A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling.

Oncogenic activation of RAS genes via point mutations occurs in 20%-30% of human cancers. The development of effective RAS inhibitors has been challenging, necessitating new approaches to inhibit this oncogenic protein. Functional studies have shown that the switch region of RAS interacts with a large number of effector proteins containing a common RAS-binding domain (RBD). Because RBD-mediated interactions are essential for RAS signaling, blocking RBD association with small molecules constitutes an attractive therapeutic approach. Here, we present evidence that rigosertib, a styryl-benzyl sulfone, acts as a RAS-mimetic and interacts with the RBDs of RAF kinases, resulting in their inability to bind to RAS, disruption of RAF activation, and inhibition of the RAS-RAF-MEK pathway. We also find that ribosertib binds to the RBDs of Ral-GDS and PI3Ks. These results suggest that targeting of RBDs across multiple signaling pathways by rigosertib may represent an effective strategy for inactivation of RAS signaling.

Structural insights into the interaction of three Y-shaped ligands with PI3Kα.

Class IA phosphoinositide 3-kinase alpha (PI3Kα) is an important drug target because it is one of the most frequently mutated proteins in human cancers. However, small molecule inhibitors currently on the market or under development have safety concerns due to a lack of selectivity. Therefore, other chemical scaffolds or unique mechanisms of catalytic kinase inhibition are needed. Here, we report the cryo-electron microscopy structures of wild-type PI3Kα, the dimer of p110α and p85α, in complex with three Y-shaped ligands [cpd16 (compound 16), cpd17 (compound 17), and cpd18 (compound 18)] of different affinities and no inhibitory effect on the kinase activity. Unlike ATP-competitive inhibitors, cpd17 adopts a Y-shaped conformation with one arm inserted into a binding pocket formed by R770 and W780 and the other arm lodged in the ATP-binding pocket at an angle that is different from that of the ATP phosphate tail. Such a special interaction induces a conformation of PI3Kα resembling that of the unliganded protein. These observations were confirmed with two isomers (cpd16 and cpd18). Further analysis of these Y-shaped ligands revealed the structural basis of differential binding affinities caused by stereo- or regiochemical modifications. Our results may offer a different direction toward the design of therapeutic agents against PI3Kα.

Cryo-EM structures of cancer-specific helical and kinase domain mutations of PI3Kα.

Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that perform multiple and important cellular functions. The protein investigated here belongs to class IA of the PI3Ks; it is a dimer consisting of a catalytic subunit, p110α, and a regulatory subunit, p85α, and is referred to as PI3Kα. The catalytic subunit p110α is frequently mutated in cancer. The mutations induce a gain of function and constitute a driving force in cancer development. About 80% of these mutations lead to single-amino-acid substitutions in one of three sites of p110α: two in the helical domain of the protein (E542K and E545K) and one at the C-terminus of the kinase domain (H1047R). Here, we report the cryo-electron microscopy structures of these mutants in complex with the p110α-specific inhibitor BYL-719. The H1047R mutant rotates its sidechain to a new position and weakens the kα11 activation loop interaction, thereby reducing the inhibitory effect of p85α on p110α. E542K and E545K completely abolish the tight interaction between the helical domain of p110α and the N-terminal SH2 domain of p85α and lead to the disruption of all p85α binding and a dramatic increase in flexibility of the adaptor-binding domain (ABD) in p110α. Yet, the dimerization of PI3Kα is preserved through the ABD-p85α interaction. The local and global structural features induced by these mutations provide molecular insights into the activation of PI3Kα, deepen our understanding of the oncogenic mechanism of this important signaling molecule, and may facilitate the development of mutant-specific inhibitors.

Nanobodies and chemical cross-links advance the structural and functional analysis of PI3Kα.

Nanobodies and chemical cross-linking were used to gain information on the identity and positions of flexible domains of PI3Kα. The application of chemical cross-linking mass spectrometry (CXMS) facilitated the identification of the p85 domains BH, cSH2, and SH3 as well as their docking positions on the PI3Kα catalytic core. Binding of individual nanobodies to PI3Kα induced activation or inhibition of enzyme activity and caused conformational changes that could be correlated with enzyme function. Binding of nanobody Nb3-126 to the BH domain of p85α substantially improved resolution for parts of the PI3Kα complex, and binding of nanobody Nb3-159 induced a conformation of PI3Kα that is distinct from known PI3Kα structures. The analysis of CXMS data also provided mechanistic insights into the molecular underpinning of the flexibility of PI3Kα.

Cryo-EM structures of PI3Kα reveal conformational changes during inhibition and activation.

Phosphoinositide 3-kinases (PI3Ks) are lipid kinases essential for growth and metabolism. Their aberrant activation is associated with many types of cancers. Here we used single-particle cryoelectron microscopy (cryo-EM) to determine three distinct conformations of full-length PI3Kα (p110α-p85α): the unliganded heterodimer PI3Kα, PI3Kα bound to the p110α-specific inhibitor BYL-719, and PI3Kα exposed to an activating phosphopeptide. The cryo-EM structures of unbound and of BYL-719-bound PI3Kα are in general accord with published crystal structures. Local deviations are presented and discussed. BYL-719 stabilizes the structure of PI3Kα, but three regions of low-resolution extra density remain and are provisionally assigned to the cSH2, BH, and SH3 domains of p85. One of the extra density regions is in contact with the kinase domain blocking access to the catalytic site. This conformational change indicates that the effects of BYL-719 on PI3Kα activity extend beyond competition with adenosine triphosphate (ATP). In unliganded PI3Kα, the DFG motif occurs in the "in" and "out" positions. In BYL-719-bound PI3Kα, only the DFG-in position, corresponding to the active conformation of the kinase, was observed. The phosphopeptide-bound structure of PI3Kα is composed of a stable core resolved at 3.8 Å. It contains all p110α domains except the adaptor-binding domain (ABD). The p85α domains, linked to the core through the ABD, are no longer resolved, implying that the phosphopeptide activates PI3Kα by fully releasing the niSH2 domain from binding to p110α. The structures presented here show the basal form of the full-length PI3Kα dimer and document conformational changes related to the activated and inhibited states.

Free Tissue Transfer for Reconstruction After Bilateral Skin Sparing Mastectomy-A Systematic Review.

BACKGROUND: Breast cancer is the most commonly diagnosed malignant neoplasia in females worldwide. Overall survival and patients' choice for bilateral mastectomy have increased. It is therefore important to offer breast reconstructive procedures to improve patient quality of life and self-esteem. The aim of this systematic literature review is to quantify the outcome and sustainability of bilateral breast reconstruction using autologous, vascularized free tissue transfer. METHODS: A systematic literature review of PubMed, Cochrane, and the Web of Science databases was performed. A total of 5879 citations were identified, and 12 studies met the inclusion criteria. RESULTS: A total of 1316 patients were included, with a mean age of 47.2 years. Overall, 32.5% of patients experienced a complication after breast reconstruction. If reported, 7.45% of patients experienced major complications, while 20.7% had minor complications.The following flaps were used for breast reconstruction, in order of reducing frequency: DIEP (45.45%), TRAM (22.73%), SIEA (9.09%), SGAP (9.09%), TUG (4.55%), TMG (4.55%), and LD/MLD (4.55%). CONCLUSIONS: Current studies indicate that bilateral breast reconstruction using autologous, vascularized free tissue transfer is a safe procedure for postmastectomy reconstruction and offers stable long-term results. This is particularly in comparison to implant-based breast reconstruction.

Nerve Decompression in the Lower Leg Results in an Improvement in Symptoms in Patients With Both Diabetic and Idiopathic Polyneuropathy.

BACKGROUND: Patients suffering from polyneuropathy often complain of pain, tingling, and numbness sensations, as well as an increased risk of falling with the corresponding subsequent complications. If symptoms persist after conservative treatment options have been exhausted, nerve decompression in the lower extremity, as described by Dellon, can bring about an improvement in symptoms in many patients. Dellon originally reported that this surgery led to very successful outcomes in patients with diabetic polyneuropathy. In this study, we compare our postsurgical results in patients with diabetic versus idiopathic polyneuropathy. METHODS: Thirty-three patients with idiopathic or diabetic polyneuropathy who had undergone Dellon nerve decompression in the lower extremity between 2011 and 2013 were included in the retrospective study. Pain (numeric rating scale [NRS] 0-10; 0, no pain; 10, worst imaginable pain), tingling, numbness, Hoffmann-Tinel sign, and Semes-Weinstein monofilament were assessed in 20 patients with diabetic polyneuropathy and in 13 patients with idiopathic polyneuropathy. RESULTS: Three months after surgery, a significant reduction in pain was evident in patients with diabetic polyneuropathy, from a preoperative level of NRS 4.9 (minimum, 0; maximum, 10) to 2 (minimum, 0; maximum, 8; P = 0.005). Ninety percent of patients complained of tingling ( P = 0.000) before surgery and 18% after surgery, whereas 100% complained of numbness before surgery and 41% ( P = 0.000) after surgery. One hundred percent of patients had no measurable surface sensitivity before surgery (measured with the Semes-Weinstein monofilament), whereas 3 months after surgery, only 24% of patients still had no measurable surface sensitivity ( P = 0.000). A positive Hoffmann-Tinel sign was recorded in 85% of patients before surgery and only in 11% 3 months after surgery ( P = 0.000). In the case of patients with idiopathic polyneuropathy, a reduction in pain was evident 3 months after surgery, from a preoperative level of NRS 3.9 (minimum, 0; maximum, 9) to 2.2 (minimum, 0; maximum, 9; P = 0.058). Seventy-seven percent of patients complained of tingling before surgery and 42% after surgery ( P = 0.111), whereas 92% complained of numbness before surgery and 50% after surgery ( P = 0.030). Seventy-seven percent of patients had no measurable surface sensitivity before surgery (measured with the Semes-Weinstein monofilament), whereas 3 months after surgery, only 33% of patients still had no measurable surface sensitivity ( P = 0.047). A positive Hoffmann-Tinel sign was recorded in 62% of patients before surgery and only in 17% 3 months after surgery ( P = 0.041). CONCLUSIONS: Not only patients with diabetic polyneuropathy but also those with idiopathic polyneuropathy benefit from Dellon nerve decompression surgery in the lower extremities.

The Use of the Symani Surgical System® in Emergency Hand Trauma Care.

Background: The use of robotic systems for microsurgery has gained popularity in recent years. Despite its drawbacks, such as increased learning time and lack of haptic feedback, robot-assisted microsurgery is beneficial for emergency care due to its reduced risk of tremor and fatigue. The Symani Surgical System® is 1 example of this advanced technology. The device offers a range of possibilities in the field of microsurgery by combining precision and dexterity, revolutionizing microsurgical procedures. This article explores the applications of the Symani in microsurgical procedures in emergency hand trauma care, highlighting its advantages and limitations. Material and Methods: We present the results of 62 anastomoses of blood vessels under .8 mm diameter after hand trauma. 31 anastomoses were conducted using the Symani Surgical System®, and the other 31 were done as a control group in hand-sewn technique. Study Sample: The patient characteristics, including sex, age, and risk factors, were matched. Results: We found no significant differences in the anastomosis surgery length when performed with the Symani (arterial 17.3 ± 1.9 min; venous 11.5 ± 1.3 min) vs the hand-sewn technique (arterial 16.1 ± 1.4 min; venous 10.2 ± 1.8 min). Additionally, the learning curve consistently decreased over time, with the 10th surgery taking 30% (arterial) less time. Conclusion: Our study indicates that robot-assisted microsurgery can help surgeons maintain a relaxed and focused state while producing results comparable to hand-sutured procedures in emergency care.

Organization of Hannover Skin Bank: Sterile culture and procurement protocols for viable cryopreserved allogeneic skin grafts of living donors.

Preserved allogeneic donor skin still represents one of the gold standard therapies in temporary wound coverage in severely burned patients or chronic wounds. Allogeneic skin grafts are currently commercially available as cryo- or glycerol-preserved allografts through skin tissue banks all over the world. Most of the skin tissue banks rely on human cadaveric skin donations. Due to the chronic shortage of human allogeneic transplants, such as skin, and increasing costs in the procurement of allografts from other skin tissue banks, Hannover Medical School has been building up its own skin tissue bank based on allogeneic skin grafts from living donors who underwent surgical treatment (i.e., body-contouring procedures, such as abdominioplasties). This article presents procedures and protocols for the procurement and processing of allogeneic skin grafts according to national legislation and European regulations and guidelines. Beside protocols, initial microbiological data regarding the sterility of the harvested grafts are presented. The results currently form the basis for further investigations as well as clinical applications. In summary, a microbiological testing and acceptance procedure is presented that ensures adequate patient safety and skin viability.

Spider silk erectile nerve reconstruction in robot-assisted radical prostatectomy: a first-in-men feasibility analysis.

PURPOSE: To investigate the safety and feasibility of spider silk interposition for erectile nerve reconstruction in patients undergoing robotic radical prostatectomy (RARP). METHODS: The major-ampullate-dragline from Nephila edulis was used for spider silk nerve reconstruction (SSNR). After removal of the prostate with either uni- or bilateral nerve-sparing, the spider silk was laid out on the site of the neurovascular bundles. Data analysis included inflammatory markers and patient reported outcomes. RESULTS: Six patients underwent RARP with SSNR. In 50% of the cases, only a unilateral nerve-sparing was performed, bilateral nerve-sparing could be performed in three patients. Placement of the spider silk conduit was uneventful, contact of the spider silk with the surrounding tissue was mostly sufficient for a stable connection with the proximal and distal ends of the dissected bundles. Inflammatory markers peaked until postoperative day 1 but stabilized until discharge without any need for antibiotic treatment throughout the hospital stay. One patient was readmitted due to a urinary tract infection. Three patients reported about erections sufficient for penetration after three months with a continuous improvement of erectile function both after bi- and unilateral nerve-sparing with SSNR up to the last follow-up after 18 months. CONCLUSION: In this analysis of the first RARP with SSNR, a simple intraoperative handling without major complications was demonstrated. While the series provides evidence that SSNR is safe and feasible, a prospective randomized trial with long-term follow-up is needed to identify further improvement in postoperative erectile function due to the spider silk-directed nerve regeneration.

Magnesium-Based Compression Screws in Acute Scaphoid Fractures and Nonunions.

BACKGROUND: Magnesium-based bioabsorbable osteosynthesis material continues to receive increasing attention. The following study documents our experience with bioabsorbable magnesium screws in scaphoid fracture treatment in hopes to capture further evidence and successful application. METHODS: Eight acute scaphoid fractures and four nonunions were treated with the magnesium-based bioabsorbable compression screw MAGNEZIX®. Objective outcome was assessed by X-ray imaging and/or CT scan for bone healing. Clinical assessment was achieved using the modified Mayo Wrist Score. Patient-reported outcome measure was performed threefold via QuickDASH, PRWE, and EQ-5D-5L questionnaires in all patients. Follow-up was 32.5 months (SD 18.7) in the acute fracture group and 31 months (SD 7.4) in the nonunion group. RESULTS: Bone healing was achieved in all eight patients with acute scaphoid fractures and in three of four patients with scaphoid nonunion. The modified Mayo Wrist Score was 95 (SD 7.1) in fractures and 80 (SD 7.1) in nonunion patients during follow-up. QuickDASH score was 3.9 (SD 5.8) in fracture and 19.3 (SD 10.6) in nonunion patients. All but one patient (87,5%) with scaphoid fractures presented with a full health state during follow-up (EQ-5D-5L). Nonunion patients had problems in 10 out of 19 dimensions in EQ-5D-5L. Acute fractures presented with a score of 3.9 (SD 7.9) and nonunions with a score of 19.7 (SD 32.4) in PRWE total scoring during follow-up. CONCLUSIONS: Magnesium-based implants have excellent clinical outcomes when used for scaphoid fractures in eight presented cases and good to moderate clinical outcomes when used for nonunions in three of four presented cases. Additional studies are required to further analyze the differentiated applicability in scaphoid nonunion as well as overall performance when compared to non-absorbable screws in larger cohorts.

An MXD1-derived repressor peptide identifies noncoding mediators of MYC-driven cell proliferation.

MYC controls the transcription of large numbers of long noncoding RNAs (lncRNAs). Since MYC is a ubiquitous oncoprotein, some of these lncRNAs probably play a significant role in cancer. We applied CRISPR interference (CRISPRi) to the identification of MYC-regulated lncRNAs that are required for MYC-driven cell proliferation in the P493-6 and RAMOS human lymphoid cell lines. We identified 320 noncoding loci that play positive roles in cell growth. Transcriptional repression of any one of these lncRNAs reduces the proliferative capacity of the cells. Selected hits were validated by RT-qPCR and in CRISPRi competition assays with individual GFP-expressing sgRNA constructs. We also showed binding of MYC to the promoter of two candidate genes by chromatin immunoprecipitation. In the course of our studies, we discovered that the repressor domain SID (SIN3-interacting domain) derived from the MXD1 protein is highly effective in P493-6 and RAMOS cells in terms of the number of guides depleted in library screening and the extent of the induced transcriptional repression. In the cell lines used, SID is superior to the KRAB repressor domain, which serves routinely as a transcriptional repressor domain in CRISPRi. The SID transcriptional repressor domain is effective as a fusion to the MS2 aptamer binding protein MCP, allowing the construction of a doxycycline-regulatable CRISPRi system that allows controlled repression of targeted genes and will facilitate the functional analysis of growth-promoting lncRNAs.

Evaluation of the predictive value of the body-mass-index choosing perforator flaps from different donor sites.

BACKGROUND: Free flap design must fulfill different criteria to ensure functional and aesthetic reconstruction of different types of defects in different body areas. A four-dimensional planning concept was used including flap length, width, thickness and tissue composition. This study evaluates if body-mass-index (BMI) has a predictive value for flap design. METHODS: A prospective study including hospitalized patients in the Department of Plastic, Aesthetic, Hand and Reconstructive Surgery was conducted. Not taking into account the reason for admission, the patients were examined based on age, weight, height, BMI and sex. The areas of a potential harvest of free fasciocutaneous and perforator flaps were measured using ultrasound examination to determine the thickness of the subcutaneous layers and prove blood perfusion. RESULTS: Over the period of four months, a total of 101 patients (36 females and 65 males) were included in this study and gave written consent. No statistical significance regarding the demographic data such as age, sex and BMI could be identified. An average to high correlation between free flap thickness and BMI was shown for the thoracodorsal artery perforator (TDAP), anterior lateral thigh (ALT) and deep inferior epigastric perforator (DIEP) flap in both, male and female patients. Free flaps of distal body parts such as the interosseous posterior flap, showed a lower correlation. No correlation using the Pearson coefficient could be found for age and volume. CONCLUSION: Our study demonstrated that the BMI is a predictive indicator that can be used in the preoperative planning of reconstructions using free flaps. Depending on the defect location, the BMI can be considered to predict the thickness of the free flap and may influence the surgeon's choice. On the other hand, a lower correlation between BMI and flap thickness encourages the use of standard flaps if more volume is desired, as the DIEP flap might be sufficient even in normal-weight women. Flaps of distal body parts, such as the forearm or lower leg, are not prone to such predictions and require other selection criteria.

Multiplanar (4-Dimension) Breast Augmentation-A Personal Surgical Concept for Dynamic Implant-Tissue Interaction Providing Sustainable Shape Stability.

BACKGROUND: In esthetic breast augmentation long-term shape stability and natural appearance remain an ongoing challenge. The authors found that to reduce the incidence of secondary deformity and increase the natural feel and appearance, a standard multiplanar procedure combining a subfascial and dual plane approach with fasciotomies will provide long-term stability and esthetic quality. PATIENTS AND METHODS: The technique involves a submuscular dissection, release of the infranipple portion of the pectoralis muscle combined with the wide subfascial release of the breast gland, and scoring of the deep plane of the superficial glandular fascia. For long-term stability, a firm fixation of the glandular fascia at the inframammary fold to the deep layer of the abdomino-pectoral fascia is critical. Long-term results were analyzed for up to 10 years. RESULTS: Postoperative measurements proved the intrinsic balance of the breasts without significant changes over time. The overall complication rate was <5%. Shape stability was observed over 10 years in more than 95% of the patients. Unsightly muscular animation could be avoided in almost every patient. CONCLUSIONS: Our results indicate that a technique of multiplane breast augmentation provides long-term stability and esthetic quality. By combining the benefits of well-established techniques of a submuscular dual plane, additional shaping through a controlled deep fasciotomy and stable inframammary fold fixation some of the existing tradeoffs of the different methods can be avoided.

Consequences and predisposing factors of self-discharge against medical advice in plastic and hand surgery.

PURPOSE: Therapeutic success of surgical interventions is significantly affected by patients' adherence. Patient autonomy can lead to unreasonable behavior. We analyzed the consequences and predisposing factors of patient self-discharge in a plastic and hand surgery cohort. STUDY DESIGN AND SETTING: Data was collected retrospectively in a case-control study with n = 73 patients who had self-discharged in a 10-year time period and n = 130 controls (discharge by the surgeon). Data was collected through the hospital information systems and a particular questionnaire. Statistical analyses were performed via chi-squared test and logistic regression analyses. RESULTS: Patients who self-discharged against medical advice had a significantly higher complication rate (p = 0.045) and a higher number of revision operations (p < 0.001). They were more often dissatisfied with the primary inpatient treatment (p < 0.05). Secondly, they lived more often in shared households (p = 0.002; OR 5.387 (1.734-16.732)) or had to take care of their children at home (p = 0.006; OR 1.481 (1.280-1.741)). There was a significantly lower pain score (NAS) on time of self-discharge (p = 0.002) as well as 24 h after self-discharge (p < 0.001) in self-discharged patients. CONCLUSION: Self-discharge was associated with predisposing factors and poorer outcomes. Patient autonomy can lead to health-compromising behavior and patients should be counseled accordingly.

Short-term efficacy and adverse effects of collagenase clostridium histolyticum injections, percutaneous needle fasciotomy and limited fasciectomy in the treatment of Dupuytren's contracture: a network meta-analysis of randomized controlled trials.

AIMS: Dupuytren's contracture (DC) is a chronic debilitating fibroproliferative disorder. Common treatment options include collagenase clostridium histolyticum injections (CI), percutaneous needle fasciotomy (NF) and limited fasciectomy (LF). Superiority of one specific treatment remains controversial. This study aims to assess the short-term efficacy and safety of CI, NF, and LF for the treatment of DC. METHODS: We included randomized controlled trials of CI compared with placebo, NF and LF for patients with DC. PubMed, Embase and the Cochrane Library were searched from inception to August 2021. Contracture reduction rates in treated joints (within 0-5° of full extension within 30 days), relative reduction in total passive extension deficit (TPED), occurrence of one or more adverse events and number of treatment-related adverse events per patient were the outcomes of interest. The Cochrane risk-of-bias tool was employed for quality assessment of the studies. A network meta-analysis was performed using MetaXL. RESULTS: Nine studies met our inclusion criteria (n = 903). Overall, risk bias was mixed and mostly low. Short term TPED reduction achieved with LF was superior compared to CI and NF. Although CI achieved greater TPED reduction compared to NF, it was associated with the highest risk of overall adverse effects. The analyzed data was limited to a maximum three-year follow-up period and therefore insufficient for long-term outcome evaluation. CONCLUSIONS: In DC, LF may be able to provide patients with severe disease, superior flexion contracture release postoperatively. CI is a valid treatment alternative to NF, however the higher risk of overall adverse effects must be considered. The quality-of-evidence is limited due to short-term follow-up periods and a lack of standardized definitions of complications and adverse events.

The Failed Breast Implant in Postmastectomy Reconstruction: A Systematic Literature Review of Complications of Implant-Based Breast Reconstruction.

BACKGROUND: Breast cancer is the most diagnosed malignant neoplasia of female patients worldwide in 2019. Survival has increased making it necessary to offer breast reconstructive procedures to improve quality of life and self-esteem. Implant-based breast reconstruction is the most common approach, making it necessary to quantify the associated complications. METHODS: A systematic literature review of the PubMed, Cochrane, and Web of Science databases was performed. A total of 9608 citations were identified, and 44 studies met the inclusion criteria. RESULTS: Studies included reported the incidence of complications either per patient or per breast leading consequently to 2 complication rates depending on the type of reporting. A total of 14.3% of patient-related and 28.8% of breast-related complications while undergoing implant-based reconstruction were reported.Among total complications reported, 72.6% of patient-related and 48.5% of breast-related complications were classified as major complications.A total of 37.6% of patients respectively 15.1% of breasts required prosthesis explantation due to severe complications. Depending on reporting, 9.7% of patients and 4% of breasts required autologous flap reconstruction due to reconstructive failure. CONCLUSIONS: High complication and failure rates are associated with implant-based breast reconstruction. Lacking randomized controlled trials, the choice between implant-based and autologous breast reconstruction has to be made individually for each patient.

Superficial Temporal Recipient Vessels for Craniofacial Microvascular Free-Flaps.

The selection of recipient vessels for microvascular free-flaps is critical in craniofacial reconstruction. Especially the suitability of the superficial temporal vessels is questioned conflictingly in the literature. The aim of this study was to share our experience with microvascular craniofacial free-flap reconstruction and to evaluate a set of factors that are related to the recipient vessels and to determine how these factors influence flap survival. We conducted a retrospective analysis of 39 free-flaps for craniofacial reconstruction that were performed from 2006 until 2020 and evaluated the indication for microvascular reconstruction, recipient vessels, various factors related to the recipient vessels and complications. The most utilized recipient artery was the facial artery, selected in 20 patients followed by the superficial temporal artery selected in 12 patients. The most commonly used recipient vein was the facial vein used in 16 patients, followed by the superficial temporal vein selected in 10 patients and the external jugular vein in 6 patients. Total flap necrosis occurred in one patient. There was no statistically significant association between the selected recipient vessels and patient comorbidities, major and minor complications, revision of anastomosis or flap loss. The results of our study have demonstrated that the superficial temporal artery and vein show similar results when used for face and scalp reconstruction. Considering their technical and aesthetic advantages they may be the first choice recipient vessels in established free-flap treatment algorithms for craniofacial reconstruction.

Complications and Disasters After Minimally Invasive Tissue Augmentation with Different Types of Fillers: A Retrospective Analysis.

BACKGROUND: The interest in youthful appearance and rejuvenating procedures is unbroken in our society. Besides surgical procedures, permanent fillers are utilized. The incorrect and unprofessional use of these substances, auto-injections in particular, have devastating results for patients and are challenging for the plastic surgeon. The aim of this retrospective study was to delineate the differences between permanent and non-permanent filler complications and appropriate treatment options. METHODS: We conducted a retrospective study and researched the hospital information system in the time period from 2001 to 2020. Patients with unprofessional use of permanent fillers, auto-injections and injections of unformulated substances were determined. Age, gender, localization, complications, length of hospital stay, comorbidities, histopathological workups and surgical salvage procedures were noted. Descriptive statistics were calculated. RESULTS: Seventeen patients were identified from 2001 till 2020. In four cases, auto-injections by the patients were the cause, whereas in the other patients the injections were performed by medical staff. Ages range from 18 to 57 years. Fourteen patients were female and three were male. The injected substances could be recognized as synthol, silicone, vaseline, fat tissue, hyaluronic acid as well as non-medical substances. Surgical procedures were necessary in eleven cases. One patient died because of the underlying diseases. CONCLUSION: Our results indicate different sequels of filler materials injected in an unprofessional way, possible complications, conservative and surgical techniques to resolve these rare complications. We suggest a staged therapy adjusted to the clinical symptoms. Milder symptoms can be handled conservatively, whereas severe infections, skin breakdowns or persistent granuloma are justifying indications for surgical treatment. 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 .

[Infections of the hand and forearm]. / Infektionen der Hand und des Unterarms.

Infections of the hand and forearm are a frequently seen surgical emergency of the hand. Patients of all age groups are affected and underlying systemic diseases are risk factors. Posttraumatic causes are the leading cause of infections. This includes cuts and stab wounds, animal and human bites but often also minor injuries. Due to the anatomical peculiarities of the hand, rapid progression of initially inconspicuous infections can occur resulting in functional limitations. If an infection is suspected, a symptom-oriented evaluation by a hand surgeon should be performed. This includes a detailed patient history, clinical examination, laboratory analyses and imaging. This is followed by the development of an individualized and interdisciplinary treatment concept with the aim of achieving the shortest possible rehabilitation period. The treatment includes surgical cleansing of the infection, accompanied by antibiotic treatment taking the expected possible spectrum of pathogens into account. Cephalosporins and aminopenicillins in combination with beta-lactamase inhibitors are the antibiotics of first choice. Follow-up treatment includes early functional exercise under the guidance of a hand therapist to minimize postinfectious restrictions in the range of motion and to enable occupational rehabilitation. In rare cases, fulminant necrotizing infections with resulting skin and soft tissue defects can occur. In these cases, secondary plastic reconstruction is usually required after cleansing of the infection.