dehiscence (n = 38) and seroma (n = 18). The mean weight of the resected tissue was 3 056 ± 1 816.5 g. CONCLUSION: The lower body lift represents an effective and safe body contouring procedure to treat massive weight loss patients with multiple regions of concern. The current study describes a modified surgical technique that reduces operating time and complications, notably. LEVEL OF EVIDENCE IV: 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 http://www.springer.com/00266 .

Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis.

OBJECTIVE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and severe skin and mucosal reactions that are associated with high mortality. Despite the severity, an evidence-based treatment protocol for SJS/TEN is still lacking. METHOD: In this systematic review and meta-analysis, the PubMed database was searched using the following terms: [Stevens-Johnson syndrome] OR [toxic epidermal necrolysis] AND [therapy] OR [treatment] over a 20-year period (1999-2019) in the German and English language. All clinical studies reporting on the treatment of SJS/TEN were included, and epidemiological and diagnostic aspects of treatment were analysed. A meta-analysis was conducted on all comparative clinical studies that met the inclusion criteria. RESULTS: A total of 88 studies met the inclusion criteria, reporting outcomes in 2647 patients. Treatment was either supportive or used systemic corticosteroid, intravenous immunoglobulin, plasmapheresis, cyclosporine, thalidomide or cyclophosphamide therapy. The meta-analysis included 16 (18%) studies, reporting outcomes in 976 (37%) patients. Systemic glucocorticoids showed a survival benefit for SJS/TEN patients in all analyses compared with other forms of treatment. Cyclosporine treatment also showed promising results, despite being used in a small cohort of patients. No beneficial effects on mortality could be demonstrated for intravenous immunoglobulins. CONCLUSION: Glucocorticoids and cyclosporine may be tentatively recommended as the most promising immunomodulatory therapies for SJS/TEN, but these results should be investigated in future prospective controlled trials.

Epidermal-Derived Hedgehog Signaling Drives Mesenchymal Proliferation during Digit Tip Regeneration.

Hand injuries often result in significant functional impairments and are rarely completely restored. The spontaneous regeneration of injured appendages, which occurs in salamanders and newts, for example, has been reported in human fingertips after distal amputation, but this type of regeneration is rare in mammals and is incompletely understood. Here, we study fingertip regeneration by amputating murine digit tips, either distally to initiate regeneration, or proximally, causing fibrosis. Using an unbiased microarray analysis, we found that digit tip regeneration is significantly associated with hair follicle differentiation, Wnt, and sonic hedgehog (SHH) signaling pathways. Viral over-expression and genetic knockouts showed the functional significance of these pathways during regeneration. Using transgenic reporter mice, we demonstrated that, while both canonical Wnt and HH signaling were limited to epidermal tissues, downstream hedgehog signaling (through Gli) occurred in mesenchymal tissues. These findings reveal a mechanism for epidermal/mesenchyme interactions, governed by canonical hedgehog signaling, during digit regeneration. Further research into these pathways could lead to improved therapeutic outcomes after hand injuries in humans.

Stevens-Johnson syndrome and toxic epidermal necrolysis: a 10-year experience in a burns unit.

OBJECTIVE: Stevens-Johnson syndrome (SJS) and its more severe counterpart, toxic epidermal necrolysis (TEN), are skin hypersensitivity reactions defined by epidermal blistering and necrosis. The exact pathophysiology of SJS/TEN is yet to be deciphered, but a number of risk factors have been identified including adverse drug reactions. The diagnosis of SJS/TEN is made on a clinical basis, and treatment consists of supportive care and occasionally immunosuppressants, such as cyclosporin, high-dose intravenous immunoglobulins and/or corticosteroids. Mortality rates can reach 20-25% in adults but are reduced with early intervention. To identify optimal treatment regimens, to better understand the patient cohort affected, and to help identify key risk factors for mortality, we report our experience with the treatment and management of SJS/TEN patients. METHODS: A retrospective review of consecutive patients with SJS and/or TEN admitted to a single burns centre in Germany, between 2008 and 2018, was conducted. The primary outcomes of demographics, clinical course, treatment and patient-reported outcomes were recorded and compared with a control group of patients with burns without a diagnosis of SJS/TEN. RESULTS: A total of 23 patients with SJS/TEN met the inclusion criteria: 17 (74%) with TEN; four (17%) with SJS/TEN overlap; and two (9%) with SJS. Of the patients, 14 (61%) were female and nine (39%) were male. Patient age ranged from 32-78 years (mean: 52 years). A matched cohort of 23 patients with burns served as the control group. All patients received standard of care with a multidisciplinary team. Compared with the control group, SJS/TEN patients had higher mortality rates (n=6, 26% versus n=8, 35%, respectively). The average age of death was 69 years in SJS/TEN patients versus 63 years in control group patients. Age and SCORTEN scores were significant predictors of mortality. CONCLUSIONS: SJS and TEN are rare but extreme reactions of the skin and mucosa, associated with high disease mortality rates. This 10-year single-centre retrospective review contributes to the bank of information for reviews evaluating the management of SJS/TEN patients.

Seasonal impact on surgical site infections and wound healing disturbance in carpal tunnel surgery: A retrospective cohort study.

Carpal tunnel syndrome is the most common entrapment syndrome of a peripheral nerve. The gold standard treatment is open carpal tunnel release which has a high success rate, a low complication rate, and predictable postoperative results. However, it has not been analysed yet if there is a seasonal influence on complications for carpal tunnel release, a highly elective procedure. In this retrospective study, we determine whether there is a seasonal impact on surgical site infections (SSI) and wound healing disorders (WHD) in primary carpal tunnel syndrome surgery. Between 2014 and 2018, we have assessed 1385 patients (65% female, 35% male) at a mean age of 61.9 (SD 15.3) years, which underwent open carpal tunnel release because of primary carpal tunnel syndrome. The seasonal data such as the warm season (defined as the period from 1st of June until 15th of September), the average daily and monthly temperature, and the average relative humidity were analysed. Patient demographics were examined including body mass index, alcohol and nicotine abuse, the use of anticoagulants and antiplatelet drugs as well as comorbidities. These data were correlated regarding their influence to the rate of surgical site infections and wound healing disorders in our study collective. A postoperative SSI rate of 2.4% and a WHD rate of 7% were detected. Our data confirms the warm season, the average monthly temperature, and male sex as risk factors for increasing rates of WHDs. Serious SSIs with subsequent revision surgery could be correlated with higher age and higher relative humidity. However there is no seasonal impact on SSIs. We therefore advise considering the timing of this elective surgery with scheduling older male patients preferably during the cold season to prevent postoperative WHDs.